Asthma affects more than 15 million adults in the United States. The incidence of asthma has risen in the past few decades. It is a significant health concern and a tremendous economic burden in modern societies. In this chapter we discuss the etiologies and pathogenesis of asthma. We also describe the current concepts and guidelines of asthma intervention and treatment.
It is estimated that 20.3 million Americans had asthma in 2001. The incidence has increased by about 60% in the past decade, not only in the United States but worldwide (Table Asthma Epidemiology: United States, 2001).From 1999 to 2001, the lifetime prevalence rate of asthma increased 27%. The asthma attack rate increased 12% during the same period of time. On the other hand, the number of deaths and hospitalizations resulting from asthma has decreased slightly in recent years. Asthma was estimated to cost approx $14 billion in 2002. It accounts for approx 14.5 million lost workdays annually.
Table Asthma Epidemiology: United States, 2001
|31.3 million lifetime prevalence|
|20.3 million current sufferers|
|15.1 million adults (7.1%) with current asthma|
|465,000 hospitalizations (year 2000)|
|14.5 million lost workdays|
|1.8 million emergency visits|
|~5000 deaths per year (14 people per day)|
|$14 billion costs|
The word asthma was derived from the Greek word for panting, or breathlessness, and thus might be considered a description of the primary symptom of this disease. Asthma can be defined clinically as recurrent airflow obstruction causing intermittent wheezing, breathlessness, chest tightness, and sometimes cough with sputum production. The National Asthma Education Panel, developed in conjunction with the National Heart, Lung and Blood Institute, defined asthma as having three components:
1. Airflow obstruction that is reversible (or nearly completely so), either spontaneously or in response to therapy
2. Airway inflammation
3. Increased airway responsiveness to a variety of stimuli
Causes of bronchial asthma
About 90% of asthmatics between the ages of 2 and 16 yr are allergic, 70% less than 30 yr are allergic, and about 50% of patients older than 30 yr are concomitantly allergic (Table Conditions That Cause and Worsen Asthma). Thus, coincidental allergies are far and away the most common underlying condition associated with the development of asthma. One should suspect allergy as a contributing factor when (1) there is a family history of allergic diseases, (2) the clinical presentation includes seasonal exacerbations or exacerbations related to exposures to recognized allergens, (3) there is concomitant allergic rhinitis or other allergic disease, (4) a slight-to-moderate eosinophilia is present (300-1000/mm3) or eosinophilia in the sputum is observed, or (5) the patient is less than 40 yr old.
Skin testing can be used to confirm immunoglobulin (immunoglobulin)E directed against incriminated allergens but does not establish a cause-and-effect relationship. Thus, patients may have a positive skin test but not have clinical symptoms of allergy or asthma when exposed to the incriminated allergen. Thus, skin testing (or radioallergosorbent test [radioallergosorbent]) is only used to confirm the history and physical examination that suggest allergy. Levels of total immunoglobulin E are of limited usefulness; only about 60% of allergic asthmatic subjects have elevated immunoglobulin E levels.
Because limiting exposure to allergens and allergy immunotherapy are both specifically helpful in treating allergic asthmatic subjects, a careful search for possible allergies is indicated innearly all asthmatics. Current recommendations are that all asthmatics who wheeze more than 2 d per week should be evaluated by an allergist or other physician skilled in identifying allergic disease in order to institute prophylactic allergen-avoidance measures.
Table Conditions That Cause and Worsen Asthma
|Conditions that cause asthma:|
|Allergic bronchopulmonary aspergillosis|
|Upper respiratory tract infections|
|Industrial-occupational or environmental exposure|
|Chemical or drug ingestion|
|Aspirin or other nonsteroidal anti-inflammatory drugs|
|Vasculitis (Churg and Straus allergic granulomatosis)|
|Conditions that may worsen asthma:|
It was once thought that allergic asthma was associated with a milder form of disease, but this contention has not been borne out. Allergic asthma is as severe as any other cause of asthma. Onset of asthma between the ages of 2 yr and puberty generally has a good prognosis, whereas asthma appearing before age 2 may be of a more severe nature. Moreover, childhood asthma was once considered a transient disease, which might be “outgrown.”
