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Flashcards in asthma Deck (35)
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1
Q

definition

A

o Heterogenous disease usually characterised by chronic airway inflammation.
o history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation – measure by lung func tests (FEV1 or PEF)

2
Q

what is asthma

A

• common and potentially serious chronic disease that can be controlled but not cured

3
Q

symptoms

A

• wheezing, shortness of breath, chest tightness and cough that vary over time in their occurrence, frequency and intensity

4
Q

cause of symptoms

A

o variable expiratory airflow:
o Bronchoconstriction (airway narrowing)
o Airway wall thickening
o Increased mucus

5
Q

• Things that trigger/worsen symptoms

A

o viral infections, allergens, tobacco smoke, exercise and stress

6
Q

pathogenesis

A

o chronic inflamm disease narrow airways
o Airway hyperresponsiveness to bronchoconstrictor substances – shown in lab with histamine/methacholine, airway remodelling, goblet cell hyperplasia, mucus production, smooth muscle contractility and proliferation
o Lead to exacerbations, fixed airway obstruction

7
Q

Airway remodelling in asthma

A

o Thicker
o Fibrosis under epithelium
o Increase number of bv
o Increase mucus production

8
Q

Diagnosis of asthma

A

o A history of characteristic symptom patterns
o Evidence of variable airflow limitation, from bronchodilator reversibility testing or other tests
o Document evidence for diagnosis before starting treatment – difficult to confirm diagnosis when treatment has been started

9
Q

asthma control

A

o Assess asthma – measure components of control: symptoms, nighttime awakenings, interference with normal activity, short acting B2 agonist use for symptom control (not prevention of EIB), FEV1 or peak flow, validated questionnaires (ATAQ, ACQ, ACT)

10
Q

• Drugs for asthma – relievers

A

o Use when get symptom of asthma – from trigger
o Short-acting β2 -adrenoceptor agonists (SABA) – for few hrs inhaled
o Long-acting β2 -adrenoceptor agonists (LABA) –for 12 hrs or more inhaled
o Muscarinic receptor antagonists (SAMA, LAMA) – inhaled

11
Q

• Drugs – controllers – anti-inflamm agents

A

o Glucocorticosteroids (GCS) – inhaled/oral
o COMBINATIONS – LABA/GCS, LABA/LAMA, triple therapy LABA/LAMA/GCS – inhaled
o Leukotriene (cysteinyl) receptor antagonists (LTRA) – oral
o Theophylline – controller – not used as much now

12
Q

previous management of asthma GINA

A

o Stepwise management
o Assess - Diagnosis, symptom control and RF (including lung function), inhaler technique and adherence, patient preference
o Adjust treatment - Asthma med, non-pharm strategies, treat modifiable RF
o Review response – symptoms, exacerbations, SE, patient satisfaction, lung function
o Initiate treatment in pt with no treatment before – determine severity and then judge at what step start
o 1 - Few/occasional symptom – consider low dose ICS, SABA as needed
o 2 - If not as good control – low dose ICS and SABA as needed
o 3 - Then combination ICS/LABA – as needed SBA, low dose ICS/formoterol
o 4 -Increase dose– as needed SBA, low dose ICS/formoterol
o Max dose at step 5, and add on other treatment – oral corticosteroids – as needed SBA, low dose ICS/formoterol

13
Q

• Synergistic action of ICS and LABA

A

o ICS = budesonide
o LABA = formoterol
o Synergistic = combination is more efficacious than either on own
o Budesonide acts on glucocorticoid receptor to have anti-inflamm effect
o formoterol on B2-adrenoceptor for bronchodilation
o causes less exacerbations

14
Q

• combination of Seretide and fluticasone proprionate

A

o seretide = salmeterol (LABA) and fluticasone propionate (ICS)
o end point – well controlled asthma after 1yr
o more go from poorly controlled asthma to well controlled with combined med than ICS alone

15
Q

mild asthma treatment change

A

o step 1 – was just reliever SABA usually salbutamol – but can get exacerbations of disease that might need treatment in hospital so now advised that they start anti-inflamm/controller treatment – consider ICS/LABA or ICS/formoterol
o risk of moderate/severe exacerbation (exacerbation needing extra treatment) – with SABA high compared to ICS and LABA wither continuous or as needed

16
Q

clinical phenotypes of asthma

A

o treat asthma on degree of control/severity, not what type of asthma
o allergic asthma eg provoked with animals – childhood onset
o occupational asthma – sensitiser induced or not
o intrinsic asthma
o air pollution induced
o infection related
o cigarette smoke induced
o obese asthma
o aspirin exacerbated
o cough variant asthma
o exacerbation prone asthma
o asthma persistent airflow limitation
o air pollution induced
o elite athelete exercise induced asthma
o categories: childhood-onset, adult-onset, eosinophilic, non-eosinophilic

17
Q

eosinophils in asthma

A

o if eosinophilia – respond well to ICS
o eosinophils damage epithelium -produce biomarkers that have effect on sm cells that cause contraction, cytokines effect fibroblasts, mast cell activation

