The optimal management of patients with COPD - Part 2: Stepwise escalation of treatment

There is currently no high-quality evidence that any medicine is able to modify the long-term decline of lung function in patients with COPD. Medicines are given to manage symptoms and reduce the risk of exacerbations. The relationship between symptom severity, airflow limitation and exacerbation frequency varies between patients, therefore treatment needs to be individualised.

As there are a large number of inhaled medicines indicated for the treatment of COPD it is important to ensure that medicine classes are not duplicated whenever changes are made to the patient’s treatment regimen.

Step 1: For all patients with symptomatic COPD

Prescribe an inhaled short-acting beta2-agonist (SABA, e.g. salbutamol or terbutaline) or a short-acting muscarinic antagonist (SAMA, e.g. ipratropium). Short-acting bronchodilators are likely to be beneficial when used by patients during periods of acute breathlessness.²

Ensure that patients are able to use inhaler devices correctly.

Patients should be educated in the correct use of inhalers and spacers before treatment with an inhaled medicine is initiated, and before stepping up treatment. Patients require sufficient dexterity and breath control to use inhaler devices and must also be able to use them when they are acutely unwell. As few as 10% of patients with COPD may use their inhalation device correctly;² the patient’s ability to use an inhaler may dictate the choice of the available medicines. If patients are using a metered dose inhaler (MDI) confirm that they are using a spacer as this overcomes coordination problems, improves lower airway deposition of medicines and increases the clinical benefit of the medicine. Placebo inhaler devices are available for demonstrating correct inhaler technique.

Step 2: For patients with COPD and persistent troublesome dyspnoea

Consider the addition of a long-acting beta2-agonist (LABA, e.g. salmeterol, indacaterol or formoterol) or a long-acting muscarinic receptor antagonist (LAMA, e.g. tiotropium or glycopyrronium under Special Authority if the patient was taking ipratropium at Step 1 and has not responded adequately).²

There is good evidence that both LABA and LAMA improve lung function and symptom severity and reduce exacerbation frequency.²

A combined LABA/LAMA inhaler can be used if treatment with a single medicine is ineffective, however, there are currently no subsidised options available.

Step 3: For patients with an FEV₁ < 50% of predicted and two or more exacerbations in a 12-month period

Consider prescribing a fixed-dose inhaled corticosteroid, in combination with a LABA, e.g. fluticasone + salmeterol or budesonide + formoterol under Special Authority.²

If the patient begins combination treatment remember to withdraw any LABA monotherapy.

Patients who continue to experience frequent exacerbations may also benefit from the addition of a LAMA to a combination corticosteroid and LABA inhaler.

When considering the use of inhaled corticosteroids in patients with COPD it is important to balance the risks versus benefits of inhaled corticosteroid treatment

The long-term use of inhaled corticosteroids (ICS) has been shown to reduce the rate of exacerbations and slow the decline in quality of life in people with COPD.^{2, 3} However, the role of ICS in the treatment of COPD is an evolving area of research and it is now accepted that their use can cause significant harm to patients with COPD; in particular, an increased risk of pneumonia and other respiratory co-morbidities.

ICS should only be considered for a patient with COPD once their condition has progressed to the point where the reduced risk of exacerbations and increased quality of life outweigh the increased risk of pneumonia and other adverse effects. The current trend among respiratory physicians in New Zealand is to tend to withdraw treatment of ICS, rather than initiate them; it is suggested that general practitioners consult a respiratory physician if they are considering initiating long-term ICS treatment in a patient with COPD.

A Cochrane systematic review of 55 studies with over 16 000 patients with stable COPD found that the use of ICS for more than six months was associated with 0.26 fewer exacerbations per patient per year. However, analysis of long-term studies (> six months) found an increased risk of pneumonia^* (odds ratio [OR] 1.56), oropharyngeal candidiasis (OR 2.65) and hoarseness (OR 1.95).⁴ The review also found that the benefits of treatment were not matched with statistically significantly reduced rates of decline in FEV₁ or mortality.⁴

An analysis of 25 trials, including over 22 000 patients, found that patients with COPD taking an ICS were more than twice as likely to develop tuberculosis than patients with COPD who were not taking an ICS.⁵

Treatment with ICS in patients with COPD has also been linked in a dose-dependent manner to an increased risk of non-tuberculous mycobacterial (NTM) pulmonary disease.⁶

Prophylactic or continuous use of antibiotics is not currently recommended to prevent exacerbations in patients with COPD on the balance of adverse effects versus benefits.³ The use of antibiotics in patients with COPD should be reserved for treating infectious exacerbations and other bacterial infections.³

Mucolytics, e.g. bromhexine hydrochloride, have a limited role in exacerbation prevention and there are currently no fully subsidised mucolytic medicines in New Zealand for the treatment of patients with COPD.

Theophylline is now rarely used in the treatment of COPD.

