Utility of cough response during hypertonic histamine challenge in diagnosing asthma.

Airway responses to bronchial provocation tests are traditionally assessed with spirometry which necessitates considerable patient co-operation. It has been shown that coughing during bronchial provocation tests is related to the degree of bronchoconstriction which, in turn, is independent of patient co-operation. The aim of the present study was to evaluate the utility of coughing induced by the hypertonic histamine challenge in the differential diagnosis of asthma in a clinically relevant patient population. The study population consisted of 25 healthy volunteers, 30 asthmatics, and 82 non-asthmatic subjects with respiratory symptoms due to other diseases. Hypertonic histamine solution was administered with ultrasonic nebuliser with the challenges being videotaped. The cough response was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). The geometric mean (95% CI) of CCR for asthmatics was 302 (166-562) coughs per mg/ml, for the symptomatic controls 29.5 (20.0-43.7) coughs per mg/ml (p<0.001) and for the healthy controls 6.61 (3.02-14.5) (p<0.001) coughs per mg/ml. According to the ROC curve, the optimal cut-off point for logCCR was 2.22, with the specificity and sensitivity to detect asthma among symptomatic subjects being 86% and 70%. Cough response to hyperosmolar challenge may be useful in the differential diagnosis of airway diseases.

Utility of hypertonic histamine challenge in distinguishing difficult-to-diagnose asthma.

INTRODUCTION: Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC). OBJECTIVE: The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients. METHODS: Fifty-seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser. RESULTS: Only the PC(20) values of asthmatic subjects differed statistically significantly from those of the healthy group (P < 0.0001). The receiver operator characteristic curve indicated that a PC(20) value of 0.83 mg/mL would be the optimal cut-off point of HHC to separate the asthmatics from the symptomatic controls with a sensitivity of 81% and specificity of 70%. With the PC(20) values of 0.1 and 4.0 mg/mL, the sensitivities were 42% and 100%, and the specificities were 96% and 40%, respectively. In these limits, HHC either confirmed or excluded asthma in 64 out of 138 patients (46%). CONCLUSION: The authors' attempt to improve the accuracy of the airway challenge test by combining direct and indirect challenges did not overcome the diagnostic limitations of previously utilised airway challenges.

Interpretation of cough provoked by airway challenges.

STUDY OBJECTIVE: To analyze the cough response to three airway challenges in order to clarify whether the recording of the provoked coughs would be beneficial in the management of asthma. DESIGN: A prospective study. SETTING: University hospital. PARTICIPANTS: Fifteen healthy subjects, 16 steroid-naïve subjects with asthma, and 16 subjects with steroid-treated asthma. INTERVENTIONS: Inhalation challenges with isotonic histamine, hypertonic saline solution, and hypertonic histamine, using an ultrasonic nebulizer and 2-min tidal breathing method. MEASUREMENTS: Airflow parameters were measured with a spirometer, and the coughs were recorded manually. RESULTS: Coughing during the isotonic histamine challenge was associated with the degree of the bronchoconstriction induced. When this was taken into account, the healthy subjects coughed as frequently as the asthmatic subjects. During the two hypertonic challenges, the asthmatic subjects coughed more frequently than did the healthy subjects when the induced bronchoconstriction had not yet developed. At that stage of the hypertonic saline solution challenge, the mean coughing frequency was 0.7 coughs per minute (95% confidence interval [CI], 0.03 to 1.3 coughs per minute) for the healthy subjects, 2.7 coughs per minute (95% CI, 0.8 to 4.5 coughs per minute) for the steroid-naïve asthmatic subjects, and 1.3 coughs per minute (95% CI, 0.6 to 1.9 coughs per minute) for the steroid-treated asthmatic subjects (p = 0.018). For the hypertonic histamine challenge, the respective values were 0.8 coughs per minute (95% CI, 0.4 to 1.2 coughs per minute), 3.6 coughs per minute (95% CI, 2.4 to 4.9 coughs per minute), and 2.1 coughs per minute (95% CI, 1.0 to 3.1 coughs per minute; p = 0.001). This cough did not correlate with airway hyperresponsiveness. CONCLUSIONS: Coughing during isotonic histamine challenge seems to be a manifestation of bronchoconstriction, and recording of the coughs may not provide additional information to airflow measurements. Frequent coughing during hypertonic saline solution and hypertonic histamine challenges in the absence of bronchoconstriction is a pathologic phenomenon. Sensitivity to the cough-provoking effect of hypertonic challenges seems to be enhanced in patients with asthma but unrelated to airway hyperresponsiveness. Therefore, the recording of the provoked coughs during these challenges may add to the information obtained from airflow measurements.

Hypertonicity of the challenge solution may increase the diagnostic accuracy of histamine challenge.

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.