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Review

The Effects of Air Pollution and Temperature on COPD

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ABSTRACT

Chronic Obstructive Pulmonary Disease (COPD) affects 12–16 million people in the United States and is the third-leading cause of death. In developed countries, smoking is the greatest risk factor for the development of COPD, but other exposures also contribute to the development and progression of the disease. Several studies suggest, though are not definitive, that outdoor air pollution exposure is linked to the prevalence and incidence of COPD. Among individuals with COPD, outdoor air pollutants are associated with loss of lung function and increased respiratory symptoms. In addition, outdoor air pollutants are also associated with COPD exacerbations and mortality. There is much less evidence for the impact of indoor air on COPD, especially in developed countries in residences without biomass exposure. The limited existing data suggests that indoor particulate matter and nitrogen dioxide concentrations are linked to increased respiratory symptoms among patients with COPD. In addition, with the projected increases in temperature and extreme weather events in the context of climate change there has been increased attention to the effects of heat exposure. Extremes of temperature—both heat and cold—have been associated with increased respiratory morbidity in COPD. Some studies also suggest that temperature may modify the effect of pollution exposure and though results are not conclusive, understanding factors that may modify susceptibility to air pollution in patients with COPD is of utmost importance.

Introduction

Chronic Obstructive Pulmonary Disease (COPD) affects 12–16 million people in the United States and is the third leading cause of death Citation(1). The prevalence and mortality of COPD is expected to increase in the coming decades Citation(2). COPD is characterized by symptoms of wheeze, shortness of breath and cough. In addition, intermittent exacerbations of disease often change the trajectory of disease course, leading to worse health related quality of life, hastened lung function decline, reduced functional capacity (Citation3, Citation4) and increased risk of death (Citation5–7). The World Health Organization (WHO) estimates that ambient air pollution is responsible for 3.7 million premature death worldwide in 2012 and 14% of these deaths were due to COPD or acute lower respiratory infections Citation(8).

Integrated exposure-response modeling suggests that the population attributable mortality risk due to ambient air pollution for COPD varies and was estimated to range from < 1 to 21% depending on country Citation(9). In particular, particulate matter (PM) which is a complex mixture of solid and liquid particles made up of a number of components [including acids, organic chemicals, metals and soil or dust particles]; nitrogen dioxide (NO2), which is a gaseous product of high-temperature combustion [including emissions from automobiles, power plants and off-road equipment Citation(10)]; and ozone (O3) which is a strong oxidizing agent with a variety of effects including lung inflammation, alveolar epithelial damage and changes in chemical composition of lung lavage fluids Citation(11) have been linked to COPD. In addition, there has been increased attention to the effects of heat exposure with the anticipated increases in temperature projected in the context of climate change (Citation12–15). Extremes of temperature may affect COPD outcomes and may even modify the effects of pollutant exposure. Therefore, understanding the effects of air pollution and temperature on COPD is a crucial step to the development of preventative strategies and patient care.

Outdoor air pollution in COPD

Prevalence and incidence of COPD

Several longitudinal studies have shown that outdoor air pollution has long-term effects on lung function with higher pollution exposure leading to more rapid lung function decline in general population cohorts (Citation16–18). This accelerated loss of lung function may contribute to the development of COPD and consistent with this literature, though studies are not definitive, results suggest that outdoor air pollution exposure is linked to COPD incidence and prevalence. For example, both PM and NO2 have been linked to a varying degree with COPD incidence and prevalence. A recent meta-analysis showed that there was a trend towards increased prevalence of COPD, defined as chronic bronchitis or bronchitic symptoms, with higher PM exposure, but this association did not reach statistical significance Citation(19). A study of 4,757 women investigated exposures to outdoor pollution over a 5-year look-back period and found that a 7 µg/m3 increase in PM10 (PM with aerodynamic diameter less than 10 µm) and 16 µg/m3 increase in NO2 concentrations were associated with an increased prevalence of COPD [odds ratio (OR) of 1.33 (95% confidence interval (CI): 1.03–1.72) and 1.43 (95% CI: 1.23–1.66), respectively](20).

A large longitudinal epidemiologic study investigated annual mean levels of NO2 over 35 years and found an increased COPD incidence associated with cumulative exposure in over 57,000 subjects Citation(21). However, in a recent large population-based cohort study of 812,063 patients in England without an initial COPD diagnosis who were followed from 2003 to 2007 for identification of first COPD diagnoses recorded either by a general practitioner or on admission to hospital, found inconclusive evidence for associations between air pollution and COPD incidence Citation(22). Similarly, a meta-analysis of five cohorts found that NO2 and PM were not significantly associated with COPD incidence or prevalence. The only statistically significant associations were seen with traffic intensity in the nearest road and COPD incidence in never smokers and in females Citation(23).

Mortality among individuals with COPD

Higher outdoor pollution levels have been related to increased mortality in general population studies, with greater effect sizes for respiratory deaths (Citation24–27). Mortality studies of COPD populations are limited but have yielded similar results. In particular, several studies have suggested a link between outdoor particulate concentrations and increased mortality in patients with COPD. For example, there was a significant association between PM10 and mortality using Medicare data of subjects discharged with a COPD diagnosis between 1985 and 1999 Citation(27). A case-crossover analysis in Barcelona, Spain found a strong association with respiratory death in COPD subjects with increases of black smoke particles (urban particle air pollution). Specifically, for an increase of 20 µg/m³ in black smoke particles, there was an 11% increased odds of mortality for all causes (OR = 1.112, 95%CI: 1.017, 1.215) and the association was stronger for respiratory causes (OR = 1.182, 95%CI: 1.025, 1.365) Citation(28).

