Respiratory conductance response to a deep inhalation in children with exercise-induced bronchoconstriction

Airway response to deep inhalation (DI) may provide information relevant to the mechanisms of airway obstruction (AO). The hypothesis examined here is that DI provokes bronchodilation in children during exercise-induced bronchoconstriction (EIB). EIB was attested in 15 children aged 10+/-3 year (mean+/-SD) by a decrease in forced expiratory volume in 1 s (FEV1) > or = 15% from baseline after a free running test. The respiratory resistance was measured by the forced oscillation technique at 12 Hz using a head generator to vary transrespiratory pressure around the head. The airway response to DI was estimated by the effect on respiratory conductance (Grs), calculated as the reciprocal of respiratory resistance in inspiration. During EIB, DI induced a variable but significant increase in Grs, from 0.085+/-0.023 to 0.101+/-0.029 l hPa(-1) s(-1) (P = 0.0003). The post- to pre-DI Grs ratio (1.19+/-0.14) was found to correlate negatively with EIB-induced reduction in FEV1 (P = 0.02), forced vital capacity (FVC) (P = 0.01) but not FEV1/FVC, i.e., DI induced more bronchodilation in those children with small EIB associated reduction in FVC. It is concluded that the bronchodilator effect of DI may be demonstrated in children with EIB. It is suggested that the associated small airway closure and lung hyperinflation may contribute to limit this response to DI.     

Respiratory impedance response to a deep inhalation in asthmatic children with spontaneous airway obstruction.

The aim of the study was to determine whether the bronchomotor effect of a deep inhalation (DI) may be detected during tidal breathing in asthmatic children with spontaneous airway obstruction (AO). Two groups of children aged 5-15 yrs were studied. AO was mild in group 1 (n=12, forced expiratory volume in one second (FEV1) > or = 75% predicted) and moderate-to-severe in group 2 (n=9, FEV1 > or = 70% pred). The forced oscillation technique at 12 Hz using a head generator allowed the determination of respiratory resistance in inspiration (Rrsi) and expiration (Rrse) before and after DI, at baseline and after salbutamol. At baseline, Rrsi but not Rrse was found to decrease significantly after DI in group 1 but not in group 2. The change induced by DI was significantly different in group 1 (-1.5+/-0.5 hPa x s x L(-1)) compared to group 2 (0.5+/-0.5 hPa x s x L(-1)) and exhibited significant negative correlation to FEV1 % pred. After salbutamol, DI had no effect. In conclusion, asthmatic children show a bronchomotor response to deep inhalation that depends on the degree of airway obstruction. The effect is more readily demonstrated in inspiration than in expiration.     

Time course and calcium dependence of sustained bronchoconstriction induced by deep inhalation in asthma.

We studied six asthmatic patients who showed a progressive decrease in FEV1 when successive forced expiratory maneuvers were performed at 1-min intervals. We determined the time course of changes in specific airway conductance following a single deep inhalation (DI) and the ratio of maximum expiratory flow at 40% of FVC from maximal and partial flow-volume curves (MEF40M/P) during a series of forced expiratory maneuvers. Specific airway conductance measured 3 s after DI was increased by 11 +/- 6 (SE)%, which was not significantly different from an increase of 23 +/- 8% observed in six healthy control subjects. Later (i.e., 10 to 40 s after DI) specific airway conductance was significantly less than the pre-DI value in asthmatic but not in healthy subjects. Mean FEV1 decreased significantly by 28% from the first to the eighth forced expiratory maneuver performed during a period of 15 min, whereas MEF40M/P was not significantly changed and remained always significantly greater than 1. The voltage-dependent calcium channel antagonist nifedipine significantly prevented the reduction of FEV1 without affecting MEF40M/P. We conclude that, in some asthmatic individuals, DI may induce a transient bronchodilatation followed by a calcium-dependent sustained bronchoconstriction. We suggest that the initial bronchodilatation is due to the mechanical interdependence between airways and lung parenchyma, whereas the sustained bronchoconstriction is due to contraction of the airway smooth muscle.     

BRL10833 in inhibiting exercise-induced bronchoconstriction in asthmatic children.

