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Background This placebo-controlled study assessed the effects of the once-daily inhaled corticosteroid ( ICS) fluticasone furoate ( FF) and long-acting beta2-agonist ( LABA) vilanterol ( VI) on early and late asthmatic responses ( EAR/ LAR) and airway hyper-responsiveness ( AHR). Methods Patients ( n = 27) were randomized to FF (100 μg), VI (25 μg), FF/ VI (100/25 μg), and placebo for 21 days (four periods). Allergen challenge was performed 1 h post-dose on day 21. AHR was assessed on day 22 using methacholine. Results Allergen challenge caused an early change (0-2 h) in minimum forced expiratory volume in 1 s ( FEV1) of −1.091 l (95% CI: −1.344; −0.837) following placebo therapy; changes were −0.955 l (−1.209; −0.702), −0.826 l (−1.070; −0.581), and −0.614 l (−0.858; −0.370) following VI, FF, or FF/ VI therapy, respectively. Treatment differences were significant for all comparisons between therapies. Mean changes in 0-2 h % FEV1 were as follows: −28.05 (placebo), −23.10 ( VI), −22.33 ( FF), and −16.10 ( FF/ VI). Following placebo, the late change (4-10 h) in weighted mean FEV1 was −0.466 l (−0.589; −0.343) and −0.298 l (−0.415; −0.181) after VI, and was +0.018 l with both FF/ VI (−0.089; 0.124) and FF (−0.089; 0.125). Treatment differences were significant for all comparisons between therapies except FF/ VI vs FF. Mean changes in 4-10 h % FEV1 were as follows: −21.08 (placebo), −14.30 ( VI), −5.02 ( FF), and −5.83 ( FF/ VI). AHR 24 h after allergen challenge was significantly reduced with FF/ VI and FF vs placebo, and FF/ VI was superior to either component. Conclusion Combined treatment with FF/ VI provides additive protection from the EAR relative to its components, significant protection over VI alone from the LAR, and confers sustained protection from hyper-responsiveness 24 h post-dose. [ABSTRACT FROM AUTHOR]

An increased risk of developing asthma has been reported among swimmers exposed to chloramine in pool arenas. The aim of the present study was to compare the prevalence of asthma and respiratory symptoms among elite aspiring swimmers compared with age-matched controls with different degrees of physical activity. We also aimed to relate these findings to mental and psychosocial factors. One hundred and one elite swimmers and 1628 age-matched controls answered a questionnaire containing questions about respiratory symptoms, lifestyle factors, mental and physical well-being. The controls were divided into three different groups according to the degree of physical activity, no physical activity, recreational training and elite training. Swimmers reported significantly more asthma symptoms, with 36.6% having physician-diagnosed asthma, compared with 16.2% among the controls. Use of regular medication was more common (14.9% vs 8.0%) and more swimmers reported an exacerbation of their asthma during the previous 12 months (16.8%) vs (5.8%) for the controls. Despite an increased prevalence of asthma symptoms, the swimmers reported best physical performance and best mental and physical well-being. They also had a healthier lifestyle without smoking and low alcohol consumption. [ABSTRACT FROM AUTHOR]

