Influence of exercise-induced bronchoconstriction on refractoriness

This study determined if the degree of exercise-induced refractoriness is determined by the degree of exercise-induced bronchoconstriction. In 12 patients with exercise-induced asthma (mean [SEM] age 27 [3] years) we performed 2 pairs of exercise challenges 45 min apart at different work loads on 2 days. Mean (SEM) total respiratory heat loss during low and high work loads was 3.4 (0.2) and 5.1 (0.4) kcal, respectively. After the first and second exercise challenge at low work loads, mean (SEM) SRaw increased by 107 (15) and 73 (16)% (n.s.), as compared to 361 (40) and 98 (25)% at high work loads (p < 0.005). We found a correlation between the initial airways response and refractoriness (r = 0.58, p < 0.005) and conclude that the degree of refractoriness after exercise-induced bronchoconstriction is in part dependent on the severity of exercise-induced bronchoconstriction. Offprint requests to: H. Magnussen     

孟鲁司特钠治疗运动诱发性支气管收缩的临床研究

目的　观察孟鲁司特钠治疗轻、中度支气管哮喘(简称哮喘)并发运动诱发支气管收缩(EIB)或运动性哮喘(EIA)的治疗及预防作用。方法　采用前瞻性开放、自身治疗前、后对照的方法。选择轻、中度哮喘并运动激发试验阳性患者30例,给予孟鲁司特钠每晚10mg治疗1个月。分别于治疗前1d、治疗后3d及4周进行运动激发试验。主要观察运动后的前60min一秒钟用力呼气容积(FEV1)自基线下降的百分比时间曲线下面积(AUC0~60min),运动后FEV1最大下降程度(FEV1最低值)及自最低FEV1恢复至运动前基值5%以内所需的时间(FEV1最低值恢复时间)。结果　孟鲁司特钠治疗前1d、治疗后3d和治疗后4周,运动激发试验后AUC0~60min分别为(39±21)、(13±14)、(12±14)%·min,治疗前、后比较差异有统计学意义(P<001);FEV1最低值分别为(18±06)、(21±06)、(23±08)L,治疗前、后比较差异有统计学意义(P<001);FEV1最低值恢复时间分别为(51±36)、(26±28)、(25±33)min,治疗前、后比较恢复时间显著缩短(P<001),并持续1个月。EIB/EIA患者孟鲁司特钠治疗前、后肺功能[FEV1、峰流速(PEFR)]均可维持接近正常且无明显变化。吸入糖皮质激素不能预防EIB/EIA。结论　孟鲁司特钠对轻度哮喘患者并发EIB/EIA疗效和预防作用显著,而且安全、快捷。     

The role of impulse oscillometry in detecting airway dysfunction in athletes

Background: Impulse oscillometry (IOS) has previously been proposed to provide greater sensitivity than spirometry when employed with indirect bronchoprovocation testing for the diagnosis of airway dysfunction in athletes. However, this recommendation is based on a highly selected population of symptomatic patients. Objective: To compare IOS, spirometry and respiratory symptoms following indirect bronchoprovocation in a screened cohort of athletes. Methods: One hundred and one recreational athletes were recruited. Respiratory symptoms were assessed via the Dyspnoea-12 questionnaire. Spirometry and IOS were performed pre and post a eucapnic voluntary hyperpnoea (EVH) challenge. Results: Ninety-four athletes completed the study. Sixteen athletes (17%) were positive for airway dysfunction based on spirometry (i.e. ≥10% fall in FEV₁) and 17 athletes (18%) based on IOS (i.e. ≥50% increase in R₅). Only nine athletes (10%) met both diagnostic thresholds. A poor relationship was observed between respiratory symptoms (i.e. Dyspnoea-12 score) and all spirometry and IOS variables. A direct relationship was observed between percentage change in R₅ (r?=?0.65), Z₅ (r?=?0.68), R_F (r?=?0.65), A_X (r?=?0.69) and the maximum fall in FEV₁ (ΔFEV₁max; p?<?0.001). A weak relationship was observed between R₂₀ (r?=?0.27), X₅ (r?=?0.37) and ΔFEV₁max (p?<?0.01). Conclusion: Impulse oscillometry and spirometry do not concur precisely following indirect bronchoprovocation. However, IOS detects additional cases of airway dysfunction in athletes and therefore may provide diagnostic value in this population. Further work is required to establish diagnostic thresholds and fully determine the place of IOS in screening athletes for airway dysfunction.     

