Masqueraders of Asthma Differential Diagnosis of Asthma in

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

asqma “asthma” aazein “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 FEV 1 50% predicted DLco 55% predicted CXR with flat diaphragms +Cat dander aeroallergen • Diagnosis?

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

Centrilobular parenchymal destruction Web. Path, University of Utah

Asthma

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

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

“Sheets” of mucus Human Bronchial Mucosa Jeffrey, 1998

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

Normal alveoli

Emphysema Web. Path, University of Utah

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

Bronchodilator (BD) Reversibility • D FEV 1 > 200 ml and >=12% pre-BD • Albuterol 4 puffs of 90 mg/puff • D FEF 25 -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) • FEV 1 measured after 30 and 90 seconds • D FEV 1 > 20%, calculate PC 20 (provocative concentration)

Chest X-Ray Large lung volumes Flattened diaphragms

Emphysema

Inspiration Thick airways Expiration Mosaic perfusion

Eosinophils Neutrophils

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

• • Wheeze, cough, dyspnea Hyperinflation Smooth muscle, bronchospasm Nocturnal wheeze Asthma COPD 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

• • • • Wheeze, cough, dyspnea Hyperinflation Smooth muscle, bronchospasm Nocturnal wheeze Bacterial colonization Bronchoprovocation Eosinophilic and CD 4+ Neutrophilic and CD 8+ Airflow limitation BD Reversibility Decreased DLco Atopy/triggers Tobacco Exercise bronchospasm Asthma COPD X X X X X

Asthma vs. COPD Tx Implications • Fixed parenchymal: progressive worsening in COPD • Tobacco cessation is critical • Eosinophilic and CD 4+-driven inflammation in asthma is more responsive to inhaled corticosteroids than neutrophilic CD 8+-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? 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