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Diffuse panbronchiolitis

Talmadge E King, Jr, MD
Section Editor
Kevin R Flaherty, MD, MS
Deputy Editor
Helen Hollingsworth, MD


Diffuse panbronchiolitis (DPB) is a rare clinicopathologic syndrome characterized by bronchiolitis and chronic sinusitis [1,2]. In the disease name, "diffuse" refers to the distribution of the lesions throughout both lungs and "pan" refers to the pathologic finding that the inflammation involves all layers of the respiratory bronchioles [1].

The predisposing factors, clinical manifestations, evaluation, diagnosis, and treatment of diffuse panbronchiolitis will be discussed here. The clinical features, diagnosis, and management of other types of bronchiolitis in adults and children are reviewed separately. (See "Bronchiolitis in adults" and "Bronchiolitis in infants and children: Clinical features and diagnosis" and "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)


The exact pathogenesis of DPB is not known. A variety of genetic, environmental, and systemic factors appear to contribute.

Genetic factors — Genetic factors are suspected to contribute to the pathogenesis of DPB based on the observation of familial cases and the association of specific human leukocyte antigen (HLA) haplotypes with the disease. In addition to familial cases noted in Japan, it is also common to identify chronic sinusitis without bronchiolitis in first-degree relatives of afflicted individuals [3-5].

Specific HLA haplotypes, such as HLA-B54 in Japan and HLA-A11 in Korea, are associated with the development of DPB [5,6]. In one report, for example, HLA-B54 was identified in 63 percent of Japanese patients with DPB versus 11 percent of normal Japanese controls (relative risk 13.3) [5]. This HLA haplotype has been reported almost exclusively in natives of Japan, China, and Korea, where it is also associated with rheumatoid arthritis and silicosis.

