Turk J Pediatr. 2022;64(2):274-284. doi: 10.24953/turkjped.2021.415.

ABSTRACT

BACKGROUND: This study aimed to evaluate the nutritional status and body composition in children with cystic fibrosis (CF), in accordance with the new nutritional targets defined by European Society for Clinical Nutrition and Metabolism (ESPEN), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Cystic Fibrosis Society (ECFS) 2016.

METHODS: In this cross-sectional study, data were collected prospectively in a single centre. A record was made for a total of 95 patients with CF of clinical data. Anthropometric data were evaluated using the World Health Organization growth standards. The bone mineral density (BMD) z-score was adjusted for height by measuring dual-energy X-ray absorptiometry (DXA). The speed of sound z-score values were measured with quantitative ultrasound (QUS).

RESULTS: The nutritional status was normal in 37.9% of patients aged < 2 years and 33.3% of patients aged 2-18 years. When the DXA BMD z-score values were corrected for height, it was determined that the BMD deficit was less. The calcaneus QUS SOS z-score mean value was lower than the mean height for age z-score adjusted BMD (BMDHAZ).

CONCLUSIONS: The malnutrition rates of CF patients were higher than the rates previously reported in literature. As there are insufficient nutritional data in Turkey, there is a need for multi-centre studies to determine the frequency of malnutrition according to the new classifications. It is clear that QUS measurements cannot replace DXA in the diagnosis of osteopenic bone disease. However, when low values are determined with QUS as the first recommended measurement in the screening of bone status, it can be considered appropriate to confirm the status with DXA.

PMID:35611416 | DOI:10.24953/turkjped.2021.415

Br J Cancer. 2022 May 24. doi: 10.1038/s41416-022-01856-w. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium.

METHODS: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer.

RESULTS: Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84).

CONCLUSION: Our results indicate a weak inverse association between tea consumption and gastric cancer.

PMID:35610368 | DOI:10.1038/s41416-022-01856-w

BMJ Case Rep. 2022 May 24;15(5):e248812. doi: 10.1136/bcr-2022-248812.

ABSTRACT

A patient, an adolescent male, presented to us with complaints of recurrent respiratory tract infections since childhood. Differentials considered were cystic fibrosis (CF), bronchial asthma with allergic bronchopulmonary aspergillosis (ABPA), primary ciliary dyskinesia (PCD) and primary immunodeficiency disorders. Sweat chloride test, total IgE and Aspergillus fumigatus specific serum IgE and IgG levels were normal ruling out CF and ABPA. Nasal nitric oxide (NO) screening test showed reduced NO levels, and high-speed video microscopy of nasal scrapings showed stiff beating cilia with reduced ciliary beat frequency confirming the diagnosis of PCD. Immunodeficiency workup showed reduced serum IgG, IgA and IgM, when repeated on two separate occasions when the patient was not harbouring any active infection, suggestive of pan-hypogammaglobulinaemia. Thus, a diagnosis of coexistent PCD and pan-hypogammaglobulinaemia was made. Detection of immunodeficiency disorders is important in patients with PCD as they may benefit from immunoglobulin replacement.

PMID:35609933 | DOI:10.1136/bcr-2022-248812

Curr Opin Pharmacol. 2022 May 19;65:102239. doi: 10.1016/j.coph.2022.102239. Online ahead of print.

ABSTRACT

Small molecular modulators of the cystic fibrosis transmembrane conductance regulator protein are transforming the care of people with cystic fibrosis. Highly effective modulators are now approved for nearly 90% of the adult CF population. They dramatically improve lung function, respiratory symptoms, and reduce pulmonary exacerbations. Recent efforts are expanding the availability of these therapies to a growing number of pediatric patients. The impact of modulators on extrapulmonary CF manifestations varies, although profound improvements in nutrition have been demonstrated. Observational studies and real-world research suggest that treatment benefits are sustained over time, and that maximal impact may be obtained with early use. The development of alternative approaches to restoring cystic fibrosis transmembrane conductance regulator (CFTR) function is needed for those with ineligible mutations.