This philosophy is a serious error in judgment for many reasons, including the availability of excellent effective treatment plans, the impairment of body image that an asthmatic child may develop, which lasts throughout life, the long-range effects of restricted physical activity on mental and physical health, and the loss of school and recreation time because of a treatable problem. Current recommendations include conditioning of the asthmatic to better prepare him for strenuous exercise, selecting swimming or biking in place of running as an exercise of choice, and using prophylactic medications to prevent exercise-related airflow obstruction.
Mast Cells and Asthma
The essential components of allergic reactions include allergens, immunoglobulin E antibodies directed at antigenic determinants on the allergen, and activated mast cells, which generate and release mediators and cytokines. In order to initiate allergic responses, exposure to an appropriate antigen and a genetically determined capacity to respond with immunoglobulin E production are required. Antigen presentation requires access of antigens to the mucous membrane, uptake by antigen-presenting cells, antigen processing, and stimulation of local antibody production. immunoglobulin E production occurs in the same local environment as antigen presentation, probably in the draining lymph nodes.
Immunoglobulin E production is regulated by locally produced helper factors, thought to include cytokines produced by local TH2 helper cells. The immunoglobulin E produced sensitizes mast cells in the same environment by binding to high-affinity receptors for immunoglobulin E on the cell surface. Although no one is certain of the precise time involved, the production of sufficient immunoglobulin E to render a subject allergic is thought to take several years or more. However, children less than 1 yr old with unquestionable allergic diseases are not uncommon.
Once sensitized, mast cells may degranulate upon subsequent allergen exposure. The bridging of immunoglobulin E receptors by aggregation of immunoglobulin E molecules bound to multivalent allergens initiates a biochemical reaction, which leads to the secretion of a range of chemical mediators from mast cells. These mediators then stimulate the surrounding tissues to elicit the allergic response.
In humans, the mast cell is found in the loose connective tissues of all organs, most notably around blood vessels, nerves, and lymphatics. Mast cells in the lung are found beneath the basement membranes of airways, near blood vessels in the submucosa, adjacent to submucosa glands, scattered throughout the muscle bundles, in the intra-alveolar septa, and in the bronchial lumen. Mast cells appear in increased numbers in the epithelium after allergen exposure and are predominant in biopsies obtained during the allergy season. In the airways, there are about 20,000 mast cells/mm3, and the mast cells represent 1-2% of alveolar cells.
Mediators of Anaphylaxis
Three categories of mediators are released during the process of mast cell degranula-tion: preformed soluble molecules stored within the cytoplasmic granules, newly formed lipid mediators, and cytokines. The consequences of mediator release occur within minutes (immediate hypersensitivity) or take hours to develop (late-phase allergic reactions). Research has revealed an expanding list of mediators whose actions may contribute to the pathological changes seen in asthma .
In addition to the granule-derived mediators, the process of degranulation leads to transcription, synthesis, and secretion of potent cytokines over several hours, which likely contribute to the late-phase allergic response. Thus, mast cells synthesize and release interleukin (IL)-3, IL-4, IL-5, and IL-6 in addition to tumor necrosis factor and other inflammatory cytokines. IL-4 helps regulate immunoglobulin E production and mast cell activation, and release of IL-4 might actually upregulate immunoglobulin E production.
Allergens in Asthma
Inhalant allergens are most frequently involved in allergic respiratory diseases such as allergic rhinitis and asthma. These antigens, which directly impact on the respiratory mucosa, are usually derived from natural organic sources such as dust mites, pollens, mold spores, and insect and animal emanations. Chemicals and irritants from the workplace have been increasingly recognized as a cause of rhinitis, asthma, or both. These chemicals can act as allergens or irritants or could influence the mucosal environment in such a manner as to predispose the individual toward developing an allergic response.
