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Background: Frailty is prevalent in patients awaiting lung transplant (LTx) and is associated with delisting, death while on the waiting list and death after LTx. Decreasing frailty of LTx-candidates could therefore be important to improve pre- and post-LTx-status. Objective: Primary aim was to investigate the effects of a comprehensive PR-program on physical frailty in LTx-candidates. Methods: 32 participants from an inpatient PR-program with a confirmed diagnosis of COPD or interstitial lung disease who were listed or were in the process to be listed for a LTx were consecutively included in this trial. Primary outcome was the change in physical frailty measured by short physical performance battery test (SPPB; score 0-12) performed at PR-admission and discharge. SPPB results can be categorized into frail (SPPB≤7), pre-frail (SPPB=8-9) and not-frail (SPPB≥10). Participants with an SPPB score≤11 were considered for final analyses. Results: 28 participants (60±5years; FEV1 49±26%pred., SPPB-baseline: frail: n=5 [17.9%], pre-frail: n=10 [35.7%]; not-frail: n=13 [46.4%]) were analysed. Baseline SPPB-score (8.8±2.2) significantly (p Conclusion: Our findings show that a comprehensive PR-program can significantly and to a clinically meaningful extent, reduce frailty in LTx-candidates.

Background: Whole-body vibration training (WBVT) performed on a vibration platform can significantly improve physical performance in COPD patients. It has been suggested that an important mechanism of this improvement is based on an improvement in balance. Aim of this study was to investigate the effects of WBVT versus conventional balance training on exercise performance. Methods: 48 patients with severe COPD (FEV1: 37±7 %pred.) and low exercise performance (6-minute walk distance (6MWD): 55±10 %pred.) were included in a randomized controlled trial during a 3-week inpatient pulmonary rehabilitation. All patients completed a standardized endurance and strength training program. Additionally, patients performed 4 different balance exercises 3x/week for 2x1 minute each either on a vibration platform (Galileo) at varying frequencies (5 - 26 Hz) (WBVT) or on a conventional therapy tool inducing an instable surface (CON). Results: 6MWD improved significantly in both groups (WBVT: 48±46m, p Conclusion: WBVT can improve balance and muscular performance significantly more compared to conventional balance training.

Patients with idiopathic pulmonary fibrosis (IPF) and concurrent hypoxaemia should be treated with oxygen therapy [1]. Oxygen therapy is commonly given by conventional nasal cannulas (CNC), but can also be delivered by other less conventional cannulas such as the Oxymizer. The Oxymizer is a nasal cannula with an internal pendant reservoir incorporated in the lumen at the patient end which has the potential to provide increased oxygenation while using the same oxygen setting as one would with CNC [2]., Something simple, like changing a nasal cannula for a technologically superior one, can improve exercise capacity and oxygenation in patients with IPF. There is a need to develop improved cannulas for comfort and patient acceptance. https://bit.ly/2NelacE

Background: International guidelines recommend the use of supplemental oxygen (O2) in IPF patients who suffer from exercise-induced hypoxemia (EIH). As short-term effects of O2 during exercise are not known in IPF patients yet, the aim of our study was to investigate the effects of O2 on the endurance walking capacity in hypoxemic IPF patients. Methods: 53 IPF patients with EIH were investigated in a prospective double-blinded randomized-controlled cross-over trial. Following an initial incremental shuttle walk test (ISWT) which assess the individual maximum gait speed, each patient performed 3 endurance shuttle walk tests (ESWT) at 85%max under following conditions: (A) with medical air (compressed room air)(ESWTMA), (B) with 2 liters/min O2 (ESWT2L) and (C) with 4 liters/min O2 (ESWT4L). Walking endurance time during ESWT was the primary outcome. Data of secondary outcomes (oxygen saturation [SpO2], heart rate [HR], breathing frequency [BF]) were compared at the end of the shortest ESWT ("isotime"). Results: 50 patients (69 y, FVC 72%pred., DLCO 33%pred., ISWT: 389m) completed the study. Endurance walking time was longer during ESWT4L> ESWT2L >ESWTMA (585 sec vs. 462 sec vs. 404 sec, F=3.483, p=0.03). SpO2ISO was higher by breathing O2 and by using a higher flow rate (ESWT4L 88% vs. ESWT2L 85% vs. ESWTMA 80%, F=123.204, p Discussion: O2 showed significant and clinically relevant benefits on walking capacity and oxygen saturation compared to compressed room air in IPF patients with EIH. A dose-dependent effect has been found showing higher vs. lower oxygen flow rates to be more beneficial.

