- Research Scientist, Respiratory Sciences
- Associate Professor, Public Health
- Associate Professor, BIO5 Institute
- Professor, Medicine - (Tenure Track)
- University of Arizona, Tucson, Arizona, United States
- University of Arizona, Tucson, Arizona, United States
- University of Milan, Milan, Italy
No activities entered.
ResearchEPID 900 (Fall 2016)
ResearchEPID 900 (Spring 2016)
Prin Genetic Assoc StdsCPH 677 (Spring 2015)
Prin Genetic Assoc StdsEPID 677 (Spring 2015)
Prin Genetic Assoc StdsGENE 677 (Spring 2015)
Prin Genetic Assoc StdsCPH 677 (Spring 2014)
Prin Genetic Assoc StdsEPID 677 (Spring 2014)
- Aguilar, D., Pinart, M., Koppelman, G. H., Saeys, Y., Nawijn, M. C., Postma, D. S., Akdis, M., Auffray, C., Ballereau, S., Benet, M., García-Aymerich, J., González, J. R., Guerra, S., Keil, T., Kogevinas, M., Lambrecht, B., Lemonnier, N., Melen, E., Sunyer, J., , Valenta, R., et al. (2017). Computational analysis of multimorbidity between asthma, eczema and rhinitis. PloS one, 12(6), e0179125.More infoThe mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes that are common to them.
- Akiki, Z., Rava, M., Diaz Gil, O., Pin, I., le Moual, N., Siroux, V., Guerra, S., Chamat, S., Matran, R., Fitó, M., Salameh, P., & Nadif, R. (2017). Serum cytokine profiles as predictors of asthma control in adults from the EGEA study. Respiratory medicine, 125, 57-64.More infoTo which extent serum cytokines may predict asthma control in adults remains understudied.
- Anto, J. M., Bousquet, J., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Lodrup Carlsen, K. C., Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., , De Carlo, G., et al. (2017). Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes. The Journal of allergy and clinical immunology, 139(2), 388-399.More infoAsthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.
- Chang, E. H., Willis, A. L., McCrary, H. C., Noutsios, G. T., Le, C. H., Chiu, A. G., Mansfield, C. J., Reed, D. R., Brooks, S. G., Adappa, N. D., Palmer, J. N., Cohen, N. G., Stern, D. A., Guerra, S., & Martinez, F. D. (2017). Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis. The Journal of allergy and clinical immunology.
- Chen, Y., Vasquez, M. M., Zhu, L., Lizarraga, R. E., Krutzsch, M., Einspahr, J., Alberts, D. S., Di, P. Y., Martinez, F. D., & Guerra, S. (2017). Effects of Retinoids on Augmentation of Club Cell Secretory Protein. American journal of respiratory and critical care medicine, 196(7), 928-931.
- DeVries, A., Wlasiuk, G., Miller, S. J., Bosco, A., Stern, D. A., Lohman, I. C., Rothers, J., Jones, A. C., Nicodemus-Johnson, J., Vasquez, M. M., Curtin, J. A., Simpson, A., Custovic, A., Jackson, D. J., Gern, J. E., Lemanske, R. F., Guerra, S., Wright, A. L., Ober, C., , Halonen, M., et al. (2017). Epigenome-wide Analysis Links SMAD3 Methylation at Birth to Asthma in Children of Asthmatic Mothers. The Journal of allergy and clinical immunology.More infoThe timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception.
- Diaz, A., others, ., Guerra, S., others, ., & Washko, D. (2017). Differences in respiratory symptoms and lung structure between Hispanic and non-Hispanic white smokers: a comparative study. COPD, Journal of the COPD Foundation.
