Front Immunol. 2023 May 15;14:1168023. doi: 10.3389/fimmu.2023.1168023. eCollection 2023.

ABSTRACT

Protein glycosylation is a widespread posttranslational modification that can impact the function of proteins. Dysregulated protein glycosylation has been linked to several diseases, including chronic respiratory diseases (CRDs). CRDs pose a significant public health threat globally, affecting the airways and other lung structures. Emerging researches suggest that glycosylation plays a significant role in regulating inflammation associated with CRDs. This review offers an overview of the abnormal glycoenzyme activity and corresponding glycosylation changes involved in various CRDs, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, non-cystic fibrosis bronchiectasis, and lung cancer. Additionally, this review summarizes recent advances in glycomics and glycoproteomics-based protein glycosylation analysis of CRDs. The potential of glycoenzymes and glycoproteins for clinical use in the diagnosis and treatment of CRDs is also discussed.

PMID:37256139 | PMC:PMC10225578 | DOI:10.3389/fimmu.2023.1168023

Front Immunol. 2023 May 15;14:1162342. doi: 10.3389/fimmu.2023.1162342. eCollection 2023.

ABSTRACT

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

PMID:37256125 | PMC:PMC10226646 | DOI:10.3389/fimmu.2023.1162342

Front Pediatr. 2023 May 15;11:1115877. doi: 10.3389/fped.2023.1115877. eCollection 2023.

ABSTRACT

BACKGROUND: Burkholderia cepacia (B. cepacia) is an emerging pathogen of nosocomial infection in pediatric patient carrying cystic fibrosis. The clinical diagnosis and treatment of B. cepacia infection remains poorly studied. This study outlined the risk factors, antimicrobial susceptibility, and clinical characteristics aiming to improve the treatment of B. cepacia infection.

METHODS: A retrospective study was conducted based on the 50 cases infection caused by B. cepacia in children without cystic fibrosis, which were diagnosed in the First Affiliated Hospital of Xiamen University, from January 1st, 2011 to December 31st, 2021.

RESULTS: A total of 50 children were infected with B. cepacia, of whom 68% had an underlying health condition, such as cardiovascular disease (23.5%), respiratory disease (17.6%), nervous system disease (14.7%), and neoplastic disease (14.7%). At the onset of B. cepacia infection, 42 (84%) pediatric patients were in an intensive care unit (ICU), 33 (66%) underwent endotracheal intubation, and 32 (64%) had a central venous catheter (CVC). In addition, hospital-acquired cases were 46 (92%), and healthcare-acquired cases were 4 (12%). The most common infectious sites of B. cepacia were the respiratory tract (68%), followed by the blood (20%), and the urinary tract (12%). It indicated that B. cepacia was the most sensitive to ceftazidime (95.65%), followed by trimethoprim-sulfamethoxazole (88.68%), meropenem (82.98%), cefepime (77.78%), and levofloxacin (55.85%). The drug resistance rate of piperacillin-tazobactam, minocycline, aztreonam, cefoperazone-sulbactam and ceftriaxone was higher than 55%. 38 cases were cured or improved, eight had treatment terminated, and four died.

CONCLUSION: B. cepacia is an opportunistic pathogen normally found in immunocompromised pediatric patients and highly likely to lead to drug resistance. Nosocomial B. cepacia infections occurred mostly in patients in the ICU based on our observations. The surveillance of B. cepacia infections including changing epidemiology and increasing resistance of the microorganism is still very important. Treatment with effective antibiotics such as ceftazidime, meropenem, trimethoprim-sulfamethoxazole is associated with a favorable prognosis.

PMID:37255574 | PMC:PMC10225540 | DOI:10.3389/fped.2023.1115877

Infect Immun. 2023 May 31:e0003723. doi: 10.1128/iai.00037-23. Online ahead of print.

