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Gerald W. Staton, Jr., m.d.Roland H. Ingram, Jr., m.d.
Definition
Asthma is characterized by narrowing of the airways in re-
sponse to various stimuli and the presence of airway inflamma-
tion of varying degree. Unlike the more fixed or permanent air-
flow obstruction typical of chronic bronchitis, emphysema,
cystic fibrosis, bronchiectasis, and bronchiolitis, the airflow ob-
struction associated with asthma may be completely reversible
[see 14:III Chronic Obstructive Diseases of the Lung]. Asthma is a
chronic disease, yet the degree of airflow obstruction can vary
widely over time and change within minutes or over a period of
days to weeks. Increased responsiveness of the airways to vari-
ous stimuli is seen even in asymptomatic asthma patients who
have normal lung function.
Increased responsiveness of the airways and reversible air-
flow obstruction are not unique to asthma. Many patients with
chronic obstructive lung disease (e.g., chronic bronchitis or cystic
fibrosis) exhibit nonspecific hyperresponsiveness, although ob-
struction is not completely reversible and some degree of ob-
struction is always present. In particular, some current or past
cigarette smokers with chronic bronchitis and airflow obstruc-
tion exhibit episodic wheezing and shortness of breath that
closely mimic asthma. There is no consensus on how such pa-
tients should be classified, but we prefer to consider their ail-
ment not as asthma but as asthmatic bronchitis, a subcategory of
chronic bronchitis that has features in common with asthma [see14:III Chronic Obstructive Diseases of the Lung]. This distinction is
important in studies of the prevalence and mortality of asthma.
There is no single pathognomonic feature by which asthma
may be recognized, nor is there a definitive diagnostic test for
asthma. Many clinical settings, such as wheezing in association
with childhood respiratory tract infections and long-standing
asthma in adults with irreversible obstruction, defy straightfor-
ward classification. Fortunately, in clinical practice, asthma is
generally far easier to recognize than it is to define.
Epidemiology
The prevalence of self-reported asthma was 7.2% in 2000, an
increase of 130% from 1982.1 The incidence of new cases of asth-
ma was highest in persons younger than 5 years. In persons old-
er than 10 years, the incidence remained at approximately 0.2 to
0.4 new cases per 100 person-years at risk. The prevalence of
asthma was higher for boys than for girls and higher in Hispanic
and African-American children than in white children, though
the difference has decreased in recent years.2 In a population sur-
vey, obesity was found to be associated with an increased preva-
lence of asthma.3 In persons older than 40 years who were newly
diagnosed as having asthma, approximately one half had a his-
tory of cigarette smoking and had been previously diagnosed as
having chronic bronchitis or emphysema; these patients would
have been more accurately diagnosed as having asthmatic bron-
chitis. Still, the number of cases of asthma that develop in per-
sons who have never smoked cigarettes is sufficiently large to
make true adult-onset asthma common.
The reported prevalence of asthma in the United States is
higher than in Japanese and in Eskimo populations but lower
than in New Zealand. It is not known whether these differences
reflect genetic or environmental factors or result from variable
diagnostic criteria. Data suggest that there are genetic markers
on multiple chromosomes that relate to bronchial hyperrespon-
siveness and atopy.4 Childhood exposure to antigen-rich envi-
ronments, such as a farm, is associated with a reduced incidence
of asthma and allergy, suggesting changes in the maturation
process of the immune system.5
In patients with chronic asthma, Mycoplasma and Chlamydiaspecies have been identified in lung specimens, suggesting a
possible role for infection in the pathogenesis.6
The prevalence of bronchial hyperreactivity far exceeds that
of clinically manifest asthma. In large population surveys, many
of the persons with hyperresponsive test results were free of respi-
ratory symptoms. In the general population, bronchial respon-
siveness occurs in a normal pattern of distribution, with a skew
toward increased reactivity. Some persons with hyperreactive
airways do not have asthma [see Figure 1] but may develop asth-
ma later in life. In patients with asthma, there is a direct relation
between heightened bronchial responsiveness and annual de-
cline in lung function.7
Complete remission of asthma is relatively common in chil-
dren; as many as 25% remain asymptomatic from adolescence
onward. Infrequent symptoms and normal pulmonary function
are favorable prognostic factors. In adults, prolonged remission
of asthmatic symptoms is considerably less common. Patients
older than 65 years tend to have severe asthma that infrequently
goes into remission; in these patients, asthma is less reversible.
