Flashcards in Fifteen Deck (23):
What are some different categories of asthma triggers? What are some examples of each?
House dust mite (Dermatophagoides)
Mold (Alternaria, Aspergillus, etc)
Cockroach (including feces)
Dusts (mineral, plant, etc)
Vapors and fumes
Specifi c foods
Gastroesophageal refl ux
Explain the hygiene hypothesis.
The immunopathogenesis of asthma is thought to be due to
the promotion of the allergic asthmatic phenotype resulting
from the predominance of Th2 over Th1 cytokine response
during early life, also referred to as the Hygiene Hypothesis
(Fig. 21.1). This theory stemmed from the observation
of increasing prevalence of asthma in industrialized Western
societies. Early childhood exposures in these industrialized
countries favoring the Th2 response include widespread use
of antibiotics, an urban rather than rural environment, and sensitization
to cockroaches, which are believed to lead to the
development of the allergic asthmatic phenotype. On the other
hand, the higher propensity for microbial exposure in developing
countries with increased prevalence of infections from
Mycobacterium tuberculosis, measles virus, and hepatitis A
virus all enhance Th-1 mediated responses which reduce the
development of an atopic/allergic immunologic phenotype.
Other factors believed to be protective against the asthma phenotype
include contact with other siblings and attendance at a
day-care facility during the fi rst 6 months of life.
What things should be performed to diagnose asthma?
The diagnosis of asthma is based on the presence of episodic
symptoms of completely or partially reversible airfl ow
obstruction and/or airway hyperresponsiveness, and only with
exclusion of alternative diagnoses. The evaluation includes at
least a detailed medical history, physical exam, and spirometry.
Additional studies may also be indicated, such as a full
pulmonary function test (PFT) combined with a methacholine bronchoprovocation challenge (see below) and chest imaging
studies (Chaps. 15 and 16).
What symptoms should lead you to think of asthma?
Symptoms consistent with
asthma include: chronic episodic cough that is worse particularly
at night; recurrent diffi culty in breathing or chest tightness;
and recurrent wheezing upon expiration (Chap. 14).
However, symptoms may vary depending on the severity of
asthma. Severe asthmatics may present having all of the symptoms
listed, while patients with mild asthma may complain of
just one symptom such as intermittent cough (the so-called
What physical exam findings might be consistent with asthma?
Physical examination fi ndings in patients with uncontrolled
asthma or an acute asthma exacerbation include tachypnea,
use of the accessory muscles of respiration, audible
wheezing, and a prolonged forced expiratory phase. However,
given the episodic nature of the airfl ow limitation in
asthma, many patients with intermittent, mild, or even moderate
asthma may have a completely normal physical exam.
It is also important to emphasize that even in patients with
severe disease, lack of wheezing does not exclude asthma,
since reduced airfl ow may attenuate chest physical fi ndings.
Physical signs of atopy such as nasal congestion and drainage
and/or nasal polyps and eczema may help support a diagnosis
of allergic asthma.
Explain what spirometry can tell you about the condition of an asthmatic patient and how.
Spirometry is the clinical mainstay to objectively confi rm
the reversibility of airfl ow obstruction in patients with asthma
(Chap. 16). Given the normal decline in spirometric airfl ow
measures with aging, the National Asthma Education and
Prevention Program (NAEPP) guidelines recommend using
age-adjusted FEV1/FVC thresholds for determining the presence
of airfl ow obstruction (Table 21.2). The FEV1/FVC is
calculated by dividing the actual FEV1 in liters (not the percent of predicted) by the actual FVC in liters and multiplying
the resulting ratio by 100%. An FEV1/FVC below the lower
limits of normal (LLN) for a patient’s age confi rms the
presence of airfl ow obstruction, and also indicates asthma
that is not well-controlled. To confi rm the reversibility of
airfl ow obstruction after baseline spirometry shows airfl ow
obstruction, a short-acting bronchodilator such as albuterol is
administered at a dose of up to 500 μg either by metered-dose
inhaler or by nebulization. A postbronchodilator increase
in the actual FEV1 of ≥12% and ≥200 mL above the prebronchodilator
baseline indicates at least partial reversibility
of airfl ow obstruction.
