Sci Rep. 2023 Jul 25;13(1):11995. doi: 10.1038/s41598-023-38300-9.

ABSTRACT

Macrophage dysfunction has been well-described in Cystic Fibrosis (CF) and may contribute to bacterial persistence in the lung. Whether CF macrophage dysfunction is related directly to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in macrophages or an indirect consequence of chronic inflammation and mucostasis is a subject of ongoing debate. CFTR modulators that restore CFTR function in epithelial cells improve global CF monocyte inflammatory responses but their direct effects on macrophages are less well understood. To address this knowledge gap, we measured phagocytosis, metabolism, and cytokine expression in response to a classical CF pathogen, Pseudomonas aeruginosa in monocyte-derived macrophages (MDM) isolated from CF F508del homozygous subjects and nonCF controls. Unexpectedly, we found that CFTR modulators enhanced phagocytosis in both CF and nonCF cohorts. CFTR triple modulators also inhibited MDM mitochondrial function, consistent with MDM activation. In contrast to studies in humans where CFTR modulators decreased serum inflammatory cytokine levels, modulators did not alter cytokine secretion in our system. Our studies therefore suggest modulator induced metabolic effects may promote bacterial clearance in both CF and nonCF monocyte-derived macrophages.

PMID:37491532 | DOI:10.1038/s41598-023-38300-9

Expert Rev Respir Med. 2023 Jul 25. doi: 10.1080/17476348.2023.2241355. Online ahead of print.

ABSTRACT

INTRODUCTION: Although historically challenging to perform in the lung, technological advancements have made Magnetic Resonance Imaging (MRI) increasingly applicable for pediatric pulmonary imaging. Furthermore, a wide array of functional imaging techniques has become available, to be leveraged alongside structural imaging for increasingly sensitive biomarkers, or outcome measures in the evaluation of novel therapies.

AREAS COVERED: In this review, recent technical advancements and modern methodologies for structural and functional lung MRI are described. These include ultrashort echo time (UTE) MRI, free-breathing contrast agent-free, functional lung MRI, and hyperpolarized gas MRI, amongst other techniques. Specific examples of the application of these methods in children are provided, principally drawn from recent research in asthma, bronchopulmonary dysplasia, and cystic fibrosis.

EXPERT OPINION: Pediatric lung MRI is rapidly growing, and is well poised for clinical utilization, as well as continued research into early disease detection, disease processes, and novel treatments. Structure/function complementarity make MRI especially attractive as a tool for increased adoption in the evaluation of pediatric lung disease. Looking toward the future, novel technologies, such as low-field MRI and artificial intelligence, mitigate some of the traditional drawbacks of lung MRI and will aid in improving access to MRI in general, potentially spurring increased adoption and demand for pulmonary MRI in children.

PMID:37491192 | DOI:10.1080/17476348.2023.2241355

Respir Care. 2023 Jul 25:respcare.10810. doi: 10.4187/respcare.10810. Online ahead of print.

ABSTRACT

BACKGROUND: Exercise-induced O2 desaturation contributes to dyspnea and exercise intolerance in various respiratory diseases. This study assessed whether automated O2 titration was superior to fixed-flow O2 to improve exertional dyspnea and walking exercise endurance. We also aimed at evaluating possible additive effects of high-flow nasal cannula coupled with automated O2 titration on these outcomes.

METHODS: Subjects with chronic respiratory diseases and exercise-induced desaturation performed a 3-min constant-speed shuttle test (CSST) and an endurance shuttle walking test (ESWT) with either (1) fixed-flow O2, (2) automated O2 titration targeting an SpO2 of 94% (± 2%), and (3) automated O2 titration + high-flow nasal cannula according to a randomized sequence. The main outcome was Borg dyspnea score at the end of the 3-min CSST. Secondary outcomes included endurance time and dyspnea during ESWT and oxygenation status during exercise.

RESULTS: Ten subjects with COPD, 10 with interstitial lung disease, 5 with pulmonary hypertension, and 3 with cystic fibrosis completed the study. Compared to fixed-flow O2, automated O2 titration did not reduce dyspnea at the end of the 3-min CSST. Endurance time during the ESWT was prolonged with automated O2 titration (mean difference 298 [95% CI 205-391] s, P < .001), and dyspnea at isotime was reduced. No further improvement was noted when high-flow nasal cannula was added to automated O2 titration. Compared to fixed-flow O2, O2 flows were higher with automated O2 titration, resulting in better oxygenation.

