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Risk factors for Pseudomonas aeruginosa airway infection and lung function decline in children with cystic fibrosis

  • Julie Mésinèle
    Affiliations
    Sorbonne Université, INSERM UMR S_938, Centre de Recherche Saint-Antoine (CRSA), Paris, France

    Sorbonne Université, Inserm, Institut Pierre Louis d'épidémiologie et de Santé Publique, IPLESP, APHP, Hôpital Saint-Antoine, Paris, France
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  • Manon Ruffin
    Affiliations
    Sorbonne Université, INSERM UMR S_938, Centre de Recherche Saint-Antoine (CRSA), Paris, France
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  • Astrid Kemgang
    Affiliations
    Sorbonne Université, INSERM UMR S_938, Centre de Recherche Saint-Antoine (CRSA), Paris, France
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  • Loïc Guillot
    Affiliations
    Sorbonne Université, INSERM UMR S_938, Centre de Recherche Saint-Antoine (CRSA), Paris, France
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  • Author Footnotes
    1 Equally contributed
    Pierre-Yves Boëlle
    Correspondence
    Corresponding author at: AP-HP, Hôpital Trousseau, Pediatric Pulmonary Department, 26 Avenue du Docteur Arnold Netter, 75012 Paris, France
    Footnotes
    1 Equally contributed
    Affiliations
    Sorbonne Université, Inserm, Institut Pierre Louis d'épidémiologie et de Santé Publique, IPLESP, APHP, Hôpital Saint-Antoine, Paris, France
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  • Author Footnotes
    1 Equally contributed
    Harriet Corvol
    Correspondence
    Corresponding author at: AP-HP, Hôpital Trousseau, Pediatric Pulmonary Department, 26 Avenue du Docteur Arnold Netter, 75012 Paris, France
    Footnotes
    1 Equally contributed
    Affiliations
    Sorbonne Université, INSERM UMR S_938, Centre de Recherche Saint-Antoine (CRSA), Paris, France

    AP-HP, Hôpital Trousseau, Service de Pneumologie Pédiatrique, Paris, France
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  • Author Footnotes
    1 Equally contributed
Published:October 07, 2021DOI:https://doi.org/10.1016/j.jcf.2021.09.017

      Highlights

      • 50% of children with cystic fibrosis (CF) acquire P. aeruginosa at 5.1 years, and 25% progress to chronic colonisation at 14.7 years.
      • P. aeruginosa chronic colonisation occurs later in life of people with CF in recent cohorts.
      • Modifier genes influence initial acquisition and chronic colonisation of P. aeruginosa.
      • CF-related diabetes and liver disease are risk factors for P. aeruginosa infection.
      • Decline in ppFEV1 increases significantly after P. aeruginosa infection.

      Abstract

      Background Cystic fibrosis (CF) lung disease is characterised by recurrent Pseudomonas aeruginosa (Pa) infections, leading to structural lung damage and decreased survival. The epidemiology of Pa infection and its impact on lung function in people with CF (pwCF), especially in recent birth cohorts, remain uncertain.
      Methods We included 1,231 French pwCF under 18 years of age. Age at initial acquisition (Pa-IA), chronic colonisation (Pa-CC), and duration from Pa-IA to Pa-CC were estimated using the Kaplan–Meier method. Demographic, clinical, and genetic characteristics were analysed as risk factors for Pa infection using Cox regression models. Lung function decline was assessed by modelling percent-predicted forced expiratory volume in 1 s (ppFEV1) before Pa infection, after Pa-IA, and after Pa-CC.
      Results Among the 1,231 pwCF, 50% had Pa-IA by the age of 5.1 years [95% confidence interval (CI) 3.8–6.2] and 25% had Pa-CC by the age of 14.7 years (95% CI 12.1 to ∞). We observed that CF-related diabetes and liver disease were risk factors for Pa, while gender, CFTR variants, and CF centre size were not. Genetic variants of TNF, DCTN4, SLC9A3, and CAV2 were confirmed to be associated with Pa. The annual rate of ppFEV1 decline before Pa was -0.38% predicted/year (95% CI -0.59 to -0.18), which decreased significantly after Pa-IA to -0.93% predicted/year (95% CI -1.14 to -0.71) and after Pa-CC to -1.51% predicted/year (95% CI -1.86 to -1.16).
      Conclusions We identified and replicated several risk factors associated with Pa infection and showed its deleterious impact on lung function in young pwCF. This large-scale study confirmed that Pa airway infection is a major determinant of lung disease severity.

      Keywords

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