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Pathophysiology of COPDWhat you really need to know
John Hurst PhD FRCP FHEA
Professor of Respiratory Medicine
UCL Respiratory
University College London, London, UK
@ProfHurst | [email protected]
UCL Respiratory
• Payments for educational and advisory work, to me and my employer (UCL), and support to attend meetings from pharmaceutical companies that make medicines to treat respiratory disease.
• I am supervising a PhD student running a RCT of protein supplementation for COPD patients during PR; the supplement is supplied by Nutricia.
• I am National COPD Audit Lead
• And I don’t know very much about nutrition.
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Conflicts of Interest
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AZ; Act on COPD
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AZ; Act on COPD AZ; Act on COPD
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What is a COPD Exacerbation?
“an acute worsening of respiratory symptoms that result in additional therapy”
GOLD: www.goldcopd.orgGOLD was launched in 1997 in collaboration with the US National Heart, Lung, and Blood Institute, US National Institutes of Health and World Health Organization.
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What is a COPD Exacerbation?
“a common preventable and treatable disease that is characterised by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases”
GOLD: www.goldcopd.orgGOLD was launched in 1997 in collaboration with the US National Heart, Lung, and Blood Institute, US National Institutes of Health and World Health Organization.
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UCL Respiratory
with verbal permission
UCL Respiratory
with verbal permission
Mortality3 million people/year, 90% in LMIC
Morbidity33 million DALYs lost in LMIC
Economic Loss
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with verbal permissionwith written permission
Mortality3 million people/year, 90% in LMIC
Morbidity33 million DALYs lost in LMIC
Economic Loss
COPD is common, and COPD is burdensome
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Key Messages
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COPD
Chronic BronchitisEmphysema
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COPD
Chronic BronchitisEmphysema
PATHOLOGICAL diagnosis
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COPD
Chronic BronchitisEmphysema
PATHOLOGICAL diagnosis
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CLINICAL diagnosis
COPD
Chronic BronchitisEmphysema
PATHOLOGICAL diagnosis
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PHYSIOLOGICAL
DIAGNOSIS:
Post-BD FEV1/FVC <0.7
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Pathology - Inflammation
COPD
Chronic BronchitisEmphysema
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PHYSIOLOGICAL
DIAGNOSIS:
Post-BD FEV1/FVC <0.7
No more ‘average patient’
No more ‘one size fits all’
Not new, but
Technology: genetics, imaging
Computational Power
[with written patient permission]
Phenotypes in COPD
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Phenotype
the set of observable characteristics of an individual resulting from the interaction of genotype and environment (…and that defines natural history or predicts a treatment response).
Endotype
a subtype of a condition, which is defined by a distinct functional or patho-biological mechanism.
Phenotypes in COPD
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[with written patient permission]
Phenotypes and Endotypes in COPD
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COPD is diverse, including phenotypes that associate with nutrition
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Key Messages
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Chronic Obstructive Pulmonary Diseasegenetically susceptible lung meeting
sufficient environmental trigger
Fletcher and Peto BMJ 1977
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Chronic Obstructive Pulmonary Diseasegenetically susceptible lung meeting
sufficient environmental trigger
12 60 24
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Why are patients with COPD breathless?
Less elasticitySmall airway collapseLuminal obstructionBronchoconstriction
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Dynamic Hyperinflation
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Chronic Obstructive Pulmonary Diseasegenetically susceptible lung meeting
sufficient environmental trigger
E x a c e r b a t i o n
12 60 24
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What is (and isn’t) a COPD Exacerbation?
…change in symptoms needing a change in treatment…
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What is (and isn’t) a COPD Exacerbation?
…change in symptoms needing a change in treatment…
in which other causes have been considered and ruled out!
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Exacerbation Aetiology
Mallia P et al. Am J Respir Crit Care Med 2011;183:734-742.
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Exacerbation Aetiology
Mallia P et al. Am J Respir Crit Care Med 2011;183:734-742.
