Diffuse panbronchiolitis
| Diffuse panbronchiolitis | |
| ICD-10 | J21.9 |
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| ICD-9 | 466.1 |
| OMIM | 604809 |
| DiseasesDB | 3804 |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Diffuse panbronchiolitis (DPB)[1] is an idiopathic (of unknown cause) inflammatory lung disease,[2] considered to be a type of COPD.[3][4] It is a severe, progressive form of bronchiolitis, mainly affecting the respiratory bronchioles (the section of the bronchioles involved in gas exchange).[2]
The term "diffuse" refers to the lesions which appear throughout both lungs, while the term "pan-" refers to the inflammation found in all layers of the respiratory bronchioles, both terms describing a common pathology for the disease.[2]
If left untreated, DPB is fatal, usually progressing to bronchiectasis, an irreversible lung conditon that causes respiratory failure.[2]
Prevalence
DPB has the highest incidence among Japanese.[2][5][6] Korean,[7][4][8] Chinese[6][9] and Thai cases[10] have been reported as well. A genetic predisposition among East Asians is indicated,[3][4][8] with a lower worldwide prevalence of DPB still usually related to Asian ancestry.[11] However, rare cases of DPB, being those in the western world in individuals with non-Asian lineage,[12] have also been noted.[13][14][12]
Symptoms
DPB can be characterized by a number of symptoms and histological features (those detected by analysis of tissues).
These include: chronic bronchial and bronchiolar inflammation, lung tissue lesions, proliferation of lymphocytes (white blood cells that fight infection), neutrophil granulocytes (white blood cells involved with inflammation) and foamy histiocytes (tissue macrophages) in the lung lumen;[2][5] detectable haemophilus influenzae (an opportunistic bacterium),[2] pseudomonas aeruginosa (another opportunistic bacterium) and pus in the sputum (coughed-up phlegm);[1][5] chronic sinusitis (inflamed paranasal sinuses),[13][14] hypoxemia (low levels of oxygen in the blood),[15] nodules within terminal and respiratory bronchioles in both lungs,[10][12] dyspnea (shortness of breath),[9][14] elevated IgG and IgA (classes of immunoglobulins),[6] occurrences of elevated rheumatoid factor (an indicator of autoimmunity),[6] and hemagglutination (clumping of antibodies in the blood).[6][16]
If left untreated, as DPB progresses, signs of bronchiectasis begin to present themselves. These symptoms include chronic shortness of breath, severe cough, pooling of sputum, thickening of bronchiolar walls, hypoxemia, and dilation (enlargement) of the bronchiolar passages.[1][14] This eventually becomes life-threatening, leading to respiratory failure.[1]
Pathogenesis
DPB remains idiopathic, which means an exact physiological, environmental, or pathogenic cause of the disease is unknown.[2] However, several known factors are involved with the pathogenesis of DPB.[3][4]
The major histocompatibility complex (MHC) is a large genomic region found in most vertebrates, that is associated with mating and the immune system. It is located on chromosome 6 in humans. A subset of the human MHC is human leukocyte antigen (HLA), which controls the antigen presenting system, as part of adaptive immunity against pathogens such as bacteria and viruses.
Genetic predisposition for DPB has been localized to two HLA haplotypes unique to Asians, particularly of East Asian descent.[3][8] HLA-B54 is associated with DPB in Japanese patients,[3] while HLA-A11 is associated with the disease in Koreans.[4] One or more candidate genes[17] (a gene suspected to be responsible for a trait or disease) within this region of class I HLA are believed to be the genetic factor responsible for DPB, allowing disease susceptibility[8] related to the structure of the antigen presenting molecules selected by these genes.[18]
Candidate genes within HLA that are most likely involved with DPB suceptibility include: C6orf37[17] and TAP2.[18]
Another such gene, though not a part of the HLA system, is the gene for interleukin 8 (IL-8)[19] located on chromosome 4. The role of IL-8 to produce inflammation by causing the proliferation of neutrophil granulocytes at any site of pathogenic involvement, in conjunction with strong microsatellite identification with DPB, implicates IL-8 as another candidate gene associated with DPB pathogenesis.[19] This also supports the idea that several factors, including those unrelated to HLA as well as non-genetic, and unknown factors, may cause the disease.[19]
The inflammation common to DPB also provides a means to determine other mechanisms of disease pathogenesis.[20] This may be partly due to the persistence of inflammation in DPB, with or without the presence of the two opportunistic bacteria sometimes found with the disease (haemophilus influenzae, pseudomonas aeruginosa).[5] Inflammation caused by the chemokine MIP-1alpha and its involvement with CD8+ T-cells is believed to be one such mechanism of DPB pathogenesis.[20]
Other factors found with DPB play a part in its pathogenesis by sometimes causing minor variations of it.
