The airway response to histamine has been shown to be related to the 24 hour urinary excretion of sodium. To assess whether this relation is likely to represent a direct causal association a randomised double blind crossover trial of slow sodium (80 mmol/day) was compared with placebo in 36 subjects having a low sodium diet. The dose of histamine causing a 20% fall in FEV, (PD20) was l5l doubling doses lower when the men were taking sodium than when they were taking placebo (p < 0 05). On the basis of PD,o values, the difference in men was 1 66 doubling doses of histamine (p < 0 05). There was no corresponding effect in women. Regressing PD,0 against urinary excretion of electrolytes with data from the two occasions during the trial and the measurements made before the trial showed a significant association with sodium excretion after allowance had been made for any effect associated with potassium or creatinine excretion, the latter being a marker of the completeness of the urine collection. Again there was no corresponding effect among women. These findings are compatible with the differences in regional mortality data for England and Wales, which show a relation between asthma mortality and regional per person purchases of table salt for men but not for women.
Two groups of eight normal subjects were investigated in separate studies to demonstrate the effects of changes in end-tidal PCO2, and of pretreatment with the calcium antagonist drug verapamil, on bronchoconstriction provoked by voluntary hyperventilation. Total respiratory resistance (Ros) was measured by the forced oscillation technique before and after 90 s voluntary hyperventilation. End-tidal PCO2 during hyperventilation was varied by altering inspired CO2 concentration. When end-tidal PCO2 fell during hyperventilation, there was a rise in Ros. This did not occur if end-tidal PCO2 was controlled at a normal resting level during hyperventilation. Specific conductance (sGaw) was measured before and after 90 s voluntary hyperventilation of air. Subjects were treated with oral verapamil or placebo for 2 1/2 days and the effect of hyperventilation on sGaw was reassessed. Verapamil reduced significantly the fall in sGaw caused by hyperventilation. Placebo had no effect. In normal humans, bronchoconstriction provoked by hyperventilating air at ambient temperature and humidity is mediated by the fall in PCO2, and is also reduced by verapamil.
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