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Vol. 67, No. 4, 2000
Issue release date: July–August 2000
Respiration 2000;67:417–425
(DOI:10.1159/000029541)

Placebo-Controlled Study of Inhaled Budesonide on Indices of Airway Inflammation in Bronchoalveolar Lavage Fluid and Bronchial Biopsies in Cross-Country Skiers

Sue-Chu M.a · Karjalainen E.-M.b · Laitinen A.c · Larsson L.d · Laitinen L.A.b · Bjermer L.a
aDepartment of Lung Medicine, University Hospital, Trondheim, Norway; bDepartment of Medicine, Helsinki University Central Hospital, and cDepartment of Anatomy, Helsinki University, Helsinki, Finland; dDepartment of Pulmonary Medicine, Östersund Central Hospital, Östersund, Sweden
email Corresponding Author

Abstract

Background: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. Objective: To investigate the effect of inhaled budesonide, 400 μg twice daily, on indices of airway inflammation in ‘ski asthma’, defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. Methods: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16–20) years for a mean (range) treatment period of 22 (10–32) weeks over the competitive season. Results: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV1. Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. Conclusions: We were unable to show any clear beneficial effect of budesonide in ‘ski asthma’. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.

Copyright © 2000 S. Karger AG, Basel


 Outline


 goto top of outline Key Words

  • Airway inflammation
  • Bronchoalveolar lavage
  • Bronchial biopsy
  • Corticosteroid, inhaled
  • Skiers
  • Tenascin
  • Asthma

 goto top of outline Abstract

Background: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. Objective: To investigate the effect of inhaled budesonide, 400 μg twice daily, on indices of airway inflammation in ‘ski asthma’, defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. Methods: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16–20) years for a mean (range) treatment period of 22 (10–32) weeks over the competitive season. Results: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV1. Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. Conclusions: We were unable to show any clear beneficial effect of budesonide in ‘ski asthma’. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.

Copyright © 2000 S. Karger AG, Basel


goto top of outline introduction

The association of exercise with asthma has been known since the end of the first century AD [1]. The dual nature of this relationship has been highlighted by recent reports of an increased prevalence of diagnosed asthma, asthma-like symptoms, bronchial hyperresponsiveness to methacholine and exercise, and frequent use of anti-asthmatic medication in elite athletes [2, 3, 4]. Moreover, it has been suggested that strenous physical exertion at low temperatures with repeated inhalation of large amounts of cold air may increase the risk for the development of asthma in healthy individuals [5].

Infiltration of the bronchial mucosa with eosinophils, mast cells, lymphocytes and macrophages and an increased thickness of the reticular basement membrane due to increased collagen deposition are characteristic morphological features in asthma [6, 7, 8]. These features, together with an increased expression of the extracellular matrix protein, tenascin in the basement membrane, are observed even in those with a short history of disease [9, 10]. We have observed macroscopic inflammatory changes in the proximal airways in young adult competitive cross-country skiers with ‘ski asthma’, defined as two or more asthma-like symptoms and bronchial hyperresponsiveness to methacholine. Moreover, the lymphocyte count is increased and the pro-inflammatory cytokine TNFα is present in the bronchoalveolar lavage (BAL) fluid [11]. Although eosinophilia and eosinophilic cationic protein are absent in BAL fluid, the bronchial submucosa of these skiers is infiltrated with lymphocytes, macrophages, neutrophils and eosinophils, and tenascin expression is increased in the reticular basement membrane (accepted for publication). While less intense than in mild asthma, the inflammatory infiltrate in ‘ski asthma’ is greater than that observed in clinically healthy non-skiing athletes with hyperresponsiveness to histamine [12].

