Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease.

Magn Reson Med. 2020 Aug 08;:

Authors: McCallister A, Chung SH, Antonacci M, Z Powell M, Ceppe AS, Donaldson SH, Lee YZ, Branca RT, Goralski JL

Abstract
PURPOSE: To quantitatively compare dynamic 19 F and single breath hyperpolarized 129 Xe MRI for the detection of ventilation abnormalities in subjects with mild cystic fibrosis (CF) lung disease.
METHODS: Ten participants with stable CF and a baseline FEV1 > 70% completed a single imaging session where dynamic 19 F and single breath 129 Xe lung ventilation images were acquired on a 3T MRI scanner. Ventilation defect percentages (VDP) values between 19 F early-breath, 19 F maximum-ventilation, 129 Xe low-resolution, and 129 Xe high-resolution images were compared. Dynamic 19 F images were used to determine gas wash-in/out rates in regions of ventilation congruency and mismatch between 129 Xe and 19 F.
RESULTS: VDP values from high-resolution 129 Xe images were greater than from low-resolution images (P = .001), although these values were significantly correlated (r = 0.68, P = .03). Early-breath 19 F VDP and max-vent 19 F VDP also showed significant correlation (r = 0.75, P = .012), with early-breath 19 F VDP values being significantly greater (P < .001). No correlation in VDP values were detected between either 19 F method or high-res 129 Xe images. In addition, the location and volume of ventilation defects were often different when comparing 129 Xe and 19 F images from the same subject. Areas of ventilation congruence displayed the expected ventilation kinetics, while areas of ventilation mismatch displayed abnormally slow gas wash-in and wash-out.
CONCLUSION: In CF subjects, ventilation abnormalities are identified by both 19 F and HP 129 Xe imaging. However, these ventilation abnormalities are not entirely congruent. 19 F and HP 129 Xe imaging provide complementary information that enable differentiation of normally ventilated, slowly ventilated, and non-ventilated regions in the lungs.

PMID: 32770779 [PubMed - as supplied by publisher]

Tissue oxygenation in peripheral muscles and functional capacity in cystic fibrosis: A cross-sectional study.

Exp Physiol. 2020 Aug 07;:

Authors: Coelho CC, Aquino EDS, Diniz ALR, Santos MDS, Oliveira LC, Poeiras PTC, Pereira DAG

Abstract
NEW FINDINGS: What is the central question of this study? How do peripheral muscle tissue oxygenation and physical conditioning levels of children and adolescents with cystic fibrosis compare to demographically matched controls? What is the main finding and is its importance? Children and adolescents with cystic fibrosis consumed more oxygen, more quickly and exhibited slower recovery, demonstrating that there may have been deficiencies in oxygen supply related to both oxygen uptake and transport.
ABSTRACT: Cystic fibrosis affects skeletal muscle performance and functional capacity. However, it is currently unclear how peripheral muscle behavior is affected, especially in children and adolescents. To examine this, we compared tissue oxygenation of children and adolescents with cystic fibrosis against healthy volunteers. We also evaluated the functional capacity of participants via the modified shuttle test (MST) and assessed for associations between performance and near-infrared spectroscopy (NIRS). A total of 124 participants enrolled. Participants were divided into either the cystic fibrosis group (CFG) or the healthy group (HG). Statistical comparisons between groups were evaluated with Mann-Whitney U tests and associations with functional capacity were evaluated using Spearman's correlation coefficient. CFG volunteers scored lower on the MST compared to the HG. They walked shorter distances (p = 0.001) with less efficiency because they performed the tests with a less efficient walking economy (p = 0.001) and a greater deoxyhemoglobin concentration (p = 0.001). Further, they experienced less tissue oxygen saturation (p = 0.037) faster than the HG. As a result, they presented lower respiratory (p = 0.001) and lower heart (p = 0.001) rate values at the end of the MST, with a longer post-test heart rate recovery time (p = 0.005). There was a significant association between deoxygenation time and functional capacity. The CFG consumed more oxygen, more quickly, with a slower recovery, reflecting impairments in the dynamics of muscle oxygen extraction. The results suggest differences in functional capacity and hemodynamic recovery in children and adolescents with cystic fibrosis. This article is protected by copyright. All rights reserved.

