Ann Med. 2025 Dec;57(1):2514787. doi: 10.1080/07853890.2025.2514787. Epub 2025 Jun 5.

ABSTRACT

INTRODUCTION: As the life expectancy of people with cystic fibrosis (CF) increases, complications related to CF, such as CF-related diabetes (CFRD), are of great concern. Oral glucose tolerance test (OGTT) is the current gold standard test to screen for CFRD, which is associated with reduced lung function and body mass index (BMI). However, this is a cumbersome test with poor adherence, and emerging evidence suggests that HbA1c or serum fructosamine might be viable alternative screening tools.

RESEARCH DESIGN AND METHODS: A multi-center study across four Canadian adult CF centers was conducted to determine the ability of HbA1c and serum fructosamine levels to predict screening OGTT results. Cross-sectional outcome data, including ppFEV1 and BMI within two months of testing, were collected.

RESULTS: A total of 183 CFRD screening encounters over five years were included. HbA1c and the fructosamine-to-albumin ratio had similar predictive performances for CFRD as determined by OGTT-defined cutoffs (AUC both 0.68) and for impaired glucose tolerance (AUC 0.69 and 0.64, respectively). However, the specificity of FAR is lower, meaning fewer OGTTs can be avoided if FAR is used as a first-step screening test when screening for either CFRD and/or IGT compared to HbA1. The optimal HbA1c cut-off for CFRD screening was ≥5.5% (sensitivity, 95%; specificity, 32%). Regression analyses demonstrated a strong inverse correlation between HbA1c and ppFEV1 (p < 0.0001), while the OGTT was inversely correlated with ppFEV1 (p < 0.05), and the fructosamine-to-albumin ratio was inversely correlated with BMI (-0.9; 95% CI -1.5, -0.4; p = 0.002), but not with ppFEV1 within 2 months of testing.

CONCLUSION: HbA1c is validated as a first step in screening for CFRD, allowing one-third of the patients to avoid the OGTT. As HbA1c demonstrated a stronger correlation with ppFEV1 than the OGTT, consideration could be made to redefine CFRD based on HbA1c.

PMID:40471094 | DOI:10.1080/07853890.2025.2514787

ERJ Open Res. 2025 Jun 2;11(3):00897-2024. doi: 10.1183/23120541.00897-2024. eCollection 2025 May.

ABSTRACT

BACKGROUND: Clinical trials with elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis were associated with significant improvements in % predicted forced expiratory volume in 1 s (FEV1 % pred), sweat chloride, weight and quality of life in the respiratory domain from the cystic fibrosis questionnaire revised (CFQ-R). Limited data exist on its effect on structural lung disease and inflammatory cytokines.

METHODS: In a real-world setting with 61 people with cystic fibrosis, we prospectively recorded FEV1, sweat chloride, body mass index (BMI) and CFQ-R at baseline, 3 and 6 months after commencement of ETI. In addition, changes in ultra-low-dose (ULD) computed tomography (CT) Bhalla score, peripheral-blood and sputum inflammatory cytokines and patient-reported outcome measures (PROMs), including sino-nasal outcomes test-22 (SNOT-22) and fatigue scale (FACIT-Fatigue).

RESULTS: Significant improvements in FEV1 % pred (p=0.0001), sweat chloride (p<0.0001) and BMI (p=0.0147) after ETI treatment were noted. ULD-CT scores demonstrated reductions in peri-bronchial thickening, mucus plugging and total Bhalla score (p<0.001), and improvements in emphysema extent (p<0.0027). Improvements in systemic inflammatory status were seen with a reduction in interleukin (IL)-1β (p=0.0049), IL-6 and IL-8 (p<0.0001), and increasing IL-10 (p=0.004). Sputum cytokine analysis was not performed as only four of 61 patients spontaneously expectorated sputum after ETI. PROMs improved significantly for the SNOT-22 (p<0.0001), FACIT-Fatigue score (p=0.0001) and CFQ-R domains, including respiratory (p<0.0001), physical (p=0.007), vitality (p=0.0004), treatment burden (p=0.0028), health (p=0.0007), social (p=0.0073), weight (p=0.0068) and role/school domain (p=0.0018).

CONCLUSION: ETI responders, demonstrate significant improvements in CT imaging, circulating cytokines and PROMs, which may be of further use evaluating cystic fibrosis transmembrane conductance regulator modulation treatment response.

