The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis.

J Cyst Fibros. 2020 Jun 13;:

Authors: Cuthbertson L, Felton I, James P, Cox MJ, Bilton D, Schelenz S, Loebinger MR, Cookson WOC, Simmonds NJ, Moffatt MF

Abstract
BACKGROUND: The prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and non-CF bronchiectasis.
METHODS: Next generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls.
RESULTS: ITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with non-CF bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20.4%), whereas in non-CF bronchiectasis sputum Candida albicans (21.8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp.
CONCLUSION: This study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases.

PMID: 32540174 [PubMed - as supplied by publisher]

Immunotyping of clinically divergent p.Phe508del homozygous monozygous cystic fibrosis twins.

J Cyst Fibros. 2020 Jun 12;:

Authors: Schamschula E, Hagmann W, Assenov Y, Hedtfeld S, Farag AK, Rösner LM, Wiehlmann L, Stanke F, Fischer S, Risch A, Tümmler B

Abstract
Blood of the three clinically most concordant and most discordant p.Phe508del homozygous monozygous twin pairs of the European Cystic Fibrosis Twin and Sibling Study was examined in two postzygotic attributes that generate diversity between monozygous twins, i.e. the repertoire of the CDR3 region of the T-cell receptor ß chains and the DNA methylation at 450,000 genomic CpG sites. Methylation patterns in peripheral blood of twins changed at selected cell-type-independent positions and the immune cells of the twins showed individual profiles of the T cell receptor repertoire reflecting the plasticity of the immune system of genetically identical humans with cystic fibrosis to cope with the environment.

PMID: 32540173 [PubMed - as supplied by publisher]

Characterization of clinical and genetic spectrum of Chinese patients with cystic fibrosis.

Orphanet J Rare Dis. 2020 Jun 15;15(1):150

Authors: Liu K, Xu W, Xiao M, Zhao X, Bian C, Zhang Q, Song J, Chen K, Tian X, Liu Y, Xu KF, Zhang X

Abstract
BACKGROUND: Cystic fibrosis (CF) is a rare autosomal recessive disorder caused by biallelic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The clinical features and mutation spectrum of CF have been well characterized in Caucasians, while limited studies were conducted in Chinese patients.
SUBJECTS AND METHODS: A total of 20 individuals from 19 families were diagnosed with CF in this study. We analyzed the clinical features and screened all coding exons of CFTR using a combination of Sanger sequencing and multiplex ligation-dependent probe amplification analysis.
RESULTS: The median age at onset was 9.3 years in our cohort, while the median age at diagnosis was 19 years. The respiratory system was most frequently affected in this study: all patients (100%, 19/19) presented diffuse bronchiectasis and 61.1% (11/18) of patients showed a forced expiratory volume in 1 s below 80% predicted. Six patients (6/20, 30%) exhibited allergic bronchopulmonary aspergillosis (ABPA). Only 4 (4/20, 20%) patients presented pancreatic exocrine insufficiency (PI). Three adult male patients receiving examinations for congenital bilateral absence of the vas deferens were all found positive for the condition. A total of 22 distinct mutations were detected in this cohort, with the variant p.G970D as the most common variant (12/38 alleles, 31.6%). Four variants (p.Y109D, p.I203F, p.D572E, and exon 2-3 deletion) were novel, which expanded the mutation spectrum of Chinese CF patients.
CONCLUSIONS: Chinese CF patients showed different clinical features and a distinct CFTR mutation spectrum compared with Caucasians. There is a significant diagnosis delay, suggesting the current underdiagnosis of CF in China.

PMID: 32539862 [PubMed - in process]

Navigating School Reentry in Lung Transplant Recipients With Cystic Fibrosis.

Prog Transplant. 2020 Jun 16;:1526924820933843

Authors: Groh JD, Dempster NR, Cole T, Hayes D

Abstract
In addition to medical and psychological support, social support plays a key role in the success of lung transplant recipients, especially in children. An important component of that social support for pediatric lung transplant recipients is school reentry. These children face daily challenges, which often have to be addressed by the transplant team with little existing guidance in the medical literature. In this article, we discuss relevant practice issues for pediatric lung transplant recipients with cystic fibrosis including heightened concern for infection risk, bullying, school performance, and body image concerns. In addition to discussing these important issues, we provide recommendations based on our experiences.

