Effect of oral lithium on bronchial reactivity in asthma.

1. Recognition that inositol phospholipid-derived second messengers are involved in the initiation and maintenance of airway smooth muscle contraction raises the possibility of new therapeutic approaches to the treatment of asthma. We anticipated that lithium, through its effects on cell signal transduction and ion-transport pathways, would be likely to protect the airways against constrictor stimuli. 2. We carried out a randomized, double-blind study of lithium carbonate in asthmatic patients. 3. After a 1 week run-in period, 27 patients were allocated lithium carbonate (800 mg) or placebo for 21 days with measurement of forced expiratory volume in 1 s, the dose of histamine causing a 20% fall in the forced expiratory volume in 1 s and serum lithium concentration on days 3, 7, 14 and 21. 4. Twenty-one patients completed the study (10 on lithium, 11 on placebo). Mean serum lithium levels for patients on active treatment were in the therapeutic range on all four occasions. 5. Lithium did not alter the forced expiratory volume in 1 s (P = 0.8) or the twice-daily peak expiratory flow (P = 0.15). It did, however, reduce histamine reactivity (the maximum difference between lithium and placebo was 1.2 doubling doses of histamine on day 21; 95% confidence interval 0.2-2.2 doubling doses), improve symptom scores (P less than 0.05) and reduce usage of beta-adrenoceptor agonist inhalers (P less than 0.05). 6. We conclude that lithium reduces bronchial reactivity in airway smooth muscle; this finding raises new therapeutic possibilities for the treatment of asthma.