Pediatric Pulmonology

Investigating the Underlying Mechanisms of Asthma Morbidity in Urban School Children

    While therapies targeting type 2 inflammation are effective for many patients with asthma, there is a subset of children that continue to have exacerbations. Thus, there is a need to better understand the underlying mechanism of disease in these patients to develop more effective targeted therapies. Plasma interleukin six (IL-6) has been identified as a potential target for asthma treatment in obese adults with severe persistent asthma and metabolic dysfunction. However, less is known about its role in children.

    Perdita Permaul, MD, Section Chief of Pediatric Allergy & Immunology at NewYork-Presbyterian/Weill Cornell Medicine, has begun investigating the role of IL-6 in children with asthma. In prior studies, Dr. Permaul found that IL-6 appeared to be associated with a specific subset of children with asthma known as the obesity-related asthma phenotype. This phenotype is becoming more prevalent, particularly in inner-city environments, where various environmental exposures may exacerbate asthma.

    Exploring the relationship between IL-6, indoor allergen exposures, and asthma outcomes

    Dr. Permaul worked with colleagues to examine the relationship between plasma IL-6, indoor allergen exposure, and asthma outcomes, and the results were published in the Journal of Allergy and Clinical Immunology. The study was conducted using data from the longitudinal School Inner-City Asthma Studies of 215 children with asthma who were recruited from inner-city elementary schools. Before starting the academic school year, each child completed a baseline evaluation that collected data on sociodemographic factors, asthma symptoms, body mass index (BMI), and fractional exhaled nitric oxide (FENO). Blood was collected to analyze plasma IL-6 levels. The children also completed skin prick testing to analyze allergen sensitization and spirometry to examine lung function. Each child was observed for one school year, and lung function was evaluated twice yearly. Additionally, vacuum dust samples were taken twice a year and assessed for allergens. As published previously, one of the most prevalent allergens was mouse allergen.

    We found that IL-6 in the blood seems to be associated with a higher BMI and worse asthma symptoms, and if exposed to mouse allergen, increases susceptibility to a decrease in your lung function. This is the first time it's been noted that there could be an interaction with indoor allergen exposure.

    — Dr. Perdita Permaul

    Additionally, the study found that IL-6 levels were associated with elevated blood neutrophil count and the inflammatory marker C-reactive protein (CRP). IL-6 was not associated with markers of type 2 inflammation, including allergic sensitization, FENO, or eosinophil count. Importantly, this study found that higher IL-6 levels were associated with increased asthma symptoms, and children with high IL-6 levels exposed to rising levels of mouse allergen had lower levels of lung function.

    This study highlights the importance of recognizing the many endophenotypes of asthma in children. Results from the study indicate that there is a distinct subset of children with asthma who are obese and don’t have allergic inflammation but rather neutrophilic inflammation. Unfortunately, we do not have good therapeutics or biologics for this subset of children. The hope is that this study can help inform future mechanistic studies on how IL-6 and other biomarkers cause airway inflammation in hopes of developing better therapies for these children. This study also highlights the importance of the environment in pediatric asthma. While schools have done a good job reducing allergens, environmental exposures may still lead to worsening asthma, especially in the inner city.

    As a next step, Dr. Permaul is partnering with Joshua Milner, MD, an allergist and immunologist at NewYork-Presbyterian/Columbia who is a leader in the field of discovery and immunopathogenesis of genetic diseases that lead to allergic symptoms, to look at IL-6 and other biomarkers in her cohort. Dr. Permaul has established a robust pediatric asthma cohort that is diverse not just in ethnicity and race but also in socioeconomic status and varying levels of asthma severity. As the population in New York City is very diverse, this cohort will benefit future asthma research targeting all child populations.

      Read More

      Akar-Ghibril N, Greco KF, Jackson-Browne M, Phipatanakul W, Permaul P. High plasma IL-6 levels may enhance the adverse effects of mouse allergen exposure in urban schools on asthma morbidity in children. J Allergy Clin Immunol. 2023;152(6):1677-1682. doi:10.1016/j.jaci.2023.06.027

      For more information

      Dr. Perdita Permaul
      Dr. Perdita Permaul
      [email protected]