Treatment Of Diffuse Panbronchiolitis Research Articles

Clinical characteristics of 32 cases of diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a chronic airway inflammation with low specificity and its diagnosis is often missed or delayed. This study aims to summarize the clinical characteristics and treatment of DPB in order to improve the understanding and diagnosis of the disease. The clinical data of 32 DPB patients were collected, analyzed and summarized from March 1, 2013 to March 1, 2022 in the Second Xiangya Hospital of Central South University. The basic information, clinical manifestations, laboratory tests, pulmonary function, imaging tests, treatment, and regression of patients were analyzed. A total of 32 patients were enrolled in the final analysis, with a male-to-female ratio at 1.67. The median age at symptom onset was 26.5 (11.0-69.0) years, and the median age of diagnosis was 47.5 (16.0-77.0) years. All patients presented with chronic cough and copious sputum production. A total of 26 patients had post activity shortness of breath and 14 patients had a positive result (blood cold agglutination test titer≥1꞉64). Pulmonary function examination was performed in 31 patients, 18 patients showed mixed pulmonary ventilation dysfunction, 12 patients showed obstructive pulmonary ventilation, and 1 patient had normal pulmonary ventilation function. A total of 31 patients had a bilateral, diffuse, small nodule pattern on chest CT. All patients were treated with macrolides. A total of 31 patients showed improvement, and 20 patients showed improvement in partial pressure of oxygen and blood oxygen saturation compared with before at discharge. A total of 12 patients were re-examined by chest CT after completing macrolides treatment, 6 cases showed less diffuse nodules, 5 cases showed no significant changes, and 1 case showed more diffuse nodules, which indicated the disease progression. Seven patients received pulmonary function tests after completing macrolides treatment, forced expiratory volume in one second (FEV1) and FEV1/forced vital capacitywere improved, but forced expiratory flow at 25% of vital capacity did not change significantly. The clinical manifestations of DPB are nonspecific. Early diagnosis and treatment are very important for the prognosis of patients.

A progress of macrolides therapy for chronic rhinosinusitis

Macrolides are a type of antibiotics with macrocyclic lactone ring, which have been commonly used in the treatment of diffuse panbronchiolitis, chronic obstructive pulmonary disease, bronchial asthma, cystic fibrosis and other diseases. Macrolides not only have effect on antibacterial, but also effect on anti-inflammatory and immunoregulation. Chronic rhinosinusitis (CRS) is a common disease entity of infectious and inflammatory diseases that involved in nasal cavity and nasal sinuses, with various clinical phenotypes. With the high prevalence of CRS, it seriously affects the quality of patients' life. In recent years, a large number of studies have shown that long-term low-dose macrolides are effective in parts of patients with CRS. Although the mechanism of macrolides for CRS has not yet been clarified. According to recent studies, it might be related with anti-inflammatory or immunoregulation of macrolides and the different phenotypes of CRS. The safety and mechanism of long-term macrolides are needed further clarification.

Macrolides for diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a chronic airways disease predominantly affecting East Asians. Macrolides, a class of antibiotics, have been used as the main treatment for DPB, based on evidence from retrospective and non-randomised studies. To assess the efficacy and safety of macrolides for DPB. We searched CENTRAL (2014, Issue 6), MEDLINE (1966 to July week 1, 2014), EMBASE (1974 to July 2014), Chinese Biomedical Literature Database (CBM) (1978 to July 2014), China National Knowledge Infrastructure (CNKI) (1974 to July 2014), KoreaMed (1997 to July 2014) and Database of Japana Centra Revuo Medicina (1983 to July 2014). Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of macrolides for DPB. Two review authors independently assessed study quality and subsequent risk of bias according to The Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes were five-year survival rate, lung function and clinical response. We used risk ratios (RR) for individual trial results in the data analysis and measured all outcomes with 95% confidence intervals (CI). Only one RCT (19 participants) with significant methodological limitations was included in this review. It found that the computerised tomography images of all participants treated with a long-term, low-dose macrolide (erythromycin) improved from baseline, while the images of 71.4% of participants in the control group (with no treatment) worsened and 28.6% remained unchanged. Adverse effects were not reported. This review was previously published in 2010 and 2013. For this 2014 update, we identified no new trials for inclusion or exclusion. There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.

