The lowest concentrations of citric acid were measured that caused coughing in 10 normal subjects who inhaled successively higher concentrations. Two subjects did not cough at any concentration. In the remaining eight the threshold concentration was significantly higher when measured in the afternoon than it was in the morning (p less than 0.05). The expected diurnal variation in peak expiratory flow rate (PEFR) was found (significant in the whole group--p less than 0.05); but PEFR did not change significantly when measured before and immediately after coughing caused by citric acid inhalations. In a second group of 10 normal subjects two series of citric acid inhalations were given, separated by one hour. The total number of coughs was significantly lower on the second run (p less than 0.05). Thus diurnal variation and adaptation of the cough response must be taken into account when antitussive drugs are tested.
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