- Guerra, S., Carsin, A. E., Keidel, D., Sunyer, J., Leynaert, B., Janson, C., Jarvis, D., Stolz, D., Rothe, T., Pons, M., Turk, A., Anto, J. M., & Probst-Hensch, N. (2017). Health-related quality of life and risk factors associated with spirometric restriction. The European respiratory journal, 49(5).More infoThe restrictive spirometric pattern is associated with a substantial morbidity and mortality burden. We sought to determine to what extent spirometric restriction is associated with impaired quality of life.We used data from two large population-based European cohorts: 6698 European Community Respiratory Health Survey (ECRHS) and 6069 Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) adult participants. The restrictive pattern was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥lower limit of normal (LLN) and FVC
- Guerra, S., Melén, E., Sunyer, J., Xu, C. J., Lavi, I., Benet, M., Bustamante, M., Carsin, A. E., Dobaño, C., Guxens, M., Tischer, C., Vrijheid, M., Kull, I., Bergström, A., Kumar, A., Söderhäll, C., Gehring, U., Dijkstra, D. J., van der Vlies, P., , Wickman, M., et al. (2017). Genetic and epigenetic regulation of YKL-40 in childhood. The Journal of allergy and clinical immunology.More infoCirculating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3-like 1 [CHI3L1]) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown.
- 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.More infoAsthma 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.
- Melén, E., & Guerra, S. (2017). Recent advances in understanding lung function development. F1000Research, 6, 726.More infoRecent years have witnessed critical contributions to our understanding of the determinants and long-term implications of lung function development. In this article, we review studies that have contributed to advances in understanding lung function development and its critical importance for lung health into adult life. In particular, we have focused on early life determinants that include genetic factors, perinatal events, environmental exposures, lifestyle, infancy lower respiratory tract infections, and persistent asthma phenotypes. Longitudinal studies have conclusively demonstrated that lung function deficits that are established by school age may track into adult life and increase the risk of adult lung obstructive diseases, such as chronic obstructive pulmonary disease. Furthermore, these contributions have provided initial evidence in support of a direct influence by early life events on an accelerated decline of lung function and an increased susceptibility to its environmental determinants well into adult life. As such, we argue that future health-care programs based on precision medicine approaches that integrate deep phenotyping with tailored medication and advice to patients should also foster optimal lung function growth to be fully effective.
- Pinto, L. A., Guerra, S., Anto, J. M., Postma, D., Koppelman, G. H., de Jongste, J. C., Gehring, U., Smit, H. A., & Wijga, A. H. (2017). Increased risk of asthma in overweight children born large for gestational age. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 47(8), 1050-1056.More infoBeing born large for gestational age (LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children.
- Vasquez, M. M., Hu, C., Roe, D. J., Halonen, M., & Guerra, S. (2017). Measurement error correction in the least absolute shrinkage and selection operator model when validation data are available. Statistical methods in medical research, 962280217734241.More infoMeasurement of serum biomarkers by multiplex assays may be more variable as compared to single biomarker assays. Measurement error in these data may bias parameter estimates in regression analysis, which could mask true associations of serum biomarkers with an outcome. The Least Absolute Shrinkage and Selection Operator (LASSO) can be used for variable selection in these high-dimensional data. Furthermore, when the distribution of measurement error is assumed to be known or estimated with replication data, a simple measurement error correction method can be applied to the LASSO method. However, in practice the distribution of the measurement error is unknown and is expensive to estimate through replication both in monetary cost and need for greater amount of sample which is often limited in quantity. We adapt an existing bias correction approach by estimating the measurement error using validation data in which a subset of serum biomarkers are re-measured on a random subset of the study sample. We evaluate this method using simulated data and data from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD). We show that the bias in parameter estimation is reduced and variable selection is improved.
- Vasquez, M. M., McClure, L. A., Sherrill, D. L., Patel, S. R., Krishnan, J., Guerra, S., & Parthasarathy, S. (2017). Positive Airway Pressure Therapies and Hospitalization in Chronic Obstructive Pulmonary Disease. The American journal of medicine, 130(7), 809-818.More infoHospitalization of patients with chronic obstructive pulmonary disease creates a huge healthcare burden. Positive airway pressure therapy is sometimes used in patients with chronic obstructive pulmonary disease, but the possible impact on hospitalization risk remains controversial. We studied the hospitalization risk of patients with chronic obstructive pulmonary disease before and after initiation of various positive airway pressure therapies in a "real-world" bioinformatics study.
