Publications
655 results found
Apps M, Walsted E, Pavitt M, et al., 2017, Time-course of changes to intrathoracic pressure induced by CPAP in normal subjects, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Pavitt MJ, Nevett J, Swanton LL, et al., 2017, Choking in London, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Patel S, Nolan CM, Barker RE, et al., 2017, Rectus femoris cross-sectional area in COPD: are there functionally relevant cut-points?, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Demeyer H, Waschki B, Polkey M, et al., 2017, The survival effect of physical activity in patients with COPD: every step counts, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Faisal A, Sadaka AS, Purcell H, et al., 2017, Reduced ventilatory efficiency and muscle endurance in smokers with normal spirometry, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Mohan D, Allinder M, Forman J, et al., 2017, Late Breaking Abstract - Co-morbid disease clusters in chronic obstructive pulmonary disease: the ERICA study, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Pavitt M, Swanton L, Hind M, et al., 2017, Effectiveness of approaches to choking due to foreign body airway obstruction - a physiological study, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
farre garros, paul R, connolly M, et al., 2017, miR-542 promotes mitochondrial dysfunction and SMAD activity and is raised in ICU Acquired Weakness, American Journal of Respiratory and Critical Care Medicine, Vol: 196, Pages: 1-12, ISSN: 1073-449X
Rationale: Loss of skeletal muscle mass and function is a common consequence of critical illness and a range of chronic diseases but the mechanisms by which this occurs are unclear. Objectives: We aimed to identify miRNAs that were increased in the quadriceps of patients with muscle wasting and to determine the molecular pathways by which they contributed to muscle dysfunction. Methods: miR-542-3p/-5p were quantified in the quadriceps of patients with COPD and intensive care unit acquired weakness (ICUAW). The effect of miR-542-3p/5p was determined on mitochondrial function and TGF-β signaling in vitro and in vivo. Measurements and main results: miR-542-3p/5p were elevated in patients with COPD but more markedly in patients with ICUAW. In vitro, miR-542-3p suppressed the expression of the mitochondrial ribosomal protein MRPS10, and reduced 12S rRNA expression suggesting mitochondrial ribosomal stress. miR-542-5p increased nuclear phospho-SMAD2/3 and suppressed expression of SMAD7, SMURF1 and PPP2CA, proteins that inhibit or reduce SMAD2/3 phosphorylation suggesting that miR-542-5p increased TGF-β signaling. In mice, miR-542 over-expression caused muscle wasting, reduced mitochondrial function, 12S rRNA expression and SMAD7 expression, consistent with the effects of the miRNAs in vitro. Similarly, in patients with ICUAW, the expression of 12S rRNA and of the inhibitors of SMAD2/3 phosphorylation were reduced, indicative of mitochondrial ribosomal stress and increased TGF-β signaling. In patients undergoing aortic surgery, pre-operative levels of miR-542-3p/5p were positively correlated with muscle loss following surgery. Conclusion; Elevated miR-542-3p/5p may cause muscle atrophy in ICU patients through the promotion of mitochondrial dysfunction and activation of SMAD2/3 phosphorylation.
Mesquita R, Spina G, Pitta F, et al., 2017, Physical activity patterns and clusters in 1001 patients with COPD, Chronic Respiratory Disease, Vol: 14, Pages: 256-269, ISSN: 1479-9723
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.
Buttery SC, Mohan D, Fisk M, et al., 2017, Longitudinal follow-up of quadriceps strength and function in a COPD cohort after 3 years, European Respiratory Journal, Vol: 50, ISSN: 0903-1936
Polkey MI, Man W, 2017, Should we get sniffy about Maximal Inspiratory Pressure?, Chest, Vol: 152, Pages: 6-7, ISSN: 1931-3543
Respiratory muscle weakness either occurs in isolation or as part of a more generalised neuromuscular process. In the former case this is very often self limiting as, for example, after iatrogenic damage to the phrenic nerve or in the case of neuralgic amyotrophy. In the latter case patients will usually have evidence of limb muscle involvement and or a known diagnosis (notable exceptions however being Pompe’s disease and about 3% of amyotrophic lateral sclerosis, ALS, presentations). From this conjecture follow the two main reasons why clinicians request evaluation of inspiratory muscle strength; either to rule-in or rule-out inspiratory muscle weakness as a cause of symptoms or to predict prognosis (or the need for non-invasive ventilation). MIP has also frequently been used as an outcome measure for trials of inspiratory muscle training.
