5th January 2024

Chronic Obstructive Pulmonary Disease (COPD)

Background

COPD is a progressive disease characterised by airflow limitation that is not fully reversible. It encompasses both emphysema and chronic bronchitis. It is primarily caused by cigarette smoking. Pathologically, emphysema is defined as an abnormal dilatation of the airways distal to the terminal bronchioles with destruction of alveolar walls. Chronic bronchitis is defined clinically as 3 months of chronic productive cough during 2 consecutive years. 

Clinically, emphysema and chronic bronchitis are used interchangeably with COPD. 

Epidemiology

COPD is more common in people aged 65 years and above. The pooled global prevalence of COPD is 15.7% in men and 9.93% in women.

Aetiology

Tobacco smoking is the main risk factor for COPD as it is responsible for 40-70% of cases due to inflammatory response, cilia dysfunction and oxidative injury. Other risk factors are air pollution, occupational exposure to dust, chemical agents, and fumes. In patients with alpha-1 antitrypsin deficiency, oxidative stress and imbalance in proteases and antiproteases are important factors in pathogenesis of COPD. Any process that influences optimum lung growth and lung function can potentially increase the risk of developing.

Presentation 

Patients commonly present with a combination of signs and symptoms of emphysema and chronic bronchitis. 

Symptoms of COPD include the following:

• Cough, which is usually productive of a small amount of colourless sputum and worse in the mornings.
• Breathlessness is one of the primary symptoms of COPD and usually exertional.
• Self-reported wheeze, generally during exercise or exacerbations.

Physical examination findings have a poor sensitivity in detecting mild to moderate disease; however, physical signs are quite specific and sensitive for severe disease. Signs in severe disease include the following:

• Tachypnoea with simple activities
• Accessory muscle use
• Cyanosis
• Peripheral oedema and elevated jugular venous pulse in cases of cor pulmonale. 
• Barrel chest (Hyperinflation of the chest)
• Wheezing on auscultation
• Reduced breath sounds
• Hyperresonance on percussion
• Coarse crackles in inspiration

References

• COPD – Symptoms, diagnosis and treatment | BMJ Best Practice [Internet]. Bmj.com. 2019. Available from: https://bestpractice.bmj.com/topics/en-gb/7
• Mosenifar Z. Chronic Obstructive Pulmonary Disease (COPD): Practice Essentials, Background, Pathophysiology [Internet]. Medscape.com. 2019. Available from: https://emedicine.medscape.com/article/297664-overview

Diagnosis

Diagnosis of COPD is suspected based on signs and symptoms and is supported by spirometry. 

Investigations 

Spirometry

Spirometry should be performed at diagnosis to reconsider diagnosis if alternative diagnosis is likely and to monitor disease progression. 

Post-bronchodilator spirometry should be performed to confirm diagnosis of COPD.

Other investigations 

For initial diagnostic evaluation, in addition to spirometry, all patients should have the following:

• Chest radiograph to exclude alternative pathologies such as bronchiectasis and to look for typical signs of COPD. Frontal and lateral chest radiographs in patients with emphysema may reveal flattening of the diaphragm, increased retrosternal air space, long and narrow heart shadow. Patients with chronic bronchitis may show cardiomegaly and increased bronchovascular markings.
• Full blood count to assess for anaemia or polycythemia.
• BMI should be calculated, as patients with abnormal BMI should be referred for dietetic advice.
• Sputum culture in case of purulent and persistent sputum
• Serial home peak flows to exclude asthma if diagnosis is unclear
• ECG, natriuretic peptides and echocardiogram to assess cardiovascular status in case of cardiac disease or if pulmonary hypertension is suspected. 
• CT scan of chest to assess suitability for lung reduction surgeries and investigate the following
  • Abnormalities seen on plain chest radiograph 
  • Signs suggestive of other lung pathologies 
  • Symptoms that are disproportionate to spirometry findings
• Transfer factor for carbon monoxide (TLCO) might be needed to investigate symptoms disproportionate to spirometric impairment and evaluate suitability for lung volume reduction surgery. 
• Serum alpha-1 antitrypsin can be measured to assess for deficiency in younger patients and minimal smoking history or family history. 

Reversibility testing

Routine spirometric reversibility is not necessary for diagnosis or planning initial therapy for most people. However, when diagnosis remains uncertain, or both asthma and COPD are present, the following findings can help to identify asthma:

• Over 400 ml response to bronchodilators.
• Over 400 ml to 30 mg oral prednisolone daily for 2 weeks.
• Serial peak flow measurements showing 20% or more of diurnal variability. 

