[Adherence and asthma control: can sports coaching can be a model?].
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Anti-Asthmatic Agents↗
Biomedical subjects
L P Boulet
Publications and source records attributed to L P Boulet.
Is asthma over- or under-diagnosed in athletes?
A high prevalence of asthma has been reported in athletes. However, studies in this population usually show an even higher prevalence of airway hyperresponsiveness (AHR) and exercise-induced bronchoconstriction (EIB). This report compares studies on self-reported or physician-diagnosed asthma in athletes with those using objective measures of airflow limitation or airway responsiveness. The higher prevalence of AHR (or EIB) measured in athletes, when compared with the prevalence of self-reported or physician-diagnosed asthma, suggests that abnormal airway responses are common in athletes, although they are infrequently associated with troublesome respiratory symptoms. This may indicate underdiagnosis of asthma in athletes, possibly due to an underreporting of respiratory symptoms or a reduction in perception of nociceptive sensations with repeated exercise over time, or it may simply mean that high-level training is associated with asymptomatic AHR. In athletes, as in the general population, the use of subjective methods such as surveys and questionnaires results in an underestimation ofthe prevalence of airway dysfunction when compared with objective measurements. The significance of these observations is unknown, and there is a need to determine their long-term consequences for athletes.
Asthma, Exercise-Induced↗
Airway inflammation in asthma with incomplete reversibility of airflow obstruction.
This study aimed to determine whether there is a persistent or different type of airway inflammation in patients with an incomplete reversibility of airflow obstruction (IRAO) despite optimal treatment and if so, whether it is associated with an accelerated decline of pulmonary function. Fifteen asthmatic patients with IRAO, and 23 with complete reversibility of airflow obstruction (CRAO) had a spirometry and an induced-sputum (IS) analysis. Past FEV1 values were recorded over 2-12 years during periods of stable asthma. Medians (range) for IS cell differentials were: lymphocytes, 0(0-3)/1(0-2)%; neutrophils, 56(13-88)/38(3-84)% and eosinophils, 2.0(0-82)/4.0(0-68)%, (all P>0.05). Among non-smoking patients, those with IRAO had more neutrophils in IS than those with CRAO (P=0.019). Mean (+/-SEM) yearly fall in FEV1 in IRAO or CRAO patients was 54+/-21/84+/-16 ml/year (P>0.05, predicted age-related decline < or = 26 ml/year, P=0.0008). In the whole group of asthmatic patients, decline of FEV1/year was inversely correlated with the % neutrophils in sputum (r(s)=-0.436, P=0.008) and, in IRAO patients, with the duration of asthma (r(s)=-0.559, P=0.037). In conclusion, persistent airway inflammation and increased decline in pulmonary function can be observed in both asthmatic patients with IRAO/CRAO and are of similar magnitude. Non-smoking patients with IRAO had more neutrophils in IS than CRAO.
Adrenal Cortex Hormones↗
Assessment and evaluation of symptomatic steroid-naive asthmatics without sputum eosinophilia and their response to inhaled corticosteroids.
Eosinophilic airway inflammation is one of the hallmarks of asthma. Sputum eosinophilia has been suggested as a predictor of the response to inhaled corticosteroids in asthma. This study sought to investigate the proportion of steroid-naive uncontrolled asthmatics without significant sputum eosinophilia (< or = 1%) and to examine whether sputum eosinophilia could predict the response to inhaled corticosteroids. A total of 51 mild uncontrolled steroid-naive asthmatics who had not been treated with oral or inhaled corticosteroids for at least 3 months were investigated. The evaluation included a spirometry, methacholine inhalation challenge and sputum induction on two occasions, one at baseline and the other after 1 month of treatment with 250 microg twice-daily fluticasone propionate. Of the 51 subjects, 15 had an eosinophil count < or = 1%, and 46 completed the two visits. Patients with baseline sputum eosinophils < or = 1% (n=14) were compared with those with sputum eosinophils > 1% (n=32). The baseline characteristics of these two groups were similar. After 1 month of treatment, respiratory symptoms, quality of life, forced expiratory volume in one second (FEV1) and provocative concentration causing a 20% fall in FEV1 improved in both groups. The absence of sputum eosinophilia does not seem to be an indicator of poor response to inhaled corticosteroid treatment in steroid-naive asthmatics. However, this finding needs to be investigated further in a double-blind, placebo-controlled study, entirely designed to answer this question.