CONCLUSIONS: Automated O2 titration was superior to fixed-flow O2 to alleviate dyspnea and improve exercise endurance during the ESWT in subjects with a variety of chronic respiratory diseases. Adding high-flow nasal cannula to automated O2 titration provided no further benefits.

PMID:37491073 | DOI:10.4187/respcare.10810

Mol Genet Genomic Med. 2023 Jul 24:e2249. doi: 10.1002/mgg3.2249. Online ahead of print.

ABSTRACT

BACKGROUND: Isolated congenital bilateral absence of vas deferens (iCBAVD) in men results in obstructive azoospermia and is mainly caused by pathogenic variants in cystic fibrosis transmembrane conductance regulator (CFTR) or adhesion G protein-coupled receptor G2 (ADGRG2).

METHODS: The next-generation sequencing (NGS) was used to screen the mutations in the proband, and Sanger sequencings were performed to validate the compound heterozygous variant of CFTR in his family members. Protein structure simulation was performed to discover the potential pathological mechanism.

RESULTS: This study reported novel compound heterozygous CFTR mutations (NM:000492.4, Intron: 5T; c.3965_3969dupTTGGG: p.R1325Gfs*5) in two brothers with obstructive azoospermia. The compound heterozygous CFTR mutations were first screened out by NGS in an infertile male patient who exhibited iCBAVD from a nonconsanguineous Chinese family. Histological analysis of the testicular biopsy from this patient revealed normal spermatogenesis and mature spermatozoa were observed in the seminiferous tubules. Surprisingly, the same compound heterozygous CFTR mutations were also observed in his brothers who also exhibited iCBAVD, with their parents being a heterozygous carrier for the mutations, as verified by Sanger sequencing. Protein structure simulation revealed that these mutations potentially led to impaired ATP-binding ability of CFTR.

CONCLUSION: We identified novel compound heterozygous CFTR mutations in two brothers and summarized the literature regarding CFTR mutation and male infertility. Our study may contribute to the genetic diagnosis of iCBAVD and future genetic counseling.

PMID:37489040 | DOI:10.1002/mgg3.2249

BMC Infect Dis. 2023 Jul 24;23(1):489. doi: 10.1186/s12879-023-08468-6.

ABSTRACT

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous, environmental bacteria that can cause chronic lung disease. Persons with cystic fibrosis (pwCF) are at high risk for NTM. Approximately 1 in 5 pwCF in the United States (U.S.) is affected by pathogenic NTM species, and incidence rates of NTM have been increasing among pwCF as well as in the general population. Prevalence of NTM pulmonary infections (PI) varies widely across the United States because of geographic variation in environmental exposures. This study will present updated region-level incidence of NTM infections in the cystic fibrosis (CF) population in the U.S.

METHODS: We used the Cystic Fibrosis Foundation Patient Registry (CFFPR) data for the period 2010 through 2019. Our study population comprised persons with CF ≥ 12 years of age who had been tested for NTM PI. We included only registry participants with NTM culture results. We defined incident cases as persons with one positive mycobacterial culture preceded by ≥ two negative mycobacterial cultures. We defined non-cases as persons with ≥ two negative mycobacterial cultures. We estimated average annual NTM PI incidence by region. Using quasi-Poisson models, we calculated annual percent change in incidence by region.

RESULTS: We identified 3,771 incident NTM infections. Of these cases, 1,816 (48.2%) were Mycobacterium avium complex (MAC) infections and 960 (25.5%) were Mycobacterium abscessus infections. The average annual incidence of NTM PI among pwCF in the U.S. was 58.0 cases per 1,000 persons. The Northeast had the highest incidence of MAC (33.5/1,000 persons tested) and the South had the highest incidence of M. abscessus (20.3/1,000 persons tested). From 2010 to 2019, the annual incidence of total NTM PI increased significantly by 3.5% per year in the U.S.

CONCLUSIONS: NTM PI incidence is increasing among pwCF. Identifying high risk areas and increasing trends is important for allocating public health and clinical resources as well as evaluating interventions.

PMID:37488500 | DOI:10.1186/s12879-023-08468-6

BMC Cardiovasc Disord. 2023 Jul 25;23(1):371. doi: 10.1186/s12872-023-03360-2.

