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Association between early respiratory viral infections and structural lung disease in infants with cystic fibrosis

  • Don B. Sanders
    Correspondence
    Corresponding author.
    Affiliations
    Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
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  • Author Footnotes
    1 These authors were at Indiana University School of Medicine at the time of the study.
    Ashley R. Deschamp
    Footnotes
    1 These authors were at Indiana University School of Medicine at the time of the study.
    Affiliations
    Department of Pediatrics, University of Nebraska Medical Center, Children's Hospital and Medical Center, Omaha, NE, USA
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  • Author Footnotes
    1 These authors were at Indiana University School of Medicine at the time of the study.
    Joseph E. Hatch
    Footnotes
    1 These authors were at Indiana University School of Medicine at the time of the study.
    Affiliations
    Department of Pediatrics, UNC Children's, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
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  • James E. Slaven
    Affiliations
    Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA
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  • Netsanet Gebregziabher
    Affiliations
    Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA
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  • Mariette Kemner-van de Corput
    Affiliations
    Department of Paediatrics, Erasmus MC – Sophia Children's Hospital, University Medial Center Rotterdam, Netherlands

    Department of Radiology and Nuclear Medicine, Erasmus MC – Sophia Children's Hospital, University Medial Center Rotterdam, Netherlands
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  • Harm A.W.M. Tiddens
    Affiliations
    Department of Paediatrics, Erasmus MC – Sophia Children's Hospital, University Medial Center Rotterdam, Netherlands

    Department of Radiology and Nuclear Medicine, Erasmus MC – Sophia Children's Hospital, University Medial Center Rotterdam, Netherlands
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  • Tim Rosenow
    Affiliations
    The Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Nedlands, Western Australia

    Children's Lung Health, Wal-yan Respiratory Research Centre, Telethon Kids Institute and School of Physiotherapy and Exercise Science, Curtin University, Perth, Australia
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  • Gregory A. Storch
    Affiliations
    Department of Pediatrics, Washington University, St. Louis Children's Hospital, St. Louis, MO, USA
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  • Graham L. Hall
    Affiliations
    Children's Lung Health, Wal-yan Respiratory Research Centre, Telethon Kids Institute and School of Physiotherapy and Exercise Science, Curtin University, Perth, Australia
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  • Stephen M. Stick
    Affiliations
    Department of Pediatrics, University of Western Australia, Telethon Kids Institute, Perth, Australia
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  • Sarath Ranganathan
    Affiliations
    Department of Respiratory and Sleep Medicine, Royal Children's Hospital, Parkville, Australia

    Infection and Immunity, Murdoch Children's Research Institute, Parkville, Australia

    Department of Paediatrics, University of Melbourne, Parkville, Australia
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  • Thomas W. Ferkol
    Affiliations
    Department of Pediatrics, Washington University, St. Louis Children's Hospital, St. Louis, MO, USA
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  • Author Footnotes
    1 These authors were at Indiana University School of Medicine at the time of the study.
    Stephanie D. Davis
    Footnotes
    1 These authors were at Indiana University School of Medicine at the time of the study.
    Affiliations
    Department of Pediatrics, UNC Children's, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
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  • Author Footnotes
    1 These authors were at Indiana University School of Medicine at the time of the study.

      Highlights

      • Infants with CF develop structural lung disease early in life.
      • We investigated whether respiratory viruses contribute to early lung disease.
      • We found limited extent of structural lung disease on chest CT at 1 year of age.
      • Detection of respiratory viruses were not associated with more severe disease.
      • Episodes of wheezing and cough were associated with more severe disease.

      Abstract

      Background

      Infants with cystic fibrosis (CF) develop structural lung disease early in life, and viral infections are associated with progressive lung disease. We hypothesized that the presence of respiratory viruses would be associated with structural lung disease on computed tomography (CT) of the chest in infants with CF.

      Methods

      Infants with CF were enrolled before 4 months of age. Multiplex PCR assays were performed on nasal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent CT imaging at approximately 12 months of age. Associations between Perth–Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) CT scores and respiratory viruses and symptoms were assessed with Spearman correlation coefficients.

      Results

      Sixty infants were included for analysis. Human rhinovirus was the most common virus detected, on 28% of tested nasal swabs and in 85% of participants. The median (IQR) extent of lung fields that was healthy based on PRAGMA-CF was 98.7 (0.8)%. There were no associations between PRAGMA-CF and age at first virus, or detection of any virus, including rhinovirus, respiratory syncytial virus, or parainfluenza. The extent of airway wall thickening was associated with ever having wheezed (ρ = 0.31, p = 0.02) and number of encounters with cough (ρ = 0.25, p = 0.0495).

      Conclusions

      Infants with CF had minimal structural lung disease. We did not find an association between respiratory viruses and CT abnormalities. Wheezing and frequency of cough were associated with early structural changes.

      Keywords

      Abbreviations:

      CT (computed tomography), ICC (Intraclass correlation coefficient), PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF)
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