Administration, Inhalation↗
Transbronchial biopsy as a tool to evaluate small-airways disease in asthma. Pros.
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Airway Obstruction↗
Effect of salmeterol on allergen-induced airway inflammation in mild allergic asthma.
A previous study suggested that the long-acting beta2-adrenergic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inflammation 6 hours after allergen exposure. To further evaluate the influence of SM on allergen-induced airway inflammation. We studied, in a randomized, double-blind, cross-over trial, 16 mild asthmatic patients who had a dual asthmatic response to allergen inhalation. Subjects received 50 microg of SM or placebo (P), twice daily for 1 week each, separated by a 2-week wash-out period. At the end of each treatment period, after withholding SM for 24 h, they had a methacholine inhalation test (medication was resumed after the test), followed 24 h later by an AC with the concentration of allergen that had induced a LAR at baseline. Airway inflammation was assessed 24 h after the AC by bronchoalveolar lavage (BAL) (n = 16) and bronchial biopsies (n = 13). As expected, SM improved baseline FEV1 and PC20 (P < or = 0.009) and decreased the allergen-induced early bronchoconstrictive response. There were no significant differences in BAL cell counts after the two treatments. On bronchial biopsies, numbers (median, mm2) of submucosal CD45 (P: 43 +/- 23; SM: 161 +/- 43, P = 0.031), CD45Ro (P: 37 +/- 19; SM: 126 +/- 41, P = 0.047) and AA1 positive cells (P: 38 +/- 6, SM: 65 +/- 17, P = 0.006) were significantly higher after SM than P treatment. The numbers of CD4 (P: 11 +/- 10; SM: 32 +/- 7, P = 0.085), HLA-DR (P: 65 +/- 30; SM: 116 +/- 36, P = 0.079) and EG2 positive cells (P: 25 +/- 15; SM: 38 +/- 26, P = 0.09) tended to increase with SM treatment. In summary, compared to placebo, 1 week of regular use of SM is associated with an increase in bronchial inflammatory cells 24 h after AC. This is in keeping with the recommendation that salmeterol should only be used with an anti-inflammatory agent, particularly in the context of significant allergen exposure.
Adolescent↗
Bronchial mucosa produced by tissue engineering: a new tool to study cellular interactions in asthma.
BACKGROUND: The use of fiberoptic bronchial biopsies has improved our understanding of the immunopathology of asthma. However, this approach offers a limited ability to perform mechanistic studies observing cell-cell and cell-matrix interactions, which are a key issue in the study of airway remodeling. Tissue engineering is a technique that combines the use of biology and engineering expertise to generate a limitless amount of tissue from small samples. This technology allows for the study of cell interactions under conditions as close as possible to the natural environment. OBJECTIVE: The aim of this study was to evaluate the feasibility of an engineered human bronchial mucosa as a model to study cellular interactions in asthma. METHODS: Human bronchial fibroblasts from normal and asthmatic donors were incorporated into collagen gel. Bronchial epithelial cells were seeded over this gel and then cultured in an air-liquid interface in the presence or the absence of T lymphocytes. Biopsy specimens from these engineered mucosa were taken for structural and ultrastructural analysis, and T lymphocytes were harvested and used to localize IL-5. RESULTS: Histologic analysis showed that engineered mucosa with normal bronchial cells presented a pseudostratified ciliated epithelium with the presence of mucus secretory cells. The electron microscopy analysis confirmed these histologic results. These features were comparable with those observed in normal bronchial tissues. However, in engineered mucosa from asthmatic subjects, the tissue structure was disorganized, particularly the epithelial cell arrangement. The percentage of IL-5(+) lymphocytes was significantly (P =.03) higher in engineered bronchial mucosa from asthmatic subjects (87% +/- 2%) compared with mucosa from normal volunteers (2% +/- 0.3%). CONCLUSION: Using tissue engineering, we produced an in vitro model of bronchial mucosa from normal and asthmatic subjects. These models could be a valuable tool to better understand key mechanisms involved in inflammation and airway repair.
