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Longitudinal variations in bronchial responsiveness to methacholine was studied in 19 male crosscountry skiers 19-21 years old during the season of their sport ...
Scad J Med Sci Sports 1994: 4: 134-139

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ScandiMvuvc Journal of M E D I C I N E & SCIENCE I N SPORTS ISSN 0905-7188

Longitudinal variations in bronchal responsiveness in cross-country shers and control subjects Heir T. Longitudinal variations in bronchial responsiveness in crosscountry skiers and control subjects. Scand J Med Sci Sports 1994: 4: 134-139. 0 Munksgaard, 1994 Longitudinal variations in bronchial responsiveness to methacholine was studied in 19 male crosscountry skiers 19-21 years old during the season of their sport and compared with the response in 22 age-matched control subjects with minimal physical activity. The methacholine concentration required for a 10%fall in the forced expiratory volume in the first second (PC,,) remained stable from August to November in the group of skiers, then decreased from November to February and finally increased from February to June. In the control group, PCloincreased from August to November, increased further to February and finally decreased from February to June. Alternative methods for expressing bronchial responsiveness as the linear dosc-response slope or the logarithmic dose-response slope gave no more information than did pCl0alone. High correlations were found between pCloand either of the dose-response slopes. PC,,and the dose response-slopes were equally reproducible when measured on two successive days. In contrary to the control group, high-performance crosscountry skiers demonstrated increased bronchial responsiveness in the winter. The PC,,was an advantageous method for studying longitudinal changes in bronchial responsiveness among healthy subjects.

Bronchial hyperresponsiveness is thought to be caused by environmental and genetic factors (1, 2). Both experimentally and in a natural setting, several environmental factors have been shown to provoke a transient increase in bronchial responsiveness (BR) in asthmatic as well as in healthy subjects (3). It has been postulated that such provoking factors that cause a transient increase in BR may also, occasionally, result in a permanent increase in BR (3). A single bout of physical exertion may cause an increase in BR in response to histamine or methacholine (4-6). However, many studies do not demonstrate such an effect (7-1 1). A high prevalence of exercise-induced bronchospasm and asthma has been reported in elite athletes (12-14). This is remarkable, since children and adolescents with asthma usually practice sports less often than non-asthmatics at the same age (15). A majority of asthmatic crosscountry skiers date the onset of their asthma to the sports-active period in late adolescence or early adult life (14). Thus, the

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1. Heir Norwegian University of Sport and Physical Education, Oslo, Norway

Kay words: airway responsiveness; bronchial provocation test methachollne compound; exertion; skiing Trond Heir, Asalveien 1, N-0876 Oslo, Norway Accepted for publication October 28, 1993

possibility exists that these athletes may have acquired bronchial hyperresponsivenessthrough sport. The aim of the present study was to examine longitudinal variations in BR over a period of 1 year with training and competition in a group of high-level cross-country skiers compared with a control group who did not engage in regular physical activity. Additionally, we wanted to compare different methods for studying longitudinal variations in BR among healthy individuals.

Material and methods Subjects The study group consisted of 22 high-level competitive male cross-country skiers, 19-21 years of age, who were picked to undergo their compulsory military service in a special setting for elite athletes during the 12-month study period. Eight were competing in biathlon and 14 in cross-country skiing. All had finished among the 20 best in the Norwegian

Effect of skiing on bronchial responsiveness Championship in cross-country skiing or biathlon during the last 2 years. Nineteen skiers (Table 1) completed the study and trained and competed as planned during the entire period. Two skiers did not show up for the necessary controls, and another skier was withdrawn after contracting mononucleosis. The control group consisted of 24 healthy, male recruits matched for age and living in the same military camp as the skiers. The control subjects had not participated in any sport event or trained systematically during the last 12 months prior to the start of the study. During the study period they were not allowed more physical activity than the minimum required in their duty service (0-2 h a week). Twentytwo control subjects completed the study (Table 1). Two dropped out because they were transferred to another military camp. All subjects in both groups were nonsmokers, and none suffered from bronchial asthma or other chronic lung diseases. Two skiers occasionally used P,-agonist inhalation before training or competition because they sporadically felt they had chest congestion with exercise, especially in cold water. Two skiers had a history of atopy: one was allergic to cat dander, the other to house dust mites. Six control subjects had a history of atopy. Only 3 of them were allergic to airborne allergens (pollen). One skier used antihistamines and nasal cromolyn sodium during the study period. Two control subjects used antihistamines. The study was approved by the local ethics committee. All subjects signed an informed consent form before entering the study.

Study design The study period lasted from July 1988 through June 1989. All subjects underwent a testing procedure in August, November, February and June, including measurements of lung function and a bronchial challenge test. The subjects recorded all respiratory symptoms. When a subject contracted an airway infection within 6 weeks prior to a planned test, the test was performed 3 and 6 weeks after the onset of symptoms. The latter test was employed in the evaluation of the results if the subject did not contract another airway infection before 6 weeks had elapsed. If he did, the test performed 3 weeks after Table 1. Physical characteristics of the skiers (n=19) and controls (n= 22). The results are expressed as mean values with total range. Variable Age (years) Height (cm) Weight (kg) Vo,max(ml . kg-’ .min-’)

Skiers 20.1 (19-21) 177.6 (163-185) 71.8 (58.0-78.7) 74.6 (67.4-80.3)

Controls 20.8 (19-21) 183.0 (161-198) 77.1 (64.0-93.5) 55.4 (46.0-62.0)

the onset of symptoms was used or the test was once more postponed for 3 weeks. All tests were performed at the same time of day. No physical activity was permitted on the day before the test. No drugs were used for at least 12 h before each test.

