Does breathing polluted air increase the risk of upper gastrointestinal bleeding from peptic ulcer disease?
Authors: Gilaad G Kaplan
Journal: The Lancet Planetary Health (2017)

Linwei Tian and colleagues1Tian L Qiu H Sun S Tsang H Chan K Leung WK Association between emergency admission for peptic ulcer bleeding and air pollution: a case-crossover analysis in Hong Kong's elderly population.Lancet Planet Health. 2017; 1: e74-e81Summary Full Text Full Text PDF Scopus (31) Google Scholar did a study to assess the effect of acute exposure to air pollution on emergency department presentation for upper gastrointestinal bleeding from peptic ulcer disease in elderly individuals (aged 65 years or older) living in Hong Kong. The analysis showed that the 5-day average exposure of nitrogen dioxide (NO2) was associated with an increased risk in emergency room visits for upper gastrointestinal bleeding secondary to peptic ulcer disease. In cities, NO2 is most often a byproduct of combustion of fossil fuels from automobiles.2Brunekreef B Holgate ST Air pollution and health.Lancet. 2002; 360: 1233-1242Summary Full Text Full Text PDF PubMed Scopus (3010) Google Scholar The results of Tian and colleagues' study are novel and provocative. They raise an important question: can the air we breathe trigger bleeding from an ulcer in the upper gastrointestinal tract? Upper gastrointestinal bleeding secondary to peptic ulcer disease is a common life-threatening medical condition.3Quan S Frolkis A Milne K et al.Upper-gastrointestinal bleeding secondary to peptic ulcer disease: incidence and outcomes.World J Gastroenterol. 2014; 20: 17568-17577Crossref PubMed Scopus (50) Google Scholar However, historically, peptic ulcer disease was an uncommon ailment. The rise in the incidence of peptic ulcer disease occurred in the mid-1800s.4Duggan JM Duggan AE The possible causes of the pandemic of peptic ulcer in the late 19th and early 20th century.Med J Aust. 2006; 185: 667-669PubMed Google Scholar At that time, studies in North America and Europe recognised peptic ulcer disease as an important cause of mortality. The incidence of peptic ulcer disease peaked in the latter part of the 19th century and into the early 1900s. However, by the mid-1900s the incidence of peptic ulcer disease began to decrease and subsequently stabilise in regions across the world.4Duggan JM Duggan AE The possible causes of the pandemic of peptic ulcer in the late 19th and early 20th century.Med J Aust. 2006; 185: 667-669PubMed Google Scholar, 5Sung JJ Kuipers EJ El-Serag HB Systematic review: the global incidence and prevalence of peptic ulcer disease.Aliment Pharmacol Ther. 2009; 29: 938-946Crossref PubMed Scopus (264) Google Scholar The fluctuation in the incidence of peptic ulcer disease over the past two centuries has been retrospectively explained, in part, by the two most common risk factors of peptic ulcer disease: non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori.6Laine L Nonsteroidal anti-inflammatory drug gastropathy.Gastrointest Endosc Clin N Am. 1996; 6: 489-504PubMed Google Scholar, 7Perez-Aisa MA Del Pino D Siles M Lanas A Clinical trends in ulcer diagnosis in a population with high prevalence of Helicobacter pylori infection.Aliment Pharmacol Ther. 2005; 21: 65-72Crossref PubMed Scopus (73) Google Scholar The first NSAID was aspirin, which was introduced in 1899 and contributed to the cause of peptic ulcer disease thereafter. H pylori is a bacterium of the stomach that is a major contributor to the incidence of peptic ulcer disease, with some researchers postulating that a virulent strain led to a spike in mortality in the 1800s.4Duggan JM Duggan AE The possible causes of the pandemic of peptic ulcer in the late 19th and early 20th century.Med J Aust. 2006; 185: 667-669PubMed Google Scholar However, peptic ulcer disease often manifests in individuals without a history of NSAID exposure and who are not colonised with H pylori. Other unknown risk factors of peptic ulcer disease are yet to be discovered. Industrialisation of societies in the 1800s led to urbanisation of populations into cities who often lived in proximity to the factories that polluted the air. The human health impacts of air pollution exposure are well known, with the earliest studies noting its effect on respiratory system.2Brunekreef B Holgate ST Air pollution and health.Lancet. 2002; 360: 1233-1242Summary Full Text Full Text PDF PubMed Scopus (3010) Google Scholar Over the past few decades, several studies have also shown the multi-organ effects of air pollution: breathing air pollution does not limit its effects on health to the lungs.1Tian L Qiu H Sun S Tsang H Chan K Leung WK Association between emergency admission for peptic ulcer bleeding and air pollution: a case-crossover analysis in Hong Kong's elderly population.Lancet Planet Health. 