Chronic obstructive pulmonary
disease
•Diagnosis
•Treatment
•Causes
•Surveillance
S C Stenton, Newcastle upon Tyne
Change in Age-Adjusted Death Rates, U.S., 1965-1998
IHD
Stroke
1965
1970
1975
1980
1985
1990
1995 2 000
Change in Age-Adjusted Death Rates, U.S., 1965-1998
COPD
IHD
Stroke
1965
1970
1975
1980
1985
1990
1995 2 000
Who gets heart disease
Who gets COPD
Investment in COPD
Devon Donkey Sanctuary
Annual income
£22,000,000 (2009)
British Lung Foundation
Annual income
£6,000,000 (2012)
COPD now a disease of women
CHRONIC OBSTRUCTIVE PULMONARY DISEASE SURVEILLANCE—UNITED STATES, 1972-2000.
Chronic obstructive pulmonary disease
(COPD)
A disease state characterized
by airflow limitation that is not
fully reversible. The airflow
limitation is usually both
progressive and associated
with an abnormal
inflammatory response of the
lungs.
COPD diagnosis
• Diagnosis based on FEV/FVC
• FEV/FVC <70%
• Severity based on FEV % predicted
•
•
•
•
Stage 1 : FEV >80%
Stage 2 : FEV 50-79%
Stage 3 : FEV 30-49%
Stage 4 : FEV <30%
(mild)
(moderate)
(severe)
(very severe)
Changes in FEV/FVC with age
Melville ERJ 2010 : 850 subjects age 45-70
Changes in FEV/FVC with age
Melville ERJ 2010 : 850 subjects age 45-70
Changes in FEV/FVC with age
Melville ERJ 2010: 850 subjects age 45-70
FEV/FVC
70% vs LLN (lower limit of normal)
for COPD diagnosis
70%
LLN
80% vs LLN (lower limit of normal)
for COPD sseverity
80%
LLN
Other issues in COPD diagnosis
• Distinguishing asthma
• Not all airflow obstruction is due to COPD
• Emphysema without airflow obstruction
• But markedly impaired gas transfer
• Combination of COPD and fibrosis
• Normal spirometry but impaired gas transfer
• Low FEV1/FVC with normal FEV and FVC
• can be a normal variant
bodybuilders, divers, rowers, firemen
Asthma v COPD
Asthma phenotype
COPD phenotype
• Family history
• Childhood symptoms
• Allergy history
• Rare before 40s
• Variable symptoms
• Good response to
treatment
• Smoking history
• Fixed symptoms
• Poor response to
treatment
Other issues in COPD diagnosis
• Distinguishing asthma
• Not all airflow obstruction is due to COPD
• Emphysema without airflow obstruction
• But markedly impaired gas transfer
• Combination of COPD and fibrosis
• Normal spirometry but impaired gas transfer
• Low FEV1/FVC with normal FEV and FVC
• can be a normal variant
• bodybuilders, divers, rowers, firemen
Treatment of COPD to prevent exacerbations
Placebo
LAMA
(Tiotropium)
Placebo
LABA + ICS
(Symbicort)
Calverley ERJ 2003
Tashkin NEJM 2008
Pharmacological treatment of COPD
• Long acting B agonist (LABA)/ Inhaled corticosteroid (ICS)
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•
•
•
•
•
Seretide (Salmeterol + Fluticasone proprionate)
Symbicort (Formoterol + Budesonide)
Fostair (Formoterol + Beclomethasone0
Relvair (Vilanterol+ Fluticasone Fumarate)
Flutiform (Formoterol + Fluticasone Fumarate)
Duoresp (Formoterol + Budesonide)
• Long acting antimuscarinic (LAMA)
• Spiriva (Tiotropium)
• Seebri (Glycopyrrinium)
• Eklira (Aclidinium)
• Long acting B agonist (LABA) + antimuscarinic (LAMA)
• Anaro (Vilanterol+ Umeclidinium)
• Ultibro (Indacaterol +glycopyrronium)
• PF-4348235, PF-3429281, GSK961081
• Phosphodiesterase inhibitors
• Rofumilast
• Triple therapy (LABA, LABA, ICS)
• tiotropium , formoterol, ciclesonide
Pharmacological treatment of COPD
• Long acting B agonist (LABA)/ Inhaled corticosteroid (ICS)
•
•
•
•
•
•
