The Global Initiative for Chronic Obstructive Lung Disease (GOLD 2021; p4) defines chronic obstructive pulmonary disease (COPD) as ‘a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases’.
COPD is an umbrella term for several different pathological processes in the lungs of susceptible individuals. These cause various persistent symptoms that usually lead to increasing disability and premature mortality for those affected. Because of the heterogeneity of COPD and its association with several important comorbidities, misdiagnosis and underdiagnosis may commonly occur (Jørgensen and Brunak, 2021). The prevalence of COPD varies internationally depending on the methods used to define it, for example self-report by study participants or rigorous investigation using standardised tests. In the UK, it is known to affect around 4.5% of the population over the age of 40, and 2% of the overall population with a prevalence slightly higher in males than females (British Lung Foundation, 2021). It is thought, however, that the true prevalence may be double the actual number diagnosed.
Signs, symptoms and risk factors in COPD
Long-term exposure to risk factors such as tobacco smoking – the most common cause of COPD – and symptoms caused by progressive lung damage are often present before individuals seek a diagnosis. The most common symptoms on presentation are:
- Breathlessness on exertion
- Chronic productive cough and
- Winter chest infections.
However, these are often dismissed by sufferers as normal, leading to delays in seeking help, or are not investigated promptly by healthcare providers. Internationally, studies have found that factors influencing diagnostic delay include low awareness of COPD in potential sufferers (Dai et al, 2021) and healthcare providers' confusion over the threshold for defining COPD; poor performance and interpretation of spirometry tests; and failure to seriously consider differential diagnoses (Hangaard et al, 2017). Moreover, the lung function changes of COPD are insidious and often give rise to such a gradual impact that individuals simply adapt to increasing breathlessness by modifying activities, normalising their symptoms as due to aging or the expected effects of smoking.
As COPD is a preventable condition, a careful history is essential to identify the probable causative risk factors when it is suspected. Tobacco smoking is the major risk factor worldwide, but even in smokers, only around 20–25% will go on to develop COPD (Lokke et al, 2006; Terzikhan et al, 2016). Thus, it is believed that individual host defence factors are also important in the disease process, of which the best known is the genetic deficiency of alpha 1 antitrypsin, a protein that protects the lungs. This rare disorder affects those of European ancestry at a rate of around 1 in 3000 people. In addition, Shaykhiev and Crystal (2013) suggest that host defence mechanisms that should protect the lung from respiratory pathogens are broadly suppressed in individuals who develop COPD, suggesting fundamental defects in their innate immune system. Duration of exposure, age when smoking commenced, and the total number of cigarettes smoked to date (so-called ‘pack years’) are all likely to influence the risk and severity of COPD.
Nearly 20% of COPD is caused by occupational exposure, rising to 31% in never smokers. Self-reported exposure to workplace dust and fumes is associated with increased risk of symptoms and lung function abnormalities. Some studies have identified women as at increased risk (Barnes, 2016), and organic (biological) dust to be more hazardous than inorganic (mineral) dust (Lytras et al, 2018). Bioaerosol exposure occurs in occupations such as compost recycling, agriculture – especially use of pesticides – poultry farming, grain and animal feed production, flour exposure in bakers, cotton and textile workers and wood and paper industries (Basu et al, 2018).
How to diagnose COPD
COPD should be considered in any patient who has symptoms and a history of exposure to risk factors for the disease (GOLD, 2021). In view of the link between COPD risk factors and other important differential diagnoses, the National Institute for Health and Care Excellence (NICE, 2019) recommends a chest X-ray and full blood count should be carried out as part of the diagnosis.
A careful history is essential as a precursor to other appropriate investigations, which are needed to establish the presence of persistent airflow obstruction. The typical symptom pattern in COPD is of gradual persistent breathlessness on exertion, with or without productive cough, especially in winter months. Frequency of chest infections should be established and recorded, along with details of treatments taken and their effectiveness. Marked variability of symptoms – especially at night – and known triggers to symptoms other than exertion, should raise suspicion of asthma as a possibility.
Other past medical history is important as this can provide hints about possible differential diagnoses. Family history of COPD should be enquired about, because susceptibility to COPD has a genetic component (Hardin and Silverman, 2014). Work history (past and current) is important to assess for duration and nature of any occupational exposure. Drug history (prescribed, over the counter and recreational) is also useful. Patients may have been prescribed respiratory medications or drugs that are known to affect the lungs in other ways such as non-steroidal anti-inflammatory drugs (NSAIDS), beta-blockers or immuno-suppressant drugs. Inhaling recreational drugs such as marijuana increases the risk of COPD when combined with tobacco (Tan et al, 2009). Likewise, both crack cocaine and heroin smoking have been found to disproportionately worsen lung function (Tashkin et al, 1992; Nightingale et al, 2020).
