Obstructive Lung Disease Flashcards
Define asthma
What is the difference between asthma and COPD? [1]
Asthma is a chronic inflammatory condition of the airways that causes episodic exacerbations of bronchoconstriction. Bronchoconstriction is where the smooth muscles of the airways (the bronchi) contract causing a reduction in the diameter of the airways. Narrowing of the airways causes an obstruction to airflow going in and out of the lungs.
Asthma is Variable: reversible airflow limitation (& therefore symptoms). COPD causes constant symptoms
What causes asthma?
Name some environmental triggers for asthma
Asthma occurs from complex gene–environment interactions
Typical Triggers
- Infection
- Night time or early morning
- Exercise
- Animals
- Cold/damp
- Dust
- Strong emotions / stress
Describe the causes of obstruction of airflow in asthma patients [5]
Chronic inflammation: Impact on Airways
- Thickening of the basement membrane & Airway smooth muscle hypertrophy
- Leukocyte infiltration
- Goblet cell hyperplasia & mucus hypersecretion
- Eosinophils in walls of airway causes inflammation: thickening of walls
- Thickening of bronchiole smooth muscle (which when it contracts causes more restriction)
Causes obstruction of airflow
what is the difference in response to allergen in normal and healthy person?
-
Normal:
- A low level T-helper (TH-2) response. This produces an IgG response
-
Asthma:
- allergen digested by antigen presenting cellsdigested and presented by MHC Class II molecules
- CD4 cells activate the TH-2 lymphocytes through the release of IL4, IL5, IL13.
- The activated TH2 cells release cytokines (IL4) which recruit multiple inflammatory cells, NK cells eosinophils, mast cells, and IgE producing Cells causes the release of histamines
- IgE mediated mechanism: (IgE: antibody associated with allergic response)
- binding of an allergen to IgE-mast cells results in their rapid degranulation and the release of inflammatory compounds, including histamine, which contribute to local inflammation and the symptoms associated with allergy.
- The activated TH2 cells release cytokines (IL4) which recruit multiple inflammatory cells, NK cells eosinophils, mast cells, and IgE producing Cells causes the release of histamines
What are the two different overriding causes of asthma?
Which is more dominant?
Predominately caused by T2 side, but also non T2 driven asthma like obesity or smoking related
Why is it difficult to do diagnose asthma solely of clinical symptoms?
How can you improve the predictive value when taking a history?
Symptoms are variable SO predictive value of isolated symptoms or signs is poor
Adults: isolated symptoms of cough, wheeze and shortness of breath are neither sensitive nor specific for asthma
Almost all children with asthma have intermittent cough, wheeze and/or exercise induced symptoms, but only about a quarter of children with these symptoms have asthma
Enquiring about the episodic nature of symptoms (for example acute attacks) as opposed to current symptoms may improve the predictive value
What symptom is an important sign that increases the chance of diagnosis of asthma?
Polyphonic ( multiple musical notes starting and ending at the same time) end expiratory wheeze, that is global across the chest (all the small airways are effected)
How do you differentiate between asthma wheeze and stridor wheeze?
Stridor is noisy breathing that occurs due to obstructed air flow through a narrowed airway. Stridor breathing is not in and of itself a diagnosis, but rather is a symptom or sign that points to a specific airway disorder.
stridor: inspiratory wheeze
asthma: expiratory wheeze
How do you diagnose patients with asthma?
Previous and current medical history:
* Looking for recurrent episodes of symptoms
* Symptm variability
* Recorded observaion of wheeze
* History of atopy
* Historical record of variable PEF or FEV1
Identify if they’re:
- Low probabilty - treat alternative illness
- Intermediate probabilty
- High probability - treat
If intermediate then undergo lung function tests - Looking for reversible airflow limitation
Explain how Spirometry works as a lung function test
Spirometry with reversibility:
- Do spirometry – show have obstructive airway disease
- Give agent that causes reversibility (e.g. salbutamol): open airways and show its variable
BEST FOR TESTING, BUT: quite resource heavy. Instead usually do peak flow chart
what does atopy mean?
Atopy is a genetic predisposition to IgE-mediated allergen sensitivity.
what is FeNo testing?
what is the % in asthma patients?
Fractional exhaled nitric oxide (FeNO)
FeNO testing is typically offered to patients being investigated for asthma at the same time as spirometry. FeNO is a newer way of testing for eosinophilic airway inflammation.
FeNO is measured in parts per billion and a level >25 ppb at 50 ml/sec is seen in 70-80% of patients with untreated asthma. Eosinophilic airway inflammation has been linked to the response to corticosteroids.
