Mixed Th2 and non-Th2 inflammatory pattern in the asthma–COPD overlap: a network approach

Abstract

Luis Pérez de Llano,1,* Borja G Cosío,2,3,* Amanda Iglesias,3 Natividad de las Cuevas,4 Juan Jose Soler-Cataluña,3,5 Jose Luis Izquierdo,6 Jose Luis López-Campos,3,7 Carmen Calero,7 Vicente Plaza,3,8–10 Marc Miravitlles,3,11 Alfons Torrego,8–10 Eva Martinez-Moragon,12 Joan B Soriano,13 Antolin Lopez Viña,14 Irina Bobolea15 On behalf of the CHACOS Study Group 1Department of Respiratory Medicine, Hospital Lucus Augusti, Lugo, Spain; 2Department of Respiratory Medicine, Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Spain; 3CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; 4Department of Allergy, Hospital 12 de Octubre, Madrid, Spain; 5Department of Respiratory Medicine, Hospital Arnau de Vilanova, Valencia, Spain; 6Department of Respiratory Medicine, Hospital Universitario de Guadalajara, Guadalajara, Spain; 7Department of Respiratory Medicine, Hospital Virgen del Rocío, Sevilla, Spain; 8Department of Respiratory Medicine, Hospital de la Santa Creu y Sant Pau, Barcelona, Spain; 9Institut d’Investigació Biomédica Sant Pau, IIB Sant Pau, Barcelona, Spain; 10Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 11Department of Respiratory Medicine, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 12Department of Respiratory Medicine, Hospital Dr Peset, Valencia, Spain; 13Instituto de Investigación Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain; 14Department of Respiratory Medicine, Hospital Puerta de Hierro, Madrid, Spain; 15Servei de Pneumologia i Alergia, Hospital Clinic, Barcelona, Spain *These authors contributed equally to this work Introduction: The asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO. Objectives: We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO. Methods: This is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity <0.70 recruited from outpatient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO. ACO was defined by a history of smoking >10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis. Results: In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61–3.57] vs 1.11 [0.12–2.42] pg/mL, respectively; p=0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61–13.12] vs 7.03 [4.69–10.44] pg/mL, respectively; p<0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions. Conclusion: Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions. Keywords: asthma mechanisms, COPD mechanisms, inflammatory cytokines, overlap, network analysis, IL-13

Keywords

• asthma mechanisms
• COPD mechanisms
• inflammatory cytokines