2017; 1: e74-e81Summary Full Text Full Text PDF Scopus (31) Google Scholar Over the past decade epidemiological studies have documented that air pollution is associated with the development of gastrointestinal diseases such as inflammatory bowel diseases and appendicitis.8Kaplan G Air pollution and the inflammatory bowel diseases.Inflamm Bowel Dis. 2011; 17: 1146-1148Crossref PubMed Scopus (8) Google Scholar, 9Kaplan GG Dixon E Panaccione R et al.Effect of ambient air pollution on the incidence of appendicitis.CMAJ. 2009; 181: 591-597Crossref PubMed Scopus (91) Google Scholar, 10Kaplan GG Tanyingoh D Dixon E et al.Ambient ozone concentrations and the risk of perforated and nonperforated appendicitis: a multicity case-crossover study.Environ Health Perspect. 2013; 121: 939-943PubMed Google Scholar Basic scientific studies have shown that air pollution might mediate gastrointestinal effects by exacerbating inflammation in the intestines and by altering the composition of the intestinal microbiome.11Kish L Hotte N Kaplan GG et al.Environmental particulate matter induces murine intestinal inflammatory responses and alters the gut microbiome.PLoS One. 2013; 8: e62220Crossref PubMed Scopus (175) Google Scholar, 12Kaplan GG Szyszkowicz M Fichna J et al.Non-specific abdominal pain and air pollution: a novel association.PLoS One. 2012; 7: e47669Crossref PubMed Scopus (50) Google Scholar Consequently, air pollution could conceivably promote upper gastrointestinal bleeding from peptic ulcer disease by influencing the inflammatory pathways in the stomach or possibly interacting with pathogens of upper gastrointestinal tract such as H pylori. My research team led one of the earliest studies to explore this hypothesis.13Quan S Yang H Tanyingoh D et al.Upper gastrointestinal bleeding due to peptic ulcer disease is not associated with air pollution: a case-crossover study.BMC gastroenterology. 2015; 15: 131Crossref PubMed Scopus (18) Google Scholar We did a multi-city (Calgary and Edmonton, AB, Canada) time-stratified case crossover study to assess the effects of NO2, sulfur dioxide, carbon monoxide, and ozone, as well as particulate matter with aerodynamic diameters of 10 μm or less and 2·5 μm or less. We assessed several models that included different exposure periods, and stratification by age (younger than and older than 70 years), and sex. Although sporadic significant associations were detected, they were not consistent across both cities. Thus, we concluded that these associations were spurious and that a strong signal connecting air pollution exposure with upper gastrointestinal bleeding secondary to peptic ulcer bleeding was not present.13Quan S Yang H Tanyingoh D et al.Upper gastrointestinal bleeding due to peptic ulcer disease is not associated with air pollution: a case-crossover study.BMC gastroenterology. 2015; 15: 131Crossref PubMed Scopus (18) Google Scholar However, our negative study does not refute the findings by Tian and colleagues,1Tian L Qiu H Sun S Tsang H Chan K Leung WK Association between emergency admission for peptic ulcer bleeding and air pollution: a case-crossover analysis in Hong Kong's elderly population.Lancet Planet Health. 2017; 1: e74-e81Summary Full Text Full Text PDF Scopus (31) Google Scholar because important differences between the studies could lead to differential results. Our study populations were distinct, with the majority of individuals in our study being Caucasian in Alberta, and in Tian and colleagues' study being Asian in Hong Kong. Additionally, exposure to air pollution is different between cities. For example, the average daily concentration of NO2 in Alberta was 23·9 μg/m3,13Quan S Yang H Tanyingoh D et al.Upper gastrointestinal bleeding due to peptic ulcer disease is not associated with air pollution: a case-crossover study.BMC gastroenterology. 2015; 15: 131Crossref PubMed Scopus (18) Google Scholar whereas the average daily concentration in Hong Kong was nearly double at 55·7 μg/m3.1Tian L Qiu H Sun S Tsang H Chan K Leung WK Association between emergency admission for peptic ulcer bleeding and air pollution: a case-crossover analysis in Hong Kong's elderly population.Lancet Planet Health. 