T2-High Endotype and Response to Biological Treatments in Patients with Bronchiectasis

Abstract

Although bronchiectasis pathophysiology has been historically understood around the presence of airway neutrophilic inflammation, recent experiences are consistent with the identification of a type 2 inflammation (T2) high endotype in bronchiectasis. In order to evaluate prevalence and clinical characteristics of bronchiectasis patients with a T2-high endotype and explore their response to biologicals, two studies were carried out. In a cross-sectional study, bronchiectasis adults without asthma underwent clinical, radiological, and microbiological assessment, along with blood eosinophils and oral fractional exhaled nitric oxide (FeNO) evaluation, during stable state. Prevalence and characteristics of patients with a T2- high endotype (defined by the presence of either eosinophils blood count ≥300 cells·µL−1 or oral FeNO ≥ 25 dpp) were reported. A case series of severe asthmatic patients with concomitant bronchiectasis treated with either mepolizumab or benralizumab was evaluated, and patients’ clinical data pre- and post-treatment were analyzed up to 2 years of follow up. Among bronchiectasis patients without asthma enrolled in the cross-sectional study, a T2-high endotype was present in 31% of them. These patients exhibited a more severe disease, high dyspnea severity, low respiratory function, and high impact on quality of life. Among the five patients with severe eosinophilic asthma and concomitant bronchiectasis included in the series, treatment with either mepolizumab or benralizumab significantly reduced the exacerbation rate with an effect that persists for up to 2 years of follow up. If validated across different settings, our data suggest the need to design randomized controlled trials on biological treatments targeting the T2-high endotype in bronchiectasis patients.

Bronchiectasis enters the inflammation era

“…Oriano et al extended these observations by also incorporating measurement of FeNO showing that a Th2‐high endotype of BE was present in 31% of patients when considering a high eosinophil count (>300 cells/μl) and a raised FeNO ≥25 dpp. Patients with T2‐high inflammation had more severe disease and worse symptoms 4 . These studies demonstrate that BE is not exclusively a neutrophilic disease.…”

“…Patients with T2-high inflammation had more severe disease and worse symptoms. 4 These studies demonstrate that BE is not exclusively a neutrophilic disease. Eosinophilic inflammation may contribute to a subset of BE exacerbations and biomarkers may be useful to target anti-eosinophil strategies such as inhaled corticosteroids or anti-IL5 therapies in future.…”

“…2 BE is a heterogeneous disease and although neutrophilic inflammation and infection represent the most common 'endotype', clinical experience and clinical trial results suggest that there are other important contributors to disease burden and exacerbation. 3,4 Eosinophils are well-established drivers of exacerbation in asthma and chronic obstructive pulmonary disease, but until recently their role in BE was not established. Shoemark et al recently reported the results of a pan-European cohort of 1007 patients with BE.…”

CXC Chemokines in the Pathogenesis of Pulmonary Disease and Pharmacological Relevance

“…Bronchiectasis is characterized by an atrocious cycle of infection, inflammation, and tissue damage [ 100 ]. The pathophysiology of bronchiectasis centers on the development of neutrophilic inflammation in the airways [ 101 ], as well as CD4+ T cells and CD68+ macrophage infiltration [ 102 ]. CXCL-8 levels were discovered to be high in both CF and non-CF bronchiectasis and comparable to COPD in neutrophilic bronchiectasis [ 103 , 104 ].…”

Precision medicine in bronchiectasis

“…Eosinophilic inflammation is increasingly recognised and can be identified using peripheral blood eosinophil counts, as has been described for COPD and asthma [ 25 , 26 ]. To date, small studies suggest that around 20% of bronchiectasis patients, excluding those with underlying asthma, have eosinophilic inflammation [ 27 – 29 ]. Although the literature on the importance of eosinophils in bronchiectasis is limited, ABPA stands as a clear example of how Type 2 inflammation can contribute to both the development of bronchiectasis and exacerbations.…”