PMID: 32539558 [PubMed - as supplied by publisher]

Real-life experience with high-frequency chest wall oscillation vest therapy in adults with non-cystic fibrosis bronchiectasis.

Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620932508

Authors: Barto TL, Maselli DJ, Daignault S, Stiglich J, Porter J, Kraemer C, Hansen G

Abstract
BACKGROUND: High frequency chest wall oscillation (HFCWO) has long been used for airway clearance for patients with cystic fibrosis. Only limited research has evaluated this therapy in adult patients with non-cystic fibrosis bronchiectasis (NCFB).
METHODS: Data from 2596 patients from a registry of adult bronchiectasis patients using HFCWO therapy was used to evaluate hospitalization patterns before and after initiation of HFCWO therapy, as well as antibiotic use and self-reported metrics of quality of life. Self-reported outcomes were also reviewed by cross-checking with sampled patient charts and found to be consistent.
RESULTS: The number of patients who had at least one respiratory-related hospitalization decreased from 49.1% (192/391) in the year before to 24.0% (94/391) in the year after starting HFCWO therapy (p-value < 0.001). At the same time, the number of patients who required three or more hospitalizations dropped from 14.3% (56/391) to 5.6% (22/391). Patients currently taking oral antibiotics for respiratory conditions decreased from 57.7% upon initiation of therapy to 29.9% within 1 year (p < 0.001). Patients who subjectively rated their "overall respiratory health" as good to excellent increased from 13.6% upon initiation of therapy to 60.5% in 1 year (p < 0.001) and those who rated their "ability to clear your lungs" as good to excellent increased from 13.9% to 76.6% (p < 0.001).
CONCLUSION: NCFB patients showed improved self-reported outcomes associated with the initiation of HFCWO therapy as measured by number of hospitalizations, antibiotic use, and the subjective experience of airway clearance. The improvement was observed early on after initiation of therapy and sustained for at least 1 year. The reviews of this paper are available via the supplemental material section.

PMID: 32538317 [PubMed - in process]

UPR modulation of host immunity by P. aeruginosa in cystic fibrosis.

Clin Sci (Lond). 2020 Jun 15;:

Authors: Bedi B, Lin KC, Maurice NM, Yuan Z, Bijli K, Koval M, Hart C, Goldberg JB, Stecenko A, Sadikot RT

Abstract
Cystic fibrosis (CF) is a progressive multi organ autosomal recessive disease with devastating impact on the lungs caused by derangements of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Morbidity and mortality are caused by the triad of impaired mucociliary clearance, microbial infections and chronic inflammation. P. aeruginosa is a main respiratory pathogen in individuals with CF infecting most patients in later stages. Despite its recognized clinical impact, molecular mechanisms that underlie P. aeruginosa pathogenesis and the host response to P. aeruginosa infection remain incompletely understood. The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ), has shown to be reduced in CF airways. In this study we sought to investigate the upstream mechanisms repressing PPARγ expression and its impact on airway epithelial host defense. Endoplasmic Reticulum-stress (ER-stress) triggered unfolded protein response (UPR) activated by misfolded CFTR and P. aeruginosa infection contributed to attenuated expression of PPARγ. Specifically, the PERK signaling pathway led to the enhanced expression of the CCAAT-enhancer-binding-protein homologous protein (CHOP). CHOP induction led to the repression of PPARγ expression. Mechanistically, we show that CHOP induction mediated PPARγ attenuation, impacted the innate immune function of normal and ∆F508 primary airway epithelial cells by reducing expression of anti-microbial peptide (AMP) and paraoxanse-2 (PON-2), as well as enhancing IL-8 expression. Furthermore, mitochondrial reactive oxygen species production (mt-ROS) and ER stress positive feedforward loop also dysregulated mitochondrial bioenergetics.Our findings implicate that PPARγ agonist pioglitazone (PIO) has beneficial effect on the host at the multicellular level ranging from host defense to mitochondrial re-energization.

PMID: 32537652 [PubMed - as supplied by publisher]

Accumulation and persistence of ivacaftor in airway epithelia with prolonged treatment.