Murphy PB, Rehal S, Arbane G, et al., 2017, Effect of home noninvasive ventilation with oxygen therapy vs oxygen therapy alone on hospital readmission or death after an acute COPD exacerbation A randomized clinical trial, JAMA: Journal of the American Medical Association, Vol: 317, Pages: 2177-2186, ISSN: 0098-7484
Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death.Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation.Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible.Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute.Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI.Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR
Coello C, Fisk M, Mohan D, et al., 2017, Quantitative analysis of dynamic F-18-FDG PET/CT for measurement of lung inflammation, EJNMMI RESEARCH, Vol: 7, ISSN: 2191-219X
Background:An inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, is present in some patients with chronic obstructive pulmonary disease (COPD). Thoracic fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has been proposed as a promising imaging biomarker to assess this inflammation. We sought to introduce a fully quantitative analysis method and compare this with previously published studies based on the Patlak approach using a dataset comprising 18F-FDG PET scans from COPD subjects with elevated circulating inflammatory markers (fibrinogen) and matched healthy volunteers (HV). Dynamic 18F-FDG PET scans were obtained for high-fibrinogen (>2.8 g/l) COPD subjects (N = 10) and never smoking HV (N = 10). Lungs were segmented using co-registered computed tomography images and subregions (upper, middle and lower) were semi-automatically defined. A quantitative analysis approach was developed, which corrects for the presence of air and blood in the lung (qABL method), enabling direct estimation of the metabolic rate of FDG in lung tissue. A normalised Patlak analysis approach was also performed to enable comparison with previously published results. Effect sizes (Hedge’s g) were used to compare HV and COPD groups.Results:The qABL method detected no difference (Hedge’s g = 0.15 [−0.76 1.04]) in the tissue metabolic rate of FDG in the whole lung between HV (μ = 6.0 ± 1.9 × 10−3 ml cm−3 min−1) and COPD (μ = 5.7 ± 1.7 × 10−3 ml cm−3 min−1). However, analysis with the normalised Patlak approach detected a significant difference (Hedge’s g = −1.59 [−2.57 −0.48]) in whole lung between HV (μ = 2.9 ± 0.5 ×&
To M, Swallow EB, Akashi K, et al., 2017, Reduced HDAC2 in skeletal muscle of COPD patients, Respiratory Research, Vol: 18, ISSN: 1465-993X
BACKGROUND: Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(HDAC) in skeletal muscle weakness in COPD. METHODS AND RESULTS: Twelve COPD patients, 8 smokers without COPD (SM) and 4 healthy non-smokers (NS) were recruited to the study. HDAC2 protein expression in quadriceps muscle biopsies of COPD patients (HDAC2/β-actin: 0.59 ± 0.34) was significantly lower than that in SM (1.9 ± 1.1, p = 0.0007) and NS (1.2 ± 0.7, p = 0.029). HDAC2 protein in skeletal muscle was significantly correlated with forced expiratory volume in 1 s % predicted (FEV1 % pred) (rs = 0.53, p = 0.008) and quadriceps maximum voluntary contraction force (MVC) (rs = 0.42, p = 0.029). HDAC5 protein in muscle biopsies of COPD patients (HDAC5/β-actin: 0.44 ± 0.26) was also significantly lower than that in SM (1.29 ± 0.39, p = 0.0001) and NS (0.98 ± 0.43, p = 0.020). HDAC5 protein in muscle was significantly correlated with FEV1 % pred (rs = 0.64, p = 0.0007) but not with MVC (rs = 0.30, p = 0.180). Nuclear factor-kappa B (NF-κB) DNA binding activity in muscle biopsies of COPD patients (10.1 ± 7.4) was significantly higher than that in SM (3.9 ± 7.3, p = 0.020) and NS (1.0 ± 1.2, p = 0.004and significantly correlated with HDAC2 decrease (rs = -0.59, p = 0.003) and HDAC5 (rs = 0.050, p = 0.012). HDAC2 knockdown by RNA interfe