Zhu et al. conducted a meta-analysis of PM10 and mortality in COPD patients and found an increased odds of COPD mortality with PM10 exposure with a 10 µg/m³ increase in daily PM10 being associated with a 1.1% (95%CI 0.8–1.4) increase risk in COPD mortality Citation(29). Although fewer studies have investigated the effect of other ambient pollutants on COPD mortality, those that do exist, suggest that other pollutants are also associated with COPD mortality. For example, several studies suggest that higher NO2 concentrations are linked to higher COPD mortality (Citation30, Citation31) and others have shown non-statistically significant associations between NO2 concentrations and mortality (Citation32, Citation33). Overall, results suggest that people with COPD are more susceptible to air pollution and at lower levels than the general population.

COPD exacerbations

Several studies link outdoor air pollution to increased risk of COPD exacerbations. The Air Pollution and Health, a European Approach (APHEA) project analyzed data from 6 European cities and found increased risk of COPD hospital admissions with several air pollutants, including NO2, O3, sulfur dioxide (SO2) and black smoke Citation(34). A study of PM10 and hospital admissions for COPD found a 2.5% increase in admissions for every 10 µg/m3 increase in PM10 Citation(35). In addition, a meta-analysis of 18 studies of PM10 and exacerbations found a 10 µg/m3 increase in daily PM10 was associated with a 2.7% increase in COPD hospitalizations Citation(29). The data linking air pollution with COPD exacerbations for O3 is also convincing as higher O3 concentrations have been shown to increase hospital and emergency department visits for lower respiratory disease, including COPD (Citation36–38).

A recent meta-analysis of the association between short-term exposure to ambient O3 and respiratory hospital admissions revealed a 1.9% increase in emergency hospitalizations for respiratory diseases per 10 ppb of 24-hour mean O3 and a 5.06% increase in COPD-related emergency hospital admissions per 10 ppb of 24-hour mean O3 Citation(35). Two decades ago, 69.7 million people were estimated to have O3 exposure levels above the National Ambient Air Quality Standards Citation(11) and ambient O3 levels are expected to continue to increase in the upcoming decades Citation(39). Therefore understanding the contribution of O3 and other outdoor pollutants to COPD morbidity should continue to be a high priority.

Lung function and respiratory symptoms among individuals with COPD

Long-term exposure to outdoor air pollution has also been linked to lung function decline and short-term changes in outdoor air pollutant concentrations have been associated with acute changes in lung function and increased respiratory symptoms among individuals with established COPD. For example, a recent study has shown that PM2.5 and O3 exposures were associated with FEV1 decline among 1,218 subjects with severe COPD enrolled in the National Emphysema Treatment Trial (NETT) followed for an average of 29.2 months Citation(40). Similarly, among 401 individuals with COPD and α-1-antitrypsin deficiency, a 10 µg/m3 increase in PM10 was associated with an additional 30 cc/year (95% CI: 2–60 cc/year) decline in FEV1 Citation(41).

There have also been several studies that have linked acute outdoor air pollution exposure to short term decrements in lung function and increased respiratory symptoms (Citation42–45). For example, Peacock et al. recruited 94 COPD subjects who filled out daily symptom diaries. PM10 was significantly associated with dyspnea and symptomatic decreases in peak expiratory flow (PEF), defined as a fall in PEF for at least 2 days plus a reported increase in dyspnea. An interquartile range (IQR) increase in PM10 was linked to an approximately 13% increase in odds of symptomatic decreases in PEF and a similar increase in odds of dyspnea Citation(46). In addition, in another study of 40 subjects with COPD, daily increases in PM10 concentrations were associated with night time chest symptoms and increases in NO2 concentrations were associated with increased rescue medication use Citation(43).

Several studies have sought to elucidate the pollutant-induced inflammatory response. These studies may shed light on the underlying pathway by which pollutant exposure is responsible for increased COPD morbidity. For example, PM, NO2 and O3 exposure have all been shown to trigger an inflammatory response, including in vitro and in vivo increases in IL-8 concentrations (Citation47–49). IL-8 is a potent neutrophil chemoattractant Citation(50), and neutrophil elastase is a powerful stimulant of mucin production Citation(51). Increased systemic and sputum IL-8 concentrations have been associated with COPD exacerbations (Citation52, Citation53). Air pollution exposure has also been linked to other markers of inflammation, which are related to outcomes in COPD. For example, Dadvand et al. found that increased exposure to ambient NO2 resulted in an 8–12% increase in systemic levels of IL-8, as well as a 51% and 10% increase in C-reactive protein and fibrinogen, two other systemic COPD biomarkers Citation(53). Similarly, air pollution exposure has been linked to increased markers of airway oxidative stress (Citation54, Citation55). It is imperative that we continue to increase our understanding of the effects of air pollution on COPD morbidity.

Indoor air pollution and COPD

Although substantial evidence shows that outdoor air pollutants impact COPD development and morbidity, there is much less evidence for the impact of indoor air on COPD, especially in developed countries. Evidence from international studies in developing countries and several U.S. studies show that high concentrations of air pollution from indoor burning of biomass fuels cause and exacerbate existing COPD (Citation56, Citation57). As a matter of fact, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document identifies indoor air pollution resulting from burning wood and other biomass fuels, as a major risk factor for COPD Citation(58).

However, exposures under these conditions are two to three orders of magnitude higher than in developed country households. Indoor air quality, even at low pollutant levels, may be important for individuals with COPD as they spend more time at home than their age-matched counterparts: approximately 82% of their time is spent indoors in their own home Citation(59). Despite the likely importance of indoor air quality, studies focusing on indoor air quality in developed countries have been limited, but is the focus of this current review, given the recent literature reviews summarizing the effect of biomass exposure on COPD Citation(60).

