Breathing new life into COPD treatment guidelines

Dr Aoifa O'Reilly, Prof Stephen Lane, Dr Iseult Browne | 16 Mar 2017 | 0 Comment(s)

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Ireland has the highest rates of COPD in the OECD, but better adherence to 2017 GOLD guidelines can lead to improvements in its assessment and treatment

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, is currently the fourth-leading cause of death worldwide and is projected to be the third-leading cause by 2020. One-in-four adults from their mid-40s onwards is likely to develop and require treatment for COPD in their lifetime. It is a common, preventable and treatable disease, but despite this, our management of COPD remains suboptimal. In this article, we discuss the 2017 guidelines published recently by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), illustrated by two case reports. These include some significant changes in the way we assess and treat COPD.

 

Case report 1 – 'Pure COPD'

A 56-year-old male was referred to our respiratory outpatient clinic in 2015 complaining of worsening dyspnoea on exertion for six months, quantified as severe, as he was unable to walk 100m before stopping. Associated symptoms included wheeze, cough and sputum production. He stated these symptoms were long-standing, having suffered from early-morning sputum for over 16 years and a ‘smoker’s cough’ since his mid-30s. He also complained of having two-to-three lower respiratory tract infections (LRTIs) per year for the past three years, which had become very disabling. These LRTIs were indeed periods when his background symptoms deteriorated. 

He had a 60-pack-year exposure to cigarettes. 

There was no ‘asthma signal’, he wasn’t chesty as a child and no personal or family history of allergies.  On exam, he had a diffuse wheeze.  His emphysematous chest x-ray and obstructed lung function spirometry is shown in Figure 1 above. 

Panel A shows a typical chest x-ray and panel B denotes very severe airflow obstruction, with an FEV1 of 32 per cent predicted associated with hyperinflation and reduced gas transfer. There is no reversibility to bronchodilator. Panel C demonstrates what his obstructed airways would look like at bronchoscopy. Panel D shows what a bronchial biopsy would look like, in other words ‘pauci-inflammatory’ chronic bronchitis, and panel E shows what his emphysema might look like on electron microscopy.

He was classified as grade D COPD on the basis of his exacerbation rate, severe breathless and his reduced lung function. He was advised as follows:

To stop smoking using whatever means necessary, for example:

a.  Nicotine replacement therapy.

b.  Varenicline.

c.  Electronic cigarette. The use of the electronic cigarette or vaping is becoming less controversial and recent position statements support it being the ‘lesser of the two evils’. Indeed, Public Health England states that it is 95 per cent less harmful to your health than cigarettes. It is our practice to recommend same and we have found it to be enormously effective in reducing nicotine exposure.

d.  To enrol in a pulmonary rehabilitation programme.

e.   To get an annual influenza vaccination and in light of his reduced lung function, a five-yearly Pneumovax to age 65.

As per the GOLD guideline operational in 2015, he was started on a combination of long-acting β-2 agonist (LABA) and inhaled corticosteroid (ICS) in the same inhaler.

The pharmacotherapy of COPD is underpinned by three classes of drugs: Long-acting antimuscarinic agents (LAMAs, ie, modern iteration of atropine); LABAs (modern iteration of adrenaline); and ICS (potent topical steroids given by inhaler). Up to 2017, GOLD advised us that  LAMAs are the mainstay of therapy and that the first-line order of introduction should be SAMA or SABA PRN (Grade A), then LABA or LAMA (Grade B) and then LABA+ICS for Grades C and D. 

Our patient, duly prescribed a LABA+ ICS, disappeared and returned a year later, still smoking. He said he was less breathless and had no visits to his GP, however, he had been admitted to another hospital with a middle-lobe pneumonia. We then reconsidered his pharmacotherapy in light of increasingly strong data demonstrating a dose-response relationship between ICS and pneumonia in COPD patients treated with ICS; a lack of improvement in mortality effects of ICS in COPD; and the recent 2017 GOLD guideline recommending a LAMA+LABA combination as more effective than a LABA/ICS combination in Grades C and D COPD. We thus felt we could safely switch him to a LAMA+LABA combination in the same inhaler and one year later his exacerbation rate has reduced, breathlessness has improved and he has not to date had a recurrence of his pneumonia.  

