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Eur Respir J 2007; 29:218-219
Copyright ©ERS Journals Ltd 2007

ACE inhibitors prevent aspiration pneumonia in Asian, but not Caucasian, elderly patients with stroke

S. Teramoto, H. Yamamoto, Y. Yamaguchi, Y. Hanaoka, M. Ishii, S. Hibi and Y. Ouchi

Dept of Geriatric Medicine, Dept of Urology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

To the Editors:

In a recent issue of the European Respiratory Journal, van de Garde et al. 1 demonstrated that the use of angiotensin-converting enzyme (ACE) inhibitors is not associated with a decreased risk of hospitalisation for community-acquired pneumonia (CAP) in a general, essentially white population. Their conclusion that the beneficial effect of ACE inhibitors on pneumonia risk is not observed in a general white population is in contrast with previous findings in Asian populations 1. This was an excellent good study examining the association of ACE inhibitor treatment of cardiovascular disease with a risk reduction of CAP using a large sample size. The results are acceptable and not surprising; however, the discussion and conclusion are misleading.

As shown in table 1Go, there are controversies regarding the ACE inhibitor effects on the risk reduction of pneumonia even in Asian countries; furthermore, the study samples are very different among the studies. In a prospective study by Sekizawa et al. 2, ACE inhibitor use reduced pneumonia incidence for 2 yrs. They did not examine the general population; subjects were hypertensive elderly patients with a history of stroke or lacuna infarction, and a mean age 10 yrs older than that of the study by van de Garde et al. 1. However, the study by Arai et al. 3 examined the association of ACE inhibitors and the risk reduction of pneumonia in the general hypertensive elderly without stroke in Japan 3. Surprisingly, they had an 8.3–8.9% incidence of pneumonia over 3 yrs, an incidence twenty times higher than the previous data 6, 7. It is hard to believe that ~3% of hypertensive elderly outpatients without major complications suffered from pneumonia. We have previously presented data showing no association of ACE inhibitor use with pneumonia risk in elderly hypertensive subjects without stroke history 4. Since ACE inhibitors, through the inactivation substance P, improve upper airway reflexes such as swallowing and cough, resulting in the reduction of aspiration pneumonia in elderly patients, they may not reduce the CAP in those patients without deglutition problems. Current evidence indicates that ACE inhibitors play a significant role in the prevention of aspiration pneumonia in the elderly, but not in common CAP in healthy adults. This was confirmed by the sub-analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). Ohkubo et al. 5 re-analysed the PROGRESS data concerning the incidence of pneumonia. ACE inhibitor-active treatment significantly reduced the risk of pneumonia among participants of Asian ethnicity (mean (95% confidence interval) 47% (14–67%), p = 0.01), with no significant effect among non-Asian participants (5% (-27–29%), p = 0.7; p for homogeneity = 0.04). These findings add to the body of evidence regarding the effects of these drugs on pneumonia. The randomised design of PROGRESS greatly reduced the likelihood of confounding of the analyses and provided an excellent opportunity to explore the validity of the associations reported in observational studies 2, 3. Thus, the key issue is the selection of elderly subjects in terms of ethnicity, post-stroke state, performance status, type of ACE inhibitor and swallowing function.


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  		Table 1— The association of angiotensin-converting enzyme (ACE) inhibitor use and the rate of pneumonia in different trials

 
The clinical epidemiology research group of Etminan et al. 8 recently reported that no association was found between the use of ACE inhibitors or angiotensin II receptor blockers (ARBs) and risk of hospitalisation secondary to CAP. The study further confirmed the limited efficacy of ACE inhibitors on the risk reduction of hospitalisation due to pneumonia in a white population. As we speculated, ARBs did not have any role in the prevention of aspiration pneumonia.

Stroke and post-stroke patients often exhibit a normal cough reflex, but not swallowing reflex, and the small volume of aspirated materials due to impaired swallowing during night is a key factor for the risk of pneumonia 9, 10. Hence, a ten times higher rate of pneumonia in post-stroke patients without significant neurological deficit, compared with the rate of pneumonia in normal elderly 5. Furthermore, the age-dependent impairment of upper airway reflexes should be carefully considered for the mechanism of CAP in the elderly irrespective of the history of stroke.

Finally, we emphasise that aspiration and silent aspiration are very important mechanisms of aspiration pneumonia. Silent aspiration is very common in patients with stroke and frail elderly patients, and nasogastric tube feeding without swallowing rehabilitation or oral care cannot reduce the pneumonia risk in patients with swallowing disorders 11.

We believe that angiotensin-converting enzyme inhibitors could prevent aspiration pneumonia in selected elderly patients. Post-stroke and the frail elderly are the best candidates for the pneumonia risk reduction by angiotensin-converting enzyme inhibitors 12. However, these merits may not be consistently observed in Caucasian elderly patients with or without stroke.

REFERENCES

  1. van de Garde EM, Souverein PC, van den Bosch JM, Deneer VH, Leufkens HG. Angiotensin-converting enzyme inhibitor use and pneumonia risk in a general population. Eur Respir J 2006;27:1217–1222.[Abstract/Free Full Text]
  2. Sekizawa K, Matsui T, Nakagawa T, Nakayama K, Sasaki H. ACE inhibitors and pneumonia. Lancet 1998;352:1069[Web of Science][Medline] [Order article via Infotrieve]
  3. Arai T, Yasuda Y, Toshima S, Yoshimi N, Kashiki Y. ACE inhibitors and pneumonia in elderly people. Lancet 1998;352:1937–1938.[Web of Science][Medline] [Order article via Infotrieve]
  4. Teramoto S, Ouchi Y. ACE inhibitors and prevention of aspiration pneumonia in elderly hypertensives. Lancet 1999;353:843[Web of Science][Medline] [Order article via Infotrieve]
  5. Ohkubo T, Chapman N, Neal B, Woodward M, Omae T, Chalmers J. Effects of an angiotensin-converting enzyme inhibitor-based regimen on pneumonia risk. Am J Respir Crit Care Med 2004;169:1041–1045.[Abstract/Free Full Text]
  6. Woodhead MA, Macfarlane JT, McCracken JS, Rose DH, Finch RG. Prospective study of the aetiology and outcome of pneumonia in the community. Lancet 1987;1:671–674.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  7. Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol 1993;137:977–988.[Abstract/Free Full Text]
  8. Etminan M, Zhang B, Fitzgerald M, Brophy JM. Do angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers decrease the risk of hospitalization secondary to community-acquired pneumonia? A nested case-control study. Pharmacotherapy 2006;26:479–482.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  9. Teramoto S, Ishii T, Yamamoto H, et al. Significance of chronic cough as a defence mechanism or a symptom in elderly patients with aspiration and aspiration pneumonia. Eur Respir J 2005;25:210–211.[Free Full Text]
  10. Teramoto S, Matsuse T, Fukuchi Y, Ouchi Y. Simple two-step swallowing provocation test for elderly patients with aspiration pneumonia. Lancet 1999;353:1243[Web of Science][Medline] [Order article via Infotrieve]
  11. Teramoto S, Ishii T, Yamamoto H, Yamaguchi Y, Ouchi Y. Nasogastric tube feeding is a cause of aspiration pneumonia in ventilated patients. Eur Respir J 2006;27:436–437.[Free Full Text]
  12. Teramoto S, Kume H, Fukuchi Y. Antihypertensive drugs in Japan. Lancet 2001;357:720–721.[Web of Science][Medline] [Order article via Infotrieve]



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