Indoor PM

There have been studies linking secondhand smoke (SHS) exposure to the development of COPD, and among those with COPD there is evidence suggesting the SHS exposure contributes to worse quality of life, dyspnea and heightened risk for COPD exacerbation (Citation61–63); however, much less investigation exists exploring the role of other indoor pollutants to COPD morbidity. Osman et al. showed in a cross-sectional study that indoor PM2.5 concentrations were associated with worse quality of life in COPD patients Citation(64). The PM2.5 concentrations were greater in homes of current smokers and the adverse effects of PM2.5 on quality of life were also greater among current smokers, suggesting that the adverse effects of PM2.5 in this population may have partly been due to active and secondhand cigarette smoke exposure. Results from Hansel et al. Citation(65) showed that PM2.5 concentrations measured in homes in the Baltimore area were independently associated with increased rescue medication use, risk of severe exacerbations and increased respiratory symptoms, including worse dyspnea, and increased risk of nocturnal symptoms and frequent wheeze among former smokers with moderate-to-severe COPD.

A 10 µg/m3 increase in PM2.5 concentrations was associated with 44% higher odds of having nocturnal symptoms and 38% higher odds of having a severe COPD exacerbation. These adverse health effects were seen even after adjusting for air and hair nicotine concentrations suggesting that PM has independent effects of respiratory health from SHS. In addition, the adverse health effects were seen even though average in-home PM levels were relatively low (mean indoor PM2.5 concentrations ∼ 12 µg/m3).

Subsequent post-hoc analyses of this study, suggest that there may be subgroups of individuals with COPD that show increased susceptibility to pollutant exposure. For instance, those who also were atopic Citation(66) or obese Citation(67) were more likely to experience increased respiratory symptoms upon exposure to higher PM levels. These findings of specific subgroups showing increased susceptibility to PM exposure is likely not unique to patients with COPD as obesity and other factors have been shown to modify the effect of pollutant exposure on health outcomes, in other chronic diseases, such as asthma Citation(68).

Indoor PM has not been consistently linked to changes in lung function among individuals with established COPD (Citation69, Citation70). A study including 35 subjects with COPD showed no association between indoor air quality and lung function Citation(69) and another panel study including 17 subjects with COPD showed no consistent association between PM2.5, PM2.5-10 or its measured components with lung function over 12 days Citation(70). Therefore, the adverse effects of indoor PM on respiratory symptoms and exacerbations in patients with COPD may be independent from changes in lung function or a result of changes in smaller caliber airways that is not adequately captured by the measurement of forced expiratory volume in one second (FEV1). Alternatively, given the relatively small size of studies of indoor air pollution and COPD, they may not have been adequately powered to detect an association between pollutant exposure and lung function.

Indoor NO2 and other pollutants

NO2, a by-product of combustion with indoor sources including gas-burning appliances, is a common indoor pollutant and may lead to worse respiratory health through airway epithelial damage or reducing resistance to viral-induced exacerbations (Citation71–73). A recent study suggests that NO2 concentrations may be associated with increased risk of obstructive airway disease as assessed by spirometry, but not self-reported COPD diagnosis in elderly residents of nursing homes Citation(74). Only few studies have investigated whether indoor NO2 concentrations affect patients with COPD. Osman et al. found no association between indoor NO2 concentrations and worse quality of life in subjects with COPD Citation(64). Though Hansel et al. also did not show a significant association between NO2 concentrations and quality of life, there was a link between indoor NO2 concentrations in the main living area and increased dyspnea and higher rescue medication use. Furthermore, bedroom NO2 concentrations were associated with higher risk of nocturnal symptoms and severe COPD exacerbations Citation(65). Importantly, this adverse effect of NO2 was independent of PM exposure.

Exposure to dust and endotoxin has been associated with decline in lung function, and risk of COPD in farming communities and occupational settings (Citation75–78) but the role of in-home endotoxin levels in urban communities and patients with COPD is less clear. A recent study suggested that formaldehyde levels were associated with increased risk of reporting COPD in elderly nursing home residents Citation(74), and few studies have suggested that exposure to aldehydes and volatile organic compounds (VOCs) may be linked to respiratory symptoms and lung function in the elderly Citation(79); however, the role of aldehydes and VOCs in COPD, to our knowledge, has not been studied.

Temperature

There has been increased attention to the effects of heat exposure with the anticipated increases in temperature projected in the context of climate change (Citation12–15). Studies of heat exposure are often conducted in the context of heat waves, sustained periods of extreme heat that occur over consecutive days. Heat waves can have startling health consequences, as was seen during the summer of 2003 when over 70,000 deaths in Europe were attributable to extreme heat Citation(80) and during the summer of 1995 when there were approximately 750 heat-related deaths in Chicago during only 5 days Citation(81). Studies have consistently found that elderly individuals and those with underlying cardiac and respiratory diseases, including COPD, are at increased risk for adverse health effects of heat exposure (Citation82–86). For example, a study across 12 U.S. cities estimated that the effect of hot temperatures during summertime can increase the risk of death attributable to COPD by as much as 25% Citation(84).

In addition to impact of temperature on mortality, studies have demonstrated that heat exposure is associated with respiratory morbidity. A study in New York City found that the risk of COPD hospitalization increased by 7.6% for every 1°C increase above a threshold temperature of 29°C Citation(87). Studies have used Medicare data to provide estimates of effect that are representative of a broader portion of the U.S. population (Citation88, Citation89). In a study that included 12.5 million elderly individuals in 213 urban U.S. counties, there was a 4.7% increased risk of hospitalization for COPD for every 10 degree F increase in ambient temperature Citation(88). Residents of more temperate climates are more likely to be adversely impacted by the effects of extreme heat exposure and access to air condition has been identified as a strong protective factor (Citation81,Citation84,Citation90). The mechanisms by which heat exposure adversely impacts COPD are not entirely understood. In addition to thermoregulatory responses to heat exposure, there may be a direct effect of heat exposure on the respiratory system. Studies in asthma suggest that breathing hot humid air may result in bronchoconstriction that is mediated via cholinergic pathways Citation(91).