Differences in the Evaluation and Management of Exercise-Induced Bronchospasm between Family Physicians and Pulmonologists

Previous studies have demonstrated that specialists and generalists differ in the evaluation and management of asthma especially in terms of use of objective testing. We speculated that there also may be differences in the diagnosis and management of exercise-induced respiratory complaints. An Internet survey was sent to samples of pulmonologists and family physicians. Our data suggests that pulmonologists are much more likely to order bronchoprovocation testing than family physicians, and family physicians are more likely to start any empiric therapy than perform bronchoprovocation testing when exercise-induced bronchospasm is suspected. These differences may lead to inaccurate or missed diagnoses and unnecessary morbidity.     

Differences in the Evaluation and Management of Exercise-Induced Bronchospasm between Family Physicians and Pulmonologists

Previous studies have demonstrated that specialists and generalists differ in the evaluation and management of asthma especially in terms of use of objective testing. We speculated that there also may be differences in the diagnosis and management of exercise-induced respiratory complaints. An Internet survey was sent to samples of pulmonologists and family physicians. Our data suggests that pulmonologists are much more likely to order bronchoprovocation testing than family physicians, and family physicians are more likely to start any empiric therapy than perform bronchoprovocation testing when exercise-induced bronchospasm is suspected. These differences may lead to inaccurate or missed diagnoses and unnecessary morbidity.     

Prevalence of work-related respiratory symptoms in Iranian farmers

BACKGROUND:

Animal exposure may be an important trigger for work-related symptoms among farmers.

OBJECTIVE:

To estimate the prevalence of work-related respiratory symptoms (WRS) in sheep breeders and agricultural farmers and to determine work-related risk factors.

METHODS:

A family doctor used a questionnaire to interview a cohort of 173 farmers comprised of 127 sheep breeders and 46 agricultural farmers in the rural area of Rokh (northeast Iran). The questionnaire pertained to recurrent wheezing, cough, breathlessness or chronic phlegm while at work (these symptoms define WRS), flu-like illness and physician-diagnosed asthma.

RESULTS:

There were 71 subjects (41%) with WRS: 10 of 46 agricultural farmers (21.7%) and 61 of 127 sheep breeders (48.0%). The proportions of sheep breeders with wheezing (16.5%), asthma (14%), cough (29%), breathlessness (31.5%) and flu-like illness (38%) were higher than in agricultural farmers. A significant dose-response relationship among the daily hours worked with animals, the number of animals and the prevalence of symptoms was established for sheep farmers. Sheep shearing and the use of pesticide were associated with an increased risk of wheezing and phlegm.

CONCLUSIONS:

The results suggest that sheep farmers in general have higher rates of work-related symptoms than agricultural farmers. The severity of work-related symptoms will increase with an increase in frequency of animal contact; therefore, these results may underestimate the impact of this exposure.     

The role of alpha-receptors in bronchoconstriction induced by beta-blockade

We examined 10 patients with an exercise-induced asthma. Physical exercise was carried out under placebo, 40 mg propranolol, 5 mg pindolol and 50 mg metoprolol, respectively, before and after alpha blockade. After exercise, we noted a distinct increase of airway resistance in all cases, the increase of which, however, was lower after a preceding alpha blockade. Under propranolol, the increase of the airway resistance and of norepinephrine, as compared with pindolol, metoprolol, and placebo, was most intensive.     

Mechanisms of bronchoconstriction induced by anaphylaxis in sensitized guinea pigs

Anaphylactic reaction in sensitized guinea pigs is known to induce bronchoconstriction when an adequate amount of antigen is administrated. This phenomenon has been established as a model of bronchial asthma. To evaluate the mechanism of bronchoconstriction in anaphylaxis, we analyzed the change of endobronchial pressure in sensitized guinea pigs. Guinea pigs weighing 300-600 g were actively sensitized by intracutaneously administrated ovalbumin (10 mg). Two weeks later they were anesthetized and mechanically ventilated with a volume type Harvard respirator. Antigen was administrated intravenously and monitoring of endotracheal pressure and systemic blood pressure was performed. Drugs to modify these reactions were administrated intraperitoneally 30 minutes before antigen challenge. In the control group, the endotracheal pressure showed a curve with the first peak between 0.5 and 1.5 minutes after the antigen challenge. When cyclooxygenase inhibitor (indomethacin) was administered before the antigen, the first peak was markedly suppressed. However, the histamine (H1)-receptor blocker did not suppress the first peak. On the other hand when 5-lipoxygenase inhibitor (AA-861) was administered before the antigen, the increase of intratracheal pressure was suppressed between 2 and 4 minutes after the antigen challenge. The above results may suggest that the first peak of intratracheal pressure derives from bronchoconstriction caused by prostaglandins or thromboxanes, and that the increase of intratracheal pressure at between 2 and 4 minutes derives from bronchoconstriction caused by leukotrienes.     

