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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.

There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection.The autopsy findings of 21 Brazilian patients with confirmed S-OIV infection are presented. These patients died in the winter of the southern hemisphere 2009 pandemic, with acute respiratory failure.Lung tissue was submitted to virologic and bacteriologic analysis with real-time reverse transcriptase polymerase chain reaction and electron microscopy. Expression of toll-like receptor (TLR)-3, IFN-gamma, tumor necrosis factor-alpha, CD8(+) T cells and granzyme B(+) cells in the lungs was investigated by immunohistochemistry.Patients were aged from 1 to 68 years (72% between 30 and 59 yr) and 12 were male. Sixteen patients had preexisting medical conditions. Diffuse alveolar damage was present in 20 individuals. In six patients, diffuse alveolar damage was associated with necrotizing bronchiolitis and in five with extensive hemorrhage. There was also a cytopathic effect in the bronchial and alveolar epithelial cells, as well as necrosis, epithelial hyperplasia, and squamous metaplasia of the large airways. There was marked expression of TLR-3 and IFN-gamma and a large number of CD8(+) T cells and granzyme B(+) cells within the lung tissue. Changes in other organs were mainly secondary to multiple organ failure.Autopsies have shown that the main pathological changes associated with S-OIV infection are localized to the lungs, where three distinct histological patterns can be identified. We also show evidence of ongoing pulmonary aberrant immune response. Our results reinforce the usefulness of autopsy in increasing the understanding of the novel human influenza A (H1N1) infection.