PMID: 32770583 [PubMed - as supplied by publisher]

Alterocin, an antibiofilm protein secreted by Pseudoalteromonas sp. 3J6.

Appl Environ Microbiol. 2020 Aug 07;:

Authors: Jouault A, Gobet A, Simon M, Portier E, Perennou M, Corre E, Gaillard F, Vallenet D, Michel G, Fleury Y, Bazire A, Dufour A

Abstract
The aim was to identify and study the antibiofilm protein secreted by the marine bacterium Pseudoalteromonas sp. 3J6. The latter is active against marine and terrestrial bacteria, including Pseudomonas aeruginosa clinical strains forming different biofilm types. Several amino acid sequences were obtained from the partially purified antibiofilm protein, named alterocin. The Pseudoalteromonas sp. 3J6 genome was sequenced and a candidate alt gene was identified by comparing the genome-encoded proteins to the sequences from purified alterocin. Expressing the alt gene in another non-active Pseudoalteromonas sp. strain, 3J3, demonstrated that it is responsible for the antibiofilm activity. Alterocin is a 139-residue protein including a predicted 20-residue signal sequence, which would be cleaved off upon export by the general secretion system. No sequence homology was found between alterocin and proteins of known functions. The alt gene is not part of an operon and adjacent genes do not seem related to alterocin production, immunity or regulation, suggesting that these functions are not fulfilled by devoted proteins. During liquid growth, the alt mRNA level peaked during the stationary phase. A single promoter was experimentally identified and several inverted repeats could be binding sites for regulators. alt genes were found in about 30% of the Pseudoalteromonas genomes, and in only few instances of other marine bacteria of the Hahella and Paraglaciecola genera. Comparative genomics yielded the hypotheses that alt gene losses occurred within the Pseudoalteromonas genus. Overall, alterocin is a novel kind of antibiofilm protein of ecological and biotechnological interest.Importance Biofilms are microbial communities that develop on solid surfaces or interfaces, and are detrimental in a number of fields including for example food industry, aquaculture, and medicine. In the latter, antibiotics are insufficient to clear biofilm infections, leading to chronic infections such as in the case of infection by Pseudomonas aeruginosa of the lungs of cystic fibrosis patients. Antibiofilm molecules are thus urgently needed to be used in conjunction with conventional antibiotics, as well as in other fields of application, especially if they are environmentally friendly molecules. Here, we describe alterocin, a novel antibiofilm protein secreted by a marine bacterium belonging to the Pseudoalteromonas genus, and its gene. Alterocin homologs were found in about 30% of Pseudoalteromonas strains, indicating that this new family of antibiofilm proteins likely plays an important albeit non-essential function in the biology of these bacteria. This work opens up the possibility of a variety of applications.

PMID: 32769182 [PubMed - as supplied by publisher]

The impact of the COVID-19 pandemic on the emotional well-being and home treatment of Belgian patients with cystic fibrosis, including transplanted patients and paediatric patients.

J Cyst Fibros. 2020 Jul 31;:

Authors: Havermans T, Houben J, Vermeulen F, Boon M, Proesmans M, Lorent N, de Soir E, Vos R, Dupont L

