Chronic obstructive pulmonary disease: diagnosis and management

Early diagnosis and medicines optimisation are fundamental to ensure timely and appropriate treatment of chronic obstructive pulmonary disease and improve a patient’s quality of life.

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In the UK, someone dies from chronic obstructive pulmonary disease (COPD) every 20 minutes and, by the end of 2020, COPD is predicted to be the third leading cause of death globally[1],[2]
. COPD mortality statistics in the UK are alarming: between 2001 and 2010, the UK had the twelfth highest mortality rate for COPD in the world; in Europe, only Denmark and Hungary had higher mortality rates[3],[4]

Each year, COPD costs the NHS an estimated £1.9bn, with around 1.2 million people formally diagnosed with COPD in the UK and a further 2 million people thought to be living without a diagnosis[1],[5]
. Research suggests prevalence is increasing; in the last decade, the number of people with COPD has increased by more than a quarter[4],[6]
. COPD is an umbrella term for a group of lung conditions characterised by respiratory symptoms and airflow obstruction, including chronic bronchitis and emphysema. Airflow obstruction is caused by a combination of obstruction of the small airways owing to inflammation (obstructive bronchiolitis) and destruction, and over-inflation of the alveoli (emphysema). Airflow obstruction is not fully reversible and is usually progressive[2],[
7]
,[8],[9]
. People with asthma with chronically undertreated airway inflammation may undergo airway remodelling that causes a chronic irreversible airflow obstruction, leading some to classify this fixed airway obstruction in asthma as COPD, although this diagnosis is controversial[2],[10]
.

The condition is most often caused by significant exposure to harmful particles or gases, usually as a result of smoking. Dust and chemicals, particularly in the context of occupational exposure, can also contribute to its development[2],[
7]
.

Being both preventable and treatable, COPD is a public health challenge. It causes chronic morbidity and mortality, with many patients having the disease for many years before being diagnosed later in life, or dying prematurely from the disease or its complications[2],[
7]
. Unfortunately, the most deprived 10% of the UK population are disproportionately affected by COPD[11]
. This is a population with higher incidence of smoking, greater exposure to poor air quality, occupational hazards and poorer housing conditions. In addition, this group are twice as likely to develop COPD and more likely to die from it, compared to the national average[11]
.

In December 2018, the National Institute for Health and Care Excellence (NICE) published guidance for COPD in people aged over 16 years, which aimed to support earlier and more accurate diagnosis so that people living with COPD can benefit from effective treatments to manage their symptoms, improving their quality of life and, therefore, keeping them healthier for longer[12]
.

This article provides an update on best practice for the diagnosis and management of COPD, including the symptoms and risk factors, differential diagnoses and pharmacological and non-pharmacological treatment options.

Symptoms and risk factors

Common symptoms of COPD include:

  • Progressive and persistent dyspnoea (i.e. difficulty breathing);
  • Chronic cough that is productive or non-productive;
  • Persistent wheeze;
  • Chest tightness;
  • Chronic sputum production;
  • Repeated lower respiratory tract infections[2],[9],[12]
    .

Daily dyspnoea is reported by around 45% of patients with COPD, with 46% reporting cough and 40% reporting sputum production[13],[14]
. Symptoms are usually progressive, although treatment can slow progression and improve symptoms[9]
. For many of the symptoms, frequency and severity can vary daily and even throughout the day[2]
.

Most of the symptoms mentioned above are associated with severe COPD, but further investigation is recommended as they may indicate other diseases (e.g. tuberculosis, cor pulmonale [enlargement of the heart] or lung cancer). Less common symptoms of COPD include weight loss, fatigue, ankle oedema, depression, anxiety, chest pain and haemoptysis (i.e. coughing up blood)[2],[12]
. If patients experience chest pain or haemoptysis, they should be advised to attend urgent care immediately as they are uncommon in COPD and will require urgent investigation[2],[12]
.

Risk factors for COPD include:

  • Tobacco smoke;
  • Indoor and outdoor air pollution;
  • Occupational exposures (e.g. dust, chemical agents and fumes);
  • Genetic factors;
  • Age (although it is unclear if age is reflective of cumulative exposure to risk factors in life or if healthy ageing can lead to COPD);
  • Sex (there is a greater burden of airway disease in women compared to men, despite similar exposure to tobacco smoke);
  • Lung growth and development;
  • Socioeconomic status;
  • Asthma;
  • Chronic bronchitis;
  • Recurrent chest infections[2],[12]
    .

