Eur J Radiol. 2022 Jun 23;154:110421. doi: 10.1016/j.ejrad.2022.110421. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have revolutionised the treatment of cystic fibrosis (CF). Chest computed tomography (CT) is key in the diagnosis and follow-up of anatomical damage to the lungs. Our study aimed to evaluate changes on lung CT scans of patients with CF after receiving elexacaftor-tezacaftor-ivacaftor (ETI) therapy for one year.

MATERIALS AND METHODS: We conducted a retrospective, observational, single-centre study between 2018 and 2021 on adult patients with CF administered ETI. We reviewed chest CT scans before and at least one year after starting ETI. The Brody-II score (BSII) was measured by two experienced radiologists who were blinded to the treatment. Paranasal sinus CT scans and clinical and functional data were also compared. Wilcoxon tests were used to compare differences, and Spearman's correlation coefficient was used to evaluate changes in forced expiratory volume in one second (FEV1) and total BSII.

RESULTS: In the period, 63 patients were given ETI, and 12 met the criteria for analysis. The inter-observer reproducibility of BSII was satisfactory (intraclass correlation coefficient = 0.83, 95% confidence interval 0.57-0.91). The BSII decreased after one year of treatment (-18 ± 16, p = 0.002) due to lower mucous plugging (-7 ± 4, p < 0.001) and peribronchial thickening (-9 ± 10, p = 0.002) scores. Bronchial, parenchymal, and hyperinflation scores were unchanged. Clinical and functional parameters were significantly improved, except for total lung capacity. The correlation between ΔFEV1 and Δtotal BSII was strong (r = 0.88, p < 0.001). The paranasal sinus CT score significantly improved with ETI treatment.

CONCLUSIONS: ETI decreased pulmonary and sinus morphological abnormalities after one year of treatment.

PMID:35772339 | DOI:10.1016/j.ejrad.2022.110421

Am J Respir Crit Care Med. 2022 Jun 30. doi: 10.1164/rccm.202204-0734OC. Online ahead of print.

ABSTRACT

RATIONALE: Previous phase 3 trials showed treatment with lumacaftor/ivacaftor was safe and efficacious in people aged ≥2 years with cystic fibrosis homozygous for F508del-CFTR (F/F genotype).

OBJECTIVES: To assess the safety, pharmacokinetics, and pharmacodynamics of lumacaftor/ivacaftor in children aged 1 to <2 years with the F/F genotype.

METHODS: This open-label, phase 3 study consisted of two parts (Part A [N = 14] and Part B [N = 46]) that enrolled two cohorts based on age (Cohort 1: 18 to <24 months and Cohort 2: 12 to <18 months). For the 15-day treatment period in Part A, lumacaftor/ivacaftor dose was based on weight at screening. Pharmacokinetic data from Part A were used to determine dose-based weight boundaries for Part B (24-week treatment period).

MEASUREMENTS AND MAIN RESULTS: The primary endpoint of Part A was pharmacokinetics and the primary endpoint for Part B was safety and tolerability. Secondary endpoints for Part B were absolute change in sweat chloride concentration from baseline at Week 24 and pharmacokinetics. Analysis of pharmacokinetic data from Part A confirmed the appropriateness of Part B dosing. In Part B, 44 children (95.7%) had adverse events which for most were either mild (52.2% of children) or moderate (39.1% of children) in severity. The most common adverse events were cough, infective pulmonary exacerbation of cystic fibrosis, pyrexia, and vomiting. At Week 24, mean absolute change from baseline in sweat chloride concentration was ‒29.1 mmol/L (95% confidence interval, ‒34.8 to ‒23.4). Growth parameters (body mass index, weight, length, and associated z-scores) were normal at baseline and remained normal during the 24-week treatment period. Improving trends in some biomarkers of pancreatic function and intestinal inflammation such as fecal elastase-1, serum immunoreactive trypsinogen, and fecal calprotectin were observed.

CONCLUSIONS: Lumacaftor/ivacaftor was generally safe and well tolerated in children aged 1 to <2 years with the F/F genotype with a pharmacokinetic profile consistent with studies in older children. Efficacy results, including robust reductions in sweat chloride concentration, suggest the potential for CF disease modification with lumacaftor/ivacaftor treatment. These results support the use of lumacaftor/ivacaftor in this population. Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT03601637.

