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The lack of data on drug–drug interactions in pediatrics represents a relevant problem in making appropriate therapeutic decisions. Our study aimed to investigate the incidence and risk factors for potential drug–drug interactions (pDDIs) in pediatric pneumonology units, including cystic fibrosis patients. We performed a 6‐month prospective observational study during which clinical pharmacists, using the Lexicomp Drug Interactions checker, screened medical records to identify pDDIs. Spearman's rank coefficient, logistic regression, and the Mann–Whitney U test were used to identify correlations, analyze risk factors for pDDIs, and compare cystic fibrosis patients with the rest, respectively. Recommendations were provided for the D and X pDDIs categories. Within the 218 patients, 428 pDDIs were identified, out of which 237 were classified as clinically significant. Almost 60% of patients were exposed to at least one relevant interaction. The number of pDDIs correlated with the number of; drugs (rs = 0.53, P <.001), hospitalization length (rs = 0.20, P <.01), and off‐label medicines (rs = 0.25, P <.001). According to the multivariate analysis, at least 6 administered medications (OR = 4.15; 95% CI = 2.21‐7.78), 4 days of hospitalization (OR = 6.41; 95% CI = 2.29‐17.97), and off‐label therapy (OR = 3.37; 95% CI = 1.69‐6.70) were the risk factor for pDDIs. Despite significant differences in the number of medications taken, comorbidities, and off‐label drugs, cystic fibrosis patients were not more exposed to pDDI. Given the lack of data on pDDIs in the pediatric population, the need for close cooperation between clinicians and clinical pharmacists to improve the safety and efficacy of pharmacotherapy is highlighted. [ABSTRACT FROM AUTHOR]

Aim: The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)‐related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD. Materials and Methods: Three hundred and three individuals living with CF underwent a 2‐h oral glucose tolerance test with blood sampling every 30 min at 12–24‐month intervals until they developed CFRD or until the end of follow‐up (up to 15 years). Indices of insulin resistance (e.g. Stumvoll) and insulin secretion were calculated from oral glucose tolerance test glucose and insulin measurements. CFRD‐free survival was assessed by survival analysis. Results: Estimated insulin resistance showed associations with glucose homeostasis and risk of progression to CFRD. The CFRD‐free survival was significantly different between quartiles of insulin resistance (p < 0.0001). When patients were subdivided according to both insulin resistance and insulin secretion (insulinogenic index), CFRD‐free survival was significantly lower in those with combined lowest insulin secretion and highest insulin resistance (Stumvoll) indices (hazard ratio: 11.2; p < 0.0001). There was no significant difference when the same analysis was performed for the nine other indices. Conclusions: Insulin resistance is correlated with glucose homeostasis and the risk of progression to CFRD. Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15‐year period. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post‐transplant follow‐up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work‐up for suspected infection during hospitalization. After a median follow‐up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post‐transplant and >2 years post‐transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Renal excretion of excess HCO3− depends on renal cystic fibrosis transmembrane conductance regulator (CFTR) and is impaired in people with cystic fibrosis (pwCF). Urine HCO3− excretion following oral NaHCO3‐loading may be a simple in vivo biomarker of CFTR function. In this study, we investigated changes in urine acid/base parameters following oral NaHCO3‐loading to comprehensively assess the physiological response to the test and evaluate HCO3− as the primary test result.Urine acid/base parameters (titratable acid (TA), NH4+, net acid excretion (NAE) and pH) were measured in bio‐banked urine samples from controls (n = 10) and pwCF (n = 50) who completed the challenged urine HCO3− test. The association between urine acid/base excretion parameters and clinical CF disease characteristics and CFTR modulator therapy‐induced changes were assessed.Before treatment, challenged urine acid/base excretion associated with important CF disease characteristics. TA excretion and NAE were lower in pwCF with residual function mutations, 7.9 and 16.6 mmol/3 h, respectively, and lower TA excretion and NAE associated with pancreatic sufficiency. A lower excretion of TA, NH4+, and NAE associated with a higher percentage of predicted FEV1 (1.3%, 2.5% and 0.8% per mmol/3 h higher, respectively). Modulator treatment decreased TA excretion and NAE (−2.9 and −5.3 mmol/3 h, respectively).Following acute NaHCO3‐loading, increased base excretion is mirrored by decreased acid excretion. Urine HCO3− excretion sufficiently represents the additional urine acid/base parameters as test result. The observed changes in acid excretion support CFTR modulator‐induced increase of CFTR‐dependent type B intercalated cell HCO3− secretion and the use of the challenged urine HCO3− test as a possible CFTR‐biomarker. [ABSTRACT FROM AUTHOR]

Chronic illness requires a web of actors, both professional and familiar, who constitute the support network of the chronically ill. This article aims to analyse how the COVID‐19 pandemic has impacted on the delicate balance of these supports. Qualitative research was conducted among people with four types of chronic diseases in France: cystic fibrosis, kidney disease, haemophilia and mental disorders. Data on social support was collected using an innovative methodology combining semi‐directive interviews (n = 54) and drawings (n = 32). During the first French lockdown (March–May 2020), the chronically ill were mainly supported by the usual support actors of their primary network: spouse and/or family. However, the COVID‐19 health crisis has led to several changes in their support network; health‐care professionals diversified their support roles and new supporting actors emerged, especially non‐human entities and patient organisations. The chronically ill have received an interweaving of emotional, instrumental and informational, formal and informal and human and non‐human support. Our study highlights the multiple and dynamic ties between these types of support and argues in favour of a comprehensive approach to social support of the chronically ill, both in social science theory and in practice of care. [ABSTRACT FROM AUTHOR]

Background Method Results Conclusion Medication adherence data are an important quality indicator in cystic fibrosis (CF) care, yet real‐time objective data are not routinely available. An online application (CFHealthHub) has been designed to deliver these data to people with CF and their clinical team. Adoption of this innovation is the focus of an National Health Service England‐funded learning health system and Quality Improvement Collaborative (QIC). This study applies the capability, opportunity, and motivation model of behavior change to assess whether the QIC had supported healthcare professionals' uptake of accessing patient adherence data.This was a mixed‐method study, treating each multidisciplinary team as an individual case. Click analytic data from CFHealthHub were collected between January 1, 2018, and September 22, 2019. Thirteen healthcare practitioners participated in semi‐structured interviews, before and after establishing the QIC. Qualitative data were analyzed using the behavior change model.The cases showed varied improvement trajectories. While two cases reported reduced barriers, one faced persistent challenges. Participation in the QIC led to enhanced confidence in the platform's utility. Reduced capability, opportunity, and motivation barriers correlated with increased uptake, demonstrating value in integrating behavior change theory into QICs.QICs can successfully reduce barriers and enable uptake of e‐health innovations such as adherence monitoring technology. However, ongoing multi‐level strategies are needed to embed changes. Further research should explore sustainability mechanisms and their impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis (CF), an inherited autosomal recessive disorder, is linked with high morbidity and mortality rates due to bacteria, filamentous, yeast and black yeast‐like fungi colonisation in the upper respiratory tract. Although Candida species are the most common fungi isolated from CF patients, azole‐resistant Aspergillus fumigatus (ARAf) is a big concern for invasive aspergillosis. Notably, the exact prevalences of Aspergillus species and the prevalence of ARAf isolates among Iranian CF patients have yet to be previously reported and are unknown. We aimed to investigate the prevalence of ARAf isolates in CF patients among Iranian populations by focusing on molecular mechanisms of the mutations in the target gene. Methods: The 1 year prospective study recovered 120 sputum samples from 103 CF patients. Of these, 55.1% (86/156) yielded Aspergillus species, screened for ARAf using plates containing itraconazole (4 mg/L) and voriconazole (1 mg/L). According to the CLSI‐M38 guidelines, antifungal susceptibility testing was performed using the broth microdilution method. In all phenotypically resistant isolates, the target of azole agents, the cyp51A gene, was sequenced to detect any possible single nucleotide polymorphisms (SNP) mediating resistance. Results: Of 120 samples, 101 (84.2%) were positive for filamentous fungi and yeast‐like relatives, with 156 fungal isolates. The most common colonising fungi were Aspergillus species (55.1%, 86/156), followed by Candida species (39.8%, 62/156), Exophiala species (3.8%, 6/156) and Scedosporium species (1.3%, 2/156). Forty out of 86 (46.5%) were identified for section Fumigati, 36 (41.9%) for section Flavi, 6 (7%) for section Nigri and 4 (4.6%) for section Terrei. Fourteen out of 40 A. fumigatus isolates were phenotypically resistant. The overall proportion of ARAf in total fungal isolates was 9% (14/156). cyp51A gene analysis in resistant isolates revealed that 13 isolates harboured G448S, G432C, T289F, D255E, M220I, M172V, G138C, G54E and F46Y mutations and one isolate carried G448S, G432C, T289F, D255E, M220I, G138C, G54E and F46Y mutations. Additionally, this study detects two novel cyp51A single‐nucleotide polymorphisms (I242V and D490E). Conclusions: This study first investigated ARAf isolates in Iranian CF patients. Due to a resistance rate of up to 9%, it is recommended that susceptibility testing of Aspergillus isolates from CF patients receiving antifungal treatment be a part of the routine diagnostic workup. However, extensive multicentre studies with a high volume of CF patients are highly warranted to determine the impact of ARAf on CF patients. [ABSTRACT FROM AUTHOR]

