Airway hyperresponsiveness and airway inflammation in elite swimmers

Introduction: The prevalence of respiratory symptoms and airway hyperresponsiveness (AHR) is high in elite athletes; swimmers have one of the highest prevalences. No consensus exists on what airway challenge to use when identifying AHR in elite athletes. Further, knowledge is sparse about when during their active sport career AHR develops and if there is an acute effect on the airway inflammation of a swimming training session. Objectives: We aimed to (i) evaluate the airway response to a methacholine challenge, a eucapnic voluntary hyperpnoea (EVH) test, a field‐based exercise test (FBT) and a laboratory‐based exercise test (LBT) in adult elite swimmers; (ii) investigate airway responsiveness and airway inflammation in adolescent elite swimmers; and (iii) evaluate the acute effect of a training session in an indoor swimming pool on airway inflammation in adolescent elite swimmers. Materials and Methods: Two groups were studied. (i) In adult elite swimmers (n = 16), we examined airway response in four airway provocation tests: methacholine challenge, EVH test, FBT and LBT. (ii) In adolescent elite swimmers (n = 33), we examined airway responsiveness to EVH and methacholine, and airway inflammation and compared the findings with those in asthmatic adolescents (n = 32) and unselected adolescents (n = 35). Further, we examined the acute effect of swimming on airway inflammation in a subpopulation of the adolescent swimmers (n = 21). Airway inflammation was evaluated using sputum induction, measurements of exhaled nitric oxide (FeNO) and exhaled breath condensate (EBC). Results: Of 16 adult swimmers, eight (50%) had AHR; five of the eight (63%) were identified with the EVH test, four (50%) with the FBT, four (50%) with the LBT and none with the methacholine challenge [provocative dose of methacholine causing a 20% fall in FEV1 (PD₂₀) ≤ 2 µmol]. There were no differences in the prevalence of AHR to either EVH or methacholine (PD₂₀ ≤ 8 µmol) among the adolescent swimmers, the asthmatic adolescents and the unselected adolescents. When looking at airway responsiveness as a continuous variable, the swimmers were more responsive to EVH than were the unselected subjects, and less responsive to methacholine than were the asthmatic adolescents. There were no differences in FeNO, EBC pH or in the cellular composition of the sputum among the three groups. Lung function, FeNO, EBC pH, EBC lactate and differential cell counts in sputum were not acutely affected by the swimming session. Conclusion: We found that the EVH test is the most sensitive test for identifying AHR in elite athletes when using the diagnostic criteria set forward by the International Olympic Committe. Whereas a high prevalence of AHR in adult swimmers was found, the prevalence of AHR in the adolescent swimmers did not differ from that in unselected adolescents nor did the adolescent swimmers have signs of airway inflammation. There was no acute effect of a swimming training session in an indoor chlorinated pool on lung function or airway composition in adolescent swimmers. We believe that elite swimming results in airway changes with AHR and airway inflammation.     

Airway inflammation, bronchial hyperresponsiveness and asthma in elite ice hockey players.

There is little information of lower respiratory symptoms, bronchial hyperresponsiveness and airway inflammation in elite ice hockey players. A total of 88 highly trained ice hockey players and 47 control subjects were studied. All the subjects were subjected to skin-prick tests, resting spirometry examinations and histamine-challenge tests. Adequate induced sputum samples were obtained from 68 of the ice hockey players and from 18 symptom-free control subjects on a separate day. Bronchial hyperresponsiveness in a histamine-challenge test was found in 21 (24%) of the athletes and in five (11%) of the controls. Current asthma (current asthmatic symptoms and increased bronchial responsiveness) was observed in 13 (15%) of the athletes and in one (2%) of the control subjects. Total asthma (current asthma or previously physician-diagnosed asthma) occurred in 19 (22%) of the athletes and in two (4%) of the controls. Atopy, according to skin-prick tests, was observed in 51 (58%) of the athletes and 17 (36%) of the control subjects. The differential cell counts of eosinophils (2.6 versus 0.2%) and neutrophils (80.9 versus 29.9%) in the sputum samples of the ice hockey players were significantly higher than in those of the control subjects. Asthma is common in elite ice hockey players and they show signs of a mixed type of neutrophilic and eosinophilic airway inflammation. Inhalation of cold air associated with exposure to indoor pollutants during intensive training is a possible causative factor.     

