Pediatr Pulmonol. 2023 Aug 10. doi: 10.1002/ppul.26631. Online ahead of print.

NO ABSTRACT

PMID:37560893 | DOI:10.1002/ppul.26631

Front Immunol. 2023 Jul 25;14:1178410. doi: 10.3389/fimmu.2023.1178410. eCollection 2023.

ABSTRACT

The epithelial sodium channel (ENaC) is a heterotrimer and is widely distributed throughout the kidneys, blood vessels, lungs, colons, and many other organs. The basic role of the ENaC is to mediate the entry of Na+ into cells; the ENaC also has an important regulatory function in blood pressure, airway surface liquid (ASL), and endothelial cell function. Aldosterone, serum/glucocorticoid kinase 1 (SGK1), shear stress, and posttranslational modifications can regulate the activity of the ENaC; some ion channels also interact with the ENaC. In recent years, it has been found that the ENaC can lead to immune cell activation, endothelial cell dysfunction, aggravated inflammation involved in high salt-induced hypertension, cystic fibrosis, pseudohypoaldosteronism (PHA), and tumors; some inflammatory cytokines have been reported to have a regulatory role on the ENaC. The ENaC hyperfunction mediates the increase of intracellular Na+, and the elevated exchange of Na+ with Ca2+ leads to an intracellular calcium overload, which is an important mechanism for ENaC-related inflammation. Some of the research on the ENaC is controversial or unclear; we therefore reviewed the progress of studies on the role of ENaC-related inflammation in human diseases and their mechanisms.

PMID:37559717 | PMC:PMC10407551 | DOI:10.3389/fimmu.2023.1178410

J Med Genet. 2023 Aug 9:jmg-2023-109362. doi: 10.1136/jmg-2023-109362. Online ahead of print.

ABSTRACT

BACKGROUND: Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication 'single autosomal recessive mutation in rare disease'. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic 'second-hit' variants.

METHODS: To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity.

RESULTS: Using these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion in CFTR and a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2-6 of ENPP1. Although ambiguous by short-read WGS, the ENPP1 variant structure was resolved using optical genome mapping and RNA analysis.

CONCLUSION: Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits.

PMID:37558402 | DOI:10.1136/jmg-2023-109362

Eur Respir Rev. 2023 Aug 9;32(169):230029. doi: 10.1183/16000617.0029-2023. Print 2023 Sep 30.

ABSTRACT

Regular exercise testing is recommended for all people with cystic fibrosis (PwCF). A range of validated tests, which integrate both strength and aerobic function, are available and increasingly being used. Together, these tests offer the ability for comprehensive exercise evaluation. Extensive research and expert consensus over recent years has enabled the adaptation and standardisation of a range of exercise tests to aid the understanding of the pathophysiology related to exercise limitation in PwCF and has led to the development of novel exercise tests which may be applied to PwCF. This article provides expert, opinion-based clinical practice guidance, along with test instructions, for a selection of commonly used valid tests which have documented clinimetric properties for PwCF. Importantly, this document also highlights previously used tests that are no longer suggested for PwCF and areas where research is mandated. This collaboration, on behalf of the European Cystic Fibrosis Society Exercise Working Group, represents expert consensus by a multidisciplinary panel of physiotherapists, exercise scientists and clinicians and aims to improve global standardisation of functional exercise testing of PwCF. In short, the standardised use of a small selection of tests performed to a high standard is advocated.

PMID:37558263 | DOI:10.1183/16000617.0029-2023

J Allergy Clin Immunol Pract. 2023 Aug 7:S2213-2198(23)00816-4. doi: 10.1016/j.jaip.2023.07.041. Online ahead of print.