Seretide (Salmeterol + Fluticasone proprionate)
Symbicort (Formoterol + Budesonide)
Fostair (Formoterol + Beclomethasone0
Relvair (Vilanterol+ Fluticasone Fumarate)
Flutiform (Formoterol + Fluticasone Fumarate)
Duoresp (Formoterol + Budesonide)
• Long acting antimuscarinic (LAMA)
• Spiriva (Tiotropium)
• Seebri (Glycopyrrinium)
• Eklira (Aclidinium)
• Long acting B agonist (LABA) + antimuscarinic (LAMA)
• Anaro (Vilanterol+ Umeclidinium)
• Ultibro (Indacaterol +glycopyrronium)
• PF-4348235, PF-3429281, GSK961081
• Phosphodiesterase inhibitors
• Rofumilast
• Triple therapy (LABA, LABA, ICS)
• tiotropium , formoterol, ciclesonide
Pharmacological treatment of COPD
• Long acting B agonist (LABA)/ Inhaled corticosteroid (ICS)
•
•
•
•
•
•
Seretide (Salmeterol + Fluticasone proprionate)
Symbicort (Formoterol + Budesonide)
Fostair (Formoterol + Beclomethasone0
Relvair (Vilanterol+ Fluticasone Fumarate)
Flutiform (Formoterol + Fluticasone Fumarate)
Duoresp (Formoterol + Budesonide)
• Long acting antimuscarinic (LAMA)
• Spiriva (Tiotropium)
• Seebri (Glycopyrrinium)
• Eklira (Aclidinium)
• Long acting B agonist (LABA) + antimuscarinic (LAMA)
• Anaro (Vilanterol+ Umeclidinium)
• Ultibro (Indacaterol +glycopyrronium)
• PF-4348235, PF-3429281, GSK961081
• Phosphodiesterase inhibitors
• Rofumilast
• Triple therapy (LABA, LABA, ICS)
• tiotropium , formoterol, ciclesonide
Treating COPD to prevent
exacerbations
Number needed to treat to prevent an exacerbation = 4
Number needed to prevent an admission =20
Pneumonia and inhaled
corticosteroids in COPD
Placebo
Salmeterol
#
Flutacisone
Seretide
Crim ERJ 2009
Non-pharmacological management of COPD
•
•
•
•
Smoking cessation
Weight control
Pulmonary rehabilitation
Anxiety management
Non-pharmacological management of COPD
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•
•
•
Smoking cessation Anxiety
Weight control
• 60% prevalence
• Catastrophic thoughts &
Pulmonary rehabilitation
impending danger.
Anxiety management • Mistaken for worsening COPD.
• Predictor of hospital admissions
Non-pharmacological management of COPD
•
•
•
•
Smoking cessation Depression
Weight control
• 40% prevalence
Pulmonary rehabilitation
• Loss of interest & enjoyment in
Anxiety management ordinary things & experiences &
low mood
• Attention shifts to physical
health problem & depression
may be overlooked
Causes of COPD
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•
•
•
•
•
Smoking
Asthma
Other genetic factors (atopy)
Biomass cooking
Environmental factors
Occupational exposures
Causes of COPD
•
•
•
•
•
•
Smoking
Asthma
Other genetic factors (atopy)
Biomass cooking
Environmental factors
Occupational exposures
3
250 ml/yr
FEV1
2
1
0
2004
2006
2008
2010
2012
2014
Causes of COPD
•
•
•
•
•
•
Smoking
Asthma
Other genetic factors (atopy)
Biomass cooking
Environmental factors
Occupational exposures
Childhood asthma persisting to adult life
3
250 ml/yr
FEV1
2
1
0
2004
2006
2008
2010
= smoking 40 cigarettes/day
2012
2014
Causes of COPD
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•
•
•
•
•
Smoking
Asthma
Other genetic factors (atopy)
Biomass cooking
Environmental factors
Occupational exposures
Causes of COPD
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•
•
•
•
•
Smoking
Asthma
Other genetic factors (atopy)
Biomass cooking
Environmental factors
Occupational exposures
Effects of coal, smoking and age on lung function
dust
smoking
age
Rogan
105
60
