Definition

• Airflow obstruction is usually progressive,

not fully reversible and does not change
markedly over several months. The disease
is predominantly caused by smoking.
 Management of COPD
BTS Guidelines 2004
• Priorities for implementation
– Diagnose COPD
– Stop smoking
– Effective inhaled Rx
– Pulmonary rehabilitation
– Manage exacerbations (NIV)
– Multidisciplinary working
 Disease Burden
• 900,000 (2,000,000) in UK
• >30,000 deaths in UK 1999
• 5% all deaths
• Health District (250,000)
– 700 admissions (10%)
– 9,600 bed days
– 14,000 GP consultations
 Chronic Bronchitis
• Irritants in smoke/Pollution
– Mucous gland hypertrophy
– Increased mucus gland secretion
– Increased polymorphs in airways
– bronchoconstriction

– Airway narrowing (small airways)

– need a lot of damage before spirometry affected
 Emphysema
Increased polymorphs → ↑ Elastase
→ loss of alveoli / pulmonary vasculature
→ ↓ area for gas exchange

→ loss of elastic supporting tissue → early

expiratory airway collapse → hyperinflation
 Diagnosis
• History
– Progressive symptoms - Cough/Wheeze/SOB
– Ex tolerance, childhood illness/atopy/ FH
– Occupation
– Smoking - 20 pack years
– Examination - not diagnostic
– Objective evidence of airway obstruction that does not
return to normal with Rx
 Investigations
• CXR (not necessary)
• Spirometry
– FEV1<80% predicted
– FEV%<70% predicted
– Little variability in expiratory flow
 Monitor Progression
• 15% smokers significant obstruction
• FEV1 (20-30 ml/yr non smokers)
• FEV1 (45-70 ml/yr smokers)
• Prognosis related to FEV1
– Mortality: Renfrew/Paisley Study, BMJ 1996
• Drug treatment does may affect natural history
(LTOT improves survival)
 Peak Flow/Spirometry
• FEV1 reproducible (160 ml)
• FVC reproducible (330 ml)
• FEV% diagnoses obstruction
• Low PEFR obstruction/restriction
• PEFR not related to FEV1
• PEFR underestimates obstruction in COPD
– COPD small airways
 Severity of COPD

• Mild - FEV1 50-80 (60-79)%

– smokers cough
• Moderate- FEV1 30-49 (40-59)%
– Cough, SOBOE, wheeze (signs)
• Severe - FEV1 <30 (<40)%
– Cough,wheeze,SOB, signs
 Severity of COPD
MRC Dyspnoea Scale
• 1. SOB strenuous exercise
• 2. SOB hurrying, slight hill
• 3. Unable to keep up with peers*
• 4. Stops for breath after 100m*
• 5.Too breathless to leave house
– SOB washing dressing
Differentiation from Asthma
Reversibility Testing
Reversibility Testing
 Reversibility Testing
• Steroids
– 30mg day, 2 weeks
– beclomethasone 500mcg bd, 6 weeks
– positive response in 10-20%
– better prognosis if positive response

– Steroid responders also respond to bronchodilators

 Reversibility Testing
• Question.
• Are we measuring the right thing ?

• Answer
• Probably not !
 Reversibility Testing
• Absolute Change
– (FEV, 160 ml, FVC 330 ml) ?
• % change ?
– FEV1 - 1.1 Pre, 1.5 post
– (1.5/1.1) x 100 = 36 % change
– (1.1/1.5) X 100 = 27 % change
– {(1.5-1.1)/(1.5+1.1)/2} x100 = 31% change
 Other Investigations
• BMI, CRP ?
• FBC -PCV >50%, alpha 1 antitrypsin
• Sputum (Pneumococcus, Haemophilus, Moraxella)
• Oximetry/ABG (or Sat >92%)
• CT - extent/distribution of emphysema
• TLC/RV comparison(body box/He dilution)
• ECG/ECHO - IHD/ Cor pulmonale
 Management of stable COPD
• Smoking
• SOB/SOBOE
• Frequent Exacerbations
• Respiratory failure
• Cor pulmonale
• Abnormal BMI
• Chronic cough
• Anxiety/Depression
• Palliative Care
 Smoking Cessation
• Stop smoking (10-30% in trials)
– sudden better than gradual
– all smokers in house
– medical advice
– nicotine (doubles quit rate)
– monitoring (co,carboxyHb,cotinine)
– antidepressant (Bupropion USA)
– Varenicline
 Smoking Cessation
• Key Fact:

