Int J Mol Sci. 2022 Dec 21;24(1):115. doi: 10.3390/ijms24010115.

ABSTRACT

ABC transporters are expressed in skin cells to protect them against harmful xenobiotics. Moreover, these transmembrane proteins have a number of additional functions that ensure skin homeostasis. This review summarizes the current knowledge about the role of specific ABC proteins in the skin, including multi-drug resistance transporters (MDR1/3), the transporter associated with antigen processing 1/2 (TAP1/2), the cystic fibrosis transmembrane conductance regulator (CFTR), sulfonylurea receptors (SUR1/2), and the breast cancer resistance protein (BCRP). Additionally, the effect of UV radiation on ABC transporters is shown. The exposure of skin cells to UV radiation often leads to increased activity of ABC transporters-as has been observed in the case of MDRs, TAPs, CFTR, and BCRP. A different effect of oxidative stress has been observed in the case of mitochondrial SURs. However, the limited data in the literature-as indicated in this article-highlights the limited number of experimental studies dealing with the role of ABC transporters in the physiology and pathophysiology of skin cells and the skin as a whole. At the same time, the importance of such knowledge in relation to the possibility of daily exposure to UV radiation and xenobiotics, used for both skin care and the treatment of its diseases, is emphasized.

PMID:36613554 | DOI:10.3390/ijms24010115

Cells. 2023 Jan 3;12(1):199. doi: 10.3390/cells12010199.

ABSTRACT

Pseudomonas aeruginosa is an important Gram-negative opportunistic pathogen which causes many severe acute and chronic infections with high morbidity, and mortality rates as high as 40%. What makes P. aeruginosa a particularly challenging pathogen is its high intrinsic and acquired resistance to many of the available antibiotics. In this review, we review the important acute and chronic infections caused by this pathogen. We next discuss various animal models which have been developed to evaluate P. aeruginosa pathogenesis and assess therapeutics against this pathogen. Next, we review current treatments (antibiotics and vaccines) and provide an overview of their efficacies and their limitations. Finally, we highlight exciting literature on novel antibiotic-free strategies to control P. aeruginosa infections.

PMID:36611992 | DOI:10.3390/cells12010199

Healthcare (Basel). 2022 Dec 21;11(1):20. doi: 10.3390/healthcare11010020.

ABSTRACT

CFHealthHub is a learning health system active in over 50% of adult CF Centres in England, supporting people with CF to develop habits of self-care around adherence to preventative inhaled therapy. This is achieved through the delivery of a behaviour change intervention, alongside collection of objective adherence data. As is common to long-term conditions, adherence to prescribed therapy is low, despite clear evidence of beneficial long-term impact on outcomes. This article explains how CFHealthHub is underpinned by coherent conceptual frameworks. We discuss how application of implementation and quality improvement strategies has facilitated CFHealthHub's progression from a pilot study to a large, randomised control trial and now to a learning health system, becoming embedded within routine care. CFHealthHub is now able to support real-time health technology assessments, quality improvement and research trials and is in the process of being implemented in routine clinical care across participating centres.

PMID:36611480 | DOI:10.3390/healthcare11010020

Rev Mal Respir. 2023 Jan 5:S0761-8425(22)00468-5. doi: 10.1016/j.rmr.2022.12.011. Online ahead of print.

NO ABSTRACT

PMID:36610851 | DOI:10.1016/j.rmr.2022.12.011

Med Mycol. 2023 Jan 4:myac097. doi: 10.1093/mmy/myac097. Online ahead of print.

ABSTRACT

The indications for nystatin as prophylaxis or treatment are limited. In the PASOAP (Paediatric Antifungal Stewardship Optimising Antifungal Prescription) study, a high use of nystatin in hospitalised children beyond the neonatal age was observed. In this report we present the data on nystatin use in infants and children ≥ 3 months who participated in the PASOAP study. Nystatin was prescribed mainly for prophylaxis. Congenital heart disease, cystic fibrosis and chronic renal disease were the most commonly reported conditions in children receiving prophylactic nystatin. There is sparse evidence supporting the use of nystatin prophylaxis beyond neonates; trials in specific paediatric patient groups are required.