PMID:35609385 | DOI:10.1016/j.coph.2022.102239

Perm J. 2022 Apr 5;26(1):73-79. doi: 10.7812/TPP/21.089.

ABSTRACT

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective cystic fibrosis transmembrane conductance regulator modulator. It has been shown to improve lung function and decrease pulmonary exacerbations in short-term clinical trials. The effect of ETI on hospitalization and intravenous (IV) antibiotic rates is not known. We performed a single-institution, retrospective review comparing these rates before and after the initiation of ETI.

METHODS: Among patients taking the cystic fibrosis modulator ETI, we compared the cumulative number of days per month hospitalized and cumulative number of days per month on IV antibiotics before and after the initiation of ETI. Electronic medical records from 37 patients were reviewed from 2016 through 2020 to identify demographic data, hospitalizations, and antibiotic use. Results were then stratified by severity of lung disease.

RESULTS: Following the initiation of ETI, there was a decline in days per month hospitalized and on IV antibiotics. The cumulative average number of days per month patients were hospitalized decreased 86% from 27 to 4 after starting ETI. The cumulative average number of days per month on IV antibiotics decreased by 80% (32.5 to 6.4). Most of these reductions occurred among patients with severe lung disease.

DISCUSSION: At our institution, we saw a decline in cystic fibrosis-related hospitalizations and in the use of outpatient IV antibiotics following the initiation of ETI. These reductions were most pronounced among patients with severe lung disease.

CONCLUSION: The initiation of ETI was associated with a decline in days hospitalized and days on IV antibiotics.

PMID:35609157 | DOI:10.7812/TPP/21.089

Pediatr Radiol. 2022 May 24. doi: 10.1007/s00247-022-05398-4. Online ahead of print.

ABSTRACT

The term bronchiectasis refers to permanent enlargement of the bronchi. It is increasingly diagnosed because of high-resolution computed investigations. It can be congenital or acquired, the latter mostly following infection. Williams-Campbell syndrome is a rare form of congenital non-cystic fibrosis bronchiectasis. Here we report a 5-month-old girl with reversible bronchiectasis treated with extracorporeal membrane oxygenation for acute respiratory distress syndrome (ARDS) caused by influenza virus following surgery for congenital heart disease. Chest CT showed an abnormally large bronchial tree mimicking Williams-Campbell syndrome. At 9 months later, chest CT showed regression of bronchiectasis and normalized caliber of previously collapsed segments in both lungs. This atypical course illustrates that influenza virus can cause reversible bronchiectasis in infants and mimic congenital disease such as Williams-Campbell syndrome.

PMID:35608662 | DOI:10.1007/s00247-022-05398-4

J Pathol. 2022 May 24. doi: 10.1002/path.5971. Online ahead of print.

ABSTRACT

The human lung is a relatively quiescent organ in the normal healthy state but contains stem/progenitor cells that contribute to normal tissue maintenance and either repair or remodeling in response to injury and disease. Maintenance or repair lead to proper restoration of functional lung tissue and maintenance of physiological functions, with remodeling resulting in altered structure and function that is typically associated with disease. Knowledge of cell types contributing to lung tissue maintenance and repair/remodeling have largely relied on mouse models of injury-repair and lineage tracing of local progenitors. Therefore, many of the functional alterations underlying remodeling in human lung disease, have remained poorly defined. However, the advent of advanced genomics approaches to define the molecular phenotype of lung cells at single cell resolution has paved the way for rapid advances in our understanding of cell types present within the normal human lung and changes that accompany disease. Here we summarize recent advances in our understanding of disease-related changes in the molecular phenotype of human lung epithelium that have emerged from single-cell transcriptomic studies. We focus attention on emerging concepts of epithelial transitional states that characterize the pathological remodeling that accompanies chronic lung diseases, including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. Concepts arising from these studies are actively evolving and require corroborative studies to improve our understanding of disease mechanisms. Whenever possible we highlight opportunities for providing a unified nomenclature in this rapidly advancing field of research. This article is protected by copyright. All rights reserved.

PMID:35608561 | DOI:10.1002/path.5971

Therapie. 2022 Mar 7:S0040-5957(22)00045-2. doi: 10.1016/j.therap.2022.01.020. Online ahead of print.

