The pathogenesis of asthma is a complex problem where environmental factors determine susceptibility. It is often triggered in children by allergens (from rodents, pets, dust mites and plant pollens) and irritants, especially cigarette smoke and other indoor and outdoor air pollutants. Air pollutants can exacerbate preexisting airway inflammation leading to increased airway hyper-responsiveness. The pollutants may also augment or modify immune responses to inhaled antigens or intensify the effect of other pollutants in the respiratory tract. Recent epidemiological studies revealed that diet is also a major risk factor in the pathogenesis of asthma. Most recently, dietary factors have been linked to poorer asthma health, pointing to a potential role for diet in perpetuating asthma morbidity. Insufficient intake of vitamins and other dietary nutrients during pregnancy, for example, have been associated with a greater risk of development of asthma and wheezing symptoms in children. The "Western-style" diet, high in animal fats, junk food and sugary drinks has been associated asthma attacks and a "Mediterranean-style" diet rich in omega-3 containing fats and antioxidant containing foods such as whole fruits and vegetables has been shown to be protective. This ASTHMA-DIET Program will focus on investigating diet-asthma relationships and mechanisms in a mice model of asthma similar to the dietary modifications being proposed in Project 2.
The aims of Project 3 are: SA#1: To determine the effect of dietary constituents (proposed in Project 2-children intervention studies) on OVA and ambient particle induced-asthma in mice models. The mice will be fed either a normal diet or a modified Mediterranean-type diet from which we will compare diets with low DHA, high DHA and a high fat diet. SA#2: We will study asthma susceptibility by measuring different endpoints such as pulmonary inflammation, Th2 cytokines, and airway hyper-responsiveness. To study the regulation of Nrf2 pathway and its downstream antioxidant gene activation due to Sulforaphane, we will use Nrf2 [+/+] and [-/-] mice to dissect the mechanism. SA#3: We will determine the effect of dietary constituents on DC maturation and Th2 polarization in the OVA and the ambient particle model of asthma. The proposed studies will help illustrate the mechanism by which diet modulates susceptibility and asthma pathogenesis.
Results from this research proposal will help us in defining and formulating dietary criteria for better asthma management. It will also elucidate the dietary interaction in the pathogenesis of asthma as well as develop therapeutic interventions. The results from this research proposal will narrow the current gap in our knowledge relating to dietary intake and asthma using our well-controlled mice model studies.
|Kim, Jung-Hyun; Thimmulappa, Rajesh K; Kumar, Vineet et al. (2014) NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation. J Clin Invest 124:730-41|
|Kaji, Deepak A; Belli, Andrew J; McCormack, Meredith C et al. (2014) Indoor pollutant exposure is associated with heightened respiratory symptoms in atopic compared to non-atopic individuals with COPD. BMC Pulm Med 14:147|
|Camargo Jr, Carlos A; Budinger, G R Scott; Escobar, Gabriel J et al. (2014) Promotion of lung health: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc 11 Suppl 3:S125-38|
|Okelo, Sande O; Riekert, Kristin A; Eakin, Michelle N et al. (2014) Pediatrician qualifications and asthma management behaviors and their association with patient race/ethnicity. J Asthma 51:155-61|
|Matsui, E C (2014) Environmental exposures and asthma morbidity in children living in urban neighborhoods. Allergy 69:553-8|
|Hackstadt, Amber J; Matsui, Elizabeth C; Williams, D'Ann L et al. (2014) Inference for environmental intervention studies using principal stratification. Stat Med 33:4919-33|
|Little, Frédéric F; Delgado, Diana M; Wexler, Philip J et al. (2014) Salivary inflammatory mediator profiling and correlation to clinical disease markers in asthma. PLoS One 9:e84449|
|Rivera-Mariani, Felix E; Matsui, Elizabeth C; Breysse, Patrick N (2014) Performance of the halogen immunoassay to assess airborne mouse allergen-containing particles in a laboratory animal facility. J Expo Sci Environ Epidemiol 24:3-8|
|Sussan, Thomas E; Ingole, Vijendra; Kim, Jung-Hyun et al. (2014) Source of biomass cooking fuel determines pulmonary response to household air pollution. Am J Respir Cell Mol Biol 50:538-48|
|Soneja, Sutyajeet; Chen, Chen; Tielsch, James M et al. (2014) Humidity and gravimetric equivalency adjustments for nephelometer-based particulate matter measurements of emissions from solid biomass fuel use in cookstoves. Int J Environ Res Public Health 11:6400-16|
Showing the most recent 10 out of 33 publications