Impaired Dendritic Cell Homing in COVID-19.

The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.

Viral mapping in COVID-19 deceased in the Augsburg autopsy series of the first wave: A multiorgan and multimethodological approach.

BACKGROUND: COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. METHODS: During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. RESULTS: Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. CONCLUSIONS: The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.

Long-Term Benefits of Adding a Pedometer to Pulmonary Rehabilitation for COPD: The Randomized Controlled STAR Trial.

Purpose: This Stay Active after Rehabilitation (STAR) study examined the effects of a pedometer-based behavioral intervention for individuals with COPD during three weeks of inpatient pulmonary rehabilitation (PR) on patients' physical activity levels six weeks and six months after PR, including steps (primary outcome), moderate-intensity physical activity, and sedentary time as well as patient quality of life, symptoms, and other psychological and clinical variables. Patients and Methods: Rehabilitation patients with COPD wore a triaxial accelerometer (ActiGraph wGT3X) for seven days two weeks before (T0) as well as six weeks (T3) and six months (T4) after PR. In addition to the three-week inpatient PR (control group, CG), the randomly allocated intervention group (IG) received a brief pedometer-based behavioral intervention with the application of the following behavior-change techniques: performing the behavior, individual goal-setting, self-monitoring, and feedback. The effects were analyzed using analysis of covariance with an intention-to-treat approach. Results: A total of 327 patients (69% male, age: 58 years, FEV1 (%): 53.5, six-minute walk distance: 447.8 m) were randomly allocated to either the IG (n = 167) or CG (n = 160). Although both groups increased their daily steps after PR (IG: MT3-T0 = 1152, CG: MT3-T0 = 745; IG: MT4-T0 = 795, CG: MT4-T0 = 300), the slightly higher increases in daily steps in the IG compared to the CG at T3 (Δ388 steps, d = 0.16) and T4 (Δ458 steps, d = 0.15) were not statistically significant (p > 0.05 for all). Patients in both groups showed moderate to high pre-post-changes in terms of secondary outcomes, but no advantage favoring the IG was found. Conclusion: The results show that adding a pedometer-based behavioral intervention to standard German three-week inpatient PR for COPD patients did not result in more physical activity in terms of steps and moderate-intensity physical activity or less sedentary time. However, both groups (IG and CG) showed remarkably enhanced physical activity levels six weeks and six months after PR, as well as improvements in other secondary outcomes (eg, quality of life).

Towards a better understanding of physical activity in people with COPD: predicting physical activity after pulmonary rehabilitation using an integrative competence model.

The integrative Physical Activity-related Health Competence (PAHCO) model specifies competences (movement competence, control competence, and self-regulation competence) that enable people to lead a physically active lifestyle. This longitudinal study analyses the predictive quality of a multidimensional PAHCO assessment for levels of physical activity (PA) and their relevance for quality of life in COPD patients after pulmonary rehabilitation. At the end of an inpatient pulmonary rehabilitation (T2), 350 COPD patients participating in the Stay Active after Rehabilitation (STAR) study underwent assessments, including a six-factor measurement of PAHCO. PA (triaxial accelerometry) and quality of life (Saint George's Respiratory Questionnaire) were recorded 6 weeks (T3) and 6 months (T4) after rehabilitation. Structural equation modelling (SEM) was used to regress the PAHCO assessment on PA, which should, in turn, influence quality of life. In univariable analysis, five and six factors of the PAHCO model were related to PA and quality of life, respectively. Multivariate modelling showed that the predictive analyses for the PA level were dominated by the 6-minute walking test representing movement competence (0.562 ≤ |ß| ≤ 0.599). Affect regulation as an indicator of control competence co-predicted quality of life at T3 and levels of PA at T4. The PA level was, in turn, significantly associated with patients' quality of life (0.306 ≤ |ß| ≤ 0.388). The integrative PAHCO model may be used as a theoretical framework for predicting PA in COPD patients following pulmonary rehabilitation. The results improve our understanding of PA behaviour in COPD patients and bear implications for person-oriented PA promotion.