Beta defensins, a family of antimicrobial peptides found in the respiratory tract, are responsible for further inflammation in DPB, when associated pathogens like pseudomonas aerugenosa are present.[21]
If present in a DPB patient, the human T-lymphotropic virus, type I, a retrovirus, modifies DPB pathogenesis by infecting CD4+ cells (Helper T-cells) and altering there effectiveness in reducing both known and unknown pathogenic involvement with DPB.[22] Conversely, an onset of DPB causes increased frequency of Adult T-cell leukemia in human lymphotropic virus sufferers.[22]
Treatment
Macrolide antibiotics, such as erythromycin, clarithromycin and roxithromycin, have proven to be an effective long-term treatment for DPB.[23][24] The successful results of macrolides in DPB and similar lung diseases stems from controlling symptoms through immunomodulation (adjusting the immune response),[24] with the added benefit of low-dose requirements.[23]
With macrolide therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil granulocyte proliferation, but also lymphocyte activity and obstructive mucus and sputum secretions in airways.[23] The antimicrobial and antibiotic effects of macrolides, however, are not believed to be involved in their beneficial effects toward treating DPB.[25] This is evident, as the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of macrolide-resistant pseudomonas aeruginosa, macrolide therapy still produces substantial anti-inflammatory results.[23]
Advanced cases of DPB, where severely excessive sputum production resistant to macrolides persists, additional therapy with the inhalant tiotropium has been shown to ease these symptoms and the related shortness of breath.[26]
See also
References
- ↑ 1.0 1.1 1.2 1.3 Homma H, Yamanaka A, Tanimoto S, Tamura M, Chijimatsu Y, Kira S, Izumi T (1983). "Diffuse panbronchiolitis. A disease of the transitional zone of the lung". Chest. 83 (1): 63–69. PMID 6848335.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Poletti V, Casoni G, Chilosi M, Zompatori M (2006). "Diffuse panbronchiolitis". Eur Respir J. 28 (4): 862–871. PMID 17012632.
- ↑ 3.0 3.1 3.2 3.3 3.4 Keicho N, Tokunaga K, Nakata K, Taguchi Y, Azuma A, Bannai M, Emi M, Ohishi N, Yazaki Y, Kudoh S (1998). "Contribution of HLA genes in genetic predisposition for diffuse panbronchiolitis". Am J Respir Crit Care Med. 158 (3): 846–850. PMID 9731015.
- ↑ 4.0 4.1 4.2 4.3 4.4 Park MH, Kim YW, Yoon HI, Yoo CD, Han SK, Shim YS, Kim WD (1999). "Association of HLA class I antigens with diffuse panbronchiolitis in Korean patients". Am J Respir Crit Care Med. 159 (2): 526–529. PMID 9927368.
- ↑ 5.0 5.1 5.2 5.3 Yanagihara K, Kadoto J, Kohno S (2001). "Diffuse panbronchiolitis--pathophysiology and treatment mechanisms". Int J Antimicrob Agents. 18 (Suppl. 1): S83–87. PMID 11574201.
- ↑ 6.0 6.1 6.2 6.3 6.4 Tsang KW, Ooi CG, Ip MS, Lam WK, Ngan H, Chan EY, Hawkins B, Ho CS, Amitani R, Tanaka E, Inoh H (1998). "Clinical profiles of Chinese patients with diffuse panbronchiolitis". Thorax. 53 (4): 274–280. PMID 9741370.
- ↑ Kim YW, Han SK, Shim YS, Kim KY, Han YC, Seo JW, Im JG (1992). "The first report of diffuse panbronchiolitis in Korea: 5 case reports". Intern Med. 31 (5): 695–701. PMID 1504438.
- ↑ 8.0 8.1 8.2 8.3 Keicho N, Ohashi J, Tamiya G, Nakata K, Taguchi Y, Azuma A, Ohishi N, Emi M, Park MH, Inoko H, Tokunaga K, Kudoh S (2000). "Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis". Am J Hum Genet. 66 (2): 501–507. PMID 10677310.
- ↑ 9.0 9.1 Chen Y, Kang J, Li S (2005). "Diffuse panbronchiolitis in China". Respirology. 10 (1): 70–75. PMID 15691241.
- ↑ 10.0 10.1 Chantarotorn S, Palwatwichai A, Vattanathum A, Tantamacharik D (1999). "Diffuse panbronchiolitis, the first case reports in Thailand". J Med Assoc Thai. 82 (8): 833–838. PMID 10511794.
