zithromax and Lung-Diseases--Interstitial

The first clinical indication of non-antibiotic benefits of macrolides was in the Far East, in adults with diffuse panbronchiolitis. This condition is characterised by chronic airway infection, often with Pseudomonas aeruginosa, airway inflammation, bronchiectasis and a high mortality. Low dose erythromycin, and subsequently other macrolides, led in many cases to complete remission of the condition, and abrogated the neutrophilic airway inflammation characteristic of the disease. This dramatic finding sparked a flurry of interest in the many hundreds of macrolides in nature, especially their anti-inflammatory and immunomodulatory effects. The biggest subsequent trials of azithromycin were in cystic fibrosis, which has obvious similarities to diffuse panbronchiolitis. There were unquestionable improvements in lung function and pulmonary exacerbations, but compared to diffuse panbronchiolitis, the results were disappointing. Case reports, case series and some randomised controlled trials followed in other conditions. Three trials of azithromycin in preschool wheeze gave contradictory results; a trial in pauci-inflammatory adult asthma, and a trial in non-cystic fibrosis bronchiectasis both showed a significant reduction in exacerbations, but none matched the dramatic results in diffuse panbronchiolitis. There is clearly a huge risk of antibacterial resistance if macrolides are used widely and uncritically in the community. In summary, Azithromycin is not the answer to anything in paediatric respiratory medicine; the paediatric respiratory community needs to refocus on the dramatic benefits of macrolides in diffuse panbronchiolitis, use modern - omics technologies to determine the endotypes of inflammatory diseases and discover in nature or synthesise designer macrolides to replicate the diffuse panbronchiolitis results. We must now find out how to do better!

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Bronchiolitis; Bronchiolitis Obliterans; Bronchiolitis, Viral; Child; Child, Preschool; Ciliary Motility Disorders; Cystic Fibrosis; Disease Progression; Drug Resistance, Bacterial; Haemophilus Infections; Humans; Infant; Lung Diseases, Interstitial; Lung Transplantation; Macrolides; Respiratory Sounds; Stem Cell Transplantation

Interstitial lung disease in children (chILD) comprises a range of different rare diseases. There is limited evidence for the treatment of chILD and no randomised clinical trials of treatment have been undertaken. Most treatments are therefore prescribed off-label based on expert opinion. The off-label nature of prescription of drugs for chILD highlights the importance of a solid understanding of the side effects to facilitate risk-benefit assessment. The European Respiratory Society chILD guidelines recommend the use of systemic glucocorticosteroids, hydroxychloroquine and azithromycin. Side effects of these drugs will be discussed followed by consideration of other drugs used for the treatment of chILD.

Topics: Anti-Bacterial Agents; Antirheumatic Agents; Azithromycin; Child; Cyclophosphamide; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lung Diseases, Interstitial; Methotrexate; Methylprednisolone; Off-Label Use; Prednisolone; Rituximab

Topics: ATP-Binding Cassette Transporters; Azithromycin; Humans; Infant, Newborn; Lung Diseases, Interstitial; Mutation; Respiratory Distress Syndrome, Newborn

Topics: Adolescent; Adrenal Cortex Hormones; Azithromycin; Cause of Death; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; Humans; Hydroxychloroquine; Infant; Kaplan-Meier Estimate; Longitudinal Studies; Lung Diseases, Interstitial; Male; Monitoring, Physiologic; Prospective Studies; Registries; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Survival Analysis; Time Factors