A double-blind controlled exercise challenge study has been performed in 16 asthmatic chlidren to show the effectiveness of BRL10833 in inhibiting exercise-induced bronchoconstriction. The children attended the respiratory laboratory on four occasions within the space of two weeks; on each occassion a routine 6-min exercise test was performed. At the first visit no drugs were given before the exercise test and all the children demonstrated abnormal exercise-induced bronchoconstriction as measured by peak expiratory flow rate (PEFR), forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC). On the other three occasions the children were given sodium cromoglycate, BRL10833 or placebo medications before the exercise test. After sodium cromoglycate administration four children showed complete blocking and four showed partial blocking of exercise-induced bronchoconstriction. After BRL10833 four children showed complete blocking and six showed partial blocking of exercise induced bronchoconstriction. Placebo administration produced complete blocking of exercise-induced bronchoconstriction in three and partial blocking in two children. The results indicated that BRL10833 was almost as effective as sodium cromoglycate in inhibiting exercise-induced bronchoconstriction and placebo, although less effective than the two preparations, did afford protection from exercise-induced bronchoconstriction in some of the children.     

Effects of inhaled lidocaine on exercise-induced asthma

Experiments were performed to determine if stimulation of afferent nerve endings in the respiratory mucosa plays a major role in the initiation of exercise-induced asthma. Five asthmatic subjects were studied in two sessions of 10 min treadmill exercise using an identical workload. In the control session the subjects were exercised without treatment; in the other session aerosol lidocaine (1.5 mg/kg) was inhaled from residual volume to total lung capacity before exercise was started. Pulmonary function tests were measured (1) to obtain baseline values before the aerosol inhalation or exercise was commenced, (2) 2-3 min after completion of lidocaine inhalation, and (3) 4 min after termination of exercise. In the control session the mean postexercise forced expiratory volume in 1 s (FEV1) and the mean forced expiratory flow during the middle half of forced vital capacity (FEF25-75%) were decreased to 61 and 44% of the baseline values, respectively. Similarly, with the lidocaine treatment the post-exercise FEV1 and FEF25-75% were decreased to 54 and 44% of the baseline values, respectively. These data indicate that the afferent nerves in the respiratory mucosa may not play a critical role in the development of exercise-induced asthma.     

3-min step test and treadmill exercise for evaluating exercise-induced asthma.

A simple exercise test would be useful for detecting exercise-induced asthma, a common problem in asthmatic children. The current study compared the 3-min step test with treadmill exercise for evaluating exercise-induced asthma in asthmatic children and assessed whether responses to both tests are influenced by baseline lung function and habitual physical activity. A series of 154 asthmatic children (84 male children; mean age 12.9 +/- 0.9 yrs) underwent a 3-min step-test and treadmill testing on different days within a week at least 24 h apart. Before both tests each subject did spirometry to obtain the baseline forced expiratory volume in one second (FEV1). After both exercise challenges all subjects did serial spirometry and the lowest FEV1 recorded over time was used to calculate the fall in FEV1 expressed as a percentage of the measured pre-exercise (baseline) value (% fall in FEV1) and the area above the FEV1 curve (AAC0-30 min) expressed as a percentage of the pre-exercise value. Changes in both exercise variables were also analysed in percentile subgroups defined by questionnaire answers on habitual physical activity in hours. The mean % fall in FEV1 was significantly higher for treadmill exercise than for the step test (15.0 +/- 7.5 versus 11.7 +/- 5.9); and the AAC0-30 min was larger for treadmill than for the step test (-261.6 +/- 139.9% versus -197.3 +/- 105.0% min). In all subgroups defined by habitual physical activity the mean % fall in FEV1 decreased more after treadmill exercise than after the step test. After step test and treadmill exercise no significant correlation was found between % fall in FEV1 and baseline lung function, or between % fall in FEV1 among groups defined by habitual physical activity. Although the 3-min step test yields a lower % fall in forced expiratory volume in one second (FEV1) and a lower value of the area above the FEV1 curve than treadmill testing, it is a quick, economical, reproducible and portable alternative procedure for identifying exercise-induced asthma in outpatients and epidemiological studies. Baseline lung function and habitual physical activity have no influence on the amount or duration of exercise-induced asthma.     

