Adv Respir Med. 2021 Dec 9. doi: 10.5603/ARM.a2021.0107. Online ahead of print.

ABSTRACT

INTRODUCTION: Nebulisation therapy plays a key role in the treatment of cystic fibrosis (CF). Its effectiveness depends on obtaining a high concentration of drugs in the respiratory tract. Particle deposition is determined by many factors resulting, inter alia, from the essence of the lung disease (mucus, structural changes such as bronchiectasis, fibrous changes, cirrhosis) and the quality of the aerosol and breathing techniques during the procedure.

AIM OF THE GUIDELINES: A large variety of available drugs that can be used in the form of aerosols (bronchodilators, mucolytics, antibiotics), a wide range of devices for their delivery, and a different approach to the practical aspect related to the use of inhalation, makes it necessary to systematize knowledge in order to optimize nebulisation therapy. The paper presents an overview of inhaled drugs used in cystic fibrosis and their administration devices.

RESULTS: The principles of inhalation antibiotic therapy, which constitute the basis for the treatment of primary and chronic respiratory tract infections of Pseudomonas aeruginosa etiology, are discussed in detail. A very important issue was raised related to the proper selection of devices and their proper operation. In the context of the key role of nebulisation therapy in cystic fibrosis, a huge problem is the limited availability of inhaled antibiotics in Poland.

CONCLUSIONS: The possibility of choosing an antibiotic and using alternating therapy increases the effectiveness of inhalation treatment, which results in slowing down the progress of bronchopulmonary disease and extending the life of patients.

PMID:34881808 | DOI:10.5603/ARM.a2021.0107

Cochrane Database Syst Rev. 2021 Dec 9;12:CD011059. doi: 10.1002/14651858.CD011059.pub4.

ABSTRACT

BACKGROUND: Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre-pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.

OBJECTIVES: To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews. Date of last search of the Group's Trials Registers: 21 June 2021.

SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.

DATA COLLECTION AND ANALYSIS: No trials matching the selection criteria were eligible for inclusion.

MAIN RESULTS: No trials matching the selection criteria were eligible for inclusion.

AUTHORS' CONCLUSIONS: The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus. Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.

PMID:34881425 | DOI:10.1002/14651858.CD011059.pub4

ISME J. 2021 Dec 8. doi: 10.1038/s41396-021-01157-9. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa biofilms exhibit an intrinsic resistance to antibiotics and constitute a considerable clinical threat. In cystic fibrosis, a common feature of biofilms formed by P. aeruginosa in the airway is the occurrence of mutants deficient in flagellar motility. This study investigates the impact of flagellum deletion on the structure and antibiotic tolerance of P. aeruginosa biofilms, and highlights a role for the flagellum in adaptation and cell survival during biofilm development. Mutations in the flagellar hook protein FlgE influence greatly P. aeruginosa biofilm structuring and antibiotic tolerance. Phenotypic analysis of the flgE knockout mutant compared to the wild type (WT) reveal increased fitness under planktonic conditions, reduced initial adhesion but enhanced formation of microcolony aggregates in a microfluidic environment, and decreased expression of genes involved in exopolysaccharide formation. Biofilm cells of the flgE knock-out mutant display enhanced tolerance towards multiple antibiotics, whereas its planktonic cells show similar resistance to the WT. Confocal microscopy of biofilms demonstrates that gentamicin does not affect the viability of cells located in the inner part of the flgE knock-out mutant biofilms due to reduced penetration. These findings suggest that deficiency in flagellar proteins like FlgE in biofilms and in cystic fibrosis infections represent phenotypic and evolutionary adaptations that alter the structure of P. aeruginosa biofilms conferring increased antibiotic tolerance.

PMID:34880458 | DOI:10.1038/s41396-021-01157-9

J Cyst Fibros. 2021 Dec 5:S1569-1993(21)02138-X. doi: 10.1016/j.jcf.2021.11.007. Online ahead of print.

ABSTRACT

BACKGROUND: Given future challenges in conducting large randomized, placebo controlled trials for future CF therapeutics development, we evaluated the potential for using external historical controls to either enrich or replace traditional concurrent placebo groups in CF trials.