PMID:36610724 | DOI:10.1093/mmy/myac097

Pediatr Pulmonol. 2023 Jan 6. doi: 10.1002/ppul.26311. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic Fibrosis (CF) and autism spectrum disorder (ASD) are life-long conditions with intense treatment burdens for patients and families. Patients with a concurrent diagnosis (CF-ASD) experience unique obstacles to CF care. This study describes the experiences of our multidisciplinary CF team in caring for patients with CF-ASD and provides insight into provider and parental perspectives on clinical management.

METHODS: This is a three-part qualitative study involving 1) retrospective chart review of patients with CF-ASD, 2) surveys with multi-disciplinary care team members, and 3) semi-structured interviews with caregivers of patients with CF-ASD. Challenges in clinical management of this specific cohort were compiled using data from chart review and care team surveys. Strategies to address these concerns were identified and rated by individual families based on relevance and practicality.

RESULTS: Within our CF center, 12 patients have an official diagnosis of ASD. Median age of patients with CF-ASD was 8.5 years (range 3-20 years), 67% were male, and 83% were on highly effective modulator therapy. Clinical barriers included sensory processing issues, environmental overstimulation, intolerance to procedures and to disrupted routines. Potentially impactful strategies include patient-specific coping plans, guided behavioral interventions, parental advocacy, and improved communication between the family and multidisciplinary team.

CONCLUSION: Children with CF-ASD face extraordinary challenges beyond the experience of neurotypical children with CF. Increased awareness of this complex dual diagnosis will help providers be sensitive to the unique needs of these patients, help build consistent and trustworthy relationships with their families and deliver effective clinical care despite limitations. This article is protected by copyright. All rights reserved.

PMID:36610056 | DOI:10.1002/ppul.26311

Cell Mol Life Sci. 2023 Jan 7;80(1):33. doi: 10.1007/s00018-022-04671-x.

ABSTRACT

The question how proteins fold is especially pointed for large multi-domain, multi-spanning membrane proteins with complex topologies. We have uncovered the sequence of events that encompass proper folding of the ABC transporter CFTR in live cells by combining kinetic radiolabeling with protease-susceptibility assays. We found that CFTR folds in two clearly distinct stages. The first, co-translational, stage involves folding of the 2 transmembrane domains TMD1 and TMD2, plus one nucleotide-binding domain, NBD1. The second stage is a simultaneous, post-translational increase in protease resistance for both TMDs and NBD2, caused by assembly of these domains onto NBD1. Our assays probe every 2-3 residues (on average) in CFTR. This in-depth analysis at amino-acid level allows detailed analysis of domain folding and importantly also the next level: assembly of the domains into native, folded CFTR. Defects and changes brought about by medicines, chaperones, or mutations also are amenable to analysis. We here show that the well-known disease-causing mutation F508del, which established cystic fibrosis as protein-folding disease, caused co-translational misfolding of NBD1 but not TMD1 nor TMD2 in stage 1, leading to absence of stage-2 folding. Corrector drugs rescued stage 2 without rescuing NBD1. Likewise, the DxD motif in NBD1 that was identified to be required for export of CFTR from the ER we found to be required already upstream of export as CFTR mutated in this motif phenocopies F508del CFTR. The highly modular and stepwise folding process of such a large, complex protein explains the relatively high fidelity and correctability of its folding.

PMID:36609925 | DOI:10.1007/s00018-022-04671-x

Cell Mol Life Sci. 2023 Jan 7;80(1):31. doi: 10.1007/s00018-022-04662-y.

ABSTRACT

BACKGROUND AND AIMS: Thiopurine-induced acute pancreatitis (TIP) is one of the most common adverse events among inflammatory bowel disease patients treated with azathioprine (AZA), representing a significant clinical burden. Previous studies focused on immune-mediated processes, however, the exact pathomechanism of TIP is essentially unclear.