Objectives: In cystic fibrosis (CF), an imbalanced lipid metabolism is associated with lung inflammation. Little is known about the role that specific lipid mediators (LMs) exert in CF lung inflammation, and whether their levels change during early disease progression. Therefore, we measured airway LM profiles of young CF patients, correlating these with disease‐associated parameters. Methods: Levels of omega (ω)‐3/6 PUFAs and their LM derivatives were determined in bronchoalveolar lavage fluid (BALF) of children with CF ages 1–5 using a targeted high‐performance liquid chromatography–tandem mass spectrometry approach. Hierarchical clustering analysis was performed on relative LM levels. Individual relative LM levels were correlated with neutrophilic inflammation (BALF %Neu) and structural lung damage (PRAGMA‐CF %Disease). Significant correlations were included in a backward multivariate linear regression model to identify the LMs that are best related to disease progression. Results: A total of 65 BALF samples were analysed for ω‐3/6 lipid content. LM profiles clustered into an arachidonic acid (AA)‐enriched and a linoleic acid (LA)‐enriched sample cluster. AA derivatives like 17‐OH‐DH‐HETE, 5‐HETE, 5,15‐diHETE, 15‐HETE, 15‐KETE, LTB4 and 6‐trans‐LTB4 positively correlated with BALF %Neu and/or PRAGMA %Dis. Contrastingly, 9‐HoTrE and the LA derivatives 9‐HoDE, 9(10)‐EpOME, 9(10)‐DiHOME, 13‐HoDE, 13‐oxoODE and 12(13)‐EpOME negatively correlated with BALF %Neu and/or PRAGMA %Dis. 6‐trans‐LTB4 was the strongest predictor for BALF %Neu. 5‐HETE and 15‐KETE contributed most to PRAGMA %Dis prediction. Conclusions: Our data provide more insight into the lung lipidome of infants with CF, and show that a shift from LA derivatives to AA derivatives in BALF associates with early CF lung disease progression. [ABSTRACT FROM AUTHOR]

Objective: Elexacaftor/tezacaftor/ivacaftor (E/T/I) has provided life‐changing pharmacotherapy for many people with cystic fibrosis (CF), but conflicting literature exists regarding the effect on mental health. While some reports suggest E/T/I may induce adverse psychiatric symptoms, others report improvements in mental health symptoms. To add to this growing body of knowledge, we retrospectively analyzed depression and anxiety symptoms before and after E/T/I initiation in adults with CF at a single large US CF center. Method: Patient Health Questionnaire‐9 (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) scores recorded in a database were studied. Patients with scores collected before and after E/T/I initiation were included. Regression analyses described associations between score changes and age, race, ethnicity, sex, CFTR variant, and prior depression and/or anxiety diagnoses. Secondary analyses examined possible confounding effects of the COVID‐19 pandemic. Results: There was no change in mean GAD‐7 (0.5 ± 5.3, p = 0.41) or PHQ‐9 (−0.02 ± 6.0, p = 0.97) scores following initiation of E/T/I (N = 86). A trend between a prior diagnosis of depression and worsening in PHQ‐9 post‐E/T/I was observed (OR 3.58; p = 0.054). Conclusions: Treatment with E/T/I does not lead to changes in depression or anxiety symptoms at the population level in this single center cohort study. A prior diagnosis of depression trended towards an increased odds of worsening PHQ‐9 scores after E/T/I initiation. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN) is a multi‐functional glycoprotein that coordinates the innate immune response, prevents nanocrystal formation in renal tubule fluid, and is a biomarker for kidney injury. OPN expression is markedly increased in cystic epithelial cells of polycystic kidney disease (PKD) kidneys; however, its role in PKD progression remains unclear. We investigated the in vitro effects of recombinant OPN on the proliferation of tubular epithelial cells from PKD and normal human kidneys and in vivo effects of OPN deletion on kidney cyst formation, fibrosis, and mineral metabolism in pcy/pcy mice, a non‐orthologous model of autosomal‐dominant PKD. In vitro studies revealed that OPN enhanced the proliferation of PKD cells but had no effect on normal kidney cells. Deletion of OPN in pcy/pcy mice significantly reduced kidney cyst burden; however, this was accompanied by increased fibrosis and no change in kidney function. The loss of OPN had no effect on kidney macrophage numbers, cyst epithelial cell proliferation, or apoptosis. Furthermore, there was no difference in kidney mineral deposition or mineral metabolism parameters between pcy/pcy mice with and without OPN expression. Global deletion of OPN reduced kidney cyst burden, while paradoxically exacerbating kidney fibrosis in mice with cystic kidney disease. [ABSTRACT FROM AUTHOR]

The vast majority of people with cystic fibrosis (pwCF) have untreated secondary chronic rhinosinusitis (CRS). Whereas the introduction of the cystic fibrosis transmembrane conductance regulator modulator (CFTRm) treatment regime has improved the lung function of pwCF, few studies have been published examining the effect on sinonasal symptoms in children. Our aim was to explore the effect of double CFTRm treatment on CRS and olfaction in children with CF. pwCF were included in this non‐randomized cross‐sectional study, where an otolaryngologist performed a complete ENT examination before initiating treatment with elaxacaftor/tezacaftor/ivacaftor (ETI). Twenty‐three pwCF aged 6–12 years were included. Eighteen of 23 patients were on a double CFTRm treatment, and 5 patients were CFTRm naive, respectively. Altogether, 19 had normal olfaction, 20 had none or mild CRS symptoms according to SNOT‐22, and 14 had a normal endoscopy. None of the patients had symptoms of chronic rhinosinusitis lasting for more than 12 weeks, thus none of the patients fulfilled the criteria for CRS. Children with CF treated with double CFTRm have few to no symptoms of CRS and normal olfaction, which is an improvement compared with children following treatment modalities prior to CFTRm. [ABSTRACT FROM AUTHOR]