J Cyst Fibros. 2020 Jun 11;:

Authors: Guhr Lee TN, Cholon DM, Quinney NL, Gentzsch M, Esther CR

Abstract
BACKGROUND: Current dosing strategies of CFTR modulators are based on serum pharmacokinetics, but drug concentrations in target tissues such as airway epithelia are not known. Previous data suggest that CFTR modulators may accumulate in airway epithelia, and serum pharmacokinetics may not accurately predict effects of chronic treatment.
METHODS: CF (F508del homozygous) primary human bronchial epithelial (HBE) cells grown at air-liquid interface were treated for 14 days with ivacaftor plus lumacaftor or ivacaftor plus tezacaftor, followed by a 14-day washout period. At various intervals during treatment and washout phases, drug concentrations were measured via mass spectrometry, electrophysiological function was assessed in Ussing chambers, and mature CFTR protein was quantified by Western blotting.
RESULTS: During treatment, ivacaftor accumulated in CF-HBEs to a much greater extent than either lumacaftor or tezacaftor and remained persistently elevated even after 14 days of washout. CFTR activity peaked at 7 days of treatment but diminished with further ivacaftor accumulation, though remained above baseline even after washout.
CONCLUSIONS: Intracellular accrual and persistence of CFTR modulators during and after chronic treatment suggest complex pharmacokinetic and pharmacodynamic properties within airway epithelia that are not predicted by serum pharmacokinetics. Direct measurement of drugs in target tissues may be needed to optimize dosing strategies, and the persistence of CFTR modulators after treatment cessation has implications for personalized medicine approaches.

PMID: 32536510 [PubMed - as supplied by publisher]

Defective BACH1/HO-1 regulatory circuits in cystic fibrosis bronchial epithelial cells.

J Cyst Fibros. 2020 Jun 11;:

Authors: Chillappagari S, Garapati V, Mahavadi P, Naehrlich L, Schmeck BT, Schmitz ML, Guenther A

Abstract
BACKGROUND: The stress-regulated enzyme hemeoxygenase-1 (HO-1) contributes to the cell response towards inflammation and oxidative stress. We previously reported on curtailed HO-1 expression in cystic fibrosis (CF) bronchial epithelial (CFBE41o-) cells and CF-mice, but the molecular mechanisms for this are not known. Here, we compared healthy and CF bronchial epithelial cells for regulatory circuits controlling HO-1 protein levels.
METHODS: In this study, we employed immunohistochemistry on CF and healthy lung sections to examine the BACH1 protein expression. Alteration of BACH1 protein levels in 16HBE14o- and CFBE41o- cells was achieved by using either siRNA-mediated knockdown of BACH1 or by increasing miRNA-155 levels. HO-1 luciferase reporter assay was chosen to examine the downstream affects after BACH1 modulation.
RESULTS: Human CF lungs and cells showed increased levels of the HO-1 transcriptional repressor, BACH1, and increased miR-155 expression. Knockdown studies using BACH1 siRNA and overexpression of miR-155 did not significantly rescue HO-1 expression in CFBE41o- cells. Elevated BACH1 expression detected in CF cells was refractory to the inhibitory function of miR-155 and was instead due to increased protein stability.
CONCLUSION: We observed defects in the inhibitory activities of miR-155 and BACH1 on HO-1 expression in CF cells. Thus various defective regulatory loops account for dysregulated BACH1 expression in CF, which in turn may contribute to low HO-1 levels.

PMID: 32534959 [PubMed - as supplied by publisher]

Clinimetric evaluation of muscle function tests for individuals with cystic fibrosis: A systematic review.

J Cyst Fibros. 2020 Jun 10;:

Authors: Combret Y, Medrinal C, Bonnevie T, Gravier FE, Le Roux P, Lamia B, Prieur G, Reychler G

Abstract
Accurate testing of muscle function is essential in individuals with cystic fibrosis (CF). A literature search was conducted in MEDLINE, CENTRAL, CINAHL, PEDro, ScienceDirect and Web of Science according to PRISMA and COSMIN guidelines from inception to September 2019 to investigate the clinimetric properties of muscle tests in individuals with CF. The search identified 37 studies (1310 individuals) and 34 different muscle tests. Maximal inspiratory pressure, inspiratory work capacity and quadriceps strength measured by computerised dynamometry were identified as reliable tests of muscle function. The one-minute sit-to-stand test was found to have high reliability but its validity to measure quadriceps strength is unknown. The clinimetric properties of other routinely used tests have not been reported in people with CF. Very different measurement procedures were identified. Inspiratory muscle and quadriceps testing can be considered as reliable but high-quality studies evaluating tests of other muscles function (e.g. muscle endurance) are lacking.