METHODS: To model TIP in vivo, we triggered cerulein-induced experimental pancreatitis in mice receiving a daily oral dose of 1.5 mg/kg AZA. Also, freshly isolated mouse pancreatic cells were exposed to AZA ex vivo, and acinar cell viability, ductal and acinar Ca2+ signaling, ductal Cl- and HCO3- secretion, as well as cystic fibrosis transmembrane conductance regulator (CFTR) expression were assessed using microscopy techniques. Ras-related C3 botulinum toxin substrate (RAC1) activity was measured with a G-LISA assay. Super-resolution microscopy was used to determine protein colocalization.

RESULTS: We demonstrated that AZA treatment increases tissue damage in the early phase of cerulein-induced pancreatitis in vivo. Also, both per os and ex vivo AZA exposure impaired pancreatic fluid and ductal HCO3- and Cl- secretion, but did not affect acinar cells. Furthermore, ex vivo AZA exposure also inhibited RAC1 activity in ductal cells leading to decreased co-localization of CFTR and the anchor protein ezrin, resulting in impaired plasma membrane localization of CFTR.

CONCLUSIONS: AZA impaired the ductal HCO3- and Cl- secretion through the inhibition of RAC1 activity leading to diminished ezrin-CFTR interaction and disturbed apical plasma membrane expression of CFTR. We report a novel direct toxic effect of AZA on pancreatic ductal cells and suggest that the restoration of ductal function might help to prevent TIP in the future.

PMID:36609875 | DOI:10.1007/s00018-022-04662-y

Commun Biol. 2023 Jan 6;6(1):16. doi: 10.1038/s42003-022-04395-5.

ABSTRACT

Microorganisms living at many sites in the human body compose a complex and dynamic community. Accumulating evidence suggests a significant role for microorganisms in cancer, and therapies that incorporate bacteria have been tried in various types of cancer. We previously demonstrated that cupredoxin azurin secreted by the opportunistic pathogen Pseudomonas aeruginosa, enters human cancer cells and induces apoptotic death1-4. However, the physiological interactions between P. aeruginosa and humans and their role in tumor homeostasis are largely unknown. Here, we show that P. aeruginosa upregulated azurin secretion in response to increasing numbers of and proximity to cancer cells. Conversely, cancer cells upregulated aldolase A secretion in response to increasing proximity to P. aeruginosa, which also correlated with enhanced P. aeruginosa adherence to cancer cells. Additionally, we show that cancer patients had detectable P. aeruginosa and azurin in their tumors and exhibited increased overall survival when they did, and that azurin administration reduced tumor growth in transgenic mice. Our results suggest host-bacterial symbiotic mutualism acting as a diverse adjunct to the host defense system via inter-kingdom communication mediated by the evolutionarily conserved proteins azurin and human aldolase A. This improved understanding of the symbiotic relationship of bacteria with humans indicates the potential contribution to tumor homeostasis.

PMID:36609683 | DOI:10.1038/s42003-022-04395-5

Pancreas. 2022 Sep 1;51(8):1029-1036. doi: 10.1097/MPA.0000000000002134.

ABSTRACT

OBJECTIVES: Early detection of cystic fibrosis (CF) related diabetes (CFRD) improves health outcomes and reduces CF-related mortality. The study aims to evaluate the ratio of islet amyloid polypeptide (IAPP) to C-peptide in CF patients with diabetes and without diabetes.

METHODS: Cross-sectional analysis was carried out in a prospective cohort of 33 participants (CF [n = 16] and CFRD [n = 18]). We examined the association of plasma IAPP:C-peptide ratio with clinical information, including glycated hemoglobin, and lung function markers.

RESULTS: The median (interquartile range) IAPP:C-peptide ratio was significantly (P = 0.004) higher in people with CFRD (4.8 [4.5]) compared with participants without CFRD (12.1 [19.7]). The ratio of IAPP to C-peptide significantly accounted for a 38% variation in the diabetes status in patients with CF (r2 = 0.399, P < 0.001). Islet amyloid polypeptide is strongly correlated with serum ferritin levels (r = 0.683, P = 0.005) and forced expiratory volume in CFRD, but not in nondiabetic participants with CF.

