Non-Invasive Markers of Airway Inflammation Flashcards
_____ plays a major role in the pathogenesis and exacerbation of lung disease. However, _____ or symptoms do not reflect the inflammation in the lung.
Assessing airway inflammation will help with _____, moitoring disease and assessment of _____ efficacy.
Inflammation plays a major role in the pathogenesis and exacerbation of lung disease. However, LFTs or symptoms do not reflect the inflammation in the lung.
Assessing airway inflammation will help with diagnosis, moitoring disease and assessment of treatment efficacy.
Bronchial biopsies and BAL are two ways of assessing airway inflammation. Give some disadvantages to these interventions (5)
- Invasive
- Can not be done repeatedly
- Can not be used in severe disease
- Can not be used in exacerbation
- Can not be used in children
Name some non-invasive markers of inflammation in the lungs (4)
- Exhaled breath
- NO, CO, Ethane, Ammonia
- Induced Sputum
- Cell counts, mediators
- Condensates
- Oxidants, mediators, metals
- Single breath measurement of bronchial blood floow
- Synthetic Absorptive Matrix (SAM)
- Mediators
Briefly describe the basis of eNO
Chemiluminescence analysis of exhaled NO
Describe how an eNO would be measured (protocol)
Inhalation
- Ambient air, NO free
- Inhale through mout to TLC over 2-3s
Exhalation
- Nasal clip: excludes nasal NO
- Exhalation flow rate of 50mL/second
- Mean 3 exhalations with <10% variability
What is the flow rate needed for eNO?
50mL/sec (0.045-0.055 L/sec)
Decided by ATS/ERS
Why is a ‘high’ flow rate required over low flow for eNO?
Low flow rate will lead to overestimation of NO
Low flow rate has steeper curve -> ↓reproducibility
NO value can be too high (not within detection limit)
What are the result ranges for eNO
LOW: <5
NORMAL: 5-20
HIGH NORMAL/INCREASED: 20-35
HIGH: >35
What could a low FeNO be caused by
Primary Ciliary Dyskinesia
Cystic Fibrosis
Bronchopulmonary Dysplasia
What coyudl a high normal/increased FeNO be caused by?
Cold/influenza
High baseline in atopic patients
What could a high FeNO indicate
Poor compliance
Steroid-resistant
Recent allergen exposure
Not all with high FeNO have symptoms
Interpret this graph
There is a significant increase in eNO in asthmatics compared to healthy controls - p<0.001
NB: This data was cllecte before the exhalation rate was standardised
Interpret this data on eNO and FEV1 after allergen challenge in n=16
FEV1 (N = 3.5-4.5 L)
- Decrease in FEV1 at 1hr after allergen exposure
- Increases back up, close to baseline at 4 hours post-exposure
- FEV1 falls again to a trough at 9 hours post-exposure
- FEV1 then increases back to baseline at 27 hours
eNO
- Sligh increase shortly after allergen exposure then decreases slightly below baseline at 1 hour.
- Steady increase to a peak at 20 hours
- Fall back to baseline at 26 hours
Significance
- There is a significant increase in eNO and decrease in FEV1 from 6-20hrs post-allergen exposure in the late phase
Interpret this data which looked at exhaled NO and airway inflammation in asthma
logPC = provocation challenge, ↓PC to cause 20% decrease in FEV, then ↑airway hyperresopnsiveness
Graph 1
- As PC20 decreased, the eNO also decreased
- There is a significant negative correlation at p<0.001
Graph 2
- As eNO increased, the sputum eosinophils also increased
- There is a significant positive correlation with p=0.003
Interpret the data
There was a significant decrease in eNO with both concentrations of budesonide compared to placebo at days 3 and 5.
There was a significant increase in eNO at day 22 when the ICS wsa stopped.
Explain the one-compartment and two-compartment model in eNO.
One-compartment model
- Measures NO from the alveoli and bronchus
- Assumes that bronchial and alveolar NO production levels are the same
- Assumes flow is the same in both alevoli and bronchus
Two-compartment model
- Splits into alveolar and conducting airway compartments through flow rates
Interpret the data
Bronchial
- In asthma there is an increased NO in the bronchi
- Suggests more inflammation in the conducting airways than in the alveoli
Alveolar
- Increased eNO in COPD when flow was from alveoli
- Even larger increase in ILD
Advantage of exhaled NO and what can it be used for
- Practical
- Reproducible
- On-line
- Patient Management
- Monitor ICS compliance
- Monitor dose of combination inhaler
Disadvantages of exhaled NO
Expensive
Home monitoring not possible
Not correlated with disease severity
Outline the protocol for an induced sputum
Inhalation of hypertonic saline
After each inhalation, subject blows nose, rinses mouth and coughs into container
What can you measure from an induced sputum
Cell count
Mediators (elastase, GF, chemokines LTs)
Explain how induced sputum could hellp manage patients
Management by sputum eosinophils seems to decrease severe exacerbations compared to management by BTS guidelines
What are some limitations for induced sputum (5)
- Safety
- Saline can be bronchoconstrictor for asthamtics/COPD
- Pro-inflammatory
- Needs time interval before can be done again
- Not reproducible
- Time consuming
- Needs specialist training
Briefly outline the protocol for condensate measurement
Subject breaths through glass chamber
Breath gets condensed as there is a cold core
Condensate gathers at the bottom
What can you measure from condesnate
Any soluble compounds from anywhere between the alveoli and the condenser
What are some advantages of using exhled breath condensate (EBC)
Non-invasive and simple
Safe
Performed in different settings
Repeated severeal times with short intervals
What are some limitations of using exhaled breath condensate
- Can’t determine anatomic source of mediators
- can only measure soluble mediators
- Nasal or oral contamination
- No reference values
- Lots of confounders (what you’ve eaten, flow rate)
Breifly outline the concept behind single breath measurement of bronchial blood flow
Begins with tidal breathing
Subject inhales gas mixture of known concentrations
Slow exhalation to residual volume
Measure the ratio of inert and highly solube:inert and highly insoluble through mass spectrometer
↓soluble gas = ↑blood flow in bronchial vessels
Describe the concept behind synthetic absorptive matrix (SAM) sampling
Nasal or through bronchoscopy
Absorbs and sample epithelial lining fluid (ELF)
Elute sample and analyse proteins
SAM is quite new but shows potential in that it has a _____ correlation in CXCL8 between the bronchus and _____. It has also shown differences in CXCL and other mediators in diseases like _____.
SAM is quite new but shows potential in that it has a positive correlation in CXCL8 between the bronchus and nasopharynx. It has also shown differences in CXCL and other mediators in diseases like COPD.