PMID:35771568 | DOI:10.1164/rccm.202204-0734OC

Mil Med. 2022 Jun 30:usac161. doi: 10.1093/milmed/usac161. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is the most common life-threatening genetic illness in the United States. People with CF as well as their caregivers are up to three times more likely to report experiencing symptoms of depression and anxiety than those without CF. In 2016, the Cystic Fibrosis Foundation and the European Cystic Fibrosis Society came together to form the International Committee on Mental Health in CF and released guidelines outlining behavioral health (BH) screening recommendations for patients with CF and at least one primary caregiver. This study sought to characterize the role of BH care in routine CF treatment within the DoD health care system and identify potential opportunities for improvement. The resultant brief report is intended to elucidate and present identified areas of improvement as well as to inform further research projects in this field.

MATERIALS AND METHODS: A representative sample of program leaders (8 of 12; five program directors and three nurse coordinators) from all six affiliate CF centers in the DoD completed a 23-item web-based survey. This study sought to identify the following: (1) What tools are DoD affiliate CF centers using to screen patients with CF and their caregiver(s) for psychological distress and how often does screening take place? (2) What is the composition of the DoD's CF BH teams by specialty and to what degree are BH personnel available to support the needs of CF patients? (3) How comfortable are program directors and nurse coordinators in screening patients with CF and their caregiver(s) for indicators of psychological distress? (4) How familiar are CF BH teams with the use of the U.S. Military's Behavioral Health Data Portal (BHDP)? This descriptive study was approved by the Human Use Committee at the Tripler Army Medical Center.

RESULTS: The results of this study indicated that 80% of the DoD affiliate CF centers are screening patients with CF who are 12 years and older and at least one caregiver at least annually for depression and anxiety with the Patient Health Questionnaire depression module and generalized anxiety disorder screening tool, respectively. Reported screening tools for suicidality were not standardized across centers. All respondents indicated that there is a designated social worker in their CF clinic team. Three-quarters of respondents reported that their social worker is physically present in CF clinics 75%-100% of the time. Other types of BH team members varied by clinic. Program directors and nurse coordinators on average indicated feeling "somewhat comfortable" in screening patients with CF for depression, anxiety, and suicidality. Eighty percent of program directors reported being "not so comfortable" in screening caregivers for depression, anxiety, and suicidality, with nurse coordinators on average reporting feeling "somewhat comfortable." Eighty percent of affiliate CF centers indicated that they are unaware of, are not utilizing, or do not have access to the BHDP to screen and record BH data for patients with CF or their caregiver(s).

CONCLUSIONS: This study characterized routine CF BH care at DoD affiliate CF centers. Areas for improvement include the standardized use of screening tools for suicidality, increased provider comfort with screening, and streamlined recording and tracking of this data using the BHDP. Limitations of this study include inherent self-report bias, specifically social desirability bias. Steps toward suggested improvements and further utilization of the BHDP may improve BH care for patients with CF and their caregiver(s) in addition to facilitating future research.

PMID:35770933 | DOI:10.1093/milmed/usac161

Eur Respir Rev. 2022 Jun 28;31(164):220046. doi: 10.1183/16000617.0046-2022. Print 2022 Jun 30.

ABSTRACT

During the 1930 Lübeck Mycobacterium bovis bacille Calmette-Guérin (BCG) disaster, 251 neonates received three oral BCG doses accidentally contaminated by virulent Mycobacterium tuberculosis; 67 (26.7%) infants died of tuberculosis. BCG reversion to pathogenicity did not occur. Detailed post mortem examinations clarified contested aspects of tuberculosis pathogenesis. Gastrointestinal infection was seldom "silent" and did not cause typical primary pulmonary lesions. In 15 infants, primary pulmonary foci were found but these resulted from vaccine ingestion and aspiration and were not caused by gastrointestinal infection spreading to the lungs without trace of its journey, as claimed by prominent researchers such as Calmette and von Behring. Further, among 60 infants in whom post mortem evaluation was completed, a "silent" gastrointestinal infection without an intestinal primary focus was found in only one. Lymphohaematogenous-disseminated tuberculosis caused death in 24/67 (35.8%) infants and tuberculous meningitis in a further 17/67 (25.4%). Gastrointestinal tuberculosis complications caused death in 26/67 (38.8%) infants. Half of the tuberculosis-attributed deaths had occurred by 3 months, 93% by 6 months and 100% by 12 months; remarkably no further deaths or tuberculosis recurrences occurred within 5 years post-vaccination/infection. These findings provide graphic confirmation that the early introduction of chemoprophylaxis in recently M. tuberculosis-infected young children is critical and urgent.

