Identification of Intrinsic Airway Acidification in Pulmonary Tuberculosis.
ABSTRACT Exhaled breath condensate acidification reflects the presence of airway acidification. Mycobacterium tuberculosis is an organism particularly sensitive to acidity. We aimed to determine if there is evidence of airway acidification in a cross section of patients with active tuberculosis.We enrolled 51 subjects with active tuberculosis in Ghana and Thailand, and compared them to control subjects. We collected exhaled breath condensate, and assayed for pH after gas standardization.Exhaled breath condensate pH from the control group revealed a median of 7.9 (7.7 - 8.0, n = 21), significantly higher than the active pulmonary tuberculosis patients who had a median pH of 7.4 (7.0 - 7.7; n = 51; p=0.002). Presence or absence of antibiotic therapy did not affect EBC pH values.These exhaled breath condensate data support the theory that airways become acidic in active tuberculosis infection. This may be a mechanism of immune response and pathology not previously considered.
Article: Growth of Mycobacterium tuberculosis in a defined medium is very restricted by acid pH and Mg(2+) levels.[show abstract] [hide abstract]
ABSTRACT: Mycobacterium tuberculosis grows within the phagocytic vacuoles of macrophages, where it encounters a moderately acidic and possibly nutrient-restricted environment. Other mycobacterial species encounter acidic conditions in soil and aquatic environments. We have evaluated the influence of pH and divalent cation levels on the growth of M. tuberculosis and seven other mycobacterial species. In a defined medium, the growth of M. tuberculosis was very restricted by acidic pH. Higher levels of Mg(2+) were required for growth of M. tuberculosis in mildly acidic media (pH 6.0 to 6.5) compared to pH 7. 0 medium. The divalent cations Ca(2+), Zn(2+), or Mn(2+) could not replace Mg(2+) during growth at pH 6.25, but Ca(2+) could at least partially substitute for Mg(2+) during growth at pH 7.0. Among eight species of mycobacteria tested, there was a diversity of growth rates in media with acidic pH and low Mg(2+) levels. M. tuberculosis was the most restricted in growth at pH 6.0, and all of this growth required elevated levels of Mg(2+). M. kansasii and M. smegmatis also grew very poorly in acidic media with limiting Mg(2+). M. fortuitum, M. marinum, M. scrofulaceum, M. avium, and M. chelonae grew at pH 6.0 in an unrestricted manner. These results demonstrate that M. tuberculosis is unique among the mycobacteria in its extreme sensitivity to acid and indicate that M. tuberculosis must acquire sufficient Mg(2+) in order to grow in a mildly acidic environment such as within the phagosome of macrophages.Infection and Immunity 09/2000; 68(8):4518-22. · 4.16 Impact Factor
Journal of the Reticuloendothelial Society 03/1980; 27(2):189-200.
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ABSTRACT: Fluid condensed from the breath of patients with acute asthma is acidic. Several features of asthma pathophysiology can be initiated by exposure of the airway to acid. In renal tubular epithelium, glutaminase produces ammonia to buffer urinary acid excretion. We hypothesized that human airway epithelium could also express glutaminase. Here, we demonstrate that human airway epithelial cells in vitro have biochemical evidence for glutaminase activity and express mRNA for two glutaminase isoforms (KGA and GAC). Glutaminase activity increased in response to acidic stress (media pH 5.8) and was associated with both increased culture medium pH and improved cell survival. In contrast, activity was inhibited by interferon-gamma and tumor necrosis factor-alpha. Glutaminase protein was expressed in the human airway in vivo. Further, ammonia levels in the breath condensate of subjects with acute asthma were low (30 microM [range: 0-233], n = 18, age 23 +/- 2.5 yr) compared with control subjects (327 microM [14-1,220], n = 24, age 24 +/- 2.4 yr, p < 0.001), and correlated with condensate pH (r = 0.58, p < 0.001). These data demonstrate that glutaminase is expressed and active in the human airway epithelium and may be relevant both to the regulation of airway pH and to the pathophysiology of acute asthmatic airway inflammation.American Journal of Respiratory and Critical Care Medicine 01/2002; 165(1):101-7. · 11.08 Impact Factor