Respiratory Module Apr 2022 MRCP Part-1

Hint

Commonly, untreated Smear-Positive Pulmonary Tuberculosis [TB] is likely to be infectious. Active disease may be indicated by Grade III / IV response to Tuberculin. Eighty percent of individuals with a history of BCG Vaccination have Grade I / II response._x000D_
All forms of Pulmonary Tuberculosis [TB] may be treated equally except Tuberculous Pleural Effusion which may require drainage (with large effusions causing breathlessness) and adjunct corticosteroids to delay reaccumulation._x000D_
The length of treatment for other forms are:_x000D_
? Bone Tuberculosis [Bone TB] ? 9 months_x000D_
? Meningitis ? 1 year_x000D_
? Drug Resistance ? 2 years._x000D_
Streptomycin has high activity against extracellular organisms whilst Pyrazinamide have high activity against intracellular organisms.

Hint

About 50% of patients have an improvement in their symptoms with steroids and 25% have improved lung function. A recent study has suggested this treatment may actually be associated with an increased mortality, but further studies are required before this is widely accepted._x000D_
High Resolution CT Scans [HRCTs] can be used to determine the Stage of Idiopathic Pulmonary Fibrosis. When Ground Glass Attenuation predominates, it usually represents an Inflammatory Cell Infiltrate which has been shown to respond well to treatment. As the disease progresses it develops a Reticular Appearance which represents Irreversible Fibrotic Changes. The presence of a predominantly Ground Glass Appearance is also an independent predictor of survival._x000D_
Both Total Lung Capacity (TLC) and Residual Volume (RV) reduce with restrictive disorders like Idiopathic Pulmonary Fibrosis, so the ratio is maintained. A raised RV / TLC Ratio suggests a combination of Airways Obstruction and Restrictive Defect not just Idiopathic Pulmonary Fibrosis as mentioned in this question._x000D_
Peak Flow measures Airway Obstruction. Idiopathic Pulmonary Fibrosis is characterised by a Restrictive Defect on Lung Function Testing._x000D_
Peak Incidence is in the Sixth Decade.

Hint

Active inflammation may be suggested by a computed tomography (CT) scan (option C) is the correct answer. A high-resolution computed tomography (HRCT) scan of the chest can show the characteristic features of idiopathic pulmonary fibrosis, such as honeycombing, traction bronchiectasis, and subpleural reticular opacities. However, these findings do not indicate active inflammation, but rather chronic fibrosis and architectural distortion of the lung parenchyma. In some cases, the high-resolution computed tomography (HRCT) scan may also show areas of ground glass attenuation, which are regions of increased lung density that do not obscure the underlying structures. Ground glass attenuation may represent an inflammatory cell infiltrate, which has been shown to respond well to corticosteroid treatment and have a better prognosis than fibrotic lesions. Therefore, the presence of ground glass attenuation on high-resolution computed tomography (HRCT) scan may suggest active inflammation in idiopathic pulmonary fibrosis.

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The other options are incorrect for the following reasons:

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• A. Lung volumes show a raised residual volume / total lung capacity ratio: This is incorrect. Lung volumes are measurements of the amount of air that the lungs can hold at different phases of the respiratory cycle. Residual volume (RV) is the amount of air that remains in the lungs after a full exhalation, and total lung capacity (TLC) is the maximum amount of air that the lungs can hold. The ratio of residual volume to total lung capacity reflects the degree of air trapping in the lungs, and a high ratio indicates reduced lung function. Idiopathic pulmonary fibrosis causes scarring and stiffening of the lung tissue, which reduces the lung’s ability to expand and contract normally. This leads to a decrease in both residual volume and total lung capacity, so the ratio is maintained or slightly reduced. A raised residual volume / total lung capacity ratio suggests a combination of airways obstruction and restrictive defect, not just idiopathic pulmonary fibrosis as mentioned in this question.

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• B. Peak incidence seen in the fourth decade: This is incorrect. The peak incidence of idiopathic pulmonary fibrosis is seen in the sixth or seventh decade of life, not the fourth. The average age of diagnosis is around 66 years, and the disease is more common in men than in women.

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• D. 80% of patients initially respond well to immunosuppression: This is incorrect. There is no evidence that immunosuppressive therapy is effective or beneficial for idiopathic pulmonary fibrosis. In fact, some studies have shown that immunosuppression may be harmful and increase the risk of mortality and infection in these patients. The only approved medications for idiopathic pulmonary fibrosis are pirfenidone and nintedanib, which can slow down the progression of the disease, but not reverse it.

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• E. Peak flow rate is a good guide to severity: This is incorrect. Peak flow rate is a measure of the maximum speed of air that can be exhaled from the lungs. It is mainly used to monitor and manage asthma, which is an obstructive lung disease that causes narrowing of the airways. Idiopathic pulmonary fibrosis, on the other hand, is a restrictive lung disease that causes reduced lung volume and compliance. Therefore, peak flow rate is not a good indicator of the severity or prognosis of idiopathic pulmonary fibrosis. A better measure is the forced vital capacity (FVC), which is the amount of air that can be forcibly exhaled from the lungs after a full inhalation.

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Hint

According to the latest National Institute for Health and Care Excellence (NICE) guidance, the combination of post-bronchodilator results that is now classed as severe airflow obstruction in chronic obstructive pulmonary disease (COPD) is option C: FEV1/FVC <0.7 & FEV1 predicted <30%. This is a change from the previous National Institute for Health and Care Excellence (NICE) guideline, which used the GOLD criteria and defined severe airflow obstruction as FEV1/FVC <0.7 & FEV1 predicted 30-49% (option A). The new National Institute for Health and Care Excellence (NICE) guidance has adopted the lower limit of normal (LLN) approach, which defines airflow obstruction as FEV1/FVC below the fifth percentile of the normal population. This means that some people who were previously classified as having severe airflow obstruction may now be reclassified as having very severe airflow obstruction, which has implications for their management and prognosis.

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What Is GOLD Criteria:

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The GOLD criteria are a set of guidelines for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (COPD). They are developed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), collaboration between the National Heart, Lung, and Blood Institute (NHLBI), the World Health Organization (WHO), and other international health organizations.

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The GOLD criteria use a combination of spirometry results, symptom assessment, exacerbation history, and comorbidity evaluation to classify COPD into four grades of severity and four groups of treatment recommendations. The spirometry results measure the degree of airflow obstruction, based on the ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) and the percentage of predicted FEV1. The symptom assessment uses either the COPD Assessment Test (CAT) or the Modified Medical Research Council (mMRC) questionnaire to evaluate the impact of dyspnoea, cough, and sputum on the patient’s quality of life. The exacerbation history counts the number and severity of chronic obstructive pulmonary disease (COPD) flare-ups in the past year. The comorbidity evaluation considers the presence of other chronic diseases that may affect the patient’s prognosis and treatment.

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The GOLD criteria are updated periodically to reflect the latest evidence and best practices in chronic obstructive pulmonary disease (COPD) care. The most recent version is the 2023 GOLD Report, which introduced some changes from the previous versions, such as a new definition of chronic obstructive pulmonary disease (COPD), a lower limit of normal (LLN) approach for spirometry, and a simplified treatment algorithm.

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NOTE:

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There have been some alterations to previous classification of airflow obstruction, based on the American Thoracic Society, GOLD and European Respiratory Society Standards.

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Below are the classifications:

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FEV1/FVC ratio is less than 0.7 in chronic obstructive pulmonary disease (COPD).

Hint

Chlamydia psittaci is endemic in birds including psittacine birds, canaries, finches, pigeons and poultry._x000D_
Pet owners, vets and zoo keepers are most at risk. It is rare in children._x000D_
Person to person transmission occurs though it is very rare._x000D_
Sputum Gram stain reveals a few leucocytes and no predominant bacteria. There are few signs and few laboratory/x ray findings._x000D_
Positive serology is with complement-fixing antibodies._x000D_
It is treated with tetracycline.

Hint

The correct answer to the above question is B. It is a cell-mediated immune response. This is the correct statement regarding this boy’s immune reaction to the Mantoux test.

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The Mantoux test, also known as the tuberculin skin test (TST), is a diagnostic tool used to detect exposure to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). Mantoux test has replaced Heaf test in 2005 in United Kingdom. It involves injecting a small amount of purified protein derivative (PPD), a substance derived from the tuberculosis (TB) bacterium, just under the surface of the skin on the inside of the forearm.

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The immune reaction to the Mantoux test is a type of delayed hypersensitivity reaction, which is mediated by T lymphocytes, a type of white blood cells that are involved in cell-mediated immunity.

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Cell-mediated immunity is a branch of the adaptive immune system that protects the body from intracellular pathogens, such as viruses, bacteria, fungi, and parasites, by activating macrophages, natural killer cells, and cytotoxic T cells.

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If the person has been exposed to the tuberculosis (TB) bacterium in the past, either by infection or vaccination, their T lymphocytes will recognize the purified protein derivative (PPD) as a foreign antigen and mount an immune response. This will cause inflammation and swelling at the site of injection, which is measured as the area of induration (hardening) after 48 to 72 hours. The size of the induration reflects the degree of the immune reaction and the likelihood of tuberculosis (TB) infection.

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The other statements are incorrect regarding his immune reaction to the Mantoux test, as follows:

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• A. The response is mediated by B lymphocytes: This is incorrect, as B lymphocytes are a type of white blood cells that are involved in humoral immunity, not cell-mediated immunity. Humoral immunity is a branch of the adaptive immune system that protects the body from extracellular pathogens, such as bacteria, toxins, and venoms, by producing antibodies. Antibodies are proteins that bind to specific antigens and neutralize or eliminate them. The Mantoux test does not measure the antibody response to the tuberculosis (TB) bacterium, but the T cell response.

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• C. The area of induration will be less than 10 mm in diameter: This is incorrect, as the area of induration may vary depending on the person’s risk factors for tuberculosis (TB) infection. In general, an induration of 5 mm or more is considered positive for people who have a high risk of tuberculosis (TB) infection, such as those who have HIV infection, close contact with tuberculosis (TB) case, or chest x-ray findings suggestive of tuberculosis (TB). An induration of 10 mm or more is considered positive for people who have a moderate risk of tuberculosis (TB) infection, such as those who have certain medical conditions, work or live in high-risk settings, or come from countries with high tuberculosis (TB) prevalence. An induration of 15 mm or more is considered positive for people who have a low risk of tuberculosis (TB) infection, such as those who have no known risk factors.

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• D. The reaction typically develops within 24 hours: This is incorrect, as the reaction to the Mantoux test is a delayed hypersensitivity reaction, which takes 48 to 72 hours to develop. This is because it takes time for the T lymphocytes to migrate to the site of injection and release inflammatory mediators. If the reaction develops within 24 hours, it may indicate an immediate hypersensitivity reaction, which is mediated by IgE antibodies and mast cells, not T lymphocytes. This type of reaction is usually seen in people who have a history of atopy, such as allergic rhinitis, asthma, or eczema.

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• E. If a skin biopsy were taken, immunohistochemistry would show immune complex deposition: This is incorrect, as immune complex deposition is a feature of type III hypersensitivity reaction, not type IV hypersensitivity reaction. Type III hypersensitivity reaction is mediated by IgG or IgM antibodies and complement, not T lymphocytes. Immune complex deposition occurs when the antibodies bind to soluble antigens and form insoluble aggregates that deposit in the tissues and blood vessels, causing inflammation and damage. This type of reaction is seen in some autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, or vasculitis. If a skin biopsy were taken from the Mantoux test site, immunohistochemistry would show T lymphocyte infiltration, not immune complex deposition.

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Hint

The most suggestive investigation of asthma in this case would be option D: Diurnal variation in peak expiratory flow rate (PEFR) >20%.

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While options A, C, and E may indicate a potential allergic predisposition, they are not specific to asthma and can be present in other conditions as well. Option B, resolution of symptoms the day after the examination, could be attributed to various factors and does not necessarily point towards asthma.

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Diurnal variation in peak expiratory flow rate (PEFR) >20% is a characteristic feature of asthma. Asthma symptoms tend to worsen during the night and early morning due to increased airway inflammation and bronchoconstriction. This results in decreased airflow and lower peak expiratory flow rate (PEFR) readings. In contrast, as the day progresses and the airways relax, the peak expiratory flow rate (PEFR) readings tend to improve. A diurnal variation of >20% in peak expiratory flow rate (PEFR) is suggestive of bronchial hyperresponsiveness, a hallmark feature of asthma.

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Therefore, option D, diurnal variation in peak expiratory flow rate (PEFR) >20%, is the most indicative investigation suggesting asthma in this case.

Hint

This patient is demonstrating Pulsus Paradoxus._x000D_
The right heart responds directly to changes in intrathoracic pressure, while the filling of the left heart depends on the pulmonary vascular volume._x000D_
At high respiratory rates, with severe air flow limitation (for example, acute asthma) there is an increased and sudden negative intrathoracic pressure on inspiration and this will enhance the normal fall in blood pressure.

Hint

The most likely explanation for this clinical sign is C. Reduced left atrial filling pressure on inspiration. This is because this boy has pulsus paradoxus, an abnormally large decrease in systolic blood pressure and pulse wave amplitude during inspiration. Pulsus paradoxus is a sign of severe asthma, as well as other conditions that affect the heart and lungs.

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Pulsus paradoxus occurs when the negative intra-thoracic pressure during inspiration causes an increased right venous return, which expands the right atrium and reduces the compliance of the left atrium due to their shared septum. This leads to a reduced left atrial filling pressure and a reduced left ventricular stroke volume, which manifests as a decrease in systolic blood pressure and pulse volume.

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The other options are incorrect because they do not explain the pulsus paradoxus phenomenon. Option A is incorrect because myocardial depression due to hypoxia would cause a global reduction in cardiac output, not a variation with the respiratory cycle. Option B is incorrect because beta-agonist bronchodilator drugs would increase the heart rate and blood pressure, not decrease them. Option D is incorrect because the heart rate usually increases slightly during inspiration, not decreases. Option E is incorrect because peripheral vasodilatation would cause a decrease in diastolic blood pressure, not systolic blood pressure.

Hint

The most appropriate next step to be incorporated into the management of this girl is B. Salbutamol via oxygen-driven nebuliser. This is because salbutamol is a short-acting beta 2 agonist that can rapidly relieve the bronchospasm and airflow obstruction in acute asthma exacerbations. Oxygen-driven nebulisation can deliver a higher dose of salbutamol than a metered-dose inhaler and can also improve the oxygen saturation of the patient. Salbutamol via oxygen-driven nebuliser is recommended for patients with moderate to severe asthma exacerbations who have a PEF of less than 50% of the predicted value.

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The other options are less appropriate for the following reasons:

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• A. Intravenous salbutamol is not routinely used for acute asthma exacerbations, as it has no proven benefit over inhaled salbutamol and may cause more adverse effects, such as tachycardia, hypokalaemia, and hyperglycaemia.

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• C. Ipratropium bromide is an anticholinergic agent that can be added to salbutamol for patients with severe asthma exacerbations who do not respond adequately to salbutamol alone. However, it is not a substitute for salbutamol and should not be used as monotherapy.

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• D. Salmeterol is a long-acting beta 2 agonist that can prevent asthma symptoms and reduce the risk of exacerbations when used as a maintenance therapy in combination with inhaled corticosteroids. However, it is not indicated for the treatment of acute asthma exacerbations, as it has a slower onset of action and a longer duration of action than salbutamol.

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1. Intravenous aminophylline is a methylxanthine that can have bronchodilator and anti-inflammatory effects in asthma. However, it is not recommended for the routine management of acute asthma exacerbations, as it has a narrow therapeutic window and a high risk of toxicity, such as nausea, vomiting, arrhythmias, and seizures. It may be considered as a rescue therapy for patients with life-threatening asthma exacerbations who do not respond to other treatments, but only under close monitoring and with serum level measurement.

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Another Approach:

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This young girl meets the criteria for acute severe asthma. In such cases, it is important to administer β2-agonists as soon as possible, preferably through nebulization with oxygen. These doses should be repeated at 15-30 minute intervals, or continuous nebulization can be used if there is an inadequate response to bolus therapy. For patients with acute severe or life-threatening asthma, or those with a poor initial response, it is recommended to add nebulized ipratropium bromide, as it provides significantly greater bronchodilation when combined with a β2-agonist.

