Front Mol Biosci. 2022 Mar 9;9:850261. doi: 10.3389/fmolb.2022.850261. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF), due to pathogenic variants in CFTR gene, is associated with chronic infection/inflammation responsible for airway epithelium alteration and lung function decline. Modifier genes induce phenotype variability between people with CF (pwCF) carrying the same CFTR variants. Among these, the gene encoding for the amino acid transporter SLC6A14 has been associated with lung disease severity and age of primary airway infection by the bacteria Pseudomonas aeruginosa. In this study, we investigated whether the single nucleotide polymorphism (SNP) rs3788766, located within SLC6A14 promoter, is associated with lung disease severity in a large French cohort of pwCF. We also studied the consequences of this SNP on SLC6A14 promoter activity using a luciferase reporter and the role of SLC6A14 in the mechanistic target of rapamycin kinase (mTOR) signaling pathway and airway epithelial repair. We confirm that SLC6A14 rs3788766 SNP is associated with lung disease severity in pwCF (p = 0.020; n = 3,257, pancreatic insufficient, aged 6-40 years old), with the minor allele G being deleterious. In bronchial epithelial cell lines deficient for CFTR, SLC6A14 promoter activity is reduced in the presence of the rs3788766 G allele. SLC6A14 inhibition with a specific pharmacological blocker reduced 3H-arginine transport, mTOR phosphorylation, and bronchial epithelial repair rates in wound healing assays. To conclude, our study highlights that SLC6A14 genotype might affect lung disease severity of people with cystic fibrosis via mTOR and epithelial repair mechanism modulation in the lung.

PMID:35372502 | PMC:PMC8965518 | DOI:10.3389/fmolb.2022.850261

SAGE Open Med. 2022 Mar 30;10:20503121221086712. doi: 10.1177/20503121221086712. eCollection 2022.

ABSTRACT

OBJECTIVE: Mental health problems among children and adolescents are increasingly observed during the outbreak of COVID-19, leading to significant healthcare concerns. Survey studies provide unique opportunities for research during this pandemic, while there are no existing systematic reviews in this setting. The objective was to summarize existing survey studies addressing the effects of the current COVID-19 pandemic on the mental health of children and adolescents.

METHODS: For this systematic review, we performed an electronic search in multiple databases from December 2019 to December 2020. The quality appraisal of the included studies was performed with the Critical Appraisal Skills Programme Qualitative Checklist. Because of the high methodological heterogeneity between studies, a narrative synthesis of the qualitative data was used.

RESULTS: In total, 35 survey studies with 65,508 participants, ranging from 4 to 19 years of age, are included in this review. Anxiety (28%), depression (23%), loneliness (5%), stress (5%), fear (5%), tension (3%), anger (3%), fatigue (3%), confusion (3%), and worry (3%) were the most common mental health issues reported. Children and adolescents with psychiatric and/or developmental disorders, such as severe obesity, chronic lung disease, attention deficit hyperactivity disorder, cystic fibrosis, and obsessive-compulsive disorders, were especially vulnerable to the mental health effects of the COVID-19 pandemic. Age, gender, psychological quality, and negative coping strategies were identified as risk factors for the development of mental health problems. Social and family support, along with a positive coping style, was associated with better outcomes.

CONCLUSION: The impact of the COVID-19 pandemic on mental health of children and adolescents is multifaceted and substantial. Survey studies regarding child and adolescent mental health amid COVID-19 indicated that anxiety, depression, loneliness, stress, and tension are the most observed symptoms. Positive coping strategies with family and social support may be important to achieving better outcomes. Due to limited available evidence, more well-designed studies in this area are urgently needed.

PMID:35371484 | PMC:PMC8972920 | DOI:10.1177/20503121221086712

Front Pharmacol. 2022 Mar 17;13:846151. doi: 10.3389/fphar.2022.846151. eCollection 2022.

