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1. Isolated abnormal diffusing capacity for carbon monoxide (iso↓DLco) is associated with increased respiratory symptom burden in people with HIV infection.

Author

Katerina L Byanova, Jessica Fitzpatrick, Amanda K Jan, Maggie McGing, Marlena Hartman-Filson, Carly K Farr, Michelle Zhang, Kendall Gardner, Jake Branchini, Robert Kerruish, Sharvari Bhide, Aryana Bates, Jenny Hsieh, Rebecca Abelman, Peter W Hunt, Richard J Wang, Kristina A Crothers, and Laurence Huang

Subjects
Medicine, Science
Abstract

ObjectivesAn isolated reduction in the diffusing capacity for carbon monoxide (DLco; iso↓DLco) is one of the most common pulmonary function test (PFT) abnormalities in people living with HIV (PWH), but its clinical implications are incompletely understood. In this study, we explored whether iso↓DLco in PWH is associated with a greater respiratory symptom burden.Study designCross-sectional analysis.MethodsWe used ATS/ERS compliant PFTs from PWH with normal spirometry (post-bronchodilator FEV1/FVC ≥0.7; FEV1, FVC ≥80% predicted) from the I AM OLD cohort in San Francisco, CA and Seattle, WA, grouped by DLco categorized as normal (DLco ≥lower limit of normal, LLN), mild iso↓DLco (LLN >DLco >60% predicted), and moderate-severe iso↓DLco (DLco ≤60% predicted). We performed multivariable analyses to test for associations between DLco and validated symptom-severity and quality of life questionnaires, including the modified Medical Research Council dyspnea scale (mMRC), the COPD Assessment Test (CAT), and St. George's Respiratory Questionnaire (SGRQ), as well as between DLco and individual CAT symptoms.ResultsMild iso↓DLco was associated only with a significantly higher SGRQ score. Moderate-severe iso↓DLco was associated with significantly higher odds of mMRC ≥2 and significantly higher CAT and SGRQ scores. PWH with moderate-severe iso↓DLco had increased odds of breathlessness, decreased activity, lower confidence leaving home, and less energy.ConclusionsIso↓DLco is associated with worse respiratory symptom scores, and this association becomes stronger with worsening DLco, suggesting that impaired gas exchange alone has a significant negative impact on the quality of life in PWH. Additional studies are ongoing to understand the etiology of this finding and design appropriate interventions.

Published
2023
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2. Markers of inflammation and immune activation are associated with lung function in a multi-center cohort of persons with HIV

Author

Laurence Huang, Daniela Moisi, Amanda K Jan, Carly K Farr, Diane Jeon, Eula Lewis, Robert Kerruish, Michael M. Lederman, Marlena Hartman-Filson, Richard J. Wang, Peter W. Hunt, Julia Moore, Maggie Mcging, and Kristina Crothers

Subjects
0301 basic medicine, Spirometry, medicine.medical_specialty, Vital capacity, Immunology, HIV Infections, Medical and Health Sciences, Gastroenterology, Article, chronic obstructive pulmonary disease, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, DLCO, Virology, Forced Expiratory Volume, Diffusing capacity, Internal medicine, Humans, Immunology and Allergy, Medicine, 030212 general & internal medicine, Lung, pulmonary disease, Inflammation, medicine.diagnostic_test, business.industry, Inflammatory and immune system, respiratory function tests, Psychology and Cognitive Sciences, Abnormal DLCO, biomarkers, HIV, Biological Sciences, respiratory system, medicine.disease, Obstructive lung disease, Good Health and Well Being, Cross-Sectional Studies, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, pulmonary gas exchange, Respiratory, HIV/AIDS, Biomarker (medicine), business, Biomarkers
Abstract

OBJECTIVES Studies have shown that people with HIV (PWH) may be at increased risk for chronic lung diseases and lung function abnormalities, which may be associated with immune activation. We tested the association of a panel of 12 immune activation and inflammation biomarkers with spirometry and single-breath diffusing capacity for carbon monoxide (DLco). DESIGN Cross-sectional, observational study. METHODS Participants were enrolled from the Inflammation, Aging, Microbes and Obstructive Lung Disease cohort of PWH at two US sites. Biomarkers were examined and standardized spirometry and DLco testing were performed. We tested associations between each biomarker and lung function, examined individually and in combination, using multi-variable linear and logistic regression. RESULTS Among 199 participants, median forced expiratory volume in 1 s (FEV1) was normal (90% predicted) and median DLco was abnormal (69% predicted). The most common lung function abnormality (57%) was a normal FEV1 to forced vital capacity ratio with an abnormal DLco of 80% or less predicted (iso↓DLco). Two markers (IL-6, high-sensitivity C-reactive protein) were associated with FEV1% predicted, whereas eight markers (soluble CD14, soluble CD163, inducible protein-10, soluble CD27, IL-6, soluble tumor necrosis factor receptors 1 and 2, D-dimer) were associated with DLco% predicted. Compared with those participants with normal spirometry and DLco, five markers (soluble CD14, soluble CD163, interferon gamma inducible protein-10, soluble tumor necrosis factor receptors 1 and 2) were associated with iso↓DLco. CONCLUSION Among PWH, different markers of immune activation and inflammation are associated with FEV1% predicted than with DLco% predicted and with an iso↓DLco, representing possible unique pathways of chronic lung disease. Identifying plausible drivers of these inflammatory pathways may clarify mechanisms underlying impaired lung function in HIV infection and may identify therapeutic avenues.

Published
2021
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