The effectiveness of interventions to improve self-management for adolescents and young adults with allergic conditions: a systematic review.

Allergy. 2020 Mar 11;:

Authors: Knibb RC, Alviani C, Garriga-Baraut T, Mortz CG, Vazquez-Ortiz M, Angier E, Blumchen K, Comberiati P, Duca B, DunnGalvin A, Gore C, Hox V, Jensen B, Pite H, Santos AF, Sanchez-Garcia S, Gowland MH, Timmermans F, Roberts G

Abstract
BACKGROUND: This systematic review aimed to review the literature on interventions for improving self-management and wellbeing in adolescents and young adults (11-25 years) with asthma and allergic conditions.
METHODS: A systematic literature search was undertaken across eight databases. References were checked by two reviewers for inclusion. Study data were extracted and their quality was assessed in duplicate. A narrative synthesis was undertaken.
RESULTS: A total of 30 papers reporting data from 27 studies were included. Interventions types were psychological (k=9); E-health (k=8); educational (k=4); peer led (k=5); breathing re-training (k=1). All interventions were for asthma. Psychological interventions resulted in significant improvements in the intervention group compared to the control group for self-esteem, quality of life, self-efficacy, coping strategies, mood and asthma symptoms. E-Health interventions reported significant improvements for inhaler technique, adherence and quality of life. General educational interventions demonstrated significantly improved quality of life, management of asthma symptoms, controller medication use, increased use of a written management plan and reduction in symptoms. The peer led interventions included the Triple A (Adolescent Asthma Action) programme and a peer-led camp based on the Power Breathing Programme. Improvements were found for self-efficacy, school absenteeism and quality of life.
CONCLUSION: Although significant improvements were seen for all intervention types, many were small feasibility or pilot studies, few studies reported effect sizes and no studies for allergic conditions other than asthma met the inclusion criteria. Research using large longitudinal interventional designs across the range of allergic conditions is required to strengthen the evidence base.

PMID: 32159856 [PubMed - as supplied by publisher]

The dual phosphodiesterase 3/4 inhibitor RPL554 stimulates rare class III and IV CFTR mutants.

Am J Physiol Lung Cell Mol Physiol. 2020 Mar 11;:

Authors: Turner MJ, Luo Y, Thomas DY, Hanrahan JW

Abstract
Over 2,000 mutations have been reported in the cftr gene, many of which cause disease but are rare and have no effective treatment. Thus, there is an unmet need for new, mutation-agnostic, therapies for cystic fibrosis (CF). Phosphodiesterase (PDE) inhibitors are one such class of therapeutics that have been shown to elevate intracellular cAMP levels and stimulate CFTR-dependent anion secretion in human airway epithelia, however the number of people with CF that could be helped by PDE inhibitors remains to be determined. Here we used Fisher Rat Thyroid (FRT) cells stably transduced with rare human CFTR mutants and studied their responsiveness to the dual phosphodiesterase 3/4 inhibitor RPL554 (Verona Pharma). Through its inhibitory effect on PDE4D, we find that RPL554 can elevate intracellular cAMP leading to a potentiation of forskolin-stimulated current mediated by R334W, T338I, G551D and S549R mutants of CFTR when used alone or in combination with CFTR modulators. We also were able to reproduce these effects of RPL554 on G551D CFTR when it was expressed in primary human bronchial epithelial cells, indicating that RPL554 would have stimulatory effects on rare CFTR mutants in human airways and validating FRT cells as a model for PDE inhibitor studies. Furthermore, we provide biochemical evidence that VX-809 causes surprisingly robust correction of several class III and IV CFTR mutants. Together, our findings further support the therapeutic potential of RPL554 for CF patients with class III/IV mutations and emphasize the potential of PDEs as potential drug targets that could benefit CF patients.

PMID: 32159371 [PubMed - as supplied by publisher]

The Cross-Talk Between Gut Microbiota and Lungs in Common Lung Diseases.

