Transplant Proc. 2022 Apr 15:S0041-1345(22)00174-9. doi: 10.1016/j.transproceed.2022.02.015. Online ahead of print.

ABSTRACT

BACKGROUND: Lung transplantation remains the only feasible option for certain patients with end-stage lung disease. Lifelong immunosuppression increases the risk of infection, including fungal infections. The aim of this study was to assess the effect of antifungal prophylaxis and treatment among lung transplant recipients in the early postoperative stage.

METHODS: This retrospective analysis included 127 patients who underwent lung transplantation between 2014 and 2021 in the lung transplant ward, 65.35% of whom were males. The most common indication for lung transplantation was cystic fibrosis (n = 59; 46.46%). All of the patients were receiving inhaled amphotericin B. Within this group there were patients who also were treated with intravenous caspofungin, intravenous/oral voriconazole, or both.

RESULTS: The difference in the efficacy against Candida spp. between caspofungin and voriconazole in the early post-transplant period was not statistically significant (χ2 = 0.5, P = .477). Moreover, the difference in the efficacy against Candida spp. between itraconazole and voriconazole during the first post-transplant year was not statistically significant (χ2 = 0.46, P = .496).

CONCLUSION: Caspofungin and voriconazole are proper and relatively efficient antifungal prophylaxis and treatment options after lung transplantation. There was no significant difference between voriconazole and caspofungin as antifungal agents used in the early post-transplant stage. There was no significant difference between voriconazole and itraconazole as antifungal agents used during the first post-transplant year. Further research on this issue is required.

PMID:35437151 | DOI:10.1016/j.transproceed.2022.02.015

mBio. 2022 Apr 18:e0246321. doi: 10.1128/mbio.02463-21. Online ahead of print.

ABSTRACT

Synthesis of polyphosphate (polyP) is an ancient and universal stress and starvation response in bacteria. In many bacteria, polyP chains come together to form granular superstructures within cells. Some species appear to regulate polyP granule subcellular organization. Despite the critical role of polyP in starvation fitness, the composition of these structures, mechanism(s) underpinning their organization, and functional significance of such organization are poorly understood. We previously determined that granules become transiently evenly spaced on the cell's long axis during nitrogen starvation in the opportunistic human pathogen Pseudomonas aeruginosa. Here, we developed a granule-enrichment protocol to screen for polyP granule-localizing proteins. We identified AlgP as a protein that associates with polyP granules. We further discovered that AlgP is required for the even spacing of polyP granules. AlgP is a DNA-binding protein with a 154 amino acid C-terminal domain enriched in "KPAA" repeats and variants of this repeat, with an overall sequence composition similar to the C-terminal tail of eukaryotic histone H1. Granule size, number, and spacing are significantly perturbed in the absence of AlgP, or when AlgP is truncated to remove the C-terminus. The ΔalgP and algPΔCTD mutants have fewer, larger granules. We speculate that AlgP may contribute to spacing by tethering polyP granules to the chromosome, thereby inhibiting fusion with neighboring granules. Our discovery that AlgP facilitates granule spacing allows us for the first time to directly uncouple granule biogenesis from even spacing, and will inform future efforts to explore the functional significance of granule organization on fitness during starvation. IMPORTANCE The mechanisms underpinning polyP's pleiotropic effects on bacterial starvation physiology remain elusive. This simple polyanion's lack of protein binding specificity has impeded validation of bona fide polyP-binding proteins. However, polyP forms granule superstructures with spatial specificity. Our granule enrichment protocol identified a polyP granule-associated protein in Pseudomonas aeruginosa, AlgP. AlgP was originally reported as a regulator of alginate, an extracellular polysaccharide important in biofilm formation, including in cystic fibrosis (CF) chronic infections. AlgP's putative role in alginate biosynthesis has recently been called into question. We establish a distinct, previously unknown function for AlgP in modulating the subcellular organization of polyP, another polymer important for pathogenesis. In CF clinical isolates, the C-terminal repeat domain of AlgP is a hot spot for genetic rearrangements. Our finding that the C-terminus of AlgP is required for granule organization lays the groundwork for exploring the functional significance of these mutations in the evolutionary trajectory of chronic infections.