Classifying the severity of airflow obstruction

NICE. Recommendations | Chronic obstructive pulmonary disease in over 16s: diagnosis and management | Guidance | NICE [Internet]. Nice.org.uk. NICE; 2018. Available from: https://www.nice.org.uk/guidance/ng115/chapter/Recommendations#diagnosing-copd

Differential Diagnosis

• Congestive heart failure (CHF)- may present with wheeze and could be difficult to differentiate from emphysema. History of orthopnea, paroxysmal nocturnal dyspnea and fine basal crackles on examination can point toward CHF. 
• Bronchiectasis- distinguishing signs and symptoms include chronic cough productive of copious and purulent sputum, coarse crackles and possible finger clubbing (COPD alone does not have clubbing). 
• Bronchiolitis obliterans- an inflammatory disease which involves both the alveoli and peripheral bronchioles. It is usually observed in younger patients with no smoking history and patients with collagen-vascular diseases. A chest CT scan might show areas of mosaic attenuation without signs of generalised emphysema. 
• Asthma- COPD may be difficult to distinguish from delayed onset of severe asthma. However, there is significant bronchodilator response on pulmonary function tests.
• Chronic cough induced by ACE-inhibitors- ACE inhibitors may cause chronic non-productive cough, which improves upon cessation of the medications.
• Gastro-oesophageal reflux disease- can cause chronic cough that might worsen at night when supine. Symptoms improve with proton pump inhibitors.
• Chronic sinusitis and post nasal drip- chronic sinusitis or rhinitis is a common cause of chronic cough. Other symptoms include headache, facial pain and rhinorrhoea. CT of sinuses, nasal endoscopy, and antihistamine aid in diagnosis. 

Management of chronic COPD

General Principles 

1. Support to stop smoking should be offered. 
2. Pneumococcal and influenza vaccinations. 
3. Pulmonary rehabilitation if required.
4. Co-develop personalised self-management care.
5. Optimise management of comorbidities. 

Pharmacological treatment

Pharmacological treatment should only be offered after consideration of the above principles and when inhaled therapies are required to relieve symptoms and improve exercise tolerance. 

Determine whether the patient has asthmatic features or features of steroid responsiveness such as previous diagnosis of asthma or atopy, elevated eosinophil count, significant FEV1 variation over time (>=400 ml) or PEF diurnal variation. 

• Start short-acting beta2 agonists (SABA) or short-acting muscarinic antagonist (SAMA) as required. Additional treatment should be offered in case of ongoing symptoms or exacerbations despite treatment. 
• COPD  with asthmatic features: 
  1. Offer LABA + ICS 
  2. Offer LABA +LAMA + ICS if symptoms impacting quality of life or in case of 1 severe or 2 moderate exacerbations in a year. 
• COPD without asthmatic features
  1. Offer LABA + LAMA
  2. Offer LABA + LAMA + LCS 

Oral theophylline

Oral theophylline is reserved for people who are unable to use inhaled therapy or after trial of SABA and LABA, as it requires regular monitoring of plasma levels and interactions. 

Oral mucolytic therapy

Mucolytic drugs may be considered for people with chronic productive cough and only continued if there is symptomatic improvement. 

Prophylactic antibiotics

Azithromycin 250 mg 3 times a week should be considered in people with COPD if they continue to have frequent (4 or more per year) exacerbations, prolonged exacerbations and exacerbations resulting in hospitalisation. Non- pharmacological management, including smoking cessation, relevant vaccinations, referral to pulmonary rehabilitation, and inhaled therapies, should be optimised before offering prophylactic antibiotics. 

The following investigations are prerequisites of starting prophylactic Azithromycin:

• Sputum culture and sensitivity, including tuberculosis, to identify causes of recurrent infection that may need specific treatment. 
• CT scan of chest to exclude bronchiectasis.
• ECG as Azithromycin can prolong QT interval.
• Liver function tests.

Prophylactic Azithromycin should be reviewed 3 months after initiation and then every 6 months. 

A non-macrolide antibiotic should be provided to patients who are at risk of exacerbations as part of exacerbation action plan. 

Long-term oxygen therapy 

The need for long-term oxygen should be evaluated in people with:

• FEV1 less than 30% predicted
• Cyanosis
• Polycythemia
• Peripheral oedema
• Raised JVP
• Oxygen saturation of 92% or less

Arterial blood gas should be measured on two occasions at least 3 weeks apart. Long-term oxygen should be considered in people with:

• PaO2 of 7.3kPa and below when stable.
• PaO2 of between 7.3 and 8 kPa with secondary polycythemia, peripheral oedema, or pulmonary hypertension. 

