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      The effectiveness of sputum pH analysis in the prediction of response to therapy in patients with pulmonary tuberculosis

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          Abstract

          Purpose. The predictive factor of response to antituberculous therapy has not been fully elucidated. Airway acidity has been thought to be a potential indicator of the bactericidal activity. Therefore, we hypothesized that monitoring airway acidity by measuring sputum pH could predict response to therapy.

          Methods. A total of 47 patients having newly diagnosed, smear-positive, active pulmonary tuberculosis were enrolled between October 2011 and March 2014. Sputum samples were serially analyzed before and after treatment. Eligible patients who initiated a standard 6-month treatment were monitored for the length of time to sputum smear and culture conversion.

          Results. There were 39 patients who completed a 2-month intensive phase of isoniazid, rifampicin, pyrazinamide, and ethambutol therapy followed by a 4-month continuation phase of isoniazid and rifampicin. Although factors including age, cavitation, sputum grade, and use of an acid-suppressant were associated with initial low sputum pH in univariate analysis, multivariate analysis revealed that only age ≥61 years was a statistically important factor predicting low pH value ( p = 0.005). Further outcome analysis showed that initial low sputum pH before treatment was the only factor significantly associated with shorter length of time to both sputum smear and culture conversion ( p = 0.034 and 0.019, respectively) independent of the effects of age, sputum bacterial load, extent of lung lesion, and cavitation. Thus, initial low sputum pH indicated favorable response to anti-tuberculosis therapy.

          Conclusions. Measuring sputum pH is an easy and inexpensive way of predicting response to standard combination therapy in patients with pulmonary tuberculosis.

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          Most cited references23

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          Global Tuberculosis Report, 2015

          (2015)
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            Endogenous airway acidification. Implications for asthma pathophysiology.

            Airway concentrations of many reactive nitrogen and oxygen species are high in asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivities/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 +/- 0.21, n = 22) than in control subjects (7.65 +/- 0.20, n = 19, p < 0. 001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values, the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology.
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              The early bactericidal activity of drugs in patients with pulmonary tuberculosis.

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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ Inc. (San Francisco, USA )
                2167-8359
                26 November 2015
                2015
                : 3
                : e1448
                Affiliations
                [1 ]Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine , Yokohama, Japan
                [2 ]Department of Pulmonology, Yokohama City University Graduate School of Medicine , Yokohama, Japan
                [3 ]Department of Respiratory Medicine, Fujisawa City Hospital , Fujisawa, Japan
                [4 ]Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine , Yokohama, Japan
                Article
                1448
                10.7717/peerj.1448
                4671190
                26644982
                af3c5092-cca1-4409-8520-2c836a5580f7
                © 2015 Masuda et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 13 July 2015
                : 6 November 2015
                Funding
                Funded by: Ministry of Education, Culture, Sports, Science, and Technology of Japan
                Award ID: 21790778
                Award ID: 23790917
                Award ID: 15K09224
                This work was supported in part by grants (Nos. 21790778, 23790917 and 15K09224 to T Sato) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Infectious Diseases
                Public Health
                Respiratory Medicine

                antituberculous therapy,pulmonary tuberculosis,airway acidity,sputum ph

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