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MEDICAL BIOLOGY: PNEUMONIA AND GASTRIC-ACID SUPPRESSIVE DRUGS

The following points are made by R.J. Laheij et al (J. Am. Med. Assoc. 2004 292:1955):

1) Gastrointestinal symptoms are common: annually, 20% to 40% of the general population has at least one episode of dyspepsia or gastroesophageal reflux disease, and 5% consult a general practitioner for these complaints.(1-2) The most effective treatment strategy for these symptoms in primary care is reduction of gastric acid secretion, which can be achieved by using H2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs).(3) Currently, a common approach in western countries is to prescribe acid-suppressive drugs for upper gastrointestinal tract symptoms without suspicion of a malignancy and to refer nonresponders for gastrointestinal endoscopy.(4) The consequence of this policy is that acid-suppressive drugs are among the most frequently prescribed drugs, whereas their use is not without risk.

2) H2-receptor antagonists and PPIs increase susceptibility to infections by increasing gastric pH.(5) Intragastric acidity constitutes a major nonspecific defense mechanism of the stomach to ingested pathogens. In normal gastric juice with a pH below 4, most pathogens are promptly killed, whereas they survive in hypochlorhydric to achlorhydric circumstances. For the effective management of upper gastrointestinal tract symptoms, the intragastric pH should, however, be maintained above 4 for at least 18 hours. Treatment with acid-suppressive drugs may therefore lead to an insufficient elimination, or even increased colonization, of ingested pathogens. There is some evidence that acid-suppressive therapy facilitates nosocomial infections.

3) The authors report a study to examine the association between the use of acid-suppressive drugs and occurrence of community-acquired (nosocomial) pneumonia. Incident acid-suppressive drug users with at least 1 year of valid database history were identified from the Integrated Primary Care Information database between January 1, 1995, and December 31, 2002. Incidence rates for pneumonia were calculated for unexposed and exposed individuals. To reduce confounding by indication, a case-control analysis was conducted nested in a cohort of incident users of acid-suppressive drugs. Cases were all individuals with incident pneumonia during or after stopping use of acid-suppressive drugs. Up to 10 controls were matched to each case for practice, year of birth, sex, and index date. Conditional logistic regression was used to compare the risk of community-acquired pneumonia between use of proton pump inhibitors (PPIs) and H2-receptor antagonists.

4) Community-acquired pneumonia was defined as certain (proven by radiography or sputum culture) or probable (clinical symptoms consistent with pneumonia). The study population comprised 364,683 individuals who developed 5551 first occurrences of pneumonia during follow-up. 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. The adjusted relative risk for pneumonia among persons currently using PPIs compared with those who stopped using PPIs was 1.89 (95% confidence interval, 1.36-2.62). Current users of H2-receptor antagonists had a 1.63-fold increased risk of pneumonia (95% confidence interval, 1.07-2.48) compared with those who stopped use. For current PPI users, a significant positive dose-response relationship was observed. For H2-receptor antagonist users, the variation in dose was restricted. The authors conclude: Current use of gastric acid-suppressive therapy is associated with an increased risk of community-acquired pneumonia.

References (abridged):

1. Jones R, Lydeard S. Prevalence of symptoms of dyspepsia in the community. BMJ. 1989;298:30-32

2. van Bommel MJ, Numans ME, de Wit NJ, Stalman WA. Consultations and referrals for dyspepsia in general practice, a one year database survey. Postgrad Med J. 2001;77:514-518

3. Delaney BC, Innes MA, Deeks J, et al. Initial management strategies for dyspepsia. Cochrane Database Syst Rev. 2000(3):CD001961

4. American Gastroenterology Association medical position statement and technical review: evaluation of dyspepsia. Gastroenterology. 1998;114:579-595

5. Howden CW, Hunt RH. Relationship between gastric secretion and infection. Gut. 1987;28:96-107

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