PMID:35435704 | DOI:10.1128/mbio.02463-21

Biom J. 2022 Apr 18. doi: 10.1002/bimj.201900255. Online ahead of print.

ABSTRACT

Cystic fibrosis and other chronic lung disease clinical trials often use time to first pulmonary exacerbation (PEx) or total PEx count as endpoints. The use of these outcomes may fail to capture patterns or timing of multiple exacerbations and how covariates influence the risk of future exacerbations. Analysis of gap times between PEx provides a useful framework to understand risks of subsequent events, particularly to assess if there is a temporary increase in a hazard of a subsequent PEx following the occurrence of a PEx. This may be useful for estimating the amount of time needed to follow patients after a PEx and predicting which patients are more likely to have multiple PEx. We propose a smoothed hazard for gap times to account for elevated hazards after exacerbations. A simulation study was conducted to explore model performance and was able to appropriately estimate parameters in all situations with an underlying change point with independent or correlated recurrent events. Models with different change-point structures and trends are compared using Early Pseudomonas Infection Control (EPIC) observational study data, using a quasi-likelihood modification of the Akaike information criterion; a model with a change-point provided a better fit than a model without one. The analysis suggests that the change point may be 1.8 years (SE 0.09) after the end of a PEx. Models including covariates in the hazard function revealed that having one or two copies of the Δ $\Delta$ F508 mutation, female sex, and higher numbers of previous PEx were significantly associated with increased risk of another PEx.

PMID:35434808 | DOI:10.1002/bimj.201900255

STAR Protoc. 2022 Apr 7;3(2):101258. doi: 10.1016/j.xpro.2022.101258. eCollection 2022 Jun 17.

ABSTRACT

We describe a protocol to identify the binding site(s) for a drug called ivacaftor that potentiates the CFTR chloride channel. We use photoaffinity probes-based on the structure of ivacaftor-to covalently modify the CFTR protein at the region that constitutes the drug binding site(s). We define the methods for photo-labeling CFTR, its membrane extraction, and enzymatic digestion using trypsin. We then describe the experimental methods to identify the modified peptides by using mass spectrometry. For complete details on the use and execution of this protocol, please refer to Laselva et al. (2021).

PMID:35434660 | PMC:PMC9006651 | DOI:10.1016/j.xpro.2022.101258

Laryngoscope Investig Otolaryngol. 2022 Feb 23;7(2):395-403. doi: 10.1002/lio2.734. eCollection 2022 Apr.

ABSTRACT

BACKGROUND: It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups.

METHODS: A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be "stabilized" (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long-term (2 years) following the endoscopic procedure.

RESULTS: Sixty-six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan-Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5-9.8], p = .01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p = .01).

CONCLUSIONS: Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3.

PMID:35434321 | PMC:PMC9008152 | DOI:10.1002/lio2.734

Open Forum Infect Dis. 2022 Mar 9;9(5):ofac114. doi: 10.1093/ofid/ofac114. eCollection 2022 May.

ABSTRACT

BACKGROUND: In September 2018, Burkholderia cepacia complex (BCC) infections in 3 patients associated with exposure to a mouthwash solution (MWS) were reported to the Robert Koch Institute (RKI). As the product was still on the market and the scale of the outbreak was unclear, a nation-wide investigation was initiated.

METHODS: We aimed to investigate BCC infections/colonizations associated with MWS. Hospitals, laboratories, and public health services were informed that BCC isolates should be sent to the RKI. These isolates were typed by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) including development of an ad hoc core genome MLST (cgMLST) scheme.

