Bronchoalveolar lavage fluid IFN-γ+ Th17 cells and regulatory T cells in pulmonary sarcoidosis.

In sarcoidosis, increased Th17 cell fractions have been reported in bronchoalveolar lavage fluid, and elevated numbers of Th17 cells producing IFN- γ have been observed in peripheral blood. The balance between Th1, Th17, and FoxP3(+) CD4(+) T cell subsets in sarcoidosis remains unclear. Bronchoalveolar lavage fluid cells, from 30 patients with sarcoidosis, 18 patients with other diffuse parenchymal lung diseases, and 15 healthy controls, were investigated with flow cytometry for intracellular expression of FoxP3. In a subset of the patients, expression of the cytokines IL17A and IFN- γ was investigated. The fractions of FoxP3(+) CD4(+) T cells and Th17 cells were both lower in sarcoidosis compared to controls (P = 0.017 and P = 0.011, resp.). The proportion of Th17 cells positive for IFN- γ was greater in sarcoidosis than controls (median 72.4% versus 31%, P = 0.0005) and increased with radiologic stage (N = 23, rho = 0.45, and P = 0.03). IFN- γ (+) Th17 cells were highly correlated with Th1 cells (N = 23, rho = 0.64, and P = 0.001), and the ratio of IFN- γ (+) Th17/FoxP3(+) CD4(+) T cells was prominently increased in sarcoidosis. IFN- γ (+) Th17 cells may represent a pathogenic subset of Th17 cells, yet their expression of IFN- γ could be a consequence of a Th1-polarized cytokine milieu. Our results indicate a possible immune cell imbalance in sarcoidosis.

Validation of the Reflux, Airway and Sleep Questionnaire (RASQ).

BACKGROUND: Airway symptoms and sleeplessness in patients with gastroesophageal reflux disease (GERD) may be of importance. This study validates a new questionnaire dealing with such symptoms. MATERIAL AND METHODS: The Reflux, Airway and Sleep Questionnaire (RASQ) is self-administered, asks about 18 symptoms or diagnoses possibly related to GERD answered on a seven-point Likert scale and with a 1-year recall period. There are questions about heartburn/regurgitation, sleeplessness, snoring, pneumonia, and upper airway infections, as well as various bronchial and laryngeal symptoms. The study included 305 patients diagnosed with GERD (n = 65), laryngitis (n = 32), asthma (n = 30), chronic obstructive pulmonary disease (n = 45), acute bronchitis (n = 39), pneumonia (n = 42), or upper airway infection (n = 52) during the last year, and 708 matched healthy controls. Concurrent validity was based on comparisons between patients and controls. Convergent validity for sleeplessness and snoring were tested by comparing the RASQ with the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Test-retest reliability was examined in patients with GERD with stable symptoms (n = 29). RESULTS: Response rates were 64% for patients and 55% for controls. Scores for RASQ as a total and all subscales were significantly higher in patients than in controls. Sleeplessness scores correlated significantly to the global PSQI score. Snoring correlated significantly with both the ESS and relevant aspects of the PSQI. Test-retest reliability and Cronbach's alpha were satisfactory, with coefficients ranging between 0.65-0.95 and 0.88-0.92, respectively. CONCLUSION: The RASQ appears to be well suited for measuring typical reflux symptoms as well as airway symptoms and sleep disturbances.

Winter sports athletes: long-term effects of cold air exposure.

Athletes such as skaters and skiers inhale large volumes of cold air during exercise and shift from nasal to mouth breathing. Endurance athletes, like cross-country skiers, perform at 80% or more of their maximal oxygen consumption and have minute ventilations in excess of 100 l/min. Cold air is always dry, and endurance exercise results in loss of water and heat from the lower respiratory tract. In addition, athletes can be exposed to indoor and outdoor pollutants during the competitive season and during all-year training. Hyperpnoea with cold dry air represents a significant environmental stress to the airways. Winter athletes have a high prevalence of respiratory symptoms and airway hyper-responsiveness to methacholine and hyperpnoea. The acute effects of exercise in cold air are neutrophil influx as demonstrated in lavage fluid and airway epithelial damage as demonstrated by bronchoscopy. Upregulation of pro-inflammatory cytokines has been observed in horses. Chronic endurance training damages the epithelium of the small airways in mice. Airway inflammation has been observed on bronchoscopy of cross-country skiers and in dogs after a 1100-mile endurance race in Alaska. Neutrophilic and lymphocytic inflammation with remodelling is present in bronchial biopsies from skiers. Repeated peripheral airway hyperpnoea with dry air causes inflammation and remodelling in dogs. As it is currently unknown if these airway changes are reversible upon cessation of exposure, preventive measures to diminish exposure of the lower airways to cold air should be instituted by all winter sports athletes.

