Pulmonary Board Review

1. Pulmonary Board Review

3. Cough 31 year old woman with hypertension presents with cough for 6 weeks non-productive incessant and disrupting sleep. She has lifelong allergies and does endorse some increase rhinorhea recently. She was also started on ramipril for hypertension 3 months ago. What should you do?

4. Respiratory symptoms: cough Cough Chronic cough = duration > 3 weeks Most common etiologies Postnasal drip syndrome Asthma GERD Others: Chronic bronchitis Bronchiectasis ACE inhibitor Post-infectious Eosinophilic bronchitis Endobronchial lesion PNDS: sinusitis, allergic rhinitis, perennial nonallergic rhinitis, postinefectious rhinitis, vasomotor rhinitis, environmental irritants Rx: first generation antihistamine with decongestant +/- intranasal coritcosteroids, avoidance of allergens, cromolyn sodium Cough variant asthma: up to 57% with asthma; often with normal PFTs thus methacholine challenge. Treatment: inhaled corticosteroid for at least 6-8 weeks to see benefit GERDPNDS: sinusitis, allergic rhinitis, perennial nonallergic rhinitis, postinefectious rhinitis, vasomotor rhinitis, environmental irritants Rx: first generation antihistamine with decongestant +/- intranasal coritcosteroids, avoidance of allergens, cromolyn sodium Cough variant asthma: up to 57% with asthma; often with normal PFTs thus methacholine challenge. Treatment: inhaled corticosteroid for at least 6-8 weeks to see benefit GERD

5. Respiratory symptoms: dyspnea Chronic dyspnea: lasting > 1 month 2/3 of patients with one of the following COPD Asthma ILD Cardiomyopathy Others: neuromuscular disease, hyperventilation syndrome, GERD, pulmonary vascular disease Work-up: History, PFTs, chest Xray Cardiopulmonary exercise testing

6. PFTs: Spirometry Approach Is it a good test? First look to see how good the test is: reproducible, adequate exahalation time (at least 6 seconds), technician comments regarding patient effort and compliance Is there obstruction? FEV1/FVC < 70% indicates obstructive disease. Severity of obstruction as follows: I: Mild FEV1/FVC < 70%; FEV1 � 80% predicted With or without chronic symptoms (cough, sputum) II: Moderate FEV1/FVC < 70%; 50% � FEV1 < 80% predicted With or without chronic symptoms (cough, sputum, dyspnea) - III: Severe FEV1/FVC < 70%; 30% � FEV1 < 50% predicted With or without chronic symptoms (cough, sputum, dyspnea) IV: Very Severe FEV1/FVC < 70%; FEV1 < 30% predicted Is there restriction? FVC < 80% predicted indicated possible restrictive disease Is there airway reactivity? Response to bronchodilator testing: > 12% or > 200mL

8. PFTs: lung volumes Total lung capacity < 80% Restrictive lung disease Structural restriction of the thoracic cage Neuromuscular disease FRC < 80% Restrictive lung disease Structural restriction of the thoracic cage Obesity Residual volume < 80% Restrictive lung disease Structural restriction of the thoracic cage

9. PFTs: lung volumes TLC > 120% Hyperinflation seen with emphysema FRC > 120% Air trapping RV > 120% Air trapping Neuromuscular disease

10. PFTs: DLCO Decreased in: Diseases that obliterate the alveolar-capillary interface: Emphysema Fibrotic lung disease Pulmonary vascular diseases Diseases that increase the thickness of the interface: Interstitial lung diseases Interstitial edema/alveolar edema Anemia

11. PFTs: flow volume loops Useful in looking for central airway obstruction

12. Flow volume volumes

13. Chest CT scanning High resolution chest CT Routine chest CT scanning Spiral CT scanning

14. Asthma All of the following are true of asthma EXCEPT: Asthma death rates have increased Normal spirometry does not exclude asthma Uncontrolled asthma can lead to irreversible airway obstruction De-escalation of asthma therapy can be considered if there has been good asthma control for 1 month

15. Asthma categories of severity 2007 NAEPP report Intermittent Mild persistent Moderate persistent Severe persistent Treatment recommendations based upon severity

