Comorbid insomnia and sleep apnea in Veterans with post-traumatic stress disorder.

PURPOSE: The purpose of this study was to determine the impact of insomnia in Veterans with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) on health-related outcomes before and after 12 weeks of continuous positive airway pressure (CPAP) treatment. METHODS: We conducted a prospective cohort study of Veterans with PTSD and documented apnea hypopnea index (AHI) ≥ 5 with and without clinically significant insomnia as determined by the Insomnia Severity Index (ISI). Health-related outcomes including PTSD checklist (PCL-M), SF-36, and Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline and 12 weeks after initiation of OSA treatment. CPAP adherence was retrieved at each visit. RESULTS: Seventy-two Veterans including 36 with comorbid insomnia and OSA (COMISA) and 36 OSA-only were enrolled. Veterans with COMISA were younger (p = 0.03), had lower BMI (p < 0.001), and were more likely to report depression than those with OSA-only (p = 0.004). Although AHI was higher in the COMISA (p = 0.01), both groups expressed comparable daytime sleepiness (p = 0.16). The COMISA group had no significant change in SF-36 and PSQI after 12 weeks of treatment and used CPAP much less frequently than OSA-only group (p = 0.001). CONCLUSIONS: COMISA in Veterans with PTSD is associated with worse quality of life than those with OSA-only. Insomnia should be assessed in Veterans with PTSD who are not adherent to CPAP treatment.

A Randomized Crossover Trial Evaluating Continuous Positive Airway Pressure Versus Mandibular Advancement Device on Health Outcomes in Veterans With Posttraumatic Stress Disorder.

STUDY OBJECTIVES: Despite the overall improvement in posttraumatic stress disorder (PTSD) symptomatology with continuous positive airway pressure (CPAP) therapy, adherence to CPAP is far worse in veterans with PTSD compared to the general population with obstructive sleep apnea (OSA). The aim of this study was to compare the efficacy, adherence, and preference of CPAP versus mandibular advancement device (MAD) and the effect of these treatments on health outcomes in veterans with PTSD. METHODS: Forty-two subjects with PTSD and newly diagnosed OSA by polysomnography were treated in a randomized, crossover trial of 12 weeks with CPAP alternating with MAD separated by a 2-week washout period. The primary outcome was the difference in titration residual apnea-hypopnea index (AHI) between CPAP and MAD. Secondary outcome measures included PTSD Checklist and health-related quality of life (Medical Outcomes Study 36-Item Short Form and Pittsburgh Sleep Quality Index). RESULTS: Analyses were limited to the 35 subjects (mean age 52.7 ± 11.6 years) who completed the trial, regardless of compliance with their assigned treatment. CPAP was more efficacious in reducing AHI and improving nocturnal oxygenation than MAD (P < .001 and P = .04, respectively). Both treatments reduced PTSD severity and ameliorated scores of the Medical Outcomes Study Short Form 36 and Pittsburgh Sleep Quality Index, although no differences were detected between the CPAP and MAD arms. The reported adherence to MAD was significantly higher than CPAP (P < .001), with 58% preferring MAD to CPAP. CONCLUSIONS: Although CPAP is more efficacious than MAD at improving sleep apnea, both treatment modalities imparted comparable benefits for veterans with PTSD in relation to PTSD severity and health-related quality of life. MAD offers a viable alternative for veterans with OSA and PTSD who are nonadherent to CPAP. CLINICAL TRIAL REGISTRATION: Title: A Randomized Cross Over Trial of Two Treatments for Sleep Apnea in Veterans With Post-Traumatic Stress Disorder; URL: https://www.clinicaltrials.gov/ct/show/NCT01569022; Identifier: NCT01569022.

The effect of continuous positive airway pressure on post-traumatic stress disorder symptoms in veterans with post-traumatic stress disorder and obstructive sleep apnea: a prospective study.