2017; 1: e74-e81Summary Full Text Full Text PDF Scopus (31) Google Scholar A threshold level of NO2 may be necessary to trigger a health event such as bleeding from an ulcer. These differences highlight the need to assess the health effects of air pollution in different regions and study populations. So could air pollution be a novel risk factor for upper gastrointestinal bleeding secondary to peptic ulcer disease in Asian populations? Although it is an intriguing hypothesis, we must consider important limitations of air pollution research. Studies using fixed-site monitoring data rather than personal monitoring data are subject to misclassification of the exposure because fixed site monitors do not account for individual mobility that affect exposure. Although, this typically results in non-differential exposure misclassification that underestimates the risk of air pollution.14Schwartz J The effects of particulate air pollution on daily deaths: a multi-city case crossover analysis.Occup Environ Med. 2004; 61: 956-961Crossref PubMed Scopus (113) Google Scholar Additionally, fixed-site monitors average the exposure of air pollution in a region, thereby not accounting for the geospatial variation of air pollution levels in a region.14Schwartz J The effects of particulate air pollution on daily deaths: a multi-city case crossover analysis.Occup Environ Med. 2004; 61: 956-961Crossref PubMed Scopus (113) Google Scholar Future studies could incorporate land use regression models to assess the interaction of spatial differences of air pollution across a city along with acute temporal variation.15Bertazzon S Johnson M Eccles K Kaplan GG Accounting for spatial effects in land use regression for urban air pollution modeling.Spat Spatiotemporal Epidemiol. 2015; 14–15: 9-21Crossref PubMed Scopus (58) Google Scholar Misclassification of the cases is also an important consideration. The study used International Classification Disease (ICD-9) codes to identify patients presenting to the emergency department with upper gastrointestinal bleeding secondary to peptic ulcer disease. All studies relying on administrative databases unfortunately include false-positive cases and miss true cases.16Molodecky NA Panaccione R Ghosh S Barkema HW Kaplan GG Alberta Inflammatory Bowel Disease ConsortiumChallenges associated with identifying the environmental determinants of the inflammatory bowel diseases.Inflamm Bowel Dis. 2011; 17: 1792-1799Crossref PubMed Scopus (72) Google Scholar Furthermore, in case crossover studies, cases serve as their own controls. Because within-individual comparisons are being made, confounding from time-independent risk factors (eg, colonization by H pylori) are controlled for by the design of the study. However, residual confounding might occur with time-dependent factors such as NSAIDs, whose use might vary day by day.14Schwartz J The effects of particulate air pollution on daily deaths: a multi-city case crossover analysis.Occup Environ Med. 2004; 61: 956-961Crossref PubMed Scopus (113) Google Scholar Air pollution studies can also be limited by multiple comparison errors because associations are explored with multiple pollutants and across several exposure time periods. Consequently, the probability of observing statistically significant findings by chance alone is increased.14Schwartz J The effects of particulate air pollution on daily deaths: a multi-city case crossover analysis.Occup Environ Med. 2004; 61: 956-961Crossref PubMed Scopus (113) Google Scholar Tian and colleagues attempted to account for chance findings by including positive control cohorts of respiratory and circulatory diseases that are well known to be affected by acute elevation in air pollution exposures. Nonetheless, replication studies are necessary in other cities in Asia with similar levels of air pollution. Tian and colleagues' Article suggests that upper gastrointestinal bleeding secondary to peptic ulcer disease might be triggered by exposure to high levels of NO2 in elderly patients living in Hong Kong. If these findings are corroborated in the future, then the association between air pollution and peptic ulcer disease would add to a growing body of scientific literature suggesting that air pollution can harm the gastrointestinal tract.17Beamish LA Osornio-Vargas AR Wine E Air pollution: an environmental factor contributing to intestinal disease.J Crohns Colitis. 2011; 5: 279-286Summary Full Text Full Text PDF PubMed Scopus (136) Google Scholar Moreover, air pollution is a modifiable and avoidable risk factor. If air pollution promotes the onset of upper gastrointestinal bleeding secondary to peptic ulcer disease, then policies to reduce emissions could be preventive policies. Additionally, clinicians can warn elderly patients at risk of peptic ulcer disease to avoid outdoor exposures on days of high NO2 levels. I declare no competing interests. Association between emergency admission for peptic ulcer bleeding and air pollution: a case-crossover analysis in Hong Kong's elderly populationShort-term elevation in ambient NO2 might trigger peptic ulcer bleeding events and increase the risk of emergency admissions for peptic ulcer bleeding in Hong Kong's elderly population. These findings strengthen the hypothesis that air pollution affects not just cardiopulmonary diseases, but also certain diseases of the digestive system. Full-Text PDF Open Access