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.     

二尖瓣狭窄患者气道高反应性与糖皮质激素吸入的治疗 …

目的 了解气道反应性增高和二尖瓣狭窄患者咳嗽及气短症状间的关系,以及糖皮质激素吸入的治疗作用。方法 测定２３例二尖瓣狭窄患者的气道反应性,对１５例（６５％）气道反应性增高者,随机分为丙酸倍氯米松治疗组（８例）和安慰剂组（７例）,治疗６周后复查。治疗前后测定患者咳嗽及气短症状评分。对８名气道反应性正常者亦吸入丙酸倍氯米松作为对照组。结果 丙酸倍氯米松吸入组治疗６周后,其气道反应性显著降低（Ｐ〈０．０     

Is asymptomatic bronchial hyperresponsiveness an indication of potential asthma? A two-year follow-up of young students with bronchial hyperresponsiveness.

To determine the possibility that asymptomatic bronchial hyperresponsiveness (BHR) develops into symptomatic asthma, a two-year follow-up study was conducted in 81 students (48 male, 33 female; 11 to 17 years) who were found to have BHR in a 3,067 population survey (BHR group). Eighty-eight age-matched students (48 male, 40 female) with normal bronchial responsiveness served as control subjects. Daily symptom cards were recorded. Peak expiratory flow rate was measured for 24 h when symptoms occurred. Histamine inhalation tests were performed at the beginning of the study and at the end of the first and the second year. In the BHR group, 58 students remained bronchial hyperresponsive at the end of follow-up. Nine of 31 students with initially diagnosed bronchial asthma had their symptoms relieved entirely, but ten asymptomatic students developed asthma. The incidence of newly diagnosed asthma (12.5 percent in the BHR group or 20 percent in the asymptomatic BHR group) and the total percentage of diagnosed asthma (39.5 percent) in the BHR group were significantly higher than those (2.27 percent, 2.27 percent) in the control group. FVC and FEV1 showed no significant difference between two groups. PD20 FEV1 values in newly diagnosed asthmatics were significantly lower than those in asymptomatic students both at the beginning (3.05 +/- 1.56 mumol vs 6.14 +/- 1.60 mumol, p < 0.05) or the end (3.47 +/- 1.73 mumol vs 6.55 +/- 1.51 mumol, p < 0.05). The percentage of early respiratory illness was significantly higher in those with newly diagnosed asthma (80 percent) than in asymptomatic students (22.3 percent), but atopic index and the percentage of parental asthma showed no difference between two groups. In nine asthmatics whose symptoms were relieved entirely in the two-year follow-up, PD20 FEV1 was undetectable within the cumulative dose of 7.8 mumol of histamine in three students and rose from 4.58 +/- 1.85 mumol to 7.62 +/- 1.02 mumol in the remaining six. The higher the BHR, the more likely the students developed asthma. About 45 percent of asymptomatic students with PD20 < or = 3.2 mumol developed asthma in the following two years and 80 percent of them had a history of early respiratory illness, suggesting that they may have subclinical or potential asthma.     

Comparative effects of oral and inhaled verapamil on antigen-induced bronchoconstriction

We investigated the comparative effects of oral and inhaled verapamil on specific airway conductance (SGaw) and allergic bronchial reactivity. Ten asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma were studied on four different days, without and with pre-treatments by oral (160 mg) or inhaled (20 mg) verapamil. Bronchial reactivity was measured as the cumulative provocative dose of ragweed antigen which caused a 35 percent decrease in SGaw, ie PD35. The amount of inhaled verapamil actually deposited in the tracheobronchial tree was estimated to be 0.56 mg. Mean SGaw was not affected by either mode of administration; mean SGaw (SE) was 0.13(.02) and 0.12(.02) L/sec-1 before and .14(.02) and 0.12(.02) L/sec-1 after oral and inhaled verapamil, respectively. Mean (SE) PD35 was reproducible on two control days, ie 0.9(.4) and 0.8(.4) breath units, respectively. Inhaled verapamil increased mean PD35 to 18.8 (10.8) breath units (p less than 0.02), while oral verapamil had no significant effect on mean PD35. This study demonstrates that route of administration of calcium antagonist verapamil is an important factor in protection against antigen-induced bronchoconstriction. Inhalation of verapamil appears to be more effective than oral administration.     

