Meal-Exercise Challenge and Physical Activity Reduction Impact on Immunity and Inflammation (MERIIT)

In a society where exercise is prescribed by physicians to increase physical condition, improve dietary habits and reduce cardiovascular risk, the impact of exercise, acute or chronic, and diet in inflammation and immunity is unknown. Specific populations can have different responses towards acute and chronic exercise. Moreover specific conditions, like the type of meal ingested, can interfere with these responses. The true effect of pre-competitive meal exercise in the immunity and inflammatory response is unknown. Acute physical inactivity periods, commonly happens during daily life, related to work or acute illness. New evidence points out that it induces immediate metabolic and endocrinological changes, these can might also be associated with changes in immune response. Aims of this project are: to assess the effect of the precompetitive meal on the inflammatory, neuro-immune and metabolic response to exercise; to assess the effects of sedentary behaviour on inflammatory, neuro-immune and metabolic response; to assess differences in changes between healthy, asthmatic and obese subjects

Two interventions will be performed for assessing the research questions and aims: A) Randomized cross-over, with a wash out period of 7 days, single-blinded trial where two different pre-competitive meals will be followed by an exercise challenge; inflammatory neuro-immune and metabolic response will be assessed before and after each challenge. Participants will be recruited from advertisement and four different groups will be compared: obese-asthmatic; asthmatic non-obese; obese without asthma and non-asthmatic and non-obese. All patients will be allocated to a meal challenge in which a high fat poor micronutrient meal followed by a Mediterranean meal or vice-versa; meal challenge order will be randomized and participants will be blinded to the intervention. The main outcome for this intervention will be airway inflammation and lung function. All outcomes will be assessed before and 3h after each meal. A group of individuals will, in the three hours after the meal, perform an exercise challenge, which is aimed to induce acute immune changes. B) Randomized controlled trial where participants, after a run-in period and eligibility evaluation, will be allocated to an intervention consisting in a reduction of physical activity by 50% or maintaining habitual physical activity for two weeks; inflammatory neuro-immune and metabolic response will be assessed before and after intervention.

Two different meals,an high fat micronutrient poor meal and Mediterranean Meal will be followed by an exercise challenge and performed at different orders accordingly to the cross over design.

Two different meals,an high fat micronutrient poor meal and Mediterranean Meal will be followed by an exercise challenge and performed at different orders accordingly to the cross over design. Each arm corresponds to a different intervention order.

The meal will be prepared by a team of nutritionist in order to comply with the demand characteristics of an high fat poor micronutrient meal.

The meal will be prepared by a team of nutritionist in order to comply with the demand characteristics of an Mediterranean meal

Lung function before and after challenge and bronchodilator response; Exhaled nitric oxide; Exhaled breath condensate (EBC);

Assessment of plasma F2-isoprostanes, lipid hydroperoxides, protein carbonyls, hydrogen peroxide and lipid soluble antioxidants

Circulating blood leukocyte-total and differential leukocyte counts and lymphocyte subpopulations assessment.

Evaluated by flow cytometry: T cell (CD4+/CD8+), and their subsets; B cells (CD19+), Natural Killer (NK) cells (CD16+/56+), their subsets; monocytes subsets; oxidative burst activity

Inclusion Criteria: controlled mild to moderate asthma; Body mass index (BMI) ≥ 25 kg/m2; healthy participants (non asthmatic with a BMI 18,5 to 25 kg/m2) will be used for comparison; Exclusion Criteria: respiratory disease other than asthma; severe asthma according to Global Initiative for Asthma (GINA) guidelines occurrence in previous 4 weeks of screening of upper/lower respiratory tract infection; smoking in the past 6 months and requiring mechanical ventilation for respiratory event within 6 months of screening. Medical conditions (hematologic, cardiovascular, renal, hepatic, neurologic or metabolic) or medication that may interfere with meal or physical activity intervention; Significant chronic infectious diseases (eg, HIV, hepatitis B or C); Abnormal electrocardiogram screening, cardiac arrhythmia, angina, congestive heart failure; renal or hepatic failure and systemic disease, mal-absorption disease history or intestinal inflammatory disease; Women breast-feeding, pregnant or intending pregnancy during study