UA Study of HIV-Related Lung Diseases to Help Understanding of Pulmonary Immunity and Vaccine Responses

Dr. Kenneth S. Knox and his UA College of Medicine – Tucson research team aim to understand the causes of HIV-associated chronic obstructive pulmonary disease (COPD), pulmonary hypertension and immune reconstitution inflammatory syndrome (IRIS), funded by a grant from the National Heart, Lung, and Blood Institute.

People infected with human immunodeficiency virus (HIV)—the virus that causes AIDS—commonly develop lung disease, including chronic obstructive pulmonary disease (COPD), pulmonary hypertension and immune reconstitution inflammatory syndrome (IRIS).

Kenneth S. Knox, MD, and his research team at the University of Arizona College of Medicine – Tucson are studying the role of pulmonary inflammation in the development of HIV-related lung diseases, funded by a collaborative U01 grant from the National Heart, Lung, and Blood Institute.

“In HIV infection, despite improvement with highly active antiretroviral therapy (HAART), the lung immune system remains imbalanced,” said Dr. Knox, who serves as a principal investigator on the multiple-PI study, which involves researchers at the UA, Indiana University and the Jackson Laboratory for Genomic Medicine. “The study’s main hypothesis is that the presence of low-level HIV infection produces chronic inflammation in the lung which drives the late pulmonary complications associated with HIV.”

“The study also will examine other pulmonary viral reservoirs beyond HIV and thus is likely to have broad implications for our understanding of pulmonary immunity and vaccine responses,” continued Dr. Knox, UA associate professor of medicine and immunobiology and chief of the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine. He also holds The Murray and Clara Walker Memorial Endowed Research Chair in Emphysema and is a member of the University of Arizona Respiratory Center.

“This study is important since viruses, such as HIV, cause persistent antigenic stimulation leading to T cell deterioration with age and likely contribute to chronic pulmonary diseases,” said Janko Nikolich-Žugich, MD, PhD, chairman of the UA Department of Immunobiology, co-director of the University of Arizona Center on Aging, Elizabeth Bowman Professor in Medical Research at the UA College of Medicine – Tucson, and a member of the UA BIO5 Institute.

The study’s participating sites will develop an extensive data and biobank, with HIV-infected participants undergoing bronchoscopy with bronchoalveolar lavage (BAL, a “lung wash” done through an endoscope) and endobronchial brushings (procedures in which cells are taken from the inside of the airways that lead to the lungs), lung function testing and CT scanning. The data and biobank will be used by investigators to determine the causes of altered lung immunity at the cellular level.

The UA team includes Joyce Wu, PhD, assistant professor of immunobiology, and University of Arizona Respiratory Center members Cristine Berry, MD, MHS, assistant professor of medicine; Heidi Erickson, RN, senior research nurse; and Lance Nesbit, MS, senior research specialist.

Study collaborators include Homer L. Twigg III, MD, associate professor of medicine, Floyd and Reba Smith Investigator of Pulmonary Disease  and  chief of the Division of Pulmonary, Allergy, Critical Care and Occupational Medicine at Indiana University School of Medicine in Indianapolis and George Weinstock, PhD, professor and associate director of Microbial Genomics at the Jackson Laboratory for Genomic Medicine in Farmington, Conn.

The study, “Genomic Analysis of Immunity and Chronic Lung Inflammation in HIV Infection,” is one of eight funded under INHALD (Investigating HIV Associated Lung Disease) aimed at furthering collaborative and translational efforts to define the cellular and molecular events, including genetic factors, that cause HIV-associated lung diseases. This work is supported by a grant of $640,000 per year for five years from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH), Award Number U01HL121831.

Dr. Knox has maintained nearly continuous NIH funding since 2001 as PI or co-PI in the field of HIV T cell responses and mucosal immunity. The mucosal immune system protects mucous membranes against infection; mucous membranes chiefly line the respiratory, digestive and urogenital tracts. T cells are types of white blood cells that defend against pathogens such as viruses and bacteria.

He is nationally known for his research and clinical expertise in immunologic lung disease, sarcoidosis and fungal diagnostics. His nationally funded research utilizes BAL to study the mucosal lymphocyte response to a variety of infectious and inflammatory diseases including HIV, cytomegalovirus (CMV), endemic fungal pathogens and rheumatologic lung disease.