Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus

Sarath Raju; Trishul Siddharthan; Meredith C. McCormack; Sanjay R. Patel; Ken M. Kunisaki; Gypsyamber D'Souza; Joshua Hyong Jin Cho; Valentina Stosor; Alison Morris; Joseph B. Margolick; Todd T. Brown; Naresh M. Punjabi

doi:10.1513/AnnalsATS.202309-757OC

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus

Sarath Raju, Trishul Siddharthan, Meredith C. McCormack, Sanjay R. Patel, Ken M. Kunisaki, Gypsyamber D'Souza, Joshua Hyong Jin Cho, Valentina Stosor, Alison Morris, Joseph B. Margolick, Todd T. Brown, Naresh M. Punjabi^*

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

Abstract

Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DL_CO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DL_CO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DL_CO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DL_CO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [Sp_O2], 90% [T90]). Structural equation models were used to assess associations of impaired DL_CO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DL_CO impairment (,80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index > 30 events/h) and impaired DL_CO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir Sp_O2 (median difference, 28.2% [95% CI, 211.4% to 24.9%]) and average Sp_O2 during sleep (median difference, 21.1% [95% CI, 22.1% to 20.01%]) than those with severe SDB and preserved DL_CO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DL_CO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DL_CO to guide testing and risk stratification strategies.

Original language	English (US)
Pages (from-to)	1085-1093
Number of pages	9
Journal	Annals of the American Thoracic Society
Volume	21
Issue number	7
DOIs	https://doi.org/10.1513/AnnalsATS.202309-757OC
State	Published - Jul 2024

Funding

Supported by National Heart, Lung, and Blood Institute grants HL164151 (S.R.), HL143957 (S.R.), HL117167 (N.M.P.), HL146709 (N.M.P.), HL118414 (N.M.P.), and R01HL154860 (S.R. and M.C.M.). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health. MWCCS (principal investigators): Atlanta Clinical Research Site (CRS) (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos, David Hanna, and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D\u2019Souza, Stephen Gange, and Elizabeth Topper), U01-HL146193; Chicago\u2013Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky, Frank Palella, and Valentina Stosor), U01-HL146240; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels and Matthew Mimiaga), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; University of Alabama at Birmingham Medical School CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, Deborah Konkle-Parker, and James B. Brock), U01-HL146192; University of North Carolina CRS (Adaora Adimora and Michelle Floris-Moore), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute, with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Nursing Research, National Cancer Institute, National Institute on Alcohol Abuse and Alcoholism, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute on Minority Health and Health Disparities and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research. MWCCS data collection is also supported by grants UL1-TR000004 (University of California, San Francisco, Clinical and Translational Science Award [CTSA]), UL1-TR003098 (Johns Hopkins University Institute for Clinical and Translational Research), UL1-TR001881 (University of California, Los Angeles, Clinical and Translational Science Institute), P30-AI-050409 (Atlanta Center for AIDS Research [CFAR]), P30-AI-073961 (Miami CFAR), P30-AI-050410 (University of North Carolina CFAR), P30-AI-027767 (University of Alabama at Birmingham CFAR), P30-MH-116867 (Miami Center for HIV and Research in Mental Health), UL1-TR001409 (DC CTSA), KL2-TR001432 (DC CTSA), and TL1-TR001431 (DC CTSA). This material is also the result of work supported with resources and the use of facilities at the Minneapolis Veterans Affairs Medical Center, Minneapolis, MN. Supported by National Heart, Lung, and Blood Institute grants HL164151 (S.R.), HL143957 (S.R.), HL117167 (N.M.P.), HL146709 (N.M.P.), HL118414 (N.M.P.), and R01HL154860 (S.R. and M.C.M.). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health. MWCCS (principal investigators): Atlanta Clinical Research Site (CRS) (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos, David Hanna, and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D'Souza, Stephen Gange, and Elizabeth Topper), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky, Frank Palella, and Valentina Stosor), U01-HL146240; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels and Matthew Mimiaga), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; University of Alabama at Birmingham Medical School CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, Deborah Konkle-Parker, and James B. Brock), U01-HL146192; University of North Carolina CRS (Adaora Adimora and Michelle Floris-Moore), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute, with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Nursing Research, National Cancer Institute, National Institute on Alcohol Abuse and Alcoholism, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute on Minority Health and Health Disparities and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research. MWCCS data collection is also supported by grants UL1-TR000004 (University of California, San Francisco, Clinical and Translational Science Award [CTSA]), UL1-TR003098 (Johns Hopkins University Institute for Clinical and Translational Research), UL1-TR001881 (University of California, Los Angeles, Clinical and Translational Science Institute), P30-AI-050409 (Atlanta Center for AIDS Research [CFAR]), P30-AI-073961 (Miami CFAR), P30-AI-050410 (University of North Carolina CFAR), P30-AI-027767 (University of Alabama at Birmingham CFAR), P30-MH-116867 (Miami Center for HIV and Research in Mental Health), UL1-TR001409 (DC CTSA), KL2-TR001432 (DC CTSA), and TL1-TR001431 (DC CTSA). This material is also the result of work supported with resources and the use of facilities at the Minneapolis Veterans Affairs Medical Center, Minneapolis, MN. Data reported in this paper were collected for MACS, now the MWCCS (MACS/WIHS [Women's Interagency HIV Study] Combined Cohort Study). The authors gratefully acknowledge the contributions of the study participants and dedication of the staff at the MWCCS sites.

