Management of COPD BTS Guidelines

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Definition

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

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Management of COPDBTS Guidelines 2004

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

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Disease Burden

• 900,000 (2,000,000) in UK
• gt30,000 deaths in UK 1999
• 5 all deaths
• Health District (250,000)
• 700 admissions (10)
• 9,600 bed days
• 14,000 GP consultations

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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

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Emphysema

• Increased polymorphs Elastase
• loss of alveoli / pulmonary vasculature
• area for gas exchange
• loss of elastic supporting tissue early
  expiratory airway collapse hyperinflation

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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

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Investigations

• CXR (not necessary)
• Spirometry
• FEV1lt80 predicted
• FEVlt70 predicted
• Little variability in expiratory flow

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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)

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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

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Severity of COPD

• Mild - FEV1 50-80 (60-79)
• smokers cough
• Moderate- FEV1 30-49 (40-59)
• Cough, SOBOE, wheeze (signs)
• Severe - FEV1 lt30 (lt40)
• Cough,wheeze,SOB, signs

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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

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Differentiation from Asthma

• Smoker / non smoker
• symptoms lt35 yr
• chronic productive cough
• SOB
• Night time waking /wheeze
• Diurnal variability symptoms

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Reversibility Testing

• Not necessary may be misleading (single test)
• but may help with diagnosis if large response
• to bronchodilators or prednisolone (30mg 2/52)

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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)

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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

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Reversibility Testing

• Question.
• Are we measuring the right thing ?
• Answer
• Probably not !

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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)/(1.51.1)/2 x100 31 change

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Other Investigations

• BMI, CRP ?
• FBC -PCV gt50, alpha 1 antitrypsin
• Sputum (Pneumococcus, Haemophilus, Moraxella)
• Oximetry/ABG (or Sat gt92)
• CT - extent/distribution of emphysema
• TLC/RV comparison(body box/He dilution)
• ECG/ECHO - IHD/ Cor pulmonale

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Management of stable COPD

• Smoking
• SOB/SOBOE
• Frequent Exacerbations
• Respiratory failure
• Cor pulmonale
• Abnormal BMI
• Chronic cough
• Anxiety/Depression
• Palliative Care

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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

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Smoking Cessation

• Key Fact
• Every Cigarette reduces life expectancy by 11
  minutes !

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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

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Inhaled Bronchodilators

• Tiotropium reduces exacerbations by 25 compared
  to ipratropium
• UPLIFT Study
• 3 yr tiotropium vs placebo. Decline in lung
  function.
• Triple therapy ?

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Phosphodiesterase Inhibitors

• Mild Bronchodilator effect
• upper end of therapeutic range
• effect may take several weeks
• Improve respiratory muscle strength
• Improve mucus clearance
• Reduce exacerbations ?

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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)

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Inhaled Steroids

• Improve symptoms ?
• Reduce inflammation ?
• Reduce decline in lung function ?
• Reduce exacerbations ?
• Increase pneumonia ?
• Interaction with beta agonists ?

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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.

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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. 3531819-23

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ISOLDE

• severe COPD (48 smoking at entry)
• 3yr randomised, double blind, placebo controlled,
  parallel group study, n750
• Inhaled Fluticasone
• No effect on progressive decline in FEV1
• Fewer exacerbations
• Fewer symptoms
• Sub group analysis
• BMJ 2000 320

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META - ANALYSIS

• 3 studies (1 abstract)
• 2 yr
• Moderate-severe COPD n95/88
• 800 -1600 mcg Beclomethasone
• Steroid group FEV1 improved by 80 ml/yr
• Van Grunsven et al, Thorax 1999.

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TORCH

• 3yr, n 6,000. smokers or ex, FEV1lt60
• Fluticasone/salmeterol, Fluticasone,
• Salmeterol, placebo
• All cause mortality no difference
• Exacerbations reduced (25) with steroid
• Improved health status with steroid

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Steroids/Pneumonia

• TORCH (NEJM 2007 356 775-789)
• Inhaled steroids increased pneumonia ?
• AJRCCM 2007 176 162-166
• Inhaled steroids increased pneumonia admissions ?

