Flashcards in Obstructive Diseases Deck (125):
Where do obstructive diseases affect?
What are examples of obstructive diseases?
Asthma, COPD- chronic bronchitis/emphysema
What is ACOS?
Asthma/COPD overlap syndrome (smokers with features of both)
ACOS is essentially COPD with what?
Reversibility and some eosinophilic inflammation which is steroid responsive
Asthma is a chronic inflammatory disease of where?
Small and large airways
What is the basic underlying disease process in asthma?
How many levels of branching does the bronchial tree consist of?
What is the conducting zone of the bronchial tree?
The first 16-17 branches which play no role in gas exchange
What is the respiratory zone of the bronchial tree?
The last 6-7 branches which is where gas exchange takes place
What zone of the respiratory tree involves the bronchi?
Which zone of the respiratory tree involves the respiratory bronchioles, alveolar ducts and sacs?
What is the size roughly of the small and large airways?
Small- <2mm, large- >2mm
Where will inhaled particles <5 microns get past?
Where will inhaled particles <2 microns get past?
8th branch of bronchioles
What three things must a patient have to have asthma?
- Eosinophilic airway inflammation
- Airway hyper-responsiveness
- Reversible airway obstruction
What does bronchoconstriction in asthma cause?
What does chronic airway inflammation in asthma cause?
Exacerbations of asthma
What does airway remodelling in asthma cause?
Irreversible fixed airway obstruction
What are triggers treated with in asthma?
What is eosinophilic inflammation treated with in asthma?
Anti-inflammatory corticosteroids and maybe cromones
What are mediators of asthma and when are they released?
Released upon antigen binding to IgE- histamine, leukotrienes, cytokines
What medication can be given to block mediators in asthma?
Anti-histamines/leukotrienes, anti-IgE, anti-IL5
What drugs are used to treat hyper-reactive muscle in asthma?
Drugs which stimulate the sympathetic nervous system to relax the airways- bronchodilators, beta2 agonists, muscarinic antagonists
What are the only drugs which restore normal mucosal architecture?
What are the most important drugs to consider as possible causes of asthma?
NSAIDs and beta-blockers
How is asthma diagnosed?
History and exam, diurnal variation of peak flow rate, reduced FVC/FEV1 ratio, reversibility to inhaled salbutamol, provocation testing leads to bronchoconstriction
What can COPD lead to?
Chronic bronchitis or emphysema
What 5 things can chronic bronchitis cause?
- Mucus hypersecretion
- Chronic neutrophilic inflammation
- Mucociliary dysfunction
- Altered lung microbiome
- Smooth muscle spasm and hypertrophy
Which out of emphysema and chronic bronchitis is partially reversible and which is irreversible?
Chronic bronchitis- partially reversible
What are characteristics of COPD?
Exacerbations and reduced lung function
What are symptoms of COPD?
Breathlessness, cough with sputum production, worsening QOL
What does cigarette smoke cause macrophages and airway epithelial cells to secrete?
Neutrophil chemotactic factors- IL8 and LTB4
What does neutrophils and macrophages releasing proteases do in COPD?
Breaks down connective tissue in the lungs and stimulates mucus hypersecretion
What might also be involved in the destruction of alveolar wall epithelial cells in COPD?
CD8+ T cells
What does an imbalance of proteases and antiproteases lead to in COPD?
Inflammatory changes in the airways including damage of the respiratory mucosa
What is neutrophil elastase?
An enzyme which can damage the cilia
What causes the loss of ciliated cells in COPD?
Recurrent bacterial infections
How do you assess COPD?
Assess symptoms, degree of airflow limitation using spirometry, risk of exacerbations, comorbidities
What are high risk factors for COPD?
2 or more exacerbations in one year, <50% FEV1
What lung sound will chronic bronchitis show?
What lung sound will emphysema show?
Reduced breath sounds
What is the chronic cascade in COPD?
Progressive fixed airway obstruction, impaired alveolar gas exchange, type 2 respiratory failure, pulmonary hypertension, cor pulmonale, death
What classifies ACOS?
COPD with blood eosinophilia >3%
Will mucosal architecture ever be restored in ACOS?
Is there reversibility to salbutamol in ACOS?
is there diurnal variability in COPD?
What do intermittent attacks of bronchoconstriction in asthma result in?
Tight chest, wheezing, difficulty breathing, cough
Chronic asthma causes changes to the bronchioles as a result of long standing inflammation. What are some examples of these changes?
- Increase smooth muscle mass
- Accumulation of fluid (oedema)
- Increased mucus
- Epithelial damage
- Sub-endothelial fibrosis
Airway narrowing and bronchoconstriction in asthma do what to PEFR and FEV1?
What are two bronchial components of asthma?
Bronchial hypersensitivity and hyperresponsiveness
What two phases does an asthma attack comprise?
Immediate bronchospasm and delayed inflammation
Describe the stages of non-atopic asthma?
Allergen, phagocytosis by dendritic cell, low level TH1 response, cell mediated immune response involving IgG and macrophages
Describe the stages of atopic asthma?
Allergen, phagocytosis by dendritic cells, strong TH2 response, antibody mediated response involving IgE
What does the initial presentation of an antigen stimulate in allergic asthma?
Adaptive immune response
What do eosinophils differentiate and activate in response to?
IL5 from TH2 cells
What do airway mast cells differentiate and activate in response to?
IL4 and IL13 from TH2 cells
What happens on subsequent presentation of an antigen in allergic asthma?
The allergen cross-links the IgE receptor
What does cross linking of the IgE receptor in allergic asthma cause release of?
