Comparison between breathing and aerobic exercise on clinical control in patients with moderate-to-severe asthma: protocol of a randomized trial

Abstract\ud \ud Background\ud Asthma is a chronic inflammatory airway disease characterized by reversible obstruction, inflammation and hyperresponsiveness to different stimulus. Aerobic and breathing exercises have been demonstrated to benefit asthmatic patients; however, there is no evidence comparing the effectiveness of these treatments.\ud \ud \ud Methods/design\ud This is a prospective, comparative, blinded, and randomized clinical trial with 2 groups that will receive distinct interventions. Forty-eight asthmatic adults with optimized medical treatment will be randomly divided into either aerobic (AG) or breathing exercises (BG). Patients will perform breathing or aerobic exercise twice a week for 3 months, totalizing 24 sessions of 40 minutes each. Before intervention, both groups will complete an educational program consisting of 2 educational classes. Before and after interventions, the following parameters will be quantified: clinical control (main outcome), health related quality of life, levels of anxiety and depression, daily living physical activity and maximal exercise capacity (secondary outcome). Hyperventilation syndrome symptoms, autonomic nervous imbalance, thoracoabdominal kinematics, inflammatory cells in the sputum, fraction of exhaled nitric oxide (FENO) and systemic inflammatory cytokines will also be evaluated as possible mechanisms to explain the benefits of both interventions.\ud \ud \ud Discussion\ud Although the benefits of breathing and aerobic exercises have been extensively studied, the comparison between both has never been investigated. Furthermore, the findings of our results will allow us to understand its application and suitability to patients that will have more benefits for every intervention optimizing its effect.\ud \ud \ud Trial registration\ud Clinicaltrials.gov; Identifier: \ud NCT02065258\ud \ud .This work was supported by São Paulo Research Foundation - FAPESP (grants\ud 2009/53904-9 and 2011/50071-6)

The effects of exercise training in a weight loss lifestyle intervention on asthma control, quality of life and psychosocial symptoms in adult obese asthmatics: protocol of a randomized controlled trial

Abstract\ud \ud Background\ud Asthma and obesity are public health problems with increasing prevalence worldwide. Clinical and epidemiologic studies have demonstrated that obese asthmatics have worse clinical control and health related quality of life (HRQL) despite an optimized medical treatment. Bariatric surgery is successful to weight-loss and improves asthma control; however, the benefits of nonsurgical interventions remain unknown.\ud \ud \ud Methods/Design\ud This is a randomized controlled trial with 2-arms parallel. Fifty-five moderate or severe asthmatics with grade II obesity (BMI ≥ 35 kg/m2) under optimized medication will be randomly assigned into either weight-loss program + sham (WL + S group) or weight-loss program + exercise (WL + E group). The weight loss program will be the same for both groups including nutrition and psychological therapies (every 15 days, total of 6 sessions, 60 min each). Exercise program will include aerobic and resistance muscle training while sham treatment will include a breathing and stretching program (both programs twice a week, 3 months, 60 min each session). The primary outcome variable will be asthma clinical control. Secondary outcomes include HRQL, levels of depression and anxiety, lung function, daily life physical activity, body composition, maximal aerobic capacity, strength muscle and sleep disorders. Potential mechanism (changes in lung mechanical and airway/systemic inflammation) will also be examined to explain the benefits in both groups.\ud \ud \ud Discussion\ud This study will bring a significant contribution to the literature evaluating the effects of exercise conditioning in a weight loss intervention in obese asthmatics as well as will evaluate possible involved mechanisms.\ud \ud \ud Trial registration\ud \ud \ud NCT02188940The study was supported by the São Paulo Research Foundation (FAPESP;\ud Grants 2012/16700-9 and 2012/16134-3) and Conselho Nacional de Pesquisa (CNPq Grants 485065/2012-6)

Context- and Cell-Dependent Effects of Delta-Like 4 Targeting in the Bone Marrow Microenvironment

This work was supported by FCT PTDC/SAU-ORG/113617/2009 (www.fct.pt). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank other members of the Angiogenesis Lab for their input and suggestions. The Program for Advanced Medical Education is sponsored by Fundacao Calouste Gulbenkian, Fundacao Champalimaud, Ministerio da Saude and Fundacao para a Ciencia e Tecnologia, Portugal.Delta-like 4 (Dll4) is a ligand of the Notch pathway family which has been widely studied in the context of tumor angiogenesis, its blockade shown to result in non-productive angiogenesis and halted tumor growth. As Dll4 inhibitors enter the clinic, there is an emerging need to understand their side effects, namely the systemic consequences of Dll4:Notch blockade in tissues other than tumors. The present study focused on the effects of systemic anti-Dll4 targeting in the bone marrow (BM) microenvironment. Here we show that Dll4 blockade with monoclonal antibodies perturbs the BM vascular niche of sub-lethally irradiated mice, resulting in increased CD31+, VE-Cadherin+ and c-kit+ vessel density, and also increased megakaryocytes, whereas CD105+, VEGFR3+, SMA+ and lectin+ vessel density remained unaltered. We investigated also the expression of angiocrine genes upon Dll4 treatment in vivo, and demonstrate that IGFbp2, IGFbp3, Angpt2, Dll4, DHH and VEGF-A are upregulated, while FGF1 and CSF2 are reduced. In vitro treatment of endothelial cells with anti-Dll4 reduced Akt phosphorylation while maintaining similar levels of Erk 1/2 phosphorylation. Besides its effects in the BM vascular niche, anti-Dll4 treatment perturbed hematopoiesis, as evidenced by increased myeloid (CD11b+), decreased B (B220+) and T (CD3+) lymphoid BM content of treated mice, with a corresponding increase in myeloid circulating cells. Moreover, anti-Dll4 treatment also increased the number of CFU-M and -G colonies in methylcellulose assays, independently of Notch1. Finally, anti-Dll4 treatment of donor BM improved the hematopoietic recovery of lethally irradiated recipients in a transplant setting. Together, our data reveals the hematopoietic (BM) effects of systemic anti-Dll4 treatment result from qualitative vascular changes and also direct hematopoietic cell modulation, which may be favorable in a transplant setting.publishersversionpublishe