Asthma Pathogenesis 2022 Flashcards
1
Q
1. Based on the International Study of Asthma and Allergies in Childhood (ISAAC), what is the closest estimate of prevalence of diagnosed childhood asthma for adolescents aged 13 and 14 years in the United States? A. < 3% B. 3 to < 6% C. 6 to 9% D. > 9%
A
- D, > 9%, p. 768-9.
The prevalence of asthma varies widely among countries from 3 to 5% in countries such as Indonesia and China, to more than 20% in countries such as Canada and New Zealand. The International Study of Asthma and Allergies in Childhood (ISAAC) reported the prevalence of diagnosed childhood asthma in adolescents ages 13 and 14 years old of > 9% in the U.S. (Figure 47.1, p.769)
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
2
Q
- A 50-year-old man with poorly controlled asthma is admitted in severe distress. On the second hospital day he dies of respiratory failure. An autopsy is performed.
What histopathologic findings are seen in the lungs?
A. Absent mucus production
B. Bacterial overgrowth
C. Decrease in angiogenic factors
D. Increased airway wall thickness
A
- D, Increased airway wall thickness, p. 771.
Airway wall thickening in asthma is related to disease severity and duration with increase from 50% to 300% in fatal asthma compared to healthy controls.
This thickening is multifactorial, including hypertrophy and hyperplasia of submucosal glands, inflammatory edema, and remodeling. Fatal asthma is also associated with increased (not absent) mucous production. Of importance is the increase in micro vessels, mainly fibroblast growth factors (Pathology, Cellular inflammation, p.770).
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
3
Q
3. Which cell type is found with smooth muscle bundles within the airway wall in patients with asthma? A. Eosinophils B. MCT mast cells C. MCTC mast cells D. Neutrophils
A
- C, MCTC mast cells, 771, 780-1.
While the majority of mucosal mast cells are of the T cell-dependent tryptase+ type (MCT), the connective tissue type (MCTC) mast cells containing tryptase, chymase, and carboxypeptidase are more commonly found in the airway wall associated with smooth muscle bundles as shown in Figure 47.13 (p. 780). The number of MCTC cells in the airway wall increases with asthma severity (Pathology, Cellular inflammation, p. 771 and Regulation of cellular inflammation, Mast cells, p. 780-781).
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
4
Q
- Subepithelial basement membrane thickening of which layer is seen in asthma in early life but is not present in infants with previous viral wheezing or subjects without asthma?
A. Lamina densa
B. Lamina lucida
C. Lamina rara
D. Lamina reticularis
A
D, Lamina reticularis, p. 771, 789.
The thickening of the basement membrane seen in asthma is confined to the lamina reticularis layer (p. 771 and p. 789). Subjects without asthma do not demonstrate the same sub-basement membrane thickening of the lamina reticularis that is seen in asthmatic patients [Figure 47.2 (A and B, p.770)].
Chapter 47: Asthma Pathogenesis Middleton’s Allergy Principles and Practice, 9th Edition4.
5
Q
- When lung function was measured annually from 5-8 years of age, the COAST study demonstrated an increased risk of subsequent asthma and reduction in lung function in
children who wheezed during the first 3 years of life.
In the COAST study, which virus were found to have an increased risk of subsequent asthma and lower lung function when measured annually?
A. Human metapneumovirus
B. Human rhinovirus (HRV)
C. Influenza virus
D. Respiratory syncytial virus (RSV)
A
- B, Human rhinovirus (HRV), p. 775.
The COAST study demonstrated an increased risk of subsequent asthma and reduction in lung function (as measured annually from 5-8 years of age) in children who wheezed during the first
3 years of life with human rhinovirus (HRV). The reduction in lung function was not seen in children who wheezed with RSV or other respiratory viruses. The Tucson Children’s Respiratory
study previously demonstrated that infection with RSV in the first 3 years of life was a significant risk factor for wheeze until age 11 years (Early Life Influences, Infection, p.775). Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
6
Q
- A 12-year-old boy has a history of asthma and allergic rhinitis with prior sensitizations to tree pollen, grass pollen, and dust mite.
Within an hour of playing outdoors, he develops shortness of breath and chest tightness. His symptoms resolve after inhalation of his short acting beta agonist (SABA) therapy. Later that
evening, he had a late-phase allergic response with audible wheezing which required an additional SABA treatment.
The late-phase allergic response is characterized by release of which cell mediators from mast cells?
A. Cysteinyl leukotrienes C4, D4 and E4
B. Histamine
C. IL-4, IL-5, and IL-13
D. Prostaglandin D2
A
- C, IL-4, IL-5, and IL-13, p. 778.