Comparison between peak expiratory flow rate and forced expiratory volume in one second in the evaluation of children suspected to have asthma

This study was conducted to evaluate whether forced expiratory volume in 1 second (FEV1) for the diagnosis of bronchial reactivity by means of the free-running exercise test and bronchodilator inhalation, could be appropriately replaced by simple measurements of peak expiratory flow rate (PEFR) in children.We studied 108 referred symptomatic children (due to chronic cough or wheezing) suspected to have asthma aged 5-14y. Forced breathing spirometry and the "Mini-Wright peak flow meter" tests were recorded before and fifteen minutes after the challenge with free- running exercise or bronchodilator (Salbutamol) inhalation, regarding the baseline FEV1 value (FEV1> 80% considered as normal).There was a high correlation between PEFR and FEV1 (in absolute value and percent predicted) measured before and after bronchodilator inhalation test (r = 0.48, P = 0.05) in comparison to the values referred to free- running exercise test (r = 0.26, P = 0.01)."forced breathing spirometry" and "Mini-Wright peak flow" cannot be used interchangeably for diagnosing asthma, and PEFR measurement should remain a procedure for monitoring and following up the patients.     

Comparison of bronchodilator responsiveness in asthma and chronic obstructive pulmonary disease

While asthmatics are known to have a greater response to bronchodilators than patients of chronic obstructive pulmonary disease (COPD), whether the pattern of response also differs has not been explored. Forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1) were measured before and 20 minutes after inhalation of 200 microg salbutamol in patients of bronchial asthma (n=133) and (COPD) (n=116). Three types of responses (defined as > or = 12% and 200 ml increase in FEV1 or FVC) were identified: increase in (i) only FVC (FVC response), (ii) only FEV1 (FEV1 response), and, (iii) both FVC and FEV1 (double response). The mean +/- SEM absolute increase in FEV1 was significantly greater in asthmatics (307+/-17ml) as compared to 120+/-12 ml in COPD patients (p<0.0001). On the other hand, the increase in FVC was not different in the two groups (296+/-22 ml and 230+/-24 ml, respectively, p>0.05). The proportion of subjects showing a > or = 200 ml increase in FEV1 was greater among asthmatics as compared to COPD (p<0.0001) but the proportions showing a > or = 200 ml in FVC were similar (p>0.05). All the three types of responses were observed in asthmatics with a double response being the commonest. In COPD, an FVC response was the predominant response while the FEV1 response was rare. Multinomial logistic regression revealed that younger subjects (below 45 years) were more likely to have a double or exclusive FEV1 response. Greater severity of obstruction was associated with higher odds for each of the three responses, the odds being especially very high for an exclusive FEV1 response. The odds for a double response and an exclusive FEV1 response were significantly increased in asthmatics as compared to COPD. For FVC response, age category and disease were not significant determinants. It was concluded that bronchodilator responsiveness in asthma and COPD differs not only quantitatively but also in the pattern.     

Comparison of bronchial responses to ultrasonically nebulized distilled water, exercise, and methacholine in asthma

We compared the responses to inhaled methacholine, ultrasonically nebulized distilled water, and exercise in 25 subjects with atopic asthma. The methacholine inhalation test and challenges with distilled water and exercise were performed on three separate days 48 hours apart. Bronchial responsiveness to methacholine and ultrasonically nebulized distilled water was measured as the concentration of methacholine (PC20M) and the volume output of the ultrasonic nebulizer (PO20 UNDW) producing a 20 percent fall in the forced expiratory volume in one second (FEV1). The response to exercise was expressed as the percentage of fall in FEV1 from the value before exercise. Seventeen subjects showed a fall in FEV1 of more than 20 percent after exercise. Eight subjects had a stimulus-response curve to distilled water that was flat up to the maximal volume output from the nebulizer, but only four of them also showed no significant response to exercise. The response to exercise correlated better with PO20 UNDW (r = -0.66; p less than 0.01) than with PC20M (r = -0.19; p greater than 0.5) in those responding to distilled water. In all of the tested subjects, exercise-induced bronchoconstriction correlated with PC20M (r = -0.61; p less than 0.01). The mean PC20M was significantly lower in the subjects with a significant response to distilled water and exercise (p less than 0.001 and p less than 0.0001, respectively). We concluded that ultrasonically nebulized distilled water and exercise provoke significant bronchoconstriction in the subjects with more severe nonspecific bronchial hyperresponsiveness. The correlation found between the two stimuli supports the hypothesis that they act by similar mechanisms.     

