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Levels of Exhaled Breath Condensate pH and Fractional Exhaled Nitric Oxide in Retired Coal Miners

  • Received : 2010.04.27
  • Accepted : 2010.06.12
  • Published : 2010.12.01

Abstract

Inhaled inorganic dusts, such as coal, can cause inflammation and fibrosis in the lungs, known as pneumoconiosis. Diagnosis of pneumoconiosis depends on morphological changes by radiological findings and functional change by pulmonary function test (PFT). Unfortunately, current diagnostic findings are limited only to lung fibrosis, which is usually irreversibly progressive. Therefore, it is important that research on potential and prospective biomarkers for pneumoconiosis should be conducted prior to initiation of irreversible radiological or functional changes in the lungs. Analytical techniques using exhaled breath condensate (EBC) or exhaled gas are non-invasive methods for detection of various respiratory diseases. The objective of this study is to investigate the relationship between inflammatory biomarkers, such as EBC pH or fractional exhaled nitric oxide ($FE_{NO}$), and pneumoconiosis among 120 retired coal miners (41 controls and 79 pneumoconiosis patients). Levels of EBC pH and FENO did not show a statistically significant difference between the pneumoconiosis patient group and pneumoconiosis patients with small opacity classified by International Labor Organization (ILO) classification. The mean concentration of $FE_{NO}$ in the low percentage $FEV_1$ (< 80%) was lower than that in the high percentage (80% $\leq$) (p = 0.023). The mean concentration of $FE_{NO}$ in current smokers was lower than that in non smokers (never or past smokers) (p = 0.027). Although there was no statistical significance, the levels of $FE_{NO}$ in smokers tended to decrease, compared with non smokers, regardless of pneumoconiosis. In conclusion, there was no significant relationship between the level of EBC pH or $FE_{NO}$ and radiological findings or PFT. The effects between exhaled biomarkers and pneumoconiosis progression, such as decreasing PFT and exacerbation of radiological findings, should be monitored.