The anticipated effects of climate change also include increases in temperature variability and in extreme cold weather conditions. Excessive cold temperatures have been linked to increases in mortality and morbidity among those with COPD. In a study of individuals over 65 years in Michigan, those with COPD had a 19% increased risk of dying on cold days Citation(92). In a New Zealand study, the death rate was 18% higher in winter versus non-winter months and 31% of excess deaths were attributable to respiratory disease Citation(93). Studies have also demonstrated an impact of cold temperatures on lung function and the risk of exacerbations among those with COPD. A large study in Taiwan using national health insurance registry data detected a 0.8% increase in COPD exacerbations for every 1°C decrease in mean daily temperature Citation(94). In East London, cold temperatures were linked to decreases in lung function in a study of 76 participants with COPD. Investigators found that FEV1 was 45cc less during the coldest versus warmest weeks during a 12-month period Citation(95). In addition to bronchoconstriction and inflammation that may occur in the setting of cold exposure Citation(96), recent evidence suggests a role for mucous hypersecretion as a potential mediator of the COPD response to cold temperature Citation(97).

There is a potentially interactive effect of high temperatures and pollutant concentrations (Citation98–100). Although there have been studies that have not detected evidence that increasing temperature modifies the effect of pollution exposure (Citation101–103), several studies have detected interactive effects (Citation104-108). Studies that have included respiratory specific outcomes have also had conflicting results. For example, studies in China and Europe suggest an interactive effect of increases in temperature and pollution on the risk for cardiac death but not respiratory death (Citation100, Citation109). A study in Brisbane, Australia did not suggest effect modification for respiratory emergency visits but demonstrated an interactive effect of increasing temperature and PM10 on respiratory hospitalizations Citation(110). Further studies are needed to clarify these inconclusive findings.

Implications

A large body of literature suggests that outdoor air pollution is associated with increased respiratory symptoms as well as increased COPD exacerbations and mortality. Similarly, though studies are limited, indoor pollutant concentrations in high-income countries, despite relatively low overall pollutant burden, appear to be linked to worse respiratory morbidity in patients with COPD. This suggests that COPD patients are particularly susceptible to even low levels of exposure. In addition, extremes of temperature, including both extremes of hot and cold, have also been linked to excessive morbidity and mortality among individuals with COPD. Studies suggest that there may even be subgroups of patients with COPD that have increased susceptibility to exposure, but these susceptible subgroups need to be further elucidated. Clearly delineating the harmful impact of air quality and temperature on susceptible groups of individuals with COPD is critical to help guide both policy recommendations and individual clinical recommendations. Furthermore, defining the harmful impact of indoor air quality on COPD morbidity is of utmost importance as indoor air pollution is a highly modifiable exposure. Feasible interventions that improve in-home air quality (Citation111–113) and optimize indoor temperature Citation(114) may represent cost-effective and novel therapeutic arenas for a disease with limited treatment options.

Declaration of interest

Dr. Hansel and Dr. McCormack report no conflicts of interest. Dr. Kim reports personal fees from Medscape and from CSA Medical, outside the submitted work. The authors alone are responsible for the content and writing of the paper.

Funding

Research support is from NIH/NIEHS grants R01 ES018845, R01ES022607, R01ES023500, and R21ES024021. Dr. Kim is supported by NHLBIK23HL094696.