Asthma was once thought to cause considerable morbidity
but not mortality. It is now clear that severe attacks of asthma
can end fatally. In the United States in 1999, the annual mortality
from asthma in persons 15 to 34 years of age was 0.59 per 100,000
population, an incidence about twice that in 1980.1 In some areas
of the United States, this increase occurred despite a decrease in
Figure 1 The change in expiratory flow, as measured by forcedexpiratory volume in 1 second (FEV1), after administration of a givenconcentration of bronchoprovocative agonist is shown for a generalpopulation. A large decrease in expiratory flow implies a greaterbronchial reactivity. Bronchial reactivity is normally distributed, with askew toward increased reactivity. The figure indicates that asthmaticpersons exhibit varying degrees of bronchial hyperreactivity and thatsome persons with increased bronchial responsiveness do not manifestclinical signs of asthma.
air pollution. Mortality was more than twice as high among
African Americans as among whites and was greatest in patients
with eosinophilia and in those who experienced major responses
to inhaled bronchodilators. Most deaths occur in places other
than the hospital and are most likely the result of asphyxiation
caused by pulmonary obstruction. Rapid progression to respira-
Figure 2 Pathogenesis of allergic asthma. Inhaled antigen is processed by dendritic cells and presented to Th0 CD4+ T cells. This resultsin the generation of either Th1 or Th2 CD4+ T cells, with Th2 CD4+ T cells predominating in asthma. B cells are stimulated by interleukinsIL-4, IL-6, and IL-13 from Th2 CD4+ T cells to produce IgE, which binds to mast cells. Inhaled antigen binds to IgE, stimulating the mastcell to degranulate, which in turn leads to the release of mediators of the immediate response and the late response. Histamine and theleukotrienes produce bronchospasm and airway edema. Released chemotactic factors, along with factors from the Th2 CD4+ T cells,facilitate eosinophil traffic from the bone marrow to the airway walls. These late responses lead to excessive mucus production, airwaywall inflammation, injury, and hyperresponsiveness. (GM-CSF—granulocyte-macrophage colony-stimulating factor; IL—interleukin)
serve to maintain this hyperinflated FRC. Except in cases involv-
ing severe airflow obstruction, total lung capacity (TLC) remains
within the normal range.
Residual abnormalities in lung function may persist even after
complete symptomatic resolution of acute episodes of asthma.
Typically, decreases in maximal flow rates and increases in resid-
ual volume may persist for days to weeks after an acute attack
and may represent persistent low-grade airway inflammation.
The transfer factor for carbon monoxide may be elevated in
some patients, possibly because of greater recruitment of cap-
illaries from higher pulmonary arterial pressure. Because of
ventilation-perfusion mismatching, an elevation in the alveo-
lar-arterial oxygen difference (A-aDO2) is common, but severe
hypoxemia is rare. The severity of hypoxemia cannot be accu-
rately determined from the degree of airflow obstruction—
an observation that has led to the idea that hypoxemia may be
related more to peripheral airway obstruction than to central
obstruction.