Respiratory impedance response to a deep inhalation in children with history of cough or asthma

The aim of this study was to describe the change in respiratory impedance induced by a deep inhalation (DI) in children who developed a positive response to inhalation of methacholine (Mch). Eighteen children aged 4.5-12.5 years, presenting with chronic cough or doctor-diagnosed asthma, were studied at baseline after inhalation of Mch and after inhalation of a bronchodilator. Respiratory resistance (Rrs) and reactance (Xrs) were measured by the forced oscillation technique, varying transrespiratory pressure at 12 Hz around the head. The tidal flow (V') and volume (V) dependence of Rrs before and after the DI was characterized according to the equation Rrs = K1 + K2 x /V'/ + K3 x V. DI induced no significant change at baseline or after inhalation of a bonchodilator. During Mch challenge, Rrs and K1 were significantly lower, and K3 and Xrs significantly less negative after DI than before, during both inspiration and expiration; there was no change in K2.We conclude that DI results in a decrease in Rrs in children with induced bronchoconstriction. The associated changes in Xrs, K1, and K3, and lack of decrease in K2, suggest that dilatation of airways occurs at the bronchial level, with little contribution of the upper airways or of a change in breathing patterns.     

Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study

A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8-16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7-14 days. After inhalation, airway caliber (FEV(1)) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV(1)). A significant increase in FEV(1) was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV(1) from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV(1) after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P = 0.038 and AUC 92.0%.min vs. 205.7%.min, respectively, P = 0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children.     

Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline.

The onset of bronchoprotection as obtained by various beta2-agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting beta2-agonists formoterol and salmeterol and the short-acting beta2-agonist terbutaline were measured. Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV1): 90% predicted; mean fall in FEV1 after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 microg Turbuhaler), salmeterol (50 microg Diskus), terbutaline (500 microg Turbuhaler) or placebo. Exercise-induced bronchoconstriction (maximum fall in FEV1 or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (p<0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (p<0.05). These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three beta2-agonists.     

Increase in airway responsiveness and effect of deep inhalation on airway caliber in allergen-induced asthma. Relationship to the late-phase response.

The airway responsiveness to methacholine (MCh) and the effect of deep inhalation (DI) on airway caliber were determined in 18 asthmatic patients at baseline and 3 and 24 h after an allergen inhalation challenge. The dose of MCh causing a 20% fall of FEV1 (PD20) was used as an index of airway responsiveness; the ratio of forced expiratory flow at 40% of FVC from maximal and partial flow/volume curves (MEF40M/P) was used to assess the effect of DI on airway caliber. Thirteen patients showed a dual asthmatic response (DAR) to allergen, 5 patients an isolated early-phase asthmatic response (EAR). In the DAR patients, 3 h after allergen challenge, when the early-phase response had resolved and the late-phase response had yet to develop, MChPD20 (geometric mean) was reduced from 202 to 71 micrograms (P less than 0.001) whereas MEF40M/P at the MCh end point was unchanged (p greater than 0.4). Twenty-four hours after allergen challenge, when late-phase response had developed, MChPD20 was further reduced to 51 micrograms (p less than 0.02), and this reduction was accompanied by a decrease of MEF40M/P at the MCh end point (p less than 0.01). In the EAR patients, neither MChPD20 nor MEF40M/P was significantly changed at any time during the study. We conclude that most of the increase in airway responsiveness that follows acute exposure to allergen precedes the late-phase response and is not determined by the same mechanisms that impair the ability of the lung to dilate airways with a DI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease.

Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease (COPD), but its relevance to exercise capacity and symptoms is uncertain. Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients. We studied 32 patients with stable COPD, mean age 65 yrs, in a double-blind, placebo-controlled, cross-over trial of the inhaled anticholinergic drug, oxitropium bromide. From the within and between day placebo spirometry, we derived the spontaneous variation in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of this population (FEV1 140 ml; FVC 390 ml) and considered responses beyond this to be significant. Oxitropium bromide increased baseline FEV1 from 0.70 (0.28) l (mean (SD)) to 0.88 (0.36) l. The 6 min walking distance increased by 7% compared with placebo, whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug. Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC, indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients.     

The effects of oral propranolol and metoprolol on lung function and exercise performance in chronic airways obstruction.

