Asthma, Airways & the Environment Research
The Division of Pulmonary, Critical Care, and Sleep Medicine implemented its research and treatment program for asthma, airways, and the environment at a time when New York City had the highest asthma morbidity and mortality rates in the country.
Our research and resulting environmental advocacy provided the basis for our response to the environmental disaster created by the destruction of the World Trade Center (WTC) towers in 2001.
The William N. Rom Environmental Lung Disease Laboratory, named in honor of our former division director, supports basic research and clinical studies on WTC-related lung diseases—asthma among them. For more information about this laboratory, see our World Trade Center research program.
Recent areas of study in our division include asthma genetics and immunology.
Genetic Studies in Asthma
Joan Reibman, MD, principal investigator, has conducted several asthma clinical trials with the American Lung Association’s Airways Clinical Research Centers (formerly the Asthma Clinical Research Centers). She also studies mucosal immunity, focusing on the effects of ambient particulate matter such as diesel exhaust particles.
Dr. Reibman’s laboratory performed the first studies demonstrating the interaction of pollutants with the human airway epithelium and airway dendritic cells that lead to a T helper type 2 (Th2) immune response supportive of asthma. Her laboratory was also the first to describe the interaction between pollutants and Th2-promoting cytokines, including thymic stromal lymphopoietin (TSLP), which is now being targeted in clinical trials on asthma.
In collaboration with Angeliki Kazeros, MD, Dr. Reibman developed techniques to enrich airway epithelial cells and dendritic cells from induced sputum, making possible noninvasive studies of discrete cell populations in airway immune responses in asthma. Together with Adriana Heguy, PhD, director of the Genome Technology Center, Dr. Reibman harnesses this technique for single-cell analyses to support studies on mucosal immunity in asthma and precision medicine.
Dr. Reibman and her team created a gene and protein bank of samples obtained from approximately 1,000 asthma patients and control subjects.
The research team, together with biostatisticians Yongzhao Shao, PhD, in the Department of Population Health, and Mengling Liu, PhD, in the Department of Medicine’s Division of Environmental Medicine, conduct studies to address hypotheses related to the microbiome and asthma, distinct biological asthma phenotypes, and gene–environment interactions that influence asthma susceptibility and severity in diverse populations.
Numerous fellows have contributed in Dr. Reibman’s research, which includes assessments of the effects of immunoglobulin E (IgE) regulation on the airway epithelium, the genetics of asthma, and associations between WTC exposures and sleep disruption.
Rakowski E … Reibman J. Variability of blood eosinophils in patients in a clinic for severe asthma. Clin Exp Allergy. 2019. DOI.
Reibman J … Lucchini RG. Destruction of the World Trade Center towers. Lessons learned from an environmental health disaster. Ann Am Thorac Soc. 2016. DOI.
Song X … Wei Y. A general and robust framework for secondary traits analysis. Genetics. 2016. DOI.
Bleck B … Reibman J. Coexpression of type 2 immune targets in sputum-derived epithelial and dendritic cells from asthmatic subjects. J Allergy Clin Immunol. 2015. DOI.
Inflammatory Lung Disease
Gabriele Grunig, DVM, principal investigator, published a seminal study in Science that describes the importance of interleukin 13 (IL-13) in the development of asthma. This cytokine is now a biotherapeutic target, and drugs that neutralize IL-13 are in clinical trials to determine their effects on several lung diseases, including asthma. Researchers in Dr. Grunig’s laboratory currently study immune mechanisms that promote inflammatory lung diseases associated with tissue remodeling and functional changes, such as asthma and pulmonary hypertension.
Studies in this laboratory also address cytokines and microRNAs that regulate the immune response and directly or indirectly control the behavior of endothelial cells and vascular smooth muscle cells in the lungs. The researchers’ long-range goal is to identify novel approaches to managing chronic inflammatory lung diseases and pulmonary hypertension.
Additional aims of research are evaluating the role of immune cells, such as T cells (Th2, Th17, T regulatory), conventional and plasmacytoid dendritic cells, B cells, eosinophils, and vascular cells (endothelial and smooth muscle cells), in inflammation and bronchospasm. Researchers use a variety of techniques involving knockout mice, specific inhibitors of cytokines, and microRNAs. Routine techniques in the laboratory include enzyme-linked immunosorbent assay analysis performed in single- or multianalyte formats, surface and intracellular flow cytometry, quantitative polymerase chain reaction analysis, and mouse model work, including right heart catheterization.
Grunig G … Pylawka S. Circulating microRNA markers for pulmonary hypertension in supervised exercise intervention and nightly oxygen intervention. 2018. Front Physiol. DOI.
Hemnes AR … Leopold JA; the PVDOMICS Study Group. PVDOMICS. A multi-center study to improve understanding of pulmonary vascular disease through phenomics. Circ Res. 2017. DOI.
Park SH … Grunig G. The effects of antigen-specific IgG1 antibody for the pulmonary-hypertension-phenotype and B cells for inflammation in mice exposed to antigen and fine particles from air pollution. PLoS One. 2015. DOI.