Transplant Proc. 2022 May 18:S0041-1345(22)00177-4. doi: 10.1016/j.transproceed.2022.02.023. Online ahead of print.

ABSTRACT

Cystic fibrosis is an autosomal progressive disease affecting the lung, pancreas, and liver. Some patients develop end-stage respiratory and liver failure. For such patients, combined lung-liver transplantation remains the only therapeutic option. In this article we present the first simultaneous lung-liver transplantation in Poland, as well as in Central and Eastern Europe, with detailed clinical history, surgical aspects, and postoperative course.

PMID:35597673 | DOI:10.1016/j.transproceed.2022.02.023

Eur J Cell Biol. 2022 May 18;101(3):151231. doi: 10.1016/j.ejcb.2022.151231. Online ahead of print.

ABSTRACT

The evolutionary relationship of cells within tissues having a similar function but located in different anatomical sites is of considerable biological interest. The development of single-cell RNA sequencing (scRNA-seq) protocols has greatly enhanced opportunities to address this topic. Here we focus on cells in the epithelium which lines two regions of the human respiratory tract and the male genital ducts to delineate the shared, differentiated functions of the different cell populations. Transcriptomic data were used to assess the gene expression profiles of human bronchial, nasal, and epididymal epithelium (HBE, HNE, and HEE). Bulk RNA-seq showed many shared genes expressed in cells from the nasal and bronchial epithelium and highlighted their divergence from the epididymal epithelium. ScRNA-seq in HBE and HNE cells demonstrated overlapping gene expression patterns within basal and secretory cell populations. Moreover, the distribution of cell types was altered in HNE cells derived from donors with cystic fibrosis (CF) when compared to cells from healthy donors. Next, the HBE and HNE datasets were merged and confirmed intersection of cell type gene expression profiles from the two sites. However, secretory and ciliated cells were the most abundant types in the HBE samples, while more basal cells were seen in the HNE populations. We then merged single-cell data from the epididymis to determine if overlapping functions of these cells corresponded to those in the airway. Of note, only the pulmonary ionocytes/epididymis clear cells showed a strongly conserved identity, which was confirmed by imputation in bulk RNA-seq datasets from the same cells.

PMID:35597096 | DOI:10.1016/j.ejcb.2022.151231

Abdom Radiol (NY). 2022 May 21. doi: 10.1007/s00261-022-03549-7. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this prospective study was to compare scan time, image quality, signal-to-noise Ratio (SNR), and apparent diffusion coefficient (ADC) values of simultaneous multi-slice accelerated diffusion-weighted imaging with motion-correction (DWI SMS Moco) to standard diffusion-weighted imaging (sDWI) in free-breathing abdominal magnetic resonance imaging (MRI) in pediatric and young adult patients with cystic fibrosis (CF).

MATERIAL AND METHODS: 16 patients (7 male and 9 female, 12-41 years old) with CF were examined prospectively in a single-center from November 2020 to March 2021 on a 1.5 Tesla clinical MR scanner. The characteristics of overall image quality and delimitability of mesenteric lymph nodes were evaluated using a 5-point Likert scale by two experienced pediatric radiologists independently from each other. Quantitative parameters with SNR and ADC values were assessed in 8 different locations and compared using a Wilcoxon signed-rank test.

RESULTS: The acquisition time for DWI SMS Moco was 32% shorter than for sDWI. Regarding quality comparison, overall image quality and delimitability of mesenteric lymph nodes were significant higher in DWI SMS Moco (p ≤ 0.05 for both readers). The readers preferred DWI SMS Moco to sDWI in all cases (16/16). Mean SNR values from DWI SMS Moco and sDWI were similar in 7 from 8 locations. The ADC values showed no significant difference between DWI SMS Moco and sDWI in any of the evaluated locations (p > 0.05).

CONCLUSIONS: The DWI SMS Moco improves overall image quality and delimitability of mesenteric lymph nodes compared to sDWI with similar SNR and ADC values and a distinguished reduction of scan time in free-breathing by one third. We conclude that MRI with DWI SMS Moco could be helpful in monitoring the effect of the high-efficiency modulator (HEM) therapy in cystic fibrosis (CF) patients homozygous or heterozygous for F508del in the abdomen.

PMID:35596778 | DOI:10.1007/s00261-022-03549-7

Folia Microbiol (Praha). 2022 May 20. doi: 10.1007/s12223-022-00973-6. Online ahead of print.

