title: Sputum mediator profiling and relationship to airway wall geometry imaging in severe asthma.
abstract: BACKGROUND
  Severe asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts.
  
  
  METHODS
  In a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses.
  
  
  RESULTS
  Independent of airway geometry, sputum MMP9 and IL-1β were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing.
  
  
  CONCLUSIONS
  We have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation.
authors: Institute for Lung Health, NIHR Respiratory Biomedical Research Unit, Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, UK.
authors: Dhananjay
authors: D
authors: Desai
authors: Sumit
authors: S
authors: Gupta
authors: Salman
authors: S
authors: Siddiqui
authors: Amisha
authors: A
authors: Singapuri
authors: William
authors: W
authors: Monteiro
authors: James
authors: J
authors: Entwisle
authors: Sudha
authors: S
authors: Visvanathan
authors: Harsukh
authors: H
authors: Parmar
authors: Radhika
authors: R
authors: Kajekar
authors: Christopher E
authors: CE
authors: Brightling
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D001249:Asthma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D054413:Chemokine CCL11 / Q000032:analysis; D003430:Cross-Sectional Studies; D004739:England; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D053582:Interleukin-1alpha / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000000981:diagnostic imaging* / Q000276:immunology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013183:Sputum / Q000276:immunology*; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
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