From the Journals

Air pollution linked to increased IBS incidence



Increased levels of air pollution were linked to a slight uptick in new diagnoses of irritable bowel syndrome (IBS) in California residents, according to an ecologic study published in Clinical Gastroenterology and Hepatology.

“These data provide support for the role of environmental pollutants, especially air pollutants, in the development of IBS,” Philip N. Okafor, MD, MPH, of Stanford (Calif.) University, and colleagues wrote. “In contrast, we found no significant relationships between the seven environmental exposures and the ZIP-code level incidence of functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis.”

Smoking chimneys of a power plant polluting the air Thomas321/iStock/Getty Images Plus

John I. Allen MD, MBA, a retired clinical professor medicine at the University of Michigan, Ann Arbor, said the findings were somewhat surprising, but he was impressed with the “fascinating and well-constructed” study.

“The differentiation between GI disorders that are linked to environmental pollutants [such as IBS] and those that are not [such as inflammatory bowel disease and eosinophilic esophagitis] is quite interesting and lends further credibility to the conclusions,” Dr. Allen said in an interview. “While definitive causal conclusions cannot rest on retrospective, population-level, studies alone, this extraordinarily detailed analysis should prompt further studies investigating root causes for these correlations,” such as gut epithelial changes secondary to ingested pollutants, for example.

The researchers noted that an “epidemiological shift in gastrointestinal diseases is underway,” with increasing incidence of inflammatory bowel disease (IBD), eosinophilic esophagitis (EoE), and disorders related to gut-brain interaction.

“While the underlying causes of this shift remain unclear, the association with industrialization suggests that environmental triggers may play a role in disease pathogenesis,” the authors wrote. Data to support that possibility, however, are lacking, Dr. Okafor said in an interview.

One potential mechanism to explain such an association could be local or systemic inflammation resulting from pollution exposure and leading to tissue injury. Others could include alterations in the gut microbiome or direct damage to the mucosal epithelial barrier from pollutants, which then results in epithelial cell death and subsequently increased intestinal permeability.

To explore whether any such associations exist, the researchers analyzed the incidence of IBS, functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis in different California ZIP codes with regard to each area’s levels of seven different pollutant markers. They used claims data for patients with Optum insurance to identify new diagnoses by ZIP code for nearly 2.9 million adult patients between 2009 and 2014 (ICD-9 era) and nearly 2.5 million patients between 2016 and 2019 (ICD-10 era). Preexisting diagnoses were excluded. The analysis included 1,365 different ZIP codes.

The measures of pollutants they assessed included the following: ozone, particulate matter less than 2.5 mcm (PM2.5), diesel emissions, drinking water contaminants, pesticides, toxic releases from industrial facilities, and traffic density. They used shoulder dislocations as a negative control in comparing incidence, and they adjusted the analysis to account for socioeconomic markers, patient-level sampling estimates, and county-level fixed effects.

Socioeconomic markers included not only income and race/ethnicity but also health insurance status, educational level, proportion of owner-occupied homes, median house prices, and the proportion of households receiving food stamps or meeting criteria for food insecurity. Given the number of potential confounders, the authors also made statistical adjustment (Bonferroni correction) to account for many multiple comparisons and reduce the likelihood of inflated statistical significance for any one finding.

The researchers found that the incidence of IBS per ZIP code was associated with the levels of PM2.5 and industrial airborne toxic releases during both time periods. An increase of 1 mcg/m3 of PM2.5 or additional 1% in toxic releases correlated with an additional 0.02 cases of IBS per 100 person-years (adjusted incidence rate ratios approximately 1.03 for IBS associated with both pollutants during both time periods).

”These associations were maintained across extensive adjustment for residual confounding and sensitivity analyses,” the authors added.

That increase in the total incidence of IBS in this study is very minor, but it’s not known how high environmental toxin levels may become in the future, Rishi D. Naik, MD, MSCI, assistant professor of medicine at Vanderbilt University Medical Center’s Esophageal Center in Nashville, Tenn., said in an interview.

“Though the increase on an absolute number currently is trivial, the percent increase if toxin releases dramatically increased can have an impact on our patients,” Dr. Naik said. “Public health policies should be in place to monitor these changes and future studies should be done prospectively to understand if this relationship is linear or has upper limits for absolute increases of incidence of IBS.”

Like the authors, however, Dr. Naik cautioned that these findings do not show causation and require further investigation. At least one potential confounder not considered in the study, Dr. Naik said, is that an increase in pharmacological therapy for IBS – which requires proper coding for insurance approval – increased during the time period as well.

Unlike EoE and IBD, IBS lacks objective pathological biomarkers for diagnosis that allow verification that “these patients truly had the disease versus were labeled with the diagnosis based on symptoms and need to obtain therapy,” Dr. Naik said. “Adjusting for prescription use and separating based on IBS-diarrhea and IBS-constipation would also help with the etiologies.”

Although the researchers also identified an association between IBS incidence and both traffic density and drinking water contaminants, these did not reach statistical significance after adjustment for multiple comparisons. Similarly, diesel particulate matter emissions were associated with functional dyspepsia and IBS until the statistical correction for multiple comparisons. None of the other conditions’ incidence was associated with any pollutant measured included in the study.

“It is important to highlight that our findings are not proof that environmental pollution causes irritable bowel syndrome but provide evidence to support further research on this topic,” Dr. Okafor said. “Our results are hypothesis generating. It would be helpful to better collect environmental hazards at a population level in a more systematic, reproducible manner so better ecological studies can be performed in the future to close knowledge gaps and improve our understanding of these diseases.”

Dr. Okafor said it would be valuable to explore potential associations between GI diseases and environmental pollutants in other states, but it would depend on how thorough data collection of pollutants is in other states. “Our study is the first step to exploring these interactions,” he noted.

“Though interesting data, the lack of patient-level data, dose response, treatment with an intervention, and the use of claims data prevent generalizability to larger populations both from a geographic perspective and also from ones based on gender, ethnicity, or socioeconomic factors,” Dr. Naik said. “Prospective studies showing incidence changes and interventions based on pollution control would help support their findings.”

Future studies could also further break down IBS incidence into IBS-diarrhea versus IBS-constipation and consider antibiotic exposure, treatment for symptoms, and symptom resolution, Dr. Naik said. “To support their association, patient-level trafficking of those who move to low and high rates of PM2.5 would help determine if individual symptoms improve with the sole intervention of geographic location,” he added.


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