三种乙酰甲胆碱激发试验在成人支气管哮喘诊断中的应用

气道高反应性是支气管哮喘的重要特征.测定气道反应性对支气管哮喘的临床诊断日益重要.潮气吸人法以及定量雾化吸入法乙酰甲胆碱激发试验以第1秒用力呼气容积(FEV1)下降20%时所吸入的乙酰甲胆碱的累计药物浓度(PC20-FEV1)或总量(PD20-FEV1)来评价气道的高反应性;而Astograph法乙酰甲胆碱激发试验是以强迫振荡原理,以连续测定的呼吸阻力作为判断气道高反应性程度的指标.本文就三种激发试验对气道高反应的评价指标及在成人应用中的特点进行综述.     

Bronchial responsiveness, oscillations of peak flow rate and symptoms in patients with mitral stenosis.

To better characterize airway hyperresponsiveness reported in cardiac patients questionnaire-recorded symptoms, bronchial responsiveness to methacholine (Mch) and to ultrasonically nebulized distilled water (UNDW), diurnal oscillations of peak expiratory flow (PEF) rate were evaluated in 32 patients with moderate mitral stenosis. Twenty patients were responsive to Mch (defined as provocative dose producing a 20% fall in forced expiratory volume in one second (PD20 FEV1) less than 3.2 mg) (geometric mean PD20 FEV1 851 +/- 154 micrograms SE). Only two patients showed a fall in FEV1 greater than 20% after UNDW challenge. Patients responsive to Mch challenge had lower FEV1 as percentage of vital capacity (FEV1/VC) (80 +/- 4.8 vs 83 +/- 3.8%, p less than 0.05), higher coefficient of variation of PEF (CV-PEF) (7.1 +/- 2.8 vs 5 +/- 2.4, p less than 0.05) and higher prevalence of wheeze (70 vs 25%, p less than 0.05) in comparison with patients non-responsive to Mch challenge. CV-PEF was significantly related to FEV1 (r = 0.347, p less than 0.05) and maximal expiratory flow at 50% expired volume (MEF50) (r = 0.405, p less than 0.05). The probability of responding to Mch bronchial challenge increased proportionally with the increase in CV-PEF and the decrease in FEV1, FEV1/VC and MEF50. Airway hyperresponsiveness of patients with mitral stenosis seems to be more similar to that reported in bronchitic than in asthmatic patients.     

A new asthma severity index: a predictor of near-fatal asthma?

Bronchial hyperresponsiveness (BHR), measured as the provocative dose of inhaled histamine or methacholine required to produce a 20% fall in forced expiratory volume in one second (FEV1) (PD20), is widely used as one of the indices of asthma severity. Excessive bronchoconstriction, reflected by the maximal percentage fall in forced vital capacity (FVC) at PD20 (deltaFVC %) during BHR testing, is considered to be the most important pathophysiological determinant in fatal asthma. The present study hypothesized that an index which combines both the ease of airway narrowing and excessive bronchoconstriction, deltaFVC %/log(PD20), may be better in assessing asthma severity, especially in those at risk of near-fatal attacks. The dose-response curves of 46 asthmatics who underwent methacholine challenge testing were studied. Group 1 (n=14) patients had mild disease, Group 2 (n=21) had moderate disease and Group 3 (n=11) had severe disease, as classified according to the Global Initiative for Asthma. Nine patients had prior intubation for near-fatal asthma. deltaFVC %/log (PD20) was better than deltaFVC % and PD20 in categorizing patients into the three severity groups (p<0.0001), but more importantly, it was able to discriminate patients with previous intubation from those without (p=0.04). It also correlated better with FEV1 (% predicted), frequency of symptoms and inhaled steroid requirement than either index alone. It is concluded that the percentage fall in forced vital capacity/log of the provocative dose causing a 20% fall in forced expiratory volume in one second combines information on the ease and excessive degrees of airway narrowing in asthma. This new index may be better at assessing asthma severity and in discriminating those at risk of near-fatal attacks.     