Respiratory health of elite athletes - preventing airway injury: a critical review.

Elite athletes, particularly those engaged in endurance sports and those exposed chronically to airborne pollutants/irritants or allergens, are at increased risk for upper and lower airway dysfunction. Airway epithelial injury may be caused by dehydration and physical stress applied to the airways during severe exercise hyperpnoea and/or by inhalation of noxious agents. This is thought to initiate an inflammatory cascade/repair process that, ultimately, could lead to airway hyperresponsiveness (AHR) and asthma in susceptible athletes. The authors review the evidence relating to prevention or reduction of the risk of AHR/asthma development. Appropriate measures should be implemented when athletes exercise strenuously in an attempt to attenuate the dehydration stress and reduce the exposure to noxious airborne agents. Environmental interventions are the most important. Non-pharmacological strategies can assist, but currently, pharmacological measures have not been demonstrated to be effective. Whether early prevention of airway injury in elite athletes can prevent or reduce progression to AHR/asthma remains to be established.

Sinonasal Symptoms in COPD: Burden and Associations with Clinical Markers of Disease.

Purpose: Sinonasal symptoms are prevalent in COPD, and knowledge of the relationship between these symptoms and clinical markers of COPD is limited. This study explores the associations between the burden of sinonasal symptoms and clinical markers and thresholds recommended for guiding treatment decisions in the GOLD guidelines. Patients and Methods: Sinonasal symptoms were quantified with the rhinological subscale of the Sino-Nasal-Outcome-Test (SNOT-22) in 93 COPD patients characterized by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012 diagnostic criteria for rhinosinusitis without nasal polyps (RSsNP). Associations between a high burden, defined as a SNOT22_rhinological score of ≥11, and the following markers were assessed by adjusted multivariable linear regressions; severity of dyspnea [modified Medical Research Council (mMRC)] and cough [Visual Analogue Scale (VAS)], physical activity [6-minute walking distance (6MWD)], mortality risk (BODE index), and HRQoL [disease-specific COPD Assessment Test (CAT) and St. Georges Respiratory Questionnaire (SGRQ), and physical component summary, Short Form-36 version 2.0 (PCS SF-36v2)]. Odds ratios for the association of a high burden and threshold levels for regular treatment were estimated by adjusted binomial logistic regression models. Results: A high burden was associated with greater severity of dyspnea and cough, lower 6MWD, higher BODE index and poorer HRQoL. The odds ratio of having CAT and SGRQ scores that are above the thresholds recommended for treatment was 5-7-fold greater in the high burden group. Conclusion: A high burden of sinonasal symptoms is positively associated with the clinical markers of symptom severity and mortality risk and is inversely associated with physical activity and HRQoL in COPD. These findings add further support that the UAD concept also applies to COPD. Enquiry about sinonasal symptoms in COPD patients should be incorporated into the clinical routine.

Rhinosinusitis without nasal polyps is associated with poorer health-related quality of life in COPD.