PMID:35768133 | DOI:10.1183/16000617.0046-2022

J Health Popul Nutr. 2022 Jun 28;41(1):26. doi: 10.1186/s41043-022-00305-x.

ABSTRACT

BACKGROUND: This study aimed to determine the prevalence and antibiotic resistance patterns in Staphylococcus aureus isolated from patients with cystic fibrosis in Middle Eastern countries.

METHODS: A systematic search was conducted in the PubMed, Web of Science (ISI), and Scopus databases for studies presenting the prevalence of MRSA strains, antibiotic resistance pattern in S. aureus strains isolated from patients who suffered from cystic fibrosis in Middle Eastern countries from 1999 to 10 June 2020. The following terms were used; prevalence, antibiotic resistance, antimicrobial drug resistance, drug resistance, Staphylococcus aureus, S. aureus, Methicillin-resistant Staphylococcus aureus, MRSA, cystic fibrosis, CF, and the Middle East. The meta-analysis was performed using Comprehensive Meta-analysis software (Version 3.3.070).

RESULTS: Patients' age ranged from 1.6 to 18 years. Females were more than males. The prevalence of S. aureus was varied between 5.6 and 77.8%. The prevalence of S. aureus was varied between 5.6 and 77.8% in different countries. The combined prevalence of S. aureus in Middle East countries from 1999 to 2020 was reported by 40.9% (95% CI 29.6-53.1). The pooled prevalence of MRSA was reported at 18.6% (95% CI 1.1-82.6), Z = 0.9, I2 = 98.6, Q = 146.7. The highest combined resistance in S. aureus strains was reported to Penicillin G (94%), followed by Ciprofloxacin (54.9%).

CONCLUSION: Regarding a quite prevalence of S. aureus and an intermediate prevalence of MRSA in CF patients, preventive measures and health policies should be implemented in the Middle East area to prevent the spread of infections caused by MRSA strains in CF patients.

PMID:35765068 | DOI:10.1186/s41043-022-00305-x

J Cyst Fibros. 2022 Jun 25:S1569-1993(22)00589-6. doi: 10.1016/j.jcf.2022.06.002. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic Fibrosis (CF) has prominent gastrointestinal and pancreatic manifestations. The aim of this study was to determine the effect of Cystic fibrosis transmembrane conductance regulator (CFTR) modulation on, gastrointestinal inflammation, pancreatic function and gut microbiota composition in people with cystic fibrosis (CF) and the G551D-CFTR mutation.

METHODS: Fourteen adult patients with the G551D-CFTR mutation were assessed clinically at baseline and for up to 1 year after treatment with ivacaftor. The change in gut inflammatory markers (calprotectin and lactoferrin), exocrine pancreatic status and gut microbiota composition and structure were assessed in stool samples.

RESULTS: There was no significant change in faecal calprotectin nor lactoferrin in patients with treatment while all patients remained severely pancreatic insufficient. There was no significant change in gut microbiota diversity and richness following treatment.

CONCLUSION: There was no significant change in gut inflammation after partial restoration of CFTR function with ivacaftor, suggesting that excess gut inflammation in CF is multi-factorial in aetiology. In this adult cohort, exocrine pancreatic function was irreversibly lost. Longer term follow-up may reveal more dynamic changes in the gut microbiota and possible restoration of CFTR function.

PMID:35764510 | DOI:10.1016/j.jcf.2022.06.002

Microb Drug Resist. 2022 Jun 28. doi: 10.1089/mdr.2021.0389. Online ahead of print.

