Methacholine Airway Responsiveness Research Articles

Spirometric Abnormalities Associated With Chronic Bronchitis, Asthma, and Airway Hyperresponsiveness Among Boilermaker Construction Workers

In a 2-year longitudinal study of boilermaker construction workers, we found a significant association between working at oil-fired, coal-fired, and gas-fired industries during the past year and reduced lung function. In the present study, we investigated whether chronic bronchitis, asthma, or baseline methacholine airway responsiveness can explain the heterogeneity in lung function response to boilermaker work. This study is part of an ongoing prospective cohort study of boilermakers. Exposure was assessed with a work history questionnaire. Spirometry was performed annually to assess lung function. A generalized estimating equation approach was used to account for the repeated-measures design. Boilermaker union members. One hundred eighteen boilermakers participated in the study. None. Self-reported history of chronic bronchitis and asthma were associated with a larger FEV1 reduction in response to workplace exposure at coal-fired and gas-fired industries. Although we found a high prevalence (39%) of airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 of < 8 mg/mL) among boilermakers, we did not find a consistent pattern of effect modification by airway responsiveness. Although chronic bronchitis and asthma were associated with a greater loss in lung function in response to hours worked as a boilermaker, and therefore they acted as effect modifiers of the exposure-lung function relationship, airway hyperresponsiveness did not. However, the high prevalence of airway hyperresponsiveness found in the cohort may be a primary consequence of long-term workplace exposure among boilermakers.

A Comparison of the Validity of Different Diagnostic Tests in Adults With Asthma

Diagnosing asthma is not always easy, and there are times when objective tests can be helpful. The extent to which these tests alter the probability of asthma depends on how much more commonly the test result is positive in subjects with asthma compared to healthy subjects and particularly subjects with conditions that are commonly confused with asthma. We set out to compare the sensitivity and specificity of different tests in this setting. Single-center, cross-sectional, observational study. Teaching hospital. Twenty-one healthy control subjects, 69 patients with asthma, and 20 subjects referred to the hospital with a diagnosis of asthma who were found to have alternative explanations for their symptoms (i.e., pseudoasthma). We measured methacholine airway responsiveness, the maximum within-day peak expiratory flow amplitude mean percentage (derived from twice-daily readings for > 2 weeks), the FEV(1)/FVC ratio, the percentage change in FEV(1) 10 min after the administration of 200 microg inhaled albuterol, and the differential eosinophil count in blood and induced sputum. We derived normal ranges (from the 95% upper or lower limit for healthy subjects), sensitivity, and specificity (ie, the percentage of subjects with pseudoasthma who had negative test results). Most tests were less specific when the reference population was composed of subjects with conditions that can be confused with asthma. Methacholine airway responsiveness and the sputum differential eosinophil count were the most sensitive (91% and 72%, respectively) and specific (90% and 80%, respectively) tests. We conclude that methacholine airway responsiveness and the sputum differential eosinophil count are the most useful objective tests in patients with mild asthma.

Asthma outcome measures

Asthma outcome measures

Factors Related to Methacholine Airway Responsiveness in Children

Studies of airway responsiveness (AR) have typically used similar dose schedules of methacholine for adults and children despite large ranges in subject size. Reported declines in AR with increasing age in children could be due to maturational changes or to proportionately smaller doses of methacholine in taller (older) children. Other investigators have related both height and various measures of lung function to AR. We examined data related to AR in 471 children, aged 6 to 8 yr, from a birth cohort. Each child underwent spirometry followed by sequential challenge with five doses of methacholine, ranging from 0.025 to 25 mg/ml, given with a dosimeter. Continuous slope and end FEV(1)-change indexes of responsiveness were computed. Using stepwise regression modeling, we found no significant association between AR and either height or age after entering a variable reflecting asthma or wheezing. In contrast, we found that baseline measures of FVC, FEV(1)/FVC, and FEF(25-75%) were significantly related to AR after controlling for other variables (p = 0.001). However, when all three of the latter measures were added to models, FEF(25-75%) was most closely related to AR. We conclude that after control for other variables, FEF(25-75%) and FVC, but not height, are significantly related to methacholine responsiveness in children.