OBJECTIVES: Previous retrospective studies have shown that continuous positive airway pressure (CPAP) exerts salutary effect on post-traumatic stress disorder (PTSD) symptoms and nightmare distress. The relative magnitude of therapeutic benefits from CPAP and the strength of associations between duration of CPAP use and PTSD symptomatology are unknown. METHODS: A prospective cohort design involving 47 combat veterans with PTSD and documented obstructive sleep apnea (OSA) by overnight polysomnography. Epworth Sleepiness Scale (ESS) score, PTSD checklist-Military (PCL-M), Nightmare Distress Questionnaire (NDQ), and Nightmare Frequency Questionnaire (NFQ) were administered at baseline and 3 months after CPAP therapy. Objective adherence was assessed at the 3-month follow-up. RESULTS: Twenty-two veterans with mild-to-moderate PTSD (PCL-M score 17-59) and 18 with severe-to-very-severe PTSD (PCL-M score 60-85) completed the study. There was a dose-dependent response of PCL-M to duration of CPAP usage (r = 0.45; p = 0.003). Veterans with severe-to-very-severe PTSD had a larger improvement in PTSD symptoms (d = 0.65; p = 0.004) compared with those with mild-to-moderate PTSD (d = 0.47; p = 0.04). CPAP usage was the only significant predictor of overall subjective improvement in PTSD symptoms (OR 10.5; p = 0.01). Significant changes in NDQ and NFQ scores following 3 months of treatment were observed in veterans adherent to CPAP, but the correlations with duration of CPAP use were not statistically significant (r = 0.24; p = 0.13 and r = 0.13; p = 0.4, respectively). CONCLUSIONS: Improvement of PTSD symptoms in veterans with OSA was more pronounced with prolonged use of CPAP. Adherence to treatment was linked to abatement in nightmare distress and frequency. Future investigation of multimodal treatment, including behavioral intervention combined with CPAP, is warranted.

Treatment of opioid-related central sleep apnea with positive airway pressure: a systematic review.

OBJECTIVE: To systematically review the various modalities of positive airway pressure (PAP) in the treatment of opioid-related central sleep apnea (CSA). DESIGN: Systematic review. INTERVENTIONS: MEDLINE, the Cochrane Library, and EMBASE were screened through March 2013 to identify articles which investigated treatment of opioid related CSA with PAP. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of eligible articles was assessed using a set of questions addressing both general and statistical methodologies. RESULTS: Five articles met the inclusion criteria for a total of 127 patients. All patients had been on opioids for at least 6 months. The dose ranged from 10 mg to 450 mg daily of morphine equivalent dose. Continuous positive airway pressure (CPAP) was proven mostly ineffective in reducing central apneic events. Bi-level positive airway pressure (BiPAP) with and without supplemental oxygen achieved elimination of central apneas in 62 percent of patients. Adaptive servo ventilation (ASV) yielded conflicting results with 58 percent of participants attaining a central apnea index <10 per hour. The presence of ataxic breathing predicted poor response to PAP. CONCLUSIONS: The available evidence on the efficacy of PAP in opioid-related CSA is inconclusive. With the increasing use of opioids, further studies are needed to assess optimal PAP therapy and predictors of success in this group of patients.

Survival benefit of CPAP favors hypercapnic patients with the overlap syndrome.

