Peak nasal inspiratory flow in chronic obstructive pulmonary disease.

BACKGROUND: The nasal airflow in chronic obstructive pulmonary disease (COPD) is poorly characterized. Peak nasal inspiratory flow (PNIF) is a valuable instrument for assessing nasal airflow and the effect of pulmonary pathology such as COPD on PNIF remains unknown. To test the hypothesis that nasal airflow is reduced in COPD, we assessed airflow using PNIF in COPD and a control group. We also explored whether there is an association between COPD, chronic rhinosinusitis without nasal polyps (CRSsNP), and other predefined covariates with PNIF. METHODOLOGY: Ninety patients with COPD and 67 controls underwent PNIF and spirometry. The associations between PNIF and COPD and pre-bronchodilator forced expiratory volume in the first second (FEV1) (% predicted) were assessed by multivariable linear regression in two separate models. RESULTS: PNIF was significantly lower in the COPD group than in the control group. Multivariable linear regression showed that COPD and pre-bronchodilator FEV1 (% predicted) were significantly associated with lower PNIF after adjustment for age, sex, CRSsNP, weight and height. CRSsNP was not associated with PNIF in either of the adjusted regression analyses. CONCLUSIONS: PNIF is lower in COPD than in a control group. The finding of a low PNIF in the absence of disease in the upper airways may be due to obstructive lower airways diseases and special care should be taken when interpreting PNIF values in patients with COPD or reduced FEV1.

Olfaction in COPD.

BACKGROUND: Olfaction is poorly characterized in COPD. To test the hypothesis that olfaction is reduced in COPD, we assessed olfaction with the "Sniffin' Sticks" test and a questionnaire addressing olfaction in COPD and a corresponding control group in respect to age and sex. We also explored whether there is an association between COPD, chronic rhinosinusitis without nasal polyps (CRSsNP), and other predefined covariates with olfactory function. METHODOLOGY: Olfactory function was assessed by the score for threshold (T), discrimination (D) and identification (I), and the composite TDI score in the "Sniffin' Sticks" test and by self-reported evaluation of impaired olfaction and of "decreased sense of smell and taste" in the 22-item Sino-Nasal Outcome Test (SNOT-22) in 90 COPD patients and 93 controls. A clinical interview and ENT-examination with nasal endoscopy, skin prick test and spirometry with reversibility were performed. RESULTS: The TDI, D and I scores were significantly lower in the COPD group than in the control group. The T score was not significantly different between the two groups. Hyposmia and anosmia were present in up to 79% of patients with COPD. The prevalence of self-reported impaired olfactory function and for "decreased sense of smell and taste" - was more than two-fold greater in the COPD than in the control group. COPD, higher age, male sex and allergy were associated with a lower TDI score, while CRSsNP was not associated with the TDI score. CONCLUSIONS: COPD is associated with olfactory dysfunction and the underlying mechanisms for this dysfunction should be elucidated.

Activated CD8+ T cells and natural killer T cells in bronchoalveolar lavage fluid in hypersensitivity pneumonitis and sarcoidosis.

BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis are diffuse parenchymal lung diseases characterized by formation of non-caseating granulomas with a bronchocentric distribution. Analysis of the white blood cell differential profile in bronchoalveolar lavage fluid can be a useful supplement in the diagnostic work-up. OBJECTIVE: Diagnostic markers that can improve the discrimination of sarcoidosis and hypersensitivity pneumonitis are wanted. METHODS: Bronchoalveolar lavage fluid fractions of CD4+ and CD8+ T cells expressing the activation marker HLA-DR and fractions of natural killer T cells determined by flow cytometry were investigated in sarcoidosis (N=83), hypersensitivity pneumonitis (N=10) and healthy control subjects (N=15). RESULTS: In hypersensitivity pneumonitis, natural killer T cell fractions were over 7-fold greater [median (IQR): 5.5% (3.5-8.1) versus 0.7% (0.5-1.2), p<0.0001], and HLA-DR+ fractions of CD8+ lymphocytes were almost two fold greater [median (IQR): 79% (75-82) versus 43% (34-52), p<0.0001] than in sarcoidosis. In healthy control subjects, natural killer T cell fractions of leucocytes and HLA-DR+ fractions of CD8+ lymphocytes were lower [median (IQR): 0.3% (0.3-0.6) and 30% (26-34), p=0.02 and p=0.01 compared to sarcoidosis]. The combined use of these two markers seems to discriminate the diseases very well. CONCLUSION: This study suggests a role for the bronchoalveolar lavage fluid lymphocyte subsets HLA-DR+ CD8+ T cells and natural killer T cells in the diagnostic work up of sarcoidosis and hypersensitivity pneumonitis.

