Respiratory Medicine II FRACP teaching – Wed 24 Oct 2007

1. Respiratory Medicine II FRACP teaching – Wed 24 Oct 2007 Respiratory Medicine Middlemore Hospital

2. Programme – 1300-1700hrs • Asthma and COPD • Jeff Garrett • Sleep disorders • Andy Veale • Pulmonary physiology and lung function tests • Conor O’Dochartaigh • Break(1510-1530) • Respiratory multi-choice questions • Anna Tai • Pulmonary infections • Conroy Wong

3. Evaluation Form • Please complete and hand-in at end of day!

4. Pulmonary infections • Pneumonia • TB • Empyema • Airway infections • Bronchiectasis • Mycobacterium avium complex (MAC) • Aspergillus infection

5. Pneumonia Which statement from the IDSA/ATS* (2007) guidelines about community-acquired pneumonia does not have Level I evidence? • Locally adapted guidelines should be implemented • Inpatients should be treated with a ß-lactam plus macrolide • Patients should be treated with antibiotics for a minimum of 5 days • The first antibiotic dose should be administered while still in ED • Healthcare workers should receive annual influenza vaccination *Infectious Diseases Society of America / American Thoracic Society

6. This patient has a community-acquired pneumonia. Which statement is true? • The CXR shows consolidation associated with a mass in the R middle lobe • The lobar distribution indicates that Streptococcus pneumoniae is likely to be the pathogen • This patient should routinely have paired serological tests • A CURB-65 score of < 2 has a 30-day mortality of < 2% • PCR for legionella is indicated for severe pneumonia

7. Legionella pneumonia – lobar Serology: acute = negative convalescent = 1024

8. Severity assessment - CURB-65 • British Thoracic Society • Severity assessment of all patients with pneumonia • Confusion (Mental status score 8 or less) • Urea > 7 mmol/L • Respiratory rate ≥ 30 • Blood pressure – systolic <90 and/or diastolic ≤ 60 • Age over 65 • Score ≥ 3 (‘Severe’) – high risk of death (>20%) • Also: Hypoxaemia (SaO2<92%), multilobar involvement

9. PSI – Pneumonia Severity Index N Engl J Med 1997;336:243

10. Procalcitonin in pneumonia Which statement about procalcitonin in community-acquired pneumonia is false? • Procalcitonin levels are increased in bacterial infections • Persistently elevated levels of procalcitonin are associated with adverse outcome • Procalcitonin guidance of antibiotic therapy reduces the duration of antibiotic use • CRP is a better marker of sepsis • Procalcitonin levels rise within 6 to 12 hours

11. A 75 year-old man presents with a 4 month history of cough and mild dyspnoea He did not respond to augmentin but has a good response to prednisone. His chest xray and CT scan are shown below. • What is the most likely diagnosis? • Chlamydia pneumonia • Legionella pneumonia • Organising pneumonia • SLE pneumonitis • Pneumocystis pneumonia

12. Organising pneumonia • Consider if non-resolving pneumonia • Causes • Cryptogenic (COP), Infection, Drugs (amiodarone) • Cough, fever, malaise • Dyspnoea usually mild • Radiology – patchy peripheral and bilateral distribution • Differential dx: chronic eosinophilic pneumonia, alveolar cell carcinoma, pulmonary lymphoma

14. Mycobacterium tuberculosis Positive acid-fast stain Positive culture

15. TB pleural effusions Which statement about tuberculous pleural effusions is false? • The diagnostic value of pleural investigations is dependent on the pretest probability • Pleural aspirates show lymphocytic predominance • Microscopy and culture for TB are often negative • Adenosine deaminase has high sensitivity and specificity in TB effusions with lymphocyte predominance • PCR is the gold standard for diagnosis

16. Isoniazid prophylaxis A medical registrar has a repeat Mantoux test after 2 years and there is a≥ 10mm increase. Isoniazid is considered. Which statement is false? • The risk of hepatitis increases with age • The risk of hepatitis is about 2% at age 60 • Isoniazid is recommended only if aged <35y • The lifetime risk of tuberculosis is 5-10% • Interferon  release assays are more specific than Mantoux tests

17. Blood tests for TB – TIGRA For T cell interferon  release assays, which of the following statements is false? • Interferon  is produced by T cells in response to antigens specific to M tuberculosis • They are more rapid than tuberculin tests • They are more specific than tuberculin tests • There is no boosting effect • They cross react with BCG more often than tuberculin tests

18. TB Interferon  release assays (Sensitised)

19. TB AG TB AG Mitogen QuantiFERON-TB Gold Assay

20.                          A                          B                          C                          D A:Null B:Antigen A C:Antigen B D:Positive T-Spot.TB assay Peripheral blood mononuclear cells

22. A 32 year-old man presents with a 2 week history of cough, fevers and pleuritic chest pain. The ALT was 192 and ALP 391. His CT scan is shown below. • What is the most likely diagnosis? • Lung abscess • Haemopneumothorax • Empyema with pneumothorax • Mesothelioma • Cavitating carcinoma with liver metastases

23. A chest drain was inserted. This obtained pus and Streptococcus milleri was cultured. • The best evidence for the role of intrapleural streptokinase for empyema indicates that: • Streptokinase is no better than saline flushes • Urokinase is superior to streptokinase • Streptokinase reduces mortality • Streptokinase reduces the need for surgical drainage • Streptokinase reduces the length of stay in hospital

