Bronchial responsiveness and work-related asthma in aluminium potroom workers: effect of removal from exposure.

Twelve subjects relocated from aluminium potrooms due to work-related asthma were followed up for 2-27 months (median 23 months). Repeated post-relocation examinations (numbering 3-7, median 6) of methacholine challenge, forced expiratory volume in one second (FEV1), eosinophil cell count and respiratory symptoms were carried out at regular intervals. At the time of relocation, bronchial hyperresponsiveness (provoking concentration producing a 20% fall in FEV1 (PC20) less than or equal to 8.0 mg.ml-1) was found in eight of the subjects. During the follow-up period a twofold increase in PC20 was found in 7 of the 8 subjects who had PC20 less than 8.0 mg.ml-1 at the time of relocation. There was an improvement of symptoms but no improvement in FEV1 or decrease of eosinophils during the follow-up examinations.     

Cough receptor sensitivity and bronchial responsiveness in normal and asthmatic subjects.

We examined whether airway cough receptor sensitivity correlates to nonspecific bronchial responsiveness. We measured cough threshold, the lowest concentration of inhaled tartaric acid eliciting five or more coughs, and the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20FEV1) in 38 normal and 11 asthmatic subjects. All subjects were nonsmokers. The geometric mean value of PC20FEV1 was 25.7 mg.ml-1 (GSEM1.29) and 0.63 mg.ml-1 (GSEM1.29) and the geometric mean value of the cough threshold was 115 mg.ml-1 (GSEM1.20) and 95.5 mg.ml-1 (GSEM1.35) in normal and asthmatic subjects, respectively. The PC20FEV1 was significantly (p less than 0.01) lower in asthmatics than in normals but the cough threshold did not differ between them. No significant correlation was observed between the cough threshold and the PC20FEV1 in normal subjects or in asthmatics. These results indicate that cough sensitivity does not directly correlate to bronchial responsiveness in normal and asthmatic subjects.     

Thromboxane A2 could be involved in bronchial hyperresponsiveness to methacholine in asthmatic subjects but not in bronchitic subjects

To determine whether the involvement of thromboxane A2 in bronchial hyperresponsiveness is specific to asthma, we examined the effects of a selective thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial responsiveness to methacholine in patients with bronchial asthma and chronic bronchitis. The provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20-FEV1) was measured before and after oral administration of OKY-046 and indomethacin in eight asthmatic and 10 bronchitic subjects. Baseline FEV1 value was not altered by OKY-046 or indomethacin. The geometric mean value of PC20-FEV1 increased significantly (p less than 0.005) from 1.78 to 4.27 mg/ml after OKY-046 in asthmatic subjects, but not in bronchitic subjects. On the other hand, PC20-FEV1 was not altered by indomethacin in all subjects. It was concluded that the involvement of thromboxane A2 in bronchial hyperresponsiveness may be specific to asthma.     

Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial hyperresponsiveness to methacholine in patients with bronchial asthma

It is unclear whether angiotensin II receptors are involved in bronchial hyperresponsiveness in asthmatic patients. We examined the effect of losartan, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in eight patients with stable asthma. Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV(1) (PC(20)-FEV(1)) and a 35% fall in standardized partial expiratory flow at 40% of FVC (PC(35)-PEF(40)), was measured on two occasions 2 wk apart. Losartan (50 mg once a day) or a placebo was orally administered for 1 wk before methacholine provocation test in a double-blind, randomized, crossover fashion. Although the PC(20)-FEV(1) values after placebo (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/ml) and losartan (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC(35)-PEF(40) values significantly (p = 0.034) increased from 0.258 (GSEM, 0.156) mg/ml with placebo to 0.456 (GSEM, 0.186) mg/ml with losartan. We conclude that AT1 receptors are involved in bronchial hyperresponsiveness in asthmatic patients. This is the first report demonstrating the involvement of AT1 receptors in bronchial asthma.     