Asthma↗
TH2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression.
BACKGROUND: The expression of IL-4 and IL-5 is increased in patients with atopic asthma compared with control subjects and correlates with indices of pulmonary function. In nonatopic asthma the expression of IL-4, unlike IL-5, fails to correlate with pulmonary function, and compared with their atopic counterparts, these patients have fewer cells expressing IL-4 receptor (IL-4R). As such, a deficiency in the IL-4 signaling pathway may be implicated in nonatopic asthma. The transcription factors GATA-3 and cMAF mediate IL-4 and IL-5 synthesis, whereas signal transducer and activator of transcription 6 (STAT-6) is critical for IL-4R signaling. OBJECTIVE: This study examines the expression profile of these transcription factors in asthma, according to atopic status. METHODS: With immunocytochemistry, the expression of GATA-3, cMAF, and STAT-6 protein was determined in sections of bronchial biopsy specimens from patients with atopic asthma (n = 7), patients with nonatopic asthma (n = 8), and control subjects (n = 8). RESULTS: Higher numbers of cells expressing GATA-3 and cMAF were observed in patients with atopic and those with nonatopic asthma than in control subjects and patients with tuberculosis (P <.001). There were also more STAT-6-immunoreactive cells in patients with atopic and those with nonatopic asthma than in control subjects (P <.0001, P <.05). Notably, however, fewer cells expressing STAT-6 protein were observed in nonatopic versus atopic asthma (P <.0001). CONCLUSIONS: These results demonstrate the upregulation of GATA-3 and cMAF in both variants of asthma and indicate that reduced IL-4R signaling, because of lower STAT-6 expression, may be a feature of nonatopic asthma.
Adult↗
Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation.
Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma. However, it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention. A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited; 98 completed the study. The first 45 patients were assigned to Group C (control; usual treatment). Thereafter, patients were randomized to either Group LE (limited education; teaching of the inhaler technique plus self- action plan given by the on call physician) or Group SE (same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations). At baseline, there was no difference between groups in asthma morbidity, medication needs, or pulmonary function. After 12 mo, only Group SE showed a significant improvement in knowledge, willingness to adjust medications, quality of life scores, and peak expiratory flows. In the last 6 mo, the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE (p = 0.03). The number (%) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE (p = 0.02). We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment.
Acute Disease↗
Regularly scheduled inhaled bronchodilators and maintenance asthma therapy.
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Administration, Inhalation↗
Ambulatory use of inhaled beta(2)-agonists for the treatment of asthma in Quebec : a population-based utilization review.