ABSTRACT

We investigated the in vitro susceptibility of ceftazidime-avibactam (CZA) resistant Stenotrophomonas maltophilia to the associations aztreonam/amoxicillin-clavulanate (ATM-AMC) and ATM-CZA. Forty clinical isolates of S. maltophilia recovered from sputum samples of 40 cystic fibrosis people were selected from the collection of the Nantes University Hospital, based on their resistance to CZA. Minimum inhibitory concentrations (MICs) of ATM-CZA and ATM-AMC were determined for each isolate by an Etest strip superposition method, and by Etest for each individual antibiotic. MICs of CZA, ATM, and AMC ranged from 12 to ≥256, ≥256, and 16 to ≥256 mg/L, respectively. Synergistic effects were observed with the ATM-CZA combination for all isolates (fractional inhibitory concentration index range of 0.01 to 0.27), with combination MICs ranging from 0.75 to 16 mg/L (MIC50/90 = 3/12 mg/L), corresponding to a decrease of at least 16-folds in the MIC of ATM. In 23 (57.5%) S. maltophilia isolates, the association of AMC to ATM was also synergistic and combination MICs were ≤16 mg/L (EUCAST breakpoint for ATM resistance in Pseudomonas aeruginosa). Our results show that ATM-CZA or ATM-AMC could be alternative therapeutic options against some highly resistant S. maltophilia. This encourages further experimental studies, in particular time-kill analyses, and clinical trials to delineate conditions required for use of these combinations in practice.

PMID:35763306 | DOI:10.1089/mdr.2021.0389

Am J Physiol Lung Cell Mol Physiol. 2022 Jun 28. doi: 10.1152/ajplung.00113.2022. Online ahead of print.

ABSTRACT

The 9th biennial conference titled "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases" was hosted virtually, due to the ongoing COVID-19 pandemic, in collaboration with the University of Vermont Larner College of Medicine, the National Heart, Lung, and Blood Institute, the Alpha-1 Foundation, the Cystic Fibrosis Foundation, and the International Society for Cell & Gene Therapy. The event was held from July 12th through 15th, 2021 with a pre-conference workshop held July 9th. As in previous years the objectives remained to review and discuss the status of active research areas involving stem cells, cellular therapeutics, and bioengineering as they relate to the human lung. Topics included: 1) technological advancements in the in situ analysis of lung tissues, 2) new insights into stem cell signalling and plasticity in lung remodelling and regeneration, 3) the impact of extracellular matrix in stem cell regulation and airway engineering in lung regeneration, 4) differentiating and delivering stem cell therapeutics to the lung, 5) regeneration in response to viral infection, and 6) ethical development of cell-based treatments for lung diseases. This selection of topics represents some of the most dynamic and current research areas in lung biology. The virtual workshop included active discussion on state-of-the-art methods relating to the core features of the 2021 conference, including in-situ protemics, lung-on-chip, iPSC-airway differentiation, and light sheet microscopy. The conference concluded with an open discussion to suggest funding priorities and recommendations for future research directions in basic and translational lung biology.

PMID:35762622 | DOI:10.1152/ajplung.00113.2022

Indian J Gastroenterol. 2022 Jun 27. doi: 10.1007/s12664-021-01225-0. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the demography and spectrum of pancreatic, hepatobiliary, and gastrointestinal (GI) manifestations in children with cystic fibrosis (CF) from the Indian subcontinent.

METHODS: In this retrospective study, relevant information from the database of all children with CF below 18 years of age was collected and analyzed.

RESULTS: Among the total 109 children, 58 (53%) were from the southern states of India. The most common manifestation was pancreatic insufficiency (PI) in 85 (83%) children. Those with PI presented at an earlier age (1.8 vs. 6.9 years). Cirrhosis with portal hypertension was documented in only one patient and meconium ileus in three (2.8%). There was significant malnutrition in the PI cohort with a mean weight-for-age Z-score of - 3.17 ± 1.79 at diagnosis. Twenty-one (19%) patients had died during the follow-up and 18 (90%) of them had PI. There was no difference in the prevalence of selected pulmonary manifestations in the PI and pancreatic sufficient (PS) groups. Among children with PI, 78 were screened for ΔF508 mutation, 16 (21%) were homozygous, and 17 (22%) were heterozygous. In the PS group, only 2 (14%) were heterozygous for ΔF508 mutation. The median duration of follow-up of the patients was 1.8 (1.5) years.

CONCLUSION: PI is the most common GI manifestation of children with CF and is associated with severe malnutrition and poor outcome. Timely identification and management of the comorbidities involving the digestive system are essential for better growth and quality of life in these children.