- ↑ Hoiby N (1994). "Diffuse panbronchiolitis and cystic fibrosis: East meets West". Thorax. 49 (6): 531–532. PMID 8016786.
- ↑ 12.0 12.1 12.2 Sandrini A, Balter MS, Chapman KR (2003). "Diffuse panbronchiolitis in a Caucasian man in Canada". Can Respir J. 10 (8): 449–451. PMID 14679410.
- ↑ 13.0 13.1 Martinez JA, Guimaraes SM, Ferreira RG, Pereira CA (2000). "Diffuse panbronchiolitis in Latin America". Am J Med Sci. 319 (3): 183–185. PMID 10746829.
- ↑ 14.0 14.1 14.2 14.3 Fitzgerald JE, King TE Jr., Lynch DA, Tuder RM, Schwarz MI (1996). "Diffuse panbronchiolitis in the United States". Am J Respir Crit Care Med. 154 (2 pt. 1): 497–503. PMID 8756828.
- ↑ Chu YC, Yeh SZ, Chen CL, Chen CY, Chang CY, Chiang CD (1992). "Diffuse panbronchiolitis: report of a case". J Formos Med Assoc. 91 (9): 912–915. PMID 1363394.
- ↑ Schulte W, Szrepka A, Bauer PC, Guzman J, Costabel U (1999). "Diffuse panbronchiolitis. A differential diagnosis of chronic obstructive lung disease". Dtsch Med Wochenschr. 124 (19): 584–588. PMID 10365176.
- ↑ 17.0 17.1 Matsuzaka Y, Tounai K, Denda A, Tomizawa M, Makino S, Okamoto K, Keicho N, Oka A, Kulski JK, Tamiya G, Inoko H (2002). "Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC". Immunogenetics. 54 (5): 301–309. PMID 12185533.
- ↑ 18.0 18.1 Keicho N, Tokunaga K, Nakata K, Taguchi Y, Azuma A, Tanabe K, Matsushita M, Emi M, Ohishi N, Kudoh S (1999). "Contribution of TAP genes to genetic predisposition for diffuse panbronchiolitis". Tissue Antigens. 53 (4 pt. 1): 366–373. PMID 10323341.
- ↑ 19.0 19.1 19.2 Emi M, Keicho N, Tokunaga K, Katsumata H, Souma S, Nakata K, Taguchi Y, Ohishi N, Azuma A, Kudoh S (1999). "Association of diffuse panbronchiolitis with microsatellite polymorphisms of the human interleukin 8 (IL-8) gene". J Hum Genet. 44 (3): 169–172. PMID 10319580.
- ↑ 20.0 20.1 Kadota J, Mukae H, Tomono K, Kohno S (2001). "High concentrations of beta-chemokines in BAL fluid of patients with diffuse panbronchiolitis". Chest. 120 (2): 602–607. PMID 11502665.
- ↑ Hiratsuka T, Mukae H, Iiboshi H, Ashitani J, Nabeshima K, Minematsu T, Chino N, Ihi T, Kohno S, Nakazato M (2003). "Increased concentrations of human beta-defensins in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis". Thorax. 58 (5): 425–430. PMID 12728165.
- ↑ 22.0 22.1 Yamamoto M, Matsuyama W, Oonakahara K, Watanabe M, Higashimoto I, Kawabata M, Osame M, Arimura K (2004). "Influence of human T lymphotropic virus type I on diffuse pan-bronchiolitis". Clin Exp Immunol. 136 (3): 513–520. PMID 15147354.
- ↑ 23.0 23.1 23.2 23.3 Keicho N, Kudoh S (2002). "Diffuse panbronchiolitis: role of macrolides in therapy". Am J Respir Med. 1 (2): 119–131. PMID 14720066.
- ↑ 24.0 24.1 Lopez-Boado YS, Rubin BK (2008). "Macrolides as immunomodulatory medications for the therapy of chronic lung diseases". Curr Opin Pharmacol. Epub ahead of print. PMID 18339582.
- ↑ Schultz MJ (2004). "Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis". J Antimicrob Chemother. 54 (1): 21–28. PMID 15190022.
- ↑ Saito Y, Azuma A, Morimoto T, Fujita K, Abe S, Motegi T, Usuki J, Kudoh S (2008). "Tiotropium ameliorates symptoms in patients with chronic airway mucus hypersecretion which is resistant to macrolide therapy". Intern Med. 47 (7): 585–591. PMID 18379141.