Abstract
BACKGROUND: Little is known about the impact of COVID-19 on patients with cystic fibrosis (CF), despite being considered a high-risk group. This study explored the early impact of COVID-19 on the emotional well-being of patients and self-reported changes in their home therapy since the start of the pandemic.
METHODS: Adult patients with CF, lung-transplanted (LTX) CF patients and parents of children with CF completed an online questionnaire, securely linked to their medical files. The questionnaire covered the emotional impact of the pandemic, changes in CF and LTX treatment, changes in health-protecting behaviours and CF-related concerns, and their perception of their COVID-19 status.
RESULTS: The response rate was 63% (80 CF, 66 LTX and 73 parents). A wide range of illness severity was included. None of the respondents had contracted COVID-19 and all strictly followed the social distancing rules. There was evident psychological impact, with many reporting increased stress, fear and worry about CF and the future. Changes in treatment were positive, including more physiotherapy for adults and better-quality nebulizing. Changes in routine were reported, such as different treatment timing. Adult patients and parents had cancelled their CF appointments more often since the start of the pandemic.
CONCLUSIONS: The initial psychological impact of COVID-19 was evident. The impact on home treatment was reassuringly small. Psychological care is needed for patients suffering prolonged psychological impact, and CF teams need to contextualize the information that patients and parents receive from the media and support them to balance the perceived risk with true risk.

PMID: 32768311 [PubMed - as supplied by publisher]

Azithromycin and tezacaftor/ivacaftor is associated with first-degree heart block in an adult with cystic fibrosis.

J Cyst Fibros. 2020 Aug 04;:

Authors: Song Y, Palacios AC, Thiagalingam A, Middleton PG

Abstract
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene is expressed in the heart, but this is not known to cause myocardial dysfunction or abnormalities in the ECG in people with CF. CFTR modulators such as tezacaftor/ivacaftor improve lung function and overall health in people with CF. Minor adverse events have been reported in the early clinical trials, but no consistent changes in the ECGs have been reported. This case highlights an unusual side effect of first degree heart block that occurred after more than 8 months of azithromycin and tezacaftor/ivacaftor in combination. Drug withdrawal and reintroduction confirmed that neither drug alone, but only the combination, caused this change. As tezacaftor/ivacaftor is also present in elexacaftor/tezacaftor/ivacaftor, care may be needed to exclude this delayed interaction with azithromycin.

PMID: 32768310 [PubMed - as supplied by publisher]

Optimizing Lung Function in Survivors of Preterm Birth: Palivizumab Is Not the Answer.

Chest. 2020 Aug;158(2):453-454

Authors: Guglani L, Lesnick BL

PMID: 32768062 [PubMed - as supplied by publisher]

Diversified Synthetic Pathway of 1, 4-Dihydropyridines: A Class of Pharmacologically Important Molecules.

Mini Rev Med Chem. 2020 Aug 07;:

Authors: Khot S, Auti PB, Khedkar SA

Abstract
The current review discusses the different synthetic pathways for one of the most important and interesting heterocyclic ring systems 1,4-dihydropyridine. This cyclic system depicts diverse pharmacological action at several receptors, channels, and enzymes. Dihydropyridine moiety plays an important role in several calcium-channel blockers. Moreover, it has been exploited for the treatment of a variety of cardiovascular diseases due to its potential antihypertensive, anti-angina, vasodilator, and cardiac depressant activities. Furthermore, it also shows antibacterial, anticancer, antileishmanial, anticoagulant, anticonvulsant, anti-tubercular, antioxidant, antiulcer, and neuroprotective properties. Several reports have demonstrated dihydropyridine derivatives as a potentiator of cystic fibrosis transmembrane conductance regulator protein, potent antimalarial agent and HIV-1 protease inhibitor. Herein, we have briefly reviewed different novel chemistry and synthesis of 1,4-dihydropyridine.

PMID: 32767934 [PubMed - as supplied by publisher]

Brave New Lungs: Aging in the Shadow of COVID-19.

J Gerontol B Psychol Sci Soc Sci. 2020 Aug 07;:

Authors: Nowakowski ACH

Abstract
As the COVID-19 pandemic continues to impact communities worldwide, this novel disease is leaving many survivors with severe lung damage. Among older patients, advanced lung damage is more likely. Survivors of all ages who have extensive lung impacts are likely to be new to managing those issues. Supporting healthy aging for these patients will require both gathering data about their unique experiences and using the existing evidence basis about adapting to managing obstructive lung disease. This article outlines key priorities for research with COVID-19 survivors aging with permanent lung damage, and highlights unique considerations for people older at age of onset. It also outlines the relevance of findings from this research for clinical care supporting people newly aging with advanced lung disease from COVID-19. In the process, it summarizes lessons from established patient populations aging with progressive lung disease-using cystic fibrosis as a prominent example from the author's lived experience-that may enhance the experiences of older COVID-19 survivors.