METHODS: The study included data from sequentially completed, randomized, controlled clinical trials, EPIC and OPTIMIZE respectively, evaluating optimal antibiotic therapy to reduce the risk of pulmonary exacerbation in children with early Pseudomonas aeruginosa infection. The primary treatment effect in OPTIMIZE, the risk of pulmonary exacerbation associated with azithromycin, was re-estimated in alternative designs incorporating varying numbers of participants from the earlier trial (EPIC) as historical controls. Bias and precision of these estimates were characterized. Propensity scores were derived to adjust for baseline differences across study populations, and both Poisson and Cox regression were used to estimate treatment efficacy.

RESULTS: Replacing 86 OPTIMIZE placebo participants with 304 controls from EPIC to mimic a fully historically controlled trial resulted an 8% reduction in risk of pulmonary exacerbations (Hazard ratio (HR):0.92 95% CI 0.61, 1.34) when not adjusting for key baseline differences between study populations. After adjustment, a 37% decrease in risk of exacerbation (HR:0.63, 95% CI 0.50, 0.80) was estimated, comparable to the estimate from the original trial comparing the 86 placebo participants to 77 azithromycin participants on azithromycin (45%, HR:0.55, 95% CI: 0.34, 0.86). Other adjusted approaches provided similar estimates for the efficacy of azithromycin in reducing exacerbation risk: pooling all controls from both studies provided a HR of 0.60 (95% x`CI 0.46, 0.77) and augmenting half the OPTIMIZE placebo participants with EPIC controls gave a HR 0.63 (95% CI 0.48, 0.82).

CONCLUSIONS: The potential exists for future CF trials to utilize historical control data. Careful consideration of both the comparability of controls and of optimal methods can reduce the potential for biased estimation of treatment effects.

PMID:34879997 | DOI:10.1016/j.jcf.2021.11.007

J Cyst Fibros. 2021 Dec 5:S1569-1993(21)02143-3. doi: 10.1016/j.jcf.2021.11.006. Online ahead of print.

NO ABSTRACT

PMID:34879996 | DOI:10.1016/j.jcf.2021.11.006

Am J Physiol Gastrointest Liver Physiol. 2021 Dec 8. doi: 10.1152/ajpgi.00290.2021. Online ahead of print.

ABSTRACT

Goblet cell hyperplasia is an important manifestation of cystic fibrosis (CF) disease in epithelial-lined organs. Explants of CF airway epithelium show normalization of goblet cell numbers; therefore we hypothesized that small intestinal enteroids from Cftr knockout (KO) mice would not exhibit goblet cell hyperplasia. Toll-like receptors 2 and 4 (Tlr2, Tlr4) were investigated as markers of inflammation and influence on goblet cell differentiation. Ex vivo studies found goblet cell hyperplasia in Cftr KO jejunum as compared to wild-type (WT). IL-13, SAM pointed domain-containing ETS transcription factor (Spdef), Tlr2 and Tlr4 protein expression was increased in Cftr KO intestine relative to WT. In contrast, WT and Cftr KO enteroids did not exhibit differences in basal or IL-13-stimulated goblet cell numbers, or differences in expression of Tlr2, Tlr4 and Spdef. Ileal goblet cell numbers in Cftr KO/Tlr4 KO and Cftr KO/Tlr2 KO mice were not different from Cftr KO mice, but enumeration was confounded by altered mucosal morphology. Treatment with Tlr4 agonist LPS did not affect goblet cell numbers in WT or Cftr KO enteroids, whereas the Tlr2 agonist Pam3Csk4 stimulated goblet cell hyperplasia in both genotypes. Pam3Csk4 stimulation of goblet cell numbers was associated with suppression of Notch1 and Neurog3 expression and upregulated determinants of goblet cell differentiation. We conclude that goblet cell hyperplasia and inflammation of the Cftr KO small intestine are not exhibited by enteroids, indicating that this manifestation of CF intestinal disease is not epithelial-automatous but secondary to the altered CF intestinal environment.