Data suggest that diesel particulates can affect some patients toward becoming allergic. Inhalant allergic diseases may be episodic, seasonal (such as hay fever), or perennial. The most important seasonal allergens are pollens. Despite popular belief, the heavy, sticky pollens of brightly colored flowers seldom cause allergy symptoms, as these pollens are spread by insects and not by wind currents. Exposure to nonseasonal allergens, mainly through inhalation but in some instances by ingestion, accounts for year-round allergies. Among the inhalants, dust mites, mold allergens, cockroaches, and animal emanations are responsible for most perennial allergic asthma.
Table Mast Cell-Derived Mediators
|Proteoglycans (heparin, chondroitin sulfate E)|
|Newly synthesized lipid mediators|
|Interleukins-la, 2, 3,4, 5, 6, 8, 10, 13, 16|
|Macrophage inflammatory proteins la and ip|
|Monocyte chemotactic and activating factor|
|tumor necrosis factor-a (both preformed and newly synthesized)|
Diagnosis of Allergy
Despite the development of in vitro methods of detecting immunoglobulin E antibodies, skin testing (prick or intradermal) with appropriate allergens is the least time-consuming, most sensitive, most useful and also the least expensive method to confirm the presence of allergen-specific immunoglobulin E. Skin testing can be performed on infants as young as 1-4 mo of age, although age dictates both the choice of allergens used and the clinical conditions for which they can be used. Under the age of 1 yr, food antigens are the likely offenders, causing eczema or asthma.
Inhalant allergens are more likely to be involved after 2-A yr of exposure, although sensitization to indoor allergens can occur much more quickly. In exceptional cases, such as in patients with extensive eczema or marked dermatographism that negates use of skin tests, in vitro assays for serum immunoglobulin E antibodies by radioallergosorbent, fluorescent-allergosorbent, multiple-thread allergosorbent, or enzyme-linked immunosorbent assay techniques might be substituted for direct testing. With either in vitro testing or skin tests, however, it is essential that the relevance of the results be correlated to the patient’s current clinical problems and their detailed history.
Table Pathological Changes in Asthma and the Putative Mediators Responsible
|Pathological changes||Mast cell mediators responsible|
|Bronchial smooth muscle contraction||Histamine|
|Leukotrienes C4, D4, E4|
|Prostaglandins and thromboxane A2|
|Leukotrienes C4, D4, E4|
|Reactive oxygen species|
|Mucosal inflammation||Inflammatory factors|
|Cytokines(IL-l, IL-6, tumor necrosis factor-a,etc.)|
|Eosinophil and neutrophil|
|Leukotrienes C4, D4, E4|
|Desquamation||Reactive oxygen species|
|Inflammatory factors and cytokines|
Allergic Bronchopulmonary Aspergillosis
Allergic bronchopulmonary aspergillosis was described in England as a progressive form of asthma leading eventually to pulmonary fibrosis. It was thought that the damp climate in England was responsible for the relatively frequent occurrence there and infrequent occurrence elsewhere. However, recent studies in the United States have revealed the presence of Allergic bronchopulmonary aspergillosis in the midwestern portion of this country as well.
Compared to other forms of asthma, Allergic bronchopulmonary aspergillosis is seen infrequently and may be heralded by its specific clinical characteristics. There are five pulmonary disease patterns elicited by exposure to Aspergillus species:
(1) allergic asthma induced by exposure to mold spores in subjects with immunoglobulin E antibodies directed at Aspergillus antigens;
(2) hypersensitivity pneumonitis in response to mold spore inhalation in nonatopic individuals who develop IgG-class antibodies and cellular immunity to Aspergillus antigens;
(3) a fungus ball or aspergilloma, which is a saprophytic colonization of a pre-existing cavity (as in old tuberculosis or sarcoidosis);
(4) invasive aspergillosis, which is an overwhelming diffuse pneumonia in reaction to Aspergillus in an immunocompromised host; and
(5) Allergic bronchopulmonary aspergillosis, which is a subacute inflammatory reaction elicited by both immunoglobulin E- and IgG-mediated immune responses directed at Aspergillus species growing in the respiratory track.
The precise incidence of Allergic bronchopulmonary aspergillosis in the United States is not known, but although the disease is not rare, it is seen uncommonly. Diagnostic criteria for Allergic bronchopulmonary aspergillosis have been established and are summarized in Table Diagnostic Criteria for Allergic Bronchopulmonary Aspergillosis.
