UMMC Internal Medicine Board Review Course Pulmonary Review

1. UMMC Internal Medicine Board Review CoursePulmonary Review Demondes Haynes, M.D., FCCP Associate Professor Fellowship Program Director Division of Pulmonary, Critical Care, and Sleep Medicine July 16, 2014

2. Disclosures • Speakers Bureau or Advisory Board Participant • Forest Pharmaceuticals, Actelion Pharmaceuticals, and Gilead Sciences

3. Asthma • Cardinal features • airway obstruction • inflammation • Hyperresponsiveness • Airway remodeling • Subepithelial fibrosis, increased smooth muscle mass, angiogenesis, hyperplasia of mucous glands and goblet cells

4. Classification of Asthma Severity

6. Asthma Pearls • Symptoms more than 2 days/week or more than 2 nights/month have persistent asthma • Inhaled corticosteroids with PRN bronchodilator is the cornerstone of therapy for persistent asthma • If not persistent, can be treated with PRN bronchodilator only

7. Occupational Asthma • Symptoms at work and improvement during times away from work • Nearly 50% have symptoms 3-4 years after cessation of exposure • RADS (reactive airways dysfunction syndrome) • high level of respiratory irritant exposure • symptoms (cough, chest tightness, wheezing, dyspnea) after exposure and may persist for years

8. Allergic Bronchopulmonary Aspergillosis (ABPA) • Manifests as severe persistent asthma • Clinical Manifestations • central bronchiectasis • pulmonary infiltrates (upper lobe predominance) • brown sputum/mucous plugs • elevated IgE levels (>1000 ng/mL) • positive skin test to Aspergillus • peripheral eosinophilia • Steroids treatment

9. Exercise-induced Asthma • Symptoms begin 10-15 minutes after exercise • Prevent with inhaled β-agonist 15 minutes before exercise (effective in more than 80% of patients) • Alternatives not as effective as β-agonists • Regular exercise may lessen the degree of exercise-induced asthma

10. Question 1 36 y/o woman with h/o anxiety, severe asthma (multiple intubations) is seen in ER with 1-day h/o severe SOB PE: ↑ RR, ↑ HR, global wheezing & stridor CXR: WNL She was intubated with resultant near-total resolution of abnormal breath sounds. Most likely diagnosis is

11. Question 1 • Acute severe asthma • ABPA • Anaphylaxis • Vocal cord dysfunction

12. Question 1 • Acute severe asthma • ABPA • Anaphylaxis • Vocal cord dysfunction

13. Question 2 Smoking cessation • Eliminates lung cancer risk • Does not reduce CAD risk • Reduces but not eliminate lung volume loss (FEV1) • Eliminates head & neck cancer risk

14. Question 2 Smoking cessation • Eliminates lung cancer risk • Does not reduce CAD risk • Reduces but not eliminate lung volume loss (FEV1) • Eliminates head & neck cancer risk

16. COPD • Cigarette smoking is most important risk factor & cessation is single most effective intervention to stop decline in lung function • Accelerated decline in lung function in smokers • O2 > 15 hrs/day increases survival, hemodynamics, exercise capacity, lung mechanics, and mental status

17. COPD Exacerbation Treatment 1. Albuterol/ipratropium 2. Glucocorticoids – 2 weeks 3. Antibiotics – none defined as better than others…except those at risk for Pseudomonas – FEV1<50%, ABX 4x in last year, recent hospitalization 4. NIPPV – decreases work of breathing, improves all outcomes 5. Endotracheal intubation 6. O2 to keep Sp02 90% • Change in dyspnea, change in cough, change in sputum volume/character • Requires only ONE of above • Usually caused by virus, inhalant/irritant

18. Alpha 1 Antitrypsin Deficiency • Screen early onset COPD (age < 50) and strong family history of lung and/or liver disease • Lower lobe emphysema predominance • Predominantly in whites of Northern European heritage

19. Active reduction of risk factor(s); influenza vaccination Addshort-acting bronchodilator (when needed) I: Mild II: Moderate III: Severe IV: Very Severe Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled corticosteroids if repeated exacerbations Addlong term oxygenif chronic respiratory failure. Considersurgical treatments

20. Question 3 The role of aggressive pulmonary rehabilitation in severe COPD is to • Improve survival • Improve exercise tolerance • Decrease oxygen requirement • Retard FEV1 decline

21. Question 3 The role of aggressive pulmonary rehabilitation in severe COPD is to • Improve survival • Improve exercise tolerance • Decrease oxygen requirement • Retard FEV1 decline

22. Question 4 75 y/o with h/o COPD, DM, HTN was brought to ER with cough, wheezes and weakness CXR: Emphysematous apices, WBC- 12,000; ABG:7.31/72/61 (on 3LPM) Apart from starting IV steroids and antibiotics, you also?