Confirming suspected COPD
The cornerstone of confirming chronic airflow obstruction is quality-assured spirometry. If there are any features of asthma from the history, reversibility testing should be carried out to assess for a significant response to bronchodilators (or steroids) that would suggest asthma rather than COPD. It is important that those carrying out spirometry testing and interpreting the tests have been assessed as competent on a continuing basis. The main recommended way to achieve this is for practitioners to be on the UK national register of competency (NHS England, 2016). This demonstrates adherence to recommended standards for spirometry (Primary Care Commissioning, 2013).
COPD is characterised by persistent obstruction of airflow that does not show significant reversibility or variability. In practice, this means that those affected by COPD are unable to empty the air out of their lungs quickly due to airway narrowing. A normal healthy person will be able to empty 70–80% of the lung vital capacity within the first second of a forced blow. Thus, the most important measurements made in spirometry testing are the vital capacity (VC) and the forced vital capacity (FVC), the forced expired volume in the first second (FEV1), and the ratio between the two (FEV1/VC or FEV1/FVC). A ratio below 0.7 (70%) is considered in most guidelines to denote airflow obstruction (NICE, 2019; GOLD, 2021). However, a major contributor to misdiagnosis is failure to recognise the importance of age and how the ratio is affected by this, since airways naturally narrow and lung volumes reduce as part of the normal aging process. This has led many experts to recommend considering the lower limit of normal (LLN) for each individual when interpreting spirometry (Schermer and Quanjer, 2007; Stanojevic et al, 2013). GOLD (2021), who favour a fixed ratio, have recommended repeating spirometry to confirm COPD diagnosis where the ratio is considered ‘borderline’, ie between 0.6-0.8 (60-80%), since in some cases the ratio may improve spontaneously. In suspected COPD if the ratio is below 0.6 (60%) then it is highly likely to remain low and suggests permanent obstruction.
While the ratio is the most important element of confirming obstruction, the FEV1 as a percentage of predicted is used to grade obstruction severity, by comparing the actual FEV1 against a healthy subject with the same demographics. Obstruction is therefore categorised as mild, moderate, severe, or very severe. The degree of obstruction has a poor correlation with severity of symptoms, but overall can suggest increasing need for support due to disease progression in most people with COPD.
Differentiating between COPD and asthma
COPD and asthma are two different and separate obstructive conditions that may, however, co-exist in the same individual. This causes confusion in both patients and clinicians leading to increased risks of misdiagnosis (Tinkelman et al, 2006). Spirometry reversibility testing is recommended in asthma guidelines as a way of identifying the much greater response to bronchodilation or corticosteroid treatment that is one way of differentiating asthma from COPD. In view of the frequent overlap between asthma and COPD, it is worth exploring this at the point of diagnosis to ensure that any treatments started are more likely to be beneficial, and to revisit this at any point in case patients have been mislabelled initially.
BTS/SIGN (2019) suggest that an improvement in FEV1 of 200 ml and 12% after bronchodilation can support a diagnosis of asthma where the history suggests asthma rather than any other likely condition. The NICE (2019) COPD guideline states that if FEV1 improves by more than 400 ml on reversibility testing or with treatment then asthma may be present instead of – or as well as – COPD.
Again, the crucial element here is the history. Central to all definitions of asthma is the presence of symptoms (more than one of wheeze, breathlessness, chest tightness, cough) caused by variable airflow obstruction. Variability of airflow obstruction is not likely to be identified easily by a single spirometry test but may be suggested by the history or records of past testing, including historically variable peak flow measurements. On the other hand, in COPD peak flow shows little variation. A further objective test useful in differentiating asthma from COPD is for the presence of eosinophilic airway inflammation using fractional exhaled nitric oxide (FeNO) measurement (Miskoff et al, 2019), or records of serum eosinophils.
The Global Initiative for Asthma (GINA, 2021) suggest that if an individual presents with a history of symptoms that vary over time and in intensity with multiple triggers, that improve spontaneously or with treatment, especially if the age of onset is below the age of 40, and has been labelled as asthma, particularly in childhood, with objective evidence of varying lung function, then this should be labelled as asthma and treated according to asthma guidelines.
If a person with some or all of these features also has a significant smoking history or occupational exposure to COPD risk factors, and in spite of adherence to asthma treatment continues to have persistent airflow obstruction with continuing symptoms of this such as breathlessness, cough or acute worsening episodes, then this is likely to be a combination of asthma and COPD, and treatment should be optimised for both conditions: in other words, inhaled corticosteroid (ICS)-containing treatment is essential. Those with both asthma and COPD often have worse outcomes than those with either condition alone (GINA, 2021).
