Inquiry. 2022 Jan-Dec;59:469580221086921. doi: 10.1177/00469580221086921.

ABSTRACT

Care for many progressive chronic diseases continues to improve, allowing patients to survive and thrive for longer periods of time1. People living with such conditions may now find themselves able to achieve long-term goals in education and career development2. Many people now occupy the dual roles of scientist and patient3. This commentary article synthesizes experiences of scientists and advocates with the progressive genetic disease cystic fibrosis (CF) who collaborated on a career development session for the Cystic Fibrosis Foundation's inaugural ResearchCon event in 2019. It explores how such collaborations affirm and transform individual perspectives on patient science and its importance in broader scientific research agenda setting. We first share our own individual insights about the experience and impact of the ResearchCon panel session before progressing to discussion and future directions centering the shared insights from one another's reflections.

PMID:35420504 | DOI:10.1177/00469580221086921

Pediatr Pulmonol. 2022 Apr 13. doi: 10.1002/ppul.25921. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the short- and medium-term repeatability of lung clearance index (LCI2.5 ) in infants and calculate the number of patients needed to enrol in a study (N) using LCI2.5 as a primary outcome.

METHODS: An 8-month follow-up observational study was employed for assessing short-term [coefficient of repeatability (CR) and intraclass correlation (ICC)] and medium-term repeatability (Bland-Altman method) of LCI2.5 in infants with cystic fibrosis (CF) or recurrent wheeze (RW) measured by the nitrogen multiple-breath washout test (N2 -MBW). Using these variability data, the N to reach 90% test power at the level of statistical significance (0.05) was calculated.

RESULTS: Forty infants with CF and 21 with RW were enrolled. Initial N2 -MBW testing was successful in 33 and 17 patients, respectively. Follow-up data were available for 23 and 11 infants, respectively. Short-term repeatability of LCI2.5 was high (CR = 1.10 and 1.04 in CF and RW patients, respectively; ICC = 0.88 and 0.83 in CF and RW patients, respectively). The between-subject standard deviation was <13% of the actual LCI2.5 value. In clinically stable patients, LCI2.5 did not significantly change during the 8-month follow-up. Mean LCI2.5 change was -0.08 (1% of baseline) in CF and -0.05 (0.6%) in RW, with 95% limits of agreement being (-1.70; 1.53) in CF and (-1.51; 1.40) in RW patients. N = 23 infants if both intra-group differences of LCI2.5 and minimal difference to be detected would be 2.0.

CONCLUSION: N2 -MBW may be a reproducible tool with reasonable test power to detect differences in infant studies. This article is protected by copyright. All rights reserved.

PMID:35419996 | DOI:10.1002/ppul.25921

Front Cell Infect Microbiol. 2022 Mar 28;12:816615. doi: 10.3389/fcimb.2022.816615. eCollection 2022.

ABSTRACT

Mycobacterium abscessus complex (MABC) is an important pathogen of immunocompromised patients. Accurate and rapid determination of MABC at the subspecies level is vital for optimal antibiotic therapy. Here we have used comparative genomics to design MABC subspecies-specific PCR assays. Analysis of single nucleotide polymorphisms and core genome multilocus sequence typing showed clustering of genomes into three distinct clusters representing the MABC subspecies M. abscessus, M. bolletii and M. massiliense. Pangenome analysis of 318 MABC genomes from the three subspecies allowed for the identification of 15 MABC subspecies-specific genes. In silico testing of primer sets against 1,663 publicly available MABC genomes and 66 other closely related Mycobacterium genomes showed that all assays had >97% sensitivity and >98% specificity. Subsequent experimental validation of two subspecies-specific genes each showed the PCR assays worked well in individual and multiplex format with no false-positivity with 5 other mycobacteria of clinical importance. In conclusion, we have developed a rapid, accurate, multiplex PCR-assay for discriminating MABC subspecies that could improve their detection, diagnosis and inform correct treatment choice.

PMID:35419298 | PMC:PMC8995789 | DOI:10.3389/fcimb.2022.816615

Front Microbiol. 2022 Mar 28;13:870104. doi: 10.3389/fmicb.2022.870104. eCollection 2022.