Abbreviations
CI=

Confidence interval

COPD=

Chronic obstructive pulmonary disease

FEV1=

Forced expiratory volume in 1 second

NO2=

Nitrogen dioxide

O3=

Ozone

OR=

Odds ratio

PM=

Particulate matter

PM10=

Particulate matter < 10 µm diameter

PM2.5=

Particulate matter < 2.5 µm diameter

SO2=

Sulfur dioxide

References

  • Mathers CD, Bernard C, Moesgaard-Iburg K, Inoue M, Ma Fat D, Shibuya K, et al. Global Burden of Disease in 2002: data sources, methods and results. Geneva: World Health Organization 2003; 54.
  • Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2015. Available from: http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html (accessed 17 June, 2015).
  • Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57(10):847–852.
  • Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157(5 Pt 1):1418–1422.
  • Miravitlles M, Murio C, Guerrero T, Gisbert R, Dafne Study Group. Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Chest 2002; 121(5):1449–1455.
  • Connors AF, Dawson NV, Thomas C, Harrell FE, Desbiens N, Fulkerson WJ, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med 1996; 154(4 Pt 1):959–967.
  • Donaldson GC, Wedzicha JA. COPD exacerbations—1: Epidemiology. Thorax 2006; 61(2):164–168.
  • World Health Organization. Ambient (outdoor) air quality and health. Geneva: World Health Organization; 2014; Fact sheet No 313.
  • Burnett RT, Pope CA, Ezzati M, Olives C, Lim SS, Mehta S, et al. An integrated risk function for estimating the global burden of disease attributable to ambient fine particulate matter exposure. Environ Health Perspect 2014; 122(4):397–403.
  • U.S. Environmental Protection Agency (US EPA). What are the six common air pollutants? 2014. Available from: http://www3.epa.gov/airquality/urbanair/ (accessed 17 June, 2015).
  • Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Health effects of outdoor air pollution. Am J Respir Crit Care Med 1996; 153(1):3–50.
  • Meehl GA, Tebaldi C. More intense, more frequent, and longer lasting heat waves in the 21st century. Science 2004; 305(5686):994–997.
  • Epstein PR. Climate change and human health. N Engl J Med 2005; 353(14):1433–1436.
  • Bernstein AS, Rice MB. Lungs in a warming world: climate change and respiratory health. Chest 2013; 143(5):1455–1459.
  • McMichael AJ, Woodruff RE, Hales S. Climate change and human health: present and future risks. Lancet 2006; 367(9513):859–869.
  • Rice MB, Ljungman PL, Wilker EH, Dorans KS, Gold DR, Schwartz J, et al. Long-term exposure to traffic emissions and fine particulate matter and lung function decline in the Framingham Heart Study. Am J Respir Crit Care Med 2015; 191(6):656–664.
  • Lepeule J, Litonjua AA, Coull B, Koutrakis P, Sparrow D, Vokonas PS, et al. Long-term effects of traffic particles on lung function decline in the elderly. Am J Respir Crit Care Med 2014; 190(5):542–548.
  • Gotschi T, Heinrich J, Sunyer J, Kunzli N. Long-term effects of ambient air pollution on lung function: a review. Epidemiology 2008; 19(5):690–701.
  • Song Q, Christiani DC, Xiaorong Wang, Ren J. The global contribution of outdoor air pollution to the incidence, prevalence, mortality and hospital admission for chronic obstructive pulmonary disease: a systematic review and meta-analysis. Int J Environ Res Public Health 2014; 11(11):11822–11832.
  • Schikowski T, Sugiri D, Ranft U, Gehring U, Heinrich J, Wichmann HE, et al. Long-term air pollution exposure and living close to busy roads are associated with COPD in women. Respir Res 2005; 6:152.
  • Andersen ZJ, Hvidberg M, Jensen SS, Ketzel M, Loft S, Sorensen M, et al. Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study. Am J Respir Crit Care Med 2011; 183(4):455–461.
  • Atkinson RW, Carey IM, Kent AJ, van Staa TP, Anderson HR, Cook DG. Long-term exposure to outdoor air pollution and the incidence of chronic obstructive pulmonary disease in a national English cohort. Occup Environ Med 2015; 72(1):42–48.
  • Schikowski T, Adam M, Marcon A, Cai Y, Vierkotter A, Carsin AE, et al. Association of ambient air pollution with the prevalence and incidence of COPD. Euro Respir J 2014; 44(3):614–626.
  • Bell ML, Dominici F, Samet JM. A meta-analysis of time-series studies of ozone and mortality with comparison to the national morbidity, mortality, and air pollution study. Epidemiology 2005; 16(4):436–445.
  • Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994. N Engl J Med 2000; 343(24):1742–1749.
  • Tao Y, Huang W, Huang X, Zhong L, Lu SE, Li Y, et al. Estimated acute effects of ambient ozone and nitrogen dioxide on mortality in the Pearl River Delta of southern China. Environ Health Perspect 2012; 120(3):393–398.
  • Zanobetti A, Bind MA, Schwartz J. Particulate air pollution and survival in a COPD cohort. Environ Health 2008; 7:48.
  • Sunyer J, Schwartz J, Tobias A, Macfarlane D, Garcia J, Anto JM. Patients with chronic obstructive pulmonary disease are at increased risk of death associated with urban particle air pollution: a case-crossover analysis. Am J Epidemiol 2000; 151(1):50–56.
  • Zhu R, Chen Y, Wu S, Deng F, Liu Y, Yao W. The relationship between particulate matter (PM10) and hospitalizations and mortality of chronic obstructive pulmonary disease: a meta-analysis. COPD 2013; 10(3):307–315.
  • Faustini A, Stafoggia M, Cappai G, Forastiere F. Short-term effects of air pollution in a cohort of patients with chronic obstructive pulmonary disease. Epidemiology 2012; 23(6):861–879.
