BACKGROUND: The effects of long-term cigarette smoke exposure on pulmonary physiology and how those effects lead to reduced exercise capacity are not well established.

METHODS: We retrospectively analyzed the spirometry, single-breath gas transfer (DLCO), peripheral muscle strength, and maximum exercise capacity data in patients referred to McMaster University Medical Centre for cardiopulmonary exercise testing between 2000 and 2012.

RESULTS: 29,441 subjects underwent CPET and had a recorded smoking history [58% male, mean age 51.1 years (S.D.±19.6), BMI 27.4 kg/m2(±5.8)]. 7081 (24%) were current or former smokers and were divided into 4 categories by packs years (mean ±S.D.): <10 (5.8±3.3), 10-20 (17.1±2.9), 20-30 (27.1±2.8), 30-40 (37.3±2.8), and >40 (53.9±12.8). Patients with greater cigarette smoke exposure had lower expiratory flow rates (FEV1, FEF50, FEF75, PEFR), DLCO, and maximum power output (MPO) during exercise. There was no association between smoke exposure and muscle strength. Modeling MPO (kpm/min) output as a function of demographic and physiologic variables showed that the data are well explained by muscle strength (kg), FEV1 (L), and DLCO (mmHg/min/mL) in similar magnitude (MPO = 42.7*Quads0.34*FEV10.34 * DLCO0.43; r = 0.84).

CONCLUSIONS: Long-term cigarette smoke exposure is associated with small airway narrowing and impaired diffusion capacity but not with peripheral muscle weakness. The effects of smoking, age, and gender on maximum power output are mediated by reductions in FEV1, muscle strength and DLCO. Exercise capacity in smokers may benefit from therapies targeting all 3 variables.