BACKGROUND: Patients with the combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), known as the "overlap syndrome," have a substantially greater risk of morbidity and mortality compared to those with either COPD or OSA alone. The study's objective was to report on the long-term outcome of hypercapnic (PaCO2 ≥ 45 mmHg) and normocapnic patients with the overlap syndrome treated with continuous positive airway pressure (CPAP). METHODS: A nonconcurrent cohort of consecutive patients with the overlap syndrome was followed for a median duration of 71 months (range 1-100) at a VA sleep center. All patients were managed according to the prevailing recommendations of both diseases. The end point of the study was all-cause mortality. RESULTS: Of the 271 patients identified, 104 were hypercapnic (PaCO2 = 51.6 ± 4.3 mmHg). Both normocapnic and hypercapnic patients had comparable apnea-hypopnea indexes (AHI) (29.2 ± 23.8 and 35.2 ± 29.2/h, respectively; p = 0.07) and similar adherence rates to CPAP (43 and 42 %, respectively, p = 0.9). Survival analysis revealed that hypercapnic patients who were adherent to CPAP had reduced mortality compared to nonadherent hypercapnic patients (p = 0.04). In contrast, the cumulative mortality rate for normocapnic patients was not significantly different between the adherent and the nonadherent group (p = 0.42). In multivariate analysis, the comorbidity index was the only independent predictor of mortality in normocapnic patients with the overlap syndrome [hazard ratio (HR) 1.68; p < 0.001] while CPAP adherence was associated with improved survival (HR 0.65; p = 0.04). CONCLUSIONS: CPAP mitigates the excess risk of mortality in hypercapnic patients but not in normocapnic patients with the overlap syndrome.

Positive airway pressure therapy in patients with opioid-related central sleep apnea.

PURPOSE: This study aims to compare treatment response and adherence rate to positive airway pressure (PAP) in patients with opioid-related central sleep apnea (O-CSA) and idiopathic central sleep apnea (I-CSA). METHODS: We performed a retrospective chart over a 5-year period performed at a VA sleep center. Continuous PAP (CPAP) was prescribed initially for all participants. For those nonresponders (apnea hypopnea index (AHI) of >10/h), bi-level PAP (BiPAP) or adaptive servoventilation (ASV) was instituted upon provider's discretion. Adherence to therapy was checked with the built-in meter. RESULTS: Thirty-four patients with O-CSA and 61 with I-CSA were included in the analysis. The two groups were comparable with respect to age, body mass index (BMI), Epworth Sleepiness Scale, and burden of comorbidities. The mean daily equivalent dose of morphine in the O-CSA was 168 mg (range 30-1,217 mg). In the O-CSA group, 24% of PAP-naïve patients responded to CPAP compared to 38% in the I-CSA group. BiPAP and ASV were comparable in eliminating central events in both O-CSA (66 versus 60 %) and I-CSA (93 versus 90%), respectively. Eight patients (24%) with O-CSA and six patients (10%) with I-CSA were considered nonresponders. The adherence rate was 48 and 24% in the I-CSA group compared to 23 and 18% in the O-CSA group at 3 and 12 months following initiation of effective treatment (p = 0.04 and p = 0.6). CONCLUSIONS: The presence of O-CSA does not preclude an adequate response to CPAP. Adherence rate to PAP was poor in both the O-CSA and I-CSA groups. Further studies are needed to define optimal adherence rate and long-term benefits of PAP in CSA.

Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.

PURPOSE: Clinical and epidemiologic investigations suggest a strong association between obesity and obstructive sleep apnea (OSA). The purpose of this study is to evaluate the currently available literature reporting on the effectiveness of dietary weight loss in treating OSA among obese patients. METHODS: Relevant studies were identified by computerized searches of PubMed, EMBASE, CINAHL, Web of Science, and The Cochrane Central Register of Controlled Trials through September 2011 as well as the reference lists of all obtained articles. Information on study design, patient characteristics, pre- and post-dietary weight loss measures of OSA and body mass index (BMI), and study quality was obtained. Data were extracted by two independent analysts. Weighted averages using a random-effects model are reported with 95 % confidence intervals. RESULTS: Nine articles representing 577 patients were selected. Dietary weight loss program resulted in a pooled mean BMI reduction of 4.8 kg/m(2) (95 % confidence interval [CI] 3.8-5.9). The random-effects pooled apnea hypopnea (AHI) indices at pre- and post-dietary intervention were 52.5 (range 10.0-91.0) and 28.3 events/h (range 5.4-64.5), respectively (p < 0.001). Compared to control, the weighted mean difference of AHI was decreased by -14.3 events/h (95 % CI -23.5 to -5.1; p = 0.002) in favor of the dietary weight loss programs. CONCLUSIONS: Dietary weight loss programs are effective in reducing the severity of OSA but not adequate in relieving all respiratory events. Weight reduction programs should be considered as adjunct rather than curative therapy.

