BACKGROUND Although wheezing and cough are the most common complaints in asthmatic persons, the mechanisms of hyperresponsiveness to bronchoconstriction and cough are nevertheless still unclear. OBJECTIVE To investigate the common mechanisms between them, we studied the relationship between ultrasonically nebulized distilled water (UNDW) inhalation challenge and acetic acid (AA) inhalation challenge. In addition, we evaluated the effect of inhaled furosemide on both provocation tests by means of a placebo-controlled study. METHODS In study 1 the UNDW, AA, and histamine inhalation challenges were performed in 40 asthmatic children (26 boys, aged from 7 to 16 years; mean +/- SD, 11.2 +/- 2.0 years). In study 2, 12 of the study 1 subjects (9 boys, 11.3 +/- 2.4 years) were subjected to each challenge test after inhalation of furosemide (10 mg/body square meters), or placebo (0.9% saline solution) on separate days. RESULTS There was a good correlation between the provocative dose causing a 20% fall in forced expiratory volume in 1 second in the UNDW inhalation challenge (UNDW-PD20) and threshold dose causing cough in the AA inhalation challenge (R = 0.527; p < 0.001). There was no relationship either between UNDW-PD20 and the provocative concentration causing a 20% fall in the histamine inhalation challenge (histamine-PC20)(R = 0.384; p > 0.1), or between histamine-PC20 and the cough threshold (R = 0.308; p > 0.05). In study 2 neither bronchoconstriction nor bronchodilation after inhalation of furosemide was observed. Inhaled furosemide exerted a protective effect on UNDW-PD20 and cough threshold of the AA inhalation challenge (p < 0.01 and p < 0.01, respectively), but did not attenuate histamine-PC20 (p > 0.1). CONCLUSIONS These data suggest that a common mechanism may cause hyperresponsiveness against both UNDW-induced bronchoconstriction and AA-induced cough in asthmatic children.