- Vasquez, M. M., Zhou, M., Hu, C., Martinez, F. D., & Guerra, S. (2017). Low Lung Function in Young Adult Life Is Associated with Early Mortality. American journal of respiratory and critical care medicine, 195(10), 1399-1401.
- Vasquez, M. M., Zhou, M., Hu, C., Martinez, F. D., & Guerra, S. (2017). Reply to: Low Lung Function in Young Adult Life is Associated with Early Mortality. American journal of respiratory and critical care medicine.
- Beamer, P. I., Klimecki, W. T., Loh, M., Van Horne, Y. O., Sugeng, A. J., Lothrop, N., Billheimer, D., Guerra, S., Lantz, R. C., Canales, R. A., & Martinez, F. D. (2016). Association of Children's Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media. International journal of environmental research and public health, 13(5).More infoArsenic exposure has been associated with decreased club cell secretory protein (CC16) levels in adults. Further, both arsenic exposure and decreased levels of CC16 in childhood have been associated with decreased adult lung function. Our objective was to determine if urinary CC16 levels in children are associated with arsenic concentrations in environmental media collected from their homes. Yard soil, house dust, and tap water were taken from 34 homes. Urine and toenail samples were collected from 68 children. All concentrations were natural log-transformed prior to data analysis. There were associations between urinary CC16 and arsenic concentration in soil (b = -0.43, p = 0.001, R² = 0.08), water (b = -0.22, p = 0.07, R² = 0.03), house dust (b = -0.37, p = 0.07, R² = 0.04), and dust loading (b = -0.21, p = 0.04, R² = 0.04). In multiple analyses, only the concentration of arsenic in soil was associated with urinary CC16 levels (b = -0.42, p = 0.02, R² = 0.14 (full model)) after accounting for other factors. The association between urinary CC16 and soil arsenic may suggest that localized arsenic exposure in the lungs could damage the airway epithelium and predispose children for diminished lung function. Future work to assess this possible mechanism should examine potential associations between airborne arsenic exposures, CC16 levels, lung function, and other possible confounders in children in arsenic-impacted communities.
- Beamer, P. I., Klimecki, W. T., Loh, M., Van Horne, Y. O., Sugeng, A. J., Lothrop, N., Billheimer, D., Guerra, S., Lantz, R. C., Canales, R. A., & Martinez, F. D. (2016). Response to García-Nieto et al. Comments on Beamer et al. Association of Children's Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media. Int. J. Environ. Res. Public Health 2016, 13, 521. International journal of environmental research and public health, 13(10).More infoWe would like to thank the editors for providing us with the opportunity to respond to the points raised by Dr. García Nieto.[...].
- Berry, C. E., Billheimer, D., Jenkins, I. C., Lu, Z. J., Stern, D. A., Gerald, L. B., Carr, T. F., Guerra, S., Morgan, W. J., Wright, A. L., & Martinez, F. D. (2016). A Distinct Low Lung Function Trajectory from Childhood to the Fourth Decade of Life. American journal of respiratory and critical care medicine, 194(5), 607-12.More infoLow maximally attained lung function increases the risk of chronic obstructive pulmonary disease irrespective of the subsequent rate of lung function decline.
- Guerra, S., Vasquez, M. M., Spangenberg, A., Halonen, M., & Martin, R. J. (2016). Club cell secretory protein in serum and bronchoalveolar lavage of patients with asthma. The Journal of allergy and clinical immunology, 138(3), 932-934.e1.
