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Pilot study of inflammatory biomarkers in matched induced sputum and bronchoalveolar lavage from 2-year-olds with cystic fibrosis
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  • Vincent Giacalone,
  • Diego Moncada Giraldo,
  • Camilla Margaroli,
  • Milton Brown,
  • George Silva,
  • Joshua Chandler,
  • Limin Peng,
  • Rabindra Tirouvanziam,
  • Lokesh Guglani
Vincent Giacalone
Emory University School of Medicine

Corresponding Author:vincent.giacalone@emory.edu

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Diego Moncada Giraldo
Emory University School of Medicine
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Camilla Margaroli
Emory University School of Medicine
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Milton Brown
Emory University School of Medicine
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George Silva
Emory University School of Medicine
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Joshua Chandler
Emory University School of Medicine
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Limin Peng
Emory University School of Public Health
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Rabindra Tirouvanziam
Emory University School of Medicine
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Lokesh Guglani
Children's Healthcare of Atlanta
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Abstract

Background: In this pilot study, we investigated whether induced sputum (IS) could serve as a viable alternative to bronchoalveolar lavage (BAL) and yield robust inflammatory biomarkers in toddlers with cystic fibrosis (CF) featuring minimal structural lung disease. Methods: We collected IS, BAL (right middle lobe and lingula) and blood, and performed chest computed tomography (CT) scans from 2-year-olds with CF (N=11), all within a single visit. Inflammatory biomarkers included 20 soluble immune mediators and neutrophil elastase (NE), as well as frequency and phenotype of T cells, monocytes / macrophages and neutrophils. Results: At the molecular level, nine mediators showed similar levels in IS and BAL (CXCL1, CXCL8, IL-1, IL-1RA, IL-6, CCL2, CXCL10, M-CSF, VEGF-A), four were higher in IS than in BAL (CXCL5, IL-1, CXCL11, TNFSF10) and two were present in IS but undetectable in BAL (IL-10, IFN-). Meanwhile, soluble NE had lower activity in IS than in BAL. At the cellular level, T-cell frequency was lower in IS than in BAL. Monocytes / macrophages were dominant in IS and BAL with similar frequencies but differing expression of CD16 (lower in IS), CD115 and surface-associated NE (higher in IS). Neutrophil frequency and phenotype did not differ between IS and BAL. Conclusions: IS collected from 2-year-olds with CF yields biomarkers of early airway inflammation with good agreement with BAL notably with regards to molecular and cellular outcomes related to neutrophils and monocytes/macrophages.
29 Jan 2022Submitted to Pediatric Pulmonology
01 Feb 2022Submission Checks Completed
01 Feb 2022Assigned to Editor
02 Feb 2022Reviewer(s) Assigned
23 Feb 2022Review(s) Completed, Editorial Evaluation Pending
26 Feb 2022Editorial Decision: Revise Major
05 Apr 20221st Revision Received
07 Apr 2022Assigned to Editor
07 Apr 2022Submission Checks Completed
07 Apr 2022Reviewer(s) Assigned
03 May 2022Review(s) Completed, Editorial Evaluation Pending
04 May 2022Editorial Decision: Revise Minor
08 May 20222nd Revision Received
09 May 2022Submission Checks Completed
09 May 2022Assigned to Editor
09 May 2022Reviewer(s) Assigned
20 May 2022Review(s) Completed, Editorial Evaluation Pending
29 May 2022Editorial Decision: Accept
20 Jun 2022Published in Pediatric Pulmonology. 10.1002/ppul.26023