Duration of tachyphylaxis in response to methacholine in healthy non-asthmatic subjects

It is well recognized that bronchial responsiveness to methacholine is reduced after methacholine-induced bronchoconstriction in non-asthmatic subjects, but not in asthmatic subjects. However, it is unknown how long the methacholine tachyphylaxis lasts. The present study was conducted to elucidate duration of the methacholine tachyphylaxis in healthy non-asthmatic subjects. Measurements of methacholine responsiveness were repeated six times at intervals of 1 h and 1, 2, 3 and 7 days in eight healthy non-asthmatic young female subjects in whom methacholine concentrations causing a 20% fall in forced expiratory volume in 1 sec (FEV1; PC20-Meth) were 40 mg/mL or less. Geometric mean value (GSEM) of PC20-Meth was 10.6 (1.44) mg/mL at the first challenge, 63.4 (1.85) at the 1-h interval, 50.2 (1.67) at the 1-day interval, 49.7 (1.68) at the 2-day interval, 17.3 (1.51) at the 3-day interval and 13.1 (1.44) mg/mL at the 7-day interval. The values at intervals of 1 h to 3 days were significantly greater than the initial value. These results indicate that measurements of methacholine responsiveness should be separated by at least 7 days to avoid the tachyphylaxis when the tests are repeated in non-asthmatic subjects.     

Asthma, asthmalike symptoms, chronic bronchitis, and the degree of bronchial hyperresponsiveness in epidemiologic surveys

Measurement of bronchial hyperresponsiveness has been suggested to be a useful test in identifying subjects with asthma in epidemiologic groups. We explored the association between the degree of bronchial hyperresponsiveness, respiratory symptoms suggestive of asthma, chronic bronchitis, and various definitions of asthma based upon information obtained from a questionnaire. We determined bronchial hyperresponsiveness by methacholine inhalation test, administered a standardized respiratory questionnaire, and performed spirometry on 1,392 male workers in various industries: 229 (16.5%) had PC20 less than 8 mg/ml, 66 (4.7%) had PC20 less than 2 mg/ml, and 8 (0.6%) had PC20 less than 0.5 mg/ml. Only 760 workers had no respiratory symptoms; no workers with PC20 less than or equal to 0.5 mg/ml, 31.0% of workers with PC20 greater than 0.5 but less than or equal to 2 mg/ml, and 38.0% of workers with PC20 greater than 2 but less than or equal to 8 mg/ml had no chest symptoms. Those reporting wheeze or breathlessness, and especially those with both symptoms, were significantly more likely to have bronchial hyperresponsiveness with a low PC20. The reporting of chest tightness did not influence this relationship, and there was no difference between the occurrence of "wheeze without a cold" and "persistent wheeze." Although there was a stronger association of PC20 less than or equal to 2 mg/ml with asthma than with chronic bronchitis, the association of PC20 greater than 2 and less than or equal to 8 mg/ml was not different with asthma than with chronic bronchitis. Bronchial hyperresponsiveness was more closely associated with asthma than with any asthmalike symptoms ascertained by a questionnaire developed for the study of chronic bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cough threshold to inhaled tartaric acid and bronchial responsiveness to methacholine in patients with asthma and sino-bronchial syndrome.

To evaluate the effect of chronic airway inflammation on cough sensitivity and bronchial responsiveness, we measured the cough threshold to tartaric acid and bronchial responsiveness to methacholine (PC20-FEV1) in 13 asthmatic, 13 bronchitic (sino-bronchial syndrome) and 49 healthy non-atopic subjects. All subjects were non-smokers. The geometric mean value of the cough threshold was 9.55, 5.62 and 12.3% in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly (p less than 0.02) lower than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.63 mg/ml) was significantly lower than those in bronchitic (8.7 mg/ml) (p less than 0.01) and normal subjects (21.4 mg/ml) (p less than 0.01). There was no correlation between cough threshold and PC20-FEV1 values [correlation coefficient (r) = 0.06, p greater than 0.1]. These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.     

Inhaled mannitol identifies methacholine-responsive children with active asthma

Inhaled mannitol has been developed for bronchial challenge testing in adults. This study determined if mannitol could identify children with active asthma and responsive to methacholine, and whether mannitol challenge was faster to complete than methacholine challenge. Twenty-five children (aged 6-13 years) responsive to methacholine and 10 nonasthmatic children unresponsive to methacholine were studied. The methacholine challenge (Cockcroft protocol) was followed by a mannitol challenge on separate days. Twenty-one asthmatic children were positive to mannitol. Three taking inhaled corticosteroids with borderline methacholine responsiveness did not respond to mannitol, and one could not complete the mannitol challenge due to cough. The geometric mean (GM) and 95% confidence interval (CI) for PD(15) for mannitol was 39 mg (19, 78), and PC(20) for methacholine was 0.6 mg/mL (0.35-1.02) (r(p) = 0.75, p < 0.001, n = 21). Responses to mannitol were repeatable: GM PD(15) for the first challenge was 29 mg (CI: 17,50), and for the second challenge, 33 mg (CI: 20, 55) (P = 0.44, n = 9). Mannitol was faster to administer than methacholine (median (range)) 14 min (5-32) vs. 29 min (19-49), respectively (P < 0.001). Time to recover to baseline FEV(1) spontaneously and after bronchodilator administration was similar for both challenges. There were no significant falls in arterial oxygen saturations. During mannitol challenge, the mean (SD) fall in FEV(1) in nonasthmatic children was 3.1% (2.9). We conclude that mannitol identifies children with airway hyperresponsiveness and is faster to perform than the methacholine challenge.     