CONCLUSIONS: Islet amyloid polypeptide:C-peptide ratio could be a potential marker of CFRD in adults with CF. Further research requires validation of this marker in longitudinal cohort studies to confirm the capability of IAPP:C-peptide to predict CFRD.

PMID:36607950 | DOI:10.1097/MPA.0000000000002134

Medicine (Baltimore). 2023 Jan 6;102(1):e32227. doi: 10.1097/MD.0000000000032227.

ABSTRACT

Survival improvement in cystic fibrosis (CF) is associated with more frequent long-term complications, including CF related bone disease (CFBD). Impact of CFBD on global health outcome remains poorly described. We aimed to assess the relationship between low bone mineral density (BMD) and spinal pain, disability, and quality of life in CF adult patients. This monocentric cross-sectional study with prospective data collection was conducted from November 2016 to December 2019 in the Department of Respiratory Diseases at the University Hospital of Reims (NCT02924818). BMD was assessed by X-ray absorptiometry (DXA). Disability was assessed by the Health Assessment Questionnaire (HAQ). Quality of life was assessed by both the St George's Respiratory Questionnaire and the Cystic Fibrosis Questionnaire for teenagers and adults (CFQ 14+). Forty patients were analyzed, 68% of men, with a median age of 25 years, a median body mass index of 21 kg/m² and a median FEV1% of 54%. Nine patients (23%) had spinal pain. Ten patients (25%) had a low BMD. Compared with patients with normal BMD, patients with low BMD had a significantly lower BMI (22 vs 19 kg/m²; P = .006) and less vitamin D supplementation (33% vs 0%; P = .035). Low BMD was not associated with spinal pain, disability and quality of life. Low BMD is frequent in CF, affecting 1-quarter of adult patients. No significant association was found between low BMD and spinal pain, disability or quality of life.

PMID:36607849 | DOI:10.1097/MD.0000000000032227

J Clin Monit Comput. 2023 Jan 6. doi: 10.1007/s10877-022-00970-7. Online ahead of print.

ABSTRACT

Clearance of secretions remains a challenge in ventilated patients. Despite high-frequency percussive ventilation (HFPV) showing benefits in patients with cystic fibrosis and neuromuscular disorders, very little is known about its effects on other patient categories. Therefore, we designed a physiological pilot study investigating the effects on lung aeration and gas exchange of short HFPV cycles in tracheostomized patients undergoing mechanical ventilation. Electrical impedance tomography (EIT) was recorded at baseline (T0) by a belt wrapped around the patient's chest, followed by the HFPV cycle lasting 10 min. EIT data was collected again after the HFPV cycle (T1) as well as after 1 h (T2) and 3 h (T3) from T0. Variation from baseline of end-expiratory lung impedance (∆EELI), tidal variation (TIV) and global inhomogeneity index (GI) were computed. Arterial blood was also taken for gas analysis. HFPV cycle significantly improved the ∆EELI at T1, T2 and T3 when compared to baseline (p < 0.05 for all comparisons). The ratio between arterial partial pressure and inspired fraction of oxygen (PaO2/FiO2) also increased after the treatment (p < 0.001 for all comparison) whereas TIV (p = 0.132) and GI (p = 0.114) remained unchanged. Short cycles of HFPV superimposed to mechanical ventilation promoted alveolar recruitment, as suggested by improved ∆EELI, and improved oxygenation in tracheostomized patients with high load of secretion.Trial Registration Prospectively registered on www.clinicaltrials.gov (NCT05200507; dated 6th January 2022).

PMID:36607533 | DOI:10.1007/s10877-022-00970-7

Metabol Open. 2022 Dec 17;17:100222. doi: 10.1016/j.metop.2022.100222. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: Management of constipation with currently available modern medicines is costly and chances of side effects are high. This limits their clinical usefulness and remain to be solved, and calls for investigations of new and better compounds. The experimental plant, Euclea racemosa L. (E. racemosa L) is among plants, which are used for management of constipation traditionally but its effect is not yet experimentally validated. Therefore, the aim of the present study is to investigate the laxative effects of this plant.

METHODS: The laxative effects of aqueous root extracts of E. racemosa L. were evaluated using gastrointestinal motility, laxative activity, and gastrointestinal secretion tests.