Inhaled corticosteroids are recommended in the management of mild to moderate asthma [13]. They are frequently used by cross-country skiers with asthma-like symptoms on exercise and advocated for the management of obstructive symptoms in athletes [14]. Although demonstrated in clinical and biopsy studies in newly diagnosed asthma [15, 16], the anti-inflammatory efficacy of inhaled corticosteroids in ‘ski asthma’ has not been investigated. The aim of this study was to investigate the effect of budesonide, 400 μg twice daily during the competitive season, on indices of inflammation in the bronchial mucosa and BAL fluid, and on tenascin immunoreactivity in the reticular basement membrane in adolescent competitive cross-country skiers with ‘ski asthma’.

 

goto top of outline material and methods

goto top of outline study design

A double-blind, placebo-controlled, randomised, parallel-group study design was used. Subjects with ‘ski asthma’ and no history of use of inhaled corticosteroids or cromolyns within the previous 12 months were recruited to the study in late autumn, prior to the start of the competitive skiing season. After assessment of lung function and atopic status, and bronchoscopic examination, subjects were randomised on the basis of maximum oxygen uptake during treadmill exercise at –15°C to treatment with either inhaled budesonide 400 μg (Pulmicort Turbuhaler®, Astra Draco, Lund, Sweden) or placebo, twice daily. In addition to the study medication, all subjects were provided with terbutaline 0.5 mg (Bricanyl Turbuhaler®, Astra Draco) for use as required. The planned study duration was 12 weeks. As competitive skiing events and school examinations or holidays precluded reattendance at the intended time, the study duration was extended. Subjects were also asked to grade treatment compliance as good, moderate or poor, and to assess whether respiratory symptoms improved, worsened or were unchanged, and whether the level of training was normal, increased or decreased during the study period.

goto top of outline subjects

The study population consisted of 25 (19 males) non-smoking, elite competitive cross-country skiers with two or more asthma-like symptoms, defined as the presence of wheeze, abnormal breathlessness or chest tightness on exertion, at rest, or on exposure to irritants, as reported in a self-completed questionnaire. Bronchial hyperresponsiveness was defined as the provocative dose of ≤1,800 μg methacholine which caused a fall of at least 20% in FEV1 from baseline (PD20 FEV1 ≤1,800 μg). It was determined with a controlled tidal volume breathing technique and an automatic inhalation synchronised dosimetric jet nebuliser (Spira Elektro 2, Respiratory Care Centre, Hameenlinna, Finland), as previously described [17]. Bronchial responsiveness to methacholine was expressed as the dose-response slope (DRS) [18]. Lung function was determined at least 8 h after bronchodilator therapy by flow volume spirometry (Microlab 3300 Mk2 spirometer, Micro Medical, Gillingham, UK). Atopic status was assessed by screening for the presence of immunoglobulin (Ig) E specific to house dust mite, cat, dog, horse, timothy grass and birch pollens, mugwort and cladosporium (Phadiotop CAPTM, Pharmacia Diagnostics, Lund, Sweden). Baseline subject characteristics are presented in table 1.

TAB01

Table 1. Baseline characteristics of studysubjects

Written informed consent was obtained from each subject and from the parents of those subjects under the age of 18 years. The study was reviewed and approved by the Regional Ethics Committee in Trondheim.

goto top of outline bronchoscopy, macroscopic inflammatory index, bronchial biopsy and bronchoalveolar lavage

Transoral fibre-optic bronchoscopy (BF-XT 20 or BF-IT 30 bronchoscope, Olympus Optical Co., Tokyo, Japan) was performed at least 2 days after methacholine provocation and under xylocaine local anaesthesia, as previously described [11, 19]. Briefly, premedication consisted of nebulised salbutamol and ipratropium bromide, and intravenous glycopyrronium, midazolam and alfentanil. Mucosal friability (susceptibility to bleeding on contact with the bronchoscope), vascularity and oedema of the mucosa, and the amount of secretions in the proximal airways were assessed in 9 subjects in both groups by an experienced bronchoscopist (L.B.) blinded to the clinical status of the subjects. Each parameter was assessed on a 5-point scale (0–4), and a maximum macroscopic inflammatory index of 16 was indicative of the presence of severe macroscopic inflammatory changes. Endobronchial biopsy specimens were obtained from the carinae of the second- and third-generation bronchi with Olympus FB35C or FB36C forceps. Finally, BAL of the medial segment of the middle lobe was performed with two 60-ml aliquots of prewarmed (37°C) phosphate-buffered saline.