The tachypnea and alveolar hyperventilation that are ob-
served during an asthmatic exacerbation result not from
chemoreceptor stimulation but from neural reflexes within the
lungs. Hypocapnia and respiratory alkalosis are the most com-
mon findings on arterial blood gas analysis. Metabolic (lactic)
acidosis may also be seen if there is severe hypoxemia in combi-
nation with the increased work of breathing. When airflow ob-
struction becomes very severe (FEV1 < 25% of normal), dead
space ventilation increases, whereas total ventilation can in-
crease no further; this results in an increase in carbon dioxide
tension (PCO2) back to normal levels. Ultimately, despite an in-
crease in CO2 production, total minute ventilation begins to fall;
as a result, alveolar ventilation decreases still further and hyper-
capnia ensues. Respiratory muscle fatigue has been postulated
as a potential cause of hypercapnic respiratory failure in patients
with asthma.
Diagnosis
clinical manifestations
The classic symptoms of asthma are wheezing, cough, and
shortness of breath. During periods of relatively normal lung
function, patients are likely to have no physical findings.
Wheezing
Wheezing is the most common finding during acute airway
obstruction, and the chest may be hyperresonant on percus-
sion. As airflow obstruction becomes severe, a number of
physical signs may become manifest and offer clues to the
severity of the attack. Tachypnea and tachycardia are com-
mon. A fall in systolic blood pressure of more than 10 to 12
mm Hg during inspiration (paradoxical pulse) is found in ap-
proximately one half of patients whose FEV1 is 1 L or less dur-
ing acute exacerbations. Accessory muscle usage and paradox-
ical pulse with decreasing intensity of breath sounds signify
severe obstruction.
Cough
The cough can be nonproductive or raise copious amounts of
sputum that, in the absence of infection, is typically mucoid and
often tenacious. Eosinophils and their debris may cause a yellow
discoloration of sputum, even when infection is absent. Occa-
sionally, cough is the only manifestation of asthma.
Dyspnea
Dyspnea tends to vary greatly over time, depending on the
severity of airflow obstruction. At times, airflow obstruction
prevents any significant physical exertion; at other times, stren-
uous exercise is possible but may trigger wheezing and short-
ness of breath [see Exercise-Induced Asthma, below]. During a
severe attack, a desperate hunger for air is the overwhelming
symptom. Chest tightness commonly occurs with dyspnea and
may be confused with angina pectoris. Most patients associate
their chest tightness with the sensation of being unable to take
in a full and satisfying breath. Older patients are less aware of
airflow obstruction.15
Bronchoconstriction can be triggered by a variety of stimuli
that have little or no impact on the airways of nonasthmatic per-
sons; these responses can be helpful diagnostically. The stimulus
need not be a specific allergen or chemical in the workplace; a
nonspecific (i.e., nonantigenic) stimulus, such as strenuous exer-
cise, especially while breathing dry air, may trigger the response.
stimuli that trigger attacks
The stimuli that trigger attacks vary among persons. For
many patients, attacks of asthma are triggered by allergens such
as ragweed or animal dander, house dust containing antigens
from dust mites and cockroaches, strong odors or fumes, and in-
gested substances such as certain foods, sulfiting agents, aspirin,
and tartrazine [see Specific Forms and Complications of Asthma,
below]. Emotional upset and stress may trigger symptoms in
some patients, but the precise role of the central nervous system
in regulating airway function is difficult to quantitate. Reflux of
gastric acid into the lower esophagus may exacerbate asthmatic
symptoms, presumably through vagally mediated parasympa-
thetic nervous reflexes,16 but the role of gastroesophageal reflux
in asthma remains controversial.17 Persistent posterior drainage
of nasal mucus may also be an aggravating factor. Indirect evi-
dence indicates that nasal and sinus disease increases airway re-
sponsiveness and thereby exacerbates asthma.18 This inference is
based on changes in responsiveness and clinical severity after
nasal administration of steroids. Other stimuli are virtually uni-
versal precipitants of asthma. Such stimuli include strenuous ex-
ercise, particularly if it is performed in cold air; respiratory ill-
nesses, usually viral in origin; inhaled irritants such as ozone,
sulfur dioxide, and smoke; and beta-adrenergic blocking agents,
angiotensin-converting enzyme inhibitors, and ethanol (in Asian
patients).19 Specific antigen responsiveness may be more severe
after exposure to environmental pollutants. Some women with
asthma have been noted to have a significant increase in exacer-
bations during the preovulatory and perimenstrual periods.20
Persons whose asthma is triggered by identifiable inhaled
antigens (aeroallergens) usually have atopic disease. Exceptions
include cases of asthma caused by certain sensitizing antigens
encountered in the workplace that may not elicit an IgE antibody
response [see Occupational Asthma, below]. Certain laboratory
test results support a diagnosis of atopic disease: peripheral
blood eosinophilia; increased total serum IgE levels; increased
specific IgE levels, determined by a radioallergosorbent test
(RAST) directed at a particular antigen; and positive wheal-and-
flare reactions to antigens pricked or injected into the skin.
