The Celedón Lab for Pediatric Asthma Research

Decoding the Enigmatic Causes of Asthma

The most common serious chronic disease in infants and children, asthma is caused by many factors, including genetics and environmental and behavioral factors such as diet, obesity, chronic stress, air pollution and more. Today, researchers are in the early stages of understanding these causes, and their precise relationship to pediatric asthma. Pulmonologist and genetic epidemiologist Juan C. Celedón, MD, DrPH, and his team have taken a leadership role in the identification of genetic factors and environmental exposures that influence the development of asthma and chronic obstructive pulmonary disease (COPD), particularly in ethnic minorities.

DNA Dr. Celedón’s team first identified MMP12 and TSLP as susceptibility genes for asthma- or COPD-phenotypes in humans, while also showing that racial ancestry partly explains marked differences in the burden of asthma and COPD between Puerto Ricans and Mexicans – the Hispanic paradox.

Moreover, Dr. Celedón’s group conducted the first epigenome-wide association study (EWAS) of atopy and atopic asthma in DNA from nasal (airway) epithelium from diverse youth in three cohorts, identifying DNA methylation changes that affect the expression of regulatory genes for epithelial integrity and immune responses, and accurately classify atopic asthma in youth. More recently, Dr. Celedón’s team showed that nasal epithelial transcriptomic profiles identify three asthma endotypes in youth, and that, contrary to prior assumptions, T2-low asthma endotypes are more common than T2-high asthma in school-aged children and young adults from predominantly minoritized groups. Such findings are paradigm-shifting and have major implications for identifying endotype-specific risk factors and developing biomarkers and novel therapeutic agents in asthma.

Dr. Celedón’s team first reported that child maltreatment is associated with asthma, and that a child maltreatment-asthma association in adults is substantially mediated by major depressive disorder and generalized anxiety disorder. Further, they have shown that violence-related distress and depression are associated with asthma and reduced bronchodilator responsiveness across life stages. Moreover, Dr. Celedón’s group first showed that post-traumatic stress disorder is associated with new-onset asthma in heavily traumatized adults. Such findings support a role for psychosocial stressors and stress-related disorders in the pathogenesis of asthma in children and adults. Based on this work and studies in omics (see above), Dr. Celedón’s team is now examining whether changes in DNA methylation and/or gene expression induced by violence or stress lead to persistent or new-onset asthma in young Puerto Rican adults, reduced response to treatment for asthma in minoritized children, and worse asthma outcomes in youth and adults.

Dr. Celedón’s team first demonstrated that overweight/obesity is associated with reduced response to inhaled corticosteroids in children with asthma, and then showed that overweight/obesity is associated with asthma in children with normal fractional exhaled nitric oxide (FeNO), but not in those with increased FeNO. More recently, they showed that obesity is associated with airway dysanapsis, and that this is linked to severe asthma exacerbations in obese children. These results support those of experimental models showing that obesity can lead to asthma through non-allergic mechanisms.

After conducting several observational studies, Dr. Celedón’s group led the first randomized placebo-controlled trial of vitamin D supplementation to prevent severe asthma exacerbations in children with low vitamin D levels, which showed no benefit in children with vitamin D levels of 14-29 ng/ml (comprising most children with vitamin D levels <30 ng/ml in the U.S.). This has helped to markedly reduce routine testing of vitamin D levels in children with asthma.

The research of the Celedón Lab combines population-based investigations plus basic laboratory research. Members of the team are currently focused on these three subject areas:

The Relationship Between Stress and Asthma
Genetics and The Hispanic Paradox
Precision Medicine in Asthma

The Celedón Lab collects data from human populations, which is studied and further analyzed in the context of its genome-wide laboratory studies, resulting in conclusions that may lead to new and novel treatments for these pulmonary conditions.

Clinical research activities of the Celedon Lab are listed below. Select a study to review a brief description and requirements. Parents or guardians of children who might be eligible are encouraged to inquire about enrollment. Contact information is listed at the end of each study. If you want to know more about the process of enrolling in a clinical study, please visit Frequently Asked Questions. Thank you for exploring these opportunities and helping us to expand our understanding of childhood asthma and its treatment.

The Relationship Between Violence, Chronic Stress and Asthma

Based on prior work in children and adults and with funding from the National Institutes of Health, Dr. Celedón is now examining whether changes in DNA methylation and/or gene expression induced by exposure to violence or chronic stress leads to asthma, reduced response to treatment, and worse asthma outcomes in minoritized children and adults.

Genetics and The Hispanic Paradox

Dr. Celedón’s Lab was the first to identify MMP12 and TSLP as susceptibility genes for asthma or chronic obstructive pulmonary disease (COPD) phenotypes in humans. The Lab has also shown that racial ancestry partly explains marked differences in the burden of asthma and COPD between Puerto Ricans and Mexicans, what is known as the Hispanic paradox. In particular, the discovered that African ancestry is inversely related to lung function in Puerto Rican children, but that Native American ancestry is positively related to lung function and inversely related to COPD in New Mexican Hispanics and Costa Ricans.

On the basis of this work, Dr. Celedón’s Lab is now conducting National Institutes of Health-funded studies of the genetics and “omics” of airway diseases in Hispanic subgroups, including Puerto Ricans and Dominicans.