Table Diagnostic Criteria for Allergic Bronchopulmonary Aspergillosis
|Positive immediate skin-test reactions to|
|IgG antibodies to Aspergillus antigens|
|Marked increase in immunoglobulin E level|
|Pulmonary infiltrates, often transitory|
|Central, saccular bronchiectasis|
|Elevated serum immunoglobulin E and IgG to A.fumigatus compared to control groups|
|Secondary criteria||Aspergillus in sputum|
|History of expectorated brown plugs or specks|
|Late-phase (or Arthus) skin-test results to|
There are five stages of Allergic bronchopulmonary aspergillosis: stage 1 is the form of Allergic bronchopulmonary aspergillosis when the diagnostic criteria listed in Table 5 are met. Generally, the patient exhibits moderate-to-severe asthma, with purulent mucus production, eosinophilia, abnormal chest X-ray, and high immunoglobulin E levels. Skin testing to Aspergillus produces a positive immediate (and often late) reaction. The possible presence of bronchiectasis is analyzed by computed tomographic scans, and serological testing for IgG antibodies directed at Aspergillus is performed. At this point patients should generally be treated aggressively with corticosteroids, with a resultant remission (stage 2).
Once the patient has had a remission, CCSs are reduced to either every-other-day use or are removed entirely. At this stage most experts continue patients on moderate doses of inhaled CCSs. Stage 3 occurs if an exacerbation eventuates and may lead to the stage where chronic CCSs (either daily or every other day) are necessary (stage 4). Diffuse pulmonary fibrosis (stage 5) can develop or be the presenting stage at which Allergic bronchopulmonary aspergillosis is recognized. The importance in making the diagnosis of Allergic bronchopulmonary aspergillosis rests on the aggressive use of oral and inhaled CCSs in order to try to prevent the development of pulmonary fibrosis.
For patients with Corticosteroids-dependent Allergic bronchopulmonary aspergillosis, the addition of itraconazole 200 mg twice a day for 16 wk and then 200 mg/d for another 16 wk can lead to significant improvement of clinical response. This treatment is generally well tolerated. The toxicity and adverse reactions induced by itracanazole are not significantly higher than those observed in patients receiving steroid treatment alone.
All patients with asthma may experience a worsening of their symptoms concurrent with upper respiratory tract infections, bronchitis, or influenza-type illnesses. Moreover, children may experience their initial asthma as a consequence of viral bronchiolitis, which commonly develops into chronic asthma. Finally, some patients have no clinical asthma except during concurrent respiratory infections. Some adult asthmatics trace their chronic asthma to a viral respiratory infection that led directly to chronic and often severe, nonallergic asthma.
Bronchiolitis is an acute viral infection of the bronchioles, generally seen only in children less than 2 yr old. It is usually accompanied by upper respiratory tract symptoms, which may precede the lower respiratory tract involvement by 2-3 d. Patients experience cough (sometimes croup), dyspnea, rapid respirations, fever, and sometimes prostration. Physical examination reveals retractions, rapid respiration, occasional rales, and wheezing. Respiratory syncytial virus (RSV) is the most frequent etiological agent, but adenoviruses, rhinovirus, parainfluenza virus, and others may also cause the disease.
RSV-related bronchiolitis has a mortality risk of 1%. Several studies suggest that atopic children develop immunoglobulin E antibodies directed at the RSV, which converts the infection into an allergic reaction. About 50% of children with bronchiolitis in whom a family history of either allergies or asthmaexists develop recurring wheezing. Inmost instances, postbronchiolitis asthma is mild in nature and largely under control or in remission by the age of 8 yr. Current studies suggest that some patients with asthma may have an underlying bronchitis caused by Mycoplasma or Chlamydia infection. Such patients generally have adult-onset disease, associated with an initial infection and some persistent cough and mucus production. In such patients, a 1 – to 2-mo trial of appropriate antibiotics (such as Clarithromycin, 500 mg bid) might be helpful. Information of the possible relationship between a low-grade infection and asthma is suggested by increased antibody titers against Mycoplasma and/or Chlamydia or the presence of bacterial RN A in lung biopsy.
