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(Chest. 2000;117:1819-1820.)
© 2000 American College of Chest Physicians

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Symptomless Dysphagia

Tadashi Arai, MD, PhD; Yo Yasuda, MD, PhD; Tadatake Takaya, MD, PhD; Satoshi Toshima, CTIAC; Yoshitomo Kashiki, MD, PhD; Naoki Yoshimii, MD, PhD and Hisayoshi Fujiwara, MD, PhD

Gihoku General Hospital Gifu University School of Medicine Gifu, Japan

Correspondence to: Tadashi Arai, MD, PhD, Department of Internal Medicine, Gihoku General Hospital, 1187–3 Takatomi-cho Yamagata-gun, Gifu 501-2105, Japan

To the Editor:

Symptomless dysphasia is one of the main causes of pneumonia in elderly people with stroke, and swallowing or the cough reflex can prevent aspiration pneumonia.1 The article by Nakayama and colleagues (May 1998),2 concerning angiotensin-converting enzyme (ACE) inhibitors and the swallowing reflex, was a fascinating and timely study. We previously reported that ACE inhibitors may cure symptomless dysphagia in hypertensive patients with stroke.3 ACE inhibitors and angiotensin II receptor antagonists (Ang II) are very important drugs for hypertensive patients. We investigated the prevention of symptomless dysphagia and treatment with different antihypertensive drugs in hypertensive patients with stroke. We investigated whether a correlation existed between patients with symptomless dysphagia with stroke and the elimination of low serum substance P concentration by ACE inibitors and Ang II.4 We excluded the immunocompromised patients.

The subjects were 53 patients with hypertension, symptomless dysphagia, and history of stroke. They were divided into group A (32 patients; 13 men and 19 women) and group B (21 patients; 10 men and 11 women). We obtained informed consent from the patients or their families.

To determine the occurrence of symptomless dysphagia, we gave 1 mL technetium tin colloid (99mTC) to patients in groups A and B during sleep via a nasal catheter.5 At 9:00 AM the next day, we checked for symptomless dysphagia by imaging.

We gave all patients in group A an ACE inhibitor (imidapril hydrochloride), 5 to 10 mg qd orally, and all patients in group B received Ang II (losartan potassium), 50 to 100 mg qd orally. We measured serum substance P before and 12 weeks after administration. The mean serum substance P before drug administration was 26.5 pg/mL in group A and 26.36 pg/mL in group B. After 12 weeks, symptomless dysphagia improved in 23 of 32 patients in group A. In these 23 patients, the mean serum substance P was 82.91 pg/mL. In six patients, symptomless dysphagia did not improve (mean serum substance P, 50.62 pg/mL) and in four of them, serum substance P was not increased (mean serum substance P, 46.12 pg/mL). Imidapril hydrochloride was stopped in the remaining patients because of excessive cough (mean serum substance P, 109.83 pg/mL). On the other hand, in all 21 patients in group B, symptomless dysphagia did not improve, and in all of them, serum substance P did not increase (mean serum substance P, 30.49 pg/mL) after 12 weeks (p < 0.0001).

We concluded that ACE inhibitors have advantage over Ang II in prevention of symptomless dysphagia in patients with stroke.

References

  1. Sekizawa, K, Ujiie, Y, Itabashi, S, et al (1990) Lack of cough reflex in aspiration pneumonia. Lancet 335,1228-1229[ISI][Medline]
  2. Nakayama, K, Sekizawa, K, Sasaki, H, et al (1998) ACE inhibitor and swallowing reflex [letter]. Chest 113,1425[Free Full Text]
  3. Arai, T, Yasuda, Y, Takaya, T, et al (1998) ACE inhibitors and symptomless dysphagia. Lancet 352,115-116[CrossRef][ISI][Medline]
  4. Tomaki, M, Ichinose, M, Miura, M, et al (1996) Angiotensin converting enzyme (ACE) inhibitor-induced cough and substance P. Thorax 51,199-201[Abstract]
  5. Kikuchi, R, Watanabe, N, Kouno, T, et al (1994) High incidence of silent aspiration in elderly patients with community-acquired pneumonia. Am J Respir Crit Care Med 150,251-253[Abstract]

Katsutoshi Nakayama, MD; Mutsuo Yamaya, MD and Hidetada Sasaki, MD, FCCP

Tohoku University School of Medicine Sendai, Japan

Correspondence to: Hidetada Sasaki, MD, FCCP, Professor and Chairman, Department of Geriatric Medicine, Tohoku University School of Medicine, Aoba-ku, Seiryo-machi 1–1, Sendai 980-8574, Japan

To the Editor:

We thank Dr. Arai et al for their interesting comments on our study.1 They report that the administration of angiotensin-converting enzyme (ACE) inhibitor could increase serum substance P (SP) and could improve the symptomless dysphagia in patients with hypertension and previous stroke, but that angiotensin II receptor antagonists (Ang II) could not. ACE inhibitors inhibit not only the activation of angiotensin II, but also the degradation of SP and bradykinin. We have shown, in a 2-year study, 2 that ACE inhibitors could upregulate impaired swallowing reflex, and that they could also reduce the risk of pneumonia by about one third, compared with results of other antihypertensive drugs used in treatment of patients with hypertension and previous stroke. However, the effect of Ang II on the swallowing reflex has not yet been examined. Dr. Arai’s experience clearly showed that the effect of ACE inhibitors on improvement of symptomless dysphagia should be independent from the angiotensin II pathway. We agree that ACE inhibitors have an advantage over Ang II in preventing symptomless dysphagia in patients with stroke.

Despite the important antihypertensive effect, ACE inhibitors also cause a side effect of excessive cough in 5 to 10% of subjects, as shown in the comment by Arai et al. Therefore, ACE inhibitors would not be useful for patients who have developed hypotension or other side effects as a result of these drugs. Another way to increase SP is through the administration of dopamine, which stimulates the synthesis of SP.3 We have shown that the IV administration of levodopa significantly improved the swallowing reflex in patients with aspiration pneumonia,4 and that amantadine, a drug that acts by the releasing dopamine from dopaminergic nerve terminals, could lower the risk of pneumonia to about 20% in patients with stroke.5 Therefore, amantadine may also be beneficial in preventing pneumonia in patients with stroke. This drug should be useful to reduce the risk of aspiration pneumonia in elderly patients with hypotension or airway hyperreactivity, for which the use of ACE inhibitors would be relatively risky.

References

  1. Nakayama, K, Sekizawa, K, Sasaki, H (1998) ACE inhibitor and swallowing reflex [letter]. Chest 113,1425
  2. Sekizawa, K, Matsui, T, Nakagawa, T, et al (1998) ACE inhibitors and pneumonia [letter]. Lancet 352,1069
  3. Jia, YX, Sekizawa, K, Ohrui, T, et al (1998) Dopamine D1 receptor antagonist inhibits swallowing reflex in guinea pigs. Am J Physiol 274,R76-R80[Abstract/Free Full Text]
  4. Kobayashi, H, Nakagawa, T, Sekizawa, K, et al (1996) Levodopa and swallowing reflex [letter]. Lancet 348,1320-1321[ISI][Medline]
  5. Nakagawa, T, Wada, H, Sekizawa, K, et al (1999) Amantadine and pneumonia [letter]. Lancet 353,1157[ISI][Medline]



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