Asthma referrals : a key component of asthma management that needs to be addressed

Peer reviewedPublisher PD

Integrating evidence for managing asthma in patients who smoke

Peer reviewedPublisher PD

Extended diagnostic criteria used for indirect challenge testing in elite asthmatic swimmers.

The aim of the study was to investigate the prevalence of asthma with or without exercise induced symptoms among elite and elite aspiring swimmers and to compare sport specific exercise provocation with mannitol provocation. METHODS: 101 adolescent swimmers were investigated with mannitol provocation and sport specific exercise challenge test. Mannitol positivity was defined as either direct FEV(1) PD15 (ordinary criteria) or as β(2)-reversibility ≥15% after challenge (extended criteria). A direct positive exercise test was defined as a drop in FEV(1) of 10% (ordinary criteria) or a difference in FEV of ≥15% either spontaneous, variability, or with β2-agonist, reversibility (extended criteria). RESULTS: We found a high prevalence of mannitol and/or exercise positivity. Twenty-six swimmers were mannitol direct positive and 14 were direct exercise positive using ordinary criteria. Using extended criteria 43 were mannitol positive and 24 were exercise positive. When including reversibility and variability to define a positive test the sensitivity for current asthma with or without exercise induced symptoms increased while the specificity remained roughly unchanged. Direct positivity for mannitol and exercise poorly overlapped using ordinary criteria but improved using extended criteria. CONCLUSION: We found a high prevalence of asthma among elite swimmers. The use of variability and reversibility (liability) as additional criteria to define a positive test provided to our mind relevant information and should be considered

Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation.

Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase. The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations

Sex differences in asthma in swimmers and tennis players

Background: Elite athletes, independent of sport, have increased risk of developing asthma, but little is known about sex difference among adolescent athletes. Objective: To investigate and compare sex-related differences according to symptoms and treatment of asthma, allergy, and health among elite athletes and a reference group. Methods: Adolescent elite swimmers (n = 101), tennis players (n = 86), and a reference group (n = 1,628) responded to a questionnaire about respiratory symptoms, allergy, health behavior, psychosomatic symptoms, self- esteem, and well-being. The athletes performed a mannitol provocation and a sport-specific exercise provocation. Atopy was assessed by skin prick tests, and fractional exhaled nitric oxide was measured. Results: The females reported more asthma symptoms than the males in both the reference group (29.1% vs 22.3%) and the athlete group (56.4% vs 40.2%). However, no significant differences were found in physician-diagnosed asthma or treatment with inhaled corticosteroids. More female athletes had a positive mannitol provocation result (48.7% vs 35.8% in male athletes), and more female swimmers had a positive exercise provocation result (15.1% vs 7.7% in male swimmers). The females in all groups had more psychosomatic symptoms compared with the respective males, and the males in the reference group reported higher self-esteem and felt more well-being compared with the reference group females. Conclusion: Overall, we found a higher prevalence of asthma symptoms in the females. However, the frequency of physician-diagnosed asthma and the prescription of inhaled corticosteroids were the same in both sexes. This finding demonstrates an insufficient diagnosis of asthma in females

The lung function profile of once-daily tiotropium and olodaterol via Respimat® is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler® (ENERGITO® study)

Background: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting beta(2)-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens. Objective: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD. Methods: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 mu g and 2.5/5 mu g) via Respimat (R) and twice-daily salmeterol + fluticasone propionate (50/500 mu g and 50/250 mu g) via Accuhaler (R) for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC(0-12)) relative to the baseline after 6 weeks. Results: Tiotropium + olodaterol 5/5 mu g and 2.5/5 mu g demonstrated statistically significant improvements in FEV1 AUC(0-12) compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 mu g and 2.5/5 mu g, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 mu g and 50/250 mu g, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC(0-24)). Conclusion: Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD

Relationship between matrix production by bronchial fibroblasts and lung function and AHR in asthma

SummaryThe reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients’ lung function and airway hyperreactivity (AHR).Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by [35S]-sulphate-incorporation/ion chromatography.Patients’ FEV1% predicted and methacholine log PD20 negatively correlated with PICP synthesized by patients’ bronchial fibroblasts (r = −0.74 and r = −0.71, respectively). PICP and proteoglycan amounts positively correlated (0.8 ≤ r ≤ 0.9) with MMP-2 and MMP-3 activity. A positive correlation (r = 0.75) was also found between proteoglycan production and TIMP-1. There was no correlation between MMP-9 activity and PICP or proteoglycan production. MMP-9 activity positively correlated with patients’ FEV1% predicted (r = 0.97) and methacholine log PD20 (r = 0.86), whereas negative associations (−0.6 ≤ r ≤ −0.7) were observed for MMP-2 and MMP-3.In stable mild-to-moderate asthma, increased procollagen I synthesis and activity of MMP-2 and MMP-3 in bronchial fibroblasts may negatively affect patients’ lung function and AHR. In contrast, MMP-9 activity was not associated with procollagen or proteoglycan production, or worsening of patients’ lung function and AHR. An enhanced production of procollagen I and proteoglycans might be a result of a negative feedback from their degradation by MMP-2 and MMP-3

Application of nitric oxide measurements in clinical conditions beyond asthma.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma

Phase I study evaluating the safety, tolerability and pharmacokinetics of a novel oral dissolvable film containing dexamethasone versus Fortecortin dexamethasone tablets

Introduction: Systemic corticosteroids are anti-inflammatory agents with dexamethasone among the most potent in the class. Within (respiratory) allergy, systemic corticosteroids are usually applied in medical emergencies. In these situations, patients may experience physical or logistic problems taking tablets. To fulfil a practical unmet need for outpatients, Dexa ODF, an oral dissolvable film containing dexamethasone, was developed. Objectives: We compared the safety, tolerability and pharmacokinetics (PK) of Dexa ODF with Fortecortin tablets in healthy subjects. Methods: Thirty subjects participated in this open label, two-way, cross-over study, consisting of two treatment visits separated by 5-10 days. On both treatment visits, subjects randomly received one single dose of Dexa ODF (one strip; 8 mg dexamethasone) or one single dose of Fortecortin (two 4 mg tablets). Safety evaluations and blood sampling for PK were conducted until 48 h post-dose and bioequivalence analysis was performed on AUC(0-t), AUC(0-8) and Cmax. Results: All subjects were dosed. Forty-five adverse events (AEs) were reported by 17 subjects and approximately 50% were deemed ` possibly treatment related' (14 on Dexa ODF; 12 on Fortecortin) with no significant difference between treatments. For all three bioequivalence parameters the 90% CIs were within the acceptance limits of bioequivalence (0.8; 1.25). Conclusion: We demonstrated good tolerability and bioequivalence of Dexa ODF (8 mg dexamethasone) compared to Fortecortin tablets (2 x 4 mg dexamethasone). Dexa ODF is currently under development as an innovative treatment for use within respiratory and allergic conditions, including emergencies