Airways Disease Flashcards
(30 cards)
What are the key features of asthma?
- History of respiratory symptoms – wheeze, dyspnoea, chest tightness, cough – that vary over time and intensity.
- Variable expiratory airflow limitation (which can become persistent in long-standing asthma).
What are the diagnostic criteria for asthma in adults (symptoms and tests)?
- History of respiratory symptoms
a. Typically >1 respiratory symptom – wheeze, dyspnoea, chest tightness, cough
b. Varying in time and intensity
c. Often worse at night or on waking
d. Often triggered – exercise, laughter, allergens, cold air
e. Often worse with viral infections - Evidence of variable expiratory airflow limitation
a. FEV1/FVC below lower limit of normal
b. Variability in expiratory lung function is greater than in healthy people
i. Post-bronchodilator increase in FEV1 by >200ml or >12%
ii. Average daily diurnal PEF variability >10% (twice daily reading, best of 3 each time over 1-2 weeks)
iii. FEV1 increases by >200ml or 12% after 4 weeks of anti-inflammatory treatment (outside respiratory infections
c. Significant bronchodilator reversibility may be absent during viral infections or severe exacerbations
How long should pre-initiated inhalers be held before spirometry?
SABA: >4hrs
BD ICS-LABAs: >24hrs
OD ICS-LABAs: >36hrs
How is asthma control assessed?
Questions (regarding the last 4 weeks)
1. Daytime symptoms >x2/week
2. Night waking due to asthma
3. SABA required >x2/week
4. Activity limitation due to asthma
Scoring
- Well controlled: 0
- Partly controlled: 1-2
- Uncontrolled: 3-4
What are the risk factors for poor asthma outcomes and exacerbations?
- Medication over usage - >2 SABA inhalers/year (1/month substantially increases mortality
- Medication adherence – ICS not prescribed, ICS non-compliance, poor technique
- Comorbidities – obesity, chronic rhinosinusitis, GORD, food allergy, anxiety/depression, pregnancy
- Exposures – smoking, e-cigarettes, allergens, air pollution
- Setting – socioeconomic problems
- Lung function – low FEV1 (especially if <60%), high bronchodilator responsiveness
- Type 2 inflammatory markers – high eosinophils, high FeNO (despite ICS treatment)
Describe when/why ICS-LABA can be used as reliever, including the specific LABA and what brands this includes
Reduces risk of severe exacerbations compared to SABA
Should not be used as reliever if patient taking different ICS-LABA
ICS-Formoterol containing inhalers include: Fostair, Symbicort, Duoresp and Flutiform
Describe the asthma treatment tracks (GINA ladder)
Track 1 (preferred) – PRN ICS-formetorol reliever
1. PRN low-dose ICS-formetorol
2. Add low-dose maintenance ICS-formetorol
3. Increase to medium-dose maintenance ICS-formetorol
4. Add LAMA and assess phenotype. Consider high-dose maintenance ICS-formetorol +/- anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP
Track 2 – PRN SABA reliever
1. PRN ICS whenever SABA required
2. Low-dose maintenance ICS
3. Low dose maintenance ICS-LABA
4. Medium/high dose maintenance ICS-LABA
5. Add LAMA and assess phenotype. Consider high-dose maintenance ICS-LABA +/- anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP
What immunotherapy is available for asthma (targets and drugs) and what phenotypes are they used for?
Anti-IgE: SC omalizumab (severe allergic asthma)
Anti-IL5: SC mepolizumab, IV reslizumab (severe eosinophilic asthma)
Anti-IL5R: SC benralizumab (severe eosinophilic asthma)
Anti-IL4RL: SC dupliumab (severe eosinophilic asthma)
Anti-TSLP: SC tezpelumab (severe asthma)
Describe the process of airway inflammation in asthma
Most common = eosinophilic bronchitis/bronchiolitis
- airway inflammation is seen with infiltration of Th2 (helper T Cells), lymphocytes, eosinophils and mast cells
- large and small airway involvement
- Cytokine production (IL-13, IL-4, IL-5, cysteinyl-leukotrienes)
25% non-eosinophilic
- largest population of this group driven by neutrophilic airway inflammation from airway infections
- minority has no inflammation -> smooth muscle dysfunction
- non-eosinophilic have poorer short-term response to ICS/OCS, often need different treatment strategy
How does airway obstruction occur in asthma?
- Inflammatory cell inflammation
- Mucus hypersecretion with plug formation
- Airway smooth muscle contraction
What causes chronic/irreversible asthma over time?
- basement membrane thickening
- collagen deposition
- epithelial desquamation
- airway remodelling with smooth muscle hypertrophy and hyperplasia
Describe the immune mechanisms of asthma
Atopic subtype
- reacts to antigen challenge
- specific IgE produce from B-lymphocytes
- IgE-antigen complex formed –> binds to mast cells, basophils and macrophages
- Causes release of preformed mediators (histamine, IL-5)
- Results in T2 eosinophilic inflammation
50% of asthma is non-allergic
- Due to irritation/insult to airway epithelium
- Also produces type 2 response
Are there any genetic associations with asthma?
Hereditary component in asthma and atopy well established
Specific genes are difficult to determine
Established susceptibility loci:-
- ADAM33
- GPRA (G protein-related receptor for asthma)
- ORMDL3 (encodes transmembrane endoplasmic reticulum proteins)
What is the gene associated with A1AD?
