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.