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To maintain oxygen saturation levels between 94-98%, oxygen should be given. If a patient’s saturation falls below 92% on air, an arterial blood gas (ABG) should be performed to rule out hypercapnia. However, it is important not to delay treatment for the arterial blood gas (ABG). Initially, high-flow oxygen is used and then gradually reduced to maintain adequate saturation levels. Unless the clinician suspects chronic obstructive pulmonary disease (COPD), there is no need to be cautious with oxygen therapy.

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Steroids play a crucial role in reducing mortality, relapses, subsequent hospital admissions, and the need for β2-agonists. Therefore, once oxygen and nebulizer therapy are established, a dose of 40-50 mg of steroids should be given. This treatment should be continued for 5 days or until recovery, and can be stopped abruptly unless the patient has been taking long-term oral corticosteroids.

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If the patient fails to respond to the above treatment steps, the use of intravenous magnesium sulphate and aminophylline may be considered. However, it is important to have a discussion with senior colleagues of the treating physician before administering these medications.

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Intensive care is necessary for patients with severe acute or life-threatening asthma who are not responding to therapy. It should be considered for patients with deteriorating peak flow, persistent or worsening hypoxia, hypercapnia, acidosis, exhaustion, or altered consciousness. When transferring patients to an Intensive Care Unit (ICU), they should be accompanied by a doctor who is capable of intubation if necessary.

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As a side note, chest radiographs are not typically necessary unless the clinician suspects pneumothorax or consolidation, or if there is life-threatening asthma, a failure to respond to treatment, or a need for ventilation.

Hint

Distal Intestinal Obstruction Syndrome occurs in 10-20% of patients with Cystic Fibrosis and incidence increases with age. About 80% of cases present for the first time in adults._x000D_
The pathogenesis is partially due to loss of CFTR Function in the Intestine which results in deregulation of chloride secretion from the crypts, bicarbonate secretion from Brunner’s glands and sodium transport. This leads to the accumulation of viscous mucus and faecal material in the terminal ileum, caecum, and ascending colon._x000D_
Investigation should include a plain abdominal radiograph which classically shows faecal loading in the right iliac fossa, dilatation of the ileum and an empty distal colon._x000D_
Ultrasound may be helpful in identifying an obstruction mass but cannot be relied upon to exclude other causes of pain and bowel obstruction._x000D_
CT can help with diagnosis and shows dilated small bowel and proximal colon with or without intestinal wall swelling._x000D_
Treatment for mild and moderate episodes is initially with hydration and full dietetic review to ensure that the pancreatic enzyme dose is titrated to fat intake. Regular laxatives should be given, for example, Senna and Lactulose._x000D_
In addition, N-Acetylcysteine can be used in moderate episodes. This loosens and softens the plugs, presumably by ‘opening’ the disulphide bonds in the abnormal intestinal mucus and maintains luminal patency._x000D_
Severe episodes can be treated with Gastrograffin or Klean-Prep, taken regularly._x000D_
If there are signs of peritoneal irritation or complete bowel obstruction, surgical review should be obtained. Surgeons will often treat initially with Intravenous Fluids and an NG Tube whilst keeping the patient nil by mouth. N-Acetylcysteine can be put down the NG Tube._x000D_
In resistant cases, Phosphate or Gastrograffin Enemas can be used, or Colonoscopy with installation of Gastrograffin.

Hint

This patient fits the criteria for Acute Severe Asthma. In such cases ?2-Agonists should be administered as soon as possible, preferably nebulised driven by oxygen. Repeat doses should be given at 15-30 minute intervals, or continuous nebulisation can be used where there is inadequate response to bolus therapy. Nebulised ipratropium bromide should be added for patients with acute severe or life threatening asthma, or those with a poor initial response. It’s addition produces significantly greater bronchodilation than a ?2-agonist alone._x000D_
Oxygen should be given to maintain saturations at 94-98%. Patients with saturations less than 92% on air should have an ABG to exclude hypercapnia. However, starting treatment should not be delayed to do the ABG. Initially high-flow oxygen is used, and then weaned to maintain adequate saturations. Unless you suspect COPD there is no need to be cautious with oxygen therapy._x000D_
Steroids reduce mortality, relapses, subsequent hospital admission and requirement for ?2-agonists1. The earlier they are given in the attack, the better the outcome. A dose of 40-50 mg should therefore be given once oxygen and nebuliser therapy has been established. This should be continued for 5 days, or until recovery, and can then be stopped abruptly unless the patient has taken long-term oral corticosteroids._x000D_
Failure to respond to the above treatment steps may warrant the use of intravenous magnesium sulphate and aminophylline. However, these should not be used without discussion with your senior colleagues._x000D_
Intensive care is indicated for patients with severe acute or life threatening asthma who are failing to respond to therapy. Consider it in patients with deteriorating peak flow, persisting or worsening hypoxia, hypercapnia, acidosis, exhaustion or altered conscious state. All patients who are transferred to an intensive care unit should be accompanied by a doctor who can intubate if necessary._x000D_
As an aside, chest radiographs are not indicated unless you suspect pneumothorax or consolidation, or there is life-threatening asthma, a failure to respond to treatment or a need for ventilation.

Hint

Option E: Bronchopulmonary aspergillosis and wheezing is the correct answer. Bronchopulmonary aspergillosis is a spectrum of lung diseases caused by an allergic or invasive reaction to the fungus Aspergillus fumigatus, which is commonly found in soil, decaying vegetation, and dust. Wheezing is a high-pitched sound produced by the air passing through narrowed airways, which can be caused by various conditions, such as asthma, bronchitis, or chronic obstructive pulmonary disease (COPD). Bronchopulmonary aspergillosis and wheezing are often associated, especially in the form of allergic bronchopulmonary aspergillosis (ABPA), which occurs in some people with asthma or cystic fibrosis who have a hypersensitivity reaction to the fungus. Allergic bronchopulmonary aspergillosis (ABPA) can cause symptoms such as coughing, fever, mucus production, and worsening of asthma.

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The other options are incorrect for the following reasons:

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• A. Pulmonary fibrosis and hypercapnia: Pulmonary fibrosis is a condition that causes scarring and stiffening of the lung tissue, impairing gas exchange. Hypercapnia is a state of elevated carbon dioxide levels in the blood, which can result from hypoventilation or ventilation-perfusion mismatch. Pulmonary fibrosis can cause hypercapnia, but it is not a specific or exclusive association, as many other lung diseases can also cause hypercapnia.

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• B. Pulmonary embolus and left bundle branch block (LBBB): Pulmonary embolus is a blockage of a pulmonary artery by a blood clot or other material, which can cause chest pain, shortness of breath, and haemoptysis. Left bundle branch block (LBBB) is a cardiac conduction abnormality that causes a delay in the electrical activation of the left ventricle, which can be seen on an electrocardiogram (ECG). Pulmonary embolus and left bundle branch block (LBBB) are not directly related, although both can affect the right ventricular function and cause pulmonary hypertension.

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• C. Lung carcinoids and pleural effusion: Lung carcinoids are rare tumours that arise from the neuroendocrine cells of the bronchial epithelium. They are usually slow-growing and have a good prognosis. Pleural effusion is an accumulation of fluid in the pleural space, which can be caused by various conditions, such as infection, malignancy, heart failure, or trauma. Lung carcinoids and pleural effusion are not commonly associated, as lung carcinoids rarely metastasize or invade the pleura.

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• D. Pneumoconiosis and clubbing: Pneumoconiosis is a group of lung diseases caused by inhalation of dust, such as coal, asbestos, or silica. Clubbing is a deformity of the fingers and nails that results from chronic hypoxia and inflammation in the lungs. Pneumoconiosis and clubbing are often associated, especially in advanced stages of the disease, but this association is not as strong as the one between bronchopulmonary aspergillosis and wheezing, as clubbing can also occur in other lung diseases, such as lung cancer, cystic fibrosis, or bronchiectasis.

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Hint

The correct answer is E. 3 months. This is because the patient has a provoked pulmonary embolism (PE), which means that the pulmonary embolism (PE) occurred in the setting of a transient risk factor, such as surgery, immobilization, or hormonal therapy. According to current guidelines, patients with provoked pulmonary embolism (PE) should be treated with anticoagulation for a duration of 3 months, as long as they return to their pre-pulmonary embolism (PE) baseline. The risk of recurrent venous thromboembolism (VTE) in these patients is low, about 1% in the first year after stopping anticoagulation and 0.5% per year after.

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The other answer options are incorrect for the following reasons:

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• A. Lifelong: Lifelong anticoagulation is recommended for patients with unprovoked pulmonary embolism (PE) or persistent risk factors, such as cancer, antiphospholipid syndrome, or thrombophilia. The risk of recurrent venous thromboembolism (VTE) in these patients is high, about 10% in the first year after stopping anticoagulation and 5% per year after. However, lifelong anticoagulation also increases the risk of bleeding, so the decision should be individualized and reassessed periodically.

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• B. 6 months: 6 months of anticoagulation is an alternative option for patients with unprovoked pulmonary embolism (PE) who have a low or moderate risk of bleeding. However, it is not superior to 3 months of anticoagulation for patients with provoked pulmonary embolism (PE), and it may increase the risk of bleeding complications.

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• C. 12 months: 12 months of anticoagulation is another alternative option for patients with unprovoked pulmonary embolism (PE) who have a low or moderate risk of bleeding. However, it is not superior to 3 months of anticoagulation for patients with provoked pulmonary embolism (PE), and it may increase the risk of bleeding complications.

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• D. 4 – 6 weeks: 4 – 6 weeks of anticoagulation is insufficient for patients with PE, regardless of the provoking factors. It increases the risk of recurrent venous thromboembolism (VTE) by approximately 50%.

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Hint

The correct answer is D. Stroke. This is because the history of this lady is suggestive of sleep apnoea, a condition that causes repeated interruptions of breathing during sleep due to upper airway obstruction. Sleep apnoea can increase the risk of stroke by several mechanisms, such as:

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• Reducing the oxygen levels in the blood and tissues, which can damage the brain cells and blood vessels

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• Increasing the blood pressure and heart rate, which can strain the heart and increase the risk of blood clots

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• Causing insulin resistance and impaired glucose tolerance, which can worsen the metabolic control and increase the risk of diabetes and its complications

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• Disrupting the sleep quality and quantity, which can affect the brain function and mood

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The other options are incorrect for the following reasons:

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• A. Osteoporosis is a condition that causes the bones to become weak and brittle, increasing the risk of fractures. It is more common in women and people assigned female at birth (AFAB) after menopause, when the levels of oestrogen decrease. Oestrogen is a hormone that helps regulate the body temperature, the production of urine, and the cognitive functions. Low oestrogen levels can cause hot flashes, night sweats, nocturia, mood swings, memory problems, and fatigue. However, these symptoms are not specific to osteoporosis and can also occur in other conditions, such as sleep apnoea. Moreover, osteoporosis does not directly predispose to stroke, although it can increase the risk of falls and fractures, which can lead to disability and reduced mobility.

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• B. Insulin sensitivity is the ability of the body to respond to insulin, a hormone that regulates the blood glucose levels. Insulin resistance is the opposite of insulin sensitivity, meaning that the body does not respond well to insulin and requires more of it to maintain normal glucose levels. Insulin resistance can lead to impaired glucose tolerance, diabetes, and its complications, such as cardiovascular disease and stroke. However, insulin sensitivity itself is not a condition, but a physiological parameter that can vary depending on several factors, such as diet, exercise, weight, age, and hormones. Therefore, it is not correct to say that insulin sensitivity predisposes to stroke, but rather that insulin resistance increases the risk of stroke.

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• C. Hypotension is a condition that causes low blood pressure, which can lead to symptoms such as dizziness, fainting, blurred vision, nausea, and fatigue. Hypotension can have various causes, such as dehydration, blood loss, medications, heart problems, or autonomic nervous system disorders. Hypotension can also occur as a result of sleep apnoea, due to the reduced oxygen levels and increased carbon dioxide levels in the blood, which can cause the blood vessels to dilate and lower the blood pressure. However, hypotension itself does not predispose to stroke, but rather is a consequence of sleep apnoea. In fact, stroke is more likely to occur when the blood pressure is too high, as in hypertension, as this can damage the blood vessels and increase the risk of blood clots.

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• E. Hypoglycaemia is a condition that causes low blood glucose levels, which can lead to symptoms such as sweating, trembling, hunger, confusion, seizures, and coma. Hypoglycaemia can have various causes, such as excessive insulin or oral hypoglycaemic agents, fasting, alcohol, liver disease, or hormonal deficiencies. Hypoglycaemia can also occur as a result of sleep apnoea, due to the increased insulin resistance and impaired glucose tolerance that sleep apnoea can cause. However, hypoglycaemia itself is not a risk factor for stroke, but rather a consequence of sleep apnoea. In fact, hyperglycaemia, or high blood glucose levels, is a more established risk factor for stroke, as it can damage the blood vessels and increase the risk of blood clots.

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Hint

This history is typical of sleep apnoea._x000D_
Sleep apnoea is an independent risk factor for stroke (and death from all causes), and is associated with hypertension, impaired glucose tolerance (IGT) and insulin resistance._x000D_
Severe Sleep Apnea and Risk of Ischemic Stroke in the Elderly. Stroke 2006. 37. 2317-2321

Hint

Low Serum Albumin and Elevated Serum Cholesterol would suggest Nephrotic Syndrome. This is defined as more than 3 gm of Proteinuria per day with Serum Albumin less than 25 g/L, Oedema, and Hypercholesterolaemia._x000D_
Other Complications Of Nephrotic Syndrome Include:_x000D_
? Susceptibility To Infection._x000D_
? Thromboses._x000D_
? Renal Failure, and_x000D_
? Protein Malnutrition._x000D_
The normal Blood Pressure makes Pre-Eclampsia unlikely. Besides, the Hypercholesterolaemia is the big clue.

Hint

Only Primary Pneumothoraces (less than 2 cm) which are not associated with dyspnoea should be managed with discharge and instructions to return if they become dyspnoeic._x000D_
In this case, aspiration should be considered._x000D_
If air aspiration is unsuccessful, a repeat can be attempted. If still unsuccessful then small bore chest drain insertion is the treatment of choice._x000D_
If there is a previous history of chest disease, the pneumothorax is considered to be secondary. If the patient is younger than 50 and the rim of air is less than 2 cm, aspiration can be attempted. If the patient is older, the rim is larger, or initial aspiration is unsuccessful then a chest drain should be inserted.

Hint

Atmospheric air drops during flights and increases in deep sea diving can cause recurrence of pneumothorax. This is due to expansion and rupture of pulmonary blebs. Many Commercial Airlines previously advised a 6-week interval between Pneumothorax and Air Travel, but this has now been amended to 1 week following full resolution._x000D_
However, the British Thoracic Society emphasises that the recurrence risk only significantly falls after 1 year, and therefore in the absence of a definitive surgical procedure patients might wish to defer travel until then.

Hint

The most likely pathogenesis of pneumothorax in the younger population is B. Ruptured apical bullae on the lung surface. A bulla is a thin-walled air-filled space in the lung that can be congenital or acquired. Smoking is a major risk factor for developing bullae, especially in young adults. When a bulla ruptures, it creates a communication between the alveolar space and the pleural space, allowing air to escape into the pleural cavity and cause a pneumothorax. This gentleman should be advised for smoking cessation.

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The other options are less likely because they are either uncommon or have different mechanisms. Underlying emphysema is a chronic lung disease that causes destruction of the alveolar walls and enlargement of the air spaces. Emphysema can cause pneumothorax, but it is usually seen in older patients with a long history of smoking. Oesophageal rupture is a rare condition that occurs when the oesophagus tears due to trauma, vomiting, or instrumentation. Oesophageal rupture can cause pneumothorax, but it is usually associated with severe chest pain, fever, and subcutaneous emphysema. Leak from pulmonary alveoli is a general term that can describe various causes of pneumothorax, such as trauma, infection, or mechanical ventilation. However, it is not a specific pathogenesis of pneumothorax in the younger population. Underlying asthma is a chronic inflammatory disease of the airways that causes bronchoconstriction and mucus production. Asthma can cause pneumothorax, but it is usually due to a severe asthma attack that causes high intrathoracic pressure and alveolar rupture.

