For patients with neuromuscular disorders, lung insufflation with positive pressure is an accepted technique to increase inspiratory volume over VC to improve peak cough flow (PCF).
The aim of the ...study was to determine the pressure or volume required to achieve the highest individual PCF.
In 40 patients dependent on noninvasive ventilation (VC, 16 ± 11% predicted; age, 20 ± 4 yr) and in 20 healthy control subjects, insufflation capacity (IC) was measured during titration from 10 to maximum 40 mbar using intermittent positive pressure breathing (IPPB) or the lung insufflation assist maneuver (LIAM) of the VENTIlogic LS ventilator.
IPPB or LIAM titration resulted in a pressure-volume curve with an estimated total compliance of 0.23 ± 0.11 L/kPa in the patients and 1.0 ± 0.3 L/kPa in the controls and a plateau for IC at pressures between 30 and 40 mbar. IPPB or LIAM improved VC from 451 ± 229 ml to a maximum IC (ICmax) of 1,027 ± 329 ml, and PCF improved from 109 ± 45 to 202 ± 62 L/min (P < 0.01 for all). The highest individual PCF was achieved with 27 ± 6 mbar and an IC of 924 ± 379 ml, which was significantly below ICmax (P < 0.01).
A submaximal insufflation is ideal for generating the best individual PCF even in patients with severely reduced compliance of the respiratory system. Optimum insufflation capacity can be achieved using IPPB or LIAM with moderate pressures. Both techniques are equally effective and considered safe.
Forced expiratory volume in 1 second (FEV
) is the only parameter currently recognized as a surrogate endpoint in cystic fibrosis (CF) trials. However, FEV
is relatively insensitive to changes in the ...small airways of patients with milder lung disease. This pilot study aimed to explore the lung clearance index (LCI) as a marker for use in efficacy trials with inhaled antibiotics in CF.
This open-label, single-arm study enrolled CF patients with Pseudomonas aeruginosa infection, who were treated with tobramycin (28-day on/off regime). FEV
, LCI and bacterial load in sputum (CFU) were assessed at baseline, after 1, 4 and 8 weeks of treatment.
All patients (n = 17) showed elevated LCI of > 11 despite 3 patients having normal FEV
(> 90% predicted) at baseline. Overall, LCI improved in 8 (47%) patients and FEV
in 9 (53%) patients. At week 4, LCI improved by 0.88, FEV
increased by 0.52%, and P. aeruginosa reduced by 30,481.3 CFU/mL. These changes were however statistically non-significant. Six adverse events occurred in 5/17 (29.4%) patients, most of which were mild-to-moderate in severity.
Due to the low evaluable sample size, no specific trend was observed related to the changes between LCI, FEV
and CFU. Based on the individual data from this study and from recently published literature, LCI has been shown to be a more sensitive parameter than FEV
for lung function. LCI can be hypothesized to be an appropriate endpoint for efficacy trials in CF patients if the heterogeneity in lung function is limited by enrolling younger patients or patients with more milder lung disease and thus, limiting the ventilation inhomogeneities.
The study is registered with ClinicalTrials.gov, identifier: NCT02248922.
Little is known about motor competence and the longitudinal development of motor performance among youth with cystic fibrosis (CF). In this study, we assessed aspects of motor performance in ...different age groups of young patients with CF and compared them with a healthy reference group of same aged children. We also examined the development of motor performance among different age groups of these children with CF, using The Deutscher Motorik Test (DMT) to assess attributes of health-related and motor performance-related fitness. We used an incremental ergometer cycle test to determine maximal exercise capacity (expressed as peak workload). We evaluated and recorded habitual physical activity (PA) as measured by the number of steps per day and the time spent in different PA intensities (expressed in metabolic equivalents). In total, 31 children and adolescents with CF agreed to participate (13 girls,18 boys) aged 6–17 years (M = 11.3, SD =3.3 years); they had a mean one second forced expiratory volume (expressed as a percentage of predicted value % pred) of 87.2% (SD = 22.3%). We found their values of health-related and motor performance-related fitness to be significantly lower (p < 0.05) than those of their healthy peer participants. In contrast to the reference group, participants with CF up to 14 years of age showed a linear improvement in these values and in their PA, followed by a plateau or even a nonsignificant decrease after age 14. These findings have important implications for the development and prescription of exercise programs for children with CF. Besides aerobic and strength exercises, we recommend that neuromuscular training be integrated into exercise programs to improve the coordinative abilities of youth with CF. More attention should be paid to vulnerable older adolescents to ensure their long-term motivation to maintain exercise participation.
Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants ...only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors' own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease.
Purpose
Sleep disturbances and poor sleep quality are known to be present in patients with CF. Regular physical activity plays an important role in the treatment of CF patients due to its positive ...influence on progression of disease and quality of life. The aim of this work is to create a home-based sleep and activity profile and to investigate the influence of habitual physical activity (HPA) on sleep quality in children, adolescents, and adults with CF.
Methods
A total of 109 CF patients (64 male, mean age 22.7 ± 12.0 years; mean ppFEV1 63.0 ± 26.7) were equipped with an actigraph for a home-based collection of data on sleep and activity over 4 weeks.
Results
Age, FEV1, and BMI affect sleep and activity in CF patients. Especially younger age and higher FEV1 show a great influence on certain aspects of sleep (SE, TST, TIB, WASO, # of awakenings) and activity and its different intensities. General HPA does not affect sleep, but there is a strong correlation between times spent in vigorous to very vigorous intensities and better sleep quality.
Conclusion
Besides younger age and higher FEV1, daily activity in higher intensities influences sleeping behavior of CF patients in a positive way. Patients with poor sleep quality and sleep disturbances possibly benefit from an intensification of physical activity in the home environment.
Trail registration
number: 14–6117-BO (University Duisburg-Essen) and NCT 03518697 (clinical trials).
Culturing of bronchoalveolar lavage (BAL) fluid is a commonly used method for pathogen detection in pneumonia. However, the sensitivity is low, especially in patients pre-treated with anti-infective ...agents. The early detection of a pathogen is crucial for the outcome of respiratory tract infections. For bloodstream infections, a multiplex polymerase chain reaction (PCR) assay (SeptiFast®, SF) is available for improved pathogen detection from blood.
The aim of the present study was to determine whether the SF assay is applicable to the BAL of children with pulmonary infections and whether the frequency of pathogen detection is enhanced by the use of this multiplex PCR method.
We investigated 70 BAL samples of 70 children simultaneously by culture and multiplex PCR. The frequency of pathogen detection was compared.
Pathogens were detected more frequently by SF than by culture (83% vs. 31%; p < 0.001). This advantage was shown for immunocompetent patients (p = 0.001) as well as for immunocompromised patients (p = 0.003). The majority (38/44; 86%) of the Gram positive cocci were only detected by SF. Fungal organisms were detected in 7/70 patients (10%) by SF and in 2/70 (3%) by culture (p = 0.125).
Compared to conventional culture, the use of the SF assay on the BAL of children with pneumonia increases pathogen detection rates and therefore adds important information to guide anti-infective therapy.
Background. Regular physical activity plays an important role in the treatment of patients with cystic fibrosis (CF). This study is aimed at investigating the effects of a 12-month partially ...supervised exercise program on attributes of health-related and motor performance fitness, lung function (ppFEV1), BMI, and habitual physical activity (HPA, steps/day) in adults with CF. Methods. Attributes of health-related and motor performance fitness were examined at the beginning (T0), after 6 (T1), and 12 months (T2) on the basis of five test items: forward bend (FB), bent knee hip extension (HE), plank leg raise (PLR), standing long jump (SLJ), and standing on one leg (OLS). Additionally, we recorded HPA by accelerometry, peak exercise performance (Wpeak) by an incremental cycle test, ppFEV1, and BMI. During the first six months, there was close supervision by an experienced sport therapist. Results. 26 CF patients (8 female, mean age 26.5±7.9 years; ppFEV1 53.7±21.0) completed the exercise program. Significant improvements were recorded from T0 to T1 (FB: p≤0.05; PLR, OLS: p≤0.01) and from T0 to T2 (FB, PLR: p≤0.01 and HE, OLS: p≤0.05). Wpeak, ppFEV1, BMI, and HPA showed no significant improvement between the single test points and over the entire study period (all p>0.05). Conclusion. Our results show trainability of adults with CF in aspects of health-related and motor performance fitness during a partially supervised exercise program. Close supervision positively influences the results. Using a simple test setup seems to be a promising tool for evaluating the effects of exercise programs in CF and could serve as an additional outcome parameter in future clinical trials. Trial registration: ClinicalTrials.gov (retrospectively registered May 8, 2018).