Rhinosinusitis without nasal polyps (RSsNP) is prevalent in COPD. Previous studies on its association with health-related quality of life (HRQoL) have limitations, and RSsNP is currently not recognized as a comorbidity. This study investigates HRQoL in COPD including a focus on RSsNP. Generic HRQoL was assessed with the Short Form-36 (SF-36v2) questionnaire and compared between 90 COPD and 93 control subjects and in subgroups with and without RSsNP. The association between RSsNP and COPD versus not and generic HRQoL was assessed by multivariable linear regression with adjustments for age, education, and body mass index (BMI). Disease-specific HRQoL was assessed by Sinonasal outcome test-22 (SNOT-22), St. Georges Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT) and compared between COPD with and without RSsNP, and their association to RSsNP was assessed by multivariable linear regression with adjustments for age, BMI, and FEV1% predicted. RSsNP was associated with poorer disease-specific HRQoL, with higher SNOT-22 total score (14.67 points; 95% CI, 7.06-22.28; P < .001) and psychological subscale score (3.24 points; 95% CI, 0.37-6.11; P = .03), SGRQ symptom score (13.08 points; 95% CI, 2.73-23.4; P = .014), and CAT score (4.41 points; 95% CI, 1.15-7.66; P = .009). Generic HRQoL was poorer in COPD patients than in the control subjects. In addition to COPD, concomitant RSsNP was associated with poorer physical functioning, general health, vitality, and physical component summary. RSsNP in COPD is associated with poorer disease-specific HRQoL that is clinically relevant and, as it is amenable for treatment, should be recognized as a comorbidity of COPD.

Airway hyperresponsiveness to methacholine, adenosine 5-monophosphate, mannitol, eucapnic voluntary hyperpnoea and field exercise challenge in elite cross-country skiers.

BACKGROUND: Methacholine hyperresponsiveness is prevalent in elite athletes. Comparative studies have hitherto been limited to methacholine, eucapnic voluntary hyperpnoea and exercise. This study investigated airway responsiveness to these stimuli as well as to adenosine 5'-monophosphate (AMP) and mannitol, in 58 cross-country ski athletes. METHODS: Exhaled nitric oxide concentration (F(E)NO), spirometry and bronchial challenge in random order with methacholine, AMP and mannitol were consecutively performed on three study days in the autumn. Specific IgE to eight aeroallergens and a self-completed questionnaire about respiratory symptoms, allergy and asthmatic medication were also performed on day 1. Eucapnic voluntary hyperventilation (EVH) and field exercise tests were randomly performed in 33 of the skiers on two study days in the following winter. RESULTS: Of 25 (43%) skiers with airway hyperresponsiveness (AHR), 23, five and three skiers were hyperresponsive to methacholine, AMP and mannitol, respectively. Methacholine hyperresponsiveness was more prevalent in subjects without asthma-like symptoms. The F(E)NO was not significantly different in skiers with and without methacholine hyperresponsiveness. Four of 14 skiers with and four of 19 skiers without methacholine hyperresponsiveness were hyperresponsive to EVH or exercise challenge. AHR to any stimulus was present in 16 asymptomatic and nine symptomatic skiers. Asthma-like symptoms were not correlated with AHR to any stimulus. CONCLUSIONS: Methacholine hyperresponsiveness is more common in asymptomatic skiers and is a poor predictor of hyperresponsiveness to mannitol and hyperpnoea. The low prevalence of hyperresponsiveness to indirect stimuli may suggest differences in the pathogenesis of methacholine hyperresponsiveness in elite skiers and non-athletes.

Rhinosinusitis without nasal polyps in COPD.

The validity of the united airway disease concept for rhinosinusitis (RS) and chronic obstructive pulmonary disease (COPD) has been questioned because of methodological limitations in previous studies. In this study we investigated the prevalence of RS without nasal polyps (RSsNP) and the severity of sinonasal symptoms in COPD and a corresponding control group. We also evaluated the diagnostic accuracy of these symptoms for RSsNP in COPD. 90 COPD patients and 93 controls were included in an observational cross-sectional study where globally accepted diagnostic criteria of RS and COPD (EPOS 2012 and GOLD) were incorporated; symptomatic and endoscopic criteria for the diagnosis of RS, and spirometry with reversibility for diagnosis of COPD. RS symptoms were identified by responses to the sinonasal outcome test (SNOT-22), nasal endoscopy identified signs of sinonasal disease and discriminated between RS with and without nasal polyps, and visual analogue scales (VAS) rated the severity of sinonasal symptoms. We found RSsNP in 51% of our COPD patients which is threefold greater than in the control group (p<0.001). Nasal discharge (72%) and nasal obstruction (62%) were the two most frequently reported symptoms in COPD. The diagnostic accuracy for RSsNP is better for the composite VAS for rhinological symptoms than for facial symptoms. We conclude that RSsNP is present in 51% of our COPD patients, which is significantly more prevalent compared to a corresponding control group. These results suggest that COPD is associated with RS.