Use of peak flow variability and methacholine responsiveness in predicting changes from pre-test diagnosis of asthma.

Asthma is usually diagnosed clinically. This study investigated how methacholine challenge and peak expiratory flow monitoring influenced change from a pretest clinical diagnosis. Records of 132 patients referred with respiratory symptoms, who subsequently had reliable measurements of both airway responsiveness (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1 (PC20)) and peak expiratory flow variability (PEFV) were reviewed. Initial and final diagnoses for each patient were classified as: a) definite asthma; b) possible asthma; and c) definitely not asthma. The predictive value of PEFV and PC20 regarding overall change from pre- to post-test diagnosis, change from initial diagnosis of possible or definitely not asthma, and change from initial diagnosis of definite asthma, were tested by multiple logistic regression analysis. Odds ratios for PC20 were expressed per doubling dose, and for PEFV per 5% variability. Clinical diagnosis of definite asthma and definitely not asthma were confirmed in 70% and 79% respectively. PC20, but not PEFV, predicted an overall change between pre- and post-test diagnosis. Both PC20 and PEFV independently predicted change to definite asthma. PEFV and interaction between PC20 and PEFV predicted a change in those whose initial diagnosis was definite asthma. Although both measurements showed a significant correlation, there was poor agreement between positive tests. Both peak expiratory flow variability and provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second influence diagnostic decision-making in patients with a high pre-test probability of asthma.     

Comparison of maximal airway narrowing to methacholine between children and adults.

Bronchial hyperresponsiveness in adults is characterized by an increased sensitivity as well as an elevated maximal response to inhaled bronchoconstrictors. In children, however, it is unknown whether the maximal response increases with increasing sensitivity. We investigated the maximal degree of airway narrowing to methacholine in nonasthmatic and asthmatic children (7-12 yrs), and compared it to that in adults. Nineteen children (9 normals, 10 asthmatics) and 19 adults (8 normals, 11 asthmatics) were selected in order to cover a wide distribution of bronchial responsiveness. All subjects underwent 2 methacholine challenge tests on separate days, by inhaling doubling doses using a standardized dosimeter technique (up to a noncumulative dose of 59 mumol). The response was measured by forced expiratory volume in one second (FEV1) and expressed as a percentage fall from baseline value. The complete dose-response curves were characterized by their position (PD20, the provocative dose causing a 20% fall in FEV1) and maximal response (MFEV1, the mean response on the plateau, defined as greater than or equal to 2 points within a 5% response range). Plateaus were observed in 13 children and 9 adults, the coefficient of repeatability of MFEV1 being 10.8 and 10.4% fall, respectively. There was an inverse relationship between log PD20 and MFEV1, which did not differ between children and adults (p greater than 0.15). In most of the asthmatic children and adults the plateau could not be measured (exceeding 50% fall in FEV1) if PD20 was less than 1 mumol. We conclude that, for a given bronchial sensitivity, the maximal response to inhaled methacholine is similar between children and adults.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in airway responsiveness to acetaldehyde and methacholine in asthma and chronic bronchitis.

Inhaled acetaldehyde may induce bronchoconstriction in asthmatic subjects and provides a new method to investigate airway responsiveness. The objective of the study was to determine whether acetaldehyde was a more specific stimulus than methacholine in differentiating asthma from chronic bronchitis with or without airflow limitation. Bronchial provocation challenges with methacholine and acetaldehyde were performed in 62 asthmatics and in 59 smokers with chronic bronchitis (32 with chronic bronchitis alone and 27 with chronic bronchitis and coexisting chronic obstructive pulmonary disease (COPD)). The response to both bronchoconstrictor agents was measured by the provocative concentration required to produce a 20% fall in forced expiratory volume in one second (FEV1; PC20). The two types of challenge yielded a similarly high level of sensitivity (100% for methacholine and 92% for acetaldehyde) in revealing airway hyperresponsiveness in asthma. However, bronchoprovocation with acetaldehyde yielded considerably greater specificity (95%) than bronchoprovocation with methacholine (24%) in separating asthma from chronic bronchitis. In subjects with asthma, methacholine and acetaldehyde responsiveness were weakly but significantly correlated (r=0.42, p=0.001) but no correlation was found between airway responsiveness to acetaldehyde and baseline FEV1 (r=0.13, p=0.33). These findings suggest that the demonstration of bronchoconstriction in response to acetaldehyde may be a more specific test than methacholine in the differentiation of asthma from chronic bronchitis. Furthermore, methacholine and acetaldehyde hyperresponsiveness are not reflecting the same pathophysiological process in the airways.     