ABSTRACT

BACKGROUND AND AIMS: Preterm birth has been linked with an increased risk of cardiovascular (CV) disease from childhood into adolescence and early adulthood. In this study, we aimed to investigate differences in CV health profiles between former term- and preterm-born infants in a cohort of Tyrolean adolescents.

METHODS: The Early Vascular Aging (EVA)-Tyrol study is a population-based non-randomized controlled trial, which prospectively enrolled 14- to 19-year-old adolescents in North Tyrol, Austria and South Tyrol, Italy between 2015 and 2018. Metrics of CV health (body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), smoking, physical activity, dietary patterns, total cholesterol and fasting blood glucose) were assessed and compared between former term- and preterm-born girls and boys.

RESULTS: In total, 1,491 study participants (59.5% female, mean age 16.5 years) were included in the present analysis. SBP and DBP were significantly higher in former preterm-born adolescents (mean gestational age 34.6 ± 2.4 weeks) compared to term-born controls (p < 0.01). In the multivariate regression analysis these findings remained significant after adjustment for potential confounders in all models. No differences were found in all other CV health metrics. The number of participants meeting criteria for all seven health metrics to be in an ideal range was generally very low with 1.5% in former term born vs. 0.9% in former preterm born adolescents (p = 0.583).

CONCLUSIONS: Preterm birth is associated with elevated SBP and DBP in adolescence, which was even confirmed for former late preterm-born adolescents in our cohort. Our findings underscore the importance of promoting healthy lifestyles in former term- as well as preterm-born adolescents. In addition, we advise early screening for hypertension and long-term follow-up in the group of preterm-born individuals.

PMID:37488472 | DOI:10.1186/s12872-023-03360-2

Paediatr Respir Rev. 2023 Jul 13:S1526-0542(23)00042-8. doi: 10.1016/j.prrv.2023.07.002. Online ahead of print.

ABSTRACT

We present a case of a 10-year-old boy initially diagnosed with CF based on NBS guidelines. However, as CF genetics knowledge has advanced, he has been reclassified as CFSPID based on normal investigations and excellent general clinical status, in line with updated CFSPID guidelines. This case highlights the significance of reviewing CF diagnoses according to the latest understanding of CFTR mutation phenotypes, as well as the patient's clinical status. In order to identify opportunities to save patients from burdensome CF treatment and management, we review current CFSPID guidelines, emphasizing care tailored to each individual case.

PMID:37487798 | DOI:10.1016/j.prrv.2023.07.002

J Cyst Fibros. 2023 Jul 23:593. doi: 10.1016/j.jcf.2023.07.007. Online ahead of print.

NO ABSTRACT

PMID:37487763 | DOI:10.1016/j.jcf.2023.07.007

Thorax. 2023 Jul 24:thorax-2022-219475. doi: 10.1136/thorax-2022-219475. Online ahead of print.

ABSTRACT

INTRODUCTION: A new UK Lung Allocation Scheme (UKLAS) was introduced in 2017, replacing the previous geographic allocation system. Patients are prioritised according to predefined clinical criteria into a three-tier system: the super-urgent lung allocation scheme (SULAS), the urgent lung allocation scheme (ULAS) and the non-urgent lung allocation scheme (NULAS). This study assessed the early impact of this scheme on waiting-list and post-transplant outcomes.

METHODS: A cohort study of adult lung transplant registrations between March 2015 and November 2016 (era-1) and between May 2017 and January 2019 (era-2). Outcomes from registration were compared between eras and stratified by urgency tier and diagnostic group.

RESULTS: During era-1, 461 patients were registered. In era-2, 471 patients were registered (19 (4.0%) SULAS, 82 (17.4%) ULAS and 370 (78.6%) NULAS). SULAS patients were younger (median age 35 vs 50 and 55 for urgent and non-urgent, respectively, p=0.0015) and predominantly suffered from cystic fibrosis (53%) or pulmonary fibrosis (37%). Between eras 1 and 2, the odds of transplantation within 6 months of registration were increased (OR=1.41, 95% CI 1.07 to 1.85, p=0.0142) despite only a 5% increase in transplant activity. Median time-to-transplantation during era-1 was 427 days compared with waiting times in era-2 of 8 days for SULAS, 15 days for ULAS and 585 days for NULAS patients. Waiting-list mortality (15% era-1 vs 13% era-2; p=0.5441) and post-transplant survival at 1 year (81.3% era-1 vs 83.3% era-2; p=0.6065) were similar between eras.

