American Journal of Respiratory and Critical Care Medicine

In 2020, chronic obstructive pulmonary disease (COPD) was the sixth leading cause of death in the United States (1). Although the majority of acute exacerbations of COPD are triggered by bacterial or viral respiratory infection, eosinophilic inflammation or pauci-inflammatory biomarker patterns of exacerbation are also common (2, 3). Although the inflammatory effects of short-term exposure to outdoor air pollution have long been known to be a risk to patients with obstructive lung disease (4, 5) or even indirectly by increasing susceptibility to respiratory infection (6), studies have also demonstrated associations with indoor air pollution (79). However, uncertainty in the specific etiology of many COPD exacerbations makes it increasingly important to minimize irritant exposures in the indoor environment. Given that patients with COPD are also at increased risk for acute cardiovascular morbidity and mortality, minimizing cardiovascular responses to such exposures is also critical.

In 1996, two international cardiology societies identified heart rate variability (HRV) as one of the most promising biomarkers of autonomic cardiac activity (10). Although HRV is a measurement that has been effectively applied in air pollution research by cardiopulmonary teams subsequently (11), it has not yet become a part of routine clinical care. HRV is a measure of the variation in time between heartbeats and serves as an indirect marker of autonomic nervous system function. Generally, but not always, higher HRV is desirable because as the variability decreases, the risk of adverse cardiac events, ventricular arrhythmias, and even sudden death increases.

In this issue of the Journal, Raju and colleagues (pp. 721–730) report that in the homes of patients with COPD who formerly smoked and participated in a randomized controlled trial of indoor, residential air cleaning, each twofold increase in indoor fine particulate matter (PM2.5) (<2.5 μm) concentration, presumably over the previous week, was associated with decreases in several measures of HRV, including standard deviation of normal-to-normal (SDNN) intervals (−3%), root mean square of differences between successive normal-to-normal intervals (RMSSD) (−4.6%), high-frequency power (−6.2%), and low-frequency power (−7.1%) (12). Although only among a small subset of patients, even greater reductions in RMSSD and high-frequency power were associated with increased ultrafine particle concentrations (<0.1 μm) and obese individuals. Furthermore, among study participants randomized to receive 6 months of indoor air cleaning in the home, the investigators observed large 25.2–31.5% increases in RMSSD, high-frequency power, and low-frequency power, and a smaller 2.7% increase in SDNN (12), demonstrating a potential cardiovascular benefit to an indoor air-cleaning intervention in the homes of patients with COPD who used to smoke.

SDNN and RMSSD intervals in msec are time-domain variables and two of the most useful parameters for calculating the variation in heart rate (13). High- and low-frequency power are measured in msec2 and are frequency-domain variables also commonly used to measure HRV. We previously reported that higher exposures to ultrafine particles (UFP) (<0.1 μm) and PM2.5 in healthy older subjects across several studies were associated with lower SDNN during the subsequent 2–5 hours and that higher exposures to PM2.5 were associated with lower RMSSD (14). Thus, even short-term PM2.5 and UFP exposures may adversely affect HRV in patients with COPD.

In addition to the large HRV improvement after 6 months of residential air cleaning and decreased HRV markers associated with increased PM2.5 and UFP among patients with COPD who used to smoke, the study is noteworthy for several other reasons. First, the study reported larger improvements in HRV measures among those with greater air-cleaning protocol adherence, thus demonstrating a pseudo dose–response relationship between adherence and the size of the HRV improvement associated with air cleaning. Second, the study found UFP, which may enter the systemic circulation directly, were associated with even larger reductions in these HRV measures. This suggests patients with COPD may benefit from reduced exposure to UFP sources in the home (e.g., frying and gas stoves for cooking).

However, this study also raises several issues to consider about the use of household air cleaning in patients with chronic lung disease who are in danger of both respiratory and cardiovascular morbidity and mortality. One unaddressed question is the durability and duration of any beneficial effect of indoor air cleaning. Therapies for COPD range from the rapidly dissipating inhaler treatment (h to d) to more durable effects of pulmonary rehabilitation (up to 12 mo) (15). Given the rapidity with which changes in temperature, humidity, and/or air quality can lead to an acute COPD exacerbation (i.e., within a few h and d), it is possible that air-cleaning interventions may have short durations of HRV benefit if stopped and air quality returns to degrees observed before filtration.

Second, on the basis of the study finding of large improvements in HRV after 6 months of residential indoor air cleaning, should air cleaning be a recommended part of a treatment strategy to minimize cardiorespiratory events and costly healthcare encounters in patients with COPD who used to smoke? Third, would we see similar HRV improvements in patients with obstructive lung disease (e.g., adults and children with asthma) and/or patients with COPD who are nonsmokers, active smokers, or who have secondhand smoke exposure?

Fourth, HRV is but one of many mechanisms thought to underlie acute cardiovascular responses to short-term air pollution exposure. Raju and colleagues suggest that further work in this study will examine whether similar post–air-cleaning associations and improvements are observed with biomarkers of inflammation, endothelial dysfunction, platelet activation and aggregation, and oxidative stress (12). Improvements in these biomarkers would suggest an even greater health benefit than improving HRV alone. Furthermore, if air cleaning were to be done in the homes of children with obstructive pulmonary disease, improvements would suggest the possibility of reducing the risk of children developing cardiopulmonary disease in adulthood.

Fifth, the efficacy of the authors’ portable air cleaner approach is notable in that improved ventilation coupled with filtration, though more labor intensive than portable air cleaners with just filtration, is typically considered the cornerstone to indoor air quality improvement. If particle filtration with charcoal filters can mitigate both particulate and gaseous pollutants to a similar degree as filtration and ventilation, improvement in indoor air quality would be easier to implement on a population scale.

Last, patients with COPD may benefit from discussions with their pulmonologist about air cleaning as part of their COPD management plan, including its feasibility, financial costs, types of air cleaners, duration, and ultimately the likelihood of benefit versus unintended harms. For example, as discussed by Britigan and colleagues, ionization in residential air cleaners (used as an adjunct to filtration) has been associated with indoor ozone formation (16), a known acute lung irritant associated with acute and chronic respiratory morbidity and mortality (11).

In summary, adding the potential cardiovascular benefit of indoor air cleaning to the known pulmonary benefit suggests it may be a practice-changing intervention for individuals with obstructive lung disease. The duration and type of indoor air cleaning, the ideal patient population, and the durability of the effect will all need to be determined before this promising intervention can be evaluated as a staple of COPD care.

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12. Raju S, Woo H, Koehler K, Fawzy A, Liu C, Putcha N, et al. Indoor air pollution and impaired cardiac autonomic function in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2023;207:721730.
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Supported by National Institute of Environmental Health Sciences Grant #1K23ES032459-01.

Originally Published in Press as DOI: 10.1164/rccm.202211-2138ED on December 5, 2022

Author disclosures are available with the text of this article at www.atsjournals.org.

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