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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.

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Oral steroids

• Maintenance therapy not recommended.
• If necessary keep dose low.
• Monitor for osteoporosis.
• Prophylaxis for osteoporosis if gt65.

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Home Nebuliser Therapy

• SOB despite maximal Rx
• MDI v Neb trials in stable COPD inconsistent
• Assessment
• home trial (St Georges AQ20), optimise Rx
• technical support/FU
• Neb Rx 3-4x more expensive than HHI

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Other measures

• Exercise
• Safe and desirable
• Nutrition
• Vaccination -Flu /Pneumococcus
• Treat depression (50)
• Travel (900-2,400 m, PaO2 15 -18 kPa)
• bullae, pneumothorax, PaO2lt6.7 kPa air

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Prevent Exacerbations

• Vaccination.
• Self management advice.
• Optimise bronchodilator Rx.
• Add inhaled steroids if FEV1 lt50 and 2 or more
  exacerbations per year.
• Rotating antibiotics.

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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)

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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

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LTOT

• ABG x 2 (3 weeks apart) - clinically stable
• PaO2 lt 7.3 kPa on air
• FEV1 lt 1.5
• Non-smokers
• 6 monthly follow-up
• Prescriber
• England GP
• Scotland Consultant Chest Physician

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Ambulatory Oxygen

• Exercise desaturation
• Exercise Test
• Symptoms
• Walk distance
• saturation
• Follow up

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Nocturnal Hypoventilationin COPD

• Reduced ventilatory drive during sleep
• Sleep deprivation (sleep apnoea) reduces
  chemoreceptor sensitivity
• Reduced muscle performance
• muscle mechanics
• acidosis

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NIV

• No recommendations at present
• May prolong survival in patients deteriorating on
  LTOT with associated hypercapnoea
• ? Mechanism of cor pulmonale

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Cor Pulmonale

• Lung disease Hypoxia Pulmonary arterial
  vasoconstriction Pulmonary HypertensionRVF
  Oedema
• Lung disease Hypoxia / Hypercapnoea Renal
  Perfusion Fluid retention

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Surgery

• Bullectomy
• Lung volume reduction
• improves symptoms/ex tolerance/QOL
• VATS/Sternotomy
• low morbidity (lt70yr,FEV1gt0.5l, PaO2gt7.3)
• ? Survival advantage (NETT USA) - no !
• Transplant (young, alpha 1 antitrypsin)

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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?

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ACUTE EXACERBATIONS

• Hospital Investigations
• CXR
• ABG
• ECG
• FBC/UE
• Sputum culture if purulent
• Blood cultures if pyrexial

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ACUTE EXACERBATIONS

• Bronchodilators
• Neb or HHI Spacer
• Pred 30mg 14/7
• Oxygen (controlled)
• Antibiotics if sputum purulent
• penicillin, macrolide,
• Theophylline
• NIV (Doxapram)
• Physiotherapy

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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

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ACUTE EXACERBATIONS

• NIV
• better ABG
• reduced LOS
• reduced complications
• reduced mortality
• reduced intubation
• Oxygen
• pulse oximeters (beware pCO2 !)

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ACUTE EXACERBATIONS

• Hospital at Home
• various models
• 1/3 patients suitable
• nurses, physios, OTs
• average hospital LOS 10 days
• saves bed days, not money !
• Patients like it !

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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)

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Referral

• Onset cor pulmonale
• LTOT
• Neb
• Oral steroids
• Bullous disease
• Rapid decline in FEV1
• Diagnostic advice

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Summary

• Stop smoking
• LABA better than SABA, combination Rx
• Inhaler technique
• ICS if FEV1 lt50 exacerbations
• LTOT if O2 sats lt 90 /- cor pulmonale
• Sudden change in symptoms - CXR
• Unsure - refer

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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 ?

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The Future ?

• PD4 inhibitors
• Leukotriene B4 inhibitors
• Adhesion molecule blockers
• Antioxidants
• resveratrol (red wine), N-acetylcysteine
• Biomarkers