Keywords

References

  1. Accordino, R., Visentin, A., Bordin, A., Ferrazzoni, S., Marian, E., Rizzato, F., Canova, C., Venturini, R. and Maestrelli, P. (2008). Long-term repeatability of exhaled breath condensate pH in asthma. Respiratory Medicine, 102(3), 377-381. https://doi.org/10.1016/j.rmed.2007.10.014
  2. American Thoracic Society; European Respiratory Society. (2005). ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am. J. Respir. Crit. Care Med., 171(8), 912-930. https://doi.org/10.1164/rccm.200406-710ST
  3. ATS Workshop Proceedings (2006). Exhaled nitric oxide and nitric oxide oxidative metabolism in exhaled breath condensate: Executive summary. Am. J. Respir. Crit. Care Med., 173(7), 811-813. https://doi.org/10.1164/rccm.2601014
  4. Balint, B., Donnelly, L.E., Hanazawa, T., Kharitonov, S.A. and Barnes, P.J. (2001). Increased nitric oxide metabolites in exhaled breath condensate after exposure to tobacco smoke. Thorax, 56(6), 456-461. https://doi.org/10.1136/thorax.56.6.456
  5. Becker, S., Soukup, J.M., Gilmour, M.I. and Devlin, R.B. (1996). Stimulation of human and rat alveolar macrophages by urban air particles: effects on oxidant radical generation and cytokine production. Toxicol. Appl. Pharmacol., 141, 637-648. https://doi.org/10.1006/taap.1996.0330
  6. Bloemen, K., Lissens, G., Desager, K. and Schoesters, G. (2007). Determinants of variability of protein content, volume and pH of exhaled breath condensate. Respiratory Medicine, 101(6), 1331-1337. https://doi.org/10.1016/j.rmed.2006.10.008
  7. Borrill, Z.L., Roy, K. and Singh, D. (2008). Exhaled breath condensate biomarkers in COPD. Eur. Respir. J., 32(2), 472-486. https://doi.org/10.1183/09031936.00116107
  8. Borrill, Z.L., Smith, J.A., Naylor, J., Woodcock, A.A. and Singh, D. (2006). The effect of gas standardisation on exhaled breath condensate pH. Eur. Respir. J., 28(1), 251-252. https://doi.org/10.1183/09031936.06.00026706
  9. Borrill, Z., Starkey, C., Vestbo, J. and Singh, D. (2005). Reproducibility of exhaled breath condensate pH in chronic obstructive pulmonary disease. Eur. Respir. J., 25(2), 269-274. https://doi.org/10.1183/09031936.05.00085804
  10. Brindicci, C., Ito, K., Resta, O., Pride, N.B., Barnes, P.J. and Kharitonov, S.A. (2005). Exhaled nitric oxide from lung periphery is increased in COPD. Eur. Respir. J., 26(1), 52-59. https://doi.org/10.1183/09031936.04.00125304
  11. Brusasco, V., Crapo, R. and Viegi, G. (2005). Series “ATS/ERS Task Force: Standardisation of lung function testing’. Eur. Respir. J., 26, 318-338.
  12. Castranova, V., Vallyathan, V., Ramsey, D.M., McLaurin, J.L., Pack, D., Leonard, S., Barger, M.W., Ma, J.Y., Dalal, N.S. and Teass, A. (1997). Augmentation of pulmonary reactions to quartz inhalation by trace amounts of iron-containing particles. Environ. Health Perspect., 105(5), 1319-1324. https://doi.org/10.2307/3433554
  13. Cohen, R.A.C., Patel, A. and Green, F.H.Y. (2008). Lung disease caused by exposure to coal mine and silica dust. Semin. Respir. Crit. Care Med., 29, 651-661. https://doi.org/10.1055/s-0028-1101275
  14. Condorelli, P., Shin, H.W., Aledia, A.S., Silkoff, P.E. and George, S.C. (2007). A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model. J. Appl. Physiol., 102(1), 417-425. https://doi.org/10.1152/japplphysiol.00533.2006
  15. Dalal, N.S., Jafari, B., Peterson, M., Green, F.H. and Vallyathan, V. (1991). Presence of stable coal radicals in autopsied coal miners’ lungs and its possible correlation to coal worker’s pneumoconiosis. Arch. Environ. Health, 46, 366-372. https://doi.org/10.1080/00039896.1991.9934404
  16. Degano, B., Mittaine, M., Herve, P., Rami, J., Kamar, N., Suc, B., Riviere, D. and Rostaing, L. (2009). Nitric oxide production by the alveolar compartment of the lungs in cirrhotic patients. Eur. Respir. J., 34(1), 138-144. https://doi.org/10.1183/09031936.00148008
  17. Effros, R.M., Casaburi, R., Su, J., Dunning, M., Torday, J., Biller, J. and Shaker, R. (2006). The effects of volatile salivary acids and bases on exhaled breath condensate pH. Am. J. Respir. Crit. Care Med., 173(4), 386-392. https://doi.org/10.1164/rccm.200507-1059OC
  18. Effros, R.M., Su, J., Casaburi, R., Shaker, R., Biller, J. and Dunning, M. (2005). Utility of exhaled breath condensates in chronic obstructive pulmonary disease: a critical review. Curr. Opin. Pulm. Med., 11(2), 135-139. https://doi.org/10.1097/00063198-200503000-00006
  19. Ferreira, I.M., Hazarim, M.S., Gutierrezm, C., Zamelm, N. and Chapmanm, K.R. (2001). Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled beclomethasone. Am. J. Respir. Crit. Care Med., 164(6), 1012-1015. https://doi.org/10.1164/ajrccm.164.6.2012139