ABSTRACT

Background: Many pediatric inflammatory bowel disease (IBD) patients are now using biosimilars of anti-tumor necrosis factor-α (TNF-α), with increasing trends in recent years. This study reviewed all available data regarding the use of biosimilars in children with IBD. Methods: PubMed, Google Scholar, Scopus, and CENTRAL databases were searched through keywords; inflammatory bowel diseases, Crohn's disease, ulcerative colitis, biosimilar and child were combined using "AND" and "OR." Original research articles involving pediatric patients receiving one of the biosimilar medications based on the anti-TNF-α biologic drugs approved for pediatric IBD treatment, independently from efficacy and drug response, were included. Results: Nine studies were included in the evidence synthesis. CT-P13 was the biosimilar used in all studies. Four studies assessed the induction effectiveness of CT-P13. Clinical response and remission rates of biosimilar treatment were 86-90% and 67-68%, respectively, and they were not significantly different to the originator group. Five prospective studies on patients elected to switch from originator IFX to CT-P13 yielded similar results. Adverse events related to CT-P13 were mostly mild. The most frequently reported were upper respiratory tract infections. The switch from the originator had no significant impact on immunogenicity. Conclusion: The current review showed reported CT-P13 effectiveness as measured by clinical response and/or remission rates after induction or during maintenance and suggest that there is no significant difference with that of the originator IFX. Further studies are warranted, including clinical, and pharmacovigilance studies.

PMID:35370732 | PMC:PMC8970685 | DOI:10.3389/fphar.2022.846151

Patient Prefer Adherence. 2022 Mar 25;16:771-780. doi: 10.2147/PPA.S353434. eCollection 2022.

ABSTRACT

PURPOSE: Low adherence to medication via nebulisers is linked to poor clinical outcomes for people with Cystic Fibrosis (PWCF). Advances in technology allow electronic monitoring of nebuliser usage and feedback of objective adherence data to PWCF and clinical teams caring for them. CFHealthHub is a new intervention that collects and displays objective adherence data in easy-to-read formats with the aim of improving nebuliser adherence and health. There is little understanding of how objective adherence data is perceived by PWCF and healthcare professionals (HCPs).

PATIENTS AND METHODS: A qualitative study using semi-structured interviews with 22 PWCF and 31 HCPs who had used the CFHealthHub intervention.

RESULTS: Objective adherence data was welcomed by the majority of PWCF in the sample, and HCP delivering the intervention, because the data allowed PWCF to reflect on patterns of adherence or non-adherence. Ease of use and characteristics of data display were important, particularly the use of a "traffic light" system to allow PWCF to easily see if they were meeting their adherence targets. For PWCF objective adherence data was used as "proof to self", offering reassurance to high adherers, and a wake-up call to those with lower levels of adherence. It could also provide 'proof to others' where PWCF had higher levels of adherence than HCP or family members believed. The data could sometimes change HCP perceptions of PWCF's identities as poor adherers. Where adherence was not high, data was used to facilitate honest discussions between PWCF and HCPs about how to increase adherence. HCPs perceived that it was important to use the data positively to motivate, rather than criticise, PWCF.

CONCLUSION: Objective nebuliser adherence data in CFHealthHub can offer proof of adherence to PWCF and HCPs. It is important to use it constructively to facilitate discussions on how to improve adherence.

PMID:35370406 | PMC:PMC8965329 | DOI:10.2147/PPA.S353434

J Cyst Fibros. 2022 Mar 31:S1569-1993(22)00086-8. doi: 10.1016/j.jcf.2022.03.009. Online ahead of print.

ABSTRACT

BACKGROUND: Elevated blood eosinophil counts are linked to worse outcomes in asthma and COPD, but have yet to be well characterized in CF. We hypothesized that higher stable visit blood eosinophil counts are associated with increased rates of lung function decline and pulmonary exacerbations (PEx).

METHODS: We performed a retrospective analysis of adult CF patients (≥19 years) enrolled from 2012 to 2018 in a prospective cohort study focused on blood biomarkers. We included individuals with at least one year of follow-up post-stable visit blood draw and compared clinical characteristics by blood eosinophil count (<300 cells/µL vs. ≥300 cells/µL). We used multivariate mixed-effects linear regression to estimate annual change in ppFEV1. Multivariable poisson and linear regression models were used to estimate rate of PEx requiring IV antibiotics and to compare CF Respiratory Symptom Diary-Chronic Respiratory Infection Symptom Scores (CFRSD-CRISS), respectively.