Explain what PEFR is and how it can be used. When are additional PFT tests (aside from spirometry) warranted?
Measurement of peak expiratory fl ow rate (PEFR) using
an inexpensive portable device has been employed in the diagnosis
and monitoring of asthma. An improvement in PEFR before
and after bronchodilator administration of 60 L/min or 20%, a
20% day-to-day PEFR variability, or a >10% intraday PEFR
variability when measured twice daily are suggestive evidence
of asthma. However, peak fl ows are highly effort-dependent
and variable, making them less reliable than spirometrically
derived airfl ow measurements. Despite its limitations, PEFR
measurement may be useful for monitoring airfl ow limitation
in patients with poor perception of their asthma symptoms. The
PEFR is also useful in identifying environmental triggers, and
in documenting work-related asthma. Additional pulmonary
function tests are not routinely necessary unless other pulmonary
conditions are suspected, for example, a reduced DLCO in
COPD or a limitation of the inspiratory fl ow-volume loop in
vocal chord dysfunction (Chaps. 16 and 33).
Explain what the methacholine challenge test is, how it is used, and what the results mean.
In patients with normal baseline spirometry, a bronchoprovocation
challenge test can be employed to demonstrate the bronchial hyperresponsiveness or airway hyperreactivity typical
of asthma. The degree of bronchial hyperresponsiveness
is classifi ed based on the [methacholine] provoking a ê 20%
reduction in FEV1 or FVC (PC20). A PC20 < 4.0 mg/mL
indicates positive bronchial hyperresponsiveness, although
some asthmatics may have values in the borderline range
< 16.0 mg/mL (Table 21.3). Although methacholine bronchoprovocation
challenge is a highly sensitive test in diagnosing
asthma, it has a low specifi city; a positive test can also be
present in allergic rhinitis, COPD, bronchiectasis, and cystic
fi brosis. Aside from methacholine, other bronchoprovocating
agents such as histamine, mannitol, patient-specifi c aeroallergens,
exercise, and dry air also are used to detect bronchial
What are two forms of allergy testing that are performed and why are they performed?
Allergy testing may be indicated in some asthmatics
with persistent asthma and can help identify asthma environmental
triggers that may be amenable to environmental
control or desensitization therapy. Skin allergy (pin-prick)
testing is considered the fi rst-line method for determining
allergic status because of its simplicity, effi ciency, relatively
lower cost, and high sensitivity. Despite its cost, serum [IgE]
testing for regional and indoor allergens is more commonly
being employed as the initial test to determine allergy status. This approach is taken particularly by physicians not trained
in skin testing, or for certain patients with severe persistent
asthma requiring moderate-to-high doses of corticosteroids or
even systemic corticosteroids. In this subset of patients, measurement
of total serum [IgE] and documentation of hypersensitivity
to an aeroallergen is a prerequisite to prescribing
therapy with a monoclonal anti-IgE antibody.
What does the fractional excretion of NO tell you?
Measurement of the fractional excretion of nitric oxide
(FeNO) is a well-studied non-invasive method of gauging the
presence of active airway infl ammation. An FeNO >45 parts
per billion (ppb) is considered a marker for active eosinophilic
airway infl ammation, while an FeNO <25 ppb is highly
predictive of its absence. These FeNO levels increase during
exacerbations of asthma and vary with titration of inhaled corticosteroid
therapy. However, recent randomized control trials
reached inconclusive results when evaluating whether the use
of FeNO to guide anti-infl ammatory therapy in predominantly
mild-to-moderate asthma improves clinical outcomes.
When might chest imaging studies be recommended?