A distinction is often made between persons with asthma
who have known allergic precipitants of their bronchoconstric-
tion (extrinsic asthma) and those who do not (intrinsic asthma).
Patients who show evidence of an atopic contribution to their
asthma may have a greater rate of decline of lung function than
simplex virus), can constitute an acute respiratory illness associ-
ated with wheezing [see 7:XXV Respiratory Viral Infections].Churg-Strauss syndrome [see 14:IV Focal and Multifocal Lung Dis-ease] is a form of vasculitis characterized by asthmalike airflow
obstruction and wheezing.
Many diseases associated with chronic airflow obstruction
[see 14:III Chronic Obstructive Diseases of the Lung] cause episodic
wheezing. Some diseases affect the airway in a manner that can
be mistaken for asthma. For example, sarcoidosis may cause en-
dobronchial granuloma formation with resultant airflow limita-
tion, cough, wheezing, and dyspnea that are refractory to the
usual bronchodilator medications. In addition, rheumatoid
arthritis may be associated with bronchiolitis, producing find-
ings that mimic refractory asthma.
Congestive heart failure and pulmonary embolism cause dys-
pnea and wheezing. Wheezing in association with interstitial
pulmonary edema is common enough to have been designated
cardiac asthma. Improvement after administration of an inhaled
bronchodilator does not exclude cardiac asthma as the cause of
wheezing. Wheezing is a rare manifestation of pulmonary em-
bolism. Although in the acute setting, either pulmonary edema
or pulmonary embolism may be mistaken for asthma, a detailed
evaluation of the patient and the clinical course should clarify
the diagnosis.
The conditions most likely to be confused with asthma over a
more protracted period are those that cause partial upper airway
obstruction [see Table 1]. In this context, the term upper airway
refers to the single lumen airway from the carina upward. Dys-
pnea and wheezing associated with upper airway obstruction
may be continuous and fail to respond to bronchodilators—a
pattern that suggests focal anatomic obstruction. However, in
other cases, signs and symptoms may be intermittent and may
be brought on by exercise (because of the increased airflow
across the narrowed orifice) or by certain postures. Epinephrine
Figure 3 Four patterns of bronchial response to an inhaled antigen aredepicted. (a) An early response occurs within a few minutes afteradministration of the stimulus and resolves without treatment over thenext 30 to 60 minutes. (b) A late response develops several hours afterthe bronchoprovocative challenge and resolves gradually over the next12 to 24 hours. (c) A dual response combines features of both the earlyand the late reaction. (d) Occasionally, decreases in expiratory flow recuron several nights after a single challenge test. Note that different timescales are used.
rine is given primarily as a subcutaneous injection for acute relief
of severe airflow obstruction. It is also sold without prescription
as an inhalant in metered-dose canisters.
Isoproterenol, a powerful nonselective beta-adrenergic ago-
nist, has a short duration of action. Although it is available as an
inhalant for the treatment of asthma, it has largely been replaced
by newer, more selective beta2-adrenergic agonists.