In some less developed countries, use of biomass fuel for cooking and heating in poorly ventilated spaces is a risk factor[2]
.

Diagnosis

There is no single diagnostic test for COPD; therefore, the disease should be suspected in any patient aged over 35 years who presents with a risk factor and with one or more symptoms[2],[12],[15]
. Quality-assured spirometry is then essential to support or exclude a diagnosis of COPD[2],[12]
.

Spirometry

A post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 0.7 confirms the presence of persistent airflow obstruction, providing that the FVC is within normal range (FVC > 80%)[16]
. This increases the probability of a COPD diagnosis in patients who present with symptoms, along with a history of exposure to one or more risk factors.

However, the use of FEV1/FVC ratio to define airflow obstruction has its limitations. For example, it may result in more frequent diagnosis of COPD in the elderly population, whose ratio may be less than 0.7, but do not have typical symptoms of COPD[2],[12]
. Equally, FEV1/FVC may result in less frequent diagnosis in adults aged younger than 45 years who present with typical symptoms of COPD, but whose ratio is above 0.7[2],[12]
. Significant airflow limitation may be present without significant dyspnoea and/or cough and sputum production and, similarly, substantial symptom burden can be present without significant airway limitation[2]
.

Alternative diagnoses should be considered in older people with an FEV1/FVC <0.7, but without typical symptoms of COPD where the obstruction may be owing to another diagnosis, such as a tumour in the airways[16]
. Younger people with symptoms of COPD who have a FEV1/FVC >0.7 may have other conditions, such as obesity or interstitial lung disease[2],[16]
.

NHS England is focusing on improving COPD care by improving early detection and accurate diagnosis — a barrier to which is access to quality-assured spirometry[17],[18]
. Establishing community-based, quality-assured spirometry facilities has therefore become a priority for commissioners
[17]
. Some parts of the UK are seeing diagnostic hubs commissioned, such as those in Lambeth and Southwark to improve local access to diagnostics[18]
.

Assessment of symptoms and severity

Symptoms of COPD may precede any airflow obstruction that is identified by spirometry by many years[2]
. A patient’s decision to seek medical advice is often determined by the impact of symptoms on a patient’s functional status[2]
.

A person suspected of having COPD should have a detailed medical history taken and the following factors considered:

  • Exposure to risk factors;
  • Addiction (e.g. alcohol dependence or substance misuse);
  • Current comorbidities — both respiratory and non-respiratory — including those that may affect activity;
  • Family history of respiratory disease (e.g. alpha-1 antitrypsin deficiency);
  • Pattern of symptom development (e.g. gradual or sudden onset, symptom variability);
  • History of exacerbations or hospitalisations for respiratory disorder;
  • Impact on activities and current physical activity;
  • Social support (i.e. the provision of psychological and material resources by a social network, aimed at improving an individual’s ability to cope with their disease)[2],[12]
    .

Assessment of disease severity in COPD is vital for quantifying the impact of the disease and can help determine the risk of future events, such as exacerbations, hospital admissions or even death, as well as help to guide therapy[2]
.

Classification of airflow obstruction

Severity of airflow obstruction in COPD, based on post-bronchodilator FEV1, is outlined in Table 1[2]
. Subsequent measurements can be used to monitor disease progression[12]
. Unfortunately, there is weak correlation between FEV1 and symptom burden; therefore, formal symptom assessment is required[19],[20]
.

Table 1. Classification of airflow obstruction (post-bronchodilator)
FEV1/FVC Percentage of predicted FEV
value
Severity of airflow obstruction
Source: Reproduced with permission Â© 2020, Global Initiative for Chronic Obstructive Lung Disease, available from: www.goldcopd.org, published in Fontana, WI, USA[2]

FEV1 = forced expiratory volume in one second
FVC = forced vital capacity

<0.7

≥ 80%

Mild

50–79%

Moderate

30–49%

Severe

<30%

Very severe

Validated tools and scales

The Medical Research Council (MRC) dyspnoea scale, adapted from Fletcher et al., is a simple tool that can be used to grade the degree of breathlessness according to functional status or activity[21]
. The 1–5 stage scale is used alongside the questionnaire to establish clinical grades of breathlessness, as outlined below:

  • Grade 1: Not troubled by breathlessness except on strenuous exercise;
  • Grade 2: Short of breath when hurrying or walking up a slight hill;
  • Grade 3: Walks slower than contemporaries on level ground because of breathlessness, or has to stop for breath when walking at own pace;
  • Grade 4: Stops for breath after walking about 100 metres or after a few minutes on level ground;
  • Grade 5: Too breathless to leave the house, or breathless when dressing or undressing[21]
    .

