A 45-year-old woman comes to the office due to frequent nighttime cough and wheezing over the past several months. Lately, she has also experienced similar episodes during the daytime. Medical history includes hypertension, hyperlipidemia, and obesity. Medications are amlodipine, lisinopril, and simvastatin. She has a 15-pack-year smoking history but quit 10 years ago. There is no personal or family history of lung disease. Blood pressure is 130/84 mm Hg, pulse is 72/min, and respirations are 16/min. Pulse oximetry shows 95% on room air. BMI is 31 kg/m². Jugular venous pressure is 3 cm H₂O above the sternal angle. The heart has a regular rate and rhythm with no murmurs. The lungs show good air movement with expiratory wheezes and no crackles. Chest x-ray is unremarkable. The results of pulmonary function testing are as follows: Which of the following is the primary pathogenesis of this patient's symptoms?

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Explanation: 11ec25c8_d101_6903_bc81_abd12a25d08d_MD0003_00 This former smoker has episodic dyspnea, wheezing, and cough. Pulmonary function testing shows reversible airflow obstruction: FEV₁/FVC ≤70% with positive bronchodilator response (≥12% increase in FEV₁ or FVC). The combination of her symptoms and spirometry is diagnostic of asthma. ₁ ₁ Although asthma is typically diagnosed in younger individuals, a significant minority are diagnosed later in life. Adult-onset asthma is characterized by a different immunophenotype with greater airway remodeling. Patients have a positive bronchodilator response, but FEV₁/FVC ratio may not fully normalize (eg, may not increase to >70%). ₁ Distinguishing asthma from chronic obstructive pulmonary disease (COPD) is a common clinical scenario, particularly in adult ever smokers. Both diseases may show airflow obstruction, but patients with COPD have no bronchodilator responsiveness; emphysematous COPD is associated with decreased DLCO due to protease-induced tissue destruction leading to loss of alveolar surface area (Choice E). asthma from chronic obstructive pulmonary disease Proper distinction guides the selection of initial inhaled therapy: The hallmark of asthma is leukocyte-induced bronchoconstriction. A combination of inhaled corticosteroid (targets the leukocytes) plus beta agonist (targets the bronchoconstriction) is recommended for asthma. The hallmark of COPD is goblet cell hyperplasia, mucus hypersecretion, and alveolar septal destruction. A long-acting muscarinic antagonist (targets airway hypersecretion) is recommended for COPD. (Choice A) Nocturnal cough and wheezing are also key symptoms of gastroesophageal reflux disease (GERD). GERD can exacerbate asthma due to constant aspiration of acid fumes into the lower airways. GERD can also cause laryngeal irritation, contributing to vocal cord dysfunction (VCD) that manifests as episodic dysphonia and inspiratory stridor. However, neither GERD by itself nor GERD-induced VCD would cause expiratory airflow obstruction. (Choice B) Pulmonary arterial hypertension (PAH) can cause dyspnea, chest tightness, and wheezing due to stretching of the pulmonary vessels and lung mechanoreceptors. It most frequently affects young adult women and often masquerades as asthma for many years prior to diagnosis. However, PAH is associated with a low DLCO value (decreased distal lung perfusion) and does not cause airflow obstruction. (Choice C) ACE inhibitors (eg, lisinopril) cause decreased bradykinin clearance; this is a common cause of dry cough, even among patients who have been taking ACE inhibitors chronically. However, these medications do not induce bronchoconstriction, wheezing, or obstruction on pulmonary function testing. Despite the increased bradykinin levels, ACE inhibitors are generally well tolerated in patients with asthma. Educational objective: Bronchodilator-responsive airflow obstruction (≥12% increase in FEV₁ or FVC) suggests asthma, regardless of age. Because late adult-onset asthma features greater airway remodeling, the FEV₁/FVC ratio may not fully normalize. ₁ ₁ References: Bronchodilator reversibility in COPD. (http://www.ncbi.nlm.nih.gov/pubmed/21972384) Adverse respiratory effect of acute ß-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials. (http://www.ncbi.nlm.nih.gov/pubmed/24202435)

A 45-Year-Old Woman Comes to the Office Due to Frequent