PMID:35761057 | DOI:10.1007/s12664-021-01225-0

J Cyst Fibros. 2022 Jun 24:S1569-1993(22)00595-1. doi: 10.1016/j.jcf.2022.06.008. Online ahead of print.

NO ABSTRACT

PMID:35760705 | DOI:10.1016/j.jcf.2022.06.008

BMJ Open Respir Res. 2022 Jun;9(1):e001221. doi: 10.1136/bmjresp-2022-001221.

ABSTRACT

INTRODUCTION: A new smartphone app (QUT Inspire) has been developed to detect inspiratory sound and deliver virtual incentive spirometry (ISy), a respiratory therapy technique used in postoperative recuperation, management of some chronic conditions and with potential applications in SARS-CoV-2 rehabilitation. The aim of this study was to compare the usability of this new app with a clinical ISy device as measured by effectiveness, efficiency and satisfaction.

METHODS: In this mixed-methods randomised usability study, healthy volunteers (aged 39.2±12.2 years, n=24) compared inspirations using the QUT Inspire app and a Triflo II clinical ISy device. A post-test questionnaire and a semi-structured interview explored dimensions of usability regarding the new app.

RESULTS: The duration of inspirations performed using the QUT Inspire app (7.3±2.0 s) were comparable with use of the Triflo II ISy device (7.5±2.3 s). No artefacts arising from the order of device testing were identified. App users held their phones adjacent but not proximal to their mouths (13.6±6.4 cm), notwithstanding instructions to keep the phone less than 5 cm away for optimal breath sound detection. The use of onscreen text or video instructional materials did not result in a significant reduction in this distance. Participants reported clear preferences for the app (100%, n=24) to motivate persistence with repeated inspirations. App gamification features such as a timer (75%, n=18) and breath counter (83.3%, n=20) were well regarded. Analysis of semi-structured interviews identified four main themes arising from this study: visual reward from responsive app animations, clinical look and feel influencing credibility, perceived effort affecting engagement and selective adoption of gamification features.

CONCLUSION: This study demonstrates that a virtual ISy app can be effective, efficient and have high satisfaction. Improvements informed by this research include use of additional phone sensors to optimise sound detection and minimising the distance that phones are held from the user's mouth. Further research in randomised controlled trials are needed to evaluate performance of this app in clinical contexts where ISy is currently employed.

PMID:35760497 | DOI:10.1136/bmjresp-2022-001221

Int J Pediatr Otorhinolaryngol. 2022 Jun 23;159:111214. doi: 10.1016/j.ijporl.2022.111214. Online ahead of print.

ABSTRACT

The management of tracheal wall lacerations is debated. Current treatments are mainly derived by the experience on adults and include conservative or surgical treatments depending on the clinical condition of the patient. We report our preliminary data with removable tracheal stents in 3 children with tracheal tears and respiratory failure. If performed in specialized centers with appropriate endoscopic and clinical follow-up, airway stents can be considered a valid and safe conservative treatment for tracheal tears and an alternative to intubation or tracheostomy. Further studies are needed to compare different therapeutic options and better define the management and duration of stent treatment.

PMID:35759914 | DOI:10.1016/j.ijporl.2022.111214

J Med Chem. 2022 Jun 27. doi: 10.1021/acs.jmedchem.2c00270. Online ahead of print.

ABSTRACT

Lung infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and is mainly dominated by Pseudomonas aeruginosa. Treatment of CF-associated lung infections is problematic because the drugs are vulnerable to multidrug-resistant pathogens, many of which are major biofilm producers like P. aeruginosa. Antimicrobial peptides (AMPs) are essential components in all life forms and exhibit antimicrobial activity. Here we investigated a series of AMPs (d,l-K6L9), each composed of six lysines and nine leucines but differing in their sequence composed of l- and d-amino acids. The d,l-K6L9 peptides showed antimicrobial and antibiofilm activities against P. aeruginosa from CF patients. Furthermore, the data revealed that the d,l-K6L9 peptides are stable and resistant to degradation by CF sputum proteases and maintain their activity in a CF sputum environment. Additionally, the d,l-K6L9 peptides do not induce bacterial resistance. Overall, these findings should assist in the future development of alternative treatments against resistant bacterial biofilms.

PMID:35759644 | DOI:10.1021/acs.jmedchem.2c00270

Pediatr Pulmonol. 2022 Jun 27. doi: 10.1002/ppul.26041. Online ahead of print.