Background & Aims: Cystic fibrosis (CF) is considered a multisystemic disorder in which CF‐associated liver disease (CFLD) is the third most common cause of mortality. Currently, no effective treatment is available for CFLD because its pathophysiology is still unclear. Interestingly, CFLD exhibits identical vascular characteristics as non‐cirrhotic portal hypertension, recently classified as porto‐sinusoidal vascular disorders (PSVD). Methods: Since endothelial cells (ECs) are an important component in PSVD, we performed single‐cell RNA sequencing (scRNA‐seq) on four explant livers from CFLD patients to identify differential endothelial characteristics which could contribute to the disease. We comprehensively characterized the endothelial compartment and compared it with publicly available scRNA‐seq datasets from cirrhotic and healthy livers. Key gene signatures were validated ex vivo on patient tissues. Results: We found that ECs from CF liver explants are more closely related to healthy than cirrhotic patients. In CF patients we also discovered a distinct population of liver sinusoidal ECs—coined CF LSECs—upregulating genes involved in the complement cascade and coagulation. Finally, our immunostainings further validated the predominant periportal location of CF LSECs. Conclusions: Our work showed novel aspects of human liver ECs at the single‐cell level thereby supporting endothelial involvement in CFLD, and reinforcing the hypothesis that ECs could be a driver of PSVD. Therefore, considering the vascular compartment in CF and CFLD may help developing new therapeutic approaches for these diseases. [ABSTRACT FROM AUTHOR]

Purpose: Hyperpolarized xenon MRI suffers from heterogeneous coil bias and magnetization decay that obscure pulmonary abnormalities. Non‐physiological signal variability can be mitigated by measuring and mapping the nominal flip angle, and by rescaling the images to correct for signal bias and decay. While flip angle maps can be calculated from sequentially acquired images, scan time and breath‐hold duration are doubled. Here, we exploit the low‐frequency oversampling of 2D‐spiral and keyhole reconstruction to measure flip angle maps from a single acquisition. Methods: Flip angle maps were calculated from two images generated from a single dataset using keyhole reconstructions and a Bloch‐equation–based model suitable for hyperpolarized substances. Artifacts resulting from acquisition and reconstruction schemes (e.g., keyhole reconstruction radius, slice‐selection profile, spiral‐ordering, and oversampling) were assessed using point‐spread functions. Simulated flip angle maps generated using keyhole reconstruction were compared against the paired‐image approach using RMS error (RMSE). Finally, feasibility was demonstrated for in vivo xenon ventilation imaging. Results: Simulations demonstrated accurate flip angle maps and B1‐inhomogeneity correction can be generated with only 1.25‐fold central‐oversampling and keyhole reconstruction radius = 5% (RMSE = 0.460°). These settings also generated accurate flip angle maps in a healthy control (RSME = 0.337°) and a person with cystic fibrosis (RMSE = 0.404°) in as little as 3.3 s. Conclusion: Regional lung ventilation images with reduced impact of B1‐inhomogeneity can be acquired rapidly by combining 2D‐spiral acquisition, Bloch‐equation–based modeling, and keyhole reconstruction. This approach will be especially useful for breath‐hold studies where short scan durations are necessary, such as dynamic imaging and applications in children or people with severely compromised respiratory function. [ABSTRACT FROM AUTHOR]

Objectives: The 22‐question SinoNasal Outcome Test (SNOT‐22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT‐22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT‐22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). Methods: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT‐22 scores were obtained at baseline and after 3–6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution‐based methods were used to assess internal consistency and calculate the MCID of the SNOT‐22. Results: A total of 184 PwCF participated with mean baseline SNOT‐22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre‐ and post‐HEMT data reported improvement in SNOT‐22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT‐22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02–1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14–18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39–20.11) were associated with greater SNOT‐22 improvement. The mean MCID calculated via distribution‐based methods was 8.5. Conclusion: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT‐22 in PwCF is 8.5 points, similar to non‐CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT‐22 has strong internal consistency in PwCF. Level of Evidence: 3 Laryngoscope, 134:3965–3973, 2024 [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta‐analysis of clinical trials to date that include functional and radiographic evidence of sinus disease.English full‐text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines were followed, and the risk of bias in non‐randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta‐analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements.Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test‐22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I2 = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I2 = 67%, p = 0.030).CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF‐related chronic rhinosinusitis promises to evolve. [ABSTRACT FROM AUTHOR]

Sweat chloride concentration, a diagnostic feature in cystic fibrosis (CF), reflects CF transmembrane conductance regulator (CFTR) activity. CFTR modulator therapies, especially elexacaftor/tezacaftor/ivacaftor (ETI), has improved CF outcomes. We report nationwide, real‐world data on sweat chloride concentration in people with CF (pwCF) with and without modulator therapies. All Danish pwCF with a minimum of one F508del allele were included. Sweat chloride measurements were stratified by genotype and modulator treatment. Differences were assessed using mixed‐effects models. We included 977 sweat chloride measurements from 430 pwCF, 71% of which were F508del homozygous. Heterozygous and homozygous ETI‐treated pwCF had an estimated mean sweat chloride concentration of 43 mmol/L (95% confidence interval: 39; 48) and 43 mmol/L (39; 47), respectively—48% and 59% lower than those without treatment. High variation in concentrations remained regardless of treatment status. Despite ETI treatment, 27% heterozygous and 23% homozygous pwCF had elevated concentrations (≥60 mmol/L). These real‐world data confirm a substantial decrease in sweat chloride concentration during modulator treatment, especially ETI, where mean concentrations halved. However, large variation remained, including persistently high concentrations. These findings emphasize the potential of sweat chloride concentration as a treatment response biomarker and the need to explore its heterogeneity and relationship with clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: We tested whether generalized beliefs that the world is safe, abundant, pleasurable, and progressing (termed "primal world beliefs") are associated with several objective measures of privilege. Methods: Three studies (N = 16,547) tested multiple relationships between indicators of privilege—including socioeconomic status, health, sex, and neighborhood safety—and relevant world beliefs, as well as researchers and laypeople's expectations of these relationships. Samples were mostly from the USA and included general population samples (Study 2) as well as focused samples of academic researchers (Study 1) and people who had experienced serious illness or trauma (Study 3). Results: Studies 1–2 found mostly negligible relationships between world beliefs and indicators of privilege, which were invariably lower than researcher predictions (e.g., instead of the expected r = 0.33, neighborhood affluence correlated with Abundant world belief at r = 0.01). Study 3 found that people who had experienced serious illness (cancer, cystic fibrosis) only showed modest differences in beliefs from controls. Conclusions: While results do not preclude that some individuals' beliefs were meaningfully affected by life events, they imply that such changes are smaller or less uniform than widely believed and that knowing a person's demographic background may tell us relatively little about their beliefs (and vice versa). [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied. Methods: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019–2023). Participants were administered the 22‐SinoNasal Outcome Test (SNOT‐22) survey and a modified SNOT‐22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT‐22 symptom importance subdomains in two sets of subgroups—those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI. Results: Among 69 participants, the highest priorities were nasal congestion (n = 48, 69.6% important), post‐nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n = 23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n = 49) (sleep median score = 19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p < 0.0001; psychological = 17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p = 0.002). ETI users had comparable SNOT‐22 total symptom importance scores to non‐ETI users (p = 0.14). Non‐ETI users (n = 34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n = 35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p = 0.055). Conclusions: Nasal congestion and post‐nasal discharge were top priorities reported by PwCF + CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre‐operative discussions. Non‐ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cystic fibrosis (CF) patients are living longer and healthier due to improved treatments, e.g. cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI), with treatment possibly occurring in pregnancy. The risk of ETI to foetuses remain unknown. Thus the effect of maternally administered ETI on foetal genetic and structural development was investigated. Experimental Approach: Pregnant Sprague Dawley rats were orally treated with ETI (6.7 mg·kg−1·day−1 elexacaftor + 3.5 mg·kg−1·day−1 tezacaftor + 25 mg·kg−1·day−1 ivacaftor) for 7 days from E12 to E19. Tissue samples collected at E19 were analysed using histology and RNA sequencing. Histological changes and differentially expressed genes (DEG) were assessed. Key Results: No overt structural abnormalities were found in foetal pancreas, liver, lung and small intestine after 7‐day ETI exposure. Very few non‐functionally associated DEG in foetal liver, lung and small intestine were identified using RNA‐seq. 29 DEG were identified in thymus (27 up‐regulated and two down‐regulated) and most were functionally linked to each other. Gene ontology enrichment analysis revealed that multiple muscle‐related terms were significantly enriched. Many more DEG were identified in cortex (44 up‐regulated and four down‐regulated) and a group of these were involved in central nervous system and brain development. Conclusion and Implication: Sub‐chronic ETI treatment in late pregnancy does not appear to pose a significant risk to the genetic and structural development of many foetal tissues. However, significant gene changes in foetal thymic myoid cells and cortical neuronal development requires future follow‐up studies to assess the risk to these organs. [ABSTRACT FROM AUTHOR]