Keywords

impaired DL
impaired diffusing capacity of the lung for carbon monoxide
nocturnal hypoxemia
sleep-disordered breathing

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1513/AnnalsATS.202309-757OC

Cite this

Raju, S., Siddharthan, T., McCormack, M. C., Patel, S. R., Kunisaki, K. M., D'Souza, G., Cho, J. H. J., Stosor, V., Morris, A., Margolick, J. B., Brown, T. T., & Punjabi, N. M. (2024). Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus. Annals of the American Thoracic Society, 21(7), 1085-1093. https://doi.org/10.1513/AnnalsATS.202309-757OC

@article{b97b51f5d256430c8a21c74e060ca426,

title = "Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus",

abstract = "Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DLCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DLCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DLCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DLCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2], 90% [T90]). Structural equation models were used to assess associations of impaired DLCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DLCO impairment (,80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index > 30 events/h) and impaired DLCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, 28.2% [95% CI, 211.4% to 24.9%]) and average SpO2 during sleep (median difference, 21.1% [95% CI, 22.1% to 20.01%]) than those with severe SDB and preserved DLCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DLCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DLCO to guide testing and risk stratification strategies.",

keywords = "impaired DL, impaired diffusing capacity of the lung for carbon monoxide, nocturnal hypoxemia, sleep-disordered breathing",

author = "Sarath Raju and Trishul Siddharthan and McCormack, {Meredith C.} and Patel, {Sanjay R.} and Kunisaki, {Ken M.} and Gypsyamber D'Souza and Cho, {Joshua Hyong Jin} and Valentina Stosor and Alison Morris and Margolick, {Joseph B.} and Brown, {Todd T.} and Punjabi, {Naresh M.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2024 by the American Thoracic Society.",

year = "2024",

month = jul,

doi = "10.1513/AnnalsATS.202309-757OC",

language = "English (US)",

volume = "21",

pages = "1085--1093",

journal = "Annals of the American Thoracic Society",

issn = "2329-6933",

publisher = "American Thoracic Society",

number = "7",

}

Raju, S, Siddharthan, T, McCormack, MC, Patel, SR, Kunisaki, KM, D'Souza, G, Cho, JHJ, Stosor, V, Morris, A, Margolick, JB, Brown, TT & Punjabi, NM 2024, 'Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus', Annals of the American Thoracic Society, vol. 21, no. 7, pp. 1085-1093. https://doi.org/10.1513/AnnalsATS.202309-757OC

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus. / Raju, Sarath; Siddharthan, Trishul; McCormack, Meredith C. et al.
In: Annals of the American Thoracic Society, Vol. 21, No. 7, 07.2024, p. 1085-1093.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus

AU - Raju, Sarath

AU - Siddharthan, Trishul

AU - McCormack, Meredith C.

AU - Patel, Sanjay R.

AU - Kunisaki, Ken M.

AU - D'Souza, Gypsyamber

AU - Cho, Joshua Hyong Jin

AU - Stosor, Valentina

AU - Morris, Alison

AU - Margolick, Joseph B.

AU - Brown, Todd T.

AU - Punjabi, Naresh M.

PY - 2024/7

Y1 - 2024/7

N2 - Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DLCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DLCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DLCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DLCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2], 90% [T90]). Structural equation models were used to assess associations of impaired DLCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DLCO impairment (,80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index > 30 events/h) and impaired DLCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, 28.2% [95% CI, 211.4% to 24.9%]) and average SpO2 during sleep (median difference, 21.1% [95% CI, 22.1% to 20.01%]) than those with severe SDB and preserved DLCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DLCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DLCO to guide testing and risk stratification strategies.

AB - Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DLCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DLCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DLCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DLCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2], 90% [T90]). Structural equation models were used to assess associations of impaired DLCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DLCO impairment (,80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index > 30 events/h) and impaired DLCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, 28.2% [95% CI, 211.4% to 24.9%]) and average SpO2 during sleep (median difference, 21.1% [95% CI, 22.1% to 20.01%]) than those with severe SDB and preserved DLCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DLCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DLCO to guide testing and risk stratification strategies.

KW - impaired DL

KW - impaired diffusing capacity of the lung for carbon monoxide

KW - nocturnal hypoxemia

KW - sleep-disordered breathing

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DO - 10.1513/AnnalsATS.202309-757OC

M3 - Article

C2 - 38498872

AN - SCOPUS:85197961211

SN - 2329-6933

VL - 21

SP - 1085

EP - 1093

JO - Annals of the American Thoracic Society

JF - Annals of the American Thoracic Society

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ER -

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus

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UN SDGs

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