Advantages and drawbacks of long-term macrolide use in the treatment of non-cystic fibrosis bronchiectasis.

Non-cystic fibrosis (non-CF) bronchiectasis is a respiratory disease characterized by persistent airway inflammation and dilation of bronchial wall driven by various causes. Patients with bronchiectasis suffer from excessive sputum production, recurrent exacerbations, and progressive airway destruction. Major therapy for bronchiectasis is focused on breaking the "vicious cycle" of mucus stasis, infection, inflammation, and airway destruction. Growing evidences have been shown that macrolides possess immunoregulatory and anti-inflammatory functions beyond their antimicrobial effects. Macrolide antibiotics have been effectively used in the treatment of diffuse panbronchiolitis, CF and bronchiolitis obliterans syndrome. Currently a number of clinical trials were performed to assess macrolide treatment in the management of non-CF bronchiectasis. The purpose of this paper is to review the efficacy and potential risks of these recent studies on the use of macrolides in non-CF bronchiectasis.

Randomised controlled trial of azithromycin in smokers with asthma: Table 1–

To the Editor: Smokers with asthma have poor symptom control, accelerated decline in lung function and an attenuated response to corticosteroids compared to nonsmokers with asthma [1]. There is an unmet need for alternative or additional drugs for smokers with asthma who are unable to stop smoking [2]. Macrolide antibiotics have anti-inflammatory activity [3] and in clinical studies there is good evidence for efficacy in the treatment of diffuse pan-bronchiolitis and cystic fibrosis, as well as in preventing chronic rejection after lung transplantation [4, 5]. In asthma, chronic treatment is associated with a reduction in bronchial hyperreactivity in mild-to-moderate asthma [6] and in exacerbation rates in non-eosinophilic severe asthma [7]. To date, no studies have examined the efficacy of macrolide antibiotics exclusively in current smokers with asthma. A randomised double-blind parallel-group trial compared azithromycin, 250 mg per day, with placebo for 12 weeks. All subjects were aged 18–70 years, were current smokers (≥5 pack-years history) with chronic asthma (>1 year duration; defined by international criteria [8]) and had to be free of exacerbation and respiratory tract infection for a minimum 6-week period prior to randomisation. A baseline visit was performed following a 4-week run-in period on inhaled corticosteroid (ICS) therapy equivalent to 400 μg beclometasone ± a long-acting β2-agonist (LABA). Ethical approval was obtained and all subjects provided written informed consent. Study visits were performed at 4, 8 and 12 weeks. Clinic visit peak expiratory flow (PEF) after 12 weeks treatment was the primary outcome measure. A sample size of 68 …

Long-term macrolide antibiotics in asthma therapy

Macrolide antibiotics drew worldwide attention when their use was dramatically successful in the treatment of diffuse panbronchiolitis in 1980s. The success was attributed to their immunomodulatory effects, rather than their antimicrobial properties. Since then, studies have shown that macrolides exert their immunomodulatory effects through several mechanisms, including suppression of proinflammatory cytokines, promoting apoptosis of inflammatory cells, improving phagocytic function, ameliorating airway hypersecretion, and inhibiting production of reactive oxygen species. Macrolides have also been studied in the treatment of asthma. This review highlights the role of macrolides in the treatment of asthma, presenting an overview of the main clinical trials. Despite favourable preclinical data and reports of anecdotal successes, the results of clinical trials are conflicting. This may be due to the heterogeneous nature of asthma. Further studies are needed to identify particular subgroup of asthma that will respond to macrolides.