Front Microbiol. 2020;11:301

Authors: Zhang D, Li S, Wang N, Tan HY, Zhang Z, Feng Y

Abstract
Emerging findings indicate there is a vital cross-talk between gut microbiota and the lungs, which is known as gut-lung axis. The gut disturbances in lung diseases including allergy, asthma, chronic obstructive pulmonary disease, cystic fibrosis and lung cancer were observed by extensive studies. Investigating how gut microbiota impact other distant organs is of great interest in recent years. Although it has not been fully understood whether the disturbance is the cause or effect of lung diseases, alterations in the gut microbial species and metabolites have been linked to changes in immune responses and inflammation as well as the disease development in the lungs. In this article, we systemically review the role and mechanisms underlying the changes in the constituent of gut microbiota and metabolites in lung diseases. In particular, the roles of gut-lung axis in mediating immune responses and reshaping inflammation are highlighted. Furthermore, we discuss the potential of strategies to manipulate the gut microbiota and metabolites as the therapeutic approach for lung diseases.

PMID: 32158441 [PubMed]

Clinical features and management of children with primary ciliary dyskinesia in England.

Arch Dis Child. 2020 Mar 10;:

Authors: Rubbo B, Best S, Hirst RA, Shoemark A, Goggin P, Carr SB, Chetcuti P, Hogg C, Kenia P, Lucas JS, Moya E, Narayanan M, O'Callaghan C, Williamson M, Walker WT, English National Children’s PCD Management Service

Abstract
OBJECTIVE: In England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children seen in this Service and compare lung function to children with cystic fibrosis (CF).
DESIGN: Multi-centre service evaluation of the English National Management PCD Service.
SETTING: Four nationally commissioned PCD centres in England.
PATIENTS: 333 children with PCD reviewed in the Service in 2015; lung function data were also compared with 2970 children with CF.
RESULTS: Median age at diagnosis for PCD was 2.6 years, significantly lower in children with situs inversus (1.0 vs 6.0 years, p<0.001). Compared with national data from the CF Registry, mean (SD) %predicted forced expiratory volume in one second (FEV1) was 76.8% in PCD (n=240) and 85.0% in CF, and FEV1 was lower in children with PCD up to the age of 15 years. Approximately half of children had some hearing impairment, with 26% requiring hearing aids. Children with a lower body mass index (BMI) had lower FEV1 (p<0.001). One-third of children had positive respiratory cultures at review, 54% of these grew Haemophilus influenzae.
CONCLUSIONS: We provide evidence that children with PCD in England have worse lung function than those with CF. Nutritional status should be considered in PCD management, as those with a lower BMI have significantly lower FEV1. Hearing impairment is common but seems to improve with age. Well-designed and powered randomised controlled trials on management of PCD are needed to inform best clinical practice.

PMID: 32156696 [PubMed - as supplied by publisher]

'Go for it, dream big, work hard and persist': A message to the next generation of CF leaders in recognition of International Women's Day 2020.

J Cyst Fibros. 2020 Mar 07;:

Authors: Langawi MA, Byrnes C, Davies JC, Hamouda S, Kabra M, Rached SZ, Sands D, Shteinberg M, Taylor-Cousar J, Tullis E, Wainwright C

Abstract
The focus for International Women's Day 2020 is gender equity:'We can actively choose to challenge stereotypes, fight bias, broaden perceptions, improve situations and celebrate women's achievements. Collectively, each one of us can help create a gender equal world.' We have come together as an international group of women holding senior positions within CF to raise awareness. There is growing recognition of gender imbalance within our sector in senior leadership, grant and publication success. Several institutions, such as National Institutes of Health, have missions to tackle this. The issues raised by our panellists were wide-ranging: decisions around starting a family, impact on career progression; experiences of bias in appointments or promotions; selfbelief. We hope that raising these issues will encourage future leaders in CF to step up, to build teams based on fairness, equity and diversity, and to catalyse steps towards this goal in their institutions and society more widely.

