Pneumonia has many causes—ranging from bacteria and viruses to fungi and aspiration of gastric contents. For the purposes of this paper, I am focusing on whether heartburn medications increase the risk of developing pneumonia. If they do, which causes the greater risk of pneumonia: heartburn or the medication preventing it?

For patients with a pulmonary disease, pneumonia can be a serious or even life-threatening development, particularly among the elderly patient population. Pneumonia decreases gas exchange, because inflammation causes fluid from the pulmonary capillaries to leak into the alveoli. The body’s immune system further complicates the situation by sending white blood cells—primarily leukocytes—into the infected area. The fluid buildup can lead to consolidation, impeding gas exchange across a thickened alveolar-capillary membrane. Increased bronchial secretions are also a problem. If the effusion gets bad enough, the alveoli can collapse, resulting in atelectasis, which leads to pulmonary shunting and further decreases gas exchange.1

Aspiration Pneumonitis

Gastric fluid with a pH of 2.5 or less can cause a serious and even fatal type of pneumonia called aspiration pneumonitis. If left untreated, it can lead to acute respiratory distress syndrome (ARDS).1 Tachycardia, dyspnea, and cyanosis are often associated with this type of pneumonia. Aspiration of gastric contents (versus aspiration of food) causes initial hypoxemia. “Such aspiration occurs in patients who receive antacids or proton pump inhibitors. If the pH is low … parenchymal damage may occur, with inflammation, edema, and hemorrhage.”1

Gastroesophageal reflux disease (GERD) is the regurgitation of stomach contents into the esophagus.1 GERD interrupts peristalsis in the distal esophagus, which can allow for aspiration. “GERD is three times more prevalent in patients with asthma than in other patients.”1

In February 2011, Eom and colleagues published the results of a study on whether heartburn medications increased the risk of pneumonia.2 They concluded, “Use of a proton pump inhibitor or histamine2 receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.”2

According to the authors, their conclusion was based on the results of more than 2,000 articles as well as five case-control studies, three cohort studies, and 23 randomized controlled trials (out of more than 8,000 randomized controlled trials).

The authors conclude, “Our results suggest that the use of acid-suppressive drugs is associated with an increased risk of pneumonia. Given the widespread use of acid-suppressive drugs, the implications of this increased risk are serious. … 24 or 25 cases of pneumonia can be expected for every 1,000 recipients of these drugs. This translates to about one case of pneumonia for every 200 in-patients treated with acid-suppressive drugs.”2

The study found a higher-than-normal dose of proton pump inhibitors was more strongly associated with a higher risk of pneumonia than the normal dose. It also determined that longer exposure to acid-suppressing drugs reduced the increased risk of pneumonia. It seemed to indicate the increased risk primarily occurred during the first 6 months of taking the drugs and was highest during the first 7 days.

Is There a Link?

Heartburn medications are the second most popular type of prescription in the United States, garnering more than $25 billion annually.3 Linking them to an increased risk of pneumonia in at-risk patients could have a significant fiscal impact on the pharmacology industry if prescription rates dropped as a result.

In 2006, The Canadian Journal of Gastroenterology published a position statement by the Canadian Association of Gastroenterology (CAG) Clinical Affairs Committee about the linkage of acid-suppressants and pneumonia. They did not find a statistically significant link between the medication and an increased risk of pneumonia.4

The committee writes, “Reviewing 60 such studies published over the last 13 years, only seven studies have reported on ‘respiratory infection’ as a secondary outcome. A review of these studies by the Canadian Association of Gastroenterology shows that three of seven have reported a numerically higher incidence of respiratory infection in the group receiving PPIs [proton pump inhibitors], while in the other four, the incidence was higher in the placebo group. The total number of patients in the seven studies was 2,271 with an overall incidence of respiratory infection of 4.3% in the group receiving PPIs and 4.9% in the group receiving placebo. … the data available until recently thus do not appear to have demonstrated a link between ASDs [acid-suppressive drugs] and pneumonia, at least in the ambulatory patient population.”4

The CAG article also cited the tendency for more immediate use of heartburn medication to create a higher risk than long-term heartburn medication users, which matches the Eom et al study results.

“[T]he risk of CAP [community-acquired pneumonia] was reduced … when one compared persons diagnosed with CAP at the time of ASD use with a group of patients diagnosed more than 30 days after their discontinuation.”4

These authors concluded that it would be “premature” to allow studies to “heavily influence prescribing practices. The risk to benefit ratio appears to be largely in favor of using ASDs for conditions in which efficacy has been demonstrated.”4

It should be noted that AstraZeneca Canada Inc, Ferring Pharmaceuticals, Janssen-Ortho Inc, McNeil Consumer Healthcare, and Rivex Pharma Inc were listed as supporters for the study. The authors also disclosed that four of the six listed committee members had received consultant fees, research grants, and/or clinical trial funding from two of the five industry sponsors.

