Chinese expert consensus for non-antiinfective effects and clinical use of macrolides / 中华内科杂志

Important/potential value of macrolides has been proved in the management of chronic respiratory diseases by increasing basic and clinical trials.Through three face-to-face discussions,10 experts examined important data and drafted this consensus related to macrolides:(1) mechanism of nonantiinfective effects;(2) clinical use in chronic respiratory diseases;(3) cautions of long-term use.The mechanism out of non-antiinfective effects includes anti-inflammatory effect,modifying airway secretion,immune-regulation related to antibacterial effect,corticoid saving effect and anti-viral effect.The efficacy of long-term use of low-dose macrolides is definitely confirmed in diffuse panbronchiolitis,chronic rhinosinusitis.It is considerably used in bronchiectasia,cystic fibrosis,severe asthma and chronic obstructive pulmonary disease.Further studies should be conducted in cryptogenic organizing pneumonia and respiratory viral infection.It should be paid attention to its possible adverse effects (including drug interactions,cardiac toxicity,ototoxicity and disturbance of intestinal flora) and drug resistance in long-term use.A Chinese consensus for non-antiinfective effects and clinical use of macrolides is developed for the first time,which aims to expand their rational use and the further research.

Diffuse panbronchiolitis in an adolescent female

Diffuse panbronchiolitis (DPB) is a progressive inflammatory respiratory disease of unknown cause mainly occurring in East Asian people. Studies on causes of the disease point to a genetic predisposition unique to Asians, but the cause remains unknown. If untreated, DPB progresses to bronchiectasis, respiratory failure, and death. The age of patients at onset of the disease varies from young to elderly people with a peak at 40-60 years. A few cases of DPB have been reported in Korean adults since 1992; however, the case of DPB in children is uncommon. Herein, we describe a 16-year-old girl with DPB who presented with chronic cough and sputum.

Single Center Experience of Five Diffuse Panbronchiolitis Patients Clinically Presenting as Severe Asthma

Diffuse panbronchiolitis (DPB) is a bronchiolitis affecting the whole lung fields which can be treated by macrolide. Especially East Asian patients are more susceptible to diffuse panbronchiolitis. As asthma and DPB both can cause airway obstruction, differential diagnosis is important for the 2 diseases. Here we report 5 patients with DPB clinically presenting as severe asthma in Korea, who were well treated by macrolide. Among the 5 patients, 2 could stop their asthma inhalers and the other 3 could reduce asthma medications after diagnosis and treatment of DPB. In conclusion, considering DPB as differential diagnosis for asthmatics in Asian ethnic groups is important.

Diffuse panbronchiolitis: Report of a rare disease from India.

Initially described by a group of Japanese clinicians and pulmonary pathologists to distinguish it from other chronic obstructive lung diseases, diffuse panbronchiolitis (DPB) is an uncommon disorder which has been reported largely from the eastern world. It is imperative to recognise this condition because of its potentially treatable nature. Recently, long-term macrolide therapy has revolutionised its management. Herein, we describe a 65-year-old male who was being managed as a case of chronic bronchitis before this diagnosis was suspected and proved.

Diffuse panbronchiolitis: not just an Asian disease: Australian case series and review of the literature

Diffuse panbronchiolitis is a disease of obscure aetiology that is traditionally associated with Asian ethnicity. We propose that this disease also occurs in Caucasians and the incidence in this population is greater than currently recognised. We further propose that high resolution computed tomography (HRCT) and response to macrolide therapy should be relied upon to make this diagnosis without verification by lung biopsy. In most circumstances, obtaining a biopsy for histopathology is not practical, and the disease may then be mistaken for other more common airway diseases. Accuracy of diagnosis is important as untreated disease is associated with a poor prognosis, and effective treatment is available. We report four out of a series of cases as evidence that DPB is in fact more common in the Western population than is currently understood.

