Pediatr Radiol. 2021 Mar 24. doi: 10.1007/s00247-021-05015-w. Online ahead of print.

ABSTRACT

BACKGROUND: Complications from liver cirrhosis are a leading cause of death in children with cystic fibrosis. Identifying children at risk for developing liver cirrhosis and halting its progression are critical to reducing liver-associated mortality.

OBJECTIVE: Quantitative US imaging, such as shear-wave elastography (SWE), might improve the detection of liver fibrosis in children with cystic fibrosis (CF) over gray-scale US alone. We incorporated SWE in our pediatric CF liver disease screening program and evaluated its performance using magnetic resonance (MR) elastography.

MATERIALS AND METHODS: Ninety-four children and adolescents with CF underwent 178 SWE exams, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and platelet measurements. Of these, 27 children underwent 34 MR elastography exams. We evaluated SWE performance using 6-MHz and 9-MHZ point SWE, and 9-MHz two-dimensional (2-D) SWE.

RESULTS: The 6-MHz point SWE was the only method that correlated with MR elastography (r=0.52; 95% confidence interval [CI] 0.20-0.74; P=0.003). SWE of 1.45 m/s distinguished normal from abnormal MR elastography (79% sensitivity, 100% specificity, 100% positive predictive value [PPV], 55% negative predictive value [NPV], area under the receiver operating characteristic [AUROC] curve 0.94). SWE of 1.84 m/s separated mild-moderate (3.00-4.77 kPa) from severe (>4.77 kPa) MR elastography (88% sensitivity, 86% specificity, 78% PPV, 93% NPV, AUROC 0.79). Elevations of AST, ALT, GGT and thrombocytopenia were associated with higher SWE. AST-to-platelet ratio index of 0.42, fibrosis-4 of 0.29, and GGT-to-platelet ratio of 1.43 all had >95% NPV for SWE >1.84 m/s.

CONCLUSION: Given its correlation with MR elastography, SWE might be a clinically useful predictor of liver fibrosis. We identified imaging criteria delineating the use of SWE to identify increased liver stiffness in children with CF. With multicenter validation, these data might be used to improve the detection and monitoring of liver fibrosis in children with CF.

PMID:33759025 | DOI:10.1007/s00247-021-05015-w

Curr Gastroenterol Rep. 2021 Mar 23;23(3):4. doi: 10.1007/s11894-021-00806-5.

ABSTRACT

PURPOSE OF REVIEW: People with cystic fibrosis (CF) are living longer. General age-related and CF-specific gastrointestinal symptoms are increasingly recognized. In this article, we review the latest data on luminal gastrointestinal manifestations in CF.

RECENT FINDINGS: People with CF have increased incidence of gastroesophageal reflux disease symptoms and often prescribed proton-pump inhibitors (PPI). PPI use may increase risk of pulmonary exacerbations. Evidence to support gastric fundoplication to improve pulmonary outcomes is limited. Features of intestinal dysmotility are common. There are distinct differences in the gut microbiome in the CF population which may have clinical implications. CF is a possible hereditary digestive cancer syndrome, particularly in regard to colorectal cancer (CRC) with earlier incidence of CRC and advanced colonic neoplasia. Early screening colonoscopy is warranted in the CF population. Gastrointestinal manifestations in CF are prevalent across all digestive organs. More study on the effect of interventions for symptomatic treatment and cancer screening is needed.

PMID:33758994 | DOI:10.1007/s11894-021-00806-5

J Thorac Imaging. 2021 Mar 24. doi: 10.1097/RTI.0000000000000588. Online ahead of print.

ABSTRACT

PURPOSE: Bronchiectasis is a chronic disease characterized by an irreversible dilatation of bronchi leading to chronic infection, airway inflammation, and progressive lung damage. Three specific patterns of bronchiectasis are distinguished in clinical practice: cylindrical, varicose, and cystic. The predominance and the extension of the type of bronchiectasis provide important clinical information. However, characterization is often challenging and is subject to high interobserver variability. The aim of this study is to provide an automatic tool for the detection and classification of bronchiectasis through convolutional neural networks.