Hint

According to the British Thoracic Society (BTS) guidelines, the feature in the presentation of this lady that is consistent with life-threatening asthma is C. Peak flow 169 ml/minute. This is because a peak flow less than 33% of predicted or best is one of the criteria for life-threatening asthma. The other features of life-threatening asthma listed in the British Thoracic Society (BTS) asthma guidelines include:

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• Silent chest, cyanosis, or feeble respiratory effort

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• Bradycardia, hypotension, dysrhythmia, or cardiac arrest

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• Exhaustion, confusion, or coma

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• Hypoxia (SpO2 <92% or PaO2 <8 kPa)

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• Hypercapnia (PaCO2 >6 kPa)

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• Normal PaCO2 in the presence of severe asthma (4.6-6 kPa)

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This lady’s respiratory rate, pO2, pH, and pCO2 are not indicative of life-threatening asthma, although they may suggest moderate to severe asthma exacerbation.

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Let us discuss all of the incorrect options one by one as below:

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• B. pO2 13.1 kPa: This is incorrect because a pO2 of 13.1 kPa is within the normal range (10-13.3 kPa) and does not indicate life-threatening asthma. In fact, hypoxia (pO2 <8 kPa) is one of the criteria for life-threatening asthma.

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• D. pH 7.44: This is incorrect because a pH of 7.44 is within the normal range (7.35-7.45) and does not indicate life-threatening asthma. In fact, acidosis (pH <7.3) is one of the criteria for life-threatening asthma.

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• E. pCO2 4.6 kPa: This is incorrect because a pCO2 of 4.6 kPa is slightly below the normal range (4.8-6.1 kPa) and does not indicate life-threatening asthma. In fact, hypercapnia (pCO2 >6 kPa) or normal pCO2 in the presence of severe asthma (4.6-6 kPa) are some of the criteria for life-threatening asthma.

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• A. Respiratory rate 34 breaths per minute: This is incorrect because a respiratory rate of 34 breaths per minute is not a specific criterion for life-threatening asthma, although it may suggest moderate to severe asthma exacerbation. The British Thoracic Society (BTS) guidelines do not provide a cut-off value for respiratory rate, but they state that tachypnoea (increased respiratory rate) is a sign of respiratory distress and should be monitored closely.

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Hint

2011 Guidelines have since been updated in 2017 which state that patients should switch to a MART regime if not deriving benefit from a LABA and ICS rather than stopping the LABA and increasing the ICS as previously stated in 2011. _x000D_
New guidelines can be found here as well as more information on MART Regimes._x000D_
Given Asthma is a Chronic Condition, Low Dose Oral Steroids are considered a treatment of last resort at Step Five._x000D_
Guidance has recently been updated in 2020 on the management of asthma in children and young people though this does not apply here.

Hint

According to the latest Global Initiative for Asthma (GINA) guidelines, which were updated in 2023, the most appropriate next step for this lady is to switch to maintenance and reliever therapy (MART) regime with low dose inhaled corticosteroids (ICS) (option A). Maintenance and reliever therapy (MART) regime is an asthma treatment plan where the patient uses one combination inhaler that contains both inhaled corticosteroids (ICS) and a fast-acting long-acting beta2-agonist (LABA) such as formoterol for both daily maintenance therapy and the relief of symptoms as required. Maintenance and reliever therapy (MART) regime can improve asthma control, reduce exacerbations, and lower the overall steroid load compared to using separate preventer and reliever inhalers.

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The other options are not recommended by the Global Initiative for Asthma (GINA) guidelines for this lady. Adding montelukast (option B) is only suggested for patients who have allergic rhinitis or exercise-induced bronchoconstriction, or who cannot tolerate long-acting beta2-agonist (LABA). Adding theophylline (option C) is not preferred due to its narrow therapeutic window and potential side effects. Adding low dose oral steroids (option D) is only indicated for patients with severe asthma who have frequent or serious exacerbations despite high dose inhaled corticosteroids (ICS) and long-acting beta2-agonist (LABA). Stopping salmeterol and increasing inhaled corticosteroids (ICS) to 800 mcg/day (option E) is not advisable as it may increase the risk of exacerbations and adverse effects without improving asthma control.

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The 2023 update of Global Initiative for Asthma (GINA) guidelines focused on the management of asthma in children and young people, and did not change the recommendations for adults with asthma.

Hint

The correct answer is D. Discharge and review in the clinic in two to three weeks. This is the most appropriate management for a small primary spontaneous pneumothorax (PSP), which is a condition where air leaks into the pleural space and causes partial collapse of the lung. Primary spontaneous pneumothorax (PSP) usually occurs in young, healthy, and tall individuals, and is often triggered by coughing, sneezing, or exercise. Primary spontaneous pneumothorax (PSP) can cause chest pain, shortness of breath, and reduced oxygen levels.

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The other answer options are not optimal because:

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• A. Pleural aspiration is a procedure that involves inserting a needle or a catheter between the ribs and removing the air from the pleural space. This can help the lung re-expand faster and prevent recurrence. However, pleural aspiration is not necessary for a small primary spontaneous pneumothorax (<15%), as the air can be absorbed naturally over time. Pleural aspiration is only recommended for larger or more symptomatic primary spontaneous pneumothoraces (PSPs), or if the patient prefers a more active intervention.

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• B. Discharge and review in 24 hours is not a sufficient follow-up for a primary spontaneous pneumothorax (PSP), as there is a risk of recurrence or worsening of the condition. This gentleman should be monitored for at least two to three weeks until the primary spontaneous pneumothorax (PSP) is resolved. He should also be advised to avoid smoking, flying, diving, or high-altitude activities until his primary spontaneous pneumothorax (PSP) is resolved. He should also be instructed to seek medical attention if he develops worsening chest pain, breathlessness, or cyanosis.

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• C. Admit for overnight oxygen therapy is not indicated for a small primary spontaneous pneumothorax (PSP), as there is insufficient evidence to support its effectiveness and safety. Oxygen therapy may increase the rate of air reabsorption and lung expansion, but it may also cause oxygen toxicity, hypercapnia, or fire hazard. Oxygen therapy may be considered for larger or more symptomatic primary spontaneous pneumothoraces (PSPs), or if the patient has hypoxia.

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• E. Chest drain is a procedure that involves inserting a flexible tube into the pleural space and attaching it to a device that continuously removes air from the chest cavity. This can help the lung re-expand and heal. However, chest drain is more invasive and costly than pleural aspiration, and is associated with more pain, complications, and longer hospital stay. Chest drain is only indicated if pleural aspiration fails in a large or symptomatic primary spontaneous pneumothorax (PSP), or if the patient has a secondary spontaneous pneumothorax (SSP), which is a complication of underlying lung disease.

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Therefore, based on the clinical presentation and the guidelines, the most appropriate management for this gentleman is to discharge him and review him in the clinic in two to three weeks. He should be advised to avoid smoking, flying, diving, or high-altitude activities until the primary spontaneous pneumothorax (PSP) is resolved. He should also be instructed to seek medical attention if he develops worsening chest pain, breathlessness, or cyanosis.

Hint

This lady’s Blood Gas Sample shows Respiratory Alkalosis, as demonstrated by the raised pH, low pCO2 and normal Bicarbonate. Her pO2 is over 8kPa, and she is therefore not technically in Type 1 Respiratory Failure, but it is important to realise she is working hard to maintain this Oxygenation. The most likely cause is an Acute Pulmonary Embolism given the relative Hypoxia, and saturation dropping on exertion. Given her age she may be taking the Oral Contraceptive Pill, which would be a risk factor._x000D_
In Acute Asthma the pCO2 may be low, as the patient has an elevated Respiratory Rate, however in this instance there should be a history of the condition, clinical signs or a reduced pO2._x000D_
Hyperventilation often demonstrates a picture of Respiratory Alkalosis on analysis, however she should have a normal pO2 and her saturations should not fall on exertion._x000D_
Respiratory Muscle Disease typically results in a Respiratory Acidosis._x000D_
Volume Depletion (from a number of causes) would typically cause a Metabolic Alkalosis.

Hint

Pulmonary embolism (PE) is a condition in which a blood clot travels to the lungs and blocks the blood flow, causing impaired gas exchange and hypoxia. Pulmonary embolism (PE) can present with chest tightness, dyspnoea, tingling, and light-headedness, especially if the clot is large or affects the right ventricle. Pulmonary embolism (PE) can also cause a drop in oxygen saturation on exertion, as the ventilation-perfusion mismatch worsens with increased demand. Pulmonary embolism (PE) can be triggered by risk factors such as oral contraceptive use, immobilization, surgery, or cancer.

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The arterial blood gas (ABG) analysis of pulmonary embolism (PE) typically shows a respiratory alkalosis, which is a condition in which the blood becomes too alkaline (basic) due to a loss of carbon dioxide (CO2) from hyperventilation. Hyperventilation is a compensatory mechanism to increase oxygen delivery and decrease CO2 levels in the blood. The arterial blood gas (ABG) of pulmonary embolism (PE) may show a high pH, a low pCO2, and normal bicarbonate. The pO2 may be low or normal, depending on the severity of the pulmonary embolism (PE) and the degree of compensation.

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The other options are not consistent with this lady’s presentation and arterial blood gas (ABG) for the following reasons:

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• A. Hyperventilation (psychogenic) is a condition that occurs when a person breathes faster or deeper than normal, causing a decrease in CO2 levels in the blood. Hyperventilation can be caused by psychological factors, such as anxiety, panic, stress, or fear. Hyperventilation can cause chest tightness, dyspnoea, tingling, and light-headedness, similar to pulmonary embolism (PE). However, hyperventilation does not cause hypoxia or a drop in saturation on exertion, as the oxygen delivery is not impaired. The pO2 and the alveolar-arterial gradient are usually normal in hyperventilation.

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• B. Volume depletion is a condition that occurs when a person loses fluid from the body, such as from vomiting, diarrhoea, or bleeding. Volume depletion can cause hypotension, tachycardia, and decreased urine output. Volume depletion does not cause hyperventilation or respiratory alkalosis, but rather a metabolic alkalosis, which is a condition in which the blood becomes too alkaline due to a loss of acid or a gain of base. The arterial blood gas (ABG) of volume depletion may show a high pH, a normal or high pCO2, and high bicarbonate.

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• C. Respiratory muscle disease is a condition that affects the muscles that control breathing, such as the diaphragm, intercostals, or accessory muscles. Respiratory muscle disease can cause dyspnoea, fatigue, and respiratory failure. Respiratory muscle disease does not cause hyperventilation or respiratory alkalosis, but rather hypoventilation or respiratory acidosis, which is a condition in which the blood becomes too acidic due to a build-up of CO2 from inadequate ventilation. The arterial blood gas (ABG) of respiratory muscle disease may show a low pH, a high pCO2, and high bicarbonate.

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• D. Acute asthma attack is a condition that occurs when the airways become inflamed, narrowed, and filled with mucus, causing difficulty breathing. Acute asthma attack can cause wheezing, coughing, chest tightness, and hypoxia. Acute asthma attack does not cause hyperventilation or respiratory alkalosis, but rather hyperventilation or respiratory acidosis in severe cases, when the ventilation-perfusion mismatch and the air trapping become significant. The arterial blood gas (ABG) of acute asthma attack may show a low or normal pH, a low or high pCO2, and normal or high bicarbonate.

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Hint

Mycoplasma pneumonia usually affects people younger than

Hint

Infectious Mononucleosis occurs most commonly in adolescents and young adults._x000D_
Clinical features occur after a two to five week incubation period and include:_x000D_
? Fever_x000D_
? Malaise_x000D_
? Pharyngitis_x000D_
? Lymphadenopathy._x000D_
Rashes occur more commonly in patients who have received penicillin or ampicillin.

Hint

The Mantoux Test replaced the Heaf Test in 2005 in the United Kingdom. One of its uses in for patients who have had close contact with a person known to have Tuberculosis._x000D_
The injection site should be reviewed 48 ? 72 hours following Intradermal Inoculation Of Tuberculin. The left forearm is typically used. Only the induration, not surrounding erythema, is used in the measurement and the longest diameter is measured in millimetres:_x000D_
? Less than 6 mm – negative test, previously unvaccinated individuals can be given the BCG (within three months) provided there are no contraindications._x000D_
? More than 6 mm but less than 15 mm – hypersensitive to tuberculin protein (may be due to previous TB infection, BCG, or atypical mycobacteria). Patients are not given the BCG if part of an immunisation programme. However, in other contexts (e.g. immigrant screening and contact tracing), further investigation should and follow-up may be indicated._x000D_
? More than 15 mm – strongly hypersensitive to tuberculin, suggestive of TB infection. Patients should be referred for further investigation and treatment._x000D_
The reaction to tuberculin protein may be suppressed by viral infections, live viral vaccines, sarcoidosis, corticosteroids, immunosuppression, severe tuberculous disease and poor nutrition._x000D_
Bronchoscopy would not usually be considered unless other investigations have proved inconclusive._x000D_
Anti-tuberculous therapy is commenced only after infection is confirmed, and patients with a positive Mantoux do not require BCG vaccination.

Hint

The correct way to manage this lady is to arrange for sputum samples to be collected, which is option C. This is because she has a positive Mantoux test result of 17 mm, which suggests that she has latent tuberculosis infection (LTBI) and may have been exposed to tuberculosis (TB) through close contact with the children in her kindergarten class (see the NOTE below). Sputum samples are used to confirm the diagnosis of tuberculosis (TB) by detecting the presence of Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB). If the sputum samples are positive, she will need to start anti-tuberculosis chemotherapy to prevent the progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease.

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The incorrect options can be ruled out with the following explanations:

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• Option A is incorrect because she is not immune to tuberculosis (TB) and requires further investigation and treatment. A positive Mantoux test result indicates that she has been infected with tuberculosis (TB) bacteria at some point in her life, but it does not mean that she has developed immunity to tuberculosis (TB). She may still develop active tuberculosis (TB) disease in the future, especially if her immune system is weakened by other factors. Therefore, she should not be reassured and that no further action is necessary is not an option.

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• Option B is incorrect because she does not need a bronchoscopy. A bronchoscopy is a procedure that involves inserting a flexible tube with a camera and a light into the airways to examine the lungs and collect samples of lung tissue or fluid. It is usually done for patients who have signs or symptoms of pulmonary tuberculosis (TB), such as cough, fever, weight loss, or chest pain, or for patients who have abnormal chest x-rays. However, she has none of these signs or symptoms and her chest is clear. Therefore, a bronchoscopy is unnecessary and invasive for her condition.

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• Option D is incorrect because she does not need to be vaccinated with Bacillus Calmette–Guérin (BCG). Bacillus Calmette–Guérin (BCG) is a vaccine that contains a weakened strain of Mycobacterium bovis, a bacterium related to tuberculosis (TB). It is used to prevent severe forms of tuberculosis (TB) in children, especially in countries where tuberculosis (TB) is endemic. However, it is not recommended for adults with latent tuberculosis infection (LTBI), as it has no proven benefit and may cause adverse reactions. Moreover, she has already been infected with tuberculosis (TB) bacteria, so Bacillus Calmette–Guérin (BCG) vaccination will not protect her from tuberculosis (TB).

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• Option E is incorrect because she does not need to start anti-tuberculosis chemotherapy without confirmation of tuberculosis (TB) infection. Anti-tuberculosis chemotherapy is a combination of drugs that are used to treat tuberculosis (TB) disease. It is usually given for at least six months and requires close monitoring and adherence. It can also cause side effects such as nausea, vomiting, liver damage, or nerve damage. Therefore, it should not be started without a definitive diagnosis of tuberculosis (TB), which can be obtained from sputum samples or other tests. Starting anti-tuberculosis chemotherapy without confirmation of tuberculosis (TB) infection may lead to unnecessary exposure to drugs, drug resistance, or toxicity.

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NOTE:

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In the United Kingdom, the Mantoux test took over from the Heaf test in 2005. One of its primary applications is for individuals who have been in close proximity to someone known to have tuberculosis.

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After the intradermal inoculation of tuberculin, the injection site should be assessed between 48 to 72 hours. Typically, the left forearm is utilized for this purpose. During measurement, only the induration (not the surrounding erythema) is considered, and the longest diameter is measured in millimeters. The interpretation of the test results is as follows:

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– A measurement of less than 6 mm indicates a negative test. Previously unvaccinated individuals can receive the Bacillus Calmette–Guérin (BCG) vaccine within three months, provided there are no contraindications.

