Page 596 - Clinical Immunology_ Principles and Practice ( PDFDrive )

574 ParT FIvE Allergic Diseases

costly of medical afflictions both in terms of total medical reducing inflammation. Immediate relief of bronchoconstriction
expenditure and in time lost from work and school. Asthma is and dyspnea is achieved with bronchodilating agents that activate
a lower respiratory tract disease that is characterized by dyspnea the β 2 adrenergic receptor on airway smooth muscle (β-agonists).
and other symptoms, including cough, chest tightness, chest For long-term control of asthma, the most effective agent class
pain, and wheezing. Persons with mild disease often only have is glucocorticosteroids, which reduce inflammation and suppress
a mild, chronic cough. In contrast to other obstructive lung airway constriction and dyspnea. For mild to moderate disease,
diseases, asthma symptoms are present intermittently and are bronchodilating agents and steroids are typically administered
characteristically relieved by bronchodilator and antiinflammatory by inhalation, which reduces but does not eliminate systemic
therapy. side effects. A secondary class of agents used for controlling
Patients with asthma are classified into distinct clinical subtypes bronchospasm comprises anticholinergics, which are antagonists
according to characteristic environmental or occupational of the muscarinic acetylcholine receptor. Severe disease may also
exposures that elicit disease symptoms, the presence or absence require treatment with steroids, which are given orally or
of concomitant atopy, temporal expression of symptoms, and intravenously for relatively brief periods to minimize the often-
responsiveness to antiinflammatory therapy. Respiratory viruses severe side effects, and high-dose inhaled β-agonists, often given
are the most frequently implicated causes of asthma attacks, by nebulizer.
especially in children, and tobacco smoke and air pollution are Additional antiinflammatory agents available for the treatment
other major inciting agents. A large minority of patients with of asthma include LT receptor antagonists, chromones, theophyl-
asthma have atopy, a term that reflects the production of IgE, a line, omalizumab (a monoclonal antibody [mAb] that reduces
genetic predisposition toward immediate-type immune reactions, circulating and mast cell-bound IgE), and most recently mepo-
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and symptoms on exposure to causative environmental agents, lizumab (an anti–IL-5 antibody). Bronchial thermoplasty (BT)
such as pollens, dust mites, fungi, and insects. If atopy is present, is a relatively new bronchoscopic technique, in which heat is
patients are referred to as having extrinsic, atopic, or allergic applied to the airways via a radiofrequency catheter to ablate
asthma, whereas those without atopy are referred to as having smooth muscle cells. Although early clinical trials have been
intrinsic or nonallergic asthma. In general, airway constriction encouraging with regard to the ability of this technique to reduce
occurs and symptoms of asthma are provoked when triggering exacerbation rates, further studies are required to understand
agents are inhaled from the environment, representing the clinical the patient subgroups that are most likely to respond to these
expression of airway hyperresponsiveness (AHR)—the exaggerated novel treatments. 13
tendency of the asthmatic airway to constrict in response to
exposure to a wide variety of provocative agents. Some of these OTHER AIRWAY ALLERGIC DISEASE SYNDROMES
agents, such as viruses and pollens, are only intermittently present,
causing seasonal asthma, whereas other agents are encountered In addition to the common allergic disorders discussed above,
continuously (e.g., fungi) and cause persistent (or perennial) several other allergic airway diseases have been described:
asthma. Occupational asthma is defined as asthma acquired in although not as common, these often cause profound morbid-
the workplace, where dozens of potentially toxic agents have ity. As with asthma, these disorders are clinically heterogeneous
been identified (Chapter 49). Numerous additional clinical subsets but are believed to share a similar pathophysiology related to
of asthma can be defined according to the factor or factors that the inhalation of antigens that provoke airway eosinophil and
most often elicit attacks of dyspnea. A final category of asthma, Th2 responses. No single clinical, pathological, or radiographic
steroid-resistant asthma, refers to the condition in patients who feature is pathognomonic for these diseases, and diagnosis relies
are relatively unresponsive to antiinflammatory steroid therapy. on a constellation of findings, especially antigen exposures,
radiographic details, and histopathology. Nonetheless, all of these
Diagnosis disorders are prominently linked by the presence of eosinophils
Asthma is often recognized on clinical grounds alone, with in peripheral blood and airway tissues.
acute attacks marked by obvious dyspnea, wheezing, cough, and Under the trophic influence of IL-5, eosinophils develop from
use of accessory muscles of respiration. Such attacks typically precursor cells present largely in bone marrow. Early mature
resolve with bronchodilator therapy. Spirometry can provide eosinophils are then released into blood, where they circulate
more objective evidence of airway obstruction as assessed by for a brief period before entering the interstitium of airway
reversible decrements in the forced expiratory volume per tissues, where they can reside for long periods. Chemotactic
second (FEV 1 ) and other measures of air flow. Nonetheless, a factors that enhance the extravasation of eosinophils include
uniformly acceptable disease definition has remained elusive, complement components, eosinophil chemotactic factor-A, LTs,
at least partly because of the nonspecific nature of symptoms tumor-associated factors, and chemokines. Putative functions
and a clinical spectrum that blends with many other disease of tissue resident eosinophils range from host defense against
processes. When the clinical presentation is uncertain, bronchial parasites, such as nematode helminths, in diseases, such as tropical
provocation tests can be used to determine the presence of AHR pulmonary eosinophilia, to mediators of end-stage tissue destruc-
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and thereby establish the diagnosis. Additional laboratory data tion and irreversible lung damage and fibrosis in other disorders,
that support a diagnosis of allergic asthma include peripheral such as acute and chronic eosinophilic pneumonia.
blood eosinophilia, elevated serum total and antigen-specific IgE The eosinophilic disorders discussed below are organized
levels, and positive skin prick test results against one or more according to whether there is an extrinsic or intrinsic cause of
allergens. the eosinophilia (Table 41.1). Inhaled or ingested extrinsic factors,
including medications and infectious agents (e.g., parasites, fungi,
Therapy mycobacteria), can trigger an eosinophilic immune response.
As with AR and RS, the therapy of asthma is generally nonspecific This may be mild and self-limiting, as in Loeffler syndrome.
and directed at improving air flow through bronchodilation and Intrinsic pulmonary eosinophilic syndromes are, by definition,