NO ABSTRACT

PMID:35606190 | DOI:10.1016/j.therap.2022.01.020

Comput Biol Med. 2022 May 13;146:105614. doi: 10.1016/j.compbiomed.2022.105614. Online ahead of print.

ABSTRACT

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel that regulates fluid homeostasis via ATP binding and uses energy to transport relevant substrates across cytomembranes. It has been reported that CFTR plays a crucial role in the incidence and development of various types of cancers by regulating proliferation, metastasis, invasion and apoptosis. However, aberrant CFTR gene expression across different cancers makes it difficult to propose CFTR as a possible pan-cancer biomarker. Here, multiple databases (ONCOMINE, PrognoScan, Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA)), were accessed to investigate the relationship between CFTR gene expression with the immunological and prognostic roles in pan-cancers. The results showed higher CFTR gene expression in tumor tissues compared to normal tissues for most cancers except for CHOL, ESCA, KICH, LAML, SKCM and STAD. Higher expression of the CFTR gene directly correlated with better prognosis for BRCA, GBM, COAD, KIRP, LAML, LUAD, PRAD, SARC and STAD, and CFTR gene expression was higher in stage Ⅰ_Ⅱ compared to stage Ⅲ_ Ⅳ. Furthermore, CFTR gene expression levels were significantly associated with immune infiltrates and immunocytes, in particular, immune checkpoints, in COAD, LIHC, LUAD and LUSC. In conclusion, CFTR can be used as a prognostic marker for nine types of cancers examined in this study where CFTR expression levels play a vital role in forecasting the clinical efficacy of immune checkpoint suppression therapy.

PMID:35605483 | DOI:10.1016/j.compbiomed.2022.105614

Eur J Med Chem. 2022 May 13;238:114457. doi: 10.1016/j.ejmech.2022.114457. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa infections pose a huge threat to cystic fibrosis patients, as well as those suffering from immunodeficiency. Antimicrobial resistance, especially multi-drug resistance, due to its ability to aggregate the compact biofilm, makes it more inefficient to treat this pathogen with traditional antibiotics. Biofilm and quorum sensing (QS) have become the alternative targets for treating P. aeruginosa infections. Previously, a cyclic dipeptide cyclo(L-Trp-L-Ser) has been identified as a QS inhibitor of P. aeruginosa. On the other hand, some monosaccharides have been proved lectin-targeting behavior and to mediate biofilm formation and adhesion of P. aeruginosa. We constructed novel cyclic dipeptide-carbohydrate conjugates as a low molecular weight dual-functional QS inhibitor, which can not only enhance its anti-QS activity but also enable good anti-biofilm and anti-adhesion ability. The IC50 of galactosylated c(WS) on biofilm formation and glass adhesion was 1/6 and 1/4 of that of the unmodified cyclic dipeptide, respectively. And the ability to eliminate the preformed biofilm was increased 10-fold. Furthermore, the carbohydrate conjugates can increase the germicidal efficiency of clinical antibiotic azithromycin when used synergistically. Our results provide a novel scaffold for developing anti-virulence adjuvants when taken with clinical antibiotics.

PMID:35605361 | DOI:10.1016/j.ejmech.2022.114457

Acta Med Port. 2022 May 23. doi: 10.20344/amp.16176. Online ahead of print.

ABSTRACT

Pandoraea species are a newly described genus of multidrug-resistant, non-fermentative Gram-negative bacilli, mainly isolated from sputum samples of cystic fibrosis patients. In immunocompromised patients or with high antibiotic selective pressure, these pathogens are generally opportunistic and invasive. Although Pandoraea spp. are rare, the true incidence of these infections may be underestimated due to difficulties in microbial identification by phenotypic methods. We present the case of a 51-year-old woman, with new-onset fever after a prolonged hospitalization and multiple courses of antibiotics. Mass spectrometry assays identified Pandoraea pnomenusa in the blood cultures taken from the central venous catheter and in the catheter tip. Fever cessation after catheter removal suggests a catheter-related bloodstream infection. To the best of our knowledge, this is the first isolation of a Pandoraea spp. in Portugal, which should raise awareness to the emergence of these opportunistic and multidrug-resistant microorganisms, and the importance of its prompt identification.

