Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, Epidemic Thunderstorm Asthma 2022 Flashcards
- A 43-year-old man with a past medical history of asthma and allergic rhinitis has had worsening symptoms of fatigue, wheezing, and productive cough with brown sputum over the last two months. He is currently on high dose inhaled corticosteroid with long-acting beta agonist, and despite some improvement with a short course of corticosteroids, has had persistent symptoms. His evaluation thus far has been notable for a peripheral eosinophil count of 1300 cells/mm3, an elevated total IgE of 1500 ng/mL, previous skin prick testing positive for Aspergillus fumigatus, and patchy transient opacities noted on serial chest imaging. What most likely played a primary role in the development of this patient’s condition?
A. Defects in IL-17 signaling
B. Dendritic cell recognition of damage-associated molecular patterns
C. Impaired mucociliary clearance
D. Th1 responses to Asp f 3, Cr f 1, Catalase 1
- C, Impaired mucociliary clearance, p. 971.
In allergic bronchopulmonary aspergillosis (ABPA), adherence of Aspergilli conidia to respiratory epithelia disrupts mucociliary clearance, allowing further fungal attachment and growth in
respiratory epithelium. The presence of persistent proliferation of Aspergillus in the airways leads to inflammatory cell recruitment with a predominant Th2 response and release of IL-4, IL5, IL-13 leading to an increase in total IgE and Aspergillus fumigatus -specific IgE. These T2 responses are triggered by a complex of pathogen-associated molecular patterns as opposed to
a single fungal component. Aspergillus antigens triggering this response include Asp f 1, Asp f 2, Asp f 3, Asp f 4, Cr f 1, and Catalase 1.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
- A 34-year-old woman with a history of cystic fibrosis has been having increased fatigue, cough, and wheezing over the last 6 weeks. Her evaluation is notable for a total IgE 2200 IU/mL,
detectable Aspergillus fumigatus IgE, and eosinophilia of 1200 cells per L. A chest CT is ordered.
Which would be an expected finding on this patient’s chest imaging?
A. Lung hypoinflation
B. Mucoid impactions
C. Peripheral bronchiectasis
D. Transient pulmonary infiltrates in the lower lobes
- B, Mucoid impactions, p. 971.
This patient has allergic bronchopulmonary aspergillosis (APBA). Common imaging findings in ABPA include central bronchiectasis, transient pulmonary infiltrates (particularly in the upper lobes), branching “finger-in-glove” opacification of the dilated bronchi (due to mucoid impaction), and pulmonary hyperinflation.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
- A 54-year-old man with a history of moderate-persistent asthma presents with 3 months of worsening cough, wheezing, and shortness of breath. He has received three short courses of
systemic steroids with initial improvement but quickly had recurrence of significant symptoms soon after completing the prescribed course. He was noted to have pulmonary infiltrates in the upper lobes on chest imaging, as well as an elevated total IgE and eosinophilia. While suspecting allergic bronchopulmonary aspergillosis (ABPA), the patient asks about initial management for his presumed condition. Which represents a common side effect of the most appropriate initial management for this condition?
A. Anaphylaxis
B. Conjunctivitis
C. Transaminitis
D. Weight gain
- D, Weight gain, p. 976-7.
For allergic bronchopulmonary aspergillosis (ABPA), the first line of treatment includes oral corticosteroids for at least 3 months. As such, weight gain with prolonged systemic steroid use
may be expected. Hepatic steatosis can occur with oral corticosteroids, and a resultant transaminitis can occur but this is less frequent. Antifungal agents such as itraconazole or
voriconazole can be used as adjunct therapy to oral corticosteroids, and transaminitis is frequently observed with use of these agents. There are case reports of the use of omalizumab in the setting of ABPA, but routine use of this is not yet recommended. Anaphylactic reactions can be observed with omalizumab. Conjunctivitis may be seen with dupilumab and is not currently indicated for ABPA.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
- A 24-year-old woman with severe persistent asthma has had significant symptoms of uncontrolled productive cough and wheezing over the last 4 months. Previous evaluation has demonstrated an elevated eosinophil count of 1300 cells/μL, an elevated total IgE level of 3000 IU/mL, and detectable serum Aspergillus fumigatus specific IgE. Chest imaging with findings of mucus impaction and “tree in bud” opacities. She was started on a standard first line therapy with improvement of symptoms.