ABSTRACT

Severe Asthma affects about 10% of the asthmatic population, and it is characterized by a low lung function and a higher count of blood leucocytes, mainly eosinophils. To date, various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. The aim of this work is to highlight a consensus for asthma remission using a Delphi method. In the context of SANI (Severe Asthma Network Italy), accounting for 57 Severe Asthma Centers and more then 2200 patients, a Board of six expert drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. 32 statements have been included in the R1 questionnaire, and then submitted to a panel of 80 experts, which used a 5-points Likert scale to measure their agreement to each statement. Then, an Interim Analysis of R1 data have been performed, items were discussed and considered to produce a consistent questionnaire for the round 2 (R2) of the analysis. After this, the Board set the R2 questionnaire, which included only the important key topics. Panelists have been asked to vote the statements in the R2 questionnaire afterwards. During R2, the criteria of complete clinical remission (the absence of need for OCS, symptoms, exacerbations/attacks, and a pulmonary function stability) and those of partial clinical remission (the absence of need for OCS, and 2 out of 3 criteria: the absence of symptoms, exacerbations/attacks, and a pulmonary stability) were confirmed. This SANI Delphi Analysis defined a valuable, independent and easy to use tool to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.

PMID:37558162 | DOI:10.1016/j.jaip.2023.07.041

Med Clin (Barc). 2023 Aug 7:S0025-7753(23)00362-7. doi: 10.1016/j.medcli.2023.06.006. Online ahead of print.

ABSTRACT

Cystic fibrosis is a genetic and multisystemic disease. The main comorbidity in adulthood is respiratory involvement, with the presence of bronchiectasis, chronic bronchial infection and airflow obstruction. Until a decade ago, treatments were aimed at favoring secretion drainage, reducing respiratory exacerbations, controlling chronic bronchial infection and slowing functional deterioration, but with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the cystic fibrosis paradigm has changed. This novel treatment goes a step further in the management of this disease, it is able to improve the production of defective CFTR protein and increase its expression on the cell surface, thus achieving a better functioning of ion exchange, fluidizing respiratory secretions and reducing airflow obstruction. In addition, there are currently different lines of research aimed at correcting the genetic defect that causes cystic fibrosis.

PMID:37558605 | DOI:10.1016/j.medcli.2023.06.006

Pediatr Pulmonol. 2023 Aug 9. doi: 10.1002/ppul.26635. Online ahead of print.

ABSTRACT

BACKGROUND: The utility of the forced oscillations technique (FOT) in cystic fibrosis (CF) remains uncertain. The aim of this study was to explore the ability of lower-frequency FOT indices, alone and after adjustment for the lung volume, to assess the extent of ventilation inhomogeneity in CF patients with varying disease severity.

METHODS: Forty-five children, adolescents, and adults with CF (age 6.9-27 years) underwent spirometry, FOT, and nitrogen multiple-breath washout (N2-MBW) measurements. The respiratory resistance and reactance at 5 Hz (Rrs5 and Xrs5, respectively) were recorded, and a novel FOT index, the specific respiratory conductance (sGrs), was computed as the reciprocal of Rrs5 divided by the functional residual capacity.

RESULTS: The sGrs correlated well with the lung clearance index (LCI) (Spearman's r: -.797), whereas the correlation of Rrs5 and Xrs5 with the LCI, albeit significant, was weaker (r: .643 and -.631, respectively). The sGrs emerged as the most robust predictor of LCI regardless of the severity of lung disease, as reflected by patients' age and lung function measurements. Most importantly, the relationship between sGrs and LCI remained unaffected by lung hyperinflation, as opposed to that of the LCI with the spirometric and standard FOT indices.

CONCLUSIONS: In CF patients, the FOT indices at 5 Hz and the novel, volume-adjusted parameter sGrs, reflect the extent of lung involvement and the underlying ventilation inhomogeneity in a way comparable to N2-MBW. Future research should explore the role of lower-frequency FOT in assessing the severity and monitoring the progression of CF lung disease.

PMID:37555768 | DOI:10.1002/ppul.26635

Ann Am Thorac Soc. 2023 Aug 9. doi: 10.1513/AnnalsATS.202302-165RL. Online ahead of print.

NO ABSTRACT

PMID:37555716 | DOI:10.1513/AnnalsATS.202302-165RL

Clin Transplant. 2023 Aug 9:e15086. doi: 10.1111/ctr.15086. Online ahead of print.