CONCLUSION: The UKLAS scheme prioritises the critically ill and improves transplantation odds. The true impact on waiting-list mortality and post-transplant survival requires further follow-up.

PMID:37487710 | DOI:10.1136/thorax-2022-219475

BMJ Case Rep. 2023 Jul 24;16(7):e252828. doi: 10.1136/bcr-2022-252828.

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic fungal disease that commonly complicates the natural course of patients with asthma and cystic fibrosis. Patients with ABPA commonly present with recurrent pulmonary infiltrates or bronchiectasis. They also experience difficulty treating asthma. Characteristic radiological findings include central bronchiectasis and high-attenuation mucus. Complete unilateral lung collapse is an uncommon presentation of ABPA, with few cases reported in published literature. We present a case of a man in his mid-40s, with acute cerebrovascular disease, who subsequently developed neurological deterioration, compounded by development of respiratory failure attributed to a complete left lung collapse, requiring invasive mechanical ventilation. Initially suspected to have aspiration pneumonia, he was eventually diagnosed with ABPA and was treated accordingly. This case illustrates an uncommon aetiology for complete lung collapse in this clinical setting and serves to remind us to consider ABPA as a differential diagnosis in such patients as well.

PMID:37487650 | DOI:10.1136/bcr-2022-252828

Clin Nutr. 2023 Jul 17;42(9):1631-1636. doi: 10.1016/j.clnu.2023.07.015. Online ahead of print.

ABSTRACT

BACKGROUND&AIMS: Cystic fibrosis (CF) -related bone disease (CFBD) is an important complication of CF, and low BMD in childhood is a precursor of CFBD. Here, we aimed to investigate bone turnover biomarkers, including osteocalcin (OC), receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in relation to low BMD in children with CF (cwCF). We also evaluated factors which could affect bone turnover with particular emphasis on fat-free mass (FFM), forced expiratory volume in 1 s (FEV1), hand grip strength (HGS), and functional capacity and physical activity.

METHODS: Sixteen cwCF aged 8-18 years with moderate low BMD (group1) and 64 cwCF with normal BMD (group2) were enrolled. Serum RANKL, OC, and OPG were determined by immunoenzymatic assays. Multiple parameters including pancreatic status, lung functions, body mass index (BMI), FFM measured by bioelectric impedance analysis (BIA), 6-minute walk test, vitamin D, nutritional intake, HGS, functional capacity and physical activity, serum and urine biomarkers were compared between the two groups.

RESULTS: We found similar serum levels of RANKL (p = 0.501), OC (p = 0.445), OPG (p = 0.380), and RANKL/OPG ratio (p = 0.449) between group1 and group2 in cwCF. BMI z-score (p < 0.001), FFMI z-score (p < 0.001), FEV1 z-score (p = 0.007), and right-HGS (%pred) (p = 0.009) significantly differed between the two groups. Multivariate linear regression revealed that the only factors that predicted BMD were FFMI z-score and HGS %pred.

CONCLUSION: Serum OC, OPG, RANKL and RANKL/OPG ratio did not predict BMD in cwCF. FFMI z-score and HGS %pred measured by non-invasive and practical methods were the best predictors of BMD.

PMID:37487275 | DOI:10.1016/j.clnu.2023.07.015

Heliyon. 2023 Jun 5;9(6):e17005. doi: 10.1016/j.heliyon.2023.e17005. eCollection 2023 Jun.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a serious autosomal recessive disorder. Early diagnosis, comorbidity prevention, and control are cornerstones for a quality life and for improving life expectancy. In Colombian Caribbean, where there is a genetically admixed population, CF is an orphan disease affecting children and adults, and it remains a challenging issue to be addressed carefully. This work describes the genetic, clinical, and paraclinical profiles of CF patients from Cartagena de Indias, Colombia.

METHODS: Thirty-six patients were included in the study. The subjects were identified and evaluated through the Regional Program for CF patients. CFTR gene mutations, anthropometric parameters, microbiological infections, and pulmonary function were analyzed. Data on demographic parameters, pharmacological treatments, and comorbidities were reported. Frequency and percentages were established for the categorical variables and mean or median for the quantitative variables. In addition, comparisons were made by sex.