In-Patient Pulmonary Rehabilitation to Improve Asthma Control­A Randomized Controlled Study (EPRA, Effectiveness of Pulmonary Rehabilitation for Patients with Asthma).

BACKGROUND: Despite the availability of effective pharmaceutical treatment options, many patients with asthma do not manage to control their illness. This randomized trial with a waiting-list control group examined whether a 3-week course of inpatient pulmonary rehabilitation (PR) improves asthma control (primary endpoint) and other secondary endpoints (e.g., quality of life, cardinal symptoms, mental stress). The subsequent observational segment of the study investigated the long-term outcome after PR. METHODS: After approval of the rehabilitation´ by the insurance providers (T0), 412 adults with uncontrolled asthma (Asthma Control Test [ACT] score < 20 points) undergoing rehabilitation were assigned to either the intervention group (IG) or the waiting-list control group (CG). PR commenced 1 month (T1) after randomization in the IG and 5 months after randomization (T3) in the CG. Asthma control and the secondary endpoints were assessed 3 months after PR in the IG (T3) as an intention-to-treat analysis by means of analyses of covariance. Moreover, both groups were observed for a period of 12 months after the end of PR. RESULTS: At T3 the mean ACT score was 15.76 points in the CG, 20.38 points in the IG. The adjusted mean difference of 4.71 points was clinically relevant (95% confidence interval [3.99; 5.43]; effect size, Cohen's d = 1.27). The secondary endpoints also showed clinically relevant effects in favor of the IG. A year after the end of rehabilitation the mean ACT score was 19.00 points, still clinically relevant at 3.54 points higher than when rehabilitation began. Secondary endpoints such as quality of life and cardinal symptoms (dyspnea, cough, expectoration, pain) and self-management showed moderate to large effects. CONCLUSION: The trial showed that a 3-week course of PR leads to clinically relevant improvement in asthma control and secondary endpoints. Patients who do not achieve control of their asthma despite outpatient treatment therefore benefit from rehabilitation.

An Internet-Based Asthma Self-Management Program Increases Knowledge About Asthma.

BACKGROUND: Asthma education (AE) is associated with reduced hospitalization and disability. We compared the effectiveness of an electronic AE program (eAEP) with a conventional face-to-face AE program (presence-based AEP; pAEP) for asthma knowledge (AK) with regard to self-management. METHODS: A randomized controlled pilot study was conducted in a pulmonary reha- bilitation clinic. AK was determined by means of the Asthma Knowledge Test (AKT). The change in AKT score within each group was calculated with a paired t-test. Group differences were estimated with adjusted linear regression models. RESULTS: In the intervention group (n = 41), the AKT score increased from 41.57 (standard deviation 5.63) at baseline to 45.82 (3.84) after completion of the eAEP (p < 0.001), and again to 47.20 (3.78) after completion of the pAEP (p = 0.046). In the control group (n = 41), the score increased from 41.73 (4.74) at baseline to 45.72 (3.65) after completion of the pAEP (p < 0.001). There was no relevant differ- ence in knowledge gain between the eAEP and the pAEP group after completion of the corresponding educational sessions (p = 0.881). The AKT score was higher in the eAEP group after obligatory participation in pAEP than in the group that only completed the pAEP (p = 0.020). CONCLUSION: An internet-based AEP could help to reduce the knowledge deficits of a large proportion of patients with asthma.

Impact of acyclovir use on survival of patients with ventilator-associated pneumonia and high load herpes simplex virus replication.