ABSTRACT

BACKGROUND: Solid organ transplant provides a lifeline for people with end stage organ failure. Each year the number of individuals in receipt of a solid organ transplant is increasing. Prevention of post-transplant sepsis and infection are critical for transplant success. The oral cavity contains more than 700 different species of bacteria and is a potential reservoir for disease causing pathogens. Prior to undergoing solid organ transplant, individuals must receive a certification of dental health from a dental practitioner. There are currently no guidelines or protocols for dental practitioners to follow when certifying a patient as dentally fit. This allows for a wide variation of the term 'dentally fit'. This survey was conducted as part of a larger study assessing the oral health of adults with cystic fibrosis ongoing in Cork University Dental School and Hospital. The aim of the study was to ascertain current practices and attitudes of dental practitioners regarding the provision of dental treatment pre and post solid organ transplantation.

METHODS: An anonymous cross sectional survey of dental practitioners in Ireland was conducted.

RESULTS: The data collected showed a wide variation in the provision of treatment for patient undergoing or in receipt of a solid organ transplant.

CONCLUSION: It demonstrates a need for further research to be conducted to ascertain the full impact solid organ transplant has on oral health, so that guidelines can be developed to aid both dental and medical professionals in the treatment of this vulnerable cohort.

PMID:37555329 | DOI:10.1111/ctr.15086

Ann Med Surg (Lond). 2023 Jul 8;85(8):4150-4152. doi: 10.1097/MS9.0000000000001048. eCollection 2023 Aug.

ABSTRACT

Cystic fibrosis is an autosomal recessive disorder that causes a broad range of clinical findings and can present unusually as electrolyte disturbance, such as hyponatremia that causes seizures in children.

CASE PRESENTATION: We report a case of a 2-month-old infant who presented with an episode of grand mal seizure induced by hyponatremia and moderate episodes of milky vomiting after breastfeeding.

CLINICAL DISCUSSION: Proper investigations showed normal cardiac and renal functions. Ultrasonography showed no pathological changes. Laboratory tests performed showed hyponatremia, mild hypokalemia, and hypochloremia. Urinary electrolyte results were normal. While broadening the scope of differential diagnosis in order to reach a final diagnosis, the sweat chloride level was elevated, which confirmed the diagnosis of cystic fibroses.

CONCLUSION: We aim to share our case to keep cystic fibroses in mind as a differential diagnosis when dealing with hyponatremic seizures in children.

PMID:37554905 | PMC:PMC10406084 | DOI:10.1097/MS9.0000000000001048

Lancet Reg Health Eur. 2023 Jul 28;32:100690. doi: 10.1016/j.lanepe.2023.100690. eCollection 2023 Sep.

ABSTRACT

BACKGROUND: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF.

METHODS: This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months.

FINDINGS: The study included 2645 pwCF from 67 centres in Germany (mean age 28.0 ± 11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1 s (ppFEV1) increased by 11.3% (95% confidence interval [CI] 10.8-11.8, p < 0.0001), body mass index (BMI) z-score increased by 0.3 (95% CI 0.3-0.4, p < 0.0001) in individuals aged 12 to <18 years and BMI in adults increased by 1.4 kg/m2 (95% CI 1.3-1.4, p < 0.0001), pulmonary exacerbations decreased by 75.9% (p < 0.0001) and mean sweat chloride concentration decreased by 50.9 mmol/L (95% CI -52.6, -49.3, p < 0.0001). Improvements in ppFEV1 over the first year of therapy were greater in pwCF who had not previously received cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (12.6% [95% CI 11.9-13.4] vs. 9.7% [95% CI 9.0-10.5] in those with prior CFTR modulator treatment.

INTERPRETATION: These real-world data are consistent with the findings of randomised clinical trials, and support the use of ETI as a highly effective treatment option for pwCF who have at least one F508del allele.

FUNDING: None.

PMID:37554663 | PMC:PMC10405057 | DOI:10.1016/j.lanepe.2023.100690

Oncoimmunology. 2023 Aug 5;12(1):2242211. doi: 10.1080/2162402X.2023.2242211. eCollection 2023.

