BREATHE Studies: Biomarkers and Respiratory imaging in Adolescents – The Hope Center Experience
As increasing numbers of children living with HIV are surviving to adolescence in low- and middle-income countries (LMICs), chronic lung disease (CLD) is emerging as an important but poorly understood complication among adolescents living with HIV. In our early lung disease research involving over 400 people at the Coptic Hope Center for Infectious Diseases, we found that evidence of CLD was common and significantly more frequent in adolescents compared to adults living with HIV. Little is known about the etiologies, risk factors and mechanisms contributing to CLD in adolescents living with HIV in LMICs.
Together with the Coptic Hope Center for Infectious Diseases, the TREE team will examine differences in the prevalence, subtypes, risk factors and mechanisms of CLD among adolescents living with HIV and uninfected adolescents in Kenya. We will also measure elements of air pollution exposure to better understand the role of inhaled pollutants in CLD and HIV infection. In addition, we will compare and contrast the prevalence, subtypes and related biomarkers of chronic inflammation, immune activation, immune imbalance and endothelial activation among adolescents living with HIV in Kenya (at the Hope Center) and in the U.S. (Pediatric HIV/AIDS Cohort Study [PHACS]).
TREE is implementing an NHLBI/NIH-funded prospective observational study (BREATHE II: Biomarkers and REspiratory imaging in Adolescents – The Hope Center Experience) at the Coptic Hope Center to achieve the overarching project goals. We will determine the role of HIV on manifestations and progression of CLD, considering the complex interplay with risk factors including malnutrition, indoor biofuel burning and smoking. To gain mechanistic insights, we will evaluate whether HIV severity, and biomarkers of chronic immune activation and inflammation are associated with – and potentially account for – increased prevalence and progression of CLD in these adolescents. CLD subtypes will be defined clinically based on published criteria and patterns of abnormal spirometry (a measure of lung function). Among adolescents living with HIV, CLD will be further characterized with baseline chest CTs. Risk factor exposure at baseline and over time will be obtained from standardized questionnaires. HIV-related variables will be extracted from Coptic Hope Center records.
The Fred Hutch/University of Washington Center for AIDS Research (CFAR) is supporting collection of air pollution exposure data in the BREATHE II cohort. We will measure personal monitor fine particulate matter (PM2.5) and carbon monoxide levels, ground-level PM2.5 and other pollutants and satellite-level PM2.5. We will then determine associations of these quantitative air pollution data with CLD outcomes, including respiratory symptoms and spirometry.
We will examine differences between the prevalence, subtypes and underlying mechanisms of CLD among youth living with HIV in Kenya and the U.S. in analyses supported by PHACS. We will leverage data collected in the BREATHE II Study and PHACS pulmonary substudy, and harmonize serum biomarker data to understand CLD in adolescents living with HIV in multiple diverse settings.
a) Attia EF, Weiss NS, Maleche-Obimbo E, McGrath CJ, Cagle A, West TE, Attwa M, El Antouny N, Crothers K, Chung MH. Risk factors for hypoxia and tachypnea among adolescents with vertically-acquired HIV in Nairobi. Pediatr Infect Dis J. 2017;36(4):e93-e97. PMCID: PMC5348269
b) Attia EF, Maleche-Obimbo E, West TE, Yatich N, Ndukwe-Wambutsi L, Kiptinness C, Cagle A, McGrath C, Eskander S, El Antouny NG, Chung MH, Crothers K. Adolescent age is an independent risk factor for abnormal spirometry among HIV-infected individuals in Kenya. AIDS. 2018;32:1353-1359. PMCID: PMC6834296
c) Attia EF, Bhatraju PK, Triplette M, Kosamo S, Maleche-Obimbo E, West TE, Richardson B, Zifodya JS, Eskander S, Njiru CD, Warui D, Kicska GA, Chung MH, Crothers K, Liles WC, Graham SM. Endothelial activation, innate immune activation, and inflammation are associated with post-bronchodilator airflow limitation and obstruction among adolescents living with HIV. J Acquir Immune Defic Syndr. 2019. In Press
These studies were led by Dr. Engi Attia and conducted in collaboration with Dr. Kristina Crothers (UW), Dr. Michael Chung (AKU), Prof. Elizabeth Maleche-Obimbo (University of Nairobi) and Dr. T. Eoin West (UW).