Distinct profile of inflammatory and remodelling biomarkers in sputum of severe asthmatic patients with or without persistent airway obstruction

Silvana Cianchetti; Cristina Cardini; Ilaria Puxeddu; Manuela Latorre; Maria Laura Bartoli; Matteo Bradicich; Federico Dente; Elena Bacci; Alessandro Celi; Pierluigi Paggiaro

doi:10.1016/j.waojou.2019.100078

Distinct profile of inflammatory and remodelling biomarkers in sputum of severe asthmatic patients with or without persistent airway obstruction

World Allergy Organ J. 2019 Dec 9;12(11):100078. doi: 10.1016/j.waojou.2019.100078. eCollection 2019 Nov.

Affiliations

¹ Respiratory Pathophysiology Unit, Department of Surgery, Medicine, Molecular Biology, and Critical Care, University of Pisa, Pisa, Italy.
² Immunology and Allergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Abstract

Background: Both inflammatory and remodelling processes are associated with irreversible airway obstruction observed in severe asthma. Our aim was to characterize a group of severe asthmatic patients with or without persistent airway obstruction in relation to specific sputum inflammatory and remodelling biomarkers.

Methods: Forty-five patients under regular high-dose inhaled corticosteroid/ß-2agonist treatment were studied, after a follow-up period of at least 2 years, with a minimum of 4 visits. Periostin, TGF-ß, RANTES, IL-8, GM-CSF, FGF-2, and cell counts were measured in induced sputum. Serum periostin was also measured.

Results: Sputum induction was successfully performed in all but 5 patients. There were no significant differences in demographic and clinical data between patients with non-persistent obstruction (NO: FEV₁/VC>88%pred.) and those with persistent obstruction (O: a not completely reversible obstruction with FEV₁/VC<88%pred. at each visit before the study visit). Patients with persistent obstruction had significantly higher sputum periostin and TGF-ß concentrations than NO patients and a trend of higher serum periostin levels. GM-CSF and FGF-2 were significantly increased in NO compared to O patients. No differences between groups were found for RANTES, IL-8 and differential cell counts. Sputum periostin inversely correlated with functional parameters (prebronch. FEV₁: rho = -0.36, p < 0.05; postbronch. FEV₁: rho = -0.33, p = 0.05). Patients with high sputum periostin concentration (>103.3 pg/ml: median value) showed an absolute number of sputum eosinophils significantly higher than patients with low sputum periostin; this behavior was unobserved when serum periostin was considered.

Conclusions: Only periostin and TGF-ß identified a subgroup of severe asthmatic patients with persistent airway obstruction. Sputum periostin was also inversely associated with FEV₁ and proved to be a more sensitive biomarker than serum periostin to identify severe asthmatics with higher sputum eosinophilia.

Keywords: Airway inflammation; BMI, body mass index; Biomarkers; FEV1, forced expiratory volume in 1 s; FGF-2, fibroblast growth factor-2; FeNO, fraction of exhaled nitric oxide; GM-CSF, granulocyte-macrophage colony-stimulating factor; ICS, inhaled corticosteroids; IFN, interferon; IL-8, interleukin-8; Induced sputum; LABA, long-acting ß-2agonist; LTRA, leukotriene receptor antagonist; RANTES, regulated on activation, normal T-cells expressed and secreted; Remodelling; Severe asthma; TGF-ß, transforming growth factor-ß-1; VC, vital capacity.