Seminars in Arthritis and Rheumatism
Volume 40, Issue 3 , Pages 241-249 , December 2010

Gastroesophageal Reflux Incites Interstitial Lung Disease in Systemic Sclerosis: Clinical, Radiologic, Histopathologic, and Treatment Evidence

  • Romy B. Christmann, MD, PhD

      Affiliations

    • Assistant Professor, Rheumatology Division, University of São Paulo, São Paulo, Brazil; Scholar Researcher, Arthritis Center, Boston University School of Medicine, Boston, MA
    • Corresponding Author InformationAddress reprint requests to Romy B. Christmann, MD, PhD, Boston University School of Medicine, Arthritis Center. 715 Albany Street, E5, Boston, Massachusetts 02118-2531
    • ,
  • Athol U. Wells, MD

      Affiliations

    • Professor of Respiratory Medicine, Royal Brompton Hospital and National Heart and Lung Institute, London, UK
    • ,
  • Vera L. Capelozzi, MD, PhD

      Affiliations

    • Pathology Division, University of São Paulo, São Paulo, Brazil
    • ,
  • Richard M. Silver, MD

      Affiliations

    • Distinguished University Professor, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC

References 

  1. Tamby MC, Chanseaud Y, Guillevin L, Mouthon L. New insights into the pathogenesis of systemic sclerosis. Autoimmun Rev. 2003;2(3):152–157
  2. Abu-Shakra M, Guillemin F, Lee P. Gastrointestinal manifestations of systemic sclerosis. Semin Arthritis Rheum. 1994;24(1):29–39
  3. Marie I, Levesque H, Ducrotte P, Denis P, Hellot MF, Benichou J, et al. Gastric involvement in systemic sclerosis: a prospective study. Am J Gastroenterol. 2001;96(1):77–83
  4. Sjogren RW. Gastrointestinal features of scleroderma. Curr Opin Rheumatol. 1996;8(6):569–575
  5. Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis Rheum. 1994;37(9):1265–1282
  6. Steen VD, Owens GR, Fino GJ, Rodnan GP, Medsger TA. Pulmonary involvement in systemic sclerosis (scleroderma). Arthritis Rheum. 1985;28(7):759–767
  7. McCarthy DS, Baragar FD, Dhingra S, Sigurdson M, Sutherland JB, Rigby M, et al. The lungs in systemic sclerosis (scleroderma): a review and new information. Semin Arthritis Rheum. 1988;17(4):271–283
  8. Simeon CP, Armadans L, Fonollosa V, Solans R, Selva A, Villar M, et al. Mortality and prognostic factors in Spanish patients with systemic sclerosis. Rheumatology (Oxford). 2003;42(1):71–75
  9. Ioannidis JP, Vlachoyiannopoulos PG, Haidich AB, Medsger TA, Lucas M, Michet CJ, et al. Mortality in systemic sclerosis: an international meta-analysis of individual patient data. Am J Med. 2005;118(1):2–10
  10. Bryan C, Knight C, Black CM, Silman AJ. Prediction of five-year survival following presentation with scleroderma: development of a simple model using three disease factors at first visit. Arthritis Rheum. 1999;42(12):2660–2665
  11. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002;165(2):277–304
  12. Fujita J, Yoshinouchi T, Ohtsuki Y, Tokuda M, Yang Y, Yamadori I, et al. Non-specific interstitial pneumonia as pulmonary involvement of systemic sclerosis. Ann Rheum Dis. 2001;60(3):281–283
  13. Bouros D, Wells AU, Nicholson AG, Colby TV, Polychronopoulos V, Pantelidis P, et al. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med. 2002;165(12):1581–1586
  14. Kim DS, Yoo B, Lee JS, Kim EK, Lim CM, Lee SD, et al. The major histopathologic pattern of pulmonary fibrosis in scleroderma is nonspecific interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2002;19(2):121–127
  15. Antoniou KM, Wells AU. Scleroderma lung disease: evolving understanding in light of newer studies. Curr Opin Rheumatol. 2008;20(6):686–691
  16. Highland KB, Silver RM. New developments in scleroderma interstitial lung disease. Curr Opin Rheumatol. 2005;17(6):737–745