PMID:40470159 | PMC:PMC12134916 | DOI:10.1183/23120541.00897-2024

ERJ Open Res. 2025 Jun 2;11(3):00675-2024. doi: 10.1183/23120541.00675-2024. eCollection 2025 May.

ABSTRACT

BACKGROUND: There are limited data on optimal management of chronic lung allograft dysfunction (CLAD). We aimed to describe the variability of diagnostic and therapeutic practices in Europe.

METHODS: A structured questionnaire was sent to 71 centres in 24 countries. Questions were related to contemporary clinical practices for workup, monitoring and treatment of CLAD. The number of lung transplant procedures and patients in follow-up were collected.

RESULTS: 44 centres (62%) responded from 20 countries, representing 74% of European activity. The prevalence of CLAD was estimated at 9.1 cases per million population (25th and 75th percentiles of 4.4, 15.7). Preferred initial workup for probable CLAD consisted of chest computed tomography (CT) (inspiratory 91% and expiratory 74%), donor-specific antibody (DSA) measurement (86%), bronchoalveolar lavage (BAL) (85%) and transbronchial biopsy (81%). For monitoring of definite CLAD, inspiratory CT (67%), DSA (61%) and BAL (43%) were preferred. Body plethysmography was unavailable for 16% of cases. Prophylaxis was based on preventing infections (cytomegalovirus 99%, inhaled antibiotics 70% and antifungals 65%), tacrolimus-based immunosuppression (96%), azithromycin (72%) and universal proton pump inhibitor treatment (84%). First-line treatment of CLAD was based on azithromycin (82%) and steroid augmentation (74%). Photopheresis was used in 26% of cases.

CONCLUSION: Current European practice CLAD detection is based on spirometry, inspiratory CT and DSA, with limited access to plethysmography and expiratory CT. Prophylactic treatment is based on azithromycin, tacrolimus-based immunosuppression and treatment of risk factors. No single treatment strategy is universally used, highlighting the need for an effective treatment of CLAD. The preferred first-line strategy is azithromycin and steroid augmentation.

PMID:40470157 | PMC:PMC12134928 | DOI:10.1183/23120541.00675-2024

Pulm Med. 2025 May 28;2025:5683225. doi: 10.1155/pm/5683225. eCollection 2025.

ABSTRACT

Background: Therapeutic drug monitoring (TDM) for vancomycin (VAN) in adult people with cystic fibrosis (pwCF) historically has utilized trough concentrations. Recent VAN TDM guidelines recommend area under the curve (AUC) monitoring to reduce the risk of acute kidney injury (AKI), despite limited evidence to support this practice in adult pwCF. Methods: This single-center, retrospective, observational cohort study included 143 adult pwCF admitted from July 1, 2017, to July 1, 2022, with an acute pulmonary exacerbation that received VAN for at least 72 h with available VAN plasma concentrations for TDM for AUC (n = 39) or trough monitoring (n = 104). Eligible patients with multiple hospital admissions during the study period were incorporated as separate encounters. The primary outcome was the incidence of AKI. Results: Receipt of concurrent nephrotoxins was more common in the AUC cohort than in the trough cohort (97% vs. 81%, p = 0.01), but the rate of AKI was similar (7.7% vs. 10.6%, p = 0.76). AUC monitoring was associated with earlier achievement of TDM goal (median 0 days (IQR 0-2) vs. 2 days (IQR 0-4), p < 0.01), lower total daily doses (34.8 mg/kg/day (IQR 27.6-49) vs. 57.5 mg/kg/day (IQR 43.9-68.6), p < 0.01), and fewer regimen changes (median 1 change (IQR 0-2) vs. 2 changes (IQR 1-3), p < 0.01). In patients with MRSA, pulmonary function recovery, readmission, and mortality were similar. Conclusion: In adult pwCF, the incidence of AKI was similar between AUC and trough monitoring cohorts; however, AUC monitoring achieved therapeutic targets sooner with fewer regimen modifications without significantly increasing the number of concentrations compared to trough monitoring.

PMID:40469479 | PMC:PMC12136855 | DOI:10.1155/pm/5683225

World Allergy Organ J. 2025 May 9;18(5):101058. doi: 10.1016/j.waojou.2025.101058. eCollection 2025 May.

