The Unmet Need in Chronic Obstructive Pulmonary Disease

and Call to Change

Background and introduction

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease that is characterised by persistent respiratory symptoms (including chronic cough, shortness of breath and sputum production), airflow limitation[i].  COPD affects an estimated 384 million people worldwide[ii] and is the third leading cause of death globally,[iii] but it is significantly under-reported and undertreated.[iv],[v]

The global burden of COPD is growing.

·       COPD is the third leading cause of death, after ischaemic heart disease and stroke and before cancers[vi]

·       COPD is the most prevalent chronic respiratory disease and most common cause of chronic respiratory disease attributable deaths7. In 2017, 3.2 million people died from COPD worldwide - an increase of 23 per cent compared to 1990[vii],[viii]

And the personal and economic burdens are significant:

·       COPD-related costs are estimated to be >$100 billion per year globally, which is mainly attributable to the cost of exacerbations, also known as ‘flare ups’1,[ix],[x]. This mirrors other leading causes of mortality worldwide such as heart failure (estimated to cost $108 billion per year globally)[xi]. Despite this, COPD does not receive the same global recognition and prioritisation

·       COPD is associated with significant reductions in quality of life in all stages of disease severity[1], which worsens during an exacerbation[xii]

A group of leading clinical experts and patient advocates have identified three policy priorities that have the greatest potential to impact on COPD patients and global healthcare systems. These are:

1.    Earlier and accurate diagnosis

2.    Access to therapies (pharmacological & non-pharmacological)

3.    Awareness of exacerbations as an opportunity for optimised management

This consensus paper summarises policy priorities and provides the evidence base detailing the current standards of care that supports our call to change.

Policy recommendations

Earlier and accurate diagnosis

·       Universal criteria for the diagnosis of COPD and identifying those at risk must be adopted globally to reduce variation in diagnosis rates. This includes in both national and regional healthcare system policies.

·       Public health bodies should increase awareness of the common COPD risk factors and symptoms in the general public, so patients are informed and empowered to seek diagnosis.

·       Governments must provide the resources necessary to educate healthcare professionals about effective COPD diagnosis and management.

·       Access to appropriate spirometry and other diagnostic equipment must be prioritised alongside healthcare professional upskilling to properly perform and interpret diagnostic results.

Access to therapies (pharmacological & non-pharmacological)

·      The use of pharmacological therapies in line with the latest global treatment guidelines published by GOLD, including maintenance therapy, must be prioritised by healthcare systems to improve clinical outcomes, health related quality of life and slow disease progression.

·      Variation in access to pulmonary rehabilitation and specialist respiratory reviews must be addressed in local and national health service provision plans and should be prioritised as part of wider strategies to address health inequalities.

·      Public health bodies must renew efforts to raise awareness of the benefits of smoking cessation and physical activity, as well as minimising exposure to indoor and outdoor pollutants, to both prevent and better manage COPD alongside other health benefit associated with co-morbidities like cardio-vascular conditions.

·      Guidance on global quality standards of care for COPD management, to support improved access to and delivery of quality care, must be developed to guide health systems reform. This should be grounded in published evidence and clinical guidelines available.

·      COPD patients should receive a personalised care approach, with a tailored action plan including pharmacological and non-pharmacological therapies based on their specific circumstances and preference.

Awareness of acute exacerbations as an opportunity for accelerated management

·      Exacerbation and mortality targets associated with COPD must be set in national and regional healthcare system policies and should be audited for performance.

·      Healthcare systems and providers should provide prompt personalised pharmacological and non-pharmacological treatment reviews post-exacerbation in order to prevent further exacerbations and irreversible lung deterioration. This should include the use of maintenance therapy to prevent or reduce further symptoms following an exacerbation.

·      COPD patients must be given easy access to the tools and resources to better understand and recognise exacerbations in order to feel empowered to take immediate action and report their experience to their healthcare team.