RESULTS: In total, 36 patients from 6 hospitals met the case definition, the last patient in November 2018. Twenty-nine isolates from 26 of these patients were available for typing. WGS analysis revealed 2 distinct cgMLST clusters. Cluster 1 (Burkholderia arboris) contained isolates from patients and MWS obtained from 4 hospitals and isolates provided by the manufacturer. Patient and MWS isolates from another hospital were assigned to cluster 2 (B. cepacia).

CONCLUSIONS: The combined clinical, epidemiological, and microbiological investigation, including whole-genome analysis, allowed for uncovering a supraregional BCC outbreak in health care settings. Strains of B. arboris and B. cepacia were identified as contaminating species of MWS bottles and subsequent colonization and putative infection of patients in several hospitals. Despite a recall of the product by the manufacturer in August 2018, the outbreak lasted until December 2018. Reporting of contaminated medical products and recalls should be optimized to protect patients.

PMID:35434175 | PMC:PMC9007922 | DOI:10.1093/ofid/ofac114

Front Mol Biosci. 2022 Mar 30;9:857000. doi: 10.3389/fmolb.2022.857000. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF) is progressive genetic disease that predisposes lungs and other organs to multiple long-lasting microbial infections. Pseudomonas aeruginosa is the most prevalent and deadly pathogen among these microbes. Lung function of CF patients worsens following chronic infections with P. aeruginosa and is associated with increased mortality and morbidity. Emergence of multidrug-resistant, extensively drug-resistant and pandrug-resistant strains of P. aeruginosa due to intrinsic and adaptive antibiotic resistance mechanisms has failed the current anti-pseudomonal antibiotics. Hence new antibacterials are urgently needed to treat P. aeruginosa infections. Structure-guided fragment-based drug discovery (FBDD) is a powerful approach in the field of drug development that has succeeded in delivering six FDA approved drugs over the past 20 years targeting a variety of biological molecules. However, FBDD has not been widely used in the development of anti-pseudomonal molecules. In this review, we first give a brief overview of our structure-guided FBDD pipeline and then give a detailed account of FBDD campaigns to combat P. aeruginosa infections by developing small molecules having either bactericidal or anti-virulence properties. We conclude with a brief overview of the FBDD efforts in our lab at the University of Cambridge towards targeting P. aeruginosa infections.

PMID:35433835 | PMC:PMC9006449 | DOI:10.3389/fmolb.2022.857000

J Clin Transl Endocrinol. 2022 Apr 4;28:100298. doi: 10.1016/j.jcte.2022.100298. eCollection 2022 Jun.

ABSTRACT

This study aimed to analyze clinical practices concerning cystic fibrosis-related diabetes (CFRD) screening in France. A web-based questionnaire was distributed between December 1, 2020 and January 31, 2021 among 47 cystic fibrosis centers including pediatric, adult, and mixed units. In accordance with guidelines, 92.8% of CF centers performed annual oral glucose tolerance tests (OGTT). Overall, 86.3% of CF centers performed 1- and 2-hour blood glucose determinations following OGTT. The OGTT was conducted before 10 years of age in 73% of pediatric centers. Continuous glucose monitoring (CGM) and laboratory glycated hemoglobin were employed for CFRD screening in 86.5% and 50% of centers, respectively. CGM was carried out in 69% of centers after glucose tolerance abnormalities had been detected in OGTT. Most CF centers used OGTT and CGM for CFRD screening. Studies are required to assess CGM usefulness as a validated tool in CFRD screening.

PMID:35433271 | PMC:PMC9010626 | DOI:10.1016/j.jcte.2022.100298

J Clin Transl Endocrinol. 2022 Mar 25;28:100297. doi: 10.1016/j.jcte.2022.100297. eCollection 2022 Jun.

ABSTRACT

BACKGROUND: Pediatric bone accrual governs peak bone mass and strength. Longitudinal studies of bone health in youth with cystic fibrosis (CF) may provide insight into CF-related bone disease (CFBD), a prevalent co-morbidity in adults with CF.