16. Intermittent asthma: Symptoms = 2 days per week Requirement for rescue albuterol = 2 days per week Nocturnal awakenings = 2 times per month No limitations in ADLs Normal PFTs RX: Intermittent albuterol

17. Mild persistent asthma Symptoms > 2 days per week or 3-4 nocturnal awakenings a month or Minor limitation in ADLs AND Normal PFTs RX: Step 2 low dose inhaled corticosteroids

18. Moderate persistent asthma Daily symptoms or > 1 nocturnal awakening per week or Moderate limitation in ADLs or Decreased FEV1 but > 60% Rx: step 3 in asthma treatment protocol Low dose inhaled corticosteroids + LABA Medium dose inhaled corticosteroid

19. Severe persistent symptoms Ongoing daily symptoms with significant exercise limitation and frequent nocturnal awakenings Rx: Step 4: High dose ICS + LABA Step 5: High dose ICS + LABA + systemic corticosteroid therapy AND consider omalizumab

20. Asthma syndromes Cough variant asthma Aspirin-induced asthma or triad asthma Exercise induced asthma Occupational asthma Allergic bronchopulmonary aspergillosis

21. 5 � 15% of all asthmatics Over 300 agents have been reported to cause OA Different prevalence for specific populations OA may develop in 2.5% for hospital workers exposed to latex 2-40% millers and bakers 20% exposed to acid anhydrides 5% exposed to toluene diisocyanate (TDI)

22. OA with a latency period: specific antigens identified, mostly HMW antigens although some LMW antigens as well IgE mediated: usually HMV antigen with a median latency period of ~ 5 years. Atopy is a risk factor Non-IgE mediated: usually LMW antigens with a median latency period of 2 years. Atopy is not a risk factor OA without a latency period: 1) nonspecific irritant-induced asthma or 2) reactive airways dysfunction syndrome

23. COPD 6th leading cause of death worldwide Underdiagnosed GOLD: stages of severity Based of spirometry Stage 0: normal spirometry but symptoms present Stage I: Mild ratio < 70% but FEV1 > 80% Stage II: Moderate IIa FEV1 50-80% IIb FEV1 30-50% Stage III: Severe

24. Fletcher and Peto found that over a lifetime, FEV1 falls gradually. However, clinically significant airflow obstruction may never develop in many smokers. In those susceptible to COPD, smoking can cause permanent obstructive changes to air passages. The researchers found that if a susceptible smoker quits smoking, rates of FEV1 loss will revert to normal, but lung function is reduced. It is possible to prevent severe or fatal COPD by screening lung function in middle-aged smokers, who could be urged to stop smoking. Main point: Decline in FEV1 is accelerated in COPD. Quitting smoking has a profound effect on the rate of decline of FEV1. Fletcher and Peto found that over a lifetime, FEV1 falls gradually. However, clinically significant airflow obstruction may never develop in many smokers. In those susceptible to COPD, smoking can cause permanent obstructive changes to air passages. The researchers found that if a susceptible smoker quits smoking, rates of FEV1 loss will revert to normal, but lung function is reduced. It is possible to prevent severe or fatal COPD by screening lung function in middle-aged smokers, who could be urged to stop smoking. Main point: Decline in FEV1 is accelerated in COPD. Quitting smoking has a profound effect on the rate of decline of FEV1.

25. COPD risk factors Tobacco: 15-20% 1ppd smokers develop COPD 25% 2ppf smokers develop COPD Genetic factors: Alpha1-antitrypsin deficiency Gender: Males more at risk than females Bronchial hyperresponsiveness Atopy and asthma Childhood illnesses Prematurity