goto top of outline bal fluid analysis

BAL fluid was processed within 2 h of collection and analysed as previously described [11]. Briefly, after pooling and filtration through nylon gauze (100 μm pore diameter), aliquots were taken for total cell counts (Technicon H1, Technicon Instruments, Tarrytown, N.Y., USA), cytospin preparations and flow cytometry. Cytospins were used for differential cell counts of macrophages, lymphocytes, neutrophils and eosinophils in 300 cells, excluding epithelial cells (May-Grünwald-Giemsa staining), and mast cell counts (toluidine blue and haematoxylin staining). Flow cytometry (FACScan flow cytometer, Becton-Dickinson Immunocytometry Systems, Mountain View, Calif., USA) was used to quantify T, T-helper, T-suppressor, primary and memory TH lymphocyte and natural killer (NK) cell phenotypes, together with HLA-DR activation status of T, T-helper and T-suppressor lymphocytes and IL-2 receptor expression on T-helper lymphocytes.

goto top of outline bronchial biopsy analysis

Biopsy specimens were snap-frozen in liquid nitrogen, stored at –70°C and prepared for immunohistochemistry as previously described [10, 19]. Briefly, 5-μm thick, air-dried and acetone-fixed cryosections were stained with murine monoclonal antibodies AA1 (dilution 1:500), Ber-Mac3 (1:25), CD3+ (1:1,000, all from Dako, Glostrup, Denmark), and EG2 (1:50; Kabi Pharmacia Diagnostic, Uppsala, Sweden) for mast cells, macrophages, T-lymphocytes and activated eosinophils, respectively. Specific antibody binding was visualized by the alkaline phosphatase anti-alkaline phosphatase method, with rabbit anti-mouse antibody as the second antibody. The total number of mast cells, macrophages, T-lymphocytes and activated eosinophils was computed from slide photographs projected onto a calibrated digitising tablet (Kurta IS/THREE, Kurta Corp., Phoenix, Ariz., USA), and expressed as cells per square millimetre of total mucosa analysed, disregarding damaged areas (AutoCad program, version 10.1, Autodesk, Sausalito, Calif., USA). Indefinable numbers of aggregated T-lymphocytes seen in slide preparations from many skiers were disregarded in the quantitation of lymphocytes.

For tenascin immunoreactivity, fixed cryosections were incubated with the primary mAb in a moist chamber at room temperature for 30 min, washed with PBS, reincubated with fluorescein isothiocyanate-conjugated sheep antimouse IgG (dilution 1:150; Jackson Immunosearch Laboratories, West Grove, Pa., USA) and mounted in Veronal-glycerol buffer (1:1, pH 8.4). Areas containing cross-sections of basement membrane were photographed, and the thickness of the tenascin immunoreactive area in the basement membrane was semiautomatically measured with a computerised image analysis programme [20].

goto top of outline observers

BAL fluid and biopsy samples were coded before processing, and analysed by observers blinded to the clinical and treatment status of the subjects. BAL fluid was analysed by the same observer in Trondheim, while biopsies were analysed by the same observer in Helsinki.

goto top of outline statistical analysis

An intention-to-treat analysis of the data was performed. Data on bronchial responsiveness, macroscopic inflammatory index, BAL and biopsy parameters were assessed statistically for across and within-group differences with the Mann-Whitney U and the Wilcoxon rank-sum W test, respectively. Across and within-group differences in lung function and study duration were assessed for statistical significance with the independent sample t and the paired sample t test, respectively. All tests were two-tailed. Correlation coefficients were calculated using Spearman’s rank method. A p value of <0.05 was considered to be statistically significant.