Current standards of care

Earlier and accurate diagnosis

There is a lack of awareness of both COPD risk factors and symptoms among the public and patients. The resulting late diagnosis can significantly impact health outcomes and increase healthcare costs.  

·       Globally, there is large variation in rates of diagnosis, with 10-95% of COPD patients under-diagnosed and 5-60% over-diagnosed.  A major reason for this variation is the different criteria used to diagnose COPD globally[xiii],[xiv]

·         Opportunities to diagnose are missed in:

o   85% of patients in the 5 years preceding diagnosis

o   58% of patients in the 6-10 years preceding diagnosis

o   42% in the 11-15 years preceding diagnosis

o   8% in the 16-20 years preceding diagnosis[xv]

·       COPD often remains undiagnosed until the disease has increased in severity15,[xvi] , which is associated with poor clinical outcomes[xvii] as lung damage is not reversible15

The reasons for late or inaccurate diagnosis:

·       Because of a lack of knowledge of COPD and its symptoms, individuals often attribute early COPD symptoms to ‘just getting older’14,[xviii] .  Additionally, due to the stigma associated with COPD and smoking, patients may ignore symptoms, dismiss them as self-inflicted[xix] or delay presentation to a clinician for fear of judgement because of previous or continued smoking[xx]

·       Patients who over- or under-perceive their symptoms, and those who have comorbidities, may experience over diagnosis leading to excessive treatment, or a misdiagnosis14

·       Accurate diagnosis of COPD can only be made using quality assured post-bronchodilator spirometry, however, access to spirometry results and skills to perform and interpret the tests vary greatly across health care settings[xxi].  Primary care physicians may decide not to incur the cost of spirometry equipment, or may be unfamiliar with the complex technology[xxii]

·       Current diagnostic procedures may lead to misdiagnosis, such as errors made in the performance and interpretation of spirometry tests 13. Errors made in primary care, due to insufficient resources or a lack of knowledge of COPD and the differentiation between other diseases, have also been noted as reasons for misdiagnosis[xxiii]

The impact of late diagnosis:

·       COPD is frequently diagnosed late when the disease has already progressed17. This is associated with higher exacerbation rates, increased comorbidities and costs17

·       Rate of FEV1[2] decline, or airflow limitation, is greater in patients with a less severe disease than those with a more severe disease22  . If the disease were diagnosed and treatment begun sooner, lung function decline would be better controlled

·       Health care utilisation and cost to health services and wider economy. Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use[xxiv]. More severe COPD was significantly associated with higher healthcare utilization through hospitalisation, as well as higher work absence, and premature retirement[xxv]

 

Access to therapies (pharmacological / non-pharmacological)

Non-pharmacological and pharmacological therapies are clinically proven to reduce mortality, symptoms and the frequency of acute exacerbations. However, there are barriers in health systems which impact timely and appropriate access to therapies. Delayed access to therapies has a negative impact on disease progression and healthcare costs.

·       COPD is a heterogenous disease1 and is associated with a number of co-morbidities which further contribute to disease severity, reduced quality of life, and poor clinical outcomes[xxvi],[xxvii]  These factors highlight the need for a combination of pharmacological and non-pharmacological therapies to manage this condition1

·       Results from recent trials have demonstrated that reducing the risk of all-cause mortality from pharmacological therapy is an achievable treatment goal in COPD[xxviii]

Healthcare system barriers to delivering earlier and better management:

·       Non-adherence to guidelines in primary, community and acute care, leading to missed diagnostic opportunities and inappropriate management[xxix],[xxx] such as variation in the use of maintenance treatment[xxxi],[xxxii]

·       As there are no adequate follow up guidelines on discharge21, patients discharged from the emergency department (ED) were less likely to have short-term treatment for their acute exacerbation compared to those being discharged from in-patient care hospital (44% versus 68%)32.  This lack of standardisation means that clinical outcomes can vary significantly

·       There is limited availability, capacity and variation in the quality of service[xxxiii] of pulmonary rehabilitation (PR)[3].  Access to PR is often dependent on location and therefore patients living in rural areas must travel further[xxxiv], further exacerbating health inequalities facing rural communities.[xxxv]