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– A measurement of more than 6 mm but less than 15 mm suggests hypersensitivity to tuberculin protein. This hypersensitivity may be due to previous tuberculosis infection, BCG vaccination, or exposure to atypical mycobacteria. If the individual is part of an immunization program, they should not receive the BCG vaccine. However, in other situations such as immigrant screening or contact tracing, further investigation and possible follow-up may be necessary.

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– A measurement of more than 15 mm strongly indicates hypersensitivity to tuberculin, which is highly suggestive of tuberculosis (TB) infection. Patients with this result should be referred for further investigation and appropriate treatment.

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It is important to note that the reaction to tuberculin protein can be suppressed by various factors including viral infections, live viral vaccines, sarcoidosis, corticosteroids, immunosuppression, severe tuberculous disease, and poor nutrition. These factors should be considered when interpreting the results of the Mantoux test.

Hint

This lady is presenting with primary pulmonary hypertension, a condition that often manifests in women after giving birth to their first child. In the initial stages of treatment, calcium antagonists are considered as the first-line therapy, but only for patients who do not exhibit signs of right-sided heart failure. However, when selecting the initial therapy, an endothelin receptor antagonist would be the preferred choice. Examples of endothelin receptor antagonists include bosentan and ambrisentan, both of which have shown significant efficacy in reducing pulmonary artery pressure (PAP). It is important to note that these medications can have adverse effects such as peripheral oedema, and regular monitoring of liver function tests (LFTs) is recommended.

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Beta blockers, despite their ability to lower peripheral blood pressure, are not recommended for the management of primary pulmonary hypertension. Their main effect is not particularly beneficial in this condition.

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It is worth mentioning that calcium antagonists are effective in only a small percentage of patients, around 10-15%, and their use is only recommended if there is no evidence of right-sided heart failure.

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Phosphodiesterase type 5 (PDE-5) inhibitors are typically used in cases of mild disease or in individuals with stage III or IV NYHA functional status, often in combination with endothelin receptor antagonists.

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Nebulized or subcutaneous prostacyclin analogues, while effective, are less convenient treatment options compared to oral medications. Therefore, they are usually reserved for combination therapy with oral drugs.

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In summary, this lady’s presentation suggests primary pulmonary hypertension, which commonly occurs in women after giving birth to their first child. The initial therapy choice depends on the absence of right-sided heart failure, with endothelin receptor antagonists being the preferred option. Calcium antagonists may be considered if right-sided heart failure is not present, although their efficacy is limited to a small percentage of patients. Beta blockers are not recommended. PDE-5 inhibitors are utilized in specific stages of the disease, and nebulized or subcutaneous prostacyclin analogues are usually reserved for combination therapy with oral medications due to their inconvenience.

Hint

This gentleman has been diagnosed with community-acquired pneumonia (CAP). Considering his recent history of influenza, Staphylococcus aureus might be considered as the underlying organism, although it is an uncommon cause of community-acquired pneumonia (CAP) in the United Kingdom. Staphylococcus aureus is more prevalent during the winter months, and approximately 40% of cases coincide with influenza-like symptoms. About 3% of influenza cases develop pneumonia, and of those admitted, 10% are confirmed to be caused by Staphylococcus aureus.

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In most cases of community-acquired pneumonia (CAP), confirmation through chest radiography is recommended before initiating antibiotic treatment. However, if patients are critically ill, they should be treated based on presumptive diagnosis. Antibiotic therapy should always be initiated within 4 hours of presentation.

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Community-acquired pneumonia caused by Staphylococcus aureus is more likely to present with multilobar shadowing, cavitation, pneumatoceles, and spontaneous pneumothorax compared to other organisms. However, there are no specific radiographic features that can definitively predict the likely pathogen. Therefore, the general treatment guidelines for community-acquired pneumonia (CAP) should be followed until the organism is identified. Staphylococcus aureus is associated with high mortality, so if suspected, initial treatment should be for severe community-acquired pneumonia (CAP) (see details below).

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Low severity community-acquired pneumonia (CAP) (CURB 0-1) can be treated with oral amoxicillin 500 mg three times daily. CURB 2 community-acquired pneumonia (CAP) should be treated with oral amoxicillin 500 mg – 1 gm three times daily and oral clarithromycin 500 mg twice daily. Alternative options are available for patients allergic to any of the above combinations. High severity community-acquired pneumonia (CAP) (CURB 3-5) should be promptly treated with intravenous co-amoxiclav 1.2 gm three times daily and oral clarithromycin 500 mg twice daily.

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For patients with low and moderate severity community-acquired pneumonia (CAP), the oral route is recommended. Patients initially treated with parenteral antibiotics should be switched to an oral regimen once clinical improvement is observed and they have been afebrile for at least 24 hours. In most cases of uncomplicated community-acquired pneumonia (CAP), a 7-day course of antibiotics is recommended. For high severity pneumonia cases where the organism is unidentified, 7-10 days of treatment is indicated, and the duration may be extended to 14-21 days if clinically necessary.

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If Staphylococcus aureus is identified, the treatment plan should be adjusted accordingly. Non-methicillin-resistant Staphylococcus aureus (MRSA) organisms should be treated with flucloxacillin and/or rifampicin. For penicillin-allergic patients, teicoplanin and rifampicin can be considered as an alternative. Methicillin-resistant Staphylococcus aureus (MRSA) should be treated with vancomycin. Prolonged antibiotic therapy is recommended in these cases.

Hint

The correct answer is C. A high inspired oxygen concentration should be used routinely. This is the correct statement regarding acute severe asthma according to National Institute for Health and Care Excellence (NICE) guidelines.

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The reason for this is that people with acute severe asthma are at risk of hypoxia (low oxygen level in the blood) and respiratory failure, which can be life-threatening. Therefore, they should receive high-flow oxygen therapy (at least 15 litres per minute) via a non-rebreather mask to maintain their oxygen saturation above 94%.

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The other statements are incorrect according to National Institute for Health and Care Excellence (NICE) guidelines, as follows:

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• A. Inhaled salmeterol is indicated as first-line therapy: This is incorrect, as salmeterol is a long-acting beta-2 agonist (LABA) that is used for maintenance therapy of asthma, not for acute exacerbations. The first-line therapy for acute severe asthma is inhaled short-acting beta-2 agonist (SABA) such as salbutamol, which provides rapid bronchodilation and relief of symptoms.

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• B. Pulsus paradoxus is a reliable sign of severity: This is incorrect, as pulsus paradoxus is a sign of increased intrathoracic pressure due to severe airway obstruction, but it is not a reliable indicator of the severity of asthma exacerbations. Pulsus paradoxus is defined as a drop in systolic blood pressure of more than 10 mmHg during inspiration, and it can be difficult to measure accurately in clinical practice. The severity of asthma exacerbations should be assessed based on the person’s symptoms, peak expiratory flow rate, oxygen saturation, and arterial blood gases.

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• D. Normal arterial pCO2 is reassuring: This is incorrect, as normal arterial pCO2 (partial pressure of carbon dioxide in the blood) in a person with acute severe asthma may indicate impending respiratory failure, rather than adequate ventilation. This is because the person may have exhausted their respiratory reserve and may not be able to increase their minute ventilation to compensate for the increased carbon dioxide production due to hypoxia and acidosis. A normal or high pCO2 in a person with acute severe asthma should prompt urgent admission to an intensive care unit for possible mechanical ventilation.

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• E. Agitation should be managed with a benzodiazepine: This is incorrect, as benzodiazepines are sedatives that can depress the respiratory drive and worsen the hypoxia and hypercapnia in a person with acute severe asthma. Agitation in a person with acute severe asthma may be a sign of hypoxia, acidosis, or anxiety, and it should be managed by correcting the underlying cause, such as increasing the oxygen therapy, administering bronchodilators, or providing reassurance. Benzodiazepines should be avoided unless there is a clear indication, such as status epilepticus or alcohol withdrawal

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Hint

The most likely diagnosis for this student is A. Infectious mononucleosis. This is a viral infection caused by the Epstein-Barr virus, which is transmitted by saliva. It typically affects young adults and causes fever, sore throat, swollen lymph nodes, and a rash that may appear on the trunk and limbs. The rash may be more prominent in people who take amoxicillin or other antibiotics.

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The other options are less likely because they do not match the clinical features of the case. Tuberculosis is a bacterial infection that causes chronic cough, weight loss, night sweats, and may affect various organs. It is usually associated with granulomatous inflammation and caseating necrosis. Sarcoidosis is an inflammatory disorder of unknown cause that also forms granulomas in various tissues, especially the lungs and lymph nodes. It may cause fever, fatigue, dyspnoea, and skin lesions such as erythema nodosum or lupus pernio. Actinomycosis is a chronic bacterial infection that causes abscesses and fistulas in the mouth, neck, chest, abdomen, or pelvis. It is often associated with poor oral hygiene or trauma. Familial Mediterranean fever is a genetic disorder that causes recurrent episodes of fever, abdominal pain, chest pain, and joint pain. It is more common in people of Mediterranean origin and may lead to amyloidosis.

Hint

The correct answer is D. Magnesium 1-2 gm IV. This is because this gentleman has severe acute asthma that is not responding to standard treatment with oxygen, nebulised bronchodilators, and systemic corticosteroids. This gentleman’s arterial blood gas shows a normal pH, a normal PaCO2, and a high PaO2, indicating that he is receiving adequate oxygen therapy but has severe airflow obstruction. This gentleman’s peak expiratory flow rate is less than 50% predicted, which is another sign of severe asthma.

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Magnesium is a smooth muscle relaxant that can reduce bronchospasm and improve lung function in patients with severe acute asthma. Magnesium can be given intravenously as a single dose of 1.2 to 2 g over 20 minutes, preferably under the supervision of a senior clinician or an Intensive Care Team. Magnesium can also reduce the risk of hospital admission and the need for mechanical ventilation.

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The other answer options are incorrect for the following reasons:

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• A. Oral aminophylline: Aminophylline is a methylxanthine drug that has bronchodilator and anti-inflammatory effects. However, aminophylline has a narrow therapeutic window and can cause serious side effects such as arrhythmias, seizures, and gastrointestinal bleeding. Aminophylline is not recommended for the routine management of acute asthma, and should only be considered as a last resort in life-threatening cases, under the guidance of a specialist.

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• B. Non-invasive ventilation (NIV): Non-invasive ventilation (NIV) is a form of mechanical ventilation that delivers positive pressure to the airways through a mask or a helmet, without the need for intubation. Non-invasive ventilation (NIV) can improve oxygenation and reduce the work of breathing in patients with respiratory failure due to various causes. However, non-invasive ventilation (NIV) is not indicated for patients with acute asthma, as it can worsen airflow obstruction, increase the risk of pneumothorax, and delay intubation if needed.

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• C. Oral prednisolone: Prednisolone is a corticosteroid that reduces inflammation and mucus production in the airways. Prednisolone is an essential component of the treatment of acute asthma, and should be given as soon as possible to all patients with moderate, severe, or life-threatening asthma. However, prednisolone alone is not sufficient to treat severe acute asthma, and should be combined with other therapies such as oxygen, bronchodilators, and magnesium. This gentleman in the question has already received hydrocortisone, which is a parenteral form of corticosteroid, so oral prednisolone is not necessary.

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• E. Intubation and ventilation: Intubation and ventilation is a life-saving procedure that involves inserting a tube into the trachea and connecting it to a machine that delivers oxygen and pressure to the lungs. Intubation and ventilation is indicated for patients with life-threatening asthma who have signs of respiratory failure, such as hypoxia, hypercapnia, acidosis, altered mental status, or exhaustion. However, intubation and ventilation is not without risks, such as barotrauma, infection, and ventilator-associated lung injury. Therefore, intubation and ventilation should be avoided if possible, and reserved for patients who do not respond to other treatments or who have imminent respiratory arrest. The gentleman in this question does not have any life-threatening features of asthma, and may benefit from magnesium therapy before considering intubation and ventilation.

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Hint

The most likely causative organism in this case is option C. Mycoplasma pneumonia. This is because the clinical presentation and the laboratory findings are consistent with a diagnosis of atypical pneumonia, which is often caused by Mycoplasma pneumoniae, a type of bacteria that does not have a cell wall and can infect the respiratory tract. Mycoplasma pneumoniae is also known to cause outbreaks of respiratory illness in young adults, especially in crowded settings such as universities. Mycoplasma pneumoniae can also cause haemolytic anaemia, which is a condition where the red blood cells are destroyed prematurely and can result in schistocytes, or fragmented red blood cells, on the blood film.

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The other options are less likely for the following reasons:

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• Option A is incorrect because Pseudomonas aeruginosa is a gram-negative bacterium that usually causes pneumonia in patients with cystic fibrosis, bronchiectasis, or immunosuppression. The student in this question has none of these risk factors and his chest x-ray shows right lower lobe pneumonia, which is not typical for Pseudomonas aeruginosa infection.

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• Option B is incorrect because Legionella pneumophila is a gram-negative bacterium that causes Legionnaires’ disease, a severe form of pneumonia that is associated with exposure to contaminated water sources. The student in this question has no history of such exposure and his laboratory findings do not show hyponatraemia, which is a common feature of Legionella pneumophila infection.

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• Option D is incorrect because Streptococcus pneumoniae is a gram-positive bacterium that causes typical pneumonia, which is characterized by a lobar or segmental consolidation on the chest x-ray, a productive cough, and a high white blood cell count. This student in the question has a dry cough, a scattered wheeze, and a normal white blood cell count, which are not consistent with typical pneumonia.

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• Option E is incorrect because Staphylococcus aureus is a gram-positive bacterium that causes pneumonia in patients with influenza, intravenous drug use, or prior lung damage. The student in the question has no history of these risk factors and his chest x-ray does not show multiple cavities or abscesses, which are common complications of Staphylococcus aureus infection.

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Hint

The most appropriate next step is E. Stop all treatments. This is because the gentleman has developed drug-induced liver injury (DILI) from antituberculous treatment (ATT), which is a serious and potentially fatal complication. This gentleman’s liver function tests (LFTs) are markedly elevated, indicating severe hepatocellular damage. The gentleman may also have symptoms such as nausea, dark urine, jaundice, or abdominal pain.

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The recommended management of antituberculous treatment (ATT)-associated drug-induced liver injury (DILI) is to stop all anti-tuberculosis drugs immediately and monitor the gentleman closely until the liver function tests (LFTs) normalize or improve significantly. After recovery, the same drugs may be safely reintroduced in most cases, following a stepwise approach. This is possible because of a phenomenon known as hepatic adaptation, which reduces the risk of drug-induced liver injury (DILI) recurrence. However, some patients may require alternative drugs or regimens, depending on the severity of drug-induced liver injury (DILI) and the availability of other options.

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The drug that may have caused drug-induced liver injury (DILI) in the above case is pyrazinamide. This is because pyrazinamide is the most hepatotoxic drug among the first-line anti-tuberculosis drugs, and it is usually the first drug to be stopped in cases of drug-induced liver injury (DILI). Pyrazinamide is metabolized to pyrazinoic acid and 5-hydroxy-pyrazinoic acid, which can cause oxidative stress and inflammation in the liver.

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The other answer options can be ruled out with the following explanations:

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• Rifampicin: Rifampicin can also cause drug-induced liver injury (DILI), but it is less likely than pyrazinamide. Rifampicin is usually the second drug to be stopped in cases of drug-induced liver injury (DILI), after pyrazinamide. Rifampicin induces the expression of cytochrome P450 enzymes, which can increase the metabolism and toxicity of other drugs.

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• Isoniazid: Isoniazid can also cause drug-induced liver injury (DILI), but it is less likely than pyrazinamide and rifampicin. Isoniazid is usually the third drug to be stopped in cases of drug-induced liver injury (DILI), after pyrazinamide and rifampicin. Isoniazid is metabolized to acetyl hydrazine and hydralazine, which can form reactive metabolites and bind to liver proteins.