PMID: 32534958 [PubMed - as supplied by publisher]

Lysophosphatidic Acid Increases Maturation of Brush Borders and SGLT1 activity in MYO5B-deficient Mice, a Model of Microvillus Inclusion Disease.

Gastroenterology. 2020 Jun 11;:

Authors: Kaji I, Roland JT, Watanabe M, Engevik AC, Goldstein AE, Hodges CA, Goldenring JR

Abstract
BACKGROUND & AIM: Myosin VB (MYO5B) is an essential trafficking protein for membrane recycling in gastrointestinal epithelial cells. The inactivating mutations of MYO5B cause the congenital diarrheal disease, microvillus inclusion disease (MVID). MYO5B deficiency in mice causes mislocalization of SGLT1 and NHE3, but retained apical function of CFTR, resulting in malabsorption and secretory diarrhea. Activation of lysophosphatidic acid (LPA) receptors can improve diarrhea, but the effect of LPA on MVID symptoms is unclear. We investigated whether LPA administration can reduce the epithelial deficits in MYO5B-knockout mice.
METHODS: Studies were conducted with tamoxifen-induced, intestine-specific knockout of MYO5B (VilCreERT2;Myo5bflox/flox) and littermate controls. Mice were given LPA, an LPAR2 agonist (GRI977143), or vehicle for 4 days after a single injection of tamoxifen. Apical SGLT1 and CFTR activities were measured in Üssing chambers. Intestinal tissues were collected, and localization of membrane transporters was evaluated by immunofluorescence analysis in tissue sections and enteroids. RNA sequencing and enrichment analysis were performed with isolated jejunal epithelial cells.
RESULTS: Daily administration of LPA reduced villus blunting, frequency of multivesicular bodies and levels of cathepsins in intestinal tissues of MYO5B-knockout mice compared to vehicle administration. LPA partially restored the brush border height and the localization of SGLT1 and NHE3 in small intestine of MYO5B-knockout mice and enteroids. The SGLT1-dependent short-circuit current was increased and abnormal CFTR activities were decreased in jejunum from MYO5B-knockout mice given LPA compared with vehicle.
CONCLUSIONS: LPA may regulate a MYO5B-independent trafficking mechanism and brush border maturation, and therefore be developed for treatment of MVID.

PMID: 32534933 [PubMed - as supplied by publisher]

Possible metabolic switch between environmental and pathogenic Pseudomonas aeruginosa strains: 1H NMR based metabolomics study.

J Pharm Biomed Anal. 2020 May 25;188:113369

Authors: Mielko KA, Jabłoński SJ, Wojtowicz W, Milczewska J, Sands D, Łukaszewicz M, Młynarz P

Abstract
The study aimed to assess whether Pseudomonas aeruginosa strains from different sources can be distinguished by the metabolomic fingerprint and to check whether antibiotic susceptibility distinctions are available through metabolomic analysis. 1H NMR spectroscopy analysis of the bacteria metabolites was performed. Twenty-nine strains were tested (18 isolated form cystic fibrosis patients and 11 environmental). Thirty-one metabolites were identified, 12 were up-regulated in strains from CF patients, while 2 were higher level in strains from the environment. Changed carbohydrate catabolic metabolism and the metabolic shift toward the utilization of amino acids is suggested in strains from CF patients.

PMID: 32534405 [PubMed - as supplied by publisher]

ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma.

Cancer Lett. 2020 Jun 10;:

Authors: Miyashita N, Horie M, Mikami Y, Urushiyama H, Fukuda K, Miyakawa K, Matsuzaki H, Makita K, Morishita Y, Harada H, Backman M, Lindskog C, Brunnström H, Micke P, Nagase T, Saito A