23. Question 4 • Intubate him to protect his airway • Start NIPPV with BIPAP at 12/5 cm • Decrease O2 to reduce PCO2 retention • Intubate him because of hypercapnic respiratory failure

24. Question 4 • Intubate him to protect his airway • Start NIPPV with BIPAP at 12/5 cm • Decrease O2 to reduce PCO2 retention • Intubate him because of hypercapnic respiratory failure

25. Bronchiectasis • Bronchial wall thickening and dilation • Causes – recurrent infection, obstruction, mucus dysfunction • Cystic fibrosis – poor sputum clearance, recurrent infections and inflammation • Post-Pneumonia • Atypical mycobacterium – MAC, etc. • Ciliary dyskinesia – poor sputum clearance (Assoc. w APKD, called Kartagener’s syndrome if situsinversus is present) • ABPA • Ig deficiencies • Collagen vascular dz – RA, systemic sclerosis Treatment involves bronchodilators, improved sputum clearance, abx.

26. Cystic Fibrosis • Autosomal recessive dz, abnormal cystic fibrosis transmembrane regulator protein – regulates Cl- secretion -Critical for proper fluid movement across resp, sweat duct, GI, and reproductive epithelia – low cl- secretion = low water secretion = thick secretions in all organs – sinus, lungs, pancreas, biliary, intestines, sweat Note: thicker mucus, less airway surface liquid, matted down cilia

27. Cystic Fibrosis CPT, high frequency oscillator vest, exercise, flutter device Mucolytics – Dornase, NAC, Hypertonic saline (7%) Bronchodilators Antibiotics (Inhaled and systemic) based on micro results Inhaled or systemic steroids Lung transplant • Suspect in young to middle age • Recurrent sinopulmonary infections • Pancreatic insufficiency or recurrent pancreatitis • Infertility (particularly men) • Diagnosis • Sweat chloride – High • Nasal potential difference • Gene mutation used when chloride is normal or borderline

28. CF Complications Pulmonary GI Cholecystitis – remember your CF pts have had cholecystectomy Pancreatic insufficiency – on pancreatic enzymes DIOS (distal intestinal obstruction syndrome) • Bronchiectasis • ABPA – Unresolving exacerbation, sputum changes to brown, hard plugs. • Massive hemoptysis • Pneumothorax • Atypical mycobacterium, Pseudomonas, MRSA in sputum • Cor pulmonale • Reactive airway dz

29. Interstitial Lung Disease • Clinical • dyspnea on exertion • nonproductive cough • abnormal CXR • HRCT most sensitive modality in evaluation • Surgical biopsy required in most patients

30. IPF • Most common of idiopathic interstitial pneumonias • Age 50 or greater • UIP on pathology • spatial and temporal heterogeneity (fibrosis and honeycomb change interspersed with normal lung) • “fibroblast foci” • Signs/symptoms • velcro-crackles • insidious onset (3 months or longer) • clubbing • lower lobe and peripheral predominance • Lung transplant improves survival and quality of life • PFT’s reveal restriction and gas exchange impairment

32. Nonspecific Interstitial Pneumonia • Younger age than IPF • Bilateral lower lobe opacities on CXR • HRCT – ground glass opacities; honeycombing uncommon • PFT’s reveal restriction and gas exchange impairment • Exclude CVD, exposures, etc. • Prognosis better than IPF • Treatment • steroids with or without cytotoxic agent

33. Cryptogenic Organizing Pneumonia (COP) • Formerly known as BOOP • 2/3 pts are nonsmokers • Presentation suggestive of LRTI • Crackles can be present but no clubbing • CXR reveals patchy consolidation (unilateral or bilateral) • PFT’s reveal restriction and gas exchange impairment • Treatment – steroids tapered over 6 months • Good prognosis

34. DIP/RBILD • Smokers • DIP – restrictive PFT’s and decreased DLCO with hypoxemia • RBILD – mixed obstructive/restrictive defect with decreased DLCO with hypoxemia • Smoking cessation is best treatment; may consider steroids