Fifteen men with chronic airways obstruction received a test dose of propranol 20 mg orally. Six developed increased breathlessness. Nine who tolerated the test dose received metoprolol (100 mg) and propranolol (80 mg) on different days in a randomized double-blind fashion. Changes in resting and exercise heart rate, spirometry and exercise tolerance were measured 1 and 6 hours later. The drugs had similar effects on heart rate. Propranolol, but not metoprolol, caused significant reduction in forced expiratory volume in one second (FEV1) and peak expiratory flow rate. Neither drug produced significant changes in forced vital capacity (FVC) or exercise performances in the group as a whole, although the range of changes was wide. Despite considerable reduction in FEV1 and FVC in some individuals, most reported no increase in symptoms. Changes in exercise tolerance at 1 hour correlated significantly with changes in FVC but not with those in FEV1. It is proposed that changes in FEV1, though of pharmacological interest, may be less relevant clinically than changes in FVC.     

The effect of inhaled naloxone on resting bronchial tone and exercise-induced asthma

We wanted to determine whether 10 mg naloxone inhaled quantitatively could modulate the resting bronchial tone and respiratory response in exercise-induced asthma (EIA). In 11 asthmatic subjects, we measured specific airway conductance (SGaw) and forced expiratory flow (FEF) before and after the inhalation of naloxone or saline. In another 10 asthmatic subjects, we measured SGaw, FEF, and the ventilatory gas exchange, heart rate, and blood pressure responses produced by a treadmill exercise during 3 separate days: without any pretreatment (Day 1) or preceded by the inhalation of either 10 mg naloxone (Day 2) or saline (Day 3). We found that after 10 mg inhaled naloxone only one of 11 subjects bronchodilated, displaying an isolated, reproducible delta SGaw greater than 40% at 30 and 60 min. In the EIA protocol, the cardiopulmonary responses during exercise remained similar on all experimental days, but in seven of 10 subjects (all with %FEV1/FVC greater than or equal to 70% delta SGaw was -60 +/- 11%, + 1 +/- 40%, and -52 +/- 7% during no treatment, naloxone, and saline days, respectively (p less than 0.05). FEF changes were comparable on all days (p greater than 0.05). In conclusion: (1) consistent with the general role of endogenous opioids, these neurotransmitter/neuromodulators can modulate a stress-related bronchoconstrictor response (EIA), but only very seldom the resting bronchial tone. (2) Naloxone does not blunt EIA through a decrease in the asthmogenic stimulus (i.e., ventilation) or airway caliber change, but presumably through competition with the endogenous opioids released during exercise.     

Beta2-agonist tolerance and exercise-induced bronchospasm

The effect of regular inhaled beta-agonist on the treatment of exercise-induced bronchoconstriction was studied. Eight subjects with exercise-induced bronchoconstriction took 1 week each of salbutamol 200 microg qid or placebo in a random-order, double-blind, crossover study. They then withheld this treatment for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work-rate previously shown to induce a 15% fall in forced expiratory volume in 1 second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and 200 microg at 5-minute intervals. The mean pre-exercise FEV1 was similar on both study days. However, pretreatment for 1 week with salbutamol led to a significantly greater fall in FEV1 after exercise. The FEV1 remained lower than during the placebo arm despite the administration of salbutamol after exercise. This difference persisted 25 minutes after exercise. It is concluded that regular beta-agonist treatment leads to increased exercise-induced bronchoconstriction and a suboptimal bronchodilator response to beta-agonist. The data suggest that previous regular beta-agonist treatment may lead to a failure to respond to emergency bronchodilator treatment during an acute asthma attack and support current opinion that regular short-acting beta-agonist therapy should not be used to treat asthma.     

Airway response to inhaled fenoterol in hyperthyroid patients before and after treatment.

Bronchodilatory response to inhaled fenoterol was studied in 15 hyperthyroid patients before and after successful treatment with antithyroid drugs. Baseline forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were lower than the predicted values in 12 and 11 patients, respectively. Improved values were seen after treatment for hyperthyroidism although statistical significance was not reached. Even if some improvement occurred in PEFR (a rise by 0.24-0.48 L/s) and FVC (increase of 73-78 ml) in the hyperthyroid state in response to fenoterol inhalation after various time intervals, the increase in different parameters of lung function was significantly more after the patients achieved euthyroid state (increases in FVC by 290-165 ml; in FEV1 by 333-193 ml; in peak expiratory flow (PEFR) by 0.75-0.52 L/s and in forced expiratory flow (FEF50%) by 0.55-0.31 L/s). In the euthyroid state the mean absolute improvements from the baseline values were significantly higher (< 0.05-0.001). These observations indicate that bronchodilatory response is impaired in the presence of excess thyroid hormones and improves after euthyroid state is achieved.     

Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults.

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.