COPD results, in the main, from smoking-induced chronic bronchitis (poor prognosis, ‘wet’ exacerbating, ‘blue bloater’) and emphysema (dry, breathless, ‘pink puffer’).  It results in progressive and premature airway closure over many years, as measured by annual forced expiratory volume in one second (FEV1) associated with a variable tendency to breathlessness (emphysema) and clinical exacerbations (chronic bronchitis). 

Indeed, GOLD classifies COPD on the basis of these three biomarkers: Yearly exacerbation rate; breathlessness; and FEV1 into Grades A through to D using a convenient four-square combined assessment grid. In contrast to the original and subsequent iterations of GOLD, which relied more heavily on spirometric FEV1 classification, the new 2017 guidelines place much more emphasis on the two clinical biomarkers, in particular the annual exacerbation rate (chronic bronchitis, ‘blue bloater’, poor prognosis). 

 

Case report 2 – Beware of asthma/COPD overlap (ACOS)

This is the same case as above, however, we have made some illustrative additions as follows:

He states that he was ‘chesty’ as a child, complains of a life-long blocked nose, had severe hay fever in his 20s and that many in his family have asthma.

He had a 40 per cent improvement in his severely reduced FEV1 to bronchodilator.

His FBC reveals a mild eosinophilia of 0.5 or 500 cells/µl.

All the other investigations are the same.  This case should ring warning bells — asthmatics are as ‘entitled’ to get COPD as anyone else. This patient has ACOS and as such, he must be treated for asthma as per Global Initiative for Asthma (GINA) guidelines.

The intense, inflammatory obstructive airway disease always trumps COPD in terms of its management.  Although the same classes of drugs are used, they are utilised oppositely in these two conditions. In other words, COPD is LAMA, LABA then ICS (GOLD); whereas asthma or ACOS is ICS, LABA then LAMA (GINA).

The following conclusions in respect to the management of COPD in Ireland, and as advised by GOLD as we commence 2017 can be made:

Ireland continues to have the highest rate of COPD admissions in the OECD. This is high on the agenda of the national clinical programme for COPD.

Smoking cessation remains the cornerstone of therapy.  Robust evidence and increasing opinion supports the use of the electronic cigarette.

Spirometry has become less important in classifying COPD, relying mainly on the clinical biomarkers of exacerbation rate and breathlessness scores.

Pharmacotherapy has been simplified, with LABA+LAMA combination now first-line therapy for Grades B,C,D.

The role of ICS is fading, but they still have a role. They cause pneumonia and the evidence for their reducing mortality in COPD is weak.

Beware the smoking asthmatic. ACOS should always be managed as per GINA guidelines in the first instance until more is known about the condition.

According to the National Healthcare Quality Reporting System 2016 Annual Report, Ireland has the highest hospital admission rates for COPD in the OECD, at 364 per 100,000 population, well above the average of 198 per 100,000. We have approximately 100,000 diagnosed cases of COPD, with 20,000 having severe disease. There remains an estimated 300,000 people with undiagnosed ‘subclinical’ COPD. In light of this disease burden and poor performance when compared even with our nearest healthcare system in Northern Ireland, there is in place a National Clinical Programme for COPD.

COPD should be considered in any patient who has dyspnoea, chronic cough or sputum production and/or a history of exposures to risk factors. All patients with chronic respiratory symptoms should have a chest x-ray to rule out sinister or unusual diagnoses.  Although screening spirometry is not advised, GOLD recommends active case-finding in primary care — in other words, performing spirometry on those with risk factors or symptoms and classifying such patients into grades A to D on the basis of exacerbation rate and breathlessness score.

References and additional figures on request

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