RATIONALE: Transforming factor beta(1) (TGF-beta(1)) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-beta(1) protein levels and clinical markers of CF lung disease severity. OBJECTIVES: To determine the association between protein levels of TGF-beta(1) in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity. METHODS: Total TGF-beta(1) 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-beta(1) 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-beta(1) was associated with elevated BALF PMN % (r = 0.67, P < 0.01). BALF TGF-beta(1) was increased in CF subjects whose FEV(1) 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-beta(1) 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-beta(1). CONCLUSIONS: In CF, BALF TGF-beta(1) is elevated compared to non-CF controls. Increased BALF TGF-beta(1) is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations.
RATIONALE: Transforming factor beta(1) (TGF-beta(1)) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-beta(1) protein levels and clinical markers of CF lung disease severity. OBJECTIVES: To determine the association between protein levels of TGF-beta(1) in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity. METHODS: Total TGF-beta(1) 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-beta(1) 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-beta(1) was associated with elevated BALF PMN % (r = 0.67, P < 0.01). BALF TGF-beta(1) was increased in CF subjects whose FEV(1) 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-beta(1) 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-beta(1). CONCLUSIONS: In CF, BALF TGF-beta(1) is elevated compared to non-CF controls. Increased BALF TGF-beta(1) is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations.
Authors: Michael D Kim; Nathalie Baumlin; Makoto Yoshida; Deepika Polineni; Sebastian F Salathe; Joseph K David; Charles A Peloquin; Adam Wanner; John S Dennis; Juliette Sailland; Philip Whitney; Frank T Horrigan; Juan R Sabater; William M Abraham; Matthias Salathe Journal: Am J Respir Crit Care Med Date: 2020-02-01 Impact factor: 21.405
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Authors: Jocelyn R Grunwell; Samantha M Yeligar; Susan Stephenson; Xiao Du Ping; Theresa W Gauthier; Anne M Fitzpatrick; Lou Ann S Brown Journal: J Immunol Date: 2018-02-02 Impact factor: 5.422
Authors: Elizabeth L Kramer; William D Hardie; Satish K Madala; Cynthia Davidson; John P Clancy Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-06-07 Impact factor: 5.464
Authors: William T Harris; J Todd Boyd; Gary L McPhail; Alan S Brody; Rhonda D Szczesniak; Leslie L Korbee; Michael L Baker; John P Clancy Journal: Ann Am Thorac Soc Date: 2016-12