Definition

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