Questioning existing diagnoses and specialist referral
Other conditions may frequently be confused with COPD. Because of common risk factors, such as smoking and inactivity, combined with increased systemic inflammation, COPD is associated with twice the risk of lung cancer (Durham and Adcock, 2015). An essential aspect of a safe COPD diagnosis is a recent chest X-ray. A chest X-ray might suggest, but cannot diagnose, COPD; however, instead it is recommended to possibly identify alternative causes for symptoms of breathlessness and cough such as lung cancer. Therefore, the history should also enquire about the presence of so called ‘red flag’ symptoms such as chest discomfort, weight loss, fatigue, or haemoptysis. A full blood count is equally recommended to exclude anaemia but also important to assess for any raised serum eosinophils.
Audits of diagnostic accuracy in primary care have suggested that most patients on COPD registers may not meet the diagnostic criteria (Healthcare Quality Improvement Programme, 2021). Interstitial lung diseases are often initially treated as COPD (Mujeeb et al, 2016) due to symptoms of cough and breathlessness combined with misinterpretation of spirometry. This group of diseases may share similar risk factors, particularly occupation, but affect the lung tissue rather than the airways, leading to normal airflow but reduced lung volumes, termed ‘restrictive’ spirometry. The over-focus on recording FEV1 at diagnosis as part of the QOF in primary care has led to those with restrictive spirometry being incorrectly labelled as COPD because of reduced FEV1, with the normal ratio being ignored. Prompt diagnosis of ILD is critical to correct treatment that might slow progression, so where spirometry records or a current test suggest someone with COPD has a restrictive (reduced FEV1 and FVC but ratio normal or high) rather than obstructive pattern (ratio low, FEV1 usually reduced, FVC and or VC normal), further investigation and specialist referral is vital.
Symptoms such as chronic productive cough with frequent chest infections can also occur in those with normal lung function. This symptom pattern is linked to both chronic bronchitis and bronchiectasis, with both these conditions potentially leading to obstructive lung function over time. Clinical bronchiectasis is defined as ‘persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi’ and is thought to occur in up to 30% of COPD patients. Around 36% of people with bronchiectasis also have COPD, and patients with both conditions are at higher risk of death (British Thoracic Society, 2019). Bronchiectasis cannot be diagnosed by chest X-ray but requires specialist referral and high-resolution computed tomography (HRCT) scan. So, in addition to being a differential diagnosis of COPD, it can develop in COPD patients and may complicate their symptoms and worsen lung function. A history that includes frequent respiratory infections in childhood, especially pneumonia, failure to respond to short courses of antibiotics for chest infections, or sputum samples showing persistent bacterial infection such as Pseudomonas can lead to suspicion of bronchiectasis.
Cardiovascular disease can also present with breathlessness, limiting activity. Symptoms of breathlessness, cough or wheeze that occur at night are unusual in COPD and with increasing age are more suggestive of a cardiac cause (although adult-onset asthma should be excluded). Further investigation should include electrocardiogram (ECG) and brain natriuretic peptide (BNP). Any history of known cardiac disease may also suggest this is complicating symptoms in people who already have a confident diagnosis of COPD. Such comorbidities become more frequent as lung function declines but may also be present at the point of diagnosis.
Conclusion
In summary, this article has explored the important elements of a safe diagnosis of COPD, along with areas for potential confusion such as asthma and other conditions that share similar risk factors and symptoms. The cornerstone of COPD diagnosis is to identify risk factors for this preventable condition, recognise and investigate any symptoms that are not commonly found in COPD, and confirm that obstruction is present with correctly performed and interpreted spirometry. In those already diagnosed, it is imperative to question or revisit the diagnosis if these foundation elements are not present.
Further reading and useful resources:
- Primary Care Commissioning. A guide to performing quality assured diagnostic spirometry. 2013. https://www.brit-thoracic.org.uk/media/70454/spirometry_e-guide_2013.pdf
- Miravitlles M. Diagnosis of asthma-COPD overlap: the five commandments. Eur Respir J. 2017;49(5):1700506. 10.1183/13993003.00506-2017
KEY POINTS:
- Chronic obstructive pulmonary disease (COPD) diagnosis is complicated by its heterogeneity
- Symptom and risk factors alone cannot confirm a COPD diagnosis but should lead to recommended investigations such as quality assured spirometry
- Misdiagnosis is common, particularly between asthma and COPD, but other conditions also share similar risk factors and symptoms
- Patients may be mislabelled as having COPD and in such cases the diagnostic process should be revisited
CPD reflective practice:
- When reviewing patients with a chronic obstructive pulmonary disease (COPD) diagnosis, what aspects of their history would make you reconsider this label, for example insignificant smoking history, no obvious COPD symptoms in an ex-smoker, or a new diagnosis of COPD in very elderly patients (whose spirometry may be normal for their age)?
- How confident do you feel about assessing the validity and interpretation of spirometry, and are reports available to view in full in your patients' records?
- How often do you consider COPD as an additional diagnosis in patients with other long-term conditions, for example in your asthma reviews or in patients with heart disease?