Precision Medicine in Asthma

UPMC Children's has about 2,700 emergency department visits and 13,000 hospitalizations for asthma per year. Yet, there is no effective tools to predict severe asthma attacks and poor asthma-related outcomes. Moreover, even though several monoclonal antibodies (collectively called “biologics”) has been proved in the past few years, there is no adequate biomarkers to predict response. Dr. Celedón’s Lab is currently leading a study to identify biomarkers of risk of severe asthma exacerbations, lung function, and response biologics in children and adolescents with asthma.

Juan Celedón, MD, DrPH

Principal Investigator
juan.celedon@chp.edu
Read more »

Franziska Rosser, MD, MPH, FAAP
Physician Scientist
franziska.rosser2@chp.edu

Kristina M. Gaietto, MD
Physician Scientist
kristina.gaietto@chp.edu

Wei Chen, PhD
Statistical Geneticist
wec47@pitt.edu

Yueh-Ying Han, PhD
Epidemiologist and Data Manager
hany2@upmc.edu

Soyeon Kim, PhD
Statistical Geneticist
soyeon.kim21@chp.edu

Christopher M. Qoyawayma
Lab Manager
qoyawaymacm2@upmc.edu

Barbara Newton
Senior Administrative Assistant
newtonba@upmc.edu

The Effects of Violence and Related Stress on Asthma.
Han YY, Celedón JC.
Ann Allergy Asthma Immunol.
2024 Jul

Long-Term PM2.5 Exposure and Upregulation of CLCA1 Expression in Nasal Epithelium from Youth with Asthma.
Rosser FJ, Yue M, Han YY, Forno E, Qoyawayma C, Manni ML, Acosta-Pérez E, Canino G, Chen W, Celedón JC.
Ann Am Thorac Soc.
2024 Jul

Persistent cat ownership and asthma in a longitudinal study of Puerto Rican youth.
Mishra PE, Han YY, Hill K, Rosser FJ, Forno E, Acosta-Pérez E, Canino G, Celedón JC.
Ann Allergy Asthma Immunol.
2024 Jun

Social vulnerability index, poverty, and asthma in a prospective study of Puerto Rican youth.
Han YY, Rosser FJ, Acosta-Pérez E, Canino G, Celedón JC.
Ann Allergy Asthma Immunol.
2024 May

Health literacy and asthma: An update.
Han YY, Gutwein A, Apter A, Celedón JC.
J Allergy Clin Immunol.
2024 May

Socioeconomic status, diet, and recurrent severe asthma exacerbations in Puerto Rican youth.
Gaietto K, Han YY, Rosser FJ, Acosta-Pérez E, Forno E, Canino G, Celedón JC.
J Allergy Clin Immunol Glob.
2024 Jan

Nasal epithelial gene expression and total IgE in children and adolescents with asthma.
Xu Z, Forno E, Sun Y, Manni ML, Han YY, Kim S, Yue M, Vonk JM, Kersten ETM, Acosta-Perez E, Canino G, Koppelman GH, Chen W, Celedón JC.
J Allergy Clin Immunol.
2024 Jan

T2-low asthma in school-aged children: unacknowledged and understudied.
Mishra PE, Melén E, Koppelman GH, Celedón JC.
Lancet Respir Med.
2023 Dec

Adverse Events during Adulthood, Child Maltreatment, and Asthma among British Adults in the UK Biobank.
Han YY, Chen W, Forno E, Celedón JC.
Ann Am Thorac Soc.
2023 Nov

Cis- and trans-eQTM analysis reveals novel epigenetic and transcriptomic immune markers of atopic asthma in airway epithelium.
Kim S, Xu Z, Forno E, Qin Y, Park HJ, Yue M, Yan Q, Manni ML, Acosta-Pérez E, Canino G, Chen W, Celedón JC.
J Allergy Clin Immunol.
2023 Oct

Long-Term Exposure to Particulate Matter <2.5 μm and Lung Function Change in Children with Asthma Receiving Inhaled Corticosteroids.
Rosser FJ, Han YY, Forno E, Guilbert TW, Bacharier LB, Phipatanakul W, Goobie GC, Nouraie SM, Martinez M, Celedón JC.
Am J Respir Crit Care Med.
2023 Sep

Gas stove use and asthma in a longitudinal study of Puerto Rican children and adolescents.
Han YY, Rosser F, Forno E, Acosta-Pérez E, Canino G, Celedón JC.
J Allergy Clin Immunol Pract.
2023 Aug

Air Quality Index and Childhood Asthma: A Pilot Randomized Clinical Trial Intervention.
Rosser FJ, Rothenberger SD, Han YY, Forno E, Celedón JC.
Am J Prev Med.
2023 Jun

Low parental numeracy and severe asthma exacerbations in a prospective study of Puerto Rican youth.
Gutwein A, Han YY, Colón-Semidey A, Alvarez M, Acosta-Pérez E, Forno E, Canino G, Apter A, Celedón JC.
Ann Allergy Asthma Immunol.
2023 Jun

The Celedón Lab is looking for talented post-doctoral fellows and graduate students interested in the identification of genetic factors and environmental exposures that influence the development of asthma and chronic obstructive pulmonary disease. Please contact Dr. Celedón via email if you are interested.