ABSTRACT

To address the discrepancy in quality of care and outcomes between cystic fibrosis centers (CFC) in high income countries and limited resources countries (LRC), a collaboration between our team at the University of Michigan CFC (UMCFC) and a CF center in Turkey (Marmara University CFC (MUCFC), Istanbul) was established. The collaboration included evaluation of all aspects of care and initiation of quality improvement (QI) measures. Teaching and implementing QI tools has led to start of improvement in MUCFC care. Close monitoring and sharing resources like UMCFC algorithms, protocols and QI processes was done. This article is protected by copyright. All rights reserved.

PMID:35759419 | DOI:10.1002/ppul.26041

Ann Am Thorac Soc. 2022 Jun 27. doi: 10.1513/AnnalsATS.202202-110OC. Online ahead of print.

ABSTRACT

RATIONALE: Hemoptysis is a common and important complication in persons with cystic fibrosis (PwCF). Despite this, there is limited literature on the impact of hemoptysis on contemporary cystic fibrosis (CF) outcomes.

OBJECTIVE: Evaluate whether hemoptysis increases risk of lung transplant or death without transplant in PwCF.

METHODS: We reviewed a dataset of PwCF ages 12 years or older from the CF Foundation Patient Registry (CFFPR) that included 29,587 individuals. We identified hemoptysis as our predictor of interest and categorized PwCF as either no hemoptysis, any hemoptysis (submassive and/or massive), or massive hemoptysis. We subsequently evaluated whether hemoptysis, as defined above, was associated with death without transplant or receipt of lung transplant via logistic regression. We adjusted for age, sex, body mass index, forced expiratory volume in one second (FEV1), number of exacerbations, supplemental oxygen use, CF-related diabetes, and Pseudomonas aeruginosa colonization status. Subgroup analyses were performed in advanced lung disease, defined as PwCF with an FEV1 < 40% of predicted.

RESULTS: PwCF with any form of hemoptysis were more likely to progress to lung transplant or die without transplant than PwCF who did not have hemoptysis [OR = 1.3 (95% CI 1.1, 1.7)]. The effect size of these associations was larger when hemoptysis events were classified as "massive" [massive hemoptysis OR = 2.2 (95% CI 1.2, 3.8)], or in PwCF with advanced lung disease [massive hemoptysis in advanced lung disease OR = 3.2 (95% CI 1.3, 8.2)].

CONCLUSIONS: Hemoptysis is associated with increased risk of lung transplant and death without transplant in PwCF, especially among those with massive hemoptysis or advanced lung disease. Our results suggest that hemoptysis functions as a useful predictor of serious outcomes in PwCF and may be important to incorporate into risk prediction models and/or transplant decisions in CF.

PMID:35759341 | DOI:10.1513/AnnalsATS.202202-110OC

Appl Environ Microbiol. 2022 Jun 27:e0043422. doi: 10.1128/aem.00434-22. Online ahead of print.

ABSTRACT

Spatially resolving chemical landscapes surrounding microbial communities can provide insight into chemical interactions that dictate cellular physiology. Electrochemical techniques provide an attractive option for studying these interactions due to their robustness and high sensitivity. Unfortunately, commercial electrochemical platforms that are capable of measuring chemical activity on the micron scale are often expensive and do not easily perform multiple scanning techniques. Here, we report development of an inexpensive electrochemical system that features a combined micromanipulator and potentiostat component capable of scanning surfaces while measuring molecular concentrations or redox profiles. We validate this experimental platform for biological use with a two-species biofilm model composed of the oral bacterial pathogen Aggregatibacter actinomycetemcomitans and the oral commensal Streptococcus gordonii. We measure consumption of H2O2 by A. actinomycetemcomitans biofilms temporally and spatially, providing new insights into how A. actinomycetemcomitans responds to this S. gordonii-produced metabolite. We advance our platform to spatially measure redox activity above biofilms. Our analysis supports that redox activity surrounding biofilms is species specific, and the region immediately above an S. gordonii biofilm is highly oxidized compared to that above an A. actinomycetemcomitans biofilm. This work provides description and validation of a versatile, quantitative framework for studying bacterial redox-mediated physiology in an integrated and easily adaptable experimental platform. IMPORTANCE Scanning electrochemical probe microscopy methods can provide information of the chemical environment along a spatial surface with micron-scale resolution. These methods often require expensive instruments that perform optimized and highly sensitive niche techniques. Here, we describe a novel system that combines a micromanipulator that scans micron-sized electrodes across the surface of bacterial biofilms and a potentiostat, which performs various electrochemical techniques. This platform allows for spatial measurement of chemical gradients above live bacteria in real time, and as proof of concept, we utilize this setup to map H2O2 detoxification above an oral pathogen biofilm. We increased the versatility of this platform further by mapping redox potentials of biofilms in real time on the micron scale. Together, this system provides a technical framework for studying chemical interactions among microbes.

