The three papers which follow furnish strong evidence that phenytoin is useful in asthma. Consistent with these findings are basic mechanism studies which show PHT's ability to relax bronchial smooth muscle, to regulate the autonomic nervous system, and to prevent the effects of hypoxia.

Shulman, New England Journal of Medicine (1942),341 selected seven cases of severe bronchial asthma, which were considered intractable because they had not responded to conventional treatment. These cases were treated with PHT. In a detailed study the author reported marked relief of asthma in six of seven cases and partial relief in the seventh. In this study PHT was used exclusively and was not begun until all other medications were eliminated. With the application of PHT six of the patients were consistently free of attacks of bronchial asthma and the seventh showed some improvement. Two of the patients had stubborn eczema which cleared to a remarkable degree with PHT. The author notes that the efficacy of PHT was further evidenced by the fact that the patients were able to successfully engage in situations and environments which formerly precipitated attacks of bronchial asthma.

341. Shulman, M. H., The use of Dilantin sodium in bronchial asthma: a preliminary report, New Eng. J. Med., 226: 260-264, 1942.

Sayer and Polvan, Lancet (1968),401 described sixteen patients with bronchial asthma, with frequent asthmatic crises. Fourteen had abnormal EEGs and two had EEGs within normal limits. All patients were taken off other medications and given PHT for an average of forty-five days. Ten patients were closely followed up during this period. Seven had neither asthmatic crises nor wheezing. One patient had occasional wheezing and in the other two cases the frequency of crises was greatly diminished.

401. Sayar, B. and Polvan, O., Epilepsy and bronchial asthma, Lancet, 1: 1038, 1968.

Shah, Vora, Karkhanis and Talwalkar, Indian Journal of Chest Diseases (1970),1535 conducted a study of the usefulness of PHT in bronchial asthma in twenty-seven patients. Both clinical and laboratory observations were made. The authors state that the prevention of the spread of electrical discharge is one of the most important, interesting and unexploited pharmacological properties of PHT. Noting that other paroxysmal disorders have responded to PHT, they felt that its use in the paroxysmal spasms of asthma should be explored.

In the study of the twenty-seven patients, careful histories were recorded, including the severity of asthma, graded by age at onset, frequency of attacks during past twelve months, absenteeism from work, number of days absent in the last month, and number of sleepless nights in the last month. Effort tolerance tests were performed during and between attacks. Appraisal of previous therapy during the last month was noted by the number of adrenaline and/or aminophylline injections and oral drugs (bronchodilators and steroids). Each patient had laboratory investigations, chest x-ray and electrocardiogram to exclude any cardiopulmonary disease simulating bronchial asthma. Ventilation studies, including maximum breathing capacity, were carried out initially and repeated at weekly follow-up examinations. At the end of the treatment period all examinations were repeated.

Before starting patients on PHT all other medicines were discontinued. Dosage was 100 mg PHT t.i.d. The trial was for one month. Assessment of subjective and objective results was verified by all participating physicians. While on PHT, twenty-five of the twenty-seven patients experienced impressive relief. Fifteen of these patients showed improved ventilation tests. Although some wheezing persisted in twelve patients, the distress was less evident. As a whole, the patients were more relaxed. The results of this study led the authors to suggest that PHT would seem to be a useful anti-asthmatic agent. (A number of people with emphysema have reported to the Dreyfus Medical Foundation that since taking PHT for other reasons they had experienced improvement in their breathing. We are not aware of published work on the use of PHT for emphysema. It would seem an area for research. (See Anti-anoxic Effects of PHT-Basic Mechanisms of Action.)

1535. Shah, J. R., Vora, G., Karkhanis, A. V., and Talwalkar, C. V., The effect of diphenylhydantoin on ventilation tests in airway obstruction, Indian J. Chest. Dis., 12: 10-14, 1970.

Jain and Jain, Journal of Asthma (1991), 3348 evaluated the efficacy of phenytoin (PHT) for the relief of chronic asthma in 190 intractable asthmatics in an open trial in a rural desert area of northwest India. Phenytoin (100 mg po b.i.d. for adults and 50 mg po b.i.d. for children), used alone or as an adjuvant to other anti-asthma medications, significantly reduced the frequency and severity of asthma attacks, coughing, nocturnal awakenings and work absenteeism. Improved effort tolerance and subjective sense of well-being were noted. Phenytoin reduced the corticosteroid requirements of steroid-dependent patients. Not only were these results sustained over the 12-month treatment period, but also more than 60% of phenytoin-treated patients were able to discontinue PHT without recurrence of symptoms.

3348. Jain, S., Jain, K.C., Effect of phenytoin sodium in the management of poorly controlled bronchial asthma at a rural health center in Phalodi, Rajasthan, India, J. Asthma, 28(3): 201-11, 1991.