Study design, patients and definitions

This prospective, single-center, observational study (ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03363698","term_id":"NCT03363698"}}NCT03363698) was performed in the Department of Internal Medicine, Pulmonary Diseases and Allergy of the Medical University of Warsaw between 2016 and 2020 and included non-smoking adults with CC suspected to have CVA. The study protocol was approved by the Institutional Review Board (KB/222/2016) and all patients signed informed consent.

Inclusion criteria were as follows: (1) age 18–85 years, (2) CC (lasting > 8 weeks), (3) no history of wheezing or dyspnea, (4) normal spirometry, (5) BHR in methacholine challenge [methacholine concentration causing 20% fall in FEV₁ (PC₂₀) below 16 mg/mL]. Exclusion criteria included: (1) acute respiratory tract infection within the previous 6 weeks, (2) treatment with inhaled corticosteroids (ICS) or long-acting β₂-agonists (LABA) or leukotriene receptor antagonist (LTRA) or oral corticosteroids (OCS) or proton pump inhibitor (PPI) or antihistamine or intranasal corticosteroids within 4 weeks before enrollment, (3) abnormal chest radiograph, (4) active (within the last 12 months) smoking.

Upper airway cough syndrome (UACS) was defined as CC in a patient with chronic rhinitis or rhinosinusitis, diagnosed according to the respective guidelines [6–8]. Gastroesophageal reflux (GER) was diagnosed in patients who reported symptoms of GER or had a history of esophagitis revealed in upper gastrointestinal endoscopy or elevated number (> 73/24 h) of reflux episodes registered in 24-h pH-impedance monitoring [9].