Which study is most appropriate to obtain periodically to monitor the patient’s long-term care?
A. Aspergillus-specific IgG
B. Chest CT
C. Peripheral eosinophil count
D. Total IgE
- D, Total IgE, p. 975-6.
As this patient has allergic bronchopulmonary aspergillosis (ABPA), the most sensitive indicator of disease progression is serial total IgE. A decline in serum total IgE of 35% is indicative of remission. A doubling of the total IgE is considered diagnostic for a relapse of ABPA. Pulmonary inflammation can occur even in absence of symptoms, and as such serial monitoring of total IgE lis important for screening for disease relapse.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
- A 57-year-old man with history of moderate persistent asthma and allergic rhinitis with sensitizations to Timothy grass, mountain cedar, short ragweed, Aspergillus fumigatus, and cat presents with 8 weeks of productive cough with brown sputum, low grade fevers, cough, and wheezing. He has an elevated total IgE of 5000 IU/mL, a peripheral eosinophil count on 1200 cells/L, and detectable serum Aspergillus specific IgE. His physician starts him on first line
management for this. If left untreated, which would be an expected complication?
A. Anaphylaxis
B. Eosinophilic myocarditis
C. Invasive fungal dissemination
D. Pulmonary fibrosis
- D, Pulmonary fibrosis, p. 973.
If left untreated, persistent inflammation can lead to progression of central bronchiectasis to involve peripheral lungs and lead to pulmonary fibrosis. Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity inflammatory response to the presence of Aspergillus in the airway; it is NOT ASSOCIATED with invasive fungal disease. Eosinophilic myocarditis is observed in hypereosinophilic syndromes, but not frequently seen in ABPA. The increase in
total IgE, driven by both Aspergillus-specific IgE as well as non-specific IgE production, does not lead to increased susceptibility to anaphylactic reactions.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
- A 72-year-old farmer has had over 10 years of cough and shortness of breath. Initially, he had episodes of fever and chills associated with these respiratory symptoms. However, over the last 5 years, he has only had the cough and dyspnea. He has lost 15 lbs over the past year. Physical exam is notable for digital clubbing. A CT scan of chest shows signs of emphysema and mild fibrosis. What cytokines would have been most characteristically expressed during the period of acute
inflammation in this patient’s condition?
A. Increased IFN-γ response
B. Increased IL-4 response
C. Increased IL-10 response
D. Increased IL-17 response
6. A, Increased IFN-γ response, p. 977-8, Fig 58.4. Hypersensitivity pneumonitis (HP) occurs as an immunologic reaction to inhaled particles, typically less than 5 m, leading to significant T-cell mediated inflammatory response. In the acute setting, a Th1 response is predominant.
However, in the subacute and chronic phases of HP, this transitions to a T2 predominant response. Furthermore, an increased Th17 response in the subacute and chronic phases leads to decreased lymphocyte apoptosis and impaired Treg
function, although absolute numbers of Tregs tend to be normal.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
- A 49-year-old woodworker with hypersensitivity pneumonitis (HP) has had 3 months of productive cough and shortness of breath. He has had decreased appetite and unintentionally lost 6 lbs over this period. His physician notes diffuse crackles on pulmonary auscultation. If lung biopsy were performed, what histopathologic patterns would most likely be seen in the patient’s current condition?
A. Centrilobular fibrosis
B. Noncaseating granulomas
C. Positive PAS staining
D. Usual interstitial pneumonia with honeycombing
- B, Noncaseating granulomas, p. 980.
For this patient with subacute hypersensitivity pneumonitis (HP), typical findings on lung histopathology include lymphocytic interstitial infiltrates, poorly formed noncaseating granulomas, and bronchiolitis.
The duration of this patient’s symptoms makes chronic HP less likely which typically takes many months-years of chronic inflammation to develop. In chronic HP, centrilobular fibrosis and bridging fibrosis can be seen, granulomas are typically absent. Chronic HP may also present with usual interstitial pneumonia pattern with honeycombing.
