Does inhaled albuterol improve diaphragmatic contractility in patients with chronic obstructive pulmonary disease?

We tested the hypothesis that the decrease in dyspnea in patients with COPD with inhaled albuterol is in part due to increased diaphragmatic contractility. Eleven patients with COPD inhaled albuterol or placebo in a double-blind randomized manner. Subsequently, dyspnea was measured while patients breathed through inspiratory resistors, and diaphragmatic contractility was quantified during maximal inspiratory efforts and after twitch stimulation of the phrenic nerves. Albuterol produced a decrease in dyspnea (5 +/- 2 to 4 +/- 2 [SD] Borg units, p < 0.01), and increases in maximal transdiaphragmatic pressure (92.4 +/- 37.2 to 102.8 +/- 37.2 cm H(2)O, p < 0.03) and potentiated twitch transdiaphragmatic pressures (21.6 +/- 7.1 to 25.2 +/- 7.6 cm H(2)O, p < 0.02). The decrease in dyspnea correlated with the increases in maximal and twitch transdiaphragmatic pressures: r = -0.64 (p = 0. 04) and r = -0.65 (p = 0.04), respectively. Compared with placebo, albuterol produced an increase in inspiratory capacity (1.87 +/- 0. 71 to 2.26 +/- 0.74 L, p = 0.002), which accounted for the increases in maximal and twitch transdiaphragmatic pressures. The decrease in dyspnea correlated with the increase in inspiratory capacity (r = -0. 62, p = 0.04), but not with the increase in FEV(1) (r = -0.13, p = 0. 72). In conclusion, albuterol relieves dyspnea and enhances respiratory muscle output in patients with COPD primarily by improving the length-tension relationship of the diaphragm rather than by improving its contractility.     

Does roflumilast improve dyspnea in patients with chronic obstructive pulmonary disease? A meta-analysis

Introduction

Although several large studies showed roflumilast (Rof) has demonstrated efficacy in patients with chronic obstructive pulmonary disease (COPD), the efficacy of Rof in dyspnea remains unclear. We therefore undertook a meta-analysis to assess the efficacy of Rof in dyspnea for COPD patients.

Methods

A computerized search through electronic databases was performed to obtain randomized controlled trials (RCTs). Dyspnea was assessed by the transition dyspnea index (TDI) and the UCSD Shortness of Breath Questionnaire (SOBQ). The quality of the included studies was assessed by the Jadad score. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I² test. The effect sizes were compared with the minimum clinically important difference (MCID).

Results

Four RCTs involving 4,767 patients with forced expiratory volume in one second (FEV₁) <80% predicted met the inclusion criteria. The Jadad score of each study was 5 scores. Rof statistically improved the TDI focal score (WMD =0.30 units; 95% CI: 0.14-0.46), but failed to decrease the SOBQ (WMD =–1.10 units; 95% CI: –4.24 to 2.04). The overall effect sizes were lower than the MCID of the TDI and the SOBQ, respectively.

Conclusions

Sufficient evidence to support Rof relieving dyspnea in COPD patients is currently lacking. Further studies are needed to investigate the effects of Rof in dyspnea, especially for COPD patients with a different phenotype.KEY WORDS : Chronic obstructive pulmonary disease (COPD), roflumilast (Rof), dyspnea, meta-analysis     

Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease?

The role of exercise-induced oxidative stress in the reduced quadriceps endurance of chronic obstructive pulmonary disease (COPD) patients has never been shown. We conducted a randomized, double-blind, and crossover study in which nine severe patients performed localized dynamic quadriceps endurance tests at 40% of maximal strength after oral treatment with the antioxidant, N-acetylcysteine (NAC), and placebo. Venous blood was sampled before, immediately after exercise, and 6 hours later. Endurance time improved by 25% after NAC treatment compared with placebo (p < 0.05). Superoxide anion (oxidant) release by stimulated phagocytes decreased after treatment (p < 0.05). No change in the antioxidant system was observed. Lipid peroxidation, an index of oxidative stress, was significantly increased 6 hours after exercise in the placebo condition (p < 0.05) but not after treatment. Advanced oxidized protein products, another index of oxidative stress, were also increased 6 hours after exercise by 139 +/- 27% in the placebo condition but only by 54 +/- 19% after treatment (p < 0.05). This study shows that NAC treatment in COPD reduced basal disturbance in the prooxidant system, improved endurance time, and prevented exercise-induced oxidative stress. Oxidative stress thus seems to be implicated in the reduced quadriceps endurance of patients with COPD.     

