Asthma

This disease is characterized by increased responsiveness of the airways to various stimuli and is manifested
by inflammation and widespread narrowing of the airways that changes in severity, either spontaneously or
as a result of treatment.

Pathology
The airways have hypertrophied smooth muscle that contracts during an attack, causing bronchoconstriction
(Figure 4-1B). In addition, there is hypertrophy of mucous glands, edema of the bronchial wall, and
extensive infiltration by eosinophils and lymphocytes (Figure 4-14). The mucus is increased and is also
abnormal; it is thick, tenacious, and slow moving. In severe cases, many airways are occluded by mucous
plugs, some of which may be coughed up in the sputum. The sputum typically is scant and white.
Subepithelial fibrosis is common in patients with chronic asthma and is part of the process called
remodeling. In uncomplicated asthma, there is no destruction of alveolar walls and there are no copious
purulent bronchial secretions. Occasionally, the abundance of eosinophils in the sputum gives a purulent
appearance, which may be wrongly ascribed to infection.

Etiology and Pathogenesis (EGANS 11TH EDITION p.536)

In the genetically susceptible host, allergens, respiratory infections, certain occupational and environmental
exposures, and many unknown hosts or environmental stimuli can produce the full spectrum of asthma,
with persistent airway inflammation, bronchial hyperreactivity, and subsequent airflow obstruction. When
inflammation and bronchial hyperreactivity are present, asthma can be triggered by additional factors,
including exercise; inhalation of cold, dry air; hyperventilation; cigarette smoke; physical or emotional
stress; inhalation of irritants; and pharmacologic agents, such as methacholine and histamine. When a
patient with asthma inhales an allergen to which he or she is sensitized, the antigen cross-links to specific
IgE molecules attached to the surface of mast cells in the bronchial mucosa and submucosa. The mast cells
degranulate rapidly (within 30 minutes), releasing multiple mediators including leukotrienes (previously
known as slow-reacting substance of anaphylaxis [SRS-A]), histamine, prostaglandins, platelet-activating
factor, and other mediators. These mediators lead to smooth muscle contraction, vascular congestion, and
leakage resulting in airflow obstruction, which can be assessed clinically as a decline in FEV1 or peak
expiratory flow rate (PEFR). This is the early (acute) asthmatic response, which is an immediate
hypersensitivity reaction that usually subsides in about 30 to 60 minutes. In approximately 50% of asthmatic
patients, however, airflow obstruction recurs in 3 to 8 hours. This late asthmatic response is usually more

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severe and lasts longer than the early asthmatic response. The late asthmatic response is characterized by
increasing influx and activation of inflammatory cells such as mast cells, eosinophils, and lymphocytes.

REMEMBER!!! (Gary Persing p. 143-144)

When the asthmatic inhales an allergen that he or she is sensitive to, mast cells located in the bronchial
mucosa and submucosa release the following chemical mediators:
a. Histamine
b. Leukotrienes
c. Platelet-activating factor
d. Prostaglandins

The release of these substances result in:

a. Bronchoconstriction
b. Mucosal edema
c. Increased mucus production
d. Accumulation of eosinophils in the blood and sputum
e. Inflammation

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 Clinical Presentation and Diagnosis

The diagnosis of asthma requires clinical assessment supported by laboratory evaluation. Because no single
measurement can establish the diagnosis with certainty and physical examination can be entirely normal
between episodes, the history plays a key role in suggesting, and later establishing, the diagnosis of asthma.
The classic symptoms of asthma are episodic wheezing, shortness of breath, chest tightness, and cough.
The absence of wheezing does not exclude asthma, and sometimes a cough can be the only manifestation
(cough-variant asthma). Not all wheezing is due to asthma, however. Obstruction of the upper airway by
tumors, laryngospasm, aspirated foreign objects, tracheal stenosis, or functional laryngospasm (vocal cord
dysfunction) can mimic the wheezing of asthma.

Confirmation of the diagnosis of asthma requires demonstration of reversible airflow obstruction.

Pulmonary function tests may be normal in asymptomatic patients with asthma, but more commonly they
reveal some degree of airway obstruction manifested by decreased FEV1 and FEV1/FVC ratio. By
convention, improvement in the FEV1 by at least 12% and 200 ml after administration of a bronchodilator
is considered evidence of reversibility. Spontaneous variation in self-recorded PEFR by 15% or more also
can provide evidence of reversibility of airway obstruction.

