It has recently been suggested that regular exercise reduces lung function decline and risk of chronic obstructive pulmonary disease (COPD) among active smokers; however, the mechanisms involved in this effect remain poorly understood.The present study evaluated the effects of regular exercise training in an experimental mouse model of chronic cigarette smoke exposure.Male C57BL/6 mice were divided into four groups (control, exercise, smoke and smoke+exercise). For 24 weeks, we measured respiratory mechanics, mean linear intercept, inflammatory cells and reactive oxygen species (ROS) in bronchoalveolar lavage (BAL) fluid, collagen deposition in alveolar walls, and the expression of antioxidant enzymes, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase (TIMP)1, interleukin (IL)-10 and 8-isoprostane in alveolar walls.Exercise attenuated the decrease in pulmonary elastance (p,0.01) and the increase in mean linear intercept (p50.003) induced by cigarette smoke exposure. Exercise substantially inhibited the increase in ROS in BAL fluid and 8-isoprostane expression in lung tissue induced by cigarette smoke. In addition, exercise significantly inhibited the decreases in IL-10, TIMP1 and CuZn superoxide dismutase induced by exposure to cigarette smoke. Exercise also increased the number of cells expressing glutathione peroxidase.Our results suggest that regular aerobic physical training of moderate intensity attenuates the development of pulmonary disease induced by cigarette smoke exposure.

Pharyngeal critical closing pressure is associated with obesity and hyoid position. Tongue dimensions, pharyngeal length, and the mandibular plane to hyoid distance are associated with obesity variables. These findings provide novel insight into the potential factors mediating upper airway collapse in obstructive sleep apnea.

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Replacement of large tracheal defects remains an unmet clinical need. While recellularization of acellular tracheal grafts appeared to be a viable pathway, evidence from the clinic suggests otherwise. In hindsight, complete removal of chondrocytes and repopulation of the tracheal chondroid matrix to achieve functional tracheal cartilage may have been unrealistic. In contrast, the concept of a hybrid graft whereby the epithelium is removed and the immune-privileged cartilage is preserved is a radically different path with initial reports indicating potential clinical success. Here, we present a novel approach using a double-chamber bioreactor to de-epithelialize tracheal grafts and subsequently repopulate the grafts with exogenous cells. A 3 h treatment with sodium dodecyl sulfate perfused through the inner chamber efficiently removes the majority of the tracheal epithelium while the outer chamber, perfused with growth media, keeps most (68.6 ± 7.3%) of the chondrocyte population viable. De-epithelialized grafts support human bronchial epithelial cell (BEAS-2B) attachment, viability and growth over 7 days. While not without limitations, our approach suggests value in the ultimate use of a chimeric allograft with intact donor cartilage re-epithelialized with recipient-derived epithelium. By adopting a brief and partial decellularization approach, specifically removing the epithelium, we avoid the need for cartilage regeneration.

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.

BACKGROUND: OSA pathogenesis is complex and may vary according to ethnicity. The anatomic component predisposing to OSA is the result of the interaction between bony structure and upper airway soft tissues and can be assessed using passive critical closing pressure (Pcrit). We hypothesized that Japanese-Brazilians and whites present different predictors of upper airway collapsibility, suggesting different causal pathways to developing OSA in these two groups.

The critical closing pressure (Pcrit) is the airway pressure at which the airway collapses and reflects the anatomical contribution to the genesis of obstructive sleep apnea. Pcrit is usually determined during non-rapid eye movement sleep at night, but has been determined under midazolam sedation during the day in the absence of sleep stage monitoring. Indeed, little is known about the effects of midazolam on sleep architecture. Moreover, deeper sedation with midazolam can decrease upper airway muscle activity and increase collapsibility compared with natural sleep. Pcrit under sedation has not been systematically compared with the usual method performed during natural sleep. Therefore, this study aimed to test the hypothesis that Pcrit following low doses of midazolam during the day would be comparable to Pcrit measured during natural sleep in the same patient. Fifteen men (age 54 ± 10 yr, body mass index 30 ± 4 kg/m(2)) with obstructive sleep apnea underwent a baseline standard overnight polysomnogram (apnea-hypopnea index 38 ± 22 events/h, range: 8-66 events/h), and Pcrit was determined during natural sleep and following midazolam. Sleep induction was obtained with low doses of midazolam (2.4 mg, range 2.0-4.4 mg), and sleep architecture was comparable to natural sleep. Natural sleep and induced sleep Pcrit were similar (-0.82 ± -3.44 and -0.97 ± 3.21 cmH(2)O, P = 0.663) and closely associated (intraclass correlation coefficient = 0.92; 95% confidence interval, 0.78-0.97, P < 0.001). Natural and midazolam-induced Pcrit correlated with obstructive sleep apnea severity, indicating that both Pcrit measures provided meaningful physiological information. Pcrit determined during the day with sleep induction is similar to natural overnight sleep and is a valid alternative approach in which to determine Pcrit.

To more precisely measure the mechanical properties of the lung periphery in asthma, we have developed a forced oscillation technique that applies a broad-band flow signal through a wedged bronchoscope. We interpreted the data from four healthy and eight mildly asthmatic subjects in terms of an anatomically accurate computer model of the wedged segment. There was substantial overlap in impedance between the two groups, with resistance (R) showing minimal frequency dependence and elastance (E) showing positive and negative frequency dependence across subjects. After direct instillation of methacholine, R rose in both groups, but compared with healthy subjects, the asthmatic subjects displayed upward, parallel shifts in their dose-response curves. The baseline frequency-response patterns of E were enhanced after methacholine. Frequency dependencies of R and E were well reproduced in two normal subjects by a computational model that employed rigid airways connected to constant-phase tissue units but were better reproduced in the other two normal and three asthmatic subjects when the model employed heterogeneous, peripheral airway narrowing and compliant airways. To capture the frequency dependencies of R and E in the remaining five asthmatic subjects, the model was modified by increasing airway wall stiffness. These results indicate that the lung periphery of mildly asthmatic subjects is not well distinguished from that of healthy subjects by measurement of mechanical impedance at baseline, but group differences are seen after challenge with methacholine. Modeling of the response suggests that variable contributions of airway narrowing and wall compliance are operative in determining overall mechanical impedance of the lung periphery in humans with asthma, likely reflecting the functional consequences of airway inflammation and remodeling.