ABSTRACT

In recent years, it was recognized that type-2 inflammation connects nasal polyposis and severe asthma (SA) in addition to other type-2 diseases. Thus, some biological drugs developed for SA appeared to exert a favourable effect also in nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies already used for SA were assessed also in chronic rhinosinusistis with nasal polyposis (CRSwNP), with promising results. Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT specialists, allergists, immunologists, pediatricians), it was felt that an updated educational and informative document was needed to better identify the indications of biological therapies in nasal polyposis. We collected the main Italian scientific societies, and prepared (under the umbrella of Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all societies, to provide a provisional statement for the future use of monoclonal antibodies (MAbs) as a medical treatment for polyposis, possibly associated with SA. The above mentioned document was the first endorsed document on this aspect, and the additional evidence required an update. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

PMID:40469214 | PMC:PMC12136883 | DOI:10.1016/j.waojou.2025.101058

Clin Genet. 2025 Jun 5. doi: 10.1111/cge.14780. Online ahead of print.

ABSTRACT

This study assessed the effect of CFTR pathogenic variant status, detected during prenatal carrier screening, for the incidence and clinical recognition of cystic fibrosis-related phenotypes. Data were queried from the Vanderbilt University Medical Center clinical genetic database (CGdb), which includes clinically reported pathogenic variants and electronic health records (EHRs) from 2001 to 2023. Based on carrier screening results, we identified individuals heterozygous for a pathogenic CFTR variant and those who tested negative. Logistic regression tested associations between CFTR carrier status and 11 cystic fibrosis (CF)-related phenotypes. A phenome-wide association study (PheWAS) was performed to identify additional phenotypic associations, and manual chart review was conducted to evaluate recognition and clinical application of CFTR carrier status in patients diagnosed with pancreatitis. Among 12,082 women tested, CFTR carriers (n = 451) were at significantly higher risk of developing acute pancreatitis (p = 3.93 × 10-6; OR = 4.68 [2.43-9.00]). No other CF-related phenotypes were significantly associated in this female cohort. Manual chart review revealed that CFTR carrier screening results were not clinically correlated with pancreatitis diagnoses. In this large cohort of women tested for prenatal carrier screening, CFTR pathogenic variants relevant to pancreatitis were overlooked, despite informing etiology, management, and prognosis.

PMID:40468859 | DOI:10.1111/cge.14780

Oncoimmunology. 2025 Dec;14(1):2515176. doi: 10.1080/2162402X.2025.2515176. Epub 2025 Jun 4.

ABSTRACT

Aclarubicin (also called aclacinomycin A) is an antineoplastic from the anthracycline class that is used in China and Japan but not in Europe nor in the USA. Aclarubicin induces much less DNA damage than the classical anthracyclines doxorubicin, daunorubicin, epirubicin, idarubicin, and the anthracene mitoxantrone, but is equally effective in inhibiting DNA-to-RNA transcription and in eliciting immunogenic stress in malignant cells. Accordingly, aclarubicin lacks the DNA damage-associated cardiotoxicity that is dose-limiting for classical anthracyclines. Conversely, aclarubicin is at least as potent as other anthracyclines in inducing immunogenic cell death (ICD), which is key for the mode of action of efficient chemotherapeutics. This combination of reduced toxicity and equivalent ICD-stimulatory activity may explain why, as compared to other anthracyclines, aclarubicin is particularly efficient against acute myeloid leukemia. As a result, we advocate for clinical studies seeking to replace the anthracyclines used in Western medicine by aclarubicin-like compounds. Such clinical studies should not only embrace hematological malignancies but should also concern solid cancers, including those in which ICD-inducing chemotherapies are followed by immunotherapies targeting the PD-1/PD-L1 interaction.

PMID:40464096 | PMC:PMC12143712 | DOI:10.1080/2162402X.2025.2515176

Nat Commun. 2025 Jun 4;16(1):5180. doi: 10.1038/s41467-025-60441-w.

ABSTRACT

Human airways contain specialized rare epithelial cells including CFTR-rich ionocytes that regulate airway surface physiology and chemosensory tuft cells that produce asthma-associated inflammatory mediators. Here, using a lung cell atlas of 311,748 single cell RNA-Seq profiles, we identify 687 ionocytes (0.45%). In contrast to prior reports claiming a lack of ionocytes in the small airways, we demonstrate that ionocytes are present in small and large airways in similar proportions. Surprisingly, we find only 3 mature tuft cells (0.002%), and demonstrate that previously annotated tuft-like cells are instead highly replicative progenitor cells. These tuft-ionocyte progenitor (TIP) cells produce ionocytes as a default lineage. However, Type 2 and Type 17 cytokines divert TIP cell lineage in vitro, resulting in the production of mature tuft cells at the expense of ionocyte differentiation. Our dataset thus provides an updated understanding of airway rare cell composition, and further suggests that clinically relevant cytokines may skew the composition of disease-relevant rare cells.