RESULTS: Of 109 patients, 17 (15.6%) had eosinophil counts ≥300 cells/µL. After adjustment for age, sex, BMI, and baseline ppFEV1, there was no association between high vs. low eosinophil group and rates of lung function decline (difference in slope -0.04%/y; 95% CI -1.5 to +1.4) or rates of PEx requiring IV antibiotics (IRR 1.46; 95% CI 0.75 to 2.65). The high eosinophil group had a higher mean CFRSD-CRISS score at stable visit (adjusted mean difference 9.3; 95% CI 2.9 to 16.0).

CONCLUSIONS: The high eosinophil group experienced increased respiratory symptoms, but the rates of lung function decline and PEx were comparable between groups.

PMID:35370086 | DOI:10.1016/j.jcf.2022.03.009

IDCases. 2022 Mar 28;28:e01491. doi: 10.1016/j.idcr.2022.e01491. eCollection 2022.

ABSTRACT

A 7-year-old cystic fibrosis patient with increased cough, new pulmonary infiltrate, and declining pulmonary function was diagnosed with clarithromycin resistant Mycobacterium abscessus infection. Treatment was initiated with clofazimine, linezolid and cefoxitin; she responded well to therapy and achieved microbiological clearance after completion of 12-month treatment. One year later, she had re-emergence of worsening symptoms and her sputum culture again grew clarithromycin resistant M. abscessus. Using a laboratory developed whole genome sequencing (WGS) test, the bacterium was determined to be the same strain with the same resistance mechanisms, indicating a relapse. This was deemed a critical element of clinical information, as the isolation of a genetically distinct organism would have indicated a new infection and would have served as evidence that a 12-month regimen was likely sufficient to achieve eradication. The confirmation of a relapse prompted the prolongation of the therapy plan to a goal of 24 months. Reinfection and relapse are great challenges in patients with cystic fibrosis who may acquire new strain of M. abscessus from the environment, may harbor multiple subpopulations of bacteria, or may have persistent infections but intermittent bacteria shedding that could not be eradicated. WGS has emerged as a powerful molecular tool to accurately differentiate re-infection from relapse thus solving this conundrum.

PMID:35369567 | PMC:PMC8968000 | DOI:10.1016/j.idcr.2022.e01491

Front Microbiol. 2022 Mar 18;13:867449. doi: 10.3389/fmicb.2022.867449. eCollection 2022.

ABSTRACT

Engineered liposomes composed of the naturally occurring lipids sphingomyelin (Sm) and cholesterol (Ch) have been demonstrated to efficiently neutralize toxins secreted by Gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. Here, we hypothesized that liposomes are capable of neutralizing cytolytic virulence factors secreted by the Gram-negative pathogen Pseudomonas aeruginosa. We used the highly virulent cystic fibrosis P. aeruginosa Liverpool Epidemic Strain LESB58 and showed that sphingomyelin (Sm) and a combination of sphingomyelin with cholesterol (Ch:Sm; 66 mol/% Ch and 34 mol/% Sm) liposomes reduced lysis of human bronchial and red blood cells upon challenge with the Pseudomonas secretome. Mass spectrometry of liposome-sequestered Pseudomonas proteins identified the virulence-promoting hemolytic phospholipase C (PlcH) as having been neutralized. Pseudomonas aeruginosa supernatants incubated with liposomes demonstrated reduced PlcH activity as assessed by the p-nitrophenylphosphorylcholine (NPPC) assay. Testing the in vivo efficacy of the liposomes in a murine cutaneous abscess model revealed that Sm and Ch:Sm, as single dose treatments, attenuated abscesses by >30%, demonstrating a similar effect to that of a mutant lacking plcH in this infection model. Thus, sphingomyelin-containing liposome therapy offers an interesting approach to treat and reduce virulence of complex infections caused by P. aeruginosa and potentially other Gram-negative pathogens expressing PlcH.

PMID:35369481 | PMC:PMC8971843 | DOI:10.3389/fmicb.2022.867449

Front Cell Infect Microbiol. 2022 Mar 16;11:764585. doi: 10.3389/fcimb.2021.764585. eCollection 2021.

