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Inflammation in CF: Key Characteristics and Therapeutic Discovery

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Cystic Fibrosis

Part of the book series: Respiratory Medicine ((RM))

Abstract

Inflammation is a cardinal feature of CF lung pathophysiology with a wide range of contributing factors. In addition to chronic airway infection leading to pulmonary inflammation, mechanisms of imbalanced oxidative stress response and pro-inflammatory lipid homeostasis as well as exuberant cytokine responses all contribute to a dysregulated inflammatory milieu in the CF host. Previous studies of anti-inflammatory steroidal and nonsteroidal interventions in CF have proven clinical benefit, but intolerance, side effects, and challenges in proper dosing have hampered their widespread use. Widely adopted in CF clinical care, azithromycin confers anti-inflammatory benefits through a variety of putative mechanisms. Current preclinical and clinical research in this area seeks to leverage endogenous anti-inflammatory mechanisms, promoting resolution of inflammation in the CF host. CFTR modulator drugs and efforts to develop gene-based therapies agnostic to CFTR mutations are key advances in the current era of CF science and medicine. It is exciting to consider how these interventions may influence the inflammatory state within the CF airway, but a need for direct anti-inflammatory interventions appears likely to persist. This chapter reviews several key pathophysiologic mechanisms contributing to CF pulmonary inflammation, along with previous and existing therapeutic strategies to mitigate this host response without impairing host defense to infection or environmental insult.

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Authors and Affiliations

  1. The University of Kansas Health System, Department of Internal Medicine, Kansas City, KS, USA

    Deepika Polineni

  2. Seattle Children’s Hospital, University of Washington School of Medicine, Department of Pediatrics, Seattle, WA, USA

    Dave Nichols

  3. Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth-Hitchcock Medical Center, Department of Pulmonary and Critical Care Medicine, Lebanon, NH, USA

    Alex H. Gifford

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  1. Deepika Polineni
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  2. Dave Nichols
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  3. Alex H. Gifford
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Correspondence to Alex H. Gifford .

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Editors and Affiliations

  1. The University of North Carolina at Chapel Hill, Department of Pediatrics, UNC Children’s Hospital, Chapel Hill, NC, USA

    Stephanie Duggins Davis

  2. Department of Pediatrics, University of Washington School of Medicine, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, Seattle, WA, USA

    Margaret Rosenfeld

  3. Department of Pediatrics, Indiana University School of Medicine, Division of Pediatric Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children at IU Health, Indianapolis, IN, USA

    James Chmiel

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Polineni, D., Nichols, D., Gifford, A.H. (2020). Inflammation in CF: Key Characteristics and Therapeutic Discovery. In: Davis, S., Rosenfeld, M., Chmiel, J. (eds) Cystic Fibrosis. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-42382-7_8

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