ABSTRACT

The bacterium Pseudomonas aeruginosa (Pa) is ubiquitous in the environment and causes opportunistic infections in humans. Pa is increasingly becoming one of the most difficult to treat microorganisms due to its intrinsic and acquired resistance to multiple antibiotics. The World Health Organization estimates that at least 700,000 people die each year from drug resistant microbial infections and have listed Pa as one of three bacterial species for which there is the most critical need for the development of novel therapeutics. Pa is a common cause of bloodstream infections (BSI) and bacterial sepsis. With nearly 49 million sepsis cases and 11 million deaths worldwide, an effective vaccine against Pa could prevent the morbidity and mortality resulting from Pa BSI and lessen our dependence on antibiotics. We reviewed the current landscape of Pa vaccines in pre-clinical and clinical stages over the last two decades. It is readily apparent that Pa vaccine development efforts have been largely directed at the prevention of pulmonary infections, likely due to Pa's devastating impact on individuals with cystic fibrosis. However, the increase in nosocomial infections, BSI-related sepsis, and the emergence of widespread antibiotic resistance have converged as a major threat to global public health. In this perspective, we draw attention to potential Pa vaccine candidates and encourage a renewed effort for prophylactic vaccine development to prevent drug-resistant Pa BSI.

PMID:35418967 | PMC:PMC8996235 | DOI:10.3389/fmicb.2022.870104

Front Microbiol. 2022 Mar 28;13:762307. doi: 10.3389/fmicb.2022.762307. eCollection 2022.

ABSTRACT

Achromobacter genus (including Achromobacter xylosoxidans, the most prevalent Achromobacter species in patients with cystic fibrosis) is poorly susceptible to most conventional antibiotics. Contribution of efflux by AxyABM, AxyXY-OprZ, and AxyEF-OprN and of target mutations were studied in clinical isolates of A. xylosoxidans and Achromobacter insuavis. Forty-one isolates longitudinally collected from 21 patients with CF were studied by whole-genome sequencing (WGS)-typing, determination of minimum inhibitory concentrations (MICs) of β-lactams, aminoglycosides, colistin, azithromycin, ciprofloxacin, chloramphenicol, and doxycycline, and expression (quantitative RT-PCR) and function (measure of the uptake of a fluorescent substrate) of efflux pumps. WGS-based typing resulted in 10 clusters comprising 2 or 3 isolates and 20 singletons. The efflux activity was high in strains with elevated MICs for amikacin or azithromycin. This work sheds a new light on the impact of efflux and target mutations in resistance of Achromobacter to several drugs.

PMID:35418957 | PMC:PMC8996194 | DOI:10.3389/fmicb.2022.762307

Emerg Microbes Infect. 2022 Apr 14:1-49. doi: 10.1080/22221751.2022.2065932. Online ahead of print.

ABSTRACT

AbstractN-chlorotaurine (NCT) a long-lived oxidant generated by leukocytes, can be synthesized chemically and applied topically as an anti-infective to different body sites, including the lung via inhalation. Here, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus (RSV).Virucidal activity of NCT was tested in plaque assays, confirmed by RT-qPCR assays. Attack on virus proteins was investigated by mass spectrometry.NCT revealed broad virucidal activity against all viruses tested at 37°C and pH 7. A significant reduction in infectious particles of SARS-CoV-2 isolates from early 2020 by 1 log10 was detected after 15 min of incubation in 1% NCT. Proteinaceous material simulating body fluids enhanced this activity by transchlorination mechanisms (1 -2 log10 reduction within 1-10 minutes). Tested SARS-CoV-2 variants B.1.1.7 (Alpha) und B.1.351 (Beta) showed a similar susceptibility. Influenza virus infectious particles were reduced by 3 log10 (H3N2) to 5 log10 (H1N1pdm), RSV by 4 log10. Mass spectrometry of NCT-treated SARS-CoV-2 spike protein and 3C-like protease, influenza virus hemagglutinin and neuraminidase, and RSV fusion glycoprotein disclosed multiple sites of chlorination and oxidation as the molecular mechanism of action.Application of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.

PMID:35418279 | DOI:10.1080/22221751.2022.2065932

Georgian Med News. 2022 Mar;(324):87-92.