Environmental allergies are an important cause of worsening asthma. In sensitized individuals, allergen provocation leads to mast-cell driven IgE-dependent early bronchoconstriction (EAR) at 0-2 hours after exposure, which is characterized by release of pre-formed mediators such as histamine, prostaglandins and cysteinyl leukotrienes. The late-phase response (LAR), 6-24 hours after exposure consists of non-specific bronchial hyperresponsiveness stimulated by the release of Th2 cytokines (IL-3, IL-4, IL-5, IL-13, and GM-CSF) from mast cells as well as leukocyte chemoattractants (CXCL8, CCL2). (Triggers of asthma and mechanisms of action: Allergens, p.778).
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
7
Q
- A female high school track athlete with well-controlled asthma has wheezing and chest tightness with exercise at the start of practice. She notes that later during practice she can run
without feeling the same symptoms (refractory period).
Release of which cell mediator is the most likely explanation for her lack of symptoms?
A. Histamine
B. LTE4
C. PGE2
D. Phospholipase A2
A
- C, PGE2, p. 779.
Exercise induced bronchoconstriction (EIB) occurs in 70 to 80% of patients with symptomatic asthma. Most asthmatics with EIB will experience an episode of bronchoconstriction followed
by a refractory period which is likely related to the release of inhibitor prostaglandins such as PGE2, which is an antagonist on airway smooth muscle and inhibitor of mast cell mediator
release. The initial bronchoconstriction is caused by airway efforts to warm the increased volume of air to body temperature, leading to release of phospholipase A2 from epithelial cells which promotes bronchoconstriction by promoting mast cells to release histamine and cystLTs.
(Triggers of asthma and mechanisms of action, Exercise-induced bronchoconstriction, p. 779)
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
8
Q
8. Following epithelial damage in chronic asthma, what is the primary signal that promotes airway remodeling via myofibroblast differentiation? A. IL-12 B. IL-17 C. TGF-β D. TNF-α
A
- C, TGF-β, p. 781, 788, 789.
Airway remodeling in asthma is a multifactorial process involving changes in the vascular compartment (associated with elevated vascular endothelial growth factor), deposition of excess connective tissue in the lamina reticularis, and increased numbers of myofibroblasts (p. 788). Myofibroblasts differentiate from fibroblasts in the presence of TGF-β, which is produced by both inflammatory cells and damaged airway epithelium (p 789).
Alveolar macrophages release anti-inflammatory cytokines like IL-10 which downregulates T cell function and IL-12 which promotes Th1 phenotype (p.781). Pro-inflammatory cytokines such as TNF-α (p. 785) augment the inflammatory response and may promote fibrosis, but do not directly act on myofibroblast
differentiation (Airway Remodeling, p.789).
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
9
Q
- A 60-year-old obese man with poorly controlled asthma is in clinic for follow up. Exam reveals no acute distress with diffuse inspiratory and expiratory wheezes bilaterally. He has been prescribed a second course of oral corticosteroids in the past 6 months for his asthma exacerbation, despite the use of high dose inhaled corticosteroid, long-acting bronchodilator,
and muscarinic antagonist controller therapy. Prior spirometry demonstrated mildly decreased FEV1 of 75% predicted with some reversibility. He has significant sputum eosinophilia. Skin testing to environmental aeroallergens was negative.
Which of the following subsets/clusters best characterizes this patient’s asthma?
A. Mild-moderate allergic asthma (cluster 2)
B. More severe older-onset asthma (cluster 3)
C. Severe fixed-airflow asthma (cluster 5)
D. Severe variable allergic asthma (cluster 4)
A
- B, More severe older-onset asthma (cluster 3), p. 790.
Asthma is a heterogeneous disorder of the airways with multiple phenotypes with variability in age of onset, presence of allergic disease and response to treatment. Cluster 3 (More severe
older-onset asthma) is characterized by older patients with higher BMI, less atopic, and frequent need for oral corticosteroids despite use of 3 or more controller medications and sputum eosinophilia (Asthma Heterogeneity, p.790, Figure 47.21)
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
10
Q
- A 34-year-old woman and her 6-year-old daughter are both followed for their asthma. The mother reports that her asthma is well-controlled and asks whether there is a difference between factors that trigger her asthma and those that trigger her child’s asthma. What is the most common trigger for asthma exacerbations in both children and adults?
A. High allergen load
B. Irritant chemicals/ air pollutants
C. Non-steroidal anti-inflammatory drugs (NSAIDs)
D. Respiratory viruses
A
- D, Respiratory viruses, p. 791.
Respiratory virus infections, especially with common cold viruses such as HRV, are the most common trigger for an exacerbation of asthma in both children and adults. Other common
causes include high allergen load, air pollution, irritant chemicals, diet, certain drugs (such as NSAIDs), stress and hormonal changes. (Asthma exacerbations, p. 791).
Chapter 47: Asthma Pathogenesis
Middleton’s Allergy Principles and Practice, 9th Edition