PMID: 32766805 [PubMed - as supplied by publisher]

Evaluation of Malnutrition Risk in Lung Transplant Candidates Using the Nutritional Risk Index.

Transplant Direct. 2020 Jul;6(7):e574

Authors: Chohan K, Park J, Dales S, Varughese R, Wickerson L, Singer LG, Stewart B, Rozenberg D

Abstract
Background: Malnutrition in lung transplant (LTx) candidates is an important risk factor for adverse outcomes. We sought to evaluate the Nutritional Risk Index (NRI) in LTx candidates, a validated measure of malnutrition risk in chronic disease. We aimed to characterize malnutrition risk using NRI, evaluate change in body weight between nutritional risk groups, and assess association of malnutrition risk with pretransplant and posttransplant outcomes.
Methods: Retrospective, single-center cohort study of LTx candidates (2014-2015) evaluated by a dietitian before listing. Nutritional parameters, weight change pretransplant and posttransplant, and clinical outcomes were abstracted up to 1-year posttransplant. NRI was calculated as follows: (1.519 × albumin) + (41.7 × current weight/ideal weight) with high malnutrition risk defined as the lowest quartile of NRI for cystic fibrosis (CF) and non-CF patients.
Results: The cohort comprises 247 LTx candidates (57% male; median age 59 y; non-CF 88%). Non-CF candidates had a greater mean NRI compared with CF patients (109 ± 11 versus 95 ± 12; P < 0.0001). 86% with high malnutrition risk maintained/gained weight (≥5%) pretransplant. In 196 LTx recipients, malnutrition risk was not associated with hospital stay, discharge disposition, or 1-year mortality. The median percent weight gain for LTx recipients in the first year was 10.5% (4.0-20.1), with high malnutrition risk recipients having comparable or greater weight gain to the low-risk group (mean difference for non CF: 6.8%; P = 0.02 and CF: -3.8%; P = 0.65).
Conclusions: Malnutrition risk assessed with NRI was not prognostic of posttransplant outcomes in this retrospective cohort. LTx candidates with high malnutrition risk were able to maintain their weight pretransplant and demonstrated considerable weight gain in the first-year posttransplant.

PMID: 32766429 [PubMed - as supplied by publisher]

Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis.

Front Immunol. 2020;11:1327

Authors: Ling KM, Garratt LW, Gill EE, Lee AHY, Agudelo-Romero P, Sutanto EN, Iosifidis T, Rosenow T, Turvey SE, Lassmann T, Hancock REW, Kicic A, Stick SM

Abstract
Early-life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with cystic fibrosis (CF). The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV), and augmented airway inflammation in CF has been attributed to dysregulated airway epithelial responses although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline. In response to RV, there were 1,442 and 896 differentially expressed genes in CF and non-CF airway epithelial cells, respectively. The core antiviral responses in CF and non-CF airway epithelial cells were mediated through interferon signaling although type 1 and 3 interferon signaling, when measured, were reduced in CF airway epithelial cells following viral challenge consistent with previous reports. The transcriptional responses in CF airway epithelial cells were more complex than in non-CF airway epithelial cells with diverse over-represented biological pathways, such as cytokine signaling and metabolic and biosynthetic pathways. Network analysis highlighted that the differentially expressed genes of CF airway epithelial cells' transcriptional responses were highly interconnected and formed a more complex network than observed in non-CF airway epithelial cells. We corroborate observations in fully differentiated air-liquid interface (ALI) cultures, identifying genes involved in IL-1 signaling and mucin glycosylation that are only dysregulated in the CF airway epithelial response to RV infection. These data provide novel insights into the CF airway epithelial cells' responses to RV infection and highlight potential pathways that could be targeted to improve antiviral and anti-inflammatory responses in CF.

