Front Pediatr. 2021 Feb 22;9:654578. doi: 10.3389/fped.2021.654578. eCollection 2021.

NO ABSTRACT

PMID:33692978 | PMC:PMC7937638 | DOI:10.3389/fped.2021.654578

Front Immunol. 2021 Feb 22;12:625597. doi: 10.3389/fimmu.2021.625597. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa is a key pathogen of chronic infections in the lungs of cystic fibrosis patients and in patients suffering from chronic wounds of diverse etiology. In these infections the bacteria congregate in biofilms and cannot be eradicated by standard antibiotic treatment or host immune responses. The persistent biofilms induce a hyper inflammatory state that results in collateral damage of the adjacent host tissue. The host fails to eradicate the biofilm infection, resulting in hindered remodeling and healing. In the present review we describe our current understanding of innate and adaptive immune responses elicited by P. aeruginosa biofilms in cystic fibrosis lung infections and chronic wounds. This includes the mechanisms that are involved in the activation of the immune responses, as well as the effector functions, the antimicrobial components and the associated tissue destruction. The mechanisms by which the biofilms evade immune responses, and potential treatment targets of the immune response are also discussed.

PMID:33692800 | PMC:PMC7937708 | DOI:10.3389/fimmu.2021.625597

Int J Mass Spectrom. 2021 May;463:116550. doi: 10.1016/j.ijms.2021.116550. Epub 2021 Feb 14.

ABSTRACT

Neutrophil elastase is a serine protease released by neutrophils, and its dysregulation has been associated with a variety of debilitating pathologies, most notably cystic fibrosis. This protein is also a prominent component of the so-called neutrophil extracellular traps (NETs), whose formation is a part of the innate immunity response to invading pathogens, but also contributes to a variety of pathologies ranging from autoimmune disorders and inflammation to cancer to thrombotic complications in COVID-19. Retention of neutrophil elastase within NETs is provided by ejected DNA chains, although this protein is also capable of interacting with a range of other endogenous polyanions, such as heparin and heparan sulfate. In this work, we evaluate the feasibility of using native mass spectrometry (MS) as a means of studying interactions of neutrophil elastase with heparin oligomers ranging from structurally homogeneous synthetic pentasaccharide fondaparinux to relatively long (up to twenty saccharide units) and structurally heterogeneous chains produced by partial depolymerization of heparin. The presence of heterogeneous glycan chains on neutrophil elastase and the structural heterogeneity of heparin oligomers render the use of standard MS to study their complexes impractical. However, supplementing MS with limited charge reduction in the gas phase allows meaningful data to be extracted from MS measurements. In contrast to earlier molecular modeling studies where a single heparin-binding site was identified, our work reveals the existence of multiple binding sites, with a single protein molecule being able to accommodate up to three decasaccharides. The measurements also reveal the ability of even relatively short heparin oligomers to bridge two protein molecules, suggesting that characterization of these complexes using native MS can shed light on the structural properties of NETs. Lastly, the use of MS allows the binding preferences of heparin oligomers to neutrophil elastase to be studied with respect to specific structural properties of heparin, such as the level of sulfation (i.e., charge density). All experimental measurements are carried out in parallel with molecular dynamics simulations of the protein/heparin oligomer systems, which are in remarkable agreement with the experimental data and highlight the role of electrostatic interactions as dominant forces governing the formation of these complexes.

PMID:33692650 | PMC:PMC7939139 | DOI:10.1016/j.ijms.2021.116550

BMC Infect Dis. 2021 Mar 10;21(1):251. doi: 10.1186/s12879-021-05944-9.

ABSTRACT

BACKGROUND: Mycobacterium (M) talmoniae isolated from a patient with cystic fibrosis was first described in 2017, and cases of M. talmoniae remain exceedingly rare.

CASE PRESENTATION: A 51-year-old woman had respiratory symptoms for 10 years. Diffuse panbronchiolitis (DPB) was detected at the first visit at our hospital. A cavity lesion in the apex of the left lung was found, and sputum and bronchoalveolar lavage fluid were acid-fast bacillus (AFB) smear- and culture-positive besides Pseudomonas aeruginosa. M. talmoniae was finally identified, and the standard combination therapy for non-tuberculous mycobacteria (NTM) was administered for 2 y referring to the drug-susceptibility test. Thereafter, the AFB culture was negative, the wall thickness of the lung cavity was ameliorated, and oxygen saturation improved.