Changes in Sputum Eosinophils Predict Loss of Asthma Control

Exacerbations of asthma are likely to be due to an increase in airway inflammation. We have studied noninvasive markers of airway inflammation in asthma exacerbations induced by reducing the dose of inhaled corticosteroids. Following a 2-wk run-in period, mild exacerbations were induced in subjects with stable asthma controlled with medium- to high-dose inhaled corticosteroids (beclomethasone dipropionate >/= 800 microg or equivalent daily) by switching them to budesonide 200 microg daily given from a dry-powder inhaler (Turbohaler). Fifteen subjects were enrolled and were seen twice weekly for 8 wk after steroid reduction. At each visit, exhaled nitric oxide (NO), and methacholine airway responsiveness were measured and spirometry and sputum induction were performed. Mild exacerbation was defined as: (1) a decrease in morning peak expiratory flow (PEF) of >/= 20% but < 30% on at least two consecutive days as compared with the mean for the last 7 d of the run-in period; (2) awakening on two consecutive nights because of asthma; or (3) increased use of a short-acting beta(2)-agonist to eight or more puffs daily. Eight subjects did not develop exacerbations during the 8-wk study, whereas seven subjects developed mild exacerbations at Week 4 (n = 1), Week 6 (n = 1), and Week 8 (n = 5). The only significant difference between these two groups at baseline was a higher baseline sputum eosinophil count in subjects with subsequent exacerbations (p < 0.05). The increases in sputum eosinophils and exhaled NO were correlated with decreases in airway function, including decreases in morning PEF and FEV(1). However, multiple regression analysis suggested that the change in sputum eosinophils is a potentially useful marker in predicting loss of asthma control reflected by loss of airway function.

The FEF25-75/FVC ratio is associated with methacholine airway responsiveness. The normative aging study.

Airway responsiveness is known to be partly explained by geometric and anatomic factors. This cross-sectional investigation was undertaken to determine whether FEF25-75/FVC as a surrogate measure of airway size relative to lung size is associated with airway responsiveness to methacholine. Posteroanterior chest radiographs and spirometry were performed on a group of 929 middle aged and older men from an ongoing longitudinal study, the Normative Aging Study, who returned for their regularly scheduled examination between 1984 and 1989. Subjects had a mean age of 60.5 +/- 7.7 yr. FEV1, FEF25-75, and FVC were taken from spirometric results and FEF25-75/FVC ratios were obtained. Main bronchus (MB) and tracheal (TR) diameters and lung area (LA) were obtained from chest radiographs, and ratios of MB/LA and TR/LA were calculated for each subject and compared with FEF25-75/ FVC as measures of airway size relative to lung size. In a multiple linear regression model adjusting for age, height, initial FEV1, smoking, eosinophil count, and IgE level, FEF25-75/FVC was significantly related to the degree of methacholine airway responsiveness as measured by Log10 dose response slope (beta = -0.37, p < 0.001). Controlling for the same variables, both MB/LA (beta = -149.07, p < 0.001) and TR/LA (beta = -125.87, p < 0.001) were significant predictors of the degree of bronchial responsiveness in separate regression models; however, their effects were greatly attenuated when FEF25-75/ FVC was present in the same model. Similar results were obtained after excluding subjects with FEV1/ FVC </= 0.70 and subjects who had any smoking history. We conclude that FEF25-75/FVC as a surrogate measure of airway size relative to lung size is significantly associated with airway responsiveness.

Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma

BACKGROUNDIt is desirable to prescribe the minimal effective dose of inhaled steroids to control asthma. To ensure that inflammation is suppressed whilst using the lowest possible dose, a sensitive and...

Effect of the leukotriene receptor antagonist pranlukast on cellular infiltration in the bronchial mucosa of patients with asthma

BACKGROUNDIt has been reported that pranlukast reduces the antigen induced immediate and late phase asthmatic responses, airway hyperreactivity to acetylcholine, and pulmonary eosinophil accumulation in guinea pigs. A study was...

The utility of methacholine airway responsiveness measurements in evaluating anti-asthma drugs

