• Airflow obstruction is usually progressive, not fully reversible and does not change markedly over several months. The disease is predominantly caused by smoking.

Definition

Management of COPDBTS Guidelines 2004

• Priorities for implementation– Diagnose COPD– Stop smoking– Effective inhaled Rx– Pulmonary rehabilitation– Manage exacerbations (NIV)– Multidisciplinary working

• 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

Disease Burden

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

• CXR (not necessary)

• Spirometry– FEV1<80% predicted

– FEV%<70% predicted

– Little variability in expiratory flow

Investigations

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 COPDMRC 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–Smoker / non smoker–symptoms <35 yr–chronic productive cough–SOB–Night time waking /wheeze–Diurnal variability symptoms

•ABG’s•ECG•Ex Tests•Haematology•Sputum

Reversibility Testing• Not necessary may be misleading (single test)

–but may help with diagnosis if large response

to bronchodilators or prednisolone (30mg 2/52)

•ABG’s•ECG•Ex Tests•Haematology•Sputum

Reversibility Testing• Salbutamol/Ipratropium

–stable free from infection–post bronchodilator FEV1 best predictor of prognosis–no bronchodilators for 6 hr–2.5-5mg salbutamol Neb (20min)–500mcg ipratropium Neb (45min)

•ABG’s•ECG•Ex Tests•Haematology•Sputum

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 ?

• 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.

European Study

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 Hypoventilationin 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 HypertensionRVF 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)

• Onset cor pulmonale

• LTOT

• Neb

• Oral steroids

• Bullous disease

• Rapid decline in FEV1

• Diagnostic advice

Referral

• 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 ?

Summary

• PD4 inhibitors

• Leukotriene B4 inhibitors

• Adhesion molecule blockers

• Antioxidants – resveratrol (red wine), N-acetylcysteine

• Biomarkers

The Future ?