Background: In patients with IPF exercise intolerance is often associated with hypoxemia. Therefore, SOT may be offered. The Oxymizer® is a nasal cannula incorporating an internal reservoir with the potential to deliver higher oxygen (O2) doses to the patient on the same O2-flow compared to a conventional nasal cannula (CNC). Objectives: Primary aim was to investigate the effects of SOT delivered via Oxymizer compared to a CNC in hypoxemic IPF-patients on walking capacity. Secondary aim was to evaluate the effects on O2-saturation (SpO2), heart- and breathing rate at isotime (end of shortest endurance shuttle walk test; ESWT). Methods: 26 patients with a confirmed diagnosis of IPF and SOT-indication during exercise were consecutively included in this trial. After an initial incremental shuttle walk test, patients performed, in randomized order and with a 24h-resting period between tests, two ESWTs - one with Oxymizer and one with CNC. Results: 22 patients (70±7years; VC:54±15%/pred) completed all tests. Walking capacity was significantly greater while using the Oxymizer compared to CNC (523±369vs.419±332sec, p=0.027). 15 patients (68%) walked longer with the Oxymizer. At isotime, SpO2 (81.6±8.8 vs.78.5±8.1%, p=0.001) was significantly higher while heart- (112±16vs.118±13bpm) and breathing rate (38±8vs.41±8bpm) were significantly (p Conclusion: SOT when provided by the Oxymizer showed significant and clinically relevant benefits on walking capacity in IPF-patients by improving physiological parameters. However, only 8 (36%) patients would prefer the Oxymizer for their daily use.

Background: Dynamic hyperinflation (DH) can occur during exercise in people with stable COPD and is associated with increased dyspnoea and reduced exercise capacity. While NIV during exercise can improve endurance time, the effect of NIV on IC (a DH marker) is unclear. Objective: To determine the effect of NIV on IC and Tlim in patients with COPD during constant load cycle exercise. Method: 20 patients with severe COPD (FEV1:32±4%pred, RV/TLC:163±29%) and who showed DH during a peak cycle test, in one day, performed three cycle endurance tests at 75% peak work rate to exhaustion, in random order: no NIV, standard NIV (expiratory positive airway pressure (EPAP) 5cmH2O), titrated NIV (individualised EPAP to maximise IC at rest). Metabolic variables, breathing pattern, oxygen saturation (SpO2), transcutaneous carbon dioxide (TcCO2), heart rate and muscular oxygenation (SmO2) (via NIRS) were measured continuously. IC and dyspnoea were measured each minute. Results: Tlim and isotime change in IC (∆IC) were significantly increased (Table 1) with standard and titrated NIV during exercise vs no NIV. In both NIV tests, TcCO2, SpO2 and SmO2 were significantly improved. There were no differences between NIV tests. Conclusion: When using NIV compared to no NIV, stable patients with severe COPD had clinically improved exercise endurance time and significantly reduced DH at isotime

Background: Pulmonary rehabilitation (PR) has been shown to improve cognitive performance in COPD patients even after adjusting for sociodemographic factors. This favourable effect of PR, however, has not been evaluated in COPD lung-transplant (LTx) recipients where immunosuppressant toxicity and/or central nervous system events may be associated with cognitive decline. We investigated the effects of PR on cognitive function in LTx-recipients for COPD. Methods: Twenty-four COPD LTx-recipients (FEV1: 75±22%pred.) were assigned to a 3-week inpatient PR program. A comprehensive neuropsychological battery was used to assess memory, learning skills, attention/ flexibility, visuospatial abilities, psychomotor speed and behavioural activation before and after PR. The magnitude of changes was interpreted by d-Effect Size (ES). Results: In response to PR, LTx-recipients presented small to large improvements (ES range: 0.23 to 1.00, all p ≤0.34) in 50% of the administered cognitive tests. Learning skills and memory ability presented the greatest benefits (Composite scores ES: 0.31 and 0.62; Figure1) that remained similar after stratification by single or bilateral LTx, and sex. Conclusions: PR has a beneficial effect on cognitive function improving memory, learning skills and psychomotor speed in post-transplant phase. Improvements in cognitive function may facilitate recovery in COPD LTx-recipients.

Background: Previous research has calculated the minimal important difference (MID) for the 1-minute sit-to-stand test (1-STST) in patients with COPD to be three repetitions and stated that the 1-STST could be an alternative to the traditional 6-minute walk test (6MWT) to measure exercise performance. Objective: The aim of our study was to prospectively estimate the MID for the 1-STST in response to a 3-week inpatient pulmonary rehabilitation program (PR) in patients with advanced COPD. Methods: 95 patients with COPD (66±8years; FEV1: 37±12%/pred.;1-STST: 19.3±6.9reps) were included in this observational study (NCT02708719). At PR-start and PR-end patients performed a 1-STST on a force platform. Patients also performed two 6MWTs and filled out the chronic respiratory questionnaire (CRQ) for performing an anchor based method. Additionally, difference distribution based methods were used to estimate the MID. Results: An anchor based method could not be used due to the lack of properly associated anchors. Neither the change in 6MWD, nor the changes in the CRQ scores correlated well with the change in 1-STST (all r Conclusion: Results from this study estimated the MID for the 1-STST after PR to be between 2.03 and 3.45 repetitions in this specific population. However, since the change in 1-STST only correlated weakly with the change in 6MWD (r=0.21) it can be assumed that the 1-STST and the 6MWT may measure different qualities of exercise performance.