PMID:40467553 | DOI:10.1038/s41467-025-60441-w

J Cyst Fibros. 2025 Jun 3:S1569-1993(25)01488-2. doi: 10.1016/j.jcf.2025.05.003. Online ahead of print.

ABSTRACT

BACKGROUND: There are great changes in cystic fibrosis (CF) disease following introduction of modulator treatments. We aimed to focus on the evolution of hepatobiliary involvement following lumacaftor-ivacaftor (LI) and elexacaftor-tezacaftor-ivacaftor (ETI) initiation.

METHODS: A retrospective monocentric observational study included 62 CF children treated with CFTR modulators. Data were collected at initiation and after one year of treatment. The primary objective was to describe the evolution of hepatobiliary involvement under CFTR modulator treatment.

RESULTS: We identified hepatobiliary involvement before treatment in 37 patients (59.7 %). Fifteen had persistently (during >6 months) elevated liver enzymes (mostly ALT); 17 had abnormal ultrasound including 3 with nodular liver and 3 with pathological elastography; 5 had isolated splenomegaly. Biliary involvement was found in 19 patients. The evolution of hepatic parameters in the overall population was not significant (p > 0.05). However, we observed a trend towards improvement in laboratory values under treatment. There was only one inaugural diagnosis of nodular liver under LI and none under ETI. All patients had preserved liver function (PT>50 %).

CONCLUSIONS: We did not find a significant improvement or worsening of hepatobiliary involvement under CFTR modulators. We hypothesize that it could be stabilized with these treatments, but this will need confirmation through further studies with longer follow-up and larger cohorts. The other hypothesis proposed is that biological monitoring may not be an accurate assessment of the hepatobiliary response to modulators. This study supports the safety of CFTR modulator use.

PMID:40467431 | DOI:10.1016/j.jcf.2025.05.003

J Cyst Fibros. 2025 Jun 3:S1569-1993(25)01489-4. doi: 10.1016/j.jcf.2025.05.004. Online ahead of print.

ABSTRACT

BACKGROUND: Air travel may cause significant hypoxemia in patients with cystic fibrosis (CF). A pre-flight algorithm has previously been validated for patients with chronic obstructive pulmonary disease (COPD). No such tools are available for CF patients. The aim of this study was to evaluate if the pre-flight algorithm for COPD patients can be used by CF patients.

METHODS: In this prospective cross-sectional study, oxygen saturation at sea level (SpO2 SL) and during exercise (SpO2 6MWT) were used to evaluate whether CF patients a) are fit for flight without further assessment, b) require in-flight supplemental oxygen, or c) need further evaluation with hypoxia-altitude simulation test (HAST). HAST was used as reference method, and SpO2 HAST ≤85 % was the criterion for recommending in-flight supplemental oxygen.

RESULTS: 79 CF patients (41 men), age 38.0 ± 13.4 years, with FEV1 of 71±23 % of predicted underwent HAST (SpO2 HAST 89.2 ± 4.0 %). Categories for SpO2 SL were >95 % (N = 53), 92-95 % (N = 25), and <92 %, (N = 1), and the cut-off value for SpO2 6MWT was <84 %. HAST showed that CF patients with SpO2 SL >95 % combined with SpO2 6MWT ≥84 % can travel by air without further assessment. Supplemental oxygen is recommended if SpO2 SL is 92-95 % combined with SpO2 6MWT <84 %, or if SpO2 SL<92 %. Otherwise, HAST should be performed. Only 21 patients (27 %) would have needed referral to HAST. The algorithm correctly identified those who needed and those did not need in-flight supplemental oxygen.

CONCLUSIONS: The algorithm for COPD patients may be used in the pre-flight evaluation of adult CF patients.

CLINICALTRIALS: gov (NCT03843723).

PMID:40467430 | DOI:10.1016/j.jcf.2025.05.004

Endocr Pract. 2025 Jun 2:S1530-891X(25)00896-1. doi: 10.1016/j.eprac.2025.05.744. Online ahead of print.