Depressive symptomatology,quality of life and disease control among individuals with well-characterized severe asthma

Abstract

Objectives: A thorough examination of the relationship of asthma severity and control with symptoms of depression is needed to identify groups of asthmatics at high risk for poor disease control outcomes. This study examines the relationship of symptoms of depression with severity and control in a well-characterized cohort of asthmatics and healthy controls. Methods: Depressive symptoms and quality of life were assessed using the Beck Depression Inventory. Disease control was measured by a composite index incorporating symptoms, activity limitation and rescue medication use. Results: Individuals with asthma (n?=?91) reported more symptoms of depression than controls (n?=?36; p?<?0.001). Those with severe asthma (n?=?49) reported more symptoms of depression (p?=?0.002) and poorer asthma control (p?<?0.0001) than those with not severe asthma. Worse asthma control was associated with more depressive symptoms in severe (r?=?0.46, p?=?0.002) but not in not severe (r?=?0.13, p?=?0.40) asthmatics. The relationship of symptoms of depression among severe asthmatics was attenuated by disease control. Exploratory analyses identified specific disease symptom characteristics, as opposed to exacerbations, as associated with symptoms of depression. Conclusions: Among individuals with severe asthma, increased symptom burden is positively associated with risk for co-morbid depression. These findings point to a need for regular mood disorder screenings and treatment referrals among this group. Further research is warranted to examine whether treatment of comorbid depression improves treatment adherence and asthma-related quality of life.     

肾上腺髓质素对组胺诱发气道痉挛的作用

目的观察肾上腺髓质素（ＡＭ）对组胺诱发麻醉豚鼠气道痉挛的影响。方法实验分为生理盐水对照组、异丙肾上腺素０．０３μｇ／ｋｇ、０．３μｇ／ｋｇ、３μｇ／ｋｇ、３０μｇ／ｋｇ四个剂量组及ＡＭ０．０２μｇ／ｋｇ、０．２μｇ／ｋｇ、２μｇ／ｋｇ、２０μｇ／ｋｇ四个剂量组，每组豚鼠７只，戊巴比妥钠麻醉状态下，分别静脉注射生理盐水、不同剂量的异丙肾上腺素和ＡＭ，同时组胺（１０－４ｍｏｌ／Ｌ）雾化吸入，采用动物体描箱测定豚鼠气道阻力和肺顺应性。结果异丙肾上腺素０．３μｇ／ｋｇ、３μｇ／ｋｇ和３０μｇ／ｋｇ剂量下能明显拮抗组胺诱导的豚鼠气道阻力增加和肺顺应性降低（Ｐ＜０．０５）。ＡＭ２μｇ／ｋｇ、２０μｇ／ｋｇ剂量下能明显拮抗组胺诱导的气道阻力增加，０．２μｇ／ｋｇ、２μｇ／ｋｇ，２０μｇ／ｋｇ剂量下能明显拮抗组胺诱导的肺顺应性降低（Ｐ＜０．０５）。结论ＡＭ具有拮抗组胺诱发豚鼠气道痉挛的作用。     

The Prevalence of Asthma in an NCAA Division I Collegiate Athletic Program

Purpose. To determine the prevalence of asthma among all varsity athletes in a large National Collegiate Athletic Association (NCAA) Division I program. Methods. We retrospectively reviewed the medical records for all varsity athletes at The Ohio State University (OSU). Data were abstracted from patient charts that contained a Medical Health Questionnaire, annual physical examinations, and medical encounters by the OSU Sports Medicine staff. A diagnosis of asthma was defined by self-report of physician diagnosis as recorded in the medical record. Results. Overall, 130 of 763 (17.0%) athletes had a diagnosis of asthma. Females (67/280 or 23.9%) had a significantly higher prevalence of asthma than males (63/483 or 13.0%) (p value = 0.001). There was no significant difference in the prevalence of asthma between high- and low-ventilation sports. (p value = 0.201). Conclusions. The prevalence of asthma among varsity athletes at The Ohio State University is 17.0%, which is significantly higher than the reported prevalence of asthma in the general United States population between 18 to 24 years of age. More females had asthma in our study population than males. These data will allow for future studies and development of focused screening programs of collegiate athletes.     