Adenosine-induced bronchoconstriction in asthma. Antagonism by inhaled theophylline

Inhaled adenosine causes bronchoconstriction in asthmatic patients. Antagonism of the bronchoconstrictor effect of endogenous adenosine has been proposed as a possible mechanism of action of theophylline in asthma. To directly investigate this, we have compared the airway responses to inhaled adenosine and histamine, with and without the prior administration of inhaled theophylline in 8 allergic asthmatic subjects. Airway response was measured both as forced expiratory volume in one second (FEV1) and as specific airway conductance (SGaw). Inhaled adenosine was less potent than histamine in producing bronchoconstriction, with geometric mean concentrations required to produce a 20% fall of FEV1 (PCf20) and a 40% fall of SGaw (PCs40) being 0.27 and 0.25 mg/ml for adenosine and 0.10 and 0.09 mg/ml for histamine. In a total nebulized dose of 37.5 mg, inhaled theophylline was a weak bronchodilator that caused maximal increases in FEV1 of 2 +/- 2% (mean +/- SE, p less than 0.05) and in SGaw of 8 +/- 4% (p greater than 0.05). However, theophylline significantly inhibited adenosine-induced bronchoconstriction, increasing the PCf20 and PCs40 values for adenosine to 1.66 (p less than 0.001) and 2.34 (p less than 0.005) mg/ml, respectively. Inhibition of histamine-induced bronchoconstriction was less marked, with PCf20 and PCs40 values of 0.19 (p greater than 0.05) and 0.21 (p less than 0.05) mg/ml. Thus, adenosine is a bronchoconstrictor in asthma whose effects are preferentially antagonized by concentrations of theophylline that cause little change in baseline airway caliber.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of three measures of the response to inhaled methacholine

In studies of asthma prevalence bronchial responsiveness has usually been measured as the provocative dose of bronchoconstrictor causing a 20% fall in FEV1 (PD20FEV1). This is relatively insensitive and only 10-20% of subjects in a general population sample will show such a response. Attempts to increase sensitivity, such as the use of the provocative dose causing a 10% fall in FEV1 (PD10FEV1), have not demonstrated any overall advantage, due to poorer repeatability. It has been suggested that measurement of bronchial reactivity using flow at low lung volumes measured from a partial flow volume curve is a more sensitive index of bronchoconstriction than PD20FEV1. If equally repeatable, it would have advantages in epidemiological practice. In 20 subjects with asthma, we compared the sensitivity and repeatability of PD10FEV1, PD20FEV1, and the provocative dose causing a 40% fall in flow at 30% of vital capacity (PD40V30P) following methacholine challenge. PD40V30P was more sensitive than both PD20FEV1 and PD10FEV1 by 1.48 and 0.35 doubling doses (DD) of methacholine, respectively. PD20FEV1 and PD40V30P showed equal repeatability, the 95% range for a single estimate of both being 2.02 DD. PD10FEV1 was less repeatable, with a 95% range of 2.35 DD. Values for the intraclass correlation co-efficient, which measures the ability of a test to discriminate between subjects, were 0.63, 0.79 and 0.69 for PD10FEV1, PD20FEV1, and PD40V30P, respectively. The increased sensitivity and comparable repeatability of measurement of bronchial reactivity for PD40V30P suggest that this method may be useful for studies of asthma prevalence.     

Improvement in bronchial hyperresponsiveness with inhaled corticosteroids in children with asthma: importance of family history of bronchial hyperresponsiveness

The extent of improvement in bronchial hyperresponsiveness (BHR) with corticosteroids varies considerably among patients with asthma, although predictive factors for improvement are largely unknown. We tested the hypothesis that the improvement may vary according to family history of BHR. Children with atopic asthma (n = 121) received inhaled budesonide (800 micro g per day) regularly for 6 months. Methacholine provocative concentration causing a 20% fall in FEV(1) was measured before treatment and again after 3 and 6 months of treatment. A methacholine challenge test was also performed in each patient's parents, and the results were analyzed with regard to their children's response to corticosteroid therapy. When the children were classified into large (n = 40) and small (n = 40) improvement groups after 6 months of treatment, the prevalence of BHR and the bronchial responsiveness index were higher in parents of the small improvement group (28.8%, 1.145 +/- 0.104) than in parents of the large improvement group (6.3%, 1.095 +/- 0.064; both, p < 0.01). The magnitude of improvement in BHR at 6 months was lower in children with at least one parent with BHR (n = 45; 1.666 +/- 1.244 doubling doses) than in children with non-BHR parents (n = 76; 2.531 +/- 1.726, p < 0.01). Our results suggest that a family history of BHR may be an important factor in the sensitivity of BHR of individuals with asthma to inhaled corticosteroids.     