PMID: 32156627 [PubMed - as supplied by publisher]

Combined Use of CFTR Correctors in LGMD2D Myotubes Improves Sarcoglycan Complex Recovery.

Int J Mol Sci. 2020 Mar 06;21(5):

Authors: Carotti M, Scano M, Fancello I, Richard I, Risato G, Bensalah M, Soardi M, Sandonà D

Abstract
Sarcoglycanopathies are rare limb girdle muscular dystrophies, still incurable, even though symptomatic treatments may slow down the disease progression. Most of the disease-causing defects are missense mutations leading to a folding defective protein, promptly removed by the cell's quality control, even if possibly functional. Recently, we repurposed small molecules screened for cystic fibrosis as potential therapeutics in sarcoglycanopathy. Indeed, cystic fibrosis transmembrane regulator (CFTR) correctors successfully recovered the defective sarcoglycan-complex in vitro. Our aim was to test the combined administration of some CFTR correctors with C17, the most effective on sarcoglycans identified so far, and evaluate the stability of the rescued sarcoglycan-complex. We treated differentiated myogenic cells from both sarcoglycanopathy and healthy donors, evaluating the global rescue and the sarcolemma localization of the mutated protein, by biotinylation assays and western blot analyses. We observed the additive/synergistic action of some compounds, gathering the first ideas on possible mechanism/s of action. Our data also suggest that a defective α-sarcoglycan is competent for assembly into the complex that, if helped in cell traffic, can successfully reach the sarcolemma. In conclusion, our results strengthen the idea that CFTR correctors, acting probably as proteostasis modulators, have the potential to progress as therapeutics for sarcoglycanopathies caused by missense mutations.

PMID: 32155735 [PubMed - in process]

Ivacaftor for the treatment of cystic fibrosis in children under six years of age.

Expert Rev Respir Med. 2020 Mar 10;:

Authors: Aoyama BC, Mogayzel PJ

Abstract
Introduction: Cystic fibrosis (CF) results from aberrant ion transport due to abnormalities or absence of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride transporter that resides on the apical surface of epithelial cells. A novel class of medications, known as CFTR modulators, specifically target the abnormal protein.Areas covered: Ivacaftor increases the open probability of CFTR located on the cell surface, leading to enhanced chloride transport, and has been shown to improve lung function, weight, and quality of life. We reviewed the sentinel studies that lead to the approval of the use of ivacaftor in people with CF age six months and older with at least one CFTR gene mutation that is responsive to ivacaftor based on clinical trial and/or in vitro data. Children with CF have the greatest potential to benefit from CFTR modulator therapy when it is initiated prior to the development of permanent damage; however, challenges remain regarding use of ivacaftor in the youngest pediatric population.Expert opinion: Ivacaftor is safe and effective CFTR modulator that can be prescribed in children over six months of age with at least one CFTR gene mutation that is responsive to ivacaftor.

PMID: 32154747 [PubMed - as supplied by publisher]

A Single "All-in-One" Helper-Dependent Adenovirus to Deliver Donor DNA and CRISPR/Cas9 for Efficient Homology-Directed Repair.

Mol Ther Methods Clin Dev. 2020 Jun 12;17:441-447

Authors: Palmer DJ, Turner DL, Ng P

Abstract
In this study, we developed a single helper-dependent adenovirus (HDAd) to deliver all of the components (donor DNA, CRISPR-associated protein 9 [Cas9], and guide RNA [gRNA]) needed to achieve high-efficiency gene targeting and homology-directed repair in transduced cells. We show that these "all-in-one" HDAds are up to 117-fold more efficient at gene targeting than donor HDAds that do not express CRISPR/Cas9 in human induced pluripotent stem cells (iPSCs). The vast majority (>90%) of targeted recombinants had only one allele targeted, and this was accompanied by high-frequency indel formation in the non-targeted allele at the site of Cas9 cleavage. These indels varied in size and nature, and included large deletions of ∼8 kb. The remaining minority of recombinants had both alleles targeted (so-called bi-allelic targeting). These all-in-one HDAds represent an important platform for accomplishing and expanding the utility of homology-directed repair, especially for difficult-to-transfect cells and for in vivo applications.