PMID:35758758 | DOI:10.1128/aem.00434-22

Mycoses. 2022 Jun 27. doi: 10.1111/myc.13488. Online ahead of print.

ABSTRACT

BACKGROUND: The diagnostic accuracy of immunoassays versus immunoprecipitation methods for detecting A.fumigatus-specific IgG in patients with allergic bronchopulmonary aspergillosis (ABPA) complicating asthma remains unclear.

METHODS: We performed a systematic review to identify studies describing both the methods in the same ABPA subjects. We assessed study quality using the QUADAS-2 tool. We derived the relative sensitivity and specificity using the HSROC meta-regression model. We calculated the number-needed-to-test using an immunoassay to detect one additional positive test in ABPA.

RESULTS: Our search yielded 20 studies (796 ABPA, 929 controls). The studies had a high risk of bias. The summary estimates for sensitivity and specificity of immunoprecipitation methods were 68.6% (95% CI, 48.4-83.5) and 93.8% (95% CI, 83.6-97.8), while for immunoassays they were 85.2% (95% CI, 73.3-92.3) and 84.6% (95% CI, 76.0-90.5), respectively. The relative sensitivity and specificity of immunoassays compared to immunoprecipitation tests were 1.29 (95% CI, 1.1-1.6) and 0.91 (95% CI, 0.85-0.97), respectively. The automated immunoassays (1.77; 95% CI, 1.1-2.8) had better relative sensitivity than the manual (1.1; 95% CI, 1.02-1.18) assays compared to immunoprecipitation. The relative specificity of manual immunoassays (0.95; 95% CI, 0.91-0.99) was significantly lower, while that of automated (0.88; 95% CI, 0.77-1.0) assays was lower but not statistically different. One additional positive result was detected for every 6 (95% CI, 5-7) tests performed with immunoassay (versus immunoprecipitation).

CONCLUSION: Manual immunoassays have higher sensitivity and lower specificity, while automated immunoassays have higher sensitivity and similar specificity than immunoprecipitation methods for detecting A.fumigatus-IgG in patients with ABPA.

PMID:35757847 | DOI:10.1111/myc.13488

Clin Transl Immunology. 2022 Jun 16;11(6):e1398. doi: 10.1002/cti2.1398. eCollection 2022.

ABSTRACT

OBJECTIVES: The contribution of adaptive vs. innate lymphocytes to IL-17A and IL-22 secretion at the end stage of chronic lung diseases remains largely unexplored. In order to uncover tissue- and disease-specific secretion patterns, we compared production patterns of IL-17A and IL-22 in three different human end-stage lung disease entities.

METHODS: Production of IL-17A, IL-22 and associated cytokines was assessed in supernatants of re-stimulated lymphocytes by multiplex assays and multicolour flow cytometry of conventional T cells, iNKT cells, γδ T cells and innate lymphoid cells in bronchial lymph node and lung tissue from patients with emphysema (n = 19), idiopathic pulmonary fibrosis (n = 14) and cystic fibrosis (n = 23), as well as lung donors (n = 17).

RESULTS: We detected secretion of IL-17A and IL-22 by CD4+ T cells, CD8+ T cells, innate lymphoid cells, γδ T cells and iNKT cells in all end-stage lung disease entities. Our analyses revealed disease-specific contributions of individual lymphocyte subpopulations to cytokine secretion patterns. We furthermore found the high levels of microbial detection in CF samples to associate with a more pronounced IL-17A signature upon antigen-specific and unspecific re-stimulation compared to other disease entities and lung donors.