ABSTRACT

The unique functionality of Akkermansia muciniphila in gut microbiota indicates it to be an indispensable microbe for human welfare. The importance of A. muciniphila lies in its potential to convert mucin into beneficial by-products, regulate intestinal homeostasis and maintain gut barrier integrity. It is also known to competitively inhibit other mucin-degrading bacteria and improve metabolic functions and immunity responses in the host. It finds a pivotal perspective in various diseases and their treatment. It has future as a promising probiotic, disease biomarker and therapeutic agent for chronic diseases. Disease-associated dysbiosis of A. muciniphila in the gut microbiome makes it a potential candidate as a biomarker for some diseases and can provide future theranostics by suggesting ways of diagnosis for the patients and best treatment method based on the screening results. Manipulation of A. muciniphila in gut microbiome may help in developing a novel personalized therapeutic action and can be a suitable next generation medicine. However, the actual pathway governing A. muciniphila interaction with hosts remains to be investigated. Also, due to the limited availability of products containing A. muciniphila, it is not exploited to its full potential. The present review aims at highlighting the potential of A. muciniphila in mucin degradation, contribution towards the gut health and host immunity and management of metabolic diseases such as obesity and type 2 diabetes, and respiratory diseases such as cystic fibrosis and COVID-19.

PMID:35596115 | DOI:10.1007/s12223-022-00973-6

Eur J Pediatr. 2022 May 20. doi: 10.1007/s00431-022-04509-5. Online ahead of print.

ABSTRACT

Bronchiectasis is a form of airway damage as a consequence of endobronchial infection and inflammation and may be present in different diseases. The underlying aetiologies include both cystic fibrosis (CF) and a group of non-cystic fibrosis diseases (NCFB) such as immunodeficiency, primary ciliary dyskinesia, or severe pulmonary infection. Although children with CF and non-cystic fibrosis bronchiectasis (NCFB) have many similar clinical features, their responses to exercise may be different. The aim of this study was to compare the efficacy of a comprehensive respiratory physiotherapy (CRP) home-program in children with CF and NCFB. Thirty children with CF and thirty children with NCFB were included in the study. Both groups performed the CRP home-program twice daily for 8 weeks. Pulmonary function, exercise capacity, and respiratory and peripheral muscle strength were assessed at baseline and after 8 weeks of training. Both groups experienced significant improvements in pulmonary function, exercise capacity, and respiratory and peripheral muscle strength (p < 0.001). Maximum expiratory pressure, exercise capacity, and peripheral muscle strength were further improved in NCFB group compared to CF (p < 0.05); however, there was a great variability in the improvements for each variable.

CONCLUSION: CRP is beneficial both for children with CF and NCFB and adherence to the program was high in both groups.

WHAT IS KNOWN: • Different physiotherapy approaches in the management of non-cystic fibrosis bronchiectasis have been based on the experience gained from the research studies performed in cystic fibrosis. • Although having similar pathophysiology, these two diseases show variation in some pulmonary and extrapulmonary features.

WHAT IS NEW: • The respiratory muscle strength and the efficacy of comprehensive respiratory physiotherapy have been compared for the first time in children with cystic fibrosis and non-cystic fibrosis bronchiectasis. • Comprehensive respiratory physiotherapy provides higher increases in children with non-cystic fibrosis bronchiectasis in exercise capacity and expiratory and peripheral muscle strength; however, there was a great variability in these improvements. Nevertheless, it can be concluded that both groups significantly benefited from the CRP program.

PMID:35595860 | DOI:10.1007/s00431-022-04509-5

Int Forum Allergy Rhinol. 2022 May 20. doi: 10.1002/alr.23016. Online ahead of print.

NO ABSTRACT

PMID:35595546 | DOI:10.1002/alr.23016

Eur Respir J. 2022 May 20:2200189. doi: 10.1183/13993003.00189-2022. Online ahead of print.

NO ABSTRACT

PMID:35595318 | DOI:10.1183/13993003.00189-2022

PLoS One. 2022 May 20;17(5):e0268622. doi: 10.1371/journal.pone.0268622. eCollection 2022.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an inherited disorder causing impaired mucociliary clearance within the respiratory tract, and is associated with bronchiectasis, chronic respiratory infections, and early death. Airway clearance therapies have long been a cornerstone of management of individuals with CF, although evidence supporting their use is lacking. We designed a randomized controlled trial to quantitatively compare the effects of different forms of airway clearance on mucociliary clearance.