Time domain and flow indices of bronchial hyperresponsiveness: association with asthma symptoms, atopy and smoking.

Conventional measures of bronchial hyperresponsiveness (BHR) are only weakly associated with respiratory symptoms in epidemiological studies. Partial and maximal forced expiratory manoeuvres were recorded during histamine challenge testing in 1,959 young male farmers. Analysis was performed to test whether novel measures of BHR, using alternative flow and time domain indices, are more closely associated with asthma symptoms, smoking status and atopy than forced expiratory volume in one second (FEV1) and conventional measures of BHR. The first moments to 75% and 90% of the forced vital capacity (FVC) were calculated from full (F) and partial (P) forced expiratory manoeuvres (i.e. alpha1 75%F, alpha1 75%P), together with the instantaneous flows when 40% and 30% of the FVC remained to be expired (MEF40 and MEF30). BHR was measured by the provocative dose causing a 20% change (PD20) in the FEV1 and alpha1 75%, and also by the method of log dose slopes (LDS). Asthma was diagnosed from symptoms associated with asthma in 158 (8.1%) of the subjects. PD20 FEV1 could only be recorded in 190 subjects (9.7%), of whom only 48 had asthma, whereas LDSFEV1 was recorded in 1,725 (88%) subjects. From the prechallenge data, alpha1 75%, expressed as standardised residuals, showed the largest difference between smokers with and without asthma symptoms, and no indices showed significant differences between nonsmokers with and without asthma symptoms. From BHR data in both smokers and nonsmokers, LDSFEV1 showed one of the largest differences between those with and without asthma symptoms. With smoking status and atopy accounted for, the greatest partial correlation with asthma diagnosis was found for LDSMEF40P, and then for LDSFEV1, but LDSMEF40P was measurable in only just over one-half of the subjects. The authors conclude that time-domain indices are promising measures for longitudinal epidemiological studies concerning the relationship between bronchial hyperresonsiveness and environmental exposures. However, indices from the partial flow-volume loop suffer from censored data.     

Effect of long-term treatment with sodium cromoglycate on nonspecific bronchial hyperresponsiveness in asthma

Several studies in the past have demonstrated a reduction in nonspecific bronchial hyperresponsiveness subjects with seasonal extrinsic asthma after long-term treatment with sodium cromoglycate. Since sodium cromoglycate is an effective drug in the prophylactic treatment of all types of asthma, we assessed the effect of a three-month treatment on nonspecific bronchial hyperresponsiveness in 11 patients with perennial asthma. Bronchial responsiveness was determined by histamine bronchoprovocation test, using SGaw as the index of lung function and expressed as PD35SGaw. During the run-in period of one month when sodium cromoglycate was not used, the histamine PD35SGaw decreased significantly from 0.15 +/- 0.30 to 0.09 +/- 0.29 mg/ml (p less than 0.001). After three months of treatment with the drug, bronchial hyperresponsiveness was reduced significantly; the PD35SGaw was 0.21 +/- 0.29 mg/ml (p less than 0.001). It was concluded that long-term treatment of patients with perennial asthma with sodium cromoglycate results in reduced bronchial hyperresponsiveness.     

An assessment of methacholine inhalation tests in elderly asthmatics

We have assessed the feasibility and value of measuring nonspecific bronchial responsiveness to methacholine in investigation of asthma in the elderly. Results from duplicated tests in 20 subjects aged 65-82 years were expressed as dose provoking a 20% decrement in 1 second forced expiratory volume (PD20.FEV1) or peak expiratory flow (PD20.PEF). Repeatability for PD20.FEV1 was satisfactory but less good than in younger subjects, 95% confidence limits being 0.39-2.57 and 0.52-1.91, respectively, x initial PD20. For PD20.PEF, confidence limits were wider (0.26-3.91 x initial PD20) but multiple PEF measurements were better tolerated than those of FEV1, which commonly caused fatigue and dizziness. PD20.FEV1 and PD20.PEF correlated closely (r = 0.95, P less than 0.0001) and both predicted bronchodilatation following a 6-week course of inhaled corticosteroid and beta agonist. This was not predicted by the response to a single dose of beta agonist. We conclude that measurement of bronchial responsiveness is feasible and clinically valuable in elderly subjects.     