The air we breathe may contain allergens of natural origin or generated as a consequence of industrial or environmental processes. In addition, chemicals in the air may irritate the airways and lower the threshold for airway responsiveness. These same irritants may in addition be allergens for susceptible individuals. Besides industrially related exposure, modern life generates pollutants that linger in the air, generally in or around cities, which may damage the lungs.
Thus, everyone is at risk of breathing potentially harmful substances, but asthmatics are at much greater risk to react adversely to them. Certain pollutants such as ozone increase airway reactivity even in normal subjects, and asthma may be exacerbated during pollution with either industrial or photochemical smog. Approximately 2-15% of all cases of adult-onset asthma in men are of occupational origin (depending on the level of airway irritants and allergens in any working area).
Suspicion of occupational lung disease should be raised by the history of cough or chest tightness in relationship to the workplace. In asthmatics, worsening of symptoms every week, especially early in the week, may be noted. Such suspicions can be strengthened by evidence of wheezing or abnormal pulmonary function after occupational exposure. Only a few appropriate antigens are available for skin testing, so provocation with the suspected airborne chemical or particulate may be the only confirmatory test available. Some of the more common occupational exposures leading to asthma are listed on Table Some Agents Capable of Causing Occupational Asthma.
Table Some Agents Capable of Causing Occupational Asthma
|Metal salts||Salts of platinum, nickel, chrome|
|Wood dusts||Oak, western red cedar (plicatic acid),redwood, mahogany|
|Vegetable dusts||Grain (mite, weevil), flour, castor bean, green coffee, gums, cottonseed, cotton dust|
|Industrial chemicals||Toluene diisocyanate, polyvinyl chloride, phthalic and trimelletic anhydrides, ethylenediamine|
|Pharmaceutical agents||Penicillin, phenylglycine acid chloride, ethylenediamine|
|Biological enzymes||Bacillus subtilis, pancreatic enzymes|
|Animal and insect materials||Rodent urine protein, canine or feline saliva or secretions|
The prevalence of occupational asthma varies with the exposure and the provocative agent. Although only about 5% of workers regularly exposed to toluene diisocyanate develop asthma, 10-45% of workers exposed to relatively high concentrations of pro-teolytic enzymes in laundry detergent in the past were affected. The pattern of response may be immediate, late, or both. The underlying mechanism involves direct irritation and/or the induction of immunological processes, including immunoglobulin E- or IgG-type responses. Removal of the worker from the workplace may reduce or reverse the airways disease, although there are many exceptions.
Chemical or Drug Exposure
Conditions associated with exacerbations of asthma
Differential diagnosis of asthma
Not all that wheezes is asthma! Diseases in which wheezing is a component are listed in Table Differential Diagnosis of Asthma. Asthma, chronic bronchitis, and emphysema affect the airways diffusely, cause airway obstruction, and may coexist in the same patient. Generally, chronic bronchitis occurs in cigarette smokers who develop chronic cough that persists for years before airflow becomes symptomatically obstructed. The bronchorrhea may vary in intensity in relation to infectious or irritant exposure, for example.
Chronic bronchitis involves hyperplasia and hypertrophy of the submucosal glands, inflammation of the small airways, and hypersecretion of mucus. Emphysema may also be heralded by longstanding cough and mucus production, but this is a diagnosis confirmed only histo-logically. Emphysema is suggested by the presence of a reduced diffusing capacity and obstructing airways disease. Most adults have some degree of emphysema at autopsy, but severe emphysema is seen only in about 10%. Emphysema is another disease that usually develops in smokers.
A small number of patients with emphysema and bronchitis have a congenital absence of a-antitrypsin and present with bronchitis and wheezing and may develop emphysema and cirrhosis of the liver.
