Test-retest reliability, construct validity and determinants of 6-minute walk test performance in adult patients with asthma.

INTRODUCTION AND OBJECTIVES: Current knowledge regarding the measurement properties of the 6-minute walk test (6MWT) in patients with asthma is limited. Therefore, the aim of this study was to assess the test-retest reliability, measurement error and construct validity of the 6MWT and identify determinants of 6-minute walk distance (6MWD) in patients with asthma. PATIENTS AND METHODS: 201 asthma patients referred for pre-pulmonary rehabilitation assessment, were retrospectively analyzed (age 61±12 years, 42% male, FEV1 78±27% predicted). Patients performed two 6MWTs on subsequent days using a 30 m straight walking course. Other measurements included resting dyspnea, maximal exercise capacity, body composition, pulmonary function, pulmonary and quadriceps muscle strength and symptoms of anxiety and depression. Measurement error (absolute reliability) was tested using standard error of measurement (SEM), minimal detectable change at 95% confidence interval (MDC95%) and Bland and Altman 95% limits of agreement, whereas test-retest reliability (relative reliability) and construct validity were assessed using the intra-class correlation coefficient (ICC2,1) and correlations, respectively. RESULTS: The 6MWD showed excellent test-retest reliability (ICC2,1: 0.91). The mean change in 6MWD after the second 6MWT was 18m (95%CI 11-24m), with 73% of the patients walking further in the second test. The SEM and MDC95% for the 6MWT were 35 m and 98 m, respectively. The best 6MWD correlated strongly with peak oxygen uptake during CPET and resting dyspnea (r = 0.61-0.64) and had no-to-moderate correlations with body composition, pulmonary function, respiratory and quadriceps muscle strength and symptoms of anxiety and depression (r = 0.02-0.45). Multiple linear regression was able to identify maximal workload, BMI, rollator use, maximal expiratory pressure, FEV1 and DLCO as independent determinants of the best 6MWD (R2 = 0.58). CONCLUSIONS: The 6MWT was considered to be reliable and valid in patients with asthma, which strengthens its clinical utility. However, the majority of patients demonstrated a considerable learning effect in the second 6MWT, providing a strong rationale for performing two 6MWTs.

Comparison between myocardial function assessed by echocardiography during hospitalization for COVID-19 and at 4 months follow-up.

In patients hospitalized for corona virus infectious disease 19 (COVID-19) it is currently unknown whether myocardial function changes after recovery and whether this is related to elevated cardiac biomarkers. In this single center, prospective cohort study we consecutively enrolled hospitalized COVID-19 patients between 1 April and 12 May 2020. All patients underwent transthoracic echocardiography (TTE) evaluation during hospitalization and at a median of 131 days (IQR; 116-136) follow-up. Of the 51 patients included at baseline, 40 (age: 62 years (IQR; 54-68), 78% male) were available for follow-up TTE. At baseline, 68% of the patients had a normal TTE, regarding left ventricular (LV) and right ventricular (RV) volumes and function, compared to 83% at follow-up (p = 0.07). Median LV ejection fraction (60% vs. 58%, p = 0.54) and tricuspid annular plane systolic excursion (23 vs 22 mm, p = 0.18) were comparable between hospitalization and follow-up, but a significantly lower RV diameter (39 vs. 34 mm, p = 0.002) and trend towards better global longitudinal strain (GLS) (- 18.5% vs - 19.1%, p = 0.07) was found at follow-up. Subgroup analysis showed no relation between patients with and without elevated TroponinT and/or NT-proBNP during hospitalization and myocardial function at follow-up. Although there were no significant differences in individual myocardial function parameters at 4 months follow-up compared to hospitalisation for COVID-19, there was an overall trend towards normalization in myocardial function, predominantly due to a higher rate of normal GLS at follow-up.

[Post-COVID-19 rehabilitation; a matter of customisation]. / Nazorg voor covid-19-patiënten.