Historically, COPD was viewed as a disease characterised by breathlessness, and a grading system, such as the MRC breathlessness scale, would have been used to categorise both disability and disease severity[2],[22]

It is now recognised that COPD has an impact beyond dyspnoea[2]
. A validated tool, such as the COPD Assessment Test (CAT), is useful for giving an indication of overall symptom burden[23],[24]
. It consists of eight statements relating to symptoms and symptom burden that patients score on a perceived scale of severity. It can also be used to identify key areas of health impairment[24]
.

Exacerbation risk

An exacerbation refers to an episode of rapid and continued worsening symptoms beyond what is usual for the patient[2],[9],[12]
. Severity and frequency of exacerbations over the previous 12 months should be assessed. The best predictor of frequent exacerbations is a history of earlier treated events[25]
. The risk of exacerbations increases as the severity of airflow obstruction increases, while hospitalisation for a COPD exacerbation is associated with a poor prognosis and increased risk of death[26],[27]
.

Assessment of comorbidities

Patients with COPD have extensive, associated physical and mental health-related comorbidities[28]
. A study by Chetty et al. in primary care in Scotland found that 86% of patients with COPD have at least one comorbidity compared to 49% of people without COPD, and 22% of patients with COPD have five or more comorbidities versus 5% of those without COPD[28]
.

COPD with concomitant chronic illness may be owing to common risk factors, such as ageing, smoking and lifestyle[27],[29],[30]
. These can have a significant impact on prognosis; increase polypharmacy; increase risk of hospitalisation; and negatively impact other conditions, such as an exacerbation of COPD, which, in turn, can exacerbate heart failure symptoms[2],[28]
.

COPD has significant extra-pulmonary effects, including weight loss, nutritional deficiencies and skeletal muscle dysfunction[2]
. Whether or not COPD and any comorbidities are related, management of COPD must include optimal management of comorbidities. Other factors to be considered when assessing severity and prognosis include smoking status, low body mass index (BMI), chronic hypoxia, signs of cor pulmonale and frailty[12]
.

Further investigations

In addition to spirometry, all patients should receive the following:

  • Chest radiograph — useful to exclude other diagnoses or establish comorbidities, such as cardiac disease or skeletal abnormalities;
  • Full blood count — used to investigate anaemia or polycythaemia as a cause for breathlessness. Eosinophilia may indicate asthmatic features;
  • BMI — low BMI is associated with worse outcomes in COPD [2],[12],[31]
    .

Other signs that may present:

  • Cyanosis (i.e. bluish tint to skin and mucous membranes);
  • Raised jugular venous pressure and peripheral oedema (may also indicate cor pulmonale);
  • Hyper-inflated chest (also referred to as barrel chest);
  • Use of accessory muscles to assist breathing (generally only engaged in respiratory distress)
  • Wheeze or quiet breath sounds when measured by a stethoscope[32]
    .

The Box outlines additional investigations that may be indicated, depending on presentation. Note that some of these investigations are useful in more severe disease to guide management[2],[12]
.

Box: Additional investigations that may be indicated for COPD

Physical examination

  • Review for presence of finger clubbing (while not specific to pulmonary disease, this may be present in those with severe emphysema, interstitial lung disease and other respiratory conditions).

Sputum culture

  • Used to identify organisms if sputum is persistent and purulent;
  • Presence of colonising bacteria may indicate bronchiectasis.

Electrocardiogram, echocardiogram and serum natriuretic peptides

  • Used to assess cardiac status if cardiac cause or pulmonary hypertension are suspected;
  • Presence of pedal oedema and raised jugular venous pressure raise suspicion of a cardiac cause.

CT scan of thorax

  • Investigates symptoms disproportionate to spirometry results; suspected alternative lung diagnosis, such as bronchiectasis or lung cancer; and abnormalities seen on a chest X-ray;
  • Indicated where lung volume reduction procedures are being considered.

Serum alpha-1 antitrypsin

  • Used to assess for alpha-1 antitrypsin deficiency if there is early onset of symptoms, minimal smoking history or family history of this condition;
  • Serum levels and genotyping help indicate the severity of the deficiency.