Effect of breathing pattern during inhalation challenge on the shape and position of the dose-response curve

To examine the effect of breathing pattern on the dose-response curve, 4 mild asthmatic and 9 normal subjects inhaled increasing concentrations of methacholine (0.03-256 mg/ml) using a quiet tidal breathing pattern or tidal breathing with a forced expiratory phase. The provocative concentration of methacholine causing a 20% decrease in the forced expired volume in 1 s (PC20FEV1) or a 200% increase in pulmonary resistance (PC 200RL) was determined. In addition, the maximal change in FEV1 and RL and the slopes of the dose-response curves were measured. The forced expiratory pattern caused an increase in the central/peripheral deposition ratio of a [99m]technetium-labeled aerosol (n = 3). There were no differences in mean tidal volume, minute ventilation, inspiratory flow rates, or baseline FEV1 or RL between the quiet breathing or forced expiration studies, although mean expiratory flows were increased in the latter (p less than 0.001). PC20FEV1 and PC200 RL decreased (p less than 0.001) but the maximal change in FEV1 and RL was unchanged in the forced expiration studies. Forced expiration during inhalation challenge did not alter the slope of FEV1 or RL dose-response curves. These results suggest that the sensitivity (PC20, PC200) and maximal response of in vivo dose-response curves may be affected independently by factors such as aerosol deposition.     

Long-term follow-up of toluene diisocyanate-induced asthma.

Eighty-seven cases of occupational asthma induced by toluene diisocyanate (TDI) were diagnosed by an inhalation challenge with TDI and methacholine. After an average follow-up interval of 11 yrs, all subjects were re-examined. Of the 87 subjects examined, 13 (15%) had remained in the same job, 44 (50.5%) had been removed from exposure for <10 yrs and 30 (34.5%) had been removed for >10 yrs. The proportion of subjects who experienced symptoms of asthma and those who were hyperresponsive to methacholine was significantly lower. Of the patients, 59% used short-acting bronchodilators, 8% long-acting bronchodilators and 18% were on regular inhaled glucocorticoids. Thus, multiple regression analysis showed a positive correlation between forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) at follow-up and FVC and FEV1 at diagnosis, and a negative correlation with smoking and with therapy with bronchodilators. Stepwise logistic regression showed that the follow-up provocative dose causing a 20% fall in the FEV1 (PD20) could be predicted from baseline PD20. These results indicate that respiratory symptoms and airway hyperresponsiveness to methacholine persist in subjects removed from exposure to TDI for >10 yrs. A more favourable prognosis was associated with a better lung function and a lower degree of airway hyperresponsiveness to methacholine at diagnosis.     

European Community Respiratory Health Survey calibration project of dosimeter driving pressures.