PMID:34878935 | DOI:10.1152/ajpgi.00290.2021

Appl Environ Microbiol. 2021 Dec 8:AEM0178921. doi: 10.1128/AEM.01789-21. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is the predominant cause of chronic biofilm infections that form in the lungs of people with cystic fibrosis (CF). These infections are highly resistant to antibiotics and persist for years in the respiratory tract. One of the main research challenges is that current laboratory models do not accurately replicate key aspects of a P. aeruginosa biofilm infection, highlighted by previous RNA-sequencing studies. We compared the P. aeruginosa PA14 transcriptome in an ex vivo pig lung (EVPL) model of CF and a well-studied synthetic cystic fibrosis sputum medium (SCFM). P. aeruginosa was grown in the EVPL model for 1, 2 and 7 days, and in vitro in SCFM for 1 and 2 days. The RNA was extracted and sequenced at each time point. Our findings demonstrate that expression of antimicrobial resistance genes was cued by growth in the EVPL model, highlighting the importance of growth environment in determining accurate resistance profiles. The EVPL model created two distinct growth environments: tissue-associated biofilm and the SCFM surrounding tissue, each cued a transcriptome distinct from that seen in SCFM in vitro. The expression of quorum sensing associated genes in the EVPL tissue-associated biofilm at 48 h relative to in vitro SCFM was similar to CF sputum versus in vitro conditions. Hence, the EVPL model can replicate key aspects of in vivo biofilm infection that are missing from other current models. It provides a more accurate P. aeruginosa growth environment for determining antimicrobial resistance that quickly drives P. aeruginosa into a chronic-like infection phenotype. Importance Pseudomonas aeruginosa lung infections that affect people with cystic fibrosis are resistant to most available antimicrobial treatments. The lack of a laboratory model that captures all key aspects of these infections hinders not only research progression but also clinical diagnostics. We used transcriptome analysis to demonstrate how a model using pig lungs can more accurately replicate key characteristics of P. aeruginosa lung infection, including mechanisms of antibiotic resistance and infection establishment. Therefore, this model may be used in the future to further understand infection dynamics to develop novel treatments and more accurate treatment plans. This could improve clinical outcomes as well as quality of life for individuals affected by these infections.

PMID:34878811 | DOI:10.1128/AEM.01789-21

Physiother Theory Pract. 2021 Dec 8:1-13. doi: 10.1080/09593985.2021.2012859. Online ahead of print.

ABSTRACT

INTRODUCTION: Airway clearance techniques, which include positive expiratory pressure (PEP) devices, are essential in the pulmonary rehabilitation of cystic fibrosis (CF). Bottle-PEP is a low-cost but an effective alternative.

OBJECTIVE: The aim of this study is to document the sustainability and safety of Bottle-PEP therapy as a home rehabilitation aid.

METHODS: The study has been designed as a prospective case series. Patients with CF at the age of 6-18 years in acute exacerbation period were included in the study. Bottle-PEP training was given by a competent physiotherapist to those patients who did not use any method, and those who currently use another device were followed up with their existing devices. Thus, patients divided into two groups were followed up for 1 year. The patients were evaluated by phone every 2 weeks for exacerbation, regular and proper use of the device, and satisfaction during their follow-up. The patients were evaluated every 3 months with pulmonary function tests, 6-minute walking test (6MWT) and quality of life.

RESULTS: Thirty-four patients were included in the study. The acute exacerbation score of the patients was 4.5 in the Bottle-PEP group and 6 in the other group, showing no significant difference (p = .1). Treatment compliance scores were compared, the median value of the Bottle-PEP group was 24 the other group was 27 and there was no significant difference (p = .6). During follow-up of, there were no significant differences in FEV1, 6MWT and quality of life data (p > .05).

CONCLUSION: Bottle-PEP treatment is not different from other devices in terms of long-term usability and safety in patients diagnosed with cystic fibrosis.

PMID:34878368 | DOI:10.1080/09593985.2021.2012859

Microbiol Spectr. 2021 Dec 8:e0183121. doi: 10.1128/Spectrum.01831-21. Online ahead of print.