UCL Respiratory
Exacerbation Aetiology
Mallia P et al. Am J Respir Crit Care Med 2011;183:734-742.
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Exacerbation Aetiology
Patient perceptions of exacerbation
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“Exacerbation and hospitalization due to exacerbation are the outcomes that COPD patients rate as most important”.
Eur Respir J 2018;52:1800222
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The ‘Frequent Exacerbator’ Phenotype
The Importance of Exacerbations
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Frequent
Exacerbation
∆15 units, p<0.001
Seemungal TAR et al. AJRCCM
1998 Soler-Cataluna JJ et al. Thorax 2005
Donaldson GC et al. Thorax 2002
32 vs. 40 ml/year, p<0.05
↑Costs
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COPD Audit
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Data ‘Highlights’: Outcomes Report
Mortality
Re-Admissions
n=30,294
(now n>200,000)
SYMPTOMS mMRC ≥2
CAT≥10
mMRC 0-1
CAT<10
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Rx
[with written patient permission]
“How many courses of antibiotics and/or steroids did you need for
you chest over the last year?”
SYMPTOMS mMRC ≥2
CAT≥10
mMRC 0-1
CAT<10
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Rx
≥2
*
1
0
RISK
Exacerbations
[with written patient permission]
SYMPTOMS mMRC ≥2
CAT≥10
mMRC 0-1
CAT<10
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Rx
≥2
*
1
0
RISK
Exacerbations
DC
A B A: Low Risk, Fewer Symptoms
B: Low Risk, More Symptoms
C: High Risk, Fewer Symptoms
D: High Risk, More Symptoms
Exacerbation Prevention
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Pharmacological
Inhaled Steroids
LABA
LAMA
Macrolide
Mucolytic
Non-Pharmacological
*Pulmonary Rehab
Vaccination
Volume Reduction
Right Intervention, Right Patient, Right Time: Precision Medicine
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NICE and “Triple Therapy”
London Respiratory “Value Pyramid”https://www.nice.org.uk/guidance/ng115
Exacerbation prevention is a major goal
Get the basics right – ‘real’ Triple Therapy
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Key Messages
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Causes of Re-admissions
Reasons for readmissions within 30 daysNACAP Data
COPD Exacerbation 39.4%
Pneumonia 13.4%
Everything Else 47.2%
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The ‘Co-Morbidome’
Divo M et al. AJRCCM 2012;186:pp 155–161
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3. COPD and Cardiovascular Risk
Cumulative incidence of first MI Cumulative incidence of first CVA
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Comparative Plumbing!Airway
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Comparative Plumbing!Airway COPD
Smoke (and more)
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Comparative Plumbing!Airway COPD
Smoke (and more)
Exacerbation
Trigger
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Comparative Plumbing!Airway COPD
Smoke (and more)
Exacerbation
Trigger
Artery Atherosclerosis ACS
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Systemic Inflammation and Vascular Risk
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COPD and Systemic Inflammation
Gan WQ et al. Thorax 2004;59:574-580
COPD is associated with systemic inflammation, and multi-morbidity
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Key Messages
➢ COPD is common
➢ COPD is burdensome
➢ COPD is diverse
➢ Exacerbations and Multi-Morbidity are major problems
➢ COPD clinicians need your help
How does nutritional status and intervention on nutritional status affect outcomes in COPD?
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Summary
Thank YouComments and Questions
John Hurst PhD FRCP FHEA
Professor of Respiratory Medicine
UCL Respiratory
University College London, London, UK
@ProfHurst | [email protected]
UCL Respiratory
![COPD en anesthesie 1 [Alleen-lezen] - uzleuven.be · surgeries. Indian journal of anesthesia. 2016. jan • West J. Pulmonary pathophysiology, the essentials 8th ed. 2012 • Duke,](https://img.pdfslide.net/doc/110x75/5e190a684100006ef572e150/copd-en-anesthesie-1-alleen-lezen-surgeries-indian-journal-of-anesthesia-2016.jpg)