Background: Measurements of airway responsiveness are frequently used to evaluate anti-asthma drugs. Objective: This study investigated the utility of methacholine airway responsiveness measurements in evaluating anti-asthma medications, both in terms of a bronchoprotective effect and the ability to attenuate allergen-induced methacholine airway hyperresponsiveness. Methods: Methacholine airway responsiveness was measured as PC 20 on two occasions (separated by 35 ± 17 days, mean ± SD) in 40 subjects with mild, stable asthma. Additional subjects had PC 20 measurements made before and after administration of either inhaled salbutamol (200 μg) ( n = 20) or allergen inhalation challenge ( n = 31). Results: The reproducibility of the methacholine PC 20 with this method was high (intraclass correlation coefficient = 0.94). The average shift in PC 20 after salbutamol was 4.11 doubling concentrations (SD = 1.08). On the basis of these results, a sample size of 12 subjects would be required to demonstrate a 1 doubling concentration difference in the bronchoprotective effect of two drugs with a 90% power. The average shift in PC 20 after allergen was 1.29 doubling concentrations. On the basis of these results and an estimated SD of 0.96, a sample size of 24 subjects would be required to demonstrate that a drug is effective in attenuating 50% of allergen-induced airway hyperresponsiveness with a 90% power. Conclusion: These results confirm the high reproducibility of methacholine PC 20 measurements in subjects with mild, stable asthma and demonstrate its utility in evaluating the effects of anti-asthma drugs. (J Allergy Clin Immunol 1998;101:342-8.)

Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells

Background: Chronic cough is a multifactorial condition, which, like asthma, can be associated with eosinophilic airway inflammation. In asthma, airway eosinophilia is believed to be mediated by cytokines such as interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF). The role of these cytokines in chronic cough is unclear. Objective: The aim of this study was to examine gene expression for IL-5 and GM-CSF in chronic cough and compare the results with those found in asthma. Methods: We studied adults with asthma ( n = 12), chronic cough responsive to inhaled corticosteroid (ICS-responsive cough) ( n = 9), and chronic cough not responsive to inhaled corticosteroid (non-ICS–responsive cough) ( n = 4). Bronchoalveolar lavage (BAL) was performed, and cytokine gene expression was assessed by using a semiquantitative reverse transcriptase polymerase chain reaction. Results: IL-5 mRNA was expressed by BAL cells from nine of 12 asthmatic subjects and six of nine subjects with ICS-responsive chronic cough. IL-5 mRNA was not detected in subjects with non-ICS–responsive chronic cough (zero of four subjects, p < 0.05). GM-CSF mRNA was expressed in BAL cells from seven of 12 asthmatic subjects and six of nine subjects with ICS-responsive cough. GM-CSF mRNA was not detected in non-ICS responsive cough subjects (zero of four subjects, p < 0.05). GM-CSF gene expression was related to the degree of methacholine airway responsiveness in asthmatic subjects (r = –0.59). Conclusion: We conclude that chronic cough, like asthma, is associated with airway inflammation and gene expression for IL-5 and GM-CSF. Ongoing expression of these cytokines is likely to be related to the persistence of airway inflammation and chronic cough. (J Allergy Clin Immunol 1998;101:320-6.)

Allergen-induced increases in IL-5 receptor alpha-subunit expression on bone marrow-derived CD34+ cells from asthmatic subjects. A novel marker of progenitor cell commitment towards eosinophilic differentiation.

We have proposed previously that hemopoietic myeloid progenitors contribute to the ongoing recruitment of proinflammatory cells, namely eosinophils, to sites of allergen challenge in allergic diseases such as asthma. In this study, we investigated the involvement of bone marrow-derived progenitors in the development of allergen-induced pulmonary inflammation in mild asthmatic subjects. By flow cytometry, we enumerated the level of expression of CD34, a hemopoietic progenitor cell marker, on bone marrow aspirates taken before and 24 h after allergen challenge. In addition, the coexpression of the alpha-subunits of IL-3 receptor (IL-3R) and IL-5 receptor (IL-5R) on CD34+ cells was investigated. After allergen-challenge, although no significant change in total BM CD34+ cell numbers was observed, a significant increase in the proportion of CD34+ cells expressing IL-5R alpha, but not IL-3R alpha, was detected in the 24-h post-allergen, compared with the pre-allergen bone marrow. This was associated with a significant blood and sputum eosinophilia and increased methacholine airway responsiveness, 24 h post-allergen. Using simultaneous in situ hybridization and immunocytochemistry, we colocalized the expression of messenger RNA for membrane-bound IL-5R alpha to CD34+ cells. In summary, our data suggest that increased expression of IL-5R alpha on CD34+ cells favors eosinophilopoiesis and may thus contribute to the subsequent development of blood and tissue eosinophilia, a hallmark of allergic inflammation.