Nolan CM, Maddocks M, Canavan JL, et al., 2017, Pedometer Step Count Targets during Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease A Randomized Controlled Trial, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 195, Pages: 1344-1352, ISSN: 1073-449X
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- Citations: 56
Nolan CM, Kon SSC, Patel S, et al., 2017, Gait speed and pedestrian crossings in COPD., Thorax, Vol: 73, Pages: 191-192, ISSN: 1468-3296
The assumed minimum walking speed at pedestrian crossings is 1.2 m/s. In this prospective cohort study, usual walking speed was measured over a 4 m course in 926 community-dwelling, ambulatory patients with stable COPD. Mean (SD) walking speed was 0.91 (0.24) m/s with only 10.7% walking at a speed equal or greater than 1.2 m/s. In order for 95% of this cohort to safely negotiate a pedestrian cross, traffic lights would have to assume a minimum walking speed of 0.50 m/s (2.4 times longer than current times). The current assumed normal walking speed for pedestrian crossings is inappropriate for patients with COPD.The studies were registered on clinicaltrials.gov and these data relate to the pre-results stage: NCT01649193, NCT01515709 and NCT01507415.
Maddocks M, Delogu V, Jones SE, et al., 2017, Exercise Training Versus Neuromuscular Stimulation in Severe Chronic Obstructive Pulmonary Disease, ARCHIVOS DE BRONCONEUMOLOGIA, Vol: 53, Pages: 357-359, ISSN: 0300-2896
Hind M, Polkey MI, Simonds AK, 2017, Homeward bound: a centenary of home mechanical ventilation, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1140-1149, ISSN: 1073-449X
The evolution of home mechanical ventilation is an intertwined chronicle of negative and positive pressure modes and their role in managing ventilatory failure in neuromuscular diseases and other chronic disorders. The uptake of noninvasive positive pressure ventilation has resulted in widespread growth in home ventilation internationally and fewer patients being ventilated invasively. As with many applications of domiciliary medical technology, home ventilatory support has either led or run in parallel with acute hospital applications and has been influenced by medical and societal shifts in the approach to chronic care, the creation of community support teams, a preference of recipients to be treated at home, and economic imperatives. This review summarizes the trends and growing evidence base for ventilatory support outside the hospital.
Lee J, Donaldson AV, Lewis A, et al., 2017, Circulating miRNAs from imprinted genomic regions are associated with peripheral muscle strength in COPD patients, European Respiratory Journal, Vol: 49, Pages: 1-4, ISSN: 1399-3003
Hind M, Jordan S, Hansell DM, et al., 2017, A man with progressive type II respiratory failure, Lancet Respiratory Medicine, Vol: 5, Pages: 456-456, ISSN: 2213-2600
Pavitt MJ, Swanton LL, Hind M, et al., 2017, Choking on a foreign body: a physiological study of the effectiveness of abdominal thrust manoeuvres to increase thoracic pressure, THORAX, Vol: 72, Pages: 576-578, ISSN: 0040-6376
The Heimlich manoeuvre is a well-known intervention for the management of choking due to foreign body airway occlusion, but the evidence base for guidance on this topic is limited and guidelines differ. We measured pressures during abdominal thrusts in healthy volunteers. The angle at which thrusts were performed (upthrust vs circumferential) did not affect intrathoracic pressure. Self-administered abdominal thrusts produced similar pressures to those performed by another person. Chair thrusts, where the subject pushed their upper abdomen against a chair back, produced higher pressures than other manoeuvres. Both approaches should be included in basic life support teaching.