- Joubert, B. R., Felix, J. F., Yousefi, P., Bakulski, K. M., Just, A. C., Breton, C., Reese, S. E., Markunas, C. A., Richmond, R. C., Xu, C., Küpers, L. K., Oh, S. S., Hoyo, C., Gruzieva, O., Söderhäll, C., Salas, L. A., Baïz, N., Zhang, H., Lepeule, J., , Ruiz, C., et al. (2016). DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. American journal of human genetics, 98(4), 680-96.More infoEpigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
- 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.More infoExercise 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.
- Vasquez, M. M., Hu, C., Roe, D. J., Chen, Z., Halonen, M., & Guerra, S. (2016). Least absolute shrinkage and selection operator type methods for the identification of serum biomarkers of overweight and obesity: simulation and application. BMC medical research methodology, 16(1), 154.More infoThe study of circulating biomarkers and their association with disease outcomes has become progressively complex due to advances in the measurement of these biomarkers through multiplex technologies. The Least Absolute Shrinkage and Selection Operator (LASSO) is a data analysis method that may be utilized for biomarker selection in these high dimensional data. However, it is unclear which LASSO-type method is preferable when considering data scenarios that may be present in serum biomarker research, such as high correlation between biomarkers, weak associations with the outcome, and sparse number of true signals. The goal of this study was to compare the LASSO to five LASSO-type methods given these scenarios.
- 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.More infoA 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.
- Balcells, E., Gimeno-Santos, E., de Batlle, J., Ramon, M. A., Rodríguez, E., Benet, M., Farrero, E., Ferrer, A., Guerra, S., Ferrer, J., Sauleda, J., Barberà, J. A., Agustí, À., Rodriguez-Roisin, R., Gea, J., Antó, J. M., & Garcia-Aymerich, J. (2015). Characterisation and prognosis of undiagnosed chronic obstructive pulmonary disease patients at their first hospitalisation. BMC pulmonary medicine, 15, 4.More infoUnder-diagnosis of COPD is an important unmet medical need. We investigated the characteristics and prognosis of hospitalised patients with undiagnosed COPD.
- Bousquet, J., Anto, J. M., Wickman, M., Keil, T., Valenta, R., Haahtela, T., Lodrup Carlsen, K., van Hage, M., Akdis, C., Bachert, C., Akdis, M., Auffray, C., Annesi-Maesano, I., Bindslev-Jensen, C., Cambon-Thomsen, A., Carlsen, K. H., Chatzi, L., Forastiere, F., Garcia-Aymerich, J., , Gehrig, U., et al. (2015). Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis. Allergy, 70(9), 1062-78.More infoAllergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.
- Chan, J. Y., Stern, D. A., Guerra, S., Wright, A. L., Morgan, W. J., & Martinez, F. D. (2015). Pneumonia in childhood and impaired lung function in adults: a longitudinal study. Pediatrics, 135(4), 607-16.More infoDiminished lung function and increased prevalence of asthma have been reported in children with a history of early lower respiratory illnesses (LRIs), including pneumonia. Whether these associations persist up to adulthood has not been established.
- Donaire-Gonzalez, D., Gimeno-Santos, E., Balcells, E., de Batlle, J., Ramon, M. A., Rodriguez, E., Farrero, E., Benet, M., Guerra, S., Sauleda, J., Ferrer, A., Ferrer, J., Barberà, J. A., Rodriguez-Roisin, R., Gea, J., Agustí, A., Antó, J. M., & Garcia-Aymerich, J. (2015). Benefits of physical activity on COPD hospitalisation depend on intensity. The European respiratory journal, 46(5), 1281-9.More infoThe present study aims to disentangle the independent effects of the quantity and the intensity of physical activity on the risk reduction of chronic obstructive pulmonary disease (COPD) hospitalisations.177 patients from the Phenotype Characterization and Course of COPD (PAC-COPD) cohort (mean±sd age 71±8 years, forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro 2 Armband accelerometer (BodyMedia, Pittsburgh, PA, USA) for eight consecutive days, providing data on quantity (steps per day, physically active days and daily active time) and intensity (average metabolic equivalent tasks) of physical activity. Information on COPD hospitalisations during follow-up (2.5±0.8 years) was obtained from validated centralised datasets. During follow-up 67 (38%) patients were hospitalised. There was an interaction between quantity and intensity of physical activity in their effects on COPD hospitalisation risk. After adjusting for potential confounders in the Cox regression model, the risk of COPD hospitalisation was reduced by 20% (hazard ratio (HR) 0.79, 95% CI 0.67-0.93; p=0.005) for every additional 1000 daily steps at low average intensity. A greater quantity of daily steps at high average intensity did not influence the risk of COPD hospitalisations (HR 1.01, p=0.919). Similar results were found for the other measures of quantity of physical activity. Greater quantity of low-intensity physical activity reduces the risk of COPD hospitalisation, but high-intensity physical activity does not produce any risk reduction.
