The Role of Bacteria and Genetic Variations in Cystic Fibrosis

Clinical Course in Cystic Fibrosis: The Effects of Pseudomonas Aeruginosa and Potential Modifier Genes

This study will examine 1) the role of hereditary factors in cystic fibrosis; i.e., the relationship of the disease to specific gene variations, and 2) the role of bacterial products involved in lung infections substances produced by bacteria may worsen the disease.

Patients with cystic fibrosis who are being followed by the Medical College of Wisconsin or the University of Wisconsin-Madison are eligible for this study. Participants will have blood tests, pulmonary function tests, a sputum culture, and buccal swabbing (cotton swabbing of the inside of the cheek to collect cells for DNA study). In addition, their medical records will be reviewed for a history of lung infections and the results of various tests, including pulmonary function studies, chest X-rays and bacterial cultures. Blood samples collected previously at the Medical College of Wisconsin or the University of Wisconsin-Madison will also be analyzed for antibodies to bacteria.

Although this is a one-time study, participants may be asked to return for repeated tests.

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Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Psuedomas Infection

Detailed Description

Individuals with cystic fibrosis (CF) are susceptible to chronic bacterial colonization by Pseudomonas aeruginosa, which results in deterioration of lung function and, eventually, death. In this study, we hope to improve our understanding of the innate immune response to infection by strains of P. aeruginosa that express type III cytotoxins and to delineate better the role of modifier genes in disease progression.

We will examine relationships between the patient's clinical course, the presence of antibodies to P. aeruginosa, and single nucleotide polymorphisms in suspected CF modifier genes.

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with cystic fibrosis (CF) are susceptible to chronic bacterial colonization by @@@Pseudomonas aeruginosa, which results in deterioration of lung function and, eventually, death. In this study, we hope to improve our understanding of the innate immune response to infection by strains of P. aeruginosa that express type III cytotoxins and to delineate better the role of modifier genes in disease progression.@@@

Description

• INCLUSION CRITERIA:

Patients with cystic fibrosis who have a defined mutation in CFTR (e.g., any of the known variants of the CFTR gene, such as the delta F508 allele) born in the state of Wisconsin since 1985 or otherwise followed by the cystic fibrosis centers at the Medical College of Wisconsin or University of Wisconsin-Madison.

Patients will have been tested or will be tested for the CFTR gene under another protocol (96-H-0100).

Patients may be colonized with P. aeruginosa or other organisms (e.g., Burkholderia cepacia).

The age range of NIH participants in this study is from 9 to 80 years old.

EXCLUSION CRITERIA:

There are no exclusion criteria.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Cystic Fibrosis; Cystic Fibrosis patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
There is a relationship between the virulence characteristics of P.aeruginosa involved inpersistent infection of the lung and the genetic profile of CF patients.	There is a relationship between the virulence characteristics of P.aeruginosa involved in persistent infection of the lung and the genetic profile of CF patients.	End of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibodies to the components of the type III secretion pathway can be used as an accurate measure of acute infection and colonization of the CF lung by virulent strains of P. aeruginosa. There is a relationship between modifier genotypes and sur...	Antibodies to the components of the type III secretion pathway can be used as an accurate measure of acute infection and colonization of the CF lung by virulent strains of P. aeruginosa. There is a relationship between modifier genotypes and survival or other measurable CF disease outcomes. 4. The bactericidal activity of sera from CF patients will neutralize components of the Type III pathway	End of Study

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066-73. doi: 10.1126/science.2475911. Erratum In: Science 1989 Sep 29;245(4925):1437.
• Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059-65. doi: 10.1126/science.2772657.
• Frizzell RA. Functions of the cystic fibrosis transmembrane conductance regulator protein. Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 2):S54-8. doi: 10.1164/ajrccm/151.3_Pt_2.S54.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2001
• Primary Completion (Actual): July 10, 2018
• Study Completion (Actual): July 10, 2018

Study Registration Dates

• First Submitted: July 13, 2006
• First Submitted That Met QC Criteria: August 6, 2002
• First Posted (Estimate): August 7, 2002

Study Record Updates

• Last Update Posted (Actual): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 25, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: ADA-SCID; Severe Combined Immune Deficiency; Adenosine Deaminase Deficiency; Immune Deficiency; SCID; Type III Secretion Pathways; Exotoxin A Polymorphisms; Cystic Fibrosis and Pseudomonas Aeruginosa
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 010198; 01-H-0198

Drug and device information, study documents

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