Spontaneous changes in bronchial responsiveness in children and adolescents: an 18-month follow-up

The purpose of this study was to investigate spontaneous changes in bronchial responsiveness to inhaled histamine over a period of 18 months. The first measurements in 495 subjects, 7 to 16 years of age, were made in 1986. Bronchial hyperresponsiveness (BHR), i.e., PC-20 FEV1 less than or equal to 8.0 mg/mL, was found in 79 (16%) individuals, of whom 28 (35%) had symptoms of asthma. Twenty asthmatic and 42 non-asthmatic subjects who had BHR (78%) were re-examined 18 months later. The asthmatics had a modest change in BHR, while in the non-asthmatics bronchial response to inhaled histamine and exercise was significantly decreased. In twenty-two subjects (36%) bronchial response was within the normal range; of these 18 were non-asthmatic. Six asthmatics (30%) and two non-asthmatics (5%) had an increased BHR at follow-up. Two subjects (5%) developed symptoms of asthma by the time of follow-up, with an unchanged degree of BHR. Sex, age, atopic symptoms, and viral respiratory infections at the first examination were unrelated to changes in bronchial responsiveness. However, changes of BHR in the non-asthmatic subjects were significantly correlated to changes in bronchial response to exercise. Although spontaneous changes in bronchial responsiveness occur in asthmatic, as well as non-asthmatic subjects, asthmatics persistently have hyperresponsive airways. Development of asthma was found to occur among subjects with persistent BHR.     

Provocative dose and dose-response curve to inhaled propranolol in asthmatic patients with bronchial hyperresponsiveness to methacholine

This study was carried out to compare bronchial responses to inhaled propranolol (P) and methacholine (M) in a group of asthmatic subjects with mild to moderate bronchial hyperresponsiveness to M; to determine the short term reproducibility of bronchial response to propranolol; and to examine the shape of dose-response curve to P relative to that of M. Doses of M and P were given in mumoles and bronchial responses to both agents were expressed as the provocative dose that induced a 20 percent fall in FEV1 (PD20 FEV1). In 16 asthmatic patients, there was no correlation between the PD20 of the two agents. Mean PD20 M (+/- SD in log scale) was approximately nine times lower than mean PD20 P (0.64 +/- 0.96 and 5.80 +/- 1.65, respectively). This difference was statistically significant (t = 4.58, p less than 0.001). In six asthmatic patients, the reproducibility of PD20 P was similar to that of M (intraclass correlation coefficient 0.969 and 0.957, respectively). The shape of the dose-response curves to P was different from that of M in five of nine asthmatic patients when all experimental points were analyzed by double-reciprocal plot. We noticed that even small doses of inhaled P may cause a severe bronchoconstriction. Therefore, special caution should be taken to increase P doses very gradually, when studying the dose-response curve. We demonstrated that P inhalation induced a measurable bronchoconstriction in subjects with mild to moderate hyperresponsiveness and it was reproducible. However, the bronchial sensitivity to P was lower than to M. Our findings suggest that P and M have different mechanisms of action.     

Dose-response slope of forced oscillation and forced expiratory parameters in bronchial challenge testing.

In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose-response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT). Five doses of carbachol (320 microg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 > or = 20% (PD20) or a rise in Rm or R10 > or = 47% (PD47,Rm and PD47,R10) were calculated by interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 delta%Rm and delta%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 > or = 20%) were assessed by receiver operating characteristic (ROC) curves. There were 23 (32%) "spirometric" reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962; p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; delta%Rm: Se=86.9%, Sp=52.1%; and delta%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of forced oscillation technique resistance, especially the dose-response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.     

Do inhaled corticosteroids affect perception of dyspnea during bronchoconstriction in asthma?