Selective beta2-adrenergic agonists have structural modifica-
tions that make them effective by oral administration as well as
by inhalation. The duration of action of these compounds is 4 to
6 hours. Examples are metaproterenol, terbutaline, and albuterol
[see Table 4]. Bitolterol has a slightly extended duration of action
of 6 to 8 hours; it is currently available only in a metered-dose
delivery system. A preparation that contains only the R isomers
of albuterol (levalbuterol) has recently been marketed with
claims of reduced side effects and complications.45 Salmeterol, an
even longer-acting beta2-adrenergic agonist with a slow onset of
action, can be given twice a day as maintenance therapy (not res-
cue therapy) and has resulted in better asthma control and qual-
ity of life than is seen with albuterol; it does not compromise the
bronchodilator response to the short-acting beta2-adrenergic ag-
onists46 and may have mild anti-inflammatory effects.47 For-
moterol, a new long-acting selective beta2-adrenergic agonist
that recently became available in the United States, has a dura-
tion of action similar to that of salmeterol but a more rapid onset
of action; formoterol thus has potential for use as a long-acting
maintenance medication and a long-acting rescue medication in
place of the short-acting beta2-adrenergic agonists.48
The frequency and severity of side effects from the beta-
adrenergic agonists depend not only on the dose but also on the
route of administration. Side effects are most prominent with
parenteral administration, are of intermediate prominence with
oral administration, and are least prominent with inhaled ad-
ministration. Common side effects are those of sympathetic
stimulation, including nervousness and agitation, muscle
tremors, and palpitations. Cardiac stimulation may lead to tachy-
cardia and cardiac arrhythmias. Intracellular shifts of potassium
can cause hypokalemia, though the clinical significance of this
finding is uncertain. Long-term administration of beta agonists
may be associated with the development of tolerance49—possi-
bly caused by decreased numbers and responsiveness of mem-
brane beta receptors related to polymorphisms of the beta recep-
tor genes50—and with increased airway responsiveness to aller-
gen and to nonspecific stimuli. Beta agonists may also have a
minimal anticorticoid effect.51 However, the effects are small, and
the magnitude of the dilator response to high doses of beta ago-
nists in an emergency situation is not diminished in those pa-
tients who use these agents regularly. Regular use of inhaled
steroids may prevent some of these adverse effects associated
with routine use of beta2-adrenergic agonists.51
Over the years, beta2-adrenergic agonists given by inhalation
have been the mainstay of treatment for asthma because of their
rapid onset of action, their effectiveness, and their convenience.
In the mid-1980s, an increase in asthma deaths occurred after the
introduction of a newer beta2-adrenergic agonist, fenoterol, in
New Zealand. A study based in Saskatchewan, Canada, howev-
er, suggested that all beta2-adrenergic agonists, especially if used
heavily, are associated with an increased risk of fatal and near-
fatal asthmatic episodes, but a meta-analysis has suggested that
the risk is very small and may be confined to beta2-adrenergic
agents given by nebulizer.52 The most obvious question concern-
ing these studies is whether the increased mortality occurred be-
cause of administration of excessive amounts of the therapeutic
agent or because of the severity of illness in those patients given
the drug. Further studies, however, have suggested a mildly in-
creased degree of airway responsiveness to allergens with regu-
lar use of beta2-adrenergic agonists. These observations must be
added to the list of potentially negative effects associated with
regular use of these drugs. These concerns have been the subject
of much debate, and as yet, no clear consensus has emerged.
One recent study suggested that there is no benefit from regular-
ly scheduled doses of albuterol as opposed to as-needed dosing
in mildly asthmatic patients.53 Another study found no deteriora-
tion in asthma control in patients with moderate to severe asth-
ma as a result of regular use of albuterol.54
When patients begin to feel the need for more frequent use and
increased doses of inhaled beta agonists, they should be seen by a
physician and evaluated for additional aggravating factors, and
the addition of other treatments should be considered. There are
not sufficient data available to justify removing inhaled beta ago-
nists from the market or even to justify significantly changing the
way in which they are used. Nonetheless, excessive reliance on
inhaled bronchodilators, without sufficient attention to the un-
derlying inflammatory component of the disease, continues to be
a problem in the way asthma is managed. Inhaled cortico-
steroids, rather than scheduled doses of beta agonists, should be
considered as first-line therapy for asthmatic patients with daily
symptoms. Daily use of inhaled corticosteroids, supplemented by
inhaled beta agonists only as needed, provides better long-term
control of asthma than scheduled doses of beta agonists.