Background: Demand oxygen delivery systems (DODS) prolong oxygen cylinder life compared to continuous flow (CONT) use, however evidence regarding their effects during use is lacking. Methods: Four databases were searched from 1980 - Jan 2018. Outcomes were oxyhaemoglobin saturation (SpO2%) at rest and during exercise and exercise performance. Risk of bias was evaluated using the Cochrane tool. Data were analyzed via meta-analysis where possible using the generic inverse variance method in Revman 5.3 and narrative synthesis. Results: 10 randomized crossover trials involving 152 COPD patients (FEV1 range 27-42% pred) were included. There was a large degree of uncertainty regarding potential bias related to allocation concealment and blinding for all studies. Data from 3 studies (n=44) showed no significant differences between DODS and CONT in terms of SpO2% at rest or during exercise (Figure). The pooled mean difference in 6-minute walk distance was 3.7m (95%CI -3.0 to 10.3; 2 studies; n=56). Findings were consistent between the meta-analysis and narrative synthesis. Conclusion: DODS and CONT appear to confer similar effects in terms of SpO2% or exercise performance for people with COPD. SpO2% testing may still be indicated for those considering DODS due to intra-individual differences that may arise from different DODS specifications.

Introduction: Dynamic hyperinflation (DHI), an increase in end-expiratory lung volume, can occur during exercise among people with COPD and can be measured by a reduction in inspiratory capacity (IC). No studies have evaluated the use of metronome paced tachypnoea (MPT) as a measurement of DHI against both an incremental peak cycle test (INC) and a constant work rate cycle test (CWR), which is more representative of daily physical activity. Aim: To compare DHI during MPT to DHI in an INC and a CWR. Methods: People with COPD and resting hyperinflation (RV/TLC > 110%) were recruited. Participants performed an MPT, INC and CWR with breath-by-breath measures. In the MPT test, participants performed an IC manoeuvre at rest and after 30 seconds of MPT at twice the resting respiratory rate (RR) with a 1:1 ratio. CWR was performed at 75% peak INC work rate. Both cycle tests were terminated at volitional fatigue. An IC manoeuver was performed before and at end exercise for the INC and CWR tests. Results: Nine participants completed the study. MPT resulted in a significantly smaller IC and higher RR when compared with INC and CWR (Table). There was a non-significant correlation between IC during MPT and INC (r=-0.21 p>0.05) and MPT and CWR (r=0.52 p>0.05). Conclusion: MPT resulted in a smaller IC (i.e greater DHI) and a higher RR than INC or CWR. There was no relationship between the degree of DHI during MPT and that during either INC or CWR and thus MPT may not be able to predict the extent of DHI in exercise.

Background The benefits of pulmonary rehabilitation (PR) on fatigue-resistant skeletal muscle fibre type I have been found to be smaller in COPD patients with alpha-1 antitrypsin deficiency (AATD) than in those without AATD. Alpha-1 antitrypsin (AAT) augmentation therapy was suggested as a potential factor of influence. Whether this finding mirrors different improvements in 6-min walk distance (6MWD) between both groups remains unknown. Methods 140 patients with AATD-related COPD (phenotype PiZZ, FEV 1 : 31 ± 8%pred.) and 280 COPD patients without AATD (FEV 1 : 31 ± 8%pred.) were matched for baseline 6MWD and included in a retrospective analysis. AATD patients were divided into those “on” (AATD AUG+ ) or “off” (AATD AUG- ) augmentation therapy. 6MWD was assessed pre and post an inpatient 4-week PR program. Plasma level of creatinine was analysed at baseline. Results In AATD and COPD patients with comparable initial 6MWD (331 ± 106 m and 326 ± 101 m, p = n.s.), improvements in 6MWD following PR were similar (+49 ± 49 m and +53 ± 52 m, intra-group change: p AUG+ : +51 ± 55 m, AATD AUG- : +47 ± 40 m, p = n.s.). Only in AATD group, higher baseline creatinine levels and lower 6MWD were positive predictors for the PR-related increase in 6MWD. Conclusions Independently of the genetic variant of AAT, COPD patients achieved the same training-related benefit in 6MWD. Augmentation therapy showed no effect on 6MWD adaptation during PR.