Toll-like receptor activity in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to chronic inflammation and cardiovascular diseases. Considerable evidence suggests that innate immune defense mechanisms might interact with proinflammatory pathways and contribute to atherogenesis. We hypothesized that the classical pathogen recognition receptors of the innate immune response, Toll-like receptors, are involved in modulating the inflammatory response in OSA. METHODS: Expression of TLR2 and TLR4 on circulating monocytes from 29 subjects with documented OSA and 18 controls were compared with the use of flow cytometry and reverse transcription-polymerase chain reaction at baseline and after 8 weeks of continuous positive airway pressure (CPAP). RESULTS: There was a significant increase in both TLR2 and TLR4 surface expression and mRNA levels on monocytes after adjustment for age, body mass index, and waist-to-hip ratio. This was paralleled by enhanced nuclear factor-κB nuclear binding and an increased release of IL-6, INF-γ, and TNF-α in OSA versus control subjects. Following 8 weeks of treatment, continuous positive airway pressure downregulated TLR2 and TLR4 expression and abrogated the release of inflammatory cytokines. CONCLUSION: OSA is associated with enhanced expression and signaling events downstream of TLR2 and TLR4 in circulating monocytes. These observations are mitigated by CPAP therapy, which suggest that TLR2 and TLR4 activation may be involved as a signaling mechanism in immune-mediated progression of atherosclerosis in OSA.

Interval training versus continuous training in patients with chronic obstructive pulmonary disease.

PURPOSE: The purpose of this study was to compare the effects of interval training (IT) and continuous steady-pace training (CT) in patients with COPD. METHODS: Patients (n = 21) (mean forced expiratory volume in 1 second ([FEV1] = 44.6% +/- 13.9%) were randomized to IT, and 20 patients (mean FEV1 = 41.7% +/- 12.6%) to CT. Outcome measures included 6-minute walk distance, maximal work capacity, endurance exercise time during constant workload exercise at 60% to 70% of maximal work capacity, and quality of life including fatigue and dyspnea. Participants exercised 3 times per week for 8 weeks, and total work was the same for both training regimens. RESULTS: Significant improvement in mean score was observed in each variable within each of the 2 groups: 6-minute walk distance (IT = 158 +/- 178 ft, CT = 106 +/- 165 ft); maximal work capacity (IT = 10.0 +/- 13.0 W, CT = 11.5 +/- 13.1 W); endurance exercise time (IT = 15.0 +/- 12.5 minutes, CT = 18.7 +/- 10.6 minutes); and quality of life domains, fatigue (IT = 3.1 +/- 3.0, CT = 2.8 +/- 4.7), and dyspnea (IT = 4.4 +/- 5.3, CT = 5.4 +/- 5.1). There was no significant difference in the extent of improvement between the 2 training regimens for any of the outcome variables. CONCLUSION: Compared with CT, IT was well tolerated and produced similar improvements in exercise performance and quality of life.

Simulated obesity-related changes in lung volume increases airway responsiveness in lean, nonasthmatic subjects.

STUDY OBJECTIVE: To determine if obesity-related changes in lung volume might contribute to airway reactivity, we investigated the effects of simulated mild obesity-related lung volume reductions on airway responsiveness in lean, nonasthmatic subjects. PARTICIPANTS AND METHODS: We simulated the lung volume reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally mass loading the chest wall and abdomen, and shifting blood volume into the lung with lower limb compression (LLC). Airway responsiveness was assessed by measuring FEV(1) before and after methacholine challenge tests (1, 2.5, 5, 10, and 25 mg/mL) with the following: (1) no intervention (control); (2) external chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung function was measured before and after CL, LLC, and COMB were applied. RESULTS: The application of CL, LLC, and COMB decreased expiratory reserve volume, functional residual capacity, and total lung capacity compared with baseline. FVC and FEV(1) decreased significantly with CL and COMB, while FEV(1)/FVC did not change compared to baseline. The maximal response to the methacholine challenge increased with CL, LLC, and COMB, with a mean maximal fall of FEV(1) of 9%, 11%, and 18%, respectively, compared to a 6% fall with control. CONCLUSIONS: We conclude that decreases in lung volume increase airway responsiveness and may account for the increased propensity for increased airway responsiveness in the obese.

