Minimising exacerbations in early COPD

Much of the attention on the management of COPD is focused on severe disease, and the latter stages of the condition, but new research suggests that many people will be losing lung function – permanently – even before they are diagnosed

Many people with a diagnosis of chronic obstructive pulmonary disease (COPD) will not be diagnosed until they have experienced several episodes of winter ‘bronchitis’ or have developed a chronic cough.

But it has emerged that very early on in the disease, at a time when the majority of people would not even have been diagnosed, patients can be losing lung function, and that the greatest loss occurs in people with mild COPD, following severe exacerbations.¹

This was a key finding from an interim report on the COPDGene study, a long-term observational study, which looked at exacerbations and lung function loss in smokers and former smokers with and without COPD, and the effect of acute respiratory events on lung function in people with and without airway obstruction.¹

Exacerbations, defined as needing treatment with either antibiotics or oral steroids, were common, reported by almost one in four participants in the study, including those without COPD.

Those with mild COPD (GOLD 1) experienced the greatest decline in FEV1, and each exacerbation in this group was associated with an additional 23 ml/year decline. Each severe exacerbation – defined as requiring hospitalisation – in this group resulted in a further 87 ml/year decline.

People with moderate or severe COPD (GOLD 2 or 3, respectively) had smaller declines in FEV1 with each exacerbation than those with mild COPD.

These results have prompted the researchers to call for a more careful approach to prevention of exacerbations. Lead author, Mark Dransfield, said: ‘The whole medical community is focused on the latter stages of COPD, when like diabetes, heart disease and other chronic diseases, we should probably be focused on preventing morbidity much earlier. Preventing exacerbations in people with [mild disease] could reduce the risk of developing severe COPD.’

This research has some important messages for clinicians in the ‘real world’. If we can do more to prevent exacerbations – and indeed to diagnose COPD earlier – we could make a real difference to the long-term trajectory of the disease.

DIAGNOSIS

NICE² recommends that a diagnosis of COPD should be considered in patients over the age of 35 who have a risk factor (generally smoking) and who present with one or more of the following symptoms:

• Exertional breathlessness
• Chronic cough
• Regular sputum production
• Frequent winter ‘bronchitis’
• Wheeze.

But there is clear evidence that many people with COPD are not being diagnosed when they present in general practice with typical symptoms, such as chronic cough, breathlessness and chest infections.³

Jones and colleagues found that:

• 85% of patients had visited their doctor or a clinic at least once with respiratory symptoms in the 5 years before diagnosis
• 58% first reported symptoms 6-10 years before diagnosis, and
• 42% had had symptoms for 11-15 years before diagnosis.

This study highlights that many people diagnosed with COPD could have benefited from earlier diagnosis and treatment, with consequent improvements in long-term morbidity and mortality.

When we are seeing people with these symptoms, we need to have an increased index of suspicion and remember to ask pertinent questions about smoking history and occupation.

SMOKING CESSATION

It hardly seems necessary to reiterate the importance of smoking cessation for all our patients, but especially those with symptoms suggestive of early COPD.

However, patients with COPD do continue to smoke. In a study based on data from the Health Survey for England, a total of 34.9% of people with spirometry-defined COPD were smokers compared with 22.4% of those without, and smoking prevalence increased with disease severity. This analysis found that smokers with spirometry-defined COPD were more cigarette-dependent but had no greater desire to quit than other smokers.⁴

INFECTION

Exacerbations can be precipitated by a number of factors but among the most common is exposure to infection, notably influenza and pneumococcal disease. Flu vaccination in patients with COPD significantly reduces the number of exacerbations, especially 3 – 4 weeks after vaccination, as well as reducing the incidence of flu-like illnesses.⁵ However, uptake rates of the vaccination in people with chronic respiratory disease has fallen from just over 49% in 2014-15 to around 47% last winter. The target for this season’s campaign is 55% in this group.⁶

Pneumococcus is the most common cause of community-acquired pneumomia, and people with chronic respiratory disease are at increased risk. Pneumococcal vaccine is recommended for all adults over the age of 65, and we need to take every opportunity to ensure that patients with COPD are immunised, by administering the vaccine at the same time as the flu jab, at annual COPD review, but especially on discharge after hospital admission.⁷

ENVIROMENTAL FACTORS

As we know, the most important cause of COPD is smoking, but past exposure to fumes, chemicals and dust at work will also have contributed to many patients’ COPD.⁸ About 15% of COPD can be attributed to workplace exposures, resulting in an estimated 4,000 COPD deaths each year in the UK. However, reports on and assessment of workplace injuries greatly understate the new cases of work-related COPD.

Substances likely to contribute to COPD include:

• Dusts – from coal, grain and silica
• Fumes and chemicals, such as welding fumes or isocyanates (used in the manufacture of foams, paints and varnishes, and building insulation materials) Certain tasks such as paint spraying can produce very high levels of exposure to isocyanates.⁹

GOLD¹⁰ recommends that clinicians emphasise primary prevention, which is ‘best achieved by elimination or reduction of exposures’ to such substances in the workplace, and through surveillance and early detection. This means that in people with symptoms of COPD, especially in those with no history of smoking, it is important to ask about occupational factors that may be contributing to the development of disease.