ABSTRACT

Achromobacter xylosoxidans (Ax) is an opportunistic pathogen and causative agent of numerous infections particularly in immunocompromised individuals with increasing prevalence in cystic fibrosis (CF). To date, investigations have focused on the clinical epidemiology and genomic comparisons of Ax isolates, yet little is known about disease pathology or the role that specific virulence factors play in tissue invasion or damage. Here, we model an acute Ax lung infection in immunocompetent C57BL/6 mice and immunocompromised CF mice, revealing a link between in vitro cytotoxicity and disease in an intact host. Mice were intratracheally challenged with sublethal doses of a cytotoxic (GN050) or invasive (GN008) strain of Ax. Bacterial burden, immune cell populations, and inflammatory markers in bronchoalveolar lavage fluid and lung homogenates were measured at different time points to assess disease severity. CF mice had a similar but delayed immune response toward both Ax strains compared to C57BL/6J mice. GN050 caused more severe disease and higher mortality which correlated with greater bacterial burden and increased proinflammatory responses in both mouse models. In agreement with the cytotoxicity of GN050 toward macrophages in vitro, mice challenged with GN050 had fewer macrophages. Mutants with transposon insertions in predicted virulence factors of GN050 showed that disease severity depended on the type III secretion system, Vi capsule, antisigma-E factor, and partially on the ArtA adhesin. The development of an acute infection model provides an essential tool to better understand the infectivity of diverse Ax isolates and enable improved identification of virulence factors important to bacterial persistence and disease.

PMID:37255468 | DOI:10.1128/iai.00037-23

J Infect Dis. 2023 May 31:jiad187. doi: 10.1093/infdis/jiad187. Online ahead of print.

ABSTRACT

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MAB) is one of the major NTM lung pathogens which disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MAB infection can persist for years, and antimicrobial treatment is frequently ineffective.

METHODS: We sequence the genomes of 175 isolates longitudinally collected from 30 patients with MAB lung infection. We contextualize our cohort amidst the broader MAB phylogeny and investigate genes undergoing parallel adaptation across patients. Finally, we test the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury resistance assays.

RESULTS: We identify highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotate non-random parallel mutations in 22 genes and demonstrate altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlight a 23 kb mercury resistance plasmid whose loss during chronic infection confers phenotypic susceptibility to organic and non-organic mercury compounds.

CONCLUSIONS: We characterize parallel genomic processes through which MAB is adapting to promote survival within the host. The within-lineage polymorphisms we observe have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival.

PMID:37254795 | DOI:10.1093/infdis/jiad187

Inflamm Res. 2023 May 31. doi: 10.1007/s00011-023-01743-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Lung cystic fibrosis (CF) is characterized by chronic infections and hyperinflammatory response of neutrophils and macrophages. P. aeruginosa (PA) and S. aureus (MSSA, MRSA) are major pathogens of advanced CF. The main goal of this study was to compare the inflammatory phenotype of murine C57BL/6 macrophages exposed to PA57 with that exposed to MSSA60, both strains isolated from the same patient with severe CF. In the present study, we used C57BL/6 mice sensitive to lung infection with P. aeruginosa.

METHODS: We measured the release of cytokines and the expression of phenotypic markers of murine neutrophils and macrophages exposed to bacterial cells and biofilm components (i.e., EPS) of the selected bacteria. In addition, a quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages.

RESULTS: Neutrophils stimulated with PA57 and MSSA60 strains produced hyperinflammatory pattern of cytokines. The pro-inflammatory impact of PA57 was significantly higher than that of MSSA60 (IL-6/IL-10 ratio: PA57 = 9.3 vs. MSSA60 = 1.7). Macrophages produced significantly lower amount of cytokines, but showed classical pattern of M1 markers (iNOS-High; arginase-1 and mannose receptor MRC1-Low). Importantly, as evidenced by proteomic analysis, PA57 and PA57-EPS were stronger inducers of M1 macrophage polarization than the MSSA60 counterparts.