Geographic and gender variability in the prevalence of bronchial responsiveness in Canada

OBJECTIVES: Geographic variability in reported prevalences of asthma worldwide could in part relate to interpretation of symptoms and diagnostic biases. Bronchial responsiveness measurements provide objective evidence of a common physiologic characteristic of asthma. We measured bronchial responsiveness using the standardized protocol of the European Community Respiratory Health Survey (ECRHS) in six sites in Canada, and compared prevalences across Canada with international sites. DESIGN: Samples of 3,000 to 4,000 adults aged 20 to 44 years were randomly selected in Vancouver, Winnipeg, Hamilton, Montreal, Halifax, and Prince Edward Island, and a mail questionnaire was completed by 18,616 individuals (86.5%). Preselected random subsamples (n = 2,962) attended a research laboratory for examination including more detailed questionnaires, lung function testing including methacholine challenge, and skin testing with 14 allergens. RESULTS: Prevalences of bronchial hyperresponsiveness, measured as cumulative dose of methacholine required to produce a 20% fall from the post-saline solution FEV1 < or = 1 mg, ranged from 4.9% (95% confidence interval [CI], 1.6 to 8.5) in Halifax to 22.0% (95% CI, 18.1 to 26.0) in Hamilton (median, 10.7%). In all Canadian sites, bronchial hyperresponsiveness was more prevalent in women than in men. Neither the geographic nor gender differences were accounted for by differences in age, smoking, skin test reactivity, or baseline FEV1. Geographic- and gender-related variability changed little when only bronchial hyperresponsiveness associated with asthma-like symptoms was considered. CONCLUSIONS: A wide variability in bronchial responsiveness can occur within one country, almost as wide as the range found across all international sites participating in the ECRHS study and not explained by differences in gender, smoking, skin test reactivity, and FEV1. While gender variability in the prevalence of bronchial responsiveness is likely due to hormonal and immunologic factors, geographic variability is likely to result from environmental factors.     

Bronchial hyperresponsiveness in subjects with gastroesophageal reflux

BACKGROUND: The relationship between gastroesophageal reflux (GER) and asthma has been widely studied in the last years. GER may interfere with airway reactivity and aggravate or even induce asthma. OBJECTIVE: To assess the prevalence of bronchial hyperresponsiveness (BHR) in patients with GER disease with a view to judging the potential influence of GER on BHR. METHODS: 30 patients with GER disease and no clinical evidence of asthma and 30 normal subjects underwent a methacholine bronchial challenge. The methacholine concentration that caused a 20% fall in the FEV(1) (PC20) was used to assess bronchial responsiveness. RESULTS: In the GER group 11 subjects of the 30 studied showed a PC20 methacholine equal to or less than 8 mg/ml while in the control group only 2 subjects had a PC20 methacholine equal to or less than 8 mg/ml (p < 0.01; ANOVA test). CONCLUSIONS: Subjects with GER had a greater increase in airway reactivity when inhaling methacholine compared to disease-free normal subjects.     

The airways effects of inhaled chlorbutol in asthmatic subjects

Chlorbutol is an antibacterial and antifungal agent incorporated in terbutaline (Bricanyl) nebulizer solution. Ten stable atopic asthmatic subjects undertook bronchial challenge testing, according to a double-blind protocol. Patients inhaled doubling concentrations of either methacholine (0.13-4.0 mg.ml-1) or chlorbutol (0.16-5.0 mg.ml-1) for 2 min until the forced expiratory volume in one second (FEV1) had fallen by 20% from baseline. If this had not occurred following the administration of the final concentration, then this highest concentration was repeated for 4 min. The nine subjects completing the study had a geometric mean provocation concentration producing a 20% fall from baseline FEV1 (PC20) methacholine of 0.16 mg.ml-1 (range less than 0.125-0.475 mg.ml-1). After inhalation of 2.5 mg.ml-1 chlorbutol one subject experienced a fall in FEV1 greater than 20%. In the remaining eight subjects, inhalation of chlorbutol did not affect airway calibre. We conclude that chlorbutol, in the concentration present in Bricanyl nebulizer solution, has no clinically significant effect on airway calibre.     