Field exercise vs laboratory eucapnic voluntary hyperventilation to identify airway hyperresponsiveness in elite cold weather athletes

STUDY OBJECTIVE: For the 2002 Winter Olympic Games, athletes were required to submit objective evidence of asthma or exercise-induced bronchoconstriction (EIB) for approval to inhale a beta(2)-agonist. Eucapnic voluntary hyperventilation (EVH) was recommended as a laboratory challenge that would identify airway hyperresponsiveness (AHR) consistent with EIB. The objective was to compare the change in FEV(1) provoked by EVH with that provoked by exercise in cold weather athletes. DESIGN: Spirometry was measured before and for 15 min after challenges. The two challenges were performed in random order at least 24 h apart. SETTING: EVH was performed in the laboratory at 19 degrees C, and exercise took place in the field in the cold (2 degrees C, 45% relative humidity). PARTICIPANTS: Thirty-eight athletes (25 female subjects; median age, 16 years). INTERVENTIONS: For the EVH, athletes inhaled dry air containing 5% carbon dioxide for 6 min at a target ventilation equivalent to 30 times baseline FEV(1). Exercise was performed by cross-country skiing, ice skating, or running for 6 to 8 min. MEASUREMENTS AND RESULTS: AHR consistent with EIB was defined as >or= 10% fall in FEV(1) from baseline after challenge. Eleven athletes were exercise positive (EX+) [FEV(1) fall, 20.5 +/- 7.3%], and 17 athletes were EVH positive (FEV(1) fall, 14.5 +/- 4.5%) [mean +/- SD]. Of 19 subjects with AHR, 58% were identified by exercise and 89% were identified by EVH. EVH identified 9 of 11 subjects who were EX+ and a further 8 subjects with potential for EIB. The average ventilation during EVH was 28 times FEV(1). CONCLUSION: Performing EVH for 6 min in the laboratory had a greater chance of identifying AHR in these athletes compared with 6 to 8 min of field exercise in the cold. The EVH test will be useful to evaluate elite summer sports athletes whose widely different forms of exercise provide an "equipment" challenge to any laboratory.     

Airway hyperresponsiveness in cigarette smoke-exposed rats

To investigate the possibility that altered airway-parenchymal interaction may account for bronchial hyperresponsiveness induced by cigarette smoke exposure, we tested the effect of administration of cigarette smoke (SM), elastase (EL), and both SM and EL on airway responsiveness in 41 Long-Evans male rats. Twelve were exposed to 30 puffs of SM for 15 weeks; 8 received a single intratracheal injection of EL (250 IU/kg); 9 received both EL and SM exposure (SE); 12 control rats were exposed to room air (CO). After 15 weeks, animals were anesthetized and mechanically ventilated (Vt = 2.5 ml, f = 80/min). Methacholine (MCh) dose-response curves (DRCs) were constructed by calculating pulmonary resistance (R_L) after ultrasonic nebulization of saline followed by doubling concentrations of MCh (0.0625–256 mg/ml). Exposure to cigarette smoking, with or without elastase, led to a significant reduction in body weight and increased total lung capacity (TLC) compared to exposure to CO. However, there was no significant change in static compliance in the experimental groups, despite increased lung volume. The concentration resulting in a doubling of R_L (EC_2OOR_L) was significantly lower in rats treated with SM (n = 7) than CO (n = 8) (3.3 vs. 56.1 mg/ml, geometric mean, p < 0.01). The concentration at which a maximal R_L was achieved was lower in SM than CO, EL, and SE (p < 0.05). To assess the possible influence of airway-parenchymal interaction on responsiveness, we measured R_L both at functional residual capacity (FRC) and at a volume above FRC equivalent to 1 tidal volume. R_L changed similarily in all groups. Despite similar effects on mechanics of both cigarette smoke exposure and elastase administration, only cigarette smoke-exposed animals exhibited evidence of hyperresponsiveness. In this model cigarette smoke-induced hyperresponsiveness is unrelated to changes in either lung elasticity or airway-parenchymal interaction. Offprint requests to: D. H. Eldelman     