The determining factors of peak nasal inspiratory flow and perception of nasal airflow in asthmatics.

BACKGROUND: The effect of pulmonary pathology on peak nasal inspiratory flow (PNIF) remains largely unknown. We investigated an association between a diagnosis of asthma and of lung function on PNIF when adjusted for possible confounders. Further, we investigated the perception of nasal obstruction in asthmatics compared to healthy controls when adjusted for PNIF. METHODOLOGY: Eighty-seven asthmatics and 92 non-asthmatic controls underwent PNIF (categorized into groups of high, medium and low), acoustic rhinometry (AR) and spirometry, and we assessed symptoms of nasal obstruction on visual analogue scales (VAS) in three categories. RESULTS: PNIF was significantly associated with asthma and forced expiratory volume in the first second (FEV1) (% predicted). Other factors associated with PNIF were the degree of nasal obstruction measured both subjectively on a VAS and objectively with AR, age and disease status. Asthma patients were 19 times more likely to be in a higher VAS category compared to non-asth- matic controls independent of PNIF group. CONCLUSION: Special care has to be taken when interpreting PNIF values in patients with asthma or reduced FEV1 (% predicted). The sensation of nasal obstruction in asthmatics is different from controls despite being in the same PNIF group.

Activated CD8(+) T cells and NKT cells in BAL fluid improve diagnostic accuracy in sarcoidosis.

PURPOSE: The clinical diagnosis of pulmonary sarcoidosis is based on the presence of noncaseating granulomas in an appropriate clinical setting with either bilateral hilar adenopathy and/or parenchymal infiltrates. Lymphocytosis with an increased CD4/CD8 T cell ratio in bronchoalveolar lavage fluid is supportive. We evaluated the diagnostic accuracy of a predictive binary logistic regression model in sarcoidosis based on sex, age, and bronchoalveolar lavage fluid cell profile with and without the inclusion of HLA-DR(+) CD8(+) T cells and natural killer T-cell fractions. METHODS: A retrospective analysis of differential cell counts and lymphocyte phenotypes by flow cytometry in bronchoalveolar lavage was performed in 183 patients investigated for possible diffuse parenchymal lung disease. A logistic regression model with age, sex, lymphocyte fraction, eosinophils, and CD4/CD8 ratio in bronchoalveolar lavage fluid (basic model) was compared with a final model, which also included fractions of HLA-DR(+) CD8(+) T cells and natural killer T cells. Diagnostic accuracy of the two models was assessed by receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curve for the basic and final model was 0.898 [95 % confidence interval (CI) 0.852-0.945] and 0.937 (95 % CI 0.902-0.972), respectively, p = 0.008. CONCLUSIONS: Assessment of HLA-DR(+) CD8(+) T cell and natural killer T-cell fractions may improve diagnostic accuracy and further strengthen the importance of bronchoalveolar lavage in the diagnostic workup of sarcoidosis.

Effect of inspired air conditions on exercise-induced bronchoconstriction and urinary CC16 levels in athletes.

