Written by P.C. Ridge; S.M. Walsh Department of Respiratory Medicine, University Hospital Galway, Ireland | National University of Ireland, Galway
Correspondence: Dr Padraic Ridge, Department of Respiratory Medicine, Galway University Hospitals, Galway, Ireland E mail: email@example.com
Chronic obstructive pulmonary disease (COPD) is a common condition characterised by persistent respiratory symptoms with non-variable airways disease (obstruction) and/or alveolar damage (emphysema). It is caused by significant exposure to noxious gases or particles. 1 In this article, we review the disease pathogenesis, epidemiology, approach to assessment, diagnosis and chronic disease management for a patient.
Cigarette smoke is the most common risk factor for COPD worldwide, accounting for approximately 80% of cases. Pipe tobacco and marijuana are other risk factors. 1 Passive exposure to cigarette smoke can also lead to COPD by increasing the total burden of inhaled particles and gases that the lungs are exposed to. Other causes include burning of biomass fuels, air pollution and occupational exposures, including those experienced by sculptors and gardeners. 2 Interestingly, not all individuals who smoke will develop COPD. Even in those who are heavy smokers, less than 50% will develop COPD during their lifetime. 3 This variability is believed to be due to a complex interplay between the type and intensity of noxious exposures and individual factors such as genetics, age, gender, airway hyper-responsiveness, infections and overall lung development 1, 4, 5 in childhood.
The prevalence of COPD is increasing worldwide and is expected to continue to rise due to ongoing exposure to COPD risk factors, particularly smoking, in developing countries and an aging population in developed countries. 3, 6 The global burden of disease study reported COPD as the third leading cause of death worldwide. 7 The estimated worldwide COPD mean prevalence is 13.1%, however data in many geographic areas is scarce. 4, 6
Assessment of a patient with suspected COPD
The three main symptoms of COPD are dyspnoea, chronic cough, and sputum production. The first and most common symptom reported by patients is dyspnoea on exertion. Less commonly, patients describe symptoms of wheeze, fatigue and anorexia.
The key findings on clinical examination of a patient with COPD are usually absent until significant impairment of lung function has occurred. 8 Tachypnoea occurs with activity, with increasing respiratory rate in proportion to disease severity. Use of accessory respiratory muscles and paradoxical indrawing of the lower intercostal spaces (Hoover sign) indicates airway hyperinflation and a flattened diaphragm. Other findings on thoracic examination include a barrel chest, hyperresonance on percussion, diffusely decreased breath sounds, and prolonged expiration.
Diagnosis and staging
Diagnosis of COPD is based on a triad of causative exposure, symptoms and spirometry. Spirometry is the most reproducible and objective measurement of airflow limitation. 1 It measures the volume of air that a patient can forcibly exhale from the point of maximal inspiration (forced vital capacity, FVC) and the volume of air that is exhaled during the first second of this manoeuvre (forced expiratory volume in one second, FEV1). The ratio of the FEV1/FVC is calculated. Airflow obstruction is a post-bronchodilator FEV1/FVC ratio less than 70%. At diagnosis patients should have the severity of their airflow limitation classified according to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines. This classifies patients with a FEV1/ FVC ratio less than 70% into four categories (GOLD 1 – 4), based on their FEV1 value (FIGURE 1).
Symptom burden should be assessed using the mMRC (Modified British Medical Research Council questionnaire) or the CAT (COPD Assessment test). An assessment of exacerbation risk should also occur. A COPD exacerbation is an acute worsening of respiratory symptoms that results in additional therapy. 9 Exacerbations can be classified as mild, moderate or severe. The best predictor of having frequent exacerbations (defined as two or more exacerbations in one year) is a history of previous exacerbations. 10 Using these variable individuals may be classified as GOLD A – D 1
(FIGURE 1). This classification system divides individuals into phenotypes of those who are relatively asymptomatic (A), symptomatic on a daily basis (B), have regular exacerbations but are asymptomatic in between episodes (C) and those who are symptomatic on a daily basis and suffer relatively frequent acute exacerbation of their symptoms requiring oral steroids (D).
This phenotypic subdivision of individuals into those who are breathless or who exacerbate frequently allows more targeted therapy. Typically those who are breathless benefit from bronchodilator therapy and those who suffer frequent exacerbations benefit from anti-inflammatory treatment 1 (FIGURE 2).