Long-term macrolide antibiotics in asthma therapy

Macrolide antibiotics drew worldwide attention when their use was dramatically successful in the treatment of diffuse panbronchiolitis in 1980s. The success was attributed to their immunomodulatory effects, rather than their antimicrobial properties. Since then, studies have shown that macrolides exert their immunomodulatory effects through several mechanisms, including suppression of proinflammatory cytokines, promoting apoptosis of inflammatory cells, improving phagocytic function, ameliorating airway hypersecretion, and inhibiting production of reactive oxygen species. Macrolides have also been studied in the treatment of asthma. This review highlights the role of macrolides in the treatment of asthma, presenting an overview of the main clinical trials. Despite favourable preclinical data and reports of anecdotal successes, the results of clinical trials are conflicting. This may be due to the heterogeneous nature of asthma. Further studies are needed to identify particular subgroup of asthma that will respond to macrolides.

Clarithromycin suppresses airway hyperresponsiveness and inflammation in mouse models of asthma

Macrolide antibiotics, a class of potent antimicrobials, also possess immunomodulatory/anti-inflammatory properties. These properties are considered fundamental for the efficacy of macrolide antibiotics in the treatment of diffuse panbronchiolitis and cystic fibrosis. In patients with asthma, macrolide antibiotics have been reported to reduce airway hyperresponsiveness and improve pulmonary function. However, their beneficial actions in asthmatics possibly could be attributed to antimicrobial activity against atypical pathogens (e.g. Chlamydia pneumoniae), corticosteroid-sparing effect (inhibition of exogenous corticosteroid metabolism), and/or their anti-inflammatory/immunomodulatory effects. In order to investigate whether efficacy of macrolide antibiotics in asthma results from their immunomodulatory/anti-inflammatory activity, the influence of clarithromycin pretreatment (2 h before challenge) was examined on ovalbumin-induced airway hyperresponsiveness and airway inflammation in the mouse. Clarithromycin treatment (200 mg/kg intraperitoneally) decreased IL-4, IL-5, IL-13, CXCL2 and CCL2 concentrations in bronchoalveolar lavage fluid and markedly reduced inflammatory cell accumulation in bronchoalveolar lavage fluid and into the lungs, as revealed by histopathological examination. Furthermore, clarithromycin-induced reduction in inflammation was accompanied by normalization of airway hyperresponsiveness. In summary, in ovalbumin-induced mouse models, clarithromycin efficiently inhibited two important pathological characteristics of asthma, airway hyperresponsiveness and inflammation. These data suggest that the efficacy of clarithromycin, as well as of other macrolide antibiotics, in asthmatic patients could be attributed to their anti-inflammatory/immunomodulatory properties, and not only to their antimicrobial activity or exogenous corticosteroid-sparing effects.

Is there a Role for Inhaled Corticosteroids and Macrolide Therapy in Bronchiectasis?

Bronchiectasis is characterised by permanent dilatation of the bronchi that arises from chronic inflammation predominantly caused by bacterial infection. This condition remains a major cause of excess respiratory morbidity and treatment is generally only partly successful. There is an urgent need for improved anti-inflammatory medication to treat bronchiectasis. Two potentially useful therapies are inhaled corticosteroids (ICS) and macrolides. The clinical trials that have been performed in bronchiectasis with these two medications can be considered to be preliminary data. This article reviews the anti-inflammatory properties, clinical efficacy and adverse effects of ICS and macrolides.ICS have a large number of potent anti-inflammatory properties. ICS remain the first-line treatment in asthma, reduce exacerbations in chronic obstructive pulmonary disease, and may improve lung function and symptoms in cystic fibrosis (CF). Four small clinical trials have assessed the effect of high-dose ICS on bronchiectasis. The main reported effect of these trials was a reduction in sputum volume and this may be a marker of decreased airway inflammation. Other possible benefits included decreased cough and sputum inflammatory cells/biomarkers. ICS have a relatively high prevalence of local adverse effects, and may be associated with ocular complications and osteoporosis. These adverse effects can be minimised by prescribing low doses of the medication. Macrolides have both antibacterial and immunomodulatory properties. Macrolides have less marked immunosuppressive properties than corticosteroids, and effects include decreasing mucous production, inhibiting virulence factors and biofilm formation of Pseudomonas aeruginosa, decreasing leukocyte numbers and altering inflammatory mediator release. Macrolides have been shown to be extremely effective in the treatment of diffuse panbronchiolitis, improve lung function and symptoms in asthma and CF, and reduce nasal polyps and secretions in sinusitis. Five small clinical trials have assessed the effect of macrolides on bronchiectasis. Reported benefits include reduced sputum volume, improved lung function and better symptom control. Macrolides are generally well tolerated, although they do have a number of drug interactions. There are concerns about the development of resistance, especially to non-tuberculous mycobacteria, with prolonged macrolide use. The evidence available suggests that both medications have a role in the management of bronchiectasis. More definitive trials of ICS and macrolides in bronchiectasis will clarify the likely benefit of these therapies.

Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis1

The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti-inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF). To evaluate the effects of a macrolide antibiotic [clarithromycin (CAM)] on the process of inflammation [by measuring IL-8, TNF-alpha, IL-10 levels and cell profiles in bronchoalveolar lavage (BAL) fluid], pulmonary function and sputum production in children with steady-state bronchiectasis, secondary to causes other than CF or primary immunodeficiencies. Seventeen patients randomized to the treatment group received CAM and supportive therapies for 3 months and 17 patients in the control group were given supportive therapies only. Compared with the control group, the treatment group showed a significant decrease in IL-8 levels, total cell count, neutrophil ratios in BAL fluid and daily sputum production at the end of the third month. There was also a significant increase in the treatment group's BAL fluid macrophage ratios. The differences in pulmonary function test parameters were not significant. Use of CAM in children with steady-state bronchiectasis results in laboratory improvement by reducing the inflammatory processes in the lungs. No corresponding clinical improvement could be shown but although this is possible with long-term use, trial validation is necessary.

Applying lessons learned in the treatment of diffuse panbronchiolitis to other chronic inflammatory diseases

In addition to having antibacterial effects, macrolides modulate inflammatory responses. Their effectiveness in treating chronic inflammatory airway disease is well documented in patients with diffuse panbronchiolitis (DPB), a chronic condition characterized by inflammation of the airways that, if left untreated, progressively leads to respiratory failure and death. Long-term treatment with certain macrolides has dramatically improved the survival of patients with DPB. The mechanisms of action for the anti-inflammatory properties of macrolides are still being studied. The effects of macrolides on inflammation include decreasing chemotaxis of neutrophils to the respiratory tract and inhibiting the expression of adhesion molecules, with decreased infiltration of neutrophils into the respiratory epithelium. Macrolides also inhibit expression of transcription factors and formation of proinflammatory cytokines, and directly and indirectly block mucus secretion. Even with long-term use, macrolides are safe and well tolerated. The effectiveness of macrolides for treating DPB has led to interest in their use in treating other chronic inflammatory airway diseases. As discussed in this article, because of the similarities between the clinical presentation of cystic fibrosis and chronic bronchitis and DPB, the effects of macrolides in patients with these diseases are currently being studied with particular interest.

Immunomodulatory effects of macrolides: Implications for practicing clinicians

Macrolides are regarded as the drugs of choice for the treatment of diffuse panbronchiolitis (DPB) due to their favorable effects on patient outcomes. These drugs decrease sputum production, thereby improving pulmonary function. Moreover, these effects are independent of dosing with respect to clarithromycin, erythromycin, and roxithromycin. The marked success of macrolides in this disease is a direct effect of impeding the inflammatory cascade. With their abilities to reduce the secretion of proinflammatory cytokines, ameliorate the infiltration of inflammatory cells into the airways, and reduce mucus secretion, macrolides are able to improve pulmonary function and quality of life in patients with chronic inflammatory diseases of the airways. Although prolonged use of macrolides raises concerns of increased adverse effects, data do not support such occurrences. With respect to concerns of resistance, it should be noted that in Japan, where macrolides are part of the treatment for DPB, these agents continue to be used effectively as antimicrobial agents. Therefore, the potential benefits of the immunomodulatory effects of macrolides in other conditions such as cystic fibrosis, chronic sinusitis, asthma, and chronic bronchitis are under investigation.

