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Notes: Background Inflammatory cells are increased in the airways of endurance athletes, but their role in causing exercise-induced respiratory symptoms and bronchoconstriction, or their possible long-term consequences, are uncertain.Aim To put the results of athlete studies in perspective, by analysing the pathogenesis of airway cell changes and their impact on respiratory function.Results Athletes of different endurance sports at rest showed increased airway neutrophils. Elite swimmers and skiers also showed large increases in airway eosinophils and lymphocytes, possibly related to chronic, exercise-related exposure to irritants or cold and dry air, respectively. Post-exercise studies reported variable responses of airway cells to exercise, but found no evidence of inflammatory cell activation in the airways, at variance with exercise-induced neutrophil activation in peripheral blood. The increase in airway inflammatory cells in athletes can result from hyperventilation-induced increase in airway osmolarity stimulating bronchial epithelial cells to release chemotactic factors. Hyperosmolarity may also inhibit activation of inflammatory cells by causing shedding of adhesion molecules, possibly explaining why airway inflammation appears ‘frustrated’ in athletes. Data on exhaled nitric oxide are few and variable, not allowing conclusions about its usefulness as a marker of airway inflammation in athletes, or its role in modulating bronchial responsiveness.Conclusions The acute and long-term effects of exercise on airway cells need further study. Airway inflammatory cells are increased but not activated in athletes, both at rest and after exercise, and airway inflammation appears to regress in athletes quitting competitions. Altogether, these findings do not clearly indicate that habitual intense exercise may be detrimental for respiratory health. Rather, airway changes may represent chronic adaptive responses to exercise hyperventilation. An improved understanding of the effects of exercise on the airways will likely have a clinical impact on sports medicine, and on the current approach to exercise-based rehabilitation in respiratory disease.

Notes: Background:  Corticosteroids play an important role in inflammation and remodelling of airways and are considered an important therapeutic target in asthma. Inflammation in asthma is characterized by a dysregulation of eosinophil apoptosis and of markers of airways remodelling. We evaluated the ability of flunisolide to inhibit in vitro the release of metalloproteinases-9 (MMP-9), tissue inhibitor metalloproteinases-1 (TIMP-1), transforming growth factor (TGF-β) and fibronectin by sputum cells (SC) as well as to induce sputum eosinophil apoptosis.Methods:  The SC, isolated from induced sputum samples of 12 mild-to-moderate asthmatics, were cultured for 24 h in the presence or absence of flunisolide (1, 10 and 100 μM). The release of mediators was assessed by enzyme-linked immunosorbent assay (ELISA) whereas apoptosis was studied by TUNEL technique.Results:  Flunisolide (10 μM) significantly reduced MMP-9 and TIMP-1 (P = 0.0011 and P 〈 0.0001 respectively) and increased MMP-9/TIMP-1 molar ratio (P = 0.004). In addition, flunisolide decreased TGF-β and fibronectin release by SC (P = 0.006; and P 〈 0.0001 respectively) and increased eosinophil apoptosis (P 〈 0.001).Conclusions:  These results demonstrate that flunisolide may play an important role in the inhibition of airway inflammation and remodelling, by promoting the resolution of eosinophilic inflammation and by inhibiting the release of MMP-9, TIMP-1, TGF-β and fibronectin.

Notes: Asthma has been associated with an exaggerated T-helper type 2 (Th2) over Th1 responses to allergic and nonallergic stimuli, which leads to chronic airway inflammation and airway remodeling. In the present article, we propose that many of the genes involved in IgE synthesis and airways (re)modeling in asthma are persistent or reminiscent fetal genes which may not be silenced during early infancy (or late pregnancy). Genes of the embryologic differentiation of ectodermic and endodermic tissues may explain some of the patterns of airway remodeling in asthma. In utero programming leads to gene expression, the persistence of which may be associated with epigenetic inheritance phenomena induced by nonspecific environmental factors. Clear delineation of these issues may yield new information on the mechanisms of asthma and new targets for therapeutic intervention and primary prevention.

Notes: In asthma a dysregulation of eosinophil apoptosis and an imbalance of metalloproteinase-9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) play an important role in airway inflammation and remodelling. We evaluated the effects of a low dose of inhaled fluticasone proprionate (FP) (100 μg bid by Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma, symptomatic and with a sputum eosinophilia ≥3% on clinical outcomes and inflammatory markers such as the induced sputum eosinophils, the induced sputum apoptotic eosinophils, the levels of MMP-9 and TIMP-1 and their molar ratio in the induced sputum supernatants. After FP treatment forced expiratory volume (FEV1) and FEV1/forced vital capacity values, PEF (L/min), sputum apoptotic eosinophils, and MMP-9/TIMP-1 molar ratio in sputum supernatants of asthmatic subjects were significantly increased in comparison with baseline, while sputum eosinophils significantly decreased. Change (Δ) in FEV1 after treatment with FP negatively correlated with the Δ in sputum eosinophils, while the Δ in MMP-9 values positively correlated with Δ in TIMP-1 values. This study shows that the clinical improvement achieved by the use of low doses of FP in asthmatics is related, at least in part, to the resolution of eosinophilic inflammation and the downregulation of remodelling markers.

Notes: Background:  Acetylcholine (ACh) plays an important role in smooth muscle contraction and in the development of airway narrowing; preliminary evidences led us to hypothesize that ACh might also play a role in the development of airways inflammation in chronic obstructive pulmonary disease (COPD).Methods:  We evaluated the concentrations of leukotriene B4 (LTB4) in induced sputum, and the expression of Ach M1, M2, and M3 receptors in sputum cells (SC) obtained from 16 patients with COPD, 11 smokers, and 14 control subjects. The SC were also treated with ACh and the production of LTB4 assessed in the presence or absence of a muscarinic antagonist (oxitropium). In blood monocytes, we evaluated LTB4 release and activation of the extracellular signal-regulated kinases (ERK) pathway after treatment with Ach.Results:  The LTB4 concentrations were higher in COPD than in controls (P 〈 0.01) and correlated with the number of neutrophil (P 〈 0.01). The M3 receptors expression was increased in COPD subjects when compared to smokers and control (P 〈 0.05 and 0.0001, respectively), while M2 expression resulted decreased (P 〈 0.05 and 0.01). The ACh-induced LTB4 production was observed in peripheral blood monocytes, and was sensitive to ERK inhibition. Similarly, ACh significantly increased neutrophil chemotactic activity and LTB4 released from SC of COPD patients only, and these effects were blocked by pretreatment with the inhibitor of ERK pathway PD98059.Conclusions:  The results obtained show that muscarinic receptors may be involved in airway inflammation in COPD subjects through ACh-induced, ERK1/2-dependent LTB4 release. Muscarinic antagonism may contribute to reduce neutrophil infiltration and activation in COPD.