ABSTRACT

Recently, a cellular mini-immune system comprising infinitely expandable dendritic cells and T cells led to the discovery that histamine receptor H1 antagonists act on T cells to stimulate their proliferation and polarization toward a Th1/Tc1 phenotype and to increase their anticancer activity in the context of immunochemotherapy.

PMID:37554311 | PMC:PMC10405763 | DOI:10.1080/2162402X.2023.2242211

EClinicalMedicine. 2023 Jul 27;62:102116. doi: 10.1016/j.eclinm.2023.102116. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: Generic and disease-specific patient-reported outcome measures (PROMs) may lack relevance and sensitivity on a patient-level in chronic diseases with differential disease expression and high individual variability, such as Cystic Fibrosis (CF). This study aimed to develop and validate a novel personalized electronic PROM (ePROM) that captures relevant aspects of quality of life in individuals with CF.

METHODS: The Q-Life app was developed as a short personalized ePROM to assess individual quality of life. Psychometric properties were assessed in a single-center cross-sectional study between September 2019 and September 2021 and in a prospective cohort study between September 2021 and September 2022.

FINDINGS: Combined studies included 223 participants (median age: 24 years, IQR: 19.0-32.5 years, range: 12.0-58.0 years). Internal consistency (Cronbach's alpha: 0.83-0.90) and test-retest reliability (intraclass correlation coefficient: 0.90; 95% CI: 0.65-0.92; p < 0.001) of quality of life (Q-Life) scores were strong. Q-Life scores were associated with overall Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores (ρ = 0.71; p < 0.001), CFQ-R respiratory domain scores (ρ = 0.57; p < 0.001) and forced expiratory volume in 1s (ρ = 0.41; p < 0.001). Furthermore, Q-Life scores improved from 65.0 (IQR: 45.0-63.3) at baseline to 84.2 (IQR: 75.0-95.0) and 87.5 (IQR: 75.0-100.0) after 3 and 6 months of elexacaftor/tezacaftor/ivacaftor treatment (change: 20.8; 95% CI: 17.5-25.0; p < 0.001), comparable to CFQ-R respiratory domain scores (change: 22.2, 95% CI: 19.4-25.0, p < 0.001).

INTERPRETATION: The Q-Life app is a reliable, valid and sensitive personalized ePROM to measure all aspects of quality of life that really matter to individuals with Cystic Fibrosis. This patient-centered approach could provide important advantages over generic and disease-specific PROMs in the era of personalized medicine and value-based healthcare.

FUNDING: Dutch Cystic Fibrosis Foundation, Health-Holland.

PMID:37554124 | PMC:PMC10404867 | DOI:10.1016/j.eclinm.2023.102116

J Clin Ultrasound. 2023 Aug 8. doi: 10.1002/jcu.23528. Online ahead of print.

ABSTRACT

Echogenic fetal bowel (EB) is a prenatal ultrasound finding (0.2%-1.4% of all pregnancies) defined as bowel of similar or greater echogenicity than surrounding bone. In fact, the ultrasound assessment is strongly subjective with inter-observer variability. The pathophysiology depends on the underlying condition, apparently related with meconium stasis and hypercellularity. It is often an isolated finding, with possible association with other structural anomalies. About the origin, it was observed in fetuses with cystic fibrosis, congenital infections, thalassemia, intraamniotic bleeding, fetal growth restriction. Fetuses with EB are at increased risk of adverse perinatal outcome, such as intrauterine growth restriction, placental dysfunction and perinatal death, highlighting the need for a thorough antenatal management and post-natal follow-up. It seems to be associated with a plenty of conditions, such as a poor fetal outcome, fetal growth restriction and placental dysfunction. Therefore management requires a multidisciplinary approach with different specialties' involvement and the prognosis is influenced by the underlying pathophysiology. In this complex scenario, the present review aims to define the clinical pathway which should be offered to pregnant women in case of finding of fetal EB ultrasound marker, to rule out any suspected pathological cause.