Asthmatics evaluated in a symptom-free period may have a normal chest x-ray examination and normal
pulmonary function tests. Under these circumstances, provocative testing can be used to induce airway
obstruction. Bronchoprovocation is a well-established method to detect and quantify AHR (Airway
Hyperresponsiveness). Pharmacologic agents, including acetylcholine, methacholine, histamine, cysteinyl
leukotrienes, and prostaglandins, and physical stimuli such as exercise and isocapnic hyperventilation with
cold, dry air have been used to detect, quantify, and characterize nonspecific AHR (Airway
Hyperresponsiveness) in asthma.

The most commonly used stimulus for bronchoprovocation is methacholine. The generally accepted
criterion for hyperresponsiveness is a decrease in FEV1 by 20% or more below the baseline value after
inhalation of methacholine. The methacholine provocation test has few false negative results (<5%), but a
false-positive result may be found in 7% to 8% of the average population and patients with other obstructive
lung diseases. Elevated IgE levels and eosinophilia may be present in patients with asthma, but their
presence is not specific, and their absence does not exclude asthma, rendering them not useful for the
diagnosis. Although arterial blood gas analysis is not helpful or necessary in diagnosing asthma, it can be
helpful in assessing the severity of an acute asthma attack. A patient experiencing an acute asthma attack
usually has a low PaCO2 as a result of hyperventilation. A normal PaCO2 in such a situation indicates a
severe attack and impending respiratory failure.

Clinical Signs and Symptoms

1. Mild wheezing and coughing initially, which may progress to severe dyspnea if the attack is not reversed.
2. The cough is initially nonproductive, progressing to a productive cough by the end of the episode.
3. Secretions contain high levels of eosinophils.
4. Intercostal and supraclavicular retractions.
5. The use of accessory muscles to breathe (in a severe attack).
6. Paradoxical pulse: systolic blood pressure is 10 mm Hg higher on expiration than on inspiration.
7. Tachycardia and tachypnea
8. ABG levels initially reveal hypoxemia and low PaCO2. PaCO2 increases as the attack worsens and the
patient begins to tire.
9. Cyanosis

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 Classifications of Asthma (based on severity)

1. Intermittent
a. This is the least severe of the four classifications.
b. Symptoms of wheezing or coughing are experienced no more than twice per week.
c. The patients in this category generally have FEV1 and peak expiratory flow (PEF) values of at least 80%
of predicted.
d. Routine management generally consists of beta-2 agonists (SABAs), as needed.
e. Exacerbation of symptoms rarely results in emergency department treatment or hospitalization.

2. Mild persistent
a. Symptoms of coughing or wheezing are experienced more than twice per week but less than once per
day.
b. Symptoms affect the patient’s daily activity and sleep during the night; nocturnal coughing, wheezing,
or dyspnea is experienced more than twice per month.
c. The patients in this category generally have FEV1 and PEF values of at least 80% of predicted.
d. Routine management generally consists of ICS therapy to control symptoms and the use of a SABA, as
needed.
e. Emergency department treatment for exacerbations occurs periodically and may occasionally result in
hospitalization.

3. Moderate persistent
a. Symptoms of coughing or wheezing are experienced almost daily in this category.
b. Exacerbation of symptoms are experienced at least twice per week and may persist for several days.
c. Symptoms affect the patient’s daily activity and sleep during the night; nocturnal coughing, wheezing,
or dyspnea is experienced more than once per week.
d. The patients in this category generally have FEV1 and PEF values of 60% to 80% of predicted.
e. Daily management generally consists of a SABA as needed for symptoms and not to exceed 3-4 times
per day; LABA for nocturnal symptoms; ICS daily. f. Patients in this category routinely require emergency
department treatment or require hospitalization.

4. Severe persistent
a. This is the worst category of the four. Symptoms of coughing or wheezing are experienced almost
continually.
b. Exacerbations are frequent and may last for weeks.
c. Symptoms affect the patient’s daily activity and sleep during the night; nocturnal coughing, wheezing,
or dyspnea is experienced almost every night.
d. The patients in this category generally have FEV1 and PEF values of 60% or less of predicted.
e. Daily management generally consists of a SABA as needed for symptoms, not to exceed 3 to 4 times per
day; LABA and oral corticosteroids for nocturnal symptoms and frequent exacerbations; ICS daily.
f. Patients in this category routinely require emergency department treatment or require hospitalization.

