1. Clinical Knowledge Summaries CKS Chronic obstructive pulmonary disease (COPD) - management
Management of stable COPD in primary care, focusing on drug treatments.
Educational slides based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

2. Key learning points and objectives
To be able to:
Describe when to consider specialist referral.
Outline which interventions are and are not recommended.
Outline which interventions should not be offered.
Describe which inhalers should be offered initially and when and why to adjust inhaler treatment.
Describe the benefits of smoking cessation and drug treatments.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

3. Assessing severity of COPD
Assess the severity according to:
The reduction of FEV1 on spirometry (post bronchodilator),
The degree of breathlessness according to the Medical Research Council (MRC) dyspnoea scale,
The BMI - (BMI of less than 20 kg/m2 is associated with increased mortality) and
Presence of cor pulmonale.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

4. Interpreting spirometry
Following spirometry, airflow obstruction can be classified as:
Stage 1 (mild) - FEV1 80% of predicted value or higher (symptoms must be present).
Stage 2 (moderate) - FEV1 50–79% of predicted value.
Stage 3 (severe) - FEV1 30–49% of predicted value.
Stage 4 (very severe) - FEV1 less than 30% of predicted value.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

5. Assessing COPD Ask if the person smokes and document smoking history.
Assess for anxiety or depression.
Perform:
Full blood count to identify anaemia or secondary polycythaemia.
Pulse oximetry - to assess the need for oxygen therapy if cyanosis or cor pulmonale is present, or if FEV1 < 50% predicted normal value.
Electrocardiography - if features of cor pulmonale.
Sputum culture - if sputum is persistently present and purulent.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

6. Clinical reasons to refer
After assessment, consider referral to a respiratory specialist:
If lung cancer is suspected (seen within 2 weeks).
If the diagnosis is uncertain.
For very severe (e.g. FEV1 less than 30% predicted) or worsening COPD (rapid decline in FEV1).
If cor pulmonale is present.
If the person has abnormal breathing patterns associated with anxiety.
Younger than 40 years, or family history of alpha1-antitrypsin deficiency.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

7. Other times to consider referral
Consider referral to a respiratory specialist to assess the need for:
Nebuliser therapy.
Lung surgery (e.g. bullous lung disease and still symptomatic on maximal therapy).
For oxygen therapy - inappropriate oxygen therapy may cause respiratory depression.
In addition consider referral:
For pulmonary rehabilitation (discussed later).
To a physiotherapist (e.g. excessive sputum).
To social services and occupational therapy (e.g. difficulty with daily activities or disability).
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

8. Overview of management
Encourage smokers to stop.
Smoking cessation is one of the most important interventions.
Offer drug treatment with inhalers.
Consider referral for pulmonary rehabilitation.
Consider a mucolytic or theophylline.
Advise an annual influenza vaccination and a once-only pneumococcal vaccination.
Reduces hospitalization and death rates in elderly people with chronic lung disease.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

9. Overview of management
Agree a self-management plan, for example:
How to recognize the early signs of an exacerbation or when COPD is getting worse and how to respond.
Manage nutritional needs, for example:
People with low BMIs may require:
Nutritional assessment, or
Referral to a specialist (e.g. BMI < 20 or person is losing weight rapidly).
Manage cor pulmonale.
Referral usually required.
Follow up regularly
At least once a year for stage 1-3 COPD and at least twice a year for stage 4 COPD.
Consider when to discuss end of life issues.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

10. Smoking cessation
Smoking cessation is the most important intervention.
Even if the person is not willing to stop smoking, cutting down may still have some symptomatic benefit.
Stopping smoking (at any age) reduces:
The rate of decline of FEV1,
Improves symptoms (cough, wheeze, and sputum production), and
Increases survival.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

11. Smoking cessation
Offer nicotine replacement therapy, varenicline, or bupropion, as appropriate, to people who are planning to stop smoking.
Combine drug treatments with an appropriate support programme (e.g. local stop smoking schemes).
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

12. Inhaled treatments for COPD
If the person is breathless and has exercise limitation prescribe a:
Short-acting beta-2 agonist (SABA, e.g. salbutamol or terbutaline) as required, or
Short-acting muscarinic antagonist (SAMA, e.g. ipratropium bromide) as required.
If there is no improvement or the person has exacerbations consider adding further inhaled treatments, but
Before changing treatment always check concordance and inhaler technique.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

13. Key prescribing points for inhalers
Always:
Provide training on how to use inhalers,
Ensure patient can demonstrate acceptable technique, and
Check technique regularly as poor technique, even after training, is very common.
Good technique is essential to ensure optimum use.
Some frail people cannot achieve minimum inspiratory flow rate required for:
Dry-powder devices, or
Breath-actuated metered-dose inhalers.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