To cite this article: Andersson CK, Tufvesson E, Aronsson D, Bergqvist A, Mori M, Bjermer L, Erjefält JS. Alveolar mast cells shift to an FcεRI-expressing phenotype in mild atopic asthma: a novel feature in allergic asthma pathology. Allergy 2011; 66: 1590-1597. Abstract Background: A unique feature of alveolar mast cells is their low high-affinity IgE receptor (FcεRI) expression. Recent discoveries in uncontrolled asthma suggest that the appearance of FcεRI-expressing alveolar mast cells may be a novel disease-specific feature of allergic asthma. This study investigates whether increased FcεRI-expressing alveolar mast cells are present in patients with mild allergic asthma or even in non-asthmatic allergic rhinitis patients (AR) who have developed bronchial hyperactivity (BHR). Methods: Bronchial and alveolar tissues were obtained from healthy controls, AR patients with or without BHR, and AR patients with concurrent asthma. Samples were processed for immunohistochemical identification of MCT and MCTC and expression of FcεRI and surface-bound IgE. Results: Bronchial mast cell expression of FcεRI was high in all groups. In contrast, in the alveolar tissue, the expression of FcεRI on mast cells was low in healthy controls and in the AR patient groups, whereas a high expression was present in AR patients with concurrent asthma ( P = 0.006 compared to controls). The asthmatics had a 29-fold increase in numbers ( P = 0.006) and a 19-fold increase in proportion ( P = 0.007) of alveolar mast cells that expressed surface-bound IgE. Conclusions: The present data show that alveolar mast cells in patients with mild atopic asthma, but not atopic patients with AR, have turned into a highly FcεRI- and IgE-expressing phenotype. These data support the hypothesis that increased FcεRI expression on alveolar mast cells is a novel disease-specific feature of allergic asthma that is important for understanding asthma phenotypes and designing new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Rationale: Mast cells have important roles in innate immunity and tissue remodeling but have remained poorly studied in inflammatory airway diseases like chronic obstructive pulmonary disease (COPD). Objectives: To perform a detailed histological characterization of human lung mast cell populations at different severities of COPD, comparing with smoking and never-smoking control subjects. Methods: Mast cells were analyzed in lung tissues from patients with mild to very severe COPD, GOLD I-IV (n = 25, 10 of whom were treated with corticosteroids). Never-smokers and smokers served as controls. The density, morphology, and molecular characteristics of mucosal and connective tissue mast cells (MC(T) and MC(TC), respectively) were analyzed in several lung regions. Measurements and Main Results: In all compartments of COPD lungs, especially at severe stages, the MC(TC) population increased in density, whereas the MC(T) population decreased. The net result was a reduction in total mast cell density. This phenomenon was paralleled by increased numbers of luminal mast cells, whereas the numbers of terminal transferase dUTP nick end labeling (TUNEL)(+) apoptotic mast cells remained unchanged. In COPD lungs, the MC(T) and MC(TC) populations showed alterations in morphology and expression of CD88 (C5a-R), transforming growth factor (TGF)-beta, and renin. Statistically significant correlations were found between several COPD-related mast cell alterations and lung function parameters. Conclusions: As COPD progresses to its severe stages, the mast cell populations in the lung undergo changes in density, distribution, and molecular expression. In COPD lungs, these novel histopathological features were found to be correlated to lung function and they may thus have clinical consequences. [ABSTRACT FROM AUTHOR]

Aim: The aims of part II is to review the current recommended treatment of exercise-induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment. Methods: The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73–88) during the work of the Task Force. To assess the evidence of the literature regarding use of β2-agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise-induced bronchoconstriction, athletes, sports, performance and β2-agonists. Evidence level and grades of recommendation were assessed according to Sign criteria. Results: Treatment recommendations for EIA and bronchial hyper-responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled β2-agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper-responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled β2-agonists with relationship to sports in healthy individuals is of high evidence, level (1+). Conclusions: Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled β2-agonists. [ABSTRACT FROM AUTHOR]

Background We have previously reported that asthma differs from rhinitis with or without bronchial hyperresponsiveness in the perception and degree of lower airway inflammation. Objective The aim of the present study was to investigate whether sputum levels of inflammatory markers could further distinguish these patient groups. Methods Patients with seasonal allergic rhinitis with or without asthma or bronchial hyperresponsiveness to methacholine were investigated. Induced sputum was performed during as well as off season, and analysed for cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other inflammatory markers. Results Asthmatic patients differentiated from those with rhinitis with or without bronchial hyperresponsiveness in levels of cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%–upper 95% confidence interval (CI) of geometric mean: 1.9–5.1) vs. 1.4 (0.9–2.2) and 0.7 (0.3–1.6) pg/μg total protein] and hyaluronan [0.30 (0.22–0.43) vs. 0.15 (0.10–0.20) and 0.20 (0.12–0.35) ng/μg total protein] in sputum. The levels of cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the levels of hyaluronan remained elevated off-season. Furthermore, elevated levels of ECP were noticed among both the asthmatic and rhinitis patients with hyperresponsiveness compared with controls [0.022 (0.014–0.033) and 0.015 (0.011–0.021) compared with 0.010 (0.007–0.014) ng/μg total protein]. The level of ECP remained elevated off season. Conclusion Cysteinyl-leukotrienes are possibly more related to mast cell-mediated inflammation and remodelling, also indicated by increased levels of hyaluronan during and off season. This inflammation may be partly different from the eosinophil-driven inflammation. [ABSTRACT FROM AUTHOR]