26. COPD Treatment: Smoking cessation Oxygen therapy Medical therapy Pulmonary rehabilitation LVRS Transplantation

29. Pnalobular emphysema <1% COPD pts, sx begin pts < 40,Pnalobular emphysema <1% COPD pts, sx begin pts < 40,

30. Interstitial lung diseases orDiffuse parenchymal lung disease DPLD of known cause: Drugs Connective tissue disease Occupational lung disease Granulomatous disease Sarcoidosis Hypersensitivity pneumonitis Idiopathic interstitial pneumonia (IIP) Idiopathic pulmonary fibrosis (i.e., usual interstitial pneumonia) Non-specific interstitial pneumonia Desquamative interstitial pneumonia Respiratory bronchiolitis interstitial lung disease Cryptogenic organizing pneumonia Acute interstitial pneumonia (Hamman Rich syndrome) Lymphocytic interstitial pneumonia Misc Lymphangioleiomyomatosis Histiocyotsis X Pulmonary alveolar proteinosis

31. DPLD Chest Xray can be normal in 10-15% patients with diffuse lung disease 30% patients with bronchiectasis 60% patients with emphysema High resolution chest CT Sensitivity of 90% and specificity approaching 100% Can provide a confident diagnosis in ~50% cases; ~93% of these cases are ultimately proven correct Findings usually seen in DPLD Ground glass opacity Findings consistent with fibrosis Interlobular and intralobular septal thickening Honeycombing

32. HRCT : ground glass opacity Nonspecific term referring to presence of a hazy increase in lung opacity without obscuration of underlying vessels. Results from volume averaging of morphologic abnormalities too small to be clearly resolved by HRCT: minimal thickening of the intralobular septa, alveolar interstitium, presence of cells or fluid partially filling alveolar spaces Often indicative of ongoing, active, potentially treatable disease Crazy paving: ground glass superimposed on reticular pattern Initially described with PAP DDX: pulmonary edema, ARDS, pulmonary hemorrhage, AIP, PCP, viral infection, BOOP, eosinophilic pneumonia, BAC, etc

34. HRCT findings: linear and reticular opacities Intralobular interstitial thickening �fine reticular pattern� with lines of opacity separated by a few mmm Fine lacy or netlike appearance When seen in fibrosis, often seen in conjunction with dilated bronchioles (�bronchiolectasis�) DDX: IPF Chronic hypersensitivity pneumonitis Pneumoconioses ILD: NSIP, DIP Lymphangitis carcinomatosis Pulmonary edema Pulmonary hemorrhage Pneumonia Alveolar proteinosis

35. HRCT findings: linear and reticular opacities Intralobular interstitial thickening �fine reticular pattern� with lines of opacity separated by a few mmm Fine lacy or netlike appearance When seen in fibrosis, often seen in conjunction with dilated bronchioles (�bronchiolectasis�) DDX: IPF Chronic hypersensitivity pneumonitis Pneumoconioses ILD: NSIP, DIP Lymphangitis carcinomatosis Pulmonary edema Pulmonary hemorrhage Pneumonia Alveolar proteinosis

36. Figure 3-24

40. Honeycombing, DDX IPF and other causes of UIP: common finding typically basal and subpleural Asbestosis: common finding in advanced disease in the basal subpleural regions Chronic hypersensitivity pneumonitis: peripheral, patchy, diffuse with midlung predominance being common Sarcoidosis: upper lobe predominant NSIP and other ILDs: uncommon

41. DPLD General approach: Timeline Smoking history Occupational history Environmental and toxin exposures Drug history Extrapulmonary symptoms and manifestations Sarcoidosis CTD Testing PFTs HRCT CTD serologies Assess for exertional hypoxemia

42. Exercise limitation and exertional hypoxemia

43. IPF Histopath: UIP Fibroblastic foci Temporally hetergeneous Minimal inflammation Lots of collagen deposition Predominantly subpleural and basilar Similar findings in abestosis, rheumatoid lung disease Progressive disease with a median survival 2-3 years from diagnosis

44. NSIP Path: temporally uniform with interstital inflammation Rad: ground glass with areas of fibrosis Often also seen with CTD such as scleroderma

45. DIP/RBILD Path: Pigmented macrophages Peribronchiolar inflammation Rad: Patchy ground glass Intralobular septal thickening Mosaic pattern