Pneumonia Risk Increased

In February 2009, Roughead and colleagues from the University of South Australia published an article citing a “small but significant increased risk of hospitalization for pneumonia” among 185,533 veterans more than 65 years old who were prescribed proton pump inhibitors between January 2002 and December 2006. The researchers concluded that while the increased risk was small, “the prevalent use of PPIs means that many people could be affected.”5

Eurich et al, from the Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Canada, presented results of a study that looked at linking antacid use with recurrent pneumonia—a new twist. The investigators found a definite link in a patient population that was 65 years old or older, had survived pneumonia, and had left the hospital with a prescription for antacids.

They write, “During 5.4 years of follow-up, 248 recurrent pneumonia cases were matched with 2,476 controls. Overall, 71 of 608 (12%) current PPI/H2 users had recurrent pneumonia, compared with 130 of 1,487 (8%) nonusers.…”6

They, too, urged caution in prescribing antacids to at-risk patients. “Acid-suppressing drug use substantially increased the likelihood of recurrent pneumonia in high-risk elderly patients. The association was confined to patients initiating PPI/H2s after hospital discharge. Our findings should be considered when deciding to prescribe these drugs in patients with a recent history of pneumonia.”6

In October 2004, the results of yet another study supporting the linkage between heartburn medications and an increased risk of pneumonia were published in the Journal of the American Medical Association.

More than 360,000 people were studied between January 1995 and December 2002. Laheij and colleagues from the Department of Gastroenterology at the University Medical Center of Nijmegen, Netherlands, found a definite link.

“The incidence rates of pneumonia in non-acid-suppressive drug users and acid-suppressive drug users were 0.6 and 2.45 per 100 person-years, respectively. … Current use of gastric acid-suppressive therapy was associated with an increased risk of community-acquired pneumonia.”7

Conclusion

There are dozens of additional studies, but most of them seem to support the idea that an increased risk of pneumonia exists among patients taking acid-suppressing drugs—especially during the first 6 months of usage.

In light of the fact that the risk seems to decrease the longer a patient is taking antacid medication, the logical response would be to weigh the increased risk caused by the drugs against the risk of heartburn itself causing aspiration pneumonitis.

Depending on the source, aspiration pneumonia accounts for between 5% and 18% of all cases of pneumonia.8 Again, depending on the source, mortality rates for aspiration pneumonitis in the elderly can range from 10% to 70%.9

It seems, therefore, that there can be a fairly high mortality rate in certain at-risk populations from aspiration pneumonia. There is also an increased risk of developing the pneumonia when the patient is within the first 6 months of an antacid prescription. I can see where caution is needed, but I also see where the risk from the drugs may be less than the risk of dying from heartburn-induced aspiration pneumonitis among the elderly population with a pulmonary disorder. Using antacids combined with stringent observation and immediate treatment of any cold- or flu-like symptoms among this patient population may be the logical middle ground.


Alicia Castelli is a recent graduate of Bowling Green State University, Bowling Green, Ky, with an associate degree in applied science. She works at Fairview Hospital, a Cleveland Clinic community hospital in Cleveland, and will be sitting for her board exams soon. For further information, contact [email protected]

References
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  2. Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183:310-9.
  3. Heartburn Drugs May Raise Pneumonia Risk. One of every 200 hospital patients taking acid-suppressing meds will develop pneumonia, study finds. Available at: www.businessweek.com/lifestyle/content/healthday/647700.html. Accessed February 16, 2012.
  4. Sinclair P, Barkun A, CAG Clinical Affairs Committee. Community-acquired pneumonia and acid-suppressive drugs: position statement. Can J Gastroenterol. 2006;20:119–21.
  5. Roughead EE, Ramsay EN, Pratt NL, Ryan P, Gilbert AL. Proton-pump inhibitors and the risk of antibiotic use and hospitalisation for pneumonia. Med J Aust. 2009;190:114-6.
  6. Eurich DT, Sadowski CA, Simpson SH, Marrie TJ, Majumdar SR. Recurrent community-acquired pneumonia in patients starting acid-suppressing drugs. Am J Med. 2010;123:47-53.
  7. Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292:1955-60.
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  9. DeLegge MD. Aspiration pneumonia: incidence, mortality, and at-risk populations. J Parenter Enteral Nutr. 2002;26(Suppl):S19-24.