  17. Gilson M, Zerkak D, Wipff J, Dusser D, Dinh-Xuan AT, Abitbol V, et al. Prognostic factors for lung function in systemic sclerosis: prospective study of 105 cases. Eur Respir J. 2010;35(1):112–117
  18. Moran TJ. Experimental aspiration pneumonia. IV. Inflammatory and reparative changes produced by intratracheal injections of autologous gastric juice and hydrochloric acid. AMA Arch Pathol. 1955;60(2):122–129
  19. Donnelly RJ, Berrisford RG, Jack CI, Tran JA, Evans CC. Simultaneous tracheal and esophageal pH monitoring: investigating reflux-associated asthma. Ann Thorac Surg. 1993;56(5):1029–1033discussion 1034
  20. Ducolone A, Vandevenne A, Jouin H, Grob JC, Coumaros D, Meyer C, et al. Gastroesophageal reflux in patients with asthma and chronic bronchitis. Am Rev Respir Dis. 1987;135(2):327–332
  21. Mansfield LE. Gastroesophageal reflux and diseases of the respiratory tract: a review. J Asthma. 1989;26(5):271–278
  22. Schnatz PF, Castell JA, Castell DO. Pulmonary symptoms associated with gastroesophageal reflux: use of ambulatory pH monitoring to diagnose and to direct therapy. Am J Gastroenterol. 1996;91(9):1715–1718
  23. Shimizu Y, Dobashi K, Zhao JJ, Kawata T, Ono A, Yanagitani N, et al. Proton pump inhibitor improves breath marker in moderate asthma with gastroesophageal reflux disease. Respiration. 2007;74(5):558–564
  24. Kiljander TO, Salomaa ER, Hietanen EK, Ovaska J, Helenius H, Liippo K. Gastroesophageal reflux and bronchial responsiveness: correlation and the effect of fundoplication. Respiration. 2002;69(5):434–439
  25. Cantu E, Appel JZ, Hartwig MG, Woreta H, Green C, Messier R, et al. J. Maxwell Chamberlain Memorial Paper (Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease). Ann Thorac Surg. 2004;78(4):1142–1151discussion 1142-51
  26. Tobin RW, Pope CE, Pellegrini CA, Emond MJ, Sillery J, Raghu G. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;158(6):1804–1808
  27. Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;27(1):136–142
  28. Patti MG, Tedesco P, Golden J, Hays S, Hoopes C, Meneghetti A, et al. Idiopathic pulmonary fibrosis: how often is it really idiopathic?. J Gastrointest Surg. 2005;9(8):1053–1056discussion 1056-8
  29. Raghu G, Yang ST, Spada C, Hayes J, Pellegrini CA. Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Chest. 2006;129(3):794–800
  30. Appel JZ, Lee SM, Hartwig MG, Li B, Hsieh CC, Cantu E, et al. Characterization of the innate immune response to chronic aspiration in a novel rodent model. Respir Res. 2007;8:87
  31. Farrell S, McMaster C, Gibson D, Shields MD, McCallion WA. Pepsin in bronchoalveolar lavage fluid: a specific and sensitive method of diagnosing gastro-oesophageal reflux-related pulmonary aspiration. J Pediatr Surg. 2006;41(2):289–293
  32. Matsuse T, Oka T, Kida K, Fukuchi Y. Importance of diffuse aspiration bronchiolitis caused by chronic occult aspiration in the elderly. Chest. 1996;110(5):1289–1293
  33. Starosta V, Kitz R, Hartl D, Marcos V, Reinhardt D, Griese M. Bronchoalveolar pepsin, bile acids, oxidation, and inflammation in children with gastroesophageal reflux disease. Chest. 2007;132(5):1557–1564
  34. Johnson DA, Drane WE, Curran J, Cattau EL, Ciarleglio C, Khan A, et al. Pulmonary disease in progressive systemic sclerosis (A complication of gastroesophageal reflux and occult aspiration?). Arch Intern Med. 1989;149(3):589–593
  35. Lock G, Pfeifer M, Straub RH, Zeuner M, Lang B, Scholmerich J, et al. Association of esophageal dysfunction and pulmonary function impairment in systemic sclerosis. Am J Gastroenterol. 1998;93(3):341–345
