Asthma

Definition
s
 Asthma: a chronic inflammatory disease of the respiratory system
characterized by bronchial hyperresponsiveness, episodic
exacerbation (asthma attacks), and reversible airflow obstruction;
manifests with reversible cough, wheezing, and dyspnea

 Acute asthma exacerbation: a reversible worsening of the

clinical features of asthma that develops over a short period
of time and can progress to life-threatening asthma; may be
the first manifestation of asthma in some patients

 Allergic asthma: the most common type of asthma; begins with

intermittent symptoms in childhood and is usually associated
with atopy (e.g., eczema, rhinitis) and a good response to
treatment (typically in childhood)

 Nonallergic asthma: an uncommon type of asthma that is not

related to atopy and is typically associated with a poor response to
standard treatment (e.g., ICS), typically > 40 years.
 Epidemiology
•Prevalence
• 5–10% of the US population
• More common in black than white patients
• For unknown reasons, the prevalence
• of asthma has been increasing over the past 20
years. [1]
•Sex: differs depending on age of onset
• ♂> ♀in patients < 18 years
• ♀ > ♂ in patients > 18 years
•Age of onset
• Allergic asthma: typically in childhood
• Nonallergic asthma: typically > 40 years
 Etiology

• The exact etiology of asthma remains unknown.

• Risk factors for asthma include:

• Family history of asthma
• Past history of allergies
• Atopic dermatitis
• Low socioeconomic status

• Several factors can trigger an initial asthma attack

or cause acute asthma exacerbation
 Asthma triggers
Allergic asthma Nonallergic asthma
(extrinsic asthma) (intrinsic asthma)

•Cardinal risk factor: atopy
•Environmental allergens: pollen (seasonal), dust mites,
domestic animals, mold spores
•Allergic occupational asthma from exposure to allergens
in the workplace (e.g., flour dust)
•Viral respiratory tract infections (one of the most
common stimuli, especially in children) [3]
•Cold air
•Physical exertion (laughter, exercise-induced asthma)
•Gastroesophageal reflux disease (GERD): often exists
concurrently with asthma
•Chronic sinusitis or rhinitis
•Medication: aspirin /NSAIDS (aspirin-induced
asthma), beta blockers
•Stress
•Irritant-induced occupational asthma (e.g., from
exposure to solvents, ozone, tobacco or wood smoke,
cleaning agents)
Pathophysiology
Pathophysiology
 Pathophysiology
• Type-specific pathophysiology

• Allergic asthma
• IgE mediated type 1 hypersensitivity to a specific allergen
• Characterized by mast cell degranulation and release of histamine
after a prior phase of sensitization

• Nonallergic asthma
• Irritant asthma: irritant enters lung → ↑ release of neutrophils
→ submucosal edema → airway obstruction

• Aspirin-induced asthma (NSAID-exacerbated respiratory disease)

is characterized by the Samter triad:
• Inhibition of COX-1 → ↓ PGE2 → ↑ leukotrienes
and inflammation → Submucosal edema
→ airway obstruction
• Chronic rhinosinusitis with nasal polyposis
• Asthma symptoms
Clinical features
Types
Diagnosis
Diagnostics
 Allergy workup: Consider if allergens are suspected to play a
significant role in exacerbations.
• Skin allergy tests: skin prick testing (SPT) or intradermal skin
testing
• CBC: possible eosinophilia
• Antibody testing, total IgE (increased), allergen-specific IgE
(increased)
 Evaluation for additional asthma triggers: e.g., see “Rhinitis”,
“Sinusitis”, “GERD”
 Additional diagnostic studies (not routinely recommended)
• Sputum analysis revealing one or more of the following:
o Curschmann spirals: whorled mucous plug in sputum
that is formed by shed bronchial epithelium
o Charcot-Leyden crystals: histopathologic finding in
patients with eosinophilic inflammation and/or
proliferation
o Creola bodies: aggregate of desquamated epithelial
cells
Differential
diagnoses
Medications
A 23-year-old man comes to the physician with dysuria and increased urinary
frequency. He is an active duty member of the US military and recently returned from
sub-Saharan Africa, where he had been stationed for the last year. The patient's
symptoms have persisted for several months and have failed to resolve following
antibiotic treatment. His blood eosinophil count is elevated. Urine microscopy shows
schistosome eggs. He is started on praziquantel and experiences improvement in his
symptoms. The elevated eosinophils in this patient contribute to the host defense
against schistosomiasis through which of the following mechanisms?