14. Inhaled treatments for COPD
Treatment options for adding inhaled treatments include adding one or more of the following:
A long-acting beta-2 agonist (LABA, e.g. salmeterol or formoterol), or
A long-acting muscarinic antagonist (LAMA, e.g. tiotropium) and discontinue SAMA, or
An inhaled corticosteroid (ICS).
The treatment strategy chosen depends on whether:
FEV1 is 50% predicted or greater, or
FEV1 is less than 50% predicted.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

15. NICE algorithm for inhaled therapy
SABA as required may continue at all stages; ** Discontinue SAMA.
Based NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

16. Key prescribing points for inhalers
A SABA (e.g. salbutamol) may be continued at all stages (as required).
If prescribing a LAMA, (e.g. tiotropium), discontinue treatment with a SAMA, (e.g. ipratropium).
An inhaled corticosteroid (ICS) should not be used as monotherapy:
They have no effect on exacerbation rates in people with mild COPD.
There is no significant difference in mortality between ICS monotherapy and placebo.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and a Drug Safety update from the MHRA (2007): Inhaled corticosteroids: pneumonia.

17. Adverse effects of ICS Local adverse effects include:
Oral candidiasis, sore mouth, dysphonia, and hoarseness.
Paradoxical bronchospasm (very rare – usually mild).
Pneumonia and bronchitis in people with COPD treated with ICS*.
Systemic adverse effects (e.g. adrenal suppression, reduced bone mineral density, bruising, glaucoma):
Very rare but may occur if high doses (> 1000 mcg beclometasone dipropionate) are used for long periods of time
Steroid card required for prolonged high doses.
Presenter notes
Very rare
Very rare is defined as <1/10,000. Taken from the SPC for QVAR Autohaler 100 micrograms. Last updated 11/02/2013.
Pneumonia
This information is based on a Drug Safety Update (DSU); Inhaled corticosteroids: pneumonia (October 2007) (see here for the full DSU article).
The MHRA state that: ‘Physicians should remain vigilant for the development of pneumonia and other infections of the lower respiratory tract (ie, bronchitis) in patients with COPD who are treated with inhaled drugs that contain steroids because the clinical features of such infections and exacerbations frequently overlap.’ This is based on evidence from the TORCH study.
The TORCH study
TOwards a Revolution in COPD Health (TORCH) 1 compared Seretide Accuhaler (50 µg salmeterol/500 µg fluticasone twice a day), 50 µg salmeterol twice a day, and 500 µg fluticasone twice a day with placebo over a 3-year period.
There was an increased risk of pneumonia for people using seretide compared with placebo Hazard ratio (HR); 1.64 (95% CI 1·33–2·02) This equates to an additional 36 events per 1000 pt years.
The Drug Safety update also has observational data suggesting an increased risk of mortality.
1) Calverley PM, et al. N Engl J Med 2007; 356: 775–89.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), the CKS topic Corticosteroids inhaled (August 2010), and a *Drug Safety Update; Inhaled corticosteroids: pneumonia (October 2007).

18. Benefits of inhalers There is evidence that compared with placebo:
SABAs (e.g. salbutamol) provide a short-term improvement in breathlessness, quality of life, and lung function.
LABAs (e.g. salmeterol) provide a general improvement in lung function, quality of life, and symptoms, and a reduction of exacerbation rates.
LAMAs (e.g. tiotropium) reduce exacerbation rates, and improve lung function, quality of life, and symptoms.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

19. Benefits of inhalers There is evidence that:
LAMAs (e.g. tiotropium), compared with SAMAs (e.g. ipratropium):
Improve quality of life and symptoms, and reduce exacerbation rates.
LAMAs (e.g. tiotropium) and LABAs (e.g. salmeterol):
Are similar in improving quality of life and symptoms.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

20. Benefits of inhalers
There is evidence that a LABA (e.g. salmeterol) plus an inhaled corticosteroid (ICS), compared with LABAs alone:
Significantly increases post-dose FEV1.
Improves quality of life.
Reduces exacerbations.
Is more cost effective than LABA alone in people with COPD with FEV1 less than 50% predicted.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

21. Benefit of triple therapy
For people with an FEV1 > 50%:
No significant difference between triple therapy and dual therapy for breathlessness, exacerbation, mortality, pneumonia, myocardial infarction, or acute arrhythmia.
A cost-effectiveness study found that triple therapy was not more cost effective than LAMA plus LABA.
For people with an FEV1 < 50%, evidence suggests that:
LABA plus ICS or LAMA alone is more cost effective than triple therapy, however
NICE found that triple therapy is more clinically effective in terms of exacerbation reduction and symptom relief.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