Introduction: Non-invasive ventilation (NIV) can increase exercise endurance time and reduce respiratory muscle work in patients with COPD. Previous studies measuring oxygen consumption (VO2) in exercise with NIV did not correct for the effect of NIV pressure on the oxygen sensor of the metabolic measuring device. We have previously published a VO2 correction factor for use with NIV. Aims: To determine the effect of NIV on VO2 (using VO2 correction) at rest and during constant work rate cycle tests (CWR) among patients with COPD. Methods: People with COPD were recruited. Two CWR were performed in random order with and without NIV. In the NIV arm, whilst participants were seated on the cycle ergometer, 10 min of resting data was collected, the last 5 min with NIV applied. Participants then cycled at 75% of their previous peak work rate until fatigue. Breath-by-breath measures of VO2 were recorded continuously. VO2 at rest with and without NIV was of the last 30 seconds of the first 5 minutes rest and the 5 minutes of rest with NIV. Exercise VO2 was calculated from a 30-second average at isotime of the trial with the shortest exercise duration. Results: Nine participants with COPD (mean ± SD) FEV1 43 ± 8 %pred, RV/TLC ratio 0.51 ± 0.10, PCO2 37 ± 4 completed the study. NIV (inspiratory pressure 16.4 ±1.9 cmH2O, expiratory 5 cmH2O) reduced VO2 at rest by a mean difference (MD) of 1.05 mL/Kg/min (95% CI: 0.38 to 1.73; p Conclusion: NIV reduced VO2 at rest and during exercise in people with normocapnic COPD compared to exercise without NIV, most likely due to a lower oxygen cost of breathing.

Aim: To compare the effect of Pulmonary Rehabilitation (PR) on cognitive function, health status, and exercise outcomes in cognitive normal (CN) and cognitive impaired (CI) patients with COPD. Methods: 60 COPD patients (FEV1: 47±15%; 42%women) referred to 3-week in-patient PR and classified as “CN” or “CI” according to the Montreal Cognitive Assessment (MoCA) cutoff-score (≤25points). Domain-specific cognitive function (MoCA, SMMSE, ACER, TICS), health status (CAT), health-related quality of life (SF-36), the 6MWT and cerebral oxygen availability during cycle endurance test (CET) at 75%WR, were assessed on admission and discharge. Results: 25 patients (42%) presented evidences of CI and low performance in cognitive tests. Compared to CN, CI patients improved visuospatial skills and fluency (effect size; ES: 0.44; 0.48), whilst similar improvements in memory (ES: 0.75), physical and social function (ES: 0.45; 0.47), vitality (ES: 0.56), general and mental health (ES: 0.47; 0.67) were observed, respectively. CI patients did not improve body pain and limitations from emotional problems as assessed by SF-36 but increased 6MWD (from 378 to 403m, p=0.052), CET (from 10.0 to 12.3min, p Conclusion: CI patients gain significant benefits in cognitive function from PR but are not responsive to improvements in body pain and emotional limitations compared to CN. Persistent body pain may have limited the effectiveness of PR and improvements in the 6MWT in CI patients with COPD.

Background: Whole-body vibration training (WBVT) has been shown to be a feasible and effective exercise modality in patients directly following lung transplantation (LTx). Aim of this study was to investigate WBVT effects in long-term LTx patients (LTx>1year). Methods: 70 long-term LTx patients (mean duration since LTx: 5.7±4.5 years) participated in this randomized controlled trial. All patients performed a comprehensive pulmonary rehabilitation program of 3-weeks duration including a standardized endurance and strength training program on 5 days per week. On top, patients were randomized into squat training groups 3x/wk performing dynamic squat exercises for 4x2 min either on a side-alternating WBVT platform at high frequencies of 24-26 Hz (WBVT group) or for the same amount on the floor (control group, CON). Results: Patients in both groups reached a significant increase in 6-minute walk distance (WBVT: 44±44m versus CON: 22±34m) which was significantly superior in favor of the WBVT-group (delta: 22m, p=0.027). Also peak cycling work rate increased significantly more in the WBVT group (15±9W versus 10±9W, between-group difference: 5W, p=0.044). Furthermore, LTx patients who performed WBVT showed a significant increase in insulin-like growth factor (+18±49ng/ml) compared to control (-14±51ng/ml, between-group difference: 32ng/ml, p=0.035). Conclusion: Squat training on a vibration platform induced significantly higher improvements in exercise capacity compared to squat training on the floor. Therefore, WBVT seems to be an effective add-on exercise modality also in long-term LTx patients.

Aim: To investigate any relationship between, i)quality of training sessions, ii)improvements in inspiratory muscle function, iii)changes in exercise capacity following well-controlled, high-intensity inspiratory muscle training (IMT), in combination with 3-months of pulmonary rehabilitation. Methods: 169 patients (FEV1 41±16%pred.) with low maximal inspiratory pressure (PImax 51±15%pred) were recruited and randomized into an intervention group (IMT ≥50%PImax) or a control group (IMT ≤10%PImax). Patients participated in daily IMT using a tapered flow resistive loading device. Subgroup analyses were performed by pooling the data of both groups and subsequently dividing it into tertiles based on improvements in PImax after the intervention. Results: Training characteristics (total inspiratory work performed/session, average peak power/session, and IMT intensity) were significantly related to improvements in PImax (Figure 1A-1C). Average training compliance (84±19%) was not associated with change in PImax (p-for-trend=0.129). Larger improvements in PImax were related to larger increases in endurance cycling time (Figure 1D). Conclusion: The quality rather than the number of performed training sessions is strongly associated with improvement in inspiratory muscle strength which in turn relates to improvements in endurance cycling time.

