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

Yalçın, Ebru; Ki̇per, Nural; Özçeli̇k, Uğur; Doğru, Deni̇z; Firat, Pınar; Şahin, Altan; Arıyürek, M.; Mocan, Gamze; Gurcan, N.; Göçmen, A

doi:10.1111/j.1365-2710.2006.00708.x

Cited by 100 publications

(75 citation statements)

References 22 publications

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“…Although the comparison of the outcomes of these studies is limited by the different treatment regimens, doses, drug formulations and clinical factors evaluated, low-dose CLM seems to be more effective, as supported also by its low-dose benefits in the treatment of diffuse panbronchiolitis which shares many similarities in clinical and pathological characteristics with CF [19–23]. Moreover, CLM treatment was shown to decrease lung inflammatory processes and chronic airways hypersecretion in non-CF patients with bronchiectasis [24,25]. Pertaining to its anti-pseudomonal effects, CLM has no bactericidal activity against P. aeruginosa , like other macrolides, but can interfere with protein synthesis and inhibit protease expression, twitching motility and biofilm maturation, promoting biofilm permeability and favoring penetration of other antimicrobial agents like ciprofloxacin and tobramycin, also used in CF therapy [26–28].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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Background: Cystic fibrosis (CF) lung infection is a complex condition where opportunistic pathogens and defective immune system cooperate in developing a constant cycle of infection and inflammation. The major pathogen, Pseudomonas aeruginosa, secretes a multitude of virulence factors involved in host immune response and lung tissue damage. In this study, we examined the possible anti-inflammatory effects of molecules inhibiting P. aeruginosa virulence factors.Methods: Pyocyanin, pyoverdine and proteases were measured in bacterial culture supernatant from different P. aeruginosa strains. Inhibition of virulence factors by sub-inhibitory concentrations of clarithromycin and by protease inhibitors was evaluated. Lung inflammatory response was monitored by in vivo bioluminescence imaging in wild-type and CFTR-knockout mice expressing a luciferase gene under the control of a bovine IL-8 promoter.Results: The amount of proteases, pyocyanin and pyoverdine secreted by P. aeruginosa strains was reduced after growth in the presence of a sub-inhibitory dose of clarithromycin. Intratracheal challenge with culture supernatant containing bacteria-released products induced a strong IL-8-mediated response in mouse lungs while lack of virulence factors corresponded to a reduction in bioluminescence emission. Particularly, sole inactivation of proteases by inhibitors Ilomastat and Marimastat also resulted in decreased lung inflammation.Conclusions: Our data support the assumption that virulence factors are involved in P. aeruginosa pro-inflammatory action in CF lungs; particularly, proteases seem to play an important role. Inhibition of virulence factors production and activity resulted in decreased lung inflammation; thus, clarithromycin and protease inhibitors potentially represent additional therapeutic therapies for P. aeruginosa-infected patients.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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“…A placebo-controlled trial of children with bronchiectasis treated with clarithromycin for 3 months showed no change in FEV1, although maximal mid-expiratory flow (FEF25-75) was significantly improved and there was a significant reduction in sputum volume [33]. A reduction in bronchoalveolar lavage (BAL) fluid IL-8 concentration was seen in the treatment arm, but no change in pathogens or other measures of inflammation, including IL-10 and tumour necrosis factor-a, was measured.…”

Section: Bronchiectasismentioning

confidence: 99%

Long-term macrolide therapy in chronic inflammatory airway diseases

Crosbie¹,

Woodhead²

2008

Eur Respir J

120

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In addition to direct antibacterial actions, 14-and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis.A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions.A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects.Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.

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“…According to the vicious cycle hypothesis, if infection is the primary driver of airway inflammation, bacterial clearance through the use of short-or long-term antibiotic therapy would be expected to reduce airway inflammation, allow airway healing and modify the long-term course of the disease. Until very recently, the role of macrolide therapy in non-CF bronchiectasis had only been investigated in studies that were small, of short duration and did not assess clinical relevant outcomes, such as pulmonary exacerbations and quality of life [44][45][46][47]. In a recently published, randomised, double-blind, placebo-controlled trial, 141 patients (aged o18 years) with a diagnosis of bronchiectasis as defined by HRCT and at least one pulmonary exacerbation requiring antibiotic treatment in the previous year, were assigned to receive azithromycin 500 mg three times per week or placebo for 6 months in a 1:1 ratio [48].…”

Section: Non-cf Bronchiectasismentioning

confidence: 99%

Long-term macrolide treatment for chronic respiratory disease

2012

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Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert antiinflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain.With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials. @ERSpublications Several studies evaluating macrolide antibiotics for the treatment of chronic respiratory diseases are underway

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

Abstract: 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.

Cited by 100 publications

References 22 publications

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

Long-term macrolide therapy in chronic inflammatory airway diseases

Long-term macrolide treatment for chronic respiratory disease

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