MATERIALS AND METHODS: Two distinct approaches were adopted: (i) direct network performing a multilabel classification of 32×32 regions of interest (ROIs) into 4 classes: healthy, cylindrical, cystic, and varicose and (ii) a 2-network serial approach, where the first network performed a binary classification between normal tissue and bronchiectasis and the second one classified the ROIs containing abnormal bronchi into one of the 3 bronchiectasis typologies. Performances of the networks were compared with other architectures presented in the literature.

RESULTS: Computed tomography from healthy individuals (n=9, age=47±6, FEV1%pred=109±17, FVC%pred=116±17) and bronchiectasis patients (n=21, age=59±15, FEV1%pred=74±25, FVC%pred=91±22) were collected. A total of 19,059 manually selected ROIs were used for training and testing. The serial approach provided the best results with an accuracy and F1 score average of 0.84, respectively. Slightly lower performances were observed for the direct network (accuracy=0.81 and F1 score average=0.82). On the test set, cylindrical bronchiectasis was the subtype classified with highest accuracy, while most of the misclassifications were related to the varicose pattern, mainly to the cylindrical class.

CONCLUSION: The developed networks accurately detect and classify bronchiectasis disease, allowing to collect quantitative information regarding the radiologic severity and the topographical distribution of bronchiectasis subtype.

PMID:33758127 | DOI:10.1097/RTI.0000000000000588

Pediatr Res. 2021 Mar 22. doi: 10.1038/s41390-021-01453-2. Online ahead of print.

ABSTRACT

BACKGROUND: This research characterized mucociliary clearance (MCC) in young children with cystic fibrosis (CF).

METHODS: Fourteen children (5-7 years old) with CF underwent: two baseline MCC measurements (Visits 1 and 2); one MCC measurement approximately 1 year later (Visit 3); and measurements of lung clearance index (LCI), a measure of ventilation inhomogeneity.

RESULTS: Median (range) percent MCC through 60 min (MCC60) was similar on Visits 1 and 2 with 11.0 (0.9-33.7) and 12.8 (2.7-26.8), respectively (p = 0.95), and reproducible (Spearman Rho = 0.69; p = 0.007). Mucociliary clearance did not change significantly over 1 year with median percent MCC60 on Visit 3 [12.8 (3.7-17.6)] similar to Visit 2 (p = 0.58). Lower percent MCC60 on Visit 3 was significantly associated with higher LCI scores on Visit 3 (N = 14; Spearman Rho = -0.56; p = 0.04).

CONCLUSIONS: Tests of MCC were reproducible and reliable over a 2-week period and stable over a 1-year period in 5-7-year-old children with CF. Lower MCC values were associated with increased ventilation inhomogeneity. These results suggest that measurements of MCC could be used in short-term clinical trials of interventions designed to modulate MCC and as a new, non-invasive test to evaluate early lung pathology in children with CF.

IMPACT: This is the first study to characterize mucociliary clearance (MCC) in children with cystic fibrosis (CF) who were 5-7 years old. Measurements of mucociliary clearance were reproducible and reliable over a 2-week period and stable over a 1-year period. Variability in MCC between children was associated with differences in ventilation homogeneity, such that children with lower MCC values had increased ventilation inhomogeneity. These results suggest that measurements of MCC could be used in short-term clinical trials of interventions designed to modulate MCC and as a new, non-invasive test to evaluate early lung pathology in children with CF.

PMID:33753897 | DOI:10.1038/s41390-021-01453-2

Eur J Hosp Pharm. 2021 Mar 22:ejhpharm-2020-002588. doi: 10.1136/ejhpharm-2020-002588. Online ahead of print.

ABSTRACT

Over a course of 7 months, four patients developed vestibulotoxicity after treatment with intravenous tobramycin. Since vestibulotoxicity is a serious adverse effect which can be irreversible, an investigation was undertaken to determine if there was a cause for the toxicity and whether the quality of care had been inadequate. In this period, 26 patients with cystic fibrosis were treated with tobramycin according to valid guidelines, of which four experienced acute dizziness which disrupted their daily activities. Two patients experienced irreversible bilateral vestibular hypofunction and two unilateral loss of the right labyrinth, with decreasing dizziness over time. No apparent cause for the vestibulotoxicity was found in these four patients and the simultaneous occurrence was not due to a lack in quality of care. Symptoms of dizziness and balance disorders should be recognised by patients and caretakers at an early stage so additional diagnostics can be done to prevent further deterioration.