PMID:35604812 | DOI:10.20344/amp.16176

Fam Syst Health. 2022 May 23. doi: 10.1037/fsh0000698. Online ahead of print.

ABSTRACT

INTRODUCTION: Persons with cystic fibrosis (CF) have higher rates of depression and anxiety compared to the general population. The Cystic Fibrosis Foundation guidelines recommend annual screening for depression and anxiety for people with CF. COVID-19 and related social distancing has created challenges for administration of mental health screening by CF centers. The aim of this quality improvement project was to evaluate the feasibility of implementing mental health screening during multidisciplinary telehealth appointments for adult patients with CF during COVID-19, adoption of screening by CF mental health providers, and patient screening results before and after introduction of telehealth.

METHOD: Patients were screened via telehealth using the PHQ-9 and GAD-7 between April and October 2020.

RESULTS: CF mental health providers implemented a mental health screening process via telehealth and 93.9% of patients seen during that time completed the screening. The screening did not increase clinic visit length and no significant differences were found between rates of depression and anxiety and 2019 clinic rates.

DISCUSSION: Implementation of mental health screening during a multidisciplinary telehealth clinic is feasible and can be adopted by providers and patients, even when health systems operations are impacted by COVID-19. It allows CF centers to maintain adherence to mental health screening and treatment guidelines. This method of screening can be applied to other patient populations and systems of care to expand access to mental health services during COVID-19 and beyond. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35604723 | DOI:10.1037/fsh0000698

Microbiol Spectr. 2022 May 23:e0042422. doi: 10.1128/spectrum.00424-22. Online ahead of print.

ABSTRACT

Given the focus of existing clinical prediction scores on identifying drug-resistant pathogens as a whole, the application to individual pathogens and other institutions may yield weaker performance. This study aimed to develop a locally derived clinical prediction model for Pseudomonas-mediated pneumonia. This retrospective study included patients ≥18 years of age who were admitted to an academic medical center between 1 July 2010 and 31 July 2020 with a CDC National Healthcare Safety Network confirmed pneumonia diagnosis and were receiving antimicrobials during the index encounter, with a positive respiratory culture. Cystic fibrosis patients were excluded. Logistic regression analysis identified risk factors associated with the isolation of Pseudomonas aeruginosa from respiratory cultures within the derivation cohort (n = 186), which were weighted to generate a prediction score that was applied to the derivation and internal validation (n = 95) cohorts. A total of 281 patients met the inclusion criteria. Five predictor variables were identified, namely, tracheostomy status (4 points), chronic obstructive pulmonary disease (5 points), enteral nutrition (9 points), chronic steroid use (11 points), and Pseudomonas aeruginosa isolation from any culture in the prior 6 months (14 points). At a score of >11, the prediction score demonstrated a sensitivity of 52.4% (95% confidence interval [CI], 36.4 to 68.0%) and a specificity of 84.9% (95% CI, 72.4 to 93.35%) in the validation cohort. Score accuracy was 70.5% (95% CI, 60.3 to 79.4%), and the area under the receiver operating characteristic curve (AUROC) was 0.77 (95% CI, 0.68 to 0.87) in the validation cohort. A prediction score for identifying Pseudomonas aeruginosa in pneumonia was derived, which may have the potential to decrease the use of broad-spectrum antibiotics. Validation with larger and external cohorts is necessary. IMPORTANCE In this study, we aimed to develop a locally derived clinical prediction model for Pseudomonas-mediated pneumonia. Utilizing a locally validated prediction score may help direct therapeutic management and be generalizable to other clinical settings and similar populations for the selection of appropriate antimicrobial coverage when data are lacking. Our study highlights a unique patient population, including immunocompromised, structural lung disease, and transplant patients. Five predictor variables were identified, namely, tracheostomy status, chronic obstructive pulmonary disease, enteral nutrition, chronic steroid use, and Pseudomonas aeruginosa isolation from any culture in the prior 6 months. A prediction score for identifying Pseudomonas aeruginosa in pneumonia was derived, which may have the potential to decrease the use of broad-spectrum antibiotics, although validation with larger and external cohorts is necessary.

