Martinez, F. D., & Guerra, S. (2017). Early Origins of Asthma: Role of Microbial Dysbiosis and Metabolic Dysfunction. American journal of respiratory and critical care medicine.
Asthma is a developmental disease that affects airway growth and is characterized by inappropriate responses to a variety of environmental stimuli. Recent advances point to two altered early life pathways as major determinants of asthma risk. In the "microbial" pathway, pre- and post-natal exposures to microbiota-loaded farm environments block gene-virus interactions (e.g., interactions between risk alleles in chromosome 17q21 and lower respiratory illnesses [LRI] by rhinovirus) that are associated with asthma development. Early colonization of the airway by pathogenic bacteria such as Streptococci and Moraxella may predispose for recurrent wheezing LRIs and subsequent asthma. Abnormal patterns of gut microbial colonization (dysbiosis) in the first months of life are associated with production of deleterious metabolic products that predispose for the development of asthma and reduction of beneficial metabolites, such as short-chain fatty acids, that may protect from the disease. The "metabolic" pathway is triggered by maternal obesity, excessive weight gain during pregnancy, and accelerated body mass index growth in the first years of life, which in turn predispose for early development of both metabolic alterations and asthma phenotypes. Notably, early gut dysbiosis is also associated with subsequent development of obesity, although it is currently unknown whether there are common intestinal microbial patterns in obesity- and asthma-associated dysbiosis. Promising avenues for asthma prevention could entail manipulating these two pathways with microbes, surrogates of animal farm exposures, or dietary supplements such as n-3 long-chain polyunsaturated fatty acids.
Vasquez, M., others, ., & Guerra, S. (2016). Low lung function in young adult life is associated with early mortality. The American Journal of Respiratory and Critical Care Medicine.
BIO5 Collaborators
Stefano Guerra, Chengcheng Hu
Ramon, M. A., Ferrer, J., Gimeno-Santos, E., Donaire-Gonzalez, D., Rodríguez, E., Balcells, E., de Batlle, J., Benet, M., Guerra, S., Sauleda, J., Ferrer, A., Farrero, E., Gea, J., Barberà, J. A., Agustí, A., Rodriguez-Roisin, R., Antó, J. M., Garcia-Aymerich, J., & , P. S. (2016). Inspiratory capacity-to-total lung capacity ratio and dyspnoea predict exercise capacity decline in COPD. Respirology (Carlton, Vic.), 21(3), 476-82.
Exercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity-to-total lung capacity (IC/TLC) ratio and exercise capacity decline in COPD.
Zhai, J., Stern, D., Sherrill, D., Spangenberg, A., Wright, A., Morgan, W., Halonen, M., Martinez, F., & Guerra, S. (2017). Trajectories and early determinants of circulating CC16 from birth to age 32 years. American Journal of Respiratory and Critical Care Medicine.
Amaral, A. F., Minelli, C., Guerra, S., Wjst, M., Probst-Hensch, N., Pin, I., Svanes, C., Janson, C., Heinrich, J., & Jarvis, D. L. (2015). The locus C11orf30 increases susceptibility to poly-sensitization. Allergy, 70(3), 328-33.
A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy.
