Management of chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary disease (COPD) is a syndrome of progressive airflow limitation caused by chronic inflammation of the airways and lung parenchyma.¹ It is estimated that 440,000 people in Ireland have COPD.²

The primary physiological abnormality is a reduction in the forced expiratory volume in one second (FEV1) in adults over 30 years of age of approximately 30ml per year to nearly 60ml per year. COPD begins with an insidious phase of deterioration in lung function. The onset of symptoms is variable but often does not occur until there has been a deterioration of 50% in the predicted value of FEV1.³ 

Further physiological abnormalities seen in COPD include a reduction in the diffusing capacity for carbon dioxide, hypoxaemia and alveolar hypoventilation. Hyperinflation of the lungs, primarily from an increase in the functional residual capacity of the lungs, further inhibits the mechanism of breathing by putting the respiratory muscles at a mechanical disadvantage. These factors all combine to increase the work of breathing and to greatly reduce exercise tolerance.⁴

Diagnosis, staging and prognosis

Because the majority of cases occur in patients who have smoked, all current or former smokers should be considered at increased risk for COPD. Other risk factors which account for far fewer cases include alpha-1 antitrypsin deficiency, airway hyper-responsiveness and indoor air pollution. In the past, FEV1 was the only parameter used in staging COPD (FEV1/FVC of < 0.70). Stage I COPD showed FEV1 > 80%; stage II showed FEV1 of 50-80%; stage III showed  FEV1 of 30-50%; and FEV1 < 30% predicted was classified as stage IV COPD. It was believed that most patients would follow a disease course where disease severity would track the severity of their airflow limitation.⁵   

However, updated guidelines from 2011 from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) reflect that COPD is more complex than the previous simplistic single-factor assessment system allows for, and that the FEV1 is an unreliable marker of overall disease severity. A combined approach to COPD assessment is now recommended, which involves assessment of the current level of patients’ symptoms, the severity of spirometric abnormality, exacerbation risk and the presence of comorbidities.²

Symptoms can be objectively assessed using either the modified British Medical Research Council (mMRC) questionnaire for assessing the severity of breathlessness or by using a more comprehensive symptom assessment tool such as the COPD assessment test (CAT). Two methods exist for assessing exacerbation risk: firstly, using GOLD spirometric classification as previously outlined; or secondly by asking the patient how many exacerbations they have had in the previous year with ≥ 2 indicating high risk. If there is a discrepancy between the two, then the higher risk indicator should be used.

The combined assessment of COPD allows a greater understanding of the impact of COPD on a patient’s health status and places them in one of four grades (see Figure 1). The groups can be summarised as follows:

• Patient group A – low risk, less symptoms
• Patient group B – low risk, more symptoms
• Patient group C – high risk, less symptoms
• Patient group D – high risk, more symptoms.

It also forms the basis for individualised management of COPD, with grade A and B management based primarily on bronchodilation, and grades C and D on bronchodilation with an anti-inflammatory agent.

Figure 1. Combined assessment of COPD according to GOLD guidelines (click to enlarge)

Management of stable COPD 

The major goals of therapy include smoking cessation, symptom relief, improvement in physiological function and limitation of complications such as abnormal gas exchange and exacerbations of the disease.

Smoking cessation

Smoking cessation is the only intervention known to be effective in modifying disease progression, and abstinence results in a 50% reduction in the rate of lung-function decline in patients with COPD.⁶ All patients should be encouraged to stop smoking and appropriate pharmacological and behavioural support should be made available.

Vaccination

Annual influenza vaccination and pneumococcal vaccination should be offered to all patients in an attempt to reduce both disease-specific mortality and mortality from all causes.⁷

Drug therapy

Inhaled bronchodilators

Inhaled bronchodilators are the mainstay for pharmacotherapy in COPD. They both reduce symptoms as well as reducing exacerbations and improving quality of life (QoL).⁸ Inhaled bronchodilators can be divided into categories based on their mechanism of action and duration of action. 

Anti-muscarinic/anti-cholinergic agents can be both short (SAMA) and long (LAMA) acting. These agents act by antagonising the bronchoconstricting effects of the parasympathetic nervous system. Examples of SAMA include ipratropium and LAMA include tiotropium and glycopyrronium. Conversely, beta-2 agonists, which can also be short (SABA) or long (LABA) acting, function by augmenting the effects of the sympathetic nervous system, thus resulting in bronchodilation. Examples of SABA are salbutamol and terbutaline, and LABA include salmeterol, formoterol and indacaterol.

Both SAMA and SABA have an immediate effect on symptoms and result in bronchodilation for four to six hours and are therefore useful in a prn capacity, and there is a role for prn monotherapy in patients with mild disease.⁹ LAMAs have been the mainstay of bronchodilator therapy in COPD since the UPLIFT study in 2008 which showed that tiotropium improved FEV1, QoL and decreased exacerbation rate.¹⁰ LABAs such as salmeterol and formoterol provide bronchodilation over approximately 12 hours. Indacaterol is a once-daily LABA licensed for use in COPD. 