RESULTS: In the laxative test, the 200 and 400 mg/kg doses of plant extract showed a significant increase in percent fecal water content. The plant extract also significantly accelerated the charcoal meal in gastrointestinal motility test of loperamide-constipated mice. Moreover, the experimental plant produced significant Gastrointestinal (GI) transit ratio at all doses but failed to produce a significantly higher fluid accumulation except 400 mg/kg doses of extract in gastrointestinal secretion test. The observed effect of the aqueous root extract might be due to the presence of secondary metabolites. The aqueous root extract of E. racemosa L. revealed the presence of terpenes, saponins, flavonoids and phenols when it was subjected to phytochemical screening.

CONCLUSION: The investigation obtained from this study suggested that E. racemosa L. has a beneficial effect in producing laxative effect and this substantiate the traditional use of the plant for its claimed indication.

PMID:36606022 | PMC:PMC9807816 | DOI:10.1016/j.metop.2022.100222

ERJ Open Res. 2023 Jan 3;9(1):00336-2022. doi: 10.1183/23120541.00336-2022. eCollection 2023 Jan.

ABSTRACT

BACKGROUND: People living with cystic fibrosis have an increased risk of lung infection with nontuberculous mycobacteria (NTM), the prevalence of which is reportedly increasing. We conducted a systematic review of the literature to estimate the burden (prevalence and incidence) of NTM in the cystic fibrosis population.

METHODS: Electronic databases, registries and grey literature sources were searched for cohort and cross-sectional studies reporting epidemiological measures (incidence and prevalence) of NTM infection or NTM pulmonary disease in cystic fibrosis. The last search was conducted in September 2021; we included reports published since database creation and registry reports published since 2010. The methodological quality of studies was appraised with the Joanna Briggs Institute tool. A random effects meta-analysis was conducted to summarise the prevalence of NTM infection, and the remaining results are presented in a narrative synthesis.

RESULTS: This review included 95 studies. All 95 studies reported on NTM infection, and 14 of these also reported on NTM pulmonary disease. The pooled estimate for the point prevalence of NTM infection was 7.9% (95% CI 5.1-12.0%). In meta-regression, sample size and geographical location of the study modified the estimate. Longitudinal analysis of registry reports showed an increasing trend in NTM infection prevalence between 2010 and 2019.

CONCLUSIONS: The overall prevalence of NTM infection in cystic fibrosis is 7.9% and is increasing over time based on international registry reports. Future studies should report screening frequency, microbial identification methods and incidence rates of progression from NTM infection to pulmonary disease.

PMID:36605902 | PMC:PMC9808535 | DOI:10.1183/23120541.00336-2022

Sci Rep. 2023 Jan 5;13(1):64. doi: 10.1038/s41598-022-26384-8.

ABSTRACT

Biallelic variants in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) are the main pathogenic factor of congenital absence of the vas deferens (CAVD), including congenital bilateral absence of the vas deferens (CBAVD) and congenital unilateral absence of the vas deferens (CUAVD). However, there are few reports about the correlation between CFTR variant and outcomes of assisted reproductive technology (ART) in CAVD patients of China. In this study, 104 patients with CAVD were recruited in Central China, and provided gene detection by the whole-exome sequencing, among them 69% (72/104) carried at least one variant in CFTR and one carried adhesion G protein-coupled receptor G2 (ADGRG2) variant. A total of 81 CAVD patients were treated with ART, of which 21 and 60 carried none or at least one variant in CFTR, respectively. The fertilization rate, cleavage rate, effective embryo rate, implantation rate, clinical pregnancy rate and live birth rate per fresh embryo transfer were compared between patients with and without CFTR variants. It was found that the ART outcomes had no significant difference whether the patients carried the CFTR variant or not. In addition, all of the offspring were healthy after follow-up. In conclusion, rare CFTR variants may play a major role in patients with CAVD in Central China, which were greatly different from other descent. There was no significant difference in ART outcomes in CAVD patients with or without CFTR variants. The limitations of this study were that there was no statistical analysis of the sperm quality through TESA and conclusions were relatively limited due to the small sample size of the study.