PMID: 32154329 [PubMed]

Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections.

Front Immunol. 2020;11:244

Authors: Secor PR, Burgener EB, Kinnersley M, Jennings LK, Roman-Cruz V, Popescu M, Van Belleghem JD, Haddock N, Copeland C, Michaels LA, de Vries CR, Chen Q, Pourtois J, Wheeler TJ, Milla CE, Bollyky PL

Abstract
Pf bacteriophage are temperate phages that infect the bacterium Pseudomonas aeruginosa, a major cause of chronic lung infections in cystic fibrosis (CF) and other settings. Pf and other temperate phages have evolved complex, mutualistic relationships with their bacterial hosts that impact both bacterial phenotypes and chronic infection. We and others have reported that Pf phages are a virulence factor that promote the pathogenesis of P. aeruginosa infections in animal models and are associated with worse skin and lung infections in humans. Here we review the biology of Pf phage and what is known about its contributions to pathogenesis and clinical disease. First, we review the structure, genetics, and epidemiology of Pf phage. Next, we address the diverse and surprising ways that Pf phages contribute to P. aeruginosa phenotypes including effects on biofilm formation, antibiotic resistance, and motility. Then, we cover data indicating that Pf phages suppress mammalian immunity at sites of bacterial infection. Finally, we discuss recent literature implicating Pf in chronic P. aeruginosa infections in CF and other settings. Together, these reports suggest that Pf bacteriophage have direct effects on P. aeruginosa infections and that temperate phages are an exciting frontier in microbiology, immunology, and human health.

PMID: 32153575 [PubMed - in process]

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine.

Front Pharmacol. 2019;10:1662

Authors: Lopes-Pacheco M

Abstract
Cystic fibrosis (CF) is a lethal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which result in impairment of CFTR mRNA and protein expression, function, stability or a combination of these. Although CF leads to multifaceted clinical manifestations, the respiratory disorder represents the major cause of morbidity and mortality of these patients. The life expectancy of CF patients has substantially lengthened due to early diagnosis and improvements in symptomatic therapeutic regimens. Quality of life remains nevertheless limited, as these individuals are subjected to considerable clinical, psychosocial and economic burdens. Since the discovery of the CFTR gene in 1989, tremendous efforts have been made to develop therapies acting more upstream on the pathogenesis cascade, thereby overcoming the underlying dysfunctions caused by CFTR mutations. In this line, the advances in cell-based high-throughput screenings have been facilitating the fast-tracking of CFTR modulators. These modulator drugs have the ability to enhance or even restore the functional expression of specific CF-causing mutations, and they have been classified into five main groups depending on their effects on CFTR mutations: potentiators, correctors, stabilizers, read-through agents, and amplifiers. To date, four CFTR modulators have reached the market, and these pharmaceutical therapies are transforming patients' lives with short- and long-term improvements in clinical outcomes. Such breakthroughs have paved the way for the development of novel CFTR modulators, which are currently under experimental and clinical investigations. Furthermore, recent insights into the CFTR structure will be useful for the rational design of next-generation modulator drugs. This review aims to provide a summary of recent developments in CFTR-directed therapeutics. Barriers and future directions are also discussed in order to optimize treatment adherence, identify feasible and sustainable solutions for equitable access to these therapies, and continue to expand the pipeline of novel modulators that may result in effective precision medicine for all individuals with CF.

PMID: 32153386 [PubMed]

Synthesis and Evaluation of Dendrimers for Autophagy Augmentation and Alleviation of Obstructive Lung Diseases.