46. DPLD: Hypersensitivity pneumonitis Disease of varying intensity and manifestation caused by the immunologic response to inhaled antigen, usually organic Hundreds of antigens have been described. Occupations with highest frequency of HP: Farmers �Farmer�s lung� Poultry workers �Poultry worker�s lung,� �Bird breeder�s lung,� �Bird fancier�s lung� Animal workers Grain processing �Grain handler�s lung� Textiles Lumber Also described with inhalation of contaminated water �Humidifier lung,� �Air conditioner lung,� �Hot tub lung�

47. DPLD: Hypersensitivity pneumonitis Disease of varying intensity and manifestation caused by the immunologic response to inhaled antigen, usually organic Hundreds of antigens have been described. Occupations with highest frequency of HP: Farmers �Farmer�s lung� Poultry workers �Poultry worker�s lung,� �Bird breeder�s lung,� �Bird fancier�s lung� Animal workers Grain processing �Grain handler�s lung� Textiles Lumber Also described with inhalation of contaminated water �Humidifier lung,� �Air conditioner lung,� �Hot tub lung�

48. Subacute HP

49. Chronic HP

50. HP: Treatment and prognosis Treatment Remove the inciting antigen from the environment or remove the patient from the environment Corticosteroids for severe cases Prognosis Acute and subacute disease have excellent outlooks Chronic can progress to end stage fibrosis

51. Non-granulomatous interstitial pneumonitis B. Poorly circumscribed collection of macrophages and multinucleate giant cells. Evolving granuloma. C. Later phase of granuloma formation. Lesion becoming more compact and circumscribed D. Fully mature non-necrotizing granuloma. Non-granulomatous interstitial pneumonitis B. Poorly circumscribed collection of macrophages and multinucleate giant cells. Evolving granuloma. C. Later phase of granuloma formation. Lesion becoming more compact and circumscribed D. Fully mature non-necrotizing granuloma.

52. Sarcoidosis: Four stages Lungs are affected in more than 90% of patients with dyspnea, np cough, and CP occurring in 1/3 to � of pts Radiographic stages Stage 4- fibrosis with hilar retraction, honeycomb changs, and large bullae and cysts Surprsingly, on exam lungs are usually clear Lungs are affected in more than 90% of patients with dyspnea, np cough, and CP occurring in 1/3 to � of pts Radiographic stages Stage 4- fibrosis with hilar retraction, honeycomb changs, and large bullae and cysts Surprsingly, on exam lungs are usually clear

53. Sarcoidosis in the lungs: Stage I Only the lymph nodes are enlarged Pulmonary function is intact 55-90% pts with Stage I sarcoidosis resolve spontaneously

54. Sarcoidosis: Stage II Lymph nodes enlarged Inflammation in the lung Lung function is impaired 40-70% pts resolve spontaneously

55. Sarcoidosis: Stage III Lymph nodes are not enlarged Only 10-20% resolve spontaneously

56. Sarcoidosis 90% with lung involvement 75% liver 20% skin 20% eyes 25% spleen 10% MSK 5% heart 5%

57. Pneumoconioses Silicosis CWP Asbestosis Talcosis Berylliosis

58. Silicosis: Exposure Mining Quarrying Tunneling Stone cutters Sandblasting Glass manufacturing Foundry work Enameling Quartz crystal manufacturing Rubber industry

59. Silicosis: clinical presentations Chronic silicosis Accelerated silicosis Progressive massive fibrosis Acute silicosis

60. Chronic silicosis Usually 10-30 years after initial exposure. Can become radiographically apparent even after removal of exposure Ranges from asymptomatic with normal PFTs to very very symptomatic with restrictive spirometry and low DLCO

61. Chronic silicosis: CXR findings Simple silicosis is the earliest finding of chronic silicosis Nodules usually 1-3 mm

62. Chronic silicosis: CXR findings As disease progresses, nodules increase in number and coalesce to form larger lesions

63. Chronic silicosis: CXR findings Eggshell calcification

64. Progressive massive fibrosis (PMF) Occurs in a minority of pts with chronic silicosis More likely to occur in pts with accelerated silicosis PFTs abnormalities: mixed obstructive/restriction, air trapping