Pulmonary infections complicate chronic lung diseases requiring attention to both the pathophysiology and complexity associated with infection management. Patients with cystic fibrosis (CF) struggle with continuous bouts of pulmonary infections, contributing to lung destruction and eventual mortality. Additionally, CF patients struggle with airways that are highly viscous, with accumulated mucus creating optimal environments for bacteria colonization. The unique physiology and altered airway environment provide an ideal niche for bacteria to change their phenotype often becoming resistant to current treatments. Colonization with multiple pathogens at the same time further complicate treatment algorithms, requiring drug combinations that can challenge CF patient tolerance to treatment. The goal of this research initiative was to explore the utilization of a microparticle antibiotic delivery system, which could provide localized and sustained antibiotic dosing. The outcome of this work demonstrates the feasibility of providing efficient localized delivery of antibiotics to manage infection using both preclinical in vitro and in vivo CF infection models. The studies outlined in this manuscript demonstrate the proof-of-concept and unique capacity of polymerized cyclodextrin microparticles to provide site-directed management of pulmonary infections. [ABSTRACT FROM AUTHOR]

INTRODUCTION METHODS RESULTS CONCLUSION Cystic fibrosis (CF) patients frequently experience gut microbiota dysbiosis. Probiotic supplementation is a potential therapeutic approach to modify gut microbiota and improve CF management through the gut–lung axis. The aim of this study was to investigate the effect of Lactobacillus reuteri supplementation on pulmonary function test, respiratory symptoms and growth in CF patients.A randomized, placebo‐controlled clinical trial was carried out on 40 children with CF aged from 6 to 20 years. Participants were designated to receive either L. reuteri or placebo daily for 4 months. Pulmonary function tests, weight, height and body mass index (BMI) z‐scores were measured pre and post treatment.The median baseline BMI of the patients was 16.28 kg m−2. A significant change in the probiotic group's BMI z‐score after the study period was observed (P = 0.034) but not for weight and height z‐scores (P > 0.05). After treatment, Pseudomonas aeruginosa grew in sputum cultures of seven in the placebo and one patient in the intervention group (P = 0.03) while at baseline it grew in the sputum of four patients in each group. There was no significant difference in forced expiratory volume in the first second, forced expiratory flow at 25–75% or forced vital capacity change between the two groups after the treatment period (P > 0.05). Additionally, no significant differences were found in pulmonary exacerbations, hospitalization frequencies or COVID‐19 infection between the two groups during the study (P > 0.05).The results suggest that L. reuteri supplementation may impact the growth of severely malnourished CF patients. Furthermore, it may be concluded that this strain might reduce P. aeruginosa in the sputum culture of CF patients. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Clinical Trials Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied.In a prospective, multi‐institutional study, adult PwCF completed the 22‐Question SinoNasal Outcome Test (SNOT‐22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD‐NS), and Cystic Fibrosis Questionnaire‐Revised (CFQ‐R). Lund–Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression.Seventy‐three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (β = ‒4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (β = ‒2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (β = ‒0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (β = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (β = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ‐R respiratory scores, and ppFEV1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT‐22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT‐22, QOD‐NS, or SIT scores.Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient‐reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF.NCT04469439 [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Elexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear.The TriNetX Analytics Research Network, consisting of 120 million global de‐identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA‐approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF‐related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS.ETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5–2.75; p‐value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54–5.85; p‐value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non‐CFTR modulator groups, except for reduced CF‐related pulmonary exacerbations from 0 to 6 months post‐FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators.In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF. [ABSTRACT FROM AUTHOR]

This document contains a collection of abstracts from the 15th Australasian Cystic Fibrosis Conference, covering various topics related to cystic fibrosis (CF) research. The abstracts provide insights into different aspects of CF management and highlight the need for further research and improved treatment strategies. The studies discussed in the document explore topics such as home spirometry, phage therapy, CFTR modulators, glucose metabolism, and antibiotic management. These studies contribute to our understanding of CF and offer potential advancements in its treatment and care. [Extracted from the article]

Background: The role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small‐molecule Akt activator SC79 induces nasal cell NO production and suppresses IL‐8 via the transcription factor Nrf‐2. We hypothesized that SC79 NO production may additionally have antibacterial effects. Methods: NO production was measured using fluorescent dye DAF‐FM. We tested effects of SC79 during co‐culture of Pseudomonas aeruginosa with primary nasal epithelial cells, using CFU counting and live–dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79‐induced NO production and tested dependence on Akt. Results: SC79 induced dose‐dependent, Akt‐dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killed P. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h. Conclusions: Together, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small‐molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies. [ABSTRACT FROM AUTHOR]

Background: Lung magnetic resonance imaging (MRI) with ultrashort echo‐times (UTE‐MRI) allows high‐resolution and radiation‐free imaging of the lung structure in cystic fibrosis (CF). In addition, the combination of elexacaftor/tezacaftor/ivacaftor (ETI) has improved CF clinical outcomes such as need for hospitalization. However, the effect on structural disease still needs longitudinal evaluation at high resolution. Purpose: To analyze the effects of ETI on lung structural alterations using UTE‐MRI, with a focus on bronchiectasis reversibility. Study Type: Retrospective. Population: Fifty CF patients (mean age 24.3 ± 9.2; 23 males). Field Strength/Sequence: 1.5 T, UTE‐MRI. Assessment: All subjects completed both UTE‐MRI and pulmonary function tests (PFTs) during two annual visits (M0 and M12), and 30 of them completed a CT scan. They initiated ETI treatment after M0 within a maximum of 3 months from the annual examinations. Three observers scored a clinical MRI Bhalla score on UTE‐MRI. Bronchiectasis reversibility was defined as a reduction in both outer and inner bronchial dimensions. Correlations were searched between the Bhalla score and PFT such as the forced expiratory volume in 1 second percentage predicted (FEV1%p). Statistical Tests: Comparison was assessed using the paired t‐test, correlation using the Spearman correlation test with a significance level of 0.05. Concordance and reproducibility were assessed using intraclass correlation coefficient (ICC). Results: There was a significant improvement in MRI Bhalla score after ETI treatment. UTE‐MRI demonstrated bronchiectasis reversibility in a subgroup of 18 out of 50 CF patients (36%). These patients with bronchiectasis reversibility were significantly younger, with lower severity of wall thickening but no difference in mucus plugging extent (P = 0.39) was found. The reproducibility of UTE‐MRI evaluations was excellent (ICC ≥ 0.95), was concordant with CT scan (N = 30; ICC ≥ 0.90) and significantly correlated to FEV1% at PFT at M0 (N = 50; r = 0.71) and M12 (N = 50; r = 0.72). Data Conclusion: UTE‐MRI is a reproducible tool for the longitudinal follow‐up of CF patients, allowing to quantify the response to ETI and demonstrating the reversibility of some structural alterations such as bronchiectasis in a substantial fraction of this study population. Level of Evidence: 4 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion This systematic review aims to describe the dietary quality, dietary intake and related behaviours of adults diagnosed with cystic fibrosis.A comprehensive literature search was conducted in four databases (Medline, CINAHL, EMBASE, CENTRAL); studies were included if they addressed dietary intake, diet quality or eating behaviours among adults (≥15 years) living with cystic fibrosis and were published from January 2000 to November 2022. The Mixed Methods Appraisal Tool was used to assess the risk of bias and quality of included studies. Findings were synthesised narratively.Nineteen observational studies (n = 2236) were included and considered high to moderate quality. Most (13/19) studies reported that individuals with cystic fibrosis were consuming high‐energy diets; where studies reported energy intake as a proportion of requirements met, energy intake was high, even when using individualised or cystic fibrosis‐specific referents. In addition, fat intakes as a proportion of energy appeared high (29%–39% of total energy), particularly as current guidelines recommend macronutrient profile similar to the general population (<30% of total energy). There was considerable variation in the reporting of fatty acid profiles and other nutrients. Five studies reported on concerns regarding diet and eating in this population.Findings from the current review suggest dietary intakes of adults with cystic fibrosis appear to be less than optimal and concerns about diet, weight and food may be emerging in this population. Future research utilising consistent measures of dietary assessment and reporting, reporting of medical therapies, and exploring potential concerns about diet and eating is warranted. [ABSTRACT FROM AUTHOR]