Methods Mol Biol. 2020;2118:155-164

Authors: Vij N

Abstract
Preservation of cellular homeostasis requires constant synthesis of fresh proteins and cellular organelles and efficient degradation or removal of damaged proteins and cellular components. This involves two cellular degradation processes or molecular mechanisms: the ubiquitin-proteasome and autophagy-lysosomal systems. Impairment of these catabolic processes has been linked to pathogenesis of a variety of chronic obstructive lung diseases such as COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Proteosomal and autophagic functions (proteostasis) are known to decline with advancing age leading to accumulation of cellular debris and proteins, initiating cellular senescence or death and accelerating lung aging. Obstructive lung diseases associated with airway hyperinflammation and mucus obstruction provide major challenges to the delivery and therapeutic efficacy of nanotherapeutics systems as they need to bypass the airway defense. Targeted autophagy augmentation has emerged, as a promising therapeutic utility for alleviating obstructive lung diseases, and promoting healthy aging. A targeted dendrimer-based approach has been designed to penetrate the airway obstruction and allow the selective correction of proteostasis/autophagy in the diseased cells while circumventing the side effects. This report describes methods for synthesis and therapeutic evaluation of autophagy augmenting dendrimers in the treatment of obstructive lung disease(s). The formulations and methods of autophagy augmentation described here are currently under clinical development in our laboratory for alleviating pathogenesis and progression of chronic obstructive lung diseases, and promoting healthy aging.

PMID: 32152978 [PubMed - in process]

Synthesis and Evaluation of Airway-Targeted PLGA-PEG Nanoparticles for Drug Delivery in Obstructive Lung Diseases.

Methods Mol Biol. 2020;2118:147-154

Authors: Vij N

Abstract
Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma. Airway inflammation and mucus obstruction present major challenges to drug or gene delivery and therapeutic efficacy of nano-based carriers in these chronic obstructive airway conditions. To achieve targeted drug delivery of NPs to the diseased cells, NPs need to bypass the obstructive airway and circumvent the airway's defense mechanisms. Although there has been increasing interest and significant progress in development of NPs for targeting cancer, relatively little progress has been made towards designing novel systems for targeted treatment of chronic inflammatory and obstructive airway conditions. Hence, we describe here methods for preparing drug loaded multifunctional nanoparticles for targeted delivery to specific airway cell types in obstructive lung diseases. The formulations and methods for selective drug delivery in the treatment of chronic airway conditions such as COPD, CF, and asthma have been evaluated using a variety of preclinical models by our laboratory and currently ongoing further clinical development for translation from bench to bedside.

PMID: 32152977 [PubMed - in process]

Author Correction: A randomised controlled trial of rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis.

Sci Rep. 2020 Mar 10;10(1):4730

Authors: McWilliam SJ, Rosala-Hallas A, Jones AP, Shaw V, Greenhalf W, Jaki T, Smyth AR, Smyth RL, Pirmohamed M

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 32152372 [PubMed - in process]

Cytokinetic bridge triggers de novo lumen formation in vivo.

Nat Commun. 2020 Mar 09;11(1):1269

Authors: Rathbun LI, Colicino EG, Manikas J, O'Connell J, Krishnan N, Reilly NS, Coyne S, Erdemci-Tandogan G, Garrastegui A, Freshour J, Santra P, Manning ML, Amack JD, Hehnly H

Abstract
Multicellular rosettes are transient epithelial structures that serve as intermediates during diverse organ formation. We have identified a unique contributor to rosette formation in zebrafish Kupffer's vesicle (KV) that requires cell division, specifically the final stage of mitosis termed abscission. KV utilizes a rosette as a prerequisite before forming a lumen surrounded by ciliated epithelial cells. Our studies identify that KV-destined cells remain interconnected by cytokinetic bridges that position at the rosette's center. These bridges act as a landmark for directed Rab11 vesicle motility to deliver an essential cargo for lumen formation, CFTR (cystic fibrosis transmembrane conductance regulator). Here we report that premature bridge cleavage through laser ablation or inhibiting abscission using optogenetic clustering of Rab11 result in disrupted lumen formation. We present a model in which KV mitotic cells strategically place their cytokinetic bridges at the rosette center, where Rab11-associated vesicles transport CFTR to aid in lumen establishment.