Two potential sources of systematic variation in output from Mefar dosimeters, the system used in the European Community Respiratory Health Survey (ECRHS) study have been evaluated: individual nebulizer characteristics and dosimeter driving pressure. Output variation from 366 new nebulizers produced in two batches for the second ECRHS were evaluated, using a solute tracer method, at a fixed driving pressure. The relationship between dosimeter driving pressure was then characterized and between-centre variation in dosimeter driving pressure was evaluated in an Internet-based survey. A systematic difference between nebulizers manufactured in the two batches was identified. Batch one had a mean+/-SD output of 7.0+/-0.8 mg x s(-1) and batch two, 6.3+/-0.7 mg x s(-1) (p<0.005). There was a wide range of driving pressures generated by Mefar dosimeters as set, ranging between 70-245 kPa, with most outside the quoted manufacturer's specification of 180+/-5%. Nebulizer output was confirmed as linearly related to dosimeter driving pressure (coefficient of determination (R2)=0.99, output=0.0377 x driving pressure-0.4151). The range in driving pressures observed was estimated as consistent with a variation of about one doubling in the provocative dose causing a 20% fall in forced expiratory volume in one second. Systematic variation has been identified that constitutes potentially significant confounders for between-centre comparisons of airway responsiveness in the European Community Respiratory Health Survey, with the dosimeter driving pressure representing the most serious issue. This work confirms the need for appropriate quality control of both nebulizer output and dosimeter driving pressure, in laboratories undertaking field measurements of airway responsiveness. In particular, appropriate data on driving pressures need to be collected and factored into between-centre comparisons. Comprehensive collection of such data to optimize quality control is practicable and has been instigated by the organizing committee for the European Community Respiratory Health Survey II.     

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.     

Hyperosmolarity-induced increases in airway responsiveness and late asthmatic responses

Airway responsiveness to inhaled methacholine was assessed before and after bronchial challenge with ultrasonically nebulized hyperosmolar saline (UNHS), and these changes were correlated with the development of late asthmatic responses (LAR). Sixteen subjects with mild to moderate asthma had two consecutive methacholine challenges before and one after a cumulative-dose challenge with UNHS. Twelve of these subjects also had a single-dose hyperosmolar challenge to document the occurrence of LAR and determine if UNHS had a significant cumulative-dose effect. If a LAR was observed, a control day without challenge completed the study. Responsiveness to methacholine was similar on the 2 baseline methacholine challenges with a provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) (mean +/- SEM) of 1.11 +/- 0.94 and 1.16 +/- 0.94 mg.ml.1 (r: 0.98). However, it was significantly increased after the inhalation of UNHS with a PC20 (mean +/- SEM) of 0.57 +/- 1.00 mg.ml.1 (p less than 0.001). Two subjects developed a late fall in forced expiratory volume in one second (FEV1) of 19 and 46% after hyperosmolar challenge. In this last subject, the LAR, not reproduced on the control day, was associated with a marked post-UNHS change in PC20, going from a baseline of 4.4 to 0.7 mg.ml.1 after UNHS. The % fall in FEV1 following the dose-response hyperosmolar challenge and the single-dose hyperosmolar challenge were not different, with mean values +/- SEM of 34.9 +/- 2.2 and 35.8 +/- 4.1, respectively, (p greater than 0.5). In conclusion, airway responsiveness to methacholine may increase following hyperosmolar saline inhalation, often unrelated to LAR.     

The effect of bronchoalveolar lavage on bronchial responsiveness in patients with airflow obstruction

This study assessed the effect of bronchoalveolar lavage (BAL) on nonspecific bronchial responsiveness in 31 patients. Of these, 20 had airflow obstruction; 11 control subjects had normal pulmonary function. Bronchial responsiveness to methacholine, expressed as the dose of inhaled methacholine required to provoke a 20 percent fall in forced expiratory volume in one second (PD20 FEV1), was measured before and after BAL. We found no evidence for the induction of responsiveness by BAL in 11 control subjects with negative methacholine tests prior to the procedure. There were small but significant falls in FEV1 following BAL in both the control group and in patients with airflow obstruction. Thus, BAL does not appear to induce nonspecific bronchial hyperresponsiveness in subjects without airflow obstruction, nor does it affect airway responsiveness in emphysema patients. Among asthmatics, bronchial responsiveness can be increased as a result of BAL; this increase was greatest in patients who were most responsive initially.     