Nutrition has played a central role in the management and outcomes of people with cystic fibrosis (pwCF) since the 1970s. Advances in therapies and practices in recent decades have led to a significant change in the patient landscape with dramatic improvements in life expectancy, as well as quality of life, bringing with it new issues. Historically, cystic fibrosis was a condition associated with childhood and malnutrition; however, changes in patient demographics, nutritional assessment and fundamental nutritional management have evolved, and it has become an increasingly prevalent adult disease with new nutritional challenges, including obesity. This paper aims to describe these changes and the impact and challenges they bring for those working in this field. Nutritional professionals will need to evolve, adapt and remain agile to the wider range of situations and support required for a new generation of pwCF. Specialised nutrition support will continue to be required, and it will be additionally important to improve and optimise quality of life and long‐term health. Key points: Traditional cystic fibrosis dietary advice focused on a default high‐fat/high‐calorie intake with limited consideration for other important nutrients. The emerging new era approach should be individualised, flexible and with an emphasis on diversity and longevity.Historically, this population was predominantly undernourished or at risk of undernutrition, but with the success and impact of nutritional guidelines, multidisciplinary teams, screening and new therapies, overnutrition is becoming an increasing concern that requires attention.Significant improvements in life expectancy mean more people with cystic fibrosis are living into old age, bringing with it age‐related complications and new opportunities that require nutritional consideration from childhood. [ABSTRACT FROM AUTHOR]

Introduction: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory‐specific quality‐of‐life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. Methods: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution‐based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. Results: Of 129 PwCF included, 65 had QOD scores before and 3–6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was −1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). Conclusion: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner. [ABSTRACT FROM AUTHOR]

Introduction: Cystic fibrosis (CF) airway disease is characterized by thick mucus and impaired mucociliary transport (MCT). Loss of functional cystic fibrosis transmembrane receptor (CFTR) leads to acidification and oxidation of airway surface mucus. Replacing bicarbonate (HCO3−) topically fails due to rapid reabsorption and neutralization, while the scavenging antioxidant, glutathione sulfhydryl (GSH), is also rapidly degraded. The objective of this study is to investigate GSH/NaHCO3 nanoparticles as novel strategy for CF airway disease. Methods: GSH/NaHCO3 poly (lactic‐co‐glycolic acid) nanoparticles were tested on primary CF (F508del/F508del) epithelial cultures to evaluate dose‐release curves, surface pH, toxicity, and MCT indices using micro‐optical coherence tomography. In vivo tests were performed in three rabbits to assess safety and toxicity. After 1 week of daily injections, histopathology, computed tomography (CT), and blood chemistries were performed and compared to three controls. Fluorescent nanoparticles were injected into a rabbit with maxillary sinusitis and explants visualized with confocal microscopy. Results: Sustained release of GSH and HCO3− with no cellular toxicity was observed over 2 weeks. Apical surface pH gradually increased from 6.54 ± 0.13 (baseline) to 7.07 ± 0.10 (24 h) (p < 0.001) and 6.87 ± 0.05 at 14 days (p < 0.001). MCT, ciliary beat frequency, and periciliary liquid were significantly increased. When injected into the maxillary sinuses of rabbits, there were no changes to histology, CT, or blood chemistries. Nanoparticles penetrated rabbit sinusitis mucus on confocal microscopy. Conclusion: Findings suggest that GSH/NaHCO3− nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Importance: The 3‐min step test is a simple option to monitor submaximal exercise capacity, although its use via remote video monitoring has not been investigated in children with cystic fibrosis (CF). Objective: This study aimed to assess the feasibility and reproducibility of performing the 3‐min step test with remote supervision. Methods: A cross‐sectional study including CF patients (6–18 years) from two CF services were performed. Demographic, anthropometric, clinical, and lung function data were collected and two 3‐min step tests were performed: (i) in‐person supervision, and (ii) remotely supervised by video monitoring. Before and after the tests, heart rate (HR), oxygen saturation (SpO2), and the Borg score for dyspnea and lower limb fatigue were monitored. Results: Twenty‐three patients (10.7 ± 3.7 years) with a mean FEV1 of 89.5% ± 23.2% were included. There were no significant differences between tests, with mean differences (95% confidence intervals) in final HR of –3.3 (–8.9, 2.4), change in HR of –1.9 (–6.1, 2.1), final SpO2 of 0.3 (–0.4, 1.0), and final dyspnea of 0.1 (–0.8, 0.9). The intraclass correlation coefficient was 0.852 (final HR), 0.762 (final SpO2), and 0.775 (final lower limb fatigue). Significant and moderate correlations were found between tests for final HR (r = 0.75), change in HR (r = 0.61), and final SpO2 (r = 0.61). The Bland–Altman analysis showed a mean difference in final SpO2 between tests of 0.3% (limit of agreement –3.0%, 3.5%). Interpretation: Physiological responses between tests were similar, indicating it was feasible to perform the 3‐min step test with remote supervision in CF children. [ABSTRACT FROM AUTHOR]

This article explores the challenges faced by cystic fibrosis (CF) patients in low- to middle-income countries in accessing the triple combination therapy of elexacaftor, tezacaftor, and ivacaftor (ETI). The therapy is currently expensive and not widely available due to regulatory approval and cost issues. The authors propose a strategy using pharmacokinetic enhancement to reduce the cost of treatment, which involves the use of boosting agents like ritonavir. They also suggest the potential use of generic ETI formulations. Preliminary data from South Africa shows promising results, but further clinical trials are needed to evaluate the effectiveness, safety, and cost-effectiveness of this approach. [Extracted from the article]

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross‐linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over‐accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS‐responsive and Vitamin A (VA) decorated micelles (named LR‐SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR‐SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS‐responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross‐linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR‐SSVA is a safe and efficient ROS‐response and PSC‐targeted drug‐delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF. [ABSTRACT FROM AUTHOR]