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Literature review current through: Nov 2017. | This topic last updated: Nov 17, 2017.
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  1. Poletti V, Chilosi M, Casoni G, Colby TV. Diffuse panbronchiolitis. Sarcoidosis Vasc Diffuse Lung Dis 2004; 21:94.
  2. Poletti V, Casoni G, Chilosi M, Zompatori M. Diffuse panbronchiolitis. Eur Respir J 2006; 28:862.
  3. Suzuki M, Usui K, Tamura N, et al. [Familial cases of diffuse panbronchiolitis (author's transl)]. Nihon Kyobu Shikkan Gakkai Zasshi 1981; 19:645.
  4. Danbara T, Matsuoki R, Nukiwa T, et al. Familial occurrence of diffuse panbronchiolitis accompanied by elevation of cold agglutinin titer in a father and his two daughters. Jpn J Thorac Dis 1982; 20:59.
  5. Sugiyama Y, Kudoh S, Maeda H, et al. Analysis of HLA antigens in patients with diffuse panbronchiolitis. Am Rev Respir Dis 1990; 141:1459.
  6. Park MH, Kim YW, Yoon HI, et al. Association of HLA class I antigens with diffuse panbronchiolitis in Korean patients. Am J Respir Crit Care Med 1999; 159:526.
  7. Hijikata M, Matsushita I, Tanaka G, et al. Molecular cloning of two novel mucin-like genes in the disease-susceptibility locus for diffuse panbronchiolitis. Hum Genet 2011; 129:117.
  8. Keicho N, Ohashi J, Tamiya G, et al. Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis. Am J Hum Genet 2000; 66:501.
  9. Kamio K, Matsushita I, Hijikata M, et al. Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis. Am J Respir Crit Care Med 2005; 171:949.
  10. Emi M, Keicho N, Tokunaga K, et al. Association of diffuse panbronchiolitis with microsatellite polymorphism of the human interleukin 8 (IL-8) gene. J Hum Genet 1999; 44:169.
  11. Keicho N, Emi M, Nakata K, et al. Promoter variation of tumour necrosis factor-alpha gene: possible high risk for chronic bronchitis but not diffuse panbronchiolitis. Respir Med 1999; 93:752.
  12. Akai S, Okayama H, Shimura S, et al. Delta F508 mutation of cystic fibrosis gene is not found in chronic bronchitis with severe obstruction in Japan. Am Rev Respir Dis 1992; 146:781.
  13. Baz MA, Kussin PS, Van Trigt P, et al. Recurrence of diffuse panbronchiolitis after lung transplantation. Am J Respir Crit Care Med 1995; 151:895.
  14. Chen F, Hasegawa S, Bando T, et al. Recurrence of bilateral diffuse bronchiectasis after bilateral lung transplantation. Respirology 2006; 11:666.
  15. Mukae H, Kadota J, Kohno S, et al. Increase in activated CD8+ cells in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis. Am J Respir Crit Care Med 1995; 152:613.
  16. Ichikawa Y, Ninomiya H, Koga H, et al. Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. Am Rev Respir Dis 1992; 146:196.
  17. Oda H, Kadota J, Kohno S, Hara K. Erythromycin inhibits neutrophil chemotaxis in bronchoalveoli of diffuse panbronchiolitis. Chest 1994; 106:1116.
  18. Hiratsuka T, Mukae H, Iiboshi H, et al. Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Thorax 2003; 58:425.
  19. Sugiyama Y. Diffuse panbronchiolitis. Clin Chest Med 1993; 14:765.
  20. Kim YW, Han SK, Shim YS, et al. The first report of diffuse panbronchiolitis in Korea: five case reports. Intern Med 1992; 31:695.
  21. Tsang KW, Ooi CG, Ip MS, et al. Clinical profiles of Chinese patients with diffuse panbronchiolitis. Thorax 1998; 53:274.
  22. Chen Y, Kang J, Li S. Diffuse panbronchiolitis in China. Respirology 2005; 10:70.
  23. Poletti V, Patelli M, Poletti G, et al. Diffuse panbronchiolitis observed in an Italian. Chest 1990; 98:515.
  24. Randhawa P, Hoagland MH, Yousem SA. Diffuse panbronchiolitis in North America. Report of three cases and review of the literature. Am J Surg Pathol 1991; 15:43.
  25. Homer RJ, Khoo L, Smith GJ. Diffuse panbronchiolitis in a Hispanic man with travel history to Japan. Chest 1995; 107:1176.
  26. Fitzgerald JE, King TE Jr, Lynch DA, et al. Diffuse panbronchiolitis in the United States. Am J Respir Crit Care Med 1996; 154:497.
  27. Martinez JA, Guimarães SM, Ferreira RG, Pereira CA. Diffuse panbronchiolitis in Latin America. Am J Med Sci 2000; 319:183.