A Case of Successful Acupuncture Treatment for Diffuse Pan-Bronchiolitis / 全日本鍼灸学会雑誌

[Aim] Diffuse pan-bronchiolitis (DPB) causes severe respiratory dysfunction and severely limits a patient's daily activities. Case: This paper reports a case of a DPB patient whose respiratory symptoms were successfully improved by acupuncture. In a case report in January 2002, a 62-year-old male visited the Department of Respiratory Internal Medicine at Gifu University Hospital, complaining of cough, pumlent sputum and dyspnea on exercise. His general condition had worsened despite ordinary medical treatment. Thus acupuncture was added to the treatment in August, 2001. Intervention: The patient received acupuncture treatments once a week for 50 weeks. The acupuncture treatment was based on the Chinese medicine theory. Measurements: Outcome measures were respiratory symptoms using the Fletcher-Hugh-Jones (F-H-J) classification, 6-minute walking distance (6 MWD), blood test, arterial blood gas and pulmonary function tests. Computed tomography (CT) was assessed. Each evaluation was done after 15 weeks and 50 weeks later.<br>[Results] After 15 weeks of acupuncture treatment, cough, pumlent sputum, walking distance, the Borg scale and respiratory function were significantly improved compared with the baseline. Moreover, the effect of the acupuncture treatment continued for 50 weeks.<br>[Conclusion] This suggests that acupuncture treatment was effective in treating the advanced case of DPB.

Erythromycin Inhibits Interleukin-6 and Interleukin-8 Expression and Promotes Apoptosis of Activated Human Neutrophils in Vitro

Diffuse panbronchiolitis (DPB) is a pulmonary disease characterized by chronic inflammation of the bronchioles and chronic infiltration of inflammatory cells in the lungs. Macrolides are effective therapeutic agents for chronic respiratory tract diseases, such as DPB. However, the mechanisms by which macrolides modulate the immune responses in patients with DPB remain unclear. To understand clinical efficacy for the treatment of DPB by macrolides, the effects of erythromycin (EM) on the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) by human neutrophils were examined. Pre-treatment with EM significantly decreased the expression of IL-6 and IL-8 transcripts by lipopolysaccharide (LPS)-stimulated human neutrophils. EM also reversed the enhanced survival of human neutrophils by LPS. These data indicate that EM has achieved therapeutic effect for patients with DPB, in part, through decreasing the expression of pro-inflammatory cytokines and the survival of neutrophils.

Correlation between cold hemoagglutinin and diffuse panbronchiolitis in Chinese / 基础医学与临床

Objective To identify a potential correlation between cold hemoagglutinin(CHA) and diffuse panbronchiolitis(DPB) in Chinese patients.Methods Eighteen patients diagnosed as DPB from December 1996 to July 2008 in Peking Union Medical College Hospital and 60 cases of DPB reported in mainland of China from 1996 to 2008 were enrolled in the study.Results Of 18 patients diagnosed as DPB in Peking Union Medical College Hospital,only one patient showed a titer of CHA≥1:64.Of 60 cases in mainland China,48 cases were CHA positive.CHA was positive in 54.1% all cases.There may be some correlation between positive rate of CHA and medication as well as population.Conclusion Low positive rate of CHA in Chinese subjects,which is different from that of Japanese DPB patients,suggests that CHA may not be applied as a diagnostic criteria for Chinese patients.

Diffuse Panbronchiolitis and Its Clinical Analysis / 中华医院感染学杂志

OBJECTIVE To highlight the characteristics of diffuse panbronchiolitis(DPB) in community hospital.METHODS One patient with DPB confirmed by clinic was described and relevant literatures were reviewed.RESULTS DPB was a chronic lower respiratory tract disease common in Japanese,rare in China,characterized by infiltration of inflammatory cells around bronchioles.Symptoms included cough,expectoration,and dyspnea after exercises.Pseudomonas aeruginosa was isolated from sputum in some cases.Some patients had the history and X-ray manifestation of sinusitis.The reason for a high misdiagnosis rate was due to unknown to its clinical findings and its diagnosis standard among doctors in community hospital.Chest high resolution CT(HRCT) could be attributed to the diagnosis of diffuse panbronchiolitis.The early treatment with macrolides was satisfied.CONCLUSIONS The patients with the history of chronic cough,expectoration and sinusitis,should be diagnosed.Long term,low dose macrolide therapy may improve the prognosis through an anti-inflammatory effect.