CONCLUSIONS: Our study demonstrated that strong biofilm P. aeruginosa strains, CF isolates, are dominant inducers of M1 macrophages, termed biofilm-associated macrophages (BAMs). We suggest that repolarization of detrimental BAMs might be a new therapeutic strategy to ameliorate the airway damage in CF.

PMID:37253897 | DOI:10.1007/s00011-023-01743-x

Br J Gen Pract. 2023 Mar 15:BJGP.2022.0268. doi: 10.3399/BJGP.2022.0268. Online ahead of print.

ABSTRACT

BACKGROUND: Timely diagnosis of cancer in patients who present with symptoms in primary care is a quality-improvement priority.

AIM: To examine possible changes to aspects of the diagnostic process, and its timeliness, before and after publication of the National Institute for Health and Care Excellence's (2015) guidance on the referral of suspected cancer in primary care.

DESIGN AND SETTING: Comparison of findings from population-based clinical audits of cancer diagnosis in general practices in England for patients diagnosed in 2018 or 2014.

METHOD: GPs in 1878 (2018) and 439 (2014) practices collected primary care information on the diagnostic pathway of cancer patients. Key measures including patient characteristics, place of presentation, number of pre-referral consultations, use of primary care investigations, and referral type were compared between the two audits by descriptive analysis and regression models.

RESULTS: Among 64 489 (2018) and 17 042 (2014) records of a new cancer diagnosis, the percentage of patients with same-day referral (denoted by a primary care interval of 0 days) was higher in 2018 (42.7% versus 37.7%) than in 2014, with similar improvements in median diagnostic interval (36 days versus 40 days). Compared with 2014, in 2018: fewer patients had ≥3 pre-referral consultations (18.8% versus 26.2%); use of primary care investigations increased (47.9% versus 45.4%); urgent cancer referrals increased (54.8% versus 51.8%); emergency referrals decreased (13.4% versus 16.5%); and recorded use of safety netting decreased (40.0% versus 44.4%).

CONCLUSION: In the 5-year period, including the year when national guidelines were updated (that is, 2015), there were substantial improvements to the diagnostic process of patients who present to general practice in England with symptoms of a subsequently diagnosed cancer.

PMID:37253630 | DOI:10.3399/BJGP.2022.0268

Respir Care. 2023 May 30:respcare.09890. doi: 10.4187/respcare.09890. Online ahead of print.

ABSTRACT

BACKGROUND: Both nasal obstruction and sleep disturbance are common in patients with cystic fibrosis (CF). In patients with obstructive sleep apnea (OSA), studies suggest that these conditions are related and that nasal congestion improves with CPAP therapy. We hypothesized that subjects admitted to hospital for therapy of an exacerbation of CF would have both nasal symptoms and sleep disturbance and that these would improve with the initiation of nocturnal high-flow nasal cannula therapy (HFNC).

METHODS: Twenty-five subjects with an exacerbation of CF were enrolled to randomly receive either 5 d of nocturnal HFNC at 20 L/min in the treatment group or 5 L/min of nocturnal nasal cannula air at ambient temperature and humidity in the low-flow group. On the first and last day of the study, the Sino-Nasal Outcome Test (SNOT-20) was administered to evaluate nasal symptoms, and sleep quality was measured using the Actiwatch 2.

RESULTS: Fifteen subjects completed the study (6 HFNC, 9 low flow). We confirmed that subjects had significant sleep disturbance that did not improve over the 5 d of the study. Subjects also had disturbing nasal symptoms that significantly improved only in those receiving HFNC (pre 14 [20] vs post 6 [13], P = .027).

CONCLUSIONS: Similar to what has been reported in older subjects with OSA, nocturnal HFNC improves sinonasal symptoms in subjects with an exacerbation of CF. There was no measurable effect on sleep quality, which may be due to the short duration of the study, or to subjects being evaluated while being treated in a hospital setting.