Chest imaging studies are not routinely recommended
for the diagnosis of asthma. However, in patients with recent
onset of asthma symptoms or in those with moderate-tosevere
symptoms who are not responding to recommended
therapy, obtaining a chest radiograph is prudent practice to
exclude other diagnoses such as pneumonitis, pulmonary
vascular congestion, and pneumothorax (Chaps. 15 and 37).
In patients with poorly controlled, severe persistent asthma,
and with fi xed airway obstruction despite maximal therapy, a
chest HRCT may reveal the presence of bronchiectasis, obliterative
bronchiolitis due to environmental chemical exposure,
or other serious pulmonary conditions.
What are some key general principles concerning asthma pharmacological treatment?
The pharmacological treatment of asthma invariably involves
selection of a rescue bronchodilator, usually a short-acting β2
adrenergic receptor agonist. In patients with persistent asthma,
one or more controller medications are usually required, such
as inhaled corticosteroids, long-acting a2 agonists, leukotriene
modifi ers, and other immunomodulators.
What are two different categories of beta agonists? How are they used? What are some examples of each?
Pharmacokinetically, the β2 adrenergic agonists are classifi
ed based on their selectivity, onset of action, and duration of
action (Table 21.4). For example, albuterol is the most widely
used rescue bronchodilator for asthma because its β2 selectivity
causes fewer cardiovascular β1 side effects like tachycardia
than do the nonselective β-agents terbutaline and epinephrine.
Albuterol has a rapid onset of action (10-15 min) but a short
duration, lasting only 4-6 hours. Long-acting a2-adrenergic
receptor agonists (LABAs) have durations of ~12 hours and
thereby allow twice-daily dosing. Of the two clinically available LABA formulations, formoterol has a more rapid onset of
action (as early as 5 min) than does salmeterol (30 min).
What are two examples of anti-cholinergics? What is the difference between them? What do they do? How are they used?
Anticholinergics play a secondary role as bronchodilator
therapy for asthma by blocking the acetylcholine released
from vagal parasympathetic nerves from activating muscarinic
type 3 (M3)-receptors on airway smooth muscle cells,
thereby reversing bronchoconstriction. Ipratropium is an
inhaled short-acting anticholinergic that may be combined
with a short-acting β2-agonist during the fi rst 24 hours of
treatment for a severe asthma exacerbation. Meanwhile, there
is preliminary evidence that the inhaled long-acting M3 anticholinergic
tiotropium may have a role as an adjunctive bronchodilator
in patients with persistent asthma.
When are inhaled corticosteroids used? What is their mechanism of action? What are the results? What are the side effects? What is an examples?
Inhaled corticosteroids are the fi rst-line treatment for
persistent asthma and are primarily responsible for controlling
airway infl ammation (Table 21.5). Corticosteroids enter
the cell nucleus to inhibit gene transcription and synthesis
of infl ammatory cytokines, enzymes, and other mediators of
asthma. By such actions, corticosteroids reduce the number
of infl ammatory cells (eosinophils, mast cells, T-lymphocytes,
macrophages, and dendritic cells) in the airway. These antiinfl
ammatory agents also increase β-adrenergic responsiveness
and reduce mucus hypersecretion and endothelial leakage.
Inhaled corticosteroids are effective in controlling asthma
symptoms, reducing frequency of exacerbations, and improving
health-related quality of life measures in asthmatics.
Side effects of inhaled corticosteroids include oral thrush
(candidiasis), respiratory infections, and mild adrenal suppression.
When are systemic glucocorticoids used? What is an examples?
On the other hand, systemic (oral or parenteral)
corticosteroids normally are reserved for patients suffering from an acute asthma exacerbation. They are also useful to
treat patients with severe persistent asthma that is uncontrolled
despite maximal therapy with high dose inhaled corticosteroid,
bronchodilators, and other immunomodulators.
What are leukotriene modifiers? What are 3 examples? How does each work? What are the results?
Leukotriene modifi ers are secondary or add-on antiinfl
ammatory controller medications for persistent asthma.