PMID:35604182 | DOI:10.1128/spectrum.00424-22

J Med Microbiol. 2022 May;71(5). doi: 10.1099/jmm.0.001431.

ABSTRACT

Introduction. The black yeast Exophiala dermatitidis has been isolated in respiratory samples from people with cystic fibrosis (CF). However, adequate detection may require longer incubation periods than the current UK national standard for CF respiratory samples. Furthermore, it is unclear whether isolation of E. dermatitidis is associated with poorer clinical outcomes in CF.Hypothesis/gap statement. E. dermatitidis does not cause clinically significant lung disease in CF adults.Aim. To evaluate differences in clinical outcomes over a 12 month period and during acute pulmonary exacerbations between CF adults with and without untreated E. dermatitidis.Methodology. Incubation times for respiratory samples on Sabouraud dextrose agar with chloramphenicol (SABC) plates at a large regional adult CF centre were extended from 2 to 7 days over a 1 month period. The number of patients from whom E. dermatitidis was isolated, and the length of incubation time prior to isolation, were recorded. Outcomes of treatment of exacerbations with intravenous antibiotics but in the absence of concomitant antifungal therapy were compared between those with and without E. dermatitidis, as were changes in lung function and body mass index (BMI) over a 12 month period.Results. Extended incubation unmasked the presence of E. dermatitidis in 22 of 132 patients; all isolations occurred after >48 h of incubation. Patients who isolated E. dermatitidis had lower rates of Pseudomonas aeruginosa isolation (P=0.02) and higher rates of non-tuberculous mycobacteria isolation (P=0.03), and were more likely to be prescribed a long-term antifungal medication (P=0.03), but had no differences in age, sex, baseline lung function or body mass index (BMI). There were no differences in response to treatment of acute exacerbations between patients with and without E. dermatitidis, or in change in forced expiratory volume in 1 s (FEV1), BMI and number of exacerbations over 12 months of follow-up.Conclusion. E. dermatitidis is not associated with worse clinical outcomes in CF. Given potential side effects and drug interactions, routine targeting of E. dermatitidis with antifungals during acute exacerbations is not advised.

PMID:35603931 | DOI:10.1099/jmm.0.001431

Front Mol Biosci. 2022 May 5;9:874186. doi: 10.3389/fmolb.2022.874186. eCollection 2022.

ABSTRACT

Background: Several members of the SLC26A family of transporters, including SLC26A3 (DRA), SLC26A5 (prestin), SLC26A6 (PAT-1; CFEX) and SLC26A9, form multi-protein complexes with a number of molecules (e.g., cytoskeletal proteins, anchoring or adaptor proteins, cystic fibrosis transmembrane conductance regulator, and protein kinases). These interactions provide regulatory signals for these molecules. However, the identity of proteins that interact with the Cl-/HCO3 - exchanger, SLC26A4 (pendrin), have yet to be determined. The purpose of this study is to identify the protein(s) that interact with pendrin. Methods: A yeast two hybrid (Y2H) system was employed to screen a mouse kidney cDNA library using the C-terminal fragment of SLC26A4 as bait. Immunofluorescence microscopic examination of kidney sections, as well as co-immunoprecipitation assays, were performed using affinity purified antibodies and kidney protein extracts to confirm the co-localization and interaction of pendrin and the identified binding partners. Co-expression studies were carried out in cultured cells to examine the effect of binding partners on pendrin trafficking and activity. Results: The Y2H studies identified IQ motif-containing GTPase-activating protein 1 (IQGAP1) as a protein that binds to SLC26A4's C-terminus. Co-immunoprecipitation experiments using affinity purified anti-IQGAP1 antibodies followed by western blot analysis of kidney protein eluates using pendrin-specific antibodies confirmed the interaction of pendrin and IQGAP1. Immunofluorescence microscopy studies demonstrated that IQGAP1 co-localizes with pendrin on the apical membrane of B-intercalated cells, whereas it shows basolateral expression in A-intercalated cells in the cortical collecting duct (CCD). Functional and confocal studies in HEK-293 cells, as well as confocal studies in MDCK cells, demonstrated that the co-transfection of pendrin and IQGAP1 shows strong co-localization of the two molecules on the plasma membrane along with enhanced Cl-/HCO3 - exchanger activity. Conclusion: IQGAP1 was identified as a protein that binds to the C-terminus of pendrin in B-intercalated cells. IQGAP1 co-localized with pendrin on the apical membrane of B-intercalated cells. Co-expression of IQGAP1 with pendrin resulted in strong co-localization of the two molecules and increased the activity of pendrin in the plasma membrane in cultured cells. We propose that pendrin's interaction with IQGAP1 may play a critical role in the regulation of CCD function and physiology, and that disruption of this interaction could contribute to altered pendrin trafficking and/or activity in pathophysiologic states.

