Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!


Asthma is a chronic inflammatory disease of the airways characterized by persistent variable symptoms that include shortness of breath, cough, and wheezing.1 It is the most common chronic lung disease and one of the most prevalent diseases in the United States, affecting more than 20 million adults and 7 million children.2 Attempts to elucidate the cellular and molecular effector pathways that contribute to asthma have led to the realization that it is a protean disease driven by many cell types and mechanisms. This degree of mechanistic variation explains the numerous clinical phenotypes that are now recognized, as well as differences in response to treatment with inhaled therapies and the targeted biologic treatments that have entered the clinic over the last decade.

Core to the pathogenesis of asthma is bronchoconstriction and variable airflow obstruction, airway hyperresponsiveness, and chronic airway inflammation.3 It is, however, the complex interplay between these factors that eventually defines the clinical expression of disease in individual patients. Here, a close examination of the cellular and molecular mediators involved in each of these components will be presented to allow for a more comprehensive understanding of this complex disease.


The inflammatory response in the airways of patients with asthma is complex, heterogenous, and evolves over time, but the prototypical events seen in most patients with asthma (65%–80%) are type 2 (T2) inflammatory responses (Fig. 43-1). T2 inflammation is currently thought of as being driven by both innate and adaptive mechanisms to varying degrees in each individual with asthma, which explains much of the heterogeneity in clinical presentation, biomarkers, and treatment response. The most well-understood T2 pathway is the allergic inflammatory response that is, largely, an adaptive immune response to initial and subsequent exposures to inhaled allergens. While the key cellular and molecular mediators will be described in greater detail later in the chapter, we now describe the evolution of the allergic response. This is the foundation upon which other concepts have been constructed and illustrates the basis for chronic variable changes that occur in the airway in asthma and in the clinical expression of disease.

Figure 43-1

Inflammatory pathways in asthma. The T2 inflammatory pathway with contributions from the adaptive and innate immune response leads to production of T2 cytokines IL-4, IL-5, and IL-13. The non-T2 pathway with activation of TH1 and TH17 cells leads to neutrophil activation. Both inflammatory pathways can lead to asthma symptoms and airway remodeling. TSLP is the target of tezepelumab; IL-5 is the target of reslizumab and mepolizumab; IgE is the target of omalizumab; CRTH2/PGD2 is the target of fevipiprant; IL-4Rα is the target of dupilumab; IL5R is the target of benralizumab. FTH, follicular T helper; ILC2, innate lymphoid cell 2; NKT, natural killer cell; TCR, T cell receptor; TSLP, thymic stromal lymphopoietin; TSLPR, TSKP receptor.

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.