Assessment of induced bronchoconstriction in anesthetized cats by the end-inflation occlusion method

Airway occlusion during constant flow inflation allows rapid determination of frequency-dependence of pulmonary resistance by estimating its extreme values: R_L,max (zero frequency) and R_L,min (high frequency). R_L,max represents the maximum resistance value that can be obtained with the prevailing time constant inequalities and stress relaxation, while R_L,min represents the resistance that would be obtained in the absence of time constant inequalities and stress relaxation. In 5 anesthetized, tracheostomized, paralyzed, and artificially ventilated cats, R_L,min, R_L,max, and static pulmonary elastance (E_L,st) have been measured following airway occlusion at the end of constant flow tidal inflations. Measurements were made before and during continuous infusion of increasing doses of serotonin (10–100 μg/kg/min IV). The development of intrinsic positive end-expiratory pressure (PEEPi) was also assessed. Cats varied greatly in their responsiveness to serotonin, but R_L,min, R_L,max, and E_L,st increased and PEEPi developed in all cats. Increases in R_L,max did not always parallel increases in R_L,min but were similar to those in E_L,st, suggesting that altered viscoelastic properties of the lung contributed to the increases in R_L,max. We conclude that time-constant inequalities, changes in the lung periphery, and hyperinflation probably all contribute to the observed increases in R_L,max and will influence conventional methods of measuring R_L. Measuring R_L,min potentially provides a better method for assessing the reduction in caliber of the conducting airways in isolation.     

Assessment of induced bronchoconstriction in anesthetized cats by the end-inflation occlusion method

Airway occlusion during constant flow inflation allows rapid determination of frequency-dependence of pulmonary resistance by estimating its extreme values: RL,max (zero frequency) and RL,min (high frequency). RL,max represents the maximum resistance value that can be obtained with the prevailing time constant inequalities and stress relaxation, while RL,min represents the resistance that would be obtained in the absence of time constant inequalities and stress relaxation. In 5 anesthetized, tracheostomized, paralyzed, and artificially ventilated cats, RL,min, RL,max, and static pulmonary elastance (EL,st) have been measured following airway occlusion at the end of constant flow tidal inflations. Measurements were made before and during continuous infusion of increasing doses of serotonin (10-100 micrograms/kg/min IV). The development of intrinsic positive end-expiratory pressure (PEEPi) was also assessed. Cats varied greatly in their responsiveness to serotonin, but RL,min, RL,max, and EL,st increased and PEEPi developed in all cats. Increases in RL,max did not always parallel increases in RL,min but were similar to those in EL,st, suggesting that altered viscoelastic properties of the lung contributed to the increases in RL,max. We conclude that time-constant inequalities, changes in the lung periphery, and hyperinflation probably all contribute to the observed increases in RL,max and will influence conventional methods of measuring RL. Measuring RL,min potentially provides a better method for assessing the reduction in caliber of the conducting airways in isolation.     

Reversibility of induced bronchoconstriction by deep inspiration in asthmatic and normal subjects

Five normal and five asthmatic subjects underwent a progressive methacholine provocation study. At each concentration inspiratory pulmonary resistance (RL) was measured, as well as isovolumic maximal flow and residual volume from both partial and complete forced expirations. Results were compared over the RL range of 6-11 cmH2O.1-1.S-1. The reversibility of bronchoconstriction by deep inspiration was quantified as the ratio of the flow increase to potential maximal increase; the reversibility of gas trapping was the ratio of decrease in residual volume to potential maximal decrease. The reversibility of bronchoconstriction did not differ between the groups. In contrast, the reversibility of gas trapping was smaller in asthmatic subjects (21 +/- 17%) than in normals (84 +/- 6%). As gas trapping reflects airway closure, our findings suggest that during induced bronchoconstriction airway closure is more resistant to the effects of deep inspiration in asthmatic than in normal subjects but the reversibility of bronchoconstriction by deep inspiration is not different.     