Reference values of the provocative concentrations of methacholine that cause 6% and 20% changes in forced expiratory volume in one second in a normal population

The provocative concentrations of inhaled methacholine that cause 6% (PC6) and 20% (PC20) falls in forced expiratory volume in one second (FEV1) were assessed in a population of 100 nonsmoking persons, equally distributed for sex, who ranged uniformly from 20 to 60 yr of age. These subjects had no respiratory symptoms, rhinitis, atopic history, or familial history of asthma. Single twofold dilutions of methacholine from 2 to 128 mg/ml were used; 81 and 34 subjects, respectively, showed PC6 and PC20 values less than 128 mg/ml. Eight subjects had PC20 values less than 16 mg/ml. In these subjects, the test had a good reproducibility (r = 0.92) when we repeated it, and serial measurements of peak expiratory flow rates did not suggest asthma. The fact that PC6 was related, although loosely, to baseline FEV, FEV/FVC, and forced expiratory flow during the middle half of the FVC (FEF) and that 4 of the 8 subjects with PC20 values less than 16 mg/ml had lower values of FEF might suggest that responsiveness to methacholine is partially linked with baseline airway caliber.     

Airway responsiveness and peak flow variability in the diagnosis of asthma for epidemiological studies.

Airway responsiveness and variability in peak expiratory flow (PEF) are widely used as objective diagnostic measures of asthma, but it is not clear how these variables should be calculated or adjusted to obtain the highest diagnostic validity for physician-diagnosed asthma in the community. Data from a community-based sample of 1,513 adults has been used. Airway responsiveness to methacholine and 7-day PEF data were obtained in 1991, asthma and respiratory symptoms were diagnosed by questionnaires in 1991 and 1999. Airway responsiveness was expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20), two-point and least-squares regression slopes. PEF variability was expressed as daily amplitude, weekly standard deviation and mean of the two lowest readings. Continuous measures were adjusted for measures of baseline airway calibre by linear regression. Measures of airway responsiveness had greater sensitivity for specificity for self-reported diagnosed asthma than expressions of PEF variability, before and after adjustment for airway calibre. Diagnostic validity was substantially better in adults aged <50 yrs; PD20 provided the best sensitivity for specificity (61% for 95% at 8.3 micromol). In those aged > or =50 yrs, no measure was closely related to diagnosed asthma. In younger age groups, provocative dose causing a 20% fall in forced expiratory volume in one second provides a valuable objective measure of asthma for epidemiological studies, but is unable to distinguish between asthma and chronic obstructive pulmonary disease in older people.     

A comparison of the Yan and a dosimeter method for methacholine challenge in experienced and inexperienced subjects.

Bronchial reactivity is being measured with increasing frequency in epidemiological studies, but there debate continues about the relative merits of the different methods used to measure reactivity, particularly for subjects with no previous experience of reactivity testing as is the case in epidemiological studies. Repeatability is likely to improve with practice, and laboratory based studies on experienced subjects may overestimate the repeatability of a test in inexperienced subjects. We have compared the repeatability of the Yan method with a dosimeter (Mefar) method of administering methacholine to 40 asthmatic subjects: 20 with experience of methacholine challenge on at least six previous occasions and 20 with no previous experience. Subjects attended the laboratory on four days within a two week period, at the same time of day. A methacholine challenge was performed on two occasions using the Yan method and on two occasions using the dosimeter. Methacholine responsiveness was measured as the provocative dose causing a 20% reduction in forced expiratory volume in one second (PD20FEV1). Geometric mean PD20FEV1 values with the Yan method were 1.14 doubling doses (DD) of methacholine higher than with the dosimeter method. In the experienced subjects, the 95% range for a single estimate was +/- 1.56 DD for the Yan method and +/- 1.37 DD for the dosimeter method. In the inexperienced subjects, the 95% ranges were +/- 2.65 and +/- 1.87 DD for the Yan and dosimeter methods, respectively. Thus, the differences in repeatability between the Yan and dosimeter methods, were small; experienced subjects gave more repeatable values than inexperienced subjects.     

