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Randomized Controlled Trial
. 2024 May;132(5):623-629.
doi: 10.1016/j.anai.2024.01.001. Epub 2024 Jan 17.

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze

Avraham Beigelman  1 , Charles W Goss  2 , Jinli Wang  2 , Mythili Srinivasan  3 , Jonathan Boomer  4 , Yanjiao Zhou  5 , Sarah Bram  3 , Timothy J Casper  6 , Andrea M Coverstone  3 , Watcharoot Kanchongkittiphon  7 , Cadence Kuklinski  3 , Gregory A Storch  3 , Kenneth B Schechtman  2 , Mario Castro  4 , Leonard B Bacharier  8
Affiliations
Randomized Controlled Trial

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze

Avraham Beigelman et al. Ann Allergy Asthma Immunol. 2024 May.

Abstract

Background: Early life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits.

Objective: To investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW).

Methods: A total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months.

Results: Upper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively).

Conclusion: Azithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV.

Trial registration: This study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

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Conflict of interest statement

Disclosures Dr Beigelman reports receiving grant support from the US-Israel Binational Science Foundation (BSF); serving as an advisor and speaker for Sanofi; and serving as a DSMB member of OM Pharma. Dr Kanchongkittiphon reports serving as a speaker for GlaxoSmithKline, Takeda, AstraZeneca, Viatris, and Organon. Dr Bacharier reports serving as a member of the GINA Science Committee; receiving grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases/National Heart, Lung, and Blood Institute; receiving personal fees from GlaxoSmithKline, Genentech/Novartis, Merck, Teva, Boehringer Ingelheim, AstraZeneca, Avillion, WebMD/Medscape, Sanofi/Regeneron, Vectura, Circassia, OM Pharma, Recludix, and Kinaset; serving for DSMB from AstraZeneca, DBV Technologies, Aravax, and Vertex; and receiving royalties from Elsevier, outside the submitted work. Dr Castro reports receiving research support from the American Lung Association, AstraZeneca, GlaxoSmithKline, National Institutes of Health, Novartis, PCORI, Pulmatrix, Sanofi-Aventis, and Shionogi; serving as a consultant for Genentech, Novartis, Sanofi-Aventis, and Teva; receiving speaker fees from AstraZeneca, Genentech, GlaxoSmithKline, Regeneron Pharmaceuticals, Inc., Sanofi, and Teva; and receiving royalties from Elsevier. The remaining authors have no conflicts of interest to report.

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