Macrolides in Cystic Fibrosis

McArdle, John R.; Talwalkar, Jaideep S.

doi:10.1016/j.ccm.2007.02.005

Cited by 36 publications

(20 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…*p , 0.05; **p , 0.01. immunomodulatory properties of macrolide antibiotics, especially azithromycin, with trials demonstrating improved lung function and body weight in those receiving azithromycin (9)(10)(11)(12). However, there are also potential challenges in using azithromycin, including the risk of selection of resistant bacteria (12,47) and our lack of mechanistic understanding of the beneficial anti-inflammatory actions of macrolides (48). Consequently, alternative anti-inflammatory agents with different modes of action and safety profiles are required to improve the outcome in CF.…”

Section: Discussionmentioning

confidence: 99%

TLR5 as an Anti-Inflammatory Target and Modifier Gene in Cystic Fibrosis

Blohmke

Park

Hirschfeld

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

New treatments are needed to improve the health of people with cystic fibrosis (CF). Reducing lung-damaging inflammation is likely to be beneficial, but specific anti-inflammatory targets have not been identified. By combining cellular immunology with a population-based genetic modifier study, we examined TLR5 as an anti-inflammatory target and modifier gene in CF. Using two pairs of human CF and control airway epithelial cells, we demonstrated that the TLR5–flagellin interaction is a major mediator of inflammation following exposure to Pseudomonas aeruginosa. To validate TLR5 as an anti-inflammatory target, we analyzed the disease modifying effects of the TLR5 c.1174C>T single nucleotide polymorphism (rs5744168) in a large cohort of CF patients (n = 2219). rs5744168 encodes a premature stop codon and the T allele is associated with a 45.5–76.3% reduction in flagellin responsiveness (p < 0.0001). To test the hypothesis that reduced TLR5 responsiveness would be associated with improved health in CF patients, we examined the relationship between rs5744168 and two clinical phenotypes: lung function and body weight. Adults with CF carrying the TLR5 premature stop codon (CT or TT genotype) had a higher body mass index than did CF patients homozygous for the fully functional allele (CC genotype) (p = 0.044); however, similar improvements in lung function associated with the T allele were not statistically significant. Although follow-up studies are needed to confirm the impact of TLR5 on nutritional status, this translational research provides evidence that genetic variation in TLR5 resulting in reduced flagellin responsiveness is associated with improved health indicators in adults with CF.

show abstract

Section: Discussionmentioning

confidence: 99%

TLR5 as an Anti-Inflammatory Target and Modifier Gene in Cystic Fibrosis

Blohmke

Park

Hirschfeld

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Long-term use of azithromycin and other macrolide antibiotics has increased as a result of reports of improved clinical outcomes in patients with cystic fibrosis (CF) (2), chronic obstructive pulmonary disease (3), panbronchiolitis (4), asthma (5), and chronic transplant rejection (6). These benefits are believed to result from its antiinflammatory effects on macrophages and neutrophils mediated through unknown mechanisms (7).…”

Section: Introductionmentioning

confidence: 99%

Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection

Renna

Schaffner²,

Brown³

et al. 2011

J. Clin. Invest.

292

264

View full text Add to dashboard Cite

“…The immunomodulatory effects on the host include suppression of the enhanced immune response and of the inflammation, inhibition of inflammatory cytokine production by alveolar macrophages, and decreased mucus hypersecretion. (11,23,26,27) Various studies have shown positive results regarding the reduction in the number of exacerbations and regarding stabilization of or increase in respiratory capacity, whereas others have failed to demonstrate these effects (Chart 2). Treatment with azithromycin can have beneficial effects in cystic fibrosis, although the optimal dosage and duration of administration have yet to be well defined.…”

Section: Cystic Fibrosismentioning

confidence: 99%

“…Kabra et al (18) RCT No differences in FEV 1 , pulmonary exacerbations, or need for antibiotics were found between the groups. McArdle et al (26) Review…”

Section: Rctmentioning

confidence: 99%

Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

et al. 2012

View full text Add to dashboard Cite

Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have anti-inflammatory effects. Macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. Clinical trials have demonstrated beneficial effects of macrolides in various chronic lung diseases. The objective of this study was to review recent data in the medical literature on the anti-inflammatory effects of macrolides in childhood lung diseases by searching the Medline (PubMed) database. We used the following search terms: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; and "macrolide and acute bronchiolitis". We selected articles published in international scientific journals between 2001 and 2012. Clinical studies and in vitro evidence have confirmed the anti-inflammatory effect of macrolides in respiratory diseases. Some clinical trials have shown the benefits of the administration of macrolides in patients with cystic fibrosis, although the risk of bacterial resistance should be considered in the analysis of those benefits. Such benefits are controversial in other respiratory diseases, and the routine use of macrolides is not recommended. Further controlled clinical trials are required in order to assess the efficacy of macrolides as anti-inflammatory drugs, so that the benefits in the treatment of each specific clinical condition can be better established.Keywords: Macrolides; Asthma; Cystic Fibrosis; Bronchiolitis. ResumoOs macrolídeos são fármacos com efeitos antimicrobianos especialmente contra patógenos intracelulares. Vários estudos têm demonstrado possíveis efeitos anti-inflamatórios dos macrolídeos. Esses medicamentos inibem a produção de algumas interleucinas e podem reduzir a inflamação neutrofílica pulmonar. Ensaios clínicos têm demonstrado efeitos benéficos dos macrolídeos em diversas doenças pulmonares crônicas. O objetivo deste estudo foi revisar os dados recentes da literatura médica sobre os efeitos anti-inflamatórios dos macrolídeos nas doenças respiratórias da infância, através da pesquisa da base de dados Medline (PubMed) dos seguintes termos em inglês: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; e "macrolide and acute bronchiolitis" Foram selecionados artigos publicados em revistas científicas internacionais entre 2001 e 2012. Estudos clínicos e evidências in vitro comprovam o efeito anti-inflamatório dos macrolídeos em doenças respiratórias. Alguns ensaios clínicos demonstram benefícios na administração de macrolídeos em pacientes com fibrose cística; porém, o risco de resistência bacteriana deve ser considerado na análise desses benefícios. Tais benefícios são controversos em outras doenças respiratórias, e seu uso rotineiro não está indicado. Mais estudos clínicos controlados são necessários para avaliar a eficácia desses medicamentos como anti-inflamatórios. Dessa forma, poderemos d...

show abstract

Macrolides in Cystic Fibrosis

Cited by 36 publications

References 65 publications

TLR5 as an Anti-Inflammatory Target and Modifier Gene in Cystic Fibrosis

TLR5 as an Anti-Inflammatory Target and Modifier Gene in Cystic Fibrosis

Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection

Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

Contact Info

Product

Resources

About