METHODS: Three different physiotherapy methods to augment cough-clearance were studied in addition to cough-clearance alone: high-frequency chest-wall oscillating vest, oscillatory positive expiratory pressure, and whole-body vibration. We used gamma scintigraphy after inhalation of radiolabeled particles to quantify mucus clearance before, during, and after physiotherapy. As secondary endpoints, we measured concentrations of small molecules in exhaled breath that may impact mucus clearance.

RESULTS: Ten subjects were enrolled and completed study procedures. No differences were identified between any method of airway clearance, including cough clearance alone. We did identify changes in certain small molecule concentrations in exhaled breath following airway clearance.

CONCLUSIONS: Due to the limitations of this study, we do not believe the negative results suggest a change in clinical practice with regard to airway clearance. Findings pertaining to small molecules in exhaled breath may serve as future opportunities for study.

PMID:35594286 | DOI:10.1371/journal.pone.0268622

Front Pediatr. 2022 May 3;10:917221. doi: 10.3389/fped.2022.917221. eCollection 2022.

NO ABSTRACT

PMID:35592838 | PMC:PMC9110688 | DOI:10.3389/fped.2022.917221

Nat Commun. 2022 May 19;13(1):2798. doi: 10.1038/s41467-022-30479-1.

ABSTRACT

TMEM16A, a calcium-activated chloride channel involved in multiple cellular processes, is a proposed target for diseases such as hypertension, asthma, and cystic fibrosis. Despite these therapeutic promises, its pharmacology remains poorly understood. Here, we present a cryo-EM structure of TMEM16A in complex with the channel blocker 1PBC and a detailed functional analysis of its inhibition mechanism. A pocket located external to the neck region of the hourglass-shaped pore is responsible for open-channel block by 1PBC and presumably also by its structural analogs. The binding of the blocker stabilizes an open-like conformation of the channel that involves a rearrangement of several pore helices. The expansion of the outer pore enhances blocker sensitivity and enables 1PBC to bind at a site within the transmembrane electric field. Our results define the mechanism of inhibition and gating and will facilitate the design of new, potent TMEM16A modulators.

PMID:35589730 | DOI:10.1038/s41467-022-30479-1

BMJ Open Qual. 2022 May;11(2):e001844. doi: 10.1136/bmjoq-2022-001844.

ABSTRACT

INTRODUCTION: The Cystic Fibrosis Foundation chronic care guidelines recommend monitoring clinical status of a patient with cystic fibrosis (CF) through quarterly interdisciplinary visits. At the beginning of the COVID-19 pandemic, the Cystic Fibrosis Learning Network (CFLN) designed and initiated a telehealth (TH) innovation lab (TH ILab) to support transition from the classic CF care model of quarterly in-person office visits to a care model that included TH.

AIM: The specific aims of the TH ILab were to increase the percentage of virtual visits with interdisciplinary care (IDC) from 60% to 85% and increase the percentage of virtual visits in which patients and families participated in shared agenda setting (AS) from 52% to 85% by 31 December 2020.

METHODS: The model for improvement methodology was used to determine the ILab aims, theory, interventions and measures. In the testing phase of the ILab, data related to process and outcome measures as well as learnings from plan-do-study-act cycles were collected, analysed and shared weekly with the TH ILab teams. Participating centres created processes for IDC and AS for TH visits and developed and shared quality improvement tools specific to their local context with other centres during the ILab weekly meetings and via a secure CFLN-maintained platform.

RESULTS: Both specific aims were achieved ahead of the expected target date. By August 2020, 85% of the TH ILab visits provided IDC and 92% of patients were seen for CF care by teams from the TH ILab that participated in AS.

CONCLUSION: Shared learning through a collaborative, data-driven process in the CFLN TH ILab rapidly led to standardised TH IDC and AS, which achieved reliable and sustainable processes which could be reproduced by other networks.

PMID:35589277 | DOI:10.1136/bmjoq-2022-001844

Pediatr Allergy Immunol Pulmonol. 2022 May 18. doi: 10.1089/ped.2021.0165. Online ahead of print.

