The purpose of this study is to determine whether IL-17 polymorphonuclear leukocytes (PMNs) are central to the disease pathology in CF. This will be determined by demonstrating that IL-17 PMNs are present in the CF airway, correlate with lung function measures, and decrease in patients being treated with IV antibiotics for a pulmonary exacerbation.
Description: In the Exacerbation/IV Antibiotics Cohort--Subjects will serve as their own controls. The percentage of neutrophils (in sputum) positive for IL-17 was determined by flow cytometry for each subject at the beginning and end of treatment for a pulmonary exacerbation. Sputum IL-17 neutrophil counts will be compared to the change in lung function (FEV1) as determined by spirometry (American Thoracic Society standards).
Measure: Change in Sputum IL-17 Neutrophils Time: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbationDescription: In the Clinically Stable Cohort--Measurement of sputum inflammatory mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and neutrophil elastase
Measure: Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and Neutrophil Elastase Time: Samples will be obtained at one outpatient clinic visit during the next calendar yearDescription: In the Exacerbation/IV Antibiotics Cohort--Measurement of sputum inflammatory mediators by multiplex assay for IL-1β, IL-6, IL-8, and IL-17A. Neutrophil elastase determined by colorimetric assay. Measurements at the beginning of IV antibiotic treatment and after 2 weeks antibiotic treatment for a pulmonary exacerbation
Measure: Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase Time: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbationCase-Only
There is one SNP
Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Fibrosis Inflammation Cystic Fibrosis Pneumonia This study consists of two parts which will be conducted in parallel. --- G551D ---
Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Fibrosis Inflammation Cystic Fibrosis Pneumonia This study consists of two parts which will be conducted in parallel. --- G551D --- --- G551D ---
Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Fibrosis Inflammation Cystic Fibrosis Pneumonia This study consists of two parts which will be conducted in parallel. --- G551D --- --- G551D --- --- G551D ---
Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Fibrosis Inflammation Cystic Fibrosis Pneumonia This study consists of two parts which will be conducted in parallel. --- G551D --- --- G551D --- --- G551D --- --- G551D ---