A Case of Diffuse Panbronchiolitis Developing in Childhood / 소아과

Diffuse panbronchiolitis(DPB) is a chronic inflammatory airway disease predominantly affecting respiratory bronchioles, with distinct clinicopathological profiles. It was first described in 1966 by Yamanaka et al. The etiology of DPB is not yet clear, and the natural history of the disease is respiratory failure leading to cor pulmonale and ultimately death. But the long-term use of low-dose macrolide has proven to be highly effective in treating patients with DPB. Usual age at diagnosis is over 40. A few cases of DPB have been reported in Korea since 1992 but there have been no reports in children. We experienced a case of DPB in a 12-year-old girl. Therefore, we report the case with a brief review of the related literature.

Relation of Epidermal Growth Factor Receptor Expression to Goblet Cell Dysplasia in Diffuse Panbronchiolitis / 결핵

BACKGROUND: Diffuse panbronchiolitis(DPB) is a chronic inflammatory lung disease that presents as coughing, copious sputum, exertional dyspnea, which progresses to bronchiectasis. The pathogenesis of bronchiectasis is controlled by inflammatory mediators, which are closely related to mucus hypersecretion, goblet cell dysplasia. In recent studies, the epidermal growth factor receptor(EGFR) system was reported to be associated with this process. It was hypothesized that a relationship exists between goblet cell dysplasia, EGFR expression, and inflammatory mediators produced by neutrophil. METHOD: Alcian blue/periodic acid -Schiff(AB/PAS) stain, MUC5AC, EGFR, CD16 immunohistochemical stain were examined to investigate a role for the EGFR system in a mucus hypersecretion in DPB using the lung biopsy specimens from 13 DPB patients and 6 controls. RESULTS: In the DPB group, the AB/PAS- and MUC5AC-stained areas were 8.31+/-3.36%, 11.46+/-4.68%, respectively. In the control group, the AB/PAS- and MUC5AC-stained areas were 50.5+/-5.77%, 53.3%+/-6.67%, which was significantly larger than in the DPB group (each comparison, p<0.05). The percentage of EGFR expression was 9.54+/-4.95% in the DPB group, but zero in of the control group. The extent of neutrophilic infiltration was 71.92+/-3.71/5HPF in the DPB group and 45.0+/-5.73/5HPF in the control group, which was statistically significant(p=0.002). CONCLUSION: The EGFR system is highly related to goblet cell dysplasia, mucus hypersecretion and neutrophilic inflammation in DPB.

Long-term Follow-up of Patients with Diffuse Panbronchiolitis after Erythromycin Therapy / 대한내과학회지