PMID: 32152267 [PubMed - in process]

Outcomes of pregnancy in women with cystic fibrosis (CF) taking CFTR modulators - an international survey.

J Cyst Fibros. 2020 Mar 06;:

Authors: Nash EF, Middleton PG, Taylor-Cousar JL

Abstract
BACKGROUND: As their long-term prognosis improves, women with CF are increasingly choosing to have children, but the safety of CFTR modulators in pregnancy and breastfeeding is currently unknown.
METHODS: A survey was sent to lead clinicians of adult CF centres in Europe, the United Kingdom (UK), United States of America (USA), Australia and Israel requesting anonymised data on pregnancy outcomes in women using CFTR modulators before and during pregnancy and lactation.
RESULTS: We identified 64 pregnancies in 61 women taking IVA (n = 31), LUM/IVA (n = 26) or TEZ/IVA (n = 7), resulting in 60 live births. In 44 pregnancies, CFTR modulators were either continued throughout pregnancy or temporarily stopped and then restarted. Two maternal complications were deemed related to CFTR modulator therapy; cessation of modulator therapy resulted in clinical decline in 9 women prompting resumption of therapy during pregnancy. No modulator-related complications were reported in infants exposed in utero and/or during breastfeeding.
CONCLUSIONS: CFTR modulators were reported to be generally well tolerated in pregnancy and breastfeeding, with only 2 maternal complications that were deemed related to CFTR modulator therapy. Women stopping CFTR modulators in pregnancy may experience a decline in clinical status and in the cases identified in this survey, restarting therapy led to a clinical improvement. Current experience remains limited and longer-term prospective follow-up is required to exclude delayed adverse effects.

PMID: 32151568 [PubMed - as supplied by publisher]

mTOR and STAT3 Pathway Hyper-Activation is Associated with evated Interleukin-6 Levels in Patients with Shwachman-Diamond Syndrome: Further Evidence of Lymphoid Lineage Impairment.

Cancers (Basel). 2020 Mar 05;12(3):

Authors: Vella A, D'Aversa E, Api M, Breveglieri G, Allegri M, Giacomazzi A, Busilacchi EM, Fabrizzi B, Cestari T, Sorio C, Bedini G, D'Amico G, Bronte V, Poloni A, Benedetti A, Bovo C, Corey SJ, Borgatti M, Cipolli M, Bezzerri V

Abstract
Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome, resulting in neutropenia and a risk of myeloid neoplasia. A mutation in a ribosome maturation factor accounts for almost all of the cases. Lymphoid involvement in SDS has not been well characterized. We recently reported that lymphocyte subpopulations are reduced in SDS patients. We have also shown that the mTOR-STAT3 pathway is hyper-activated in SDS myeloid cell populations. Here we show that mTOR-STAT3 signaling is markedly upregulated in the lymphoid compartment of SDS patients. Furthermore, our data reveal elevated IL-6 levels in cellular supernatants obtained from lymphoblasts, bone marrow mononuclear and mesenchymal stromal cells, and plasma samples obtained from a cohort of 10 patients. Of note, everolimus-mediated inhibition of mTOR signaling is associated with basal state of phosphorylated STAT3. Finally, inhibition of mTOR-STAT3 pathway activation leads to normalization of IL-6 expression in SDS cells. Altogether, our data strengthen the hypothesis that SDS affects both lymphoid and myeloid blood compartment and suggest everolimus as a potential therapeutic agent to reduce excessive mTOR-STAT3 activation in SDS.

PMID: 32150944 [PubMed]

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A Systematized review of experiences of individuals in Arnett's emerging adulthood stage who live with or are at-risk for genetic conditions.

