Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients.
BACKGROUND
Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)-assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms.


OBJECTIVE
The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes.


METHODS
Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes.


RESULTS
Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm(3) [SD, 112.6 mm(3)], 259.0 mm(3) [SD, 53.3 mm(3)], 366.4 mm(3) [SD, 195.3 mm(3)], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects.


CONCLUSIONS
Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies.
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom; Radiology Department, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom. Electronic address: drsumitgupta@yahoo.com.
Sumit
S
Gupta
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Ruth
R
Hartley
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Umair T
UT
Khan
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Amisha
A
Singapuri
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Beverly
B
Hargadon
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
William
W
Monteiro
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Ian D
ID
Pavord
Respiratory Therapy Unit, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
Ana R
AR
Sousa
Respiratory Therapy Unit, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
Richard P
RP
Marshall
Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom.
Deepak
D
Subramanian
Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom.
David
D
Parr
Radiology Department, Wellington Hospital, Capital and Coast District Health Board, Wellington, New Zealand.
James J
JJ
Entwisle
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Salman
S
Siddiqui
Radiology Department, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
Vimal
V
Raj
Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Christopher E
CE
Brightling
D000328:Adult; D000368:Aged; D056151:Airway Remodeling; D001249:Asthma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014057:Tomography, X-Ray Computed / Q000379:methods*
Asthma; CT; airway remodeling; cluster analysis; distal airway; fractal analysis; phenotypes; quantitative imaging