OBJECTIVE: The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons.
DESIGN: Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test.
METHODS: We performed linear regression of baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC and their longitudinal slopes on log2-transformed baseline biomarkers with adjustment for age, sex, race, region, smoking status, baseline CD4+ T-cell counts and baseline HIV-RNA. Biomarkers included D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-27, serum amyloid A, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, albumin and total bilirubin.
RESULTS: Among 903 included participants, baseline median age was 36 years, CD4+ cell count was 647 cells/μl, and 28.5% were current smokers. In adjusted analyses, elevated markers of systemic inflammation (hsCRP, IL-6 and serum amyloid A) were associated with lower baseline FEV1 and FVC. Elevated D-dimer and IL-6 were associated with worse airflow obstruction (lower FEV1/FVC). Despite these cross-sectional associations at baseline, no associations were found between baseline biomarkers and subsequent longitudinal lung function decline over a median follow-up time of 3.9 years (3293 spirometry-years of follow-up).
CONCLUSION: Commonly available biomarkers, in particular markers of systemic inflammation, are associated with worse cross-sectional lung function, but do not associate with subsequent lung function decline among HIV-positive persons with early HIV infection and baseline CD4 T-cell counts more than 500 cells/μl.
Bibliographical noteFunding Information:
G.C., J.V.B., M.C., E.L., V.P., D.E.N. and K.M.K. received grant support from the National Institutes of Health (R01 HL096453, UM1 AI068641 and UM1 AI120197) for conduct of this study.
The START Pulmonary Substudy reported here was supported by the National Heart Lung and Blood Institute (R01 HL096453); the parent START trial was primarily supported by the National Institute of Allergy and Infectious Diseases Division of AIDS (UM1 AI068641 and UM AI120197) with additional support from the German Ministry of Education and Research, the European AIDS Treatment Network (NEAT), the Australian National Health and Medical Research Council, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), National Research Foundation (Denmark) and the UK Medical Research Council and National Institute for Health Research. The Veterans Health Administration Office of Research and Development also provided protected research time in support of this study. The University of Minnesota served as sponsor of the study. None of the funders nor sponsor had any input regarding the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
- chronic obstructive pulmonary disease
- longitudinal studies
PubMed: MeSH publication types
- Journal Article