- Guerra, S., Halonen, M., Vasquez, M. M., Spangenberg, A., Stern, D. A., Morgan, W. J., Wright, A. L., Lavi, I., Tarès, L., Carsin, A., Dobaño, C., Barreiro, E., Zock, J., Martínez-Moratalla, J., Urrutia, I., Sunyer, J., Keidel, D., Imboden, M., Probst-Hensch, N., , Hallberg, J., et al. (2015). Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study. The Lancet. Respiratory medicine, 3(8), 613-20.More infoLow concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population.
- Huang, S., Vasquez, M. M., Halonen, M., Martinez, F. D., & Guerra, S. (2015). Asthma, airflow limitation and mortality risk in the general population. The European respiratory journal, 45(2), 338-46.More infoAsthma and chronic obstructive pulmonary disease co-exist in a significant proportion of patients. Whether asthma increases mortality risk among subjects with airflow limitation remains controversial. We used data from 2121 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease cohort. At enrolment (1972-1973), participants completed questionnaires and lung function tests. Participants were categorised into four groups based on the combination of airflow limitation (AL; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)
- Kubesch, N. J., de Nazelle, A., Westerdahl, D., Martinez, D., Carrasco-Turigas, G., Bouso, L., Guerra, S., & Nieuwenhuijsen, M. J. (2015). Respiratory and inflammatory responses to short-term exposure to traffic-related air pollution with and without moderate physical activity. Occupational and environmental medicine, 72(4), 284-93.More infoExposure to traffic-related air pollution (TRAP) has been associated with adverse respiratory and systemic outcomes. Physical activity (PA) in polluted air may increase pollutant uptake and thereby health effects. The authors aimed to determine the short-term health effects of TRAP in healthy participants and any possible modifying effect of PA.
- Kubesch, N., De Nazelle, A., Guerra, S., Westerdahl, D., Martinez, D., Bouso, L., Carrasco-Turigas, G., Hoffmann, B., & Nieuwenhuijsen, M. J. (2015). Arterial blood pressure responses to short-term exposure to low and high traffic-related air pollution with and without moderate physical activity. European journal of preventive cardiology, 22(5), 548-57.More infoShort-term exposure to traffic-related air pollution (TRAP) has been associated with adverse cardiovascular outcomes. Physical activity (PA) in polluted air may increase pollutant uptake and increase these effects.
- Lange, P., Celli, B., Agustí, A., Boje Jensen, G., Divo, M., Faner, R., Guerra, S., Marott, J. L., Martinez, F. D., Martinez-Camblor, P., Meek, P., Owen, C. A., Petersen, H., Pinto-Plata, V., Schnohr, P., Sood, A., Soriano, J. B., Tesfaigzi, Y., & Vestbo, J. (2015). Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. The New England journal of medicine, 373(2), 111-22.More infoChronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms.
- Parthasarathy, S., Vasquez, M. M., Halonen, M., Bootzin, R., Quan, S. F., Martinez, F. D., & Guerra, S. (2015). Persistent insomnia is associated with mortality risk. The American journal of medicine, 128(3), 268-75.e2.More infoInsomnia has been associated with mortality risk, but whether this association is different in subjects with persistent vs intermittent insomnia is unclear. Additionally, the role of systemic inflammation in such an association is unknown.