BACKGROUND: Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients. However, the clinical significance remains poorly defined. We investigated whether patients with ventilator-associated pneumonia not responding to antibiotics and in whom high levels of HSV could be detected in respiratory secretions benefit from acyclovir treatment. METHODS: Respiratory secretions (bronchoalveolar lavage fluid or tracheal aspirates) were tested for HSV replication by quantitative real-time PCR. ICU survival times, clinical parameters, and radiographic findings were retrospectively compared between untreated and acyclovir treated patients with high (> 105 HSV copies/mL) and low (103-105 HSV copies/mL) viral load. RESULTS: Fifty-seven low and 69 high viral load patients were identified. Fewer patients with high viral load responded to antibiotic treatment (12% compared to 40% of low load patients, p = 0.001). Acyclovir improved median ICU survival (8 vs 22 days, p = 0.014) and was associated with a significantly reduced hazard ratio for ICU death (HR = 0.31, 95% CI 0.11-0.92, p = 0.035) in high load patients only. Moreover, circulatory and pulmonary oxygenation function of high load patients improved significantly over the course of acyclovir treatment: mean norepinephrine doses decreased from 0.05 to 0.02 µg/kg body weight/min between days 0 and 6 of treatment (p = 0.049), and median PaO2/FiO2 ratio increased from 187 to 241 between day 3 and day 7 of treatment (p = 0.02). Chest radiographic findings also improved significantly (p < 0.001). CONCLUSIONS: In patients with ventilator-associated pneumonia, antibiotic treatment failure, and high levels of HSV replication, acyclovir treatment was associated with a significantly longer time to death in the ICU and improved circulatory and pulmonary function. This suggests a causative role for HSV in this highly selected group of patients.

Impact of Disease-Specific Fears on Pulmonary Rehabilitation Trajectories in Patients with COPD.

Disease-specific fears predict health status in chronic obstructive pulmonary disease (COPD), but their role in pulmonary rehabilitation (PR) remains poorly understood and especially longer-term evaluations are lacking. We therefore investigated changes in disease-specific fears over the course of PR and six months after PR, and investigated associations with PR outcomes (COPD assessment test (CAT) and St. Georges respiratory questionnaire (SGRQ)) in a subset of patients with COPD (n = 146) undergoing a 3-week inpatient PR program as part of the STAR study (Clinicaltrials.gov, ID: NCT02966561). Disease-specific fears as measured with the COPD anxiety questionnaire improved after PR. For fear of dyspnea, fear of physical activity and fear of disease progression, improvements remained significant at six-month follow-up. Patients with higher disease-specific fears at baseline showed elevated symptom burden (CAT and SGRQ Symptom scores), which persisted after PR and at follow-up. Elevated disease-specific fears also resulted in reduced improvements in Quality of Life (SGRQ activity and impact scales) after PR and at follow-up. Finally, improvement in disease-specific fears was associated with improvement in symptom burden and quality of life. Adjustment for potential confounding variables (sex, smoking status, age, lung function, and depressive symptoms) resulted in comparable effects. These findings show the role of disease-specific fears in patients with COPD during PR and highlight the need to target disease-specific fears to further improve the effects of PR.

Physical Activity and Sedentary Behaviour Patterns in 326 Persons with COPD before Starting a Pulmonary Rehabilitation: A Cluster Analysis.

This study applies a cluster analysis to identify typical physical activity (PA) and sedentary behaviour (SB) patterns in people with chronic obstructive pulmonary disease (COPD) before starting pulmonary rehabilitation (PR). We implemented an observational design which assessed baseline data of objectively measured PA and SB from the STAR (Stay Active after Rehabilitation) study. A total of 355 persons wore an accelerometer (Actigraph wGT3X) for seven days before the start of their PR. Sociodemographic and disease-related parameters were assessed at the start of PR. We applied cluster analysis and compared clusters applying univariate variance analyses. Data was available for 326 persons (31.6% women; age ø = 58 years). Cluster analysis revealed four movement clusters with distinct PA and SB patterns: Sedentary non-movers (28.5%), sedentary occasional movers (41.7%), sedentary movers (19.6%), and sedentary exercisers (10.1%). The four clusters displayed varying levels of moderate PA before rehabilitation (Ø daily min: 9; 28; 38; 70). Notably, all four clusters displayed considerably long average sedentary time per day (Ø daily minutes: 644; 561; 490; 446). The clusters differed significantly in disease-related parameters of GOLD severity, FEV1, CAT, and 6-Min-Walk-Test. In addition to PA promotion, PR programs should consider the reduction of sedentary behaviour as a valuable goal.

