title: Hypertonicity of the challenge solution may increase the diagnostic accuracy of histamine challenge.
abstract: There is significant overlap in the responsiveness to direct airway challenges, such as the histamine challenge, between asthmatic and non-asthmatic subjects, which decreases their accuracy in the diagnosis of asthma. To minimise this overlap, a new test, hypertonic histamine challenge, was developed. Fifteen healthy subjects, 16 subjects with steroid-naive asthma, and 16 asthmatic subjects undergoing inhaled corticosteroid treatment underwent inhalation challenges with hypertonic saline, isotonic histamine, and hypertonic histamine, using an ultrasonic nebuliser and 2-min tidal breathing method. The increase in histamine solution tonicity decreased the histamine PC20 values only in the steroid-naive asthmatic subjects (1.1 (0.5-2.7) vs. 0.5 (0.2-1.2) mg/ml, P = 0.047). Using 1mg/ml as the cut-off value, the sensitivity, specificity, and accuracy of the hypertonic histamine challenge to detect steroid-naive asthma was 81%, 100%, and 90%. The respective values for the isotonic histamine challenge were 56%, 100%, and 77%. Furthermore, there was a statistically significant difference in the hypertonic histamine PC20 between steroid-naive and steroid-treated asthmatic subjects, which could not be detected in the isotonic histamine PC20. The hypertonic histamine PC20 was highly repeatable, with a single determination 95% range of +/-1.35 doubling concentrations. The hypertonic histamine challenge was safe but provoked more cough and throat irritation than the other two challenges. In conclusion, compared with a conventional, isotonic histamine challenge, hypertonic histamine challenge may be more accurate in the diagnosis of asthma and also, more capable to detect the effects of inhaled corticosteroid treatment.
authors.affiliation: Department of Respiratory Medicine, Kuopio University Hospital, P.O. Box 1777, Kuopio 70211, Finland. heikki.koskela@kuh.fi
authors.forename: Heikki O
authors.initials: HO
authors.lastname: Koskela
authors.forename: Kirsi M
authors.initials: KM
authors.lastname: Kontra
authors.forename: Minna K
authors.initials: MK
authors.lastname: Purokivi
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Randell
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006632:Histamine; D006801:Humans; D006982:Hypertonic Solutions; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D012680:Sensitivity and Specificity; D012907:Smoking
chemical_list: D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D006982:Hypertonic Solutions; D006632:Histamine