T2-High Endotype and Response to Biological Treatments in Patients with <i>Bronchiectasis</i>
Martina Oriano,
Andrea Gramegna,
Francesco Amati,
Alice D’Adda,
Michele Gaffuri,
Marco Contoli,
Francesco Bindo,
Edoardo Simonetta,
Carlotta Di Francesco,
Martina Santambrogio,
Giovanni Sotgiu,
Francesco Blasi,
Stefano Aliberti
Affiliations
Martina Oriano
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Andrea Gramegna
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Francesco Amati
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy
Alice D’Adda
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Michele Gaffuri
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Department of Otolaryngology and Head and Neck Surgery, 20122 Milan, Italy
Marco Contoli
Respiratory Unit, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
Francesco Bindo
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Edoardo Simonetta
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Carlotta Di Francesco
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Martina Santambrogio
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Giovanni Sotgiu
Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Francesco Blasi
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, 20122 Milan, Italy
Stefano Aliberti
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy
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.