In our practice we obtain a chest radiograph in all new suspected COPD patients. While it does not diagnose COPD, it can be useful at excluding alternative diagnoses and establishing the presence of comorbidities including pulmonary fibrosis, pleural disease, kyphoscoliosis and cardiomegaly. We obtain routine laboratory investigations, including FBC to check for eosinophilia. We screen for alpha one antitrypsin deficiency in concordance with WHO recommendations. 11 For those with recurring exacerbations we check an immunoglobulin level to screen for hypogammaglobinaemia.
1. Smoking Cessation
The cornerstone of treatment for COPD is smoking cessation and must be stressed with those who continue to smoke at every encounter. 1 Individuals should be offered both non-pharmacological and pharmacological (nicotine replacement therapy, bupropion, varenicline etc.) assistance to quit. 1 Unfortunately, COPD is invariably a progressive disease as damaged lung is unrecoverable and lung function will continue to decline with age regardless of smoking status. However if individuals continue to smoke lung function will decline much more rapidly and ultimately result in a much higher symptom burden at a much earlier stage. 12
Electronic cigarettes (e cigarettes/ vaping) have increased in popularity as an alternative to cigarettes. In addition to nicotine, they can contain other chemicals, the long-term health effects of which are largely unknown. 1 However, they have been associated with vaping-associated lung injury, alveolar haemorrhage and death. 1 E-cigarette use is increasing among Irish teenagers. 13 There is a perception that e-cigarettes may be healthier than cigarettes in this age group. There is a lack of information about e-cigarettes from school education programmes on smoking. 13
2. Bronchodilator therapy
Dyspnoea is multi-factorial in COPD. Contributing factors include:
- Airway obstruction
- Parenchymal destruction
- Dynamic hyper-inflation leading to air trapping, small airways collapse and negative effect on compliance resulting in increased work of breathing and subjective shortness of breath (SOB) 14
- Systemic effects of COPD including sarcopenia 15
Bronchodilators address the airways obstruction, altering airway smooth muscle tone, leading to widening of the airways and improving dynamic hyperinflation. Available inhalers include short acting and long acting beta agonists (SABA/LABA) and muscarinic antagonists (SAMA/ LAMA). These therapies have been shown to improve dyspnoea, improve exercise performance and reduce the frequency of exacerbations. In asthma, LABA monotherapy (without an inhaled corticosteroid) is associated with an increased mortality. This is not the case with COPD where monotherapy is safe 1 (FIGURE 2).
Combination bronchodilator therapy of a LABA and a LAMA in a single inhaler demonstrate improved patient reported outcomes, compared to monotherapies alone, with improved quality of life demonstrated. 1
Exacerbations in COPD are predominantly due to viral infections and airway inflammation. Therefore anti-inflammatory therapies form a cornerstone in COPD therapy for those who are frequent exacerbators.
Inhaled corticosteroids (ICS) in combination with LABA therapy are useful for dampening airway inflammation, thereby reducing exacerbation frequency. They also have a positive effect on lung function and dyspnoea. 1 There is an ever growing body of evidence that eosinophilia is a useful biomarker for predicting a positive response to ICS therapy. 16 While ICS therapy has been shown to reduce exacerbations and improve symptoms, they have been associated with a slight increase in pneumonia, especially in those with eosinophils <0.3u/L and more severe disease. We therefore consider ICS therapy in those with two or more exacerbations per year, eosinophils ≥0.3u/L or a history of asthma/atopy.
Azithromycin is a macrolide antibiotic. It has antimicrobial effects but also has an anti inflammatory effect in the airway and interferes with biofilm formation. It can be added on to therapy in former smokers who continue to exacerbate despite maximal inhaled therapy. It is recommended to be continued for one year but in practice individuals remain on it for much longer due to its’ exacerbation lowering effects. 1 Prior to initiating therapy, sputum samples should be checked, and non-tuberculous mycobacterial colonisation should be excluded as this is a contra-indication to therapy. As it can cause QT prolongation, an ECG should be performed prior to initiating therapy and one month post initiating therapy. Patients should be counselled to monitor for signs of ototoxicity, palpitations and diarrhoea. 18 Data is limited in those who are active smokers. 19
Roflumilast is a phosphodiesterase inhibitor and works by reducing intracellular cyclic adenosine monophosphate (cAMP). It reduces inflammation in the airway but has no immediate bronchodilator effect. It may be a reasonable add-on therapy in selected patients with a chronic bronchitic phenotype of COPD with severe airflow obstruction and a history of exacerbations. In some individuals, roflumilast may be intolerable as it can be associated with severe, nausea, headaches, diarrhoea and weight loss. 20 We avoid starting this treatment in those with a low body mass index. Roflumilast is not approved for reimbursement under the community drug schemes in Ireland.
