Transforming growth factor-β1 in bronchoalveolar lavage fluid from children with cystic fibrosis

Authors

  • William T. Harris MD,

    Corresponding author
    1. Division of Pulmonology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
    • 620 ACC Building, 1600 7th Avenue South, Birmingham, AL 35233-1711.
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  • Marianne S. Muhlebach MD,

    1. Division of Pulmonology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Robert A. Oster PhD,

    1. Division of Preventative Medicine, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, Alabama
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  • Michael R. Knowles MD,

    1. Division of Pulmonary Medicine, Department of Internal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Terry L. Noah MD

    1. Division of Pulmonology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • The authors have no financial conflicts of interest to discuss.

Abstract

Rationale

Transforming factor β1 (TGF-β1) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-β1 protein levels and clinical markers of CF lung disease severity.

Objectives

To determine the association between protein levels of TGF-β1 in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity.

Methods

Total TGF-β1 was measured in BALF from 30 pediatric CF patients and 12 non-CF disease controls undergoing clinically indicated flexible bronchoscopy, and compared to four indicators of clinical disease: infection, inflammation, pulmonary function, and recent/recurrent hospitalization.

Results

TGF-β1 was elevated in CF BALF compared to non-CF controls (135 ± 15 pg/ml vs. 57 ± 10 pg/ml, P < 0.01). In CF BALF, increased TGF-β1 was associated with elevated BALF PMN % (r = 0.67, P < 0.01). BALF TGF-β1 was increased in CF subjects whose FEV1 after the completion of antibiotic therapy remained below CF age-normative median values (205.9 ± 20.5 pg/ml vs. 106.4 ± 24.0, P = 0.01). BALF TGF-β1 was increased in CF children hospitalized in the previous year compared to those not recently hospitalized (169.9 ± 21.6 pg/ml vs. 107.5 ± 17.5 pg/ml, P = 0.04). Neither the presence of a bacterial pathogen nor bacterial quantity was associated with BALF TGF-β1.

Conclusions

In CF, BALF TGF-β1 is elevated compared to non-CF controls. Increased BALF TGF-β1 is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations. Pediatr Pulmonol. 2009; 44:1057–1064. ©2009 Wiley-Liss, Inc.

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