Icenticaftor (QBW251) is a potentiator of the cystic fibrosis transmembrane receptor. Based on its mechanism of action, icenticaftor is expected to provide benefits in patients with chronic obstructive pulmonary disease by restoring mucociliary clearance, which would eventually lead to a reduction of bacterial colonization and related inflammatory cascade. A placebo‐ and positive‐controlled, 4‐way crossover thorough QT study was conducted in 46 healthy participants with the objective to assess the effect of therapeutic (300 mg twice daily for 6 days) and supratherapeutic (750 mg twice daily for 6 days) oral doses of icenticaftor on electrocardiogram parameters, including concentration‐corrected QT (QTc) analysis. Moxifloxacin (400 mg, oral) was used as a positive control. In the concentration‐QTc analysis performed on pooled data from Day 1 and Day 6 (steady state), the estimated population slope was shallow and slightly negative: –0.0012 ms/ng/mL. The effect on the Fridericia corrected QT (QTcF) interval (∆ΔQTcF) was predicted to be −1.3 milliseconds at the icenticaftor 300‐mg twice‐daily peak concentration (geometric mean was 1094 ng/mL) and −5.5 milliseconds at the 750‐mg twice‐daily peak concentration (geometric mean Cmax was 4529 ng/mL) indicated a mild shortening effect of icenticaftor on QTcF interval length. The results of the by‐time‐point analysis indicated least squares placebo corrected mean ∆∆QTcF across time points ranged from –7.9 to 0.1 milliseconds at 1 and 24 hours after dosing both on Day 6 in the 750‐mg dose group compared with –3.7 to 1.6 milliseconds at 1.5 and 24 hours after dosing on Day 1 in the 300‐mg dose group. Assay sensitivity was demonstrated with moxifloxacin. The large accumulation of exposures, especially the 4.3‐fold increase in peak plasma concentration observed at the icenticaftor 750‐mg twice‐daily dosage compared with Icenticaftor 300 mg twice daily (2.3‐fold) on Day 6 provided a large concentration range (up to 9540 ng/mL) to evaluate the effect of icenticaftor on ΔΔQTcF. Based on the concentration–QTc analysis, an effect on ΔΔQTcF exceeding 10 milliseconds can be excluded within the full observed ranges of plasma concentrations on icenticaftor, up to approximately 9540 ng/mL. Icenticaftor at the studied doses demonstrated a mild shortening in QTcF, which is unlikely to be of clinical relevance in a therapeutic setting. [ABSTRACT FROM AUTHOR]

Background and Aims: The experience of outpatient care may differ for select patient groups. This prospective study evaluates the adult patient experience of multidisciplinary outpatient cystic fibrosis (CF) care with videoconferencing through telehealth compared with face‐to‐face care the year prior. Methods: People with CF without a lung transplant were recruited. Patient‐reported outcomes were obtained at commencement and 12 months into the study, reflecting both their face‐to‐face and telehealth through videoconferencing experience, respectively. Three patient cohorts were analysed: (i) participants with a regional residence, (ii) participants with a nonregional including metropolitan residence and (iii) participants with colonised multiresistant microbiota. Results: Seventy‐four patients were enrolled in the study (mean age, 37 ± 11 years; 50% male; mean forced expiratory volume in the first second of expiration, 60% [standard deviation, 23]) between February 2020 and May 2021. No differences between models were observed in the participants' rating of the health care team, general and mental health rating, and their confidence in handling treatment plans at home. No between‐group differences in the Cystic Fibrosis Questionnaire – Revised (CFQ‐R) were observed. Travel duration and the cost of attending a clinic was significantly reduced, particularly for the regional group (4 h, AU$108 per clinic; P < 0.05). A total of 93% respondents preferred to continue with a hybrid approach. Conclusion: In this pilot study, participants' experience of care and quality of life were no different with face‐to‐face and virtual care between the groups. Time and cost‐savings, particularly for patients living in regional areas, were observed. Most participants preferred to continue with a hybrid model for outpatient care. [ABSTRACT FROM AUTHOR]

This research note discusses the role of individual sinus inflammation in chronic rhinosinusitis (CRS) and olfaction after highly effective modulator therapy. The study found that individual sinus opacification (ISO) can be measured using a convolutional neural network approach. ISO decreased over a two-year period after initiating modulator therapy. However, ISO did not correlate with quality of life or olfaction in adults with cystic fibrosis. The study highlights the importance of understanding disease in specific sinuses for targeted treatments. Another article discusses the relationship between sinus opacification (SO) and patient outcomes in individuals with cystic fibrosis (CF) who have undergone highly effective modulator therapy. The study found that greater sphenoid SO was correlated with worse rhinologic and extranasal rhinologic scores after 24 months of therapy. However, the clinical significance of this correlation is unknown. The study also found that there was no consistent correlation between SO and other outcome measures such as health utility value and smell identification test scores. The findings suggest that further research is needed to understand the impact of individual sinus inflammation on chronic rhinosinusitis and olfaction in individuals with CF. [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) is common in individuals with cystic fibrosis (CF) and is marked by chronic inflammation and episodes of infection that negatively impact quality of life. Several studies have shown that elexacaftor-tezacaftor-ivacaftor (ETI) improves symptoms and examination findings in CF-CRS. The current study determines the effect of ETI on the sinonasal microbiota in CF. Methods: Sinonasal samples were collected under endoscopic visualization before and after starting ETI. Samples were subjected to 16S amplicon sequencing and sequences were processed with the QIIME2 pipeline with subsequent analysis using the vegan R-package. Results: Twenty-nine individual baseline samples and 23 sample pairs pre-/post-ETI were available. At baseline, the cohort had samples dominated by Staphylococcus, and alpha diversity was lower than that of a published reference set of individuals without sinonasal disease. Individuals with prior sinus surgery had lower alpha diversity as measured by Shannon Index, Observed Richness, and Faith's phylogenetic diversity Index. Beta diversity differed between individuals with and without allergic rhinitis, with higher Staphylococcus abundance in those with allergic rhinitis. No change in alpha or beta diversity was seen after a median of 9 months on ETI. With ETI, the Pseudomonas genus and the genus containing Burkholderia decreased in samples containing these taxa at baseline. Pseudomonas abundance decreased with treatment as measured by qPCR. Core sinonasal microbiome members Staphylococcus, Corynebacterium, and Streptococcus were unchanged, while Moraxella increased with ETI. Conclusions: Treatment with ETI leads to a reduction in Pseudomonas abundance within the sinonasal microbiome of individuals with Pseudomonas at baseline. [ABSTRACT FROM AUTHOR]

Aim: To investigate the prevalence of gingivitis and periodontitis, and the oral hygiene status of adults with cystic fibrosis (CF) in the Republic of Ireland. Materials and Methods: A case–control study in the form of a clinical examination of 92 adults with a diagnosis of CF was carried out in the adult CF unit in Cork University Hospital. A 40‐item questionnaire was used to capture socio‐demographic variables and medical and dental information. Two calibrated examiners carried out a periodontal assessment on participants, using the WHO‐recommended CPI‐modified index, and oral hygiene status was measured using the Greene–Vermillion index. The results were compared with a population‐based control group of similar socio‐demographic profile. Results: Oral hygiene levels (plaque and calculus) were significantly worse in people with CF, with a median plaque index of 0.83 (interquartile range [IQR] 0.333–1.542) in the CF group compared with 0.5 (IQR 0.167–0.667) in the non‐CF group. Calculus index in the CF group was 0.33 (IQR 0.17–0.83) compared with 0.33 (IQR 0.125–0.33) in the non‐CF group. However, periodontal disease levels were significantly lower in the CF group. Gingivitis (bleeding on probing ≥ 10% sites) was seen in 67.4% of the CF group, compared with 83.7% of the non‐CF group, OR 0.365 (95% confidence interval [CI] 0.181–0.736), relative risk (RR) 0.779 (95% CI 0.655–0.928). Mild periodontitis (periodontal probing depth [PPD] < 5 mm) was seen in 15.2% of the CF group, compared with 31.5% of the non‐CF group, OR 0.390 (CI 0.190–0.800), RR 0.483 (95% CI 0.273–0.852). Severe periodontitis (PPD ≥ 6 mm) was seen in 0% of the CF group, compared with 9.8% of the non‐CF group. There was a tendency, albeit non‐significant, towards reduced periodontitis in PWCF who regularly took antibiotics, particularly azithromycin. Conclusions: In this study, adults with CF had poor oral hygiene practices, with high levels of plaque and calculus. Despite this finding, adults with CF had lower levels of clinical gingivitis and periodontitis than seen in a non‐CF control group. Further study is required to examine the causes of this phenomenon. [ABSTRACT FROM AUTHOR]