In allergic asthma, what does Ca++ cause release of to cause airway obstruction?
Secretory granules containing histamine and more
In allergic asthma, what does Ca++ cause release of to cause inflammation?
Release of platelet activating factor and prostaglandins to attract cells
What are reliever (bronchodilator) drugs used in asthma?
Beta2 agonists, CysLT receptor antagonists
What are controller/preventer (anti-inflammatory) drugs used in asthma?
Glucocorticoids, cromones, monoclonal IgE antibodies
What asthma drugs have bronchodilator and anti-inflammatory effects?
What is step 1 of asthma treatment?
Mild asthma- prescribe SABA to be used as needed
When do patients need to move to step 2 of asthma treatment?
When the SABA is needed more than once daily
What is step 2 of asthma treatment?
Add inhaled glucocorticoid
If there is still inadequate control, what is step 3 of asthma treatment?
Add a LABA
If once added, a LABA is beneficial for asthma, what should you do?
If once added, a LABA is beneficial but not adequate for asthma, what should you do?
Increase dose of ICS but keep up LABA
If once added, a LABA is not beneficial for asthma, what should you do?
Take off LABA, increase dose of ICS
If asthma is still poorly controlled, what is step 4 of asthma treatment?
Increase dose of ICS and add-on therapy e.g. CysLT1 antagonist, methylxanthine, oral beta2 agonist
If still uncontrolled, what is step 5 of asthma treatment?
Introduce oral steroid, refer to specialist
How do beta adrenoceptor agonists cause smooth muscle relaxation?
Decrease intracellular Ca++ and activate large K+ conductance channels
What are salbutamol and terbutaline examples of?
When are SABAs taken?
How are SABAs taken?
Usually inhaled, can be oral for children and IV for emergencies but these are unlikely
How long do SABAs last?
They act rapidly and last 3-5 hours
Apart from relaxation of smooth muscle, what other functions do SABAs have?
Increase mucus clearance, decrease mediator release from mast cells and monocytes
What are some side effects of SABAs?
Fine tremor, tachycardia, dysrhythmia, hypokalaemia
What are salmeterol and formoterol examples of?
How long do LABAs last?
8 hours roughly
What is the most important rule for prescribing LABAs?
Never use alone- always co-administer with glucocorticoid
Where are CysLT1 receptors usually found?
Mast cells and infiltrating inflammatory cells
What are montelukast and zafirlukast examples of?
CysLT1 receptor antagonists
How are CysLT1 receptor antagonists administered?
When are CysLT1 receptors not used?
For severe, acute relief
What are some side effects of CysLT1 receptor antagonists?
Headaches, GI disturbance
What are theophylline and aminophylline examples of?
What does theophylline activate to increase anti-inflammatory actions of glucocorticoids?
What are methyxanthines used in combination with?
Beta2 agonist and steroid
How are methyxanthines administered?
What side effects can methylxathines cause at normal concentrations?
Nausea, vomiting, abdominal discomfort and headache
What side effects can Methylxanthines cause at high concentrations?
dysrhythmias, seizures, hypotension
What makes Methylxanthines problematic?
Many drug interactions including some antibiotics
What is the main glucocorticoid hormone?
What are glucocorticoids used for in asthma?
How are glucocorticoids usually delivered?
How do glucocorticoids enter the cell membrane?
What are some side effects of inhaled glucocorticoids?
Hoarse/weak voice, candidiasis
When can oral prednisolone be used?
In acute, severe, rapidly deteriorating asthma alongside inhaled steroids
What are cromones used for?
2nd line treatment only really used in children
What are cromones often described as?
Mast cell stabilisers (suppress histamine release from mast cells)
What is an example of a cromone?
What do monoclonal IgE antibodies do?
Suppress mast cell response to allergen
How are monoclonal antibodies given?
What is the treatment for an acute asthma attack? (OH SHIT MAN)
S- salbutamol nebulised
H- hydrocortisone IV/oral
I- ipratropium nebulised with salbutamol
M- magnesium sulphate
What is the acute treatment for COPD? (iSOAP)
O- oxygen (24-28% in venture mask)
A- antibiotics (amoxicillin if non-severe)
What 4 things indicate severe asthma?
Inability to complete sentences, tachycardia, tachypnoea, PEFR < 50% predicted
1 or more of what 5 things indicate life-threatening asthma?
PEFR <33% predicted, hypoxaemia, hypercapnia, silent chest, exhaustion
What can treatment for COPD do?
Slow, but not reverse disease progression, ease chronic symptoms and prevent acute exacerbations
How do muscarinic receptor antagonists work?
By blocking activation of M3 muscarinic receptors by ACh to prevent bronchoconstriction
What is an example of a SAMA?
What is an example of a LAMA?
Which receptors does ipratropium block?
M1, 2 and 3
Which receptor does tiotropium block?
Block of which muscarinic receptors is desirable and which is not?
M3 and M1 are desirable but M2 is not
What does a combination of a LAMA and a LABA cause in COPD?
Increased FEV1 and smooth muscle relaxation
What risk comes with steroids (particularly oral) in COPD?
What are mucolytics such as carbocysteine used for in COPD?
To reduce sputum viscosity
What are PDE4 inhibitors used for in COPD but what are their side effects?
Used to reduce exacerbations but can cause nausea, diarrhoea, headache and weight loss
What does O2 therapy do in patients with daytime hypoxaemia?
Prolongs life by slowing progression of cor pulmonale
How are corticosteroids used in COPD?
Combination with a LABA to reduce exacerbations in eosinophilic COPD
What can happen if an inhaled drug hits the larynx?
What is omalizumab?