PMID:37253609 | DOI:10.4187/respcare.09890

Cell Chem Biol. 2023 May 22:S2451-9456(23)00125-3. doi: 10.1016/j.chembiol.2023.05.001. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is caused by mutations that compromise the expression and/or function of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Most people with CF harbor a common misfolded variant (ΔF508) that can be partially rescued by therapeutic "correctors" that restore its expression. Nevertheless, many other CF variants are insensitive to correctors. Using deep mutational scanning, we quantitatively compare the effects of two correctors on the plasma membrane expression of 129 CF variants. Though structural calculations suggest corrector binding provides similar stabilization to most variants, it's those with intermediate expression and mutations near corrector binding pockets that exhibit the greatest response. Deviations in sensitivity appear to depend on the degree of variant destabilization and the timing of misassembly. Combining correctors appears to rescue more variants by doubling the binding energy and stabilizing distinct cotranslational folding transitions. These results provide an overview of rare CF variant expression and establish new tools for precision pharmacology.

PMID:37253358 | DOI:10.1016/j.chembiol.2023.05.001

AACE Clin Case Rep. 2023 Apr 19;9(3):93-96. doi: 10.1016/j.aace.2023.04.007. eCollection 2023 May-Jun.

ABSTRACT

BACKGROUND/OBJECTIVE: Total pancreatectomy is performed for pain relief in chronic pancreatitis. Concomitant autologous islet cell transplantation can be performed to improve glycemic control. We report the case of a patient with chronic pancreatitis who underwent a total pancreatectomy with autologous islet cell transplantation with increasing insulin requirements and its association with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder.

CASE REPORT: A 40-year-old woman presented with abdominal pain and had elevated levels of serum lipase. She was treated for acute pancreatitis. In the subsequent 2 years, she had 4 additional episodes of pancreatitis and eventually developed chronic abdominal pain. She underwent total pancreatectomy for pain relief with autologous intrahepatic islet cell transplantation. She experienced repeated episodes of pneumonia and underwent screening for cystic fibrosis, which showed a 7T/7T polymorphic variant at CFTR intron 8. The follow-up at 8 years after procedure showed increasing hemoglobin A1c levels despite increasing insulin use with multiple hospitalizations for hyperglycemia. The patient was transitioned to continuous subcutaneous insulin infusion with improvement in hemoglobin A1c levels.

DISCUSSION: Chronic pancreatitis can be a manifestation of an undiagnosed CFTR-related disorder, which in this case was followed by total pancreatectomy. Autologous islet cell transplantation was performed with declining postprocedural glycemic control. Interval failure of the transplanted islets is present in up to two thirds of the patients but is not affected by the presence of cystic fibrosis.

CONCLUSION: A gradual decline in glycemic control may be expected in patients with autologous islet cell transplantation and can be improved with the use of continuous subcutaneous insulin infusion.

PMID:37251971 | PMC:PMC10213614 | DOI:10.1016/j.aace.2023.04.007

Front Oncol. 2023 May 12;13:1104630. doi: 10.3389/fonc.2023.1104630. eCollection 2023.

ABSTRACT

BACKGROUND: The treatment landscape for ovarian cancer has changed in recent years with the introduction of targeted therapies to treat patients with advanced disease. We investigated patient demographic and clinical factors associated with use of targeted therapies as a part of the first-line treatment for ovarian cancer.

METHODS: This study included patients diagnosed with stage I-IV ovarian cancer between 2012 and 2019 from the National Cancer Database. Information on demographic and clinical characteristics were collected and described using frequency and percent across receipt of targeted therapy. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (CI) associating patient demographic and clinical factors with receipt of targeted therapy.

RESULTS: Among 99,286 ovarian cancer patients (mean age 62 years), 4.1% received targeted therapy. The rate of targeted therapy receipt across racial and ethnic groups over the study period was fairly similar; however, non-Hispanic Black women were less likely to receive targeted therapy than their non-Hispanic White counterparts (OR=0.87, 95% CI: 0.76-1.00). Patients who received neoadjuvant chemotherapy were more likely to receive targeted therapy than those who received adjuvant chemotherapy (OR=1.26; 95% CI: 1.15-1.38). Moreover, among patients who received targeted therapy, 28% received neoadjuvant targeted therapy, with non-Hispanic Black women being most likely to receive neoadjuvant targeted therapy (34%) compared with other racial and ethnic groups.