Asthma and the elite athlete: summary of the International Olympic Committee's consensus conference, Lausanne, Switzerland, January 22-24, 2008.

Respiratory symptoms cannot be relied on to make a diagnosis of asthma and/or airways hyperresponsiveness (AHR) in elite athletes. For this reason, the diagnosis should be confirmed with bronchial provocation tests. Asthma management in elite athletes should follow established treatment guidelines (eg, Global Initiative for Asthma) and should include education, an individually tailored treatment plan, minimization of aggravating environmental factors, and appropriate drug therapy that must meet the requirements of the World Anti-Doping Agency. Asthma control can usually be achieved with inhaled corticosteroids and inhaled beta(2)-agonists to minimize exercise-induced bronchoconstriction and to treat intermittent symptoms. The rapid development of tachyphylaxis to beta(2)-agonists after regular daily use poses a dilemma for athletes. Long-term intense endurance training, particularly in unfavorable environmental conditions, appears to be associated with an increased risk of developing asthma and AHR in elite athletes. Globally, the prevalence of asthma, exercise-induced bronchoconstriction, and AHR in Olympic athletes reflects the known prevalence of asthma symptoms in each country. The policy of requiring Olympic athletes to demonstrate the presence of asthma, exercise-induced bronchoconstriction, or AHR to be approved to inhale beta(2)-agonists will continue.

Air quality and temperature effects on exercise-induced bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) is exaggerated constriction of the airways usually soon after cessation of exercise. This is most often a response to airway dehydration in the presence of airway inflammation in a person with a responsive bronchial smooth muscle. Severity is related to water content of inspired air and level of ventilation achieved and sustained. Repetitive hyperpnea of dry air during training is associated with airway inflammatory changes and remodeling. A response during exercise that is related to pollution or allergen is considered EIB. Ozone and particulate matter are the most widespread pollutants of concern for the exercising population; chronic exposure can lead to new-onset asthma and EIB. Freshly generated emissions particulate matter less than 100 nm is most harmful. Evidence for acute and long-term effects from exercise while inhaling high levels of ozone and/or particulate matter exists. Much evidence supports a relationship between development of airway disorders and exercise in the chlorinated pool. Swimmers typically do not respond in the pool; however, a large percentage responds to a dry air exercise challenge. Studies support oxidative stress mediated pathology for pollutants and a more severe acute response occurs in the asthmatic. Winter sport athletes and swimmers have a higher prevalence of EIB, asthma and airway remodeling than other athletes and the general population. Because of fossil fuel powered ice resurfacers in ice rinks, ice rink athletes have shown high rates of EIB and asthma. For the athlete training in the urban environment, training during low traffic hours and in low traffic areas is suggested.

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

STUDY OBJECTIVES: To compare the effect of montelukast and the long-acting beta(2)-agonist salmeterol on cardiopulmonary exercise economy and physical performance in adult patients with asthma during exercise. DESIGN AND PATIENTS: Asthmatic patients (n = 18), aged 18 to 35 years with exercise-induced bronchoconstriction (EIB), using a double-blind, double-dummy cross-over design. Montelukast, 10 mg/d, was compared to inhaled salmeterol, 50 microg bid. The study medication was administered for at least 5 days prior to testing, with a washout period of at least 5 days. Treadmill exercise tests (5.3% inclination, -15 degrees C ambient temperature) were performed at work loads of 80% of maximal oxygen uptake (Vo(2)max) [6 min], rest (4 min), 60% of Vo(2)max (6 min), and finally step increments until exhaustion. MEASUREMENTS AND RESULTS: We investigated parameters of gas exchange, physical performance, and lung function. After montelukast, the oxygen pulse was higher than after salmeterol, at 80% of Vo(2)max (p = 0.035), and 6 min at 60% of Vo(2)max (p = 0.011). Lung function during exercise, running time to exhaustion, Borg score, lactate levels, Vo(2)max, carbon dioxide elimination, minute ventilation, ventilatory equivalents, respiratory exchange ratio, and heart rate were not significantly different between the two treatments. The maximal postexercise fall in FEV(1) from baseline occurred 2 min after run to exhaustion, and was greater after salmeterol than after montelukast: mean, 16.2% (SD, 11.0) vs 10.0% (SD, 12.2) [p < 0.001]. CONCLUSIONS: In adult asthmatics with EIB, montelukast may have a more favorable effect on the oxygen pulse, thus suggesting improved gas exchange during exercise.