Demeyer H, Louvaris Z, Frei A, et al., 2017, Physical activity is increased by a 12 week semi-automated telecoaching program in patients with COPD, a multicenter randomized controlled trial, Thorax, Vol: 72, Pages: 415-423, ISSN: 1468-3296
RationaleReduced physical activity (PA) in patients with COPD is associated with a poor prognosis. Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group. ObjectivesTo investigate the effectiveness of a 12 week semi-automated telecoaching intervention on PA in COPD patients in a multicenter European RCT. Methods343 patients from 6 centers, including a wide disease spectrum, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014. This 12 weeks intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application. The latter provided an individualized daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators. Physical activity was measured using accelerometry during 1 week preceding randomization and during week 12. Secondary outcomes included exercise capacity and health status. Analyses were based on intention-to-treat.Main resultsBoth groups were comparable at baseline in terms of factors influencing PA. At 12 weeks, the intervention yielded a between group difference of mean, 95% [ll-ul] +1469, 95% [971 – 1965] steps.day-1 and +10.4, 95% [6.1 - 14.7] min.day-1 moderate physical activity; favoring the IG (all p≤0.001). The change in six minute walk distance was significantly different (13.4, 95% [3.40 - 23.5]m, p<0.01), favoring the IG. In IG patients an improvement could be observed in the functional state domain of the CCQ (p=0.03), when compared to UCG. Other health status outcomes did not differ.ConclusionsThe amount and intensity of PA can be significantly increased in COPD patients using a 12 week semi-automated telecoaching intervention including a stepcounter and an application installed on a smartphone.
Schoser B, Fong E, Geberhiwot T, et al., 2017, Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: a comprehensive review of the literature, ORPHANET JOURNAL OF RARE DISEASES, Vol: 12, ISSN: 1750-1172
Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure. Our analysis supports the utility of MIP for the early evaluation of respiratory muscle strength, especially of the diaphragm, in patients with NMD and as a surrogate endpoint in clinical trials of therapies for NMD.
Boutou AK, Franks R, Mohan D, et al., 2017, Exercise-induced changes in QT interval are smaller in COPD patients and have no impact on mortality, European Respiratory Journal, Vol: 49, ISSN: 0903-1936
Kon SSC, Jolley CJ, Shrikrishna D, et al., 2017, ACE and response to pulmonary rehabilitation in COPD: two observational studies, BMJ Open Respiratory Research, Vol: 4, ISSN: 2052-4439
IntroductionSkeletal muscle impairment is an important feature of chronic obstructive pulmonary disease (COPD). Renin-angiotensin system activity influences muscle phenotype, so we wished to investigate whether it affects the response to pulmonary rehabilitation.MethodsTwo studies are described; in the first, the response of 168 COPD patients (mean FEV1 51.9%predicted) to pulmonary rehabilitation was compared between different ACE Insertion/Deletion polymorphism genotypes. In a second, independent COPD cohort (n=373), baseline characteristics and response to pulmonary rehabilitation were compared between COPD patients who were or were not taking angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor antagonists (ARB).ResultsIn study 1, the incremental shuttle walk distance improved to a similar extent in all three genotypes; DD/ID/II (n=48/91/29) 69(67)m, 61(76)m, 78(78)m respectively (p>0.05). In the second study, fat free mass index was higher in those on ACE-I/ARB (n=130) than those who were not (n=243) 17.8(16.0, 19.8)kgm-2 vs 16.5(14.9,18.4) kgm-2 (p<0.001). However change in fat free mass, walking distance or quality of life in response to pulmonary rehabilitation did not differ between groups.ConclusionWhile these data support a positive association of ACE-I/ARB treatment and body composition in COPD, neither treatment to reduce ACE activity nor ACE(I/D) genotype influence response to pulmonary rehabilitation.
Alqurashi Y, Moss J, Nakamura T, et al., 2017, The Efficacy Of In-Ear Electroencephalography (eeg) To Monitor Sleep Latency And The Impact Of Sleep Deprivation, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Polkey M, Qiu Z, Zhou L, et al., 2017, Comparison Of The Adjunctive Effects Of Tai Chi And Pulmonary Rehabilitation On The Effect Of Indacaterol In Treatment Naive Patients With COPD, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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Hopkinson NS, Polkey, Shah P, et al., 2016, Endobronchial valves for patients with heterogeneous emphysema and without interlobar collateral ventilation – open label treatment following the BeLieVeR-HIFi study, Thorax, Vol: 72, Pages: 277-279, ISSN: 1468-3296
Outcomes in early trials of bronchoscopic lung volume reduction using endobronchial valves for the treatment of patients with advanced emphysema were inconsistent. However improvements in patient selection with focus on excluding those with interlobar collateral ventilation and homogeneous emphysema resulted in significant benefits in the BeLieVeR-HIFi study compared to sham treated controls. In this manuscript we present data from the control patients in the BeLieVeR-HIFi study who went on to have open label endobronchial valve treatment after completion of the clinical trial (n=12), combined with data from those in the treatment arm who did not have collateral ventilation (n=19). Three months after treatment the forced expiratory volume in the 1st second increased by 27.3(36.4)%, residual volume reduced by 0.49(0.76)L, the 6 minute walk distance increased by 32.6(68.7) m, and the St George Respiratory Questionnaire for COPD score improved by 8.2(20.2) points. These data extend the evidence for endobronchial valve placement in appropriately selected patients with COPD.