RESULTS: The average age of the patients was 11.9 ± 5.3 years and the median age at diagnosis was 14 months. 55.5% were women and 44.5% were men. The mean values for weight, height, and body mass index were 35 ± 17.6 kg, 139.9 ± 28 cm, and 16.5 ± 2.9 kg/m2, respectively. The clinical manifestations that occurred more frequently were steatorrhea (65.4%) and recurrent pneumonia (46.2%). Chronic airway infection with Pseudomonas aeruginosa was identified in 71.4% of the cases and the p.F508del mutation was found in 47.2% of the subjects.

CONCLUSION: The current profile of CF patients from the Colombian Caribbean showed some concerning features, such as nutritional status; however, progress in early diagnosis and clinical follow-up could contribute to improve the general conditions of patients. It is necessary to continue efforts to increase the life expectancy and quality of life of the patients.

PMID:37484404 | PMC:PMC10361099 | DOI:10.1016/j.heliyon.2023.e17005

Stat Sin. 2023 May;33(Spec Issue):1295-1318. doi: 10.5705/ss.202021.0006.

ABSTRACT

In this work, we propose a longitudinal quantile regression framework that enables a robust characterization of heterogeneous covariate-response associations in the presence of high-dimensional compositional covariates and repeated measurements of both response and covariates. We develop a globally adaptive penalization procedure, which can consistently identify covariate sparsity patterns across a continuum set of quantile levels. The proposed estimation procedure properly aggregates longitudinal observations over time, and ensures the satisfaction of the sum-zero coefficient constraint that is needed for proper interpretation of the effects of compositional covariates. We establish the oracle rate of uniform convergence and weak convergence of the resulting estimators, and further justify the proposed uniform selector of the tuning parameter in terms of achieving global model selection consistency. We derive an efficient algorithm by incorporating existing R packages to facilitate stable and fast computation. Our extensive simulation studies confirm the theoretical findings. We apply the proposed method to a longitudinal study of cystic fibrosis children where the association between gut microbiome and other diet-related biomarkers is of interest.

PMID:37483468 | PMC:PMC10361693 | DOI:10.5705/ss.202021.0006

ERJ Open Res. 2023 May 22;9(3):00449-2022. doi: 10.1183/23120541.00449-2022. eCollection 2023 May.

ABSTRACT

AIM: To examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016, i.e. the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV1 decline.

METHODS: The study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008-2016). The evolution of FEV1 % predicted (%FEV1) with age, and the yearly change in %FEV1 were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator (-CFTR) mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level.

RESULTS: We used 199 604 FEV1 recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV1, but a higher yearly %FEV1 loss between the ages of 15 and 25 years. We showed stabilisation and even improvement in %FEV1 over age in adults with a class III CFTR mutation, but a steady decline in patients homozygous for F508del or with both mutations of classes I/II. A faster decline in %FEV1 was found in patients from low-income countries compared to a similar %FEV1 evolution in patients from middle- and high-income countries.

CONCLUSIONS: These longitudinal FEV1 data reflect the reality of cystic fibrosis across Europe in the era pre-HEMT, and can serve as baseline for comparison with the post-HEMT era. The similar evolution in middle- and high-income countries underlines opportunities for low-income countries.

PMID:37483280 | PMC:PMC10359040 | DOI:10.1183/23120541.00449-2022

Dig Liver Dis. 2023 Jul 20:S1590-8658(23)00760-0. doi: 10.1016/j.dld.2023.07.008. Online ahead of print.

ABSTRACT

BACKGROUND: The natural history of ulcerative proctitis (UP) has been poorly investigated in children.

AIMS: We aimed to compare the disease course of children with UP at diagnosis to the other locations and to identify extension predictors.

METHODS: This was a multicenter, observational study carried out from data prospectively entered in the SIGENP-IBD-Registry. Children with ulcerative colitis (UC) diagnosis and at least 1-year follow-up were included. On the basis of Paris classification UP patients were identified and compared with the other locations.