Inspiratory stridor in elite athletes

STUDY OBJECTIVES: Diagnosis and medical intervention for exercise-induced bronchospasm (EIB) are often based on self-reported symptoms, without spirometric confirmation. Inspiratory stridor (IS), a symptom of vocal cord dysfunction (VCD), is frequently mistaken for EIB wheeze. Athletes with exercise IS that spontaneously resolves on activity cessation are suspect for VCD and may not have EIB. This study estimated IS prevalence in elite athletes and determined its relationship to EIB. Subjects/methods: Three hundred seventy athletes (174 female and 196 male subjects) provided a medical history, and underwent spirometry before and after exercise challenge. Exercise challenges were conducted in cold, dry ambient conditions. EIB positive (EIB +) was defined as a > or = 10% postexercise fall in FEV(1). Athletes were monitored for IS during exercise; 78.4% of the athletes in this study (n = 290) were tested on multiple occasions. RESULTS: EIB was identified in 30% of 370 athletes tested (58 female and 53 male subjects). IS was observed in 5.1% (18 female and 1 male subjects) during exercise and spontaneously resolved in these subjects within 5 min after exercise cessation. Ten IS-positive (IS +) athletes (52.6%) were EIB +, and 8 of these athletes had a previous EIB diagnosis; however, beta(2)-agonist treatment resolved IS in only 2 subjects. Eight of nine IS +/EIB-negative (EIB -) athletes had a previous EIB diagnosis; seven subjects received beta(2)-agonist treatment with no IS resolution. Resting spirometric measurements did not distinguish IS, but postexercise mid-flow (FEF(50)/FIF(50)) ratio > 1.5 was more frequent (33%, p < 0.05) among IS + athletes. The FEF(50)/FIF(50) ratio was higher for IS +/EIB + athletes than for IS -/EIB + athletes (1.97 +/- 1.69 vs 0.81 +/- 0.39, p < 0.05). The postexercise fall in FVC was greater (p < 0.05) for IS +/EIB - athletes (9.2 +/- 5.0%) than for IS-negative (IS -) /EIB - athletes (5.3 +/- 4.3%). No difference in postexercise FEV(1) was identified between IS + and IS - athletes (within EIB + or EIB - groups). CONCLUSIONS: Five percent of athletes were IS +, with EIB comorbidity observed in 53% of these subjects. Misdiagnosis of IS as EIB is common. The lack of a beta(2)-agonist response in combination with postexercise serial spirometry can be useful in excluding solitary IS and confirming EIB diagnosis.     

Airway hyperresponsiveness and late asthmatic responses

Late inflammatory sequelae following allergen (and occupational low molecular weight sensitizing chemical) exposure, including the late asthmatic response and increased nonallergic airway responsiveness, are now felt to be more important in the pathogenesis of atopic allergic and occupational asthma than are the early bronchospastic responses. These late sequelae can be inhibited by sodium cromoglycate and by corticosteroids but not by bronchodilators. Recognition that allergic and occupational (and likely all forms of) asthma are inflammatory conditions underscores the rationale for the early use of anti-inflammatory therapeutic strategies in the management of asthma. Such "anti-inflammatory" therapeutic strategies include environmental control, sodium cromoglycate, and both inhaled and oral corticosteroids.     

Airways hyperresponsiveness in high school athletes.

Adult athletes have a higher prevalence (11%-50%) of exercise-induced bronchoconstriction (EIB) and airways hyperresponsiveness (AHR) than the population at large (7%-11%): reports describing EIB/AHR in adolescent athletes are scant. Hypotheses: 1) a minimum AHR prevalence of 20% would be revealed in a group of high school athletes; 2) demographic data would predict AHR; 3) AHR-positive athletes would preferentially choose low ventilation sports. Eucapnic voluntary hyperpnea (EVH) was used to test for AHR in 23% of all athletes (79 of 343) of a midwestern high school. The AHR was defined by at least a 10%, 20%, or 25% decline in FEV1, FEF25-75, or PEFR at 1, 5, 10, or 15-min post-EVH, respectively. Results: 30 of 79 (38%) tested positive for AHR; demographic data tended to predict AHR, as correlations between the total number of years exercised with the greatest decline in FEV1 and the total number of days exercised with the greatest decline in FEV1 following the EVH challenge tended to be significant (r = 0.354; p = 0.055 and r=0.314; p = 0.091, respectively); and 69% of AHR-positive students played only low ventilation sports. CONCLUSION: AHR prevalence was 38% in athletes of a midwestern high school; demographic data tended to predict AHR; those with AHR preferentially play low ventilation sports.     