Nolan CM, Maddocks M, Canavan JL, et al., 2016, Pedometer step count targets during pulmonary rehabilitation in COPD: a randomized controlled trial, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1344-1352, ISSN: 1535-4970
RATIONALE: Increasing physical activity is a key therapeutic aim in COPD. Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence regarding its ability to improve physical activity levels. OBJECTIVE: To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate intensity physical activity (time ≥ 3METs) in people with COPD. METHODS: In this single-blinded randomized controlled trial, participants were assigned 1:1 to receive control (PR comprising 8 weeks, two supervised sessions/week) or intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 weeks). The randomisation process used minimisation to balance groups for age, sex, FEV1 % predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was by intention-to-treat and the trial registered with clinicaltrials.gov (Ref. NCT01719822). MEASUREMENTS: The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time ≥3METs. MAIN RESULTS: 152 participants (72% male; mean (SD) FEV1 % predicted 50.5 (21.2); median (Q1, Q3) time ≥3METS 46 (21, 92) minutes) were enrolled to intervention (n=76) or control (n=76). There was no significant difference in change in time ≥3METs between the intervention and control groups at 8 weeks (median (Q1, Q3) difference 0.5 (-1.0, 31.0) minutes; p=0.87) or at the 6 month follow-up (7.0 (-9, 27) minutes; p=0.16). CONCLUSION: Pedometer-directed step count targets during an outpatient PR program did not enhance moderate intensity physical activity levels in people with COPD. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01719822.
Curtis KJ, Meyrick VM, Mehta B, et al., 2016, Angiotensin-converting enzyme inhibition as an adjunct to pulmonary rehabilitation in COPD, American Journal of Respiratory and Critical Care Medicine, Vol: 194, Pages: 1349-1357, ISSN: 1535-4970
Rationale: Epidemiological studies in older individuals have found an association between use of ACE-inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation. Objectives: We investigated the hypothesis that enalapril, an ACE-inhibitor, would augment the improvement in exercise capacity seen during pulmonary rehabilitation. Methods: We performed a double-blind, placebo-controlled, parallel-group randomised controlled trial. COPD patients, with at least moderate airflow obstruction and taking part in pulmonary rehabilitation, were randomised to either 10 weeks therapy with an ACE-inhibitor (10mg enalapril) or placebo. Measurements: The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Main Results: Eighty patients were enrolled, seventy-eight randomised (age 67±8years, FEV1 48±21% predicted), and sixty-five completed the trial (34 placebo, 31 ACE-inhibitor). The ACE-inhibitor treated group demonstrated a significant reduction in systolic blood pressure (Δ-16mmHg, 95% CI -22 to -11) and serum ACE activity (Δ-18IU/L, 95% CI -23 to -12) versus placebo (between group differences p<0.0001). Peak power increased significantly more in the placebo group (placebo Δ+9 Watts, 95% CI 5 to 13 vs. ACE-I Δ+1 Watt, 95% CI -2 to 4, between group difference 8 Watts, 95% CI 3 to 13, p=0.001). There was no significant between group difference in quadriceps strength or health-related quality of life. Conclusion: Use of the ACE-inhibitor enalapril alongside a programme of pulmonary rehabilitation, in patients without an established indication for ACE-inhibition, reduced the peak work rate response to exercise training in COPD patients. Clinical trial registration available at www.controlled-trials.com, ID ISRCTN79038750.
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