 

goto top of outline results

The study duration was not different in the budenoside and placebo groups (mean 22.3 (10.0–32.0) vs. 22.8 (20.0–27.0) weeks, p = 0.78).

goto top of outline clinical response

One budesonide-treated skier withdrew from the study at 10 weeks because of a deterioration of asthma-like symptoms and repeated upper respiratory tract infections. Compliance was reported as good by 23 skiers, and as moderate by 2 placebo-treated skiers. Of those with good compliance, asthma-like symptoms were unchanged in 15 subjects, improved in 2 placebo-treated subjects, and worsened in 3 subjects in each group. The level of training and/or competition was reported as normal in 22 skiers and as decreased in 3 (2 budesonide, 1 placebo) skiers.

Data on FEV1, bronchial responsiveness and macroscopic inflammatory index are shown in figure 1. At follow-up, FEV1 was significantly improved within the budesonide group. Methacholine provocation was performed in 24 skiers after treatment. There was a high degree of improvement in responsiveness in both groups, and hyperresponsiveness was persistent in 5 subjects in each group. The methacholine dose-response slope and inflammatory index were significantly reduced within the placebo group.

FIG01

Fig. 1. FEV1 (a), DRS (b) and macroscopic inflammatory index (c) at baseline and at follow-up (post) in placebo and budesonide groups. Positive methacholine test in 5 subjects in each group after treatment. Dotted line = Cut-off for positive methacholine test; bar = mean value for FEV1 and median value for DRS and inflammatory index.

goto top of outline bal fluid analysis

A minimal volume of 40 ml BAL fluid was recovered from each subject on both occasions. Data on total and differential cell counts are presented in figure 2. At follow-up, the macrophage count was increased and the lymphocyte count was decreased within both groups, and cell counts were not significantly different across groups.

FIG02

Fig. 2. Total and differential cell counts in BAL fluid at baseline (base) and at follow-up (post). Data presented as box and whiskers. Mann-Whitney U test for between group comparison and Wilcoxon signed-rank test for within-group comparison.

Lymphocyte phenotypes were not significantly different either at baseline or after treatment across the groups (data not shown). Of the activation markers, HLA-DR expression was decreased in T-lymphocytes in the placebo group and in T-suppressor lymphocytes within both groups, while IL2 receptor expression in T-helper lymphocytes was decreased within the budesonide group (fig. 3). The T-helper memory cell count was increased within the budesonide group [median interquartile range 92 (67–98) vs. 99% (98–99), p = 0.004], and both total and CD3-negative NK cell counts were increased within the placebo group (fig. 4).

FIG03

Fig. 3. HLA-DR activation status in (a) CD3, (b) CD8, (c) CD4 lymphocytes, and IL2 receptor expression on (d) CD4 lymphocytes at baseline and at follow-up (post) in BAL fluid from placebo and budesonide groups. Bar = Median value.

FIG04

Fig. 4. Total (a) and CD3-negative (b) NK cells at baseline and at follow-up (post) in BAL fluid from placebo and budenoside groups. Bar = Median value.

goto top of outline bronchial biopsy analysis

Assessable biopsies at baseline and at the end of the study were obtained from 11 placebo- and 10 budesonide-treated skiers. At follow-up, inflammatory cell counts were not significantly different either across or within groups. Within the budesonide group, there was a trend towards a decrease in tenascin immunoreactivity (fig. 5).

FIG05

Fig. 5. Inflammatory cell counts (cells/mm) in bronchial mucosa, and tenascin immunoreactivity (μm) in basement membrane at baseline and at follow-up (post). a T-lymphocytes. b Macrophages. c Activated eosinophils. d Mast cells. e Tenascin. Bar = Median value.

goto top of outline correlations

At inclusion, the inflammatory index was positively correlated to the neutrophil count and negatively correlated to the macrophage count in the BAL fluid, and the DRS was significantly correlated with the density of mast cells in the bronchial mucosa (fig. 6). There were no significant correlations between counts of mast cells, macrophages and eosinophils in the BAL fluid and biopsies.