Airway vascular damage in elite swimmers

We postulated that high level swimming can promote airway inflammation and thus asthma by enhancing local vascular permeability. We aimed to test this hypothesis by a cross-sectional study comparing swimmers (n = 13, 17 ± 3 years, competing 7 ± 4 years, training 18±3 h per week), asthmatic-swimmers (n = 6, 17 ± 2 years, competing 8 ± 3 years, training 16 ± 4 h per week), and asthmatics (n = 19, 14 ± 3 years).Subjects performed induced sputum and had exhaled nitric oxide, lung volumes, and airway responsiveness determined. Airway vascular permeability index was defined as the ratio of albumin in sputum and serum.Results from the multiple linear regression showed each unit change in airway vascular permeability index was associated with an increase of 0.97% (95%CI: 0.02 to 1.92; p = 0.047) in sputum eosinophilis, and of 2.64% (95%CI:0.96 to 4.31; p = 0.006) in sputum neutrophils after adjustment for confounders. In a general linear model no significant differences between airway vascular permeability between index study groups existed, after controlling for sputum eosinophilis and neutrophils.In conclusion, competitive swimmers training in chlorine-rich pools have similar levels of airway vascular permeability than asthmatics. Although competitive swimming has been associated with asthma, airway inflammation and airway hyperesponsiveness do not seem to be dependent on increased airway vascular permeability.     

Airway hyperresponsiveness and mucus secretion]

A large amount of mucus and mucoid impaction are observed in the autopsied lungs of bronchial asthmatics. It is possible that mucus hypersecretion and accumulation of intrabronchial mucus result in bronchial obstruction and structural bronchial hyperresponsiveness. Bronchial gland plays a main role in human airway secretion. We describe here some results using isolated gland preparation which enable us to examine airway mucus secretion in a well-defined condition. Chemical mediators released from mast cells augment the secretory responses induced by cholinergic nerve stimulation through accelerated acetylcholine release in the nerve terminals. PAF produces an increase in mucus glycoprotein secretion in the presence of platelets mainly through the thromboxane release from platelets. Substance P which is released by an axon reflex in response to various stimuli and inflammations in the airways, also produced an increase in mucus secretion. Epithelial cells release an inhibitory factor to mucus glycoprotein secretion from bronchial glands. Epithelial cell damages due to inflammation in the airways may induced a reduction of the inhibitory factor release in bronchial asthmatics, resulting in mucus hypersecretion.     

Airway hyperresponsiveness to methacholine in chemical warfare victims

BACKGROUND: The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard gas. Pulmonary complications as a result of this gas range from severe bronchial stenosis to mild or no symptoms. Airway hyperresponsiveness (AHR) which is usually assessed as response to inhaled methacholine is the most characteristic feature of asthma. AHR is reported in chronic obstructive pulmonary disease patients and smokers, and may also show in chemical warfare victims. However, there are little reports regarding AHR in chemical warfare victims. OBJECTIVE: Therefore, in this study, airway responsiveness to methacholine in victims of chemical warfare was examined. METHODS: The threshold concentrations of inhaled methacholine required for a 20% change in forced expiratory flow in 1 s (FEV1; PC20) or a 35% change in specific airway conductance (PC35) were measured in 15 chemical war victims and 15 normal control subjects. RESULTS: In 10 out of 15 chemical warfare victims (two thirds), PC20 and PC35 methacholine could be measured and subjects were called responders. AHR to methacholine in responder chemical war victims (PC20 = 0.41 and PC35 = 0.82 g/l) was significantly lower than in normal subjects (PC20 = 5.69 and PC35 = 4.60 g/l, p < 0.001 for both cases). There was a significant correlation between FEV1 and PC20 methacholine (r = 0.688, p < 0.001). The correlations between PC20 and PC35 were statistically significant as well (r = 0.856, p < 0.001). CONCLUSION: Results showed increased airway responsiveness of most chemical warfare victims to methacholine which correlated with the FEV1 value and which may be related to chronic airway inflammation or irreversible airway changes.     