ABSTRACT

To date, investigations of the microbiota in the lungs of people with Cystic Fibrosis (PWCF) have primarily focused on microbial community composition in luminal mucus, with fewer studies observing the microbiota in tissue samples from explanted lung tissue. Here, we analysed both tissue and airway luminal mucus samples extracted from whole explanted lungs of PWCF and unused donor lungs. We determined if the lung microbiota in end-stage CF varied within and between patients, was spatially heterogeneous and related to localized structural damage. Microbial community composition was determined by Illumina MiSeq sequencing and related to the CF-Computed Tomography (CT) score and features of end-stage lung disease on micro-CT. Ninety-eight CF tissue (n=11 patients), 20 CF luminal mucus (n=8 patients) and 33 donor tissue (n=4 patients) samples were analysed. Additionally, we compared 20 paired CF tissue and luminal mucus samples that enabled a direct "geographical" comparison of the microbiota in these two niches. Significant differences in microbial communities were apparent between the 3 groups. However, overlap between the three groups, particularly between CF and donor tissue and CF tissue and CF luminal mucus was also observed. Microbial diversity was lower in CF luminal mucus compared to CF tissue, with dominance higher in luminal mucus. For both CF and donor tissue, intra- and inter-patient variability in ecological parameters was observed. No relationships were observed between ecological parameters and CF-CT score, or features of end-stage lung disease. The end-stage CF lung is characterised by a low diversity microbiota, differing within and between individuals. No clear relationship was observed between regional microbiota variation and structural lung damage.

PMID:35368453 | PMC:PMC8966769 | DOI:10.3389/fcimb.2021.764585

J Cyst Fibros. 2022 Mar 30:S1569-1993(22)00084-4. doi: 10.1016/j.jcf.2022.03.007. Online ahead of print.

ABSTRACT

BACKGROUND: Club cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF).

METHODS: We used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEV1 levels in adolescence (LLF and HLF groups, respectively; N = 130-per-group). Single nucleotide variants (SNVs) in the SCGB1A1, EHF-APIP loci were tested for association with circulating CC16 and with decline of FEV1 and FEV1/FVC% predicted levels between ages 7-16 using mixed models.

RESULTS: Compared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p = 0.0002) and higher levels of the normalized inflammatory score (-0.21 vs 0.21, p = 0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p<0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEV1/FVC and, marginally, FEV1 (p = 0.003 and 0.025, respectively; N = 611 participants, 20,801 lung function observations).

CONCLUSIONS: Serum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240 A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.

PMID:35367162 | DOI:10.1016/j.jcf.2022.03.007

J Pediatr Nurs. 2022 Mar 30:S0882-5963(22)00073-2. doi: 10.1016/j.pedn.2022.03.007. Online ahead of print.

ABSTRACT

PURPOSE: The experience of healthcare transition from pediatric to adult care in cystic fibrosis (CF) remains poorly understood, particularly among racially and ethnically diverse adolescents and young adults (AYAs) with CF. The objective of this qualitative study was to explore the perspectives of a diverse sample of AYAs with CF at one urban academic medical center regarding healthcare transition.

DESIGN AND METHODS: Guided by qualitative descriptive methodology, we purposively selected AYAs who represented the pre and post transition experience: some AYAs had experienced the transition preparation program CF R.I.S.E. Demographic information and responsibility for self-management behaviors were collected using an online survey. Semi-structured video interviews were conducted following an iterative interview guide. A codebook directed inductive coding. QSR NVivo Version 12 software was used to organize the data.

RESULTS: 12 AYAs with CF were enrolled (25% female, 25% Black AYA, 33% Hispanic/Latina/o AYA, 50% White AYA; mean age 20.8 years). Three themes were identified: independent care of the whole self, preparing for change and the unknown and transition experiences vary.

CONCLUSIONS: Not all participants experienced a smooth transition. Participants identified suggestions for the development of transition preparation interventions, specifically around involving AYAs in transition decisions and beginning transition preparation early in adolescence.

PRACTICE IMPLICATIONS: Participants expressed uncertainty about transition when they felt little control over the process or lacked sufficient information about adult care. Therefore, comprehensive early transition preparation for all AYAs with CF with a focus on involving AYAs in transition decisions is recommended.