• Every Cigarette reduces life expectancy by

11 minutes !
 Inhaled Bronchodilators
• Improve FEV1/symptoms
• Combination better
• Long acting –greater clinical benefit, health
status and lower exacerbation rate
• Steroid /LABA combination –greater
improvement than either alone
 Inhaled Bronchodilators
• Tiotropium reduces exacerbations by 25%
compared to ipratropium
• UPLIFT Study
– 3 yr tiotropium vs placebo. Decline in lung function.
• Triple therapy ?
 Phosphodiesterase Inhibitors
• Mild Bronchodilator effect
– upper end of therapeutic range
– effect may take several weeks
• Improve respiratory muscle strength
• Improve mucus clearance
• Reduce exacerbations ?
 Phosphodiesterase Inhibitors
• Anti inflammatory action - low dose
– suppresses inflammatory genes (HDAC)
– potentiate anti-inflammatory effects of Pred

– caution with macrolides and quinolones

– Roflumilast, Cilomilast (PDE4 inhibitors)
 Inhaled Steroids
• Improve symptoms ?
• Reduce inflammation ?
• Reduce decline in lung function ?
• Reduce exacerbations ?
• Increase pneumonia ?
• Interaction with beta agonists ?
 European Study
• Smokers with mild COPD
– 912 current smokers
– Randomised, double blind placebo controlled,
parallel group study, 3yr
– Budesonide 400 ug bd
– No effect on progressive decline in FEV1

– Pauwels et al, NEJM, 1999.

 Copenhagen Lung Study
• 76% current smokers, n =290
– mild COPD
– Randomised, double blind, placebo controlled, parallel
group study, 3yr
– Budesonide 400 ug bd
• No effect on progressive decline in FEV1
– Vestbo et al, Lancet 1999. 353:1819-23
 ISOLDE
– severe COPD (48% smoking at entry)
– 3yr randomised, double blind, placebo controlled,
parallel group study, n=750
– Inhaled Fluticasone
– No effect on progressive decline in FEV1
– Fewer exacerbations
– Fewer symptoms
– Sub group analysis
– BMJ 2000 320
 META - ANALYSIS
• 3 studies (1 abstract)
• 2 yr
• Moderate-severe COPD n=95/88
• 800 -1600 mcg Beclomethasone
• Steroid group FEV1 improved by 80 ml/yr
– Van Grunsven et al, Thorax 1999.
 TORCH
• 3yr, n = 6,000. smokers or ex, FEV1<60%
– Fluticasone/salmeterol, Fluticasone,
– Salmeterol, placebo
• All cause mortality no difference
• Exacerbations reduced (25%) with steroid
• Improved health status with steroid
 Steroids/Pneumonia
• TORCH (NEJM 2007 356: 775-789)
– Inhaled steroids increased pneumonia ?

• AJRCCM 2007 176: 162-166

– Inhaled steroids increased pneumonia
admissions ?
 Steroids/Beta Agonists
• Steroids
– increase expression of beta2 receptors.
– decrease loss due to long term exposure

• Beta 2 Agonists
– potentiate molecular mechanism of steroid
action.
 Oral steroids
• Maintenance therapy not recommended.
• If necessary keep dose low.
• Monitor for osteoporosis.
• Prophylaxis for osteoporosis if >65.
 Home Nebuliser Therapy
• SOB despite maximal Rx
• MDI v Neb trials in stable COPD
inconsistent
• Assessment
– home trial (St George’s AQ20), optimise Rx
– technical support/FU
– Neb Rx 3-4x more expensive than HHI
 Other measures
• Exercise
– Safe and desirable
• Nutrition
• Vaccination -Flu /Pneumococcus
• Treat depression (50%)
• Travel (900-2,400 m, PaO2 15 -18 kPa)
– bullae, pneumothorax, PaO2<6.7 kPa air
 Prevent Exacerbations
• Vaccination.
• Self management advice.
• Optimise bronchodilator Rx.
• Add inhaled steroids if FEV1 <50% and 2 or
more exacerbations per year.
• Rotating antibiotics.
 Pulmonary Rehabilitation
• Proven value (randomised trials)
• MRC grade 3 and above
• Ex tolerance, Psychosocial
• Reduce hospital admissions/LOS ?
• A cynics definition of Exercise -”An
enthusiasm lasting about 3 weeks, which is
readily soluble in alcohol” (Newcastle study)
 LTOT
• MRC study(1981) -15 hr/day
– 5 yr survival 25% / 41%
– Less polycythaemia
– Prevention of progression of PHT
– Improved sleep quality
– Improved psychologically (QOL)
– Reduction in cardiac arrhythmias
 LTOT
• ABG x 2 (3 weeks apart) - clinically stable
• PaO2 < 7.3 kPa on air
• FEV1 < 1.5
• Non-smokers
• 6 monthly follow-up
• Prescriber
– England: GP
– Scotland: Consultant Chest Physician
 Ambulatory Oxygen
• Exercise desaturation
• Exercise Test
– Symptoms
– Walk distance
– saturation
• Follow up
 Nocturnal Hypoventilation
in COPD
• Reduced ventilatory drive during sleep
• Sleep deprivation (sleep apnoea) reduces
chemoreceptor sensitivity
• Reduced muscle performance
– muscle mechanics
– acidosis
 NIV
• No recommendations at present
• May prolong survival in patients
deteriorating on LTOT with associated
hypercapnoea