Transfer factor for carbon monoxide

  • Assesses gas transfer in the alveoli;
  • Useful for when breathlessness is disproportionate to spirometry results;
  • Reduced gas transfer is often seen in patients with emphysema and interstitial lung disease.

Lung volumes

  • Used to identify gas trapping, leading to lung hyperinflation;
  • Helps characterise severity of COPD but does not change management.

Sources: GOLD Report 2020[2]
National Institute for Health and Care Excellence[12]

Referral for specialist advice

Whilst many patients with suspected or confirmed COPD can be managed appropriately in primary care, there are several scenarios where a referral for specialist advice or care is appropriate (see Table 2). Referral can be appropriate at any stage of the disease; it is not reserved for the clinically unwell or more complex cases[12]
.

Table 2. When to refer for specialist advice
Reason Purpose

Diagnostic uncertainty or suspected severe COPD or cor pulmonale

Confirm diagnosis and optimise therapy

Rapid decline in FEV1

Early intervention

Onset of symptoms in a patient aged under 40 years or a family history of alpha-1 antitrypsin deficiency

Identify alpha-1 antitrypsin deficiency, consider therapy and screen family

Symptoms disproportionate to lung function deficit

Look for alternative explanations, including cardiac impairment, pulmonary hypertension, depression

Frequent infections

Exclude bronchiectasis

Haemoptysis, especially if associated with weight loss

Exclude carcinoma

Abnormal chest X-ray

Confirm or exclude a range of respiratory conditions depending on nature of abnormality

Assessment for oxygen therapy (in context of oxygen saturations <92%, or clinical signs of need)

Measurement of arterial blood gases is essential for assessing requirement

Source: GOLD Report 2020[2]
, National Institute for Health and Care Excellence[12]

Controversy in diagnosis

Occasionally, it can be difficult to clinically differentiate between COPD and asthma (e.g. some patients with chronically undertreated asthma develop irreversible fixed airflow obstruction, secondary to airway remodelling, which presents similarly to COPD)[33]
. Asthma has even been identified as a risk factor for developing COPD[34],[35]
.

However, untreated COPD and asthma are usually distinguishable based on history at initial presentation[12]
. For example, clinical features of COPD include:

  • Chronic productive cough;
  • The patient being a smoker or ex-smoker;
  • Symptoms consistent, with little day-to-day variation;
  • Symptoms later in life;
  • Chronic and progressive breathlessness[2],[12]
    .

Whereas clinical features of asthma include:

  • Non-productive cough;
  • Variable breathlessness;
  • Early diagnosis (early in life);
  • Day-to-day symptom variation;
  • Personal/family history of atopy (e.g. hay fever and eczema);
  • Night-time waking with breathlessness and/or wheeze[12],[36]
    .

Airflow obstruction in asthmatic non-smokers and non-asthmatic smokers is pathologically very different, even when patients present with similar lung function decline[37],[38]
. This suggests the two disease states remain distinct entities, casting doubt on the suggestion that asthma with fixed airway obstruction should come under the umbrella term of COPD.

The term asthma-COPD overlap syndrome (ACOS) was previously used to describe patients with clinical features of both diseases[39]
. Current NICE guidelines do not address ACOS and the 2020 GOLD report states ACOS is not a recognised term[2],[12],[39]
. GOLD guidelines aim to improve prevention and treatment of COPD globally and are widely recognised and used across the UK. The report emphasises that asthma and COPD are different disorders, sharing some traits and clinical features, including eosinophilia and reversibility[2]
.

Furthermore, a proportion of patients will still have a dual diagnosis of both COPD and asthma, although this is often over-diagnosed, usually owing to diagnostic uncertainty. A recent review of primary care data found that 53% of COPD patients were also coded as having asthma, when in fact a validated diagnosis of concurrent asthma was likely in only 15% of these patients[40]
.

When considering a diagnosis of asthma instead of, or in addition to, COPD, a low probability on initial, structured clinical assessment as outlined in the British Thoracic Society guidelines reduces the likelihood of an asthma diagnosis[36]
. However, some people may still have COPD with asthmatic features.

Management

Management aims to reduce exacerbations, prevent hospital admissions, reduce morbidity and prevent premature mortality (see Table 3)[17]
.

COPD is complex as managing it as a single disease is not possible. GPs may be best to support COPD patients with comorbidities, but it can be argued that respiratory specialists should play a role[28]
.