PMID:36604502 | DOI:10.1038/s41598-022-26384-8

J Allergy Clin Immunol. 2023 Jan 2:S0091-6749(22)02591-X. doi: 10.1016/j.jaci.2022.12.818. Online ahead of print.

ABSTRACT

BACKGROUND: Food challenges (FC) form the basis of assessing efficacy outcomes in interventional studies for food allergy, however different studies have used a variety of similar but not identical criteria to define a challenge reaction, some including subjective (non-objective) symptoms in a single organ system as being considered dose-limiting.

OBJECTIVE: To undertake a secondary analysis of 4 interventional studies to assess the impact of using less objective criteria to determine challenge-stop on reaction thresholds and their reproducibility.

METHODS: Analysis of individual participant data (IPD) including IPD meta-analysis, using three different published challenge-stop criteria: (i) PRACTALL; (ii) CoFAR v3 with at least 1 moderate/severe grade symptom; or (iii) CoFAR v3 with at least 2 mild symptoms occurring in different organ systems. Reproducibility of challenge threshold was also assessed in participants undergoing subsequent repeat FC.

RESULTS: 4 studies, with detailed challenge data from a total of 592 participants, were included. Applying CoFAR v3 definitions for dose-limiting symptoms (DLS) resulted in an underestimate of reaction thresholds compared to PRACTALL (P<0.001), equivalent to almost a single dosing increment when using a semi-log dosing regimen. Reproducibility was also reduced when applying CoFAR v3 (P<0.001, N=223). Using the least conservative interpretation of CoFAR v3 (≥2 mild symptoms occurring in different systems) resulted in a significant overestimate of 15% when assessing OIT efficacy. Applying a data-driven, minor modification to CoFAR v3 resulted in a new set of challenge-stop criteria with similar validity to PRACTALL, but simpler in implementation and one where significant gastrointestinal discomfort with observable decreased activity remains a DLS.

CONCLUSION: The use of less objective symptoms to define challenge-stop compromises the reproducibility of FC as a tool to assess efficacy outcomes in interventional studies, and potentially over-estimates the efficacy of the intervention tested.

PMID:36603776 | DOI:10.1016/j.jaci.2022.12.818

JCI Insight. 2023 Jan 5:e161961. doi: 10.1172/jci.insight.161961. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is characterized by chronic bacterial infections leading to progressive bronchiectasis and respiratory failure. Pseudomonas aeruginosa (Pa) is the predominant opportunistic pathogen infecting the CF airways. The guanine nucleotide exchange factor Vav3 plays a critical role in Pa adhesion to the CF airways by inducing luminal fibronectin deposition that favors bacteria trapping. Here we report that Vav3 overexpression in CF is caused by upregulation of the mRNA-stabilizing protein HuR. We found that HuR accumulates in the cytoplasm of CF airway epithelial cells, binds to and stabilizes Vav3 mRNA. Interestingly, disruption of HuR-Vav3 mRNA interaction improved the CF epithelial integrity, inhibited the formation of the fibronectin-made bacterial docking platforms and prevented Pa adhesion to the CF airway epithelium. These findings indicate that targeting HuR represents a promising anti-adhesive approach in CF to prevent initial stages of Pa infection in a context of emergence of multidrug resistant pathogens.