PMID: 32765492 [PubMed - as supplied by publisher]

Targeting IgG Autoantibodies for Improved Cytotoxicity of Bactericidal Permeability Increasing Protein in Cystic Fibrosis.

Front Pharmacol. 2020;11:1098

Authors: McQuillan K, Gargoum F, Murphy MP, McElvaney OJ, McElvaney NG, Reeves EP

Abstract
In people with cystic fibrosis (PWCF), inflammation with concurrent infection occurs from a young age and significantly influences lung disease progression. Studies indicate that neutrophils are important effector cells in the pathogenesis of CF and in the development of anti-neutrophil cytoplasmic autoantibodies (ANCA). ANCA specific for bactericidal permeability increasing protein (BPI-ANCA) are detected in people with CF, and correlate with infection with Pseudomonas aeruginosa. The aim of this study was to determine the signaling mechanism leading to increased BPI release by CF neutrophils, while identifying IgG class BPI-ANCA in CF airways samples as the cause for impaired antimicrobial activity of BPI against P. aeruginosa. Plasma and/or bronchoalveolar lavage fluid (BAL) was collected from PWCF (n = 40), CF receiving ivacaftor therapy (n = 10), non-CF patient cohorts (n = 7) and healthy controls (n = 38). Plasma and BAL BPI and BPI-ANCA were measured by ELISA and GTP-bound Rac2 detected using an in vitro assay. The antibacterial effect of all treatments tested was determined by colony forming units enumeration. Levels of BPI are significantly increased in plasma (p = 0.007) and BALF (p < 0.0001) of PWCF. The signaling mechanism leading to increased degranulation and exocytosis of BPI by CF neutrophils (p = 0.02) involved enhancement of Rac2 GTP-loading (p = 0.03). The full-length BPI protein was detectable in all CF BAL samples and patients displayed ANCA with BPI specificity. IgG class autoantibodies were purified from CF BAL complexed to BPI (n=5), with IgG autoantibody cross-linking of antigen preventing BPI induced P. aeruginosa killing (p < 0.0001). Results indicate that the immune-mediated diminished antimicrobial defense, attributed to anti-BPI-IgG, necessitates the formation of a drug/immune complex intermediate that can maintain cytotoxic effects of BPI towards Gram-negative pathogens, with the potential to transform the current treatment of CF airways disease.

PMID: 32765284 [PubMed - as supplied by publisher]

Investigating the Effect of Nano-Curcumin on the Expression of Biofilm Regulatory Genes of Pseudomonas aeruginosa.

Infect Drug Resist. 2020;13:2477-2484

Authors: Sharifian P, Yaslianifard S, Fallah P, Aynesazi S, Bakhtiyari M, Mohammadzadeh M

Abstract
Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes serious nosocomial infections, especially in immunodeficient patients and cystic fibrosis, cancer, and burned individuals. The biofilm that plays an important role in the virulence of P. aeruginosa is under the regulation of quorum sensing and two-component regulatory systems of bacteria. Curcumin, an active phenolic extract of turmeric has shown an inhibitory effect on the biofilm formation of some pathogenic bacteria. Thus, the present study aims to evaluate the effect of Nano-Curcumin on the expression of major regulatory genes involved in biofilm formation of P. aeruginosa.
Materials and Methods: The biofilm formation of P. aeruginosa ATCC 10145 was assessed in the presence of 15, 20, and 25 µg/mL concentrations of Nano-Curcumin using the microplate titer method. The effect of Nano-Curcumin on the expression level of regulatory genes were determined by relative reverse transcriptase-realtime PCR.
Results: In the absence of Nano-Curcumin, P. aeruginosa strain ATCC 10145 strongly produced biofilm (3+) and in the presence of 15 and 20 µg/mL, biofilm formation was reduced to moderate (2+) and weak biofilm producer (1+), respectively. Nano-Curcumin at a concentration of 25µg/mL inhibited biofilm formation in P. aeruginosa. The expression of regulatory genes was not affected by biofilm inhibitory concentrations of Nano-Curcumin.
Conclusion: The antibiofilm mechanism of Curcumin is not related to the downregulation of regulatory systems of P. aeruginosa and probably it prevents the formation of a complete biofilm structure.