- Pinart, M., Albang, R., Maier, D., Duran-Tauleria, E., Mena, G., Gimeno-Santos, E., Solà, I., Garcia-Aymerich, J., Guerra, S., Stein, R. T., Benet, M., Carlsen, K., Herr, M., Jacquemin, B., Momas, I., Pin, I., Rancière, F., Smit, H. A., Varraso, R., , Bonfill, X., et al. (2015). Systematic Review on the Definition of Allergic Diseases in Children: The MeDALL Study. International archives of allergy and immunology, 168(2), 110-21.More infoDuring the last decades, a large number of phenotypes and disease classifications of allergic diseases have been proposed. Despite the heterogeneity across studies, no systematic review has been conducted on phenotype classification and the criteria that define allergic diseases. We aimed to identify clinically expressed, population-based phenotypes of allergic diseases and their interrelationships, to explore disease heterogeneity and to evaluate the measurements employed in disease diagnosis.
- Rava, M., Le Moual, N., Dumont, X., Guerra, S., Siroux, V., Jacquemin, B., Kauffmann, F., Bernard, A., & Nadif, R. (2015). Serum club cell protein 16 is associated with asymptomatic airway responsiveness in adults: Findings from the French epidemiological study on the genetics and environment of asthma. Respirology (Carlton, Vic.), 20(8), 1198-205.More infoClub cell secretory protein (CC-16) is a sensitive biomarker of airways epithelium integrity. It has gained interest as a biological marker in chronic lung diseases because of its presumed relationship to inflammation. Little is known about the association between CC-16 serum level and asthma, lung function and airway responsiveness (AR).
- Tischer, C., Zock, J., Valkonen, M., Doekes, G., Guerra, S., Heederik, D., Jarvis, D., Norbäck, D., Olivieri, M., Sunyer, J., Svanes, C., Täubel, M., Thiering, E., Verlato, G., Hyvärinen, A., & Heinrich, J. (2015). Predictors of microbial agents in dust and respiratory health in the Ecrhs. BMC pulmonary medicine, 15, 48.More infoDampness and mould exposure have been repeatedly associated with respiratory health. However, less is known about the specific agents provoking or arresting health effects in adult populations. We aimed to assess predictors of microbial agents in mattress dust throughout Europe and to investigate associations between microbial exposures, home characteristics and respiratory health.
- Guerra, S. (2015, September). Early life risk factors and COPD: is the evidence enough?. Annual Congress of the European Respiratory Society. Amsterdam, The Netherlands: European Respiratory Society.
- Carr, T., Stern, D., Guerra, S., Wright, A., Halonen, M., & Martinez, F. (2017, May). Lung function deficits to age 32 are associated with history of transient wheeze during RSV-positive lower respiratory illness. 2017 ATS Conference.
- Ledford, J., Guerra, S., others, ., & Kraft, M. (2017, May). The Role of Club Cell Secretory Protein During Mycoplasma Pneumoniae Pulmonary Infection. 2017 ATS Conference.
- Ledford, J., others, ., Guerra, S., others, ., & Kraft, M. (2017, May). Club Cell Secretory Protein Deficiency Leads to Altered Lung Function in Naive Mice. 2017 ARS Conference.
- Lothrop, N., others, ., Guerra, S., others, ., & Beamer, P. (2017, Fall). Modeling Historic Air Pollution Concentrations with Land Use Regression in Tucson, AZ. 2017, International Society of Exposure Science Conference.
- Xu, C., others, ., Guerra, S., others, ., & Koppelman, G. (2017, Fall). Epigenome wide Meta-analysis Reveals DNA Hypomethylation Patterns Associated With Asthma Throughout Childhood. 10th World Congress on Developmental Origins of Health and Disease (Oct 15-18), Rotterdam, The Netherlands.