Mutations in adenosine triphosphate-binding cassette transporter A3 (ABCA3) (OMIM: 601615) gene constitute the most frequent genetic cause of severe neonatal respiratory distress syndrome (RDS) and interstitial lung disease (ILD) in children. Interstitial lung disease in children and especially in infants, in contrast to adults, is more likely to appear as a result of developmental deficits or is characterized by genetic aberrations of pulmonary surfactant homeostasis not responding to exogenous surfactant administration. The underlying ABCA3 gene mutations are commonly thought, regarding null mutations, to determine the clinical course of the disease while there exist mutation types, especially missense variants, whose effects on surfactant proteins are difficult to predict. In addition, clinical and radiological signs overlap with those of surfactant proteins B and C mutations making diagnosis challenging. We demonstrate a case of a one-term newborn male with lethal respiratory failure caused by homozygous missense ABCA3 gene mutation c.3445G>A (p.Asp1149Asn), which, to our knowledge, was not previously reported as a causative agent of newborn lethal RDS. Therapeutic strategies for patients with ABCA3 gene mutations are not sufficiently evidence-based. Therefore, the description of the clinical course and treatment of the disease in terms of a likely correlation between genotype and phenotype is crucial for the development of the optimal clinical approach for affected individuals.

Topics: Adrenal Cortex Hormones; ATP-Binding Cassette Transporters; Azithromycin; Humans; Hydroxychloroquine; Infant, Newborn; Lung Diseases, Interstitial; Male; Mutation; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Tomography, X-Ray Computed

Topics: Abscess; Anti-Bacterial Agents; Azithromycin; Ethambutol; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Leg; Lung Diseases, Interstitial; Middle Aged; Mycobacterium avium-intracellulare Infection; Mycophenolic Acid; Polymyositis; Prednisone; Rifabutin; Skin Diseases, Bacterial

Acute exacerbation of chronic fibrosing interstitial pneumonia (AE-CFIP) is an often fatal condition with no established treatment. Recently, macrolides were found to be beneficial in cases of acute lung injury.. To examine the clinical effectiveness and safety of intravenous azithromycin in patients hospitalized for AE-CFIP.. A prospective, open-label study with historical controls was conducted. Twenty consecutive patients with AE-CFIP received azithromycin. They were compared with a historical cohort treated with fluoroquinolone (n = 56). All patients received high-dose steroid pulse therapy. The primary end point was mortality at 60 days. The secondary end point was safety of intravenous azithromycin in patients with AE-CFIP. Inverse probability of treatment weighting (IPTW) using the propensity score was performed to investigate the relationship between azithromycin use and survival time.. Mortality was significantly lower in the patients treated with azithromycin than in those treated with fluoroquinolone (mortality rate at 60 days: 20 vs. 69.6%, p < 0.001; median survival time: not reached vs. 29.5 days, p < 0.001). The IPTW adjusted hazard of mortality at 60 days in patients receiving azithromycin was 0.17 (95% CI 0.05-0.61). No serious adverse events were observed.. Azithromycin was associated with improved outcomes in patients with AE-CFIP. Further studies are needed to verify this finding (Clinical trial JMA-IIA00095).

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Disease Progression; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Japan; Lung Diseases, Interstitial; Male; Prospective Studies; Steroids; Survival Analysis; Treatment Outcome

Pulmonary surfactant deficiency caused by mutations in ABCA3 (ATP-binding cassette transporter of the A subfamily, member 3) gene results in diffuse parenchymal lung disease (DPLD) in children. So far, systemic steroids are the main treatment, with however limited efficacy. We report the case of a young boy showing a dramatic long-term improvement of respiratory disease by low-dose azithromycin (AZM) with no side effect after 6 years of treatment. Cellular and molecular studies are ongoing to progress in the understanding of the mechanisms involved. On behalf of the National Reference Center for rare lung diseases in France (Respirare, http://www.respirare.fr), clinical studies on AZM in various forms of DPLD in children have been initiated and should provide information on the types of paediatric DPLD that may benefit from this treatment.

Topics: Azithromycin; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Lung Diseases, Interstitial; Male; Pulmonary Surfactants; Treatment Outcome

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; ATP-Binding Cassette Transporters; Azithromycin; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Hydroxychloroquine; Infant, Newborn; Lung Diseases, Interstitial; Lung Transplantation; Male; Methylprednisolone; Pulmonary Alveolar Proteinosis; Respiration, Artificial; Respiratory Distress Syndrome, Newborn