Prevalence of positional sleep apnea in patients undergoing polysomnography.

STUDY OBJECTIVES: The primary aim of this study was to determine the prevalence of positional obstructive sleep apnea using a functional definition. Positional sleep apnea was defined as a total apnea-hypopnea index (AHI) > or = 5 with a > 50% reduction in the AHI between the supine and nonsupine postures, and an AHI that normalizes (AHI < 5) in the nonsupine posture. A secondary aim was to determine if positional sleep apnea can be diagnosed accurately during a split-night study. DESIGN: Retrospective chart review. SETTING: Two sleep centers in Buffalo, NY, one a Veterans Affairs Western New York Healthcare System Sleep Center (VAWNY) and the other a freestanding ambulatory center (Associated Sleep Center [ASC]). PATIENTS: Three hundred twenty-six patients from the VAWNY, including 57 patients who underwent a split-night study and 242 patients from the ASC who underwent polysomnography. INTERVENTIONS: None. MEASUREMENTS: Patient characteristics and sleep study results. RESULTS: Positional sleep apnea was seen in 49 of 99 patients (49.5%) with mild sleep apnea (AHI, 5 to 15/h), 14 of 72 patients (19.4%) with moderate sleep apnea (AHI, 15 to 30/h), and 5 of 77 patients (6.5%) with severe sleep apnea (AHI > 30/h). Sufficient sleep (> 15 min) in both postures was not seen in 104 of 269 patients (38.7%) and 80 of 242 overnight studies (33.1%) at the VAWNY and ASC, respectively, and was not seen in 47 of 57 split-night studies (82.5%). The percentage of studies with insufficient sleep in both postures was significantly greater for split-night studies (p < 0.0001). CONCLUSIONS: Positional sleep apnea is common particularly in patients with mild disease. Positional sleep apnea cannot usually be assessed during a split-night study.

Omeprazole absorption from a compounded transdermal formulation in healthy volunteers.

OBJECTIVE: To evaluate the plasma concentration versus time profile of omeprazole following the administration of a compounded transdermal gel formulation in healthy volunteers. DESIGN: Single-dose transdermal pharmacokinetic (PK) study including a comparison with historical data from an oral PK study. SETTING: Academic clinical research center. PARTICIPANTS: Eight healthy volunteers between 18 and 50 years of age. INTERVENTIONS: Omeprazole gel 40 mg (0.8 mL) was applied to the ventral surface of the forearm covering an area of 7 x 15 cm without an occlusive dressing. Blood samples were collected just before application and then at 1, 2, 3, 4, 6, and 8 hours. Plasma concentrations of omeprazole were determined using a validated liquid chromatography tandem mass spectrometry method. MAIN OUTCOME MEASURES: PK parameters (maximal plasma concentration [C(max)], the time of C(max), [T(max)], the area under the omeprazole concentration versus time curve from 0 to 8 hours, the elimination rate constant, and the half-life of the elimination phase) following transdermal administration, compared with historical controls who had received an oral omeprazole 40 mg dose during a previous study. RESULTS: Of the eight volunteers, five had undetectable plasma omeprazole concentrations throughout the 8-hour study, precluding a complete PK analysis. For the three volunteers with detectable plasma omeprazole concentrations, the values ranged from 0.204 to 0.552 ng/mL. Including values of 0 for the patients with undetectable levels, the mean (+/- SD) C(max) was 0.153 +/- 0.241 ng/mL, and the T(max) in patients with detectable levels occurred at approximately 6 hours. The plasma concentrations following transdermal administration were approximately 1,000-fold lower than those observed with oral dosing. CONCLUSION: Transdermal absorption from a single dose of the omeprazole gel formulation used in this study was poor. This transdermal gel formulation is clearly not bioequivalent to the oral capsule.

