Appl Microbiol Biotechnol. 2023 Apr 25. doi: 10.1007/s00253-023-12530-3. Online ahead of print.

ABSTRACT

Small non-coding RNAs (sRNAs) are key regulators of post-transcriptional gene expression in bacteria. Despite the identification of hundreds of bacterial sRNAs, their roles on bacterial physiology and virulence remain largely unknown, as is the case of bacteria of the Burkholderia cepacia complex (Bcc). Bcc is a group of opportunistic pathogens with relatively large genomes that can cause lethal lung infections amongst cystic fibrosis (CF) patients. To characterise sRNAs expressed by Bcc bacteria when infecting a host, the nematode Caenorhabditis elegans was used as an infection model by the epidemic CF strain B. cenocepacia J2315. A total of 108 new and 31 previously described sRNAs with a predicted Rho independent terminator were identified, most of them located on chromosome 1. RIT11b, a sRNA downregulated under C. elegans infection conditions, was shown to directly affect B. cenocepacia virulence, biofilm formation, and swimming motility. RIT11b overexpression reduced the expression of the direct targets dusA and pyrC, involved in biofilm formation, epithelial cell adherence, and chronic infections in other organisms. The in vitro direct interaction of RIT11b with the dusA and pyrC messengers was demonstrated by electrophoretic mobility shift assays. To the best of our knowledge this is the first report on the functional characterization of a sRNA directly involved in B. cenocepacia virulence. KEY POINTS: • 139 sRNAs expressed by B. cenocepacia during C. elegans infection were identified • The sRNA RIT11b affects B. cenocepacia virulence, biofilm formation, and motility • RIT11b directly binds to and regulates dusA and pyrC mRNAs.

PMID:37097504 | DOI:10.1007/s00253-023-12530-3

Pediatr Pulmonol. 2023 Apr 25. doi: 10.1002/ppul.26413. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of this study was to conduct a web-based questionnaire to investigate self-reported phenotypes and disease burdens of individuals living in Australia and diagnosed with cystic fibrosis (CF) using a case-control study design.

METHODS: An online questionnaire was distributed to individuals with CF and healthy control subjects. Overall health rating, medications, family history, education, clinical indicators of disease, and symptoms, including their severity and frequency, were evaluated.

RESULTS: There was a total of 119 respondents consisting of 59 people living with CF and 60 controls. The CF cohort had significantly lower tertiary educational levels compared to controls. The analysis specific to the CF cohort depicted a significant correlation between the frequency of hospitalizations and the level of education in the CF cohort. Of the 26 self-reported symptoms of CF that were analyzed, 14 were significantly higher in the people living with CF. The CF cohort reporting symptoms of chronic pain (25%) described an increase in the burden of disease, depicting a 30% longer mean hospitalization, increased consumption of medications and significant relationships with four other symptoms, including muscle aches, digestive issues, pancreatic insufficiency, and abdominal swelling.

CONCLUSIONS: The nationwide survey identified a diverse range of clinical manifestations experienced by the Australian CF population. Chronic pain, linked to aging and the changing landscape of disease, was a significant indicator of the burden of disease. A comprehensive understanding of the phenotypic profiles and symptom variability will contribute to future research and provide insights into the impacts of disease and the burden of therapy, particularly in children, at the start of their health journey.

PMID:37097078 | DOI:10.1002/ppul.26413

Pediatr Pulmonol. 2023 Apr 25. doi: 10.1002/ppul.26419. Online ahead of print.

ABSTRACT

BACKGROUND: Procedural anxiety involves acute distress around medical procedures and may lead to avoidance or resistance behaviors that interfere with effective cystic fibrosis (CF) care and health outcomes. While individuals with CF commonly endure uncomfortable and/or distressing medical procedures, procedural anxiety among children and adolescents with CF has received little research attention. This study investigated the prevalence and correlates of procedural anxiety among individuals with CF aged 6-18 and their parents.

METHOD: Eighty-nine parents of children with CF completed surveys examining child procedural anxiety, anxiety, and health behaviors (including treatment adherence); and parent vicarious procedural anxiety.