Baseline health status and setting impacted minimal clinically important differences in COPD: an exploratory study.

OBJECTIVES: Minimal clinically important differences (MCIDs) are used as fixed numbers in the interpretation of clinical trials. Little is known about its dynamics. This study aims to explore the impact of baseline score, study setting, and patient characteristics on health status MCIDs in chronic obstructive pulmonary disease (COPD). STUDY DESIGN AND SETTING: Baseline and follow-up data on the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and St. George's Respiratory Questionnaire (SGRQ) were retrospectively analyzed from pulmonary rehabilitation (PR) and routine clinical practice (RCP). Anchor- and distribution-based MCID estimates were calculated and tested between settings, gender, age, Global initiative for Obstructive Lung Disease (GOLD) classification, comorbidities, and baseline health status. RESULTS: In total, 658 patients were included with 2,299 change score measurements. MCID estimates for improvement and deterioration ranged for all subgroups 0.50-6.30 (CAT), 0.10-0.84 (CCQ), and 0.33-12.86 (SGRQ). Larger MCID estimates for improvement and smaller ones for deterioration were noted in patients with worse baseline health status, females, elderly, GOLD I/II patients, and patients with less comorbidities. Estimates from PR were larger. CONCLUSION: Baseline health status and setting affected MCID estimates of COPD health status questionnaires. Patterns were observed for gender, age, spirometry classification, and comorbidity levels. These outcomes would advocate the need for tailored MCIDs.

Thresholds for clinically important deterioration versus improvement in COPD health status: results from a randomised controlled trial in pulmonary rehabilitation and an observational study during routine clinical practice.

OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease. Preventing deterioration of health status is therefore an important therapy goal. (Minimal) Clinically Important Differences ((M)CIDs) are used to interpret changes observed. It remains unclear whether (M)CIDs are similar for both deterioration and improvement in health status. This study investigates and compares these clinical thresholds for three widely-used questionnaires. DESIGN AND SETTING: Data were retrospectively analysed from an inhouse 3-week pulmonary rehabilitation (PR) randomised controlled trial in the German Klinik Bad Reichenhall (study 1), and observational research in Dutch primary and secondary routine clinical practice (RCP) (study 2). PARTICIPANTS: Patients with COPD aged ≥18 years (study 1) and aged ≥40 years (study 2) without respiratory comorbidities were included for analysis. PRIMARY OUTCOMES: The COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) were completed at baseline and at 3, 6 and 12 months. A Global Rating of Change scale was added at follow-up. Anchor-based and distribution-based methods were used to determine clinically relevant thresholds. RESULTS: In total, 451 patients were included from PR and 207 from RCP. MCIDs for deterioration ranged from 1.30 to 4.21 (CAT), from 0.19 to 0.66 (CCQ), and from 2.75 to 7.53 (SGRQ). MCIDs for improvement ranged from -3.78 to -1.53 (CAT), from -0.50 to -0.19 (CCQ), and from -9.20 to -2.76 (SGRQ). Thresholds for moderate improvement versus deterioration ranged from -5.02 to -3.29 vs 3.89 to 8.14 (CAT), from -0.90 to -0.72 vs 0.42 to 1.23 (CCQ), and from -15.85 to -13.63 vs 7.46 to 9.30 (SGRQ). CONCLUSIONS: MCID ranges for improvement and deterioration on the CAT, CCQ and SGRQ were somewhat similar. However, estimates for moderate and large change varied and were inconsistent. Thresholds differed between study settings. TRIAL REGISTRATION NUMBER: Routine Inspiratory Muscle Training within COPD Rehabilitation trial: #DRKS00004609; MCID study: #UMCG201500447.