Dermatologic manifestations of cystic fibrosis (CF) include nutrient deficiency dermatoses, vasculitis, transient reactive papulotranslucent acrokeratodema, digital clubbing, and increased rates of atopy and drug reactions. Few cases of a characteristic eruption in patients with episodic arthritis of CF have been described with prior reports primarily occurring outside of the dermatology literature. We report four cases consistent with this presentation to add to the literature and propose a new and unifying name to recognize this entity as cystic fibrosis dermatitis arthritis syndrome (CF‐DAS). Clinical suspicion should remain high in young female patients with cystic fibrosis presenting with episodic joint pain and rash, independent of pulmonary exacerbations. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cardiopulmonary and skeletal muscle impairment and poor physical activity are potential contributors to reduced functional capacity in cystic fibrosis (CF). The Glittre‐ADL test (TGlittre) has great potential for clinical use in adult CF adults, as it meets the need for a comprehensive assessment of physical function using tasks similar to activities of daily living. This study aimed to evaluate the performance of TGlittre in CF adults compared to the 6‐min walk test (6MWT) and, secondarily, to quantify the associations of their results with pulmonary function, muscle strength, and health‐related quality of life (HRQoL). Methods: This cross‐sectional study evaluated 34 CF adults and compared them with 34 subjects from a control group. The participants underwent the following assessments: functional capacity using TGlittre and 6MWT; spirometry; respiratory muscle strength; handgrip strength (HGS); and HRQoL using the Cystic Fibrosis Questionnaire‐Revised (CFQ‐R). Results: While CF patients showed a longer time to perform TGlittre compared to controls (134 (119–150) versus 107 (95–126) % of the predicted time p = 0.0002), no difference between these groups was observed in the 6MWT. When the second TGlittre was compared to the first TGlittre, there was a significant decrease in total time for both CF patients (p < 0.0001) and controls (p = 0.0001). TGlittre time correlated with 6MWT distance (6MWD) (rs = −0.641, p < 0.0001), HGS (rs = −0.364, p = 0.034), peripheral oxygen saturation at the end of the test (rs = −0.463, p = 0.006) and the "digestive symptoms" domain of CFQ‐R (rs = 0.376, p = 0.028). TGlittre time was shorter in patients who engaged in regular physical activity (3.10 (2.49–3.39) min versus 3.28 (2.95–3.53) min, p = 0.016). Conclusions: TGlittre is more effective than the 6MWT in detecting limitations during exercise. There is an important learning effect of TGlittre in adult CF patients. TGlittre time was correlated with 6MWD, HGS, oxygen saturation level, and the patient's level of physical activity. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre‐emptive treatment of lung disease and other CF‐related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high‐dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side‐effects and costs. [ABSTRACT FROM AUTHOR]

Introduction: Poor oral hygiene can cause infections and inflammatory diseases. Data on its impact on outcome after lung transplantation (LuTX) is scarce. Most transplant centers have individual standards regarding dental care as there is no clinical guideline. This study's objective was to assess LuTX‐listed patient's dental status and determine its effect on postoperative outcome. Methods: Two hundred patients having undergone LuTX from 2014 to 2019 were selected. Collected data comprised LuTX‐indication, periodontal status, and number of carious teeth/fillings. A preoperative panoramic dental X‐ray and a dentist's consultative clarification were mandatory. Results: 63.5% had carious dental status, differing significantly regarding TX‐indication (p < 0.001; ILD: 41.7% vs. CF: 3.1% of all patients with carious teeth). Mean age at the time of LuTX differed significantly within these groups. Neither preoperative carious dental status nor periodontitis or bone loss deteriorated post‐LuTX survival significantly. No evidence was found that either resulted in a greater number of deaths related to an infectious etiology. Conclusion: This study shows that carious dental status, periodontitis, and bone loss do not affect post‐TX survival. However, literature indicates that they can cause systemic/pulmonary infections that deteriorate post‐LuTX survival. Regarding the absence of standardized guidelines regarding dental care and LuTX, we strongly recommend emphasizing research in this field. [ABSTRACT FROM AUTHOR]

Background: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality‐of‐life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied. Methods: Adult PwCF + CRS were enrolled into a prospective, observational, multi‐institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS. Results: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT‐22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire‐9‐Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire‐Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT‐22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02–1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004–0.34, p = 0.004) was associated with pursing medical therapy. Conclusions: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden. [ABSTRACT FROM AUTHOR]

Lefamulin is being evaluated as a treatment for bacterial exacerbations in cystic fibrosis (CF). Ivacaftor is approved for the treatment of patients with CF. Lefamulin is a moderate CYP3A inhibitor and co‐administration with ivacaftor may result in a drug–drug interaction (DDI). A CF population was built based on literature using the Simcyp Simulator. A previously developed and validated physiologically‐based pharmacokinetic (PBPK) model for ivacaftor was used. A PBPK model for lefamulin was developed and verified. Predicted concentrations and pharmacokinetic (PK) parameters for both ivacaftor and lefamulin in healthy subjects and patients with CF were in reasonable agreement with observed data (within 1.4‐fold, majority within 1.25‐fold). The lefamulin model as a CYP3A4 perpetrator was validated using a different Ki value for oral (p.o.) and intravenous (i.v.) routes. The simulated changes in area under the curve of ivacaftor in patients with CF when co‐administered with p.o. and i.v. lefamulin were weak‐to‐moderate. The predicted change in ivacaftor PK when co‐administered with oral lefamulin was less than observed between ivacaftor and fluconazole. These results suggest a low liability for a DDI between lefamulin and ivacaftor in patients with CF. [ABSTRACT FROM AUTHOR]

Introduction: The introduction of the highly effective modulator therapy elexacaftor‐tezacaftor‐ivacaftor (ETI) has revolutionized the care of persons with cystic fibrosis (PwCF) with major improvements seen in lung function and body mass index. The effects of ETI therapy in real‐world cohorts on other parameters such as cholesterol levels are largely unknown. Methods: A single‐center, retrospective chart review study was conducted to assess the change in lipid panels before and after ETI initiation. The study investigated total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglyceride levels using both a univariate and multivariate mixed‐effects model to evaluate the change after initiation of ETI in a cohort of PwCF. Results: There were 128 adult PwCF included in the analysis. Statistically significant changes were seen in both univariate and multivariate analyses for TC, LDL‐C, and HDL‐C. On multivariate analysis, TC increased by an average of 15.0 mg/dL after ETI initiation (p < 0.0001), LDL‐C increased by an average of 9.3 mg/dL (p < 0.001), and HDL‐C increased by an average of 3.8 mg/dL (p < 0.001) after ETI initiation. Conclusion: In this real‐world cohort of PwCF, cholesterol parameters increased after initiation with ETI therapy. Further consideration may need to be given for PwCF in regards to screening for cardiometabolic risk factors as PwCF age as well as the potential need for cholesterol‐lowering therapies. [ABSTRACT FROM AUTHOR]

