Medicine

Purpose: There is evidence suggesting that physical activity has anti-inflammatory effects in many chronic diseases; however, the role of exercise in airway inflammation in asthma is poorly understood. We aimed to evaluate the effects of an aerobic training program on cosinophil inflammation (primary aim) and nitric oxide (secondary aim) in patients with moderate or severe persistent asthma. Methods: Sixty-eight patients randomly assigned to either control (CG) or aerobic training (TG) groups were studied during the period between medical consultations. Patients in the CG (educational program + breathing exercises; N = 34) and TG (educational program + breathing exercises + aerobic training; N = 34) were examined twice a week during a 3-month period. Before and after the intervention, patients underwent induced sputum, fractional exhaled nitric oxide (FeNO), pulmonary function, and cardiopulmonary exercise testing. Asthma symptom-free days were quantified monthly, and asthma exacerbation was monitored during 3 months of intervention. Results: At 3 months, decreases in the total and cosinophil cell counts in induced sputum (P = 0.004) and in the levels of FeNO (P = 0.009) were observed after intervention only in the TG. The number of asthma symptom-free days and VO 2 m•, also significantly improved (P < 0.001), and lower asthma exacerbation occurred in the TG (P < 0.01). In addition, the TG presented a strong positive relationship between baseline FeNO and eosinophil counts as well as their improvement after training (r = 0.77 and r = 0.9, respectively). Conclusions: Aerobic training reduces sputum cosinophil and FeNO in patients with moderate or severe asthma, and these benefits were more significant in subjects with higher levels of inflarmnation. These results suggest that aerobic training might be useful as an adjuvant therapy in asthmatic patients under optimized medical treatment.

Ischemia-reperfusion injury (IRI) is one of the principal obstacles for the lung transplantation (LTx) success. Several strategies have been adopted to minimize the effects of IRI in lungs, including ex vivo conditioning of the grafts and the use of antioxidant drugs, such as methylene blue (MB). We hypothesized that MB could minimize the effects of IRI in a LTx rodent model. Forty rats were divided into four groups (n = 10) according to treatment (saline solution or MB) and graft cold ischemic time (3 or 6 h). All animals underwent unilateral LTx. Recipients received 2 mL of saline or MB intraperitoneally before transplantation. After 2 h of reperfusion, arterial blood and exhaled nitric oxide samples were collected and bronchoalveolar lavage performed. Then animals were euthanized, and histopathology analysis as well as cell counts and cytokine levels measurements in bronchoalveolar lavage fluid were performed. There was a significant decrease in exhaled nitric oxide, neutrophils,...

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotalineinduced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

To determine whether a serine protease inhibitor treatment can prevent or minimize emphysema in mice. C57BL/6 mice were subjected to porcine pancreatic elastase (PPE) nasal instillation to induce emphysema and were treated with a serine protease inhibitor (rBmTI-A) before (Protocol 1) and after (Protocol 2) emphysema development. In both protocols, we evaluated lung function to evaluate the airway resistance (Raw), tissue damping (Gtis) and tissue elastance (Htis). The inflammatory profile was analyzed in the bronchoalveolar lavage (BALF) and through the use of morphometry; we measured the mean linear intercept (Lm) (to verify alveolar enlargement), the volume proportion of collagen and elastic fibers, and the numbers of macrophages and metalloprotease 12 (MMP-12) positive cells in the parenchyma. We showed that at both time points, even after the emphysema was established, the rBmTI-A treatment was sufficient to reverse the loss of elastic recoil measured by Htis, the alveolar enla...

Tacrolimus and mycophenolate have now become the most widely used combination for maintenance immunosuppressive regimens after lung transplantation in comparison with cyclosporine and azathioprine. However, limited information is available with respect to their effects on cells, other than those from the immunologic compartment. We hypothesized that different triple therapies could have different effects on airway mucociliary clearance, playing an important role in respiratory infections observed after lung transplantation. Ninety rats were assigned to three groups (n = 30 each): control = vehicle, therapy 1 = tacrolimus + mycophenolate + prednisone, and therapy 2 = cyclosporine + azathioprine + prednisone. After 7, 15, or 30 days of treatment by gavage, the animals were killed and the following parameters were studied: mucus transportability, ciliary beating frequency, mucociliary transport velocity, and neutral and acid mucus production. There was a significant decrease in ciliary beating frequency, mucociliary transport velocity, and neutral mucus production in all immunosuppressed animals; indeed, both therapies, mainly therapy 1, caused an increase in acid mucus production for as long as 15 days of treatment. Both triple therapies impaired airway mucociliary clearance of rats, but therapy 1 had a more deleterious effect. These data suggest that these undesirable effects can contribute to the high incidence of respiratory infections observed in patients undergoing lung transplantation.

Ischemia-reperfusion injury (IRI) is one of the principal obstacles for the lung transplantation (LTx) success. Several strategies have been adopted to minimize the effects of IRI in lungs, including ex vivo conditioning of the grafts and the use of antioxidant drugs, such as methylene blue (MB). We hypothesized that MB could minimize the effects of IRI in a LTx rodent model. Forty rats were divided into four groups (n = 10) according to treatment (saline solution or MB) and graft cold ischemic time (3 or 6 h). All animals underwent unilateral LTx. Recipients received 2 mL of saline or MB intraperitoneally before transplantation. After 2 h of reperfusion, arterial blood and exhaled nitric oxide samples were collected and bronchoalveolar lavage performed. Then animals were euthanized, and histopathology analysis as well as cell counts and cytokine levels measurements in bronchoalveolar lavage fluid were performed. There was a significant decrease in exhaled nitric oxide, neutrophils,...