Bronchial responsiveness in a Norwegian community

Bronchial responsiveness to methacholine was examined in a Norwegian general population sample (n = 490) 18 to 73 yr of age. Altogether, 20 and 6% of the sample had PC20 less than or equal to 32 mg/ml and PC20 less than or equal to 8 mg/ml, respectively. The relationship of bronchial responsiveness to the following potential predictors were examined: sex, age, smoking habits, airway caliber (FEV1), FEV1 percent predicted (%FEV1), urban-rural area of residence, occupational airborne exposure in present job, and total serum IgE. After adjusting for age and FEV1, the odds ratio for PC20 less than or equal to 32 mg/ml was higher for men than for women in smokers and in ex-smokers, but did not vary by sex in nonsmokers, the adjusted odds ratio for PC20 less than or equal to 32 mg/ml in male compared with female smokers being 8.4 (95% Cl: 2.5-37.4). Irrespective of smoking status the sex- and FEV1-adjusted odds ratio for PC20 less than or equal to 32 mg/ml fell with increasing age. For every 10-yr increase in age the adjusted odds ratio for PC20 less than or equal to 32 mg/ml methacholine in nonsmokers decreased by 2.0 (95% Cl: 1.3-3.3). Also FEV1 and %FEV1 were predictors of PC20 less than or equal to 32 mg/ml after adjusting for sex and age irrespective of smoking status. Bronchial responsiveness (PC20 less than or equal to 8 mg/ml) was more prevalent in rural than in urban areas, the adjusted odds ratio being 2.5 (95% Cl: 1.1-5.9) for bronchial responsiveness in rural compared with urban residents after adjusting for sex, age, smoking habits, and FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Airway responsiveness to inhaled acetaldehyde in subjects with allergic rhinitis: relationship to methacholine responsiveness

BACKGROUND: Asthmatic subjects have an exaggerated airway response to inhaled acetaldehyde, but no information is available on airway responsiveness to this bronchoconstrictor agent in subjects with allergic rhinitis. OBJECTIVE: The aim of this study was to determine the effect of inhaled acetaldehyde on lung function in nonasthmatic subjects with allergic rhinitis. METHODS: A total of 78 adults (43 subjects with allergic rhinitis, 16 asthmatics and 19 healthy subjects) were challenged with increased concentrations of acetaldehyde and methacholine. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV(1) (PC(20)). RESULTS: The geometric mean PC(20) acetaldehyde value for asthmatics was 35.5 mg/ml compared with 67.6 mg/ml in subjects with allergic rhinitis and with 80.0 mg/ml in healthy subjects (p < 0.001). The PC(20) acetaldehyde values in the allergic rhinitis group were also significantly lower than in the healthy control group (p = 0.04). All of the subjects with allergic rhinitis and increased responsiveness to acetaldehyde showed airway hyperresponsiveness to methacholine, but 9 patients with hyperresponsiveness to methacholine failed to respond to acetaldehyde. CONCLUSIONS: We conclude that subjects with allergic rhinitis are less responsive to inhaled acetaldehyde than asthmatic subjects, but more than healthy controls. Furthermore, only approximately half the patients with allergic rhinitis and airway hyperresponsiveness to methacholine exhibit bronchoconstriction with inhaled acetaldehyde, thus suggesting that airway hyperresponsiveness to methacholine may not be the sole factor leading to bronchoconstriction in response to acetaldehyde.     

