title: Plasma TGF-β₁ in pediatric cystic fibrosis: potential biomarker of lung disease and response to therapy.
abstract: BACKGROUND
  Transforming growth factor beta-1 (TGF-β₁) is an important genetic modifier of lung disease severity in cystic fibrosis (CF), yet the mechanism behind this disease association remains unknown. Initial steps in the investigation of the relationship between TGF-β₁ and CF lung disease include determining the most appropriate available biospecimen for TGF-β₁ protein measurement.
  
  
  OBJECTIVE
  In hospitalized pediatric CF patients, plasma TGF-β₁ is increased in association with clinical parameters of lung disease severity.
  
  
  METHODS
  Serum and plasma were obtained pre- and post-intravenous antibiotic therapy in pediatric CF patients hospitalized for a pulmonary exacerbation. Total TGF-β₁ , measured via ELISA, was compared with markers of lung disease, including airway microbiology, lung function, and response to therapy.
  
  
  RESULTS
  Forty CF children were studied, 15 of whom underwent bronchoalveolar lavage (BAL) at the time of admission. Plasma TGF-β₁ positively correlated with BAL fluid (BALF) TGF-β₁ (r=0.59, P<0.05). Admission plasma TGF-β₁ was increased in subjects positive for Pseudomonas aeruginosa (P=0.014) and was inversely associated with diminished lung function (P<0.038) after therapy. Treatment with antibiotics significantly decreased plasma TGF-β(1) (P<0.001). Serum TGF-β₁ was not associated with plasma TGF-β(1) , BALF TGF-β₁, or these clinical parameters of lung disease.
  
  
  CONCLUSIONS
  In pediatric CF, plasma (but not serum) TGF-β₁ is increased in association with Pseudomonas infection and lung disease, and is reduced in response to therapy. These findings emphasize the importance of optimizing biospecimen selection for future studies investigating the role of TGF-β(1) in CF lung disease.
authors.affiliation: Division of Pulmonology, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, Birmingham, AL 35233-1711, USA. tharris@peds.uab.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Harris
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Muhlebach
authors.forename: Robert A
authors.initials: RA
authors.lastname: Oster
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
authors.forename: J P
authors.initials: JP
authors.lastname: Clancy
authors.forename: Terry L
authors.initials: TL
authors.lastname: Noah
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D018893:Bronchoalveolar Lavage; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012129:Respiratory Function Tests; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D053773:Transforming Growth Factor beta1