·       Staffing levels and the availability of specialist respiratory review are linked to mortality and quality of service21, [xxxvi] – patients who received specialist review when admitted to hospital for a COPD exacerbation were 14% less likely to die as an inpatient than those who did not receive specialist review21

The need for timely access to pharmacological therapies: 

·       Pharmacological intervention in early COPD is likely to improve clinical outcomes[xxxvii]. Early initiation of treatment has been shown to slow disease progression and improve Health-Related Quality of Life (HRQoL)[xxxviii]

·       Inability to access maintenance therapy (MT) dramatically increases the risk of future exacerbations[xxxix]. Prompt initiation of maintenance therapy after a COPD-related hospitalisation or visit to the ED is associated with a reduction in the likelihood of another exacerbation the following year40. If MT is delayed, there is a 68% increased likelihood of an exacerbation resulting in hospitalisation, an ED visit or physician visit plus prescription within 5 days, and increased COPD-related costs (US$3,931 compared to US$4,857 for prompt initiation of MT)[xl]

·       There is limited data on the effects of earlier pharmacological intervention for COPD. Further studies are needed to assess the impact on not only lung function, but also breathlessness, symptoms and quality of life38

·       National flu and pneumococcal vaccines. Vaccinating against commons viruses is important for COPD patients as the flu puts extra strain on the lungs and there is evidence that respiratory failure happens more often during or immediately after an acute inflammatory illness, such as flu[xli]

Alongside therapies, patient self-management is important:

·       Self-management is linked to improved HRQoL, a lower probability of respiratory-related hospitalisation, and a reduction in breathlessness[xlii],[xliii]

·       Patient adherence to their written action plan, which is a set of instructions to follow when symptoms deteriorate, is associated with a reduction in exacerbation recovery time[xliv]

·       Additionally, caregivers of individuals with COPD have a key role in maintaining patient adherence and optimizing patient function[xlv]

Non-pharmacological therapies include:

·       Smoking cessation.  This therapy has been shown to reduce lung function decline at all stages of COPD, reduce morbidity and mortality38,[xlvi],[xlvii].  Compared to current smokers, former smokers are at a significantly decreased risk of exacerbations[xlviii]

·       Physical activity. More frequent and longer low-intensity physical activity reduces the risk of COPD hospitalisations and mortality[xlix],[l]

·       Pulmonary rehabilitation.  PR should be considered a foundational intervention in the management of COPD given that is an important indicator of clinical outcomes and is associated with health benefits, including a reduced rate of exacerbations33and mortality[li]

 

Awareness of acute exacerbations as an opportunity for accelerated management

Exacerbations are linked to mortality, lung function decline and psychological deterioration. As well as the personal burden, most COPD-related costs are associated with hospitalisations and therefore the impact on healthcare system utilisation is substantial. Some patients do not receive appropriate therapies after an exacerbation, meaning their disease management is not optimised and this places them at greater risk of recurring events. 

The burden of exacerbations:

·       Acute exacerbations are a worsening or “flare up” of COPD symptoms, which may be triggered by a bacterial or viral infection in the lungs, exposure to environmental pollutants, or an unknown trigger[lii]

·       Between 49%-~74% of patients will have at least 1 exacerbation within 3 years of diagnosis[liii],[liv],[lv]

·       Acute exacerbations can occur at all stages of disease severity, however, they are more frequent in patients with a more advanced disease1.  However, irreversible lung function decline following an exacerbation is greatest in patients with mild COPD[lvi]

·       Hospitalisations resulting from severe exacerbations account for approximately 60-70% of all healthcare costs associated with COPD[lvii]

·         Exacerbations appear to have a significant impact on patient well-being, including psychological well-being[lviii],[lix]

·         One exacerbation increases frequency of exacerbations and decreases the time between these events or death[lx]

