Mapping Chemical and Microbiological Heterogeneity Throughout Explanted Cystic Fibrosis Lung Specimens

NCT02128711 | Completed DMC

• 2 other identifiers: PACCS-2018-273764R00HL114862-02
• Study Type: observational
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

There is plenty of evidence to suggest that the lung is not uniform. The internal surface area is 30 times that of skin, and the different bronchioles/bronchi/alveoli differ greatly in blood perfusion, temperature, oxygen tension, and pH. Also, particularly in the context of respiratory disease, notable differences are present in the structure of epithelial cells, cilia, production of mucus, and inflammatory/immune responses. All of these factors are known to impact the physiology of bacteria, yet, there is very little understanding of how they impact a) the presence/absence of particular bacterial species throughout the respiratory tract, or b) the metabolic processes used by these bacteria within the human host environment. A greater understanding of the relationships between environmental (chemical) gradients in the lungs of diseased patients (particularly those with cystic fibrosis) and the microbial communities that are present may lead to novel hypotheses about manipulation of the respiratory environment for therapeutic benefit. To investigate this further, the investigators propose to use explanted lung specimens from cystic fibrosis patients to test the following hypothesis: Hypothesis: In patients with cystic fibrosis, bacterial community composition, metabolism and environmental chemistry will vary depending on their spatial location within the airways.

Conditions

Cystic Fibrosis

Keywords

lung; cystic fibrosis; bacteria; positive diagnosis of CF,

Outcome Measures

Primary Outcomes (1)

• Composition of bacterial communities throughout an explanted lung

  16S culture-independent sequencing will be used to characterize the spatial distribution of bacterial pathogens throughout the lungs of cystic fibrosis patients. Explanted lung specimens will be dissected into 5 separate lobes, and mucus material will be collected, homogenized, and processed for bacterial species identification.

  Entire study (3 years)

Secondary Outcomes (1)

• Levels of bacterial gene expression

  Entire study (3 years).

Other Outcomes (1)

• Distribution of bacterial gene expression

  Entire study (3 years)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will include those undergoing single or double lung transplantation as part of their normally scheduled therapy for cystic fibrosis disease.

You may qualify if:

• diagnosis of cystic fibrosis
• eligible for lung transplantation
• exhausted other available therapies without success
• informed consent

Sponsors & Collaborators

• University of Minnesota: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (2)

• Hunter RC, Asfour F, Dingemans J, Osuna BL, Samad T, Malfroot A, Cornelis P, Newman DK. Ferrous iron is a significant component of bioavailable iron in cystic fibrosis airways. mBio. 2013 Aug 20;4(4):e00557-13. doi: 10.1128/mBio.00557-13.

  PMID: 23963183 BACKGROUND

• Hunter RC, Klepac-Ceraj V, Lorenzi MM, Grotzinger H, Martin TR, Newman DK. Phenazine content in the cystic fibrosis respiratory tract negatively correlates with lung function and microbial complexity. Am J Respir Cell Mol Biol. 2012 Dec;47(6):738-45. doi: 10.1165/rcmb.2012-0088OC. Epub 2012 Aug 3.

  PMID: 22865623 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Explanted lung specimens from cystic fibrosis patients. This tissue, that would otherwise be discarded, is being retained for microbiological analysis.

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Ryan C Hunter, PhD

  University of Minnesota Medical School (Microbiology)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2014
• First Posted: May 1, 2014
• Study Start: July 1, 2014
• Primary Completion: November 22, 2024
• Study Completion: July 31, 2025
• Last Updated: October 14, 2025

Record last verified: 2025-10

Locations

US (1)