Background: There is only little evidence on the acute effects of non-invasive ventilation (NIV) during exercise in hypercapnic COPD patients. Methods: Fifteen hypercapnic COPD patients (age: 62±7 yrs, FEV1: 18±4 %pred., pCO2: 51±5mmHg) were recruited. Patients underwent a two-day assessment. On the first day an incremental cycling test was performed to determine peak work rate. On the second day patients performed two constant work rate cycling tests (CWRT) at 60% of peak work rate until exhaustion. CWRTs were randomly assigned to 2 conditions; a) with oxygen supplementation (4±2lpm) only, and b) with the same oxygen supplementation plus effective NIV (inspiratory pressure: 25±2 cmH20, expiratory pressure: 6±1 cmH20) including one hour of rest in between. Results: There was a clinically relevant change concerning a longer cycle endurance time with the use of NIV (627±384 sec versus 506±291 sec, p=0.34). Furthermore, NIV limited CO2 retention. At isotime (the shortest test between the two experimental conditions in a given subject) CO2 increased from 50.7±6.8mmHg up to 55.7±6.9mmHg without NIV and from 45.1±5.8mmHg to 49.9±5.8mmHg with NIV (p=0.019). Furthermore, oxygen saturation at isotime tended to be higher with NIV (96.0±4.5% versus 92.5±5.9%, p=0.081). Dyspnea rated on the Borg scale was significantly lower at the end of the CWRT with NIV (3.2±1.9 pts versus 5.3±1.5 pts, p=0.006). Conclusion: NIV during exercise in hypercapnic COPD patients prevented CO2 retention and reduced dyspnea. This might provide the basis for a feasible and safe endurance training program in this specific cohort of patients with very advanced COPD.

Background: Cognitive impairment (CI) is a prevalent extrapulmonary manifestation in COPD. Potential disturbances in cerebral circulation and oxygen delivery due to reduced ventilatory efficiency and ventilatory drive may be associated with higher rates of CI. We assessed cerebral tissue oxygen index (TOI) and cerebral hemodynamics at exertion in COPD patient with and without CI. Method: 52 COPD patients (aged: 68±8yrs; FEV1: 45±14%; 40%women) underwent a comprehensive cognitive assessment. Patients were assigned to “CI” and “non-CI” groups according to Montreal Cognitive Assessment (MoCA) cutoff score ≤25points. Patients performed cycle endurance test (CET) at 75% of peak work rate while transcutaneous carbon-dioxide partial-pressure (TCPCO2), cerebral tissue oxygen index (TOI) and hemoglobin responses were recorded by SenTec and Portalite systems, respectively. Results: 23 patients (44%) presented evidences of CI (MoCA≤25) with also lower scores in other cognitive tests (all p Conclusion: COPD patients have the capacity to autoregulate cerebral cortex blood flow in response to hypercapnia and hypoxemia, at least during exercise, and thus to normalize cerebral tissue oxygenation. These findings suggest that exercise is safe and can be beneficial regarding to cognitive function in COPD.

Background: Chronic respiratory failure can be associated with CO2 retention and hypercapnia during exercise in COPD patients. A continuously monitoring of transcutaneous CO2 levels (TcPCO2) may be useful to screen CO2 trends and to identify patients with exercise-induced hypercapnia (EIH). Objective: The aim of this study was to investigate the accuracy of the SenTec Digital Monitoring System (SDMS, SenTec AG, Therwil, Switzerland) during the 6-minute walk test (6MWT) in COPD patients. Methods: 10 COPD patients were enrolled in this prospective, pilot study. Capillary blood gases (CBG) from the earlobe were taken by the same investigator pre-6MWT and directly following 6MWT withTcPCO2 levels recorded simultaneously. To ensure a valid comparison between CBG and TcPCO2, values were taken at the same time point. An independent person set digital markers in the SenTec device concurrently with the taking of the CBG. Results: The agreement of PCO2 recording between CBG and SenTec device showed a very strong intra-class correlation coefficient for pre-walk (ICC=0.98, 95%CI: 0.93-0.99) and post-walk (ICC=0.98, 95CI: 0.73-0.99) values of the 6MWT (see Figure). Conclusion: Transcutaneously measured PCO2 values by the SDMS during 6MWT were highly accurate. The strong correlation with CBG and the continuous, non-invasive method could be advantageous to detect patients with EIH during the 6MWT.