PMID:33753422 | DOI:10.1136/ejhpharm-2020-002588

Pediatr Pulmonol. 2021 Mar 10. doi: 10.1002/ppul.25364. Online ahead of print.

ABSTRACT

INTRODUCTION: The prognosis of people diagnosed with cystic fibrosis (CF) has dramatically improved over the past decade in France, largely due to advances in CF care management, including emphasis on chronic maintenance medications. Currently, the majority of French CF patients are adults, which means that they went through a transition process from receiving care at a pediatric CF center to receiving care at an adult CF center. To determine the impact of transfer on clinical evolution, we report the transition procedure of our CF center in Lyon.

MATERIALS AND METHODS: From January 2006 to December 2016, 97 CF patients underwent a standardized process of transitioning from the pediatric to the adult CF center in Lyon. We compared the clinical evolution of these patients during 3 periods starting the year prior to transition and ending the year after transition. Clinical data taken into account were Forced Expiratory Volume in 1 second (FEV1 in liters), Body Mass Index (BMI in kg/m2 ), pulmonary colonization, number of antibiotic courses, number of days of hospitalization per year and outpatient visits per year.

RESULTS: No significant differences were observed between respiratory and nutritional status, respiratory microbiome, number of antibiotic courses, or number of hospitalizations or visits when comparing the 3 periods of observation around transition (the year before, the first year after and the second year after transfer).

CONCLUSION: The standardized transition procedure used in Lyon is associated with the clinical stability of our CF patients. This article is protected by copyright. All rights reserved.

PMID:33751837 | DOI:10.1002/ppul.25364

Transplant Proc. 2021 Mar 6:S0041-1345(21)00113-5. doi: 10.1016/j.transproceed.2021.02.004. Online ahead of print.

ABSTRACT

Liver allografts are unique in solid organ transplantation as they are less susceptible to both acute and chronic rejection. Operational tolerance, defined as prolonged graft survival in the absence of immunosuppression, is also achieved more frequently with liver allografts. It is unknown if the presence of multiple allografts in the same individual, levels of immunosuppression, or the presence of cystic fibrosis (CF) impacts the livers ability to ward off rejection or achieve operational tolerance. We describe an unsensitized, ABO-compatible patient with CF who underwent double lung transplantation and several years later a combined liver-kidney transplant. He developed isolated late acute T-cell mediated rejection of his liver allograft despite a high level of immunosuppression (IS) required for his lung and kidney allografts. To our knowledge, this is the first case of isolated liver rejection in a patient with 3 separate organ allografts, or in a patient with CF, to be reported in the literature. This isolated liver rejection is out of keeping with typically accepted ideas about orthotopic liver tolerance.

PMID:33750588 | DOI:10.1016/j.transproceed.2021.02.004

Am J Med Genet C Semin Med Genet. 2021 Mar 22. doi: 10.1002/ajmg.c.31899. Online ahead of print.

ABSTRACT

Latin America is a region consisting of 20 countries that present a wide diversity in terms of a geographic area as well as demographics, ethnicity, economy, social, and healthcare systems. This diversity also applies to the newborn screening (NBS) activities, as demonstrated by the start dates and modalities of implementation as organized programs, the panel of diseases screened for, the available technologies for testing, the coverage, the legislation in force, and the degree of development and success reached. Based on these characteristics, Latin American countries can currently be classified into five groups ranging from fully established national programs to no program at all. Sixteen countries have national or regional NBS programs, but up to date only 14 are actively working. The other 2 have organized programs conducted by different health services providers, but without any unified national coordination. Only six countries have coverage ≥ 90% and 12 ≥ 70%. Thirteen countries have legislation in force defining NBS as mandatory. The 16 countries that have active NBS programs screen for congenital hypothyroidism, 14 for phenylketonuria, 12 for congenital adrenal hyperplasia and cystic fibrosis, and 8 for galactosemia. NBS by tandem mass spectrometry is implemented at a national level only in two countries. Despite these disparities, sustained and significant growth has become evident in the last decade, highlighted by the implementation of new programs, the increase in coverage, the expansion of the panel diseases, the enactment of new NBS laws, and the increasing involvement of government and public health authorities.

PMID:33749987 | DOI:10.1002/ajmg.c.31899

FASEB J. 2021 Apr;35(4):e21441. doi: 10.1096/fj.202001952R.

