Open Access Research

Sputum mediator profiling and relationship to airway wall geometry imaging in severe asthma

Dhananjay Desai12, Sumit Gupta12, Salman Siddiqui12, Amisha Singapuri12, William Monteiro12, James Entwisle123, Sudha Visvanathan4, Harsukh Parmar4, Radhika Kajekar4 and Christopher E Brightling12*

Author Affiliations

1 Institute for Lung Health, NIHR Respiratory Biomedical Research Unit, Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, UK

2 Department of Respiratory Medicine University Hospitals of Leicester NHS Trust, Leicester, UK

3 Department of Radiology, Wellington Hospital, Leicester, New Zealand

4 Department of experimental Medicine, Hoffmann-La Roche, Nutley, NJ, USA

For all author emails, please log on.

Respiratory Research 2013, 14:17  doi:10.1186/1465-9921-14-17

Published: 11 February 2013

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.

Keywords:
Asthma; Remodelling; RB1 bronchus