In children, most conditions likely to be confused with asthma begin in infancy, so it is in the wheezing infant that the differential diagnosis of asthma is important. The most common differential is an aspirated foreign body. A history of aspiration, findings of unilateral wheezing or hyperinflation on physical examination, or a persistent infiltrate on chest radiology suggests the need for further evaluation. Other illnesses encountered in wheezing infants include bronchopulmonary dysplasia, cystic fibrosis, gastroesophageal reflux, and immunoglobulin deficiency.
Table Differential Diagnosis of Asthma
|Nonasthmatic conditions associated with wheezing|
|Cardiac failure (“cardiac asthma“)|
|Tumors in the central airways|
|Aspiration (gastroesophageal reflux)|
|Vocal cord dysfunction|
|Laryngeal or tracheal obstruction|
|Immotile cilia syndrome, Kartagener’s syndrome|
|Chronic bronchitis and emphysema|
Factors predisposing to asthma
When differentiating asthma from other obstructive airways disease, it is always relevant to ask if family members experience the same symptoms. It is well recognized that asthma is the result of both genetic and environmental influences. Asthma, as with many other medical conditions, such as hypertension and diabetes mellitus, is a complex genetic disorder. It cannot be classified as an autosomal-dominant, recessive, or sex-linked pattern of inheritance. At the present time, several chromosomal regions have been identified to be strongly associated with asthma, suchas5q31,6, llql3,12q, 13ql4, and so on. The 5q31, for example, is on chromosome 5. It influences total immunoglobulin E production, eosinophil count, IL-4, IL-5, and IL-13 production, CD14 expression, and so on. The completion of human genome sequencing will certainly help facilitate the process of identifying genes involved in asthma.
An imbalance of the autonomic nervous system with a blunted p-adrenergic response and hyperresponsiveness of the ” p-adrenergic and cholinergic systems have been documented in asthmatics, although this defect is not unique for asthma. The exact contribution of the disarray of autonomic imbalances found in asthmatic subjects is not clear. Some of the abnormalities are also found in allergic subjects and in patients suffering from cystic fibrosis. These data suggest that asthmatics have an inherently reduced ability to sustain open airways and a tendency for airflow obstruction based on an inherent defect in their autonomic balance.
The classic symptoms of asthma include intermittent, reversible episodes of airflow obstruction manifested by cough, wheezing, chest tightness, and dyspnea. When the clinical situation permits, a detailed history should be taken that includes the following: (1) family and personal history of atopic disease; (2) age of onset of asthma, frequency and severity of attacks; (3) times (including seasons) and places of occurrence of asthmatic attacks; (4) known provocative stimuli and any previous correlating skin-test reactions; (5) the severity of the disease as reflected in the wheezing episodes per day, the number of missed school or work days per year, whether sleep is interrupted, the necessity for emergency room visits, and the number of hospitalizations for asthma; and (6) previous pharmacological or immunological therapy and its efficacy.
Early symptoms often include a vague, heavy feeling of tightness in the chest, and, in the allergic patient, there may be associated rhinitis and conjunctivitis. The patient may experience coughing, wheezing, and dyspnea. Although the cough (if present) is initially nonproductive, it may progress to expectoration of a viscous, mucoid, or purulent and discolored sputum. There appears to be a subgroup of asthmatics whose asthma is characterized solely by cough without overt wheezing, the “cough variant of asthma.” (Just as all that wheezes is not asthma, all that is asthma does not necessarily wheeze.) If this syndrome is suspected, patient’s airways should be examined by spirometry before and after bronchodilator inhalation or after receiving a methacholine inhalation challenge.
Patients who appear to have allergic asthma, as demonstrated by seasonal exacerbations or clearly recognized allergen-related triggering events, may be sensitive to pollens, dust mite, animal dander, mold spores, occupational dusts, or insects. Less frequently, children may also be allergic to certain foods. If the offending allergen can be identified from the patient’s history and avoided, further workup may not be necessary. However, the fact that atopic patients may be allergic to many allergens or may react to such small amounts of crude allergens (i.e., dust mite) indicates that the association is not clear-cut. Moreover, allergic asthmatics may respond to many nonallergic conditions (such as cigarette smoke, noxious fumes, upper respiratory tract infections, or weather conditions) by wheezing.
