Presence of variable extrathoracic airflow limitation in patients with a negative methacholine challenge test

Determine whether variable extrathoracic airflow limitation (VEAL) is observed in patients with negative methacholine challenge tests (MCT).

Electronic medical records of patients undergoing MCT at Jesse Brown VA Medical Center between January 2017 and December 2019 were reviewed. Only patients with negative MCT were selected. Pertinent demographic, clinical, and pulmonary function tests (PFT) and MCT data were abstracted from each record. Spirometric flow-volume loops recorded during each test were inspected by one co-author to determine the first inhaled methacholine concentration at which FEF₅₀/FIF₅₀ was either > 1 or further increased if baseline FEF₅₀/FIF₅₀ after nebulized saline (vehicle) already exceeded 1. Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant.

One hundred and twenty-seven consecutive patients with normal baseline PFT and negative MCT were identified. Thirteen patients (10.2%) had negative MCT and FEF₅₀/FIF₅₀ > 1 after testing. They were predominately obese (BMI, 31.3 ± 6.6), non-smoking (10), White (8) males (9) aged 51.3 ± 14.1 years (mean ± SD) referred for symptoms suggestive of asthma (n = 7) or for chronic cough (n = 6). Five had obstructive sleep apnea, three gastroesophageal reflux disease, and two chronic rhinosinusitis. FEF₅₀/FIF₅₀ increased significantly from 0.72 ± 0.21 after nebulized saline (vehicle) to 1.21 ± 0.13 after inhaled methacholine (p < 0.001). Median inhaled methacholine concentration eliciting these responses was 1.0 mg/mL (range, 0.25-16 mg/mL).

VEAL is observed in a subset of patients with a negative MCT. This phenomenon should be recognized and reported to the referring healthcare providers and its clinical significance addressed as indicated.