  36. Marie I, Dominique S, Levesque H, Ducrotte P, Denis P, Hellot MF, et al. Esophageal involvement and pulmonary manifestations in systemic sclerosis. Arthritis Rheum. 2001;45(4):346–354
  37. Marie I, Ducrotte P, Denis P, Hellot MF, Levesque H. Oesophageal mucosal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy. Aliment Pharmacol Ther. 2006;24(11-12):1593–1601
  38. Tutuian R, Castell DO. Use of multichannel intraluminal impedance to document proximal esophageal and pharyngeal nonacidic reflux episodes. Am J Med. 2003;115(Suppl 3A):119S–123S
  39. Savarino E, Bazzica M, Zentilin P, Pohl D, Parodi A, Cittadini G, et al. Gastroesophageal reflux and pulmonary fibrosis in scleroderma: a study using pH-impedance monitoring. Am J Respir Crit Care Med. 2009;179(5):408–413
  40. Troshinsky MB, Kane GC, Varga J, Cater JR, Fish JE, Jimenez SA, et al. Pulmonary function and gastroesophageal reflux in systemic sclerosis. Ann Intern Med. 1994;121(1):6–10
  41. Barnes TW, Vassallo R, Tazelaar HD, Hartman TE, Ryu JH. Diffuse bronchiolar disease due to chronic occult aspiration. Mayo Clin Proc. 2006;81(2):172–176
  42. Mukhopadhyay S, Katzenstein AL. Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens. Am J Surg Pathol. 2007;31(5):752–759
  43. de Souza RB, Borges CT, Capelozzi VL, Parra ER, Jatene FB, Kavakama J, et al. Centrilobular fibrosis: an underrecognized pattern in systemic sclerosis. Respiration. 2009;77(4):389–397
  44. de Carvalho ME, Kairalla RA, Capelozzi VL, Deheinzelin D, do Nascimento Saldiva PH, de Carvalho CR. Centrilobular fibrosis: a novel histological pattern of idiopathic interstitial pneumonia. Pathol Res Pract. 2002;198(9):577–583
  45. Bhalla M, Silver RM, Shepard JA, McLoud TC. Chest CT in patients with scleroderma: prevalence of asymptomatic esophageal dilatation and mediastinal lymphadenopathy. AJR Am J Roentgenol. 1993;161(2):269–272
  46. Vonk MC, van Die CE, Snoeren MM, Bhansing KJ, van Riel PL, Fransen J, et al. Oesophageal dilatation on high-resolution computed tomography scan of the lungs as a sign of scleroderma. Ann Rheum Dis. 2008;67(9):1317–1321
  47. Imokawa S, Sato A, Hayakawa H, Kotani M, Urano T, Takada A. Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. Am J Respir Crit Care Med. 1997;156(2 Pt. 1):631–636
  48. Mogulkoc N, Brutsche MH, Bishop PW, Murby B, Greaves MS, Horrocks AW, et al. Pulmonary (99m)Tc-DTPA aerosol clearance and survival in usual interstitial pneumonia (UIP). Thorax. 2001;56(12):916–923
  49. Kon OM, Daniil Z, Black CM, du Bois RM. Clearance of inhaled technetium-99m-DTPA as a clinical index of pulmonary vascular disease in systemic sclerosis. Eur Respir J. 1999;13(1):133–136
  50. Fanti S, De Fabritiis A, Aloisi D, Dondi M, Marengo M, Compagnone G, et al. Early pulmonary involvement in systemic sclerosis assessed by technetium-99m-DTPA clearance rate. J Nucl Med. 1994;35(12):1933–1936
  51. Satoh H, Kurishima K, Ishikawa H, Ohtsuka M. Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med. 2006;260(5):429–434
  52. Hant FN, Ludwicka-Bradley A, Wang HJ, Li N, Elashoff R, Tashkin DP, et al. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol. 2009;36(4):773–780

 Richard Silver receives grant support from Actelion, Bristol Myers Squibb, Boehringer Ingelheim, and United Therapeutics and acts as Speakers bureau for Actelion, Genentech, and Takeda.

 Romy Beatriz Christmann and Athol Wells have no conflicts of interest to disclose.

PII: S0049-0172(10)00044-2

doi: 10.1016/j.semarthrit.2010.03.002

Seminars in Arthritis and Rheumatism
Volume 40, Issue 3 , Pages 241-249 , December 2010

Article Tools

* Image Usage & Resolution