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Ethambutol: Ethambutol is the least hepatotoxic drug among the first-line anti-tuberculosis drugs, and it is usually the first drug to be restarted in cases of drug-induced liver injury (DILI). Ethambutol is mainly excreted unchanged in the urine, and its metabolism is not affected by cytochrome P450 enzymes

Hint

The most likely complication for the case that has been described above is fat embolism syndrome (FES). This is a condition where fat droplets from the bone marrow enter the bloodstream and block the blood vessels in the lungs, brain, and other organs. Fat embolism syndrome (FES) usually occurs 12 to 72 hours after a long bone fracture, especially of the femur. Fat embolism syndrome (FES) can cause shortness of breath, chest pain, mental confusion, coma, and a pinpoint rash (called a petechial rash) that often appears on the chest, head, and neck area.

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Therefore, the correct answer to this question is C. Multiple petechiae in both axillae. This is a sign of a petechial rash, which is a common skin manifestation of fat embolism syndrome (FES). The other options are not relevant for fat embolism syndrome (FES), as they are associated with different conditions, such as:

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• Target lesions on the chest: These are circular lesions with a central dark spot and a lighter ring around it. They are seen in erythema multiforme, a hypersensitivity reaction to infections or drugs.

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• Vesicular lesions on the torso: These are fluid-filled blisters that can be caused by various infections, such as chickenpox, herpes zoster, or impetigo.

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• Palpable purpura on buttocks and legs: These are raised purple spots that indicate bleeding under the skin. They are seen in vasculitis, an inflammation of the blood vessels due to autoimmune or infectious causes.

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• Tender red nodules on the shins: These are painful lumps that occur on the front of the lower legs. They are seen in erythema nodosum, an inflammatory reaction of the fat tissue under the skin, often related to infections, drugs, or inflammatory diseases.

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Hint

The appearance of Multiple Petechiae in the distribution of the Axilla or Upper Body is characteristic of a Fat Embolism._x000D_
Unlike emboli that arise from a thrombus, fat emboli are small and multiple producing widespread effects. They may occur one to three days following a fracture and are more common in closed fractures on the long bones or pelvis._x000D_
The clinical features of fat emboli are predominately:_x000D_
? Pulmonary (shortness of breath, hypoxia)_x000D_
? Neurological (confusion and agitation)_x000D_
? Dermatological (petechiae), and_x000D_
? Haematological (thrombocytopenia, anaemia)._x000D_
The petechial rash is pathognomonic of this syndrome, but occurs in only 30-50% of cases.

Hint

Acute respiratory distress syndrome (ARDS) is a serious condition that causes fluid in the lungs and low oxygen levels in the blood. The goal of treatment for acute respiratory distress syndrome (ARDS) is to improve oxygen levels and treat the underlying cause. Oxygen therapy is the main treatment for acute respiratory distress syndrome (ARDS), and most people with acute respiratory distress syndrome (ARDS) need a mechanical ventilator and/or oxygen therapy to improve blood oxygen levels. Other treatments aim to prevent complications and make the patient comfortable.

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The lady in this question is currently receiving the highest level of ventilatory support available but is still experiencing hypoxia. The elevated level of carbon dioxide (CO2) in her blood is a deliberate strategy known as permissive hypercapnia, which is employed to prevent excessive lung distension caused by high tidal volumes.

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Treating patients in this condition used to present significant challenges, as no technique showed substantial improvements in prognosis. However, in 2010, the CESAR trial provided a breakthrough. This trial demonstrated that the use of extracorporeal membrane oxygenation (ECMO) significantly increased survival rates without resulting in significant disability.

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Based on the above discussion, the most likely treatment to decrease mortality in this patient group is extracorporeal membrane oxygenation (ECMO). Extracorporeal membrane oxygenation (ECMO) is a life support technique that uses a machine to pump blood outside the body, add oxygen to it, and then return it to the body. Extracorporeal membrane oxygenation (ECMO) can improve oxygenation and reduce the risk of ventilator-induced lung injury in patients with severe acute respiratory distress syndrome (ARDS). However, extracorporeal membrane oxygenation (ECMO) is not widely available and has some serious risks, such as bleeding, infection, and blood clots. Therefore, it should be used only when other treatments have failed or are not available.

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The other options are less likely to decrease mortality in this patient group, and some may even be harmful. Here is a brief summary of each option:

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• Inhaled nitric oxide therapy: Nitric oxide is a gas that can relax the blood vessels in the lungs and improve blood flow. However, there is no clear evidence that inhaled nitric oxide therapy reduces mortality or improves outcomes in patients with acute respiratory distress syndrome (ARDS). It may also cause side effects such as low blood pressure, bleeding, and kidney problems.

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• High frequency oscillatory ventilation (HFOV): High frequency oscillatory ventilation (HFOV) is a type of mechanical ventilation that delivers very small breaths at a very high rate. High frequency oscillatory ventilation (HFOV) can reduce the risk of overstretching the lungs and causing more damage. However, high frequency oscillatory ventilation (HFOV) has not been shown to reduce mortality or improve outcomes in patients with acute respiratory distress syndrome (ARDS). It may also increase the risk of low blood pressure, low cardiac output, and air leaks in the lungs.

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• Increasing tidal volume and respiratory rate on the ventilator: Tidal volume is the amount of air that moves in and out of the lungs with each breath, and respiratory rate is the number of breaths per minute. Increasing tidal volume and respiratory rate on the ventilator may seem to improve oxygenation, but it can also cause more lung injury and inflammation. Studies have shown that lower tidal volumes (6 mL per kg) and higher positive end-expiratory pressure (PEEP) values (12 cm H2O) improve outcomes and reduce mortality in patients with acute respiratory distress syndrome (ARDS).

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• Prone position: Prone position means lying on the stomach instead of the back. Prone position can improve oxygenation and lung mechanics in patients with acute respiratory distress syndrome (ARDS) by redistributing the lung volume and reducing the pressure on the lungs. Prone position has been shown to reduce mortality in patients with severe acute respiratory distress syndrome (ARDS), but not in patients with mild or moderate acute respiratory distress syndrome (ARDS). Prone position also requires careful monitoring and frequent repositioning to prevent complications such as pressure ulcers, facial oedema, and nerve injuries.

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Hint

This lady is on Maximal Ventilatory Therapy but is still Hypoxic. Her High CO2 is a reflection of permissive Hypercapnia to prevent Overdistension of the Lungs with High Tidal Volumes._x000D_
Treatment of these patients used to be extremely difficult, with no significant improvement in prognosis seen will any technique. However, in 2010 the CESAR trial demonstrated a significant increase in survival without significant disability with the use of Extracorporeal Membrane Oxygenation (ECMO)._x000D_
Extracorporeal Membrane Oxygenation [ECMO] involves connecting a patient’s circulation to an external oxygenator and pump, via a catheter placed in the right side of the heart. It requires the continuous infusion of anticoagulant, and as such bleeding is the most commonly associated complication. Infection and haemolysis are also a risk. Extracorporeal Membrane Oxygenation (ECMO) is a treatment option considered for Acute Respiratory Distress Syndrome (ARDS) patients who are refractory to conventional treatments. However, treatment with Extracorporeal Membrane Oxygenation [ECMO] has not shown significant reduction of mortality which may be due to inappropriate selection criteria._x000D_
A recent study1 published in the NEJM concluded that prone positioning improved outcome in severe Acute Respiratory Distress Syndrome [ARDS]. However, it is only one study in a controversial area. There are a number of studies, including one by the same group, which have not shown a mortality benefit (and others which show a detrimental effect on mortality). Prone positioning is therefore not yet widely accepted in clinical practice, although this may change in the future.

Hint

This woman has familial Primary Pulmonary Hypertension (PPH). This is evidenced by her age, and particularly symptoms such as increased shortness of breath and recurrent syncope. The increased right sided pressures are also a give away with respect to the diagnosis._x000D_
The fact her aunt and mother suffered from a similar disease points to an inherited component._x000D_
The condition is recognised to account for 15-20% of cases of Primary Pulmonary Hypertension (PPH) and is due to an inherited mutation in the BMPR2 Gene which codes for a receptor in the TGF Beta family. Hereditary Haemorrhagic Telangiectasia, another cause of Inherited Pulmonary Hypertension, also carries an Autosomal Dominant Inheritance pattern._x000D_
The occurrence of Pulmonary Hypertension in a number of family members makes a de novo mutation highly unlikely._x000D_
Of the other modes of inheritance listed, only autosomal dominant is correct.

Hint

This gentleman’s occupation as a mushroom picker raises the possibility of Mushroom Picker’s Lung, a form of Hypersensitivity Pneumonitis. Optimal management is removal of exposure to the antigen, although in the short term a course of oral corticosteroids is likely to be appropriate._x000D_
Inhaled Anticholinergics are used in the management of Chronic Obstructive Pulmonary Disease (COPD) and are therefore not appropriate here._x000D_
Inhaled Corticosteroids are not as effective as Oral Corticosteroids in managing Subacute or Chronic Hypersensitivity Pneumonitis, so Oral Prednisolone is the treatment of choice after removal of exposure to the antigen has occurred._x000D_
There is no role for Antibiotic Therapy.

Hint

The treatment approach for tuberculosis (TB) mediastinal lymphadenitis is generally the same as that for pulmonary tuberculosis (TB). Both conditions require a comprehensive treatment regimen to effectively combat the infection.

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During the course of tuberculosis (TB) treatment, a phenomenon known as a ‘paradoxical reaction’ may occur. This reaction can lead to the development of new lesions or the worsening of existing lesions. The timing of this reaction is unpredictable, and it can manifest anywhere from a few days to several months after the initiation of treatment. The duration and severity of the reaction can vary greatly, making it challenging to differentiate from treatment failure, drug resistance, or a superadded infection. Paradoxical reactions are commonly observed in cases involving lymph node or cerebral disease, with approximately 30% of cases experiencing enlargement of affected lymph nodes. Fortunately, in most instances, these reactions tend to resolve on their own over time.

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Corticosteroids have proven to be effective in reducing lymph node enlargement and inflammation associated with tuberculosis (TB) mediastinal lymphadenitis. By alleviating these symptoms, corticosteroids can help alleviate stridor and breathlessness in affected individuals. However, it is important to note that if the compression is occurring at the carina, the placement of a tracheal stent or tracheostomy will not provide relief from the obstruction.

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In the case of tuberculosis (TB) mediastinal lymphadenitis, additional diagnostic procedures such as mediastinoscopy and biopsy, as well as a computed tomography (CT) scan of the mediastinum, may not yield any additional valuable information since the diagnosis is already established.

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While standard tuberculosis (TB) treatment typically involves the administration of ethambutol, rifampicin, isoniazid, and pyrazinamide for an initial period of two months, the use of ethambutol may not always be necessary, especially when the susceptibility of the organism is known. It is unlikely that the exclusion of ethambutol has led to treatment failure, and therefore, reintroducing it at this point is unlikely to alleviate the symptoms.

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In summary, the treatment approach for tuberculosis (TB) mediastinal lymphadenitis is similar to that for pulmonary tuberculosis (TB). Paradoxical reactions may occur during tuberculosis (TB) treatment, causing new lesions or the worsening of existing ones. Corticosteroids can be beneficial in reducing lymph node enlargement and inflammation. Additional diagnostic procedures may not be necessary if the diagnosis is already established. The omission of ethambutol in the treatment regimen is unlikely to be the cause of treatment failure and may not provide symptom relief if reintroduced.

Hint

The history of recurrent infections in this young patient should lead you to consider Immunosuppression as an underlying diagnosis and therefore Pneumocystis jiroveci pneumonia._x000D_
Pneumocystis jiroveci is a eukaryotic microorganism. In immunosuppressed patients it can cause a pneumonia, which is most recognised in patients with Acquired Immune Deficiency Syndrome [AIDS] but can also be seen in those with Organ Transplants or when undergoing Chemotherapy. A CD4 Count of less than 200 is associated with significant risk. In Europe, the USA and Australia P. jiroveci pneumonia in HIV-positive patients is seen largely in those unaware of their HIV Status. Unfortunately, it is a major cause of death in Africa, especially in children. Previously it was thought that disease was caused by reactivation of latent infection acquired in childhood, but de novo infection is increasingly recognised._x000D_
The pneumonia caused by P. jiroveci is potentially severe and fatal in immunosuppressed patients. Clinically it presents with several weeks’ history of dry cough, fever and dyspnoea. Examination findings are often subtle, but include tachypnoea, tachycardia, cyanosis and fine respiratory crackles. Typically, patients desaturate markedly on exertion. There may be Reduced Transfer Factor, Vital Capacity and Total Lung Capacity on Spirometry. Bronchoalveolar Lavage or Induced Sputum can be used to demonstrate the organism (Open Lung Biopsy is Gold Standard, but rarely performed in clinical practice). Giemsa, Papanicolaou and Grocott’s Stains are used._x000D_
There are a variety of different chest radiograph findings. Typically it causes bilateral symmetrical perihilar reticular or granular interstitial shadowing. Less often there can be asymmetric shadowing, or progression to a reticular-alveolar pattern. The following can occasionally be seen:_x000D_
? lobar Consolidation_x000D_
? Nodular Lesions_x000D_
? Prominent Pulmonary Arteries_x000D_
? Pneumothorax_x000D_
? Pneumomediastinum_x000D_
? Cysts, or_x000D_
? Pneumatoceles._x000D_
In patients who have been on prophylactic inhaled pentamidine the infiltrates may predominantly affect the upper lobes. A normal chest x-ray does not exclude the diagnosis. Pleural effusions and lymphadenopathy are not typical, but be aware of the possibility of multiple disease processes in an immunosuppressed patient._x000D_
If allowed to progress, P. jiroveci can disseminate via the lymphatic and haematogenous routes to affect the thyroid, liver, bone marrow, lymph nodes and spleen._x000D_
If PCP is suspected, treatment with full dose Co-Trimoxazole should be started as soon as possible. It should be given for 21 days in HIV-Positive cases, but shorter doses can be used in other causes of immunosuppression. In patients who are intolerant or Co-Trimoxazole, Intravenous Pentamidine can be used. Some studies have shown that Corticosteroids can reduce the risk of respiratory failure, and they are therefore used in some cases._x000D_
Prophylaxis should be used in immunosuppressed patients who are at risk of developing PCP: all those with a CD4 Count of <200, patients started on High Dose Steroids, and those on Chemotherapeutic Regimens associated with significant immunosuppression. Co-Trimoxazole is also the First Line Prophylactic Agent._x000D_
It would be unusual for someone this young to develop Chronic Obstructive Pulmonary Disease [COPD], even if they are a heavy smoker. Asthma would have classical signs on examination if severe enough to cause hypoxia. If the patient had a Lung Abscess you would expect some systemic features of sepsis. A Pulmonary Embolism could account for these clinical signs, but there are no risk factors given in the question which makes PCP more likely.

Hint

Pneumothorax can be classified as either Primary or Secondary. However, more important in this case is the presence of tension._x000D_
Tension Pneumothorax results from progressive build-up of air within the pleural space, which is not able to return. This build-up of pressure pushes the mediastinum to the opposite hemithorax and obstructs venous return. The patient then develops severe breathlessness, hypotension, mediastinal shift and, ultimately, cardiac arrest (often electromechanical dissociation: PEA). The classical signs of a Tension Pneumothorax are deviation of the trachea away from the side of tension, hyper-expanded chest that moves minimally with respiration and increased percussion note. Jugular Venous Pressure (JVP) may be raised. However, more commonly the only signs are Tachycardia, Tachypnoea and Hypoxia._x000D_
Management of Tension Pneumothorax is immediate Chest Decompression with Needle Thoracostomy. A 14-16G Intravenous Cannula is inserted into the Second Rib Space in the Mid-Clavicular Line, on the side of the Pneumothorax. By acting as a valve, this converts a Tension Pneumothorax into a Simple Pneumothorax._x000D_
Definitive treatment of a Tension Pneumothorax is Chest Drain Insertion. This is usually done in the Emergency Department with Ultrasound Guidance. Once the Pleura is entered, the tension is relieved and the remainder of the procedure can be undertaken with less time pressure._x000D_
In this case, the option of Needle Thoracostomy is on the incorrect side, so the correct option is inserting a chest drain on the right side. High-Flow Oxygen is indicated whilst performing this, and Chest X-Ray should be ordered to check the position of the Drain. Arterial Blood Gases may be indicated once the drain is in situ._x000D_
Although the above explanation remains correct for the MRCP Examination, it is important to be aware that there has been discussion about the use of Needle Thoracostomy in the medical literature. It has been shown that on occasion it is ineffective in relieving a Tension Pneumothorax, especially in patients who have very thick chest walls. In addition they are prone to blockage, kinking and dislodging, and can cause a lung laceration which subsequently can lead to air embolisation (especially if a Pneumothorax was not present). Some groups are therefore recommending an urgent Chest X-Ray if there is no haemodynamic compromise.