BACKGROUND: Some of the disagreements on the perception of dyspnea (PD) during bronchoconstriction in asthma patients could depend on the interrelationships among the following: (1) the influence of baseline airflow obstruction on the patient's ability to detect any further increase in airway resistance; (2) the effect of eosinophilic inflammation on the airway; (3) bronchial hyperresponsiveness (BHR); and (4) the effect of inhaled corticosteroids (ICSs). OBJECTIVE: We hypothesized that if the inflammation of the airway wall influences to some extent and in some way the PD in asthma patients, ICSs reverse the effect of airway inflammation on the PD. METHODS: We studied 100 asthma patients who were divided into the following four groups: patients with obstruction who were either ICS-naive (group I) or were treated with ICSs (group II); and nonobstructed patients who were either ICS-naive (group III) or were treated with ICSs (group IV). PD on the visual analog scale (VAS) was assessed during a methacholine-induced FEV(1) decrease and specifically was quantified as the VAS slope and score at an FEV(1) decrease of 5 to 20%. BHR was assessed in terms of the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). Eosinophil counts in induced sputum samples also were performed. Regression analysis, univariate analysis of variance, and factor analysis were applied for statistical evaluation. RESULTS: For a 5 to 20% fall in FEV(1) from the lowest point after saline solution induction, VAS score was lowest in group II, slightly higher in group I, slightly higher still in group IV, and the highest in group III. In the patients as a whole, BHR related to PD, but age, clinical score, duration of the disease, and presence of baseline airway obstruction did not. In patients with obstruction who were treated with ICSs, eosinophil counts related to PD negatively. Factor analysis yielded the following four factors that accounted for 70% of the variance in the data: ICS; eosinophil counts; FEV(1); and PC(20) loaded on separated factors with PD loading on the same factors as PC(20). The post hoc analysis carried out dividing the patients into ICS-treated and ICS-naive, showed that in the former group eosinophil counts and BHR proved to be factors negatively associated with PD, while in the latter group eosinophil counts were positively associated with PD. CONCLUSIONS: We have shown that eosinophilic inflammation of the airway wall may increase PD and that the association of eosinophil counts with ICSs may result in lessening the PD.     

Bronchial hyperresponsiveness decreases through childhood

Limited knowledge exists about development of bronchial hyperresponsiveness (BHR) through adolescence. We aimed to assess changes in and risk factors for BHR in adolescence. From a Norwegian birth cohort 517 subjects underwent clinical examinations, structured interviews and methacholine challenges at age 10 and 16. BHR was divided into four categories: no BHR (cumulative methacholine dose required to reduce FEV(1) by 20% (PD(20)) >16 μmol), borderline BHR (PD(20) ≤16 and >8 μmol), mild to moderate BHR (PD(20) ≤8 and >1 μmol), and severe BHR (PD(20) ≤ 1 μmol). Logistic regression analysis was used to assess risk factors and possible confounders. The number of children with PD(20) ≤ 8 decreased from 172 (33%) to 79 (15%) from age 10-16 (p < 0.001). Most children (n = 295, 57%) remained in the same BHR (category) from age 10-16 (50% with no BHR), whereas the majority 182 (82%) of the 222 children who changed BHR category, had decreased severity at age 16. PD(20) ≤ 8 at age 10 was the major risk factor for PD(20) ≤ 8 6 years later (odds ratio 6.3), without significant confounding effect (>25% change) of gender, active rhinitis, active asthma, height, FEV(1)/FVC, or allergic sensitization. BHR decreased overall in severity through adolescence, was stable for the majority of children and only a minority (8%) had increased BHR from age 10 to 16. Mild to moderate and severe BHR at age 10 were major risk factors for PD(20) ≤ 8 at 16 years and not modified by asthma or body size.     

Prevalence and nature of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease

The prevalence, nature, and severity of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease (COPD) is not known. To determine these factors, a 1 in 4 random sample of adults attending the Busselton population survey was studied. Subjects answered a modified Medical Research Council questionnaire and had spirometric function tested. They were defined as having COPD or asthma from the questionnaire. Bronchial responsiveness to histamine was measured using the rapid method, and results in the subjects with COPD were compared with those in asthmatic subjects with abnormal lung function. Fifty-nine subjects with COPD had a histamine inhalation test, and of these, 27 had bronchial hyperresponsiveness (BHR) (PD20FEV1 less than 3.9 mumol). The position of the dose response curves of the subjects with COPD overlapped considerably with those obtained from the 17 asthmatics. The geometric mean values for PD20FEV1 for these 2 groups were significantly different (p less than 0.001). There was a good correlation between FEV1/FVC and PD20FEV1 values in the subjects with COPD but not in the asthmatic subjects. Pretreatment with 600 micrograms of aerosolized fenoterol significantly improved the PD20FEV1 values in 11 subjects with COPD (1.26 to 6.16 mumol; p less than 0.001). The results suggest that approximately half the subjects with COPD in a general population have BHR but this BHR has different characteristics from that occurring in asthmatic subjects.     