  • Naess O, Nafstad P, Aamodt G, Claussen B, Rosland P. Relation between concentration of air pollution and cause-specific mortality: four-year exposures to nitrogen dioxide and particulate matter pollutants in 470 neighborhoods in Oslo, Norway. Am J Epidemiol 2007; 165(4):435–443.
  • Gan WQ, FitzGerald JM, Carlsten C, Sadatsafavi M, Brauer M. Associations of ambient air pollution with chronic obstructive pulmonary disease hospitalization and mortality. Am J Respir Crit Care Med. 2013; 187(7):721–727.
  • Sunyer J, Basagana X. Particles, and not gases, are associated with the risk of death in patients with chronic obstructive pulmonary disease. Int J Epidemiol 2001; 30(5):1138–1140.
  • Burnett RT, Brook JR, Yung WT, Dales RE, Krewski D. Association between ozone and hospitalization for respiratory diseases in 16 Canadian cities. Environ Res 1997; 72(1):24–31.
  • Ji M, Cohan DS, Bell ML. Meta-analysis of the Association between Short-Term Exposure to Ambient Ozone and Respiratory Hospital Admissions. Environ Res Lett 2011; 6(2): pii: 02400.
  • Kousha T, Rowe BH. Ambient ozone and emergency department visits due to lower respiratory condition. Int J Occup Med Environ Health 2014; 27(1):50–59.
  • Medina-Ramon M, Zanobetti A, Schwartz J. The effect of ozone and PM10 on hospital admissions for pneumonia and chronic obstructive pulmonary disease: a national multicity study. Am J Epidemiol 2006; 163(6):579–588.
  • Zanobetti A, Schwartz J, Dockery DW. Airborne particles are a risk factor for hospital admissions for heart and lung disease. Environ Health Perspect 2000; 108(11):1071–1077.
  • Pfister GG, Walters S, Lamarque JF, Fast J, Barth MC, Wong J, et al. Projections of future summertime ozone over the U.S. J Geophys Res Atmos 2014; 119(9):5559–5582.
  • Kariisa M, Foraker R, Pennell M, Buckley T, Diaz P, Criner GJ, et al. Short- and long-term effects of ambient ozone and fine particulate matter on the respiratory health of chronic obstructive pulmonary disease subjects. Arch Environ Occup Health 2015; 70(1):56–62.
  • Wood AM, Harrison RM, Semple S, Ayres JG, Stockley RA. Outdoor air pollution is associated with rapid decline of lung function in alpha-1-antitrypsin deficiency. Occup Environ Med 2010; 67(8):556–561.
  • Pope CA, III, Kanner RE. Acute effects of PM10 pollution on pulmonary function of smokers with mild to moderate chronic obstructive pulmonary disease. Am Rev Respir Dis 1993; 147(6 Pt 1):1336–1340.
  • Harre ES, Price PD, Ayrey RB, Toop LJ, Martin IR, Town GI. Respiratory effects of air pollution in chronic obstructive pulmonary disease: a three month prospective study. Thorax 1997; 52(12):1040–1044.
  • Brauer M, Ebelt ST, Fisher TV, Brumm J, Petkau AJ, Vedal S. Exposure of chronic obstructive pulmonary disease patients to particles: respiratory and cardiovascular health effects. J Expo Anal Environ Epidemiol 2001; 11(6):490–500.
  • Lagorio S, Forastiere F, Pistelli R, Iavarone I, Michelozzi P, Fano V, et al. Air pollution and lung function among susceptible adult subjects: a panel study. Environ Health 2006; 5:11.
  • Peacock JL, Anderson HR, Bremner SA, Marston L, Seemungal TA, Strachan DP, et al. Outdoor air pollution and respiratory health in patients with COPD. Thorax 2011; 66(7):591–596.
  • Jaspers I, Flescher E, Chen LC. Ozone-induced IL-8 expression and transcription factor binding in respiratory epithelial cells. Am J Physiol 1997; 272(3 Pt 1):L504–511.
  • Richman-Eisenstat JB, Jorens PG, Hebert CA, Ueki I, Nadel JA. Interleukin-8: an important chemoattractant in sputum of patients with chronic inflammatory airway diseases. Am J Physiol 1993; 264(4 Pt 1):L413–418.
  • Ling SH, van Eeden SF. Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2009; 4:233–243.
  • Park JA, He F, Martin LD, Li Y, Chorley BN, Adler KB. Human neutrophil elastase induces hypersecretion of mucin from well-differentiated human bronchial epithelial cells in vitro via a protein kinase C{delta}-mediated mechanism. Am J Pathol 2005; 167(3):651–661.
  • Barnes PJ, Chowdhury B, Kharitonov SA, Magnussen H, Page CP, Postma D, et al. Pulmonary biomarkers in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006; 174(1):6–14.
  • Hurst JR, Donaldson GC, Perera WR, Wilkinson TM, Bilello JA, Hagan GW, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006; 174(8):867–874.
  • Dadvand P, Nieuwenhuijsen MJ, Agusti A, de Batlle J, Benet M, Beelen R, et al. Air pollution and biomarkers of systemic inflammation and tissue repair in COPD patients. Eur Respir J 2014; 44(3):603–613.
  • Manney S, Meddings CM, Harrison RM, Mansur AH, Karakatsani A, Analitis A, et al. Association between exhaled breath condensate nitrate + nitrite levels with ambient coarse particle exposure in subjects with airways disease. Occup Environ Med 2012; 69(9):663–669.
  • Pirozzi C, Sturrock A, Weng HY, Greene T, Scholand MB, Kanner R, et al. Effect of naturally occurring ozone air pollution episodes on pulmonary oxidative stress and inflammation. Int J Environ Res Public Health 2015; 12(5):5061–5075.
  • Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet 2009; 374(9691):733–743.
  • Sood A, Petersen H, Blanchette CM, Meek P, Picchi MA, Belinsky SA, et al. Wood smoke exposure and gene promoter methylation are associated with increased risk for COPD in smokers. Am J Respir Crit Care Med 2010; 182(9):1098–1104.
  • Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (revised 2011). 2011:1–90. Available from: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2011_Feb21.pdf (accessed 17 June, 2015).