Table 3. Components of COPD management
  Management
Source: Developed by the Primary Care Respiratory Society UK, included in NHS RightCare Pathway: COPD[17]

Primary prevention

  • Health promotion/education;
  • Advice on smoking;
  • Physical activity promotion;
  • Air quality legislation.

Early and accurate diagnosis

  • Joint working across primary care;

  • Upskilling primary care clinicians in identifying and managing COPD;
  • Education on spirometry interpretation;
  • Promotion of local respiratory services;
  • Create efficient referral pathways across primary care;
  • Smoking cessation training for primary care staff. 

Management of stable COPD and exacerbations

  • Pulmonary rehabilitation;
  • Inhaler technique;
  • Written self-management plans;
  • Appropriate pharmacological and non-pharmacological respiratory prescribing
  • Vaccination;
  • Anticipatory prescribing and education;
  • Disease education;
  • Chest clearance and breathing techniques;
  • Smoking cessation. 

Complex/severe disease

  • Integrated working between secondary and shared care;

  • Oxygen assessment;
  • Non-invasive ventilation;
  • Consultant and specialist clinics (community or hospital based);
  • Psychological support and interventions;
  • Optimal management of comorbidities and liaison with other specialties. 

Pharmacological treatment

There are a wide range of treatments used in patients with COPD to reduce the impact of symptoms and help prevent exacerbations. It is important to note that geographical regions may have their own guidelines in place, which may vary to the NICE guideline[12]

Inhaled treatment

When prescribing any inhaled medicine, patients should be coached on how to use the inhaled device and be able to consistently demonstrate good inhaler technique, which should be reassessed at every opportunity[2]
. Long-acting inhalers should be prescribed by brand to ensure patients receive the intended device (see Table 4)[12]
. A spacer should be prescribed alongside all metered-dose inhalers to improve lung deposition[41]
. When using a spacer, single breath or tidal breathing techniques are equally effective[12]
.

The NICE guideline recommends a short-acting bronchodilator, either a short-acting beta-2 agonist (SABA) or a short-acting muscarinic antagonist (SAMA) as initial therapy[2]
. In practice, SAMA’s are rarely used because they would be required to stop once a long-acting muscarinic antagonist (LAMA) is initiated, owing to increased anti-muscarinic side effects. SAMAs are not included in the GOLD guidelines[2],[12]
.

The decision to step up to long-acting therapy should be considered based on a combination of lung function, symptoms, treatment effectiveness and the effect of symptoms on daily activity and exercise capacity. Long-acting therapy refers to inhalers containing a combination of LAMA, long-acting beta-2 agonist (LABA), and inhaled corticosteroids (ICS)[12]
.

NICE advices that when stepping up treatment from a short-acting bronchodilator that a LAMA plus LABA should be offered to people who do not have asthmatic features and remain breathless or have exacerbations despite short-acting therapy[12]
. This allows increased bronchodilation without increased risk of side-effects, by increasing the dose of either agent individually[42]
.

Moreover, the benefits of dual bronchodilation, compared to single agent, include improved quality of life, improved lung function and decreased breathlessness[43],[44],[45],[46]
. Alternatively, an ICS plus LABA should be considered for people who have asthmatic features[12]
. ICS in addition to regular bronchodilating agents reduces exacerbation rates to a greater extent than bronchodilators alone in people with higher eosinophil concentrations and those with a higher exacerbation risk[47]
.

Before commencing triple therapy with LAMA and LABA plus ICS, patients currently taking either a LABA plus ICS or LAMA plus LABA should fulfil one of the following criteria:

  • Have daily symptoms that negatively affect their quality of life;
  • Have a severe exacerbation requiring a hospital admission;
  • Have had two moderate exacerbations in the last 12 months[12]
    .

Triple therapy, when compared to LABA plus ICS alone, has demonstrated improved lung function and reduced exacerbation rates [32],[33],[34]
. When compared to LAMA plus LABA, triple therapy reduces exacerbation rates and hospitalisations[35]
[47].
Pharmacists should be familiar with the different inhalers used in COPD (see common examples in Table 4)[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61]
.
In addition, there is a need to be able to recognise the side effects of these therapies (see Table 5) and provide advice on avoiding them[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63],[64]
.