  28. Sandrini A, Balter MS, Chapman KR. Diffuse panbronchiolitis in a Caucasian man in Canada. Can Respir J 2003; 10:449.
  29. Adams NP, Congelton J. Diffuse panbronchiolitis. Eur Respir J 2008; 32:237.
  30. McGrath EE, McLaughlin AM, Fitzgerald MX. Diffuse panbronchiolitis: East meets West. Eur Respir J 2007; 29:817.
  31. Homma H, Yamanaka A, Tanimoto S, et al. Diffuse panbronchiolitis. A disease of the transitional zone of the lung. Chest 1983; 83:63.
  32. Xie GS, Li LY, Liu HR, et al. Diffuse panbronchiolitis with histopathological confirmation among Chinese. Chin Med J (Engl) 2004; 117:1299.
  33. Kudoh S, Keicho N. Diffuse panbronchiolitis. Clin Chest Med 2012; 33:297.
  34. Koyama H, Nishimura K, Mio T, et al. Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis. Thorax 1994; 49:540.
  35. Akira M, Kitatani F, Lee YS, et al. Diffuse panbronchiolitis: evaluation with high-resolution CT. Radiology 1988; 168:433.
  36. Nishimura K, Kitaichi M, Izumi T, Itoh H. Diffuse panbronchiolitis: correlation of high-resolution CT and pathologic findings. Radiology 1992; 184:779.
  37. Akira M, Higashihara T, Sakatani M, Hara H. Diffuse panbronchiolitis: follow-up CT examination. Radiology 1993; 189:559.
  38. Ichikawa Y, Hotta M, Sumita S, et al. Reversible airway lesions in diffuse panbronchiolitis. Detection by high-resolution computed tomography. Chest 1995; 107:120.
  39. Nagai H, Shishido H, Yoneda R, et al. Long-term low-dose administration of erythromycin to patients with diffuse panbronchiolitis. Respiration 1991; 58:145.
  40. Yamanaka A, Saiki S, Okamoto K. [Characteristics of the small airway area and etiology of airway diseases]. Nihon Rinsho 1978; 36:2427.
  41. Sato A, Chida K, Iwata M, Hayakawa H. Study of bronchus-associated lymphoid tissue in patients with diffuse panbronchiolitis. Am Rev Respir Dis 1992; 146:473.
  42. Iwata M, Colby TV, Kitaichi M. Diffuse panbronchiolitis: diagnosis and distinction from various pulmonary diseases with centrilobular interstitial foam cell accumulations. Hum Pathol 1994; 25:357.
  43. Feng RE, Xu WB, Shi JH, et al. Pathological and high resolution CT findings in Churg-Strauss syndrome. Chin Med Sci J 2011; 26:1.
  44. Desai SJ, Gephardt GN, Stoller JK. Diffuse panbronchiolitis preceding ulcerative colitis. Chest 1989; 95:1342.
  45. Homma S, Kawabata M, Kishi K, et al. Diffuse panbronchiolitis in rheumatoid arthritis. Eur Respir J 1998; 12:444.
  46. Sugiyama Y, Ohno S, Kano S, et al. Diffuse panbronchiolitis and rheumatoid arthritis: a possible correlation with HLA-B54. Intern Med 1994; 33:612.
  47. Ono K, Shimamoto Y, Matsuzaki M, et al. Diffuse panbronchiolitis as a pulmonary complication in patients with adult T-cell leukemia. Am J Hematol 1989; 30:86.
  48. Kadota J, Mukae H, Fujii T, et al. Clinical similarities and differences between human T-cell lymphotropic virus type 1-associated bronchiolitis and diffuse panbronchiolitis. Chest 2004; 125:1239.
  49. Fujii M, Sumi Y, Atarashi K, et al. Muscle weakness in extremities and diffuse centrilobular nodules in lungs. HTLV-1-associated bronchiolo-alveolar disorder. Thorax 2011; 66:546.
  50. Okada F, Ando Y, Yoshitake S, et al. Pulmonary CT findings in 320 carriers of human T-lymphotropic virus type 1. Radiology 2006; 240:559.
  51. Yamashiro T, Kamiya H, Miyara T, et al. CT scans of the chest in carriers of human T-cell lymphotropic virus type 1: presence of interstitial pneumonia. Acad Radiol 2012; 19:952.
  52. Izumi T. A nation-wide survey of diffuse panbronchiolitis and the high incidence of diffuse panbronchiolitis seen in Japanese respiratory clinics. In: Sarcoidosis and Other Granulomatous disorders, Grassi C, Rizzato G, Pozzi E (Eds), Elsevier Science Publishers, New York 1988. p.753.
  53. Nakada K, Inatomi K. Annual report on the study of diffuse interstitial lung disease. Grant-in-Aid from the Ministry of Health and Welfare, 1981.
  54. Lin X, Lu J, Yang M, et al. Macrolides for diffuse panbronchiolitis. Cochrane Database Syst Rev 2015; 1:CD007716.
