Chapter 1 Chapter 1
Chapter 1
DEFINITION, DIAGNOSIS, AND CLASSIFICATION
DEFINITION
Few aspects of asthma generate more discussion and disagreement than its definition. Previous attempts to define asthma in terms of airflow obstruction, its reversibility, and bronchial hyperresponsiveness have fallen short because of a lack of understanding of the disease mechanism(s).
Clinicians have long recognized an association of sputum and blood eosinophilia with asthma, and the presence of widespread airway inflammation as a prominent feature of death from asthma; but until recently there has been difficulty relating these pathological features to clinical and physiological indices of the disease. The application of fiberoptic bronchoscopy to obtain mucosal lavage and biopsy samples has provided an opportunity to study the local inflammatory events of adult and childhood asthma. In allergic, late onset, and toluene diisocyanate (TDI) occupational asthma, there is ample evidence for mast cells and eosinophils being effector cells through their capacity to secrete a range of inflammatory mediators. T-lymphocytes and macrophages are important in orchestrating this immune reaction through the elaboration of specific cytokines, and neural mechanisms serve to amplify the inflammatory response. Although there is no direct measure of airway inflammation that can be used routinely, the degree of airway narrowing and its variability assessed by peak expiratory flow (PEF) monitoring may be used as functional correlates.
Longitudinal studies in asthma, particularly of patients with poorly controlled disease, have demonstrated the progressive acquisition of a "fixed" element to the airways obstruction superimposed on the reversible component. The presence of a bronchodilator-insensitive increased peripheral airflow resistance in asthma might have a similar mechanism. Organization of the inflammatory exudate and deposition of interstitiaI collagen provides one explanation for these findings.
These different perspectives of asthma can be drawn together into an operational definition:
Asthma is a chronic inflammatory disorder of the airways in which many cells play a role, including mast cells and eosinophils. In susceptible individuals this inflammation causes symptoms which are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment, and causes an associated increase in airway responsiveness to a variety of stimuli.
Although the diagnosis of asthma can be elusive, the clinical history usually provides the necessary clues. The most common symptoms-wheezing, breathlessness, chest tightness, cough, and sputum-in themselves are not diagnostic. What is important is a history of recurrent exacerbations (or attacks) often provoked by exogenous factors such as allergens, irritants, exercise, and virus infections. Nocturnal (including early morning) asthma symptoms are particularly characteristic.
Because asthma symptoms are characteristically episodic, the physical examination may be completely normal. The examination may also be normal when the patient is symptomatic. Further, asthma patients frequently have poor recognition of symptoms and poor perception of the severity of their disease. Thus, objective measures of airflow obstruction and its variability are critical in establishing a diagnosis.
Demonstrating allergen-specific IgE by skin testing and/or demonstrating specific IgE antibodies in the serum can help categorize asthma, but these tests have low diagnostic precision since more than 30 percent of the population is atopic. However, these tests are of particular value when attempting to confirm a single causative allergen for the purposes of undertaking avoidance strategies for the asthma therapy. Deliberate provocation of the airways with a suspected sensitizing agent may be helpful in establishing causation especially in the occupational setting, but it is not recommended for routine use largely on the grounds of safety. Evidence for airway inflammation may be sought by examining spontaneously produced or hypertonic saline-induced sputum for eosinophils and metachromatic staining cells. Direct investigative methods, which include fiberoptic bronchoscopy with brushings, lavage, and mucosal biopsies, can be useful in children and adults but should only be used in exceptional circumstances such as research protocols.
Classification Based on Etiology
Asthma may be described either in etiological terms or in accordance with the clinical pattern and severity of airflow obstruction. This classification may help the clinician in the diagnosis and treatment of the disease and give an indication of prognosis.
From mechanistic and therapeutic standpoints, it is appropriate to differentiate those factors that induce inflammation with associated airway narrowing and hyperresponsiveness (inducers) from those that precipitate acute constriction in susceptible individuals (inciters). There have been many attempts to classify asthma according to etiology, particularly with regard to environmental sensitizing agents. Such a classification is severely hampered by the existence of a group of patients in whom no environmental cause can be identified, and these have traditionally been described as having intrinsic (cryptogenic) asthma. Conversely, patients extrinsic asthma include those whose symptoms are associated with atopy, a genetic predisposition for directing an IgE mast cell and eosinophil response to common environmental allergens. Sensitization of the airways to a single agent involving IgE or non-IgE mechanisms underlies occupational asthma. The recent associations found between serum IgE and indices of asthma in all age group-including individuals who are "not atopic"-raises the possibility that all forms of this disease relate to a mucosal inflammatory response to environmental or endogenous antigens.
Asthma in infancy and early childhood is particularly difficult to categorize because under the age of 5 year it is recognized on purely clinical grounds. Clinicians are being discouraged from using such terms as wheezy bronchitis, wheezy baby syndrome, or recurrent bronchiolitis; the clinician should make the appropriate diagnosis and use the correct term of asthma in order to encourage the implementation of antiasthma strategies.
Classification Based on Severity and Pattern of Airflow Obstruction
When decisions have to be made about treatment, the pattern and severity of airflow obstruction are important. A classification of a patient's asthma based on disease severity over the preceding year has been shown to relate to pathological indices of airway inflammation. Other classifications describe asthma in terms of patterns of airflow obstruction monitored by PEF recording. Descriptions of levels of disease severity based on a combination of such clinical criteria as symptoms and treatment requirements as well as objective measurements differ little among countries that have developed asthma management guidelines (see Chapter 5, Resources). A modified classification scheme is presented in figure i, studies to validate this scheme will be important. These descriptions of asthma severity are useful because asthma therapy has a stepwise approach in which the level of therapy is increased as the severity of the disease increases (see Chapter 2, Six-Part Asthma Management Program).
The severity of an exacerbation of acute severe asthma is often underestimated by patients, their relatives, and their physicians. This is largely because of failure to use objective measurements of assessment. If acute severe asthma is not recognized and not treated appropriately such exacerbations can be fatal. It is important to recognize that it is possible for any patient with asthma, however mild on a chronic basis, to have an acutely severe asthma exacerbation. However, factors have been identified that are associated with a higher risk of asthma mortality. These include a previous history of acute life-threatening attacks, hospitalization within the previous year, psychosocial problems, a history of intubation for asthma, recent reductions or cessation of corticosteroids, and noncompliance with recommended medical therapy. Populations who are low income, medically underserved, live in the inner city, or who have cultural differences are at especially high risk. Deaths usually occur because of failure to appreciate the severity of the exacerbation and to initiate appropriate emergency treatment that includes the early introduction of corticosteroids.