Monotherapy: Key cause of macrolide-resistant Mycobacterium avium complex disease.

BACKGROUND: Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by appropriate screening and treatment practices. METHODS: Patients with macrolide-resistant MAC isolates between March 2019 and March 2022 were retrieved from the mycobacteriology reference laboratory database at Radboudumc, Nijmegen, the Netherlands. Clinical consultation reports were extracted from the database to assess the cause of macrolide resistance. RESULTS: Sixteen patients with macrolide-resistant MAC disease were included, from a total of 815 patients with MAC isolates (2%); Macrolide monotherapy in bronchiectasis or CF was the most frequent cause of development of macrolide-resistance MAC disease (n = 8; 50%). Short (n = 3; mean duration 9 months, range 6-12) or guideline non-compliant (n = 2) treatment regimens and patient non-adherence (n = 2) were other key causes of macrolide-resistance. CONCLUSIONS: Macrolide monotherapy after inappropriate screening is the most frequent cause of macrolide-resistant Mycobacterium avium complex disease in the Netherlands. Educational efforts are needed to prevent this.

Isotonic quadriceps endurance is better associated with daily physical activity than quadriceps strength and power in COPD: an international multicentre cross-sectional trial.

Knowledge about modifiable determinants of daily physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is crucial to design effective PA interventions. The present study aimed to determine the contribution of quadriceps strength, power and endurance to daily PA in COPD. Additionally, for quadriceps endurance, we also aimed to determine to what extent the association varies according to the mode of movement (isotonic, isometric, or isokinetic). Using a multicentre cross-sectional trial design we determined the contribution of quadriceps function to daily PA (steps, sedentary time and time spent doing moderate-to-very-vigorous physical activity [MVPA]) using bivariate and partial Pearson correlation analysis (r) and multiple linear regression models (ΔR2). Pre-determined controlling factors were sex, age, body mass index (BMI), COPD-assessment test, forced expiratory volume in one second in percent of the predicted value (FEV1pred), and distance walked on the 6-minute walk test. Eighty-one patients with COPD (mean ± SD: age 67 ± 8 years, FEV1pred 57 ± 19%, daily steps 4968 ± 3319, daily sedentary time 1016 ± 305 min, and MVPA time 83 ± 45 min) were included. Small to moderate bivariate correlations (r = .225 to .452, p < .05) were found between quadriceps function and measures of PA. The best multiple linear regression models explained 38-49% of the variance in the data. Isotonic endurance was the only muscle contributor that improved all PA models; daily steps (ΔR2 = .04 [relative improvement 13%] p = .026), daily sedentary time (ΔR2 = .07 [23%], p = .005) and MVPA-minutes (ΔR2 = .08 [20%], p = .001). Isotonic endurance was also independently associated with most PA variables, even when controlling for strength, power or isometric-isokinetic endurance properties of the muscle (r = .246 to .384, p < .05). In contrast, neither strength, power, isometric-or isokinetic endurance properties of the muscle was independently associated with PA measures when controlling for isotonic endurance (r = .037 to .219, p > .05). To conclude, strength, power, and endurance properties of the quadriceps were low to moderately associated with PA in patients with COPD. Isotonic quadriceps endurance was the only quadriceps property that was independently associated with the different measures of PA after controlling for a basic set of known determinants of PA, quadriceps strength or power, or isometric or isokinetic quadriceps endurance. Future longitudinal studies should investigate its potential as a modifiable determinant of PA.

Specific Contribution of Quadriceps Muscle Strength, Endurance, and Power to Functional Exercise Capacity in People With Chronic Obstructive Pulmonary Disease: A Multicenter Study.