PMID:35601831 | PMC:PMC9117723 | DOI:10.3389/fmolb.2022.874186

Hosp Pharm. 2022 Apr;57(2):223-229. doi: 10.1177/00185787211010149. Epub 2021 Apr 24.

ABSTRACT

Background: The 2019 Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend antimethicillin- resistant Staphylococcus aureus (MRSA) therapy in patients with CAP based on previously identified risk factors for MRSA with an emphasis on local epidemiology and institutional validation of risk. Thus, we sought to assess the ability of guideline-recognized risk factors to predict MRSA CAP at our institution. Methods: This was a single-center, retrospective cohort study from January 2016 to March 2020. Patients were included if they were >18 years old, diagnosed with CAP, and had a MRSA nasal screen and respiratory culture obtained on admission. Patients were excluded if CAP diagnosis was not met, respiratory cultures were not obtained within 48 hours of antibiotic initiation, or they had cystic fibrosis. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios (LR) were calculated using Vasser Stats 2019. Pre/post-test odds and pre/post-test probabilities were calculated using Excel 2019. Results: Of 705 screened patients, 221 were included. MRSA prevalence in CAP patients at our institution was 3.6%. History of MRSA isolated from a respiratory specimen had high specificity (98%), high positive LR of 20 (95% CI 5.3-74.8), and high post-test probability of 42.8%. Receipt of IV antibiotics during hospitalization within the past 90 days had a positive LR of 1.9 (95% CI 0.74-4.84). A positive MRSA nasal screen on admission had a positive LR of 6.9 (95% CI 4.0-12.1), negative LR 0.28 (95% CI 0.08-0.93), positive post-test probability of 20.7%, and negative post-test probability of 1.04%. Conclusion: Our study utilized institutional data to validate guideline recognized risk factors for MRSA CAP specifically at our institution. Risk factors including history of MRSA isolated from a respiratory specimen, and positive post-admission MRSA nasal screen were validated as significant risk factors; receipt of IV antibiotics during hospitalization within the past 90 days was not shown to be a risk factor for MRSA CAP based on our institutional data. Validated risk factors may help providers discern which patients with CAP at our institution would benefit most from empiric MRSA treatment.

PMID:35601723 | PMC:PMC9117777 | DOI:10.1177/00185787211010149

Respiration. 2022 May 20:1-9. doi: 10.1159/000524773. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep-disordered breathing (SDB) and disturbed sleep are common, often underrecognized, comorbidities in people with cystic fibrosis (pwCF).

OBJECTIVES: We studied the effect of CFTR triple combination therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on sleep in pwCF.

METHOD: This was a prospective, observational sleep study in clinically stable adult pwCF. All participants underwent overnight polysomnography (PSG), before (T0) and after (T1) initiation of CFTR modulator therapy with ELX/TEZ/IVA. In addition, pulmonary function tests, calculation of BMI, and sweat chloride testing were performed.