ABSTRACT

Background: Previous studies reported that the prevalence of drug allergy is higher in patients with cystic fibrosis (CF) than in the general population. It is important to exclude or confirm the drug allergy diagnosis with detailed allergic evaluation for preventing drug allergy overdiagnosis. Our study aims to determine the actual frequency of drug allergy proven by diagnostic tests in children with CF and to compare it with the control group. Methods: Patients diagnosed with CF who were followed up in the Pediatric Pulmonology Clinic were included in the study group. Children with similar gender and age characteristics who did not have any chronic diseases and who applied to the Pediatric Polyclinics were included in the control group. We reviewed the medical data of patients with CF. Also, we evaluated the parents of the patients via phone conversation and/or during the control of the outpatient clinic and questioned them in terms of drug allergy. In addition, we assessed those with suspected drug allergies in the pediatric allergy clinic for diagnostic tests and compared it to the control group. Results: CF patients (n = 44) and control group (n = 100) were included in the study. Only 1 patient (2.2%) out of the 44 patients in the study group had a suspicion of drug-related hypersensitivity history. In the control group, 1 patient had a history of rash, provocation test was performed to rule out drug hypersensitivity reaction, and it was evaluated as a negative result. Conclusions: The result of our study showed that the frequency of drug allergy in children diagnosed with CF was not different from the control group. However, it will be useful to confirm the data of pediatric patients with CF in larger groups. In the presence of suspicion of drug allergy, a diagnostic evaluation can prevent unnecessary drug allergy diagnoses.

PMID:35588286 | DOI:10.1089/ped.2021.0165

Genome Biol Evol. 2022 May 19:evac074. doi: 10.1093/gbe/evac074. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is among the most problematic opportunistic pathogens for adults with cystic fibrosis (CF), causing repeated and resilient infections in the lung and surrounding airways. Evidence suggests that long-term infections are associated with diversification into specialized types but the underlying cause of that diversification and the effect it has on the persistence of infections remains poorly understood. Here, we use evolve and re-sequence experiments to investigate the genetic changes accompanying rapid, de novo phenotypic diversification in lab environments designed to mimic two aspects of human lung ecology: spatial structure and complex nutritional content. After ∼220 generations of evolution, we find extensive genetic variation present in all environments, including those that most closely resemble the CF lung. We use the abundance and frequency of nonsynonymous and synonymous mutations to estimate the ratio of mutations that are selectively neutral (hitchhikers) to those that are under positive selection (drivers). A significantly lower proportion of driver mutations in spatially structured populations suggests that reduced dispersal generates subpopulations with reduced effective population size, decreasing the supply of beneficial mutations and causing more divergent evolutionary trajectories. In addition, we find mutations in a handful of genes typically associated with chronic infection in the CF lung, including one gene associated with antibiotic resistance. This demonstrates that many of the genetic changes considered to be hallmarks of CF lung adaptation can arise as a result of adaptation to a novel environment and do not necessarily require antimicrobial treatment, immune system suppression, or competition from other microbial species to occur.

PMID:35588237 | DOI:10.1093/gbe/evac074

Clin Transplant. 2022 May 19:e14713. doi: 10.1111/ctr.14713. Online ahead of print.

ABSTRACT

INTRODUCTION: There is no gold standard criterion for the diagnosis of cystic fibrosis related liver disease (CFRLD) and there is uncertainty over its impact on the outcome of lung transplantation.

METHOD: Lung recipients (n = 238) were divided into two groups - CFRLD and non-CFRLD based on a modified aspartate aminotransferase-to-platelet ratio index (APRI) score (mAPRI) to diagnose CFRLD and predict severity of liver disease. Groups were compared to assess validity of the diagnosis and survival outcomes.

RESULT: The new diagnostic criterion was effective at differentiating CFRLD from non- CFRLD. There was no significant difference in the survival between two groups at short, medium, or long term demonstrated by the Kaplan-Meier plot with survival of 85%, 73%, 47%, 18.6% and 4.7% at one, two, five, ten and 15 years respectively. A mAPRI score of greater than 0.2 had a sensitivity of 43.0% but a specificity of 82.5 % for diagnosis of CFRLD and 46.5% sensitivity but 100% specificity in predicting an ultrasound/biopsy proven hepatic abnormality associated with CFRLD.

CONCLUSION: A mAPRI sore is a highly specific non-invasive tool for diagnosis of CFRLD. Recipients with CFRLD but grossly preserved hepatocellular function have a similar outcome to patients without CFRLD. This article is protected by copyright. All rights reserved.

PMID:35587587 | DOI:10.1111/ctr.14713

J Med Microbiol. 2022 May;71(5). doi: 10.1099/jmm.0.001505.

