Principal stratification analysis to determine health benefit of indoor air pollution reduction in a randomized environmental intervention in COPD: Results from the CLEAN AIR study

Background: Indoor air quality represents a modifiable exposure to Chronic Obstructive Pulmonary Disease (COPD) health. In a randomized controlled trial (CLEAN AIR study), air cleaner assignment had causal effect in improving COPD outcomes. It is unclear, however, what is the treatment effect among those for whom intervention reduced air pollution and whether it was reduction in fine particulate matter (PM2.5) or nitrogen dioxide (NO2) that contributed to such improvement. Because pollution is a posttreatment variable, treatment effect cannot be assessed while control-ling for pollution using intention-to-treat (ITT) analysis. Objective: Using principal stratification method, we assess indoor pollutants as the intermediate variable, and deter-mine the causal effect of reducing indoor air pollution on COPD health.Method: In randomized controlled trial, former smokers with COPD received either active or placebo HEPA air cleaners and were followed for 6 months. Saint George's Respiratory Questionnaire (SGRQ) was the primary outcome and secondary measures included SGRQ subscales, COPD assessment test (CAT), dyspnea (mMRC), and breathlessness, cough, and sputum scale (BCSS). Indoor PM2.5 and NO2 were measured. Principal stratification analysis was performed to assess the treatment effect while controlling for pollution reduction.Results: Among those showing at least 40 % PM2.5 reduction through air cleaners, the intervention showed improve-ment in respiratory symptoms for the active (vs. placebo), and the size of treatment effect shown for this subgroup was larger than that for the overall sample. In this subgroup, those with active air cleaners (vs. placebo) showed