ABSTRACT

The purpose of the work was to demonstrate that an early stage diagnosis of the interstitial lung disease would allow establishing the proper treatment course and as a result, increase life expectancy and quality in patients with this disorder. More than 200 acute and chronic conditions with inflammatory and fibroproliperative changes comprise the group of diffuse lung diseases. Definitive diagnosis cannot be made based on chest X-ray only. Diffuse lung disease (DLD) is difficult to differentiate from bacterial lung diseases, such as pneumonia and tuberculosis, which frequently results in incorrect treatment, disease progression and poor outcome. All of the these factors emphasize the importance of the issue of differential diagnosis. Professionals especially pay attention to idiopathic forms of diffuse lung disease, which is characterized with severe clinical course and poor prognosis due to progressive fibrous processes. The right method of approach is to rule out more common conditions, such as infectious diseases of lungs, structural abnormalities of the respiratory airway, immune deficiencies, congenital heart diseases, cystic fibrosis. Thus, DLD is a diagnostic challenge for pediatricians and pulmonologists. Article presents the case report of 4-month old infant with DLD that was analyzed according to the diagnostic and management approach. It includes anamnesis, clinical and diagnostic criteria of the disease, established by multiple studies, different methods of treatment, outcome and recommendations.

PMID:35417867

Cell Rep. 2022 Apr 12;39(2):110663. doi: 10.1016/j.celrep.2022.110663.

ABSTRACT

Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hallmarks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells.

PMID:35417692 | DOI:10.1016/j.celrep.2022.110663

J Bacteriol. 2022 Apr 13:e0056821. doi: 10.1128/jb.00568-21. Online ahead of print.

ABSTRACT

Biofilms are aggregates of microorganisms embedded in an extracellular matrix comprised largely of exopolysaccharides (EPSs), nucleic acids, and proteins. Pseudomonas aeruginosa is an opportunistic human pathogen that is also a model organism for studying biofilms in the laboratory. Here, we define a novel program of biofilm development used by mucoid (alginate-overproducing) P. aeruginosa in the presence of elevated calcium. Calcium cations cross-link negatively charged alginate polymers, resulting in individual cells being suspended in an alginate gel. The formation of this type of structurally distinct biofilm is not reliant on the canonical biofilm EPS components Psl and Pel or the matrix protein CdrA. We also observed that mucoid P. aeruginosa biofilm cells do not have the typical elevated levels of the secondary messenger cyclic di-GMP (c-di-GMP), as expected of biofilm cells, nor does the overproduction of alginate rely on high c-di-GMP. This contrasts with nonmucoid biofilms in which the production of the matrix components Psl, Pel, and CdrA is positively regulated by elevated c-di-GMP. We further demonstrate that calcium-gelled alginate biofilms impede the penetration of the antibiotic tobramycin, thus protecting the biofilm community from antibiotic-mediated killing. Finally, we show that bacterial aggregates with a dispersed cell arrangement like laboratory-grown calcium-alginate biofilm structures are present in explanted cystic fibrosis (CF) lung samples. Our findings illustrate the diverse nature of biofilm formation and structure in P. aeruginosa. IMPORTANCE The opportunistic pathogen Pseudomonas aeruginosa produces a complex biofilm matrix comprised of exopolysaccharides (EPSs), nucleic acids, and proteins. P. aeruginosa biofilm formation canonically depends on a variable combination of the exopolysaccharides Psl and Pel and the matrix protein CdrA. We demonstrate that mucoid P. aeruginosa, which overproduces the EPS alginate, possesses an entirely alternate and calcium-dependent method of biofilm formation. These mucoid biofilm structures do not require Psl, Pel, or CdrA, and they display a unique organization of individually suspended cells similar to bacterial aggregates observed in cystic fibrosis airways. Furthermore, calcium-gelled mucoid biofilms impede the penetration and killing action of the antibiotic tobramycin, illustrating their potential clinical significance. Our findings highlight the compositional and structural variety of P. aeruginosa biofilm aggregates.

PMID:35416688 | DOI:10.1128/jb.00568-21

ERJ Open Res. 2022 Apr 11;8(2):00724-2021. doi: 10.1183/23120541.00724-2021. eCollection 2022 Apr.