STUDY OBJECTIVES: To assess whether the utilization of inhaled short-acting beta(2)-agonists (ISAB) and inhaled long-acting beta(2)-agonists (ILAB) for the treatment of asthma was appropriate according to the 1996 Canadian Asthma Consensus Conference recommendations. DESIGN: Population-based retrospective drug utilization review using pharmacists' billing data of the Prescription Drug Insurance Plan administered by the Quebec health insurance board. However, the database used did not contain complete patient clinical information to accurately assess severity of asthma. SETTING: Province of Quebec, Canada. PATIENTS: Persons who received at least one outpatient prescription of ISAB (age range, 5 to 45 years) or ILAB (age range, 12 to 45 years) for the treatment of asthma between August 1997 and April 1998. MEASUREMENTS: Percentages of patients whose use was appropriate according to three criteria regarding the average daily dose of ISAB (criterion 1), the renewal interval of ILAB (criterion 2), and the concomitant daily use of corticosteroids for the expected length of utilization of ILAB (criterion 3). RESULTS: Overall proportions of appropriate use according to criterion 1 were as follows: 75% (without inhaled corticosteroids [ICS]) and 84% and 43% (with one or more than one prescription of ICS, respectively). Appropriateness was slightly higher for female patients, younger patients (5 to 18 years old), and those treated by pediatricians. However, appropriateness was only 9% among patients who received at least two prescriptions of ISAB during the study period. The proportion of appropriate use was 19% according to criterion 2 and 15% according to criterion 3; there were few differences by gender or by age, but the appropriateness according to criterion 2 was somewhat higher for patients of respirologists. CONCLUSION: Compared to the 1996 Canadian asthma consensus conference recommendations, ISAB are overused, ICS are underused, and ILAB are often used improperly. Close collaboration between health professionals and patients is essential to improve the pharmacotherapy of asthma.
Administration, Inhalation↗
Prevalence and mechanisms of development of asthma and airway hyperresponsiveness in athletes.
A high prevalence of asthma and airway hyperresponsiveness (AHR) has been reported in the athlete population. Factors potentially predisposing athletes to these conditions have not been clearly identified. Although moderate exercise has been shown to be beneficial in patients with asthma, repeated high-intensity exercise could possibly contribute to the development of asthma and AHR. This report provides an overview of the prevalence and possible mechanisms of development of asthma and AHR in the athlete population. The prevalence of asthma and AHR are higher in athletes than in the general population, particularly in swimmers and athletes performing sports in cold air environments. Possible mechanisms involved in the development of asthma in athletes are still uncertain; however, the content and physical characteristics of the inhaled air seem to be important factors, while immune and neurohumoral influences could play a modulatory role. This report stresses the need for further studies to better define the aetiologic factors and mechanisms involved in the development of asthma and AHR in athletes, and proposes relevant preventive and therapeutic measures.
Air Pollution↗
Electrocardiographic findings in athletes: the prevalence of left ventricular hypertrophy and conduction defects.
OBJECTIVES: To determine whether there are electrocardiographic differences or distinctive abnormalities between athletes and sedentary subjects, and to verify the relationship between vagal activity measured by heart rate variability (SD of all normal-to-normal intervals [SDNN]) and possible electrocardiographic abnormalities. SUBJECTS AND METHODS: Resting electrocardiograms and heart rate variability measurements were performed separately during a single visit on 100 athletes and 50 nonathlete control subjects aged 18 to 55 years. The athletes were from the following various sports disciplines: long-distance running, mountain biking, cross-country skiing, biathlon, speed skating, swimming and triathlon. RESULTS AND CONCLUSIONS: There were significantly longer RR intervals, PR intervals and QT intervals in athletes than in control subjects (all P<0.05). The QRS complex and QTc did not show significant differences (both P>0.05). The prevalence of left ventricular hypertrophy (LVH) and incomplete right bundle branch block (IRBBB) was 10% and 7%, respectively, in athletes, but these conditions were absent in control subjects; among athletes, 2% presented with both conditions. LVH and IRBBB were more common among long-distance runners (six of 14 and four of 14, respectively) and could be attributed to normal, long term adaptation to intense, repeated exercise. LVH was related to age (P=0.04), whereas IRBBB was influenced by the number of years of training in the respective sports discipline (P=0.03). The mean SDNN value was significantly more elevated in athletes (P=0.0001), reflecting a higher parasympathetic tone than in sedentary control subjects. However, there was no relationship between vagal activity and LVH or IRBBB (both P>0.05).
Adolescent↗
Evidence for association and linkage between atopy, airway hyper-responsiveness, and the beta subunit Glu237Gly variant of the high-affinity receptor for immunoglobulin E in the French-Canadian population.