RESULTS: Seventy-five percent of participants rated at least one CF-related procedure as "extremely" anxiety-inducing for their child. Parental vicarious procedural anxiety was reported in 80.9% of participants. Procedural anxiety significantly correlated with child anxiety, treatment-resistive behaviors, and parent-vicarious procedural anxiety. Procedural anxiety was associated with younger age and frequency of distressing procedures, but not with forced expiratory volume in 1 s, body mass index, hospitalizations, or exposure to general anesthesia.

CONCLUSION: Procedural anxiety is common among children, adolescents, and caregivers, and is associated with child anxiety and treatment resistance, emphasizing the importance of screening and interventions for procedural anxiety as part of routine CF care from early childhood. Implications for screening and intervention are discussed.

PMID:37097054 | DOI:10.1002/ppul.26419

Stat Med. 2023 Apr 22. doi: 10.1002/sim.9718. Online ahead of print.

ABSTRACT

Longitudinal observational data on patients can be used to investigate causal effects of time-varying treatments on time-to-event outcomes. Several methods have been developed for estimating such effects by controlling for the time-dependent confounding that typically occurs. The most commonly used is marginal structural models (MSM) estimated using inverse probability of treatment weights (IPTW) (MSM-IPTW). An alternative, the sequential trials approach, is increasingly popular, and involves creating a sequence of "trials" from new time origins and comparing treatment initiators and non-initiators. Individuals are censored when they deviate from their treatment assignment at the start of each "trial" (initiator or noninitiator), which is accounted for using inverse probability of censoring weights. The analysis uses data combined across trials. We show that the sequential trials approach can estimate the parameters of a particular MSM. The causal estimand that we focus on is the marginal risk difference between the sustained treatment strategies of "always treat" vs "never treat." We compare how the sequential trials approach and MSM-IPTW estimate this estimand, and discuss their assumptions and how data are used differently. The performance of the two approaches is compared in a simulation study. The sequential trials approach, which tends to involve less extreme weights than MSM-IPTW, results in greater efficiency for estimating the marginal risk difference at most follow-up times, but this can, in certain scenarios, be reversed at later time points and relies on modelling assumptions. We apply the methods to longitudinal observational data from the UK Cystic Fibrosis Registry to estimate the effect of dornase alfa on survival.

PMID:37086186 | DOI:10.1002/sim.9718

Funct Integr Genomics. 2023 Apr 22;23(2):135. doi: 10.1007/s10142-023-01050-y.

ABSTRACT

The precise molecular events initiating human lung disease are often poorly characterized. Investigating prenatal events that may underlie lung disease in later life is challenging in man, but insights from the well-characterized sheep model of lung development are valuable. Here, we determine the transcriptomic signature of lung development in wild-type sheep (WT) and use a sheep model of cystic fibrosis (CF) to characterize disease associated changes in gene expression through the pseudoglandular, canalicular, saccular, and alveolar stages of lung growth and differentiation. Using gene ontology process enrichment analysis of differentially expressed genes at each developmental time point, we define changes in biological processes (BP) in proximal and distal lung from WT or CF animals. We also compare divergent BP in WT and CF animals at each time point. Next, we establish the developmental profile of key genes encoding components of ion transport and innate immunity that are pivotal in CF lung disease and validate transcriptomic data by RT-qPCR. Consistent with the known pro-inflammatory phenotype of the CF lung after birth, we observe upregulation of inflammatory response processes in the CF sheep distal lung during the saccular stage of prenatal development. These data suggest early commencement of therapeutic regimens may be beneficial.

PMID:37085733 | DOI:10.1007/s10142-023-01050-y

Clin Chest Med. 2023 Jun;44(2):385-393. doi: 10.1016/j.ccm.2022.11.013. Epub 2022 Nov 22.

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes an acute respiratory tract infection known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 enters cells by binding the ACE2 receptor and coreceptors notably TMPRSS2 or Cathepsin L. Severe COVID-19 infection can lead to acute lung injury. Below we describe the current evidence of the impact of common chronic lung diseases (CLDs) on the development of COVID-19. The impact of treatment of CLD on COVID-19 and any risk of vaccination in patients with CLD are considered.

PMID:37085227 | DOI:10.1016/j.ccm.2022.11.013

J Cyst Fibros. 2023 Apr 21:S1569-1993(23)00115-7. doi: 10.1016/j.jcf.2023.04.012. Online ahead of print.