FeNO > 40 ppb: supports a diagnosis of asthma
FeNO 25-39 ppb: suggestive of a diagnosis of asthma. Peak flow variability useful.
FeNO < 25 ppb: does not support a diagnosis of asthma
What alterative testing methods for ID of asthma do conduct if can’t do spirometry? [2]
FeNO testing [1]
Eosinophil raised levels in blood count [1]
Draw lung function (volume / time) spirometry recording of a healthy person vs asthma Ptx
what are FVC and FEV1? 2]
what are FVC, FEV1 and FEV1/FVC in asthma patients? [3]
FVC: the forced (expiratory) vital capacity is a persons maximal expiration following full inspiration.
FEV1: the forced expiratory volume in one second, i.e the volume of FVC expelled after one second.
The following changes are seen in obstructive lung disease:
FVC: may be normal but often reduced due to air trapping.
FEV1: reduced.
FEV1/FVC: < 70%.
Draw a flow-volume curve for a normal and asthmatic patient
Normal patient:
- Breath out: get sudden upstroke of expiratory volume -> PEF
- Breath in: nice curve
Asthma:
- straight line collapses due to small airways collapsing when they breathe out. PEF reduces.
What do you need to consider when conducting spirometry tests?
Asthmatic patients who have disease well controlled will likely have nromal spirometry.
Only acute asthmatics are likely to have spirometry that suggests asthma
What improvement in FEV1 when doing bronchodilator reversiblity test indicates positive for an adult and for a child?
Adults: FEV1 improvement ≥12% and ≥200 ml as a positive test
Children: FEV1 improvement ≥12% as a positive test
How do you diagnose Ptx using peak expiratory flow?
Peak expiratory flow (PEF) 3 best attempts
PEF is best used to provide an estimate of variability of airflow from multiple measurements made over at least two weeks
Increased likelihood of asthma ≥20% variability across 2 week peak flow chart
Take 3 measurements in morning, 3 middle in afternoon and 3 last of the day. Worse in morning)
Treatment should bring about a reduction in variability of airflow (and flat line in graph below)
What is responsible for the accumulation of eosinophils in asthma?
Eosinophils are attracted by chemotactic factors released by mast cells and by the chemokine eotaxin. The latter is produced by bronchial epithelial cells. Eosinophil accumulation is also favored by IL-5, a T-cell derived cytokine.
What happens upon re-exposure to an allergen during the:
a) immediate phase?
b) late phase?
Immediate phase:
On re-exposure to antigen (Ag), the immediate reaction is triggered by Ag-induced cross-linking of IgE bound to Fc receptors on mast cells. These cells release preformed mediators that directly and via neuronal reflexes induce bronchospasm, increased vascular permeability, mucus production, and recruitment of leukocytes.
Late phase:
Leukocytes recruited to the site of reaction (neutrophils, eosinophils, and basophils; lymphocytes and monocytes) release additional mediators that initiate the late phase of asthma. Several factors released from eosinophils (e.g., major basic protein, eosinophil cationic protein) also cause damage to the epithelium.
What is the mechanism of the early symptoms, and what are the causes of effects that appear several hours after exposure to an allergen?
An exaggerated TH2 response to harmless environmental antigens is a fundamental mechanism of asthma.
This exaggerated response stimulates** B cells** to produce IgE.
In the acute early-phase reaction, exposure of pre-sensitized IgE-coated mast cells to the same or cross-reacting antigens results in the release of histamine (which causes bronchospasm), leukotrienes (which attract leukocytes and eosinophils and release mucus), and platelet-activating factor (which causes more release of histamine and serotonin from platelets).
Cytokines released by leukocytes, eosinophils, and basophils recruited during the early phase contribute to the late-phase effects
Histamine from basophils causes further bronchoconstriction and edema; neutrophils cause inflammatory damage; and the major basic protein of eosinophils causes epithelial damage and shedding and contributes to bronchoconstriction
What does atopy mean?
What is the classic atopy triad? [3]
Atopic refers to sensitization of an allergen with immune activation. Patients with “atopic syndrome” develop type I hypersensitivity reactions that can cause multiple conditions.
The classic “atopic triad” includes
atopic asthma (eczema),
atopic dermatitis, and
allergic rhinitis.
What is the meaning of the term asthmatic bronchitis?
Some patients with clinically manifest chronic bronchitis (persistent productive cough for at least 3 consecutive months in at least 2 consecutive years) have hyperresponsive airways and intermittent episodes of bronchospasm. This condition is called asthmatic bronchitis.