CONCLUSIONS: We encountered a rare case of M. talmoniae with DPB, for which standard combination therapy was effective. M. talmoniae may be considered a potential pathogen of lung disease, especially in patients with bronchiectatic lesions.

PMID:33691626 | DOI:10.1186/s12879-021-05944-9

Eur J Med Chem. 2021 Jan 30;216:113240. doi: 10.1016/j.ejmech.2021.113240. Online ahead of print.

NO ABSTRACT

PMID:33691259 | DOI:10.1016/j.ejmech.2021.113240

PLoS Pathog. 2021 Mar 10;17(3):e1009375. doi: 10.1371/journal.ppat.1009375. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated neutrophilic inflammation in model systems. In this study, we investigated how lasR mutants modulate airway epithelial membrane bound ICAM-1 (mICAM-1), a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo. We demonstrated that LasR-deficient strains induce increased mICAM-1 levels in airway epithelial cells compared to wild-type strains, an effect attributable to the loss of mICAM-1 degradation by LasR-regulated proteases and associated with enhanced neutrophil adhesion. In a subacute airway infection model, we also observed that lasR mutant-infected mice displayed greater airway epithelial ICAM-1 expression and increased neutrophilic pulmonary inflammation. Our findings provide new insights into the intricate interplay between lasR mutants, LasR-regulated proteases and airway epithelial ICAM-1 expression, and reveal a new mechanism involved in the exaggerated inflammatory response induced by lasR mutants.

PMID:33690714 | DOI:10.1371/journal.ppat.1009375

Am J Physiol Cell Physiol. 2021 Mar 10. doi: 10.1152/ajpcell.00481.2020. Online ahead of print.

ABSTRACT

Adenosine receptors (ADORs) are G-protein coupled purinoceptors that have several functions including regulation of chloride secretion via CFTR in human airway and kidney. We cloned an ADOR from Squalus acanthias (shark) that likely regulates CFTR in the rectal gland. Phylogenic- and expression- analyses indicate that elasmobranch ADORs are non-olfactory, and appear to represent extant predecessors of mammalian ADORs. We therefore designate the shark ADOR as the A0 receptor. We co-expressed A0with CFTR in Xenopus laevis oocytes and characterized the coupling of A0to the chloride channel. Two electrode voltage clamping was performed and current-voltage (I-V) responses were recorded to monitor CFTR status. Only in A0- and CFTR- co-injected oocytes did adenosine analogs produce a significant concentration-dependent activation of CFTR consistent with its electrophysiological signature. A pharmacological profile for A0 was obtained for ADOR agonists and antagonists that differed markedly from all mammalian ADOR subtypes (agonists: R-PIA > S-PIA > CGS21680 > CPA > 2ClADO > CV1808 = DPMA > NECA) and (antagonists: DPCPX > PD115199 > 8PT > CGC > CGS15943). Structures of human ADORs permitted a high-confidence homology model of the shark A0 core which revealed unique structural features of ancestral receptors. We conclude: (1) A0 is a novel and unique adenosine receptor ancestor by functional and structural criteria; (2) A0 likely activates CFTR in vivo and this receptor activates CFTR in oocytes indicating an evolutionary coupling between ADORs and chloride secretion; and (3) A0 appears to be a non-olfactory evolutionary ancestor of all four mammalian ADOR subtypes.

PMID:33689481 | DOI:10.1152/ajpcell.00481.2020

Respir Care. 2021 Mar 9:respcare.07702. doi: 10.4187/respcare.07702. Online ahead of print.

ABSTRACT

BACKGROUND: The treatment of cystic fibrosis involves the use of drugs delivered by nebulizer systems, and adequate functioning of the compressors and nebulizers is essential. We hypothesized that compressors of nebulizer systems used by individuals with cystic fibrosis would not work properly. Therefore, we aimed to assess the performance of the compressors from nebulizer systems used by individuals with cystic fibrosis.

METHODS: This is a cross-sectional study to assess the performance of compressors from nebulizer systems used by subjects with cystic fibrosis registered at the Cystic Fibrosis Patient Association in Minas Gerais, Brazil. Compressors ( Proneb Ultra II) brought by the individuals were tested with new nebulizer parts (Pari LC plus) to assess the variables of nebulization efficiency, including residual volume, solution output, and aerosol output rate. Compression performance was assessed by measuring the operating pressure using a PARI PG101 manometer.