• ? Mechanism of cor pulmonale

 Cor Pulmonale
• Lung disease → Hypoxia → Pulmonary
arterial vasoconstriction → Pulmonary
Hypertension→RVF→ Oedema

• Lung disease → Hypoxia / Hypercapnoea

→ ↓ Renal Perfusion → Fluid retention
 Surgery
• Bullectomy
• Lung volume reduction
– improves symptoms/ex tolerance/QOL
– VATS/Sternotomy
– low morbidity (<70yr,FEV1>0.5l, PaO2>7.3)
– ? Survival advantage (NETT USA) - no !
• Transplant (young, alpha 1 antitrypsin)
 ACUTE EXACERBATIONS ?
• Referral Criteria
– Cope at home?
– Absence of cyanosis?
– Normal level of conciousness?
– Mild breathlessness?
– Good general condition?
– Not receiving LTOT?
– Good level of activity?
– Good social circumstances?
 ACUTE EXACERBATIONS
• Hospital Investigations
– CXR
– ABG
– ECG
– FBC/U+E
– Sputum culture if purulent
– Blood cultures if pyrexial
 ACUTE EXACERBATIONS
• Bronchodilators
– Neb or HHI +Spacer
– Pred 30mg 14/7
– Oxygen (controlled)
– Antibiotics if sputum purulent
• penicillin, macrolide,
• Theophylline
– NIV (Doxapram)
– Physiotherapy
STEROIDS/EXACERBATIONS
– 80 8/52 High dose oral Prednisolone
– 80 2/52 High dose oral prednisolone
– 111 Placebo
• Steroids:
– less treatment failure (intubation etc)
– faster improvement in FEV1
– Shorter Hospital Stay
– Niewoehner et al, NEJM 1999
 ACUTE EXACERBATIONS
• NIV
– better ABG
– reduced LOS
– reduced complications
– reduced mortality
– reduced intubation
• Oxygen
– pulse oximeters (beware pCO2 !)
 ACUTE EXACERBATIONS
• Hospital at Home
– various models
– 1/3 patients suitable
– nurses, physios, OT’s
– average hospital LOS 10 days
– saves bed days, not money !
– Patients like it !
 Follow Up
– Mild Yearly, Severe 6 monthly
• smoking status
• symptom control(SOB ex tolerance exacerbations)
• inhaler technique, review Rx
• Nutrition
• ? Pulmonary Rehab ? LTOT
• Spiro, BMI, MRC dyspnoea (Sa O2 severe)
 Referral
• Onset cor pulmonale
• LTOT
• Neb
• Oral steroids
• Bullous disease
• Rapid decline in FEV1
• Diagnostic advice
 Summary
• Stop smoking
• LABA better than SABA, combination Rx
• Inhaler technique
• ICS if FEV1 <50% + exacerbations
• LTOT if O2 sats < 90% +/- cor pulmonale
• Sudden change in symptoms - CXR
• Unsure - refer
 Summary
• Management plan
– Antibiotics
• pneumococci, moraxella, H influenzae
– PO steroids for exacerbations

• 24% O2 or 2 l/min via nasal cannulae safe

• Useful tool - AQ 20 ?
 The Future ?
• PD4 inhibitors
• Leukotriene B4 inhibitors
• Adhesion molecule blockers
• Antioxidants
– resveratrol (red wine), N-acetylcysteine
• Biomarkers