24. 1 Sept 2005 28 Oct 2005

25. Largest clinical trial in pleural infection

26. UK: Multicenter Intra-Pleural Sepsis Trial (MIST) • 52 centers • Pleural fluid >1 of criteria: • purulent • Gram stain +ve • Culture +ve • pH<7.2 & clinical evidence • of pneumonia • 430 patients(age >18): • Most have severe disease • 80% frankly purulent fluid • Pleural fluid pH 6.8 (mean)

27. MIST trial - results • Streptokinase has no benefit over placebo for the following endpoints • Primary • Mortality or surgery at 3 months • Secondary • Mortality • Surgery • Radiograph outcome • Length of hospital stay • SK group had increased serious adverse events (p=0.08)

28. Conclusion • No benefit of streptokinase over saline flushes • For any outcome measure • Not to be used routinely • Also metaanalysis (Tokuda. Chest 2006;129) • 5 trials with 575 patients • MIST II – DNAse v TPA v DNAs + TPA v Placebo

29. Bronchiectasis

30. Treatment of bronchiectasis Which one of these statements is (most) correct? • Oral steroids are beneficial for acute exacerbations? • Inhaled steroids are beneficial for stable bronchiectasis? • Prolonged antibiotics are superior to standard courses of antibiotics for patients with bronchiectasis? • Physiotherapy is recommended but has not been shown to be effective • Short-acting beta-agonists are effective in bronchiectasis

31. Steroids for bronchiectasis • Oral steroids for bronchiectasis • Cochrane review • No randomised trials • Benefit unknown • Inhaled steroids for bronchiectasis • Cochrane review • Three trials • Limited, if any, effect on any outcomes • May improve lung function (trend) and sputum volume • Benefit unclear

32. Antibiotics and bronchiectasis • Cochrane review • 6 trials, 302 patients • One study contributed 40% • Antibiotics for between 4 weeks and 1 year • Prolonged antibiotics • Improved response rates (OR 3.4) • No effect on exacerbations • Conclusions • Limited data. Small benefit from prolonged antibiotics

33. Mycobacterium avium complex (MAC) Which one of these statements is correct? • MAC is found in various sources including water, house dust, soil and animals? • ‘Hot tub lung’ is MAC infection that responds to antibiotic therapy • MAC lung disease rarely occurs in patients with pre-existing lung disease or immunosuppression? • In patients without pre-existing lung disease, MAC usually affects young men? • The presence of bronchiectasis and multiple small nodules are not predictive of MAC lung disease?

34. 2007 ATS/IDSA criteria for diagnosis • Clinical features • Radiographic • Fibrocavitary disease • CXR - cavitary opacities • Noncavitary disease • CXR – nodular opacities • HRCT Multifocal bronchiectasis with multiple small nodules • Bacteriologic • Sputa – two positive in one year • Bronch wash – one positive culture • Tissue – positive culture or granuloma & +ve sputum/wash

35. Multifocal bronchiectasis MAC infection Peripheral nodules

36. Which statement is correct about macrolide antibiotics? • They act by disrupting cell membranes of microorganisms • They have no activity against Pseudomonas aeruginosa • They have minimal anti-inflammatory effects on neutrophils and macrophages • They substantially reduce mortality in panbronchiolitis? • Low dose azithromycin taken for 6 months improves lung function in patients with cystic fibrosis but causes irreversible hearing loss

37. Macrolide antibiotics • Anti-infective, anti-inflammatory, immunomodulatory properties • Low dose azithromycin is effective in cystic fibrosis • Highly effective in panbronchiolitis

38. 20 yr Indian man with panbronchiolitis

39. Allergic bronchopulmonary aspergillosis Which statement is false? • ABPA occurs more commonly in patients with cystic fibrosis than in chronic asthmatics? • ABPA is unlikely if the total IgE level is less than 400 IU/mL • Skin prick testing is a useful screening test to identify patients with ABPA • Almost 100% of patients with an established aspergilloma have aspergillus precipitins • Proximal bronchiectasis is a prerequisite for diagnosis

40. ABPA • Key diagnostic features • Asthma* • Positive skin prick test to Aspergillus fumigatus* • Total IgE > 400 IU/mL (1000 ng/mL)* • Elevated specific IgE (and IgG) to Aspergillus* • Aspergillus precipitins (IgG) • Pulmonary infiltrates • Proximal bronchiectasis • Also eosinophilia, sputum culture

41. ABPA • Poorly controlled asthma • Eosinophilia – 1.1 • Total IgE - 3959 IU/ml • Precipitins – negative • Specific IgE – 3+ • Asp. skin prick – 7mm • HRCT – ‘central bronchi have irregular walls’ (2004) June 04

42. Which one of the following adverse effects does not occur with itraconazole treatment Itraconazole • Rise in ALT • Nausea • Peripheral neuropathy • Cholestatic jaundice • SIADH

43. Itraconazole and ABPA • Cochrane review • 2 studies only • Reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01) • More likely to have decline in serum IgE over 25% or more (OR 3.3) • number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03).

44. Aspergilloma Almost all pts have +ve aspergillus precipitins