RESULTS: 872 children were enrolled (median age at diagnosis: 11.2 years; M/F: 426/446), of whom 78 (9%) with UP. Kaplan-Meier analysis demonstrated increased cumulative probabilities of disease extension in the E1 group [1 year: 20.3%; 5 years: 52.7%; 10 years: 72.4%] compared to E3 group [1 year: 8.5%; 5 years: 24.9% and 10 years: 60.1%, p=0.001]. No differences were observed comparing E1 and E2 groups [p=0.4]. Cumulative probabilities of surgery at 1, 5 and 10 years were 1.3, 2.8 and 2.8% in the E1 group and 2.5, 8 and 12.8% in the E2-E3-E4 group, respectively (p=0.1). Cox regression analysis demonstrated that PUCAI>35 at diagnosis was associated with endoscopic extension (HR=4.9; CI 95% 1.5-15.2, p=0.006).

CONCLUSIONS: UP is associated with similar short and long-term outcomes compared to other locations.

PMID:37481430 | DOI:10.1016/j.dld.2023.07.008

Eur J Pharm Biopharm. 2023 Jul 19:S0939-6411(23)00188-1. doi: 10.1016/j.ejpb.2023.07.010. Online ahead of print.

ABSTRACT

Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eudragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release, showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 106-107 CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery.

PMID:37479064 | DOI:10.1016/j.ejpb.2023.07.010

Pediatr Pulmonol. 2023 Jul 21. doi: 10.1002/ppul.26601. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the growing awareness of cystic fibrosis (CF) in China, few cases have been reported in Henan, which is the most populous province in the country. This study aimed to describe the clinical phenotype and genotype of children with CF in Henan.

METHODS: We retrospectively recruited 18 Chinese children with CF who presented to Children's Hospital affiliated to Zhengzhou University from January 2019 to June 2023. The demographic data, imaging examinations, and laboratory tests of the patients were reviewed to clarify the clinical phenotype. Whole exome sequencing was conducted to identify the genotype.

RESULTS: Respiratory diseases were the main clinical manifestation, including recurrent/persistent pneumonia (88.9%), sinusitis (77.8%), bronchiectasis (77.8%). CF-related liver disease and pancreatic insufficiency were less common. Infant cases had high frequency of pseudo-Bartter Syndrome (80.0%). Chest computed tomography showed bronchiectasis in older children and air trapping in infant cases. The most common pathogens in the airway were Pseudomonas aeruginosa (72.2%) and Staphylococcus aureus (66.7%). Twenty-five different cystic fibrosis transmembrane conductance regulator (CFTR) gene variants were detected, including five novel observations (c.1064C>G[p. Pro355Arg], c.1209+1G>C, c.1925C>G[p. Ser642X], c.2810T>G[p. Leu937Arg], and c.3792delA[p. Gly1265GlufsX13]). The most common variant was c.2909G>A(p. Gly970Asp), with a detected rate of 21.9%.

CONCLUSION: Children with CF in Henan had varied clinical phenotypes by age, with respiratory disease being predominant. The most frequent CFTR gene variant was c.2909G>A(p. Gly970Asp). This study is the first and most comprehensive one on the clinical phenotype and genotype of children with CF in Henan, China. We also reported the first CF case of Mycobacterium abscessus infection in China.

PMID:37477516 | DOI:10.1002/ppul.26601

Pediatr Pulmonol. 2023 Jul 21. doi: 10.1002/ppul.26612. Online ahead of print.

ABSTRACT

BACKGROUND: Telehealth has been rapidly adopted by cystic fibrosis (CF) centers and ongoing use in routine CF care is endorsed by CF consumers. However, data describing CF clinician perceptions regarding telehealth are scarce. We aimed to describe clinician experiences and attitudes towards telehealth in CF care among health professionals across Australia.

METHODS: CF multidisciplinary health professionals from all CF clinics in Australia were sent an anonymous electronic survey.

RESULTS: Eighty-five responses were received representing 15 of 23 (65%) centers. Most clinicians reported using telehealth for routine clinic visits, and a range of other clinical encounters (69.9%). Telehealth was widely perceived as acceptable (91.8%), and clinicians were comfortable/very comfortable (81.2%) integrating telehealth into future CF care. Despite this, 64.1% of respondents considered telehealth clinics to be much worse than face-to-face clinics and 57.5% reported quality of care was somewhat/much worse using telehealth. Home spirometry was available in 73.7% of centers, however, only 26.7% of clinics could provide spirometers for >75% eligible patients. Growth and microbiology assessments were often missed in telehealth clinics and 75.7% reported a technical issue had prevented a telehealth consultation from occurring.