METHODS: This one-year longitudinal study of youth with pancreatic insufficient CF, enrolled in a nutrition intervention study [n = 62 (36 M/26F)] 1) examined dual-energy x-ray absorptiometry (DXA)-defined lumbar spine (LS) and total body less head (TBLH) bone accrual and 2) compared their changes in peripheral quantitative computed tomography (pQCT) cortical and trabecular tibial bone density and geometry to those of a healthy reference group [n = 143 (68 M/75F)].Main outcome measures were 1) DXA: lumbar spine areal bone mineral density (LSaBMD) and total body less head bone mineral content (TBLH-BMC), sex- and pubertal status-specific, height velocity (HV)-adjusted or HV and lean body mass velocity (HV-LBMV)-adjusted annualized velocity-Z scores and 2) pQCT: age, sex, pubertal status and, when appropriate, tibial length adjusted Z-scores for bone architecture measures.DXA velocity-Z were compared to expected mean of 0 and correlations with clinical parameters (age, BMI-Z and FEV1%-predicted) tested. Within-subject comparisons of HV-adjusted and LBMV-HV-adjusted DXA velocity-Z were conducted in CF.pQCT Z-scores were compared between the two groups over one year using longitudinal models. Longitudinal relationships between measures of bone health and clinical parameters (age, BMI-Z and FEV1%-predicted) were examined in individuals with CF.

RESULTS: DXA velocity-Z were higher than normal in females (p < 0.05) but not males with CF. HV-adjusted and LBMV-HV-adjusted velocity-Z did not differ for LSaBMD or TBLH-BMC.In males with CF, both HV-adjusted and LBMV-HV-adjusted LSaBMD velocity-Z scores correlated negatively with age (HV rho: -0.35; p = 0.045 and LBMV-HV rho: -0.47; p = 0.0046). In males with CF BMI-Z correlated positively with HV-adjusted LSaBMD velocity-Z (rho: 0.37; p = 0.034), but this relationship did not persist for LBMV-HV (rho: 0.14; p = 0.42). In females with CF, no correlations between LSaBMD velocity-Z scores and age or BMI-Z were found (all p > 0.05). No correlations between LSaBMD velocity-Z scores and FEV1%-predicted were seen in either sex (all p > 0.12). TBLH-BMC velocity Z-scores were not correlated with clinical parameters in either sex (all p > 0.1).At baseline, multiple pQCT parameters were lower in CF (p < 0.05). pQCT Z-scores did not differ between baseline and one-year in either CF or reference group. In a longitudinal model comparing pQCT-Z changes in CF and reference, multiple pQCT-Z outcomes remained lower in CF, but the changes in parameters did not differ in CF vs reference (all p > 0.26). Lower pQCT outcomes in CF were largely restricted to males (CF group*female sex interaction beta coefficients > 0). In this combined longitudinal model, of both CF and reference, BMI-Z was positively associated with pQCT-Z parameters(p < 0.001).Multiple pQCT-Z outcomes positively correlated with both BMI-Z and FEV1%-predicted in males with CF, and with FEV1%-predicted in females with CF (p < 0.05). Age was negatively associated with section modulus (p = 0.001) in males and with cortical density-Z in females (p < 0.001).

CONCLUSIONS: With improved longevity, bone health in CF is of increasing importance. On average, bone accrual was preserved in youth with CF, and while deficits in bone geometry and strength were found, these deficits did not worsen over the one-year study. Lower LS bone accrual with increasing age suggests emerging adulthood is a period of vulnerability in CF while the role of LBM in bone health is underscored by the lack of relationship between LBMV-adjusted accrual and BMI. These findings may be useful in targeting screening practices and interventions.

PMID:35433270 | PMC:PMC9006323 | DOI:10.1016/j.jcte.2022.100297

Front Physiol. 2022 Mar 30;13:834664. doi: 10.3389/fphys.2022.834664. eCollection 2022.

