Inflammatory Cellular Patterns in Asthma

Airway inflammation, sustained by a multitude of pro-inflammatory mediators such as cytokines and chemokines produced by both immune-inflammatory and airway structural cells, is a hallmark of asthma [1, 2]. Several inflammatory phenotypes of asthma have been characterized, which include eosinophilic, neutrophilic, mixed and paucigranulocytic patterns [3, 4]. Eosinophils are the inflammatory cells most frequently infiltrating the airways of asthmatic patients; indeed, their maturation, activation, survival and recruitment within the bronchial wall and airway lumen are crucially implicated in the development of both allergic and non-allergic asthma [5, 6]. Eosinophilic asthma originates from the activation of immunopathologic and pro-inflammatory pathways, mainly coordinated by T-helper 2 (Th2) lymphocytes, which release interleukin-5, interleukin-4 and interleukin-13 (IL-5, IL-4 and IL-13) (Fig. 2.1). In addition to being driven by adaptive immune responses, airway eosinophilia can also arise from innate immune mechanisms, which are mediated by intercellular communications involving dendritic cells, bronchial epithelial cells and innate lymphoid cells [7, 8]. Whilst bronchial eosinophilic infiltration is mostly responsible for mild-to-moderate asthma, more severe disease is often characterized by mixed patterns of inflammation including both eosinophils and neutrophils, with the latter which can represent the predominant inflammatory cells detectable in the induced sputum obtained from patients experiencing uncontrolled asthmatic symptoms and exacerbations. Neutrophilic airway inflammation, associated with severe asthma, is triggered by Th1 and especially Th17 lymphocytes (Fig. 2.1) [9, 10]. Within this pathobiologic context, a pivotal role is played by dendritic cells, which direct the commitment to the various Th lineages. In particular, polarization towards the different Th subsets is closely linked to the particular airway milieu consisting of specific co-stimulatory molecules and cytokines, which drive the various Th cell programmes [11].