ABSTRACT

An excessive, non-resolving inflammatory response underlies severe COVID-19 that may have fatal outcomes. Therefore, the investigation of endogenous pathways leading to resolution of inflammation is of interest to uncover strategies for mitigating inflammation in people with SARS-CoV-2 infection. This becomes particularly urgent in individuals with preexisting pathologies characterized by chronic respiratory inflammation and prone to bacterial infection, such as cystic fibrosis (CF). Here, we analyzed the immune responses to SARS-CoV-2 virion spike 1 glycoprotein (S1) of macrophages (MΦ) from volunteers with and without CF and tested the efficacy of resolvins (Rv) D1 and D2 in regulating the inflammatory and antimicrobial functions of MΦ exposed to S1. S1 significantly increased chemokine release, including interleukin (IL)-8, in CF and non-CF MΦ, while it enhanced IL-6 and tumor necrosis factor (TNF)-α in non-CF MΦ, but not in CF cells. S1 also triggered the biosynthesis of RvD1 and modulated microRNAs miR-16, miR-29a, and miR-103, known to control the inflammatory responses. RvD1 and RvD2 treatment abated S1-induced inflammatory responses in CF and non-CF MΦ, significantly reducing the release of select chemokines and cytokines including IL-8 and TNF-α. RvD1 and RvD2 both restored the expression of miR-16 and miR-29a, while selectively increasing miR-223 and miR-125a, which are involved in NF-κB activation and MΦ inflammatory polarization. During Pseudomonas aeruginosa infection, S1 stimulated the MΦ phagocytic activity that was further enhanced by RvD1 and RvD2. These results provide a map of molecular responses to SARS-CoV-2 in MΦ, key determinants of COVID-19-related inflammation, unveiling some peculiarity in the response of cells from individuals with CF. They also demonstrate beneficial, regulatory actions of RvD1 and RvD2 on SARS-CoV-2-induced inflammation.

PMID:33749902 | DOI:10.1096/fj.202001952R

EMBO J. 2021 Mar 22:e107238. doi: 10.15252/embj.2020107238. Online ahead of print.

ABSTRACT

Glycosphingolipids are important components of the plasma membrane where they modulate the activities of membrane proteins including signalling receptors. Glycosphingolipid synthesis relies on competing reactions catalysed by Golgi-resident enzymes during the passage of substrates through the Golgi cisternae. The glycosphingolipid metabolic output is determined by the position and levels of the enzymes within the Golgi stack, but the mechanisms that coordinate the intra-Golgi localisation of the enzymes are poorly understood. Here, we show that a group of sequentially-acting enzymes operating at the branchpoint among glycosphingolipid synthetic pathways binds the Golgi-localised oncoprotein GOLPH3. GOLPH3 sorts these enzymes into vesicles for intra-Golgi retro-transport, acting as a component of the cisternal maturation mechanism. Through these effects, GOLPH3 controls the sub-Golgi localisation and the lysosomal degradation rate of specific enzymes. Increased GOLPH3 levels, as those observed in tumours, alter glycosphingolipid synthesis and plasma membrane composition thereby promoting mitogenic signalling and cell proliferation. These data have medical implications as they outline a novel oncogenic mechanism of action for GOLPH3 based on glycosphingolipid metabolism.

PMID:33749896 | DOI:10.15252/embj.2020107238

Spec Care Dentist. 2021 Mar 22. doi: 10.1111/scd.12586. Online ahead of print.

ABSTRACT

AIMS: Dental clearance is typically part of the evaluation process prior to placement on the lung transplant waiting list. Individuals with cystic fibrosis (CF) are thought to be at low risk for dental disease. We hypothesized that individuals with CF in need of lung transplantation would have lower dental disease prevalence and shorter waitlist evaluation time than individuals with non-CF lung diseases.

METHODS AND RESULTS: We conducted a retrospective study of individuals who received a lung transplant between 2011 and 2017 at the University of Washington (Seattle, WA, USA) (N = 280). Untreated dental disease was assessed by the individual's dentist. Waitlist evaluation time was defined as the time, in days, from the initial evaluation by a transplant pulmonologist to placement on the lung transplant waiting list. We used logistic and linear regression models for hypothesis testing. The prevalence of untreated dental disease did not differ by CF status (p = 0.99). There was no difference in waitlist evaluation time for transplant recipients by CF status (p = 0.78) or by dental disease status (p = 0.93).

