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History of tuberculosis is associated with lower exhaled nitric oxide levels in HIV-infected children

Sovershaeva, Evgeniyaa; Kranzer, Katharinab,c,d; Mchugh, Graced; Bandason, Tsitsid; Majonga, Edith D.b,d; Usmani, Omar S.e; Rowland-Jones, Sarahf; Gutteberg, Toreg; Flægstad, Trondh,i; Ferrand, Rashida A.b,d; Odland, Jon Ø.a,j,k

doi: 10.1097/QAD.0000000000002265
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Objective: HIV disrupts host defense mechanisms and maintains chronic inflammation in the lung. Nitric oxide (NO) is a marker of lung inflammation and can be measured in the exhaled air. We investigated the relationship between exhaled NO (eNO), HIV status and airway abnormalities in perinatally HIV-infected children aged 6 to 19 years.

Design: Cross-sectional study.

Methods: HIV-infected individuals on antiretroviral therapy and HIV-uninfected children with no active tuberculosis (TB) or acute respiratory tract infection were recruited from a public hospital in Harare, Zimbabwe. Clinical history was collected and eNO testing and spirometry was performed. The association between eNO and explanatory variables (HIV, FEV1 z-score, CD4 count, viral load, history of TB) was investigated using linear regression analysis adjusted for age, sex and time of eNO testing.

Results: In total 222 HIV-infected and 97 HIV-uninfected participants were included. Among HIV-infected participants 57 (25.7%) had a history of past TB; 56 (25.2%) had airway obstruction, but no prior TB. HIV status was associated with lower eNO level (mean ratio 0.79 (95% CI 0.65–0.97), p = 0.03). Within the HIV-infected group, history of past TB was associated with lower eNO levels after controlling for age, sex and time of eNO testing (0.79 (95% CI 0.67–0.94), p = 0.007).

Conclusion: HIV infection and history of TB were associated with lower eNO levels. eNO levels may be a marker of HIV- and TB-induced alteration in pulmonary physiology; further studies focused on potential causes for lower eNO levels in HIV and TB are warranted.

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aDepartment of Community Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway

bClinical Research Department, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

cNational Tuberculosis Reference Laboratory, Research Centre Borstel, Borstel, Germany

dBiomedical Research and Training Institute, 10 Seagrave Road, Harare, Zimbabwe

eNational Heart and Lung Institute, Imperial College London, London SW3 6LY, UK

fNuffield Department of Medicine, University of Oxford, Oxford, UK

gDepartment of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway

hDepartment of Pediatrics, University Hospital of North Norway, N-9038, Tromsø, Norway

iPediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway

jDepartment of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU The Norwegian University of Science and Technology, NO-7491, Trondheim, Norway

kSchool of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, South Africa.

Correspondence to Evgeniya Sovershaeva, Department of Community Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Hansine Hansens veg 18, 9019, Tromso, Norway. Tel: +4746310426; e-mail: evgeniya.sovershaeva@uit.no

Received 27 February, 2019

Revised 20 April, 2019

Accepted 27 April, 2019

Copyright © 2019 Wolters Kluwer Health, Inc.