Hint

This patient has shortness of breath and a raised KCO, which leads to you to a diagnosis of Alveolar Haemorrhage. The condition which links Epistaxis and Alveolar Haemorrhage in the list above is Granulomatosis with Polyangiitis. KCO measures the uptake of carbon monoxide by the lungs, and is equivalent to the transfer factor._x000D_
Granulomatosis with Polyangiitis is a multi-organ autoimmune disease, which can be fatal. The classical triad consists of Necrotising Granulomatous Inflammation of the Respiratory Tract, Glomerulonephritis and a Small-Vessel Vasculitis. A prolonged history of epistaxis or sinusitis is commonly found in Granulomatosis with Polyangiitis, which in some patients is also associated with an Eosinophilia. The detection of Antineutrophil Cytoplasmic Antibodies directed against Proteinase-3 is highly specific, but is found in only 50% of patients with disease localised to the respiratory tract and 95% with generalised Granulomatosis with Polyangiitis._x000D_
Standard Therapy is with Cyclophosphamide and Corticosteroids. TNF-Alpha Blocking Agents, Anti-Thymocyte Globulin and Monoclonal Anti T-Cell Antibodies can be used in disease refractory to these agents._x000D_
Systemic Inflammation and Vasculitis contribute to accelerated Atherosclerosis in patients with Granulomatosis with Polyangiitis and there is therefore a significantly increased incidence of Stroke, Myocardial Infarction and Occlusive Artery Disease._x000D_
Alveolar Proteinosis is a rare diffuse lung condition, characterised by alveolar and interstitial accumulation of phospholipid protein derived from surfactant. It can be congenital, secondary or acquired, and patients often present with recurrent respiratory infections. Transfer factor (KCO) is typically reduced._x000D_
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis which affects small and medium sized vessels, in association with asthma. Patients initially present with allergic rhinitis and asthma, followed by eosinophilia and associated infiltrative disease (e.g. gastroenteritis) and then granulomatous inflammation classically within 3 years._x000D_
Goodpasture’s syndrome is an important, and potentially rapidly fatal, cause of alveolar haemorrhage. It is caused by circulating antiglomerular basement membrane antibodies, and typically causes an acute glomerulonephritis. Epistaxis is not as common an association._x000D_
Microscopic Polyangiitis is a Small Vessel Vasculitis which Classically Spares the Upper Respiratory Tract.

Hint

The most likely diagnosis here is Allergic Bronchopulmonary Aspergillosis (ABPA); as such Aspergillus Precipitins can contribute significantly to confirming the diagnosis._x000D_
Oral Steroids are the mainstay of initial treatment and Anti-Fungals such as Itraconazole may also improve resolution of symptoms in some cases._x000D_
Whilst both chest X-Ray and CT Scan Thorax may show evidence of infiltrates this is relatively non-specific and therefore would not be optimal investigations; they may, however, prove useful in assessing severity of disease._x000D_
IgE is elevated in Allergic Bronchopulmonary Aspergillosis [ABPA] but is not as specific an investigation as Aspergillus Precipitins._x000D_
Sputum Culture may be positive but negative culture would not exclude the disease.

Hint

Based on the provided information, the most probable diagnosis in this case is allergic bronchopulmonary aspergillosis (ABPA). Aspergillus precipitins, a type of antibody specific to the fungus Aspergillus, can play a crucial role in confirming this diagnosis.

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Allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to the presence of Aspergillus in the respiratory system. This condition primarily affects individuals with underlying asthma or cystic fibrosis. Common symptoms include wheezing, coughing, shortness of breath, and recurrent respiratory infections.

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To confirm the diagnosis of allergic bronchopulmonary aspergillosis (ABPA), laboratory tests can be performed to detect the presence of specific antibodies known as aspergillus precipitins. These antibodies indicate an immune response to Aspergillus and can significantly contribute to confirming the diagnosis.

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It is important to accurately diagnose allergic bronchopulmonary aspergillosis (ABPA) as early as possible to initiate appropriate management, which may involve antifungal medications, corticosteroids, and management of underlying respiratory conditions. The presence of aspergillus precipitins can provide valuable evidence to support the diagnosis of allergic bronchopulmonary aspergillosis in this case.

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Therefore, correct answer to the above question is D. Aspergillus precipitins. This is a blood test that detects antibodies to Aspergillus, a type of fungus that can cause allergic reactions and infections in the lungs. Aspergillus precipitins can help diagnose allergic bronchopulmonary aspergillosis (ABPA), a condition that affects some people with asthma and causes inflammation, mucus plugging, and bronchiectasis. Allergic bronchopulmonary aspergillosis (ABPA) can also cause haemoptysis, which is the coughing up of blood from the lungs.

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Other investigations for asthma and haemoptysis may include:

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• A. Computed tomography (CT) scan of thorax: This is an imaging test that can show detailed pictures of the lungs and the airways. It can help identify the cause and the source of haemoptysis, such as lung cancer, tuberculosis, bronchiectasis, or pulmonary embolism. It can also help evaluate the extent and severity of allergic bronchopulmonary aspergillosis (ABPA).

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• B. IgE: This is a blood test that measures the level of immunoglobulin E, a type of antibody that is involved in allergic reactions. IgE levels are usually elevated in people with asthma and allergic bronchopulmonary aspergillosis (ABPA). However, IgE levels can also be affected by other factors, such as parasitic infections, eczema, or anaphylaxis. Therefore, IgE alone is not a specific test for allergic bronchopulmonary aspergillosis (ABPA) or haemoptysis.

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• C. Sputum culture: This is a laboratory test that analyses the mucus that is coughed up from the lungs. It can help identify the presence and the type of bacteria, fungi, or viruses that may cause infection or inflammation in the lungs. Sputum culture can be useful for diagnosing pneumonia, tuberculosis, or aspergillosis, which are possible causes of haemoptysis.

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• E. Chest x-ray: This is a simple and quick imaging test that can show the shape and size of the lungs and the heart. It can help detect abnormalities such as masses, nodules, consolidation, or cavitation, which may indicate lung cancer, tuberculosis, pneumonia, or pulmonary oedema. However, chest x-ray has limited sensitivity and specificity for diagnosing the cause of haemoptysis, and it may miss subtle or early changes in the lungs.

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Hint

The most obvious initial investigation is to get the patient to keep a peak flow diary with multiple measurements at different times in the day and involving both weekdays and weekends._x000D_
Detailed Pulmonary Function Tests, and Radioallergosorbent (RAST) or Skin Testing may also be part of the work up, but the peak flow diary is the best way to establish the temporal relationship between Asthma and the Paint Spraying. Once the specific trigger is identified, he may either need to be given special equipment to protect him from exposure, or moved to a different role._x000D_
Simply treating his asthma with appropriate medication is not appropriate.

Hint

Patients with Pneumocystis pneumonia often present with signs and symptoms of respiratory distress, although on examination of the chest there is often no abnormality detected._x000D_
Although initially reported as a disease associated with Acquired Immune Deficiency Syndrome [AIDS], Pneumocystis pneumonia (PCP) can affect any Immunocompromised patient including Transplant Patients._x000D_
The Trophozoite does not enter the Blood Stream, and the organism is usually identified in Pulmonary Secretions._x000D_
Co-Trimoxazole (Septrin) or Pentamidine are the treatments of choice.

Hint

Usually all stenotic and regurgitant valvular lesions with different types of murmur are best being heard during squatting position (due to increased intensity) and become less audible (due to decreased intensity). Only in Hypertrophic Obstructive Cardiomyopathy (HOCM) and Mitral Prolapse the murmur becomes louder during Valsalva Manoeuvre.

Hint

The best plan of action for this gentleman is A. Video assisted thoracoscopic surgery (VATS).

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Video assisted thoracoscopic surgery (VATS) is a minimally invasive surgical procedure that involves making small incisions in the chest wall and inserting a camera and instruments to perform various operations on the lung. Video assisted thoracoscopic surgery (VATS) can be used to treat pneumothorax by removing the air from the pleural space and creating adhesions between the lung and the chest wall to prevent recurrence. Video assisted thoracoscopic surgery (VATS) has several advantages over other methods, such as faster recovery, less pain, lower risk of complications, and higher success rate.

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Video assisted thoracoscopic surgery (VATS) is indicated in several conditions, including:

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1. Second ipsilateral pneumothorax: This refers to a recurrence of a collapsed lung on the same side as a previous episode. Video assisted thoracoscopic surgery (VATS) can be performed to address the underlying cause and prevent further recurrences.

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2. Bilateral spontaneous pneumothorax: In some cases, both lungs may experience a spontaneous collapse. Video assisted thoracoscopic surgery (VATS) can be used to treat both sides simultaneously, reducing the risk of future collapses.

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3. Spontaneous haemothorax: This condition occurs when blood accumulates in the pleural space without any apparent cause. Video assisted thoracoscopic surgery (VATS) allows for the identification and management of the bleeding source, helping to resolve the haemothorax.

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4. Persistent air leak: If a patient continues to have air leakage from the lung for more than five to seven days, video assisted thoracoscopic surgery (VATS) can be employed to locate and repair the site of the leak, promoting lung re-expansion and preventing complications.

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5. Certain occupations, such as pilots or divers: Individuals in professions that require excellent lung function, such as pilots or divers, may undergo video assisted thoracoscopic surgery (VATS) to address any underlying lung conditions or complications that could potentially impact their performance and safety.

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In summary, video assisted thoracoscopic surgery (VATS) is a valuable surgical approach for various conditions, including recurrent pneumothorax, bilateral pneumothorax, spontaneous haemothorax, persistent air leaks, and specific occupational considerations. It offers a minimally invasive option for diagnosis, treatment, and prevention of complications, ultimately improving patient outcomes and quality of life.

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The other options are not optimal because:

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·         B. Chemical pleurodesis is a procedure that involves injecting a chemical agent (such as talc, doxycycline, or bleomycin) into the pleural space to cause inflammation and scarring, which seals the leak and prevents recurrence. Chemical pleurodesis can be effective, but it is associated with more pain, longer hospital stay, and higher risk of infection, and lower success rate than video assisted thoracoscopic surgery (VATS). Moreover, chemical pleurodesis is a treatment option employed in elderly patients who experience recurrent pneumothorax and are deemed high-risk candidates for surgery. As already mentioned earlier, this procedure involves the instillation of a chemical agent into the pleural space to induce inflammation and adhesion formation, ultimately preventing the recurrence of pneumothorax. However, it is important to note that the success rates of chemical pleurodesis can range from 10% to 20%, meaning that there is a possibility of the procedure not achieving the desired outcome in some cases.

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• Removing the drain and discharging the gentleman without any definitive treatment is not advisable, as he has a high risk of recurrence due to his history of previous pneumothorax, his occupation as a welder, and his ex-smoking status. Recurrent pneumothorax can cause more lung damage, respiratory failure, and even death.

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• Rechecking if the gentleman still smokes and advising him to quit is a good preventive measure, as smoking is a major risk factor for pneumothorax. However, it is not sufficient as a definitive treatment, as he may still have a recurrence even if he quits smoking. Smoking cessation should be combined with a definitive procedure such as video assisted thoracoscopic surgery (VATS) or chemical pleurodesis.

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• Advising the gentleman to rest for two weeks and then repeat the chest x-ray is not an effective treatment, as it does not address the underlying cause of the pneumothorax or prevent recurrence. Resting may help this gentleman to recover from the symptoms, but it does not seal the leak or prevent air from re-entering the pleural space. Repeating the chest x-ray may help to monitor the condition, but it does not provide a definitive diagnosis or treatment.

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Hint

The correct answer is B. Extravascular eosinophils on vascular biopsy. Extravascular eosinophils are a hallmark of eosinophilic granulomatosis with polyangiitis (EGPA), as they indicate tissue infiltration and damage by these cells. Vascular biopsy is the gold standard for diagnosing eosinophilic granulomatosis with polyangiitis (EGPA), as it can reveal necrotizing vasculitis, granulomas, and eosinophils in the vessel wall or surrounding tissue. However, biopsy is not always feasible or positive, so other clinical and laboratory criteria are also used to support the diagnosis.

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Let us now discuss the other answer options:

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1. Fixed pulmonary infiltrates on chest radiographs: This is an incorrect answer. Fixed pulmonary infiltrates are not specific for eosinophilic granulomatosis with polyangiitis (EGPA), as they can be seen in other conditions that cause chronic lung inflammation or fibrosis, such as chronic eosinophilic pneumonia, sarcoidosis, or tuberculosis. Eosinophilic granulomatosis with polyangiitis (EGPA) can cause various pulmonary manifestations, such as asthma, eosinophilic pneumonia, pleural effusion, or pulmonary haemorrhage, but these are usually transient or migratory, not fixed.

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2. Peripheral ‘stocking’ neuropathy: This is not the correct answer because peripheral ‘stocking’ neuropathy is a type of peripheral nerve damage that affects the lower limbs in a symmetric pattern, usually starting from the toes and ascending upwards. It can be caused by various factors, such as diabetes mellitus, alcoholism, or vitamin B12 deficiency. Eosinophilic granulomatosis with polyangiitis (EGPA) can also cause peripheral neuropathy, but it is usually asymmetric and affects the upper and lower limbs, often sparing the feet. It is due to vasculitis of the vasa nervorum, the small blood vessels that supply the nerves.

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3. Peripheral alveolar filling infiltrate predominantly in the upper lobes on a chest radiograph: This is an incorrect answer because peripheral alveolar filling infiltrate is a radiographic pattern that shows fluffy or hazy opacities in the lung periphery, usually indicating alveolar oedema, pneumonia, or lung cancer. It is not a typical feature of eosinophilic granulomatosis with polyangiitis (EGPA), which tends to cause more central or diffuse pulmonary involvement. Moreover, eosinophilic granulomatosis with polyangiitis (EGPA) does not have a predilection for the upper lobes, unlike other granulomatous diseases such as tuberculosis or histoplasmosis.

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4. Peak flow <300 L/minute: This is an incorrect answer because peak flow is a measure of the maximum speed of expiration, which reflects the degree of airway obstruction. A peak flow <300 L/minute indicates severe airflow limitation, which can be seen in various respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), or bronchiectasis. It is not specific for eosinophilic granulomatosis with polyangiitis (EGPA), which can cause mild to severe asthma, depending on the individual patient. Furthermore, peak flow is not a reliable indicator of eosinophilic granulomatosis with polyangiitis (EGPA) activity, as it can vary depending on the time of day, medication use, or environmental factors.

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Hint

The Serum Levels of some of the Common Genotypes are:_x000D_
? PiMM: 100% (Normal)._x000D_
? PiMS: 80% of Normal Serum Level Of A1AT._x000D_
? PiSS: 60% Of Normal Serum Level Of A1AT._x000D_
? PiMZ: 60% Of Normal Serum Level Of A1AT._x000D_
? PiSZ: 40% Of Normal Serum Level Of A1AT._x000D_
? PiZZ: 10-15% (Severe Alpha 1-Antitrypsin Deficiency)._x000D_
Cigarette Smoking is especially harmful to those with A1AT Deficiency and can Accelerate the Progression of Emphysema by 10 years.

Hint

This question addresses the phenomena of Acute Respiratory Distress Syndrome [ARDS] and its causes both Direct and Indirect._x000D_
Direct Pulmonary causes include:_x000D_
? Inhalation of Gastric Contents (pH <2)_x000D_
? Infective (Pneumonia, Tuberculosis)_x000D_
? Pulmonary Trauma_x000D_
? Near Drowning_x000D_
? Toxic Gas Inhalation and_x000D_
? Oxygen Toxicity._x000D_
Indirect causes include:_x000D_
? Sepsis_x000D_
? Non-Thoracic Trauma_x000D_
? Uraemia_x000D_
? Bowel Infraction_x000D_
? Anaphylaxis and_x000D_
? Burns._x000D_
Acute Respiratory Distress Syndrome [ARDS] Mortality is generally high (40%), but is determined by the cause with Aspiration Pneumonia having a mortality rate of almost 80% when associated with Acute Respiratory Distress Syndrome [ARDS].