Abstract
The master regulator of neuroendocrine differentiation, achaete-scute complex homolog 1 (ASCL1) defines a subgroup of lung adenocarcinoma. However, the mechanistic role of ASCL1 in lung tumorigenesis and its relation to the immune microenvironment is principally unknown. Here, the immune landscape of ASCL1-positive lung adenocarcinomas was characterized by immunohistochemistry. Furthermore, ASCL1 was transduced in mouse lung adenocarcinoma cell lines and comparative RNA-sequencing and secretome analyses were performed. The effects of ASCL1 on tumorigenesis were explored in an orthotopic syngeneic transplantation model. ASCL1-positive lung adenocarcinomas revealed lower infiltration of CD8+, CD4+, CD20+, and FoxP3+ lymphocytes and CD163+ macrophages indicating an immune desert phenotype. Ectopic ASCL1 upregulated cyclin transcript levels, stimulated cell proliferation, and enhanced tumor growth in mice. ASCL1 suppressed secretion of chemokines, including CCL20, CXCL2, CXCL10, and CXCL16, indicating effects on immune cell trafficking. In accordance with lower lymphocytes infiltration, ASCL1-positive lung adenocarcinomas demonstrated lower abundance of CXCR3-and CCR6-expressing cells. In conclusion, ASCL1 mediates its tumor-promoting effect not only through cell-autonomous signaling but also by modulating chemokine production and immune responses. These findings suggest that ASCL1-positive tumors present a clinically relevant lung cancer entity.

PMID: 32534174 [PubMed - as supplied by publisher]

Comparative In Vitro Activities of Meropenem in Combination with Colistin, Levofloxacin, or Chloramphenicol Against Achromobacter xylosoxidans Strains Isolated from Patients with Cystic Fibrosis.

J Glob Antimicrob Resist. 2020 Jun 10;:

Authors: Çelik DD, Nørskov-Lauritsen N, Çelik BÖ

Abstract
OBJECTIVES: Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Relatively little is known about its clinical impact and optimal management. In the present study, the in vitro bactericidal activities of meropenem, either alone or in combination with colistin, levofloxacin, or chloramphenicol, were assessed using A. xylosoxidans strains isolated from CF patients. The synergistic interactions of these combinations were also investigated.
METHODS: Minimal inhibitory concentrations were determined by microbroth dilution. Bactericidal and synergistic effects of the tested antibiotic combinations were assessed by using the time-kill curve technique.
RESULTS: Based on the time-kill curves, we found that meropenem-colistin combinations have bactericidal and synergistic activities for 24hours against A. xylosoxidans strains both at 1xMIC and 4xMIC. Although synergistic interactions were seen with meropenem-levofloxacin combinations, no bactericidal interactions were observed. Additionally, the meropenem-chloramphenicol combinations were found to be neither bactericidal nor synergistic. No antagonism was observed with any combination tested.
CONCLUSIONS: This study's findings could have important implications for empirical or combination antimicrobial therapy with tested antibiotics.

PMID: 32534046 [PubMed - as supplied by publisher]

Recognizing genetic disease: A key aspect of pediatric pulmonary care.

Pediatr Pulmonol. 2020 Jul;55(7):1794-1809

Authors: Yonker LM, Hawley MH, Moschovis PP, Lu M, Kinane TB

Abstract
Advancement in technology has improved recognition of genetic etiologies of disease, which has impacted diagnosis and management of rare disease patients in the pediatric pulmonary clinic. This review provides an overview of genetic conditions that are likely to present with pulmonary features and require extensive care by the pediatric pulmonologist. Increased familiarity with these conditions allows for improved care of these patients by reducing time to diagnosis, tailoring management, and prompting further investigation into these disorders.

PMID: 32533909 [PubMed - as supplied by publisher]

Childhood rare lung disease in the 21st century: "-omics" technology advances accelerating discovery.

Pediatr Pulmonol. 2020 Jul;55(7):1828-1837

Authors: Vece TJ, Wambach JA, Hagood JS

Abstract
Childhood rare lung diseases comprise a large number of heterogeneous respiratory disorders that are individually rare but are collectively associated with substantial morbidity, mortality, and healthcare resource utilization. Although the genetic mechanisms for several of these disorders have been elucidated, the pathogenesis mechanisms for others remain poorly understood and treatment options remain limited. Childhood rare lung diseases are enriched for genetic etiologies; identification of the disease mechanisms underlying these rare disorders can inform the biology of normal human lung development and has implications for the treatment of more common respiratory diseases in children and adults. Advances in "-omics" technology, such as genomic sequencing, clinical phenotyping, biomarker discovery, genome editing, in vitro and model organism disease modeling, single-cell analyses, cellular imaging, and high-throughput drug screening have enabled significant progress for diagnosis and treatment of rare childhood lung diseases. The most striking example of this progress has been realized for patients with cystic fibrosis for whom effective, personalized therapies based on CFTR genotype are now available. In this chapter, we focus on recent technology advances in childhood rare lung diseases, acknowledge persistent challenges, and identify promising new technologies that will impact not only biological discovery, but also improve diagnosis, therapies, and survival for children with these rare disorders.