ABSTRACT

Cross-sectional studies have reported lower pulmonary and aerobic function during exercise in people with cystic fibrosis-related diabetes (CFRD) compared to non-CFRD counterparts. However, this association has yet to be longitudinally investigated. Therefore, this study examines these differences over time between people with cystic fibrosis (CF) of differing glycaemic status. Annual review data, including cardiopulmonary exercise tests and pulmonary function tests, were retrospectively analysed at baseline (T0, n = 82) and at a one-year follow-up (T1, n = 54). Data was analysed in three groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and CFRD. Further analyses were undertaken, with a dichotomous split of NGT and a combined IGT/CFRD group. At baseline, a significant reduction in the majority of variables, including forced expiratory volume in one second (FEV1) and maximal oxygen uptake (VO2max), was observed in the CFRD (n = 19) group compared to NGT (n = 58). At follow-up, no significant differences were observed, and no interaction effect between CFRD status and time was identified. FEV1 and VO2max presented with varying directions and magnitudes of change within patients. In summary, patients with CFRD have a reduced aerobic and pulmonary function compared to non-CFRD counterparts, although such changes disappeared at follow up. Varying responses for FEV1 and VO2max highlight the need to consider both variables as independent markers of function in CF.

PMID:35431976 | PMC:PMC9005891 | DOI:10.3389/fphys.2022.834664

Mycopathologia. 2022 Apr 16. doi: 10.1007/s11046-022-00631-y. Online ahead of print.

ABSTRACT

BACKGROUND: Whether cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations contribute to the high prevalence of allergic bronchopulmonary aspergillosis (ABPA) in India remains unknown. We aimed to evaluate the occurrence of CFTR mutations in subjects with ABPA complicating asthma.

METHODS: We sequenced the CFTR gene using genomic DNA from blood on the Illumina NextSeq500 platform. Before undertaking zygosity analysis by genome analysis toolkit, the known or novel single nucleotide polymorphisms (SNPs) and indels were called. For rigorous analysis, we included only high-quality SNPs (scores > 500) and coverage ranging from 30 × 150x.

RESULTS: We included 18, 12, and eight adult participants of ABPA, asthma, and healthy controls, respectively. The frequency of SNPs was higher in asthmatic subjects than ABPA or healthy controls, albeit not statistically significant (9/12 [75%] vs. 11/18 [61.1%] vs. 3/8 [37.5%], p = 0.24). Of the 38 subjects, 23 yielded 50 variants (healthy controls [n = 5], ABPA [n = 22], asthma [n = 23]) corresponding to six SNPs not previously linked with ABPA. Of these, four SNPs (rs213950, rs200735475, rs1800113, and rs1800136) were catalogued in the NCBI database. We identified two novel SNPs (chr7:117250703, chr7:117282655) in four (ABPA [n = 1], asthma [n = 3]) subjects without corresponding reference SNP. Most SNPs (85.5%) were heterozygous. The frequency of SNPs was higher in ABPA subjects with high-attenuation mucus (52.2%) and bronchiectasis (39.1%) than serological ABPA (8.7%).

CONCLUSIONS: Our study suggests the role of CFTR mutations in the pathogenesis of ABPA. The SNPs in the CFTR gene may contribute to disease severity in ABPA. Larger studies are required to confirm our findings.

PMID:35430640 | DOI:10.1007/s11046-022-00631-y

Soc Sci Med. 2022 Apr 12;301:114972. doi: 10.1016/j.socscimed.2022.114972. Online ahead of print.