Routine follow-up is essential

As the patient’s lung function can be expected to decline, routine follow-up is an important part of COPD management to assess efficacy of treatment and also reduce problematic polypharmacy. The success of treatment should be largely determined by the patient’s response as improvements in lung function may not be reliably detected on spirometry. A period of six weeks is reasonable to detect clinically significant changes in symptoms such as dyspnoea, however, longer periods are likely to be required to detect changes in the patient’s quality of life.²

Patients with COPD who have frequent exacerbations are more likely to experience a rapid decline in FEV₁ and are more likely to die of COPD-related complications.² Prompt treatment of exacerbations is important as a delay of greater than 24 hours in presentation for the treatment of an exacerbation approximately doubles the likelihood of hospital admission.² An exacerbation in the previous 12 months is the greatest risk factor for a future exacerbation.²

Management of a patient with an acute exacerbation of COPD includes:

• Inhaled bronchodilator (increased dose), every three to four hours
• Breathing relaxation techniques
• Oral corticosteroids for five days, if moderate to severe exacerbation
• Oral antibiotics for five to ten days, but only if signs of chest infection

Symptom control during an exacerbation

Advise patients to take increased doses of bronchodilators during exacerbations, e.g. salbutamol, 400 – 800 micrograms (four to eight puffs of a standard strength, 100 micrograms per puff inhaler), every three to four hours, titrated to response.² If the patient requires an inhaled bronchodilator more frequently than three-hourly during an exacerbation they should be advised to seek medical assistance.² Correct device usage is essential during an exacerbation.

If during an exacerbation the patient feels panicked and overwhelmed, the following advice may help them relax:

1. Stop what you are doing
2. Relax your shoulders and neck
3. Breathe low and slow using a pursed lip technique, i.e. in through the nose and out slowly through pursed lips, with the diaphragm moving and the chest and shoulders relaxed
4. In a comfortable position concentrate on a relaxed breathing rhythm

Airway clearing techniques, e.g. percussion, vibration, or active cycles of breathing, may be useful for patients if secretions are troublesome.² The active cycle of breathing involves controlled breathing to relax the airways, then deep breathing to get air behind sputum lodged in the small airways, and finally huffing to dislodge sputum where it can then be removed by coughing.

Five-day course of corticosteroids improves outcomes

Oral corticosteroids reduce the severity of COPD exacerbations and improve recovery time for the patient. They have the advantage of being rapid-acting, more convenient, and may be more effective than intravenous corticosteroids.² Prednisone 30 – 50 mg, once daily in the morning, for five days can be prescribed for patients with moderate or severe exacerbations.² Prescribing corticosteroids for periods of 14 days to reduce the severity of exacerbations is no longer considered necessary.⁸ Corticosteroid use does not need to be tapered in patients prescribed treatment courses of less than two weeks.

For further information see: “Shorter courses of oral corticosteroids for the management of exacerbations in patients with COPD”.

When to prescribe antibiotics

If patients show clinical signs of infection, i.e. fever, increased volume or colour of sputum, they can be prescribed oral antibiotics for five to ten days. Bacterial infection is thought to be involved in approximately half of COPD exacerbations.² Antibiotic regimens for the treatment of patients with infective COPD exacerbations vary. Recommended treatments include: amoxicillin, 500 mg, three times daily or doxycycline, 100 mg, twice daily*.² Sputum culture is not routinely required unless the patient is not responding to antibiotic treatment or has had multiple bacterial infections over a period of several months.² Intravenous antibiotics are unlikely to be required in a community setting and are only appropriate for patients with an impaired mental state, inability to swallow, or X-ray evidence of pneumonia requiring hospitalisation.²

Prophylactic or continuous use of antibiotics is not currently recommended to prevent exacerbations in patients with COPD on the balance of benefits versus adverse effects.³

* Recommended doses for doxycycline for acute exacerbations of COPD range from 100 – 200 mg, twice daily on day one, followed by 100 mg, once or twice daily, on days two to five.

Consider “back-pocket” prescriptions for select patients

Patients with COPD who are considered to have good self-management skills can be provided with “back-pocket” prescriptions for antibiotics and corticosteroids for the treatment of exacerbations.² A written action plan should be provided to the patient that indicates how to recognise if their condition has changed, what to do if this occurs and the medicines, doses and action that should be taken.²

When to refer to hospital

Patients with COPD who are experiencing an exacerbation should be considered for referral to hospital if they display:²

• A significant increase in symptom intensity
• An inadequate response to community-based treatments
• An inability to walk between rooms when they were previously mobile
• Dyspnoea that is affecting their ability to sleep or eat
• An inability to cope at home
• Features suggestive of respiratory failure, i.e. confusion, drowsiness, restlessness, and cyanosis
• New-onset arrhythmia
• SpO₂ < 92% on pulse oximetry
• Deteriorating cor pulmonale

Controlled oxygen, delivered at a rate of 0.5 – 2.0 L/min, is indicated for patients with hypoxaemia during a COPD exacerbation.² High-flow oxygen is avoided in patients with COPD as this may cause hypoventilation and acute respiratory failure.²

Pulmonary embolism should be considered if a patient’s condition merits hospitalisation, but the typical features of an exacerbation of COPD are absent, such as fever, productive cough and wheezing.² It is estimated that as many as one in four patients with an atypical COPD exacerbation may have an underlying pulmonary embolism causing acute dyspnoea.⁹