Evaluation of single-dose inhaled corticosteroid activity with an allergen challenge model

Background: Inhaled corticosteroids are the most commonly used antiinflammatory agents for asthma. There is no simple way to compare objectively the relative potency of inhaled corticosteroids. The allergen-induced late asthmatic response (LAR) can be suppressed by a single dose of inhaled corticosteroid. Objective: This study was undertaken to evaluate LAR as a model for the determination of the relative potency of single doses of inhaled corticosteroids. Methods: We compared doses of 200 and 800 μg of a highly active inhaled corticosteroid (budesonide) with placebo and a marginally active investigational inhaled corticosteroid (D5159). Ten atopic patients with asthma completed a randomized, double-blind, double-dummy, multicenter, four-way, crossover trial. A standardized allergen challenge with the identical dose of allergen was performed 10 minutes after each of four blinded, single-dose treatments: 200 μg of budesonide, 800 μg of budesonide, 8 mg of D5159, and placebo, all administered from Turbuhaler. The LAR was recorded as the maximum percent fall in FEV 1 between 4 and 7 hours, and the allergen-induced increase in methacholine airway responsiveness at 24 hours was recorded as the Δ log PC 20 from the day before to the day after allergen challenge. Results: There were no significant differences in the early asthmatic responses during the 4 days; the mean maximum percent in FEV 1 fall ranged between 19.5% and 22%. D5159 produced a slight inhibition of the LAR with maximum percent fall in FEV 1 recorded as 28.8% ± 5.0% for D5159 versus 34.1% ± 4.8% for placebo ( p < 0.05). There was a greater reduction recorded after administration of the two doses of budesonide. The mean LAR was 15.1% ± 3.8% for 200 μg of budesonide and 11.2% ± 2.3% for 800 μg of budesonide ( p < 0.01 compared with placebo and D5159). The two doses of budesonide were not statistically different. Airway responsiveness to methacholine increased by 1.07 doubling doses 24 hours after allergen challenge. This increased airway responsiveness was slightly, but not significantly, reduced by the three active treatments (0.6 to 0.91 doubling doses). Conclusion: The allergen-induced LAR model was able to differentiate a single dose of an active inhaled corticosteroid from placebo and a highly potent inhaled corticosteroid from a weak inhaled corticosteroid. The model did not differentiate between 2 fourfold doses of the highly active inhaled corticosteroid (at the doses used in this study), neither for the fall in FEV 1 nor for the increase in airway hyperresponsiveness. (J Allergy Clin Immunol 1997;100:65-70.)

Volume history effects and airway responsiveness in middle-aged and older men. The Normative Aging Study.

In persons with asthma, a deep inhalation (DI) to total lung capacity may lead to bronchoconstriction. The intensity of this effect has been shown to correlate positively with the severity of inflammatory airflow obstruction and the level of methacholine airway responsiveness. The correlates of lung volume history effects in the general population, however, are unknown. We analyzed combined maximal and partial expiratory flow-volume data, pre- and postbronchodilator spirometry data, and methacholine challenge data from 89 middle-aged and older men participating in the Normative Aging Study. The ratio of maximal to partial expiratory flow rates (VM/VP) was significantly correlated with methacholine airway responsiveness, even after adjustment for age and baseline FEV1. The direction of this correlation indicated that men with higher VM/VP ratios (i.e., greater dilator effect of a DI) tended to have greater methacholine airway responsiveness. Subjects with a higher VM/VP ratio also tended to have a greater response to a bronchodilator. These results suggest that, in the general population, airway responsiveness relates in part to airway smooth muscle tone. The correlations suggest that this relatively simple maneuver might play a role in future epidemiologic studies.

Effects of long-acting and short-acting beta-agonists on methacholine dose-response curves in asthmatics

Regular use of short-acting beta-agonists may decrease control of asthma and increase airway responsiveness to bronchoconstrictor stimuli. The aim of this study was to determine the effects of regular treatment with the long-acting beta-agonist, salmeterol, on the methacholine dose-response curve (DRC) in mild-to-moderate asthmatics. Changes in methacholine airway responsiveness were measured in 14 stable adult asthmatics, randomized in a double-blind, three-way cross-over design to receive salmeterol 50 micrograms, salbutamol 200 micrograms or placebo, each twice daily for 4 days. Two baseline methacholine DRC, were performed, one without premedication and one following a single dose of 200 micrograms salbutamol. Following 4 days of regular treatment, methacholine DRC to plateau were carried out commencing 15 min after the final dose of trial medication. There were no significant differences in mean baseline forced expiratory volume in one second (FEV1) between treatments. Four days treatment with salmeterol and salbutamol shifted the DRC to the right, but salmeterol provided less protection than salbutamol. The point of inflection of the curve from baseline moved 1.9 and 3.2 doubling doses, respectively, compared to placebo (p < or = 0.001), and the provocative concentration of methacholine required to produce a 20% fall in FEV1 (PC20) increased 1.6 and 3.1 doubling doses, respectively (p < or = 0.001). The slope of the DRC was increased slightly by both beta-agonists compared to placebo (log slope 3.11, 3.06 and 2.77 for salmeterol, salbutamol and placebo, respectively). This effect of regular salmeterol on slope was more marked in subjects with lower baseline FEV1. Maximal response plateaus did not differ between the three treatments. These results suggest that regular use either of short- or long-acting beta-agonists could increase the risk of a more precipitous asthma episode associated with "breakthrough" bronchoconstrictor responses, particularly in those with more severe initial airflow obstruction, if subjects are exposed to a sufficiently potent stimulus.