PMID: 32533908 [PubMed - as supplied by publisher]

Infections Within the First Month After Pediatric Lung Transplantation: Epidemiology and Impact on Outcomes.

J Pediatric Infect Dis Soc. 2020 Jun 13;:

Authors: Onyearugbulem C, Coss-Bu J, Gazzaneo MC, Melicoff E, Das S, Lam F, Mallory GB, Munoz FM

Abstract
BACKGROUND: Despite successes in lung transplantation, with infection as the leading cause of death in the first year following lung transplantation, there remains a lag in survival compared with other solid organ transplants. Infections that occur early after transplantation may impact short- and long-term outcomes in pediatric lung transplant recipients (LTRs).
METHODS: We performed a retrospective review of pediatric LTRs at a large quaternary-care hospital from January 2009 to March 2016 to evaluate both epidemiologic features of infection in the first 30 days post-transplantation and mortality outcomes. The 30 days were divided into early (0-7 days) and late (8-30 days) periods.
RESULTS: Among the 98 LTRs, there were 51 episodes of infections. Cystic fibrosis (CF) was associated with early bacterial infections (P = .004) while non-CF was associated with late viral (P = .02) infections. Infection after transplantation was associated with worse survival by Kaplan-Meier analysis (P value log rank test = .007). Viral infection in the late period was significantly associated with 3-year mortality after multivariable analysis (P = .02).
CONCLUSIONS: Infections in pediatric LTRs were frequent in the first 30 days after transplant, despite perioperative antimicrobial coverage. The association of 3-year mortality with late viral infections suggests a possible important role in post-transplant lung physiology and graft function. Understanding the epidemiology of early post-lung transplant infections can help guide post-operative management and interventions to reduce their incidence and the early- and long-term impact in this population.

PMID: 32533840 [PubMed - as supplied by publisher]

Visuomotor Reaction Time and Dynamic Balance in Children with Cystic Fibrosis and Non-Cystic Fibrosis Bronchiectasis: A Case-Control Study.

Pediatr Pulmonol. 2020 Jun 13;:

Authors: Dik J, Saglam M, Tekerlek H, Vardar-Yagli N, Calik-Kutukcu E, Inal-Ince D, Arikan H, Eryilmaz-Polat S, Dogru D

Abstract
OBJECTIVE: Extrapulmonary involvement such as balance and reaction time is unclear in cystic fibrosis (CF) patients. The aim of this study was to evaluate visuomotor reaction time (VMRT) and dynamic balance in children with CF and non-CF bronchiectasis compared to healthy children.
DESIGN/METHODS: Demographic and clinical characteristics were recorded. All children were evaluated with pulmonary function test (PFT) using a spirometer, incremental shuttle walk test (ISWT) for exercise capacity, Fitlight TrainerTM for VMRT, and functional reach test (FRT) for dynamic balance.
RESULTS: Fourteen children with CF (10.71±2.94 years, 7 females), 17 children with non-CF bronchiectasis (12.75±2.81 years, 8 females), and 21 healthy children (11.36±3.28 years, 11 females) were included. Children with CF had longer total VMRT (p=0.027), poorer FRT performance (p=0.001), and shorter ISWT distances (p=0.03) compared to the children with non-CF bronchiectasis and controls. Although total VMRT was longest in the CF group, there was no significant difference in mean VMRT among the CF, non-CF bronchiectasis, and control groups (p>0.05).
CONCLUSION: Dynamic balance and VMRT show greater impairment in children with CF than in children with non-CF bronchiectasis compared to healthy controls. Our findings suggest that VMRT and dynamic balance should be taken into consideration for assessments and exercise programs in pulmonary rehabilitation. This article is protected by copyright. All rights reserved.

PMID: 32533804 [PubMed - as supplied by publisher]

Dietary Macronutrient Distribution and Nutrition Outcomes in Persons with Cystic Fibrosis: An Evidence Analysis Center Systematic Review.