ABSTRACT

BACKGROUND: People with cystic fibrosis are at increased risk of pulmonary nontuberculous mycobacteria (NTM) disease. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are associated with reduced lung infection with pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. This association has not been studied with NTM.

METHODS: Using encounter-level data from the US Cystic Fibrosis Foundation Patient Registry from 2011 to 2018, we identified individuals aged >12 years with one or more NTM-negative sputum culture and information on receipt of ivacaftor therapy. We used a Cox proportional hazards model to assess the relationship between CFTR modulator usage (any and monotherapy versus combination therapy) and NTM sputum culture positivity, controlling for sex, least severe class of CFTR mutation, receipt of chronic macrolides, age, body mass index and percentage predicted forced expiratory volume.

RESULTS: Out of 25 987 unique individuals, 17 403 individuals met inclusion criteria. During follow-up, 42% of individuals received CFTR modulator therapy, and 23% had incident NTM. The median (interquartile range) time to event was 6.1 (4.0-7.3) years for those ever receiving CFTR modulators compared to 4.0 (1.6-6.5) years in those never receiving CFTR modulators. CFTR modulator use was associated with a significantly reduced hazard of NTM culture positivity (hazard ratio (HR) 0.88, 95% CI 0.79-0.97); there was no significant difference in the hazard between those receiving ivacaftor monotherapy versus combination therapy (combination HR 1.01, 95% CI 0.79-1.23).

CONCLUSIONS: CFTR modulator therapy is associated with a decreased risk of NTM positivity in individuals with cystic fibrosis.

PMID:35415188 | PMC:PMC8995538 | DOI:10.1183/23120541.00724-2021

BMJ. 2022 Apr 12;377:o966. doi: 10.1136/bmj.o966.

NO ABSTRACT

PMID:35414604 | DOI:10.1136/bmj.o966

J Cyst Fibros. 2022 Apr 9:S1569-1993(22)00091-1. doi: 10.1016/j.jcf.2022.04.001. Online ahead of print.

NO ABSTRACT

PMID:35414443 | DOI:10.1016/j.jcf.2022.04.001

Sci Rep. 2022 Apr 12;12(1):6132. doi: 10.1038/s41598-022-09678-9.

ABSTRACT

Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for Cystic Fibrosis (CF). The most common CF-causing mutation is the deletion of the 508th amino-acid of CFTR (F508del), leading to dysregulation of the epithelial fluid transport in the airway's epithelium and the production of a thickened mucus favoring chronic bacterial colonization, sustained inflammation and ultimately respiratory failure. c407 is a bis-phosphinic acid derivative which corrects CFTR dysfunction in epithelial cells carrying the F508del mutation. This study aimed to investigate c407 in vivo activity in the F508del Cftrtm1Eur murine model of CF. Using nasal potential difference measurement, we showed that in vivo administration of c407 by topical, short-term intraperitoneal and long-term subcutaneous route significantly increased the CFTR dependent chloride (Cl-) conductance in F508del Cftrtm1Eur mice. This functional improvement was correlated with a relocalization of F508del-cftr to the apical membrane in nasal epithelial cells. Importantly, c407 long-term administration was well tolerated and in vitro ADME toxicologic studies did not evidence any obvious issue. Our data provide the first in vivo preclinical evidence of c407 efficacy and absence of toxicity after systemic administration for the treatment of Cystic Fibrosis.

PMID:35413967 | DOI:10.1038/s41598-022-09678-9

FASEB J. 2022 May;36(5):e22270. doi: 10.1096/fj.202100458RRR.

