Diffuse panbronchiolitis: Difference between revisions
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== Symptoms == | == Symptoms == | ||
== Pathogenesis == | == Pathogenesis == | ||
Revision as of 15:45, 24 September 2012
| Diffuse panbronchiolitis | |
| ICD-10 | J21.9 |
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| ICD-9 | 466.1 |
| OMIM | 604809 |
| DiseasesDB | 3804 |
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Diffuse panbronchiolitis Microchapters |
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Differentiating Diffuse panbronchiolitis from other Diseases |
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Diffuse panbronchiolitis On the Web |
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American Roentgen Ray Society Images of Diffuse panbronchiolitis |
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Risk calculators and risk factors for Diffuse panbronchiolitis |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Prevalence
Symptoms
Pathogenesis
DPB remains idiopathic, which means an exact physiological, environmental, or pathogenic cause of the disease is unknown.[1] However, several known factors are involved with the pathogenesis of DPB.[2][3]
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.[2][4] HLA-B54 is associated with DPB in Japanese patients,[2] while HLA-A11 is associated with the disease in Koreans.[3] One or more candidate genes[5] (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[4] related to the structure of the antigen presenting molecules selected by these genes.[6]
Candidate genes within HLA that are most likely involved with DPB suceptibility include: C6orf37[5] and TAP2.[6]
Another such gene, though not a part of the HLA system, is the gene for interleukin 8 (IL-8)[7] 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.[7] 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.[7]
The inflammation common to DPB also provides a means to determine other mechanisms of disease pathogenesis.[8] 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).[9] Inflammation caused by the chemokine MIP-1alpha and its involvement with CD8+ T-cells is believed to be one such mechanism of DPB pathogenesis.[8]
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.[10]
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.[11] Conversely, an onset of DPB causes increased frequency of Adult T-cell leukemia in human lymphotropic virus sufferers.[11]
Treatment
Macrolide antibiotics, such as erythromycin, clarithromycin and roxithromycin, have proven to be an effective long-term treatment for DPB.[12][13] The successful results of macrolides in DPB and similar lung diseases stems from controlling symptoms through immunomodulation (adjusting the immune response),[13] with the added benefit of low-dose requirements.[12]
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.[12] The antimicrobial and antibiotic effects of macrolides, however, are not believed to be involved in their beneficial effects toward treating DPB.[14] 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.[12]
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.[15]
See also
References
- ↑
- ↑ 2.0 2.1 2.2
- ↑ 3.0 3.1
- ↑ 4.0 4.1
- ↑ 5.0 5.1 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.
- ↑ 6.0 6.1 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.
- ↑ 7.0 7.1 7.2 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.
- ↑ 8.0 8.1 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.
- ↑ 11.0 11.1 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.
- ↑ 12.0 12.1 12.2 12.3 Keicho N, Kudoh S (2002). "Diffuse panbronchiolitis: role of macrolides in therapy". Am J Respir Med. 1 (2): 119–131. PMID 14720066.
- ↑ 13.0 13.1 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.