Contrasting Pressure-Support Ventilation and Helium-Oxygen During Exercise in Severe COPD: O. Hussain, E. G. Collins, N. Adiguzel, W. E. Langbein, M. J. Tobin, F. Laghi (Respir Med 2010 Sep 17). [Epub ahead of print]
Helium-oxygen mixtures and pressure-support ventilation have been used to unload the respiratory muscles and increase exercise tolerance in COPD. Considering the different characteristics of these techniques, we hypothesized that helium-oxygen would be more effective in reducing exercise-induced dynamic hyperinflation than pressure-support.
We also hypothesized that patients would experience greater increases in respiratory rate and minute ventilation with helium-oxygen than with pressure-support. The hypotheses were tested in 10 patients with severe COPD (FEV1 = 28 ± 3% predicted [mean ± SE]) during constant-load cycling (80% maximal workrate), while breathing 30% oxygen-alone, helium-oxygen, and pressure-support in randomized order. As hypothesized, helium-oxygen had greater impact on dynamic hyperinflation than did pressure-support (end-exercise; p = 0.03).
For the most part of exercise, respiratory rate and minute ventilation were greater with helium-oxygen than with pressure-support (p ≤ 0.008). During the initial phases of exercise, helium-oxygen caused less rib-cage muscle recruitment than did pressure-support (p < 0.03), and after the start of exercise it caused greater reduction in inspiratory reserve volume (p ≤ 0.02). Despite these different responses, helium-oxygen and pressure-support caused similar increases in exercise duration (oxygen-alone: 6.9 ± 0.8 min; helium-oxygen: 10.7 ± 1.4 min; pressure-support: 11.2 ± 1.6 min; p = 0.003) and similar decreases in inspiratory effort (esophageal pressure-time product), respiratory drive, pulmonary resistance, dyspnea and leg effort (p < 0.03). In conclusion, helium-oxygen reduced exercise-induced dynamic hyperinflation by improving the relationship between hyperinflation and minute ventilation. In contrast, pressure-support reduced hyperinflation solely as a result of lowering ventilation. Helium-oxygen was more effective in reducing exercise-induced dynamic hyperinflation in severe COPD, and was associated with greater increases in respiratory rate and minute ventilation than pressure-support. PMID: 20851591 [PubMed –as supplied by publisher]
Comment: Heliox mixtures have been suggested as beneficial in acute settings of severe upper and lower airway obstruction. Pressure support ventilation has been shown to be very helpful during acute exacerbations of COPD often avoiding the need for endotracheal intubation. Although there were very few subjects in this study, the random testing of the different modalities in each patient and that each patient was tested with all three techniques supports that heliox may be superior to pressure support ventilation in improving exercise tolerance and training. It is also appealing as it is much less cumbersome for patients to wear while exercising.
Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease: J. R. Hurst, J. Vestbo, A. Anzueto, N. Locantore, H. Müllerova, R. Tal-Singer, B. Miller, D. A. Lomas, A. Agusti, W. Macnee, P. Calverley, S. Rennard, E. F. Wouters, J. A. Wedzicha (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators, N Engl J Med 2010 Sep 16; 363(12):1183–1184).
Background. Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity.
Methods. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years.
Results. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count.
Conclusions. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
Comments: This study is providing a wealth of information about the nature and impact of exacerbations on patients with COPD. It indeed adds further credence to the notion that the patients with frequent exacerbations may indeed be a distinct phenotype. Some have suggested that this group may also be associated with more rapid of rate of decline in FEV1. It is not clear which is the cart and which the horse. Do more frequent exacerbations cause a more rapid decline in FEV1 or is this a group who are rapid decliners, due to other factors (genetics) and are more prone to exacerbations for some reason? The findings from this study should lead both the ATS and GOLD guidelines to suggest that frequent exacerbators (2 or more per year should be considered for therapy to reduce exacerbations rather than suggesting that only frequent exacerbators with an FEV1 of less than 50% be considered for such therapy as combination inhaled corticosteroids and long-acting bronchodilators. This subphenotype may be programmed to have a rapid decline and starting such therapies earlier could potentially have an impact on preventing the rate of decline in FEV1. This study also found that a history of GERD was higher in this group and this may indeed be a significant cause for more frequent exacerbations and an integral mechanistic feature for this frequent exacerbation group. This will be an interesting subgroup to further study with regard to genetics and other clinical features that may explain their tendency for more frequent exacerbations.
Cardiovascular Events in Patients with COPD: TORCH Study Results: P. M. Calverley, J. A. Anderson, B. Celli, G. T. Ferguson, C. Jenkins, P. W. Jones, C. Crim, L. R. Willits, J. C. Yates, J. Vestbo; TORCH Investigators (Thorax, 2010 Aug; 65(8):719–725).
Background. Previous studies have suggested that long-term use of beta agonists to treat chronic obstructive pulmonary disease (COPD) may increase the risk of cardiovascular adverse events. In this post hoc analysis, data from the Towards a Revolution in COPD Health (TORCH) study were used to investigate whether use of the long-acting beta(2) agonist salmeterol over 3 years increased the risk of cardiovascular adverse events in patients with moderate to severe COPD.
Methods. TORCH was a randomised, double-blind, placebo controlled study conducted at 444 centres in 42 countries. Patients (n = 6184; safety population) received twice daily combined salmeterol 50 microg plus fluticasone propionate 500 microg (SFC), either component alone, or placebo. Adverse events were recorded every 12 weeks for 3 years.
Results. The probability of having a cardiovascular adverse event by 3 years was 24.2% for placebo, 22.7% for salmeterol, 24.3% for fluticasone propionate and 20.8% for SFC. Although a history of myocardial infarction doubled the probability of cardiovascular adverse events, the event rates remained similar across treatment groups.
Conclusion. Post hoc analysis of the 3-year TORCH dataset showed that salmeterol alone or in combination (SFC) did not increase the risk of cardiovascular events in patients with moderate-to-severe COPD. PMID: 20685748 [PubMed –indexed for MEDLINE]
Comment. There have been concerns about possible adverse effects of long acting beta agonists in patients with COPD because of their propensity to have associated cardiovascular disease and in view of the results of the SMART trial, even though that trial was conducted in asthmatics. This large multicenter randomized controlled trial did not show an increased risk for cardiovascular events when comparing placebo and fluticasone alone to salmeterol alone or combination therapy. This finding of no increased risk should reassure clinicians who have been concerned about potential cardiovascular events related to long-acting beta agonist use as a treatment for COPD.