Habitual physical activity (PA) and exercise training are accepted as important aspects of care for people with cystic fibrosis (pwCF) to improve health-related measures of physical fitness, which in ...turn have a positive impact on quality of life and prognosis. In the last decade, effective CFTR modulator therapies have become a promising treatment for pwCF by targeting the underlying cause of CF. This highly effective therapy improves clinical outcomes and quality of life in people with specific CFTR mutations. Little is known about the longitudinal pattern of PA or the impact of the highly effective modulator therapy with Elexacaftor/Tezacaftor/Ivacaftor (ETI) on PA in adult pwCF. This study assessed the course of device-based PA measurement in adult pwCF and evaluated the effects of ETI on habitual physical activity in those who were eligible for ETI.
Data from adult pwCF (aged ≥18 years) were analysed at baseline and follow-up, using identical assessments at both time points. Outcome parameters were PA in steps/day and the intensity of PA. The group that received ETI was treated for an average of 33 weeks and not for the entire duration of the period. The data were collected between 2021 and 2022, following the removal of absolute pandemic restrictions/lockdowns.
Follow-up duration was 5.6 years in pwCF with ETI (ETI group,
= 21) and 6.5 years in pwCF without ETI (non-ETI group,
= 6). From baseline to follow-up, pwCF treated with ETI had a significant increase in steps/day (+25%,
= 0.019) and a non-significant increase in moderate-to-vigorous intensity time (+5.6%,
= 0.352). Conversely, individuals in the non-ETI group showed a non-significant decrease in both steps/day -3.2%,
= 0.893) and moderate-to-vigorous intensity time (-25%,
= 0.207). The ETI group showed a significant decrease in percent predicted forced expiratory volume in 1 s (ppFEV
) and FEV
z-score before the start of ETI treatment, both of which improved significantly after therapy initiation. Body weight and body mass index also improved significantly with ETI use.
These data suggest that ETI treatment has a positive effect on habitual physical activity behavior in the adult pwCF studied.
Background: Longitudinal data on changes in health-related quality of life (HRQoL) in adult people with cystic fibrosis (pwCF) and the longitudinal effects of Elexacaftor/Tezacaftor/Ivacaftor therapy ...(ETI) on HRQoL or HRQoL domains are currently scarce. This study aimed to investigate the effects of ETI on HRQoL and compare them with those of pwCF who did not receive highly effective CFTR modulators over a longer period. Methods: Baseline assessment and follow-up data for 5.6 years in pwCF with (n = 21) and 6.5 years in pwCF without (n = 6) ETI (≥18 years) were evaluated. The assessment of HRQoL and clinical parameters was identical at both time points. HRQoL was assessed using the CFQ-R, and clinical outcomes included BMI, ppFEV1, and FEV1 z-score. Results: ETI was found to improve all HRQoL domains at more than four points over time, and their increases were significant except for vitality, digestion, treatment burden, and social functioning (p < 0.05). Without ETI, psychosocial domains remained almost constant, whereas most physical domains decreased over time. Conclusions: The results of the present study show that ETI therapy has a positive effect on HRQoL and clinical outcomes over time but not in pwCF without ETI treatment. Furthermore, our results suggest that disease progression over time affects the physical domains of HRQoL more than the psychosocial domains. Due to the small sample size and the heterogeneity of the study population (CFTR mutation genotype), the results should be interpreted with some caution.
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