Respiratory Exacerbations and Lung Function Decline in People with Smoking History and Normal Spirometry.

Rationale: The impact of respiratory exacerbation on chronic obstructive pulmonary disease (COPD) is well established. The effects of respiratory exacerbations in people with cigarette smoking but normal spirometry are unknown.
Objective: To assess the association of respiratory exacerbations with lung function decline and mortality in people with normal spirometry and current or former cigarette smoking history.
Methods: We analyzed data from COPDGene participants with ≥10 pack-years cigarette smoking and normal spirometry at enrollment (Visit 1) defined as post-bronchodilator forced expiratory volume in 1 second (FEV ₁ )/forced vital capacity (FVC) ≥lower limit of normal (LLN) and FEV ₁ ≥LLN. We examined whether respiratory exacerbations occurring between Visits 1 and the 5-year follow-up visit (Visit 2) were associated with FEV ₁ decline, and all-cause mortality.
Measurements and Main Results: Among 2,939 participants with cigarette smoking history and normal lung function at Visit 1, each additional exacerbation between visit 1 and 2 was associated with a 2.96 ml/year FEV ₁ decline (95%CI 1.81 to 4.12; P<0.001) at Visit 2. Experiencing ≥1 severe exacerbation between Visits 1 and 2 was associated with 14.6 ml/year FEV ₁ decline relative to those with no severe exacerbations (95% CI 8.56 to 20.6; P<0.001). Individuals with ≥1 severe exacerbation between Visits 1 and 2 had increased mortality compared to those with no severe exacerbations (17.1% vs. 9.8%; adjusted hazard ratio 1.97;95% CI 1.40 to 2.77; P<0.001).
Conclusions: Respiratory exacerbations in people with cigarette smoking but normal spirometry were associated lung function decline. Experiencing a severe respiratory exacerbation was associated with increased mortality.