in the membranous bronchioles (the initial non-cartilaginous section of the bronchiole, that divides from the tertiary bronchus) up to the secondary bronchus. ob is a bronchiolar disease with worldwide prevalence, while dpb has more localized prevalence, predominantly in japan. prior to clinical recognition of dpb in recent years, it was often misdiagnosed as bronchiectasia, copd, ipf, phthisis miliaris, sarcoidosis or alveolar cell carcinoma. treatment molecular structure of erythromycin a, an antibiotic used to treat dpb macrolide antibiotics, such as erythromycin, are an effective treatment for dpb when taken regularly over an extended period of time. clarithromycin or roxithromycin are also commonly used. the successful results of macrolides in dpb and similar lung diseases stems from managing certain symptoms through immunomodulation (adjusting the immune response), which can be achieved by taking the antibiotics in low doses. treatment consists of daily oral administration of erythromycin for two to three years, an extended period that has been shown to dramatically improve the effects of dpb. this is apparent when an individual undergoing treatment for dpb, among a number of disease-related remission criteria, has a normal neutrophil count detected in bal fluid, and blood gas (an arterial blood test that measures the amount of oxygen and carbon dioxide in the blood) readings show that free oxygen in the blood is within the normal range. allowing a temporary break from erythromycin therapy in these instances has been suggested, to reduce the formation of macrolide-resistant p. aeruginosa. however, dpb symptoms usually return, and treatment would need to be resumed. although highly effective, erythromycin may not prove successful in all individuals with the disease, particularly if macrolide-resistant p. aeruginosa is present or previously untreated dpb has progressed to the point where respiratory failure is occurring. with erythromycin therapy in dpb, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil proliferation, but also lymphocyte activity and obstructive mucus and water secretions in airways. the antibiotic effects of macrolides are not involved in their beneficial effects toward reducing inflammation in dpb. this is evident because the treatment dosage is much too low to fight infection, and in dpb cases with the occurrence of macrolide-resistant p. aeruginosa, erythromycin therapy still reduces inflammation. a number of factors are involved in suppression of inflammation by erythromycin and other macrolides. they are especially effective at inhibiting the proliferation of neutrophils, by diminishing the ability of interleukin 8 and leukotriene b4 to attract them. macrolides also reduce the efficiency of adhesion molecules that allow neutrophils to stick to bronchiolar tissue linings. mucus production in the airways is a major culprit in the morbidity and mortality of dpb and other respiratory diseases. the significant reduction of inflammation in dpb attributed to erythromycin therapy also helps to inhibit the production of excess mucus. prognosis untreated dpb leads to bronchiectasis, respiratory failure, and death. a journal report from 1983 indicated that untreated dpb had a five-year survival rate of 62.1%, while the 10-year survival rate was 33.2%. with erythromycin treatment, individuals with dpb now have a much longer life expectancy due to better management of symptoms, delay of progression, and prevention of associated infections like p. aeruginosa. the 10-year survival rate for treated dpb is about 90%. in dpb cases where treatment has resulted in significant improvement, which sometimes happens after about two years, treatment has been allowed to end for a while. however, individuals allowed to stop treatment during this time are closely monitored. as dpb has been proven to recur, erythromycin therapy must be promptly resumed once disease symptoms begin to reappear. in spite of the improved prognosis when treated, dpb currently has no known cure. epidemiology dpb has its highest prevalence among the japanese, at 11 per 100,000 population. korean, chinese, and thai individuals with the disease have been reported as well. a genetic predisposition among east asians is suggested. the disease is more common in males, with the male to female ratio at 1.4–2:1 (or about 5 men to 3 women). the average onset of the disease is around age 40, and two-thirds of those affected are non-smokers, although smoking is not believed to be a cause. the presence of hla-bw54 increases the risk of diffuse panbronchiolitis 13.3-fold. in europe and the americas, a relatively small number of dpb cases have been reported in asian immigrants and residents, as well as in individuals of non-asian ancestry. misdiagnosis has occurred in the west owing to less recognition of the disease than in asian countries. relative to the large number of asians living in the west, the small number of them thought to be affected by dpb suggests non-genetic factors may play some role in its cause. this rarity seen in western asians may also be partly associated with misdiagnosis. history in the early 1960s, a relatively new chronic lung disease was being observed and described by physicians in japan. in 1969, the name "diffuse panbronchiolitis" was introduced to distinguish it from chronic bronchitis, emphysema, alveolitis, and other obstructive lung disease with inflammation. between 1978 and 1980, the results of a nationwide survey initiated by the ministry of health and welfare of japan revealed more than 1,000 probable cases of dpb, with 82 histologically confirmed. by the 1980s, it was internationally recognized as a distinct disease of the lungs. before the 1980s, the prognosis or expected outcome of dpb was poor, especially in cases with superinfection (the emergence of a new viral or bacterial infection, in addition to the currently occurring infection) by p. aeruginosa. dpb continued to have a very high mortality rate before generalized antibiotic treatment and oxygen therapy were beginning to be used routinely in the effort to manage symptoms. around 1985, when long-term treatment with the antibiotic erythromycin became the standard for managing dpb, the prognosis significantly improved. in 1990, the association of dpb with hla was initially asserted.