RESULTS: Twenty-nine pwCF (mean age 32 ± 8 years; 15 female) participated in the study. Mean time between T0 and T1 was 194 ± 21 days. Total sleep time (TST) was 298 ± 40 min, with decreased sleep efficiency (SE) (76 ± 109) and increased sleep latency (SL) (73 ± 38 min). Sleep stages for NREM (N1-3) and REM sleep were within the normal range. Nocturnal respiratory events mainly occur during REM sleep (T0: AHI REM 8.3 ± 9.0/h; ODI REM 9.4 ± 10.6/h), whereas the overall AHI was normal (3.6 ± 3.7/h). After initiation of ELX/TEZ/IVA, we saw significant improvements in ppFEV1 (p < 0.001) and BMI (p < 0.001) and a reduction in sweat chloride levels (p < 0.001). In parallel, there was a reduction in AHI (p = 0.003), ODI (p = 0.001), and nocturnal respiratory rate (p < 0.001), both in total, REM and NREM sleep. Neither TST, SL, SE, nor sleep architecture was influenced (all p > 0.05).

CONCLUSIONS: Initiation of ELX/TEZ/IVA resulted in significant improvements in SDB in adult pwCF.

PMID:35598598 | DOI:10.1159/000524773

Nutr Metab (Lond). 2022 May 21;19(1):37. doi: 10.1186/s12986-022-00670-8.

ABSTRACT

BACKGROUND: Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females.

METHODS: Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses.

RESULTS: Mitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = - 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = - 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr.

CONCLUSIONS: These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.

PMID:35597962 | DOI:10.1186/s12986-022-00670-8

ISME J. 2022 May 21. doi: 10.1038/s41396-022-01252-5. Online ahead of print.

ABSTRACT

Antibiotics are our primary approach to treating complex infections, yet we have a poor understanding of how these drugs affect microbial communities. To better understand antimicrobial effects on host-associated microbial communities we treated cultured sputum microbiomes from people with cystic fibrosis (pwCF, n = 24) with 11 different antibiotics, supported by theoretical and mathematical modeling-based predictions in a mucus-plugged bronchiole microcosm. Treatment outcomes we identified in vitro that were predicted in silico were: 1) community death, 2) community resistance, 3) pathogen killing, and 4) fermenter killing. However, two outcomes that were not predicted when antibiotics were applied were 5) community profile shifts with little change in total bacterial load (TBL), and 6) increases in TBL. The latter outcome was observed in 17.8% of samples with a TBL increase of greater than 20% and 6.8% of samples with an increase greater than 40%, demonstrating significant increases in community carrying capacity in the presence of an antibiotic. An iteration of the mathematical model showed that TBL increase was due to antibiotic-mediated release of pH-dependent inhibition of pathogens by anaerobe fermentation. These dynamics were verified in vitro when killing of fermenters resulted in a higher community carrying capacity compared to a no antibiotic control. Metagenomic sequencing of sputum samples during antibiotic therapy revealed similar dynamics in clinical samples. This study shows that the complex microbial ecology dictates the outcomes of antibiotic therapy against a polymicrobial infection.

PMID:35597889 | DOI:10.1038/s41396-022-01252-5

Rev Mal Respir. 2022 May 18:S0761-8425(22)00168-1. doi: 10.1016/j.rmr.2021.03.012. Online ahead of print.

ABSTRACT

INTRODUCTION: Medical progress affords patients with cystic fibrosis (CF) the opportunity to become parents.

OBJECTIVE: To assess the psychological issues of parenthood in persons with cystic fibrosis.

MATERIAL AND METHODS: Semi-structured interviews on parenthood, conducted by a psychologist with CF parents treated at the Cystic Fibrosis Center and the Transplantation Center of Foch hospital (Suresnes, France).

RESULTS: Twenty-one (21) fathers and 22 mothers participated ; 84 % had become parents through pregnancy, 14% via adoption and one woman by means of surrogacy; 73% of the women and 67% of the men had done so prior to lung transplantation, while 25% had achieved parenthood without or against medical advice. As parents, they suffered from a lack of familial and medical support for their parental projects and a lack of recognition of their reproductive difficulties.

CONCLUSION: While the desire for a child may be initially repressed by potentially life-threatening risks, a loving couple with a satisfying sexual life may in many instances surmount the repression and express the desire, which is not only the desire for a potentially life-bearing body, but also the desire to start a family.

PMID:35597727 | DOI:10.1016/j.rmr.2021.03.012