Bronchial provocation challenges with exercise and methacholine were performed on the same day or within a short interval in 52 children with asthma, 22

An analysis was undertaken to determine the optimal cut-off separating an asthmatic from a normal response to a bronchial provocation challenge by exercise and the inhalation of methacholine or histamine in children and young adults. Data were extracted, after appropriate correction, from published studies available in Medline of large random populations that complied with preset criteria of suitability for analysis, and the distribution of bronchial reactivity in the healthy population for exercise and inhalation challenges were derived. Studies on the response to exercise and methacholine inhalation in 232 young asthmatics of varying severity were carried out by the authors and the distribution of bronchial reactivity of a young asthmatic population obtained. Comparisons of the sensitivity and specificity of the challenges were aided by the construction of receiver operating characteristic curves. The optimal cut-off point of the fall in forced expiratory volume in one second (FEV1) after exercise was 13%, with a sensitivity (power) of 63% and specificity of 94%. For inhalation challenges, the optimal cut-off point for the dose of methacholine or histamine causing a 20% fall in FEV1 was 6.6 micromol, with a sensitivity of 92% and a specificity of 89%. The cut-off values were not materially affected by the severity of the asthma and provide objective data with which to evaluate the results of bronchial provocation challenges in children and young adults.

To study wheezing as an indicator of bronchial responsiveness during methacholine challenge (MC) in children, we used computer analysis of respiratory sounds and compared wheeze measurements to routine spirometry. MC was performed in 30 symptomatic subjects (sympt), age 11 +/- 3.1 years (mean +/- SD), with suspected asthma and in 12 controls (contr), age 10 +/- 3.4 years. Respiratory rate (RR), spirometry, arterial oxygen saturation (SaO2), and cough were registered until the concentration provoking a > or = 20% fall in forced expiratory flow in 1 second (FEV1;PC20), or the end point (8 mg/mL) was reached. For 1 min after each inhalation, sounds over the trachea and posterior right lower lobe were recorded together with calibrated airflow. Computer analysis of respiratory sounds was used for objective wheeze quantification. Wheezing was measured as its duration relative to inspiration (Tw/Ti) and expiration (Tw/Te). Seventeen of the sympt group developed wheezing (sympt/W) with > or = 5% Tw/Ti or > or = 5% Tw/Te. Thirteen of the sympt did not wheeze (sympt/no W). Three contr developed wheeze (contr/W) while 9 did not (contr/no W). In sympt/W, RR increased from 20 +/- 6.2 per min at baseline to 25 +/- 9.2 (P < 0.05) at the MC concentration provoking wheeze (PCw), and SaO2 decreased from 97.4 +/- 1.2% to 95.3 +/- 2.4 (P < 0.05). In contr/W, RR did not change, but SaO2 decreased from 97.3 +/- 1.5% to 95.7% +/- 1.2% (P < 0.05). Wheezing occurred at both recording sites and was as common during inspiration as during expiration.(ABSTRACT TRUNCATED AT 250 WORDS)

A proportion of patients with cystic fibrosis (CF) suffer from increased airway hyperreactivity but their response to bronchodilators is variable. Adrenergic agents may produce an increase, no change or a decrease in forced expiratory volume in 1 second (FEV1). We hypothesized that the variable response might be related to poor aerosol distribution caused by the presence of secretions. Therefore, in 11 children with CF and airway hyperreactivity the influence of pretreatment with either 0.9% saline, salbutamol, or ipratropium bromide on the methacholine challenge test was evaluated in a double-blind, randomized, cross-over study. FEV1 (mean +/- S.E.) did not change following pretreatment with saline, salbutamol, or ipratropium (1.64 +/- 0.22, 1.63 +/- 0.16 and 1.67 +/- 0.19, respectively). All patients demonstrated airway hyperreactivity with a PC20 below 8 mg/mL (geometric mean, 0.41 mg/mL) after saline pretreatment. Salbutamol inhalation significantly increased the PC20 to 1.24 mg/mL (P less than 0.01), but ipratropium bromide was found to be even more effective than salbutamol (PC20 = 7.37 mg/mL) (P less than 0.0001). We conclude that the variable response to bronchodilator is not secondary to impaired aerosol distribution since ipratropium bromide effectively blocked the response to methacholine. The improvement in PC20 without a change in baseline FEV1 following salbutamol suggests that the adrenergic agent altered the contractile mechanism of smooth muscle.