Fungal staining with PAS would not be expected. Other key features of HP include clinical history of pneumonitis symptoms with evidence of serum precipitins to suspected causative agent, chest imaging with reticular, nodular, or ground glass opacities, bronchoalveolar lavage (BAL) lymphocytosis >20% with low CD4:CD8 ratio <1 (although this is not sensitive nor specific), histopathology showing noncaseating granulomas or a mononuclear cell infiltrate, symptoms on re-exposure to suspected causative agent
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
8. A 54-year-old man who works as a farmer has had two episodes of acute onset fevers, nonproductive cough, chills, and nausea over the past 4 months. He is noted to have diffuse fine crackles on pulmonary auscultation. Given the recurrent nature of these symptoms, his physician orders a chest CT which demonstrates diffuse ground glass opacities. This patient’s clinical symptoms are most likely secondary to an immunologic response towards which of the following antigens? A. Aspergillus fumigatus B. Candida albicans C. Thermoactinomyces vulgaris D. Trichosporum cutaneum
- C, Thermoactinomyces vulgaris, p. 977-8.
Thermophilic actinomyteces such as Saccharopolyspora rectivirgula or Thermoactinomyces vulgaris found in moldy hay, grain, or compost are common causes of hypersensitivity pneumonitis in farmers, also known as “farmer’s lung”.
Aspergillus species are found in malt in malt worker’s lung or contaminated grain or flour in Wheat weevil or miller’s lung. Candida albicans has been implicated in moldy wind instruments, such as in saxophonist’s lung. Trichosporum cutaneum was described in contaminated houses in Japan and increase in the
summer leading to the name summer type hypersensitivity pneumonitis.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
9. A 62-year-old woman bought a vineyard a few years ago. Over the past year, she has had a gradual onset of productive cough, shortness of breath, fatigue, and weight loss while developing hypersensitivity pneumonitis (HP). Which is associated with a decreased risk in developing this patient’s condition? A. Cigarette smoking B. Positive precipitating antibodies C. Recurrent episodes of symptoms D. Weight loss
- A, Cigarette smoking, p. 980.
The following factors are predictors for developing hypersensitivity pneumonitis: exposure to known offending antigen, positive precipitating antibodies against suspected causative antigens, recurrent episodes of symptoms, inspiratory crackles, symptoms 4-8 hours after exposure, weight loss.
Cigarette smoking is associated with a decreased risk for hypersensitivity pneumonitis.
Lacasse Y, Selman M, Costabel U, et al. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003 Oct 15;168(8):952-8. doi: 10.1164/rccm.200301-137OC. Epub 2003 Jul 3. PMID: 12842854.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma Middleton’s Allergy Principles and Practice, 9th Edition
- An 18-year-old man from Kansas spends his summer working in a wheat field. He develops fevers, cough, shortness of breath, and chills. He has never had respiratory symptoms before.
Which is the most likely non-infectious cause of his symptoms?
A. Byssinosis
B. Organic dust toxic syndrome
C. Thermophilic actinomycetes hypersensitivity pneumonitis
D. Toxic fume bronchiolitis
- B, Organic dust toxic syndrome, p. 980.
The patient’s symptoms are consistent with hypersensitivity pneumonitis (HP). While one of the most common causes of HP is thermophilic actinomycetes found in moldy hay or grain (also known as farmer’s lung), it must be differentiated from organic dust toxic syndrome (ODTS).
ODTS is 30-50 times more common than farmer’s lung and can present clinically similar. ODTS is a non-infectious inflammatory process driven by dust contaminated by toxin-producing fungi in grain or hay. It typically affects younger patients, and no prior sensitization is required. Unlike farmer’s lung, there is no serologic response to fungal antigens.
Toxic fume bronchiolitis is caused by nitrogen and sulfur dioxide exposure. Byssinosis is a syndrome marked by bronchoconstriction secondary to exposure to dust inhalation of cotton. It typically approves over time even in the setting of continued exposure.
Chapter 58: Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma
Middleton’s Allergy Principles and Practice, 9th Edition