PMID: 32765020 [PubMed - as supplied by publisher]

SARS-CoV2 disrupts clinical research - the role of a rare disease-specific trial network.

Eur Respir J. 2020 Aug 06;:

Authors: van Koningsbruggen-Rietschel S, Dunlevy F, Bulteel V, Downey D, Dupont L

PMID: 32764115 [PubMed - as supplied by publisher]

Complete Genome Sequence of Stenotrophomonas maltophilia Strain CF13, Recovered from Sputum from an Australian Cystic Fibrosis Patient.

Microbiol Resour Announc. 2020 Aug 06;9(32):

Authors: Hamidian M, Lazenby J, To J, Hartstein R, Soares J, McNamara S, Whitchurch CB

Abstract
Stenotrophomonas maltophilia isolate CF13 is a multidrug-resistant isolate that was recovered in Sydney, Australia, in 2011, from a sputum sample from an individual with cystic fibrosis. The genome sequence of CF13 was completed using long- and short-read technologies.

PMID: 32763931 [PubMed - as supplied by publisher]

COVID-19 in a complex obstetric patient with cystic fibrosis.

Infect Dis Health. 2020 Jul 23;:

Authors: Walczak A, Wilks K, Shakhovskoy R, Baird T, Schlebusch S, Taylor C, Reid D, Choong K

Abstract
We report the first case of COVID-19 in a pregnant patient with cystic fibrosis. We describe the diagnosis, clinical course and management of the patient and their family with regards to clinical, social and infection control measures around delivery. This case highlights the importance of the cooperation of multidisciplinary teams to achieve good clinical outcomes in complex patients with COVID-19.

PMID: 32763024 [PubMed - as supplied by publisher]

Trikafta and Psychopathology in Cystic Fibrosis: A Case Report.

Psychosomatics. 2020 Jul 02;:

Authors: Tindell W, Su A, Oros SM, Rayapati AO, Rakesh G

PMID: 32763020 [PubMed - as supplied by publisher]

Cystic fibrosis drug approved for patients aged 6-11 years worked well in clinical practice.

Acta Paediatr. 2020 Aug 06;:

Authors: Loukou I, Petrocheilou A, Moustaki M, Katsagoni CN, Douros K

Abstract
Ivacaftor (IVA) and lumacaftor (LUM) modulate the cystic fibrosis (CF) transmembrane conductance regulator protein. IVA targets gating defects and LUM improves the conformational stability of the F508del mutation. This combined drug was approved for homozygous F508del CF patients aged 12 years or more in 2015 and was extended to children aged 6-11 in 2018.

PMID: 32762058 [PubMed - as supplied by publisher]

Pseudo-Bartter Syndrome in Chinese Children with Cystic Fibrosis: Clinical Features and Genotypic Findings.

Pediatr Pulmonol. 2020 Aug 06;:

Authors: Yuelin S, Xiaolei T, Jinrong L, Huiming L, Shunying Z

Abstract
OBJECTIVES: To characterize the clinical and genotypic features of Cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS) in Chinese children.
METHODS: We recruited and characterized the clinical manifestations of 12 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, and abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and sanger sequencing validation were performed to define the genotypes.
RESULTS: CF-PBS was accompanied by recurrent and/or persistent pneumonia (91.7%), pancreatitis (83.3%), vomiting and/or diarrhea (66.7%), failure to thrive and liver disease (58.3% respectively) among our patients. The predominant organisms found in the airways were Pseudomonas aeruginosa (83.3%) and Staphylococcus aureus (75.0%). The mean concentrations of blood gas and electrolytes were: pH 7.58, bicarbonate 40.8 mmol/L, sodium 125.9 mmol/L, chloride 77.5 mmol/L, and potassium 2.6 mmol/L. A high recurrence rate (50.0%) of CF-PBS was observed despite continued electrolyte supplementation during follow up. 19 different variants of CFTR gene were identified, and 10 of these were found to be novel observations (c.262_266delTTATA[p.L88FfsX21], c.579+2insACAT, c.1210-3C>G, c.1733T>C[p.L578P], c.2236_2246delGAGGCGATACTinsAAAAATC[p.E746KfsX8], c.3068T>G [p.I1023R], c.3635delT[p.V1212AfsX16], c.3859delG[p.G1287EfsX2], c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A[p.G970D] was the most common variant, with an allele frequency of 16.6%. A homozygous genotype of c.1521_1523delCTT[p.F508del] was discovered for the first time in patients of Chinese origin.
CONCLUSIONS: In China, CF-PBS usually presents early and recurs frequently in infancy, accompanied by multiple comorbidities. Recurrence of CF-PBS in school-going patients does occur but is rare. The p.G970D is the most frequent variant, with a significant ethnic tendency of Chinese origin. This article is protected by copyright. All rights reserved.

PMID: 32761997 [PubMed - as supplied by publisher]

Lung Function Deterioration in School Children with Cystic Fibrosis.

Pediatr Pulmonol. 2020 Aug 06;:

Authors: Walicka-Serzysko K, Postek M, Milczewska J, Sands D

Abstract
INTRODUCTION: Lung disease in cystic fibrosis (CF) begins early in life but the capabilities for detecting abnormalities of pulmonary dysfunction in children remain limited.
OBJECTIVES: The study aimed to evaluate the early progression of lung function by the analysis of pulmonary hyperinflation, ventilation inhomogeneity (VI), trapped gas and airway obstruction with age.
METHODS: One hundred CF children aged 7-18, divided into two groups aged 7-12 (n=40) and 13-18 (n=60), were enrolled. Patients performed MBNW tests and plethysmography for measurements of lung clearance index (LCI), functional residual capacity (FRCpleth , FRCMBNW ), volume of trapped gas (VT ), total resistance (Rtot ), and effective and specific effective airway resistance (Reff , sReff ).
RESULTS: We obtained a positive correlation of FRCpleth , FRCMBNW , and LCI with age. A linear correlation between FRCMBNW and FRCpleth (p<0.0001) was observed. Ventilation inhomogeneity was higher in the group of older patients (9.79 in the group aged 7-12 and 11.67 in the group aged 13-18). An increased effective specific airway resistance (sReff >2 z-score) was present in 58% of all subjects (50%, 63.3% respectively). Pulmonary hyperinflation (FRCpleth >2 z-score) was observed in 33% of all patients: 25%, 36.6 % respectively. Trapped gas (VT >2 z-score) was present in 18% of all children: 30%, 10% respectively.
CONCLUSIONS: A gradual decline in lung function is associated with an increase in ventilation inhomogeneity, airway obstruction, pulmonary hyperinflation and development of trapped gas. In children who cannot perform either spirometry or plethysmography, MBNW can deliver a measurement of LCI connecting with VI as well as FRCMBNW to indicate indirectly the increase of hyperinflation. This article is protected by copyright. All rights reserved.

PMID: 32761970 [PubMed - as supplied by publisher]

Rituximab for treating inhibitors in people with inherited severe hemophilia.

Cochrane Database Syst Rev. 2020 Aug 03;8:CD010810

Authors: Jiang L, Liu Y, Zhang L, Santoro C, Rodriguez A

Abstract
BACKGROUND: Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review.
OBJECTIVES: To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries. Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 19 March 2020.
SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia.
DATA COLLECTION AND ANALYSIS: No randomized controlled trials matching the selection criteria were eligible for inclusion.
MAIN RESULTS: No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified.
AUTHORS' CONCLUSIONS: We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

PMID: 32761818 [PubMed - in process]