Dependence of bronchoconstrictor and bronchodilator responses on thoracic gas compression volume

Background and objective During forced expiration, alveolar pressure (PALV) increases and intrathoracic gas is compressed. Thus, 1-s forced expiratory volume measured by spirometry (FEV1-sp) is smaller than 1-s forced expiratory volume measured by plethysmography (FEV1-pl). Thoracic gas compression volume (TGCV) depends on the amount of gas within the lung when expiratory flow limitation occurs in the airways. We therefore tested the hypothesis that bronchoconstrictor and bronchodilator responses using FEV1-sp are biased by height and gender, which are major determinants of lung volume. Methods We studied 54 asthmatics during methacholine challenge and 55 subjects with airway obstruction (FEV1-sp increase >200 mL and >12% after salbutamol) measuring at the same time FEV1-sp or FEV1-pl. Results During methacholine challenge, TGCV increased more in males than females, correlated with PALV, total lung capacity (TLC) and height, and the provocative dose was lower using FEV1-sp than FEV1-pl. With salbutamol, FEV1-pl increased <200 mL and <12% in 28 subjects, predominantly tall males, with larger TLC, TGCV and PALV. Conclusions Bronchoconstrictor and bronchodilator responses are overestimated by standard spirometry in subjects with larger lungs because of TGCV.