Table 4. Inhaler examples used for the management of COPD
Short-acting bronchodilator LAMA + LABA ICS + LABA LAMA + LABA + ICS
Source: Electronic medicines compendium[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60]
, British National Formulary
[61]

ICS: inhaled corticosteroids; LABA: long-acting beta-2 agonist; LAMA: long-acting muscarinic antagonist; SABA: short-acting beta-2 agonist; SAMA: short-acting muscarinic antagonist.

 

SABA

  • Salbutamol metred dose inhaler (MDI) 100mcg
  • Salbutamol Easyhaler 100mcg (Orion Pharma UK Limited)
  • Salbutamol breath actuated device 100mcg

SAMA

  • Ipratropium MDI 20mcg
  • Ultibro Breezhaler (glycopyrronium bromide, indacaterol maleate) (Novartis Pharmaceuticals UK)
  • Duaklir Genuair (formoterol fumarate dihydrate,aclidinium bromide) (AstraZeneca UK Limited)
  • Anoro Ellipta (vilanterol trifenatate, umeclidinium bromide) (GlaxoSmithKline UK)
  • Spiolto Respimat (tiotropium bromide monohydrate, olodaterol hydrochloride) (Boehringer Ingelheim Limited)

 

  • Relvar Ellipta 92/22 (fluticasone furoate, vilanterol trifenatate) (GlaxoSmithKline UK)
  • Fostair NEXThaler 100/6 (beclometasone dipropionate, formoterol fumarate dihydrate) (Chiesi Limited)
  • Fostair MDI 100/6 (beclometasone dipropionate, formoterol fumarate dihydrate) (Chiesi Limited)
  • Symbicort Turbohaler 200/6 (budesonide, formoterol fumarate dihydrate) (AstraZeneca UK Limited)
  • Trimbow MDI (beclometasone dipropionate, formoterol fumarate dihydrate, glycopyrronium bromide) (Chiesi Limited)
  • Trelegy Ellipta (fluticasone furoate, vilanterol trifenatate, umeclidinium bromide) (GlaxoSmithKline UK) 
  • Fostair NEXThaler 100/6 +any LAMA (budesonide, formoterol fumarate dihydrate) (Chiesi Limited)

 

Table 5. Side effects of inhaled therapy for COPD
Frequency SABA and LABASAMA and LAMAICS
Source: Electronic medicines compendium [48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60]
,[62],[63],[64]
;British National Formulary
[61]

ICS: inhaled corticosteroids; LABA: long-acting beta-2 agonist; LAMA: long-acting muscarinic antagonist; SABA: short-acting beta2 agonist; SAMA: short-acting muscarinic antagonist.

CommonTremor, headache, palpitations, coughDry mouth, headache, cough, nasopharyngitis, urinary tract infectionsCandidiasis of the mouth and throat, pneumonia, bronchitis, contusions, dysphonia
Less CommonHypokalaemia, taste disturbances, tachycardia, throat irritation, muscle crampsConstipation, dysphonia, oropharyngeal candidiasis, urinary retentionBlurred vision, cutaneous skin reactions, anxiety, sleep disorder, throat irritation, dysphonia 
Rare/very rareBronchospasm paradoxical, dyspnoeaBronchospasm, tachycardia, palpitations, blurred vision, glaucomaBronchospasm, hyperglycaemia, adrenal suppression

Oral mucolytic therapy

Mucolytic drug therapy should be considered for people with a chronic productive cough or high sputum burden; for example, carbocisteine 750mg taken orally three times per day[12],[65]
. However, it is necessary to ensure patients are adequately hydrated, unless fluid restrictions are in place, prior to initiation. Effectiveness of mucolytic therapy should be assessed and stopped if there is no symptomatic improvement[12]
. Use of carbocisteine in patients with active peptic ulceration is contraindicated[65]
.

Oral corticosteroids

Avoid using long-term oral corticosteroids where possible. It is sometimes unavoidable in advanced COPD where patients struggle to wean off oral corticosteroids following an exacerbation. If patients require long-term treatment, the dose should be as low as possible and patients should be monitored for side effects, including osteoporosis[2],[12]
. Primary and secondary prevention (e.g. calcium and vitamin D3 supplements and/or bisphosphonates where appropriate) for osteoporosis should be given in all patients aged over 65 years on long-term oral corticosteroids, and where appropriate for those aged under 65 years[12]
. Stomach protection (e.g. proton pump inhibitors or H2 receptor antagonists) may also be appropriate owing to gastrointestinal side effects of oral corticosteroids[66]

Oral theophylline

Oral theophylline should be reserved for patients who have trialled SABAs and long-acting bronchodilators unsuccessfully, or those unable to use inhaled therapy[12]
. It is not commonly prescribed owing to its narrow therapeutic index and multiple medication interactions, including cigarette smoke, and is generally initiated by a respiratory specialist[12]

Roflumilast

Roflumilast (an oral phosphodiesterase-4 inhibitor) is a long-acting inhibitor of the enzyme phosphodiesterase-4 that has anti-inflammatory effects and is an option for severe COPD[67]
.