RESULTS: The performance of 146 compressors was analyzed. Fifty-seven (39%) of the compressors were ineffective, with operating pressure values well below the manufacturer's technical reference and the compressor time used for a median time of 36 (15 days to 156 months). The systems with low pressure values demonstrated significantly worse results for nebulization efficiency variables, and a significant correlation was found between residual volume (r = -0.5, P < .001), solution output (r = +0.5, P < .001), and aerosol output rate (r = +0.5, P < .001), and operating pressure values.

CONCLUSIONS: A significant number of compressors generate low operating pressure values. These systems showed a compromised efficiency of nebulization, indicating that the pressure generated by the compressor is a critical aspect of treatment efficiency.

PMID:33688089 | DOI:10.4187/respcare.07702

mBio. 2021 Mar 9;12(2):e02863-20. doi: 10.1128/mBio.02863-20.

ABSTRACT

In cystic fibrosis, dynamic and complex communities of microbial pathogens and commensals can colonize the lung. Cultured isolates from lung sputum reveal high inter- and intraindividual variability in pathogen strains, sequence variants, and phenotypes; disease progression likely depends on the precise combination of infecting lineages. Routine clinical protocols, however, provide a limited overview of the colonizer populations. Therefore, a more comprehensive and precise identification and characterization of infecting lineages could assist in making corresponding decisions on treatment. Here, we describe longitudinal tracking for four cystic fibrosis patients who exhibited extreme clinical phenotypes and, thus, were selected from a pilot cohort of 11 patients with repeated sampling for more than a year. Following metagenomics sequencing of lung sputum, we find that the taxonomic identity of individual colonizer lineages can be easily established. Crucially, even superficially clonal pathogens can be subdivided into multiple sublineages at the sequence level. By tracking individual allelic differences over time, an assembly-free clustering approach allows us to reconstruct multiple lineage-specific genomes with clear structural differences. Our study showcases a culture-independent shotgun metagenomics approach for longitudinal tracking of sublineage pathogen dynamics, opening up the possibility of using such methods to assist in monitoring disease progression through providing high-resolution routine characterization of the cystic fibrosis lung microbiome.IMPORTANCE Cystic fibrosis patients frequently suffer from recurring respiratory infections caused by colonizing pathogenic and commensal bacteria. Although modern therapies can sometimes alleviate respiratory symptoms by ameliorating residual function of the protein responsible for the disorder, management of chronic respiratory infections remains an issue. Here, we propose a minimally invasive and culture-independent method to monitor microbial lung content in patients with cystic fibrosis at minimal additional effort on the patient's part. Through repeated sampling and metagenomics sequencing of our selected cystic fibrosis patients, we successfully classify infecting bacterial lineages and deconvolute multiple lineage variants of the same species within a given patient. This study explores the application of modern computational methods for deconvoluting lineages in the cystic fibrosis lung microbiome, an environment known to be inhabited by a heterogeneous pathogen population that complicates management of the disorder.

PMID:33688005 | DOI:10.1128/mBio.02863-20

Clin Otolaryngol. 2021 Mar 8. doi: 10.1111/coa.13751. Online ahead of print.

ABSTRACT

OBJECTIVES: Chronic rhinosinusitis (CRS) is prevalent in the Cystic Fibrosis (CF) population. CRS exacerbations in CF are thought to contribute to pulmonary exacerbations. Literature regarding the impact of endoscopic sinus surgery (ESS) is inconclusive. This study examines rates of lung function decline and pulmonary exacerbation in CF patients who have undergone ESS.

DESIGN: Retrospective review of medical records.

SETTING: Academic Hospital.

PARTICIPANTS: 40 adult CF patients.

MAIN OUTCOME MEASURES: Rate of lung function decline (% predicted Forced Expiratory Volume in 1 second [ppFEV1 ]), number of pulmonary exacerbations (IV/oral antibiotic therapy +/- hospital admission) and total number days hospitalized 2 years post-operatively was collected. CRS patients undergoing ESS were matched to those without ESS by gender, age, and F508del genotype.

RESULTS: Forty patients (mean age 37.4, 60% male) were reviewed. No significant difference was found between the surgical group and controls in baseline ppFEV1 (72.5% vs. 72.7%, p=0.98), 2-year pre-operative number of pulmonary exacerbations (3.05 vs. 1.65, p=0.10), or Lund-Mackay scores (12.25 vs. 11.55, p=0.71). No significant difference was found in 1-year (70.5% vs. 72.8%, p=0.84) or 2-year (70.4% vs. 72.6% p=0.80) post-operative ppFEV1 and 2-year post-operative pulmonary exacerbations (1.7 vs. 1.45, p=0.87). A significant increase was identified in total number days hospitalized post-operatively (4.85, p=0.02). In the surgical group, no significant difference was identified between preoperative and postoperative ppFEV1 , 1 -year (-2.51%, p=0.32) and 2-years after ESS (-3.10%, p=0.51), postoperative rate of pulmonary exacerbations (-1.28, p=0.11), or in total number days hospitalized (3.74, p=0.14).