ABSTRACT

We report here how the triple combination of drugs elexacaftor/tezacaftor/ivacaftor (ETI) alters the balance of the de-novo synthethic pathway of sphingolipids in primary cells of human bronchial epithelium. The treatment with ETI roughly doubles the levels of dihydrosphingolipids, possibly by modulating the delta(4)-desaturase enzymes that convert dihydroceramides into ceramides. This appears to be an off-target effect of ETI, since it occurs in a genotype-independent manner, for both cystic fibrosis (CF) and non-CF subjects.

PMID:37088636 | DOI:10.1016/j.jcf.2023.04.012

J Cyst Fibros. 2023 Apr 21:S1569-1993(23)00092-9. doi: 10.1016/j.jcf.2023.04.002. Online ahead of print.

ABSTRACT

BACKGROUND: Aminoglycosides (AGs), such as tobramycin, are essential antibiotics in the management of pulmonary infections in patients with cystic fibrosis (CF). They induce ototoxicity without the relationship being clearly described in the literature. Our aim is to propose a mathematical and statistical model describing the relationship between the estimated cumulative exposure (Area Under the Curve, AUC) to tobramycin and ototoxicity with audiogram interpretation in young patients with CF.

METHODS: Cumulative AUCs were estimated for each course of tobramycin, for the 106 individuals with CF (between 4 and 22 years of age) enrolled in this retrospective study (35 who had received IV tobramycin, 71 controls). Mean hearing loss was calculated for each audiogram and a statistical model was developed to predict hearing loss.

RESULTS: The model confirms a significant relationship between cumulative tobramycin exposure and changes in hearing acuity: Meanhearingloss=2.7+(3×10-5)×AUC_tobramycin+individual_susceptibility However, the ototoxic effect is not clinically perceptible (mean hearing loss: 3.8 dB). The impact of AUC on hearing loss is minor in these subjects who received a limited number of courses of tobramycin (median: 5 courses).

CONCLUSION: A significant relationship between cumulative exposure to tobramycin and ototoxicity was demonstrated. Individual treatment susceptibility should not be overlooked. As ototoxicity is not clinically perceptible in the study subjects, hearing tests should be continued during adulthood to provide individualized medical guidance and to obtain a lifetime analysis of the relationship between exposure and hearing loss.

PMID:37088635 | DOI:10.1016/j.jcf.2023.04.002

J Allergy Clin Immunol Pract. 2023 Apr 21:S2213-2198(23)00420-8. doi: 10.1016/j.jaip.2023.04.009. Online ahead of print.

ABSTRACT

BACKGROUND: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients remains unclear and is likely different across geographic locales.

OBJECTIVE: To systematically review the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in adults with bronchial asthma.

METHODS: We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in asthma with AS. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression.

RESULTS: Of the 11,801 records retrieved, 86 studies with 25,770 asthmatic subjects met the inclusion criteria. Most of the studies were from tertiary centers. The pooled prevalence of ABPA in asthma (47 studies; 9822 asthmatics) was 11.3% (95% confidence intervals [CI], 8.7-14.2). The pooled prevalence of AS in asthma (73 studies; 23,003 asthmatics) was 25.1% (95% CI, 20.5-30.0), while the prevalence of ABPA in AS (36 studies; 2954 asthmatics) was 37.0% (95% CI, 27.9-46.6). Multivariate meta-regression identified studies published from India (OR 1.11; 95% CI, 1.01-1.23) as the only factor associated with higher ABPA prevalence. There was presence of significant statistical heterogeneity and publication bias.

CONCLUSIONS: We found a high prevalence of ABPA in adult asthmatics, underscoring the need for screening all asthmatic subjects attending tertiary care for ABPA.

PMID:37088374 | DOI:10.1016/j.jaip.2023.04.009

J Heart Lung Transplant. 2023 Apr 21:S1053-2498(23)01828-4. doi: 10.1016/j.healun.2023.04.004. Online ahead of print.

ABSTRACT

BACKGROUND: Acute cellular rejection (ACR) is common after lung transplant (LTx). We sought to determine if transplant center volume affected ACR-related outcomes in children after LTx.