The role of cyclooxygenase products on bronchial responsiveness to methacholine in patients with sino-bronchial syndrome

The role of cyclooxygenase products on bronchial responsiveness to methacholine was studies in 9 patients with sino-bronchial syndrome. Provocative concentrations of methacholine, producing a 20% fall in forced expiratory volume in one second (FEV1)(PC20-FEV1) and a 35% fall in inverse respiratory resistance (Grs) (PC35-Grs), were measured before and after oral administration of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin). Baseline values of FEV1 and respiratory resistance (Rrs) were not altered by OKY-046 or indomethacin. Geometric mean values of PC20-FEV1 and PC35-Grs were significantly (p less than 0.005 and p less than 0.05) increased from 2.19 mg/ml (GSEM, 1.58) and 0.79 mg/ml (GSEM, 1.70) to 8.13 mg/ml (GSEM, 1.92) and 1.55 mg/ml (GSEM, 1.38) by indomethacin, whereas these values were not significantly increased by OKY-046. These findings indicate that not thromboxane A2 but bronchoconstricting prostaglandins may play a role in bronchial hyperresponsiveness in sino-bronchial syndrome.     

Lack of effect of 4 weeks of oral H1 antagonist on bronchial responsiveness.

Ten patients with stable chronic asthma completed a randomized double-blind placebo controlled crossover study examining the effect of 120mg terfenadine twice daily for 4 weeks on bronchial responsiveness. Bronchial responsiveness was measured by methacholine inhalation tests performed by the tidal breathing technique at 0, 2 and 4 weeks of active and placebo treatment periods separated by a one week washout period. There were no significant differences in mean baseline forced expired volume in 1 sec (FEV1) for placebo and terfenadine treatments (p greater than 0.05) and there were no differences between geometric mean provocative concentrations of methacholine to cause a 20% fall in FEV1 (PC20M) at 2 and 4 weeks of terfenadine (0.89 and 0.99 mg.ml.1) from placebo (0.94 and 0.84 mg.ml.1) (p greater than 0.05). Examination of individual PC20M values during terfenadine treatment showed that 5 patients had PC20M's outside their 95% confidence interval; 2 increased both 2 and 4 week values, 1 increased one value and 2 decreased one value each. It is concluded that terfenadine does not produce clinically significant changes in stable asthmatics.     

Need for monitoring nonspecific bronchial hyperresponsiveness before and after isocyanate inhalation challenge

BACKGROUND: Specific and nonspecific bronchial responsiveness may decline or disappear after cessation of exposure in the workplace in patients with occupational asthma, leading to false-negative specific inhalation challenge (SIC) results. METHODS: Twenty-two patients with suspected diisocyanate-induced asthma were studied. SIC with diisocyanates (toluene diisocyanate [TDI] or hexamethylene diisocyanate [HDI]) was carried out in a 7-m(3) dynamic chamber up to a maximum concentration of 19 parts per billion for 120 min. Methacholine inhalation challenges were performed before and 24 h after SIC with TDI or HDI. Patients who did not show an asthmatic reaction after SIC but had a greater than twofold reduction in provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) after the first isocyanate challenge underwent a second isocyanate SIC 2 days later. RESULTS: The first SIC with isocyanates elicited an asthmatic reaction in 13 patients (59%). In five patients who did not show an asthmatic reaction after the first SIC, PC(20) exhibited more than a twofold reduction. In three of the five patients, a second SIC with isocyanates elicited an immediate positive asthmatic reaction. Therefore, 3 of 16 patients (19%) were ultimately shown to have bronchial responsiveness to isocyanate; occupational asthma was demonstrated due to post-SIC monitoring of bronchial hyperresponsiveness to methacholine. CONCLUSION: PC(20) should be systematically assessed before and after SIC with isocyanates in the absence of significant changes in FEV(1) during SIC to avoid false-negative results.     

Bronchoalveolar lavage does not alter airway responsiveness in asthmatic subjects

Bronchoalveolar lavage (BAL) during fiberoptic bronchoscopy is being used increasingly for the investigation of asthma. Airway responsiveness to methacholine is a sensitive indicator of the presence and severity of asthma. Therefore, we studied the effect of BAL on methacholine airway responsiveness in stable asthmatics. Geometric mean methacholine PC20 was 1.34 mg/ml before and 1.80 mg/ml after BAL (p = 0.26) in asthmatics. Immediate symptoms of airway narrowing after BAL occurred only in the 3 asthmatics with moderate to severe hyperresponsiveness. These symptoms were rapidly relieved by inhaled bronchodilator. There was no relationship between the occurrence of symptoms and the amount of topical lidocaine used for local anaesthesia or the volume of lavage fluid returned. The absence of an effect of BAL on airway responsiveness supports the safety of this procedure in the controlled asthmatic patient with near normal FEV1, irrespective of the level of baseline airway responsiveness.     

Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling.