ABSTRACT

OBJECTIVE: Hypoglycemia in hospitalized patients is a persistent adverse event. Three quality improvement interventions were implemented with the aim of reducing hypoglycemia. Each intervention was targeted at one component of typical inpatient insulin management (basal, prandial, and correction) to attempt to achieve this singular quality improvement aim.

METHODS: Incidence of hypoglycemia in non-obstetrics patients ≥ 19 years of age at a tertiary hospital receiving scheduled insulin before and after the implementation of quality improvement initiatives was compared. Incidence was defined as the number of unique patients with a hypoglycemic event in each month, divided by all admissions for that month. The interventions included integrating weight-based insulin guidance into the electronic medical record (EMR), the addition of a carbohydrate-limited diet, and increasing the threshold for correction insulin administration from 150 mg/dL to 180 mg/dL.

RESULTS: After implementation of the interventions, there was a significantly lower incidence of hypoglycemia associated with prandial insulin (p = 0.02) and correction insulin (p < 0.001). There was not a significant decrease in hypoglycemia associated with basal insulin in the overall sample (p =0.25). There was a significant decrease in a subgroup analysis focused on hospital-associated hyperglycemia and type 2 diabetes (via exclusion of patients with type 1 diabetes or cystic fibrosis-related diabetes) (p = 0.005). Notably, following the interventions, there was a reduction in institutional blood glucose readings within goal range (71-179 mg/dL), which presumably translates to an increase in hyperglycemia given the known decrease in hypoglycemia (p value <0.0001).

CONCLUSION: Through a multipronged approach consisting of three unique QI interventions - each targeting one aspect of inpatient insulin management - our academic institution was able to significantly reduce the number of inpatient hypoglycemic events.

PMID:40467034 | DOI:10.1016/j.eprac.2025.05.744

Clin Infect Dis. 2025 Jun 4;80(5):e65-e77. doi: 10.1093/cid/ciaf009.

ABSTRACT

Transformative changes in care for people with cystic fibrosis (CF; pwCF) have occurred, including most recently, the widespread use of CF transmembrane regulator modulator therapy. These novel therapies improve lung function, decrease pulmonary exacerbations, increase life expectancy, and improve quality of life. Changes in the CF population have also occurred. There are now more adults than children living with CF. A growing proportion of pwCF are black and/or Hispanic, many of whom are ineligible for modulator therapy due to their CF transmembrane regulator mutations, which may further exacerbate disparities in healthcare. Management of pulmonary exacerbations-including shared decision making between pwCF and providers, the limitations of antimicrobial susceptibility testing to predict treatment response, and the role of antimicrobial stewardship-is increasingly recognized by the CF community. Collaborations among infectious diseases specialists, antimicrobial stewards, CF care teams, and clinical microbiology laboratories are increasingly needed to optimize these newer care paradigms.

PMID:40465484 | DOI:10.1093/cid/ciaf009

Clin Infect Dis. 2025 Jun 4;80(5):939-941. doi: 10.1093/cid/ciaf010.

NO ABSTRACT

PMID:40465483 | DOI:10.1093/cid/ciaf010

J Community Genet. 2025 Jun 4. doi: 10.1007/s12687-025-00807-1. Online ahead of print.

ABSTRACT

Recent reports confirm that cystic fibrosis (CF) is a global disease. In Asian populations, both the spectrum of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and the clinical course differ from those observed in Western populations. Although the recognition of CF is increasing in South Asia, comprehensive data from Southeast Asian countries remain sparse. The underdiagnosis of CF in Southeast Asia is attributed to limited awareness among healthcare professionals and restricted access to sweat chloride testing. Until 2021, CF had not been documented in the indigenous population of Vietnam. This study presents the first three confirmed cases of CF in native Vietnamese individuals. Additionally, a literature review of CF cases reported across Southeast Asia was conducted to provide insights into its prevalence and variations in CFTR mutation profiles within the region. A total of 50 cases were identified, distributed across Malaysia (30 cases), Thailand (8), the Philippines (6), Vietnam (5), and Indonesia (1), revealing a mutation spectrum distinct from that observed in Caucasian populations. The most common mutations included p.Phe508del and p.Ile1295PhefsX32, each found in 11.5% of cases. These findings highlight the need for increased clinical awareness, expanded access to sweat chloride testing, and the establishment of CF centers and regional CF registries to better understand and manage CF in Southeast Asia.

PMID:40465100 | DOI:10.1007/s12687-025-00807-1

World J Pediatr. 2025 Jun 3. doi: 10.1007/s12519-025-00916-4. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric lung transplant (pLTX) is a rare procedure globally; its characteristics and survival outcomes in China remain unknown.

