Marília Beltrão

Substance P antagonist improves both obesity and asthma in a mouse model

Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P (SP), involved in neurogenic inflammation by acting through its receptor NK1‐R, seems to participate in obese–asthma phenotype in mice.

Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association?

ABSTRACT Aim: A number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice. Methods: High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi. Results: Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R2 = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001). Conclusions: Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.

Meal-exercise challenge and physical activity reduction impact on immunity and inflammation (MERIIT trial)

Background The effect of a pre-exercise meal as countermeasure to exercise induced immunodepression is poorly known. Also, sedentary behavior is associated with increased cardiometabolic risk but studies on immune changes are lacking. Therefore, we aimed to assess: 1) the impact of a pre-exercise Mediterranean meal (MdM) compared with a fast-food type meal (FFM) on exercise-induced immunological changes and 2) the impact of an induced acute period of sedentary behavior on neuro-immune-endocrine status. Methods /Design: This is a two steps clinical trial including: (a) randomized crossover clinical trial, comparing the effect a high-fat/low-nutrient dense meal, FFM, with an isoenergetic similar high-nutrient dense meal, MdM, in the immune response to an exercise challenge (EC) and (b) a pilot trial assessing the neuro-immune-endocrine change induced by acute decreasing by half the usual physical activity level. Results A total of 46 participants (26 females), median aged 25 years were included. Of those 39-completed protocol, including overweight, physical active and inactive and participants with asthma. There were no differences in the EC between interventions. Dietary factors and physical activity were closely monitored during interventions and kept similar. During physical inactivity induction, 31% reached the target of 50% reduction in mean step number and 77% reached a 30% reduction. Conclusion The use of a pre-exercise meal to modulate immune response and the understanding of the immunological impact of physical inactivity might help to establish future recommendations on how to practice exercise in a safer way and to recognize the potential impact of inactivity.

Esputo induzido nas doencas pulmonares intersticiais --- Um estudo piloto

INTRODUCTION Induced sputum with hypertonic saline has been suggested as a safer and cheaper alternative to bronchoalveolar lavage for evaluation of patients with interstitial lung diseases (ILD). OBJECTIVE To evaluate the safety and feasibility of sputum induction in ILD and to compare sputum cellular profiles with paired bronchoalveolar lavage fluid results. MATERIAL AND METHODS Twenty patients underwent sputum induction with 4.5% saline within 2 weeks of bronchoalveolar lavage. Total, differential cell counts and cellular viability were assessed. Wilcoxon test and Spearmans rank correlation coefficient were used and a p<0,05 was considered statistically significant. RESULTS From a total of 20 subjects (mean age 49.4±16.4 years, 70% male) a satisfactory sputum sample was obtained in 15 subjects (75%). Induction was stopped in one subject, due to a significant decrease in PEF. The cell profiles for induced sputum and bronchoalveolar lavage fluid (BALF) were different (P <.05), except for eosinophils, and there were no significant correlations between the two methods. Compared to sputum reference values there was an increase of lymphocytes (3.2% vs 0.5%) and eosinophils (1.4% vs 0.0%). Comparing sarcoidosis and hypersensitivity pneumonitis sputum, both diseases had an increase in lymphocytes (4.4 vs 3.9%), with a significant higher neutrophil count in hypersensitivity pneumonitis (65.4% vs 10.6% P <0.05), a finding also seen in BALF. CONCLUSION Induced sputum is feasible and safe in interstitial lung diseases. Although sputum cellular counts are not correlated with bronchoalveolar lavage fluid, sputum cellular profiles may help to distinguish different ILD.