Is exercise important in chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease impairs the ability of patients to perform maximal physical exercise, particularly in patients with severe lung disease. However, differing perceptions of the meaning and importance of exercise to patients and caregivers is likely to impair patient-physician communication about current medical status and outcomes of therapeutic interventions. Other outcomes of importance to patients including actual performance of functional activity during daily life and health-related quality of life may also be affected by impaired exercise capacity. However, the relationships between exercise, activity, and quality of life are inconsistent. Thus, measurement of physiologic and patient-centered outcomes may provide the best approach to assessing responses to therapeutic interventions. These concepts were explored in a conference sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. and Pfizer Inc and reviewed in the articles generated from the symposium in this issue of COPD.     

Does long-term oxygen therapy reduce hospitalisation in hypoxaemic chronic obstructive pulmonary disease?

The aim of this study was to determine whether long-term oxygen therapy (LTOT) reduces hospitalisation in hypoxaemic patients with chronic obstructive pulmonary disease (COPD). The circumstances of initiation of LTOT (start during hospitalisation versus start as an outpatient) and compliance with oxygen were also investigated (continuous oxygen therapy (COT) > or = 15 h daily versus noncontinuous oxygen therapy (NCOT) <15 h daily). A total 246 COPD patients were studied, with each patient acting as their own control. Patients were divided into four groups: 125 patients on COT who started LTOT in conjunction with hospitalisation, 37 patients on COT who started LTOT as outpatients, 58 patients on NCOT who started LTOT in conjunction with hospitalisation and 26 patients on NCOT who started LTOT as outpatients. Admission rates, days spent in hospital and number of patients with at least one hospitalisation (ever hospitalised) were compared in two periods of 10 months before and after initiation of LTOT. Overall during the LTOT period, in comparison with the preoxygen period, the admission rates, hospital days and "ever hospitalised" were reduced by 23.8%, 43.5% and 31.2%, respectively. Among patients who started LTOT as outpatients, a tendency towards a higher effect in the compliant group was observed. This study shows that in hypoxaemic chronic obstructive pulmonary disease patients, long-term oxygen therapy is associated with a reduction in hospitalisation.     

Do chronic inhaled steroids alone or in combination with a bronchodilator prolong life in chronic obstructive pulmonary disease patients?

PURPOSE OF REVIEW: Inhaled corticosteroids with or without long-acting beta2 adrenergic agonists are commonly used to treat patients with chronic obstructive pulmonary disease to attenuate symptoms and to prevent exacerbations. Whether these medications prolong survival is uncertain. RECENT FINDINGS: Inhaled corticosteroids attenuate airway and systemic inflammation, reduce airway hyperreactivity, improve patient symptoms and prevent exacerbations in chronic obstructive pulmonary disease patients. The data on mortality are mixed. A pooled analysis of published randomized controlled trials indicated that inhaled corticosteroids reduced mortality by around 25%; however other studies have failed to show a beneficial effect on mortality. The addition of long-acting beta2 adrenergic agonists to inhaled corticosteroids enhances the clinical effectiveness of these medications and confers incremental mortality benefits to patients. Interestingly, these medications appear to be especially beneficial in reducing cardiovascular morbidity and mortality, though large randomized controlled trials powered specifically on these endpoints are needed to confirm these early findings. SUMMARY: Inhaled corticosteroids, especially with long-acting beta2 adrenergic agonists, reduce airway inflammation and appear to prolong survival in chronic obstructive pulmonary disease patients. They may be particularly effective in reducing cardiovascular morbidity and mortality of patients, pending confirmation by additional clinical studies powered specifically on these endpoints.     

Can diaphragmatic contractility be assessed by twitch airway pressures in patients with chronic obstructive pulmonary disease?

In healthy subjects and in patients without lung diseases, twitch airway pressure (Paw(tw)) responses to phrenic nerve stimulation can be used to predict twitch esophageal pressure (Pes(tw)) and twitch transdiaphragmatic pressure (Pdi(tw)), thus overcoming the need for placement of esophageal and gastric balloons. The aim of this study was to determine whether measurements of Paw(tw) combined with simple maneuvers could be used to predict Pes(tw), and possibly Pdi(tw), in patients with severe chronic obstructive pulmonary disease (COPD) (n = 12). Stimulations delivered at relaxed FRC produced a correlation coefficient (r) between Paw(tw) and Pes(tw) of 0.44 (p < 0.001) and of 0.62 (p < 0.001) during stimulations while patients performed a gentle exhalation from FRC. Stimulations performed during a gentle inhalation produced a good correlation between Paw(tw) and Pes(tw) (r = 0.92, p < 0.001); however, the limits of agreement between Paw(tw) and Pes(tw) were wide. Correlations between Paw(tw) and Pdi(tw) during the three experimental conditions were weak. In conclusion, during a gentle inspiratory effort in patients with severe COPD the correlation between Paw(tw) and Pdi(tw) was weak, whereas the correlation between Paw(tw) and Pes(tw) was good, but it was not sufficient to allow the prediction of Pes(tw) from Paw(tw) in all patients.