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Asthma—A Heterogeneous Disease

Asthma is a chronic inflammatory disorder of the airways characterized by marked variability in airflow obstruction that is often reversible, either spontaneously or with treatment.1 This inflammation presents clinically in susceptible patients with recurrent symptoms of wheezing, chest tightness, cough, and, occasionally, dyspnea and contributes to the heightened airway hyperresponsiveness to specific and nonspecific stimuli; a pathognomonic feature of asthma. Increased airway hyperresponsiveness manifests in patients as intolerance to smoke, dust, air pollution, and strong odors, where exposure to such agents in healthy individuals does not induce such symptoms. Asthma is not a single disease entity with a unique pathogenesis, but rather recognized to be a clinical syndrome and heterogeneous disease;2 that is, asthma comprises multiple endotypes that manifest common symptoms, but have distinct and probably different pathophysiologic and etiologic mechanisms with an interplay between genetic and environmental factors. This phenotypic heterogeneity in the expression of asthma is multidimensional and includes variability in pathologic, clinical, and physiologic parameters among different patients.3 Recent attention has directed focus on traits that are identifiable and treatable in patients with asthma, such as persistently elevated blood eosinophils, in order to achieve precision treatment with the hope of better patient outcomes.4

Risk Factors for Asthma 

Several risk factors for asthma are considered below.

Atopy and Allergens

The most important factor predisposing to asthma is atopy (Table 46-1). Asthma has been classified as atopic (extrinsic) or nonatopic (intrinsic) depending on the suspected role of allergens as etiologic factors. Atopic asthma involves an exaggerated immune response characterized by immunoglobulin E (Ig-E) activation and mast cell degradation. Atopy can be clinically elicited with a positive skin prick test or specific antibodies to IgE in serum against common aeroallergens such as house dust mite, grass and tree pollens, cat and dog fur, rodents (in laboratory workers), and cockroaches (in inner city populations). House dust mite is recognized as a significant cause of asthma throughout the developed world, although the relative importance of different indoor allergens may vary among populations. Patients with atopic asthma commonly suffer from other atopic diseases, including allergic rhinitis that may be seasonal (hayfever), and may be found in over 80% of asthmatic patients; allergic conjunctivitis; and atopic dermatitis (eczema). Nonatopic asthmatic patients (approximately 10%) have a negative skin prick test, normal serum IgE concentrations, and usually show later onset of disease (adult-onset asthma). In this group, their asthma is more severe, persistent, there is more sensitivity to aspirin and commonly they have concomitant nasal polyps. This classification, although appropriate from a pathologic perspective, does not readily help clinicians as it does not aid in establishing an etiologic diagnosis ...

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