ABSTRACT

The IR Biotyper and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using ClinProTools software (MALDI-TOF MS-ClinProTools) are two novel typing methods that rely on the analysis of carbohydrate and peptide residues in intact bacterial cells. These two methods have shown promising results in the rapid and accurate typing of bacteria. In this study, we evaluated these novel typing methods in comparison with genotypic typing for cluster analysis of Burkholderia cenocepacia epidemic strain ET12, isolated from adult cystic fibrosis patients. Sixty-six isolates of B. cenocepacia were used in this study, 35 of which were identified as the ET12 strain and 31 as non-ET12 strains by repetitive-element PCR (rep-PCR). Twelve isolates were used for the creation of typing models using IR Biotyper and MALDI-TOF MS-ClinProTools, and 54 isolates were used for external validation of the typing models. The IR Biotyper linear discriminant analysis (LDA) model had a diagnostic sensitivity of 84.6% for typing the epidemic strain, ET12. At a cutoff of 70%, MALDI-TOF MS-ClinProTools had 87.5% diagnostic sensitivity in detecting the ET12 strain (P = 1.00). Both methods had a diagnostic specificity of ≥80% for detecting the ET12 strain. In conclusion, IR Biotyper and MALDI-TOF MS-ClinProTools offer rapid typing using proteomics and analysis of small cellular molecules with a low running cost. Our pilot study showed suboptimal accuracy of both methods for typing outbreak strains of B. cenocepacia. Extending the spectral region analyzed by the IR Biotyper can improve the accuracy and has the potential of improving the generalizability of this technique for typing other organisms. IMPORTANCE Respiratory infections due to Burkholderia cenocepacia, particularly the ET12 epidemic strain, are considered sentinel events for persons with cystic fibrosis, as they are often associated with person-to-person transmission and accelerated decline in lung function and early mortality. Current typing methods are generally only available at reference centers, with long turn-around-times, which can affect the identification of outbreaks and critical patient triage. This pilot study aims to add to the growing literature illustrating the potential utility of Fourier transform infrared spectroscopy (FTIR), a novel rapid method, for the successful typing of clinically significant bacteria. In this study, we evaluated its utility to discriminate between the ET12 clone and non-ET12 isolates of B. cenocepacia and compared it to proteomics cluster analysis using MALDI-TOF MS and ClinProTools software. Both methods had encouraging but suboptimal accuracy (≥85% sensitivity and ≥83% specificity), which will likely be improved by extending the spectral region analyzed by the IR Biotyper with updated software.

PMID:34878338 | DOI:10.1128/Spectrum.01831-21

CPT Pharmacometrics Syst Pharmacol. 2021 Dec 8. doi: 10.1002/psp4.12751. Online ahead of print.

ABSTRACT

Cystic fibrosis is a lethal autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The common ΔF508-CFTR mutation results in protein misfolding and proteasomal degradation. If ΔF508-CFTR trafficks to the cell surface, its anion channel function may be partially restored. Several in vitro strategies can partially correct ΔF508-CFTR trafficking and function, including low-temperature, small molecules, overexpression of miR-138, or knockdown of SIN3A. The challenge remains to translate such interventions into therapies and to understand their mechanisms. One approach for connecting such interventions to small molecule therapies that has previously succeeded for cystic fibrosis and other diseases is via mRNA expression profiling and iterative searches of small molecules with similar expression signatures. Here, we query the Library of Integrated Network-based Cellular Signatures (LINCS) using transcriptomic signatures from previously generated CF expression data, including RNAi- and low temperature-based rescue signatures. This LINCS in silico screen prioritized 135 small molecules that mimicked our rescue interventions based on their genome-wide transcriptional perturbations. Functional screens of these small molecules identified eight compounds that partially restored ΔF508-CFTR function, as assessed by cAMP-activated chloride conductance. Of these, XL147 rescued ΔF508-CFTR function in primary CF airway epithelia, while also showing cooperativity when administered with C18. Improved CF corrector therapies are greatly needed and this integrative drug prioritization approach offers a novel method to both identify small molecules that may rescue ΔF508-CFTR function and identify gene networks underlying such rescue.

PMID:34877817 | DOI:10.1002/psp4.12751

World J Clin Cases. 2021 Nov 6;9(31):9469-9480. doi: 10.12998/wjcc.v9.i31.9469.

ABSTRACT

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is said to be associated with numerous conditions both within and outside the gastrointestinal (GI) system. The majority of research has been concerned with conditions that reduce the volume of functioning pancreatic tissue or prevent adequate drainage to the small bowel, such as chronic pancreatitis, cystic fibrosis, pancreatic cancer and pancreatic resection. However, the evidence base supporting an association with extra-pancreatic conditions, such as coeliac disease, diabetes mellitus and congestive cardiac failure, is heterogeneous.

AIM: To strengthen the evidence base by studying all previously reported associations with PEI in a large cohort of outpatients.

METHODS: A single-centre retrospective study was performed. General gastroenterology outpatients tested for PEI with faecal elastase-1 (FE1) were identified and information retrieved from the electronic patient record. PEI was defined as FE1 < 200 μg/g. Patients already taking pancreatic enzyme replacement therapy were excluded. Multiple imputation was used to handle missing data. Univariable logistic regression was used to study which presenting symptoms predicted PEI. Multivariable logistic regression was used to explore the relationship between all previously reported associations and PEI.