Following detection of linkage between atopy and chromosome 11q13 markers, association between this disorder and variants of the beta subunit of the high-affinity receptor for immunoglobulin E (FcepsilonRI-beta, a candidate gene for asthma-related conditions co-localizing within the same region) was reported in Australian, British and Japanese populations. Investigations in several other ethnic groups failed to replicate these observations. Due to the complexity of defining intermediate phenotypes related to asthma, detection of such associations may have been hampered by clinical misclassifications. To assess whether the FcepsilonRI-beta gene was involved in atopy and/or airway hyperresponsiveness (AHR) in the French-Canadian population, we conducted a case-control study in 200 subjects using strict criteria for asthma and related conditions. The Ile181Leu and Glu237Gly FcepsilonRI-beta sequence variants were tested exploiting two amplification refractory mutation systems. No association was detected between atopy or AHR and the Ile181Leu FcepsilonRI-beta variant. However, a strong association was observed between atopy and the Glu237Gly FcepsilonRI-beta variant (odds ratio=12.25). Four large Eastern Québec families (n=106 subjects) were also recruited to perform a genetic linkage study. We observed suggestive evidence of linkage between atopy and the Glu237Gly FcepsilonRI-beta variant (Zmax=2.30). This study is the first to detect the presence of an association between atopy and the Glu237Gly FcepsilonRI-beta variant in French-Canadians. Our data suggest that a susceptibility locus for atopy is located on chromosome 11q13 in this population.
Adult↗
Influence of sympatho-vagal balance on airway responsiveness in athletes.
The increased prevalence of airway hyperresponsiveness (AHR) observed among athletes suggests that high-level training may contribute to the development of AHR. We investigated the possible influence of the sympatho-vagal balance on this phenomenon in 40 athletes and 10 sedentary controls. Each subject filled out a respiratory questionnaire, had a methacholine challenge, and measurements were made of their baseline plasma catecholamines [epinephrine (E), norepinephrine (NE) and dopamine (DA)] as a reflection of sympathetic tone, and their heart rate variability (SDNN: standard deviation of all normal-to-normal intervals) as an indicator of parasympathetic tone. The athletes had a 45% prevalence of AHR (defined as PC20 < 16 mg/ml, where PC20 is the concentration of methacholine inducing a 20% fall in the forced expiratory volume in 1 s, FEV1) with a mean PC20 of 21.2 mg/ml compared with 10% prevalence (mean PC20: 74.4 mg/ml) in sedentary subjects (P < 0.01). Plasma catecholamine values were not significantly different between the two groups (all P > 0.05), but the estimated parasympathetic tone was higher in athletes (P = 0.01). When data from all subjects were analyzed together, plasma E and NE correlated with PC20 (r = 0.39, P = 0.005 and r = 0.29, P < 0.005) but DA and SDNN did not (both P > 0.05). However, the ratios E/SDNN, NE/SDNN and DA/SDNN showed significant correlations with PC20 (r = 0.42, P < 0.01; r = 0.33, P < 0.005 and r = 0.31, P < 0.05, respectively) This study suggests that the sympatho-vagal balance may contribute to the increased AHR in the population studied but this influence alone cannot explain the higher prevalence of AHR in athletes.
Adult↗
Synergistic action of endothelin (ET)-1 on the activation of bronchial fibroblast isolated from normal and asthmatic subjects.
