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Wise et al.

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that symptoms and airflow limitation characteristically vary over time and in intensity and may resolve spontaneously or in response to medication. Discussion of chronic airway inflammation is included in all guideline documents. This has been characterized by several important cellular elements including mast cells, eosinophils, T-cells, macrophages, and neutrophils, but none of the guidelines require demonstration of inflammation by invasive or noninvasive methods. The Global Initiative of Asthma guidelines 1744 specify that asthma is usually associated with bronchial hyperresponsiveness but highlight that demonstration of airway hyperresponsiveness and inflammation are not necessary or sufficient to make the diagnosis. Asthma is also classified by severity (ie, mild, moderate, severe) and by persistence (ie, intermittent vs persistent); however, the specific definitions of these categories vary dependent upon the specific guideline. Since asthma is defined as a heterogeneous disease, or rather as a syndrome, there appear to exist significant and variable etiologies that may manifest in similar phenotypes. Consequently, in the last decade, the definition of asthma has sought to include recognizable clusters of clinical and/or pathophysiological characteristics to more accurately characterize endotypes that exist. 1748,1749 X.A.2. Asthma association with allergic and non-allergic rhinitis— Most patients with asthma (both allergic and non-allergic) also have rhinitis, whereas 10% to 40% of patients with AR have comorbid asthma. 101,1167 Asthma and allergy may have similar underlying pathogenesis and immunologic mechanisms. IgE-mediated inflammation can involve both the upper and lower airways, suggesting an integration of the involved areas of the airway. This pattern of similarities gave rise to the concept of the unified airway model, which considers the entire respiratory system to represent a functional unit that consists of the nose, paranasal sinuses, larynx, trachea, and distal lung. 1750 Some, but not all, studies suggest that asthma is more common in patients with moderate-to severe persistent rhinitis than in those with mild rhinitis. 25,1751-1753 Other large studies found a link between the severity and/or control of both diseases in children and adults. 1754-1758 Adults and children with asthma and documented concomitant AR experience more asthma-related hospitalizations and doctors’ visits and also incur higher asthma drug costs than adults with asthma alone 1759-1764 (Table X.A.2). Concerning changes in prevalence of rhinitis and asthma, some studies have demonstrated a parallel increasing prevalence of asthma and rhinitis, 1765,1766 whereas others have not. 1767-1775 It appears that in regions of highest prevalence, the proportion of subjects suffering from asthma or rhinitis may be reaching a plateau. Rhinitis and asthma are closely associated and thus AR should be evaluated in asthmatic patients, and likewise, the possibility of a diagnosis of asthma should be evaluated in patients with AR. • Aggregate Grade of Evidence: C (Level 3b: 7 studies; Table X.A.2).

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X.A.3. Allergic rhinitis as a risk factor for asthma

AR and NAR are risk factors for developing asthma. This has been demonstrated in several large epidemiological studies (Table X.A.3). The Children’s Respiratory Study 597 showed

Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.