65. PMF: CXR findings The nodules coalesce into conglomerate masses Calcified lymph nodes �eggshell calcification�

66. Coal worker�s pneumoconiosis AKA, black lung disease or anthrasilicosis Rate and quantity of dust accumulation most important factor in pathogenesis of CWP Clinical presentations similar to silicosis: Simple Chronic PMF

67. Asbestos-related lung diseases Pleural plaques Benign asbestos related pleural effusion Asbestosis Mesothelioma

68. Asbestos: Pleural plaques Usually first identified > 20 years after initial exposure Occur in 50% persons exposed to asbestos Parietal pleura adjacent to ribs, particularly along 6th-9th ribs and along diaphragm Calcifications on CXR in 20% and on chest CT in 50% Anterolateral or posterolat surface of parietal pleua Gray white in color Central tendon when diaphgram involvedAnterolateral or posterolat surface of parietal pleua Gray white in color Central tendon when diaphgram involved

69. Asbestos: Pleural plaques

70. Benign asbestos pleural effusion Most common pleuropulmonary manifestation within the first 20 years of exposure� but can present <1 post-exposure to >50 years after first exposure Typical presentation: acute pleuritic CP, fever, other systemic sx but can be insidious Can resolve spontaneously Pleural fluid analysis: exudative, serosanguinous, predominance of eosinophils, cytology with atypical macs, occasionally positive for RF Rounded atelectasis and/or diffuse pleural thickening may be sequelae

71. Rounded atelectasis

72. Asbestos: Mesothelioma Annual incidence 1:1,000,000/year Incidence peaking now b/c of inadequate control measures in 60s and 70s Any level of exposure may be a risk factor Usually presents 20-40 years after exposure

73. Asbestosis Presents > 30 years after initial exposure Requires long term, heavy exposure Criteria for diagnosis: History of asbestos exposure Dyspnea Basilar crackles in two or more locations Reduced lung volumes Radiographic abnormalities

74. Talc related diseases Talcosilicosis: caused talc mined with a high silica content Talcoasbestosis: crystalline talc contaminated by asbestos fibers Talcosis: inhalated of pure talc leading to bronchitis IV talc injection: from cutting heroin with talc ? formation of granulomas within the pulmonary vasculature ? pulmonary hypertension

75. Berylliosis Think aerospace, automotive, computer, ceramics, and nuclear industries Clinical manifestations: Acute disease due to direct irritant effects: rhinitis, pharyngitis, tracheobronchitis, chemical pneumonitis Chronic disease: Think sarcoidosis except we have an etiology. Dx: finding beryllium somewhere or lymphocyte transformation test.

76. Diagnostic evaluation of pleural effusion Thoracentesis Helpful in 75% cases Can be therapeutic as well Routine labs: LDH, total protein, glucose, pH, gram stain and culture, cytology, cell count and differential Additional labs that may be helpful Albumin, cholesterol, triglycerides, amylase, adenosine deaminase, AFB

77. Pleural fluid analysis: Light�s criteria Pleural fluid protein/serum protein > 0.5 Pleural fluid LDH / serum LDH > 0.6 Pleural fluid LDH > 2/3 upper limits of normal for serum LDH *Very accurate at identifying exudates (~98%) but less accurate with transudates

78. Pleural fluid analysis: Other pleural chemistries to help differentiate exudate from transudate Cholesterol Absolute pleural fluid cholesterol > 45- 60mg/dL Pleural fluid albumin gradient < 1.2 g/dL Bilirubin: pleural fluid bilirubin/serum bilirubin > 0.6 Cholinesterase: pleural fluid/serum > 0.23 Light�s criteria superior to any of the above in identifying exduates. Howver, less accurate in identifying transudates, Albumin graidnet can be utilized.Light�s criteria superior to any of the above in identifying exduates. Howver, less accurate in identifying transudates, Albumin graidnet can be utilized.

