Host and Bacterial Mechanisms During Cystic Fibrosis Pulmonary Exacerbations

Host and Bacterial Mechanisms in Recovering FEV1 After Pulmonary Exacerbations in Patients With Cystic Fibrosis

Cystic fibrosis pulmonary exacerbations (CF PEx) vary greatly in their severity, their pathogens, and their treatment responses. A failure to return to baseline lung function after treatment may be due to persistent infection or chronic inflammation or both. This constant infection and inflammation are believed to be tightly connected, making it difficult to know the exact reason why some patients fail to respond to treatment. The purpose of this study is to evaluate both infection and inflammation during CF PEx to allow for more personalized approaches to improve lung function responses and better CF PEx outcomes. Subjects will be asked to be in the study if they have CF, are 18 years of age or older, and are starting on IV antibiotics due to worsening lung infection. Subjects will stay in the study for up to 5 years, with visits occurring once a year if hospitalized for a CF PEx. Each visit will have blood, sputum, and urine collected and analyzed for changes in expression of certain genes and proteins. These changes may relate to improvements felt by people living with CF and determine what treatments are most helpful.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients followed by the Colorado Adult CF Center will be eligible. A subject will have a diagnosis of cystic fibrosis, be 18 years or older, and been diagnosed by clinical faculty with a pulmonary exacerbation (PEx) and need to be hospitalized to start on IV antibiotic treatment.

Description

Inclusion Criteria:

• CF patients 18 years or older
• hospitalized for IV treatment of an acute pulmonary exacerbation
• not on investigational drugs
• who can provide written consent and are willing to comply with study procedure

Exclusion Criteria:

• the presence of a condition or abnormality that, in the opinion of the Principal Investigator, would compromise the safety of the patient or the quality of the data.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change between FEV1 and Th17/PD-1 expression during the course of treatment for pulmonary exacerbations using flow cytometry	There is a Th17 skewing association with a failure to return to baseline FEV1 values post pulmonary exacerbation, as measured using conventional flow cytometry followed by linear mixed effects models.	Onset and end of CF pulmonary exacerbations, on average 10 days apart
Change between FEV1 and Th17/PD-1 expression over time using flow cytometry	There is a Th17 skewing association with a failure to return to baseline FEV1 values post pulmonary exacerbation, as measured using conventional flow cytometry followed by linear mixed effects models.	From initial CF pulmonary exacerbation to subsequent CF pulmonary exacerbation, assessed over a period of 60 months
Change in FEV1 and Th1/Th2/Th17 gene expression during the course of treatment for pulmonary exacerbations using single cell sequencing	Gene expression changes, with a particular emphasis on the relationship between changing cell composition (Th1, Th2, and Th17) single cell gene expression and FEV1 recovery, as measured by single cell sequencing of CD4+CD45RO+ memory cells, may be associated with a failure to return to baseline FEV1 during the course of treatment.	Onset and end of CF pulmonary exacerbations, on average 10 days apart
Change in FEV1 and Th1/Th2/Th17 gene expression over time using single cell sequencing	Gene expression changes, with a particular emphasis on the relationship between changing cell composition (Th1, Th2, and Th17) single cell gene expression and FEV1 recovery, as measured by single cell sequencing of CD4+CD45RO+ memory cells, may be associated with a failure to return to baseline FEV1 over time.	From initial CF pulmonary exacerbation to subsequent CF pulmonary exacerbation, assessed over a period of 60 months
Comparison of Th17 vs Th2 TCR repertoires during the course of treatment for pulmonary exacerbations through bulk TCR beta sequencing	Examining if an expanded clone within the Th17 lineage translates to greater inflammation and poorer FEV1 response during the course of treatment as measured by bulk TCR beta sequencing.	Onset and end of CF pulmonary exacerbations, on average 10 days apart
Comparison of Th17 vs Th2 TCR repertoires over time through bulk TCR beta sequencing	Examining if an expanded clone within the Th17 lineage translates to greater inflammation and poorer FEV1 response over time as measured by bulk TCR beta sequencing.	From initial CF pulmonary exacerbation to subsequent CF pulmonary exacerbation, assessed over a period of 60 months

Collaborators and Investigators

• Sponsor: National Jewish Health

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Actual): September 21, 2021
• Study Completion (Actual): September 22, 2023

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis
• Other Study ID Numbers: SAAVED19G0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No