18
Q

type 2 inflammation

A

o eosinophils drive asthma through type 2 inflammation
o Th2 cells are central mediators of the adaptive response in type 2 immunity
o adaptive cells – Tfh cell, Th2 cell
o innate – ILC2, mast cell, basophil, eosinophil
o Both Th2 and innate cells produce the key cytokines involved in type 2 inflammation
o cytokines – IL4, Il13, IL5

19
Q

IL5

A

effect on eosinophil maturation in bone marrow – when mature they kleave marrow and target lungs
o In lungs IL 5 increase survival of eosinophils in lungs

20
Q

IL4 and IL13

A
o	Mediate adhesion of eosinophils and migration from endothelium into the lung tissue 
o	IL13 – increase mucus goblet cells and secretion and increase proliferation of sm proliferation = subepithelial fibrosis and collagen deposition 
o	Mainly IL4, but some IL13 – involved in B cell class switching and IgE production – switch B cell from producing IgG to IgE – IgE latch onto receptors on mast cell = activation of mast cell = mast cell production of leukotrienes, histamine, PGD2 = airflow obstruction -> exacerbation, bronchial obstruction, impaired lung function, symptoms
21
Q

affect of allergens, viruses and irritants

A

o Activate type 2 inflammation

22
Q

• Relevance of type 2 inflamm

A

o Med target the cytokines
o Anti-IgE: omalizumab – recommended for allergic asthma
o Anti-IL5 (mepolizumab, reslizumab), anti-IL-5Ra (benralizumab)
o Anti-IL-4Ra blocking IL-4/IL13 signalling (dupilumab)
o Treatments recommended aty step 5 in pts with sever asthma

23
Q

severe asthma

A

o 5% pts with asthma
o Pts get treatment recommended and still not responding – poor symptom control, serious/frequent exacerbations, airflow obstruction (FEV1)
o “asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.”
o Uncontrolled asthma while on high dose therapy = GINA step 4 and 5
o Controlled asthma that becomes uncontrolled on tapering of high-dose corticosteroids – GINA 5

24
Q

• Effectiveness of mepolizumab

A

o Block the eosinophils

o Reduction of approx. 50% rate of exacerbations, and improvement in FEV1 and QOL

25
Q

when do you treat for severe asthma

A

o Step 5
o Criteria of type 2 inflammation:
o Blood eosinophils ≥150/μL and/or • FeNO ≥20 ppb and/or • Sputum eosinophils ≥2% and/or • Clinically allergen-driven • Need for maintenance OC

26
Q

what are other types of asthma than T2 inflammation

A

o Neutrophilic inflammation

o Remodelling/repair

27
Q

precision medicine

A

o an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.

28
Q

• Systems biology of asthma

A

o Clinical phenotypes – symptoms, physiology, inflamm markers
o Molecular phenotypes – RNA, DNA, proteins – tell mechanism driving disease = specific treatment
o Endotypes
o Biological responses
o Therefore understand how exposome, lifestyle and genome influence the biological responses

29
Q

• T2-high mechanisms/pathways

A

o TAC1
o IL-33R, TSLPR, CCR3
o Severe airflow obstruction Highest exacerbation Nasal polyps Oral corticosteroid dependent Highly Eosinophilic (some neutrophilia)

30
Q

• T2-low/non-T2 mechanisms/pathways - TAC2

A

 IFN & TNF pathways Moderate airflow obstruction More eczema High C-Reactive protein levels Highly Neutrophilic (+ eosinophilia)

31
Q

• T2-low/non-T2 mechanisms/pathways TAC3

A

 Oxidative stress Ageing

 Moderate airflow obstruction Least exacerbations Paucigranulocytic/ eosinophilic

32
Q

• Type 2 inflammation types of asthma

A

o Allergic
o Late onset eosinophilic
o Exercise induced

33
Q

• Non-type 2 inflammation

A

o Very late onset
o Obesity associated
o Smoking associated neutrophilic
o Smooth-muscle mediated, paucigranulocytic

34
Q

GINA treatment

A
step 1: 
As-needed
low-dose
ICS-formoterol, Low-dose ICS
taken whenever
SABA is taken, 
step 2 
Daily low-dose inhaled corticosteroid (ICS),
or as-needed low-dose ICS-formoterol, Leukotriene receptor antagonist (LTRA), or
low-dose ICS taken whenever SABA taken, 
step 3
Low-dose
ICS-LABA, Medium-dose
ICS, or low-dose
ICS + LTRA
step 4 
Medium-dose
ICS-LABA, High-dose ICS,
add-on
tiotropium, or
add-on LTRA
step 5 
High-dose
ICS-LABA
Refer for
phenotypic
assessment
± add-on
therapy,
eg tiotropium,
anti-IgE,
anti-IL-5/-5R,
anti-IL-4R, Add low-dose
OCS, but
consider
side effects
35
Q

relievers used - GINA

A

As-needed low-dose ICS-formoterol

As-needed short-acting β2 agonist (SABA)