All patients should be asked if they can take aspirin or nonsteroidal anti-inflammatory drugs without ill effects, and this line of inquiry is even more important in patients with sinusitis or nasal polyps. Occupational asthma should be suspected if patient worsens early each week and then improves during the course of the week, or if asthma is worse during the week as com pared to weekends or during travel. It may be necessary to have the patient use a peak flow meter at work during the course of a week to help determine what exacerbates the disease, or to conduct a bronchial challenge with materials to which the patient is exposed at work.
Table Asthma Diagnosis: Episodic Symptoms of Airflow Obstruction
|Shortness of breath (with or without exercise)|
|Chest tightness (below sternum)|
|Cough (throat vs chest, quantity and quality of sputum)|
|Morning vs evening symptoms|
|Emergency room visits|
Table Initial History (Determine Days/Week/Month for Each)
|Do you wheeze?|
|Shortness of breath?|
|Tightness in the chest (inability to take a full breath)?|
|Exercise? Need pretreatment with bronchodilator?|
|Cough? Throat vs chest, sputum quality/quantity?|
|Use of bronchodilator?|
|Peak flow meter use; average, best and worst reading?|
|Emergency room visits, hospitalizations?|
Chest X-rays should be repeated every 3-5 yr, and a yearly complete blood count is a reasonable precaution in most patients. Some subjects worsen reliably with every upper respiratory infection, and it may be necessary to treat them prophylactically with antibiotics and/or CCSs to prevent these exacerbations.
Many subjects are unaware of their chest disability and benefit from frequent peak flow readings. We routinely provide a peak flow meter to all asthmatics and request that readings are taken twice a day, in the morning and at night. These readings are an invaluable adjunct to the management of most asthmatics.
In the completely asymptomatic patient, results of chest examination will be normal, although head, eye, ear, nose, and throat examination may disclose concomitant serous otitis media, allergic conjunctivitis, rhinitis, nasal polyps, paranasal sinus tenderness, signs of postnasal drip, or pharyngeal mucosal lymphoid hyperplasia. Clubbing of the fingers is extremely rare in uncomplicated asthma, and this finding should direct the physician’s attention toward diseases such as bronchiectasis, cystic fibrosis, pulmonary neoplasm, or cardiac disease. With an acute exacerbation, patients may be restless, agitated, orthopneic, tachypneic, breathing through pursed lips with a prolonged expiratory phase, using accessory muscles of respiration, diaphoretic, coughing frequently, or audibly wheezing and cyanotic.
Table Peak Flow Meter Characteristics
|Easy to use|
|Provide “real-life” measurements at worst and best time of day am and pm, monitor range between the measurements|
|Obtain “personal-best” measurement|
Cyanosis occurs only with profound arterial oxygen desaturation and is a grave sign that appears late in the course of severe asthma. Vital signs will confirm the physician’s impression that the patient is tachypneic, and evaluation of the blood pressure may show that the patient has a widened pulse pressure and a pulsus paradoxus. The latter sign, when present, is a relatively reliable indicator of severe asthma. Although a low-grade fever may be of viral origin, the presence of an elevated temperature should alert the physician to search for a possible bacterial infection requiring antibiotic therapy.
Examination of the chest will often show signs of hyperinflation, such as hyperresonance on percussion and low, immobile diaphragms. In milder stages of asthma, wheezing may be detected only on forced expiration, but with increasing severity, wheezing may also be heard on inspiration. In some episodes of severe asthma, wheezing may be heard early in the course of disease, but with increasing obstruction of the airways, the wheezing may seem to “improve” as increasing difficulty in ventilating develops. This abatement of wheezing may, unfortunately, be taken as a clinical sign of improvement and result in less than optimal treatment. As the patient does improve, one may notice the reverse situation; namely, that wheezing may increase in intensity.
Again, this finding should not be erroneously interpreted as worsening of the asthma. The major point is that in judging the severity of asthma, the physician must rely on many physical findings (such as the use of accessory muscles and the presence of paradoxical pulse) as well as the degree of wheezing. As the patient recovers, the improvement takes place most often in reverse order of the appearance of symptoms,that is, there is a sequential loss of mental status abnormalities, cyanosis, pulsus paradoxus, use of accessory muscles, dyspnea, tachypnea, and, finally, wheezing.
