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PAM PATTON
SENIOR RESPIRATORY NURSE
HINCHINGBROOKE HOSPITAL
AIMS OF THE SESSION
 Look at COPD as not just a Lung disease
 Look at the development of systemic
consequences and common co-morbidities
 Look at possible mechanisms by which they
develop
What is COPD?
 A disease state characterised by airflow limitation that is not fully
reversible and is usually progressive
 Associated with an enhanced chronic inflammatory response in the
airways and the lungs to noxious particles or gases
 Predicted to be 3rd leading cause of death worldwide by 2020
 Treatable but not curable
Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial
update
NICE guidelines [CG101] Published date: June 2010
COPD definition - GOLD
Most recent update by Global Initiative for COPD (GOLD) 2015
defines COPD as
“ a preventable and treatable disease with some
significant extrapulmonary effects that may contribute
to the symptom characterised by airflow limitation that
is not fully reversible”
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung
Disease (GOLD) 2015.
We know that

Cigarette smoking is the
commonest cause of
COPD

Only a percentage of
smokers(so called
susceptible smokers)
develop the disease
(approx 25%)

20% patients are non
smokers
Developing COPD: a 25 year follow up study of the general
population
Thorax2006;61:935-939 doi:10.1136/thx.2006.062802
Cigarette smoke
 Cigarette associated noxious agents injure the airway
epithelium and drive the key process that leads to
specific airway inflammation
 So if we remove the agent, repair process should bring
the airways back to their normal structure
 But!!!
However
 This inflammatory response is enhanced and fails to resolve after
quitting smoking in patients who develop COPD
 Switch from a self limiting inflammation to chronic persistent
inflammation
 This clearly indicates that the regulation of the inflammatory
response is abnormal
 This inflammatory process contributes to remodelling of
pulmonary tissue
Rennard S I Inflammation in COPD : a link to systemic comorbidities European Respiratory Review 1 September 2007
What we do know
 COPD is associated with clinically significant systemic alterations in
biochemistry and organ function
 Altered circulating levels of inflammatory mediators and acute-phase
proteins (CRP) rise with severity of COPD
 Altered levels of several cytokines such as interleukin-1 and tumour
necrosis factor alpha (TNFα)
 Oxidative stress is over activated in COPD causing tissue damage

Stockley RA, Systemic inflammation and comorbidity in COPD: a result of overspill of inflammatory mediators from
the lungs? Thorax 2010;65 930-936
So although the
 Ventilatory system is clearly
dysfunctional
 Inflammatory mediators
generated in the lung enter
the blood stream and may
have systemic effects on
other susceptible areas of the
body

Nussabaumer-Ochsner Y, Rabe KF Syestemic
manifestations of COPD. Chest 2011 Jan;139(1) 165-73
Systemic effects and Mortality
 Can seriously affect
quality of life
 Worsen clinical
prognosis
Some common co- morbidities include
 Skeletal muscle





dysfunction
Weight loss
Cardiovascular disease
Diabetes
Osteoporosis
Anxiety/Depression
 Hypertension
 Lung Cancer
 Pulmonary hypertension
 Cor Pulmonale
 Sleep Apnoea
 GORD
 Anaemia
Skeletal Muscle Dysfunction
(SMD)
SMD
 Lower muscle strength
 Lower muscle endurance
 Sarcopenia (loss of
muscle cells) and
abnormal function of
remaining cells
 Together called “skeletal
muscle dysfunction”
SMD
 Exercise limitation has
traditionally been
explained by the
increased work of
breathing and dynamic
hyperinflation
 However SMD is often a
very significant
contributor in these
patients
 Each muscle is made up of millions of fibers
 In COPD these fibers can become smaller, weaker and
may even waste away entirely
 Some research suggests this is part of the systemic
inflammatory process that weakens and damages
muscles over time
Hypoxia
 Low oxygen levels over
time decreases the size
of muscle fibers
 Leads to muscle
weakness
Muscle symptoms - multifactorial
 Inactivity
 Poor diet
 Inflammation
 muscle fatigue – exercise intolerance
 Poor health status
Weight loss in COPD
Weight loss in COPD
 Studies of body composition
in COPD show that both fat
mass and fat-free mass are
lost.
 Increased breakdown of
muscle proteins , a typical
feature of cachexia, has been
demonstrated in patients
with COPD
 Poor prognostic factor
Causes
 Less interest in food
 difficulty swallowing or
chewing due to dysponea
 Full stomach
 Using more energy and
nutrients – more energy to
breathe or do any physical
activity
 Steroids – breaks down
muscle tissue
Weight loss cont’d
 chronic mouth breathing, which can alter the





taste of food
chronic mucous production
coughing;
fatigue;
depression
side effects of medications.
NICE Guidelines on Nutritional Factors
 1.2.12.6 BMI should be calculated in patients with COPD:
 the normal range for BMI is 20 to less than 25[8]
 if the BMI is abnormal (high or low), or changing over time, the patient
should be referred for dietetic advice
 if the BMI is low patients should also be given nutritional supplements
to increase their total calorific intake
 Be encouraged to take exercise (anobolic stimulus) to augment the
effects of nutritional supplementation.
1.2.12.7 Refer to 'Nutrition support in adults' (NICE clinical guideline 32). [2004]
Combination of the 2
Muscle Weakness
 weight loss
Muscle weakness with weight
loss
 Body breaks down
muscle and makes
the patient weaker
 Leads to more
shortness of breath
and less activity
 Leads to weaker
muscles
Cycle of deconditioning
 Patients who are
breathless avoid exercise
and other physical
activities that make
them sob
 Muscles start to lose
strength and endurance
 Can be difficult to break
the cycle
Pulmonary rehabilitation
 Goals
 To reduce symptoms
 disability
 handicap
 improve their quality
of life
Pulmonary rehabilitation
 Positive outcomes
include:

a reduction in
exacerbations

improved
prognosis

improved quality
of life
Cardiovascular disease in COPD
Cardiovascular disease
 Evidence has shown that COPD is associated with
cardiovascular risk
 As FEV1 fell increase in the arterial wall stiffness was
found
 Patients with severe airflow obstruction more likely to
have electrocardiogram evidence of ischemic heart
disease compared to no airflow obstruction
Targeted treatment in COPD: a multi-system approach for a multi-system disease.
Anderson D1, Macnee W. Int J Chronic obstructive Pulmonary Dis 2009;4:321-35. Epub 2009 Sep 1.
So
 Is the systemic
inflammation as a result
of COPD causing
vascular endothelial
damage?
 Higher levels of systemic
inflammation were
found in COPD patients
with evidence of IHD
COPD Inflammation Can Contribute
to Cardiovascular
Disease
Lung Inflammation
Acute
Chronic
TNF-α
C-reactive
Protein
Autonomic
Instability
IL-6
GM-CSF
Fibrinogen
Neutrophils
Arrhythmias
Coagulation
Progressive
Atherosclerosi
GM-CSF
= granulocyte-macrophage colony stimulating factor
s
IL = interleukin
TNF = tumor necrosis factor
Rennard SI. Proc Am Thorac Soc. 2005;2:94-100. Permission requested.
Inflammation
Diabetes in COPD
Risk factors
 Risk appears to exist
regardless of the severity
of COPD
• An increase in body
mass index (BMI)
• Inflammation
 Oral corticosteroids
 Inhaled corticosteroids
Chicken and egg – which came first?
 Some of the same
inflammatory markers
are increased in diabetes
and COPD
 Inflammation may
induce insulin
resistance by blocking
signalling through the
insulin receptor and
increase the risk of type
2 diabetes
High glucose levels
 Elevated levels of blood glucose
are associated with abnormal
lung function.
 loss of respiratory compliance
(ability of the lungs to distend)
associated with diabetes
 weakened respiratory muscles
 can cause a reduction in the ability of
the lung tissue to transfer oxygen
(diffusing capacity)
Goldman MD Lung Dysfunction in Diabetes. Diabetes Care June 2003
Vol 26 no 6 1915-1918
Osteoprosis
 Often overlooked and undertreated
 Clinically a silent disease until it manifests in the
form of a pathological fracture
 Primary focus is to improve and maintain lung
function
 Don’t realise patients have low bone mass
 Increased risk factors identified:







Smoking
Increased alcohol intake
Low Vitamin D Levels
Genetic factors
Treatment with corticosteroids
Reduced skeletal muscle mass and strength
Low BMI
Ionescu AA, Schoon E. Osteoporosis in chronic obstructive pulmonary disease. Eur Respir J.
2003;22 (Suppl 46):64s-75s.
cont’d
Chronic Systemic Inflammation
 Inflammation exerts significant influence on
bone turn over
 Pro inflammatory cytokines play a critical role in
regulating osteoblasts and osteoclasts
Ginaldi L, et al Immunity and aging 2005;14-18
Inflammatory Mediators in
Osteoporosis
 IL-1
 IL-6
 IL-11
 TNF-
 Transforming growth factor (TGF) -
 Nitric oxide (NO)
 Receptor activator of NFB (RANK)/RANK ligand
(RANKL)
Ginaldi L, et al. Immunity and Aging. 2005;2:14-18.
Anxiety and Depression
Anxiety and depression
 Depression may not
always be recognised
 Depression is two or
three times more
common in patients
with chronic diseases
than in those who have
good physical health.
NICE Clinical Guideline (October 2009)
Risk factors include:
 Severe dyspnoea
 Physical disability
 Long term oxygen therapy
 Low body mass index
 FEV1 ≤50% predicted
 Poor quality of life
 Presence of comorbidity
 Living alone
 Have been seen or admitted to hospital for an exacerbation

Maurer J RebbapragadaV, Borson et al. Anxiety and depression in COPD :current understanding, unanswered questions and
research needs. Chest. 2008;134 (4suppl) 43S-56S
Systemic inflammation in depression
 Suggested that depression may be influenced by
systemic inflammation
 Higher levels of TNF-α interleukin-6 (IL-6) were
found independent of the severity of airflow
obstruction.
ATS 2013 Hilary Strollo, M.S., a graduate of the University of Pittsburgh School of Health and Rehabilitation Sciences.
Key Questions? During the last month
have you:1) often been feeling down,
depressed or hopeless
2)Have you found little
interest or pleasure in
doing things
3) Do you feel upset or
frightened by your attacks
or breathlessness
 Consider more formal
assessment if patients
answer yes
 Hospital Anxiety and
Depression Scale
(HADS)
 Patient health
questionaire-9
In Conclusion
 COPD is associated with high levels of systemic
inflammation, secondary to pulmonary inflammation
 Will the development of therapies that target
inflammation in the lung reduce the risk for
comorbidities
 Will the medications have the potential to improve
survival, function and quality of life
Thank you
 Any questions?