METHODS: This retrospective study analyzed data from pLTX recipients aged ≤ 17 years between January 2019 and December 2023 from the China Lung Transplantation Registry. Pre-, intra-, and post-operative characteristics were described and compared between children aged 2-11 years and 12-17 years and between pLTX conducted in centers with high and low transplant volumes. The Kaplan‒Meier method was used to estimate the postoperative survival rates and 95% confidence intervals (CIs). One-year postoperative survival rates were compared between pediatric and adult lung transplant (LTX) patients via log-rank tests.

RESULTS: Between 2019 and 2023, 63 transplants were performed in 62 pediatric patients, accounting for 1.8% of the total LTX in China. The primary indication for pLTX was bronchiolitis obliterans syndrome (46.0%), followed by cystic fibrosis (12.7%) and idiopathic pulmonary arterial hypertension (11.1%). Infection was the most common complication after pLTX (63.9%), and the incidence of bronchial anastomotic stenosis was slightly higher among recipients aged 2-11 years than among those aged 12-17 years (14.3% vs. 2.9%, P = 0.244). High-volume hospitals had a higher incidence of infections (72.7% vs. 41.2%, P = 0.021) and primary graft failure (20.0% vs. 5.9%, P = 0.260) among pediatric recipients. However, acute rejection was exclusively observed in low-volume hospitals (0.0% vs. 17.6%, P = 0.018). The in-hospital mortality rate was 16.1% (95% CI = 6.7-25.5). The 30-day and one-year survival rates after pLTX were 93.5% (95% CI = 87.6-99.9) and 80.6% (95% CI = 71.4-91.1), respectively, and were significantly higher than those of adult recipients (82.0% and 58.7%, all P < 0.05).

CONCLUSIONS: This research identified the trends, indications, donor and recipient characteristics, and complications of pLTX in China. Despite its small size, pLTX is growing gradually and has favorable outcomes. Future research on the long-term follow-up of pLTX recipients is needed to identify factors associated with the prognosis of pLTX patients.

PMID:40461919 | DOI:10.1007/s12519-025-00916-4

J Cyst Fibros. 2025 Jun 2:S1569-1993(25)01486-9. doi: 10.1016/j.jcf.2025.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: Real-world data demonstrate variability in the response to elexacaftor/tezacaftor/ivacaftor (ETI) treatment among people with CF (pwCF). The aim of this study was to evaluate long-term outcomes in pwCF that had not shown early improvement in the percentage of predicted FEV1 (ppFEV1) following ETI treatment.

METHODS: A single-center prospective study in pwCF who initiated ETI. Patients were categorized as 'early responders' if showing an improvement of at least 10 % in ppFEV1 within three months of treatment or 'non-early responders' if not. Patients with pretreatment ppFEV1 of above 99 % predicted were excluded. Respiratory and non-respiratory outcomes 18 to 24 months after ETI initiation were evaluated.

RESULTS: A total of 52 pwCF (median age 30 (22-34), 22 (42 %) female) were included, of whom 21 (40 %) were 'non-early responders'. In a multivariable analysis, previous CFTR modulator therapy (p = 0.002), higher pretreatment ppFEV1 (p = 0.002), and higher pretreatment BMI (p = 0.018), were negatively associated with early change in ppFEV1. After 18 to 24 months of ETI therapy, ppFEV1 did not significantly improve in the 'non-early responders' group (p = 0.29). However, rates of ppFEV1 decline (p < 0.001), BMI (p < 0.005), number of pulmonary exacerbations (p < 0.02), days of intravenous antibiotic treatment (p < 0.01), and chest CT scores (p < 0.05), all significantly improved in both patient groups.

CONCLUSIONS: This study provides evidence for the long-term clinical benefits of ETI in pwCF lacking an early ppFEV1 response. The data suggest that a lack of early improvement should not deter clinicians from treatment continuation.

PMID:40461393 | DOI:10.1016/j.jcf.2025.05.005

Enferm Infecc Microbiol Clin (Engl Ed). 2025 Jun-Jul;43(6):309-316. doi: 10.1016/j.eimce.2024.08.008.

ABSTRACT

BACKGROUND: We investigate bronchopulmonary colonization patterns in Spanish people with CF (pwCF), gathering clinical, demographic, and microbiological data to supplement nine years of registry information, comparing 2021 findings with a similar multicenter study conducted in 2013.