RESULTS: Of 1027 patients were included. 182 patients (17.7%) were diagnosed with PEI. Steatorrhoea [odds ratios (OR): 2.51, 95% confidence intervals (CI): 1.58-3.98] and weight loss (OR: 1.49, 95%CI: 1.08-2.06) were the only presenting symptoms that predicted PEI. Chronic pancreatitis (OR: 7.98, 95%CI: 3.95-16.15), pancreatic cancer (OR: 6.58, 95%CI: 1.67-25.98), upper GI surgery (OR: 2.62, 95%CI: 1.32-5.19), type 2 diabetes (OR: 1.84, 95%CI: 1.18-2.87), proton pump inhibitor therapy (OR: 1.87, 95%CI: 1.25-2.80) and Asian ethnicity (OR: 2.11, 95%CI: 1.30-3.42) were significantly associated with PEI in the multivariable analysis. None of the other historically reported associations with PEI were significant after adjustment for the other variables included in our multivariable analysis.

CONCLUSION: PEI is common in patients with chronic pancreatitis, pancreatic cancer, upper GI surgery and type 2 diabetes. Proton pump inhibitor therapy may also be associated with PEI or a false positive FE1.

PMID:34877281 | PMC:PMC8610880 | DOI:10.12998/wjcc.v9.i31.9469

NPJ Aging Mech Dis. 2021 Dec 7;7(1):27. doi: 10.1038/s41514-021-00080-9.

NO ABSTRACT

PMID:34876577 | DOI:10.1038/s41514-021-00080-9

BMJ Open Respir Res. 2021 Dec;8(1):e001140. doi: 10.1136/bmjresp-2021-001140.

NO ABSTRACT

PMID:34876481 | DOI:10.1136/bmjresp-2021-001140

J Heart Lung Transplant. 2021 Nov 4:S1053-2498(21)02573-0. doi: 10.1016/j.healun.2021.10.017. Online ahead of print.

NO ABSTRACT

PMID:34876356 | DOI:10.1016/j.healun.2021.10.017

Int Forum Allergy Rhinol. 2021 Dec 7. doi: 10.1002/alr.22935. Online ahead of print.

ABSTRACT

BACKGROUND: No studies have investigated when endoscopic sinus surgery (ESS) is best performed in lung transplant patients with cystic fibrosis (CF). We sought to examine the effects of ESS timing on pulmonary health in this population.

METHODS: A retrospective review of all adult lung transplant patients with CF who underwent ESS at our academic medical center over a near 25-year period was performed. Patients were split into two groups based on median time from lung transplantation to ESS. Twenty-three patients were included (12 ESS early and 11 ESS delayed). Outcomes included changes in pulmonary function tests (PFTs) from baseline, pre-operative to post-operative measurements, the number and duration of hospitalizations for pulmonary exacerbations, and the number of antibiotic courses used specifically to treat pulmonary exacerbations during the 12 months before and after ESS.

RESULTS: Baseline demographics, operative history, and pulmonary function characteristics were similar between groups. While the ESS early group saw significant improvement from pre-operative percent predicted FEV1 (ppFEV1 ) at 12 months post-operatively (CI: 0.729 - 11.452, P = 0.030), there were no significant post-operative PFT changes for the ESS delayed group. Post-operative improvement in FEV1 and ppFEV1 at 12 months was significantly higher for the ESS early group relative to the ESS delayed group (CI: 0.010 - 0.583, P = 0.043; CI: 1.240 - 16.692, P = 0.025; respectively). The ESS early group had a significant reduction in the need for total antibiotic courses compared to the ESS delayed group (ESS early median: -1, IQR: -1.5 to -0.5 vs ESS delayed median: 0, IQR: 0 to 0; P = 0.027).

CONCLUSION: Earlier ESS interventions following lung transplantation may improve pulmonary function and attenuate pulmonary exacerbations in CF patients. This article is protected by copyright. All rights reserved.

PMID:34875144 | DOI:10.1002/alr.22935

ACS Biomater Sci Eng. 2021 Dec 7. doi: 10.1021/acsbiomaterials.1c01031. Online ahead of print.