Air quality and exercise-induced bronchoconstriction in elite athletes.

A higher prevalence of airway hyperresponsiveness, airway remodeling, and asthma has been identified among athletes who compete and train in environmental conditions of cold dry air and/or high air pollution. Repeated long-duration exposure to cold/dry air at high minute ventilation rates can cause airway damage. Competition or training at venues close to busy roadways, or in indoor ice arenas or chlorinated swimming pools, harbors a risk for acute and chronic airway disorders from high pollutant exposure. This article discusses the effects of these harsh environments on the airways, and summarizes potential mechanisms and prevalence of airway disorders in elite athletes.

Nasal flow, volumes, and minimal cross sectional areas in asthmatics.

BACKGROUND: The Unified Airways hypothesis suggests an involvement of the upper airways in asthma. Critical parameters of the nasal airway can be quantified objectively with acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF). OBJECTIVE: We aimed to investigate nasal airway patency in asthmatics compared to non-asthmatic controls. Nasal volume, cross sectional area and flow were measured using acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF) in 87 asthmatics and 93 non-asthmatic controls before and after decongestion with xylometazoline. Nasal congestion index (NCI) was calculated, and allergy status was assessed by skin prick test or specific IgE. RESULTS: We found significantly smaller minimum cross sectional area and nasal cavity volume in asthmatics than controls, and the cross sectional area is at its minimum at 2-3 cm from the nasal orifice in both groups. AR and PNIF measurements are not different in allergic and non allergic subjects in either group. The effect of xylometazoline is not significantly different between the 2 groups with regard to AR, but there is a significant improvement in PNIF for the asthmatics when assessed by the NCI. CONCLUSION: The present study demonstrates a significantly smaller nasal airway when assessed by minimum cross sectional area and nasal cavity volume in asthmatics than controls, and these findings apply to asthmatics and controls irrespective of allergy status.

Sino-nasal characteristics in asthmatic patients.

OBJECTIVE: The Unified Airways Hypothesis suggests an involvement of the upper airways in asthma. We aimed to evaluate the association between subjective sino-nasal complaints, nasal air flow, and sino-nasal quality of life (QOL) in patients with asthma compared with nonasthmatic subjects. STUDY DESIGN: Case-control study. SETTING: A tertiary referral center. SUBJECTS AND METHODS: Symptoms, quality of life, and nasal airflow were assessed in 91 asthmatics and 95 nonasthmatic controls with Visual Analog Scale (VAS, 0-100), Sino-Nasal Outcome Test (SNOT-20), and Peak Nasal Inspiratory Flow (PNIF), respectively. Asthma and allergy status were assessed by Asthma Control Questionnaire (ACQ) and skin prick test or specific IgE. RESULTS: Asthmatic patients (men/women, 37/54; mean age, 43.7 years; range, 19-64 years) reported significantly more nasal obstruction (mean VAS, 37 mm; SD = 26, 95% CI, 32-43 vs 9 mm, SD = 11, 95% CI, 7-11, P < .001) and lower sino-nasal quality of life (mean SNOT-20, 1.3; SD = 0.8, 95% CI, 1.1-1.5 vs 0.4, SD = 0.5, 95% CI, 0.3-0.5, P < .001) than controls (men/women, 42/53; mean age, 43.8 years; range, 20-65 years). PNIF was significantly lower in asthmatic patients than controls (mean PNIF, 84 l/min; SD = 24, 95% CI, 79-89 vs 100 l/min SD = 24, 95% CI, 95-105, P < .001). CONCLUSION: Both allergic and nonallergic asthma were associated with increased sino-nasal symptoms, reduced sino-nasal QOL, and reduced inspiratory nasal air flow compared to controls. This provides further evidence of the clinical importance of the upper airway in the diagnostic and therapeutic management of asthma patients beyond the scope of allergy.

Hyperpnea-induced bronchoconstriction and urinary CC16 levels in athletes.