  • Leech JA, Smith-Doiron M. Exposure time and place: do COPD patients differ from the general population? J Expo Sci Environ Epidemiol 2006; 16(3):238–241.
  • Perez-Padilla R, Ramirez-Venegas A, Sansores-Martinez R. Clinical characteristics of patients with biomass smoke-associated COPD and chronic bronchitis. J COPD Fndn 2013; 1(1):23–32.
  • Eisner MD, Balmes J, Yelin EH, Katz PP, Hammond SK, Benowitz N, et al. Directly measured secondhand smoke exposure and COPD health outcomes. BMC Pulm Med 2006; 6:12.
  • Eisner MD, Iribarren C, Yelin EH, Sidney S, Katz PP, Sanchez G, et al. The impact of SHS exposure on health status and exacerbations among patients with COPD. Int J Chron Obstruct Pulmon Dis 2009; 4:169–176.
  • Eisner MD, Jacob P, Benowitz NL, Balmes J, Blanc PD. Longer term exposure to secondhand smoke and health outcomes in COPD: impact of urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Nicotine Tob Res 2009; 11(8):945–953.
  • Osman LM, Douglas JG, Garden C, Reglitz K, Lyon J, Gordon S, et al. Indoor air quality in homes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007; 176(5):465–472.
  • Hansel NN, McCormack MC, Belli AJ, Matsui EC, Peng RD, Aloe C, et al. In-home air pollution is linked to respiratory morbidity in former smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013; 187(10):1085–1090.
  • Kaji DA, Belli AJ, McCormack MC, Matsui EC, Williams DL, Paulin L, et al. Indoor pollutant exposure is associated with heightened respiratory symptoms in atopic compared to non-atopic individuals with COPD. BMC Pulm Med 2014; 14:147.
  • McCormack MC, Belli AJ, Kaji DA, Matsui EC, Brigham EP, Peng RD, et al. Obesity as a susceptibility factor to indoor particulate matter health effects in COPD. Eur Respir J 2015; 45(5):1248–1257.
  • Lu KD, Breysse PN, Diette GB, Curtin-Brosnan J, Aloe C, Williams DL, et al. Being overweight increases susceptibility to indoor pollutants among urban children with asthma. J Allergy Clin Immunol 2013; 131(4):1017–23, 23.e1–3.
  • de Hartog JJ, Ayres JG, Karakatsani A, Analitis A, Brink HT, Hameri K, et al. Lung function and indicators of exposure to indoor and outdoor particulate matter among asthma and COPD patients. Occup Environ Med 2010; 67(1):2–10.
  • Hsu SO, Ito K, Lippmann M. Effects of thoracic and fine PM and their components on heart rate and pulmonary function in COPD patients. J Expo Sci Environ Epidemiol 2011; 21(5):464–472.
  • Bevelander M, Mayette J, Whittaker LA, Paveglio SA, Jones CC, Robbins J, et al. Nitrogen dioxide promotes allergic sensitization to inhaled antigen. J Immunol 2007; 179(6):3680–3688.
  • Chauhan AJ, Inskip HM, Linaker CH, Smith S, Schreiber J, Johnston SL, et al. Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children. Lancet 2003; 361(9373):1939–1944.
  • Persinger RL, Poynter ME, Ckless K, Janssen-Heininger YM. Molecular mechanisms of nitrogen dioxide induced epithelial injury in the lung. Mol Cell Biochem 2002; 234-235(1–2):71–80.
  • Bentayeb M, Norback D, Bednarek M, Bernard A, Cai G, Cerrai S, et al. Indoor air quality, ventilation and respiratory health in elderly residents living in nursing homes in Europe. Eur Respir J 2015; 45(5):1228–1238.
  • Heederik D, Brouwer R, Biersteker K, Boleij JS. Relationship of airborne endotoxin and bacteria levels in pig farms with the lung function and respiratory symptoms of farmers. Int Arch Occup Environ Health 1991; 62(8):595–601.
  • Schwartz DA, Thorne PS, Yagla SJ, Burmeister LF, Olenchock SA, Watt JL, et al. The role of endotoxin in grain dust-induced lung disease. Am J Respir Crit Care Med 1995; 152(2):603–608.
  • Zejda JE, Barber E, Dosman JA, Olenchock SA, McDuffie HH, Rhodes C, et al. Respiratory health status in swine producers relates to endotoxin exposure in the presence of low dust levels. J Occup Med 1994; 36(1):49–56.
  • Monso E, Riu E, Radon K, Magarolas R, Danuser B, Iversen M, et al. Chronic obstructive pulmonary disease in never-smoking animal farmers working inside confinement buildings. Am J Ind Med 2004; 46(4):357–362.
  • Yoon HI, Hong YC, Cho SH, Kim H, Kim YH, Sohn JR, et al. Exposure to volatile organic compounds and loss of pulmonary function in the elderly. Eur Respir J 2010; 36(6):1270–1276.
  • Robine JM, Cheung SL, Le Roy S, Van Oyen H, Griffiths C, Michel JP, et al. Death toll exceeded 70,000 in Europe during the summer of 2003. C R Biol 2008; 331(2):171–178.
  • Semenza JC, Rubin CH, Falter KH, Selanikio JD, Flanders WD, Howe HL, et al. Heat-related deaths during the July 1995 heat wave in Chicago. N Eng J Med 1996; 335(2):84–90.
  • Anderson BG, Bell ML. Weather-related mortality: how heat, cold, and heat waves affect mortality in the United States. Epidemiology 2009; 20(2):205–213.
  • Zanobetti A, O'Neill MS, Gronlund CJ, Schwartz JD. Summer temperature variability and long-term survival among elderly people with chronic disease. Proc Natl Acad Sci USA 2012; 109(17):6608–6613.
  • Braga AL, Zanobetti A, Schwartz J. The effect of weather on respiratory and cardiovascular deaths in 12 U.S. cities. Environ Health Perspect 2002; 110(9):859–863.
  • Monteiro A, Carvalho V, Oliveira T, Sousa C. Excess mortality and morbidity during the July 2006 heat wave in Porto, Portugal. Int J Biometeorol 2013; 57(1):155–167.
  • Liu L, Breitner S, Pan X, Franck U, Leitte AM, Wiedensohler A, et al. Associations between air temperature and cardio-respiratory mortality in the urban area of Beijing, China: a time-series analysis. Environ Health 2011; 10:51.
