Nasal Epithelial Cells/Blood Lymphocyte Markers for Cystic Fibrosis (CF)/CF Pulmonary Exacerbations

NCT ID: NCT00381628

Last Updated: 2019-02-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 59 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2011-09-30

Brief Summary

Study Hypothesis: We hypothesize that cellular markers from nasal epithelial cells and blood lymphocytes can serve as potential biomarkers reflect the underlying inflammatory state of the lung and will be helpful in determining the presence of a CF pulmonary exacerbation and its overall severity.

Detailed Description

Cystic fibrosis (CF) is the most common lethal genetic disease in the US afflicting approximately 30,000 people. Chronic disease of the respiratory tract, which is responsible for early death, affects both the upper and lower airways.

We propose to utilize cells (blood lymphocytes and nasal epithelial cells) that are readily accessible and are known to express the cystic fibrosis transmembrane conductance regulator (CFTR) and therefore candidates to express markers of the downstream consequences of CFTR deficiency.

A marker that indicates the inflammatory state of the lung would be useful to identify infective/inflammatory exacerbations as opposed to worsening due to pulmonary vascular disease or simply upper airway infection. This marker might help to guide therapy for intensity and duration. Evidence in mice suggest that lymphocytes may be a driving force for inflammation in the CF lung, particularly during exacerbations, and also that human CF lymphocytes have dysfunctional production of cytokines.

Specific Aims:

To identify markers in nasal epithelial cells or blood lymphocytes that distinguish CF patients from those with functional CFTR (healthy volunteers and patients with asthma). If successful this could become a marker for CFTR correction by drugs or other systemic therapies.

To identify markers in blood lymphocytes that will identify inflammatory status (ie, distinguish an active exacerbation from return to clinical stability) in CF patients. This could become a marker for infectious exacerbations of CF airway disease.

Conditions

Cystic Fibrosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Stable subjects with CF

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) when they are in their usual state of well-health. These cells will be studied in vitro.

epithelial cells and blood lymphocyte extraction

Intervention Type: PROCEDURE

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Exacerbating subjects with CF

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) at the beginning and end of treatment for a pulmonary exacerbation. These cells will be studied in vitro.

epithelial cells and blood lymphocyte extraction

Intervention Type: PROCEDURE

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Stable subjects with asthma

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) when they are in their usual state of well-health. These cells will be studied in vitro. This is the disease control group.

epithelial cells and blood lymphocyte extraction

Intervention Type: PROCEDURE

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Healthy volunteers

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) when they are in their usual state of well-health. These cells will be studied in vitro. This is the control group

epithelial cells and blood lymphocyte extraction

Intervention Type: PROCEDURE

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Interventions

epithelial cells and blood lymphocyte extraction

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Male or female >= 15 years of age
• Confirmed diagnosis of CF
• Clinically stable with no evidence of acute upper respiratory tract infection or current pulmonary exacerbation within the previous month
• Ability to understand and sign a written informed consent and comply with the requirements of the study

• Male or female >= 15 years of age
• Physician diagnosed asthma
• Clinically stable with no evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the previous month

• Male or female >= 18 years of age
• Free of any chronic medical condition
• Clinically stable with no evidence of acute upper or lower respiratory tract infection within the previous month
• Ability to understand and sign a written informed consent and comply with the requirements of the study

Exclusion Criteria

• Chronic use of a medication with anti-neutrophil or anti-inflammatory effect (ibuprofen, systemic or inhaled corticosteroids, or other immunosuppressive agents, etc
• Oxygen saturation <92% on room air
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data

CF patients with pulmonary exacerbations:

Male of female >= 15 years of age Confirmed diagnosis of CF

Patient meets a modified definition for a pulmonary exacerbation based upon Fuchs criteria which is treated with intravenous antibiotics for any 4 of the following 12 signs or symptoms:

• Increased sputum production
• New or increased coughing up of blood
• Increased cough
• Increased dyspnea with exertion
• Malaise, fatigue or lethargy
• Anorexia or weight loss
• Fever
• Sinus pain or tenderness
• Changes in sinus discharge
• New findings on chest examination
• Decline in forced expiratory volume in 1 second (FEV1) > 10% since previous visit
• Radiographic changes indicative of pulmonary infection
• Ability to understand and sign a written informed consent and comply with the requirements of the study

• Concurrent use a medication with anti-neutrophil or anti-inflammatory effect within the previous 4 weeks
• Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data.

• Chronic use of a medication with anti-neutrophil or anti-inflammatory effect within the previous 4 weeks
• Treated for an asthma exacerbation with the previous 4 weeks
• Treated with oral corticosteroids within the previous 4 weeks
• Oxygen saturation <92% on room air
• Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data.

• Use of a medication with anti-neutrophil or anti-inflammatory effect within the previous 4 months
• Presence of any chronic medical condition
• Oxygen saturation <92% on room air
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role: lead

Responsible Party

James F. Chmiel

Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James F Chmiel, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center

Locations

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

Protocol 08-06-23

Identifier Type: -

Identifier Source: org_study_id