In 2014, PM less than 10 mm in diameter and less than 2.5 mm in diameter accounted for at least 3 million deaths and 85 disability-adjusted life years, primarily because of impacts on chronic cardiovascular and pulmonary conditions.Recently, air pollution in the United States has begun increasing for the first time since 2016 .Ambient pollution is a risk factor not only for the development or worsening of chronic illnesses but also for acute illness. For example, a case control study of older adults in Canada found that long-term exposure to PM 2.5 and NO2 was independently associated with an increased risk of hospitalization for community-acquired pneumonia.Short-term exposure to increasing levels of PM 2.5 was also shown to increase the risk of hospital admission for cardiac and respiratory disease in the United States.Several recent studies have demonstrated that exposure to even low to moderate levels of ambient pollutants increases the risk of developing ARDS. In a prospectively enrolled cohort of patients with ARDS in the Southeastern United States, long-term ozone exposure was associated with the development of ARDS in a dose-dependent manner.This association was most pronounced among patients with trauma as their primary risk factor. Although the association between ozone exposure and the development of ARDS remained significant when controlling for potential confounders including smoking status, there was a statistically significant interaction between ozone exposure and smoking. When patients were stratified by smoking status, ozone exposure remained significantly associated with ARDS only among smokers. The investigators concluded that cigarette smoking likely potentiates the risk from ozone exposure.A subsequent study of patients from a prospectively enrolled cohort in Philadelphia further investigated the relationship between exposure to pollutants and ARDS development among patients with trauma.This study analyzed exposure to low to moderate levels of ozone, NO2, SO2, PM 2.5, and carbon monoxide . Long-term exposure to each of the pollutants was independently associated with an increased odds of developing ARDS. Furthermore,growing tables even 6 weeks of exposure to NO2, SO2, and PM 2.5 increased the odds of developing ARDS.
Differences between the findings of the 2 studies might be accounted for by regional variation in levels of pollutants and air quality monitoring and by the shared risk factor of the population in the second study. Together these studies suggest that exposure to ambient pollution even at low to moderate levels for time periods as short as 6 weeks increases the risk of ARDS. Large epidemiologic studies have also found associations between exposure to ambient pollution and an increased risk of developing ARDS. An observational study of more than 1 million hospitalizations between the years 2000 and 2012 among Medicare beneficiaries who developed ARDS used advanced modeling drawing on multiple data sources to predict average annual levels of ambient pollution across more than 30,000 zip codes.The investigators found that the rate of ARDS hospitalizations increased with increasing levels of both PM 2.5 and ozone. These findings were consistent even in regions where pollutant levels were within national air quality standards. The effect of PM 2.5 was most pronounced among patients whose primary risk factor was sepsis. Ozone exposure had the greatest effect among patients with pneumonia or trauma as their primary risk factor. Although fully accounting for confounding factors in observational studies can be difficult, results were similar in a propensity matched analysis that included variables such as demographic variations and percent of ever-smokers.The results of this large study demonstrate that the association between ambient pollution and ARDS is present outside of the trauma population in patients who are older with comorbid conditions. Another retrospective cohort study of more than 90,000 patients found that increases in average annual PM 2.5 and ozone concentrations independently increased the odds of death from ARDS, suggesting that ambient pollution impacts not only ARDS incidence but also its outcomes.High levels of ambient pollution have also been associated with incidence and adverse outcomes in the coronavirus disease 2019 pandemic, although further studies in this area are needed.
The preponderance of the literature examining the connection between ARDS and ambient pollution has revealed an association between long-term rather than short term exposure to pollutants and ARDS incidence and outcomes. For example, the investigators who found a link between long-term ozone exposure and ARDS did not find the same association for 3-day exposure to environmental pollutants.However, one study from Guangzhou, China, demonstrated an association between short-term PM exposure and incident ARDS.This association may be related to the exceptionally poor air quality of the region in contrast to the other studies, which focused on settings with low to moderate levels of pollutants. There is some evidence, however, that short-term exposure to low levels of ambient pollution is associated with adverse pulmonary outcomes in critically ill patients. A study from Antwerp, Belgium—an area with historically low levels of ambient pollution—found that short-term pollution exposure was associated with longer mechanical ventilation.This study included a broad range of critically ill patients, some of whom did not have ARDS, but does suggest that a deleterious effect from short-term pollution exposure is not limited to areas with exceptionally poor air quality. Various underlying biological mechanisms may explain the basis for the relationship between environmental pollution and ARDS. A meta-analysis of exposure studies in healthy volunteers found that ozone increases the number of bronchoalveolar lavage neutrophils,which are implicated in ARDS pathogenesis.Ozone exposure also increased total protein levels in this analysis,reflecting loss of alveolar epithelial/endothelial barrier integrity.Many components of air pollution exert deleterious effects on pulmonary surfactant.Urban air particles directly stimulate an inflammatory response by pulmonary macrophages in vitro.PM has also been shown to increase markers of apoptosis, oxidative stress, and inflammation and to directly cause lung injury in mouse models.In humans, increased PM 2.5 levels are associated with circulating markers of endothelial injury,which is one of the key pathophysiological mechanisms in the development of ARDS.Although environmental pollutants alone may not be sufficient to induce severe pulmonary injury in humans, they likely increase susceptibility to other causes of ARDS such as respiratory infection and prime the alveolus for damage in these settings.