Follow-up after discharge from hospital

Following discharge from hospital it is reasonable for the primary care team to expect to receive a hospital discharge plan within 24 hours.² The patient should then be followed-up by a member of the primary care team within seven days. Follow-up should include an assessment of the patient’s:²

• Level of physical activity
• Coping ability
• FEV₁ (if equipment and skills to perform spirometry) and performance status (e.g. Modified Medical Research Council Dyspnoea Scale)
• Medicine adherence and ability to use inhaler devices
• Effectiveness of treatments, with optimisation if necessary using a stepwise approach
• Influenza and pneumococcal vaccination status
• Risk of osteoporosis
• Risk of future exacerbations with a review of the patient’s action plan

Following an exacerbation requiring hospitalisation, patients with COPD should be referred for pulmonary rehabilitation, once they are stable.² Patients with abnormalities on X-ray should be followed up within four to six weeks of discharge from hospital.² Depending on the clinical circumstances, a follow-up x-ray may be required.

Low-dose morphine, benzodiazepines, and eventually oxygen, may be considered for patients with COPD who have reached the stage when their lung function cannot be improved.

Opioids can relieve dyspnoea at low-doses by decreasing the patient’s respiratory rate without causing hypercapnia or hypoxia.¹⁰ Initially, low doses of morphine can be trialled on an “as needed” basis for refractory dyspnoea, e.g. 2 mg of morphine oral solution pre-measured in a syringe or 2.5 mg of an immediate-release tablet (one-quarter of a 10 mg tablet of morphine). If the patient requires regular dosing, 2 – 2.5 mg of morphine can given every four to six hours; this dose can increased in steps of 30% if tolerated.¹¹ It is unknown what the exact mechanism for opioids relieving dyspnoea is. One possibility is that opioids modulate the patient’s perception of dyspnoea, in the same way they do for pain, without reducing the patient’s ventilation drive.¹²

Benzodiazepines can be very effective at reducing the anxiety associated with dyspnoea, although there is no evidence that they can relieve breathlessness itself.¹¹ Lorazepam 0.5 mg (half of a 1 mg tablet), every four to six hours, as required, is an appropriate starting dose.¹¹

For further information see: “Managing breathlessness in palliative care”, BPJ 47 (Aug, 2012).

Oxygen treatment in a consistently hypoxic patient may reduce polycythaemia, improve sleep quality, prevent right-sided heart failure and reduce mortality.^{2, 13} Patients with COPD who are stable but have persistent hypoxaemia, consistent with a SpO₂ < 92% on pulse oximetry, should be referred to a respiratory physician to assess their need for long-term oxygen therapy.² For patients to be eligible for long-term treatment with oxygen it is a requirement that the patient and their home be smoke-free.

Nutritional advice for patients with COPD

Weight loss and reduced muscle mass are common in people with advanced COPD as they need to exert more energy while breathing. This can result in a deterioration in lung and heart function, a reduced ability to exercise and increased mortality.¹⁴ People with COPD need to ensure that their nutritional intake is adequate enough to support their extra energy requirements. It is estimated that approximately 23% of people with COPD are malnourished, but it is unclear whether this is the cause of their deterioration or a part of the disease process.^{14, 15}

Five key questions that can be asked to assess food intake and nutritional status are:¹⁶

• “How is your appetite?”
• “Are you managing to eat like you usually do?”
• “Have you noticed any change in your body weight?”
• “Have you noticed any other changes to your body shape or muscle strength?”
• “Do you have concerns about your diet or food intake?”

Nutritional advice for patients with COPD

Patients with BMI <20 kg/m² or any patients with unintentional weight or muscle loss:

1. “Food First”. Maximise nutritional intake from the diet:

• Eat small, frequent meals that are high in protein (meat, chicken, fish, eggs, cheese and milk) and fat (cream, cheese, butter, peanut butter, gravy, sauces and fried foods)
• Consume six to eight drinks per day; water, milk drinks and soup are better than tea or coffee
• Offer referral to a “Meals-on-wheels” or a similar service

A patient leaflet about nutritional advice in underweight patients is available from www.copdeducation.org.uk/graphics/pdf/Red-Leaflet.pdf

2. Oral nutritional supplements can be considered as an adjunct to the “food first” strategy in patients with a BMI <20 kg/m² or in any patients who continue to experience unintentional weight or muscle loss despite optimising dietary intake.¹⁶

The recommended dose of oral nutritional supplements is 600 kcal, daily, for three months, with monthly reviews where possible.¹⁶ If there is no improvement after three months referral to a dietitian is recommended.

Pulmocare is a high-fat, reduced-carbohydrate formula indicated for patients with CO₂– retentive respiratory conditions such as COPD.⁷ The formula is available subsidised with Special Authority on application from a vocationally registered general practitioner, specialist or dietitian for patients who have COPD and hypercapnia (CO₂ value of > 55 mmHg). It is designed to reduce carbon dioxide production and supply nutrients without compromising respiratory function.⁷