lecture 19: Airflow limitation: from bench to bedside Flashcards
1
Q
What is asthma?
A
- a chronic inflammatory disorder of the airways
- often associated with atopy → group of allergic type disorders e.g. hayfever, eczema
- frequently involves chronic inflammation, associated with airway hyperresponsiveness
- symptoms: recurrent episodes of wheezing, breathlessness, chest tightness, and coughing
- widespread, variable, usually reversible airflow limitation
2
Q
What is the pathophysiology of asthma?
A
- most often occurs in response to an allergen, though not always
- the inciting event will stimulate one of two different effector cell types
- most commonly the mast cell
- resident leukocytes within the lung, in particular macrophages
- mucus production
- goblet cell hyperplasia → mucus hypersecretion → thickening of airway wall and sputum production
- angiogenesis and increased tissue within the submucosal layer → smooth muscle and inflammatory cell infiltrate
3
Q
What remodelling occurs in the asthamatic?
A
- goblet cell metaplasia
- subepithelial collagen thickening
- infiltration of inflammatory cells and increased mucosal vascularity
- increased smooth muscle volume
- rarely see smooth muscle in a normal airway biopsy
4
Q
What are the clinical consequences of asthma?
A
- acute inflammation
- symptoms → bronchoconstriction
- symptoms
- chronic inflammation
- exacerbations, non-specific hyperreactivity → exacerbations
- different clinical phenotype
- much more persistent symptoms
- much higher degrees of airway hyperresponsiveness
- can have chronic cough because of those persistent issues
- airway remodelling → persistent airflow obstruction → exacerbations
- if chronic inflammation is not addressed the changes can become fixed
- fixed airway obstruction
- not typically how we envision asthma to be
- occurs with poorly controlled disease
- epithelial collagen thickening, smooth muscle hypertrophy → fixed, persistent airway obstruction so that even when they are well they have ventilatory limitation
5
Q
What is impact of airway wall remodelling on function?
A
- thin-walled airway and therefore large luminal diameter → significant bronchoconstriction of the smooth muscle producing only a modest amount of increase in airway resistance
- Poiseuille’s law → resistance of a gas travelling through a tube → the narrower the luminal diameter the markedly higher the airway resistance will be
- therefore people with chronic airflow obstruction have a significant limitation even in between episodes
- not only significantly reduced luminal diameter through which breathing can occur, but also much higher airway resistance → much higher work of breathing
6
Q
To what does airway narrowing lead?
A
- airflow limitation (obstruction)
- FEV1 = amount of air they can push out within 1 second
- FVC = entirety of large breath
- FEV1 is what is most affected in patients with obstructive lung disease, moreso than FVC
- particularly with mild to moderate airway obstruction, patients will have a relatively conserved FVC
- much slower rate of expiration of their lung capacity
- narrower airway therefore takes longer for air to be exhaled
- FEV1 is the parameter by which degree of airway obstruction is measured
7
Q
Why do patients feel breathless with obstructed airways?
A
- there is a change in the “work of breathing”
- change in the “load” (resistive, elastic)
- breathlessness → a recognition of an inappropriate degree of respiratory work for body workload
- often a very significant limitation for patients
8
Q
What is the burden of asthma?
A
- asthma is one of the most common chronic diseases worldwide – estimated 300 million affected individuals
- prevalence increasing in many countries, especially in children
- 1 in 6 children, 1 in 9 adults
- a major cause of school/work absence
- important condition from a public health perspective
9
Q
What are factors that exacerbate asthma?
A
- allergens (#1)
- respiratory infections (#3, particularly viral)
- exercise and hyperventilation
- weather changes
- pollutants (sulfur dioxide, occupational fumes) (#2, smoking, still seen in some people who have asthma)
- food, additives, drugs
- emotion
10
Q
How do we make a diagnosis of asthma?
A
- appropriate clinical setting
- need to demonstrate reversible airflow obstruction (difficult to prove in the setting of an acute exacerbation)
- peak flow
- spirometry
- ratio of FEV1 to FVC less than 0.7 is highly consistent with asthma
- airway obstruction that improves using bronchodilater therapy → will see signficant improvement in FEV ratio
- bronchoprovocation test
- measures airway hyperreactivity (AHR)
- direct (methacholine, histamine) or indirect (exercise, mannitol, hypertonic saline)
- used on people who have intermittent/variable asthma e.g. exercise induced
- generally want symptoms to be recurrent or variable as opposed to persistent (less likely to be asthma)
- respiratory function report
- first look at FVC → normal range
- FEV1/FVC % → less than 0.70
- FEV1 → reduced
- significant scolloping of respiratory limb ?
- long tail of expiration commonly seen in patients with airflow obstruction (would expect to see a respiratory limb that takes a much straighter trajectory with exhalation)
- patient undergoes bronchodilator treatment → significant improvement in FEV1 (to within normal range is what we would hope and expect to see in asthma)
- significant improvement in FVC → representing relief of gas trapping → small amount of gas trapped at the end of each breath, inhaled but not fully exhaled
- FVC doesn’t actually change much, it is the residual volume that reduces
- relief of airway obstruction has relieved some of the dynamic hyperinflation and therefore the measured FVC improves
11
Q
What is the common view and treatment of asthma?