Injury to the airway epithelium has been proposed as a key susceptibility factor for exercise-induced bronchoconstriction (EIB). Our goals were to establish whether airway epithelial cell injury occurs during EIB in athletes and whether inhalation of warm humid air inhibits this injury. Twenty-one young male athletes (10 with a history of EIB) performed two 8-min exercise tests near maximal aerobic capacity in cold dry (4°C, 37% relative humidity) and warm humid (25°C, 94% relative humidity) air on separate days. Postexercise changes in urinary CC16 were used as a biomarker of airway epithelial cell perturbation and injury. Bronchoconstriction occurred in eight athletes in the cold dry environment and was completely blocked by inhalation of warm humid air [maximal fall in forced expiratory volume in 1 s = 18.1 ± 2.1% (SD) in cold dry air and 1.7 ± 0.8% in warm humid air, P < 0.01]. Exercise caused an increase in urinary excretion of CC16 in all subjects (P < 0.001), but this rise in CC16 was blunted following inhalation of warm humid air [median CC16 increase pre- to postchallenge = 1.91 and 0.35 ng/µmol in cold dry and warm humid air, respectively, in athletes with EIB (P = 0.017) and 1.68 and 0.48 ng/µmol in cold dry and warm humid air, respectively, in athletes without EIB (P = 0.002)]. The results indicate that exercise hyperpnea transiently disrupts the airway epithelium of all athletes (not only in those with EIB) and that inhalation of warm moist air limits airway epithelial cell perturbation and injury.

Photoinduced color changes in two different qualities of riboflavin in the solid state and in various tablet formulations photoreactivity of biologically active compounds. XX.

There has been a gradual change in the relative amounts of synthetic and biosynthetic bulk riboflavin (RF) supplied to the overall market over the past years. The two sources of drug substance seem to have different photochemical properties that cannot be readily predicted. Alternating between the two qualities of RF therefore seems to influence the photochemical properties of the final product in a rather unpredictable way. A change in production method introduces the possibility of a change in polymorphic form which may alter the photoreactivity of the substance. The drug substance and tablets become green upon light exposure. The biosynthetic bulk material appears to be less photostable than the synthetic bulk material after inadvertent exposure to radiation or at elevated humidity. The observed color change cannot be explained by the formation of degradation products but is strongly dependent on the humidity level within the drug substance or preparation. The change in color was dramatically increased (by a factor up to 7) when the drug substance was formulated as tablets. Interactions were observed between RF and individual tablet components by mixing and compression at low pressure prior to exposure.

Influence of lag-time between light exposure and color evaluation of riboflavin in the solid state.

The lag-time between sample light exposure and evaluation of the samples strongly influences the observed change in surface color of riboflavin bulk substance and tablets. The decrease in total color change (deltaE*ab) as a function of time after exposure is ascribed to a change in the surface moisture content of the samples during storage. Our results emphasize the need for a standardization of the lag-time between light exposure and sample evaluation in the photostability testing protocol of drug substances and products.

Effects of montelukast on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction.

Leukotriene antagonists are effective in the treatment of exercise-induced bronchoconstriction. Montelukast is a specific cysteinyl-leukotriene receptor1 antagonist without known effects on the pulmonary vessels, which in theory should be advantageous with respect to gas exchange. In addition to lung function, we investigated the effects of montelukast on parameters of gas exchange and physical performance in 16 asthmatics with exercise-induced bronchoconstriction in a double-blind cross-over placebo-controlled study. Subjects were tested at an ambient temperature of -15 degrees C with a tread mill exercise protocol consisting of consecutive workloads of 80% V'O(2max) (6 min), rest (4 min), 60% V'O(2max) (6 min) and step increments of exercise until exhaustion. Montelukast reduced the maximum post-exercise fall in FEV1 (P < 0.01), improved the running time to exhaustion in 11 of 16 test subjects (one unchanged) (P = 0.03), and reduced the Borg score at exhaustion (P = 0.03) and the breathing frequency after 3 min at 60% V'O(2max) (P = 0.03). V'(O2), V'CO(2), minute ventilation, ventilatory equivalents, respiratory exchange ratio, heart rate and oxygen pulse were not significantly different after montelukast and placebo. We conclude that montelukast has a beneficial effect on physical performance in most adults with exercise-induced asthma without any observed effect on gas-exchange parameters.