FIG06

Fig. 6. Spearman’s correlation coefficient for macroscopic inflammatory index with counts of neutrophils (a) and macrophages (b) in BAL fluid, and mast cells in bronchial mucosa at baseline (c).

At follow-up, the change in DRS was not significantly correlated with changes in counts of lymphocytes, macrophages and markers of lymphocyte activation in the BAL fluid or of inflammatory cells in the bronchial biopsies.

 

goto top of outline discussion

In the present study, we were not able to demonstrate an effect of inhaled budesonide, 400 μg twice daily for a mean period of 22 weeks, as compared to placebo, on the inflammatory indices in the bronchial mucosa or the BAL fluid or on tenascin expression in the subepithelial basement membrane in skiers with ‘ski asthma’. There was a great degree of intrasubject variability for changes in mucosal cell counts in both groups, which may have precluded the achievement of statistical significance for the effect of budesonide. However, it is also plausible that the parallel improvement seen in the two groups may represent the natural course of events in the competitive season rather than an effect from budesonide itself. Nevertheless, we found changes of the inflammatory and clinical profile that may be of interest.

Despite the overall good self-reported treatment compliance, the majority of the skiers in the budesonide group, in accordance with the placebo group, did not report any change in asthma-like symptoms. Despite this, budesonide-treated skiers did have a significant improvement in FEV1, and rather surprisingly, placebo-treated skiers had a high degree of spontaneous improvement in bronchial responsiveness and macroscopic inflammatory index. The improved bronchial responsiveness in the present study is partly in accordance with another study of skiers which reported a variation in bronchial responsiveness in relation to changes in training intensity [21]. Unlike that study, training intensity in the present study was greater in late autumn than during the competitive season. Moreover, the duration of each training session in autumn was commonly in excess of 2 h, and thus longer than in the competitive season. If long-term hyperpnea is a significant pathogenetic factor, then the training programme in autumn provides a more potent provocation to the airways than competitive events in winter, which seldom exceed 1 h in duration. The observation of a high degree of spontaneous improvement in responsiveness in both groups indicates that this may be the case.

Despite an improvement in bronchial responsiveness after the competitive season, there was no decrease of mucosal inflammation in either group in the present study. The absence of an anti-inflammatory effect of budesonide in ‘ski asthma’ is in contrast to that reported for inhaled steroids in placebo-controlled studies of atopic asthmatics. In those studies, a similar daily dose of budesonide for 4–6 weeks in the birch pollen season or beclomethasone dipropionate, 500 μg twice daily over 4 months, was accompanied by a significant reduction in mucosal mast cell and eosinophil counts and tenascin expression [10, 22].

The lack of change in inflammatory indices in the placebo group at the end of the study may question whether the inflammatory changes at inclusion are indeed associated with ‘ski asthma’. However, hyperpnea and cold air are potent stimuli of inflammatory cellular infiltration of the airways. Increased counts of granulocytes and macrophages are observed in BAL fluid after 2 h of light intermittent work at –23°C in healthy subjects [23], while mucosal leukocyte infiltration is still present 24 h after a 5-min challenge of hyperventilation with dry air in dogs [24]. The different responses of the inflammatory process in ‘ski asthma’ and allergic asthma may suggest that the driving stimulus for the inflammatory response is different in these two ‘asthma phenotypes’.