CONCLUSIONS: Telehealth for CF in Australia is considered feasible and acceptable by CF clinicians, although use of telehealth varies widely between centers. Concerns exist around the impact of telehealth on health outcomes, especially given core assessments are frequently omitted. Guidelines may help ensure the benefits of telehealth are realized for people with CF without compromising the standard of care.

PMID:37477510 | DOI:10.1002/ppul.26612

Zhonghua Nan Ke Xue. 2022 May;28(5):432-436.

ABSTRACT

OBJECTIVE: To observe the therapeutic efficacy of Baihe Yuzi Prescription (BYP) in the treatment of clinical syndrome-free asthenospermia and its effects on semen parameters, sperm DNA fragmentation index (DFI) and the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in the sperm.

METHODS: We randomly divided 112 patients with clinical syndrome-free asthenospermia into a control group (n = 55) and an experimental group (n = 57), the former treated orally with L-carnitine liquid combined with vitamin E capsules and the latter with BYP in addition, both for 3 months. After treatment, we obtained the total sperm count, sperm motility, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), sperm DFI and expression of CFTR in the sperm, and compared the above parameters between the two groups of patients before and after medication.

RESULTS: The total effectiveness rate was significantly higher in the experimental group (82.46%) than in the control (65.45%) (P < 0.05). Compared with the baseline, the patients in the experimental group showed significant improvement after treatment in the total sperm count (��53.5��3.5�� vs ��86.5��3.9�� ��106, P < 0.05), sperm motility (��23.5��3.5��% vs ��38.8��3.7��%, P < 0.05), PMS (��20.1��3.2��% vs ��30.3��3.3��%, P < 0.05), MNS (��2.3��0.3��% vs ��3.9��0.4��%, P < 0.05), sperm DFI (��37.3��3.1��% vs ��25.2��3.4��%, P < 0.05) and the expression of CFTR (P < 0.05), and even better improvement than the controls in sperm motility (��23.8��3.7��% vs ��30.2��3.4��%, P < 0.05), PMS (��19.6��3.1��% vs ��25.3��2.9��%, P < 0.05), MNS (��2.4��0.4��% vs ��3.1��0.3��%, P < 0.05), and sperm DFI (��36.6��3.3��% vs ��30.3��3.1��%, P < 0.05). The total sperm count and the expression of CFTR, however, were not significantly improved in the control group after treatment (P > 0.05).

CONCLUSION: Baihe Yuzi Prescription can increase sperm count and motility, improve sperm morphology and DFI in patients with clinical syndrome-free asthenospermia, which may be related to the up-regulated expression of CFTR in the sperm.

PMID:37477483

Open Forum Infect Dis. 2023 Jul 3;10(7):ofad335. doi: 10.1093/ofid/ofad335. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: Mycobacterium abscessus is a virulent human pathogen. Treatment is complex and often poorly tolerated with suboptimal rates of eradication, highlighting the need for improved therapeutics. This study reports clinical experience with omadacycline for treatment of M abscessus infections at five large nontuberculous mycobacterial (NTM) disease clinics across the United States to better understand long-term safety and tolerability.

METHODS: We conducted a multicenter retrospective chart review of adults with M abscessus infections. All patients treated with omadacycline as part of a multidrug therapeutic regimen through December 2021 were included. Clinical data from time of omadacycline initiation and up to 12 months of follow-up were collected. Descriptive statistics were performed.

RESULTS: Analysis included 117 patients. Among patients with M abscessus isolate subspeciation, 58 of 71 (81.7%) were M abscessus spp abscessus. In isolates with reported drug susceptibility testing, 15 of 70 (21.4%) had confirmed susceptibility to macrolides. The most common site of infection was lungs. Median duration omadacycline treatment was 8 months (range, 0.25-33 months; interquartile range, 4-15 months). Omadacycline was discontinued in 60 patients (51.3%); 20 completed planned treatment course, 23 experienced intolerance or adverse event leading to drug cessation, and 17 stopped due to cost, death (unrelated to NTM infection or therapy), or another reason. In those with pulmonary disease, 44 of 95 (46%) had 1 or more negative cultures at time of final microbiological assessment, with 17 of 95 (18%) achieving culture conversion.

CONCLUSIONS: This study reports data supporting long-term safety and tolerability of omadacycline along with signal of effectiveness in treatment of M abscessus infections.

PMID:37476076 | PMC:PMC10354853 | DOI:10.1093/ofid/ofad335