METHODS: The United Network for Organ Sharing (UNOS) Registry was queried for patients <18-years-of-age who underwent LTx 1987-2020. Cohorts were children who survived the first-year post transplant and were treated for ACR within that first year (ACR group) and those not treated for ACR (non-ACR). LTx center volume was defined as: high volume center (HVC) (>5LTxs/year), medium volume center (MVC) (>1≤5 LTxs/year), and low volume center (LVC) (≤1LTxs/year).

RESULTS: 1320 patients were enrolled into the study; 269 (20.4%) did not experience ACR. The ACR cohort was older (median 14 [11-16] vs 13 [7-16] years, p<0.001), female (65.3% vs 57.3%, p=0.016), cystic fibrosis diagnosis (62.3% vs 45.5%, p<0.001), and higher lung allocation score (37.3 [34.6-47.8] vs 35.8 [33-42.6], p=0.029). The ACR cohort trended (p=0.06) towards lower survival at 5-year (37% vs 47%) and 10-year (25% vs 34%) post-LTx. Among children at HVCs, ACR occurred in 17% of recipients (n=98/574), compared to 18.5% (n=73/395) at MVCs and 27% (n=100/369) at LVCs. Children treated for ACR at HVCs had higher survival than LVCs at 5-years (52% vs 29%) and 10-years (36% vs 15%) (p<0.001) but similar survival to MVCs at 5-years (52% vs 43%) and 10-years (36% vs 24%) (p=0.081). No survival differences were detected in MVCs vs LVCs (p=0.14).

CONCLUSIONS: ACR treated within the first post-LTx year influence survival of children. ACR incidence was lowest at higher volume centers whereas post-ACR treatment survival outcomes were also superior.

PMID:37088340 | DOI:10.1016/j.healun.2023.04.004

J Heart Lung Transplant. 2023 Apr 21:S1053-2498(23)01829-6. doi: 10.1016/j.healun.2023.04.007. Online ahead of print.

ABSTRACT

BACKGROUND: Prior studies suggest that being underweight by body mass index percentiles (BMI%) or thinness grade did not affect post-transplant survival in pediatric lung transplant (LTx) recipients regardless of cystic fibrosis (CF) or non-CF diagnosis. Graft and overall survival from the time of listing was instead evaluated based on listing BMI%, the current standard of practice for BMI definitions in pediatrics, to ascertain the impact of a "severely low" subcategory.

METHODS: The UNOS registry was queried for children listed for LTx (aged 2 to <18 years) from January 1986 to March 2020. BMI% at listing and transplant were calculated per CDC guidelines according to age in years, sex, and reported BMI%. Patients were divided by listing BMI%: severely low (<3rd), low (3-<5th), normal (5-<85th), overweight (85-<95th), and obese (≥95th). Kaplan-Meier curves were generated to assess differences in overall survival since listing based on BMI% classes. Cox proportional-hazards models were developed to assess risk factors for overall and graft survival, including listing BMI%, transplant listing era (≥2005), and listing age, by reporting hazard ratios (HR).

RESULTS: Listing BMI% was calculable for 1,876 patients. The proportion of patients with CF differed significantly between BMI% groups (p<0.001). Patients listed with a non-CF diagnosis comprised 34% of those in the severely low category, and 88% of those listed with an obese BMI%. Compared to patients with a normal listing BMI%, the cohort with severely low BMI% had worse overall survival regardless of LTx (p=0.009) and graft survival (p=0.034). Compared to patients with a low BMI%, those with a severely low BMI% had significantly poorer graft survival as well (p=0.040). Mean graft survival was not significantly different between groups that remained at listing BMI% versus those that improved in category despite an overall small sample size. Independent predictors of poorer survival from the time of listing include severely low vs low-normal BMI% (HR=1.20) and listing age (HR=1.02).

CONCLUSION: The proportion of children listed at severely low BMI% has steadily decreased with time, yet pediatric LTx candidates listed with a severely low BMI% had poorer graft and overall survival compared to those of normal BMI%. Severely low listing BMI% was an independent prognostic factor for higher mortality risk from the time of placement on the waitlist. BMI% may be a modifiable target for improving survival regardless of transplantation.