PMID:35367087 | DOI:10.1016/j.pedn.2022.03.007

Pathophysiology. 2021 Mar 10;28(1):155-188. doi: 10.3390/pathophysiology28010011.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the CF Transmembrane Conductance Regulator (CFTR) gene determine the expression of a dysfunctional protein that, in turn, triggers a pathophysiological cascade, leading to airway epithelium injury and remodeling. In vitro and in vivo studies point to a dysregulated regeneration and wound repair in CF airways, to be traced back to epithelial CFTR lack/dysfunction. Subsequent altered ion/fluid fluxes and/or signaling result in reduced cell migration and proliferation. Furthermore, the epithelial-mesenchymal transition appears to be partially triggered in CF, contributing to wound closure alteration. Finally, we pose our attention to diverse approaches to tackle this defect, discussing the therapeutic role of protease inhibitors, CFTR modulators and mesenchymal stem cells. Although the pathophysiology of wound repair in CF has been disclosed in some mechanisms, further studies are warranted to understand the cellular and molecular events in more details and to better address therapeutic interventions.

PMID:35366275 | DOI:10.3390/pathophysiology28010011

J Thorac Cardiovasc Surg. 2022 Mar 1:S0022-5223(22)00228-8. doi: 10.1016/j.jtcvs.2022.01.048. Online ahead of print.

NO ABSTRACT

PMID:35365362 | DOI:10.1016/j.jtcvs.2022.01.048

BMC Pulm Med. 2022 Apr 1;22(1):122. doi: 10.1186/s12890-022-01903-5.

ABSTRACT

BACKGROUND: Lung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE).

METHODS: Data were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE.

RESULTS: We collected 313 multiple breath washout tests on 125 children aged 5.5-16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV1 but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval [CI] 2.6-4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34-0.62).

CONCLUSIONS: LCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV1. A less severe phenotype translates into a lower risk of PE relapse.

PMID:35365111 | DOI:10.1186/s12890-022-01903-5

BMC Genomics. 2022 Apr 1;23(1):252. doi: 10.1186/s12864-022-08466-z.

ABSTRACT

Cystic fibrosis (CF, MIM# 219,700) is an autosomal recessive disease caused by pathogenic variants within the CFTR gene. It was shown that genetic variants located in cis can affect disease severity or treatment response because of additive or epistatic effects. Studies on the prevalence of complex alleles in Russian CF patients have just begun. Aim To evaluate frequencies and genetic background of complex alleles carrying c.1521_1523delCTT (F508del) and c.1399C>T (L467F), c.2562T>G (T854=) or c.4389G>A (Q1463=) in cis; to determine clinical consequences of complex allele c.[1399C>T;1521_1523delCTT] ([L467;F508del]) in Russian CF patients. Methods Sequencing of coding regions of CFTR gene and analysis of polymorphic markers in CF patients carrying F508del variant. Comparing of clinical features in two groups patients having genotypes [L467F;F508del];[F508del] (group 1) and [F508del];[F508del] (group 2). Results Frequency of [L467F;F508del] allele linked to 2-2-21-6-17-13 haplotype was 4.42%, of [F508del;T854=;Q1463=] allele linked to haplotype 1-2-21-6-17-13 - 2.2% in F508del chromosomes. No differences in disease severity in patients carrying complex allele [L467F;F508del] and patients homozygous for F508del was found. Conclusion The frequency of complex alleles associated with F508del was at least 6.6% in Russian CF patients, which should be taken into account for the decision on optimal treatment options with CFTR modulators.

PMID:35365085 | DOI:10.1186/s12864-022-08466-z

Curr Opin Pharmacol. 2022 Mar 29;64:102206. doi: 10.1016/j.coph.2022.102206. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a multi-organ genetic disease caused by loss of function of CFTR, a cAMP-regulated chloride channel expressed in epithelial cells. In airway epithelia, CFTR-dependent chloride secretion is required to humidify mucosal surface and to allow efficient mucociliary clearance. In CF patients, CFTR deficit causes chronic bacterial infections and airway obstruction by mucus accumulation. Airway epithelial cells also express TMEM16A (ANO1), a second type of chloride channel, whose activity is controlled by cytosolic calcium concentration. Pharmacological stimulation of TMEM16A could be beneficial to bypass CFTR defect. However, the relationship of TMEM16A with mucus hypersecretion needs to be clarified. Multiple large scale screenings have been carried out to identify inhibitors and activators/potentiators of TMEM16A, including CaCCinh-A01, T16inh-A01, Ani9, TMinh-23, MONNA, Eact, and ETX001. Such compounds are important as research tools, to assess the role of TMEM16A in health and disease, and as possible therapeutic agents.

PMID:35364521 | DOI:10.1016/j.coph.2022.102206

Am J Respir Cell Mol Biol. 2022 Apr 1. doi: 10.1165/rcmb.2021-0341LE. Online ahead of print.