35. Lymphangioleiomyomatosis (LAM) • Proliferation of atypical smooth muscle cells • Primarily women of childbearing age • 3rd -4th decade of life • Pneumothorax • PFT’s – obstruction, normal or increased lung volumes, ↓DLCO • Diffuse thin-walled cysts • Chylous pleural effusions • Lung transplant • slowly progressive disease

37. Pulmonary Langerhans Cell Histiocytosis • Eosinophilic granuloma, histiocytosis x • Young (< 40) smokers • Obstructive (or mixed restrictive-obstructive) PFT’s with ↓DLCO • Combination of cysts and nodules in mid and upper lung zones • CD1a and S-100 protein • “Birbeck granules”

40. Sarcoidosis • Non-caseating granulomas and exclusion of specific cause • Bronchovascular and subpleural nodules • >90% have lung involvement • CD4 lymphocyte predominance on BAL • Endobronchial and transbronchial biopsy diagnostic in up to 90% of cases • 50-90% spontaneous remission in stage I disease

41. Hypersensitivity Pneumonitis • CD8+ lymphocyte predominance on BAL • HRCT more sensitive than CXR • Antigen avoidance with steroids for treatment • Pathology – cellular bronchiolitis, interstitial infiltrate, poorly formed non-necrotizing granulomas • Chronic HP may lead to pulmonary fibrosis with UIP pattern

42. Miscellaneous ILD from exposures Hypersensitivity pneumonitis – may be obstructive PFT’s – mold, birds, hay, hot tubs (occurs shortly after exposures) Byssinosis – raw cotton, hemp, flax Berryliosis (just like sarcoid) – beryllium – fluorescent lighting factory Cobalt – (Giants cell pneumonitis) drill bits

43. Drug Induced Lung Dz • MTX • Hypersensitivity interstitial pneumonitis • Most common cause of non-cytotoxic reaction • Gold • Reversible by stopping drug • Bleomycin, Amiodarone, Nitrofurantoin (fibrosis) • Dose related pulmonary dz • Bleo most common cause of cytotoxic pulmonary toxicity • Crack • Hypersensitivity, alveolar hemorrhage, bronchiolitis obliterans • ATRA syndrome– fevers, alveolarinfiltrates, hypotension

44. Asbestos Exposure Asbestosis ILD – requires long-term exposure to asbestos dust/fibers. Basilar predominance Restrictive PFT’s May have other findings related to asbestos exposure Treatment - supportive • Calcified pleural plaques • Benign asbestos pleural effusion (BAPE) • Exudative, eosinophilic • Increased risk of lung cancer • Increased risk of mesothelioma (less than other cancers)

45. Coal Workers Pneumoconiosis • Primarily in upper lobes • Caplan Syndrome • When associated with seropositive RA

46. Silicosis • Exposures • Mining, glass making, ceramics, sand blasting, foundry work • Primarily in upper lobes • Increases susceptibility to TB – check PPD in new silicosis • Progressive massive fibrosis – rare

47. Pleural Effusions • Light’s criteria • Protein ratio > 0.5 • LDH ratio > 0.6 • LDH > 2/3 ULN • Modified Light’s • Protein >2.9 • Cholesterol >45 • LDH >60% Upper Limit Normal • Serum-Pleural albumin <1.2gm Serum-Pleural Albumin gradient <1.2 on diuresis is transudative (pseudoexudate)

48. Pleural Effusion • Transudates • CHF, cirrhosis, nephrotic syndrome • Exudates • infection, inflammation, malignancy • Bloody pleural effusion with associated with pulmonary embolism not a contraindication to anticoagulant therapy

49. Malignant Pleural Effusions • Exudative • Lymphocyte predominant • Cytology • initial negative, then repeat tap with cytology • pleural biopsy (VATS) increases yield to >66% • Recurrent malignant effusions • pleurodesis • long-term indwelling catheter

50. Parapneumonic Effusion • Exudative, neutrophil predominant, complicates bacterial pneumonia • TPA-Dnase for nonimproving • Indications for chest tube drainage • loculations on CT • PF pH <7.0 (or 7.2) • positive PF gram stain • pus in pleural space • Surgical intervention • persistent sepsis or loculations despite drainage • TPA-Dnase