PMID:37088338 | DOI:10.1016/j.healun.2023.04.007

Pediatr Pulmonol. 2023 Apr 21. doi: 10.1002/ppul.26427. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has spread across the world, leading to government measures associated with a negative impact on mental health. The aim of this study was to evaluate the impact of the pandemic on depression, anxiety and resilience in Dutch people with cystic fibrosis (PwCF) or primary ciliary dyskinesia (PwPCD) and their caregivers.

METHODS: Adolescents (12-17 years) and caregivers of children (0-17 years) with CF, and adolescents, adults and caregivers of children with PCD completed questionnaires on depression, anxiety and resilience between September 2020 and February 2021. The psychosocial impact of COVID-19 was measured by the Exposure and Family Impact Survey (CEFIS) Part 2. Mixed model analyses compared depression and anxiety results to participants' prepandemic scores.

RESULTS: One hundred ten participants (10 PwCF, 31 PwPCD, 52 CF caregivers, 17 PCD caregivers) completed questionnaires during the pandemic. Prepandemic outcomes were available for 87 participants. The prevalence of symptoms of depression and anxiety (PHQ-9 or GAD-7 scores ≥5) in PwCF and PwPCD and their caregivers before and during the pandemic was high, with an increase in depression in PwCF (2.75; 95% confidence interval: 0.82-4.68) and increase in anxiety in CF caregivers (1.03; 0.09-1.96) during the pandemic. Resilience was within the normal range for all groups, CEFIS scores corresponded to a low to normal impact.

CONCLUSION: PwCF and PwPCD and their caregivers were at risk of elevated depression and anxiety symptoms both before and during the pandemic, which emphasizes the importance of mental health screening and psychological care in CF and PCD.

PMID:37083207 | DOI:10.1002/ppul.26427

J Cyst Fibros. 2023 Apr 20:S1569-1993(23)00091-7. doi: 10.1016/j.jcf.2023.04.001. Online ahead of print.

ABSTRACT

BACKGROUND: We previously documented that elevated HE4 plasma concentration decreased in people with CF (pwCF) bearing the p.Gly551Asp-CFTR variant in response to CFTR modulator (CFTRm) ivacaftor (IVA), and this level was inversely correlated with the FEV1% predicted values (ppFEV1). Although the effectiveness of lumacaftor (LUM)/IVA in pwCF homozygous for the p.Phe508del-CFTR variant has been evaluated, plasma biomarkers were not used to monitor treatment efficacy thus far.

METHODS: Plasma HE4 concentration was examined in 68 pwCF drawn from the PROSPECT study who were homozygous for the p.Phe508del-CFTR variant before treatment and at 1, 3, 6 and 12 months after administration of LUM/IVA therapy. Plasma HE4 was correlated with ppFEV1 using their absolute and delta values. The discriminatory power of delta HE4 was evaluated for the detection of lung function improvements based on ROC-AUC analysis and multiple regression test.

RESULTS: HE4 plasma concentration was significantly reduced below baseline following LUM/IVA administration during the entire study period. The mean change of ppFEV1 was 2.6% (95% CI, 0.6 to 4.5) by 6 months of therapy in this sub-cohort. A significant inverse correlation between delta values of HE4 and ppFEV1 was observed especially in children with CF (r=-0.7053; p<0.0001). Delta HE4 predicted a 2.6% mean change in ppFEV1 (AUC: 0.7898 [95% CI 0.6823-0.8972]; P < 0.0001) at a cut-off value of -10.7 pmol/L. Moreover, delta HE4 independently represented the likelihood of being a responder with ≥ 5% delta ppFEV1 at 6 months (OR: 0.89, 95% CI: 0.82-0.95; P = 0.001).

CONCLUSIONS: Plasma HE4 level negatively correlates with lung function improvement assessed by ppFEV1 in pwCF undergoing LUM/IVA CFTRm treatment.

PMID:37087300 | DOI:10.1016/j.jcf.2023.04.001

Eur Respir J. 2023 Apr 20;61(4):2300308. doi: 10.1183/13993003.00308-2023. Print 2023 Apr.