PURPOSE: Exercise-induced bronchoconstriction (EIB) is a common condition in both individuals with asthma and otherwise healthy elite athletes. Although excessive water loss by peripheral airways during hyperpnea is regarded as the initial trigger for EIB, the cascade of events that follows remains unclear. Our goal was to establish whether transient disruption of the airway epithelial barrier occurs after a short period of hyperpnea of dry air in athletes with EIB. METHODS: Urinary concentration of the pneumoprotein Clara cell (CC16) was used as an assumed biomarker of lung epithelial cell damage or dysfunction. Samples were collected at baseline and for 90 min after an 8-min eucapnic voluntary hyperpnea (EVH) test in 50 female individuals (28 athletes and 22 untrained). RESULTS: Nineteen subjects (10 athletes) demonstrated a sustained bronchoconstriction after EVH (mean±SE forced expiratory volume in the first second (FEV1) fall from baseline=23.4%±2.6%). The remaining subjects had a negative challenge result with an FEV1 fall of 5.9%±0.6%. An increase (P<0.001) in urinary CC16 concentration was noticed after EVH in all but one subject, with no group difference (median CC16 increase before to after challenge: athletes EVH 0.083 ng·µmol, athletes EVH 0.223 ng·µmol, untrained EVH 0.074 ng·µmol, untrained EVH 0.571 ng·µmol; P>0.05). CONCLUSIONS: Urinary levels of CC16 are increased after EVH in all individuals (trained and untrained, with and without EIB) suggestive of dehydration-induced perturbation of the distal respiratory epithelium during episodes of hyperventilation.

Bronchial challenges in athletes applying to inhale a beta2-agonist at the 2004 Summer Olympics.

BACKGROUND: The International Olympic Committee Medical Commission required a medical justification for athletes to inhale a beta2-agonist before an event at the Summer Games in Athens in 2004. OBJECTIVE: We sought to establish the percentage of athletes applying to use an inhaled beta2-agonist on the basis of the results of objective tests to establish a diagnosis of asthma or exercise-induced bronchoconstriction. We also sought to compare this percentage with the percentage of athletes simply notifying the intention to use a beta2-agonist at the previous Summer Games in Sydney in 2000. METHODS: An analysis was made of tests that measured the change in FEV1 in response to a bronchodilator or in response to a provoking stimulus, such as exercise, eucapnic voluntary hyperpnea, hypertonic saline, or methacholine. RESULTS: Ten thousand six hundred fifty-three athletes competed in Athens; 4.2% were approved to use a beta2-agonist, and 0.4% were rejected. This approval rate was 26% less than the notifications in 2000 in Sydney (5.7%). Compared with Sydney 2000, there was a significant reduction of submissions and approvals for athletes from the United States, New Zealand, Australia, and Canada and in triathlon and swimming sports. CONCLUSION: The need to provide objective testing has resulted in a reduction in the number of athletes seeking approval to use an inhaled beta2-agonist. Objective evidence has provided information for the doctor that is likely to improve the health of the athlete because many athletes appeared to be undertreated at the time of testing. CLINICAL IMPLICATIONS: We show that documentation of airway narrowing in athletes, particularly in response to exercise or surrogate stimuli for exercise, aids in the diagnosis and management of asthma by providing evidence of bronchial hyperresponsiveness that will respond to treatment with inhaled corticosteroids and is usually associated with a reduction in respiratory symptoms on exercise.

A study of the association between exercise-induced wheeze and exercise versus methacholine-induced bronchoconstriction in adolescents.

Among asthmatics, exercise-induced wheeze (EIW) is a frequent symptom, and 40-77% of asthmatics demonstrate exercise-induced bronchoconstriction (EIB). In the North-Trøndelag population-based survey of 8,571 adolescents (YOUNG-HUNT), 26% reported wheeze during the previous 12 months (current wheeze). Of those subjects, 50% reported EIW. The aim of the present study was to investigate the association between EIW and EIB in randomly selected adolescents with EIW as the only or predominant asthma-like symptom, and to relate our findings to results from methacholine bronchoprovocation tests (MT) and measurements of exhaled nitric oxide (ENO). Sixty-three subjects with current wheeze induced by exercise, but not by allergen exposure, were investigated using a treadmill exercise test (ET) and measurements of ENO. Fifty-eight subjects completed a MT on a separate study day. EIB was defined as a fall of >or= 10% in the forced expiratory volume in 1 second (FEV1) after exercise (DeltaFEV1%ex). Twenty-one subjects (33%) had EIB and 33 (57%) had a positive MT. The degree of reported dyspnea during the ET was not correlated to the DeltaFEV1%ex. The correlation between EIB and methacholine-induced bronchoconstriction (MIB) was poor, and the DeltaFEV1%ex was more pronounced in smokers than in non-smokers. Moreover, ENO was not increased in subjects with positive vs. negative ET. Hence, EIW, when reported as the only or predominant asthma-like symptom, was linked to EIB in only one-third of the patients. We conclude that EIW is a poor predictor of EIB in epidemiological studies. The poor correlation between EIB and MIB indicates that these two tests measure different mechanisms of bronchial hyper-responsiveness.