Oral prophylactic antibiotic therapy

A prophylactic antibiotic may be considered in patients who continue to have frequent or severe exacerbations. Before considering this, as with any step-up or additional therapy, ensure other treatments, lifestyle changes and non-pharmacological treatments have been considered[12]
.

Complete sputum cultures and sensitivities to exclude other causes of recurrent infection and obtain a CT thorax scan to rule out other lung pathologies, including bronchiectasis
[12]
. Azithromycin is the prophylactic antibiotic of choice and is prescribed at 250–500mg orally three times per week[2],[12]
. Before commencing azithromycin, an electrocardiogram should be performed and baseline liver function should be checked[12]
. Patients should be informed of the risk of hearing loss and tinnitus when taking this medicine, and informed that they should contact a healthcare professional if this occurs[12]
. Patients should be advised that they can continue azithromycin during an acute exacerbation of COPD but ensure that a non-macrolide antibiotic is used for acute treatment[12]
.

Nebulised treatment

Nebulised treatment should only be commenced following assessment by a specialist[12]
. It should be considered for those with severe breathlessness despite optimised inhaled therapy use and good inhaler technique[12]
. Patients with severe dementia or a severe learning disability may benefit from nebulised therapy where inhalers are not an option, owing to difficulty following advice.

Non-pharmacological management

Smoking cessation

Smoking cessation has the greatest capacity to influence and halt the progression of COPD[2]
. Patients with COPD who are still smoking should be encouraged to stop at every opportunity, and support should be offered[12]
.

Patients who are ready to quit should be identified and, ideally, referred to a local smoking cessation service or given information on how to self-refer[68]
. Interventions include behavioural therapy and pharmacological therapy, such as nicotine replacement therapy (NRT), varenicline and bupropion[68],[69]
. A combination of behavioural support and medication has shown a smoking cessation rate double compared to behavioural therapy alone[69]
. All pharmacological therapies have been shown to be effective, with varenicline and NRT proven the most effective[68]
. A history of mental health disorder should not be a barrier to prescribing varenicline[70]
.

Increasingly, patients are enquiring about e-cigarettes as a means of smoking cessation. In this instance, patients should be advised that there is less evidence available for the safety and effectiveness of using e-cigarettes as a means of stopping smoking, but that it is considered safer than continuing to smoke tobacco[69]
.

Pulmonary rehabilitation

Pulmonary rehabilitation is defined as a multidisciplinary programme of care for people with COPD, individually tailored and designed to optimise each person’s physical and social performance[12]
. Pulmonary rehabilitation should incorporate a programme of physical training, disease education, and nutritional, psychological and behavioural intervention[12]
.

This treatment has been proven to be the most effective therapeutic strategy to improve breathlessness, health status and exercise tolerance in patients with COPD
[2]
. Pulmonary rehabilitation should be offered and encouraged to those who have had a recent hospitalisation for an acute exacerbation and those with an MRC score of ≥3[12]
.

Vaccination

All patients with COPD should be offered the annual influenza vaccine and a one-off pneumococcal vaccine[12]
. It should be recognised that local pneumococcal vaccine schedules may be more frequent. The influenza vaccine has been shown to reduce the rate of serious illness, exacerbations and death in patients with COPD, while the pneumococcal vaccine reduces the likelihood of developing community-acquired pneumonia and reduces exacerbation rates[2],[71],[72]
.

Long-term oxygen therapy

Patients with stable COPD, receiving optimal medical management but with a persistent resting oxygen saturation of ≤92%, should be assessed for long-term oxygen therapy (LTOT) suitability[12]
. In hypoxic patients, LTOT can improve survival rates, pulmonary haemodynamics, polycythaemia and neuropsychological health[
7]
.
It is important to understand that it does not relieve breathlessness or benefit all patients, and inappropriate oxygen therapy can cause respiratory depression[12]
.