What happens to the pattern of variability in PEF in asthma lung function tests before and after treatment? [1]
Goes from variable airflow obstruction: get peak flow to be flat
What is the rescue medication for patient with symptomatic asthma? [1]
What treatment is provided for long term control of asthma? [2]
What is SMART / MART treatment? [1]
Rescue medication: SABA, e.g salbutamol
Achieve control with a maintenance / preventor medication:
First line therapy: Low dose inhaled ICS (if need, may required higher doses)
Add on therapy: ICS + inhaled long acting beta 2 agonists (LABA) or long acting anti muscarini (LAMA)
Add on therapy: ICS + LAMA / LABA + specialist therapies
MART / SMART: reliever and maintanence medication (SABA & inhaled CS)
How do you take asthma aerosol drugs? [1]
How do you take dry power inhaler drugs? [1]
How do you take asthma aerosol drugs? [1]
SLOW AND STEADY
How do you take dry power inhaler drugs? [1]
QUICK AND DEEP
How do ICS work? [2]
Why do we start on low dose of ICS? [1]
ICS bind to glucocorticoid receptor on cytoplasm, move to nucleus & bind to glucocorticoid response element: reduces levels of CXCL8, IL-6, TNF-a
Low dose of ICS: cause AE from blocking all other systems in body
- Explain the MoA of beta 2 agonists for asthma treatment
What type of treatment are SABAs?
Explain the rationale for treatment of SABA & ICS effects
Beta2 agonists: Beta2-adrenergic receptor agonists bind to beta2-adrenergic receptor. Causes a cascade of signal transduction events = airway smooth muscle relaxation
Also treat beta 2 receptors of mucus production and wall
Together, ICS and SABAs have anti-inflammatory and bronchodilation effects
What is the difference between COPD and asthma? [2]
Both obstuctive airway diseases
COPD: Progressive airflow limitation. Neutrophilic and CD8-driven
Asthma: Airflow limitation is reversible. eosinophilic and CD4-driven
in asthma, and in COPD
What is a key risk factor for COPD? [1]
Long-term exposure to noxious environmental particles, genetics & lung development
Describe 3 changes to lungs occur because of COPD
Chronic inflammation: inflammatory pathway driven
- destruction of alveoli (emphysema)
- mucous hypersecretion
- narrowed bronchioles
Explain the pathophysiology of COPD
Cigarette smoke (major risk factor) = irritates & activates epithelial cells & macrophages → inflammatory mediators
Macrophages release CXCL8, which attracts neutrophils.
Epithelial cells release CXCL9 & CXCL10, which attracts T helper 1 (TH1) cells and type 1 cytotoxic T (TC1) cells
TC1 & neutrophils cause the release of proteases (e.g. metalloproteinase 9 (MMP9), which causes elastin degradation
Neutrophil elastase causes mucus hypersecretion
Epithelial cells & macrophages release transforming growth factor-β (TGFβ) = stimulates fibroblast proliferation = fibrosis in the small airways
Steroid response: Asthma (Good / Bad?) vs. COPD (Good / Bad?)
Steroid response: Asthma (Good) vs. COPD (Poor)
How would you diagnose COPD?
-
Previous and current history: Severity of Symptoms
i) chronic cough
ii) dysnpea (worsening over time)
iii) chronic sputum production
iv) recurrent lower resp tract infection - Lung function tests
i) FEV1 decreases
ii) FEV1/ FVC decreases below 0.7 - History of risk factors
What two lung function tests would you do for COPD? [2]
i) FEV1 decreases
ii) FEV1/ FVC (score below 0.7)
How do you decide who get what treatment for COPD?
What is first line maintenance therapy for COPD? [1]
What is first line maintenance therapy for COPD? [1]: Long acting bronchodilators (A)
What is effect of beta 2 agonists on COPD patients?
The obstructive picture does not show a dramatic response to reversibility testing with beta-2 agonists such as salbutamol during spirometry testing. If there is a large response to reversibility testing them consider asthma as an alternative diagnosis.
What would you give Ashma Ptx who has elevated blood eiosoniphil, in hospital or frequent exaserbations?
Triple therapy:
- LABA
- LAMA
- ICS
Which muscarinic receptor is found in longs?
What does activation of this receptor cause?
M3
Ach on M3 causes vasoconstriction
Beta 2 Adrenoreceptors and SABA / LABA MoA?
Beta 2 adrenoreceptors are bound to by the Beta2 agonists (SABAs or LABAs)
Causes protein kinase A to be released
Protein kinase A activates myosin-light chain kinase
Myosin-light chain kinase facilitates the binding of actin / myosin bridge
results in airway smooth muscle relaxation and hence bronchodilation. (double check !!)
Asthma Management: First line therapy = []?
COPD Management: First-line therapy = []
Asthma Management: First line therapy = ICS
COPD Management: First-line therapy = bronchodilators