Lung function tests Lung function was measured by maximal expiratory flow volume curves (Flowmate, Erich Jaeger GmbH & Co. KG, Wurzburg, Germany) according to the standards of the American Thoracic Society (16). The following indices of lung function were used in the analysis: forced vital capacity (FVC), forced expiratory volume in the first second (FEV’), the FEVJFVC ratio, peak expiratory flow (PEF), maximal expiratory flows at 50% and 25% of remaining FVC (MEF,, and MEF,,), and mean flow between 25% and 75% of FVC (MEF25-75). Bronchial challenge tests Methacholine inhalation tests were performed according to the method described by Cockcroft et al. (17). Aerosols of the test solution were generated by a Wright nebulizer (M.G. Medical, Colchester, UK) with output 0.135+0.005 ml .min-’; The output was calibrated weekly by weighing the nebulizer before and after nebulizing. After inhalation of isotonic phosphate-buffered saline, methacholine was inhaled for 2 min in consecutively doubling concentrations in the range from 2.0 mg/ml until FEVl was reduced at least 20%, or when the maximum concentration of 128 mg/ml had been reached. BR was expressed as the test concentration causing a fall in the FEV, by 10% from the initial saline inhalation (PC,,), estimated by linear interpolation of the logarithmic dose-response curve. If FEV, did not decrease 10% even at the maximum inhaled concentration of 128 mg.ml-’, PClo was estimated by linear extrapolation. Extrapolations above 256 mgaml-’ were assigned the cut-off value of 256 mg.ml-*. Additionally, dose-response slopes were used in the analysis. An “individual standard methacholine concentration” was defined for every subject. This had to be a concentration that had been given that subject in every test, and indeed, the highest of such concentrations. Then the percentage reduction in FEVl induced by the individual standard methacholine concentration (GFEV,) was calculated. This was the origin for both the linear dose-response slope (IinDRS) calculated as GFEV, versus the actual concentration and the logarithmic dose-response slope (logDRS) determined as GFEVI versus the logarithm of the concentration (18).

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Heir Reproducibility of the bronchial challenge tests The reproducibilities of PC,, and GFEV, were evaluated by bronchial challenge tests on 2 successive days using 17 subjects randomly selected from the total sample of 19 skiers and 22 controls. The GFEV, was chosen because this was the common basis of the dose-response slopes. Simple scalar transformations are adequate to get from GFEV, to the slopes, and thus, the reproducibilities for linDRS and logDRS should be identical with that of GFEV,.

Statistical methods The results are expressed as mean values with 95% confidence intervals (CI), standard deviations or total ranges. The confidence intervals were calculated by using the Student procedure (19). In evaluation of PClo,logarithmictransformation of the data were used. All tests were two-tailed, and differences were considered statistically significant with P10.05. Analysis of variance with repeated measurements with groups and time as class variables (20) was used for comparison of groups. Because of sigmficant interactions, analysis of variance with the start values as covariate was used for comparison of groups with regard to changes between time points (21). Additionally, changes within groups were evaluated by Student’s test for paired samples (20) with Bonferroni’s correction of the si@cance level (22). Changes within groups and between the two groups were also evaluated after the exclusion of subjects with a history of atopy. The reproducibility of PClo and GFEVI was studied by a linear regression model (21). The reliability coefficients were estimated using the kappa model (23) and defined as @,-pJ( l-pc) where p , is the frequency of observed conformity and pc the stocastic expected frequency of confonnity.

Results Lung function Lung function values did not differ between the two study groups at any visit and remained stable during the study period for both groups (Table 2). Reproducibility of bronchial responsiveness The mean change in PClofrom one day to the next was one tenth of the two-fold concentration difference (95% CI: -0.164.35), with a range from -0.91 to 1.06 (P2=0.68). The linear regression between the first and the second measurement of PC,, was y = -0.33+ 1 . 1 5 (Fig. ~ 1). and the constant 0.33 did not differ significantly from zero (P=0.88).The reliability coefficient for PC,, was 0.73. The mean change in GFEV, from the first to the second test was 0.3 (95% CI: -0.8-1.5), with a range from -3.6 to 3.7 (P2=0.55). The linear regression between the first and the second measurement of GFEV, was y=0.40+0.99x (Fig. 2). The constant 0.40 was not significant different from zero (P= 0.73). The reliability coefficient for GFEV, was 0.70. The reproducibilities for linDRS and logDRS are identical with that for GFEV, because the provocation concentration was individually standardized, and for each subject the same scalar transformation was done to get from every GFEV, to the actual dose-response slope. Changes in bronchial responsiveness In the group of skiers the geometric mean of PCl0 did not change significantly from August (76.6 mg/ ml) to November (81.1 mg/ml). It was lower (P