PMID:36602863 | DOI:10.1172/jci.insight.161961

J Clin Microbiol. 2023 Jan 5:e0155822. doi: 10.1128/jcm.01558-22. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is characterized by mutations of CFTR that lead to increased viscous secretions, bacterial colonization, and recurrent infections. Chronic Pseudomonas aeruginosa infection in persons with CF is associated with progressive and accelerated lung function decline despite aggressive antibiotic treatment. We report the management of respiratory infections in persons with CF with antibiotic therapy that was based on the recommendations of AtbFinder, a novel, rapid, culture-based diagnostic test system that employs a novel paradigm of antibiotic selection. AtbFinder mimics bacterial interactions with antibiotics at concentrations that can be achieved in affected tissues or organs and models conditions of interbacterial interactions within polymicrobial biofilms. This open-label, single-arm, investigator-initiated clinical study was designed to identify the efficacy of antibiotics selected using AtbFinder in persons with CF. Microbiological and clinical parameters were assessed following the change of antibiotic therapy to antibiotics selected with AtbFinder between January 2016 and December 2018 and retrospectively compared with clinical data collected between January 2013 and December 2015. We enrolled 35 persons with CF (33 with chronic P. aeruginosa colonization). Antibiotics selected using AtbFinder resulted in clearance of P. aeruginosa in 81.8% of subsequent cultures, decreased pulmonary exacerbations from 1.21 per patient per annum to 0, and an increase in predicted percent predicted forced expiratory volume in 1 s up to 28.4% from baseline. The number of systemic antibiotic courses used in patients after switching to the AtbFinder-selected therapy was reduced from 355 to 178. These findings describe the superiority of antibiotic regimens selected with AtbFinder compared with routine antimicrobial susceptibility testing.

PMID:36602344 | DOI:10.1128/jcm.01558-22

Saudi Pharm J. 2022 Dec;30(12):1736-1747. doi: 10.1016/j.jsps.2022.10.002. Epub 2022 Oct 8.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease that affects the exocrine glands and is caused by cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. Lung disease is the leading cause of morbidity in patients. Target-specific treatment of CF has been achieved using monoclonal antibodies (mAbs). The purpose of this article is to discuss the possibility of treating CF with mAbs through their significant target specificity. We searched electronic databases in Web of Science, PubMed, EMBASE, Scopus, and Google Scholar from 1984 to 2021. We discussed the critical role of targeted therapy in cystic fibrosis, as it will be more effective at suppressing the molecular networks. After conducting a critical review of the available literature, we concluded that it is critical to understand the fundamental molecular mechanisms underlying CF prior to incorporating biologics into the therapy regimen. Omalizumab, Mepolizumab, Benralizumab, Dupilumab and KB001-A have been successfully screened for asthma-complicated CF, and their efficacies have been well reported. Despite the availability of effective targeted biologics, treating CF has remained a difficult task, particularly when it comes to reduction of secondary inflammatory mediators. This review emphasizes the overall views on CF, the immunological mechanism of CF, and the prospective therapeutic use of mAbs as potential targeted biologics for enhancing the overall status of human health.

PMID:36601503 | PMC:PMC9805982 | DOI:10.1016/j.jsps.2022.10.002

J Asthma Allergy. 2022 Dec 29;15:1861-1875. doi: 10.2147/JAA.S389985. eCollection 2022.

ABSTRACT

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) primarily complicates the course of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Mortality data of ABPA and the difference in all-cause mortality between ABPA with and without COPD are not available.

OBJECTIVE: We investigated the difference in all-cause mortality between ABPA with and without COPD.

METHODS: A retrospective review was performed among patients with the diagnosis of ABPA at Peking University People's Hospital between January 2010 and March 2022. Logrank test was performed to investigate the difference between all-cause mortality for ABPA with and without COPD and Cox regression analysis was performed to investigate the independent risk factors for all-cause mortality in patients with ABPA.

RESULTS: Sixty-one patients with ABPA were enrolled in this study. The follow-up duration was 50.38 months (3-143 months). In the COPD group, 7 patients died (7/10), while in the non-COPD group, 4 patients died (4/51). The 1-year survival rates of ABPA with and without COPD were 60% and 97.8%, respectively. The 5-year survival rates of ABPA with and without COPD were 40% and 94%, respectively. The Cox regression analysis showed that higher C-reactive protein (CRP) (HR = 1.017, 95% CI 1.004-1.031, P = 0.013) and complicating COPD (HR = 8.525, 95% CI 1.827-39.773, P = 0.006) were independent risk factors associated with mortality in patients with ABPA.

CONCLUSION: The all-cause mortality for ABPA with COPD is higher than that for ABPA without COPD. Higher CRP and complicating COPD are independent risk factor for mortality in patients with ABPA.

PMID:36601290 | PMC:PMC9807121 | DOI:10.2147/JAA.S389985