J Acad Nutr Diet. 2020 Jun 09;:

Authors: McDonald CM, Bowser EK, Farnham K, Alvarez JA, Padula L, Rozga M

Abstract
Cystic fibrosis (CF) increases risk for undernutrition and malabsorption. Individuals with CF traditionally have been counseled to consume a high-fat diet. However, a new era of CF care has increased lifespan and decreased symptoms in many individuals with CF, necessitating a re-examination of the high-fat CF legacy diet. A literature search was conducted of Medline (Ovid), Embase, and CINAHL (EBSCO) databases to identify articles published from January 2002 to May 2018 in the English language examining the relationships between dietary macronutrient distribution and nutrition outcomes in individuals with CF. Articles were screened, risk of bias was assessed, data were synthesized narratively, and each outcome was graded for certainty of evidence. The databases search retrieved 2,519 articles, and 7 cross-sectional articles were included in the final narrative analysis. Three studies examined pediatric participants and 4 examined adults. None of the included studies reported on outcomes of mortality or quality of life. Very low certainty evidence described no apparent relationship between dietary macronutrient distribution and lung function, anthropometric measures, or lipid profile in individuals with CF. The current systematic review demonstrates wide ranges in the dietary macronutrient intakes of individuals with CF with little to no demonstrable relationship between macronutrient distribution and nutrition-related outcomes. No evidence is presented to substantiate an outcomes-related benefit to a higher fat-diet except in the context of achieving higher energy intakes in a lesser volume of food.

PMID: 32532674 [PubMed - as supplied by publisher]

Effect of CFTR Modulators on Anthropometric Parameters in Individuals with Cystic Fibrosis: An Evidence Analysis Center Systematic Review.

J Acad Nutr Diet. 2020 Jun 09;:

Authors: Bailey J, Rozga M, McDonald CM, Bowser EK, Farnham K, Mangus M, Padula L, Porco K, Alvarez JA

Abstract
There is a strong positive association between nutrition status and lung function in cystic fibrosis (CF). Improvements in clinical care have increased longevity for individuals with CF, and it is unknown how cystic fibrosis transmembrane regulator (CFTR) modulation therapy affects nutrition status over time. The objective of this systematic review of the literature was to examine anthropometric (height, weight, and body mass index [BMI; calculated as kg/m2]) and body composition outcomes of CFTR modulation therapy. A literature search of Medline (Ovid), Embase, and CINAHL (EBSCO) databases was conducted for randomized controlled trials examining the effect of CFTR modulation therapy on anthropometric and body composition parameters, published in peer-reviewed journals from January 2002 until May 2018. Articles were screened, data were synthesized qualitatively, and evidence quality was graded by a team of content experts and systematic review methodologists. Significant weight gain with ivacaftor was noted in children and adults with at least 1 copy of G551D mutation. In adults with at least 1 copy of R117H the effect of ivacaftor on BMI was not significant. Effects on BMI were mixed in adults with class II mutations taking ivacaftor with lumacaftor. There was no significant change in BMI in children homozygous for F508del who took ivacaftor with tezacaftor. Elexacaftor-tezacaftor-ivacaftor increased BMI and body weight in individuals 12 years of age and older who were hetero- or homozygous for the F508del mutation. The effect of CFTR modulation therapy on anthropometric parameters depends on the genetic mutation and the type of modulation therapy used. More research is needed to understand the long-term clinical impact of these drugs on nutritional status, including body composition and the role of dietary intake.

PMID: 32532673 [PubMed - as supplied by publisher]

Comparison of Functional Free-Breathing Pulmonary 1H and Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Cystic Fibrosis.

Acad Radiol. 2020 Jun 10;:

Authors: Couch MJ, Munidasa S, Rayment JH, Voskrebenzev A, Seethamraju RT, Vogel-Claussen J, Ratjen F, Santyr G

Abstract
RATIONALE AND OBJECTIVES: Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF).
MATERIALS AND METHODS: 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice.
RESULTS: The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p < 0.0001) and elevated LCI (p < 0.0001). PREFUL and HP 129Xe VDP were significantly different between the CF PEx and healthy groups (p < 0.05). In the stable CF group, PREFUL and HP 129Xe VDP were not significantly different from the healthy group (p = 0.18 and 0.08, respectively). There was a correlation between PREFUL and HP 129Xe VDP (R2 = 0.31, p = 0.004), and both parameters were significantly correlated with FEV1 and LCI.
CONCLUSION: PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.

PMID: 32532639 [PubMed - as supplied by publisher]