Mutations of the SERPINA1 gene
What is the pathology of COPD?
Chronic Bronchitis
* MUC5B (produced by surface secretory cells throughout airways and submucosal glands)
* Levels are markedly increased in COPD due to submucosal gland hyperplasia, leading to airway occlusion
* Levels also increased by viruses and cytokines (IL-4, IL-13, IL-17, IL-23 and IL-25)
Inflammatory Cells:-
* Associated with increased macrophages, activated neutrophils and lymphocytes
* Affects peripheral airways, lung parenchyma and pulmonary vessels
* Some cross-over with asthma (eosinophils and ILC2 cells
What are the diagnostic criteria of COPD?
- Non-fully reversible airflow limitation (FEV1:FVC <0.7 post-bronchodilation)
- Pre-COPD or PRISm (Preserved Ratio Impaired Spirometry)
- Structural lesions (eg. Emphysema)
- Physiological abnormalities (low-normal FEV1, gas trapping, hyperinflation, reduced DLCO)
What are the severity classifications of COPD?
- Mild/GOLD 1: FEV1 ≥ 80%
- Moderate/GOLD 2: FEV1 50-79%
- Severe/GOLD 3: FEV1 30-49%
- Very severe/GOLD 4: FEV1 ≤30%
What are the points of the mMRC?
- 0 = dyspnoea with strenuous exercise
- 1 = dyspnoea with hurrying of flat or walking up slight hill
- 2 = slower walking than others due to dyspnoea, or stopping on the flat at own pace
- 3 = stopping for breath at 100m or a few minutes on the flat
- 4 = dyspnoea when dressing/undressing, unable to leave home
How would you classify COPD based on the GOLD assessment tool?
- Exacerbation History (per year)
- ≥2 moderate exacerbation -> E
- Any exacerbations leading to hospitalisation -> E
- ≥1 moderate exacerbations (and no hospitalisation) -> A or B
- Symptoms
- mMRC 0-1 and/or CAT <10 -> A
- mMRC ≥2 and/or CAT ≥10 -> B
What physiological Tests are used in COPD?
- Spirometry: FEV1/FVC ration <0.7, FEV1 (mild ≥80%, mod 50-79%, sev 30-49%, v. sev ≤30%
- Lung volumes:-
- ↑RV = gas trapping
- ↑TLC = static hyperinflation
- DLco (<60% associated with increased symptoms, decreased exercise capacity, worse health status and increased risk of death)
- Oximetry and ABG
- Measure sats if any signs of respiratory or right heart failure
- If oximetry <92% -> ABG
- Exercise testing: 6MWT (self-paced) and Shuttle Walk Test (paced) – can assess disability, risk of mortality and effectiveness of pulmonary rehab
When should you consider asthma or asthma + COPD as a diagnosis (based on investigations)
- > 400ml increase in FEV1 with bronchodilators
- > 400ml increase in FEV1 with 2/52 30mg prednisolone
- Serial PEFR showing ≥20% diurnal or day-day variation
What are poor prognostic factors in COPD?
- Low FEV1
- Active smokers
- High mMRC
- Chronic hypoxia and/or cor pulmonale
- Low BMI
- Severe/high frequency of exacerbations
- Hospital admissions
- Symptom burden (high CAT score)
- Poor exercise capacity (eg 6MWT)
- Low DLCO
- Fits criteria for LTOT/domiciliary NIV
- Multimorbid
- Frail
What are the non-pharmacological options in COPD (by non-pharmacological, this is more in relation to indirect COPD treatment)
Smoking Cessation
* NRT
* Bupropion (NDRI/norepinephrine-dopamine re-uptake inhibitor)
* Nortriptyline (TCA)
* Varenicline (nicotinic partial agonist + cholinergic agonist
Vaccinations
* Influenza (annual)
* Pneumococcal (5 yearly)
Pulmonary Rehab
What are the different pharmacological options for COPD?
- Beta-2 Agonists – stimulate beta-20adrenoreceptors, increases cAMP causing antagonism to bronchoconstriction
- Antimuscarinics - block bronchoconstrictor effects of acetylcholine on M3 muscarinic receptors (SAMAs are also antagonists of (inhibitory) M2 receptors –> block vagally induced bronchoconstriction
- Methylxanthines (theophylline) – non-selective phosphodiesterase inhibitor
- ICS – useful with: GOLD E, eosin ≥0.3, history of/concomitant asthma
- OCS – only useful in acute exacerbations
- PDE4 Inhibitors (eg Roflumilast) – reduce inflammation by inhibiting breakdown of intracellular cAMP
- Must be chronic bronchitis GOLD 3/4E despite x3 therapy
- Abx (eg azithromycin 250mg OD/500mg x3/week) – reduces risk of exacerbations in exacerbation-prone patients
- Must be non-smokers with frequent (≥4 yearly) exacerbations or prolonged exacerbations with sputum or hospitilisation
- Mucolytics (eg. Carbocysteine) – can reduce exacerbations
- LTOT – assess via ABG twice at least 3 weeks apart, must not smoke
- PaO2 <7.3 when stable
- PaO2 7.3-8 when stable with any of: secondary polycythaemia, peripheral oedema, PHTN
- Must be for minimum 15hrs/day