Regulatory Effects of Macrolides on Bacterial Virulence: Potential Role as Quorum-Sensing Inhibitors

Pseudomonas aeruginosa is an opportunistic pathogen, and this organism is a major cause of pulmonary damage and mortality in patients with cystic fibrosis (CF), diffuse panbronchiolitis (DPB) and other forms of bronchiectasis. A break-through in the treatment of DPB and associated chronic P. aeruginosa pulmonary infection was realized when a patient with DPB improved dramatically after treatment with erythromycin for years. Now, long-term macrolide therapy has become a first line of treatment in DPB patients, and the immunomodulatory properties have now been extended to other clinical settings, including CF. An important factor in the pathogenesis of chronic P. aeruginosa infection is a bacterial cell-to-cell signaling mechanism, referred to as "quorum sensing", which enables bacteria to coordinately turn on and off specific virulence genes through the production of autoinducer molecules. Interference or blocking of quorum-sensing systems has been considered an attractive therapeutic strategy. Clinical and basic science data suggests the potential of macrolides as relevant inhibitors of the Pseudomonas quorum-sensing system. In fact, certain macrolides strongly suppressed quorum-sensing associated genes and autoinducer production, in addition to inhibition of a variety of virulence factors. In this review, clinical efficacy of macrolides on DPB and CF patients will be briefly summarized. Additionally, the mechanisms of action of macrolides will be discussed from the standpoint of sub-MIC macrolide effects on P. aeruginosa, particularly the ability of this antibiotic to suppress quorum-sensing systems, which may be crucial in the pathogenesis of chronic P. aeruginosa infection.

Influence of human T lymphotrophic virus type I on diffuse pan-bronchiolitis.

Human T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4(+) lymphocytes and is thought to modify their function and a possible association with pulmonary diseases has also been suggested. However, little is known about the influence of HTLV-I on diffuse pan-bronchiolitis (DPB), a chronic inflammatory lung disease with infiltration of lymphocytes and hyperplasia of the bronchus-associated lymphoid tissue. In this study, 35 DPB patients with and without HTLV-I infection were examined. HTLV-I positive DPB patients were likely to have a larger affected area with lower FEV(1). The CD3(+)/CD25(+) lymphocyte percentage was significantly higher in the BALF of HTLV-I positive patients than in negative patients. MIP-1 alpha, IP-10 and levels in BALF were also significantly higher in HTLV-I positive patients than in negative patients. The levels of MCP-1 and IL-8 were not significantly different. In HTLV-I positive patients, the MIP-1 alpha and IP-10 levels showed a significant positive correlation with the percentage of CD3(+)/CD25 lymphocytes. BALF cells of all HTLV-I positive DPB patients showed expression of p40(tax) mRNA. We suggest that HTLV-I infection may modify DPB pathogenesis via activation of T cells. We also found that the frequency of ATL development in HTLV-I positive DPB patients was significantly higher than in all HTLV-I positive patients (OR = 8.22, 95% CI = 2.61-25.9, P < 0.01). The levels of TGF-beta in patients who developed ATL were significantly lower than in patients who did not develop ATL. Sensitivity and specificity were 80% and 85.7%, respectively (cut-off = 20 pg/ml). We also propose that these features should be taken into consideration in the treatment of DPB in HTLV-I infected individuals.

Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis.

Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins. Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB). Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults. The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects. DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls. In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8. Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells. In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8. Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.

マクロライド系抗生物質の好中球機能に対する影響

Since "small-dose and long-term" administration of erythromycin (EM) was shown to be efficacious in the treatment of chronic respiratory disease, the modulation of host defense responses by EM has attracted much attention. Although there is considerable controversy, it was recently demonstrated that EM activity reduces neutrophil function. In this study, we investigated the in vitro effects of the macrolides erythromycin (EM), a 14-membered ring, azithromycin (AZM), a 15-membered ring and rokitamycin (RKM), a 16-membered ring macrolide, on neutrophil function. The DCFH-DA method and cytochrome C method were used for assay of active oxygen generation and the Boyden-chamber method was used for assay of chemotaxis. EM and AZM, both of which have been shown to be clinically effective in the treatment of Diffuse panbronchiolitis (DPB), significantly suppressed active oxygen generation and chemotaxis of neutrophils at low concentrations equivalent to therapeutic doses (0.5 approximately 1.0 microgram/ml, p < 0.05), whereas the clinically ineffective RKM did not. The in vitro inhibitory effects of EM and AZM on active oxygen generation and chemotaxis of neutrophils demonstrated in the present study may be responsible for the therapeutic efficacy of these 14-membered and 15-membered ring macrolides in the treatment of DPB patients.