Effect of Inhaled Prostaglandin E2on Methacholine and Leukotriene D4Airway Responsiveness in Asthmatic Subjects

Previous studies in asthmatics have demonstrated that the endogenous release of inhibitory prostaglandins limits the bronchoconstrictor response to repeated challenges with exercise and histamine, and that inhaled prostaglandin (PG) E2attenuates allergen-induced asthmatic responses and exercise bronchoconstriction in asthmatics. Inhaled PGE2does not significantly attenuate methacholine airway responsiveness. These results, taken together, indicate that inhaled PGE2attenuates the bronchoconstriction caused by stimuli, such as allergen and exercise, that result in bronchoconstriction through cysteinyl leukotriene (LT) release. The purpose of this study was to determine whether inhaled PGE2could selectively attenuate LTD4-induced bronchoconstriction in seven stable asthmatic subjects. Each subject was studied on four different study days. On two occasions the subjects inhaled 100 mg PGE2, 30 mins before a methacholine, or LTD4challenge test. On the other two study days, the subjects were pretreated with its diluent. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20). PGE2pretreatment significantly increased the LTD4PC20, but not the methacholine PC20. The mean LTD4PC20increased from 2.00 mg/mL (%SEM 1.65) after diluent pretreatment to 3.01 mg/mL (%SEM 1.64) after PGE2pretreatment (P=0.008). The mean methacholine PC20was 1.28 mg/mL (%SEM 1.68) after diluent pretreatment and 1.62 mg/mL (%SEM 1.46) after PGE2pretreatment (P=0.28). These results suggest that PGE2partially attenuates LTD4-induced bronchoconstriction; however, the magnitude of the effect is unlikely to account for its attenuation of exercise and allergen-induced bronchoconstriction.

Increased peak flow variability in children with asymptomatic hyperresponsiveness.

The relevance of increased methacholine airway responsiveness detected in children with no current or past symptoms of asthma is not known. We wished to determine whether the presence of airway hyperresponsiveness in asymptomatic children is also associated with abnormal variability of peak expiratory flow (PEF). In 12 asymptomatic children with methacholine hyperresponsiveness, we examined the diurnal variation of peak expiratory flow (PEF) and response to inhaled bronchodilator. Twelve asthmatic children with a comparable range of methacholine hyperresponsiveness, and 12 normal children without methacholine responsiveness, were used as positive and negative controls. The children were aged 11 (range 9-14) yrs. The mean diurnal variation of PEF in those children with asymptomatic hyperresponsiveness was increased at 9.3%, to a degree comparable to the symptomatic asthmatic children (10.7%), and greater than the normal children (5.7%). Methacholine stimulated airway constriction was associated with symptoms in subjects from each group, indicating that the children were capable of perceiving airway constriction. We conclude that asymptomatic children with methacholine airway hyperresponsiveness have other evidence of mild variable airflow obstruction with increased diurnal PEF variability, and can perceive airflow limitation. The lack of symptoms in the children with airway hyperresponsiveness could be due to an insufficient stimulus to cause symptomatic obstruction, or the absence of eosinophilic airway inflammation, which may be a requirement for the development of symptomatic airway hyperresponsiveness.

A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: the Normative Aging Study.