Combined use of exhaled nitric oxide and airway hyperresponsiveness in characterizing asthma in a large population survey.

The aim of the present study was to see whether measurements of airway hyperresponsiveness (AHR) and nitric oxide (NO) in exhaled air (ENO) either separately or in combination, could differentiate between asthmatics and healthy control subjects in a population based survey. In central Norway 8,571 adolescents participated in a large-scale epidemiological survey (Young Helseunders?kelsen i Nord-Tr?ndelag (Health Survey in North-Tr?ndelag; HUNT). Asthmatic symptoms when exposed to pollen, pets or house-dust were reported by 7.8% (suspected asthmatics), while 56% reported no asthmatic or allergic symptoms (control subjects). From these respective groups 151 and 213 adolescents were investigated with allergy screening, measurements of exhaled and nasal NO, and methacholine challenge test. AHR (provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20) <2 mg) was confirmed in 75% of the suspected asthmatics versus 25% of the control subjects, whereas 52% versus 20% had elevated levels of ENO (> or =8 parts per billion (ppb)). ENO and dose response ratio to methacholine (DRR) were positively correlated (r=0.41, p<0.001). ENO was significantly elevated in atopic versus nonatopic suspected asthmatics (11.7 ppb and 5.6 ppb respectively, p<0.001). Suspected asthmatics with both AHR and atopy had the highest levels of ENO (14.2 ppb). It is concluded that measurements of nitric oxide in exhaled air alone are not a useful tool in diagnosing asthma in population surveys, but that the combination of airway hyperresponsiveness and elevated nitric oxide in exhaled air is a very specific finding for allergic asthma. The use of dose response ratio to methacholine did not provide any additional information to the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second in this study.     

Methacholine inhalation challenge: a shorter, cheaper and safe approach.

Increased nonspecific bronchial hyperresponsiveness to pharmacological agents such as histamine or methacholine (MCh) is a hallmark of asthma. The measurement of airway reactivity is quite sensitive but testing is tedious, and time and money consuming. The present aim was, therefore, to design the shortest possible, yet safe inhalation challenge protocol applicable for a lung function referral centre. All records of studies performed in our institution during 1996 were analyzed retrospectively with a baseline ratio (bl) of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) > or = 0.7 (n=449). It was questioned what the initial dose should be, and whether some inhalation steps could have been skipped without losing pertinent information and/or causing an adverse response (a fall in FEV1 >40%). When unavailable, provocative dose causing a 20% fall in FEV1 (PD20) values were obtained by linear inter- or extrapolation of the existing data. The present study showed that three-fold concentration steps could have been employed with minimal change in outcome. Only 151449 patients (3.3%) would have experienced a severe response. Five subjects (of 169, 3.0%) with FEV1/FVCbl 0.7-0.8 reacted to inhalation up to 0.073 micromol. Four subjects (of 280, 1.4%) with FEV1/ FVCbl> or =0.8 reacted to inhalation up to 0.219 micromol. The authors suggest that: 1) an initial dose of 0.219 micromol (initial concentration= 0.21 mg.mL(-1)) may be used when the baseline ratio of forced expiratory volume in one second to forced vital capacity > or =0.8 and 0.073 micromol (initial concentration=0.07 mg.mL(-1)) when the baseline ratio is <0.8; 2) a tripling dose protocol is easier to perform, cheaper and 30.2%, faster, yet just as safe; and 3) other abbreviated protocols used in epidemiologic settings may not be applicable in a referral centre setting.     