Hint

A direct pulmonary cause of acute respiratory distress syndrome (ARDS) is a cause that directly damages the lung tissue and leads to fluid leakage and inflammation in the air sacs (alveoli). Based on this definition, the correct answer is A. Tuberculosis. Tuberculosis is an infectious disease that affects the lungs and can cause granulomas, cavities, and fibrosis in the lung parenchyma. These lesions can impair the integrity of the alveolar-capillary membrane and allow fluid to accumulate in the alveoli, resulting in acute respiratory distress syndrome (ARDS).

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The other options are incorrect, because they are indirect causes of acute respiratory distress syndrome (ARDS), meaning that they cause systemic inflammation or injury that affects the lungs secondarily. These include:

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• B. Sepsis, which is a serious and widespread infection of the bloodstream that can trigger a cytokine storm and increase the permeability of the alveolar-capillary membrane.

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• C. Anaphylaxis, which is a severe allergic reaction that can cause bronchoconstriction, vasodilation, and increased vascular permeability.

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• D. Post arrest, which refers to the period after a cardiac arrest, when the lack of blood flow and oxygen to the lungs can cause ischaemia-reperfusion injury and oxidative stress.

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• E. Burns, which can cause a systemic inflammatory response syndrome and increase the capillary leakage in the lungs.

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Hint

This question requires an understanding of the definition of Multi-Drug-Resistant Tuberculosis (MDR-TB) and the differences in treatment duration._x000D_
Multi-Drug-Resistant Tuberculosis (MDR-TB) as the name suggests is Mycobacterium tuberculosis resistant to two or more first line agents, which most commonly are isoniazid and rifampicin. There can be monoresistance to each of the first line agents, but this is not Multi-Drug-Resistant Tuberculosis (MDR-TB)._x000D_
Treatment of Multi-Drug-Resistant Tuberculosis (MDR-TB) is complex and time consuming. Treatment must be continued for a minimum of 18 months, with at least 9 months of treatment after the patient becomes culture-negative. _x000D_
Risk factors for acquiring Multi-Drug-Resistant Tuberculosis (MDR-TB) include previous Tuberculosis (TB) Treatment, Human Immunodeficiency Virus (HIV) Infection, Contact With Drug Resistant Disease and Treatment Failure._x000D_
Initial treatment includes the use of five agents until sputum is negative and then continuation of three to which the Tuberculosis (TB) is sensitive to for a minimum of nine months but sometimes up to 24 months.

Hint

The autoantibodies that are most associated with granulomatosis with polyangiitis (GPA) are B. PR3-anti-neutrophil cytoplasmic antibodies (ANCA)¹². These are a type of autoantibodies that target proteinase 3 (PR3), an enzyme found in the cytoplasm of neutrophils. PR3-anti-neutrophil cytoplasmic antibodies (ANCA) are thought to play a role in the pathogenesis of granulomatosis with polyangiitis (GPA), as they can activate neutrophils and cause inflammation and damage to the blood vessels. PR3-anti-neutrophil cytoplasmic antibodies (ANCA) are detected in about 80-90% of patients with active granulomatosis with polyangiitis (GPA), and their levels may correlate with disease activity.

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The other options are not associated with granulomatosis with polyangiitis (GPA), because:

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• A. MPO-anti-neutrophil cytoplasmic antibodies (ANCA) are another type of autoantibodies that target myeloperoxidase (MPO), an enzyme found in the cytoplasm of neutrophils. MPO-anti-neutrophil cytoplasmic antibodies (ANCA) are more commonly associated with microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), which are two other forms of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis.

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• C. Anti-dsDNA are autoantibodies that target double-stranded DNA, a component of the genetic material of cells. Anti-dsDNA are specific for systemic lupus erythematosus (SLE), a chronic autoimmune disease that can affect various organs.

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• D. Anti-GBM are autoantibodies that target the glomerular basement membrane (GBM), a part of the kidney’s filtration system. Anti-GBM are responsible for anti-GBM disease, also known as Goodpasture syndrome, a rare condition that causes kidney failure and lung haemorrhage.

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• E. p-anti-neutrophil cytoplasmic antibodies (p-ANCA) are a subtype of anti-neutrophil cytoplasmic antibodies (ANCA) that target perinuclear antigens, such as myeloperoxidase (MPO) or elastase. p-anti-neutrophil cytoplasmic antibodies (p-ANCA) are not specific for any disease, but they can be found in various conditions, such as inflammatory bowel disease, rheumatoid arthritis, or drug-induced vasculitis.

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Hint

Anti-Neutrophil Cytoplasmic Antibodies (ANCA) are diagnostic Markers for Vasculitis, although they may not be pathological. They are characterised by Neutrophil Staining; Cytoplasmic Staining Uptake (c-ANCA) and Peri-Nuclear (p-ANCA)._x000D_
These are largely synonymous with PR3-ANCA (targeting peroxidise-3) and MPO-ANCA (targeting myeloperoxidase)._x000D_
PR3-ANCA has 60-90% sensitivity and more than 90% specificity for Granulomatosis with Polyangiitis._x000D_
Churg-Strauss and Microscopic Polyangiitis are more commonly associated with MPO-Anti-Neutrophil Cytoplasmic Antibodies [ANCA] or p-Anti-Neutrophil Cytoplasmic Antibodies [ANCA], although may be positive for PR3 Anti-Neutrophil Cytoplasmic Antibodies [ANCA] also._x000D_
Goodpasture’s is associated with Anti-Glomerular Basement Membrane Antibody (Anti-GBM)._x000D_
Systemic Lupus Erythematosus (SLE) is associated with Anti-dsDNA antibodies.

Hint

Multiple sleep latency test (option E) is the correct answer because the multiple sleep latency test (MSLT) is the most useful test for diagnosing narcolepsy in adults, according to the NICE guidelines. The MSLT measures how quickly a person falls asleep during the day and how often they enter rapid eye movement (REM) sleep. People with narcolepsy typically have a short sleep latency (less than 8 minutes) and at least 2 sleep-onset rapid eye movement (REM) periods. The multiple sleep latency test (MSLT) is usually done after an overnight polysomnography, which records the brain activity, eye movements, muscle tone, heart rate, and breathing during sleep. The multiple sleep latency test (MSLT) can help differentiate narcolepsy from other causes of excessive daytime sleepiness, such as sleep apnoea, idiopathic hypersomnia, or insufficient sleep syndrome.

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The incorrect answer options can be ruled out with appropriate explanation for each of them as follows:

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1. Trial of continuous positive airway pressure (CPAP): This is an incorrect answer because continuous positive airway pressure (CPAP) is a treatment for obstructive sleep apnoea, not narcolepsy. Continuous positive airway pressure (CPAP) delivers pressurized air through a mask to keep the airway open during sleep. Continuous positive airway pressure (CPAP) can improve the quality of sleep and reduce daytime sleepiness in people with sleep apnoea, but it has no effect on the symptoms of narcolepsy, such as cataplexy, sleep paralysis, or hallucinations.

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2. Genetic analysis: This is an incorrect answer because genetic analysis is not useful for diagnosing narcolepsy. Narcolepsy is not caused by a single gene, but by a complex interaction of genetic and environmental factors. About 98% of people with narcolepsy type 1 (with cataplexy) have a specific gene variant called HLA-DQB1*0602, but this gene is also present in 12% to 38% of the general population. Therefore, genetic testing cannot confirm or exclude the diagnosis of narcolepsy, and it is not recommended by the National Institute for Health and Care Excellence (NICE) guidelines.

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3. Polysomnography: This is an incorrect answer because polysomnography alone is not sufficient for diagnosing narcolepsy. Polysomnography is a test that records the brain activity, eye movements, muscle tone, heart rate, and breathing during sleep. Polysomnography can help rule out other sleep disorders, such as sleep apnoea, periodic limb movement disorder, or rapid eye movement (REM) sleep behaviour disorder. However, polysomnography cannot detect the abnormal sleep patterns that are characteristic of narcolepsy, such as short sleep latency and frequent sleep-onset rapid eye movement (REM) periods. Therefore, polysomnography is usually followed by the multiple sleep latency test (MSLT), which is the definitive test for narcolepsy.

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4. High hypocretin levels in cerebrospinal fluid (CSF) analysis: This is an incorrect answer because high hypocretin levels in cerebrospinal fluid (CSF) analysis are not a reliable marker of narcolepsy. Hypocretin (also known as orexin) is a neurotransmitter that regulates wakefulness and arousal. People with narcolepsy type 1 (with cataplexy) usually have low or undetectable levels of hypocretin in their cerebrospinal fluid (CSF), due to the loss of hypocretin-producing neurons in the hypothalamus. However, hypocretin levels can vary depending on the time of day, the stage of sleep, and the severity of the condition. Moreover, hypocretin levels are normal in people with narcolepsy type 2 (without cataplexy) and in some people with narcolepsy type 1. Therefore, hypocretin levels in cerebrospinal fluid (CSF) analysis are not a consistent or specific indicator of narcolepsy, and they are not recommended by the National Institute for Health and Care Excellence (NICE) guidelines.

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Hint

Immotile Cilia Syndrome, also known as Primary Ciliary Dyskinesia and includes Kartagener’s Syndrome, is an inherited condition where the cilia lining the airways fail to function or function ineffectively._x000D_
A defect in the Dynein Molecule causes the cilia either totally to cease to function or to function ineffectively._x000D_
Kartagener’s Syndrome is a subset of patients that account for about half of all people with Immotile Cilia Syndrome._x000D_
Other associated conditions of Immotile Cilia Syndrome are:_x000D_
? Male Infertility_x000D_
? Congenital Heart Defects_x000D_
? Deafness_x000D_
? Hydrocephalus._x000D_
Cystic Fibrosis is unlikely to present at this age._x000D_
Infertility is not typically associated with Hypogammaglobulinaemia.

Hint

The most likely causative agent for the condition of this gentleman is C. Thermophilic Actinomyces bacteria.

_x000D_

Thermophilic Actinomyces bacteria are a group of bacteria that thrive in warm and moist environments, such as hay, compost, and animal bedding. They can cause a type of hypersensitivity pneumonitis, also known as farmer’s lung, which is an allergic reaction to inhaled organic dusts.

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Farmer’s lung typically presents with breathlessness, dry cough, fever, and malaise, especially after exposure to the offending dust. The symptoms may be acute, subacute, or chronic, depending on the frequency and intensity of exposure.

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The chest x-ray of farmer’s lung may show fluffy nodular shadowing, which represents areas of inflammation and fibrosis in the lung parenchyma. The nodules are usually bilateral and symmetric, and may coalesce to form larger opacities.

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The other options are less likely for the following reasons:

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_x000D_
• Penicillium species are fungi that can cause allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction to Aspergillus antigens in the airways. Allergic bronchopulmonary aspergillosis (ABPA) usually affects patients with asthma or cystic fibrosis, and presents with wheezing, cough, and expectoration of brownish plugs. The chest x-ray of allergic bronchopulmonary aspergillosis (ABPA) may show central bronchiectasis, mucoid impaction, or transient infiltrates.

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• Epicoccum nigrum is a fungus that can cause allergic fungal sinusitis (AFS), a hypersensitivity reaction to fungal antigens in the paranasal sinuses. Allergic fungal sinusitis (AFS) usually affects patients with chronic rhinosinusitis, and presents with nasal congestion, discharge, and polyps. The chest x-ray of allergic fungal sinusitis (AFS) is usually normal, unless there is secondary pulmonary involvement.

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• Avian proteins are proteins derived from birds, such as feathers, droppings, or serum. They can cause bird fancier’s lung, another type of hypersensitivity pneumonitis, which is similar to farmer’s lung but occurs in people who are exposed to birds or their products. The chest x-ray of bird fancier’s lung may also show fluffy nodular shadowing, but the history of working as a stablehand makes this less likely than farmer’s lung.

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• Klebsiella is a bacterium that can cause pneumonia, especially in patients with underlying lung disease, alcoholism, or diabetes. Klebsiella pneumonia usually presents with fever, productive cough, and pleuritic chest pain. The chest x-ray of Klebsiella pneumonia may show lobar consolidation, cavitation, or abscess formation.

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Hint

The most common example of Allergic Alveolitis is Farmer’s Lung._x000D_
This is caused by dust from mouldy hay contaminated with Thermophilic Actinomyces bacteria, and as a Stablehand this gentleman is likely to have been in close contact with this allergen. Typically symptoms tend to occur several hours after exposure. Chest X-Ray may demonstrate fluffy nodular shadowing or ground glass appearances._x000D_
Avian Proteins are the allergen responsible for pigeon fancier’s lung._x000D_
Penicillium species are responsible for respiratory disease in cheese and cork workers and are due to fungal contaminants of materials._x000D_
Klebsiella and Epicoccum nigrum are other bacterial causes of Allergic Alveolitis and are found in contaminated water, wood shavings, etc.

Hint

This patient is immunocompromised and given the clinical history and radiological findings, the likely diagnosis in this lady is Pneumocystis pneumonia (PCP). She is also pregnant which affects treatment choice._x000D_
Although Pneumocystis pneumonia (PCP) is officially a fungal infection it does not respond to anti-fungal medications._x000D_
Trimethoprim-Sulfamethoxazole (TMP-SMX / Co-Trimoxazole / Septrin) has been shown to be as effective as Intravenous Pentamidine and more effective than other alternative treatment regimens._x000D_
TMP-SMX is the preferred initial therapy during pregnancy according to consensus guidelines. The BNF States that there is a Teratogenic Risk in the First Trimester (as Trimethoprim is a Folate Antagonist), and Neonatal Haemolysis and Methaemoglobinaemia in the Third Trimester. However, there is also considerable risk of harm to the foetus if the mother is unwell. The benefits in this situation therefore outweigh the risks, and it should be used._x000D_
For the treatment of infections that are resistant to TMP-SMX, the combination of Clindamycin and Primaquine is likely to be more effective than Intravenous Pentamidine._x000D_
Rifampicin, Ethambutol, Isoniazid, Pyrazinamide are the first line drugs to treat Tuberculosis (TB). Although this woman is at risk from Tuberculosis (TB) infection, the clinical history is more in keeping with a diagnosis of Pneumocystis pneumonia (PCP)._x000D_
Adjuvant Steroid Therapy is indicated in patients with severe Pneumocystis pneumonia (PCP) infection who have underlying Human Immunodeficiency Virus [HIV] Infection.

Hint

The two diagnoses which should be considered first in this scenario are Pulmonary Embolism and Fat Embolism._x000D_
Although the patient is at high risk of Pulmonary Embolism, and appropriate measures should be undertaken to reduce this, the clinical scenario is more suggestive of Fat Embolism. Fat Embolism is thought to occur as a result of release of Lipid Globules from Damaged Bone Marrow Fat Cells. Another mechanism that has been suggested is the Increased Mobilisation Of Fatty Acids Peripherally._x000D_
The effects that are seen clinically depend on what part of the Microvasculature is affected by the Lipid Globules._x000D_
Pulmonary Symptoms are caused by Ventilation Perfusion Mismatch._x000D_
Confusion (Cerebral Effects) may be seen, as well as a petechial rash caused by capillary damage in the skin.

Hint

Based on the clinical history and family history of this gentleman in this question, the most likely diagnosis is E. Alpha-1 antitrypsin deficiency. This is a genetic disorder that causes low levels of a protein (alpha-1 antitrypsin) that protects the lungs from damage. People with this condition are at risk of developing emphysema, cirrhosis, and other diseases, especially if they smoke or are exposed to dust.

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Some of the clues that point to this diagnosis are:

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• The gentleman is a lifelong non-smoker, yet he has symptoms of obstructive lung disease similar to emphysema.

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• The father of this gentleman has severe chronic obstructive pulmonary disease (COPD) at a young age, despite smoking only a few cigarettes per day. This suggests a familial predisposition to lung disease.

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• The gentleman has evidence of lower lobe emphysema on chest x-ray, which is typical of alpha-1 antitrypsin deficiency.

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• The gentleman has elevated serum alanine aminotransaminase (ALT), which indicates liver damage. This can be caused by the accumulation of abnormal alpha-1 antitrypsin in the liver.

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• The gentleman’s other blood tests are normal or near normal, which rules out other causes of lung disease such as asthma, silicosis, extrinsic allergic alveolitis, or chronic bronchitis.

