Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp Review Combined allergic rhinitis and asthma syndrome (CARAS) Laércia K.D. Paiva Ferreira a , Larissa A.M. Paiva Ferreira a , Talissa M. Monteiro a , Grasiela Costa Bezerra a , Larissa Rodrigues Bernardo b , Marcia Regina Piuvezam a,b, ⁎ a Department of Physiology and Pathology, Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, PB, Brazil b Department of Physiology and Pathology, Graduate Program in Development and Technological Innovation of Medicines, Federal University of Paraíba, João Pessoa, PB, Brazil ARTICLE INFO Keywords: Asthma Rhinitis Allergic syndrome Allergic infammation Disease of the airway ABSTRACT Combined allergic rhinitis and asthma syndrome (CARAS) is a concept of “one airway – one disease” or “unifed airway disease “. The upper and lower airway infammation characterizes allergic rhinitis and asthma, respec- tively and both diseases have shown an intimate connection in their genesis, coexistence and similarities as triggered by the same etiological agents; the same infammatory cell profle and share therapeutic treatment. This review highlights the concept of CARAS by its phenotype, endotype and biomarker classifcation. Indeed, rhinitis is divided into four major phenotypes: allergic rhinitis; infectious rhinitis; non-infective/non-allergic rhinitis and mixed rhinitis. On the other hand, asthma has no common consensus yet; however, the most ac- cepted classifcation is based on the stage of life (early- or late- onset asthma) in which the clinical symptoms are presented. Experimental researches where animals develop a syndrome similar to CARAS have been contributed to better understand the pathogenesis of the syndrome. Therefore, the aim of this review is to clarify current terms related to CARAS as defnition, phenotypes, endotypes/biomarkers, physiopathology and treatments. 1. Introduction The upper and lower airways are classifed as unifed morphological and functional units. The nose, located at the entrance of the upper airway plays a fundamental role of protection for the lungs, acting in the selection of particles inhaled by the inspired air. The heating, fl- tration and humidifcation of the air promotes a cleaning of the air for its entrance to the lungs. In the breathing process most particles with an equivalent aerodynamic diameter (AED) > 15 μm are deposited in the upper respiratory tract. Particles with AED > 2.5 μm are deposited mainly in the trachea and bronchi, whereas those with lower AED pe- netrate the gas exchange region of the lungs. In this context the size and nature of the allergens directly interfere in promoting the immune re- sponse at the site of their deposition, promoting the clinical manifes- tation of the disease [1]. Combined allergic rhinitis and asthma syndrome (CARAS) is char- acterized, nowadays, as a single disease related with upper and lower airway infammation. Allergic rhinitis and asthma have shown an in- timate connection in their genesis, the concept of coexistence and si- milarities such as a. triggered by the same etiological agents; b. have the same infammatory cell profle; c. present in the respiratory system and d. share therapeutic treatment. Experimental researches where animals develop a syndrome similar to CARAS have been contributed to better understand the pathogenesis of the syndrome as well as to de- velop new pharmacological drugs to added to the arsenal therapeutic for the treatment of this allergic syndrome due to some patients have not respond to the conventional therapeutic strategy [2–5]. Therefore, the aim of this review is to clarify current terms related to CARAS as defnition, phenotypes, endotypes and biomarkers, physiopathology and treatments. 2. Characterization and epidemiology of CARAS Rhinitis is a general term that describes the appearance of nasal symptoms as nasal congestion, rhinorrhea, sneezing and pruritus (itching/nasal rubbing), resulting from an infammatory process and/or dysfunction of the nasal mucosa. In addition, it causes sleep defciency, behavioral and psychological changes, leading to compromise patient's quality of life and being considered a risk factor for trafc safety. This illness presents signifcant morbidity by interfering with social life, school and intellectual performance as well as work productivity [2,3,6]. Rhinitis is one of the most common diseases worldwide and it is estimated about 25% of the total world population sufer from allergic rhinitis (AR) [4,5] and, more important, is a risk factor for the https://doi.org/10.1016/j.intimp.2019.105718 Received 18 February 2019; Received in revised form 30 May 2019; Accepted 21 June 2019 ⁎ Corresponding author at: Universidade Federal da Paraíba Campus I, PO 5009, João Pessoa, PB 58–051–970, Brazil. E-mail address: mrpiuvezam@ltf.ufpb.br (M.R. Piuvezam). International Immunopharmacology 74 (2019) 105718 1567-5769/ © 2019 Elsevier B.V. All rights reserved. T