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J Acquir Immune Defic Syndr. 2020 Jan 7. doi: 10.1097/QAI.0000000000002255. [Epub ahead of print]

Endothelial activation, innate immune activation, and inflammation are associated with post-bronchodilator airflow limitation and obstruction among adolescents living with HIV.

Author information

1
University of Washington, Division of Pulmonary, Critical Care and Sleep Medicine, Seattle, WA.
2
University of Washington, International Respiratory and Severe Illness Center, Seattle, WA.
3
Fred Hutchinson Cancer Research Center, Clinical Research Center, Seattle, WA.
4
University of Washington, Department of Medicine, Seattle, WA.
5
University of Nairobi, Department of Paediatric and Child Health, Nairobi, Kenya.
6
University of Washington, Department of Global Health, Seattle, WA.
7
Coptic Hospital, Nairobi, Kenya.
8
Coptic Hope Center for Infectious Diseases, Nairobi, Kenya.
9
University of Washington, Department of Radiology and Cardiothoracic Imaging, Seattle, WA.
10
University of Washington, Department of Epidemiology, Seattle, WA.
11
VA Puget Sound Health Care System, Division of Pulmonary, Critical Care and Sleep Medicine, Seattle, WA.
12
University of Washington, Department of Pathology, Seattle, WA.
13
University of Washington, Department of Pharmacology, Seattle, WA.

Abstract

BACKGROUND:

Chronic inflammation, innate immune activation, T-cell imbalance and endothelial activation have been linked with lung diseases. We sought to determine whether markers of these pathophysiologic pathways were associated with spirometry and chest CT abnormalities among adolescents living with HIV (ALWH).

SETTING:

Coptic Hope Center for Infectious Diseases in Nairobi, Kenya METHODS:: We performed a cross-sectional study of ALWH (10-19 years old). Participants underwent chest CT, spirometry and venipuncture for serum biomarkers. We also collected demographic, anthropometric, T-cell subset, antiretroviral therapy, and exposure data. We compared characteristics and biomarkers by airflow obstruction (post-bronchodilator FEV1/FVC z-score [zFEV1/FVC] < -1.64). We used multivariable linear regression to determine associations of log10-transformed biomarkers and chest CT abnormalities with lower post-bronchodilator zFEV1/FVC (airflow limitation). We performed exploratory principal components analysis on biomarkers, and determined associations of factors with post-bronchodilator zFEV1/FVC and chest CT abnormalities.

RESULTS:

Of 47 participants with acceptable quality spirometry, 21 (45%) were female, median age was 13 years and 96% had perinatally-acquired HIV. Median CD4 was 672 cells/┬ÁL. Overall, 28% had airflow obstruction and 78% had a chest CT abnormality; airflow obstruction was associated with mosaic attenuation (p=0.001). Higher endothelial activation (sVCAM-1, sICAM-1), inflammation and innate immune activation (SAA, sTREM-1, sCD163), and T-cell imbalance (lower CD4/CD8) markers were associated with airflow limitation. Factors comprising endothelial and innate immune activation were associated with airflow limitation.

CONCLUSIONS:

Endothelial activation, innate immune activation, T-cell imbalance, and chronic inflammation are associated with airflow limitation and obstruction, providing insights into chronic lung disease pathophysiology among ALWH.

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