A. Antibody-dependent cell-mediated cytotoxicity

B. B lymphocyte chemotaxis
C. Complement activation
D. Immediate hypersensitivity
E. E. MHC class I antigen processing
A 23-year-old man comes to the physician with dysuria and increased urinary
frequency. He is an active duty member of the US military and recently returned from
sub-Saharan Africa, where he had been stationed for the last year. The patient's
symptoms have persisted for several months and have failed to resolve following
antibiotic treatment. His blood eosinophil count is elevated. Urine microscopy shows
schistosome eggs. He is started on praziquantel and experiences improvement in his
symptoms. The elevated eosinophils in this patient contribute to the host defense
against schistosomiasis through which of the following mechanisms?

A. Antibody-dependent cell-mediated cytotoxicity

B. B lymphocyte chemotaxis
C. Complement activation
D. Immediate hypersensitivity
E. E. MHC class I antigen processing
Eosinophils perform the following functions:

• Parasitic defense: Eosinophil proliferation and activation during multicellular parasitic infection is stimulated
by IL-5 produced by TH2 and mast cells (not to be confused with IL-4, which stimulates IgE production).
When a parasite invades the mucosa or enters the bloodstream, it is coated by IgG and IgA antibodies that
bind the Fc receptors located on the eosinophil cell surface. This triggers eosinophil degranulation and
release of cytotoxic proteins (eg, major basic protein) and reactive oxygen intermediates, substances that
damage and destroy antibody-bound parasites. This mechanism is an example of antibody-dependent cell-
mediated cytotoxicity (ADCC), which is also used by macrophages, neutrophils, and natural killer cells.

• Type I hypersensitivity reactions: Eosinophils also synthesize prostaglandins, leukotrienes, and cytokines
that contribute to the inflammation seen in late-phase type 1 hypersensitivity and chronic allergic reactions.
An 18-year-old man is evaluated for recurrent episodes of shortness of breath,
wheezing, runny nose, and watery eyes. The patient reports that his symptoms
have recently worsened since he started training outdoors for an upcoming
marathon. He does not use tobacco, alcohol, or illicit drugs. Skin testing is
performed to determine symptom triggers. A pricking device is used to apply
allergen extract underneath the skin. After 15 minutes, the patient develops
raised, erythematous plaques with surrounding erythema at the application
site. Which of the following mediators is the first to be released during the
pathogenesis of this patient's skin findings?

A. Histamine
B. Leukotriene D4
C. Major basic proteins
D. Platelet-activating factor
E. Prostaglandin D2a
An 18-year-old man is evaluated for recurrent episodes of shortness of breath,
wheezing, runny nose, and watery eyes. The patient reports that his symptoms
have recently worsened since he started training outdoors for an upcoming
marathon. He does not use tobacco, alcohol, or illicit drugs. Skin testing is
performed to determine symptom triggers. A pricking device is used to apply
allergen extract underneath the skin. After 15 minutes, the patient develops
raised, erythematous plaques with surrounding erythema at the application
site. Which of the following mediators is the first to be released during the
pathogenesis of this patient's skin findings?

A. Histamine
B. Leukotriene D4
C. Major basic proteins
D. Platelet-activating factor
E. Prostaglandin D2a
• This patient's shortness of breath and wheezing are suggestive of asthma, and his
rhinorrhea and watery eyes are suggestive of allergic rhinitis. Both of these
conditions are examples of type I hypersensitivity, which involves the triggering of
an allergic response via the binding of previously recognized antigen to IgE
antibodies on mast cells. Many type I hypersensitivity reactions are composed of
both an early and late phase.

• Histamine is housed in preformed granules of unactivated mast cells and plays an