ABSTRACT

As whole genome sequencing is being considered as a tool to deliver expanded newborn screening (NBS) globally, the range of equivocal results it could produce are gaining increased attention. For cystic fibrosis (CF) screening, the use of next generation sequencing within existing UK NBS programmes would increase the number of uncertain designations returned within results, including that of Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CFSPID). However, the experiences of families already living with this designation have been under-explored. This study uses in-depth interviews to explore the perspectives of sixteen parents who received positive results from CF NBS, with varying degrees of prognostic un/certainty; parents with a child diagnosed with CF (n = 6), CF carrier status (n = 3) and those with the CFSPID designation (n = 7). The biographically disruptive nature of positive NBS results-regardless of immediate relevance to the child-dominated early experiences of positive results across all groups. For those with CF, biographical reparation involved becoming 'a CF family', underscoring biological kinship bonds and reinforcing familial identity. For those with uncertain results, biographical re-calibration was more complex. Diagnostic and prognostic uncertainty posed a barrier to entry for both the 'CF world' and the 'healthy kid' world, leading parents to attempt to minimise its role, either through rejection, or re-interpretation of their child's result. Other parents, however, experienced biographical reparation more dynamically. The concept of 'genetic nomadism' captures accounts of oscillation between the two worlds; movements that were responsive to evolving health experiences, as well as social, environmental and temporal factors. Through the concept of genetic nomadism, this paper delineates both the productive, as well as divisive, nature of uncertainty for biographical reparation in the aftermath of NBS, as well as the strategies parents use to harness it, in order to successfully navigate the world with a child with an ambiguous genetic future.

PMID:35430463 | DOI:10.1016/j.socscimed.2022.114972

Pediatr Pulmonol. 2022 Apr 15. doi: 10.1002/ppul.25925. Online ahead of print.

ABSTRACT

RATIONALE: Forced Expiratory Volume in 1 second (FEV1) decline (ΔFEV1) is associated with pulmonary exacerbation (PEx) diagnosis in cystic fibrosis (CF). Spirometry may not be available during telehealth visits and could impair clinician ability to diagnose PEx. This study aims to 1) identify the associations between degrees of ΔFEV1 (decrease of <5% predicted vs 5-9% predicted vs ≥10% predicted from baseline), clinical symptoms, and clinician-diagnosed PEx and 2) evaluate the correlation between respiratory symptoms, ΔFEV1, and antibiotic treatment.

METHODS: Retrospective, descriptive study of PEx diagnosis and management in 628 outpatient clinical encounters with spirometry in 178 patients with CF ages 6-17 years at Riley Hospital for Children during 2019. Odds ratios of symptoms associated with clinician-defined PEx diagnosis and antibiotic management stratified by ΔFEV1 decline were determined.

RESULTS: Clinician-diagnosed PEx occurred at 199 (31.7%) visits; increased cough (77.4%) and sputum/wet cough (57.8%) were the most frequently reported symptoms. Compared to no ΔFEV1, the odds of a clinician-diagnosed PEx were increased when ΔFEV15-9% and ΔFEV1≥10% was present with increased cough (OR 1.56, 95% CI 1.25-1.94 and OR 1.82, 95% CI 1.52-2.19, respectively), increased sputum (OR 1.59, 95% CI 1.20-2.12 and OR 1.78, 95% CI 1.37-2.32, respectively), and increased cough and sputum together (OR 1.51, 95% CI 1.08-2.13 and OR 1.68, 95% CI 1.22-2.31, respectively).

CONCLUSIONS: ΔFEV1 is associated with increased likelihood that cough and sputum are diagnosed as a PEx. Spirometry is essential for PEx diagnosis and treatment and is a necessary component of all clinical encounters. This article is protected by copyright. All rights reserved.

PMID:35429154 | DOI:10.1002/ppul.25925

Thorax. 2022 Apr 15:thoraxjnl-2021-218347. doi: 10.1136/thoraxjnl-2021-218347. Online ahead of print.

ABSTRACT

BACKGROUND: The limits of reproducibility of the lung clearance index (LCI) are higher in children with cystic fibrosis (CF) compared with healthy children, and it is currently unclear what defines a clinically meaningful change.