CONCLUSIONS: Our findings provide further evidence that individuals with CF are not at low risk for dental disease. Ensuring optimal oral health is important for all individuals with lung diseases.

PMID:33749871 | DOI:10.1111/scd.12586

Clin Respir J. 2021 Mar 22. doi: 10.1111/crj.13365. Online ahead of print.

ABSTRACT

Sputum cytology is currently the gold standard to evaluate cellular inflammation in the airways and phenotyping patients with airways diseases. Sputum eosinophil proportions have been used to guide treatment for moderate to severe asthma. Furthermore, raised sputum neutrophils are associated with poor disease control and impaired lung function in both asthma and COPD and small airways disease in cystic fibrosis. However, induced-sputum analysis is subjective and resource heavy, requiring dedicated specialist processing and assessment; this limits its utility in most clinical settings. Indirect blood eosinophil measures have been adopted in clinical care. However, there are currently no good peripheral blood biomarkers of airway neutrophils. A resource-light sputum processing approach could thus help integrate induced sputum more readily into routine clinical care. New mechanical disruption (MD) methods can rapidly obtain viable single cell suspensions from sputum samples. The aim of this study was to compare MD sputum processing to traditional methods for cell viability, granulocyte proportions and sputum cytokine analysis. Sputum plugs were split and processed using traditional methods and the MD method, and samples were then compared. The MD method produced a homogeneous cell suspension in 62 seconds; 70 minutes faster than the standard method used. No significant difference was seen between the cell viability (p=0.09), or the concentration of eosinophils (p=0.83), neutrophils (p=0.99) or interleukin-8 (p=0.86) using MD. This cost-effective method of sputum processing could provide a more pragmatic, sustainable means of directly monitoring the airway milieu. Therefore, we recommend this method be taken forward for further investigation.

PMID:33749082 | DOI:10.1111/crj.13365

Gastroenterol Rep (Oxf). 2021 Jan 15;9(1):38-48. doi: 10.1093/gastro/goaa091. eCollection 2021 Jan.

ABSTRACT

BACKGROUND: Medical literature on the prevalence of genetic liver disease is lacking. In this study, we investigated the in-hospital healthcare and economic burden from genetic causes of non-alcoholic chronic liver disease (NACLD) and non-alcoholic liver cirrhosis (NALC) in the USA.

METHODS: Data were abstracted from the National Inpatient Sample database between 2002 and 2014 using ICD9 codes for patients discharged with NACLD and NALC secondary to genetic diseases including alpha-1 antitrypsin deficiency (A1ATd), cystic fibrosis (CF), Wilson disease (WD), hereditary hemochromatosis (HHC), glycogen storage disease, and disorders of aromatic amino-acid metabolism (DAAAM).

RESULTS: Throughout the study period, there were 19,332 discharges for NACLD associated with the six genetic diseases including 14,368 for NALC. There were $1.09 billion in hospital charges, 790 in-hospital deaths, and 955 liver transplants performed. Overall, A1ATd was associated with 8,983 (62.52%) hospitalizations for NALC followed by WD, CF, and HHC. The highest in-hospital mortality was seen with HHC. The greatest frequency of liver transplants was seen with DAAAM.

CONCLUSION: The number of hospitalizations for genetic liver diseases continues to increase. With increased funding and directed research efforts, we can aim to improve medical treatments and the quality of life for patients at risk for liver deterioration.

PMID:33747525 | PMC:PMC7962742 | DOI:10.1093/gastro/goaa091

Clin Transl Immunology. 2021 Mar 15;10(3):e1255. doi: 10.1002/cti2.1255. eCollection 2021.

ABSTRACT

OBJECTIVE: Ligelizumab is a humanised IgG1 anti-IgE antibody that binds IgE with higher affinity than omalizumab. Ligelizumab had greater efficacy than omalizumab on inhaled and skin allergen provocation responses in mild allergic asthma. This multi-centre, randomised, double-blind study was designed to test ligelizumab in severe asthma patients not adequately controlled with high-dose inhaled corticoids plus long-acting β2-agonist.

METHODS: Patients received 16 weeks ligelizumab (240 mg q2w), omalizumab or placebo subcutaneously, and ACQ-7 was measured as primary outcome at Week 16. In addition, the study generated dose-ranging data of ligelizumab and safety data.