Mechanism of efficacy of erythromycin on diffuse panbronchiolitis--effect of erythromycin on cytokine mRNA expression in human whole blood model

Recently, "low-dose and long-term" erythromycin (EM) has been reported to be effective in treatment of diffuse panbronchiolitis (DPB), but its mechanism is still obscure. We studied the effect of EM on cytokine mRNA expression by using LPS-stimulated human whole blood as an experimental vivo model. IL-8 mRNA was expressed in biphasic fashion with peak expression at 6 hours and 20 hours from the start of LPS stimulation. When whole blood was pretreated with EM (2 micrograms/ml) for 1 hours. IL-8 mRNA expression was depressed at 20 hours (p < 0.025) from the start of LPS (1 microgram/ml) stimulation. However, when pretreated for 12 hours, it was not depressed. EM (2 micrograms/ml) also depressed IL-1 beta (p < 0.025) and TNF alpha (p < 0.05) mRNA expressions at 6 hours from the start of LPS stimulation. From the above results, it was suggested that the direct inhibition of IL-1 beta and TNF alpha production by EM resulted in subsequent depression of production of IL-8 that is a potent chemotactic factor for neutrophil, and consequently, EM acts to protect the bronchiole tissues of DPB patients from destruction by proteolytic enzymes released from neutrophils. This assumption seems to be supported by our previous observation that when patients with DPB were treated with EM a marked decrease in number of neutrophil in bronchoalveolar lavage fluid (BALF) was accompanied by clinical and radiographic improvement.

Ofloxacin and Macrolides in the Treatment of Diffuse Panbronchiolitis

Ofloxacin and Macrolides in the Treatment of Diffuse Panbronchiolitis

Erythromycin inhibition of lipopolysaccharide-stimulated tumor necrosis factor alpha production by human monocytes in vitro.

The mechanism of clinical effectiveness of low-dose and long-term erythromycin (EM) treatment for diffuse panbronchiolitis, sinobronchial syndrome, and associated otitis media with effusion was investigated by studying the effects of EM on tumor necrosis factor alpha (TNF-alpha) production by cultured human monocytes stimulated with lipopolysaccharide. At concentrations of 0.1 microgram/mL or more, EM inhibited TNF-alpha release from human monocytes stimulated by lipopolysaccharide in a dose-dependent manner. Of the other macrolides tested, roxithromycin, an EM derivative, also showed significant inhibition of TNF-alpha production, whereas josamycin failed to inhibit TNF-alpha release from monocytes. Nonmacrolidic drugs such as minocycline hydrochloride, ofloxacin, or penicillin G had no significant effect on TNF-alpha production. These results suggest that the clinical improvement of chronic respiratory diseases by EM may depend on the suppression of production of inflammatory cytokines such as TNF-alpha.

副鼻腔気管支症候群とその周辺 治療 とくにびまん性汎細気管支炎に対するエリスロマイシン小量長期投与

Diffuse panbronchiolitis (DPB) which is the representative of Japanese sinobronchial syndrome is grave in prognosis. Eighteen paients with DPB, including sixteen cases with H. influenzae infection and two with P. aeruginosa infection, were treated with 600mg of Erythromycin (EM) per day for 19.8 months on an average. After the therapy, dyspnea on exertion, body weight, chest X-ray findings, pulmonary function data including VC, FEV1.0 and RV/TLC, PaO2, cold agglutinin titer and IgM level were significantly improved. There were no significant side effects. There was no change of bacterial flora in sputum except one.Low-dose, long-term chemotherapy of EM could be useful in treatment of DPB.