In the early phase of the COVID-19 pandemic, knowledge about the natural course of recovery of COVID-19 is limited. We therefore describe - based on generic knowledge of post IC syndrome (PICS) and (pulmonary) rehabilitation - the possibilities to organize personalized rehabilitation programs in several care settings. To illustrate variety in need for rehabilitation, we described three cases of critical COVID-19 disease survivors after treatment in the intensive care unit. Some patients require immediate rehabilitation following hospitalization, but rehabilitation may also be initiated in the home environment. For the latter population monitoring of progress and recovery should be organized to assess whether a more intensified multidisciplinary rehabilitation program is needed. This may be initiated in one of the medical rehabilitation centers or in pulmonary rehabilitation centers. Post-COVID-19 rehabilitation, regardless of the specific form, should be patient-centered and multidisciplinary organized.

The clinical effectiveness of the COPDnet integrated care model.

RATIONALE: Integrated care models have the potential to improve outcomes for patients with COPD. We therefore designed the COPDnet integrated care model and implemented it in two hospitals and affiliated primary care regions in the Netherlands. The COPDnet model consists of a comprehensive diagnostic trajectory ran in secondary care followed by a non-pharmacological intervention program of both monodisciplinary and multidisciplinary components. OBJECTIVE: To assess the clinical effectiveness of the COPDnet integrated care model on health status change in patients with COPD. METHODS: A total of 402 patients with COPD were offered care according to the COPDnet model. At baseline and between 7- and 9-months later health status was measured with the Clinical COPD Questionnaire (CCQ). Primary analysis was carried out for the sample at large. In addition, subgroup analyses were performed after stratification for the type of non-pharmacological intervention where patients had been referred to. RESULTS: The CCQ total score improved statistically significantly from 1.94 ± 1.04 to 1.73 ± 0.96 (P < 0.01) in the 154 patients with valid follow-up measurements. Subgroup analyses revealed significant improvements in the patients receiving pulmonary rehabilitation only. No change in health status was found in patients receiving pharmacotherapy only, carried out self-treatment or who participated in mono-disciplinary primary care offered by allied healthcare professionals. CONCLUSIONS: An improved health status was found in patients with COPD who received care according to the COPDnet integrated care model. Subgroups participating in an interdisciplinary pulmonary rehabilitation program predominantly accounted for this effect.

Classical NF-κB activation impairs skeletal muscle oxidative phenotype by reducing IKK-α expression.

BACKGROUND: Loss of quadriceps muscle oxidative phenotype (OXPHEN) is an evident and debilitating feature of chronic obstructive pulmonary disease (COPD). We recently demonstrated involvement of the inflammatory classical NF-κB pathway in inflammation-induced impairments in muscle OXPHEN. The exact underlying mechanisms however are unclear. Interestingly, IκB kinase α (IKK-α: a key kinase in the alternative NF-κB pathway) was recently identified as a novel positive regulator of skeletal muscle OXPHEN. We hypothesised that inflammation-induced classical NF-κB activation contributes to loss of muscle OXPHEN in COPD by reducing IKK-α expression. METHODS: Classical NF-κB signalling was activated (molecularly or by tumour necrosis factor α: TNF-α) in cultured myotubes and the impact on muscle OXPHEN and IKK-α levels was investigated. Moreover, the alternative NF-κB pathway was modulated to investigate the impact on muscle OXPHEN in absence or presence of an inflammatory stimulus. As a proof of concept, quadriceps muscle biopsies of COPD patients and healthy controls were analysed for expression levels of IKK-α, OXPHEN markers and TNF-α. RESULTS: IKK-α knock-down in cultured myotubes decreased expression of OXPHEN markers and key OXPHEN regulators. Moreover, classical NF-κB activation (both by TNF-α and IKK-ß over-expression) reduced IKK-α levels and IKK-α over-expression prevented TNF-α-induced impairments in muscle OXPHEN. Importantly, muscle IKK-α protein abundance and OXPHEN was reduced in COPD patients compared to controls, which was more pronounced in patients with increased muscle TNF-α mRNA levels. CONCLUSION: Classical NF-κB activation impairs skeletal muscle OXPHEN by reducing IKK-α expression. TNF-α-induced reductions in muscle IKK-α may accelerate muscle OXPHEN deterioration in COPD.