RESULTS: A total of 471 patients, age 47.4 ± 13.36 years, were included in the study. Treatment with ligelizumab did not significantly improve asthma control (ACQ-7) and exacerbation rates compared to omalizumab and placebo. Therefore, primary and secondary objectives of the study were not met. The compound was well tolerated, and the safety profile showed no new safety findings. Pharmacokinetic data demonstrated faster clearance and lower serum concentrations of ligelizumab than historical omalizumab data, and exploratory in vitro data showed differential IgE blocking properties relative to FcεRI and FcεRII/CD23 between the two compounds.

CONCLUSION: Ligelizumab failed to demonstrate superiority over placebo or omalizumab. Although ligelizumab is more potent than omalizumab at inhibiting IgE binding to the high-affinity FcεRI, there is differential IgE blocking properties relative to FcεRI and FcεRII/CD23 between the two compounds. Therefore, the data suggest that different anti-IgE antibodies might be selectively efficacious for different IgE-mediated diseases.

PMID:33747510 | PMC:PMC7958305 | DOI:10.1002/cti2.1255

Front Microbiol. 2021 Mar 3;12:617784. doi: 10.3389/fmicb.2021.617784. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa and Staphylococcus aureus are the two most prevalent bacteria species in the lungs of cystic fibrosis (CF) patients and are associated with poor clinical outcomes. Co-infection by the two species is a frequent situation that promotes their interaction. The ability of P. aeruginosa to outperform S. aureus has been widely described, and this competitive interaction was, for a long time, the only one considered. More recently, several studies have described that the two species are able to coexist. This change in relationship is linked to the evolution of bacterial strains in the lungs. This review attempts to decipher how bacterial adaptation to the CF environment can induce a change in the type of interaction and promote coexisting interaction between P. aeruginosa and S. aureus. The impact of coexistence on the establishment and maintenance of a chronic infection will also be presented, by considering the latest research on the subject.

PMID:33746915 | PMC:PMC7966511 | DOI:10.3389/fmicb.2021.617784

J Cyst Fibros. 2021 Mar 18:S1569-1993(21)00048-5. doi: 10.1016/j.jcf.2021.02.013. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease characterized by chronic sinopulmonary symptoms and chronic gastrointestinal symptoms that begins in infancy. Children with CF are increasingly being included in clinical trials. In order to fully evaluate the impact of new therapies in future clinical trials, an understanding of baseline adverse event (AE) rates in children with CF is needed. To address this, we determined the rates of common AEs in pediatric patients with CF who participated in two clinical trials.

METHODS: We reviewed AEs for placebo recipients in the AZ0004 study and inhaled tobramycin recipients in the Early Pseudomonas Infection Control (EPIC) clinical trial. AEs were categorized based on Medical Dictionary for Regulatory Activities (MedDRA) coding classifications and pooled into common, batched AE descriptors. AE rates were estimated from negative binomial models according to age groups, severity of lung disease, and season.

RESULTS: A total of 433 children had 8,266 total AEs reported, or 18.1 (95% CI 17.0, 19.2) AEs per person per year. Respiratory AEs were the most commonly reported AEs, with a rate of 7.6 events per person-year. The total SAE rate was 0.33 per person per-year. Cough was the most commonly reported respiratory AE, with 61% of subjects reporting at least one episode of cough within 4 months. The rate ratio of any AE was higher in Spring, Fall, and Winter, compared with Summer.

CONCLUSIONS: AEs occur commonly in pediatric CF clinical trial participants. Season of enrollment could affect AE rates.

PMID:33745860 | DOI:10.1016/j.jcf.2021.02.013

J Pediatr Surg. 2021 Feb 24:S0022-3468(21)00182-2. doi: 10.1016/j.jpedsurg.2021.02.048. Online ahead of print.

ABSTRACT

This is a commentary on the manuscript titled "Early Management of Meconium Ileus in Infants with Cystic Fibrosis: A Prospective Population Cohort Study" by Long A-M, et al.

PMID:33745742 | DOI:10.1016/j.jpedsurg.2021.02.048

Clin Nutr ESPEN. 2021 Apr;42:407-409. doi: 10.1016/j.clnesp.2021.01.015. Epub 2021 Feb 5.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a multi-organ genetically inherited disease that leads to progressive lung disease and nutrient malabsorption. The aim of this study was to assess the effectiveness of cyproheptadine (CH) (Periactin®) as an appetite stimulant on improving the nutrition status of paediatric patients with CF.

