Objective: We conducted a targeted evidence update to support the US Preventive Services Task Force in updating its 2016 recommendation on Screening for Chronic Obstructive Pulmonary Disease (COPD). Our review addressed three key questions: 1) Does screening for COPD improve health-related quality of life or reduce morbidity or mortality?, 2) Does treatment of screen-detected or mild to moderate COPD improve health-related quality of life or reduce morbidity or mortality?, 3) What are the adverse effects of COPD treatments in this population?; and one contextual question: 1) Does identifying asymptomatic adults with COPD improve the delivery and uptake of targeted preventive services (e.g., smoking cessation, recommended immunizations, lung cancer screening)?
Data Sources: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and CINAHL from January 1, 2015, to January 22, 2021, to identify literature published since the previous recommendation. Because the previous review did not include non-pharmacologic interventions, we supplemented these searches by examining reference lists of relevant recent reviews to identify studies prior to 2015.
Study Selection: Two investigators independently reviewed abstracts and full-text articles against a set of a priori inclusion and quality criteria. Inclusion criteria for treatment benefits and harms specified persons with mild (defined as forced expiratory volume in 1 second [FEV1] ≥ 80 percent predicted) to moderate (FEV1 50-79 percent predicted) COPD or a mean population FEV1 ≥ 60 percent predicted.
Data Analysis: One investigator abstracted data into an evidence table and a second investigator checked these data. We provide a narrative synthesis of the newly identified evidence for each question; quantitative synthesis was not appropriate due to heterogeneity and few trials for any given intervention and outcome.
Results: We found no trials examining the effectiveness of screening or active case finding for COPD on health outcomes. We included 16 trials evaluating the treatment of mild to moderate, or minimally symptomatic, COPD: 3 trials (n=20,058) evaluated long acting beta agonists (LABA), long acting muscarinic antagonists (LAMA), and/or inhaled corticosteroids (ICS), and 13 trials (n=3,657) evaluated non-pharmacologic interventions (i.e., self-management interventions, exercise counseling interventions, supervised exercise and pulmonary rehabilitation interventions, and clinician education interventions). Two trials (SUMMIT and UPLIFT) found that LABA, LAMA, ICS, or LABA/ICS reduced exacerbations or clinically important deterioration in persons with fairly symptomatic moderate COPD. One trial (UPLIFT) found that LAMA, specifically tiotropium, also reduced exacerbations in a subgroup analysis (n=357) of persons with minimal symptoms (i.e., GOLD category A). Overall, there was no consistent benefit observed for any type of non-pharmacologic intervention across a range of patient outcomes. One of the two trials (n=114) evaluating the same exercise-focused web-based intervention in a VA population demonstrated a reduction in COPD exacerbations at 65 weeks. Other trials, not conducted in the US, evaluating more intensive self-management interventions, supervised exercise, and pulmonary rehabilitation interventions in persons with mild to moderate COPD, or minimal symptoms, did not demonstrate a reduction in exacerbations or other outcomes. Only three included trials reported on smoking cessation, vaccination, or lung cancer screening outcomes. These trials, combined with six additional comparative studies evaluating the incremental value of receipt of spirometry on smoking cessation, found no consistent improvement in smoking cessation. Only one trial evaluating a clinician training intervention to improve COPD care reported vaccination outcomes and demonstrated an improvement in uptake of influenza vaccination. None of the included treatment trials that reported adverse effects found significant harms. Two large observational studies in a screen-relevant population demonstrated an association of the initiation of LAMA or LABA with the risk of a serious cardiovascular event in treatment-naïve patients and an association of ICS use with the risk of developing diabetes.
Limitations: It is unclear how generalizable the observed treatment benefit, the reduction of exacerbations, is to a screen-detected population, as these findings were primarily in persons with fairly symptomatic moderate COPD. It is unclear if and how small sample sizes, usual care comparators in trials conducted outside the US, and/or poor adherence to the non-pharmacologic interventions contributed to the largely null findings of these trials. The small number of included participants and limited length of followup in the majority of included trials (or their relevant subgroup analyses) limits the ability to detect uncommon harms or longer-term harms. Harms of LABA, LAMA, and ICS demonstrated in the included observational trials should be interpreted in context of the larger body of literature on harms of inhaled therapies.
Conclusions: The findings of this targeted evidence update are generally consistent with the findings of the previous systematic review supporting the 2016 recommendation. To date, there are still no comparative studies on the effectiveness of screening or active case finding for COPD on patient health outcomes. The demonstrated benefits of pharmacologic treatment for COPD are still largely limited to persons with moderate airflow obstruction; and there was no consistent benefit observed for a range of non-pharmacologic interventions in mild to moderate COPD, or in minimally symptomatic persons with COPD.