Mucoid Pseudomonas aeruginosa and regional inflammation in the cystic fibrosis lung

  • Sankalp Malhotra
    Affiliations
    Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA

    The Ohio State University College of Medicine, Columbus, OH, USA
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  • Don Hayes Jr
    Affiliations
    The Ohio State University College of Medicine, Columbus, OH, USA

    Department of Pediatrics, The Ohio State University, Columbus, OH, USA

    Section. of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH, USA
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  • Daniel J. Wozniak
    Correspondence
    Corresponding author at: 704 BRT, 460W 12th Ave Columbus, OH 43210, USA.
    Affiliations
    Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA

    The Ohio State University College of Medicine, Columbus, OH, USA

    Department of Microbiology, The Ohio State University, Columbus, OH, USA
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Published:April 26, 2019DOI:https://doi.org/10.1016/j.jcf.2019.04.009

      Highlights

      • P. aeruginosa mucoid/nonmucoid variants are distributed throughout the CF lung
      • CF lung upper lobes are slightly more inflamed compared to the lower lobes
      • P. aeruginosa mucoid variants are associated with greater regional inflammation

      Abstract

      Background

      Pseudomonas aeruginosa is the prominent bacterial pathogen in the cystic fibrosis (CF) lung and contributes to significant morbidity and mortality. Though P. aeruginosa strains initially colonizing the CF lung have a nonmucoid colony morphology, they often mutate into mucoid variants that are associated with clinical deterioration. Both nonmucoid and mucoid P. aeruginosa variants are often co-isolated on microbiological cultures of sputum collected from CF patients. With regional variation in bronchiectasis, tissue damage, inflammation, and microbial colonization, lobar distribution of nonmucoid and mucoid P. aeruginosa variants may impact local microenvironments in the CF lung, but this has not been well-studied.

      Methods

      We prospectively collected lobe-specific bronchoalveolar lavage (BAL) fluid from a CF patient cohort ( n = 14) using a standardized bronchoscopic protocol where collection was performed in 6 lobar regions. The lobar BAL specimens were plated on P. aeruginosa-selective media and proinflammatory cytokines (IL-1, TNF, IL-6 and IL-8) were measured via cytokine array. Correlations between infecting P. aeruginosa variants (nonmucoid, mucoid, or mixed-variant populations), the lobar regions in which these variants were found, and regional proinflammatory cytokine concentrations were measured.

      Results

      P. aeruginosa mucoid and nonmucoid variants were homogenously distributed throughout the CF lung. However, infection with mucoid variants (found within single- or mixed-variant populations) was associated with significantly greater regional inflammation. The upper and lower lobes of the CF lung did not exhibit differences in inflammatory cytokine concentrations.

      Conclusions

      Mucoid P. aeruginosa infection is a microbial determinant of regional inflammation within the CF lung.

      Keywords

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