17th February 2025

Chronic obstructive pulmonary disease

Overview of COPD

COPD is an umbrella term used to encompass chronic bronchitis and emphysema. It is a chronic, life-limiting condition, with causes including:

• Smoking – the most important cause
• Alpha-1 antitrypsin (AAT) deficiency – should be considered in younger patients with no smoking history or a positive family history
• Occupational – secondary to exposure to cadmium, coal, cement or cotton

Prevalent features are productive cough, dyspnoea, reduced exercise tolerance, wheeze and recurrent ‘winter bronchitis’.

Diagnosis of COPD

Typical investigation findings include the following:

• Blood tests: FBC and CRP to identify anaemia and secondary polycythaemia, and rule out infection 
• Chest X-ray: flattened diaphragm, hyperexpanded lungs, bullae
• Lung function tests, especially post-bronchodilator spirometry, which should show an obstructive picture (FEV1/FVC <70%) to be in keeping with a diagnosis of COPD
• BMI: low BMI or weight loss is common in severe COPD and associated with a worse prognosis. It can also be associated with a co-existing lung cancer

Image Source: Wikimedia Commons (2010). COPD, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:COPD.JPG (Accessed: 19 January 2024).

FEV₁ is used to determine the severity of COPD:

Table 3 Staging of COPD using FEV₁

Management of COPD

Acute exacerbation of COPD

An acute exacerbation of COPD can be infective or non-infective. Key pathogens include:

• Bacterial: Haemophilus influenzae (most common bacterial pathogen in COPD), Streptococcus pneumoniae
• Viral: rhinovirus is the most common

Management is as follows:

• ABG to determine target SaO2: normally aim for 88-92%, but increase to 94-98% if normal pCO2
• Keep saturations 88-92% with a history of T2RF (type 2 respiratory failure), chronic hypercapnia or if baseline saturations are known to be <94%
• Bronchodilators: nebulised delivery and increased frequency are often required during an exacerbation
• Steroids: 30 mg prednisolone for 5 days
• Antibiotics are indicated only with signs of infection, e.g. purulent sputum, raised inflammatory markers or chest X-ray changes

Non-invasive ventilation (NIV) is typically indicated in the presence of T2RF with acidosis:

• Recommended with pH 7.25-7.35
• If pH <7.25, ITU involvement and possible intubation should be considered
• NIV delivers different air pressures for inspiration and expiration. The inspiratory positive airway pressure (IPAP) is set higher to improve ventilation and aid the patient’s own respiratory effort. The expiratory positive airway pressure (EPAP) recruits collapsed alveoli to increase gas exchange and allow removal of exhaled gases. Typical initial settings for NIV are IPAP 10-15 cmH₂O and EPAP 4-5 cmH₂O

Long-term management of COPD

The most important intervention is smoking cessation. Other facets to long-term management include vaccinations (once-off pneumococcal and annual influenza), pulmonary rehabilitation and inhaler therapy as per NICE guidelines:

• Step 1 (new diagnosis): SABA or short-acting muscarinic antagonist (SAMA) as needed
  Beyond this stage, it is important to check for features of asthma or steroid responsiveness, e.g. history of asthma, high eosinophils, diurnal variation in PEF or FEV1
• Step 2a (no features of steroid responsiveness): SABA (PRN) + LABA + LAMA
• Step 2b (features of steroid responsiveness): SABA or SAMA (PRN) + LABA + ICS
• Step 3: SABA (PRN) + LABA + LAMA + ICS

Box 3 Common medications used in COPD

Other treatments may include:

• Theophylline if symptomatic with maximal inhaler therapy
• Mucolytic, e.g. carbocisteine, in cases of ongoing productive cough
• Prophylactic antibiotics in selected cases, e.g. azithromycin (usually 3 times a week) can be considered for non-smokers already receiving optimal medical management with frequent (>4 per year) or severe (prolonged or resulting in hospitalisation) exacerbations of COPD
• Surgical input (for selected patients), e.g. lung reduction surgery or bullectomy
• Diuretics if evidence of cor pulmonale (right-sided heart failure due to chronic raised pulmonary pressures)

Long-term oxygen therapy is indicated for non-smokers in selected cases:

• pO₂ on room air <7.3 kPa OR
• pO₂ on room air 7.3-8.0 kPa and one of secondary polycythaemia, pulmonary hypertension or fluid overload

End-stage COPD

COPD is a chronic progressive illness and the end stage of the disease will typically feature a progressive decline with increasing frequency and severity of acute exacerbations.

Factors that may indicate a patient is approaching end-stage COPD and end of life care are:

• Increasing frequency of hospitalisation and worsening severity of acute exacerbations
• Low body mass index
• Poor lung function on spirometry testing
• Other comorbidities such as cardiac disease or malignancy

Management of end-stage COPD should involve advance care planning and ensuring optimal medical management. MDT approach should involve respiratory specialist nurses, district nurses, palliative care team and social services/occupational therapy as appropriate.

It is important to ensure management of symptoms associated with COPD in conjunction with palliative care specialists:

• Breathlessness: simple breathing exercises, home oxygen, opiates and benzodiazepines
• Cough and secretions
• Pain
• Anxiety and depression

Alpha-1 antitrypsin deficiency

AAT deficiency is an inherited condition which causes reduced levels of alpha-1 antitrypsin, a protease inhibitor that inhibits elastase, an enzyme that causes inflammatory damage to the lungs. It should be considered in younger non-smokers who present similarly to COPD.

Genetics of AAT deficiency

The inheritance for alpha-1 antitrypsin deficiency is co-dominant.

The affected gene is on chromosome 14. Many different alleles have been identified but the most common are the M allele (normal), S allele (partially defective) and Z allele (nearly fully defective).

• MM – normal phenotype
• MS/MZ – reduced levels of AAT (50-75% of normal) but if non-smoker, risk of developing COPD is low
• SS/SZ – increased risk of developing COPD compared to the general population
• ZZ – worst prognosis, with an almost 100% chance of developing COPD

Features of AAT deficiency

Pulmonary manifestations include COPD and bronchiectasis, which is worse in smokers. Hepatic manifestations include cirrhosis, increased risk of hepatocellular carcinoma and cholestasis. There are also skin manifestations such as panniculitis and vasculitis (particularly ANCA-positive disease).

Management of AAT deficiency

Smoking cessation is crucial. Other treatments include bronchodilator therapy, alpha-1 antitrypsin augmentation therapy and surgical management options (lung transplant or lung volume reduction surgery).

References

• National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management [Internet]. 2018 [cited 2022 Jan 31] Available from: https://www.nice.org.uk/guidance/ng115/resources/chronic-obstructive-pulmonary-disease-in-over-16s-diagnosis-and-management-pdf-66141600098245
• The National Institute for Health and Care Excellence. Oxygen [Internet]. NICE; 2019 [cited 2022 March 28] Available from: https://bnf.nice.org.uk/treatment-summary/oxygen.html
• Sethi S. Bacteria in Exacerbations of Chronic Obstructive Pulmonary Disease: Phenomenon or Epiphenomenon? Proceedings of the American Thoracic Society. 2004 Apr 1;1(2):109–14
• Davidson AC, Banham S, Elliott M, Kennedy D, Gelder C, Glossop A, et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax. 2016 Mar 14;71(Suppl 2):ii1–35
• Chapman S. Oxford handbook of respiratory medicine. Oxford; New York: Oxford University Press; 2005