Management
The goal of asthma management is to maintain a high quality of life for the patient, uninterrupted by asthma
symptoms, side effects from medications, or limitations on the job or during exercise. This goal can be
accomplished by preventing acute exacerbations, with their potential mortality and morbidity, or by
returning the patient to a stable baseline when exacerbations occur. Asthma management relies on the

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following four integral components recommended by the National Asthma Education Program (NAEP)
expert panel:
1. Objective measurements and monitoring of lung function
2. Pharmacologic therapy
3. Environmental control
4. Patient education

outlines the stepwise approach currently recommended for long-term management of asthma. This
approach provides a framework for an individually tailored dose of medication based on the severity of
asthma in any patient at a particular time. This approach acknowledges that asthma is a chronic and dynamic
disease, which needs optimum control. Control of asthma is defined as minimal to no chronic diurnal or
nocturnal symptoms, infrequent exacerbations, minimal to no need for beta-2 agonists, no limitation to
exercise activity, PEFR or FEV1 greater than 80% predicted with less than 20% diurnal variation, and
minimal to no adverse effects of medication.

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Asthma Preventative Drugs
1. Cromolyn sodium (Intal): mast cell stabilizer referred to as a non-corticosteroid anti-inflammatory drug
2. Leukotriene modifiers: zafirlukast (Accolate) or montelukast (Singulair)

Respiratory Medications
I. Treatment (During an Attack)
1. Rescue SABAs such as albuterol or Xopenex
2. IV fluids
3. O2 therapy
4. IV corticosteroids

Status Asthmaticus: a severe asthmatic attack that responds poorly to bronchodilator therapy and is
associated with signs or symptoms of potential respiratory failure
1. Patient should be hospitalized immediately
2. Hydration
3. IV corticosteroids
4. Supplemental O2 5. Close monitoring of ABG levels and pulse oximetry (SpO2)
6. Bronchodilating agents
7. Severe asthma resulting in respiratory failure (hypoxemia, hypercapnia and increased work of breathing)
requires ventilator support.

Nocturnal Asthma
1. Nocturnal (nighttime) symptoms are seen in up to 75% of all patients with asthma and even in those who
have mild intermittent or mild persistent asthma.
2. Mechanisms resulting in nocturnal symptoms may be related to changes in vagal tone, body temperature,
mediators, epinephrine, inflammation, and β2-receptor function during sleep.
3. Other causes may include aspiration, sleep apnea, increased mucus production, sinusitis,
gastroesophageal reflux, and the normal decrease in lung function when the patient is sleeping.
4. First line management is ICS. May also be managed by LABA.

Occupational Asthma

1. Characterized by increased wheezing or coughing while at work or within several hours after leaving
work and improving on days off from work.
2. Diagnosis may be made by measuring peak flows while at work.
3. The most common workplace causes include formaldehyde, grain dust, cigarette smoke, and avian
proteins.

Exercise-Induced Asthma (EIA)

1. Characterized by symptoms occurring 5 to 15 minutes after strenuous exercise that spontaneously resolve
in about 1 hour.
2. The exact cause of EIA is not clear but may be related to:
a. Heat or water loss from the respiratory tract mucosa
b. Hyperventilation, resulting in the release of bronchoconstricting chemical mediators
c. Rapid rewarming of the airway, resulting in vascular congestion, increased permeability, and
edema causing airway obstruction
3. SABAs and/or LABAs may be used beneficially before exercise along with asthma preventives such as
cromolynsodium, Singulair, ornedocromil sodium (Tilade) or the leukotriene modifiers such as zafirlukast
or montelukast.
4. Some non-asthma medications such as inhaled furosemide (Lasix) and inhaled heparin have also been
used to treat EIA.

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5. Nonpharmacologic measures used to reduce the incidence of EIA include:
a. Wear a mask to cover the nose and mouth during exercise in cold weather.
b. Warm up before exercise.
c. Exercise in warm, humidified environments.
d. Allow for a cooling down period after exercise.

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