CONCLUSION: Our results show that both adaptive and innate lymphocyte populations contribute to IL-17A-dependent pathologies in different end-stage lung disease entities, where they establish an IL-17A-rich microenvironment. Microbial colonisation patterns and cytokine secretion upon microbial re-stimulation suggest that pathogens drive IL-17A secretion patterns in end-stage lung disease.

PMID:35757569 | PMC:PMC9202301 | DOI:10.1002/cti2.1398

J Belg Soc Radiol. 2022 Jun 14;106(1):57. doi: 10.5334/jbsr.2812. eCollection 2022.

ABSTRACT

OBJECTIVES: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy effects on respiratory function, pulmonary exacerbations and quality of life have been well documented. However, CFTR modulator therapy effects on sinus disease have not been so well reported. A previous study reported that ivacaftor improves appearance of sinus disease on Computed Tomography (CT) in cystic fibrosis (CF) patients with G551D mutation. The aim of this study was to evaluate the effect of CFTR modulator therapy in sinus disease using CT scores in a wider CF patient population.

MATERIALS AND METHODS: Forty-eight adult patients with CF underwent at least one CT sinus examination before CFTR modulator therapy (ivacaftor, lumacaftor, ivacaftor/lumacaftor or elexcaftor/tezacaftor/ivacaftor) and one CT sinus examination one year after CFTR modulator therapy initiation. Two radiologists assessed the images in consensus. The Lund-Mackay score (LM score) and the Sheikh-Lind CT sinus disease severity scoring system (SL score) were used. The 22-item SinoNasal Outcome Test (SNOT-22) questionnaire was evaluated before CFTR modulator therapy and one year after CFTR modulator therapy initiation.

RESULTS: CT sinus examination after CFTR modulator therapy showed statistically significant lower mean LM, SL and SNOT-22 scores than CT sinus examination before CFTR modulator therapy (p < 0.001).

CONCLUSION: Evolution of imaging findings on CT during follow-up closely correlate with improved SNOT-22 score one year after CFTR modulator therapy initiation, indicating that CT may be a useful adjunct during follow-up of CF patients under this treatment as an objective measure of sinonasal disease improvement.

PMID:35757498 | PMC:PMC9205366 | DOI:10.5334/jbsr.2812

Front Nutr. 2022 Jun 9;9:884104. doi: 10.3389/fnut.2022.884104. eCollection 2022.

ABSTRACT

BACKGROUND: Children with cystic fibrosis (CF) are expected to have suboptimal serum vitamin D status and altered gut microbiota. The altered gut microbiota is hypothesized to have a pro-inflammatory effect that further complicates the existing respiratory inflammation. Emerging evidence suggests an association between vitamin D and gut microbiota. The aim of this study was to assess the relationships between 25-hydroxyvitamin D [25(OH)D] status, pulmonary function, and fecal bacteria in children with CF.

METHODS: In this cross-sectional study, a total of 35 children with CF (8.7 ± 2.83 years) and 24 controls without CF (9 ± 2.7 years) were included in this study. Serum 25(OH)D status was measured using the Elecsys vitamin D total II assay. In the CF group, gut microbiota composition was assessed using real-time PCR analysis. Pulmonary function tests (PFTs) were measured using spirometry. Comparisons between the CF and non-CF controls were conducted using the independent sample t-test. In the CF group, one-way analysis of variance (ANOVA) was used to assess differences in PFTs and gut microbiota composition across the three vitamin D subgroups. The correlations between 25(OH)D status and PFTs, or gut microbiota composition, and PFTs with gut microbiota composition were analyzed using the Pearson's correlation coefficient test.

RESULTS: Children with CF had significantly lower serum 25(OH)D levels compared with children without CF (44.3 ± 22.4 vs. 59 ± 25.5, respectively, P = 0.026). Children with CF with optimal serum 25(OH)D level had significantly higher levels of Bacteroidetes, Firmicutes, and total bacteria (P = 0.007, P = 0.007, and P = 0.022, respectively). The level of Firmicutes was found to be significantly higher in mild forced expiratory volume in 1 s (FEV1) compared with moderate FEV1 (P = 0.032), whereas the level of the other bacteria species was comparable across FEV1 severity groups.

CONCLUSION: Our findings may encourage studies that target and modify gut microbiota to potentially achieve better outcomes in terms of respiratory function in CF.

PMID:35757256 | PMC:PMC9218790 | DOI:10.3389/fnut.2022.884104