Limited maximal airway narrowing in nonasthmatic subjects. Role of neural control and prostaglandin release

In nonasthmatic subjects with normal airway responsiveness to methacholine, maximal airway narrowing is limited to a mild or moderate degree. We investigated whether the maximal response plateau or the position of the dose-response curve is due to functional inhibition by neurogenic mechanisms or to prostaglandin release. Four nonasthmatics inhaled doubling concentrations of methacholine up to 256 mg/ml (67 mg delivered during tidal breathing), followed by 4-fold-increasing doses of salbutamol up to 80 mg/ml (24 mg during tidal breathing) on 5 separate days. On each day 30 min before the test, the subjects inhaled (using a dosimeter) saline, propranolol (11 mg), or hexamethonium (910 mg) or, 2 h before the test, ingested indomethacin (75 mg) or placebo. The response to methacholine was measured from volume history standardized partial and complete maximal expiratory flow-volume curves, as FEV1 and the flows at 40% of the control FVC (V40p and V40c). Compared with saline, on average, baseline V40p was 18% lower after propranolol and 18% higher after hexamethonium. Indomethacin did not affect baseline values. There was no systematic difference between the 5 days in the dose of methacholine to cause a 10% fall in FEV1 or a 40% fall in V40p, or in the maximal response with FEV1, V40p, and V40c, or in V40p/V40c at 256 mg/ml methacholine. We conclude that limited maximal airway narrowing to methacholine in nonasthmatics is not due to a change in adrenergic, cholinergic, or ganglion-transmitted-nonadrenergic inhibitory activity nor to the release of prostaglandins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of CPAP on asthmatic patients with obstructive sleep apnoea.

The impact of continuous positive airway pressure (CPAP) treatment on the airway responsiveness of asthmatic subjects with obstructive sleep apnoea (OSA) has scarcely been studied. A prospective study was performed comparing the changes in airway responsiveness and quality of life in stable asthmatic OSA patients, before and 6 weeks after their nocturnal CPAP treatment. A total of 20 subjects (11 males and nine females) participated in the study. With the nocturnal CPAP treatment, the apnoea/hypopnoea index dropped from 48.1 +/- 23.6 x h(-1) to 2.6 +/- 2.5 x h(-1). There were no significant changes in airway responsiveness after CPAP treatment (provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV(1); PC(20) 2.5 mg x mL(-1) (1.4-4.5)) compared with baseline (PC(20) 2.2 mg x mL(-1) (1.3-3.5)). There was no significant change in FEV(1) either. However, the asthma quality of life of the subjects improved from 5.0 +/- 1.2 at baseline to 5.8 +/- 0.9 at the end of the study. In conclusion, nocturnal continuous positive airway pressure treatment did not alter airway responsiveness or forced expiratory volume in one second in subjects with stable mild-to-moderate asthma and newly diagnosed obstructive sleep apnoea. However, nocturnal continuous positive airway pressure treatment did improve asthma quality of life.     

The effect of gas cooking on bronchial hyperresponsiveness and the role of immunoglobulin E.

Some studies have shown an association between gas cooking and respiratory symptoms. This study investigated whether gas cooking affects bronchial responsiveness and whether particular subjects are more sensitive to this effect. Multiple linear regression analysis was performed with the dose-response slope (Percentage fall in forced expiratory volume in one second (FEV1) divided by total dose of methacholine given) as the dependent variable in 1,921 subjects from a random sample of the Dutch population, aged 20-70 yrs. Whether the association was different according to sex, age, total immunoglobulin (Ig)E, specific IgE to inhalant allergens or smoking habits was tested by including interaction terms into the regression model. Subjects who used gas for cooking had a higher prevalence of bronchial hyperresponsiveness (provocative dose causing a 20% fall in FEV1 (PD20) < or = 2 mg) than those who used electricity (21% versus 14%) and this was dependent on the presence of atopy. Especially subjects with total IgE levels in the highest quartile had a significantly higher dose-response slope when using gas for cooking. This was independent of the presence of specific IgE to inhalant allergens. These results show increased bronchial responsiveness with gas cooking, which was only found in subjects with high total immunoglobulin E levels. This suggests that atopic subjects are sensitive to adverse effects of gas cooking on respiratory health.