Elevated cysteinyl-leukotriene levels in asthmatic airways
cause bronchoconstriction, airway hyperresponsiveness, mucus
hypersecretion, and plasma transudation. In this context, the
leukotriene modifi ers improve asthma airway infl ammation by
inhibiting 5-lipoxygenase as with zileuton, or by binding tocysteinyl-leukotriene receptors, as do montelukast and zafirlukast.
Leukotriene modifi ers have been shown to signifi cantly
improve the FEV1, although they do so with less potency than
either inhaled corticosteroids or bronchodilators.
What are some examples of combo-inhalers? Why are they useful?
Several studies have demonstrated that combining two or more
types of anti-infl ammatory agents and bronchodilators may
provide additive benefi ts in terms of improvements in lung
function and symptom control. Combinations of inhaled corticosteroids
and LABAs are delivered via special inhalational
devices, with several of the more common pairings being salmeterol/
fl uticasone, budesonide/formoterol, and mometasone/
formoterol. These combinations also may help improve a
patient’s adherence to a simplifi ed asthma regimen.
What are high affinity anti-IgE antibodies? How do they work? What are the results? What is an example?
Allergic asthma is characterized by elevation of specifi c IgE
levels against one or more aeroallergens, contributing to airway
infl ammation and bronchial hyperresponsiveness. Omalizumab
is a humanized monoclonal antibody that blocks the binding
of IgE to the high-affi nity IgE receptors found on mast cells,
thus preventing their activation and release of histamine and
other infl ammatory mediators. Omalizumab has been shown
to signifi cantly reduce the number of asthma exacerbations, as
well as the dose of inhaled or oral corticosteroids in patients
with steroid-dependent persistent allergic asthma.
Classification of asthma
Memorize the chart.
Explain how asthma is treated pharmacologically based on the stepwise approach.
Intermittent asthma only requires the as-needed use
of a short-acting β-agonist bronchodilator such as albuterol.
Persistent asthma describes patients with daytime symptoms
more than twice per week, as well as those who experience
nocturnal awakenings 3-4 times per week or use their rescue
bronchodilator (eg, albuterol) more than twice per week. Persistent
asthma also includes those patients with functional
limitations at home, school, or work, or who require oral/
systemic corticosteroids for exacerbations at least twice a year.
Such persistent asthma patients require controller anti-infl ammatory
medications, particularly inhaled corticosteroids. For
patients with moderate-to-severe degrees of persistent asthma,
adding other initial therapies may be necessary, such as longacting
bronchodilators, leukotriene modifi ers, monoclonal
anti-IgE antibodies, and even oral corticosteroids. All patients
should be assessed periodically for their asthma control based
on symptom frequency, use of rescue bronchodilators, and
periodic spirometry or daily self-reported peak airfl ow measurements.
Therapy should be “stepped up” using the NAEPP
guidelines if asthma is not well controlled by adding one or
more controller medications. If a patient’s asthma has been
well-controlled for at least three months, then a “step-down”
along the same guidelines should be considered, such as
reducing their inhaled corticosteroid dosing.
Explain the two types of asthma immunotherapy and how they're performed.
Asthma immunotherapy, or the injection of increasing concentrations
of a specifi c allergen over time, has long been
employed by allergists, otorhinolaryngologists, and some pulmonologists
in the treatment of allergic asthma. Such immunotherapy
stimulates the patient’s synthesis of IgE-blocking
antibodies as well as allergen-specifi c IgG, thereby reducing
IgE-mediated allergic asthma responses. Such injection allergen immunotherapy reduces asthma symptoms and bronchial
hyperresponsiveness, as well as the need for asthma medications.
Sublingual allergen immunotherapy is also available
for patients who are averse to injection immunotherapy.
Patients undergoing immunotherapy should be monitored for
side effects that can include local and systemic hypersensitivity
reactions. An epinephrine injection kit and resuscitation
equipment should be available for use by a trained personnel
in case of an anaphylactic reaction.