·         The best predictor of future exacerbations is a history of exacerbations and therefore this history identifies a high-risk group[lxi]

 

Examples of poor exacerbation management:

·       The current global treatment paradigm is one of failure-driven escalation, whereby escalation in treatment is only considered following a worsening of symptoms, such as severe breathlessness (dyspnea) or exacerbations1

·       On average globally, over 1 in 3 patients receive no maintenance therapy, treatments offered to prevent or reduce symptoms, after an exacerbation:

o   US – between 36% and 75% are not on appropriate therapy post-exacerbation32,[lxii]

o   Canada – ~50% are not on appropriate therapy post-exacerbation[lxiii]

o   China – 53% are not on appropriate therapy post-exacerbation[lxiv]

·         Approximately 40% of COPD patients take no immediate action when having an exacerbation[lxv]

·       Exacerbations are often not reported by patients[lxvi],[lxvii] . There may be many reasons for this. Some patients make the decision to self-manage, meaning that they are not subsequently treated with the appropriate medication[lxviii]

Exacerbations and poor exacerbation management can result in:

·       An increased risk of mortality as even a single exacerbation can significantly reduce life expectancy and increases the risk of death[lxix],[lxx]

·       Long-term decline and disease progression39,56,[lxxi]. Symptoms may not return to pre-exacerbation baseline if not reported to a clinician66

·       Lung function decline: patients with milder disease levels have a greater rate of decline after each event56and some patients will not recover from the effects of an exacerbation71. Given that GOLD recommends escalation of treatment after >2 severe exacerbations, it is reasonable to suggest that the patient has already experienced significant and perhaps irreversible decline   

·       An increased risk of cardiovascular complications, such as myocardial infarctions (MI) and strokes.  The risk of MI doubles within 5 days of the start of an exacerbation, and then returns to baseline over time, and the risk of stoke increases by 40% within 10 days[lxxii]

·       A societal burden, with a significant increase in healthcare resource utilisation for COPD patients who have experienced an exacerbation compared with those who have not10,57

·       A worsening of quality of life in the short- and long-term[lxxiii], related to a number of factors including anxiety, dystopia, depression and decreased exercise capacity59

COVID-19 and COPD

COVID-19 has intensified this unmet need even further, with the disease causing a significant impact on risk of poor outcomes[lxxiv]. COPD patients infected with COVID-19 may have up to 60% increased mortality risk versus non-COPD patients[lxxv].

COVID-19 has not only impacted those COPD patients who have contracted the illness, but all patients, who are not receiving the same type or regularity of care they previously did, despite efforts with virtual consultations and telehealth. Pulmonary rehabilitation, which improves health outcomes, including hospitalisations33, was in some cases not carried out during the pandemic. Patients who may have normally presented to the hospital during an exacerbation might choose to stay home for fear of exposure, resulting in delayed care and potentially death[lxxvi].

Inability to carry out spirometry at pre-pandemic levels, due to it being an aerosol emitting equipment, will most likely have created a backlog of undiagnosed patients[lxxvii]. The long-term impacts of this pause or significant reduction in diagnostic services and routine care are yet to be fully understood.


[1] The Global Initiative for Chronic Obstructive Lung Disease (GOLD) develops annual evidence-based strategy documents for COPD management. Classification of severity is based on airflow limitation and falls into four  categories based on FEV1 (forced expiratory volume) (% predicted): GOLD 1 (>80 FEV1 - mild), GOLD 2 (50 – 79 FEV1 - moderate), GOLD 3 (30-49 FEV1 - severe) and GOLD 4 (<30 FEV1 – very severe). Classification of severity is separated from assessment of symptoms/ risk of exacerbations and does not inform therapeutic decisions

[2] FEV1 (forced expiratory volume) is the amount of air that can be forced from the lungs in 1 second, measured through a spirometry test. FEV1 score is used to classify COPD severity.   

[3] A PR course, which usually lasts between six to eight weeks, consists of a physical exercise programme, and information and advice on managing COPD



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