SEVEN YEAR-OLD BOY
WITH COUGH
Stanley Lipper M.D.
Graphics, Arrangements, Presentation
Dr. Viera Lima
Presenting complaint
A seven year-old boy is brought to your office
by his mother. She has observed over the last 2
days that he has developed a persistent cough
and an audible wheeze at night and in the early
morning. This is especially noticeable on
exercise.
Past medical history
In the past year she has noticed that he often
coughs and exhibits shortness of breath with
exercise. With viral illnesses, he coughs for 2
weeks and he also wheezes. He has had no
hospitalizations or trips to the emergency with
chest symptoms. He has only been treated with
antibiotics and cough syrups. He complains of
year-round nasal stuffiness, some sneezing and
rubbing of the nose and eyes.
Family history
The child’s father smokes in the home and
his mother suffers from hay fever. He has no
siblings. There are no pets.
Physical examination
The child appears lethargic. He is afebrile and
exhibits tachypnea and tachycardia. On chest
auscultation, there are sibilant rhonchi
(wheezes) and he is using accessory breathing
muscles. His height and weight are normal for
age.
Special investigations
Chest X ray is normal. Hemoglobin is normal
and there is a mildly elevated white cell
count with a peripheral eosinophilia.
Abundant eosinophils are present in the
sputum. Spirometry is normal with FEV1
93% of predicted value and FEV1/FVC ratio
of 0.80. Skin tests are positive for dust
mites, cat dander and seasonal molds.
WHAT IS YOUR
DIAGNOSIS?
ASTHMA
Clinicopathological Correlation
Objectives
1. Discuss a typical example of childhood asthma.
2. Become familiar with Type 1, atopic hypersensitivity in this clinical
setting.
3. Understand the pathogenesis of this disease.
4. Become familiar with the morphological changes in this disease.
Definition of asthma
A chronic inflammatory disorder of the airways that
causes episodic wheezing, breathlessness, chest
tightness and cough associated with partially
reversible bronchospasm, (bronchoconstriction)
and airflow obstruction/limitation in susceptible
individuals.
Airway Hyperresponsiveness
Asthmatic airways constrict in response to various
triggering stimuli such as environmental allergens,
cold air, exercise and viral respiratory infections.
Asthma Triggers
Various triggers in susceptible individuals result
in acute and chronic airway inflammation and
bronchial hyperresponsiveness which might
progress to airway remodeling unless treated
effectively.
Asthma Triggers (allergens):
"Seasonal" pollens. Year-round dust mites,
molds, pets, and insect parts. Foods, such
as fish, egg, peanuts, nuts, cow's milk, and
soy. Additives, such as sulfites. Work-related
agents, such as latex.
Asthma Triggers (irritants):
Respiratory infections, such as those caused by viral "colds," so-called non atopic asthma (rhinovirus,
parainfluenza virus).
Drugs, such as aspirin, other NSAIDs (nonsteroidal anti-inflammatory drugs), and Beta Blockers (used to treat
blood pressure and other heart conditions).
Tobacco smoke.
Outdoor factors, such as smog, weather changes, and diesel fumes.
Indoor factors, such as paint, detergents, deodorants, chemicals, and perfumes..
GERD (gastro-esophageal reflux disorder).
Exercise, especially under cold dry conditions.
Work-related (occupational) factors, such as chemicals, dusts, gases, and metals.
Emotional factors, such as laughing, crying, yelling, and distress.
Hormonal factors, such as in premenstrual syndrome.
PATHOGENESIS OF ALLERGIC
ASTHMA
1. Atopy: immediate hypersensitivity
reaction - allergen reacting with IgE
antibody bound to mast cells in
previously sensitized individual.
2. Genetic predisposition:
susceptible individuals with bronchial
hyperresponsiveness have a genetic
predisposition to type 1 (atopic)
hypersensitivity and are prone to
acute and chronic airway
inflammation.
Role of inflammation
Many cell types and inflammatory mediators
Model for allergic asthma
1. Inhaled allergen encounters an airway dendritic cell, eliciting a TH2 response producing interleukins
which stimulate B cells causing IgE Ab production. This reacts with mast cell IgE Fc receptor and
interleukins are produced causing eosinophil recruitment (priming or sensitization). TH2 cells also
produce interleukins and granulocyte monocyte colony stimulating factor (GM-CSF) which recruit
eosinophils.
Role of inflammation
2. Re-exposure to allergen: immediate reaction triggered by Ag induced cross linking of IgE bound to IgE
receptors on presensitized mast cells. They release mediators that open tight junctions between epithelial
cells so that Ags can enter the mucosa and activate mucosal mast cells and eosinophils which release
additional mediators. Mediators induce bronchospasm, increase vascular permeability and mucus production
and recruit additional mediator-releasing cells from blood (neutrophils, eosinophils, basophils, lymphocytes,
monocytes). Fresh round of mediator release from leukocytes, endothelium and epithelial cells. Eosinophils
release major basic protein, eosinophil cationic protein which damage epithelium and cause airway
constriction.
Morphology
1. Overdistention because of overinflation: occlusion of bronchi and bronchioles by thick, tenacious
mucus plugs. Plugs contain whorls of shed epithelium (Curschmann spirals). Many eosinophils and
Charcot-Leyden crystals (eosinophil membrane protein).
2. Airway remodeling: thickened bronchial epithelial BM, edema and inflammatory infiltrate in
bronchial walls, eosinophils and mast cells, hypertrophy of submucosal glands, hypertrophy of
bronchial wall muscle.
Curschmann spiral Charcot-Leyden crystal
Bronchus
Eosinophils in wall of bronchus
Wall of bronchus with thick BM,
smooth muscle hypertrophy
Clinical Course
Classic asthma attack lasts several hours and is followed by coughing up of copious mucus.
In some patients, symptoms persist at a low level all the time. In its most severe form,
status asthmaticus occurs with cyanosis and even death.
Hyperinflated lungs in status asthmaticus
Cut surface essentially appears normal
Suggested Reading Material
Robbins Pathologic Basis of
Disease, 7th Edition. 723-727