  20. George, S.C., Hogman, M.M., Permutt, M.S. and Silkoff, M.P.E. (2004). Modeling pulmonary nitric oxide exchange. J. Appl. Physiol., 96(3), 831-839. https://doi.org/10.1152/japplphysiol.00950.2003
  21. Girgis, R.E., Gugnani, M.K., Abrams, J. and Mayes, M.D. (2002). Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease. Am. J. Respir. Crit. Care Med., 165(12), 1587-1591. https://doi.org/10.1164/rccm.2104003
  22. Goldbart, A.D., Krishna, J., Li, R.C., Serpero, L.D. and Gozal, D. (2006). Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome. Chest, 130(1), 143-148. https://doi.org/10.1378/chest.130.1.143
  23. Grob, N.M., Aytekin, M. and Dweik, R.A. (2008). Biomarkers in exhaled breath condensate: a review of collection, processing and analysis. J. Breath Res., 2(3), 1-18.
  24. Gulumian, M., Borm, P.J.A., Vallyathan, V., Castranova, V., Donaldson, K., Nelson, G. and Murray, J. (2006). Mechanistically identified suitable biomarkers of exposure, effect, and susceptibility for silicosis and coal-worker’s pneumoconiosis: a comprehensive review. J. Toxicol. Environ. Health., Part B, 9, 357-395. https://doi.org/10.1080/15287390500196537
  25. Horvath, I., Hunt, J. and Barnes, P.J. (2005). ATS/ERS Task Force. Exhaled breath condensate: methodological recommendations and unresolved questions. Eur. Respir. J., 26(3), 523-548. https://doi.org/10.1183/09031936.05.00029705
  26. Hunt, J. (2007). Exhaled breath condensate pH assays. Immunol. Allergy Clin. North Am., 27(4), 597-606. https://doi.org/10.1016/j.iac.2007.09.006
  27. Hunt, J.F., Erwin, E., Palmer, L., Vaughan, J., Malhotra, N., Platts-Mills, T.A. and Gaston, B. (2002). Expression and activity of pH-regulatory glutaminase in the human airway epithelium. Am. J. Respir. Crit. Care Med., 165(1), 101-107. https://doi.org/10.1164/ajrccm.165.1.2104131
  28. Hunt, J.F., Fang, K., Malik, R., Snyder, A., Malhotra, N., Platts-Mills, T.A. and Gaston, B. (2000). Endogenous airway acidification. Implications for asthma pathophysiology. Am. J. Respir. Crit. Care Med., 161(3 Pt 1), 694-699. https://doi.org/10.1164/ajrccm.161.3.9911005
  29. IARC (1997). IARC Monograph on the evaluation of the carcinogenic risk of chemicals to humans. In: Silica, some silicates, coal dust and para-aramid fibrils, Vol. 68. IARC Press, Geneva, Switzerland.
  30. ILO (2002). Guidelines for the use of the ILO international classification of radiographs of pneumoconiosis. Geneva, International Labor Organization.
  31. Kharitonov, S.A. and Barnes, P.J. (2002). Biomarkers of some pulmonary diseases in exhaled breath. Biomarkers, 7(1), 1-32. https://doi.org/10.1080/13547500110104233
  32. Kharitonov, S.A. and Barnes, P.J. (2006). Exhaled biomarkers. Chest, 130(5), 1541-1546. https://doi.org/10.1378/chest.130.5.1541
  33. Kharitonov, S.A., Donnelly, L.E., Montuschi, P., Corradi, M., Collins, J.V. and Barnes, P.J. (2002). Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma. Thorax, 57(10), 889-896. https://doi.org/10.1136/thorax.57.10.889
  34. Kostikas, K., Papatheodorou, G., Ganas, K., Psathakis, K., Panagou, P. and Loukides, S. (2002). pH in expired breath condensate of patients with inflammatory airway diseases. Am. J. Respir. Crit. Care Med., 165(10), 1364-1370. https://doi.org/10.1164/rccm.200111-068OC
  35. Lehtonen, H., Oksa, P., Lehtimaki, L., Sepponen, A., Nieminen, R., Kankaanranta, H., Saarelainen, S., Jarvenpaa, R., Uitti, J. and Moilanen, E. (2007). Increased alveolar nitric oxide concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath condensate in patients with asbestosis. Thorax, 62(7), 602-607. https://doi.org/10.1136/thx.2006.067868
  36. Malinovschi, A., Janson, C., Holmkvist, T., Norback, D., Merilainen, P. and Hogman, M. (2006). Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide exchange parameters. Eur. Respir. J., 28(2), 339-345. https://doi.org/10.1183/09031936.06.00113705
  37. Maziak, W., Loukides, S., Culpitt, S., Sullivan, P., Kharitonov, S.A. and Barnes, P.J. (1998). Exhaled nitric oxide in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 157(3 Pt 1), 998-1002. https://doi.org/10.1164/ajrccm.157.3.97-05009
  38. Montes de Oca, M., Loeb, E., Torris, S.H., Sanctis, J.D., Hernadez, N. and Talamo, C. (2008). Peripheral muscle alterations in non-COPD smokers. Chest, 133, 13-18. https://doi.org/10.1378/chest.07-1592
  39. Montuschi, P. (2005). Exhaled breath condensate analysis in patients with COPD. Clinica. Chimica. Acta, 356, 22-34. https://doi.org/10.1016/j.cccn.2005.01.012
  40. Montuschi, P., Collins, J.V., Ciabattoni, G., Lazzeri, N., Corradi, M., Kharitonov, S.A. and Barnes, P.J. (2000). Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am. J. Respir. Crit. Care Med., 162(3 pt1), 1175-1177. https://doi.org/10.1164/ajrccm.162.3.2001063