Wildfire smoke is an increasingly prevalent source of environmental pollution. Climate change has led to more frequent wildfires over a longer season.In the United States, PM air quality has improved over the past 3 decades except in areas that are prone to wildfires.Wildfires are associated with acute increases in ozone and PM as well as other pollutants such as volatile organic compounds.As noted earlier, previous studies of the relationship between ambient pollution and ARDS have generally focused on the average exposure in various regions over time, rather than on events that might be expected to acutely increase ambient pollution. In addition, smoke from wildfires may have chemical properties that make its risk profile different from that of PM or smoke from other sources.Although it is clear that wildfire-related pollution contributes to increased respiratory morbidity and health utilization overall,the specific relationship between ARDS and exposure to pollutants generated by wildfire smoke has not been studied . In vitro evidence demonstrates that wood smoke exposure diminishes alveolar barrier function and increases alveolar endothelial oxidative stress and apoptosis.In mice, PM collected during wildfires induced a more pro-inflammatory response and greater oxidative stress than ambient PM collected in the absence of wildfires.Wood fire smoke exposure has also been shown to induce a pulmonary and systemic inflammatory response in healthy volunteers.It is mechanistically plausible that the increased inflammation,grow tables 4×8 oxidative stress, and lung micro-vascular permeability in response to wood fire smoke demonstrated under experimental conditions would translate to an increased risk of ARDS. Future research should test whether ARDS incidence and outcomes change during or after wildfire events.The link between cigarette smoke and adverse health outcomes is well established, and reducing cigarette use has been a major focus of public health efforts over the past half century.Although rates of tobacco smoking have generally declined globally, they remain unacceptably high, and cigarette smoking is a leading cause of avoidable death. For example, the 2015 Global Burden of Disease Study found that approximately 11% of women and 14% of men in the United States report daily smoking and that smoking accounted for 6.4 million deaths globally.Alternative tobacco and nicotine delivery systems such as electronic cigarettes , or vapes, are increasingly popular, an especially concerning trend among children and adolescents.Although their long-term health consequences are not well established, e-cigarettes cause a specific lung injury syndrome, e-cigarette- or vaping-associated lung injury .E-cigarettes will be discussed in detail in a separate section. Although some retrospective studies have not found an association between cigarette smoking and ARDS,many studies demonstrate that both active smoking and passive cigarette smoke exposure are associated with ARDS, especially among certain clinical populations. Importantly, this association is independent of alcohol use, which is frequently associated with smoking and is a known risk factor for ARDS.A retrospective cohort study of patients in Northern California found that ARDS was more common among self-reported smokers in a dose-dependent manner. The investigators estimated that smoking carried an attributable risk in ARDS of 50%.A 2014 study of 381 patients with ARDS previously enrolled in randomized clinical trials examined the relationship between tobacco exposure and ARDS.Rather than relying on patient or surrogate reports, which lack sensitivity when compared with biomarkers for tobacco exposure,urine levels of NNAL -1–1-butanol were used to determine smoking history. The rate of active smoking among patients with ARDS in this study was significantly higher than the population average .
Smokers were younger and had fewer comorbidities than nonsmokers despite similar ARDS severity. Although unadjusted mortality among smokers was significantly lower than in nonsmokers, there was no significant difference after adjusting for comorbidities and severity of illness,suggesting that smokers develop ARDS when their illness is less severe than that of otherwise similar patients. Current cigarette smoking conferred increased odds for the development of transfusion-related acute lung injury in a two center prospective case-control study.Donor smoking history increased the odds of grade 3 primary graft dysfunction in a multi-center prospectively enrolled cohort of lung transplant recipients.A prospective study of the association between tobacco exposure and the development of ALI after blunt trauma used plasma levels of cotinine to differentiate between active and passive smoke exposure and to quantify exposure levels.Active smokers and passively exposed patients in this cohort from a single level 1 trauma center had similarly increased odds of developing ARDS independent of confounding factors, including alcohol use and trauma severity. Higher levels of plasma cotinine were associated with higher odds of developing ARDS.Another prospective study of patients with trauma enrolled between 2005 and 2015 confirmed that cigarette smoke exposure remains an important risk factor for ARDS and highlighted a particularly elevated risk among passive smokers in later years.In patients with trauma, impaired platelet aggregation likely mediates at least part of the effect of cigarette smoke exposure on ARDS risk.In addition, cigarette smoke alters the microbiota in patients with trauma such that their pulmonary microbiome is enriched for specific pathologic bacteria that are associated with ARDS development.In a prospectively enrolled cohort with diverse predisposing risk factors for ARDS, active cigarette smoking both by self-report and urine NNAL was associated with an increased odds of ARDS among patients with non-pulmonary sepsis as their primary predisposing risk factor.Patients with trauma and transfusion as their primary risk factor were not included in this study because of the previously established link between smoking and ARDS in these populations. Again, the mortality rate of active smokers was lower in an unadjusted analysis, but mortality was similar after adjusting for baseline severity of illness.This finding is consistent with the previous one that smokers are at increased risk of developing ARDS when their underlying illness is comparatively less severe. Similarly to ambient pollution, cigarette smoke exposure likely predisposes the lung to injury in the setting of a second insult such as trauma, multiple transfusions, or sepsis . This concept was elegantly demonstrated in an experimental model in healthy humans who were exposed to inhaled lipopolysaccharide .BAL and plasma biomarkers for alveolar epithelialcapillary permeability, inflammation, and alveolar endothelial dysfunction were compared between self-reported smokers and nonsmokers. Absolute measurements were consistent with more alveolar permeability to protein and inflammation in smokers, and statistical tests of interaction demonstrated that smoking potentiated these responses to LPS.In mice, cigarette smoke exposure itself does not cause frank lung injury, but mice exposed to cigarette smoke develop worse pulmonary edema, increased vascular permeability, worse histologic injury, and increased biomarker evidence of inflammation after exposure to LPS.