Measures of perception of bronchoconstriction and clinical and functional data are not interrelated in asthma

BACKGROUND: Sensitivity and absolute perceptual magnitude characterize the perception of bronchoconstriction (PB). OBJECTIVES: To define whether clinical and functional characteristics and level of bronchial hyperresponsiveness (BHR) correlate with these two PB indexes during bronchial challenge in asthma. METHODS: PB on both the Borg scale and the visual-analogue scale (VAS) was assessed in 45 consecutive asthmatics during a methacholine-induced decrease in forced expiratory volume in 1 s (FEV(1)) and specifically quantified as Borg and VAS slope, as a measure of sensitivity, whereas scores at a 20% FEV(1) decrease (PB(20)) were assessed as a measure of absolute perceptual magnitude. Clinical score and BHR were also assessed. RESULTS: PB(20) related to slope on both the Borg scale and the VAS (p < 0.0001). PB(20) and slope related neither to clinical score nor to baseline functional data on both scales. The relationship between the level of BHR and PB(20) on either scale was of questionable clinical significance (r(2) = 7%). CONCLUSIONS: Irrespective of the scale employed, our data indicate the need for directly assessing PB rather than deriving it from clinical and functional data and level of BHR.     

Assessing bronchial responsiveness to hypertonic saline using the stepwise protocol of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC II)

Measurement of bronchial responsiveness to hypertonic saline was applied in 22 study centers worldwide as part of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two). Because the amount of inhaled saline was difficult to standardize during the stepwise protocol with inhalation periods of increasing duration, we evaluated different statistical procedures based on inhalation time in relation to wheeze and current asthma. Data on random samples on 9 to 11-year-old children (n = 1,418) from two German centers were analyzed. The following statistical approaches were evaluated: (1) bronchial hyperreactivity (BHR) defined dichotomously as a fall in FEV1 (forced expiratory volume in 1 s) >or=15%; (2) PT15: the provocation time causing BHR using survival-analyses methods; (3) time-response-slope (continuous) of the individual FEV1-courses calculated by a linear model after comparing different mathematical models. The sensitivity and specificity of BHR versus current asthma were 47% and 87%, respectively. Analyses of the provocation time indicated an increased risk (adjusted hazard-ratio: 4.3; 95% CI: 2.8-6.5) for a fall in FEV1 >or= 15% among children with current asthma in comparison to those without. The time-response-slope differed markedly between children with and without wheeze and current asthma (P < 0.0001). BHR is meaningful and relatively easy to use, but has low sensitivity. Time-response-slopes utilize the available information from the stepwise protocol better than BHR and survival-analysis based on PT15. Response parameters based on inhalation time discriminate well between children with and without asthma and will be compared in the analyses of ISAAC Phase Two data.     

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.     

Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness

Allergic rhinitis can be associated with bronchial hyperresponsiveness (BHR), and carries an increased risk for the development of asthma. The aim of this study was to evaluate the ability of specific immunotherapy (SIT) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR. Forty-four subjects monosensitized to Dermatophagoides pteronyssinus, with perennial rhinitis and BHR to methacholine, were randomly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr. After 1 yr of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV(1) (PD(20)FEV(1)) was recorded in the SIT-treated group (95% confidence interval [CI]: 3.98- to 2.09-fold; p < 0.001), with a further increase to fourfold at the end of Year 2 (95% CI: 2.9- to 5.7-fold; p < 0.001). At the end of the study, the methacholine PD(20)FEV(1) was within the normal range in 50% of treated subjects (p < 0.0001), and was significantly higher in this group than in the group receiving placebo (p < 0.0001). In contrast, no changes in methacholine PD(20)FEV(1) were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with SIT did. This study suggests that SIT, when administered to carefully selected, monosensitized patients with perennial allergic rhinitis, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.