  41. Nicolaou, N.C., Lowe, L.A., Murray, C.S., Woodcock, A., Simpson, A. and Custovic, A. (2006). Exhaled breath condensate pH and childhood asthma: unselected birth cohort study. Am. J. Respir. Crit. Care Med., 174(3), 254-259. https://doi.org/10.1164/rccm.200601-140OC
  42. Niimi, A., Nguyen, L.T., Usmani, O., Mann, B. and Chung, K.F. (2004): Reduced pH and chloride levels in exhaled breath condensate of patients with chronic cough. Thorax, 59(7), 608-612. https://doi.org/10.1136/thx.2003.012906
  43. Noriaki, T., Fumihiko, J. and Fumiyuki, A. (1993). Simultaneous determination of cotinine and creatinine by high performance liquid chromatography. Jpn. J. Ind. Health, 35, 198-199.
  44. Nowak, D., Antczak, A., Krol, M., Pietras, T., Shariati, B., Bialasiewicz, P., Jeczkowski, K. and Kula, P. (1996). Increased content of hydrogen peroxide in the exhaled breath of cigarette smokers. Eur. Respir. J., 9(4), 652-657. https://doi.org/10.1183/09031936.96.09040652
  45. Nowak, D., Kalucka, S., Bial⁄asiewicz, P. and Krol, M. (2001). Exhalation of $H_2O_2$ and thiobarbituric acid reactive substances (TBARs) by healthy subjects. Free Radic. Biol. Med., 30(2), 178-186. https://doi.org/10.1016/S0891-5849(00)00457-3
  46. Paget-Brown, A.O., Ngamtrakulpanit, L., Smith, A., Bunyan, D., Hom, S., Nguyen, A. and Hunt, J.F. (2006). Normative data for pH of exhaled breath condensate. Chest, 129(2), 426-430. https://doi.org/10.1378/chest.129.2.426
  47. Paredi, P., Sergei, A., Kharitonov, S.A. and Barnes, P.J. (2002). Analysis of expired air for oxidation products. Am. J. Respir. Crit. Care Med., 166(12 Pt 2), S31-37. https://doi.org/10.1164/rccm.2206012
  48. Porter, D.W., Hubbs, A.F., Mercer, R., Robinson, V.A., Ramsey, D., McLaurin, J., Khan, A., Battelli, L., Mrumbaugh, K., Teass, A. and Castranova, V. (2004). Progression of lung inflammation and damage in rats after cessation of silica inhalation. Toxicol. Sci., 79, 370-380. https://doi.org/10.1093/toxsci/kfh110
  49. Pryor, W.A. (1997). Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ. Health Perspect., 105(4), 875-882. https://doi.org/10.2307/3433297
  50. Rosias, P.P., Den Hartog, G.J., Robroeks, C.M., Bast, A., Donckerwolcke, R.A., Heynens, J.W., Suykerbuyk, J., Hendriks, H.J., Jobsis, Q. and Dompeling, E. (2006). Free radicals in exhaled breath condensate in cystic fibrosis and healthy subjects. Free Radic. Res., 40(9), 901-909. https://doi.org/10.1080/10715760500522648
  51. Schins, R.P.F. and Borm, P.J.A. (1999). Mechanisms and mediators in coal dust induced toxicity: A review. Am. Occup. Hyg., 43(1), 7-33. https://doi.org/10.1016/S0003-4878(98)00069-6
  52. Shoemaker, D.A., Pretty, J.R., Ramsey, D.M., McLaurin, J.L., Khan, A., Teass, A.W., Castranova, V., Pailes, W.H., Dalal, N.S., Miles, P.R., Bowman, L., Leonard, S., Shumaker, J., Vallyathan, V. and Pack, D. (1995). Particle activity and in vivo pulmonary response to freshly milled and aged alpha-quartz. Scand. J. Work Environ. Health, 21(2), 15-18. https://doi.org/10.5271/sjweh.3
  53. Tourmann, J.L. and Kaufmann, R. (1994). Biopersistence of the mineral matter of coal mine dusts in silicotic human lungs: is there a preferential release of iron? Environ. Health Perspect., 102(5), 265-268. https://doi.org/10.1289/ehp.94102s3265
  54. Tsoukias, N.M. and George, S.C. (1998). A two-compartment model of pulmonary nitric oxide exchange dynamics. J. Appl. Physiol., 85(2), 653-666. https://doi.org/10.1152/jappl.1998.85.2.653
  55. Vallyathan, V. (2004). Oxygen/nitrogen radicals-lung injury and disease: Oxidative stress: antioxidant status in health and disease (Vallyathan et al., Ed). Marcel Deckker, New York, pp. 35-58.
  56. Vaughan, J., Ngamtrakulpanit, L., Pajewski, T.N., Turner, R., Nguyen, T.A., Smith, A., Urban, P., Hom, S., Gaston, B. and Hunt, J. (2003). Exhaled breath condensate pH is a robust and reproducible assay of airway acidity. Eur. Respir. J., 22(6), 889-894. https://doi.org/10.1183/09031936.03.00038803
  57. Wallaert, B., Lassalle, P., Fortin, F., Aerts, C., Bart, F., Fournier, E. and Voisin, C. (1990). Superoxide anion generation by alveolar inflammatory cells in simple pneumoconiosis and in progressive massive fibrosis of nonsmoking coal workers. Am. Rev. Respir. Dis., 141, 129-133. https://doi.org/10.1164/ajrccm/141.1.129
  58. Wells, K., Vaughan, J., Pajewski, T.N., Hom, S., Ngamtrakkulpanit, L., Smith, A., Nguyen, A., Turner, R. and Hunt, J. (2005). Exhaled breath condensate pH assays are not influenced by oral ammonia. Thorax, 60(1), 27-31. https://doi.org/10.1136/thx.2003.020602

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  1. vol.11, pp.2, 2017, https://doi.org/10.1080/17476348.2017.1281746