Background/aim Allergic rhinitis (AR) is a risk factor for developing clinical asthma. Moreover, AR is often associated with bronchial hyper-responsiveness (BHR). The aim of the present study was to investigate whether patients with AR and asthma differed from AR with or without BHR in degree of perception of dyspnoea and airway inflammation, measured as fractionated exhaled nitric oxide (NO). Materials Twenty-nine patients with seasonal AR (timothy) were investigated with metacholine challenge test. Fourteen healthy non-reactive subjects served as controls. Methods (1) Metacholine challenge test, cut-off value forced expiratory volume in 1 s (FEV1) PD20 2000 μg. Slope value for metacholine was calculated as %fall in FEV1/mol metacholine. Dyspnoea during challenge was measured with a 10-graded modified Borg score. (2) Measurement of fractional-exhaled nitric oxide (FENO) at flow rate 50 mL/s. Results Eighteen patients reported AR only, without asthma symptoms, and 12 (67%) were BHR. Eleven subjects had both rhinitis and asthma symptoms. Patients with rhinitis and asthma reported significantly more dyspnoea per percent fall in FEV1 compared with those with rhinitis and BHR. Moreover, those with rhinitis and asthma had significantly higher NO values compared with those with rhinitis and BHR. Conclusion The difference between rhinitis patients with or without asthma symptoms seems to be mainly a question of perception of dyspnoea. However, FENO measurement indicates that dyspnoea may also be associated with increased inflammatory activity in the peripheral airways. [ABSTRACT FROM AUTHOR]

Inadequately controlled allergic rhinitis (AR) in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. We assessed asthma-related medical resource use and attacks in asthmatic patients who did and did not have concomitant AR and were adding montelukast or salmeterol to baseline treatment with inhaled fluticasone. A post hoc resource use analysis of a 52-week, double-blind multicentre clinical trial (IMPACT: IMProving Asthma Control Trial) including 1490 adults with chronic asthma, aged 15–72 years, with FEV1 50–90% of predicted and ⩾12% increase in FEV1 after salbutamol administration, treated with either montelukast 10 mg daily or salmeterol 50 μg twice daily in addition to fluticasone 200 μg, was undertaken. Asthma-related medical resource use included medical visits (defined as either an unscheduled visit [to a general practitioner, a specialist or a non-medical provider] or a specialist visit), emergency room visits and hospitalizations during follow-up. Asthma attacks were defined as the worsening of asthma requiring unscheduled visit, emergency visit, hospitalization or oral/intravenous/intramuscular corticosteroids. A self-reported history of concomitant AR was identified in 60% of the patients ( n=893). Univariate analysis suggests that significantly more patients with concomitant AR experienced emergency room visits (3.6% vs. 1.7%, P=0.029) and asthma attacks (21.3% vs. 17.1%, P=0.046). Multivariate analysis adjusting for treatment group, age and baseline asthma severity confirmed these results since the presence of concomitant AR in patients with asthma increases the likelihood of emergency room visit (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.12–4.80) and asthma attack (OR=1.35, 95% CI=1.03–1.77). Patients with asthma alone compared with patients with both conditions did not differ in terms of unscheduled or specialist visits and hospitalizations. Presence of self-reported concomitant AR in patients with asthma resulted in a higher rate of asthma attacks and more emergency room visits compared with asthma patients without concomitant AR. [ABSTRACT FROM AUTHOR]

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°C with a tread mill exercise protocol consisting of consecutive workloads of 80% V'O[sub2max] 6 min), rest 4 min), 60% V'O[sub2max] 6 min) and step increments of exercise until exhaustion. Montelukast reduced the maximum post-exercise fall in FEV[sub1] 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[sub2max] P = 0.03). V'O[sub2], V'CO[sub2], 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. [ABSTRACT FROM AUTHOR]

Studies have indicated that women are more vulnerable to the effect of tobacco smoking compared with men. The aim of this study was to explore the prevalence of reported respiratory symptoms and diseases according to smoking burden, age and sex. Questionnaire in a cross sectional population based study. The BONT (Bronchial obstruction in Nord-Trondelag) study is part of a comprehensive health survey of all inhabitants aged above 19 years in the county of Nord-Trondelag, Norway, which was carried out from 1995 to 1997. A total of 65 717 subjects, 71.3% of the total population aged 20-100, answered the main questionnaire. In all, 12.7% men and 12.1% women reported episodes of wheezing or breathlessness during the past 12 months, 8.8% men and 8.4% women reported that they had or had had asthma, 7.5% men and 8.2% women had ever used asthma medication, and 4.0% men and 3.0% women reported chronic bronchitis. Thirty per cent of men and 31% of women were smokers, and average pack years of smoking were 15.9 and 10.3, respectively. Among previous and current smokers, significant more women reported episodes of wheezing or breathlessness, current asthma and persistent coughing compared with men with the same smoke burden (pack years) and daily number of cigarettes. The prevalence of reported asthma and use of asthma medication was higher than reported in previous Scandinavian studies. Respiratory symptoms increased by smoking burden. Comparing the prevalence of symptoms and current asthma among women and men with the same smoke burden or daily cigarette consumption, women seemed to be more susceptible to the effect of tobacco smoking than men. [ABSTRACT FROM AUTHOR]