79. Pleural fluid analysis: Cell count and differential Neutrophils Present in transudates and exudates Eosinophils Significant numbers (>10%): air, blood most common etiologies. Other etiologies: Parapneumonic #1, malignancy, tuberculosis, BAPE, drugs (dantrolene, bromocriptine, nitrofurantoin), parasites, Churg-Strauss Lymphocytes: >50% lymphocytes: malignancy, tuberculosis or s/p CABG Mesothelial cells: Uncommon in tuberculous effusions. Major exception: AIDS

80. Pleural fluid analysis: Cell count and differential Neutrophils Present in transudates and exudates Eosinophils Significant numbers (>10%): air, blood most common etiologies. Other etiologies: Parapneumonic #1, malignancy, tuberculosis, BAPE, drugs (dantrolene, bromocriptine, nitrofurantoin), parasites, Churg-Strauss Lymphocytes: >50% lymphocytes: malignancy, tuberculosis or s/p CABG Mesothelial cells: Uncommon in tuberculous effusions. Major exception: AIDS

81. Pleural fluid analysis: cell count Red blood cells Blood-tinged fluid typically 5000 to 10000 RBC/mm3 Grossly bloody: 100000 RBC mm3 Trauma Malignancy Pulmonary embolism Infection Hemothorax: pleural fluid hct to blood hct > 50%

82. Pleural fluid analysis: Glucose Glucose < 60mg/dL suggestive of the following disorders Parapneumonic effusion: the lower the glucose, the more complicated the effusion Malignant effusion: 15-25% pts with malignant effusion have low pleural glucose levels. The lower the glucose, the higher the tumor burden Rheumatoid disease: majority of pts with rheumatoid effusion (78%) have pleural glucose < 30mg/dL Tuberculous effusion Rare: Paragonimiasis, hemothorax, Churg-Strauss, lupus pleuritis

83. Pleural fluid analysis: amylase Elevated levels suggestive of 1 of 3 dx Pancreatitis: often higher than serum levels **Pseudocyst communication: amylase > 1000U/L Esophageal rupture Malignant effusions: amylase level elevated in 10%

84. Pleural fluid analysis: LDH Serial LDHs can be helpful: Increasing levels: worsening process Decreasing levels: resolving process LDH isoenzymes: Mostly LDH-4 and LDH-5 If predominance LDH-1, the increase is due to blood

85. Pleural fluid analysis: pH pH < 7.2: Parapneuymonic effusion Esophageal rupture Rheumatoid pleuritis Tuberculous pleuritis Malignant pleural disease Hemothorax Systemic acidosis Paragonimiasis Lupus pleuritis Urinothorax Reasons for caution Often not measured correctly: must be measured using a blood gas machine Must be collected anaerobically in a heparinized syringe Lidocaine may falsely lower the pH

86. Pleural fluid analysis: other ADA level > 50 U/L in pts without empyema or rheumatoid arhtritic is virtually diagnostic of a tuberculous effsuion Interferon-gamma level > 3.7 U/mL also quite good at distinguishing tuberculous effusions RF: Pleural fluid titer > 1:320 strongly suggestive of rheumatoid effusion ANA: tends to correlate with serum ANA

87. Pleural fluid analysis: lipid studies Triglycerides > 110 mg/dL ? diagnostic of chylothorax Triglycerides 50-110mg/dL ? equivocal Triglycerides < 50: not a chylothorax

88. Pleural fluid analysis: lipid studies Triglycerides > 110 mg/dL ? diagnostic of chylothorax Triglycerides 50-110mg/dL ? equivocal Triglycerides < 50: not a chylothorax

89. Parapneumonic effusions and empyemas Pleural fluid characteristics associated with need for pleural fluid drainage Pus in the pleural space Positive gram stain or culture Glucose < 40 pH < 7.0 LDH > 3 x the ULN Loculated pleural fluid

90. ACCP recommedations Class I: Small < 10mm on decubitus film No thoracentesis needed Class II: Typical parapneumonic effusion More than 10mm on decubitus film ? needs sampling Pleural fluid characteristics: Glucose > 40 pH > 7.2 LDH < 3x ULN Treatment: antibiotics alone Class III: Borderline complicated pH 7.0 -7.2 or LDH > 3x ULN Normal glucose Negative pleural micro Treatment: Antibiotics plus serial thoracenteses Class IV through VII: Complicated pH < 7.0 or glucose < 40 or pleural fluid micro positive ? tube thoracostomy

91. Whew!