Responses to bronchial challenge submitted for approval to use inhaled beta2-agonists before an event at the 2002 Winter Olympics.

BACKGROUND: There has been an increase in the number and percentage of athletes competing in Olympic Games notifying use of beta2-agonists, from 1.7% at Los Angeles (1984) to 5.5% at Sydney (2000). For Salt Lake City (2002), the International Olympic Committee requested objective evidence to use beta2-agonists for asthma or exercise-induced asthma (EIA). OBJECTIVE: The objective of this study was to evaluate the evidence submitted for approval to use a beta2-agonist. METHODS: Objective evidence for asthma or EIA included (1) an increase of 12% or more of the predicted FEV1 in response to bronchodilator, (2) a reduction in FEV1 of 10% or greater from baseline in response to exercise or eucapnic voluntary hyperpnea, (3) a PD20 FEV1 to methacholine or histamine at a dose of less than 200 microg (2 mg/mL) or less than 1320 microg (13.2 mg/mL) for those taking inhaled corticosteroids for 3 months. RESULTS: There were 165 applications. Of these, 147 (89%) included evidence of a challenge, bronchodilator response, or both, and 163 test results were submitted. One hundred thirty (5.2%) applications were approved. For those with positive responses, the median value (1) was 16.2% of predicted FEV1 for response to a bronchodilator (n = 13), (2) was a 15.9% decrease in FEV1 for response to a physical challenge (n = 36), and, (3) for PD20 FEV1, was 173 microg for response to a pharmacologic challenge (n = 45). CONCLUSION: The analysis demonstrated that it is feasible to request objective evidence to justify use of beta2-agonists on the medical grounds of asthma or EIA.

Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma.

BACKGROUND: The clinical benefit of combining long-acting beta(2)-agonists with inhaled corticosteroids rather than doubling the dose of corticosteroid has been well-documented. However, there are concerns that this might result in a masking of underlying airway inflammation. OBJECTIVE: The aim of this study was to test the hypothesis that the addition of the long-acting beta(2)-agonist salmeterol (SALM) to a low dose of the inhaled corticosteroid fluticasone propionate (FP) has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid. METHODS: Fifty-six asthmatic subjects, previously not well-controlled on inhaled corticosteroids, were randomized to receive 3 months of treatment with inhaled FP 500 microg twice a day (FP 1000) or FP 200 microg twice a day plus SALM 50 microg twice a day (FP 400 + SALM). Fluticasone propionate 200 microg twice a day served as the control (FP400). Bronchial mucosal biopsy specimens, bronchial washings (BW), and bronchoalveolar lavage were obtained before and after treatment. The primary end points for the study were submucosal mast cell and eosinophil counts. RESULTS: There was a significant improvement in FEV(1) in the FP400 + SALM group compared to both the FP400 and FP1000 groups. This was accompanied by a significant improvement in peak expiratory flow in the FP400 + SALM group in both the morning and evening compared to the FP1000 group. There were no significant between treatment differences in the change in the number of submucosal mast cells or eosinophils. However, in the FP400 + SALM group there was a significant decrease in submucosal mast cells after 12 weeks of treatment. The addition of SALM to FP was not associated with any increases in airway inflammation in the biopsy specimens, bronchoalveolar lavage, or bronchial washings. CONCLUSION: These findings confirm that addition of SALM to FP has clinical benefits but does not mask or exacerbate airway inflammation and suggest that long-acting beta(2)-adrenoceptor agonists might influence mast cell numbers.