Background: Cognitive impairment (CI) is a prevalent extrapulmonary manifestation in COPD. We assessed the prevalence and the determinants of CI in COPD. Method: 52 COPD patients (aged: 68±8yrs; FEV 1 : 45±14%; 40%women) underwent a comprehensive cognitive assessment. Patients were assigned to “CI” and “non-CI” groups according to Montreal Cognitive Assessment (MoCA) cutoff score ≤25points. Clinical data including medical history, respiratory function, health/ mood status evaluation by Saint-George respiratory questionnaire (SGRQ) and hospital anxiety-depression scale (HADS) were collected. Patients performed six-minute walk test (6MWT) and cycle endurance test (CET) at 75% of peak work rate. Results: 23 patients (44%) presented evidences of CI (MoCA≤25) with also lower scores in the other cognitive tests (all p 1 %, health and mood status (SGRQ, HADS), and exercise capacity (6MWD: 359 ±85m vs 380 ±116m, p=0.48; CET: 616 ±329sec vs 551 ±370sec, p=0.51) but greater oxygen desaturation during the CET (SpO 2 nadir: 92.3 ±2.9% vs 89.9 ±3.9%, p=0.014). Certain threshold of SpO 2 nadir (≤90%) increased the risk for CI after adjustment for oxygen-use (p=0.026). Conclusion: CI is highly prevalent in patients with COPD and affects several cognitive domains. It is associated with the years of education and the oxygen desaturation during the CET, however, it seems that is not associated with exercise capacity in COPD patients.

Background: Inspiratory muscle dysfunction occurs in patients with chronic obstructive pulmonary disease (COPD) and is associated with dyspnea and decreased exercise capacity. Aim of this study was to investigate additional benefits of adding inspiratory muscle training (IMT) to a general exercise training program during pulmonary rehabilitation (PR) in COPD patients with inspiratory muscle weakness. Methods: 70 COPD patients (FEV1: 39±13%pred., PImax: 51±14 cmH2O) participated in this randomized controlled trial. All patients performed a 3-week comprehensive inpatient PR including standardized endurance and strength training. On top, patients performed supervised IMT on 7 days/wk randomized into an intervention group and a Sham-IMT group (initial IMT pressure: 61±15% of PImax and 13±8% of PImax, respectively) Results: At 3 weeks, PImax improved significantly more in the IMT group (IMT: 18±12cmH2O vs. 6±11cmH2O, p Conclusion: A complementary inspiratory muscle training on top of a general exercise training program in COPD patients with inspiratory muscle weakness significantly improved inspiratory muscle function. However, these benefits did not transfer into further improvements of functional exercise capacity.

Background: Carbon dioxide pressure (pCO2) can be reliably measured transcutaneously and may be of clinical relevance in COPD. Retention of CO2 and exercise-induced hypercapnia (EIH) has been scarcely studied as disease marker in COPD. The aims of this study were (1) to study pCO2 response during the 6MWT and (2) to compare clinical characteristics amongst patients with and without CO2 retention and those with and without EIH during the 6MWT. Methods: Sixty-two COPD patients (age: 63±8years, FEV1: 33±10%pred) participated in study. Transcutaneous carbon dioxide pressure (tcpCO2) was measured continuously during the 6MWT by the use of SenTec device. Measurements where repeated after 1 week and data from the longest 6MWT were analyzed. Results: Half of the patients (50%) had CO2 retention (ΔtcpCO2 >4mmHg from baseline) while the rest preserved or reduced tcpCO2 levels. Nineteen patients (31%) exhibited EIH (tcpCO2 >45mmHg) during the 6MWT. Physiological characteristics of CO2 retainers were similar with non-retainers but patients with EIH were characterized by higher resting tcpCO2 levels within the normal range, lower inspiratory pressures (Pimax), lower BMI, more severe FEV1 and higher dyspnoea at rest compared to non-EIH. The determinants of pCO2 retention were pre-walk dyspnoea and FEV1 while pre-walk dyspnoea and baseline pCO2 levels were crucial for EIH. Conclusions: The pCO2 response to 6MWT is highly heterogeneous in COPD. CO2 retention is related to more pre-walk dyspnoea and worse FEV1 while EIH is associated with more pre-walk dyspnoea and higher baseline PaCO2 levels. Monitoring of pCO2 changes during 6MWT might help to identify patients who need special attention regarding to EIH.