NO ABSTRACT

PMID:37080577 | DOI:10.1183/13993003.00308-2023

Eur Respir J. 2023 Apr 20:2202022. doi: 10.1183/13993003.02022-2022. Online ahead of print.

ABSTRACT

BACKGROUND: Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (βENaC-Tg mice).

METHODS: We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetyl cysteine [NAC] and rhDNase) using rheology to measure the elastic modulus (G') of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in βENaC-Tg mice to determine its mucolytic efficacy in vivo.

RESULTS: In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G', was faster in decreasing sputum G' by 50%, and caused mucolysis of a larger proportion of sputum samples within 15 min of drug addition. Compared to vehicle control, three treatments with MUC-031 in one day in adult βENaC-Tg mice decreased airway mucus content (16.8±3.2 versus 7.5±1.2 nl·mm-2, p<0.01) and bronchoalveolar lavage cells (73,833±6,930 versus 47,679±7736 cells·mL-1, p<0.05). Twice daily treatment with MUC-031 for two weeks also caused decreases in these outcomes in adult and neonatal βENaC-Tg mice and reduced mortality from 37% in vehicle-treated to 21% in MUC-031 treated in βENaC-Tg neonates (p<0.05).

CONCLUSION: MUC-031 is a potent and fast acting mucolytic that decreases airway mucus plugging, lessens airway inflammation, and improves survival in βENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.

PMID:37080569 | DOI:10.1183/13993003.02022-2022

J Med Internet Res. 2023 Apr 20;25:e45249. doi: 10.2196/45249.

ABSTRACT

BACKGROUND: The COVID-19 pandemic disrupted the needs and concerns of the cystic fibrosis community. Patients with cystic fibrosis were particularly vulnerable during the pandemic due to overlapping symptoms in addition to the challenges patients with rare diseases face, such as the need for constant medical aid and limited information regarding their disease or treatments. Even before the pandemic, patients vocalized these concerns on social media platforms like Reddit and formed communities and networks to share insight and information. This data can be used as a quick and efficient source of information about the experiences and concerns of patients with cystic fibrosis in contrast to traditional survey- or clinical-based methods.

OBJECTIVE: This study applies topic modeling and time series analysis to identify the disruption caused by the COVID-19 pandemic and its impact on the cystic fibrosis community's experiences and concerns. This study illustrates the utility of social media data in gaining insight into the experiences and concerns of patients with rare diseases.

METHODS: We collected comments from the subreddit r/CysticFibrosis to represent the experiences and concerns of the cystic fibrosis community. The comments were preprocessed before being used to train the BERTopic model to assign each comment to a topic. The number of comments and active users for each data set was aggregated monthly per topic and then fitted with an autoregressive integrated moving average (ARIMA) model to study the trends in activity. To verify the disruption in trends during the COVID-19 pandemic, we assigned a dummy variable in the model where a value of "1" was assigned to months in 2020 and "0" otherwise and tested for its statistical significance.

RESULTS: A total of 120,738 comments from 5827 users were collected from March 24, 2011, until August 31, 2022. We found 22 topics representing the cystic fibrosis community's experiences and concerns. Our time series analysis showed that for 9 topics, the COVID-19 pandemic was a statistically significant event that disrupted the trends in user activity. Of the 9 topics, only 1 showed significantly increased activity during this period, while the other 8 showed decreased activity. This mixture of increased and decreased activity for these topics indicates a shift in attention or focus on discussion topics during this period.

CONCLUSIONS: There was a disruption in the experiences and concerns the cystic fibrosis community faced during the COVID-19 pandemic. By studying social media data, we were able to quickly and efficiently study the impact on the lived experiences and daily struggles of patients with cystic fibrosis. This study shows how social media data can be used as an alternative source of information to gain insight into the needs of patients with rare diseases and how external factors disrupt them.

PMID:37079359 | DOI:10.2196/45249

Expert Rev Vaccines. 2023 Apr 20. doi: 10.1080/14760584.2023.2204154. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the safety and effectiveness of the BNT162b2 vaccine in immunocompromised adolescents and young adults.