The assessment for LTOT consists of measuring arterial blood gases on two consecutive occasions at least three weeks apart. If the patient is deemed clinically suitable, there is a need to carry out a structured risk assessment as it can do harm[12],[73]
. LTOT should be used for a minimum of 15 hours per day and should not be offered to people who continue to smoke[12]
.

Ambulatory oxygen

In people with COPD who have exercise desaturation, ambulatory oxygen could be considered if they show an improvement in exercise capacity with oxygen[12]
. It is also suitable for people on LTOT who wish to use oxygen therapy outside of the home[12]
.

Other treatments

Lung surgery and lung volume reduction procedures

Procedures to reduce the volume of the lungs or lung transplant are generally reserved for those patients with severe COPD, with FEV1 less than 50% and breathlessness that affects their quality of life, despite optimal medical treatment. In order to be considered for these treatments, they must not be current smokers and have completed pulmonary rehabilitation[12]
.

Lung volume reduction procedures include:

  • Lung volume reduction surgery in which the diseased part of the lung is removed to improve airflow, diaphragm and chest wall mechanics, and alveolar gas exchange in the healthy lung tissue[74]
    ;
  • Bronchoscopic interventions, such as endobronchial valves and coils: these interventions allow better air flow to the healthier part of the lung, which aims to improve gas exchange and lung function[2]
    .

Lung transplant can be considered if specified criteria are met and there are no contraindications for transplantation, such as significant comorbidity or frailty [2],[12]
.

A bullectomy can be considered if the patient is breathless and a CT scan shows a bulla — lung tissue not contributing to gas exchange or that compresses adjacent lung tissue. The bulla must occupy at least one third of the hemi-thorax[2]
. A bullectomy can decrease breathlessness, and improve exercise tolerance and lung function[2],[12]
.

Self-management

Individualised written self-management plans should be developed in collaboration with each patient and their carer, as appropriate[12]
. The plan should include education on COPD, smoking cessation, breathlessness management, physical activity and pulmonary rehabilitation, pharmacological treatment, vaccinations, how to identify and manage exacerbations and how to access further support[12]
.

The exacerbation plan should encourage prompt response to symptoms and may include adjusting SABA to treat symptoms; taking a short course of oral corticosteroids; and taking a short course of antibiotics (only if the exacerbation is infective)[12]
. If the person experiences breathlessness that is frightening, their action plan may include some coping strategies to manage their anxiety, such as cognitive behavioural therapy[12]
.

COVID-19

In light of the recent COVID-19 pandemic, there is a need to consider the COPD patient cohort and how this may change their care, both acutely and over time. Notwithstanding the obvious overlap of common presenting symptoms of COVID-19 and an exacerbation of COPD which presents clinicians with diagnostic difficulty, patients with COPD are also at increased risk of complications from COVID-19[75]
. This is not only by virtue of their chronic respiratory disease, but also because this cohort are more likely to be elderly, socially deprived and have multiple comorbidities.

Whilst it was important for patients with more severe COPD to shield as per government advice, this did not come without its consequences. The major changes to day-to-day life meant that many of the COPD cohort have been less mobile over several months, and a pattern of deconditioning and reduced exercise tolerance is emerging[76]
. The long-term impact of this remains to be seen.

As seen across the NHS, COPD services have been forced to adapt to the risk posed by COVID-19. As the pandemic reached the UK, diagnostic services, such as spirometry, were forced to close to all but the most essential referrals, owing to the aerosol generating nature of the procedure. This has an obvious impact on patients awaiting diagnosis and waiting lists are increasing by the day. Pulmonary rehabilitation has also been forced to adapt; face-to-face classes have been replaced with virtual pulmonary rehabilitation, which is not without its challenges.

Face-to-face appointments have largely been replaced by phone appointments, where appropriate; however, risk stratification is important to ensure patients continue to be reviewed so that those requiring face-to-face care still receive it.

Acknowledgements

The authors would like to thank Gráinne d’Ancona for her support and guidance.

Financial and conflicts of interest disclosure

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript. No writing assistance was used in the production of this manuscript.

About the authors

Alicia Piwko and Maeve Savage are both highly specialist pharmacists in COPD and integrated respiratory care, Guy’s and St Thomas’ NHS Foundation Trust & Quay Health Solutions.

Email address: alicia.piwko@nhs.net; maeve.savage1@nhs.net

 

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The Pharmaceutical Journal, PJ October 2020, Vol 305, No 7942;305(7942)::DOI:10.1211/PJ.2020.20208431

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