ABSTRACT

Mutations in the CFTR gene lead to cystic fibrosis, a genetic disease associated with chronic infection and inflammation and ultimately respiratory failure. The most common CF-causing mutation is F508del and CFTR modulators (correctors and potentiators) are being developed to rescue its trafficking and activity defects. However, there are currently no modulators that stabilize the rescued membrane F508del-CFTR which is endocytosed and quickly degraded resulting in a shorter half-life than wild-type (WT). We previously reported that the extracellular signal-regulated kinase (ERK) MAPK pathway is involved in CFTR degradation upon cigarette smoke exposure. Interestingly, we found that ERK phosphorylation was increased in CF human bronchial epithelial (HBE) cells (CF-HBE41o- and primary CF-HBE) compared to non-CF controls, and this was likely due to signaling by the epidermal growth factor receptor (EGFR). EGFR can be activated by several ligands, and we provide evidence that amphiregulin (AREG) is important for activating this signaling axis in CF. The natural osmolyte ectoine stabilizes membrane macromolecules. We show that ectoine decreases ERK phosphorylation, increases the half-life of rescued CFTR, and increases CFTR-mediated chloride transport in combination with the CFTR corrector VX-661. Additionally, ectoine reduces production of AREG and interleukin-8 by CF primary bronchial epithelial cells. In conclusion, EGFR-ERK signaling negatively regulates CFTR and is hyperactive in CF, and targeting this axis with ectoine may prove beneficial for CF patients.

PMID:35412656 | DOI:10.1096/fj.202100458RRR

Am J Physiol Regul Integr Comp Physiol. 2022 Apr 12. doi: 10.1152/ajpregu.00225.2021. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) patients often suffer from skeletal muscle atrophy, most often attributed to physical inactivity and nutritional factors. CF is also characterized by abnormally elevated systemic inflammation. However, it is unknown whether the lack of a functional CF transmembrane conductance regulator (CFTR) gene predisposes to exaggerated inflammation-induced muscle proteolysis.

METHODS: CF mice (CFTR-/-) and their wild-type (WT=CFTR+/+) littermate controls were systemically injected with Pseudomonas-derived lipopolysaccharide (LPS). After 24 hours, the diaphragm and limb muscles (fast-twitch tibialis anterior, slow-twitch soleus) were assessed for induction of inflammatory cytokines (TNFa, IL1b, IL6), oxidative stress, canonical muscle proteolysis pathways (Calpain, Ubiquitin-Proteasome, Autophagy), muscle fiber histology, and diaphragm contractile function.

RESULTS: At baseline, CF and WT muscles did not differ with respect to indices of inflammation, proteolysis, or contractile function. After LPS exposure, there was significantly greater induction of all proteolysis pathways (Calpain activity; Ubiquitin-Proteasome: MuRF1 and Atrogin1; Autophagy: LC3B, Gabarapl-1, BNIP3) in CF mice for the diaphragm and tibialis anterior, but not the soleus. Proteolysis pathway upregulation and correlations with inflammatory cytokine induction were most prominent in the tibialis anterior. Diaphragm force normalized to muscle cross-sectional area was reduced by LPS to an equivalent degree in CF and WT mice.

CONCLUSIONS: CF skeletal muscles containing a high proportion of fast-twitch fibers (diaphragm, tibialis anterior) exhibit abnormally exaggerated upregulation of multiple muscle wasting pathways after exposure to an acute inflammatory stimulus, but not under basal conditions.

PMID:35411814 | DOI:10.1152/ajpregu.00225.2021

Med Phys. 2022 Apr 12. doi: 10.1002/mp.15669. Online ahead of print.

ABSTRACT

BACKGROUND: Electrical impedance tomography (EIT) is a non-ionizing imaging technique for real-time imaging of ventilation of patients with respiratory distress. Cross-sectional dynamic images are formed by reconstructing the conductivity distribution from measured voltage data arising from applied alternating currents on electrodes placed circumferentially around the chest. Since the conductivity of lung tissue depends on air content, blood flow, and the presence of pathology, the dynamic images provide regional information about ventilation, pulsatile perfusion, and abnormalities. However, due to the ill-posedness of the inverse conductivity problem, EIT images have coarse spatial resolution. One method of improving the resolution is to include prior information in the reconstruction.

PURPOSE: In this work, we propose a technique in which a statistical prior built from an anatomical atlas is used to post-process EIT reconstructions of human chest data. The effectiveness of the method is demonstrated on data from two patients with cystic fibrosis.