J Genet Couns. 2020 Mar 07;:

Authors: Shelley AR, McCarthy Veach P, LeRoy B, Redlinger-Grosse K

Abstract
Emerging adulthood, a distinct developmental period between ages 18 and 29 years, comprises five features: identity exploration, experimentation/possibilities, negativity/instability regarding one's outlook, self-focus, and feeling in-between adolescence and adulthood. A growing literature examines the impact of genetic conditions on individuals who chronologically fit the emerging adulthood period. This systematized literature review uses the emerging adulthood theory to determine whether individuals living with or at-risk for a genetic condition experience the features of this period as well as similarities and differences between these two groups. A literature search yielded 1,303 peer-reviewed papers from the 17 years since emerging adulthood theory was published. Ten papers met inclusion criteria-five for those Living With a genetic condition (e.g., cystic fibrosis) and five for those At-Risk for a genetic condition (e.g., hereditary breast and ovarian cancer). Content analysis yielded themes consistent with the five emerging adulthood features for both individuals Living With and At-Risk for genetic conditions. Negativity/instability was most prevalent, and feeling in-between was least prevalent in both groups. Results further suggest unique challenges related to one's genetic conditions/risk with respect to independence (from family, healthcare providers), career/education, relationships/social life, family planning, and life perspective experiences. Salient differences were apparent between the groups in their experiences of the emerging adulthood features. For instance, Living With individuals reported challenges concerning their ongoing physical symptoms, whereas At-Risk individuals reported challenges regarding genetic testing decisions and anticipation of physical symptoms. Thus, emerging adults Living With and At-Risk for genetic conditions appear to experience the main emerging adulthood features, but they face unique challenges related to their genetic conditions/risk. Understanding emerging adults' experiences can aid genetic counselors in addressing their specific concerns.

PMID: 32146730 [PubMed - as supplied by publisher]

[SLC6A14, a modifier gene in cystic fibrosis].

Rev Mal Respir. 2020 Mar 04;:

Authors: Ruffin M, Mercier J, Calmel C, Mésinèle J, Corvol H, Guillot L

Abstract
Although cystic fibrosis is a monogenic disease, a considerable clinical phenotypic variability is observed in patients with the same CFTR mutations. Thanks to the development of new and powerful tools for carrying out genetic studies, several genes called "modifier genes" have been identified as being associated with the severity of the lung function disorder in cystic fibrosis patients. Among these genes, SLC6A14 may modulate the anti-infective response and epithelial integrity of the airways, thus providing a potential therapeutic target to improve the patient's lung function.

PMID: 32146055 [PubMed - as supplied by publisher]

Sleep disorders in cystic fibrosis: A systematic review and meta-analysis.

Sleep Med Rev. 2020 Feb 19;51:101279

Authors: Reiter J, Gileles-Hillel A, Cohen-Cymberknoh M, Rosen D, Kerem E, Gozal D, Forno E

Abstract
Cystic fibrosis (CF) is a genetic disorder that leads to airway mucus accumulation, chronic inflammation, and recurrent respiratory infections - all likely impacting sleep. However, controlled studies of sleep in CF patients are limited, and have shown mixed results. We reviewed all publications on CF and sleep indexed in PubMed, CINAHL, and Scopus through April 2019. In the meta-analysis, we calculated pooled weighted mean differences for sleep quality, sleepiness, oximetry, and polysomnographic (PSG) parameters, using fixed or random-effects models as appropriate. A total of 87 manuscripts were reviewed. Compared to controls, children with CF had lower nighttime oxygen saturation nadirs, decreased sleep efficiency and a higher respiratory event index, with no differences in the percentage of REM sleep. Adults with CF had lower oxygen saturation nadirs, with a trend towards reduced sleep efficiency and no differences in REM sleep. In addition, patients with CF cough more during sleep and experience painful events that interfere with sleep. Actigraphy and questionnaires suggest disturbed sleep and daytime sleepiness. Noninvasive ventilation appears to improve gas exchange and symptoms. We conclude that when sleep is evaluated objectively or subjectively in patients with CF, perturbations are common, emphasizing the importance of their identification and treatment and inclusion as part of routine care. Additional research, with larger sample sizes and standardized outcomes, are necessary.

PMID: 32145647 [PubMed - as supplied by publisher]