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Creatine supplement is the most popular nutritional supplement, and has various metabolic functions and sports medicine applications. Creatine supplementation increases muscle mass and can decrease muscular inflammation. Some studies have also suggested a beneficial role of creatine supplementation on chronic pulmonary diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Among athletes, the prevalence of asthma is high, and many of these individuals may be taking creatine. However, the effects of creatine supplementation on chronic pulmonary diseases of allergic origin have not been investigated. In the present study, we analyzed the effects of creatine supplementation on a model of chronic allergic lung inflammation. Thirty-one Balb/c mice were divided into four groups: control, creatine (Cr), ovalbumin (OVA), and OVA+Cr. OVA and OVA+Cr groups were sensitized with intraperitoneal injections of OVA on Days 0, 14, 28, and 42. OVA challenge (OVA 1%) and Cr treatment (0.5 g/kg/d) were initiated on Day 21 and lasted until Day 53. We determined the index of hyperresponsiveness, the serum levels of OVA-specific immunoglobulin (Ig)E and IgG(1), and the total and differential cell counts in bronchoalveolar lavage fluid. We also quantified airway inflammation, and the airway density of IL-4+, IL-5+, IL-2+, IFN-gamma+, and insulin-like growth factor (IGF)-1+ cells, collagen and elastic fibers, and airway smooth muscle thickness. Our results showed that creatine in OVA-sensitized mice increased hyperresponsiveness; eosinophilic inflammation; airway density of IL-4+, IL-5+, and IGF-1 inflammatory cells; airway collagen and elastin content; and smooth muscle thickness. The results show that creatine supplementation exacerbates the lung allergic response to OVA through a T helper cell type 2 pathway and increased IGF-1 expression.

Aerobic conditioning improves exercise capacity and decreases symptoms in patients with asthma. However, its benefits in the context of allergic airway inflammation are poorly understood.To evaluate the effects of two intensities of aerobic exercise on airway inflammation and remodeling in a model of chronic allergic lung inflammation.Mice were subjected to chronic ovalbumin (OVA) sensitization and to 4 weeks of low (OVA+Low) or moderate (OVA+Mod) exercise training in a treadmill. Airway inflammation and remodeling and expression of helper T-cell type 1 and 2 cytokines were evaluated.OVA-induced allergic airway inflammation and remodeling were characterized by an increase in collagen (288%), elastic fiber (56%), smooth muscle (380%), and epithelial (402%) contents (P0.001) when compared with the control group. OVA+Low and OVA+Mod groups presented a decrease in bronchoalveolar lavage fluid eosinophils (respectively, 84 and 75%; P0.01) and airway walls (respectively, 94 and 58%; P0.001) when compared with the OVA group. OVA+Low and OVA+Mod groups also presented a reduction in the number of peribronchial inflammatory cells expressing IL-4 (respectively, 85 and 75%; P0.01) and IL-5 (respectively, 88 and 89%; P0.01) when compared with the OVA group. Aerobic conditioning did not change the expression of either IFN-gamma or IL-2 by inflammatory cells or plasma levels of IgE or IgG1. OVA+Low and OVA+Mod groups presented an increase in the expression of IL-10 (P0.001). Low and moderate aerobic conditioning also reduced airway remodeling in OVA-sensitized mice when compared with the OVA group.We concluded that low and moderate aerobic exercise decreases airway inflammation and remodeling in a murine model of asthma.

Small airway disease is thought to contribute significantly to functional impairment caused by asthma. Functional evidence of airway-parenchyma uncoupling in asthma, such as loss of deep breath bronchodilator effect in bronchoconstrictive episodes and enhanced airway closure, has been previously demonstrated. Elastic fibers are essential to maintain adequate elastic recoil of the lungs. In this study, we hypothesized that alveolar attachments could be abnormal and that elastic fibers could be damaged in the distal lungs of patients with fatal asthma. For this purpose, we measured the number of abnormal alveolar attachments and quantified the content of elastic fibers in the adventitial layer of small airways and in the peribronchial and distal alveolar septa of 15 patients who died of asthma (FA) and 9 control subjects (CTRL). Our data (geometric mean [range]) showed an increased proportion of abnormal alveolar attachments per centimeter of basement membrane perimeter in fatal asthma (FA, 0.18 [0.03-4.00]; CTRL, 0.00 [0.00-0.12]; p0.001) and decreased elastic fiber content in the small airway adventitial layer (FA, 4.08 [2.22-11.46] microm; CTRL, 6.79 [5.62-10.0] microm; p = 0.01) and in the peribronchial alveoli (FA, 1.08 [0.46-1.91] microm; CTRL, 1.81 [1.22-1.74] microm; p = 0.003), but not in the distal alveoli. We propose that structural alterations at the peribronchiolar level might contribute to the pathogenesis of some functional abnormalities observed in patients with severe asthma.

Fibers of the elastic system (FES) are important in regulating airway patency and lung elastic recoil. Their possible role in modulating bronchoconstriction is not fully understood. Chronic inflammation and mechanical stretching present in asthma could lead to conformational alterations in the FES, participating in the mechanism of airway remodeling observed in this disease. In airway mucosa, two layers of FES are discernible: one superficial network, attached to the basement membrane, and a deeper network, lying close to the airway smooth muscle. Using image analysis and conventional morphometry, we analyzed airway content of FES in central and peripheral airways in 31 cases of fatal asthma and in 10 control lungs. Slides were stained using the oxidized resorcin-fuchsin method. Optical analysis revealed fragmentation of the FES in the superficial network of central asthmatic airways. Morphometry showed the presence of elastosis in central asthmatic airways when the entire thickness of the mucosa was considered. In the superficial network elastic fiber content was significantly decreased. These results indicate that FES participate in airway remodeling in asthma. We also suggest that disrupture of fiber attachments at the basement membrane in the superficial layer could impair the mechanism of airway recoil in asthmatic patients.

We studied the effects of capsaicin on airway and lung tissue mechanics in anesthetized and tracheostomized guinea pigs that were mechanically ventilated at constant tidal volume (8 ml/kg) and breathing frequency (60 breaths/min). Dose-response curves to intravenously infused capsaicin (1, 10, and 100 micrograms/kg) were performed (five animals for each dose, one dose per animal). We measured airflow, volume (by integration of the flow signal), tracheal pressure, and alveolar pressure with an alveolar capsule. Capsaicin induced a dose-dependent increase in airway resistance, tissue resistance, and dynamic elastance. The relationship between airway pressure and flow was fitted by a quadratic (Rohrer) equation. Airflow became more turbulent after infusion of capsaicin. After infusion of 100 micrograms/kg capsaicin, airway pressure (at flow rates of 10 ml.s-1) increased from 3.03 +/- 0.40 (mean +/- SEM) to 9.58 +/- 1.88 cm H2O, whereas the pressure corresponding to viscoelastic properties of lung tissue increased from 0.92 +/- 0.14 to 8.58 +/- 1.12 cm H2O. We conclude that infusion of capsaicin results in mechanical effects in both airways and pulmonary tissue.