OBJECTIVE: Various functional muscle properties affect different aspects of functional exercise capacity in people with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the contribution of quadriceps muscle strength, endurance, and power to 6-Minute Walking Distance (6MWD) and 1-minute sit-to-stand test (1STS) performance in people with COPD. METHODS: The study was a prospective, multicenter, cross-sectional study. Anthropometrics, Medical Research Council dyspnea scale, lung function, 6MWD, and 1STS number of repetitions were assessed. Isometric quadriceps strength and endurance, isotonic quadriceps endurance, isokinetic quadriceps strength, and power were assessed on a computerized dynamometer while functional quadriceps power was determined during 5 sit-to-stand repetitions. Univariate and multivariate analyses were performed to determine the contribution of functional muscle properties to the 6MWD and the 1STS number of repetitions. RESULTS: The study included 70 people with COPD (mean % predicted forced expiratory volume in 1 second = 58.9 [SD = 18.2]). The 6MWD correlated with each functional muscle property except the isometric quadriceps endurance. The number of repetitions during the 1STS correlated with each functional muscle property except isometric measurements. Multivariate models explained 60% and 39% of the variance in the 6MWD and 1STS number of repetitions, respectively, with quadriceps power determined during 5 sit-to-stand repetitions being the muscle functional property with the strongest contribution to the models. CONCLUSION: Except for isometric endurance, quadriceps strength, endurance, and power were associated with functional exercise capacity in people with moderate COPD. Among these functional muscle properties, muscle power contributed the most to the 6MWD and 1STS number of repetitions, suggesting that muscle power is more relevant to functional exercise capacity than muscle strength or endurance in people with COPD. IMPACT: Understanding the individual contribution of muscle properties to functional status is important to designing interventions. This study provides the guidance that muscle power may be more important to functional exercise capacity than muscle strength or endurance in people with COPD.

Pulmonary rehabilitation, physical activity and aortic stiffness in COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and cardiovascular disease is a major cause of death in COPD. The current literature indicates that changes in cardiovascular risk during pulmonary rehabilitation (assessed using aortic stiffness) are heterogeneous suggesting that there may be sub-groups of patients who do and do not benefit. OBJECTIVES: To investigate the characteristics of COPD patients who do and do not experience aortic stiffness reduction during pulmonary rehabilitation, examine how changes relate to physical activity and exercise capacity, and assess whether changes in aortic stiffness are maintained at 6 weeks following rehabilitation. METHODS: We prospectively measured arterial stiffness (aortic pulse-wave velocity), exercise capacity (Incremental Shuttle Walk Test) and physical activity (daily step count) in 92 COPD patients who started a six week pulmonary rehabilitation programme, 54 of whom completed rehabilitation, and 29 of whom were re-assessed six weeks later. RESULTS: Whilst on average there was no influence of pulmonary rehabilitation on aortic stiffness (pre- vs. post pulse-wave velocity 11.3 vs. 11.1 m/s p = 0.34), 56% patients responded with a significant reduction in aortic stiffness. Change in aortic stiffness (absolute and/or percentage) during rehabilitation was associated with both increased physical activity (rho = - 0.30, p = 0.042) and change in exercise capacity (rho = - 0.32, p = 0.02), but in multivariable analysis most closely with physical activity. 92% of the responders who attended maintained this response six weeks later. CONCLUSION: Elevated aortic stiffness in COPD is potentially modifiable in a subgroup of patients during pulmonary rehabilitation and is associated with increased physical activity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03003208. Registered 26/12/ 2016.

Inter-day test-retest reliability and feasibility of isokinetic, isometric, and isotonic measurements to assess quadriceps endurance in people with chronic obstructive pulmonary disease: A multicenter study.

The aims were to determine reliability and feasibility of measurements to assess quadriceps endurance in people with chronic obstructive pulmonary disease. Sixty participants (forced expiratory volume in one second (mean ± standard deviation) 55 ± 18% of predicted, age 67 ± 8 years) were tested in an inter-day, test-retest design. Isokinetic, isometric, and isotonic protocols were performed using a computerized dynamometer. Test-retest relative and absolute reliability was determined via intraclass correlation coefficient (ICC), coefficient of variation (CV%), and limits of agreement (LoA%). Isokinetic total work demonstrated very high relative reliability (ICC: [95% confidence interval] = 0.98 [0.94-0.99]) and the best absolute reliability (CV% (LoA%) = 6.5% (18.0%)). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64 [0.46-0.77], 0.88 [0.76-0.94], 0.91 [0.85-0.94]), and measures of absolute reliability (CV% (LoA%)) were 20.3% (56.4%), 14.9% (40.8%), and 15.8% (43.1%). For isokinetic total work and isometric measurements, participants performed better on retest (4.8% and 10.0%, respectively). The feasibility was similar across protocols with an average time consumption of less than 7.5 minutes. In conclusion, isokinetic, isometric, and isotonic measurements of quadriceps endurance were feasible to a similar extent and presented low-to-very high relative reliability. Absolute reliability seems to favor isokinetic total work measurements.