The impact of disease-specific fears on outcome measures of pulmonary rehabilitation in patients with COPD.

Anxiety is a highly prevalent psychological comorbidity in patients with chronic obstructive pulmonary disease (COPD) and has detrimental effects on pulmonary rehabilitation (PR) outcomes. It has been suggested that disease-specific fears could play an even more important role in COPD patients' disease progression. However, little is known about how different disease-specific fears impact COPD. This study examined how different disease-specific fears relate to different PR outcome measures in COPD patients and how these relationships evolve over the course of PR. Before and after a 3-week inpatient PR program, COPD patients (N = 104) underwent a 6-min walking test to measure functional exercise capacity. Disease-specific fears (fear of physical activity, fear of dyspnea, fear of disease progression, fear of social exclusion) were assessed with the COPD-Anxiety-Questionnaire-Revised. Health-related quality of life (HQoL), COPD health status, dyspnea in daily life, depression, and anxiety were measured using validated questionnaires. Multiple regression showed that greater disease-specific fears at the start of PR were associated with worse functional exercise capacity, HQoL, health status, and depression at the start and end of PR (controlling for age, sex, lung function, smoking status, and general anxiety). Patients who showed a stronger decrease in disease-specific fears improved more in PR outcome measures over the course of PR. Furthermore, different disease-specific fears were related to different PR outcome measures. The results show that disease-specific fears are associated with treatment outcome measures, both cross-sectionally and prospectively. Therefore, disease-specific fears should be addressed in COPD patients as they might play a significant role in disease progression.

The interrelations among aspects of dyspnea and symptoms of depression in COPD patients - a network analysis.

BACKGROUND: Depression is a frequent comorbidity in COPD. COPD symptoms such as dyspnea may play an important role in the causal relationship between COPD and depression. We investigated the interrelations among different aspects of dyspnea and other COPD parameters and symptoms of depression in COPD patients. METHODS: This is a secondary analysis of N = 590 COPD patients. At the beginning (T0) and the end (T1) of a 3-week inpatient pulmonary rehabilitation, dyspnea aspects intensity (BORG scale), frequency (2 CCQ items), functioning (CCQ-function) and cognitive/emotional response (2 SGRQ items) as well as cough (2 CCQ items), functional capacity (6MWD), lung function (FEV1) and symptoms of depression (PHQ-9) were assessed. Regression analyses with PHQ-9 sum score as dependent variable as well as network analysis using PHQ-9 single items were performed. Structural invariance over time was examined. RESULTS: Dyspnea frequency, function, and cognitive/emotional response showed conditional independent relationships with PHQ-9 sum score. Network analysis showed that dyspnea frequency and dyspnea functioning were primarily associated with somatic depression symptoms (for example, sleep problems, loss of energy), while cognitive/emotional response was primarily related to cognitive-affective depression symptoms (for example, feeling down/depressed/hopeless). Regression parameters, network structure and network global strength did not differ between T0 and T1. LIMITATIONS: Models are based on between-person relationships. Results should be confirmed using time-series data. CONCLUSIONS: Dyspnea and depression seem to be interrelated through a variety of different and complex pathways in COPD patients. Results may be used to explain intervention effects and develop new intervention strategies to reduce depression in COPD.

Including changes in dyspnea after inpatient rehabilitation improves prediction models of exacerbations in COPD.