CONCLUSIONS: We observed differences in receipt of targeted therapy by factors such as age at diagnosis, stage, and comorbidities present at diagnosis, as well as factors related to healthcare access-including neighborhood education level and health insurance status. Approximately 28% of patients received targeted therapy in the neoadjuvant setting, which could negatively impact treatment outcomes and survival due to the increased risk of complications associated with targeted therapies that may delay or prevent surgery. These results warrant further evaluation in a cohort of patients with more comprehensive treatment information.

PMID:37251932 | PMC:PMC10213306 | DOI:10.3389/fonc.2023.1104630

HRB Open Res. 2023 Apr 28;5:22. doi: 10.12688/hrbopenres.13500.2. eCollection 2022.

ABSTRACT

Background Cystic Fibrosis (CF) is an autosomal recessive inherited multi-system disease that primarily affects the lungs and digestive system. New drug therapies and treatments are improving the lives of many people with CF. With improved life expectancy and increased quality of life, many people with CF are now contemplating parenthood and becoming pregnant, an aspiration that decades ago was almost unheard of. Given this quickly evolving and more positive health landscape, it is vital to understand how people with CF experience the care they receive whilst accessing and utilising fertility and maternity services. It is also important to explore the experiences of healthcare professionals involved in providing care during this period. The overall aim of the mixed-methods systematic review will be to explore the barriers and enablers experienced by people with CF and the healthcare professionals involved in their care in the pre-conception to post-partum period. Methods The proposed review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for convergent integrated mixed methods systematic reviews. A systematic search of Medline (Ebsco), Cinahl, Embase, APA PsychINFO and Cochrane Library from inception to February 2022 will be conducted. Quantitative, qualitative and mixed methods studies pertaining to the experience of pre-conception to post-partum care for people with CF and their healthcare professionals will be included. Two independent reviewers will screen titles, abstracts and full texts with disagreements being resolved by a third reviewer. Conclusion This review will help to determine the potential barriers and facilitators experienced by people with Cystic Fibrosis and the health care professionals involved in their care during the pre-conception to post-partum period. The results will be of benefit specifically to the CF population and their healthcare providers when planning further studies in the area of fertility and pregnancy for this population and when delivering care.

PMID:37251363 | PMC:PMC10220422 | DOI:10.12688/hrbopenres.13500.2

Physiother Can. 2023 Feb 8;75(1):1-9. doi: 10.3138/ptc-2021-0051. eCollection 2023 Winter.

ABSTRACT

Purpose: This study surveyed physiotherapists working at Canadian cystic fibrosis (CF) specialized centres to investigate the current practice, barriers to, and facilitators of exercise testing and training. Method: Physiotherapists were recruited from 42 Canadian CF centres. They responded to an e-questionnaire regarding their practice. The data were analyzed using descriptive statistics. Results: Eighteen physiotherapists responded (estimated response rate of 23%); median years of clinical experience was 15 (range, min-max, 3-30) years. Aerobic testing was administered by 44% of respondents, strength testing by 39%, aerobic training by 78%, and strength training by 67%. The most frequently reported barriers across all four types of exercise testing and training were insufficient funding (reported by 56%-67% of respondents), time (50%-61%) and staff availability (56%). More late career than early career physiotherapists reported utilizing aerobic testing (50% vs. 33% of respondents), strength testing (75% vs. 33%), aerobic training (100% vs. 67%), and strength training (100% vs. 33%). Conclusions: Exercise testing and training is underutilized in Canadian CF centres. Experienced physiotherapists reported utilizing exercise testing and training more than less-experienced physiotherapists. Post-graduate education and mentorship, especially for less-experienced clinicians, are recommended to emphasize the importance of exercise testing and training. Barriers of funding, time, and staff availability should be addressed to further improve quality of care.