22. Limitations of inhaler therapy
Unlike stopping smoking there is no evidence that inhalers:
Reduce the rate of decline of FEV1, or increase survival.
Unlike pulmonary rehabilitation there is no evidence that inhalers improve exercise capacity.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

23. Benefits of pulmonary rehabilitation
NICE found evidence that compared with ‘usual care’, pulmonary rehabilitation:
Improves health-related quality of life and exercise capacity.
Is cost effective in the outpatient setting compared with ‘usual care’.
NICE recommend referral for pulmonary rehabilitation:
If the person considers themselves functionally disabled by COPD, or
Has had a recent hospitalization for an acute exacerbation.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

24. COPD – comparison of cost/QALY
Stop Smoking Support with pharmacotherapy
£2,000/ quality adjusted life-years (QALY).
Pulmonary Rehabilitation
£2,000-8,000/QALY.
Tiotropium
£7,000/QALY.
LABA
£5,000-8,000/QALY.
Triple Therapy
£7,000 to £187,000/QALY
Based NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

25. When to consider mucolytics
Consider a trial of a mucolytic if there is a chronic cough productive of sputum.
Carbocisteine and mecysteine hydrochloride are licensed for COPD.
Only continue if there is symptomatic improvement.
Do not use mucolytics to prevent exacerbations.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

26. Benefits of mucolytics
Very low quality evidence suggests that in people with chronic bronchitis and COPD mucolytics reduce:
Exacerbation frequency, and
Duration of disability.
NICE recommend a mucolytic only for people with stable COPD who have a chronic cough productive of sputum.
This is based on evidence from a cost-effectiveness analysis.
Presenter notes
The statement regarding very low quality evidence has been taken directly from the NICE guidance.
NICE guidance use the following GRADE system to assess the quality of evidence:
High quality— Further research is very unlikely to change our confidence in the estimate of effect
Moderate quality— Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality— Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality— Any estimate of effect is very uncertain
Reference: GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Gordon H Guyatt BMJ 2008;336;
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

27. Oral theophylline Consider theophylline if the person:
Is still symptomatic after a trial of short-acting and long-acting bronchodilators (with or without inhaled corticosteroids), or
Cannot use inhaler devices successfully.
When prescribing theophylline:
It has a narrow therapeutic window, and plasma levels should be monitored closely.
Take care when prescribing to elderly people because of:
Differences in pharmacokinetics.
Increased likelihood of comorbidities, and
The interactions with other medications.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

28. Benefits of theophylline
There is evidence that compared with placebo, theophylline improves lung function but does not:
Improve symptoms (wheeze, dyspnoea, or walking distance).
Decrease use of rescue medication, or
Reduce exacerbations.
The higher rate of adverse effects with theophylline needs to be balanced against any benefits.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

29. Oral corticosteroids
Maintenance use of oral corticosteroid therapy in COPD is not normally recommended.
Refer to a respiratory specialist if long-term treatment is being considered.
For people who have been started on long-term treatment by a specialist:
Ensure that they are monitored for the development of osteoporosis and/or given appropriate prophylaxis.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

30. Evidence on long-term steroids
NICE found that:
There are no published studies that establish which people with COPD may benefit from long-term oral steroid therapy.
A small group of people with frequent exacerbations or severe breathlessness may benefit from long-term oral steroids.
Some people with advanced COPD may require maintenance with oral corticosteroids when these cannot be withdrawn following an exacerbation.
Based on the CKS topic Chronic obstructive pulmonary disease (November 2010), and NICE guidance; Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (2010).

31. Other licensed drugs
Four new medicines have recently gained a license for COPD:
Aclidinium bromide, glycopyrronium bromide, fluticasone furoate plus vilanterol, roflumilast.
NICE new medicines evidence summaries are available for:
Aclidinium bromide.
Glycopyrronium bromide.
Fluticasone furoate plus vilanterol.
Roflumilast - NICE Health Technology Appraisal:
Only recommended for use as part of a clinical trial for adults with severe COPD.

32. Summary
Smoking cessation is one of the key interventions for people with COPD.
Initially offer all people with COPD an inhaled SABA or a SAMA.
Good inhaler technique is essential to ensure optimum use – training should be provided and assessed regularly.
Triple inhaler therapy has the highest cost per QALY of interventions for COPD.
Pulmonary rehabilitation is a treatment option.
Consider a trial of a mucolytic if there is a chronic cough productive of sputum. Stop if there is no improvement.
Before prescribing theophylline, consider the risks and benefits, especially in older people.
Inhaled corticosteroids should not be used as monotherapy – no evidence of benefit and increased risk of pneumonia.
Refer to a specialist if considering long-term oral corticosteroids.