It is important to note, however, that when the attack appears to have ended clinically, abnormal pulmonary function test results are still present and may persist for several days. At this point in the course of the illness, there is usually a residual volume twice that of normal, an FEVj 60% of that predicted, and a maximum mid-expiratory flow rate 30% of that predicted. Such findings support the contention that treatment should be continued well past the symptomatic period and that close outpatient follow-up is indicated.
Classification of Asthma
Asthma may be divided into four clinical phases, based on symptoms and pulmonary function testing. These stages allow physicians to communicate about asthma severity and provide general guidelines on treatment. The four categories include mild intermittent asthma, mild persistent asthma, moderate persistent asthma, and severe persistent asthma. These categories advance in severity and a patient may move from one to another depending on various circumstances. Table Classification of Asthma Severity shows details of the current classification scheme.
Table Classification of Asthma Severity
|Category||Symptoms||Nocturnal symptoms||Pulmonary function|
|Mild intermittent||Less than twice weekly Normal between attacks||Less than twice monthly||Both FEVi and peak expiratory flow rate >80% predicted|
|Attacks brief and usually mild|
|Mild persistent||More than twice a week, less than daily||More than twice weekly||Both FEV! and peak expiratory flow rate >80% predicted|
|Attacks limit activity monthly|
|Moderate persistent||Daily symptomsDaily use of medications||More than weekly||FEVi and peak expiratory flow rate 60-80% predicted|
|Attacks affect activity|
|Attacks usually more than twice a week and may be severe and last days to weeks|
|Severe persistent||Continuous symptoms Limited physical activity Frequent exacerbations||Frequent, up to every night||FEV! and peak expiratory flow rate <60% predicted|
Mild intermittent asthma occurs less than twice weekly, and the patient is asymptomatic otherwise. Pulmonary function is normal except during periods of disease, and exacerbations are brief and usually easily treated.
Mild persistent disease occurs more than twice a week, but less than once a day. Symptoms are severe enough to interfere with daily activities and may interrupt sleep up to twice a month. Moderate persistent disease occurs on a daily basis and requires regular use of medications. This stage of asthma is moderately inconvenient, with patients constantly aware of their disease, requiring medications on a daily basis, having their sleep interrupted at least weekly, and having to accommodate their lifestyle to the disease.
Severe asthmahas continuous symptoms despite medications, which limit activity and are associated with frequent exacerbations and sleep interruptions.
A patient with mild persistent disease can be exposed to allergens or develop a cold and have a severe exacerbation of his asthma symptoms, which places him in the severe persistent classification until the attack is resolved. Conversely, a patient with severe persistent symptoms can be treated effectively and have resolution of symptoms, with reclassification to a mild persistent category while he or she takes medications.
Exercise is a well-established nonspecific stimulus to airflow obstruction, and this phenomenon can be demonstrated in most patients with asthma. Thus, exercise-induced asthma might better be thought of as a reflection of increased nonspecific airway hyperresponsiveness than as a distinct form of asthma. It is most common in children and adolescents (probably because they exercise more strenuously than do most adults). The problem is clinically important in at least two-thirds of adolescents with asthma because it interferes with school and recreational activities.
The mechanisms by which exercise causes bronchial obstruction is unknown, but a fall in the temperature and humidity of the intrathoracic airways is a critical initiating event. The exact roles of mast cell mediator release and reflex responses (perhaps regulating blood flow in response to the temperature change) in this syndrome are unclear. Exercise asthma usually begins after about 6-10 min of exercise or after the exercise is completed. Exercise asthma can be reproduced by having subjects hyperventilate cold, dry air.
Swimming and activities that necessitate only brief intervals of exercise are likely to be best tolerated. Breathing warm and humidified air (as in jogging with a face mask) and the use of prophylactic drug therapy (b-agonists usually) generally afford adequate protection against exercise-induced asthma.
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