More recently, the first once-daily combination inhaler was made available on the Irish market. It combines both a LAMA (glycopyrronium) and a LABA (indacaterol) and is indicated in grade B, C and D COPD patients who remain symptomatic on single-agent bronchodilator therapy, in combination with an inhaled corticosteroid in grade C and D.²

Inhaled corticosteroids  

Initial studies using improvement in FEV1 as their primary outcome proved disappointing for inhaled corticosteroid (ICS) use in the management of COPD. However, some of the same studies also showed that ICS improved patient symptoms, frequency of exacerbations and overall health status.^11,12 The ISOLDE trial showed that patients with a mean FEV1 of approximately 50% predicted, who were treated with ICS, showed a 25% reduction in frequency of exacerbations.¹³ These findings suggest that inhaled corticosteroids do provide clinical benefit to patients independent of their FEV1 response. ICS use is therefore recommended in patients with moderate-to-severe airflow limitation who have ongoing symptoms and frequent exacerbations despite optimal bronchodilator therapy (grade C and D). 

Theophylline

In addition to maximal inhaler therapy, low-dose oral theophylline has been shown to improve FEV1, forced vital capacity (FVC) and gas exchange over placebo.¹⁴ Its mechanisms are controversial and theophylline can be toxic, however it is thought to provide additional bronchodilation. Frequent monitoring for supratherapeutic levels is critical.

Oral corticosteroids and other pharmacological drugs

Oral corticosteroids are useful in managing an acute exacerbation of COPD. Although a trial of oral corticosteroids may be useful in detecting coexisting asthma, it is a poor predictor of the response to inhaled corticosteroids among patients with COPD. Therefore oral corticosteroids should not be used in the routine management of stable COPD.¹⁵ Other pharmacological drugs that have been found to be beneficial in COPD patients include phosphodiesterase-4 inhibitors, mucolytics and antioxidants.

Pulmonary rehabilitation

Pulmonary rehabilitation has been shown to improve QoL and exercise tolerance, and to reduce the number of hospitalisations related to COPD.^16,17 It should be considered for patients with clinically significant exertional symptoms. Pulmonary rehabilitation is best delivered via a multi-disciplinary approach, incorporating a personalised aerobic programme, disease education, psychosocial counselling and nutritional support. 

Supplementary oxygen 

Testing for hypoxaemia is critical. Clinical trials have shown that supplementary oxygen for 15 or more hours a day improves survival and QoL in hypoxic patients with COPD.¹⁸ It should be initiated in all stable patients who have chronic hypoxaemia at rest (SpO2 < 88% or PaO2 < 7.3 kPa).¹⁹ Supplemental oxygen should be titrated to maintain an oxygen saturation of at least 90% at all times. To quantify the need for supplementary oxygen during exercise, rest and sleep, pulse oximetry must be performed during all three conditions. 

Hypercapnoea resulting from an increase in CO2 production or a decrease in alveolar ventilation is a feature of advanced disease. Patients on supplementary oxygen are at an increased risk of developing worsening hypercapnoea, thought to be due to the reduced capacity for oxygenated haemoglobin to carry carbon dioxide, known as the Haldane effect. Safe administration of oxygen in these patients can be achieved by close monitoring of arterial blood gas and slow titration of inspired oxygen in small increments to achieve the desired oxygen saturation.

Trials of non-invasive positive-pressure ventilation have been conducted in patients with stable COPD. Although hypercapnoea can be improved, improvement often comes at the cost of increased hyperinflation. A two-year trial of non-invasive positive-pressure ventilation in addition to supplementary oxygen in patients with alveolar hypoventilation demonstrated improvements in dyspnoea and QoL but only small improvement in arterial carbon dioxide levels.

Surgery

Lung volume reduction surgery can reduce hyperinflation and should be considered in patients with severe upper lobe emphysema and reduced exercise tolerance who are not faring well with medical therapy alone. The National Emphysema Trial, which enrolled 1,218 patients and randomised two groups to either lung volume reduction surgery or maximal medical therapy, demonstrated varying benefits between patient groups. Survival benefit was most marked in patients with predominantly upper lobe emphysema and low exercise capacity. However, an increase in mortality was noted in severe patients with a FEV1 < 20% and either a diffusing capacity for carbon monoxide < 20% or non-upper lobe emphysema on chest CT.²⁰

Single-lung transplantation is a surgical option for patients with end-stage emphysema. It is usually reserved until the FEV1 is < 20% of predicted value, the diffusing capacity of the lung for carbon monoxide (DLCO) is < 20% or the clinical course becomes life-threatening. Although functional capacity has been shown to improve following the procedure, it does not appear to significantly improve survival.²¹

Conclusion

COPD is a preventable and treatable chronic disease and is often underdiagnosed and undertreated in clinical practice. Although new drugs are constantly emerging on the market, primary prevention should always remain the first line in the management plan. Awareness of the strong link between COPD and smoking should constantly be stressed to healthcare professionals, healthcare providers and the general public. 

References

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