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Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Karolinska Hospital.
Armauer Hansen Research Institute.
Gondar University.
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2008 (English)In: BMC Infectious Diseases, ISSN 1471-2334, Vol. 8, no 146Article in journal (Refereed) Published
Abstract [en]

Background: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO).

Methods: In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia.

Results: The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate.

Conclusion: In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.

Place, publisher, year, edition, pages
2008. Vol. 8, no 146
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-16238DOI: 10.1186/1471-2334-8-146OAI: diva2:133497
Original Publication: Jonna Idh, Anna Westman, Daniel Elias, Feleke Moges, Assefa Getachew, Aschalew Gelaw, Tommy Sundqvist, Tony Forslund, Addis Alemu, Belete Ayele, Ermias Diro, Endalkachew Melese, Yared Wondmikun, Sven Britton, Olle Stendahl and Thomas Schoen, Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection, 2008, BMC INFECTIOUS DISEASES, (8), 146. Publisher: BioMed Central from: 2009-01-16 Created: 2009-01-09 Last updated: 2012-05-07Bibliographically approved
In thesis
1. The Role of Nitric Oxide in Host Defence Against Mycobacterium tuberculosis: Clinical and Experimental Studies
Open this publication in new window or tab >>The Role of Nitric Oxide in Host Defence Against Mycobacterium tuberculosis: Clinical and Experimental Studies
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), responsible for significant morbidity and mortality worldwide, especially in low-income countries. Considering aggravating factors, such as HIV co-infection and emerging drug resistance, new therapeutic interventions are urgently needed. Following exposure to M. tuberculosis, surprisingly few individuals will actually develop active disease, indicating effective defence mechanisms. One such candidate is nitric oxide (NO). The role of NO in human TB is not fully elucidated, but has been shown to have a vital role in controlling TB in animal models.

The general aim of this thesis was to investigate the role of NO in the immune defence against M. tuberculosis, by combining clinical and experimental studies. In pulmonary TB patients, we found low levels of NO in exhaled air, and low levels of NO metabolites in urine. HIV coinfection decreased levels of exhaled NO even further, reflecting a locally impaired NO production in the lung. Low levels of exhaled NO were associated with a decreased cure rate in HIV-positive TB patients. Household contacts to sputum smear positive TB patient presented the highest levels of both urinary NO metabolites and exhaled NO. Malnutrition, a common condition in TB, may lead to deficiencies of important nutrients such as the amino acid L-arginine, essential for NO production. We therefore assessed the effect of an argininerich food supplement (peanuts) in a clinical trial including pulmonary TB patients, and found that peanut supplementation increased cure rate in HIV-positive TB patients.

We also investigated NO susceptibility of clinical strains of M. tuberculosis, and its association to clinical outcome and antibiotic resistance. Patients infected with strains of M. tuberculosis with reduced susceptibility to NO in vitro, showed a tendency towards lower rate of weight gain during treatment. Moreover, there was a clear variability between strains in the susceptibility to NO, and in intracellular survival within NO-producing macrophages. A novel finding, that can be of importance in understanding drug resistance and for drug development, was that reduced susceptibility to NO was associated with resistance to firstline TB drugs, in particular isoniazid and mutations in inhA.

Taken together, the data presented here show that NO plays a vital role  in human immune defence against TB, and although larger multicentre studies are warranted, arginine-rich food supplementation can be recommended to malnourished HIV co-infected patients on TB treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 86 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1304
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-77145 (URN)978-91-7519-911-5 (ISBN)
Public defence
2012-06-07, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Available from: 2012-05-07 Created: 2012-05-07 Last updated: 2012-05-14Bibliographically approved

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