Montelukast does not affect exercise performance at subfreezing temperature in highly trained non-asthmatic endurance athletes.

Anti-leukotriene therapy represents a new principle in asthma treatment. As elite athletes can have asthma, this double-blind, placebo-controlled, randomised cross-over study investigated the effect of 10 mg oral montelukast, a specific and potent cysteinyl leukotriene receptor antagonist, on physiological responses to submaximal and maximal aerobic exercise at -15 degrees C in 14 non-asthmatic highly trained endurance male athletes (maximal oxygen uptake [VO2 max] > 70 ml x kg(-1) x min(-1)). Heart rate, capillary blood lactate, minute ventilation with tidal volume and breathing frequency, respiratory exchange ratio and oxygen uptake were measured during the warm-up run of 10 min at 50%, runs of 10 min at 90% and 5 min at 80% VO2max, and a timed run to exhaustion. Spirometry was performed at baseline, at four hours after tablet ingestion, after warm-up and exercise at 80% VO2max, and in the post exercise period. Compared to placebo, montelukast did not increase baseline FEV1, have a beneficial effect on physiological performance variables, or increase the mean (SD) running time to exhaustion (montelukast: 332.3 [45.8] s, placebo: 340.1 [53.3] s, P = 0.22). These findings do not suggest the need for disallowing the use of this drug by asthmatic athletes.

Placebo-controlled study of inhaled budesonide on indices of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsies in cross-country skiers.

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 mug 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 FEV(1). 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.

Combined use of exhaled nitric oxide and airway hyperresponsiveness in characterizing asthma in a large population survey.

The aim of the present study was to see whether measurements of airway hyperresponsiveness (AHR) and nitric oxide (NO) in exhaled air (ENO) either separately or in combination, could differentiate between asthmatics and healthy control subjects in a population based survey. In central Norway 8,571 adolescents participated in a large-scale epidemiological survey (Young Helseundersøkelsen i Nord-Trøndelag (Health Survey in North-Trøndelag; HUNT). Asthmatic symptoms when exposed to pollen, pets or house-dust were reported by 7.8% (suspected asthmatics), while 56% reported no asthmatic or allergic symptoms (control subjects). From these respective groups 151 and 213 adolescents were investigated with allergy screening, measurements of exhaled and nasal NO, and methacholine challenge test. AHR (provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20) <2 mg) was confirmed in 75% of the suspected asthmatics versus 25% of the control subjects, whereas 52% versus 20% had elevated levels of ENO (> or =8 parts per billion (ppb)). ENO and dose response ratio to methacholine (DRR) were positively correlated (r=0.41, p<0.001). ENO was significantly elevated in atopic versus nonatopic suspected asthmatics (11.7 ppb and 5.6 ppb respectively, p<0.001). Suspected asthmatics with both AHR and atopy had the highest levels of ENO (14.2 ppb). It is concluded that measurements of nitric oxide in exhaled air alone are not a useful tool in diagnosing asthma in population surveys, but that the combination of airway hyperresponsiveness and elevated nitric oxide in exhaled air is a very specific finding for allergic asthma. The use of dose response ratio to methacholine did not provide any additional information to the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second in this study.

Evidence of airway inflammation and remodeling in ski athletes with and without bronchial hyperresponsiveness to methacholine.