  55. Steel HC, Theron AJ, Cockeran R, et al. Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics. Mediators Inflamm 2012; 2012:584262.
  56. Altenburg J, de Graaff CS, van der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics - part 1: biological mechanisms. Respiration 2011; 81:67.
  57. Nelson S, Summer WR, Terry PB, et al. Erythromycin-induced suppression of pulmonary antibacterial defenses. A potential mechanism of superinfection in the lung. Am Rev Respir Dis 1987; 136:1207.
  58. Goswami SK, Kivity S, Marom Z. Erythromycin inhibits respiratory glycoconjugate secretion from human airways in vitro. Am Rev Respir Dis 1990; 141:72.
  59. Kadota J, Sakito O, Kohno S, et al. A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis. Am Rev Respir Dis 1993; 147:153.
  60. Sugiyama Y, Sugama Y, Takeuchi K, et al. [Analysis of peripheral lymphocyte subsets and changes due to erythromycin therapy in patients with diffuse panbronchiolitis]. Nihon Kyobu Shikkan Gakkai Zasshi 1990; 28:1574.
  61. Morikawa T, Kadota JI, Kohno S, Kondo T. Superoxide dismutase in alveolar macrophages from patients with diffuse panbronchiolitis. Respiration 2000; 67:546.
  62. Hashimoto N, Kawabe T, Hara T, et al. Effect of erythromycin on matrix metalloproteinase-9 and cell migration. J Lab Clin Med 2001; 137:176.
  63. Kanai K, Asano K, Hisamitsu T, Suzaki H. Suppression of matrix metalloproteinase production from nasal fibroblasts by macrolide antibiotics in vitro. Eur Respir J 2004; 23:671.
  64. Kudoh S, Uetake T, Hagiwara K, et al. [Clinical effects of low-dose long-term erythromycin chemotherapy on diffuse panbronchiolitis]. Nihon Kyobu Shikkan Gakkai Zasshi 1987; 25:632.
  65. Tredaniel J, Zalcman G, Gerber F, et al. Diffuse panbronchiolitis: efficacy of low-dose erythromycin. Respir Med 1993; 87:229.
  66. Kudoh S, Azuma A, Yamamoto M, et al. Improvement of survival in patients with diffuse panbronchiolitis treated with low-dose erythromycin. Am J Respir Crit Care Med 1998; 157:1829.
  67. Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest 2010; 138:1202.
  68. Mikasa K, Sawaki M, Kita E, et al. [Long-term chemotherapy using erythromycin (EM) for chronic lower airway infection: effectiveness of clarithromycin in EM ineffective cases--the fourth report]. Kansenshogaku Zasshi 1992; 66:1097.
  69. Kadota J, Mukae H, Ishii H, et al. Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis. Respir Med 2003; 97:844.
  70. Tamaoki J, Takeyama K, Tagaya E, Konno K. Effect of clarithromycin on sputum production and its rheological properties in chronic respiratory tract infections. Antimicrob Agents Chemother 1995; 39:1688.
  71. Kadota J, Sakito O, Kohno S, et al. [Roxithromycin treatment in patients with chronic lower respiratory tract disease--its clinical efficacy and effect on cytokine]. Kansenshogaku Zasshi 1994; 68:27.
  72. Nakamura H, Fujishima S, Inoue T, et al. Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection. Eur Respir J 1999; 13:1371.
  73. Li H, Zhou Y, Fan F, et al. Effect of azithromycin on patients with diffuse panbronchiolitis: retrospective study of 51 cases. Intern Med 2011; 50:1663.
  74. Kobayashi H, Takeda H, Sakayori S, et al. [Study on azithromycin in treatment of diffuse panbronchiolitis]. Kansenshogaku Zasshi 1995; 69:711.
  75. Hanon S, Verbanck S, Schuermans D, et al. Evidence of improved small airways function after azithromycin treatment in diffuse panbronchiolitis. Respiration 2012; 84:75.
  76. Hui D, Yan F, Chen RH. The effects of azithromycin on patients with diffuse panbronchiolitis: a retrospective study of 29 cases. J Thorac Dis 2013; 5:613.
  77. Tamaoki J, Chiyotani A, Tagaya E, et al. Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis. Thorax 1994; 49:545.
  78. Sugimoto S, Miyoshi K, Yamane M, Oto T. Lung transplantation for diffuse panbronchiolitis: 5 cases from a single centre. Interact Cardiovasc Thorac Surg 2016; 22:679.
  79. Onishi Y, Kawamura T, Morimoto A, et al. A case of diffuse panbronchiolitis, associated with severe pulmonary hypertension, managed with bilateral lung transplantation from a brain-dead donor. Respir Investig 2015; 53:242.