BACKGROUND: Reducing the probability of future exacerbations is one of the main goals of pulmonary rehabilitation (PR) in COPD. Recent studies identified predictors of future exacerbations. However, PR might alter both predictors and number of exacerbations. OBJECTIVES: This secondary analysis examined which predictors assessed at both the beginning and the end of PR predict the risk of moderate (i.e. use of cortisone and/or antibiotics) and severe (hospitalization) exacerbations in the year after PR. METHODS: A total of n = 383 COPD patients (34.7% female, mean age = 57.8 years (SD = 7.1), mean FEV1%pred = 51.0 (SD = 14.9)) who attended a 3-week inpatient PR were included. Number of moderate and severe exacerbations were assessed one year after PR (T2) via questionnaires. Potential predictors were assessed at the beginning (T0) and the end (T1) of PR. Negative binomial regression models were used. RESULTS: The mean numbers of severe (Ms)/moderate (Mm) exacerbations in the year after PR (Ms,t2 = 0.19; Mm, t2 = 1.07) was reduced compared to the numbers of exacerbations in the year before PR (Ms,t1 = 0.50, p < 0.001; Mm,t1 = 1.21, p = 0.051). Previous exacerbations, retirement, change in dyspnea (for severe exacerbations) and dyspnea at T1 (for moderate exacerbations) were identified as significant predictors. CONCLUSIONS: PR might alter associations between predictors and future exacerbations. Dyspnea at the end of PR or change in dyspnea are better predictors than dyspnea at the beginning of PR.

[Patient perspective of the importance of asthma- and COPD-specific rehabilitation components: A secondary data analysis]. / Reha-Komponenten im Patientenfokus ­ Sekundärdatenauswertung der Befragungen von COPD- und Asthma-Rehabilitanden.

Little is known about the importance that patients attribute to individual rehabilitation components (RCs) and about which factors influence the patients' perspective and the impact of this judgment on the perceived success of the rehabilitation process. To address these questions, the data of 759 patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma, who were interviewed at the end of their rehabilitation about the subjective importance of various RCs, were analysed retrospectively. The patients were pooled from our previous studies "Prospektive Katamnesestudie zur Asthma-Rehabilitation" (ProKAR) and "Routinemäßiges Inspirationsmuskeltraining in der COPD-Rehabilitation" (RIMTCORE). Asthma patients and COPD patients differed in their assessments. Their evaluation was also affected by personal parameters such as sex, comorbidities, quality of life and the perceived effectiveness of the "rehabilitation as a whole". Patients considered all RCs to be essential, with minor differences. However, the patients' assessment of the importance of the RCs was in the closest possible agreement with the evidence available for the effectivity of multimodal rehabilitation. The added value of the proposed study is to generate further insight into the upcoming scientific field of personal rating of therapy components.

Assessment of depression before and after inpatient rehabilitation in COPD patients: Psychometric properties of the German version of the Patient Health Questionnaire (PHQ-9/PHQ-2).

BACKGROUND: Depression is a frequent comorbidity of COPD and leads to worse clinical COPD-outcomes. PHQ-9 and PHQ-2 are two widely used brief instruments to assess depression. However, psychometric properties in COPD patients are unknown. This study examines factorial validity, measurement invariance and composite reliability (CR) of PHQ-9/PHQ-2, respectively, and concordance between both tools. METHODS: This is a secondary analysis of N = 561 COPD patients who filled out the PHQ-9 at the begin (T0), the end (T1) and 3/6/9/12 (T2/T3/T4/T5) months after pulmonary inpatient rehabilitation. Structural equation modeling was used to examine factorial validity and measurement invariance between gender, GOLD disease severity groups and over time. Concordance was assessed using Cohen's Kappa, Yules Y, positive and negative agreement. RESULTS: A one-factor model (with one freed residual covariance) showed best model fit. At least partial scalar invariance could be established. Concordance between both instruments was substantial. 31.7% (26.2%) COPD patients showed clinically relevant depression according to PHQ-9 (PHQ-2) at T0. At T0-T2, PHQ-9 classified more patients as depressed than did PHQ-2. According to both measures, depression rates declined after rehabilitation. Reliability was high for both PHQ-9 (CR = 0.94) and PHQ-2 (CR = 0.89). LIMITATIONS: No gold-standard (clinical interview) to assess depression was used. Therefore, diagnostic accuracy for PHQ-9/PHQ-2 remains unclear. CONCLUSIONS: PHQ-9 and PHQ-2 fulfill important psychometric criteria (factorial validity, invariance, reliability) for measuring depression in COPD. The results support their use in clinical practice to assess severity of depression. Diagnostic accuracy to identify major/minor depression of both instruments should be examined in future studies.

