nasal epithelial cells/blood lymphocyte markers for cystic fibrosis (cf)/cf pulmonary exacerbations

Conditions: Cystic Fibrosis

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.

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.

Eligibility 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 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

Keywords: anatomy cells epithelial cells blood cells cystic fibrosis equipment and supplies disposable equipment reagent kits