Asthma-like symptoms, methacholine hyperresponsiveness, and use of asthma medication are prevalent in elite cross-country skiers. We quantitated mucosal inflammatory cell infiltration and tenascin expression in the subepithelial basement membrane in endobronchial biopsy specimens of the proximal airways from 40 elite, competitive skiers (mean: 17.5; range: 16 to 20 yr) without a diagnosis of asthma, in 12 subjects with mild asthma, and in 12 healthy controls, through immunohistochemistry and indirect immunofluorescence, respectively. All of the subjects were nonsmokers. T-lymphocyte, macrophage, and eosinophil counts were, respectively, greater by 43-fold (p < 0.001), 26-fold (p < 0.001), and twofold (p < 0.001) in skiers, and by 70-fold (p < 0.001), 63-fold (p < 0.001), and eightfold (p < 0.001) in asthmatic subjects than in controls. In skiers, neutrophil counts were more than twofold greater than in asthmatic subjects, and mast cell counts were not significantly different than in controls. Tenascin expression (as measured through the thickness of the tenascin-specific immunoreactivity band in the basement membrane) was increased in skiers (median: 6.7 microm; interquartile range [IQR]: 5.3 to 8.5 microm, p < 0.001) and asthmatic subjects (mean: 8.8 microm; IQR: 7.2 to 10.8 microm, p < 0. 001) compared with controls (mean: 0.8 microm; IQR: 0 to 3.1 microm) and did not correlate with inflammatory cell counts. Inflammatory changes were present irrespective of asthmalike symptoms, hyperresponsiveness, or atopy. Prolonged repeated exposure of the airways to inadequately conditioned air may induce inflammation and remodeling in competitive skiers.

Non-invasive evaluation of lower airway inflammation in hyper-responsive elite cross-country skiers and asthmatics.

Asthma-like symptoms and bronchial hyper-responsiveness (BHR) to methacholine are prevalent in competitive cross-country skiers. Whether these symptoms (ski asthma) in these athletes are caused by asthma remains uncertain. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and nitric oxide (NO) concentration in exhaled air, both indirect markers of asthmatic airway inflammation, were investigated in two non-smoking study populations of skiers and asthmatics. Of 18 skiers with ski asthma, 15 non-steroid and 14 steroid-treated asthmatics, BHR to AMP was present in five (28%), six (40%) and 10 (71%) subjects respectively. Although the groups were not significantly different in responsiveness to methacholine, responsiveness to AMP increased in order of magnitude from ski asthma < non-steroid-treated < steroid-treated asthma. Exhaled NO in 44 (nine with ski asthma) skiers was not significantly different from 82 healthy non-atopic controls [median [interquartile range (IQR)] 6.5 (4.1-9.9) vs. 5.2 (4.2-6.5) ppb]. Exhaled NO in 29 subjects with mild intermittent asthma was three-fold greater [median (IQR) 19.2 (5.1-25.6) ppb, P < 0.01] than in skiers. Exhaled NO was two- and four-fold greater in atopic than non-atopic subjects in the skier (P < 0.001) and asthmatic (P < 0.01) groups, respectively, and was correlated to methacholine responsiveness in atopic asthmatics (n = 22, rho = 0.55, P < 0.01). Exhaled NO was not elevated in ski asthma and may be more useful as a marker of atopic status than inflammation in the lower airway in skiers. Few skiers were hyper-responsive to AMP, indicating that pre-activated mucosal mast cells are not a predominant feature in ski asthma.

Bronchoscopy and bronchoalveolar lavage findings in cross-country skiers with and without "ski asthma".