4. Pulmonary Rehabilitation
Pulmonary rehabilitation has been shown to be of tremendous benefit in patients with COPD. It improves dyspnoea and quality of life. In those discharged from hospital, pulmonary rehabilitation reduces the re-admission rate by approximately 50%. It is recommended for GOLD B-D patients and for those discharged from hospital with an exacerbation of COPD (ideally within 4 weeks of discharge). Pulmonary rehabilitation consists of an 8-12 week course consisting of a supervised incremental physiotherapy program where patients build up their muscle strength. Patients also receive education regarding their condition, lifestyle advise, dietetic input (if required) and are taught breathing exercises and the benefit of pacing. 24
Interestingly while pulmonary rehabilitation improves dyspnoea it has no direct effect on lung function. COPD is a systemic disease resulting in inefficient sarcopenic muscles. Pulmonary rehab works by increasing aerobic fitness, reducing lactic acidosis production and thus breathlessness. 15
5. Long Term Oxygen Therapy (LTOT), Ambulatory Oxygen Therapy (AOT) and Non-invasive Ventilation (NIV)
LTOT is indicated in the following scenarios: 25
- PaO2 ≤7.3kPa (3 weeks apart)
- PaO2 ≥7.3kPa to ≤8kPa with pulmonary hypertension, pedal oedema or raised haematocrit
- Palliative reasons
Ambulatory oxygen is indicated in those who: 26
- Are on LTOT and are active outside the house (to help them get the required 15 hours per day)
- Significantly desaturate on exertion and can walk further with the use of AOT
Non-invasive ventilation (NIV) is indicated in those who:
- Demonstrate symptomatic hypercapnia (headache, confusion, lethargy)
- Are post hospitalisation if PaCO2 is persistently raised 28
- Require LTOT but develop hypercapnia from same
6. Other interventions
Vaccination against Influenza virus, Pneumococcus and SARS-Cov-2 (COVID-19) are recommended by GOLD. 1 Vaccination reduces serious illness, exacerbations and mortality in COPD patients.
COPD is associated with a number of comorbidities, including cardiovascular disease, metabolic syndrome, skeletal muscle dysfunction, osteoporosis, gastro-oesophageal reflux, sinus disease, anxiety, depression and lung cancer. 1 These comorbidities influence mortality and hospitalisations in a patient with COPD. Therefore, they should be sought for and treated appropriately. 1 In very severe COPD, palliative care input should be sought to aid with refractory dyspnoea. 1
COPD Support Ireland is Ireland’s national support and advocacy body for people affected by COPD. By providing patients with knowledge of their condition, how to take their inhalers, how to control the sensation of breathlessness, it enables patients to live well with COPD. There are local COPD support groups throughout Ireland, providing regular exercise classes. Every patient should have a self management plan for their COPD (FIGURE 3).
7. Surgery and bronchoscopic interventions
In those with predominantly upper lobe emphysematous disease or bullous disease there are surgical options to help with dyspnoea. This can be done surgically through bullectomy or lung volume reduction surgery. Here the dead space or area of wasted ventilation is removed. This allows the healthier, compressed lung to re-expand and contribute more to ventilation. 29 The same effect can achieved bronchoscopically by blocking off the ineffectual lung endoscopically, leading to its’ collapse allowing the more effective lung to re-expand. 1
Those with very severe COPD who are deemed fit should be referred for lung transplantation assessment. 1
COPD is a prevalent disease with a high disease burden. Management focuses predominantly on early diagnosis, improving symptoms of shortness of breath and reducing exacerbations for which we have a growing armament of treatment options.
References available on request
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