DISCUSSION
In this study, people with constipation had a 1.91-fold higher risk for developing asthma than non-constipated individuals, regardless of age, gender, comorbidities or medications. As far as we know, this is the largest epidemiological research by using a nationwide longitudinal population-based dataset to expound the association between constipation and asthma. This relationship might be of pathophysiological and clinical importance. Our findings emphasize the considerably higher risk of asthma in individuals with constipation. Constipation might be influential in the development of asthma. Physicians should take care about the possibility of asthma in patients with constipation. Correspondingly, constipated patients should be informed of the probable risk of asthma and be offered with applicable management for asthma as required. Our findings further highlight the importance of maintaining fair bowel habits in order to avoid constipation, which could in turn mitigate risk of asthma.
We also observed that the risk of developing asthma was significantly increased in patients with hypertension, chronic obstructive pulmonary disease (COPD), chronic liver disease, and autoimmune disease. Most of these comorbidities, such as COPD or autoimmune disease, were connected to chronic inflammation, which could contribute to release of serum cytokines and activate T-cell response. In addition, we further extended to suggest that constipation severity is associated with the risk of asthma. There seemed to be a dose-dependent relationship between constipation and subsequent risk of asthma, which strengthened our hypothesis.
The pathophysiological mechanisms underlying the association between constipation and asthma remain ambiguous. Currently, there has been considerable studies conducted between intestinal microbiota and asthma.[17-21] The extended “’hygiene hypothesis” discloses that the initial composition of the infant gut microflora plays a vital role in the development of atopic diseases.[22-24] Another research in United Kingdom, which analyzed the gut microbiome of the people with asthma, showed that there were abundant with Clostridiums spp. whereas Faecalibacterium prausnitzii and Bacteroides stercoris were depleted in individuals with asthma.[25] Similarly, some researches have suggested that alterations in the intestinal microflora would lead to constipation and constipation-related symptoms.[5, 7] In contrast to the healthy individuals, constipated patients had relatively higher amount of potentially pathogenic microbes, such as Clostridiums spp. and Pseudomonas aeruginosa, and relatively lower amount of Bacteroides spp., Bifidobacterium, and Lactobacillus.[26] These alternates in the intestinal surroundings could affect bowel motility by the active materials. Some studies exhibited that microbial-derived metabolites, mainly short-chain fatty acids (SCFAs), acted as pivotal drivers of T-cell subset activity and proliferation.[27] Furthermore, it has been disclosed that production of bowel microbial SCFAs could down-regulate proinflammatory reactions at the area of allergen insult.[28] Moreover, SCFAs might influence bowel motility via stimulating the contraction of colonic smooth muscles, thereby assisting to present or relieve constipation.[29, 30] By contrast, immune homeostasis would be devastated by proinflammatory dietary type, or ”Westernized dietary style”, which might be described as being low in fiber and high in fat, changing the intestinal microbiota, and leading to decrease SCFAs production. Hence, less fiber intake, such as fewer fresh fruits, in patients with constipation might be also pivotal role in developing atopy.[31, 32] Organizing the presently available corroboration suggests that the gut microbiota might be a key mechanistic part linking asthma and constipation. It is not known how constipation influence the configuration of the intestinal microflora and how applicable this condition is to asthma. Nevertheless, constipation appears to be the predisposing point for asthma. Further comprehensive metabolomic and metagenomic analyses of the gut microbiome in constipated individuals are warranted to clarify the potential mechanisms underlying these connections.
The major advantages of this study were the relatively large sample size and long follow-up period. An integrated past history of used medical services was accessible for all cases. Therefore, there was slightest selection, information, and recall bias. As such, it was feasible to properly examine our hypothesis. However, there some potential limitations existed in our study. First, the NHIRD does not include data on covariates, such as social adversity, personal lifestyle, family history, laboratory data and environmental factors. Although we adjusted for several comorbidities and matched propensity scores, these unmeasured confounding factors could have influenced our results. Second, the diagnoses of asthma and constipation were totally dependent on the ICD-9 codes in the administrative dataset. We did not undergo a review of the patients’ medical documents so that it was not probable to check the accuracy of diagnoses, and thus there might have some misclassifications existed. It is worth noting, however, that any misclassifications were more probably to be random, and connections were often underestimated rather than overestimated. Besides, clinical judgment might be different among clinicians, and so diagnoses would not have been consistent, which might have affected the validity. However, Taiwan’s National Health Insurance administration monitors the accuracy of the claims data to prevent violations. Finally, it keeps unclear as to if the findings of our study may be extrapolated to other ethnic groups, as the majority of our subjects were Taiwanese. Further clinical research should include other nationalities and ethnicities to define the generalizability of the relationship observed herein.