Bronchial hyperresponsiveness to methacholine with asthma-like symptoms ("ski asthma") is frequent in elite cross-country skiers. To further the understanding of "ski asthma", 10 nonasthmatic, nonatopic controls and 30 adolescent elite skiers were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Nine skiers were atopic without allergy symptoms. Compared with controls, the macroscopic inflammatory index in the proximal airways in skiers was three-fold greater (median (interquartile range) 3.0 (2.0-5.0) versus 1.0 (0.8-2.3), p=0.008). In the BAL fluid, skiers had significantly greater total cell (p<0.05) and percentage lymphocyte (p<0.01) and mast cell counts (p<0.05). Neutrophil and eosinophil counts were not significantly different and eosinophil cationic protein was not detected. Tumour necrosis factor-alpha and myeloperoxidase were detected in 12 (40%) and six (20%) skiers, respectively. In skiers with ski asthma, the inflammatory index was greater than in nonasthmatic skiers. Lymphocyte subtypes and activation markers, and concentration of albumin, fibronectin and hyaluronan were not different from those in controls. Cross-country skiers have a minor to moderate degree of macroscopic inflammation in the proximal airways at bronchoscopy and a bronchoalveolar lavage fluid profile which differs in several respects from healthy controls. Skiers with ski asthma tend to show even higher degrees of bronchial inflammation.

Exhaled and nasal NO levels in allergic rhinitis: relation to sensitization, pollen season and bronchial hyperresponsiveness.

Exhaled nitric oxide is a potential marker of lower airway inflammation. Allergic rhinitis is associated with asthma and bronchial hyperresponsiveness. To determine whether or not nasal and exhaled NO concentrations are increased in allergic rhinitis and to assess the relation between hyperresponsiveness and exhaled NO, 46 rhinitic and 12 control subjects, all nonasthmatic nonsmokers without upper respiratory tract infection, were randomly selected from a large-scale epidemiological survey in Central Norway. All were investigated with flow-volume spirometry, methacholine provocation test, allergy testing and measurement of nasal and exhaled NO concentration in the nonpollen season. Eighteen rhinitic subjects completed an identical follow-up investigation during the following pollen season. Exhaled NO was significantly elevated in allergic rhinitis in the nonpollen season, especially in perennially sensitized subjects, as compared with controls (p=0.01), and increased further in the pollen season (p=0.04), mainly due to a two-fold increase in those with seasonal sensitization. Nasal NO was not significantly different from controls in the nonpollen season and did not increase significantly in the pollen season. Exhaled NO was increased in hyperresponsive subjects, and decreased significantly after methacholine-induced bronchoconstriction, suggesting that NO production occurs in the peripheral airways. In allergic rhinitis, an increase in exhaled nitric oxide on allergen exposure, particularly in hyperresponsive subjects, may be suggestive of airway inflammation and an increased risk for developing asthma.

Salmeterol and physical performance at -15 degrees C in highly trained nonasthmatic cross-country skiers.

The aim of this double-blind, placebo-controlled, cross-over study was to investigate possible improvement in physical performance at an ambient temperature of -15 degrees C by an inhaled dose of 50 micrograms salmeterol in 8 highly trained nonasthmatic cross-country skiers. FEV1 was measured before, during and after the treadmill exercise protocol, which consisted of a warm-up run, runs of 10 min at 90% and 5 min at 80% VO2max, followed by a timed run to exhaustion. Despite a significant improvement in FEV1, salmeterol did not have a beneficial effect on heart rate, blood lactate concentration, respiratory exchange ratio, oxygen uptake or minute ventilation during the exercise protocol. Running time to exhaustion was not significantly different from placebo. This lack of enhancement of exercise performance in healthy endurance athletes further supports the recent approval of salmeterol for prophylactic use by asthmatic athletes during training and competition.

Lymphoid aggregates in endobronchial biopsies from young elite cross-country skiers.