RESEARCH DESIGN AND METHODS: The study conducted a meta-analysis of post-marketing studies examining BNT162b2 vaccination efficacy and safety among immunocompromised adolescents and young adults worldwide. The review included nine studies and 513 individuals aged between 12 and 24.3 years. The study used a random effect model to estimate pooled proportions, log relative risk, and mean difference, and assessed heterogeneity using the I2 test. The study also examined publication bias using Egger's regression and Begg's rank correlation and assessed bias risk using ROBINS-I.

RESULTS: The pooled proportions of combined local and systemic reactions after the first and second doses were 30% and 32%, respectively. Adverse events following immunization (AEFI) were most frequent in rheumatic diseases (40%) and least frequent in cystic fibrosis (27%), although hospitalizations for AEFIs were rare. The pooled estimations did not show a statistically significant difference between immunocompromised individuals and healthy controls for neutralizing antibodies, measured IgG, or vaccine effectiveness after the primary dose. However, the evidence quality is low to moderate due to a high risk of bias, and no study could rule out the risk of selection bias, ascertainment bias, or selective outcome reporting.

CONCLUSIONS: This study provides preliminary evidence that the BNT162b2 vaccine is safe and effective in immunocompromised adolescents and young adults, but with low to moderate evidence quality due to bias risk. The study calls for improved methodological quality in studies involving specific populations.

PMID:37078534 | DOI:10.1080/14760584.2023.2204154

J Cyst Fibros. 2023 Apr 19:S1569-1993(23)00113-3. doi: 10.1016/j.jcf.2023.04.009. Online ahead of print.

ABSTRACT

BACKGROUND: Previously, we adapted a mobile health platform (Genia) to the needs of patients and families in a pediatric CF center in the United States. In this feasibility study, we tested the impact of Genia on measures of patient-centered care.

METHODS: In a one-group pre-post study with adolescents with CF and caregivers of children with CF, we tested Genia's effect over 6 months on patient satisfaction with chronic illness care (PACIC) and shared decision-making (CollaboRate). Feasibility and acceptability were assessed with exit interviews and app analytics.

RESULTS: The intervention included 40 participants: 30 caregivers of children with CF age ≤14 years and 10 patients with CF age ≥15 years. The use of Genia was associated with increased satisfaction with care (p = 0.024), including delivery system and decision support (p = 0.017), goal setting (p = 0.006), and shared decision-making (p<0.001). The use of Genia was associated with nominal improvements in all QOL domains and symptom scales. The platform was feasible, with participants recording more than 4,400 observations (mean 84.2) and submitting 496 weekly reports (mean 13.8) and 70 quarterly reports (mean 1.8), and acceptable (95% retention rate). For participants, the most useful app feature was pre-visit reports (66.7%), and the top symptom trackers were those for cough (23.7%), appetite (21.1%), energy (18.4%), and medicines (18.4%).

CONCLUSION: The use of Genia over 6 months was feasible, acceptable, and associated with improved measures of patient-centered care. Study results support wider use of Genia in clinical settings. Efficacy for clinical outcomes should be assessed in a randomized clinical trial.

PMID:37085386 | DOI:10.1016/j.jcf.2023.04.009

J Infect. 2023 Apr 18:S0163-4453(23)00209-8. doi: 10.1016/j.jinf.2023.04.009. Online ahead of print.

NO ABSTRACT

PMID:37080255 | DOI:10.1016/j.jinf.2023.04.009

RSC Adv. 2023 Apr 17;13(17):11838-11852. doi: 10.1039/d3ra00106g. eCollection 2023 Apr 11.

ABSTRACT

Human neutrophil elastase (HNE) and proteinase 3 (Pr3) released from neutrophils at inflammatory sites are the major causes of pathogens in chronic obstructive pulmonary disease (COPD) and various lung tissue derangements, among which cystic fibrosis and blockade of airway passages are chronic. These proteolytic mediatory agents combined with induced oxidative reactions sustain pathogenicity. Cyclic diketone indane-1,3-dione derivatives were designed, and toxicity evaluation predictions were performed in silico. Benzimidazole and hydrazide derivatives of indanedione were synthesized and characterized. Synthesized compounds were run using neutrophil elastase inhibition assay protocols. The compounds exhibit considerable inhibition of neutrophil elastase enzymes.

PMID:37077993 | PMC:PMC10107027 | DOI:10.1039/d3ra00106g