CONCLUSIONS: In this study, ESS does not appear to significantly improve ppFEV1 or decrease the number of pulmonary exacerbations post-operatively.

PMID:33686728 | DOI:10.1111/coa.13751

Cochrane Database Syst Rev. 2021 Mar 9;3:CD007923. doi: 10.1002/14651858.CD007923.pub6.

ABSTRACT

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review.

OBJECTIVES: To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis.

SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings. Date of the most recent search: 12 October 2020.

SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We assessed the quality of the evidence using GRADE.

MAIN RESULTS: We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant. In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence).

AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

PMID:33686652 | DOI:10.1002/14651858.CD007923.pub6

Thorax. 2021 Mar 8:thoraxjnl-2020-216007. doi: 10.1136/thoraxjnl-2020-216007. Online ahead of print.

ABSTRACT

INTRODUCTION: The benefits of unsupervised exercise programmes in obstructive lung disease are unclear. The aim of this systematic review was to synthesise evidence regarding the efficacy of unsupervised exercise versus non-exercise-based usual care in patients with obstructive lung disease.

METHODS: Electronic databases (MEDLINE, CINAHL, Embase, Allied and Complementary Medicine Database, Web of Science, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database) and trial registers (ClinicalTrials.gov, Current Controlled Trials, UK Clinical Trials Gateway and WHO International Clinical Trials Registry Platform) were searched from inception to April 2020 for randomised trials comparing unsupervised exercise programmes with non-exercise-based usual care in adults with chronic obstructive pulmonary disease (COPD), non-cystic fibrosis bronchiectasis or asthma. Primary outcomes were exercise capacity, quality of life, mortality, exacerbations and respiratory cause hospitalisations.

RESULTS: Sixteen trials (13 COPD, 2 asthma, 1 chronic bronchitis: 1184 patients) met the inclusion criteria. Only data on COPD populations were available for meta-analysis. Unsupervised exercise resulted in a statistically but not clinically significant improvement in the 6-Minute Walk Test (n=5, MD=22.0 m, 95% CI 4.4 to 39.6 m, p=0.01). However, unsupervised exercise did lead to statistically significant and clinically meaningful improvements in St. George's Respiratory Questionnaire (n=4, MD=-11.8 points, 95% CI -21.2 to -2.3 points, p=0.01) and Chronic Respiratory Disease Questionnaire domains (dyspnoea: n=4, MD=0.5 points, 95% CI 0.1 to 0.8 points, p<0.01; fatigue: n=4, MD=0.7 points, 95% CI 0.4 to 1.0 points, p<0.01; emotion: n=4, MD=0.5 points, 95% CI 0.2 to 0.7 points, p<0.01; mastery: unable to perform meta-analysis) compared with non-exercise-based usual care.

DISCUSSION: This review demonstrates clinical benefits of unsupervised exercise interventions on health-related quality of life in patients with COPD. High-quality randomised trials are needed to examine the effectiveness of prescription methods.

PMID:33685962 | DOI:10.1136/thoraxjnl-2020-216007

J Cyst Fibros. 2021 Mar 5:S1569-1993(21)00047-3. doi: 10.1016/j.jcf.2021.02.012. Online ahead of print.

ABSTRACT

BACKGROUND: Retrospective studies indicate that more cystic fibrosis (CF) pulmonary exacerbations (PEx) are treated with oral (PO) than with intravenous (IV) antimicrobials despite little knowledge of the relative effects of PO treatment on lung function recovery or long-term impacts on lung disease progression. Previous studies have suggested that PO treatment may be associated with slower lung function recovery compared with IV treatment. We used longitudinal home spirometry data from the eICE study (NCT01104402) to compare PO versus IV antimicrobial treatment responses for PEx diagnosed by home spirometry and symptom assessment.