Intratracheal administration of phosphodiesterase III inhibitor attenuates bronchoconstriction in cats: A preliminary report

The effects of intratracheal administration of MKS 492, selective phosphodiesterase (PDE) 111 inhibitor, were studied in five anesthetized bronchoconstricted cats. The animals were challenged by four repeated doses of intratracheal methacholine (67 μg/kg), and the degree of bronchoconstriction was assessed from increases in respiratory system resistance (Rrs). All animals demonstrated good bronchoconstrictive responses (i.e., 86–99% increases in Rrs) to methacholine without tachyphylaxis. On separate day, the cats received the same four doses of methacholine after being pretreated with either intratrachael saline or three different doses of MKS 492 (0.17, 1.7, and 17 μg/kg). The increases in Rrs with 1.7 μg/kg [;52.6 ± 8.4% (SE)] and 17 μg/kg of MKS 492 (44.4 ± 10.1%) were smaller than those with saline pretreatment (88.1 ± 16.8%) (P < 0.05). There were no treatment-associated changes in mean arterial pressure or heart rate during administration of MKS 492. We conclude that intratracheal MKS 492 effectively reduced methacholine-induced bronchoconstriction in dose-dependent fashion without substantial systemic effects. These preliminary results suggest that inhalation of isozyme-selective PDE inhibitors may deserve consideration for clinical trials provided that more extensive preclinical investigations justify such trials. © 1995 Wiley-Liss, Inc.     

Two distinct phenotypes of asthma in elite athletes identified by latent class analysis

Introduction: Clusters of asthma in athletes have been insufficiently studied. Therefore, the present study aimed to characterize asthma phenotypes in elite athletes using latent class analysis (LCA) and to evaluate its association with the type of sport practiced. Methods: In the present cross-sectional study, an analysis of athletes’ records was carried out in databases of the Portuguese National Anti-Doping Committee and the Norwegian School of Sport Sciences. Athletes with asthma, diagnosed according to criteria given by the International Olympic Committee, were included for LCA. Sports practiced were categorized into water, winter and other sports. Results: Of 324 files screened, 150 files belonged to asthmatic athletes (91 Portuguese; 59 Norwegian). LCA retrieved two clusters: “atopic asthma” defined by allergic sensitization, rhinitis and allergic co-morbidities and increased exhaled nitric oxide levels; and “sports asthma”, defined by exercise-induced respiratory symptoms and airway hyperesponsiveness without allergic features. The risk of developing the phenotype “sports asthma” was significantly increased in athletes practicing water (OR?=?2.87; 95%CI [1.82–4.51]) and winter (OR?=?8.65; 95%CI [2.67–28.03]) sports, when compared with other athletes. Conclusion: Two asthma phenotypes were identified in elite athletes: “atopic asthma” and “sports asthma”. The type of sport practiced was associated with different phenotypes: water and winter sport athletes had three- and ninefold increased risk of “sports asthma”. Recognizing different phenotypes is clinically relevant as it would lead to distinct targeted treatments.     

Single-dose effect of astemizole on bronchoconstriction induced by histamine in asthmatic subjects.

STUDY OBJECTIVE: Astemizole, administered for seven days to asthmatic subjects, had an effect of bronchoconstriction induced by inhaled histamine for a mean period of 42 days. This study evaluates whether a single dose of astemizole would have the same effect. SUBJECTS: Sixteen adult asthmatic subjects took part in the study. DESIGN: They first underwent three inhalation tests and skin prick tests with histamine on three different days. On the last day, a methacholine inhalation test was also performed. They subsequently received either a placebo or an active preparation of astemizole. The histamine inhalation test was repeated one day, two days, one week, and/or ten days after administering the drug. RESULTS: Overall, no significant change in mean PC20 or in the mean diameter of the skin reaction to histamine was observed. However, three out of the eight subjects (38 percent) receiving active and none receiving placebo medication showed significant increases in PC20 histamine (p = 0.05). This effect lasted for one to two days. CONCLUSIONS: We conclude that a single dose of 10 mg/ml of astemizole can have a significant effect on bronchial but not cutaneous reactivity to histamine. This effect is of short duration (one to two days).     

Quality of Life and Clinical Symptoms in Asthmatic Subjects

Objective: Quality of Life (QoL) measurements are more responsive to clinically significant changes than conventional clinical measures. The aim of the study was to evaluate the relationship between asthma symptoms and QoL in asthmatic patients. Methods: A total of 277 asthmatics subjects, divided into three groups showing different symptoms, underwent complete clinical evaluation, baseline respiratory function, and methacholine challenge test and completed an Asthma Quality of Life Questionnaire (AQLQ). Results: One hundred and forty‐five subjects with asthmatic crisis, chest tightness, and dyspnea (group 3) reported a significantly lower median value in single domains and all items compared to the values scored by the 97 subjects with wheezing, rhinitis, and conjunctivitis (group 2) (p < 0.01). No statistical significance was found between the 35 patients of group 1 (with only cough) and group 3. Conclusions: The main advantage for the clinician is to evaluate important areas in which QoL could be improved and the possibility to correct and optimize compliance to chronic therapy.