This document summarizes a Cochrane review on the use of bisphosphonates for osteoporosis in individuals with cystic fibrosis (CF). The review included nine clinical trials and found that bisphosphonates may increase bone mineral density (BMD) in the spine and hip after 12 months of treatment. However, there was no significant difference in fracture rates between the treatment and control groups. Bisphosphonates may also cause bone pain. The authors concluded that while bisphosphonates may increase BMD in individuals with CF, more research is needed to determine their effectiveness in reducing fractures. Preventive care and collaboration among healthcare professionals are important in managing CF-related bone health. [Extracted from the article]

A recent study published in Clinical Otolaryngology evaluated the association between triple combination therapy and the need for endoscopic sinus surgery (ESS) in adult patients with cystic fibrosis (CF) and chronic rhinosinusitis. The study included 128 patients, with 51 receiving triple combination therapy and the remaining patients serving as a control group. The results showed that the group receiving triple combination therapy had a statistically significant reduction in the number of ESS procedures performed compared to the control group. Additionally, the therapy was associated with improvements in sinus CT scores and sinonasal quality of life. However, the study has limitations, and further research is needed to confirm these findings. [Extracted from the article]

"Lung perfusion" in the context of imaging conventionally refers to the delivery of blood to the pulmonary capillary bed through the pulmonary arteries originating from the right ventricle required for oxygenation. The most important physiological mechanism in the context of imaging is the so‐called hypoxic pulmonary vasoconstriction (HPV, also known as "Euler‐Liljestrand‐Reflex"), which couples lung perfusion to lung ventilation. In obstructive airway diseases such as asthma, chronic‐obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma, HPV downregulates pulmonary perfusion in order to redistribute blood flow to functional lung areas in order to conserve optimal oxygenation. Imaging of lung perfusion can be seen as a reflection of lung ventilation in obstructive airway diseases. Other conditions that primarily affect lung perfusion are pulmonary vascular diseases, pulmonary hypertension, or (chronic) pulmonary embolism, which also lead to inhomogeneity in pulmonary capillary blood distribution. Several magnetic resonance imaging (MRI) techniques either dependent on exogenous contrast materials, exploiting periodical lung signal variations with cardiac action, or relying on intrinsic lung voxel attributes have been demonstrated to visualize lung perfusion. Additional post‐processing may add temporal information and provide quantitative information related to blood flow. The most widely used and robust technique, dynamic‐contrast enhanced MRI, is available in clinical routine assessment of COPD, CF, and pulmonary vascular disease. Non‐contrast techniques are important research tools currently requiring clinical validation and cross‐correlation in the absence of a viable standard of reference. First data on many of these techniques in the context of observational studies assessing therapy effects have just become available. Level of Evidence: 5 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Background: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is associated with severe lung damage and requires specific therapeutic management. Repeated imaging is recommended to both diagnose and follow‐up response to treatment of ABPA in CF. However, high risk of cumulative radiation exposure requires evaluation of free‐radiation techniques in the follow‐up of CF patients with ABPA. Purpose: To evaluate whether Fourier decomposition (FD) functional lung MRI can detect response to treatment of ABPA in CF patients. Study Type: Retrospective longitudinal. Population: Twelve patients (7M, median‐age:14 years) with CF and ABPA with pre‐ and post‐treatment MRI. Field Strength/Sequence: 2D‐balanced‐steady‐state free‐precession (bSSFP) sequence with FD at 1.5T. Assessment: Ventilation‐weighted (V) and perfusion‐weighted (Q) maps were obtained after FD processing of 2D‐coronal bSSFP time‐resolved images acquired before and 3–9 months after treatment. Defects extent was assessed on the functional maps using a qualitative semi‐quantitative score (0 = absence/negligible, 1 = <50%, 2 = >50%). Mean and coefficient of variation (CV) of the ventilation signal‐intensity (VSI) and the perfusion signal‐intensity (QSI) were calculated. Measurements were performed independently by three readers and averaged. Inter‐reader reproducibility of the measurements was assessed. Pulmonary function tests (PFTs) were performed within 1 week of both MRI studies as markers of the airflow‐limitation severity. Statistical Tests: Comparisons of medians were performed using the paired Wilcoxon‐test. Reproducibility was assessed using intraclass correlation coefficient (ICC). Correlations between MRI and PFT parameters were assessed using the Spearman‐test (rho correlation‐coefficient). A P‐value <0.05 was considered as significant. Results: Defects extent on both V and Q maps showed a significant reduction after ABPA treatment (4.25 vs. 1.92 for V‐defect‐score and 5 vs. 2.75 for Q‐defect‐score). VSI_mean was significantly increased after treatment (280 vs. 167). Qualitative analyses reproducibility showed an ICC > 0.90, while the ICCs of the quantitative measurements was almost perfect (>0.99). Changes in VSI_cv and QSI_cv before and after treatment correlated inversely with changes of FEV1%p (rho = −0.68 for both). Data Conclusion: Non‐contrast‐enhanced FD lung MRI has potential to reproducibly assess response to treatment of ABPA in CF patients and correlates with PFT obstructive parameters. Evidence Level: 4 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: Pancreatic stiffness and extracellular volume fraction (ECV) are potential imaging biomarkers for pancreatic fibrosis. Clinically relevant postoperative fistula (CR‐POPF) is one of the most severe complications after pancreaticoduodenectomy. Which imaging biomarker performs better for predicting the risk of CR‐POPF remains unknown. Purpose: To evaluate the diagnostic performance of ECV and tomoelastography‐derived pancreatic stiffness for predicting the risk of CR‐POPF in patients undergoing pancreaticoduodenectomy. Study type: Prospective. Population: Eighty patients who underwent multiparametric pancreatic MRI before pancreaticoduodenectomy, among whom 16 developed CR‐POPF and 64 did not. Field Strength/Sequence: 3 T/tomoelastography and precontrast and postcontrast T1 mapping of the pancreas. Assessment: Pancreatic stiffness was measured on the tomographic c‐map, and pancreatic ECV was calculated from precontrast and postcontrast T1 maps. Pancreatic stiffness and ECV were compared with histological fibrosis grading (F0‐F3). The optimal cutoff values for predicting CR‐POPF were determined, and the correlation between CR‐POPF and imaging parameters was evaluated. Statistical tests: The Spearman's rank correlation and multivariate linear regression analysis was conducted. The receiver operating characteristic curve analysis and logistic regression analysis was performed. A double‐sided P < 0.05 indicated a statistically significant difference. Results: Pancreatic stiffness and ECV both showed a significantly positive correlation with histological pancreatic fibrosis (r = 0.73 and 0.56, respectively). Patients with advanced pancreatic fibrosis had significantly higher pancreatic stiffness and ECV compared to those with no/mild fibrosis. Pancreatic stiffness and ECV were also correlated with each other (r = 0.58). Lower pancreatic stiffness (<1.38 m/sec), lower ECV (<0.28), nondilated main pancreatic duct (<3 mm) and pathological diagnosis other than pancreatic ductal adenocarcinoma were associated with higher risk of CR‐POPF at univariate analysis, and pancreatic stiffness was independently associated with CR‐POPF at multivariate analysis (odds ratio: 18.59, 95% confidence interval: 4.45, 77.69). Data Conclusion: Pancreatic stiffness and ECV were associated with histological fibrosis grading, and pancreatic stiffness was an independent predictor for CR‐POPF. Level of Evidence: 1 Technical Efficacy Stage: 5 [ABSTRACT FROM AUTHOR]