Peripheral blood innate lymphoid cell profiles of patients with COPD reflect their clinical phenotype as identified by cluster analysis

Introduction Chronic obstructive pulmonary disease (COPD) has a heterogeneous clinical and immunological presentation. Although proportions of group 1 innate lymphoid cells (ILC1) in peripheral blood were shown to correlate with COPD severity, no analysis of ILC subsets in relation to clinical outcomes has been performed yet. Our aim was to explore the relationship between clinical phenotype clusters and ILC subsets in COPD.Methods 24 patients with COPD were included in this explorative cross-sectional study. Forced expiratory volume in 1 s (FEV1), diffusion capacity for carbon monoxide, COPD Assessment Test (CAT) and body mass index (BMI) values were collected. Clinical clusters were defined, ILC populations in peripheral blood were quantified and characterised by flow cytometry. Data were analysed using a combination of multiple factor and principal component analysis.Results First, we identified three clinical clusters. C1 (n=12) had low FEV1 and BMI values and the highest disease burden, as determined by CAT. C2 (n=11) comprised older patients with increased BMI and the most pack-years. C3 (n=11) had the highest FEV1 values and fewer exacerbations. Based on leucocyte differentiation and phenotypic characterisation of ILC subsets, two immunological clusters of patients with COPD were identified. C1, the most severe COPD group, was associated with reduced frequencies of circulating ILCs with a potentially inflammatory phenotype.Conclusions The finding that clinical clusters of patients with COPD were strongly associated with peripheral blood immunophenotype and ILC profile suggests a role for ILCs in disease course and may have relevance for the development of personalised therapies.