Effect of respiratory muscle endurance training in patients with COPD undergoing pulmonary rehabilitation.

BACKGROUND: Respiratory muscle endurance training (hyperpnea training) has been shown to have beneficial effects in patients with COPD. STUDY OBJECTIVES: The purpose of this study was to determine whether hyperpnea training, when added to an endurance exercise training program, would lead to additional benefits compared with endurance training alone in patients with COPD. SETTING AND PARTICIPANTS: Patients with COPD entering an 8-week outpatient pulmonary rehabilitation program. Fifteen patients (mean [+/- SE] FEV1, 45 +/- 6% predicted) were randomized to combined therapy, and 14 patients (mean FEV1, 44 +/- 4% predicted) were randomized to endurance training. METHODS: Peak exercise capacity, exercise endurance time during constant workload cycle exercise, 6-min walk distance, quality of life as measured by the chronic respiratory questionnaire, respiratory muscle strength and endurance, and quadriceps fatigability were measured before and after endurance or combined training. RESULTS: After rehabilitation, peak exercise capacity, exercise endurance time, 6-min walk distance, and quality of life all increased in both groups, but there was no significant difference in the extent of improvement between groups. Mean respiratory muscle endurance increased to a significantly greater extent in the combined therapy group (17.5 +/- 2.7 vs 8.5 +/- 2.5 min, respectively; p = 0.02). Respiratory muscle strength was significantly increased, and quadriceps fatigability was significantly reduced after rehabilitation in the combined therapy group but not in the endurance training group, but the difference between groups did not reach statistical significance. CONCLUSION: The endurance of the respiratory muscles can be improved by specific training beyond that achieved by endurance training alone in patients with COPD. However, this improvement did not translate into additional improvement in quality of life or exercise performance.

Cytochrome P450 mRNA expression in peripheral blood lymphocytes as a predictor of enzyme induction.

OBJECTIVE: Previous reports have supported the concept that messenger ribonucleic acid (mRNA) concentrations for cytochrome P450 (CYP) enzymes in peripheral blood mononuclear cells may be predictive of systemic enzyme activity. We investigated whether changes in mRNA expression for CYP1A2,CYP2C19, CYP2D6 and CYP3A4 in peripheral blood lymphocytes (PBLs) may serve as surrogate markers for changes in CYP enzyme activity following the administration of rifampin. METHODS: On day 1 and day 9 of the study, 12 healthy volunteers were administered caffeine 100 mg, debrisoquine 10 mg and omeprazole 40 mg orally, along with midazolam 0.025 mg/kg intravenously. Blood samples and urine were collected for 8 h after drug administration. The subjects took rifampin 300 mg (n = 6) or 600 mg (n = 6) daily on days 2-8. Total RNA was isolated from PBLs on day 1 and day 9, and mRNA expression for the CYP enzymes and hGAPDH were determined by means of quantitative, real-time, reverse-transcriptase polymerase chain reaction. CYP1A2 activity was estimated by calculating the plasma paraxanthine to caffeine AUC ratio (caffeine metabolic ratio; CMR), CYP2C19 activity by the 2-h omeprazole hydroxylation index (HI), CYP2D6 activity by the urinary debrisoquine recovery ratio (DBRR) and CYP3A4 activity by midazolam clearance. RESULTS: Median midazolam clearance (0.362 to 0.740 l/kg/h), omeprazole HI (0.752 to 0.214), CMR (0.365 to 0.450) and DBRR (0.406 to 0.479) all changed significantly following rifampin, consistent with the expected enzyme induction. CYP1A2,CYP2D6 and CYP3A4 mRNA content were measurable in all samples. CYP2C19 mRNA was inconsistently detectable. There were no significant correlations between changes in enzyme activity and mRNA expression by Spearman's rank order correlation. CONCLUSION: The results do not support the use of mRNA expression assays for CYP1A2, CYP2C19, CYP2D6 and CYP3A4 enzymes in PBLs as surrogates for quantifying changes in systemic enzyme activity in the setting of enzyme induction.

