Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis

Abstract

Background: Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV(1)) are correlated with changes in patient-reported outcomes.

Methods: Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV(1). Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.

Results: With increasing positive ΔFEV(1), TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV(1) was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV(1) and outcomes.

Conclusions: These results suggest that larger improvements in FEV(1) are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.

Trial registration: ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286.

Figure 1

Outcome means in ΔFEV₁ categories versus category midpoint value. Plots show data with Loess smooth curves superimposed. ΔFEV₁, change from baseline in trough forced expiratory volume in 1 second; TDI, Transition Dyspnoea Index; ΔSGRQ, change from baseline in St George's Respiratory Questionnaire.

Figure 2

Outcomes versus ΔFEV₁: curves fitted from model-based analysis. SGRQ and TDI data is for Week 24/26. Exacerbations are reported counts normalised to 1 year. Rescue medication use is reported numbers of puffs normalised to 1 day. For plotting predicted curves, 'moderate' refers to baseline FEV₁ 1.595 l (third quartile of observed values) and GOLD 2 (moderate or less [19]); 'severe' refers to baseline FEV₁ 0.95 l (first quartile of observed values) and GOLD 3 (severe or greater [19]). For TDI, 'moderate' and 'severe' refer to BDI at quartiles 2 and 1, respectively. For ΔSGRQ, 'moderate' and 'severe' refer to baseline SGRQ at quartiles 31.3 and 58.13, respectively; ΔFEV₁, change from baseline in trough forced expiratory volume in 1 second; ΔSGRQ, change from baseline in St George's Respiratory Questionnaire; TDI, Transition Dyspnoea Index; GOLD, Global initiative for chronic Obstructive Lung Disease; BDI, Baseline Dyspnoea Index; ICS, inhaled corticosteroid.