It has been hypothesized that nonspecific airway hyperresponsiveness is a risk factor for accelerated pulmonary-function decline during aging and the development of chronic airflow obstruction. We tested this hypothesis in a prospective, longitudinal study of 912 middle-aged and older men (median age, 60 yr; range, 41 to 86 yr) participating in the Normative Aging Study (NAS). Subjects underwent methacholine challenge testing and spirometry at the time of a regularly scheduled NAS examination, and follow-up spirometry was performed after a median interval of 3.3 yr. Allergy skin testing with a panel of four aeroallergens (mixed grasses, mixed trees, ragweed, and house dust) was also performed at the initial examination. Methacholine responsiveness was expressed as the dose-response slope (DRS) (i.e., the slope of a line connecting the origin with the last point of the methacholine dose-response plot) in units of percent decline FEV1/mumol methacholine. The relationship of the methacholine DRS to the subsequent rate of annual decline in lung function (FEV1, FVC, and FEV1/FVC) was examined using multiple linear-regression models with the rates of pulmonary-function decline as the outcome variables. After adjusting for age, height, smoking status, and initial level of lung function, the log10 DRS was a significant predictor of the rate of decline of FEV1 (regression coefficient beta = 12.8, p = 0.03) and FEV1/FVC x 100 (beta = 0.506, p = 0.0001), and a borderline significant predictor of FVC (beta = 15.3, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic cough with eosinophilic bronchitis: examination for variable airflow obstruction and response to corticosteroid

The purpose of this study was to examine airway responsiveness, sputum cells and the effects of inhaled corticosteroid in the chronic cough syndrome associated with eosinophilic bronchitis. We studied nine consecutive referrals with chronic cough, sputum with > 10% eosinophils, normal spirometry, and normal methacholine airway responsiveness. Clinical assessment, sputum analysis, allergy skin tests and a methacholine inhalation test were performed at the first visit. Peak expiratory flow (PEF) was measured twice daily for 1 week followed by an adenosine monophosphate (AMP) inhalation test. Subjects were then treated with inhaled beclomethasone 0.4 mg twice daily for 7 days. Sputum analysis and measurement of methacholine responsiveness were then repeated. Excessive airway narrowing to methacholine was not present in any of the subjects. A methacholine plateau response was present in five subjects. Hyperresponsiveness to AMP was absent in six of the nine subjects, and PEF variability was not increased for eight subjects. Corticosteroid therapy led to a reduction in sputum eosinophil counts from 40.1 (SD 21.4)% to 4.0 (4.5)% but there was no significant change in metachromatic cell counts (0.8 SD 0.5% vs 0.6 SD 0.6%) or total cell counts. Methacholine responsiveness improved within the normal range in the three subjects in whom it could be determined. Chronic cough associated with eosinophilic airway inflammation can occur in the absence of variable airflow obstruction (asthma) and can improve after treatment with inhaled corticosteroid. This treatment can reduce the level of methacholine responsiveness within the normal range and reduces sputum eosinophils but not mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of longitudinal change in methacholine airway responsiveness among middle-aged and older men: the Normative Aging Study.

Increasing nonspecific airway responsiveness during aging may precede and predispose to the development of asthma in later life. Characteristics potentially related to longitudinal change in methacholine airway responsiveness were examined over a 3-yr follow-up interval among 435 middle-aged and older men. Initial and follow-up evaluation included spirometry, allergy skin testing with common aeroallergens, measurement of the serum concentration of total IgE, and blood cell counts (total leukocytes and eosinophils, basophils, and neutrophils as a percentage of total leukocytes). The initial values and annual rates of change of these characteristics were examined by multiple linear regression as potential predictors of annual change in methacholine dose-response slope. Annual change in basophil count was directly related to change in dose-response slope (p = 0.02). Initial values and annual rates of change of other cell counts, pulmonary function, allergy skin test reactivity, and serum total IgE concentration were not significantly related to change in dose-response slope. Cigarette smoking history was also not significantly related to longitudinal change in dose-response slope. These data suggest that inflammatory mechanisms involving the basophil may be important in the development of increasing nonspecific airway responsiveness during aging.

Asthme Et Hyperreactivite Bronchique Non Specifique

Bronchial hyperresponsiveness is a hallmark of asthma although it can also be present, to a lesser extent, in other diseases. The level of bronchial responsiveness depends on immuno-inflammatory processes modifying the functional status of airway smooth muscle as well as the structure of the bronchial wall. The responsiveness toward a direct constricting pharmacological agent is poorly correlated to the one toward an indirect constricting agent or a physical stimulus which cause airway obstruction through a more complex mechanism. Transversal studies show a relationship between the severity of asthma and the level of methacholine airway responsiveness. Long term treatment with corticoids can reduce the bronchial hyperresponsiveness of asthmatics.