Effecting positive outcomes through positive pressure ventilation in COPD

COPD is one of the leading causes of mortality worldwide.1 Every year, nearly 3 million people die directly from this disorder and millions more are hospitalized. Discouragingly, over the next 20 years, COPD mortality is expected to more than double, such that by 2030, it will be responsible for 10% of the world's total mortality (currently 7%), accounting for 7 million deaths annually.1 Patients with COPD are most vulnerable to mortality during periods of exacerbations, especially if the exacerbations are associated with acute hypoxaemia and hypercapnia. In such cases, the case fatality rate is high, ranging from 20% to 30%.2 Patients who require intubation and mechanical ventilation have the worst prognosis with most succumbing to their disease during their hospitalization.3 Thankfully, with the advent of non-invasive mechanical ventilation (NIMV) delivered through a face mask, the fate and expectations of COPD patients with respiratory failure have markedly improved. High-quality randomized controlled trials (RCT) have shown that treatment with NIMV mitigates the need for intubation and mechanical ventilation and reduces overall mortality by 55%.4 Thus, hypercapnic respiratory failure is no longer a terminal event for most patients with COPD; non-invasive positive pressure ventilation applied acutely and appropriately saves lives! Although undoubtedly NIMV represents a major breakthrough in the management of acute exacerbations, several important questions remain unresolved. First, while on ‘average’, patients presenting to the emergency department with acute hypercapnic respiratory failure benefit from NIMV therapy, NIMV is not effective in all patients. The risk factors for poor outcomes following NIMV therapy are largely unknown. Second, although in the acute setting, NIMV is life-preserving, it is not known whether or not the survival benefits of NIMV are durable and extend materially beyond the acute exacerbating period. In this issue of Respirology, Chung et al. provide new data that answer these questions. They followed 100 patients with COPD, who were successfully treated with NIMV during an acute exacerbation, for up to 5 years.5 They found that the overall survival of these patients was 72% at 1 year, 52% at 2 years and 26% at 5 years of follow-up and, notably, over 50% of these patients required readmission to hospital within 1 year of being discharge from their index hospitalization.5 Although superficially, these data appear to be dismal, compared with historical data, they are in fact quite encouraging. In the early 1990s before the widespread use of NIMV therapy, the in-hospital mortality for COPD patients with hypercapnic respiratory failure was 24% and the 1-year mortality was nearly 60%.3 In contrast, in Chung et al.'s study only 28% of the patients died within 1 year of NIMV therapy, suggesting that NIMV makes a material difference to one-year survival. Unfortunately, however, the beneficial effects of NIMV are not durable. By 2 years of follow-up, nearly half of the original patients in Chung et al.'s study died and by 5 years, three out of the four patients were dead. These data highlight the urgent and pressing need to find new therapies that can be used in conjunction with NIMV to enhance the long-term survival of COPD patients. The second notable finding in Chung's study was that reduced BMI and use of domiciliary oxygen therapy were the two major independent risk factors for mortality in these patients. As large RCT have clearly shown that domiciliary oxygen therapy in patients with resting hypoxaemia extends survival,6 the latter finding is likely a surrogate for severe disease. Low BMI, on the other hand, is likely to be in the causal pathway by contributing to poor muscle strength, worsening respiratory status and reduced quality of life.7-9 Importantly, reduced BMI is a potentially modifiable risk factor. A recent study by Weekes et al. indicates that 6 months of dietary counselling and advice on food fortification to patients with COPD can lead to weight gains and importantly to fewer symptoms and better clinical outcomes including less dyspnea and enhanced quality of life,9 suggesting that lifestyle changes can effect positive outcomes in underweight COPD patients. In sum, the data by Chung et al. are both encouraging and sobering. They not only reinforce the notion that NIMV is life-preserving for patients who experience a severe COPD exacerbation associated with acute hypercapnic respiratory failure, but also suggest that its survival benefit is time-limited and largely wears off by 2 years of follow-up. Thus, it would appear that one-time use of NIMV is not a panacea for patients with severe COPD. Although NIMV saves these patients from intubation, mechanical ventilation and acute mortality, many of these patients continue to struggle with severe breathlessness and require frequent hospitalizations to manage their disease. Unfortunately, there is a dearth of therapies that can enhance patient symptoms and improve survival in patients with severe COPD.10 Intriguingly, several studies suggest that the chronic use of NIMV may enhance patient health outcomes including survival in patients with severe COPD.11, 12 However, before the widespread use of long-term NIMV therapy can be advocated, a large multicentre clinical trial powered on mortality is desperately needed. Until then, it may be reasonable for the practising clinician to consider long-term NIMV therapy for patients with severe COPD, who remain extremely breathless and hypercapnic despite the optimal use of all other supportive measures. Additionally, in patients who are underweight, it may also be useful to institute aggressive dietary counselling and follow-up to ensure that these patients maintain their body weight within the acceptable range.9 Although the management of COPD has improved considerably over the past two decades, it remains a lethal disease in patients who are hospitalized with respiratory failure. Acute therapy with NIMV can be life-preserving in this setting; however, according to data by Chung et al.,5 the effects are not durable. To this end, the study by Chung et al. has challenged the scientific community to do better in improving both the short-term and long-term prognosis of these patients by finding novel therapies that can enhance the survival of patients with respiratory failure from COPD.

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