Inspiratory muscle training does not improve clinical outcomes in 3-week COPD rehabilitation: results from a randomised controlled trial.

The value of inspiratory muscle training (IMT) in pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) is unclear. The RIMTCORE (Routine Inspiratory Muscle Training within COPD Rehabilitation) randomised controlled trial examined the effectiveness of IMT added to pulmonary rehabilitation.In total, 611 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received a 3-week inpatient pulmonary rehabilitation, of which 602 patients were included in the intention-to-treat analyses. The intervention group (n=300) received highly intensive IMT and the control group (n=302) received sham IMT. The primary outcome was maximal inspiratory pressure (PImax). The secondary outcomes were 6-min walk distance, dyspnoea, quality of life and lung function. Outcomes were assessed pre- and post-pulmonary rehabilitation. ANCOVA was used.The intervention group showed higher effects in PImax (p<0.001) and forced inspiratory volume in 1 s (p=0.013). All other outcomes in both study groups improved significantly, but without further between-group differences. Sex and pulmonary rehabilitation admission shortly after hospitalisation modified quality of life effects.IMT as an add-on to a 3-week pulmonary rehabilitation improves inspiratory muscle strength, but does not provide additional benefits in terms of exercise capacity, quality of life or dyspnoea. A general recommendation for COPD patients to add IMT to a 3-week pulmonary rehabilitation cannot be made.

Effects of a brief, pedometer-based behavioral intervention for individuals with COPD during inpatient pulmonary rehabilitation on 6-week and 6-month objectively measured physical activity: study protocol for a randomized controlled trial.

BACKGROUND: Pulmonary rehabilitation programs often fail to substantially enhance long-term physical activity in patients with chronic obstructive pulmonary disease (COPD). The reasons for successful physical activity changes in patients with COPD are not well understood. The need to better understand the determinants of physical activity in patients with COPD and effective rehabilitation strategies to improve physical activity is evident. METHODS/DESIGN: The STAR study (Stay Active after Rehabilitation) investigates, in a randomized controlled trial, the additional effect of a pedometer-based behavior-change intervention during inpatient pulmonary rehabilitation on objectively measured physical activity 6 weeks and 6 months post rehabilitation. The intervention uses the behavior-change techniques (1) instruction on how, where and when to perform the behavior, (2) prompt goal setting for physical activity, (3) prompt self-monitoring of behavior, and (4) feedback on behavior. The primary outcome of physical activity will be measured using a physical activity monitor (Actigraph wGT3X-BT) for a period of 7 days, firstly 2 weeks before rehabilitation begins (t0) as well as 6 weeks and 6 months after rehabilitation (t3, t4). Additionally, to predict physical activity progression after rehabilitation, a complex personal diagnostics battery, including questionnaires as well as functional assessments, is to be carried out at the start and end of rehabilitation (t1, t2). This battery is based on the foundational ideas of the Physical Activity-Related health Competence model. Five hundred and two patients with COPD, aged 18 years or older and admitted for an approved pulmonary rehabilitation, will be enrolled in the STAR study. DISCUSSION: The STAR study is designed as a randomized controlled trial to gain a better understanding of the personal determinants of physical activity in patients with COPD and to evaluate a pedometer-based physical activity-change intervention in the context of inpatient pulmonary rehabilitation. The results enable the future identification of patients with COPD who will find it difficult to engage in long-term physical activity after rehabilitation. Based on this, intervention strategies to promote physical activity in the content of pulmonary rehabilitation can be optimized. TRIAL REGISTRATION: Clinicaltrials.gov, ID: NCT02966561 . Registered retrospectively after the start of the recruitment in June 2016 on 22 November 2016. All protocol modifications will be registered in the trial registry.

