Cystic Fibrosis
Conditions
Keywords
Anatomy, cells, epithelial cells, blood cells, cystic fibrosis, equipment and supplies, disposable equipment, reagent kits
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.
Interventions
PROCEDUREepithelial 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.
Sponsors
Cystic Fibrosis Foundation
University Hospitals Cleveland Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Stable CF Patients: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Blood and Sputum Samples Collected | Baseline | Blood and sputum samples for general science research collaborators |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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: 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. | 18 |
| 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: 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. | 27 |
| 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: 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. | 0 |
| 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: 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. | 14 |
| Total | 59 |
Baseline characteristics
| Characteristic | Stable Subjects With CF | Exacerbating Subjects With CF | Healthy Volunteers | Total | Stable Subjects With Asthma |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 0 Participants | 4 Participants | — |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants | — |
| Age, Categorical Between 18 and 65 years | 15 Participants | 25 Participants | 14 Participants | 54 Participants | — |
| Region of Enrollment United States | 18 Participants | 27 Participants | 14 Participants | 59 Participants | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 9 Participants | 23 Participants | — |
| Sex: Female, Male Male | 14 Participants | 17 Participants | 5 Participants | 36 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 18 | 0 / 27 | 0 / 0 | 0 / 14 |
| serious Total, serious adverse events | 0 / 18 | 0 / 27 | 0 / 0 | 0 / 14 |
Outcome results
Primary
The Number of Participants With Blood and Sputum Samples Collected
Blood and sputum samples for general science research collaborators
Time frame: Baseline
Population: These samples were to be distributed to research collaborators and were not part of a clinical trial. These samples were not analyzed for a specific outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stable Subjects With CF | The Number of Participants With Blood and Sputum Samples Collected | 18 Participants |
| Exacerbating Subjects With CF | The Number of Participants With Blood and Sputum Samples Collected | 27 Participants |
| Stable Subjects With Asthma | The Number of Participants With Blood and Sputum Samples Collected | 0 Participants |
| Healthy Volunteers | The Number of Participants With Blood and Sputum Samples Collected | 14 Participants |