NO ABSTRACT

PMID:35363994 | DOI:10.1165/rcmb.2021-0341LE

Sci Adv. 2022 Apr;8(13):eabm9718. doi: 10.1126/sciadv.abm9718. Epub 2022 Apr 1.

ABSTRACT

Cystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway model of CF revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Using proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, CF sputum proteomics analyses revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and in SMGs of the CF lung.

PMID:35363522 | DOI:10.1126/sciadv.abm9718

Pediatr Pulmonol. 2022 Mar 31. doi: 10.1002/ppul.25917. Online ahead of print.

ABSTRACT

Cystic fibrosis liver disease (CFLD) is the third leading cause of mortality in cystic fibrosis (CF), with a wide spectrum of manifestations This article is protected by copyright. All rights reserved.

PMID:35362232 | DOI:10.1002/ppul.25917

BMJ Open. 2022 Mar 31;12(3):e053625. doi: 10.1136/bmjopen-2021-053625.

ABSTRACT

INTRODUCTION: Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disorder that causes destruction and permanent dilatation of the airways, resulting in excessive sputum production, repeated infection and inflammation. A need for high-quality and specialised care has been highlighted in recent years. N-acetylcysteine (NAC) is a widely used mucolytic agent in respiratory diseases that not only possesses a property to enhance secretion clearance, but also exhibits antioxidant and anti-inflammatory effects. However, the efficacy and safety of NAC are not well described in idiopathic or postinfective non-CF bronchiectasis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of NAC in patients with idiopathic or postinfective non-CF bronchiectasis.

METHODS AND ANALYSIS: PubMed/Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials will be searched from inception to 1 March 2022 for eligible randomised controlled trials that investigating the effects of NAC on exacerbations, health-related quality of life, lung functions, sputum volume and colour, inflammation markers, exercise capacity and adverse events in patients with idiopathic or postinfective non-CF bronchiectasis, with ongoing trials being identified by searches on the websites of Chinese Clinical Trial Registry and ClinicalTrials.gov. Two independent reviewers will identify eligible studies, two will fulfil the data extraction and three will perform the quality appraisal. To generate more accurate analyses, the Grading of Recommendations Assessment, Development and Evaluation will be used to grade the evidence. χ2 test and I2 statistic will be used to assess heterogeneity. Subgroup analyses and meta-regression will be used to explore potential sources of heterogeneity. The potential publication bias will be examined using funnel plots.

ETHICS AND DISSEMINATION: No research ethics approval is required in this study because it is a systematic review. The results of this study are expected to be disseminated through peer-reviewed journals and conferences.

TRIAL REGISTRATION NUMBER: CRD42021239438.

PMID:35361640 | DOI:10.1136/bmjopen-2021-053625

Dig Liver Dis. 2022 Mar 9:S1590-8658(22)00198-0. doi: 10.1016/j.dld.2022.02.010. Online ahead of print.

ABSTRACT

BACKGROUND: Aim of the present report was to investigate the repercussions of COVID-19 pandemic on the procedural volumes and on the main indications of pediatric digestive endoscopy in Italy.

METHODS: An online survey was distributed at the beginning of December 2020 to Italian digestive endoscopy centers. Data were collected comparing two selected time intervals: the first from 1st of February 2019 to 30th June 2019 and the second from 1st February 2020 to 30th June 2020.

RESULTS: Responses to the survey came from 24 pediatric endoscopy Units. Globally, a reduction of 37.2% was observed between 2019 and 2020 periods with a significant decrease in median number of procedures (111 vs 57, p < 0.001). Both the median number of procedures performed for new diagnoses and those for follow-up purposes significantly decreased in 2020 (63 vs 36, p < 0.001 and 42 vs 21, p< 0.001, respectively). We reported a drastic reduction of procedures performed for suspected Celiac Disease and Functional Gastrointestinal Disorders (55.1% and 58.0%, respectively). Diagnostic endoscopies for suspected IBD decreased of 15.5%, whereas procedures for Mucosal Healing (MH) assessment reduced of 48.3%.

CONCLUSIONS: Our study provides real-world data outlining the meaningful impact of COVID-19 on pediatric endoscopy practice in Italy.

PMID:35361566 | DOI:10.1016/j.dld.2022.02.010