important role in the early phase of type I hypersensitivity. Upon activation, mast
cells rapidly release histamine via degranulation, making histamine the first
chemical mediator to take effect. Once released, histamine triggers smooth muscle
contraction leading to bronchoconstriction, increases vascular permeability leading
to edema, and increases mucus secretion from glandular tissue.
A 22-year-old man comes to the office due to an intermittent cough for the past 6 months. He experiences slight
wheezing and difficulty breathing, especially in the nighttime and early morning. The patient has no recent history of
fever, chills, rigors, sputum production, or upper respiratory tract infections. During a basketball game last week, he had
an episode of wheezing for which he went to the emergency department; after 2 nebulizer treatments, the wheezing
resolved. He has been otherwise healthy and takes no medications. The patient does not use tobacco, alcohol, or illicit
drugs. He has lived in the same house for several years and has no pets. There is no family history of lung disease. Vital
signs are within normal limits. Lung examination reveals normal tactile fremitus and percussion on both sides. There
are no crackles, wheezing, or other adventitious sounds heard on lung auscultation. Cardiac examination reveals regular
heart sounds with no murmurs. The posteroanterior and lateral chest radiographs reveal no abnormalities. What will be
the most likely finding on pulmonary function tests?
A. Increased FEV1/FVC ratio
B. Normal testing but an obstructive pattern following methacholine challenge
C. Normal testing but decreased diffusing capacity of the lungs for carbon monoxide (DLCO)
D. Reduced FEV1/FVC and reduced DLCO
E. Reduced total lung capacity with normal FEV1/FVC
A 22-year-old man comes to the office due to an intermittent cough for the past 6 months. He experiences slight
wheezing and difficulty breathing, especially in the nighttime and early morning. The patient has no recent history of
fever, chills, rigors, sputum production, or upper respiratory tract infections. During a basketball game last week, he had
an episode of wheezing for which he went to the emergency department; after 2 nebulizer treatments, the wheezing
resolved. He has been otherwise healthy and takes no medications. The patient does not use tobacco, alcohol, or illicit
drugs. He has lived in the same house for several years and has no pets. There is no family history of lung disease. Vital
signs are within normal limits. Lung examination reveals normal tactile fremitus and percussion on both sides. There
are no crackles, wheezing, or other adventitious sounds heard on lung auscultation. Cardiac examination reveals regular
heart sounds with no murmurs. The posteroanterior and lateral chest radiographs reveal no abnormalities. What will be
the most likely finding on pulmonary function tests?
A. Increased FEV1/FVC ratio
B. Normal testing but an obstructive pattern following methacholine challenge
C. Normal testing but decreased diffusing capacity of the lungs for carbon monoxide (DLCO)
D. Reduced FEV1/FVC and reduced DLCO
E. Reduced total lung capacity with normal FEV1/FVC
This patient has exercise-induced respiratory symptoms causing decreased athletic
performance. Symptoms are exclusive to exercise but absent at other times of day.
Bronchoprovocation testing reveals an exerciseinduced decline in expiratory airflow of
25% (normal: <10%). Taken together, this presentation is consistent with exercise-
induced bronchoconstriction (EIB).

During exercise, minute ventilation increases. Rapid movement of large volumes of air
overwhelms the normal heating and humidification capacity of the upper airway (eg,
mouth instead of nose breathing). Therefore, the air entering the lower respiratory
tract is relatively cool and dry. This disrupts the airway surface lining fluid to trigger
mast cell degranulation, leading to bronchospasm.

In addition to these thermophysical effects on the airway surface, a role for

leukotrienes and T-helper cell 2– predominant inflammation has been identified in
patients with recurrent episodes of EIB. Therefore, EIB is often considered to be a
subtype of intermittent asthma , and premedication is recommended with an inhaled
corticosteroid (ICS) and beta agonist (eg, budesonide-formoterol).
A 24-year-old woman with a history of intermittent asthma is experiencing an increase
in asthma symptoms in her 29th week of pregnancy. Her symptoms had been well
controlled with occasional inhaled albuterol, but she now requires her inhaler up to 10
times per week. Based on a detailed review of her symptoms, it is determined that she
now has mild persistent asthma . Which of the following is the best approach to
management?

A. Add daily oral montelukast

B. Prescribe a short course of oral glucocorticoids
C. Add a daily inhaled corticosteroid
D. Do not change therapy until after delivery
E. Add daily inhaled salmeterol
A 24-year-old woman with a history of intermittent asthma is experiencing an increase
in asthma symptoms in her 29th week of pregnancy. Her symptoms had been well
controlled with occasional inhaled albuterol, but she now requires her inhaler up to 10
times per week. Based on a detailed review of her symptoms, it is determined that she
now has mild persistent asthma . Which of the following is the best approach to
management?

A. Add daily oral montelukast

B. Prescribe a short course of oral glucocorticoids
C. Add a daily inhaled corticosteroid
D. Do not change therapy until after delivery
E. Add daily inhaled salmeterol
This patient has asthma that has progressed to a classification of mild persistent
during pregnancy. It is appropriate to increase her pharmacologic therapy to Step 2
with a low-dose, daily, inhaled glucocorticoid (e.g., fluticasone, budesonide, etc.).
Patients with asthma who become pregnant may experience a change in their asthma
symptoms. For worsening symptoms, it is important to modify treatment in a stepwise
approach similar to that used for a non-pregnant patient. Medications commonly used
for asthma control appear to carry minimal or no extra risk during pregnancy,
including teratogenicity. Studies conducted during the first trimester are often
equivocal, do not adequately control for confounders, and/or find adverse effects only
at high doses. It is good practice to consult the latest evidence before prescribing any
medication during pregnancy.