METHODS: A direct reconstruction algorithm known as the D-bar method was used to compute a 2-D reconstruction of the conductivity distribution in the plane of the electrodes. Reconstructions using one step in an iterative (regularized) Newton's method were also computed for comparison. An anatomical atlas consisting of 1,589 synthetic EIT images computed from X-ray computed tomography (CT) scans of 74 adult male subjects was computed for use as a statistical prior. The resolution of the D-bar images were then improved by maximizing the conditional probability density function of an image that is consistent with the a priori information and the statistical model. A new method to evaluate the accuracy of the EIT images using CT scans of the imaged patient as ground truth is presented. The novel approach is tested on data from two patients with cystic fibrosis.

RESULTS AND CONCLUSIONS: The D-bar images resulted in better structural similarity index measures (SSIM) and multi-scale (MS) SSIM measures for both subjects using the mask or amplitude evaluation approach than the one-step (regularized) Newton's method. Further improvement was achieved using the Schur complement (SC) approach, with MS-SSIM values of 0.718 and 0.682 using SC evaluated with the mask and amplitude approach, respectively, for Patient 1, and MS-SSIM values of 0.726 and 0.692 using SC evaluated with the mask and amplitude approach, respectively, for Patient 2. The results from applying an anatomical atlas and statistical prior to EIT data from two patients with cystic fibrosis suggest that the spatial resolution of the EIT image can be improved to reveal pathology that may be difficult to discern in the original EIT image. The novel metric of evaluation is consistent with the appearance of improved spatial resolution and provides a new way to evaluate the accuracy of EIT reconstructions when a CT scan is available. This article is protected by copyright. All rights reserved.

PMID:35411573 | DOI:10.1002/mp.15669

medRxiv. 2022 Apr 4:2022.03.28.22272848. doi: 10.1101/2022.03.28.22272848. Preprint.

ABSTRACT

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We find the percent solids and protein content are greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibit heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observe increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factorâ€"stimulated gene-6 (TSG6) staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicate that increases in HA and DNA in COVID-19 respiratory secretion samples correlate with enhanced inflammatory burden and suggest that DNA and HA may be viable therapeutic targets in COVID-19 infection.

PMID:35411348 | PMC:PMC8996635 | DOI:10.1101/2022.03.28.22272848

Trials. 2022 Apr 11;23(1):292. doi: 10.1186/s13063-022-06256-2.

ABSTRACT

BACKGROUND: Globally, bronchiectasis (BE) unrelated to cystic fibrosis (CF) is recognized as a major cause of respiratory morbidity, mortality, and healthcare utilization. Children with BE regularly experience exacerbations of their condition resulting in frequent hospitalizations and decreased health-related quality of life (HR-QoL). Guidelines for the treatment and management of BE call for regular exercise as a means of improving aerobic fitness and HR-QoL. Moreover, research in adults with BE has shown that exercise can reduce the frequency of exacerbations, a potent predictor of future lung function decline and respiratory morbidity. Yet, to date, the health benefits resulting from therapeutic exercise have not been investigated in children with BE. The BREATH, Bronchiectasis - Exercise as Therapy, trial will test the efficacy of a novel 8-week, play-based therapeutic exercise program to reduce the frequency of acute exacerbations over 12 months in children with BE (aged ≥ 4 and < 13 years). Secondary aims are to determine the cost-effectiveness of the intervention and assess the program's impact on aerobic fitness, fundamental movement skill (FMS) proficiency, habitual physical activity, HR-QoL, and lung function.

METHODS: This multi-center, observer-blinded, parallel-group (1:1 allocation), randomized controlled trial (RCT) will be conducted at three sites. One hundred and seventy-four children ≥ 4 and < 13 years of age with BE will be randomized to a developmentally appropriate, play-based therapeutic exercise program (eight, 60-min weekly sessions, supplemented by a home-based program) or usual care. After completing the baseline assessments, the number of exacerbations and secondary outcomes will be assessed immediately post-intervention, after 6 months of follow-up, and after 12 months of follow-up. Monthly, parental contact and medical review will document acute respiratory exacerbations and parameters for cost-effectiveness outcomes.