To study the physiopathology and significance of asymptomatic airway hyperresponsiveness (AHR), the clinical and bronchial immunohistological parameters were evaluated in subjects with asymptomatic and symptomatic AHR. Asymptomatic subjects with AHR (eight females/two males, no respiratory symptoms, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) <8 mg x mL(-1) and no treatment) were compared with asthmatic subjects paired for age, sex and PC20, and with nonatopic, nonasthmatic controls paired for age and sex. All three groups were evaluated once at baseline, whilst the asymptomatic AHR subjects were re-evaluated after 1 and 2 yrs. Measurements included spirometry, methacholine challenge, serum immunoglobulin (Ig)E, blood eosinophils, and bronchoscopy (at baseline and after 2 yrs only). At first evaluation, the mean blood eosinophil count, total serum IgE level, atopic index, baseline forced expiratory volume in one second (FEV1) and the degree of bronchial epithelial desquamation of the asymptomatic AHR subjects were similar to those of asthmatic subjects. However, they presented focal rather than the continuous bronchial subepithelial fibrosis observed in asthmatics. Their mucosal CD3, CD4, CD25, EG1 and EG2-positive cell counts were intermediate between those of the control subjects and asthmatics. At the end of the 2-yr follow-up, four of them had developed asthma symptoms. At this time, bronchial biopsies revealed an increase in the extent of subepithelial fibrosis and in the number of CD25 and CD4-positive cells, and a decrease in the number of CD8+ cells, particularly in subjects who developed asthma symptoms. These data suggest that asymptomatic airway hyperresponsiveness is associated with airway inflammation and remodelling, and that the appearance of asthma symptoms is associated with an increase in these features, particularly the CD4/CD8 ratio and airway fibrosis. Consequently, this study proposes an association between asymptomatic airway hyperresponsiveness and airway inflammation, structural changes and asthma although these relationships remain to be further evaluated.     

Comparison of two standardized methods of methacholine inhalation challenge in young adults.

In the European Community Respiratory Health Study (ECRHS), airway responsiveness to methacholine was determined using the Mefar dosimeter protocol. Elsewhere, the 2-min tidal breathing method has become the preferred standardized method. The relationship between measurements of responsiveness by these two methods is not well established. This study measured airway responsiveness to methacholine by dosimeter and tidal breathing methods in 47 healthy asthmatic subjects aged 20-44 yrs. Tests were performed within 1 week and in random order. Baseline forced expiratory volume in one second (FEV1) varied by <10% between tests in 42/47 subjects. There was a close association between responsiveness determined by the two methods. A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) value of < or =8.0 mg x mL(-1) (tidal method) used to categorize airway hyperresponsiveness agreed most closely with a provocative dose of methacholine causing a 20% fall in FEV1 (PD20) value of < or =0.5 mg (dosimeter method) (kappa statistic 0.78). Each doubling or halving of PC20 to define a level of hyperresponsiveness agreed closely with a doubling or halving of PD20. Assessment of airway responsiveness as provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second by the Mefar dosimeter protocol gave a close and predictable relationship with provocative concentration of methacholine causing a 20% fall in expiratory volume in one second assessed using the tidal breathing method. Airway hyperresponsiveness as determined by the accepted criterion of provocative concentration of methacholine causing a 20% fall in expiratory volume in one second < or =8 mg x mL(-1) was best correlated with provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second <0.5 mg by Mefar dosimeter.     

Effect of output from jet nebulizers on PC20 values in asthmatic children

This study aimed to assess the effects of two different nebulizer outputs on airway responsiveness to methacholine in asthmatic children. Twenty-seven atopic asthmatic children aged 6 to 14 years inhaled methacholine according to the Cockroft method until FEV1% had decreased 20% with respect to saline inhalation (PC20). The bronchial challenge tests were performed using two different types of jet nebulizer: Ava Neb 1780 and Hudson UP Draft II 1730, the outputs of which were 205 +/- 13 mg/min and 356 +/- 31 mg/min, respectively (p < 0.05). For 9 out of 27 patients (33%) the PC20 values were significantly different (one or more double concentrations) for the two nebulizers. However, 7 of those 9 children showed significantly lower bronchial responsiveness when the challenge tests were conducted with the low output jet nebulizer. This study suggests that using jet nebulizers with different outputs can markedly influence the results of methacholine challenge tests in asthmatic children. Such an influence could introduce significant bias in the assessment of bronchial responsiveness in comparative measurements in a single individual or in populations.