Furthermore, treatment of asthma not only can improve airflow limitations and reduce symptoms but also can modify underlying AHR. These observations have given insight into the factors and mechanisms that affect AHR and, in particular, the role and contribution, if any, of airway inflammation in the variety of processes that determine and possibly direct AHR.
To more fully appreciate the role of inflammation in AHR, it is helpful to identify the components that likely make up AHR, review studies that have used either therapeutic interventions or provocative models to modify AHR, and, from these observations, attempt to gain a more comprehensive view of the complexity of processes, including inflammation, that ultimately determine AHR.
What Are the Components
In studying, discussing, and understanding the components that comprise AHR, it is helpful, and possibly informative, to divide the factors that contribute to AHR into two categories: persistent and variable (Fig 2). Under this concept, which may be an oversimplification of this feature of asthma, the persistent aspects of AHR have been largely attributed to structural changes in the airway, which can include subendothelial thickening, subbasement membrane thickening, smooth muscle hypertrophy, matrix deposition, and altered vascular components (Fig 3). These structural changes are often part of the histopathology found in asthma, particularly in those patients with more severe or longstanding disease; these structural changes alter the architecture of the airways to make them thicker, less compliant, and more narrowed, all features associated with a greater degree of constriction and closure when stimulated by contractile substances. The other component of AHR, the variable aspect, is believed to relate to inflammatory events in the airway, which are variable and influenced by numerous environmental events (ie, allergens, respiratory infections, and treatment). In arbitrarily dividing the components of AHR into these two principal components, it is understood that these processes are interrelated and likely interdependent.