Background Most endurance training programs rely on continuous or interval cycling. Objective Aim of this study was to determine the feasibility of these training modalities during treadmill walking. Methods 42 COPD patients (FEV 1 : 37±14% pred.) were enrolled in this prospective, randomized 4-arm study. Patients were randomized to one of four treadmill walking programs (a 15 sessions). Training modalities consisted of 2 constant walking speed groups (MIC group walking speed [WS]: 60% from mean baseline 6-minute walking test [6MWT] speed/ HIT group WS: 120% from mean 6MWT speed for 1 min alternating with 1 min of rest) and 2 symptom orientated groups (MIC-Borg group [BG]/ HIT-BG) where WS was adjusted to dyspnea scores of 4-6 on a 10 point Borg scale (BS). Total walking time was increased from 10 up to 32 minutes in all groups. Dyspnea, leg fatigue, heart rate (HR) and oxygen saturation (SpO 2 ) were recorded during each session. Results Levels of dyspnea (BS: MIC: 4.3±1.4 vs. MIC-BG: 4.1±1.1, p=n.s. and HIT: 3.6±1.0 vs. HIT-BG: 3.7±0.9, p=n.s.) and leg fatigue (BS: MIC: 2.6±1.7 vs. MIC-BG: 3.2±1.2, p=n.s. and HIT: 2.5±1.4 vs. HIT-BG: 1.7±1.0 p=n.s.) were comparable during exercise. Also mean SpO 2 and HR were comparable. MIC-BG had markedly, but not significantly less unintended breaks (n) during training than MIC group (0.8±2 vs. 13±20) and trained at a higher walking speed (p=0.02) than predicted. In all groups no adverse events were observed. Conclusion It seems that all 4 treadmill-based walking training modalities are feasible and safe for patients with severe COPD.

Background There is growing evidence that patients with idiopathic pulmonary fibrosis (IPF) benefit from pulmonary rehabilitation (PR) in terms of exercise capacity and health related quality of life (HRQL). However, the effects of PR on mental aspects of HRQL are still unknown. Objective The aim of our study was to investigate (a) short-term effects of an inpatient PR and (2) sustainability after 3 months in IPF patients. Methods 33 IPF patients were randomized into a PR group (PRG) receiving 3 weeks of inpatient PR (n=18, 68±9y, FVC: 73±17%pred.) and a control group (CG) with usual care (n=15, 65±10y; FVC: 72±21%pred.). Data were collected at the begin of the study [T1], after 6 weeks of usual care (CG) or following PR (PRG)[T2], and at 3 months follow-up (n=24)[T3]. Results From T1 to T2, PRG but not CG improved significantly in HADS scores (anxiety: -1.5±2.7pts., depression: -1.7±2.3pts.), mental score of SF36 questionnaire (6.1±7.9pts.), and CRQ categories of mastery (0.7±1.2pts.), fatigue (0.9±1.5pts.) and emotion (0.9±1.1pts.). CRQ dyspnea score worsened significantly in CG (-0.5±0.7pts.). At T3, PRG improved clinically relevant in all CRQ domains (>0.5pts.) and HADS scores (each >1.0pts.) compared to CG. 6-minute walking distance (6MWD) increased from T1 to T2 in PRG (+60±94m, p Conclusion PR improves anxiety and depression, HRQL and 6MWD in IPF patients. The benefit of PR was sustained after 3 months to a clinical relevant extent regarding HRQL, symptoms of anxiety and depression but not 6MWD.

Background: There are several studies that have shown that whole body vibration training (WBVT) is able to improve exercise capacity in patients with COPD. However, the underlying mechanisms remain unknown. Objective: To evaluate the effect of WBVT on balance and muscle power in patients with severe COPD. Methods: Fifty patients (age: 63±7 ys, FEV 1 : 35±10 %pred.) were recruited during a 3-week inpatient pulmonary rehabilitation program (PR). On top of conventional endurance and strength training patients performed dynamic squat training sessions (4x2min, 3x/wk) randomized into a WBVT-group performing squat training on a vibration platform or a control group (CON) exercising on the floor. To assess balance patients were asked to stand still for 10 sec in different static positions (Romberg stand, tandem stand, 1-leg stand with open and closed eyes). Muscle power tests consisted of 2-leg jumps, 5-repetition sit-to-stand test (STST) as well as the 1-min STST. All tests were performed on a force measurement platform pre and post PR. Results: After PR the WBVT-group could improve balance significantly more in 2 out of 4 domains compared to the CON-group (tandem stand: WBVT +10% vs. CON -14%, p=0.008 and 1-leg stand: WBVT +6% vs. CON -9%). Also some measures of muscle power like jump height (WBVT: +26% vs. CON: +1%, p=0.010) and the 5-STST (WBVT: -5.2±5.1sec vs. CON: -2.4±0.9sec) improved significantly more in the WBVT-group. Conclusion: This is the first study that investigated potential mechanisms of the beneficial effect of WBVT. It was found that neuromuscular adaptations like improvements in balance and muscle power may explain some of these positive effects.

Aim: With this large, multi-center, randomized controlled trial we aimed to examine the effects of a well-controlled, high-intensity inspiratory muscle training (IMT) program in a combination with a 3-month pulmonary rehabilitation (PR) on functional exercise capacity in COPD patients with inspiratory muscle weakness. Methods: Patients with reduced maximal inspiratory pressure (PImax 2 O or Results: While most baseline characteristic of patients were comparable between groups, the intervention group was more impaired in some pulmonary function characteristics and limb muscle strength. Conclusion: Inclusions will be completed by September 2016 and preliminary results of between group comparisons will be presented then.

