Spirometric predictors of lung function decline and mortality in early chronic obstructive pulmonary disease

Abstract

Rationale: The course of lung function decline for smokers with early airflow obstruction remains undefined. It is also unclear which early spirometric characteristics identify individuals at risk for rapid decline and increased mortality.

Objectives: To determine the association between spirometric measures and 5-year decline in FEV(1) and 12-year mortality.

Methods: We analyzed longitudinal data from the Lung Health Study, a clinical trial of intensive smoking cessation intervention with or without bronchodilator therapy in 5,887 smokers with mild to moderate airflow obstruction. Participants were stratified into bins of baseline FEV(1) to FVC ratio, using bins of 5%, and separately into bins of Z-score (difference between actual and predicted FEV(1)/FVC, normalized to SD of predicted FEV(1)/FVC). Associations between spirometric measures and FEV(1) decline and mortality were determined after adjusting for baseline characteristics and time-varying smoking status.

Measurements and main results: The cohort was approximately two-thirds male, predominantly of white race (96%), and with mean age of 49 ± 7 years. In general, individuals with lower lung function by any metric had more rapid adjusted FEV(1) decline. A threshold for differential decline was present at FEV(1)/FVC less than 0.65 (P < 0.001) and Z-score less than -2 (2.3 percentile) (P < 0.001). At year 12, 575 (7.2%) of the cohort had died. Lower thresholds of each spirometric metric were associated with increasing adjusted hazard of death.

Conclusions: Smokers at risk or with mild to moderate chronic obstructive pulmonary disease have accelerated lung function decline. Individuals with lower baseline FEV(1)/FVC have more rapid decline and worse mortality.

Figure 1.

Adjusted mean FEV₁ slope stratified by bins of baseline FEV₁/FVC ratio. Model adjusted for randomization group, race, sex, sex–time interaction, age, height, body mass index, average number of cigarettes smoked per day over the previous year at each annual visit, subject’s smoking status in each of the 2 prior years (defined as smoker or nonsmoker), and smoking status–time interaction. Error bars represent 95% confidence intervals.

Figure 2.

Adjusted mean FEV₁ slope stratified by bins of baseline FEV₁/FVC Z-score. The Z-score represents the difference between the actual FEV₁/FVC and the predicted FEV₁/FVC, normalized to the SD of the predicted FEV₁/FVC. Model adjusted for randomization group, race, sex, sex–time interaction, age, height, body mass index, average number of cigarettes smoked per day over the previous year at each annual visit, subject’s smoking status in each of the 2 prior years (defined as smoker or nonsmoker), and smoking status–time interaction. Error bars represent 95% confidence intervals.

Figure 3.

Adjusted mean FEV₁ slope stratified by bins of baseline post-bronchodilator FEV₁% predicted. Model adjusted for randomization group, race, sex, sex–time interaction, age, height, body mass index, average number of cigarettes smoked per day over the previous year at each annual visit, subject’s smoking status in each of the 2 prior years (defined as smoker or nonsmoker), and smoking status–time interaction. Error bars represent 95% confidence intervals.

Figure 4.

Adjusted hazard ratio of death comparing different thresholds of baseline spirometric predictors. Point estimate and 95% error bars represent the hazard ratio comparing spirometric indices above the threshold to below the threshold, adjusted for baseline age, race, sex, and smoking status at last visit.