Theophylline
Theophylline is a methylxanthine closely related in structure
to caffeine.55 It was thought that theophylline acted by increasing
Figure 4 This posteroanterior chest radiograph shows an asthmaticpatient with allergic bronchopulmonary aspergillosis. Characteristicradiographic findings include the migratory nature of the infiltrates, thepredominant upper lobe involvement, and the associated atelectasis.The minor fissure forms the lower border of the upper right lobeinfiltrate; the minor fissure is displaced cephalad, indicating loss ofvolume in the right upper lobe.
cAMP levels by inhibiting the activity of phosphodiesterase, an
enzyme that facilitates the conversion of cAMP to the noncyclic
5′ AMP. Other modes of action for theophylline have been ex-
plored, including antagonism of adenosine at its receptor. Theo-
phylline may also have anti-inflammatory effects that include re-
duction of inflammatory cell numbers, expression of cytokines,
and acceleration of neutrophil apoptosis.56,57
Theophylline is almost completely absorbed from the gastroin-
testinal tract. The rate of absorption, however, can vary greatly,
depending on the formulation. A rapid onset of action can be
achieved with the elixir of theophylline (peak effect at approxi-
mately 60 minutes), whereas a long duration of action results
from slow-release preparations (peak effect at 6 to 8 hours), mak-
ing once- or twice-daily dosing schedules possible. Amino-
phylline (the ethylenediamine salt of theophylline) and oxtri-
phylline (the choline salt of theophylline) are more water soluble
than theophylline. Aminophylline is the preparation used for I.V.
administration; its bronchodilator activity is solely attributable to
theophylline, which by weight constitutes 85% of aminophylline.
Oxidation and demethylation of theophylline take place in the
liver; hepatic metabolites, along with a small amount of unal-
tered theophylline, are excreted in the urine. The average serum
Oral or parenteral therapy asso-ciated with significant sideeffects; use short-actingdrugs/inhaler p.r.n. ratherthan on regular schedule; uselong-acting drugs regularly
Can worsen prostatism, glauco-ma; can be combined withbeta-adrenergic agonists
Relatively weak bronchodilator;only used when all otheragents optimized; significanttoxicity, must monitor levels
q.d. initially, then wean off, ifpossible, or switch to q.o.d.
q.d. initially, then wean off, ifpossible, or switch to q.o.d.
Oral therapy as effective
Various inhaled corticosteroidagents differ in potency [seeTable 5]
Used more in children; nosteroid side effects
No steroid side effects
As a group, less effective thaninhaled corticosteroids; helpwith associated allergic rhini-tis; should be used in aspirin-sensitive patients
Note q.h.s. dosing; no lab moni-toring or restrictions related tomeals
Should be taken at least 1 hrbefore or 2 hr after meals
Must monitor LFTs
Toxic drug, must monitor bloodcounts and LFTs closely;should only be given by asth-ma expert
LFT — liver function test
Relative Efficacy
First choice for rescue
Only for exacerba-tions
Third choice
Usual oral agent
Less commonly used oral agent
Usual I.V. agent
First choice of anti-inflammatoryagents
Much less potentthan inhaledsteroids
Much less potentthan inhaledsteroids
First choice ofleukotrieneinhibitors
Efficacy contro-versial
Cost
$10.00–19.99
$5.00/mo
$9.00–43.00/mo
$24.00–26.99/day
$30.00–39.99/canister
$50.00–59.99/mo
$60.00–69.99/mo
$50.00–59.00/mo
$79.00–89.99/mo
$10.00–19.99/mo
half-life of theophylline in nonsmoking adults is approximately
7 to 9 hours, but differences in metabolic rates among people
and in the same person over time lead to considerable variability
in theophylline serum concentrations after a given dose. Clear-
ance of theophylline is accelerated in children, in cigarette smok-
ers, and in persons receiving phenytoin; its clearance is delayed
by numerous influences, such as primary liver disease, right
ventricular failure, and the use of several drugs, including cime-
tidine, erythromycin, ciprofloxacin, and oral contraceptives.