Observation of bronchus-associated lymphoid tissue (BALT) in whole lung specimens from healthy nonsmoking adults has questioned the hypothesis that BALT is not constitutively present in healthy adult human lungs. In our study, we investigated endobronchial biopsies of the second- and third-generation carinae from 44 cross-country ski athletes and 12 healthy control subjects, all nonsmoking young adults. The skiers had a prevalence of respiratory allergy (18%), asthma-like symptoms (59%), beta2 agonist medication (25%), and methacholine bronchial hyperresponsiveness (79%). Biopsy sections were stained by immunohistochemical and hematoxylin-eosin-saffran methods. Lymphoid aggregates of more than 50 cells were identified in 28 (64%) skiers and three (25%) control subjects (p = 0.02). They were small in comparison to those found in rabbits and rats, contained T and B lymphocytes and macrophages, and were seen more frequently in skiers using beta2 agonists (p = 0.04) and with bronchial hyperresponsiveness to methacholine (p = 0.053). The frequency of these aggregates was not significantly different at the two carinal levels (p = 0.6). The aggregates were not associated with a history of respiratory allergy or asthma-like symptoms. These aggregates share some resemblance with what is usually defined as BALT. However, their exact nature and function await further clarification.

Effect of cold exposure (-15 degrees C) and salbutamol treatment on physical performance in elite nonasthmatic cross-country skiers.

The effects of whole-body exposure to ambient temperatures of -15 degrees C and 23 degrees C on selected performance-related physiological variables were investigated in elite nonasthmatic cross-country skiers. At an ambient temperature of -15 degrees C we also studied the effects of the selective beta2-adrenergic agonist Salbutamol (0.4 mg x 3) which was administered 10 min before the exercise test. Eight male cross-country skiers with known maximal oxygen uptakes (VO2max) of more than 70 ml x kg(-1) x min(-1) participated in the study. Oxygen uptake (VO2), heart rate (fc), blood lactate concentration ([La-]b) and time to exhaustion were measured during controlled submaximal and maximal running on a treadmill in a climatic chamber. Lung function measured as forced expiratory volume in 1 s (FEV1) was recorded immediately before the warm-up period and at the conclusion of the exercise protocol. Submaximal VO2 and [La-]b at the two highest submaximal exercise intensities were significantly higher at -15 degrees C than at 23 degrees C. Time to exhaustion was significantly shorter in the cold environment. However, no differences in VO2max or fc were observed. Our results would suggest that exercise stress is higher at submaximal exercise intensities in a cold environment and support the contention that aerobic capacity is not altered by cold exposure. Furthermore, we found that after Salbutamol inhalation FEV1 was significantly higher than after placebo administration. However, the inhaled beta2-agonist Salbutamol did not influence submaximal and maximal VO2, fc, [La-]b or time to exhaustion in the elite, nonasthmatic cross-country skiers we studied. Thus, these results did not demonstrate any ergogenic effect of the beta2-agonist used.

Prevalence of asthma in young cross-country skiers in central Scandinavia: differences between Norway and Sweden.

An increased prevalence of asthma in cross-country skiers has been reported previously. This study was conducted in order to evaluate the prevalence of asthma among young, elite cross-country skiers in Trøndelag, Norway and Jämtland, Sweden. These two regions in central Scandinavia have different climates during the winter season, with a coastal type in Trøndelag while Jämtland is characterized by a colder, drier, inland type of climate. The study population consisted of 171 skiers (118 from Norway, 53 from Sweden). The investigation included an asthma questionnaire, spirometry and methacholine provocation testing. The prevalence of self-reported asthma-related symptoms was 46% in Norway and 51% in Sweden. The prevalence of bronchial hyper-responsiveness (BHR) was significantly different between the two regions. In Norway, 14% of the skiers were hyper-responsive to methacholine compared to 43% in Sweden (P < 0.001). Moreover, the estimated prevalence of clinically diagnosed asthma was 12% in Norway and 42% in Sweden (P < 0.001). The self-reported frequency of respiratory allergy was higher in Sweden (32%) than in Norway (11%). However, on an individual basis, self-reported allergy did not predict occurrence of asthma or BHR. In conclusion, there is a high prevalence of BHR and asthma among young, elite cross-country skiers in central Scandinavia, especially in Sweden. Cross-country skiing may be a risk factor for the development of asthma. Longitudinal studies of cross-country skiers, and studies to acquire further knowledge of the mechanisms involved in the development of asthma are indicated.