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

Completed

Conditions: Cystic Fibrosis

Interventions: Procedure: epithelial cells and blood lymphocyte extraction

Registration Number: NCT00381628

Lead Sponsor: University Hospitals Cleveland Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 59

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

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

Exclusion criteria for CF patients with pulmonary exacerbation:

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.

Inclusion Criteria - Asthma patients

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

Exclusion Criteria - Asthma patients

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.

Inclusion Criteria for Healthy Volunteers

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 for Healthy Volunteers

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

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy volunteers	epithelial cells and blood lymphocyte extraction	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
Stable subjects with CF	epithelial cells and blood lymphocyte extraction	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.
Exacerbating subjects with CF	epithelial cells and blood lymphocyte extraction	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.
Stable subjects with asthma	epithelial cells and blood lymphocyte extraction	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.