Background: The Oxymizer ® device is a special oxygen nasal cannula that provides a higher luminal diameter in combination with an incorporated oxygen reservoir. In the past we found that Oxymizer® was beneficial in hypoxemic COPD patients by increasing oxygenation during exercise. Objective: Aim of this prospective cross-over study was to investigate the effects of an Oxymizer® in comparison to a conventional nasal cannula (CNC) during exercise in hypoxemic patients with pulmonary fibrosis. Methods: 24 patients with pulmonary fibrosis (m:f=:15:9; VC=54±22%pred.; DLCO=20±12mmol/kg/min; PaO 2 =54,90±7,3mmHg; PaCO 2 =40,5±5,5mmHg, peak work rate [PWR]=74±21Watt) were recruited during pulmonary rehabilitation. After an initial incremental cycle test, patients performed 4 constant cycling work rate tests (CWRT) at 70% of their PWR (twice with Oxymizer ® and twice with CNC in random order). Results: Endurance time (581sec.[351-1142] vs. 498sec.[303-796], p=0.009) and oxygen saturation during exercise (90%[87-93] vs. 88%[85-91], p=0.002) were significantly higher by using Oxymizer® compared to CNC. No significant differences were found between Oxymizer® and CNC regarding PaCO2 (37.8mmHg [33.5-41.0] vs. 37.6mmHg [33.3-41.5], p=n.s.) and perceived dyspnea rated on the modified Borg scale (7.5pts. [7-8] vs. 7.5pts. [6-8], p=n.s.). Discussion: This study showed that oxygen delivery via Oxymizer ® is superior to CNC in patients with pulmonary fibrosis with regard to a longer endurance time and although a better oxygenation during exercise. Oxymizer ® seems to be a simple and useful device in hypoxemic patients with pulmonary fibrosis.

Background: In a former study we have shown that squat exercises during whole body vibration training (WBVT) seem to be superior in improving exercise capacity in patients with COPD in comparison to squat exercises on the floor. However, cardiorespiratory capacity during WBVT remains unknown. Objective: To quantify differences in oxygen uptake and symptoms during squat exercises with and without WBVT in patients with severe COPD. Methods: Eight patients (age: 64±5 ys, FEV1: 42±2 %pred.) performed an assessment on two consecutive days. Day 1: incremental, symptom-limited spiroergometry on a bicycle. Day 2: six short bouts of external paced squatting exercises (10 repetitions per minute) for 1, 2 or 3 minutes on the floor and on a WBVT-platform (Galileo®) respectively. All squat exercises were performed in random order using mobile spiroergometry. Results: Oxygen uptake (%VO2peak) was significantly (p

Background: Exercise training improves exercise capacity in patients with chronic obstructive pulmonary diseases (COPD). In a retrospective analysis, we found that COPD patients (PiMM) showed higher improvements of exercise capacity following training intervention than Alpha-1 antitrypsin deficiency patients (A1ATD, PiZZ). Objective: We investigated if this different change in exercise capacity is reflected by different skeletal muscle adaptations. Methods: 6 A1ATD (PiZZ, age: 57±7y, FEV1: 38±6%pred., Prolastin®: n=6) and 10 COPD patients (PiMM, age: 62±7y, FEV1: 28±4%pred.) prospectively performed a 3-week training therapy. Before and after, each patient underwent muscle biopsy (m.vastus lateralis) and peak work rate (PWR) test. Results: Prospective data showed that exercise capacity improved in both groups, however the improvement was smaller in A1ATD patients (PWR: A1ATD:+10±11Watt, p

Background: Supplemental oxygen (O 2 ) improves exercise capacity, oxygenation and dyspnea in patients with hypoxemic chronic obstructive pulmonary disease (COPD). Evidence regarding the effect of O 2 in normoxemic COPD patients or comparing its effects in normoxemic and hypoxemic patients is still scarce. Objective: The aim of our study was to investigate the effect of O 2 in patients with (LTOT) and without indication for long term oxygen therapy (nonLTOT). Methods: 124 COPD patients underwent two 6-minute walking tests (day 2+3) after a pretest (day 1). One test was performed using O 2 and the other using compressed room air in randomized order and a single-blinded fashion. Results: O 2 resulted in a significant increase in 6MWD (+26m, p 2 seems to be the individual level of exercise performance (6MWD) at baseline (r=-0.337, p Comparing LTOT- and nonLTOT-patients, we found that LTOT-patients benefit more from O 2 regarding the walking distance (+33m vs. +15m, p 2 -level (+7.0 vs. +3.4 percentage points, p 2 only when suffering from severe airflow obstruction (r=-0.257, p Discussion: O 2 improves 6MWD, oxygenation and dyspnea in normoxemic and hypoxemic COPD-patients. However, these short-term effects were more pronounced in patients with indication for LTOT than in those without. NonLTOT-patients suffering from severe airflow obstruction or severe exercise-induced dyspnea seem to show a relevant benefit from O 2 .