- Xu, C., others, ., Guerra, S., others, ., & Koppelman, G. (2017, May). Large Scale Epigenome wide Meta-analysis Reveals DNA Hypomethylation Patterns Associated With Asthma Throughout Childhood. 2017 ATS Conference.
- Alsuheel Asseri, A., others, ., Guerra, S., others, ., & Morgan, W. J. (2016, September). Impulse Oscillometry Compared to Spirometry in Adults with a History of Bronchitis. CHEST (American College of Chest Physicians) meeting, Los Angeles, CA.
- DeVries, A., others, ., Guerra, S., others, ., & Vercelli, D. (2016, May). Neonatal SMAD3 promoter hypermethylation predicts asthma in children of asthmatic mothers from three birth cohorts. American Thoracic Society International Conference, San Francisco, CA.
- Vasquez, M., others, ., & Guerra, S. (2016, May). Circulating Biomarkers of Smoking and Lung Function Deficits. American Thoracic Society International Conference, San Francisco, CA.
- Vasquez, M., others, ., Guerra, S., & Parthasarathy, S. (2016, May). Positive Airway Pressure Therapies and Hospitalization Risk in Chronic Obstructive Pulmonary Disease. American Thoracic Society International Conference, San Francisco, CA.
- Wright, A. L., others, ., Guerra, S., others, ., & Martinez, F. D. (2016, May). Protective Effect of Exclusive Breastfeeding on Frequent Cough in Adulthood. American Thoracic Society International Conference, San Francisco, CA.
- Beamer, P., Guerra, S., Lothrop, N., Stern, D., Lu, Z., Billheimer, D. D., Halonen, M., Wright, A. L., & Martinez, F. (2015, May). Childhood CC16 Levels are Associated with Diesel Exposure at Birth. American Thoracic Society International Conference.
- Berry, C. E., Lu, Z. J., Jenkins, I. C., Billheimer, D., Stern, D. A., Gerald, L. B., Carr, T. F., Guerra, S., Wright, A. L., Morgan, W. J., & Martinez, F. D. (2015, May). Lung Function Trajectories in the Tucson Children's Respiratory Study. American Thoracic Society. Denver, CO: American Thoracic Society.
- Dijk, N., Co-authors, O., Guerra, S., Co-authors, O., & Koppelman, G. L. (2015, May). (Epi)genetic Regulation of Expression of IL1RL1 mRNA and IL1RL1-a Protein Levels in Asthma. American Thoracic Society International Conference.
- Hiranrattana, A., Stern, D., Guerra, S., Halonen, M., Wright, A. L., Martinez, F., & Morgan, W. J. (2015, May). Alternaria Sensitization is Associated with Increased Airway Reactivity in Overweight/Obese Non-Asthmatics. American Thoracic Society International Conference.
- Parthasarathy, S., Vasquez, M., Halonen, M., Martinez, F., & Guerra, S. (2015, May). Insomnia is Independently Associated with Hospitalization. American Thoracic Society International Conference.
- Sorino, C., Pedone, C., Guerra, S., & Scichilone, N. (2015, September). 15-years mortality in asthma-COPD overlap syndrome (ACOS) in an elderly population. Annual Congress of the European Respiratory Society. Amsterdam, The Netherlands: European Respiratory Society.
- Vasquez, M., Zhou, M., Hu, C., Martinez, F., & Guerra, S. (2015, May). Lung Function in Young Adult Life and Mortality Risk. American Thoracic Society International Conference.
- Voraphani, N., Guerra, S., Stern, D., Halonen, M., Wright, A. L., Morgan, W. J., & Martinez, F. (2015, May). Circulating CC16 In Childhood Differentiates Between Persistent And Remitting Severe Asthma In Adult Life. American Thoracic Society International Conference.
- Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Lodrup Carlsen, K. C., Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., , De Carlo, G., et al. (2016. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015(pp 1513-1525).More infoMeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.