METHODS: Adolescent and adult eICE participants performed home spirometry twice weekly for one year. PEx were diagnosed by a protocol-defined algorithm of change in percent predicted forced expiratory volume in 1 second (ppFEV1) and/or respiratory signs and symptoms. PO- and IV-treated PEx were grouped by initial ppFEV1 drop magnitude. Group ppFEV1 treatment responses were modeled with multivariate, repeat-measure linear regression.

RESULTS: Of 87 qualifying PEx from 56 participants, 62 were PO-treated and 25 were IV-treated. The average drop from best ppFEV1 to PEx start was 11.0 [95%CI: 8.5, 13.5] with similar treatment group means (p=0.72). Participants with IV-treated PEx averaged 0.72 [0.24, 1.20] ppFEV1/day greater response than those treated with PO, who experienced minimal ppFEV1 recovery. Many PO-treated participants who had <10 ppFEV1 drop from baseline tended to worsen or show no ppFEV1 improvement.

DISCUSSION: These results suggest that, in this cohort, PO antimicrobial treatment of CF PEx were less effective than IVs at improving ppFEV1 during treatment.

PMID:33685776 | DOI:10.1016/j.jcf.2021.02.012

Stem Cell Res. 2021 Feb 25;53:102251. doi: 10.1016/j.scr.2021.102251. Online ahead of print.

ABSTRACT

Cystic fibrosis is one of the most common inherited diseases caused by mutations in CFTR gene, of which F508del is the most frequent. Currently, the possibility of cell therapy including genome editing is widely discussed. We generated induced pluripotent stem cells from fibroblasts obtained from a 22-year-old woman with clinically manifested and genetically proven disease by using non-viral, non-integrating RNA reprogramming vector that contains five reprogramming factors: OCT4, KLF4, SOX2, GLIS1, and c-MYC. The established cell line can express endogenous pluripotency markers, possesses a normal karyotype, and has the ability to differentiate into three germ layers in spontaneous differentiation assay.

PMID:33684631 | DOI:10.1016/j.scr.2021.102251

Pediatr Pulmonol. 2021 Mar 8. doi: 10.1002/ppul.25334. Online ahead of print.

NO ABSTRACT

PMID:33684256 | DOI:10.1002/ppul.25334

Environ Microbiol. 2021 Mar 8. doi: 10.1111/1462-2920.15451. Online ahead of print.

ABSTRACT

The Burkholderia cepacia complex is a group of Burkholderia species which are opportunistic pathogens causing high mortality rates in patients with cystic fibrosis. An environmental stress often encountered by these soil-dwelling and pathogenic bacteria is phosphorus limitation, an essential element for cellular processes. Here, we describe cellular and extracellular proteins differentially regulated between phosphate-deplete (0 mM, no added phosphate) and phosphate-replete (1 mM) growth conditions using a comparative proteomics (LC-MS/MS) approach. We observed a total of 128 and 65 unique proteins were down-regulated and up-regulated, respectively, in the B. cenocepacia proteome. Of those down-regulated proteins, many have functions in amino acid transport/metabolism. We have identified 24 up-regulated proteins which are directly/indirectly involved in inorganic phosphate or organic phosphorus acquisition. Also, proteins involved in virulence and antimicrobial resistance were differentially regulated, suggesting B. cenocepacia experiences a dramatic shift in metabolism under these stress conditions. Overall, this study provides a baseline for further research into the biology of Burkholderia in response to phosphorus stress. This article is protected by copyright. All rights reserved.

PMID:33684254 | DOI:10.1111/1462-2920.15451

Ir J Med Sci. 2021 Mar 8. doi: 10.1007/s11845-021-02564-9. Online ahead of print.

ABSTRACT

BACKGROUND: The 6-min walk test (6MWT) is a sub-maximal exercise test and has been widely used for evaluating of exercise capacity of patients with cystic fibrosis (CF) in recent years. Few studies have examined the relationship between 6MWT and parameters used to assess the severity of the disease in children with CF. In this study, we have examined this relationship to find out if 6MWT can be a marker of the severity of cystic fibrosis.

METHODS: A cross-sectional study was done to analyze the correlations among spirometry parameters, body mass index (BMI), chest tomography (CT), and 6MWT. CF patients, aged 7-14 years, were involved.

