Masqueraders of Asthma: Differential Diagnosis of Asthma in Adults George Su, MD SFGH/UCSF Division of Pulmonary and Critical Care San Francisco Asthma Task Force Networking Forum November 5, 2010

 “asthma”  “aazein”

Wheeze A continuous, coarse, whistling sound produced in the respiratory tract during breathing Some part of the respiratory tract must be narrowed or obstructed, or airflow velocity increased

Case 1 58 yo male, presents with worsening shortness of breath over the past 7 months. +Wheeze, is noted nearly daily, and is elicited reproducibly by cold weather and exposure to fumes and cats. +Moderately productive cough daily. Up to 2 packs of cigarettes a day over the past 40 years, current smoker. PMH: DM, HTN Works as a custodian at the local university.

Case 1 Spirometry FEV1 50% predicted DLco 55% predicted CXR with flat diaphragms +Cat dander aeroallergen Diagnosis?

Chronic bronchitis Emphysema Chronic bronchiolitis Obstructive Lung Diseases Chronic asthma/ Chronic bronchitis

Centrilobular parenchymal destruction WebPath, University of Utah

Asthma

Goblet cell hyperplasia Chronic Bronchitis Pseudostratified columnar epithelium Ciliary brush border injury

Human Bronchial Mucosa Jeffrey, 1998 “Flakes” of mucus Ciliated epithelium

Human Bronchial Mucosa Jeffrey, 1998 “Sheets” of mucus

Chronic bronchitis Jeffrey, 1998 Bacterial colonization of epithelial membranes Ciliary damage Epithelial slough

Normal alveoli

Emphysema WebPath, University of Utah Emphysema

Pulmonary function testing NormalSevere Obstruction Moderate Obstruction Bronchodilator reversibility, bronchoprovocation Diffusion capacity (DLco)

Bronchodilator (BD) Reversibility  FEV1 > 200 ml and >=12% pre-BD Albuterol 4 puffs of 90  g/puff  FEF25-75 should not be used (invariably increases with BDs)

Bronchoprovocation Methacholine Sxs consistent with asthma, but normal spirometry and no BD response Atypical sxs of bronchospasm (chest tightness, insomnia, cough-variant, etc.) Optimal diagnostic value when pretest probability 30-70% More useful in excluding diagnosis (negative predictive power is very good)

Methacholine Challenge Standard doubling dilutions (starting at 16 mg/ml) FEV1 measured after 30 and 90 seconds  FEV1 > 20%, calculate PC20 (provocative concentration)

Chest X-Ray Flattened diaphragms Large lung volumes

Emphysema

Inspiration Expiration Mosaic perfusion Thick airways

NeutrophilsEosinophils

Clinical Presentation Younger patients Non-smokers Reversible obstruction Triggers for airways hyperresponsiveness Atopy Older patients >40 yo Smokers Irreversible obstruction Progressive Occupational exposures Chronic bronchitis: Cough/secretions Most days 3 mo/year  2 successive years

Asthma COPD Wheeze, cough, dyspnea Hyperinflation  Smooth muscle, bronchospasm Nocturnal wheeze X X X X X X

Nocturnal asthma Exposure to dust mite, animal dander GERD Post nasal drip Decreased cortisol level Increased parasympathetic activity Increased level of histamine Increased sensitivity to histamine Early morning fall in circulating adrenaline Overnight changes in vagal tone

Asthma COPD Wheeze, cough, dyspnea Hyperinflation  Smooth muscle, bronchospasm Nocturnal wheeze  Bacterial colonization Bronchoprovocation Eosinophilic and CD4+ Neutrophilic and CD8+ Airflow limitation BD Reversibility Decreased DLco Atopy/triggers Tobacco Exercise bronchospasm X X X X X X XX X X X X X X X X X X

Asthma vs. COPD Tx Implications Fixed parenchymal: progressive worsening in COPD Tobacco cessation is critical Eosinophilic and CD4+-driven inflammation in asthma is more responsive to inhaled corticosteroids than neutrophilic CD8+-driven (COPD) Bacterial colonization (antibiotics?) Emphasis on ICS therapy in asthma Resting dynamic hyperinflation is more severe in COPD Emphasis on routine bronchodilator use in COPD

Clinical Presentation Overlap syndrome Overlap syndrome? Patients with characteristics of both?

Asthma/COPD “Overlap syndrome” Exhibits features of both conditions Incompletely reversible airflow obstruction +Increased variability of airflow (BD response, increased airways hyperresponsiveness) Dlco deficit Worse prognosis 1, higher utilization of resources These patients are excluded from clinical trials, so results are not generalizable to them 30% asthmatics are smokers 1. Shaya et al., 2008

Case 2 43 yo F with long standing history of “asthma” Wheeze and shortness of breath with exercise and stress Treated with maximum dose ICS Has received multiple prednisone courses Presents to you, Cushingoid Inspiratory wheeze