Oxygen therapy should be offered to patients who do not smoke. Risk of falls from tripping over equipment and risk of burns should be evaluated and documented prior to commencing oxygen. 

Patients should breathe supplemental oxygen for minimum of 15 hours per day.

Non-invasive ventilation (NIV)

The following patients should be referred to specialist centre for consideration of NIV:

• Who are on optimum treatment but have chronic type 2 respiratory failure and have required either invasive or non-invasive ventilation during an exacerbation.
• Who are acidotic or hypercapnic on long-term oxygen therapy.

Lung surgery and lung reduction procedures

Respiratory and surgical review can be offered to patients who meet the following criteria:

• Patients with severe COPD with FEV1 less than 50% and breathlessness despite optimum medical treatment.
• Non-smokers
• Patients who can complete 6 minutes of at least 140 meters of distance.

Management of Acute Exacerbation of COPD 

Exacerbation of COPD is an acute worsening of patient’s symptoms from a stable state. Multiple factors, including viral infections and smoking, can trigger an exacerbation.

Pharmacological management

Inhaled therapy

Both nebulisers and inhalers can be used as delivery systems for inhaled therapy during exacerbations of COPD. However, the choice of delivery system depends on patients’ ability to use the device, the available resources, and the dose of the drugs. In case of hypercapnia or acidosis, nebulisers should be driven by air rather than oxygen to prevent worsening hypercapnia. 

 Nebulisers should be switched to inhalers as soon as the patient’s condition is stabilised to facilitate earlier discharge from hospital. 

Steroids

Systemic corticosteroids should be offered to patients with COPD exacerbation in the absence of significant contraindications. 30 mg of oral Prednisolone for 5 days is recommended. 

Antibiotics

Antibiotics are recommended in case of bacterial exacerbation of COPD. Antibiotic choice should be guided by most recent sputum culture and susceptibilities whenever available. First-choice of empiric oral antibiotics is either Amoxicillin 500 mg three times a day for 5 days, Doxycycline 200 mg on first day, then 100 mg once a day for 5-day course in total or Clarithromycin 500 mg twice a day for 5 days. 

If symptoms fail to improve after 2 to 3 days, an alternative first-choice antibiotics could be used. Second-choice antibiotics are co-amoxiclav 500/125 mg three times a day for 5 days, Co-trimoxazole 960 mg twice a day for 5 days or Levofloxacin 500 mg once a day for 5 days. 

First-choice IV antibiotics are used if patient is severely unwell or unable to take oral medications as follows:

• Amoxicillin: 500 mg three times a day
• Co-amoxiclav: 1.2 g three times a day
• Clarithromycin: 500 mg twice a day
• Co-trimoxazole: 960 mg twice a day
• Piperacillin with tazobactam; 4.5 g three times a day

Theophylline and other methylxanthines

Intravenous Theophylline can be used in addition to other exacerbation management in case of inadequate response to nebulised bronchodilators. Theophylline level should be monitored within the first 24 hours. 

Oxygen therapy 

Arterial blood gases should be measured in all patients with COPD exacerbation, and Oxygen should be prescribed to maintain the oxygen saturation within the target range. 

Non-invasive and invasive ventilation

NIV is the treatment of choice for type 2 respiratory failure that is persistent despite optimal medical therapy. When patients are started on NIV, ceiling of care should be clear in event of deterioration. 

Invasive ventilation on intensive care units should be considered when necessary after careful assessment of suitability of patient for intensive care. 

Respiratory physiotherapy

Chest physiotherapy aiming at clearing sputum should be considered in selected patients using positive expiratory pressure devices.

Respiratory stimulants

Doxapram is recommended only when NIV is unavailable or inadequate.

References

• Chronic Obstructive Pulmonary Disease (COPD) Differential Diagnoses [Internet]. Medscape.com. 2019. Available from: https://emedicine.medscape.com/article/297664-differential 
• NICE. Recommendations | Chronic obstructive pulmonary disease in over 16s: diagnosis and management | Guidance | NICE [Internet]. Nice.org.uk. NICE; 2018. Available from: https://www.nice.org.uk/guidance/ng115/chapter/Recommendations#diagnosing-copd
• NICE Guideline. COPD (acute exacerbation): antimicrobial prescribing [Internet]. 2019. Available from: https://www.nice.org.uk/guidance/ng114/resources/guide-to-resources-pdf-6602624893