A
- inflammation (preventer therapy e.g. glucocorticoids) → more important to target
- airway smooth muscle (reliever therapy e.g. B2-adrenoceptor agonists) → doesn’t help and can be a hindrance in the longer term
- airway hyperresponsiveness (AHR)
- symptoms (avoid triggers)
- remember that asthma treatment is more than just pharmacotherapy (although this is very important)
12
Q
How does asthma medication try to minimise the underlying pathophysiology?
A
- beta 2 agonists (symptom relievers)
- long and short acting
- relax smooth muscle, improve airway patency
- inhaled corticosteroids (ICS, preventer)
- reduce airway inflammation and AHR
- mainstay of asthma treatment in general
- oral corticosteroids (usually only at times of exacerbation)
- combines inhalers (ICS, LABA)
- leukotriene receptor antagonists
- anti-IgE
13
Q
What is the dose-response curve for inhaled corticosteroids?
A
- daily dose of inhaled steroid (FP ug) vs clinical effect
- only need a modest amount of steroids to produce very good airway control of inflammation
- dosing for asthma significantly reduced compared with COPD
- 100/200mg bd = standard dose = 90% max
- people prescribed 500mg don’t have much increased clinical benefit especially when compared with the adverse effects
- if people are still symptomatic at low doses → combination therapy e.g. long acting beta agonists
14
Q
What is the main focus of asthma control?
A
- impairment - quality of life
- remodelling and progression
- decline in lung function
- increase in BHR
- airway inflammation
- while less significant (cf death) due to the prevalence of asthma this is where the largest societal burden occurs
- days with poor control
- puffs of rescue
- no nights of awakening
- control of the two largest sections of the pyramid → reduce more significant adverse outcomes
- moderate exacerbations
- severe exacerbation
- death
- significant and potential outcome before the use of corticosteroids
- now a much smaller issue
15
Q
What is COPD?
A
- group of disorders characterised by airway inflammation and airflow limitation that is not fully reversible
- heterogeneous phenotype of airway obstruction
- broadly speaking divided into two different conditions:
- emphysema: loss of airway tissue
- chronic bronchitis: chronic airway inflammation and sputum production
- patients will have a variable amount of those two components of COPD → very different clinical presentations
- a progressive condition associated with an abnormal inflammatory response to noxious stimuli → almost always cigarette smoking
- fully reversible asthma is not COPD
17
Q
What is the only major cause of death that has increased significantly in recent years?
A
- COPD
- 163%
- (coronary heart disease, -59%, stroke -64%, other CVD -35%, all other causes -7%)
20
Q
What is the pathogenesis of COPD?
A
- noxious agent
- inflammation
- small airway disease → airway inflammation, remodelling
- parenchymal destruction → loss of alveolar attachments, loss of elastic recoil
- airflow limitation
21
Q
What happens to the lung in emphysema?
A
- small airway disease, mucus
- part of the role of lung tissue is to provide elastic recoil for the airways → holds them open
- small airways don’t have cartilage or anything to keep them open
- when you lose that tissue you lose the elastic recoil
- not as much lung structure keeping the airways open → airways collapse shut
22
Q
What are differences in inflammation and its consequences between asthma and COPD?
A
- end result for both conditions is airflow limitation
- asthma is a much more acute inflammatory response
- immune cell driven
- exert their effects only as long as they are triggered
- reversible phenomenon
- COPD is generally caused by cigarette smoking
- chronic injury to respiratory epithelium and resident alveolar macrophages
- a lot of that inflammation then becomes self-sustaining which is why patients very frequently remain symptomatic even if they are able to quit smoking
- irreversible destruction of alveolar tissue
- persistent small airway obstruction
23
Q
What are the ‘multicomponents’ of COPD?
A
- inflammation at its core leading to mortality
- mucociliary dysfunction
- structural changes
- airway inflammation
- systemic component
- airflow limitation
- lead to:
- declining lung function
- symptoms
- exacerbations
- decreased exercise tolerance
- deteriorating health status and increasing morbidity
- now recognised to be a systemic inflammatory disease
- greater degree of systemic involvement equates to poorer prognosis
28
Q
What is the importance of smoking cessation?
A
- smoking cessation is the single most effective way to reduce the risk of developing COPD
- slows the accelerated decline in lung function seen in COPD
- reduces mortality due to lung cancer, cardiovascular disease and other comorbid conditions associated with COPD
- from the age of 25 onwards everyone loses a small amount of lung capacity each year (30 to 50mL / year)
- most people who have never smoked or are not susceptible to smoke will never reach the point of disability or death in regards to FEV1 value
- smokers will have double or even triple the decline in lung function per year → likely to get to a point where they develop symptoms based on their FEV1
- if you stop people smoking the trajectory of their lung decline returns to that of a non-smoker
- at any point there is value to stopping smoking → if you can get them to stop before 50 the likelihood of them having a respiratory something is cut by about 90%
