Lung inflammation and simulated airway resistance in infants with cystic fibrosis

AREST CF

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Abstract

Cystic fibrosis (CF) is characterized by small airway disease; but central airways may also be affected. We hypothesized that airway resistance estimated from computational fluid dynamic (CFD) methodology in infants with CF was higher than controls and that early airway inflammation in infants with CF is associated with airway resistance. Central airway models with a median of 51 bronchial outlets per model (interquartile range 46,56) were created from chest computed tomography scans of 18 infants with CF and 7 controls. Steady state airflow into the trachea was simulated to estimate central airway resistance in each model. Airway resistance was increased in the full airway models of infants with CF versus controls and in models trimmed to 33 bronchi. Airway resistance was associated with markers of inflammation in bronchoalveolar lavage fluid obtained approximately 8 months earlier but not with markers obtained at the same time. In conclusion, airway resistance estimated by CFD modeling is increased in infants with CF compared to controls and may be related to early airway inflammation.

Original languageEnglish
Article number103722
JournalRespiratory Physiology and Neurobiology
Volume293
DOIs
Publication statusPublished - Nov 2021

Bibliographical note

Funding Information:
Supported by NHLBI Viral Pathogenesis of Early CF Lung Disease study ( R01HL116211 ) PI Davis, Ferkol, Ranganathan, DeBoer 18A0 Cystic Fibrosis Foundation, and AREST CF NHMRC1043768 PI Ranganathan, and NIH/NCATS Colorado CTSI UL1 TR002535. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views.

Funding Information:
Supported by NHLBI Viral Pathogenesis of Early CF Lung Disease study (R01HL116211) PI Davis, Ferkol, Ranganathan, DeBoer 18A0 Cystic Fibrosis Foundation, and AREST CF NHMRC1043768 PI Ranganathan, and NIH/NCATS Colorado CTSI UL1 TR002535. Contents are the authors? sole responsibility and do not necessarily represent official NIH views.Dr. DeBoer reports grants from Cystic Fibrosis Foundation, grants from NIH/NCATS Colorado CTSI, during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Triple Endoscopy, outside the submitted work. In addition, Dr. DeBoer has a patent Endoscopic methods and technologies pending. Dr. Kimbell reports grants from Indiana University, during the conduct of the study; grants from Applied Research Associates, Inc., grants from Kitware, Inc., outside the submitted work;. Dr. Rosenow has a patent PCT/AU2016/000079 issued. Dr. Tiddens is heading the Erasmus MC core laboratory Lung Analysis which is a not-for-profit core image analysis laboratory. The financial aspects of the laboratory are handled by the department of Radiology and by the Sophia Research BV. FLUIDDA has developed computational fluid dynamic modelling based on chest-CTs obtained from Erasmus MC-Sophia for which royalties are received by Sophia Research BV. Dr. Ferkol reports several grants from NIH during the conduct of the study; and support from Parion Sciences and Aerocrine Pharmaceuticals (Circassia) for clinical and device trials unrelated to the work presented in this manuscript. Dr. Davis reports grants from NHLBI, grants from Cystic Fibrosis Foundation, during the conduct of the study. Outside the submitted work, she was a reviewer of grants for Vertex Pharmaceuticals and is currently an editor for a book on cystic fibrosis for Springer. The other authors have nothing to disclose.

Funding Information:
Dr. DeBoer reports grants from Cystic Fibrosis Foundation , grants from NIH/NCATS Colorado CTSI , during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Triple Endoscopy, outside the submitted work. In addition, Dr. DeBoer has a patent Endoscopic methods and technologies pending. Dr. Kimbell reports grants from Indiana University , during the conduct of the study; grants from Applied Research Associates, Inc. , grants from Kitware, Inc. , outside the submitted work;. Dr. Rosenow has a patent PCT/AU2016/000079 issued. Dr. Tiddens is heading the Erasmus MC core laboratory Lung Analysis which is a not-for-profit core image analysis laboratory. The financial aspects of the laboratory are handled by the department of Radiology and by the Sophia Research BV. FLUIDDA has developed computational fluid dynamic modelling based on chest-CTs obtained from Erasmus MC-Sophia for which royalties are received by Sophia Research BV. Dr. Ferkol reports several grants from NIH during the conduct of the study; and support from Parion Sciences and Aerocrine Pharmaceuticals (Circassia) for clinical and device trials unrelated to the work presented in this manuscript. Dr. Davis reports grants from NHLBI , grants from Cystic Fibrosis Foundation , during the conduct of the study. Outside the submitted work, she was a reviewer of grants for Vertex Pharmaceuticals and is currently an editor for a book on cystic fibrosis for Springer. The other authors have nothing to disclose.

Publisher Copyright:
© 2021 Elsevier B.V.

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