PMID:37250729 | PMC:PMC10211377 | DOI:10.3138/ptc-2021-0051

Front Med (Lausanne). 2023 May 12;10:1159227. doi: 10.3389/fmed.2023.1159227. eCollection 2023.

ABSTRACT

Impaired airway clearance in patients with non-cystic fibrosis bronchiectasis causes frequent bacterial infection, chronic inflammation, and progressive tissue destruction. We aimed to evaluate whether an oscillating positive expiratory pressure (OPEP) device could allow effective sputum expectoration and prevent acute exacerbations in patients with bronchiectasis who had frequent acute exacerbations. This open-label, single-arm, prospective study included 17 patients who experienced three or more acute exacerbations in the past year. We evaluated the prevention of acute exacerbations, subjective symptom improvement, and change in sputum amount during the use of the Aerobika (Trudell Medical International, London, ON) OPEP device twice daily for 6 months. Of all enrolled patients, only two acute exacerbations occurred during the study period, indicating a significant decrease compared with the number of acute exacerbations before the device use (p < 0.001). Additionally, Bronchiectasis Health Questionnaire score changed from 58.7 to 66.6, showing significant improvement over the treatment period (p < 0.001). The largest sputum volume was observed 3 months after OPEP device use (baseline: 10 ml, 3rd month 25 ml, p = 0.325). There were no major adverse events related to the use of OPEP devices. Twice-daily physiotherapy with OPEP device in patients with bronchiectasis who have frequent exacerbations may facilitate symptomatic improvement and prevention of acute exacerbations without serious adverse events.

PMID:37250647 | PMC:PMC10213442 | DOI:10.3389/fmed.2023.1159227

Front Microbiol. 2023 May 11;14:1162470. doi: 10.3389/fmicb.2023.1162470. eCollection 2023.

ABSTRACT

SARS-CoV-2, the etiological cause of the COVID-19 pandemic, can cause severe illness in certain at-risk populations, including people with cystic fibrosis (pwCF). Nevertheless, several studies indicated that pwCF do not have higher risks of SARS-CoV-2 infection nor do they demonstrate worse clinical outcomes than those of the general population. Recent in vitro studies indicate cellular and molecular processes to be significant drivers in pwCF lower infection rates and milder symptoms than expected in cases of SARS-CoV-2 infection. These range from cytokine releases to biochemical alterations leading to morphological rearrangements inside the cells associated with CFTR impairment. Based on available data, the reported low incidence of SARS-CoV-2 infection among pwCF is likely a result of several variables linked to CFTR dysfunction, such as thick mucus, IL-6 reduction, altered ACE2 and TMPRSS2 processing and/or functioning, defective anions exchange, and autophagosome formation. An extensive analysis of the relation between SARS-CoV-2 infection and pwCF is essential to elucidate the mechanisms involved in this lower-than-expected infection impact and to possibly suggest potential new antiviral strategies.

PMID:37250046 | PMC:PMC10213757 | DOI:10.3389/fmicb.2023.1162470

Eur Arch Otorhinolaryngol. 2023 May 30. doi: 10.1007/s00405-023-08028-3. Online ahead of print.

ABSTRACT

BACKGROUND: Studies investigating the impact of sinus surgery for cystic fibrosis (CF) patients performed early after lung transplantation (Ltx) are scarce. Recent studies evaluating frequency of respiratory infections and graft outcomes are not available.

OBJECTIVES/HYPOTHESIS: To determine whether there is a difference in allograft infection, allograft function and overall survival among CF lung transplant recipients with and without concomitant sinus surgery.

STUDY DESIGN: Retrospective single-center study.

METHODS: We examined 71 CF patients who underwent Ltx between 2009 and 2019 at our center. Fifty-nine patients had sinus surgery before or/and after transplantation and twelve did not undergo sinus surgery. We assessed the survival, the diagnosis of chronic allograft dysfunction (CLAD) and all elevated (> 5 mg/l) c-reactive protein episodes during the observed period. The infectious events of the upper and lower airways were categorized in mild infections (5-15 mg/l CRP) and severe infections (> 15 mg/l CRP).