ABSTRACT

Achromobacter xylosoxidans is associated with resilient nosocomial infections, with bacteraemia, pneumonia and chronic cystic fibrosis lung infection being the most common clinical presentations. Innate multi-drug resistance and a suite of virulence factors select for A. xylosoxidans infection during long-term antibiotic therapy, contributing to its persistence, treatment recalcitrance, association with poor clinical outcomes and emergence as a problematic pathogen. Horizontal gene transfer and maintenance of large genomes underpin the resilience and cosmopolitan lifestyle of A. xylosoxidans, and complicate its phylogenetic characterization.

PMID:35587447 | DOI:10.1099/jmm.0.001505

ACS Med Chem Lett. 2022 Apr 11;13(5):757-758. doi: 10.1021/acsmedchemlett.2c00140. eCollection 2022 May 12.

NO ABSTRACT

PMID:35586427 | PMC:PMC9109511 | DOI:10.1021/acsmedchemlett.2c00140

Am J Respir Cell Mol Biol. 2022 May 18. doi: 10.1165/rcmb.2022-0182ED. Online ahead of print.

NO ABSTRACT

PMID:35585759 | DOI:10.1165/rcmb.2022-0182ED

J Cyst Fibros. 2022 May 15:S1569-1993(22)00111-4. doi: 10.1016/j.jcf.2022.05.001. Online ahead of print.

ABSTRACT

INTRODUCTION: Deterioration in mental health has been reported in a minority of individuals with cystic fibrosis starting elexacafor/tezacaftor/ivacaftor (ELX/TEZ/IVA). We report our experience of using sweat chloride and markers of clinical stability to titrate dose reduction with the aim of minimising adverse events and maintaining clinical stability.

METHOD: Adults (n = 266) prescribed ELX/TEZ/IVA, were included. Adverse events, sweat chloride, lung function and clinical data were collected.

RESULTS: Nineteen (7.1%) individuals reported anxiety, low mood, insomnia and "brain fog" with reduced attention and concentration span. Thirteen underwent dose reduction with sweat chloride remained normal (<30 mmol l-1) or borderline (30-60 mmol l-1) in six (46.2%) and seven (53.2%) cases respectively. Improvement or resolution of AEs occurring in 10 of the 13 cases.

CONCLUSION: Dose adjustment of ELX/TEZ/IVA was associated with improvement in mental health AEs without significant clinical deterioration. Sweat chloride concentration may prove useful as a surrogate marker of CFTR function.

PMID:35585012 | DOI:10.1016/j.jcf.2022.05.001

J Cyst Fibros. 2022 May 15:S1569-1993(22)00120-5. doi: 10.1016/j.jcf.2022.05.005. Online ahead of print.

NO ABSTRACT

PMID:35585011 | DOI:10.1016/j.jcf.2022.05.005

J Cyst Fibros. 2022 May 15:S1569-1993(22)00113-8. doi: 10.1016/j.jcf.2022.05.003. Online ahead of print.

ABSTRACT

BACKGROUND: Concerns related to stool consistency are common in the first year of life among children with cystic fibrosis (CF). However, normal stool patterns for infants with CF have not been described.

METHODS: Secondary analysis was completed from the previously described BONUS cohort which followed 231 infants with CF through the first 12 months of life. Pain, stool category, stool frequency, feeding type, PERT dose, acid suppression medication, antibiotics usage, stool softener usage and fecal calprotectin were described at 3, 6, and 12 months. Repeated measure ANOVA was used to test the difference in mean stool number. Generalized linear mixed models were used to investigate the relationship between stool characteristics and various factors.

RESULTS: The frequency of constipation was stable throughout the first year of life (10-13%) while watery stool significantly decreased from 21.3% at 3 months to 5.8% at 12 months (p=<0.001). The number of stools at months 6 (mean=2.40) and 12 (mean=2.50) are significantly lower than in month 3 (mean=2.83), p<0.025. Exclusive breast feeding was associated with an increased risk for constipation (OR=2.64 [1.60-4.37], p = 0.002) while exclusive formula feeding and acid suppression was associated with decreased risk for constipation (OR=0.40 [0.26-0.61], p=<0.0001 and OR=0.59 [0.39-0.89], p = 0.01 respectively). Pain was not significantly associated with stool consistency.

CONCLUSION: Stool frequency and consistency evolves in infant with CF in a fashion similar to that reported in non-CF infants over the first year. Constipation was not associated with pain and was less common among infants receiving acid suppression or exclusively formula feeding.

PMID:35585010 | DOI:10.1016/j.jcf.2022.05.003