  • Lin S, Luo M, Walker RJ, Liu X, Hwang SA, Chinery R. Extreme high temperatures and hospital admissions for respiratory and cardiovascular diseases. Epidemiology 2009; 20(5):738–746.
  • Anderson GB, Dominici F, Wang Y, McCormack MC, Bell ML, Peng RD. Heat-related emergency hospitalizations for respiratory diseases in the Medicare population. Am J Respir Crit Care Med 2013; 187(10):1098–1103.
  • Gronlund CJ, Zanobetti A, Schwartz JD, Wellenius GA, O'Neill MS. Heat, heat waves, and hospital admissions among the elderly in the United States, 1992–2006. Environ Health Perspect 2014; 122(11):1187–1192.
  • Naughton MP, Henderson A, Mirabelli MC, Kaiser R, Wilhelm JL, Kieszak SM, et al. Heat-related mortality during a 1999 heat wave in Chicago. Am J Prev Med 2002; 22(4):221–227.
  • Hayes D, Collins PB, Khosravi M, Lin RL, Lee LY. Bronchoconstriction triggered by breathing hot humid air in patients with asthma: role of cholinergic reflex. Am J Respir Crit Care Med 2012; 185(11):1190–1196.
  • Schwartz J. Who is sensitive to extremes of temperature? A case-only analysis. Epidemiology 2005; 16(1):67–72.
  • Davie GS, Baker MG, Hales S, Carlin JB. Trends and determinants of excess winter mortality in New Zealand: 1980 to 2000. BMC Publ Health 2007; 7:263.
  • Tseng CM, Chen YT, Ou SM, Hsiao YH, Li SY, Wang SJ, et al. The effect of cold temperature on increased exacerbation of chronic obstructive pulmonary disease: a nationwide study. PloS One 2013; 8(3):e57066.
  • Donaldson GC, Seemungal T, Jeffries DJ, Wedzicha JA. Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease. Eur Respir J 1999; 13(4):844–849.
  • Koskela HO, Koskela AK, Tukiaineu HO. Bronchoconstriction due to cold weather in COPD. The roles of direct airway effects and cutaneous reflex mechanisms. Chest 1996; 110(3):632–636.
  • Li M, Li Q, Yang G, Kolosov VP, Perelman JM, Zhou XD. Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism. J Allergy Clin Immunol 2011; 128(3):626-34 e1–5.
  • Katsouyanni K, Pantazopoulou A, Touloumi G, Tselepidaki I, Moustris K, Asimakopoulos D, et al. Evidence for interaction between air pollution and high temperature in the causation of excess mortality. Arch Environ Health 1993; 48(4):235–242.
  • Ren C, Williams GM, Mengersen K, Morawska L, Tong S. Does temperature modify short-term effects of ozone on total mortality in 60 large eastern US communities? An assessment using the NMMAPS data. Environ Int 2008; 34(4):451–458.
  • Analitis A, Michelozzi P, D'Ippoliti D, De'Donato F, Menne B, Matthies F, et al. Effects of heat waves on mortality: effect modification and confounding by air pollutants. Epidemiology 2014; 25(1):15–22.
  • Kelsall JE, Samet JM, Zeger SL, Xu J. Air pollution and mortality in Philadelphia, 1974–1988. Am J Epidemiol 1997; 146(9):750–762.
  • Basu R, Feng WY, Ostro BD. Characterizing temperature and mortality in nine California counties. Epidemiology 2008; 19(1):138–145.
  • Zanobetti A, Schwartz J. Temperature and mortality in nine US cities. Epidemiology 2008; 19(4):563–570.
  • Stafoggia M, Schwartz J, Forastiere F, Perucci CA, Group S. Does temperature modify the association between air pollution and mortality? A multicity case-crossover analysis in Italy. Am J Epidemiol 2008; 167(12):1476–1485.
  • Katsouyanni K, Zmirou D, Spix C, Sunyer J, Schouten JP, Ponka A, et al. Short-term effects of air pollution on health: a European approach using epidemiologic time series data. The APHEA Project. Air Pollution Health Effects—A European Approach. Public Health Rev 1997; 25(1):7–18; discussion 9–28.
  • Ren C, Williams GM, Morawska L, Mengersen K, Tong S. Ozone modifies associations between temperature and cardiovascular mortality: analysis of the NMMAPS data. Occup Environ Med 2008; 65(4):255–260.
  • Ren C, O'Neill MS, Park SK, Sparrow D, Vokonas P, Schwartz J. Ambient temperature, air pollution, and heart rate variability in an aging population. Am J Epidemiol 2011; 173(9):1013–1021.
  • Pattenden S, Armstrong B, Milojevic A, Heal MR, Chalabi Z, Doherty R, et al. Ozone, heat and mortality: acute effects in 15 British conurbations. Occup Environ Med 2010; 67(10):699–707.
  • Qian Z, He Q, Lin HM, Kong L, Bentley CM, Liu W, et al. High temperatures enhanced acute mortality effects of ambient particle pollution in the “oven” city of Wuhan, China. Environ Health Perspect 2008; 116(9):1172–1178.
  • Ren C, Williams GM, Tong S. Does particulate matter modify the association between temperature and cardiorespiratory diseases? Environ Health Perspect 2006; 114(11):1690–1696.
  • Hansel NN, Breysse PN, McCormack MC, Matsui EC, Curtin-Brosnan J, Williams DL, et al. A longitudinal study of indoor nitrogen dioxide levels and respiratory symptoms in inner-city children with asthma. Environ Health Perspect 2008; 116(10):1428–1432.
  • McCormack MC, Breysse PN, Hansel NN, Matsui EC, Tonorezos ES, Curtin-Brosnan J, et al. Common household activities are associated with elevated particulate matter concentrations in bedrooms of inner-city Baltimore pre-school children. Environ Res 2008; 106(2):148–155.
  • Paulin LM, Diette GB, Scott M, McCormack MC, Matsui EC, Curtin-Brosnan J, et al. Home interventions are effective at decreasing indoor nitrogen dioxide concentrations. Indoor Air 2014; 24(4):416–424.
  • Viggers H, Howden-Chapman P, Ingham T, Chapman R, Pene G, Davies C, et al. Warm homes for older people: aims and methods of a randomised community-based trial for people with COPD. BMC Publ Health 2013; 13:176.

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