RESULTS: There was no difference in the long-time overall survival (p = 0.87) and no benefit in the short-term survival at 4 year post-transplant (p = 0.29) in both groups. There was no difference in both groups concerning CLAD diagnosis (p = 0.92). The incidence of severe upper and lower airway infections (CRP > 15 mg/l) was significantly decreased in the sinus surgery group (p = 0.015), whereas in mild infections there was a trend to decreased infections in the sinus surgery group (p = 0.056).

CONCLUSIONS: CF patients undergoing Ltx benefit from extended endoscopic sinus surgery (eESS) in terms of frequency of severe infectious events of the upper and lower airways. There was no difference in overall survival and frequency of CLAD in the two groups.

PMID:37249595 | DOI:10.1007/s00405-023-08028-3

J Cyst Fibros. 2023 May 26:S1569-1993(23)00143-1. doi: 10.1016/j.jcf.2023.05.013. Online ahead of print.

ABSTRACT

BACKGROUND: SHIP-CT showed that 48-week treatment with inhaled 7% hypertonic saline (HS) reduced airway abnormalities on chest CT using the manual PRAGMA-CF method relative to isotonic saline (IS) in children aged 3-6 years with cystic fibrosis (CF). An algorithm was developed and validated to automatically measure bronchus and artery (BA) dimensions of BA-pairs on chest CT. Aim of the study was to assess the effect of HS on bronchial wall thickening and bronchial widening using the BA-analysis.

METHODS: The BA-analysis (LungQ, version 2.1.0.1, Thirona, Netherlands) automatically segments the bronchial tree and identifies the segmental bronchi (G0) and distal generations (G1-G10). Dimensions of each BA-pair are measured: diameters of bronchial outer wall (Bout), bronchial inner wall (Bin), bronchial wall thickness (Bwt), and artery (A). BA-ratios are computed: Bout/A and Bin/A to detect bronchial widening and Bwt/A and Bwa/Boa (=bronchial wall area/bronchial outer area) to detect bronchial wall thickening.

RESULTS: 113 baseline and 102 48-week scans of 115 SHIP-CT participants were analysed. LungQ measured at baseline and 48-weeks respectively 6,073 and 7,407 BA-pairs in the IS-group and 6,363 and 6,840 BA-pairs in the HS-group. At 48 weeks, Bwt/A (mean difference 0.011; 95%CI, 0.0017 to 0.020) and Bwa/Boa (mean difference 0.030; 95% 0.009 to 0.052) was significantly higher (worse) in the IS-group compared to the HS-group representing more severe bronchial wall thickening in the IS-group (p=0.025 and p=0.019 respectively). Bwt/A and Bwa/Boa decreased and Bin/A remained stable from baseline to 48 weeks in the HS while it declined in the IS-group (all p<0.001). There was no difference in progression of Bout/A between two treatment groups.

CONCLUSION: The automatic BA-analysis showed a positive impact of inhaled HS on bronchial lumen and wall thickness, but no treatment effect on progression of bronchial widening over 48 weeks.

PMID:37246053 | DOI:10.1016/j.jcf.2023.05.013

Sci Rep. 2023 May 27;13(1):8617. doi: 10.1038/s41598-023-35416-w.