Endurance and strength training in patients with COPD.

STUDY OBJECTIVES: The purpose of this study was to compare the effects of endurance training only to endurance plus strength (combined) training in a randomized trial of patients with COPD. METHODS: Twenty-four patients completed the study: 11 patients in the combined training group (FEV(1) 45 +/- 5% predicted), and 13 patients in the endurance training group (FEV(1) 40 +/- 4% predicted) [mean +/- SE]. Muscle strength, quality of life, exercise performance, and quadriceps fatigability were measured before and after rehabilitation. RESULTS: Combined training led to significant improvements in quadriceps (23.6%), hamstring (26.7), pectoralis major (17.5%), and latissimus dorsi (20%) muscle strength. Endurance training alone did not produce significant improvements in muscle strength: quadriceps (1.1% decrease), hamstring (12.2% increase), pectoralis major (7.8% increase), and latissimus dorsi (2.8% decrease). The increase in strength after training was significantly greater in the combined group compared to the endurance group for the quadriceps and latissimus dorsi muscles but not for the hamstring and pectoralis major muscles. Six-minute walk distance, endurance exercise time, and quality of life (as measured by the Chronic Respiratory Questionnaire) significantly increased in both groups after rehabilitation with no significant differences in the extent of improvement between groups. The extent of improvement in quadriceps fatigability after training (assessed by quadriceps twitch force before and after exercise) was not significantly different between groups. CONCLUSION: Strength training can lead to significant improvement in muscle strength in elderly patients with COPD. However, this improvement in muscle strength does not translate into additional improvement in quality of life, exercise performance or quadriceps fatigability compared to that achieved by endurance exercise alone.

Quadriceps fatigability after single muscle exercise in patients with chronic obstructive pulmonary disease.

The purpose of this study was to compare quadriceps fatigability in patients with varying severity of chronic obstructive pulmonary disease with age-matched control subjects. Ten healthy control subjects, 8 patients with severe disease (FEV1 less than 35% predicted), and 11 patients with mild to moderate disease were studied. The FEV1 was 1.75 +/- 0.13 L (SE), 50.4 +/- 2.9% of predicted in the mild to moderate group, and 0.87 +/- 0.06 L, 25.9 +/- 1.9% of predicted in the severe group. Quadriceps fatigue was quantified by the reduction in potentiated twitch force after a potentially fatiguing task. All subjects performed three sets of 10 maximum voluntary contractions of the right quadriceps muscle. Quadriceps maximum voluntary contraction force was 58.3 +/- 3.3 kg for the healthy older group, 49.0 +/- 4.2 kg in the mild to moderate group, and 44.3 +/- 4.7 kg in the severe group. The fall in potentiated twitch force after exercise was significantly greater in the patients with severe disease than in the healthy control subjects. In conclusion, the quadriceps in patients with severe chronic obstructive pulmonary disease are more fatigable than those in age- and sex-matched healthy control subjects.

Quadriceps fatigue after cycle exercise in patients with COPD compared with healthy control subjects.