Bronchial subepithelial fibrosis is an histological characteristic of asthma. Cytokines and other mediators, such as PDGF-BB, TGF-beta1 and ET-1 found in the asthmatic submucosa can potentially activate a repair process that leads to fibroblast proliferation and collagen synthesis. The mechanisms of modulation of the repair process leading to extracellular matrix deposition are still to be documented. In this study, we assessed the in vitro proliferation and collagen synthesis of bronchial fibroblasts isolated from normal and asthmatic subjects in response to ET-1, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-beta1 alone or in combination, in the presence or absence of dexamethasone. The combination of ET-1 with one of the other two growth factors, or the triple combination, significantly increased DNA synthesis and collagen production of bronchial fibroblasts isolated from both normal and asthmatic subjects, but the same growth factors used separately had no significant effect on the same parameters. These results suggest that the simultaneous presence of ET-1, PDGF-BB and TGF-beta1 in both normal and asthmatic subjects is necessary to activate bronchial fibroblast proliferation and collagen synthesis. As these mediators are present in the submucosa of the asthmatic bronchi, they could be responsible, at least in part, for the accumulation of collagen in the mucosa.
Analysis of Variance↗
Asthma and airway hyper-responsiveness in adults who required hospital admission for bronchiolitis in early childhood.
Viral respiratory infections in infancy may contribute to the development of airway hyper-responsiveness (AHR) in childhood but their effects on respiratory function at the adult age are still uncertain. A group of 42 subjects aged 17-35 with a pediatrician-made diagnosis of severe bronchiolitis in infancy (Br) were compared for the presence of asthma and AHR to a control group (C) paired for age and gender, without evidence of lower respiratory disease in infancy. All had a respiratory and environmental questionnaire, allergy skin prick tests, blood eosinophil count, total serum IgE determination and measurements of expiratory flows and airway response to methacholine. In Br and C groups, respectively, 38 and 12% of subjects had a physician-made diagnosis of asthma, 26 and 7% used bronchodilators and 12 and 0% an inhaled corticosteroid; 71 and 67%, respectively, were atopic, 50 and 24% were smokers and 43 and 17% had a first-degree relative with asthma. Mean baseline FEV1 and FEV1/FVC ratio were lower in the Br than in the C group, with 94/103% (P=0.002) and 80/87 (P<0.0001) of the predicted value, respectively. Geometric mean PC20 methacholine was significantly lower in the Br than in the C group 3.9/20.3 mg ml(-1) (P<0.0001). Mean blood eosinophil count and serum IgE levels were similar in both groups (P> 0.05). In conclusion, asthma and AHR were found more frequently in young adults with a past history of bronchiolitis, suggesting that this type of respiratory infection may contribute to altered pulmonary function in adulthood, although it may also represent an early manifestation of asthma. The influence of potential confounding factors, such as familial predisposition and exposure to cigarette smoke on the development of asthma and AHR in the Br group, cannot be excluded.
Adolescent↗
Cytokine expression in the lower airways of nonasthmatic subjects with allergic rhinitis: influence of natural allergen exposure.
BACKGROUND: Natural exposure to pollen provokes an increase in airway responsiveness in nonasthmatic subjects with seasonal allergic rhinitis. This natural exposure may induce inflammatory cell recruitment and cytokine release, leading to lower airway inflammation. OBJECTIVE: The aim of this study was to characterize lower airway inflammation in nonasthmatic pollen-sensitive subjects. METHODS: We performed immunohistochemical tests on bronchial biopsy specimens from subjects with rhinitis who had no past or current history of asthma to evaluate cytokine expression and inflammatory cell numbers and activation both in and out of the pollen season. RESULTS: The number of CD4(+), CD8(+), and CD45RO(+) lymphocyte subpopulations were significantly higher during the pollen season compared with the out-of-season period (P <.04). Furthermore, EG1(+) cells tended to increase after natural pollen exposure (P =.06). The number of IL-5(+) cells increased significantly after natural exposure to pollen compared with out-of-season numbers (P <.01). This increase in IL-5 expression was correlated with the numbers of CD3(+), CD4(+), CD45RO(+), and EG1(+) cells. The numbers of tryptase-positive, IFN-gamma(+), and IL-4(+) cells did not change after natural exposure. CONCLUSION: This study showed that natural pollen exposure was associated with an increase in lymphocyte numbers, eosinophil recruitment, and IL-5 expression in the bronchial mucosa of nonasthmatic subjects with allergic rhinitis.
Adult↗