12 - Asthma Flashcards
What are the major cell types involved in the pathogenesis of asthma? What major mediator molecules are involved?
cells:
- TH2 lymphocytes
- mast cells
- eosinophils
mediators:
- IL-4
- IL-5
- IL-13
- histamine
- leukotrienes
What are the risk factors for asthma?
- atopy
- obesity
- airway hyperresponsiveness (AHR)
- indoor allergens
- pollution
- smoking
What leads to narrow airways in asthma?
- chronic inflammation
- airway remodeling
What are the characteristics of the early and late phases of asthma? What does this imply for treatment?
early phase - bronchospasm
- crosslinked IgE antibodies activate mast cells –> cells release histamine and leukotrienes (inflammatory mediators) –> bronchospasm, vasodilation, edema, mucus secretion
late phase - bronchospasm, edema, inflammation
- eosinophils are activated and recruited by cytokines
Anti-inflammatory therapy is important for minimizing the late phase
What is the pathophysiology of nocturnal asthma?
- circadian changes lead to increased inflammation around 4 am
- supine position and sleep lead to decreased lung function
Why is a bronchoprovocation test useful in testing for asthma?
- negative test rules out asthma
- positive response correlates with disease severity
What are the principal clinical findings of asthma?
- recurrent wheezing
- nocturnal cough and dyspnea
- cough or wheeze post-exercise
- symptoms after exposure to allergens or pollutants
- colds take long time to resolve
- symptoms improve with asthma treatment
What PFT results are seen in someone with asthma?
- obstructive pattern
- positive bronchodilator response
- normal DLCO
What is the differential diagnosis for asthma?
children:
- cystic fibrosis
- viral bronchiolitis
- vascular rings
- upper airway obstruction / foreign body aspiration
adults
- GERD
- post-nasal drip
- bronchiectasis
- sarcoidosis
- COPD
- cardiac problem
- upper airway obstruction
- malignancy
- medication side effect
- pulmonary emboli
- vocal cord dysfunction
What are the goals of long-term asthma management?
- achieve and maintain control of symptoms
- maintain normal activity levels, including exercise
- maintain pulmonary function as close to normal levels as possible
- prevent asthma exacerbations
- avoid adverse effects from asthma medication
- prevent asthma mortality
How should you assess and treat asthma?
- assess daytime and nocturnal symptoms
- assess need for rescue treatment
- avoid triggers
- relievers vs. controllers
- determine the best mechanism of action/effect of key agents (inhaled steroids, LABAs, leukotriene modifiers, omalizumab, anti-cytokine therapy)
What are the three hallmarks of asthma?
- airway inflammation
- airway hyperresponsiveness
- airflow obstruction
What takes place during airway remodeling in asthma?
- subepithelial fibrosis
- smooth muscle hypertrophy/hyperplasia
- angiogenesis
- mucus cell hyperplasia
** this is irreversible
What is the pathophysiology of exercise-induced asthma? How does it differ from normal asthma?
- cough, dyspnea, chest tightness occurs 10-15 minutes after exercise
- airway water loss (from large volumes of cool, dry air) –> increases airway tone –> decreased FEV1
- increased inflammatory cells and mediators after exercise
Difference - there is no or minimal late phase
How do you diagnose asthma?
clinical diagnosis based on:
- history and pattern of symptoms
- physical exam
- PFTs (can be normal)
- measurement of airway hyperresponsiveness (bronchoprovocation testing)
