Long-Term Macrolide Antibiotic Therapy in the Treatment of Chronic Small Airway Disease Clinically Mimicking Diffuse Panbronchiolitis

Kadota, Jun‐ichi; Mukae, Hiroshi; Mizunoe, Syunji; Kishi, Kenji; Tokimatsu, Issei; Nagai, Hirokazu; Tomono, Kazunori; Kohno, Shigeru; Nasu, Masaru

doi:10.2169/internalmedicine.44.200

Cited by 16 publications

(5 citation statements)

References 28 publications

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“…The same authors later reported on longterm macrolide antibiotic therapy in the treatment of chronic small-airway disease that clinically mimicked DPB but had a very different histology. Unlike the 80 to 90% response to long-term erythromycin therapy reported for DPB, pulmonary function, total cell counts, and neutrophil percentages in bronchoalveolar lavage fluid did not improve in these patients (121). However, similar to the case for patients with DPB, there were no reported side effects seen with long-term use.…”

Section: Long-term Macrolide Safetymentioning

confidence: 41%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

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Section: Long-term Macrolide Safetymentioning

confidence: 41%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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“…This kind of heterogeneity in the response to macrolides is similar to that observed in participants with diffuse panbronchiolitis and small airways disease, where clinical improvements were observed in both groups but only those with diffuse panbronchiolitis had reductions in neutrophils [31]. The study of Albert and colleagues elegantly show the improvement in exacerbation rate and health status in COPD, however they did not assess changes in airway inflammation.…”

Section: Discussionmentioning

confidence: 52%

The Effect of Azithromycin in Adults with Stable Neutrophilic COPD: A Double Blind Randomised, Placebo Controlled Trial

et al. 2014

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BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis. Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD. Despite current available therapies to control inflammation, neutrophilic bronchitis remains common. This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as bacterial load. We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis.MethodsEligible participants (n = 30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications. Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment. Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit. Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment. A sub-group of participants underwent chest computed tomography scans (n = 15).ResultsNine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×107 cfu/mL. Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load. The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI): 0.37 (0.11,1.21), p = 0.062). For participants who underwent chest CT scans, no alterations were observed.ConclusionsIn stable COPD with neutrophilic bronchitis, add-on azithromycin therapy showed a trend to reduced severe exacerbations sputum neutrophils, CXCL8 levels and bacterial load. Future studies with a larger sample size are warranted.Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12609000259246

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“…However, they have a different genetic background, so these cases may be forme fruste cases of DPB or cases without the full-blown morphological and clinical expression, and may be more frequent in this population than previously thought. The beneficial effects of macrolides have been documented in some of these cases [93].…”

Section: Resultsmentioning

confidence: 99%

Diffuse panbronchiolitis

Poletti¹

2006

Eur Respir J

131

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Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease, well recognised in Japan and principally affecting the respiratory bronchioles, causing a progressive suppurative and severe obstructive respiratory disorder. If left untreated, DPB progresses to bronchiectasis, respiratory failure and death.It was first described in the early 1960s. Subsequently, in 1969, the disease was named DPB to distinguish it from chronic bronchitis. ''Diffuse'' refers to the distribution of the lesions throughout both lungs, and ''pan-'' refers to the involvement of inflammation in all layers of the respiratory bronchioles.The distinctive imaging and histological features, the coexisting sinusitis, and the isolation of Haemophilus influenzae and Pseudomonas aeruginosa in the sputum enhance disease recognition. Histologically, DPB is characterised by chronic inflammation, localised mainly in the respiratory bronchioles and adjacent centrilobular regions, with characteristic interstitial accumulation of foamy histiocytes, neutrophils and lymphocyte infiltration. Neutrophils and Tlymphocytes, particularly CD8+ cells, together with the cytokines interleukin-8 and macrophage inflammatory protein-1, are believed to play key roles in the development of DPB.A significant improvement in the prognosis of this potentially fatal disease has been recently reported thanks to the use of long-term therapy with macrolide antibiotics, the effect of which is attributed to an anti-inflammatory and immunoregulatory action.

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Long-Term Macrolide Antibiotic Therapy in the Treatment of Chronic Small Airway Disease Clinically Mimicking Diffuse Panbronchiolitis

Cited by 16 publications

References 28 publications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

The Effect of Azithromycin in Adults with Stable Neutrophilic COPD: A Double Blind Randomised, Placebo Controlled Trial

Diffuse panbronchiolitis

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