BACKGROUND: Diffuse panbronchiolitis(DPB) is a chronic inflammatory disease affecting the respiratory bronchioles which was first described in Japan in 1966. DPB is prevalent in Japan and is known to be very rare in western countries. The first cases of DPB were reported in Korea in 1992 and the number of the patients has been increasing. The prognosis of DPR had been very poor because there had been no effective treatment for the disease. Hut it has been dramatically changed since the introduction of low-dose long-term erythromycin therapy. In Korea, there is rare experience of 1ong-term follow-up of DPH patients and we presents the results of mean 21.6 months of follow-up after erythromycin treatment. METHODS: We analyzed the long-term follow-up data of 25 DPH patients who were diagnosed in Seoul National University Hospital during the period from September 1989 to December 1994 and followed up more than 6 months with erythromycin therapy. We tried erythromycin 250mg b.i.d. on all the patients and analyzed the changes of subjective symptoms, physical signs, pulmonary function tests, and chest X-rays. RESULTS: 1) The mean follow-up period was 21.6 months. 2) Subjective symptoms improved in 96% of the patients within 3 months and 76% of the patients showed no symptom after 18 months of treatment. 3) Crackles and wheezing decreased in all patients within 3 months and completely disappeared in 76% of the patients after 18 months of treatment. 4) Diffuse small nodular lesions on chest X-ray decreased in 56% of the patients within 3 months and chest PA was normal in 32% of the patients after 12months of treatment. 5) FVC and FEV1 increased remarkably during the first 3 months and slowly increased thereafter, reaching normal level after 12 months of treatment. FEV1/FVC was 60.4% before treatment and in- creased slowly reaching 76.1% after 24 months of treatment. 6) Erythromycin therapy could be finished in 7 patients. The mean duration of medication was 26 months and no evidence of recurrence was found in 6 months of follow-up. 7) No patients had experienced the side effect of erythromycin, CONCLUSION: The prognosis of DPR is very goad when treated with erythromycin. And at least 2 years of erythromycin treatment seems to be needed for DPB patients.

Multiple Small Nodular Lung Lesions with Severe Dyspnea / 결핵

Diffuse panbronchiolitis is a chronic inflammatory lung disease of unknown etiology which is characterized by chronic airflow limitation and airway inflammation, predominantly localized in the respiratory bronchioles with infiltration of inflammatory cells, and has typical clinical, radiological and pathological features. Obstructive respiratory functional impairment, occasional symptoms of wheezing, and also cough and sputum resemble the feature of emphysema, bronchial asthma, or chronic bronchitis, respectively. We experienced a case of pathologically proven advanced diffuse panbronchiolitis in a 55-year-old man with productive cough and exertional dyspnea. The chest radiography showed multiple tiny nodular densities on whole lung fields. It was confirmed by thoracoscopy-guided lung biopsy and the patient was improved after initiation of treatment with low-dose erythromycin

Clinical Effect of Low-dose Long-term Erythromycin on Diffuse Panbronchiolitis / 결핵

BACKGROUND: Diffuse panbronchiolitis(DPB) is a chronic inflammatory lung disease of unknown etiology which has characteristic clinical, radiological and pathological features, and is distinguished from bronchial asthma, chronic bronchitis, pulmonary emphysema, bronchiectasis, or alveolitis. Clinically, patients with DPB have chronic cough, purulent sputum, exertional dyspnea, and finally respiratory failure. Until a few years ago, the prognosis of DPB had been thought to be very grave, because there had been no effective treatment for the disease. But recently, low-dose long-term erythromycin was found to be very effective on DPB. Even though DPB is prevalent in Japan, and is known to be rare outside of Japan, we have already reported the clinical features of 16 DPB cases in Korea. We tried low-dose long-term erythromycin on DPB patients and analyzed the clinical effect of erythromycin. METHODS: We analyzed the changes of subjective symptoms, physical signs, pulmonary function tests and chest X-rays on 14 DPB patients with more than 6 months erythromycin treatment during the period from September 1989 to August 1992 in Seoul National University Hospital. RESULTS: 1) Subjective symptoms improved in all patients within 2-3 months, and 54.5% of the patients shorted no symptom after one year of treatment. 2) Crackles and wheezing decreased in 92.9% of the patients after 3 months and completely disappeared in 63.5% of the Patients after one year of treatment. 3) FVC and FEV1 increased remarkably during the first 3 months, and slowly increased thereafter, reaching normal level after one year of treatment. 4) Small nodular lesions on chest X-ray decreased in all patients, and chest PA was normal in 36.4% of the patients after one year of treatment. 5) There was side effect in one patient, stopping medication because of dyspepsia. One patient stopped medication because of no symptom after 16 months of treatment, but her symptom recurring after one month, improving again after retreatment. CONCLUSION: Low-dose long-term erythromycin showed ramarkable effectiveness on DPB. Further studies are needed on the mechanism of the drug and the duration of the treatment.