ABSTRACT

Injured or diseased airway epithelium due to repeated environmental insults or genetic mutations can lead to a functional decline of the lung and incurable lung diseases. Bioengineered airway tissue constructs can facilitate in vitro investigation of human lung diseases and accelerate the development of effective therapeutics. Here, we report robust tissue manipulation modalities that allow: (i) selective removal of the endogenous epithelium of in vitro cultured airway tissues and (ii) spatially uniform distribution and prolonged cultivation of exogenous cells that are implanted topically onto the denuded airway lumen. Results obtained highlight that our approach to airway tissue manipulation can facilitate controlled removal of the airway epithelium and subsequent homogeneous distribution of newly implanted cells. This study can contribute to the creation of innovative tissue engineering methodologies that can facilitate the treatment of lung diseases, such as cystic fibrosis, primary ciliary dyskinesia, and chronic obstructive pulmonary disease.

PMID:34874712 | DOI:10.1021/acsbiomaterials.1c01031

N Engl J Med. 2021 Dec 2;385(23):2208. doi: 10.1056/NEJMc2115966.

NO ABSTRACT

PMID:34874646 | DOI:10.1056/NEJMc2115966

N Engl J Med. 2021 Dec 2;385(23):2207-2208. doi: 10.1056/NEJMc2115966.

NO ABSTRACT

PMID:34874645 | DOI:10.1056/NEJMc2115966

Infection. 2021 Dec 7. doi: 10.1007/s15010-021-01737-z. Online ahead of print.

ABSTRACT

PURPOSE: To describe the clinical course of COVID-19 in patients with cystic fibrosis (CF) and to identify risk factors for severe COVID-19.

METHODS: We conducted a prospective study within the Italian CF Society. CF centers collected baseline and follow-up data of patients with virologically confirmed SARS-CoV-2 infection between March 2020 and June 2021. Odds ratios (ORs) for severe SARS-CoV-2 (as defined by hospital admission) were estimated by logistic regression models.

RESULTS: The study included 236 patients with positive molecular test for SARS-CoV-2. Six patients died, 43 patients were admitted to hospital, 4 admitted to intensive care unit. Pancreatic insufficiency was associated with increased risk of severe COVID-19 (OR 4.04, 95% CI 1.52; 10.8). After adjusting for age and pancreatic insufficiency, forced expiratory volume in one second (FEVp) < 40% (OR 4.54, 95% CI 1.56; 13.2), oxygen therapy (OR 12.3, 95% CI 2.91-51.7), underweight (OR 2.92, 95% CI 1.12; 7.57), organ transplantation (OR 7.31, 95% CI 2.59; 20.7), diabetes (OR 2.67, 95% CI 1.23; 5.80) and liver disease (OR 3.67, 95% CI 1.77; 7.59) were associated with increased risk of severe COVID-19, while use of dornase alfa was associated with a reduced risk (OR 0.34, 95% CI 0.13-0.88). No significant changes were observed in FEVp from baseline to a median follow-up of 2 months (median difference: 0, interquartile range: - 4; 5, P = 0.62).

CONCLUSION: Clinical features indicative of severe form of CF are associated with increased risk of COVID-19 hospitalization. SARS-CoV-2 infected patients do not experience a deterioration of respiratory function.

PMID:34874541 | DOI:10.1007/s15010-021-01737-z

Acta Clin Belg. 2021 Dec 7:1-5. doi: 10.1080/17843286.2021.2012948. Online ahead of print.

ABSTRACT

OBJECTIVES: Prevalence of MRSA in patients with CF has risen over the past decades, and chronic infection with MRSA is associated with worse outcome in this patient group.

METHODS: This retrospective observational study investigated long-term eradication rate in pediatric and adult CF patients with chronic MRSA infection, using a 6-month eradication regimen containing 2 oral antibiotics, combined with topical decolonisation measures. Respiratory tract cultures were performed at least every three months, from the first MRSA-positive culture onwards.

RESULTS: A total of 24 patients with chronic MRSA infection were identified from our CF patient registry, of which 13 patients underwent an eradication attempt. The regimen consisted of 2 oral antibiotics: a combination of rifampicin, fusidic acid, clindamycin and co-trimoxazol, based on the sensitivity pattern of the MRSA strain. At the end of the study period (median 8.2 years), 12 out of 13 patients (92%) were MRSA negative. None of the patients interrupted treatment due to side-effects.

CONCLUSIONS: Eradication of chronic MRSA infection is feasible, well-tolerated and highly successful, and can offer a long-lasting MRSA-negative status, obviating the need for patient segregation.

PMID:34874240 | DOI:10.1080/17843286.2021.2012948