RESULTS: Seventy-six patients, 32F/44M, mean age 10.49 ± 3.18 years, were studied. The mean distance in 6MWT was 447 ± 84.1. The following correlations versus distance were found: FEV1 (r = 0.255, p = 0.026), FVC(r = 0.285, p = 0.013), FEF25-75% (r = 0.546, p < 0.001), BMI (r = 0.163, p = 0.160), and CT (r = 0.075, p = 0.520).The following correlations versus O2 saturation (SpO2) decline were found: FEV1 (r = -0.393, p < 0.001), FVC (r = -0.431, p < 0.001), FEF25-75% (r = -0.296, p = 0.010), BMI (r = 0.042, p = 0.721), and CT (r = -0.196, p = 0.090). There was a significant correlation between 6MWT (distance and SpO2 decline) and pulmonary function test. There was no significant correlation between BMI, chest CT, and 6MWT.

CONCLUSIONS: 6MWT can be applied beside spirometry and chest CT for CF patients follow up.

PMID:33683561 | DOI:10.1007/s11845-021-02564-9

Biotechnol Lett. 2021 Mar 8. doi: 10.1007/s10529-021-03101-5. Online ahead of print.

ABSTRACT

OBJECTIVE: Chromovert® Technology is presented as a new cell engineering technology to detect and purify living cells based on gene expression.

METHODS: The technology utilizes fluorogenic oligonucleotide signaling probes and flow cytometry to detect and isolate individual living cells expressing one or more transfected or endogenously-expressed genes.

RESULTS: Results for production of cell lines expressing a diversity of ion channel and membrane proteins are presented, including heteromultimeric epithelial sodium channel (αβγ-ENaC), sodium voltage-gated ion channel 1.7 (NaV1.7-αβ1β2), four unique γ-aminobutyric acid A (GABAA) receptor ion channel subunit combinations α1β3γ2s, α2β3γ2s, α3β3γ2s and α5β3γ2s, cystic fibrosis conductance regulator (CFTR), CFTR-Δ508 and two G-protein coupled receptors (GPCRs) without reliance on leader sequences and/or chaperones. In addition, three novel plasmid-encoded sequences used to introduce 3' untranslated RNA sequence tags in mRNA expression products and differentially-detectable fluorogenic probes directed to each are described. The tags and corresponding fluorogenic signaling probes streamline the process by enabling the multiplexed detection and isolation of cells expressing one or more genes without the need for gene-specific probes.

CONCLUSIONS: Chromovert technology is provided as a research tool for use to enrich and isolate cells engineered to express one or more desired genes.

PMID:33683511 | DOI:10.1007/s10529-021-03101-5

Radiat Prot Dosimetry. 2021 Mar 4:ncab017. doi: 10.1093/rpd/ncab017. Online ahead of print.

ABSTRACT

PURPOSE: Digital tomosynthesis (DTS) is currently undergoing validation for potential clinical implications. The aim of this study was to investigate the potential for DTS as a low-dose alternative to computed tomography (CT) in imaging of pulmonary pathology in patients with cystic fibrosis (CF).

METHODS: DTS and CT were performed as part of the routine triannual follow-up in 31 CF patients. Extent of disease was quantified according to modality-specific scoring systems. Statistical analysis included Spearman's rank correlation coefficient (r) and Krippendorff's alpha (α).

MAJOR FINDINGS: The median effective dose was 0.14 for DTS and 2.68 for CT. Intermodality correlation was very strong for total score and the subscores regarding bronchiectasis and bronchial wall-thickening (r = 0.82-0.91, P < 0.01). Interobserver reliability was high for total score, bronchiectasis and mucus plugging (α = 0.83-0.93) in DTS.

CONCLUSION: Chest tomosynthesis could be a low-dose alternative to CT in quantitative estimation of structural lung disease in CF.

PMID:33683309 | DOI:10.1093/rpd/ncab017

Rev Med Liege. 2021 Mar;76(3):202-207.

ABSTRACT

In cystic fibrosis, lung disease is early and insidious. It almost always conditions the prognosis. A pragmatic way of looking at prognostic factors is to distinguish those on which care management has little (environmental factors) or no grip (genetic factors) and those related to the quality of care, the latter being crucial. Recently, a triple-combination CFTR («Cystic Fibrosis Transmembrane conductance Regulator») modulator regimen has been shown a highly effective therapy. Ultimately, at least 90 % of Belgian patients with cystic fibrosis should benefit from this drug. However, its official price is extremely high (712 €/day), lacks transparency and illustrates problematic aspects of current orphan legislations. For the majority of citizens in Western Europe, a social ideal still prevails that healthcare should be accessible to all in an equitable fashion. Somewhere between this price and the necessity for national health systems based on solidarity to keep the costs of orphan drugs at a sustainable level, patients are looking like hostages.

PMID:33682390