In mild to moderate asthma, the bronchodilator response
varies directly with the theophylline serum concentration. Sig-
nificant bronchodilatation occurs at theophylline concentra-
tions as low as 5 to 8 mg/L; at concentrations exceeding 20
mg/L, side effects become increasingly common. Thus, a ther-
apeutic range of 10 to 20 mg/L has been recommended. How-
ever, recent evidence suggests that lower levels may be effective
against inflammation.58 At levels greater than 40 mg/L, serious
toxic reactions can be observed, including seizures and ventric-
ular arrhythmias. Occasionally, life-threatening toxic reactions
occur at lower serum levels (i.e., 25 to 40 mg/L). This relatively
narrow therapeutic index, along with highly variable clearance
rates, has necessitated measurement of serum theophylline
concentrations in many clinical circumstances—especially in
patients with severe airflow obstruction, in whom maximal
bronchodilator effect is desired.
Side effects are common with theophylline and may occur at
serum concentrations at or even below the target therapeutic
range. GI complaints include nausea and vomiting, abdominal
pain, and diarrhea. Headache, nervousness, insomnia, and
tremors are the most common neurologic side effects. Cardiac
stimulation may lead to sinus tachycardia, extrasystoles, and atri-
al arrhythmias. In cases of severe theophylline toxicity caused by
overdosage (theophylline concentration > 40 mg/L and especial-
ly at levels > 60 mg/L), clearance of theophylline can be accelerat-
ed by administration of activated charcoal, either orally or by na-
sogastric tube; this will remove any theophylline remaining in the
stomach or intestine. On rare occasions, charcoal hemoperfusion
is necessary to reduce theophylline concentrations rapidly.
pressure minus plateau pressure), and the presence and degree
of intrinsic positive end-expiratory pressure (dynamic hyperin-
flation). Baseline measurements can be compared to subsequent
values as a means to assess response to therapy or need for accel-
erated treatment. If initial values reflect only modest obstruction
in a hypercapneic asthmatic patient, a substantial contribution of
respiratory muscle fatigue or weakness to the respiratory failure
is likely [see 14:VIII Respiratory Failure]. Extreme measures, such
as I.V. administration of isoproterenol, bronchial lavage to re-
move mucous plugs, and general anesthesia, are potentially
dangerous and rarely indicated.
Ancillary measures include use of controlled supplemental
oxygen for patients with arterial oxygen desaturation (O2 satura-
tion < 90%) and empirical broad-spectrum antibiotic therapy
(e.g., ampicillin, tetracycline, erythromycin, or trimethoprim-sul-
famethoxazole) for patients with fever and sputum purulence
that is not caused by eosinophils. There is at best only marginal
benefit from vigorous hydration, inhaled saline mists, mucolytic
therapy (e.g., acetylcysteine), and chest physiotherapy.
Additional Information
Additional information on asthma can be obtained from the
National Heart, Lung, and Blood Institute (www.nhlbi.nih.gov/
health/prof/lung/asthma/practgde.htm), the American Lung
Association (www.lungusa.org), and the American Thoracic
Society (www.thoracic.org). Information on occupational asthma
can be obtained at the Health, Environment, and Work Web site
(http://www.agius.com/hew/resource/ocasthma.htm).
Gerald W. Staton, Jr., M.D., participates in the speakers’ bureaus for Glaxo-SmithKline, Merck & Co., Inc., and InterMune, Inc.
Roland H. Ingram, Jr., M.D., has no commercial relationships with manufac-turers of products or providers of services discussed in this subsection.
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