PMID:37553773 | DOI:10.1002/jcu.23528

Biometrics. 2023 Aug 8. doi: 10.1111/biom.13918. Online ahead of print.

ABSTRACT

Missing data are a pervasive issue in observational studies using electronic health records or patient registries. It presents unique challenges for statistical inference, especially causal inference. Inappropriately handling missing data in causal inference could potentially bias causal estimation. Besides missing data problems, observational health data structures typically have mixed-type variables - continuous and categorical covariates - whose joint distribution is often too complex to be modeled by simple parametric models. The existence of missing values in covariates and outcomes makes the causal inference even more challenging, while most standard causal inference approaches assume fully observed data or start their works after imputing missing values in a separate preprocessing stage. To address these problems, we introduce a Bayesian nonparametric causal model to estimate causal effects with missing data. The proposed approach can simultaneously impute missing values, account for multiple outcomes, and estimate causal effects under the potential outcomes framework. We provide three simulation studies to show the performance of our proposed method under complicated data settings whose features are similar to our case studies. For example, Simulation Study 3 assumes the case where missing values exist in both outcomes and covariates. Two case studies were conducted applying our method to evaluate the comparative effectiveness of treatments for chronic disease management in juvenile idiopathic arthritis and cystic fibrosis.

PMID:37553770 | DOI:10.1111/biom.13918

Pediatr Res. 2023 Aug 7. doi: 10.1038/s41390-023-02755-3. Online ahead of print.

NO ABSTRACT

PMID:37550488 | DOI:10.1038/s41390-023-02755-3

Acad Radiol. 2023 Aug 5:S1076-6332(23)00358-6. doi: 10.1016/j.acra.2023.07.009. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: Ultra short echo time (UTE) magnetic resonance imaging (MRI) pulse sequences have shown promise for airway assessment, but the feasibility and repeatability in the pediatric lung are unknown. The purpose of this work was to develop a semiautomated UTE MRI airway segmentation pipeline from the trachea-to-tertiary airways in pediatric participants and assess repeatability and lumen diameter correlations to lung function.

MATERIALS AND METHODS: A total of 29 participants (n = 7 healthy, n = 11 cystic fibrosis, n = 6 asthma, and n = 5 ex-preterm), aged 7-18 years, were imaged using a 3D stack-of-spirals UTE examination at 3 T. Two independent observers performed airway segmentations using a pipeline developed in-house; observer 1 repeated segmentations 1 month later. Segmentations were extracted using region-growing with leak detection, then manually edited if required. The airway trees were skeletonized, pruned, and labeled. Airway lumen diameter measurements were extracted using ray casting. Intra- and interobserver variability was assessed using the Sørensen-Dice coefficient (DSC) and intra-class correlation coefficient (ICC). Correlations between lumen diameter and pulmonary function were assessed using Spearman's correlation coefficient.

RESULTS: For airway segmentations and lumen diameter, intra- and interobserver DSCs were 0.88 and 0.80, while ICCs were 0.95 and 0.89, respectively. The variability increased from the trachea-to-tertiary airways for intra- (DSC: 0.91-0.64; ICC: 0.91-0.49) and interobserver (DSC: 0.84-0.51; ICC: 0.89-0.21) measurements. Lumen diameter was significantly correlated with forced expiratory volume in 1 second and forced vital capacity (P < .05).

CONCLUSION: UTE MRI airway segmentation from the trachea-to-tertiary airways in pediatric participants across a range of diseases is feasible. The UTE MRI-derived lumen measurements were repeatable and correlated with lung function.

PMID:37550154 | DOI:10.1016/j.acra.2023.07.009

Ann Epidemiol. 2023 Aug 5:S1047-2797(23)00151-5. doi: 10.1016/j.annepidem.2023.07.008. Online ahead of print.