METHODS: In a prospective multisite observational study of children with CF and healthy controls (HCs), we measured LCI, FEV1% predicted and symptom scores at quarterly visits over 2 years. Two reviewers performed a detailed review of visits to evaluate the frequency that between visit LCI changes outside ±10%, ±15%, ±20% represented a clinically relevant signal. In the setting of acute respiratory symptoms, we used a generalised estimating equation model, with a logit link function to determine the ability of LCI worsening at different thresholds to predict failure of lung function recovery at follow-up.

RESULTS: Clinically relevant LCI changes outside ±10%, ±15% and ±20% were observed at 25.7%, 15.0% and 8.3% of CF visits (n=744), respectively. The proportions of LCI changes categorised as noise, reflecting biological variability, were comparable between CF and HC at the 10% (CF 9.9% vs HC 13.0%), 15% (CF 4.3% vs HC 3.1%) and 20% (CF 2.4% vs HC 1.0%) thresholds. Compared with symptomatic CF visits without a worsening in LCI, events with ≥10% LCI increase were more likely to fail to recover baseline LCI at follow-up.

CONCLUSION: The limits of reproducibility of the LCI in healthy children can be used to detect clinically relevant changes and thus inform clinical care in children with CF.

PMID:35428702 | DOI:10.1136/thoraxjnl-2021-218347

J Cyst Fibros. 2022 Apr 12:S1569-1993(22)00093-5. doi: 10.1016/j.jcf.2022.04.003. Online ahead of print.

NO ABSTRACT

PMID:35428535 | DOI:10.1016/j.jcf.2022.04.003

Pediatr Transplant. 2022 Apr 15:e14281. doi: 10.1111/petr.14281. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic poses an increased risk of infection, severe illness, hospitalization and mortality for young people who are immunosuppressed, including lung transplant (LTx) recipients. The aim of this study was to explore the intersection between immunosuppression and COVID-19, through the impacts of the pandemic upon the daily lives of young LTx recipients residing in the Australian state of Victoria.

METHODS: An exploratory qualitative research study was undertaken via consumer engagement. A purposive sample of 11 LTx recipients, residing in Victoria, was recruited during the first year of the COVID-19 pandemic. Semi-structured interviews were conducted to gain insights into their daily life and healthcare experiences, including the impacts of the COVID-19 pandemic. Data were interpreted using thematic analysis.

RESULTS: Four major themes were identified: (1) occupational deprivation due to the intersection of COVID-19 and lung transplant; (2) resilience and acceptance of restrictions; (3) infection control and vigilance about risk; and (4) care experiences of telehealth.

CONCLUSIONS: Occupational deprivation emerged as a common theme, specifically in the context of loss of access to meaningful everyday activities of developmental significance. However, participants also commonly reflected upon their ability to flexibly adjust to changing socially regulated community and healthcare environments. A high degree of acceptance and compliance with public health orders was self-reported, may be indicative of this cohort's long-term experience of chronic illness and their understanding of the importance of minimizing infection risks. Youth-informed healthcare strategies were identified as keystone to engaging them in institutional change and program adaptation during a pandemic.

PMID:35427443 | DOI:10.1111/petr.14281

RSC Adv. 2022 Mar 18;12(14):8691-8707. doi: 10.1039/d1ra07888g. eCollection 2022 Mar 15.

ABSTRACT

Electronic skins (e-skins) are soft (deformable and stretchable) state-of-the-art wearable devices that emulate the attributes of human skin and act as a Human-Machine Interface (HMI). Recent advances in e-skin for real-time detection of medical signals such as pulse, temperature, electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), and other bioelectric signals laid down an intelligent foundation for early prediction and diagnosis of diseases with a motive of reducing the risk of the ailment reaching to the end stage. In particular, sweat testing has been employed in diverse applications ranging from medical diagnosis of diabetes, cystic fibrosis, tuberculosis, blood pressure, and autonomic neuropathy to evaluating fluid and electrolyte balance in athletes. Typically, sweat testing techniques are done by trained experts and require off-body measurements, which prevent individuals from de-coding health issues quickly and independently. With the onset of soft electronics, wearable sweat sensors overcome this disadvantage via in situ sweat measurements with real-time feedback, timely diagnosis, creating the potential for preventive care and treatment. Over the past few decades, wearable microfluidic-based e-skin sweat sensors have paved a new way, promising sensing interfaces that are highly compatible with arranging medical and electronic applications. The present review highlights the recent research carried out in the microfluidic-based wearable sweat sensors with a critical focus on real-time sensing of lactate, chloride, and glucose concentration; sweat rate, simultaneously with pH, and total sweat loss for preventive care, timely diagnosis, and point-of-care health and fitness monitoring.