DISCUSSION: The BREATH trial is the first fully powered RCT to test the effects of a therapeutic exercise on exacerbation frequency, fitness, movement competence, and HR-QoL in children with bronchiectasis. By implementing a developmentally appropriate, play-based exercise program tailored to the individual needs of children with bronchiectasis, the results have the potential for a major paradigm shift in the way in which therapeutic exercise is prescribed and implemented in children with chronic respiratory conditions. The exercise program can be readily translated. It does not require expensive equipment and can be delivered in a variety of settings, including the participant's home. The program has strong potential for translation to other pediatric patient groups with similar needs for exercise therapy, including those with obesity, childhood cancers, and neurological conditions such as cerebral palsy.

TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register (ANZCTR) ACTRN12619001008112.

PMID:35410363 | DOI:10.1186/s13063-022-06256-2

Int J Environ Res Public Health. 2022 Mar 29;19(7):4069. doi: 10.3390/ijerph19074069.

ABSTRACT

Cystic fibrosis (CF) is the most common autosomal recessive inherited monogenic disease in Caucasians. As medical technology progresses and the quality of patient care improves, the survival time of patients with CF has increased, which results in more frequent comorbidities such as cystic fibrosis-related diabetes (CFRD). CFRD is the result of abnormal glucose metabolism characterized primarily by insulin deficiency, exacerbated periodically by insulin resistance. The aim of our study was to analyze the epidemiology of patients with CFRD in Poland on the basis of data collected from six CF treatment centers. Analyses were performed on 1157 CF patients who were treated at one of the six CF care centers. CFRD was diagnosed according to standard criteria. All data including demographics, types of CFTR mutations, CFRD duration, and microorganisms in the sputum were obtained from the patients' medical history. Our study indicates that the prevalence of CFRD in Poland is 12.9%. CFRD was most often diagnosed between the ages of 11 and 20 (60% of patients), while 23% of patients were diagnosed between 21 and 30 years of age. Furthermore, we observed that approximately 3-5% of patients under the age of 10 had CFRD. We found out that the type of mutation did not affect the frequency of CFRD development. Factors that increased the risk of developing CFRD include underweight and chronic Pseudomonas aeruginosa infection. Due to the extended lifespan of CF patients, the number of CFRD patients is currently increasing. We believe that the results of our study may complement information from other studies or may be useful in planning health policy in Poland.

PMID:35409752 | DOI:10.3390/ijerph19074069

Int J Environ Res Public Health. 2022 Mar 29;19(7):4037. doi: 10.3390/ijerph19074037.

ABSTRACT

BACKGROUND: The purpose of this pilot study was to compare body composition metrics obtained by two portable bioelectrical impedance analysis (BIA) devices with dual-energy X-ray absorptiometry (DXA) among adolescents with cystic fibrosis (CF) before and after a resistance exercise training program.

METHODS: Participants with CF were assessed using DXA, single-frequency BIA (SFBIA), and multiple-frequency BIA (MFBIA) to quantify percent body fat (%Fat), fat mass (FM), and fat-free mass (FFM) at baseline and after a home-based resistance training intervention comprised of 36, 1 h sessions completed in 12-14 weeks. Repeated measures analysis of variance, paired samples t-tests, Cohen's d effect sizes, and Pearson's correlations were used to compare differences between and within methods at baseline and post-intervention.

RESULTS: Ten participants (15.8 ± 2.2 yr, 60.1 ± 15.1 kg) completed the assessments. At baseline, both SFBIA and MFBIA scales significantly underestimated %Fat and FM and overestimated FFM, with small to moderate effect sizes. Post-intervention, small, non-significant differences were found between DXA and both BIA scales for all body composition metrics. Significant changes in %Fat and FFM were observed with DXA. MFBIA displayed less constant error than SFBIA when compared to DXA for pre- and post-intervention assessments for %Fat (MFBIA: pre and post -2.8 and -0.8 vs. SFBIA: -4.6 and -2.0), FM (-0.4 and -0.4 vs. -3.0 and -1.1), and FFM (+0.8 and +0.6 vs. +3.1 and +1.3). Near-perfect correlations were observed at both time points between DXA and each BIA scale. Conclusions: Portable BIA results should be interpreted with caution, and further validation studies in CF patients are needed prior to clinical use.

PMID:35409718 | DOI:10.3390/ijerph19074037