ABSTRACT

Cystic fibrosis-related diabetes (CFRD) is associated with reduced life expectancy in adults with cystic fibrosis (CF). Voice analysis may be a convenient method for diagnosing and monitoring CFRD. This study aims to determine the relationship between voice characteristics and markers of glucose and glycemic control and to identify if voice analysis can predict high blood glucose levels and glycemic control in adults with CFRD. We conducted a prospective cross-sectional study in adults with CF from March to December 2021. We recorded 3-second voice samples of a sustained /a/ vowel and analyzed voice characteristic using the Computerized Speech Lab with the Multi-Dimensional Voice Program. In female participants with CFRD, the noise-to-harmonic ratio was significantly lower in those with HbA1c ≥ 7. Furthermore, fundamental frequency variation was significantly lower in both male and female participants with CFRD who had a glucose level of 200 mg/dL or higher at the time of collection. This finding was also associated with a high level of point-of-care glucose. The human voice has potential as a non-invasive tool for measuring glucose levels and glycemic control status in CFRD patients in the future.

PMID:37244957 | DOI:10.1038/s41598-023-35416-w

J Cyst Fibros. 2023 May 25:S1569-1993(23)00141-8. doi: 10.1016/j.jcf.2023.05.011. Online ahead of print.

ABSTRACT

BACKGROUND: Home spirometry is increasingly used to monitor lung function in people with cystic fibrosis (pwCF). Although decreases in lung function in the setting of increased respiratory symptoms are consistent with a pulmonary exacerbation (PEx), the interpretation of home spirometry during asymptomatic periods of baseline health is unclear. The aims of this study were to determine the variation in home spirometry in pwCF during asymptomatic periods of baseline health and to identify associations between this variation and PEx.

METHODS: Near-daily home spirometry measurements were obtained from a cohort of pwCF enrolled in a long-term study of the airway microbiome. Associations between the degree of variation in home spirometry and the time to next PEx were evaluated.

RESULTS: Thirteen subjects (mean age of 29 years and mean percent predicted forced expiratory volume in one second [ppFEV1] of 60) provided a median of 204 spirometry readings taken during 40 periods of baseline health. The mean week-to-week within-subject level of variation in ppFEV1 was 15.2 ± 6.2%. The degree of variation in ppFEV1 during baseline health was not associated with time to PEx.

CONCLUSIONS: Variation in ppFEV1 measured with near-daily home spirometry in pwCF during periods of baseline health exceeded the variation in ppFEV1 expected in clinic spirometry (based on ATS guidelines). The degree of variation in ppFEV1 during baseline health was not associated with time to PEx. These data are relevant for guiding interpretation of home spirometry.

PMID:37244842 | DOI:10.1016/j.jcf.2023.05.011

J Cyst Fibros. 2023 May 25:S1569-1993(23)00139-X. doi: 10.1016/j.jcf.2023.05.009. Online ahead of print.

ABSTRACT

BACKGROUND: There is a well described sex-disparity in outcomes of individuals with cystic fibrosis (CF), with females faring worse than males. Given the dramatic improvement in overall health of people with CF using CF transmembrane conductance regulator (CFTR) modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), the sex-disparity in CF warrants re-examination.

METHODS: We evaluated the effects of ETI use by sex prior to versus after initiation of ETI by pulmonary exacerbations (PEx), percent predicted forced expiratory volume in one second (ppFEV1), presence of Pseudomonas aeruginosa in sputum cultures, and body mass index (BMI). We used univariate and multivariable longitudinal regression adjusting for key confounders, such as age, race, CFTR modulator taken prior to ETI and baseline ppFEV1.

RESULTS: We included 251 individuals started on ETI between January 2014 to September 2022. We collected data for a mean of 5.45 years pre-ETI and 2.38 years post-ETI. We found the adjusted presence of PEx decreased more in males than females pre- to post-ETI with the odds of having a PEx in males being 0.57 (43% reduction) versus females 0.75 (25% reduction) (p = 0.049). We found no statistical difference by sex for ppFEV1, presence of Pseudomonas aeruginosa or BMI pre- to post-ETI by sex.

CONCLUSION: After treatment with ETI, there was a greater decline in PEx in males versus females. Long-term impact of ETI by sex is still unknown, but we will need to seek ways to effectively tailor care for individuals with CF and consider pharmacokinetic studies of ETI comparing males to females.

PMID:37244841 | DOI:10.1016/j.jcf.2023.05.009