PMID:35424805 | PMC:PMC8985157 | DOI:10.1039/d1ra07888g

J Cyst Fibros. 2022 Apr 11:S1569-1993(22)00095-9. doi: 10.1016/j.jcf.2022.04.005. Online ahead of print.

ABSTRACT

We report elexacaftor-tezacaftor-ivacaftor (ETI) treatment of a F508del carrier who was pregnant with a F508del homozygous fetus. At 23-weeks gestation meconium ileus (MI) was evident on ultrasound including dilated, hyperechoic bowel, which persisted on subsequent imaging. Through shared decision-making, the mother began ETI at 32 weeks with intent to treat fetal MI. The ultrasound findings persisted at treatment day 13, but bowel dilation had resolved by imaging on treatment day 27. A female infant was delivered vaginally at 36 weeks with no complications. The mother continued ETI while breastfeeding. Stool elastase at age 2 weeks was 240 mcg/g. Sweat chloride measurement was 64 and 62 mEq/L. Maternal and infant liver function testing have been normal. Maternal ETI treatment likely led to resolution of the MI and there is evidence supporting continued infant benefit through breastmilk. Logistical and ethical considerations regarding treatment of a carrier mother for infant benefit are discussed.

PMID:35422395 | DOI:10.1016/j.jcf.2022.04.005

Soc Work Health Care. 2022 Apr 14:1-15. doi: 10.1080/00981389.2022.2060422. Online ahead of print.

ABSTRACT

People with cystic fibrosis experience rates of anxiety and depression that are considerably higher than those of the general population. Research suggests low mental health functioning can lead to poor health outcomes and quality of life for this population. Consequently, recognition of the need for routine mental health screening and referral in cystic fibrosis care is increasing. Yet to date, less is known about the actual mental health care needs of people with cystic fibrosis. This scoping review sought to address this gap by examining the mental health care needs of adults and adolescents living with cystic fibrosis, and how are these needs are (or are not) being met. Findings suggest current efforts at mental health care provision do not adequately meet the needs of people with cystic fibrosis, highlighting the urgency of conducting high quality intervention research to support effective mental health care for this population.

PMID:35422201 | DOI:10.1080/00981389.2022.2060422

Commun Biol. 2022 Apr 13;5(1):356. doi: 10.1038/s42003-022-03302-2.

ABSTRACT

Although the impact of genome variation on the thermodynamic properties of function on the protein fold has been studied in vitro, it remains a challenge to assign these relationships across the entire polypeptide sequence in vivo. Using the Gaussian process regression based principle of Spatial CoVariance, we globally assign on a residue-by-residue basis the biological thermodynamic properties that contribute to the functional fold of CFTR in the cell. We demonstrate the existence of a thermodynamically sensitive region of the CFTR fold involving the interface between NBD1 and ICL4 that contributes to its export from endoplasmic reticulum. At the cell surface a new set of residues contribute uniquely to the management of channel function. These results support a general 'quality assurance' view of global protein fold management as an SCV principle describing the differential pre- and post-ER residue interactions contributing to compartmentalization of the energetics of the protein fold for function. Our results set the stage for future analyses of the quality systems managing protein sequence-to-function-to-structure broadly encompassing genome design leading to protein function in complex cellular relationships responsible for diversity and fitness in biology in response to the environment.

PMID:35418593 | DOI:10.1038/s42003-022-03302-2