STUDY OBJECTIVES: Quadriceps fatigue can occur in patients with COPD after exhaustive cycle exercise. The purpose of this study was to determine whether the degree of fatigue elicited by cycle exercise was greater in patients with COPD compared with matched control subjects. SUBJECTS: Nine male patients with COPD with a mean (+/- SE) age of 66 +/- 3 years and mean FEV(1) values of 1.31 +/- 0.15 L and 36 +/- 5% predicted were compared to nine healthy male subjects with a mean age of 66 +/- 2 years. METHODS: Patients with COPD exercised at 60% of peak work capacity until exhaustion. Healthy elderly subjects exercised at a workload that was chosen to produce a similar absolute oxygen uptake (O(2)) during constant-load exercise as that obtained by the patients with COPD. Quadriceps fatigue was detected by measuring twitch force (unpotentiated twitch force [TwQu] and potentiated twitch force [TwQp]) before and after cycle exercise. RESULTS: Patients with COPD exercised for a mean duration of 8.4 +/- 1.8 min. O(2) during exercise was 50 +/- 6% of predicted. The healthy elderly control subjects exercised for 10 min, generating a O(2) of 48 +/- 1% predicted. TwQu fell significantly postexercise in the patients with COPD but not in the matched control subjects. TwQp fell significantly postexercise in both groups, but the fall in TwQp postexercise was significantly greater in the patients with COPD. CONCLUSION: For the same absolute O(2) and duration of cycle exercise, the amount of fatigue elicited was significantly greater in the patients with COPD compared to age-matched healthy control subjects.

Comparison of potentiated and unpotentiated twitches as an index of muscle fatigue.

Recent data suggest that the potentiated twitch is a more sensitive index of contractile fatigue than is the unpotentiated twitch. We hypothesized that after a potentially fatiguing load, the fall in twitch amplitude of the potentiated twitch would be significantly greater than that of an unpotentiated twitch. We compared the response of the potentiated and unpotentiated twitches to a series of potentially fatiguing loads using magnetic stimulation of the femoral nerve in 10 healthy subjects. The baseline unpotentiated quadriceps twitch force (TwQu), potentiated quadriceps twitch force (TwQp), and maximal voluntary contraction (MVC) were 129 plus minus 6 N, 198 plus minus 6 N, and 622 plus minus 25 N, respectively. During a fatigue protocol that was designed to induce a spectrum of fatigue from mild to marked, the percent fall in quadriceps twitch force was significantly greater for the potentiated method than for the unpotentiated method at all levels of fatigue (P <.005). The within-subject within-day coefficient of variation was 7.5 plus minus 0.5% for TwQu and 5.6 plus minus 0.9% for TwQp. Thus, TwQp is reproducible and is superior to TwQu for detecting early muscle fatigue.

Bilateral anterolateral magnetic stimulation of the phrenic nerves can detect diaphragmatic fatigue.

BACKGROUND AND STUDY OBJECTIVES: Measurement of twitch transdiaphragmatic pressure (TwPdi) during bilateral phrenic nerve stimulation is presently the best method to detect diaphragmatic fatigue in humans. The stimulation methods that are currently employed (ie, transcutaneous electrical stimulation [TES] and cervical magnetic stimulation [CMS]) have limitations. Bilateral anterolateral magnetic stimulation of the phrenic nerves (BAMPS) was recently described. The purpose of this study was to determine whether BAMPS can reliably detect diaphragmatic fatigue, and to compare the results with BAMPS with those obtained with the other stimulation techniques. SUBJECTS: Twelve healthy subjects participated in the study. METHODS: TwPdi was measured during TES, CMS, and BAMPS before and 10, 30, and 60 min after a potentially fatiguing task. Voluntary hyperpnea to task failure was used as the fatiguing task because this task has previously been shown to reliably produce contractile fatigue of the diaphragm. To determine the reproducibility of BAMPS, TwPdi was measured before and after a nonfatiguing task in 10 of the subjects. RESULTS: TwPdi fell significantly after the hyperpneic task with all three stimulation techniques, and the amount by which TwPdi fell after hyperpnea was not significantly different for the different stimulation techniques. The percentage fall in TwPdi after hyperpnea was significantly correlated between stimulation techniques (CMS vs BAMPS, r = 0.72; TES vs BAMPS, r = 0.84; and TES vs CMS, r = 0.67). The mean (+/- SE) within-subject, between-trial coefficient of variation for TwPdi during BAMPS was 5.1 +/- 0.1%. CONCLUSION: BAMPS is highly reproducible and at least as good at detecting diaphragmatic fatigue as the other stimulation techniques.