METHODS: We conducted a retrospective study of 15 patients with a suboptimal nutrition status prescribed CH for ≥12 months from 2013 to 2018. Change in Body Mass Index (BMI) z-score and lung function before vs. after treatment with CH were measured as well as dose-response relationship.

RESULTS: The mean change in BMI z-score over 12 months of treatment with CH was +0.91 compared to -0.52 in the previous 12 months (p∗∗∗ = 0.0002). There was also a trend towards an improvement in lung function over the 12 months of CH treatment compared to the 12 months prior (+2.79 vs -6.2% (p = 0.07)). No dose-response relationship was observed.

CONCLUSION: These results suggest that CH is effective at improving the nutrition status of paediatric CF patients with suboptimal nutrition.

PMID:33745614 | DOI:10.1016/j.clnesp.2021.01.015

Clin Nutr ESPEN. 2021 Apr;42:206-211. doi: 10.1016/j.clnesp.2021.01.038. Epub 2021 Feb 9.

ABSTRACT

BACKGROUND & AIMS: Cystic Fibrosis (CF) may impact nutritional status. Handgrip strength (HGS) may be used for nutrition assessment. The objective of the study was to evaluate changes in HGS over time in children with CF compared to children without CF. A secondary purpose was to analyze the relationship of clinical characteristics of CF with HGS.

METHODS: A prospective, longitudinal study was conducted. The non-CF group (n = 76) was recruited from a school and the CF group (n = 75) from an accredited CF center. Height, weight, mid-upper arm circumference, triceps skinfold, and HGS were measured at baseline and approximately three and six months in both groups. Data for pulmonary function, nutrition risk, enteral supplementation, CF transmembrane conductance regulator modulator, steroids, antibiotics, vitamin levels, CF related diabetes (CFRD), and recent hospitalization were collected for the CF group. A mixed model determined the difference in the change in HGS between the CF group and the non-CF group. For all analyses, p=<0.05 was significant.

RESULTS: The rate of change in HGS z-score in the CF-group (0.18 ± 0.05) versus the non-CF group (0.06 ± 0.06) was not significant (p = 0.15). Initial mean dominant HGS z-score was significantly lower (p = 0.02) in those with vitamin D deficiency (-1.35 ± 0.09) versus those without (-1.02 ± 0.11). HGS z-score significantly (p = 0.02) decreased over time in children with CFRD (-0.19 ± 0.22) versus children without CFRD (0.32 ± 0.14), p = 0.02.

CONCLUSION: Serial measurements of HGS may help detect changes in muscle function related to CFRD and vitamin D deficiency. Further investigation is warranted to elucidate HGS's role in nutrition assessment of children with CF.

PMID:33745579 | DOI:10.1016/j.clnesp.2021.01.038

Pediatr Radiol. 2021 Apr;51(4):544-553. doi: 10.1007/s00247-020-04706-0. Epub 2021 Mar 20.

ABSTRACT

Thoracic computed tomography (CT) is the imaging reference method in the diagnosis, assessment and management of lung disease. In the setting of cystic fibrosis (CF), CT demonstrates increased sensitivity compared with pulmonary function tests and chest radiography, and findings correlate with clinical outcomes. Better understanding of the aetiology of CF lung disease indicates that even asymptomatic infants with CF can have irreversible pulmonary pathology. Surveillance and early diagnosis of lung disease in CF are important to preserve lung parenchyma and to optimise long-term outcomes. CF is associated with increased cumulative radiation exposure due to the requirement for repeated imaging from a young age. Radiation dose optimisation, important for the safe use of CT in children with CF, is best achieved in a team environment where paediatric radiologists work closely with paediatric respiratory physicians, physicists and radiography technicians to achieve the best patient outcomes. Despite the radiation doses incurred, CT remains a vital imaging tool in children with CF. Radiologists with special interests in CT dose optimisation and respiratory disease are key to the appropriate use of CT in paediatric imaging. Paediatric radiologists strive to minimise radiation dose to children whilst providing the best possible assessment of lung disease.

PMID:33743038 | DOI:10.1007/s00247-020-04706-0