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The diagnosis can be confirmed by measuring the level of alpha-1 antitrypsin in the blood or by genetic testing.

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The treatment of alpha-1 antitrypsin (AAT) deficiency may include medications, intravenous infusions of alpha-1 antitrypsin protein, or in severe cases, lung or liver transplantation. This gentleman should also avoid smoking and environmental dust, and receive vaccinations for influenza, pneumococcus, and hepatitis.

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The other answer options in the above question can be ruled out based on the following explanations:

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• A. Asthma is a chronic inflammatory disorder of the airways that causes reversible bronchoconstriction and increased mucus production. Asthma is usually associated with a history of atopy, allergic triggers, episodic symptoms, and a positive response to bronchodilators. Asthma does not typically cause lower lobe emphysema or elevated serum alanine aminotransaminase (ALT).

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• B. Silicosis is an occupational lung disease caused by inhalation of silica dust, which is commonly found in stone masonry, mining, and sandblasting. Silicosis causes fibrotic nodules in the upper lobes of the lungs, which can coalesce into progressive massive fibrosis. Silicosis also increases the risk of tuberculosis and lung cancer. Silicosis does not cause wheeze, lower lobe emphysema, or elevated serum alanine aminotransaminase (ALT).

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• C. Extrinsic allergic alveolitis, also known as hypersensitivity pneumonitis, is an immune-mediated lung disease caused by repeated inhalation of various organic antigens, such as molds, bacteria, bird droppings, or animal proteins. Extrinsic allergic alveolitis causes granulomatous inflammation and fibrosis in the lung parenchyma and small airways. Extrinsic allergic alveolitis may present with acute, subacute, or chronic symptoms, depending on the type and duration of exposure. Extrinsic allergic alveolitis does not cause lower lobe emphysema or elevated serum alanine aminotransaminase (ALT).

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• D. Chronic bronchitis is a form of chronic obstructive pulmonary disease (COPD) characterized by a productive cough for at least three months in each of two consecutive years. Chronic bronchitis is usually caused by cigarette smoking or other environmental irritants. Chronic bronchitis causes inflammation and mucus hypersecretion in the large airways, leading to airflow obstruction and increased risk of respiratory infections. Chronic bronchitis does not cause lower lobe emphysema or elevated serum alanine aminotransaminase (ALT).

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Hint

The presence of bronchiectasis in this gentleman is supported by several clinical findings. Firstly, he regularly produces sputum and experiences breathlessness, which are common symptoms of bronchiectasis. Additionally, he has a history of recurrent lung infections, which is another characteristic feature of this condition. Furthermore, the presence of bilateral inspiratory crackles during lung examination is indicative of widespread disease in the bronchial tubes. Bronchiectasis is a chronic condition characterized by the permanent dilation and damage of the bronchial tubes, leading to the accumulation of mucus and recurrent infections. The production of sputum, breathlessness, and lung infections are all consequences of the impaired clearance of mucus from the airways. The bilateral inspiratory crackles heard during lung examination suggest that the bronchiectasis has affected multiple areas of the lungs, further supporting the diagnosis of widespread disease in this gentleman.

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Here, the answer to above question is B. Postural drainage. This is a type of airway clearance technique that involves positioning the body in different ways to help drain mucus from the lungs. Postural drainage can reduce the risk of infections and improve lung function in people with bronchiectasis.

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Other treatments for bronchiectasis may include antibiotics, mucus thinning medication, airway clearance devices, chest physical therapy, oxygen therapy, or surgery, depending on the severity and cause of the condition. It is also important to quit smoking, maintain a healthy diet, stay hydrated, and get vaccinated to prevent complications and flare-ups.

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The other options given in the above question are not likely to decrease the frequency of exacerbations in this gentleman because:

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_x000D_
• A. Inhaled corticosteroids: These are anti-inflammatory drugs that can help reduce airway inflammation and improve lung function in some people with bronchiectasis. However, they do not directly affect the frequency of exacerbations, and their long-term use may have adverse effects such as osteoporosis, diabetes, and cataracts.

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• C. Cyclical antibiotic therapy: This is a preventive strategy that involves taking antibiotics regularly for a certain period of time, such as every month or every other month, to reduce the bacterial load and prevent infections. It may be beneficial for some people with frequent or severe exacerbations, but it is not recommended for everyone, as it may increase the risk of antibiotic resistance, side effects, and drug interactions.

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• D. Surgical resection: This is a procedure that involves removing the diseased part of the lung that is affected by bronchiectasis. It may be considered as a last resort for people who have localized bronchiectasis that does not respond to medical therapy, or who have life-threatening complications such as massive haemoptysis (coughing up blood). However, it is not a common or routine treatment, as it carries significant risks and does not cure the underlying condition.

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• E. Nebulised bronchodilators: These are drugs that are inhaled through a nebulizer, a device that turns liquid medicine into a fine mist that can be breathed in. They work by relaxing the muscles around the airways and making it easier to breathe. They may be helpful for some people with bronchiectasis, who also have asthma or chronic obstructive pulmonary disease (COPD), but they do not directly affect the frequency of exacerbations, and their use should be guided by a lung function test.

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Hint

This man has Bronchiectasis as evidenced by his regular production of sputum associated with breathlessness, his repeated lung infections and the signs of bilateral inspiratory crackles._x000D_
Retained mucus is the most important reason why bronchiectatic patients become infected. Postural drainage is, therefore, the cornerstone to treating bronchiectasis and should be undertaken at least once per day and more frequently during exacerbations._x000D_
There have been trials looking at regular antibiotic therapy versus symptomatic treatment in patients with cystic fibrosis colonised with Pseudomonas (for example, Elborn JS et al. Thorax 2000;55: 355-358) but there is currently no evidence that this approach is of benefit in bronchiectasis._x000D_
Similarly, inhaled corticosteroids should not be used routinely in bronchiectasis until further evidence of their effect on lung function and exacerbation frequency is available._x000D_
Surgical resection as a curative procedure can be performed for localised disease when underlying causes such as primary ciliary dyskinesia have been excluded._x000D_
In this patient, the bilateral crackles suggest widespread disease.

Hint

Churg-Strauss Syndrome (CSS) is a rare form of small-vessel vasculitis, characterised by asthma, allergic rhinitis and prominent peripheral blood eosinophilia. Two of these are present in the history and should lead you to the diagnosis of Churg Strauss._x000D_
The most commonly involved organ is the lung, followed by the skin. CSS, however, can affect any organ system, including the cardiovascular, gastrointestinal, renal, and central nervous systems. The unifying feature of patients presenting with CSS is asthma. Vasculitis involving the peripheral nervous system is also a characteristic feature, and mononeuritis multiplex occurs in 75% of patients._x000D_
Vasculitis of extrapulmonary organs is largely responsible for the morbidity and mortality associated with CSS. 40-60% are associated with positive ANCA, usually pANCA/MPO._x000D_
ANCA are antineutrophil cytoplasmic antibodies. Several different staining patterns and antigen specificities are recognised. The cytoplasmic staining pattern, cANCA, and specificity for the PR3 antigen is most specific for Granulomatosis with polyangiitis. Perinuclear staining, pANCA, and/or antibody to MPO are far less specific than cANCA and can be present in a range of inflammatory conditions such as microscopic polyangitis, Churg-Strauss syndrome and Goodpasture’s syndrome. MPO and pANCA may also be present in SLE, rheumatoid arthritis, Sj?gren’s syndrome and occasionally in chronic infections._x000D_
Intravenous Glucocorticoid is used for initial therapy of acute multi-organ involvement in Churg-Strauss Syndrome, followed by Oral Glucocorticoid Therapy, often with Azathioprine as a steroid-sparing agent._x000D_
Granulomatosis with Polyangiitis is a multi-organ autoimmune disease, which can be fatal. The classical triad consists of Necrotising Granulomatous Inflammation of the Respiratory Tract, Glomerulonephritis and a Small-Vessel Vasculitis. A prolonged history of Epistaxis or Sinusitis is commonly found in Granulomatosis with Polyangiitis, which in some patients is also associated with an Eosinophilia._x000D_
Microscopic Polyangiitis is microscopically similar to WG, but does not tend to involve the Nasopharynx. It has an association with Hepatitis B and C._x000D_
Acute Respiratory Distress Syndrome (ARDS) describes an Acute Diffuse Inflammatory Lung Injury, often in previously healthy lungs. It has an acute onset, and patients often require respiratory support. It can be precipitated by a number of insults, including drugs and pancreatitis._x000D_
The presence of systemic symptoms makes a diagnosis of asthma alone unlikely.

Hint

The most anticipated diagnosis for this lady is A. Sarcoidosis. Sarcoidosis is a chronic inflammatory disorder that can affect multiple organs, especially the lungs and lymph nodes. It causes the formation of granulomas, which are clusters of immune cells that can interfere with normal organ function. Sarcoidosis is more common in people of African or Caribbean descent, and often presents with respiratory symptoms, such as breathlessness, cough, and chest pain. Sarcoidosis can also cause elevated serum calcium levels, due to increased production of vitamin D by the granulomas. Sarcoidosis can affect the liver and spleen, causing enlargement and dysfunction. Sarcoidosis is diagnosed by blood tests, chest x-ray, and biopsy of affected tissues.

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The other options are less likely, based on the clinical presentation of this lady and her investigations. Some reasons for this are as below:

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• B. Hyperparathyroidism is a condition in which the parathyroid glands produce too much parathyroid hormone, which regulates calcium and phosphorus metabolism. Hyperparathyroidism can cause hypercalcaemia, but it does not typically cause bilateral enlarged hilar lymph nodes, interstitial lung disease, or hepatosplenomegaly. Hyperparathyroidism is diagnosed by measuring parathyroid hormone levels, along with calcium, phosphorus, and vitamin D levels.

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• C. Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis, which mainly affects the lungs, but can also spread to other organs. Tuberculosis can cause pulmonary symptoms, such as cough, fever, and weight loss, and can also cause enlarged lymph nodes, liver, and spleen. In this case, tuberculosis (TB) is indeed a differential diagnosis. However, tuberculosis usually causes caseating granulomas, which are different from the non-caseating granulomas seen in sarcoidosis. Tuberculosis is diagnosed by sputum smear and culture, chest x-ray, and skin or blood tests.

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• D. Coccidioidomycosis is a non-infective fungal infection caused by inhaling spores of the fungus Coccidioides immitis, which is endemic in certain regions of the south-western United States, Mexico, and Central and South America. Coccidioidomycosis can cause pulmonary symptoms, such as cough, fever, and chest pain, and can also disseminate to other organs, such as the skin, bones, and meninges. Coccidioidomycosis can cause granulomas and elevated serum calcium levels, but it is less common than sarcoidosis, and the patient does not have any history of travel or exposure to endemic areas. Coccidioidomycosis is diagnosed by blood tests, sputum culture, and tissue biopsy.

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• E. Hypervitaminosis D is a rare but potentially serious condition that occurs when there is too much vitamin D in the body, either from excessive intake of supplements, or from certain medical conditions or medications that increase vitamin D levels. Hypervitaminosis D can cause hypercalcaemia, but it does not cause bilateral enlarged hilar lymph nodes, interstitial lung disease, or hepatosplenomegaly. Hypervitaminosis D is diagnosed by measuring vitamin D levels, along with calcium, phosphorus, and kidney function tests.

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Hint

This is an Oncological Emergency._x000D_
Mediastinal Radiotherapy leads to symptomatic relief in 80% of patients, although case studies have shown this does not always correlate to patency of the superior vena cava. _x000D_
If possible, an attempt should be made to obtain a tissue diagnosis, as some tumours respond to radiotherapy whereas others are more sensitive to chemotherapy. Tumours which are very chemosensitive, such as germ cell and lymphoma, can cause superior vena cava obstruction. _x000D_
Therefore the active pursuit of a diagnosis with active treatment of the SVCO is indicated and not merely palliative measures, especially in a patient this young._x000D_
Non-Small Cell Cancer and Small Cell Malignancy may both cause Superior Vena Cava Obstruction [SVCO]._x000D_
Intravenous Dexamethasone at high dose is of benefit in severe cases of SVCO._x000D_
It is important to note that in 2004 NICE recommended considering stenting in the majority of cases of Superior Vena Cava Obstruction [SVCO]. This is a minimally invasive procedure which relieves symptoms quicker than chemotherapy or radiotherapy.

Hint

Based on the clinical presentation of this lady and her investigations, the most likely confirmative diagnosis for her is B. Interstitial fibrosis. Interstitial fibrosis is a type of interstitial lung disease (ILD) that causes progressive scarring of the lung tissue. It is a common complication of systemic sclerosis (SSc), a connective tissue disease that affects the skin and multiple internal organs. The risk of developing interstitial lung disease (ILD) is higher in patients with diffuse cutaneous systemic sclerosis (SSc), anti-Scl-70/anti-topoisomerase I antibody, and in the absence of anti-centromere antibody.

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This lady’s history of systemic sclerosis (SSc), peripheral calcinosis, and Raynaud’s disease are suggestive of diffuse cutaneous systemic sclerosis (SSc). Her symptoms of increasing shortness of breath and dry cough, along with the physical findings of inspiratory crackles and the chest x-ray showing bilateral interstitial infiltrates, are consistent with interstitial lung disease (ILD). The elevated erythrocyte sedimentation rate (ESR) and serum creatinine indicate inflammation and renal impairment, which are also common in systemic sclerosis (SSc). The echocardiogram shows a normal ejection fraction, which makes pulmonary oedema unlikely. The other options (idiopathic pulmonary fibrosis, eosinophilic pneumonitis, and bacterial pneumonia) are less likely because they are not associated with systemic sclerosis (SSc) and have different clinical and radiographic features (we will rule out these options elaborately with explanations below).

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To confirm the diagnosis of interstitial fibrosis, this lady may need further tests, such as high-resolution computed tomography (HRCT) of the chest, pulmonary function tests, and bronchoscopy or surgical lung biopsy. The treatment of interstitial fibrosis depends on the severity and progression of the disease, and may include immunosuppressant therapies, ant fibrotic agents, and lung transplantation.

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The incorrect answer options for the above question can be ruled out as follows:

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• A. Pulmonary oedema: This is a condition where fluid accumulates in the lungs, causing difficulty in breathing. It can be caused by heart failure, kidney failure, lung infections, or high altitude. This lady does not have any signs of heart failure, such as elevated jugular venous pressure, peripheral oedema, or S3 gallop. Her serum sodium and potassium are normal, which makes kidney failure unlikely. She does not have any signs of infection, such as fever, chills, or purulent sputum. She does not have any history of exposure to high altitude as well. The chest x-ray of pulmonary oedema typically shows bilateral alveolar infiltrates with a bat-wing pattern, which is different from the interstitial pattern seen in this case.

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• C. Idiopathic pulmonary fibrosis: This is a type of interstitial lung disease that has no known cause. It is characterized by progressive fibrosis of the lung parenchyma, leading to respiratory failure. This lady has a known cause of interstitial lung disease, which is systemic sclerosis. Therefore, the diagnosis of idiopathic pulmonary fibrosis is excluded by definition. The chest x-ray of idiopathic pulmonary fibrosis typically shows bilateral reticular opacities with honeycombing and traction bronchiectasis, which may not be seen in this case.

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• D. Eosinophilic pneumonitis: This is a type of interstitial lung disease that is caused by an allergic reaction to inhaled antigens, such as dust, fungi, or parasites. It is characterized by eosinophilic infiltration of the lung tissue, leading to inflammation and fibrosis. This lady does not have any history of exposure to allergens, such as farming, bird keeping, or travel to endemic areas. She does not have any signs of allergy, such as rash, wheezing, or eosinophilia. The chest x-ray of eosinophilic pneumonitis typically shows bilateral patchy or diffuse opacities with a peripheral or upper lobe predominance, which is different from the interstitial pattern seen in this case.

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• E. Bacterial pneumonia: This is a type of lung infection that is caused by bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. It is characterized by inflammation and consolidation of the lung alveoli, leading to impaired gas exchange. This lady does not have any signs of infection, such as fever, chills, or purulent sputum. Her total leucocyte count and platelet count are normal, which makes infection unlikely. The chest x-ray of bacterial pneumonia typically shows focal or lobar consolidation with air bronchograms, which is different from the interstitial pattern seen in this case.

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