ABSTRACT

Deaths among those lost to follow-up (LTFU) in the Cystic Fibrosis Foundation Patient Registry (CFFPR) are critically important to the epidemiology of cystic fibrosis (CF). Unreported deaths could impact estimates of survival if LTFU is associated with disease trajectory. We characterized the LTFU population (1986-2017) from the CFFPR and identified deaths via linkage with the National Death Index (NDI). Median predicted survival age was estimated using a Cox proportional hazards model and calculated with and without additional deaths and person-time from the NDI. Of the 10,582 individuals LTFU in the CFFPR, 2,460 (23.2%) matched to an NDI death record. Individuals who died after LTFU were 43.0% female, 90.9% Caucasian race, 58.9% had advanced CF lung disease based on last CFFPR recorded forced expiratory volume in one second (FEV1) % predicted of <40 and 18.1% were post-lung transplant. Inclusion of deaths and additional person-time among those LTFU changed the point estimate of median predicted survival for most time periods and increased the point estimate from 2009 onwards. Median predicted survival age during the most recent period available, 2013-2017, increased from 44.3 years (95% CI: 43.2, 45.7) to 45.8 years (95% CI 44.5, 47.1) with the inclusion of NDI data.

PMID:37549758 | DOI:10.1016/j.annepidem.2023.07.008

Am J Respir Crit Care Med. 2023 Aug 7. doi: 10.1164/rccm.202307-1200VP. Online ahead of print.

NO ABSTRACT

PMID:37549229 | DOI:10.1164/rccm.202307-1200VP

Eur Radiol. 2023 Aug 7. doi: 10.1007/s00330-023-09912-6. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate whether 3D phase-resolved functional lung (PREFUL)-MRI parameters are suitable to measure response to elexacaftor/tezacaftor/ivacaftor (ETI) therapy and their association with clinical outcomes in cystic fibrosis (CF) patients.

METHODS: Twenty-three patients with CF (mean age: 21; age range: 14-46) underwent MRI examination at baseline and 8-16 weeks after initiation of ETI. Morphological and 3D PREFUL scans assessed pulmonary ventilation. Morphological images were evaluated using a semi-quantitative scoring system, and 3D PREFUL scans were evaluated by ventilation defect percentage (VDP) values derived from regional ventilation (RVent) and cross-correlation maps. Improved ventilation volume (IVV) normalized to body surface area (BSA) between baseline and post-treatment visit was computed. Forced expiratory volume in 1 second (FEV1) and mid-expiratory flow at 25% of forced vital capacity (MEF25), as well as lung clearance index (LCI), were assessed. Treatment effects were analyzed using paired Wilcoxon signed-rank tests. Treatment changes and post-treatment agreement between 3D PREFUL and clinical parameters were evaluated by Spearman's correlation.

RESULTS: After ETI therapy, all 3D PREFUL ventilation markers (all p < 0.0056) improved significantly, except for the mean RVent parameter. The BSA normalized IVVRVent was significantly correlated to relative treatment changes of MEF25 and mucus plugging score (all |r| > 0.48, all p < 0.0219). In post-treatment analyses, 3D PREFUL VDP values significantly correlated with spirometry, LCI, MRI global, morphology, and perfusion scores (all |r| > 0.44, all p < 0.0348).

CONCLUSIONS: 3D PREFUL MRI is a very promising tool to monitor CFTR modulator-induced regional dynamic ventilation changes in CF patients.

CLINICAL RELEVANCE STATEMENT: 3D PREFUL MRI is sensitive to monitor CFTR modulator-induced regional ventilation changes in CF patients. Improved ventilation volume correlates with the relative change of mucus plugging, suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement.

KEY POINTS: • 3D PREFUL MRI-derived ventilation maps show significantly reduced ventilation defects in CF patients after ETI therapy. • Significant post-treatment correlations of 3D PREFUL ventilation measures especially with LCI, FEV1 %pred, and global MRI score suggest that 3D PREFUL MRI is sensitive to measure improved regional ventilation of the lung parenchyma due to reduced inflammation induced by ETI therapy in CF patients. • 3D PREFUL MRI-derived improved ventilation volume (IVV) correlated with MRI mucus plugging score changes suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement 8-16 weeks after ETI therapy.

PMID:37548691 | DOI:10.1007/s00330-023-09912-6