Several changes in lymphocyte phenotypes in BAL fluid were observed at the end of the study. Firstly, there was an apparent spontaneous downregulation of the chronic activation marker HLA-DR in CD8+ lymphocytes in both groups. This may be related to a decreased training intensity during the winter months, as this marker is upregulated in CD8+ lymphocytes in BAL fluid in skiers in autumn, in comparison to non-athletic controls [11] and in the peripheral blood in runners with high training intensity [25]. Secondly, the absence of a significant change in IL2 receptor expression in the placebo group may suggest that T-helper lymphocytes are not acutely stimulated during the competitive season. This is in accordance with that observed in the BAL fluid of healthy subjects after cold air hyperventilation and exercise [23] and in the peripheral blood of atopic asthmatics after isocapnic cold air hyperventilation [26]. In contrast, this marker is upregulated in the pollen season in asthmatic subjects with pollen allergy [27]. Finally, there was a significant increase in CD3-negative NK cells in the placebo group. This can be related to exercise or recent viral infection. Traffic of these cells out of the circulation is increased after exercise through an upregulation of LFA-1 integrin adhesion molecule [28]. However, recent viral infection is a less likely cause, as this is often accompanied by an increase in bronchial responsiveness [29].

In summary, we were unable to show any clear beneficial effect of inhaled budesonide on airway inflammatory changes, tenascin expression, or clinical manifestations in subjects with ‘ski asthma’ in this study. A large degree of spontaneous improvement occurred, most probably associated with changes in training intensity over the follow-up period. We propose that more attention should be directed at reducing environmental stress to the airways than at attempting to modulate the induced inflammatory changes by pharmacological means.

 

goto top of outline acknowledgment

This study was financially supported by Astra Draco, Lund, Sweden.


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    External Resources

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 goto top of outline Author Contacts

Dr. Malcolm Sue-Chu
Department of Lung Medicine, University Hospital
N–7006 Trondheim (Norway)
Tel. +47 73 86 7410, Fax +47 73 86 7424
E-Mail lunge@medisin.ntnu.no,malcolm.suechu@st.telia.no


 goto top of outline Article Information

Received: Received: August 9, 1999
Accepted after revision: December 9, 1999
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 1, Number of References : 29


 goto top of outline Publication Details

Respiration (International Review of Thoracic Diseases)
Founded 1944 as ‘Schweizerische Zeitschrift für Tuberkulose und Pneumonologie’ by E. Bachmann, M. Gilbert, F. Häberlin, W. Löffler, P. Steiner and E. Uehlinger, continued 1962–1967 as ‘Medicina Thoracalis’

Vol. 67, No. 4, Year 2000 (Cover Date: July-August 2000)

Journal Editor: C.T. Bolliger, Cape Town
ISSN: 0025–7931 (print), 1423–0356 (Online)

For additional information: http://www.karger.com/journals/res


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Abstract

Background: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. Objective: To investigate the effect of inhaled budesonide, 400 μg twice daily, on indices of airway inflammation in ‘ski asthma’, defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. Methods: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16–20) years for a mean (range) treatment period of 22 (10–32) weeks over the competitive season. Results: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV1. Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. Conclusions: We were unable to show any clear beneficial effect of budesonide in ‘ski asthma’. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.

Copyright © 2000 S. Karger AG, Basel



 goto top of outline Author Contacts

Dr. Malcolm Sue-Chu
Department of Lung Medicine, University Hospital
N–7006 Trondheim (Norway)
Tel. +47 73 86 7410, Fax +47 73 86 7424
E-Mail lunge@medisin.ntnu.no,malcolm.suechu@st.telia.no


 goto top of outline Article Information

Received: Received: August 9, 1999
Accepted after revision: December 9, 1999
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 1, Number of References : 29


 goto top of outline Publication Details

Respiration (International Review of Thoracic Diseases)
Founded 1944 as ‘Schweizerische Zeitschrift für Tuberkulose und Pneumonologie’ by E. Bachmann, M. Gilbert, F. Häberlin, W. Löffler, P. Steiner and E. Uehlinger, continued 1962–1967 as ‘Medicina Thoracalis’

Vol. 67, No. 4, Year 2000 (Cover Date: July-August 2000)

Journal Editor: C.T. Bolliger, Cape Town
ISSN: 0025–7931 (print), 1423–0356 (Online)

For additional information: http://www.karger.com/journals/res


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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    External Resources

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