Prevalence of bronchial hyperresponsiveness in highly trained athletes

Previous studies indicated that the prevalence of symptomatic asthma is about 4 to 7 percent. No similar studies exist to suggest the prevalence of asthma in highly trained competitive athletes, since asthma is thought to be an uncommon disease in this population. We became concerned, therefore, when a large number of football players developed symptoms consistent with asthma during preparation in California for the Rose Bowl in December 1981. We studied the team and found 12 percent of the football players admitted to a history of asthma, whereas none of the members of the university basketball team and 7 percent of a group of sophomore medical students and physician assistant students gave a history of asthma. Furthermore, 19 percent of the football players indicated that at some time they had chest tightness, cough, wheezing, or prolonged shortness of breath after exercise; 12 percent of the basketball players and 37 percent of the students indicated such a history. We examined each of these three groups for non-specific bronchial hyperresponsiveness to inhaled methacholine using a modified methacholine bronchoprovocation (MBP) challenge and found that 76 of 151 (50 percent) football players tested had positive tests; 76 percent of those with symptoms had positive results of inhalation tests and 47 percent of those with minimal or no symptoms had positive test results. In addition, four of 16 (25 percent) basketball players and 69 of 167 (41 percent) students had positive MBP tests. These studies indicate that bronchial hyperresponsiveness to inhaled methacholine is much more common in these young adults than has previously been suspected.     

Airway hyperresponsiveness to cigarette smoke in ovalbumin-sensitized guinea pigs

This study was carried out to determine if the bronchoconstrictive effect of cigarette smoke (CS) is enhanced when airway hyperresponsiveness is induced by ovalbumin (Ova) sensitization, and if so, whether an increase in endogenously released tachykinins is involved. The bronchoconstrictive effects of an acute CS inhalation challenge (15 ml; 50% concentration) were compared between guinea pigs sensitized with aerosolized Ova and matching control animals (receiving saline aerosol). In Ova-sensitized animals, there were marked increases in the numbers of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by an elevated bronchomotor response to acetylcholine (ACh). The baseline lung resistance (RL) and dynamic pulmonary compliance (Cdyn) were not significantly different between the two groups; however, the same CS inhalation challenge evoked a significantly more intense bronchoconstriction in the Ova-sensitized group (control group: DeltaRL = 68 +/- 8%, DeltaCdyn = -26 +/- 6%; Ova group: DeltaRL = 425 +/- 76%; DeltaCdyn = -47 +/- 8%). The levels of substance P-like immunoreactivity (SP-LI) and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) measured in the bronchoalveolar lavage (BAL) collected after CS inhalation challenge were also significantly greater in Ova-sensitized animals than in control animals. Furthermore, pretreatment with SR-48968, a selective antagonist of neurokinin-2 (NK(2)) receptor, inhibited more than 85% of the enhanced bronchomotor responses to CS challenge, but did not significantly reduce the airway hyperresponsiveness to ACh in Ova-sensitized guinea pigs. These results show that Ova sensitization induces airway hyperresponsiveness to inhaled CS, and that the endogenous tachykinins evoked by CS-induced activation of lung C fibers play a primary role in this augmented response.     

Airway hyperresponsiveness and pulmonary function in adult asthma.

BACKGROUND: Airway hyperresponsiveness (AHR) is a very important factor in the pathogenesis of bronchial asthma. OBJECTIVES: To examine the relationship between airway obstruction and AHR in adult asthma. METHODS: This study was a retrospective study in 161 adult asthmatic patients. Nonspecific AHR to methacholine was measured. We examined the correlations between AHR and pulmonary function, severity of asthma, type of asthma and age. RESULTS: In the moderate and severe groups, peripheral airway obstruction was more aggravated compared to the mild group, and AHR was significantly more severe. Analysis of AHR by age showed that the degree of airway obstruction increased with aging, but age did not clearly correlate with airway sensitivity. Airway reactivity decreased with aging. Aspirin-induced asthma tended to be severe. In fatal asthma, central airway obstruction was significantly more severe. Although AHR in fatal asthma did not significantly differ from that in the severe group, airway sensitivity and airway reactivity tended to be increased. CONCLUSIONS: AHR is an important factor determining the severity of asthma, and airway obstruction is an important index for the prediction of death from asthma. An evaluation of the degree of AHR and airway obstruction is considered to be the first step in controlling asthma.