PHARMACOTHERAPY

According to GOLD, one of the key aims of treating COPD is to reduce the risk of exacerbations (in addition to improving symptoms).¹⁰ The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points (ECLIPSE) study showed that the patients most at risk of having exacerbations in the future are those who are already having exacerbations.¹¹ This effect was seen across all patients, regardless of their disease severity. Those individuals having two or more exacerbations (or one exacerbation that was serious enough to require admission to hospital) are most likely to benefit from being treated with inhaled corticosteroids (ICS) combined with a long acting beta2 agonist (LABA).¹² Those who have no history of exacerbations had significantly less risk of exacerbating in the future and would have least to gain from an ICS/LABA.

Most guidelines recommend either a LABA (plus ICS) or a long-acting muscarinic antagonist as the first-line treatment for patients with COPD, but the recently-published FLAME study showed that patients who were given both LABA and LAMA (dual bronchodilator therapy) had an 11% lower rate of exacerbations than those treated with LABA + ICS. There was also a longer time to first exacerbation, and a lower annual rate of moderate or severe exacerbations in the dual bronchodilator group.¹³

For a detailed review of dual bronchodilation in COPD, see Dual bronchodilators in chronic obstructive pulmonary disease, by Beverley Bostock-Cox. Practice Nurse May 2016;46(05):14-18

PULMONARY REHABILITATION (PR)

The evidence for the effectiveness of PR as a treatment for patients with COPD is unequivocal.²

It can lead to:

• Statistically significant and clinically meaningful improvements in health-related quality of life
• Improved functional exercise capacity
• Increased maximum walking distance
• Reduced breathlessness.

Pulmonary rehabilitation is also cost effective in COPD. It leads to a reduction in hospital admissions and readmissions, with a number needed to treat (NNT) of only 4 to prevent an admission.¹⁴ The London Respiratory Team15 (LRT) has calculated the cost per Quality Adjusted Life Year (QALY) for common interventions in the treatment of COPD, which places PR as one of the most cost-effective interventions, second only to flu immunisation and smoking cessation support plus pharmacotherapy. The LRT therefore recommends referral for PR ahead of initiating ‘triple therapy’ (short acting beta agonist, long acting muscarinic antagonist and combination inhaled corticosteroid and long acting beta agonist).

CONCLUSION

The evidence is mounting not only for the greatest predictor of exacerbations in COPD being a previous exacerbation, but also for the long-term damage that exacerbations cause, even in people with mild disease.

This gives weight to recommendations to consider the prevention of exacerbations as well as the relief of symptoms in patients with COPD. And the latest studies discussed here suggest that we should be doing more to identify patients with COPD earlier in the progression of their disease – much earlier.

REFERENCES

1. Dransfield MT, Kunisaki KM, Strand MJ, et al. Acute exacerbations and long function loss in smokers with and without COPD. Am J Resp Crit Care Med 2016; DOI: 10.1164/rccm.201605-1014OC

2. NICE. Chronic obstructive pulmonary disease in over-16s: diagnosis and management. CG101, 2010. https://www.nice.org.uk/guidance/cg101

3. Jones RCM. Price D, Ryan D, et al. Opportunities to diagnose chronic obstructive pulmonary disease in routine care in the UK: a retrospective study of a clinical cohort. The Lancet Respiratory Medicine 2014; 2(4): 267-76 www.thelancet.com/journals/lanres/article/PIIS2213-2600(14)70008-6/abstract

4. Shahab L, Jarvis MJ, Britton J, West R. Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax 2006;61:1043-47. http://thorax.bmj.com/content/61/12/1043.full.pdf

5. Poole PJ, Chacko E, Wood-Baker RW, et al. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006;25(1):CD002733

6. Public Health England. National flu immunisation programme 2016-17, 2016. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/529954/Annual_flu_letter_2016_2017.pdf

7. Public Health England. Immunisation against infectious diseases (The Green Book). Chapter 25: Pneumococcal, 2013. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/263318/Green-Book-Chapter-25-v5_2.pdf

8. Health and Safety Executive. Work-related Chronic Obstructive Pulmonary Disease (COPD) in Great Britain, 2014. http://www.hse.gov.uk/Statistics/causdis/copd/index.htm

9. Health and Safety Executive. Construction hazardous substances: isocyanates, 2015. http://www.hse.gov.uk/construction/healthrisks/hazardous-substances/isocyanates.htm

10. Global Initiative for Chronic Obstructive Lund Disease (GOLD). COPD diagnosis, management and prevention: a guide for health care professionals, 2016. http://goldcopd.org/global-strategy-diagnosis-management-prevention-copd-2016/

11. Agusti A, Calverly PM, Celli B. et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Rev 2010;11:122

12. Spencer S, Evans DJ, Karner C, et al. Inhaled corticosteroids versus long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2011;(10):CD007033

13. Wedzicha JA, Bannerji D, Chapman KR, et al for the FLAME investigators. Indacaterol-Glycopyrroniium versus Salmeterol-Fluticasone for COPD. N Eng J Med 2016;374:2222-34

14. Garcia-Aymerich J, Lange P, Benet M, et al. Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax 2006;61:772–8

15. London Respiratory Team Cost Pyramid http://www.london.nhs.uk/webfiles/London%20Respiratory%20Team/Value%20Pyramid.pdf