Effectiveness of pulmonary rehabilitation for patients with asthma: study protocol of a randomized controlled trial (EPRA).

BACKGROUND: Asthma patients are enrolled in multimodal pulmonary rehabilitation (PR) programs. However, available data for the effectiveness of PR in asthma are sparse. Therefore, the primary aim of this randomized control trial (RCT) is to evaluate short-term (end of rehabilitation) and intermediate-term effectiveness (3 months after rehabilitation) of PR for patients with asthma regarding asthma control (primary outcome) and other outcomes. Secondly, moderator effects of gender, age, baseline asthma control, quality of life, and anxiety will be examined. Thirdly, a longitudinal follow-up study will explore the course of the outcomes over one year and the annual costs. METHODS: The EPRA study is a single-center randomized controlled waiting-list trial in the Bad Reichenhall Clinic. Inclusion criteria include a referral diagnosis for uncontrolled asthma, no cognitive impairment and no very severe co-morbidities that indicate significantly greater illness morbidity than asthma alone. In the intervention group (IG), participants will start PR within 4 weeks after randomization; participants of the control group (CG) will start PR 20 weeks after randomization. Data will be assessed at randomization (T0), after 4 weeks (T1; IG: begin of PR), 7 weeks (T2; IG: end of PR), and 20 weeks (T3, CG: begin of PR). The primary outcome is asthma control at T2/T3. Secondary outcomes are health-related quality of life, functional exercise capacity, dyspnea, anxiety, depression, subjective self-management skills, illness perceptions, sick leave and subjective work ability. Outcomes will be analyzed with analysis of covariance, including baseline values of the respective outcomes as covariates. Healthcare costs will be analyzed with a gamma model with a log-link. A longitudinal follow-up study will generate additional data at 3/6/9/12 months after PR for both IG and CG. Latent change models will be used to analyze the course of the primary and secondary outcomes. Annual cost differences before and after rehabilitation will be compared by paired t-test. DISCUSSION: This RCT will determine the effectiveness of a complex inpatient PR for asthma patients concerning asthma control. Furthermore, important medical and economic information regarding the effectiveness of PR as part of the long-term management of patients with uncontrolled asthma will be generated. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00007740 , May 15, 2015). Protocol version: 1.0 (December, 23, 2016).

A multicentre validation of the 1-min sit-to-stand test in patients with COPD.

Our aim was to comprehensively validate the 1-min sit-to-stand (STS) test in chronic obstructive pulmonary disease (COPD) patients and explore the physiological response to the test.We used data from two longitudinal studies of COPD patients who completed inpatient pulmonary rehabilitation programmes. We collected 1-min STS test, 6-min walk test (6MWT), health-related quality of life, dyspnoea and exercise cardiorespiratory data at admission and discharge. We assessed the learning effect, test-retest reliability, construct validity, responsiveness and minimal important difference of the 1-min STS test.In both studies (n=52 and n=203) the 1-min STS test was strongly correlated with the 6MWT at admission (r=0.59 and 0.64, respectively) and discharge (r=0.67 and 0.68, respectively). Intraclass correlation coefficients (95% CI) between 1-min STS tests were 0.93 (0.83-0.97) for learning effect and 0.99 (0.97-1.00) for reliability. Standardised response means (95% CI) were 0.87 (0.58-1.16) and 0.91 (0.78-1.07). The estimated minimal important difference was three repetitions. End-exercise oxygen consumption, carbon dioxide output, ventilation, breathing frequency and heart rate were similar in the 1-min STS test and 6MWT.The 1-min STS test is a reliable, valid and responsive test for measuring functional exercise capacity in COPD patients and elicited a physiological response comparable to that of the 6MWT.