1840
Soutar
133
8
1640
Attfield
120
208
1240
Seixas
525
118
1680
Average
221
98
1600
Mean effects (ml) on FEV1 of 40 years exposure
Coal miners and emphysema
Occupational COPD
FEV1
normal
Smokers
Or
occupational
exposures
Susceptible
individuals
0
10
20
30
40
50
60
70
age
80
Occ Env Med 2005
Agents reported to cause chronic airflow
obstruction
Inorganic dusts
Coal
Silica/ hard rock mining
Asbestos
Wollastoninte
Carbon Black
Iron dust/ steelworkers
Ceramic fibres
Organic dusts
Cotton
Grain
Wood
Gases/ fume/chemicals
Ammonia
Welding fume
Sulphur dioxide/ paper mills
Firefighting
Isocyanates
Biases in occupational epidemiology
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•
•
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•
Healthy worker effect
Survivor effect
Smoking
Uncertainty about exposures
Recall biases
Biases in occupational epidemiology
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•
•
•
•
Healthy worker effect
Survivor effect
Smoking
Uncertainty about exposures
Recall biases
General population : predictors of
respiratory symptoms
• 12,000 Newcastle residents, 40-75 yr
• Questionnaire
• Respiratory symptoms
• Occupations, social status, diagnosis, treatment
• 850 laboratory studies
• Lung function tests
• Detailed questionnaire
Melville ERJ 2010
Accuracy of diagnosis of COPD
139
49
188 reported diagnosis
of COPD
(bronchitis, emphysema etc)
36
85 had COPD by lung
function criteria
General population : predictors of
respiratory symptoms
odds ratio
wheeze, SOB, cough
Melville ERJ 2010
General population : predictors of
respiratory symptoms
Melville ERJ 2010
Occupational exposures account for 15% of COPD
Exposures to vapours gases dusts and fumes
and COPD development
low
high
mild COPD
low
high
severe COPD
Metha Am J Respir Crit Care Med 2014
Relevance of current occupational COPD for
current exposure standards exposure limits
Occupational exposure limits
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•
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•
Silica
0.1 mg/m3
Coal (US) 1.5 mg/m3
Coal (UK) 2.0 mg/m3
Dust
4.0 mg/m3
Surveillance for COPD
FEV1
normal
Susceptible
individual
0
10
20
30
40
50
60
70
age
80
Surveillance for COPD
FEV1
normal
Susceptible
individual
0
10
20
30
40
50
60
70
age
80
Surveillance for COPD
FEV1
normal
Susceptible
individual
0
10
20
30
40
50
60
70
age
80
Surveillance for COPD
FEV1
normal
30 ml/yr
Susceptible
Individual 60 -90ml/yr
0
10
20
30
40
50
60
70
age
80
Surveillance for COPD
FEV1
normal
Susceptible
Individual
0
10
20
30
40
50
60
70
age
80
Surveillance for COPD
FEV1
normal
Susceptible
Individual
0
10
20
30
40
50
60
70
age
80
Surveillance for COPD
FEV1
normal
Susceptible
Individual
0
10
20
30
40
50
60
70
age
80
Surveillance for COPD
FEV1
normal
Susceptible
Individual
0
10
20
30
40
50
60
70
age
80
SPIROLA
A case of occupational COPD (?)
-60 ml/yr
A case of occupational COPD (?)
COPD - summary
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Is common
Pharmacological management is evolving
Anxiety and depression are important
Is not just caused by smoking
Occupational exposures are important
There are no ‘nuisance’ dusts
Proper control of exposures is important
Surveillance for COPD is complex
Surveillance for COPD
FEV1
normal
Smokers/
occupational
exposure
Susceptible
individuals
0
10
20
30
40
50
60
70
age
80
Average adverse effect of mining
-242 ml
-128 ml
age 40 yr
50 yr
Lewis Thorax 1996