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Background: Physical effort is one of the natural stimuli capable of triggering airway obstruction in asthmatics, the so called exercise-induced bronchoconstriction in asthma (EIBa). This study was performed in subjects with mild persistent asthma suspected for EIBa, aiming to find predictors among functional parameters at rest and during exercise for developing EIBa. Methods: In 20 subjects with mild asthma in stable conditions who reported respiratory symptoms on exertion in the past, measurements of baseline functional respiratory parameters and airways responsiveness by a methacholine challenge were obtained on the first day of the study after an adequate pharmacological washout. The day after, a maximal symptom-limited incremental cardiopulmonary exercise test (CPExT) was performed, with subsequent, repeated maneuvers of maximal full forced expiration to monitor the FEV1 change at 1,3,5,7,10 and 15 minutes after the end of exercise for diagnosing EIBa.Results: 19 subjects aged 27±5 years completed the two-days protocol. No functional parameters both at rest and during effort were useful to predict EIBa after stopping exercise that actually occurred in 12 individuals. In contrast to asthmatics without EIBa, in those with EIBa, however, mean Inspiratory Capacity (IC) did not increase with increasing ventilatory requirements during CPExT because 6 of them (50%) displayed dynamic pulmonary hyperinflation (DH) throughout the exercise, as documented by the progressive increase of end-expiratory lung volume. This subgroup of asthmatics with EIBa who in turn showed earlier and greater post-exercise FEV1 fall had significantly lower forced mean expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) at rest (p20FEV1 (pConclusions No functional respiratory parameters either at rest or during the effort seem to predict EIBa in mild asthmatics after maximal exercise test. In those with EIBa, however, a subgroup developed DH during exercise, and this was associated with baseline reduced forced expiratory flow-rates at lower lung volumes and higher airway hyperresponsiveness, suggesting a prominent small airways impairment.

BackgroundEvidence for association between asthma and the unfolded protein response is emerging. Endoplasmic reticulum resident protein 57 (ERp57) is an endoplasmic reticulum-localized redox chaperone involved in folding and secretion of glycoproteins. We have previously demonstrated that ERp57 is upregulated in allergen-challenged human and murine lung epithelial cells. However, the role of ERp57 in asthma pathophysiology is unknown.ObjectivesHere we sought to examine the contribution of airway epithelium-specific ERp57 in the pathogenesis of allergic asthma.MethodsWe examined the expression of ERp57 in human asthmatic airway epithelium and used murine models of allergic asthma to evaluate the relevance of epithelium-specific ERp57.ResultsLung biopsy specimens from asthmatic and nonasthmatic patients revealed a predominant increase in ERp57 levels in epithelium of asthmatic patients. Deletion of ERp57 resulted in a significant decrease in inflammatory cell counts and airways resistance in a murine model of allergic asthma. Furthermore, we observed that disulfide bridges in eotaxin, epidermal growth factor, and periostin were also decreased in the lungs of house dust mite-challenged ERp57-deleted mice. Fibrotic markers, such as collagen and α smooth muscle actin, were also significantly decreased in the lungs of ERp57-deleted mice. Furthermore, adaptive immune responses were dispensable for house dust mite-induced endoplasmic reticulum stress and airways fibrosis.ConclusionsHere we show that ERp57 levels are increased in the airway epithelium of asthmatic patients and in mice with allergic airways disease. The ERp57 level increase is associated with redox modification of proinflammatory, apoptotic, and fibrotic mediators and contributes to airways hyperresponsiveness. The strategies to inhibit ERp57 specifically within the airways epithelium might provide an opportunity to alleviate the allergic asthma phenotype.

Background: Achieving asthma control is a major challenge in children, otherwise symptoms perception remain poor especially at this age. The aim of this study is to evaluate the relationship between Asthma Control Test (ACTTM), Asthma Therapy Assessment Questionnaire (ATAQTM) and exercise-induced bronchospasm (EIB). Methods: We studied 80 asthmatic children. Airways hyperresponsiveness (AHR) was assessed by exercise-induced bronchospasm (Balke Protocol). Asthma control was evaluated using two questionnaires in all subjects: ACT (composed by Childhood-ACT and ACT) and ATAQ. In addition the use of short acting beta 2 agonist agents (SABAs) was assessed for each patient. Non-parametric variables were compared by Chi Square Test. Binomial logistic regression was performed to estimate the two questionnaires Odds Ratio (OR) in finding AHR. Results: We have found that ATAQ has a sensitivity and a specificity of 0.72 and 0.45 respectively; instead, ACT has a sensitivity and a specificity of 0.5 and 0.39 respectively in evaluating AHR. Patients with uncontrolled asthma according to ATAQ revealed a significant higher percentage of AHR compared with ACT (72% vs 50%, p < 0.01). Confirming this finding, patients declaring uncontrolled asthma to ATAQ have a significantly higher percentage (34%) of frequent SABAs use than the group with uncontrolled asthma to ACT (21%) (p

Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4), and interleukin 5 (IL-5) in bronchoalveolar lavage fluid (BALF). Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.