Continuous PPI Use Is Associated With Acute Gastroenteritis during Winter Periods
JAMA Network: November, 2019
Proton pump inhibitors (PPIs) are
drugs widely prescribed to reduce gastric acidity. Although they are considered
globally safe, observational studies have reported significant
adverse effects associated with their long-term use, such as
osteoporotic-related fractures, vitamin B12 deficiency, kidney
disease, or infections, particularly pulmonary and digestive tract infections.
An increased risk of acute
bacterial enteric infections such as isolated and recurrent Clostridium
difficile infections has been reported among patients receiving proton
pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral
origin associated with continuous PPI exposure has been less studied.
Objective: To
investigate the association between continuous PPI therapy and AGE occurrence
during winter epidemic periods when the circulation of enteric viruses is the
highest.
TAKE-HOME MESSAGE
Question Is
continuous use of proton pump inhibitors (PPIs) associated with an increased
risk of acute gastroenteritis during periods of highest circulation of enteric
viruses?
Findings In
this matched cohort study comparing 233 596 patients receiving continuous PPI
therapy with 626 887 patients not receiving PPI therapy, the adjusted relative
risk of occurrence of acute gastroenteritis during periods of highest
circulation of enteric viruses was 1.81 times higher in patients receiving
continuous PPI therapy than in those not receiving PPI therapy.
Meaning Continuous
exposure to PPI therapy among individuals aged 45 years and older was
associated with an increased risk of developing acute gastroenteritis (enteric
viral infections) during periods of highest circulation of enteric viruses.
PPI Use and the Risk of Viral
Gastroenteritis
Here is a summary of the effects
based on growing research suggesting harm with chronic PPI use.
No acid for
absorption. Acid is needed to absorb iron, B vitamins, magnesium,
and calcium. Malabsorption of these nutrients can lead to negative
consequences, such as an increased rate of fracture (calcium malabsorption).
No acid for
digestion. An acidic environment is needed to activate protease to
help digest protein. The inability to digest protein exposes the gut-associated
lymphoid tissue (GALT) to more foreign proteins, triggering immune reactions
that may explain the rise in conditions, such as eosinophilic esophagitis and
non-celiac gluten sensitivity.
No acid for
lysosome function. Lysosomes are the chimney sweeps of the
endothelium. Each lysosome has a proton pump, and, if turned off, is no longer
able to lyse. This is one hypothesis that may help explain the higher rates of
heart disease, kidney disease, and mortality rates with long-term PPI use.
No acid for defense. Acid is needed to prevent infection, and use of PPIs may explain the higher rates of community-acquired pneumonia, C. diff infection, small bowel bacterial overgrowth, and, in this study, viral gastroenteritis (VGE).
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Importance: An
increased risk of acute bacterial enteric infections has been reported among
patients receiving proton pump inhibitor (PPI) therapy. The risk of acute
gastroenteritis (AGE) of viral origin associated with continuous PPI exposure
has been less studied.
Objective: To
investigate the association between continuous PPI therapy and AGE occurrence
during winter epidemic periods when the circulation of enteric viruses is the
highest.
Design, setting, and
participants: A matched cohort study was performed using a
prospectively collected drug dispensing database from a large panel of
community pharmacies in continental France. All patients recorded in the
database during the 2015 to 2016 winter season, with documented age, sex, and
use of an identifiable regular panel pharmacy, were eligible for the study.
Each patient exposed to continuous PPI therapy was matched to 3 unexposed
patients, according to year of birth, sex, and identifiable regular panel
pharmacy. Analyses were performed between January 2017 and December 2018.
Exposure: Continuous
PPI use during the 2015 to 2016 AGE winter epidemic.
Main outcomes and measures: The
occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter
epidemic was the main outcome. Episodes of AGE were identified using a
previously validated algorithm based on drug dispensing data. Relative risks of
AGE were estimated using a multivariable log-binomial model adjusted for age,
sex, and treatments for chronic conditions.
Results: There were
233 596 patients receiving PPI therapy (median [interquartile range] age, 71
[62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI
therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female)
included in the analyses. At least 1 AGE epidemic episode was identified in
3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not
receiving PPI therapy. The adjusted relative risk of AGE for those receiving
PPI therapy was 1.81 for all ages considered, 1.66 among those aged 45 to 64
years, 2.19 among those aged 65 to 74 years, and 1.98 among those aged 75 years
and older.
Conclusions and relevance: Continuous
PPI therapy was associated with an increased risk of developing AGE during
periods of highest circulation of enteric viruses. These findings support the
hypothesis that PPI use is associated with an increased risk of enteric viral
infections.
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