Azithromycin to Prevent Recurrent Wheeze Following Severe Respiratory Syncytial Virus Bronchiolitis

Beigelman, Avraham; Srinivasan, Mythili; Goss, Charles W.; Wang, Jinli; Zhou, Yanjiao; True, Kelly; Ahrens, Elizabeth; Burgdorf, Dana; Haslam, Matthew D.; Boomer, Jonathan S.; Bram, S; Casper, Timothy J.; Coverstone, Andrea M.; Kanchongkittiphon, Watcharoot; Kuklinski, Cadence; Storch, Gregory A.; Wallace, Meghan A.; Yin‐Declue, Huiqing; Castro, Mario; Schechtman, Kenneth B.; Bacharier, Leonard B.

doi:10.1056/evidoa2100069

Cited by 16 publications

(6 citation statements)

References 44 publications

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“…Azithromycin did not reduce the risk of recurrent wheeze episodes, in fact, risk was 46% in the azithromycin group compared to 36% in the placebo group. 25 Worryingly, there was a signal among children who had never previously received antibiotics of increased risk of recurrent wheezing if they were in the azithromycin group.…”

Section: Not All Neutrophils Are Pathogenicmentioning

confidence: 99%

“…A very carefully conducted clinical trial has highlighted azithromycin does not prevent the progression of bronchiolitis to recurrent preschool wheezing. 25 The Azithromycin to Prevent Recurrent…”

Section: Not All Neutrophils Are Pathogenicmentioning

confidence: 99%

“…A very carefully conducted clinical trial has highlighted azithromycin does not prevent the progression of bronchiolitis to recurrent preschool wheezing 25 . The Azithromycin to Prevent Recurrent Wheeze following severe RSV bronchiolitis (APW‐II) trial included 200 children aged 1–18 months who were hospitalised with RSV bronchiolitis.…”

Section: Mechanisms Underlying Preschool Wheeze To Identify Disease‐m...mentioning

confidence: 99%

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Preventing progression of preschool wheezing to asthma: Opportunities for intervention

Saglani

2024

Pediatric Allergy Immunology

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Recurrent wheezing in preschool children is heterogeneous and results from numerous genetic and environmental risk factors, which result in the same final clinical manifestation of acute episodes of wheezing but have distinct underlying mechanisms. Effective disease‐modifying approaches, therefore, need to target the pathways driving the symptoms. We have good evidence to show that targeting airway eosinophilia alone in early‐life preschool wheezing and using inhaled corticosteroids is not disease‐modifying. Although airway remodelling develops early in preschool wheezing, the challenge is identifying suitable treatments for structural airway changes. There is increasing evidence for the role of lower airway bacterial infection contributing to wheeze episodes, but clinical trials investigating the impact of targeted antibiotic treatment on disease modification are needed. There is also increasing data supporting an association between lower airway neutrophilia and wheezing in a subgroup of preschool children, but direct causation and the role of neutrophil function remain unknown. Finally, there is encouraging preliminary data for the role of inactivated mixed bacterial lysates in children with non‐allergic, infection‐associated wheeze episodes, but the impact on longer‐term outcomes and their mechanism of action is unknown. This review outlines a range of potential novel targets and approaches that may enable secondary prevention of asthma from preschool wheezing. In parallel, the potential for harm when interventions are introduced indiscriminately is highlighted. Some of the challenges that need to be addressed, including trial designs allowing tailored interventions, the need for non‐invasive biomarkers for targeted interventions, and ensuring extended and long‐term follow‐up after intervention, are highlighted.

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Section: Not All Neutrophils Are Pathogenicmentioning

confidence: 99%

Section: Not All Neutrophils Are Pathogenicmentioning

confidence: 99%

Section: Mechanisms Underlying Preschool Wheeze To Identify Disease‐m...mentioning

confidence: 99%

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Preventing progression of preschool wheezing to asthma: Opportunities for intervention

Saglani

2024

Pediatric Allergy Immunology

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“…IRF7lo responders have increased TGF-b/SMAD3 signaling, exaggerated T2 inflammation that fails to resolve (IL-25, IL-33, eosinophils, ILC2), and prolonged symptoms (37,42,43). exacerbations in adults (86), but it does not have any long-term beneficial effects on prevention of recurrent wheeze following severe RSV bronchiolitis (87). Azithromycin also has effects on the gut microbiota (88), and the composition of the airway microbiota modifies the effect of azithromycin on asthma-like illnesses in children (89), and therefore it is likely that the efficacy of azithromycin therapy depends on the specific pathogenic and commensal bacteria and the viral trigger.…”

Section: Interferon Responses To Viral Versus Bacterial Stimulimentioning

confidence: 99%

“…For instance, azithromycin enhances type I and III interferon responses in airway epithelial cells infected with rhinovirus ( 84 ). Notably, azithromycin treatment reduces the duration of asthma-like episodes in young children ( 85 ) and the frequency of asthma exacerbations in adults ( 86 ), but it does not have any long-term beneficial effects on the prevention of recurrent wheeze following severe RSV bronchiolitis ( 87 ). Azithromycin also has effects on the gut microbiota ( 88 ), and the composition of the airway microbiota modifies the effect of azithromycin on asthma-like illnesses in children ( 89 ), and therefore it is likely that the efficacy of azithromycin therapy depends on the specific pathogenic and commensal bacteria and the viral trigger.…”

Section: Interferon Responses To Viral Versus Bacterial Stimulimentioning

confidence: 99%

Emerging role for interferons in respiratory viral infections and childhood asthma

Bosco

2023

Front. Immunol.

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Respiratory syncytial virus (RSV) and Rhinovirus (RV) infections are major triggers of severe lower respiratory illnesses (sLRI) in infants and children and are strongly associated with the subsequent development of asthma. Decades of research has focused on the role of type I interferons in antiviral immunity and ensuing airway diseases, however, recent findings have highlighted several novel aspects of the interferon response that merit further investigation. In this perspective, we discuss emerging roles of type I interferons in the pathogenesis of sLRI in children. We propose that variations in interferon response patterns exist as discrete endotypes, which operate locally in the airways and systemically through a lung-blood-bone marrow axis. We discuss new insights into the role of interferons in immune training, bacterial lysate immunotherapy, and allergen-specific immunotherapy. Interferons play complex and diverse roles in the pathogenesis of sLRI and later asthma, providing new directions for mechanistic studies and drug development.

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Macrolide Use in Preschool-Aged Children with Acute or Recurrent Respiratory Tract Illnesses with Wheezing

Benton,

Martinez

2024

Progress in Inflammation Research

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Azithromycin to Prevent Recurrent Wheeze Following Severe Respiratory Syncytial Virus Bronchiolitis

Cited by 16 publications

References 44 publications

Preventing progression of preschool wheezing to asthma: Opportunities for intervention

Preventing progression of preschool wheezing to asthma: Opportunities for intervention

Emerging role for interferons in respiratory viral infections and childhood asthma

Macrolide Use in Preschool-Aged Children with Acute or Recurrent Respiratory Tract Illnesses with Wheezing

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