METHODS: Sixteen CF units from 14 hospitals across Spain participated, each randomly recruiting around 20 patients. Patients provided sputum samples for culture. The clinical, demographical, microbiological, and treatment data from the previous year were recorded.

RESULTS: Overall, 326 patients (48.5% females) were recruited: 185 adult and 141 pediatrics, with a median age [q3-q1] of 30 [38-24] and 12 [16-6] years, respectively. p.Phe508del mutation was present in 30.6% and 46.4% of patients with homozygosis or heterozygosis, respectively. Median FEV1 (%) was significantly lower in adults (62%, range 75-43%) compared with pediatrics (90%, range 104-81%) (p<0.001). Pancreatic insufficiency was observed in 77.3%, carbohydrate metabolism alteration in 27.3%, and CF-related diabetes in 19.6% of patients. Lower prevalence of Staphylococcus aureus and Pseudomonas aeruginosa colonization were noted compared to 2013, along with a significantly lower correlation in lung function among pwCF colonized by P. aeruginosa (p<0.001). Half of pwCF (51%) exhibited a single pathogen in culture, two in 30%, and three or more in 2.4%. Co-colonization of P. aeruginosa and S. aureus (36.1%) was the most prevalent combination. High resistance rates were observed in P. aeruginosa and methicillin resistant S. aureus isolates.

CONCLUSIONS: We provide a valuable and representative current insight into the observed evolution in the clinical, demographic, and microbiological aspects in recent years among pwCF in Spain.

PMID:40461090 | DOI:10.1016/j.eimce.2024.08.008

Enferm Infecc Microbiol Clin (Engl Ed). 2025 Jun-Jul;43(6):307-308. doi: 10.1016/j.eimce.2025.04.004.

NO ABSTRACT

PMID:40461089 | DOI:10.1016/j.eimce.2025.04.004

Future Oncol. 2025 Jun 3:1-9. doi: 10.1080/14796694.2025.2514417. Online ahead of print.

ABSTRACT

The DNAJ/HSP40 family consists of three distinct subfamilies (DNAJA, DNAJB, and DNAJC) and is the largest and most diverse co-chaperone proteins for HSP70. The DNAJA subfamily, comprising four members, assumes a pivotal role in various pathological conditions such as cystic fibrosis, neurodegenerative disorders, and cancer. This review comprehensively investigates the participation and underlying mechanisms of DNAJA proteins in tumor proliferation and metastasis, with a specific focus on their influence on the accumulation of mutant p53 proteins. Furthermore, we conducted an extensive examination of compounds utilizing computer-based techniques that specifically target DNAJA or its associated pathways, thereby offering novel insights for the development of cutting-edge combination therapies in the realm of cancer treatment. Our findings highlight the potential significance of targeting the DNAJA subfamily as a promising approach for anti-tumor therapy. Simultaneously, we also highlighted the limitations of current DNAJA research and proposed future directions for advancement in this field. We anticipate that DNAJA will emerge as a novel therapeutic target for anti-tumor interventions.

PMID:40459049 | DOI:10.1080/14796694.2025.2514417

World Allergy Organ J. 2025 May 5;18(5):101056. doi: 10.1016/j.waojou.2025.101056. eCollection 2025 May.

ABSTRACT

Asthma and obesity are both chronic diseases. Obesity is a common comorbidity and a risk factor of severe asthma, associated with increased asthma exacerbation risk, poorer asthma control and reduced quality of life. However, the responsible mechanisms are poorly understood. The aim of this study was to detect parameters associated with obesity in patients with severe asthma in order to check different pattern of inflammation in obese asthmatics. Baseline data from the Severe Asthma Network in Italy (SANI) registry were analysed in 1922 patients with severe asthma. Demographic, clinical and functional features were compared, according to body mass index (BMI). The prevalence of overweight and obesity among severe asthma patients was 34,8 and 20,3, respectively. Females were more prevalent in the obese cluster (p < 0.001). Asthma onset age in overweight and obese patients was higher than in normal population (p < 0.001). Obese subjects reported less frequently chronic rhinosinusitis with nasal polyposis (CRSwNP) and more frequently impaired sleep quality, cardiovascular disease, and type-2 diabetes (p < 0.001). Severe asthma patients with obesity had lower predicted FVC values (89.0 ± 19.2 vs 93.5 ± 20.2; p 0.002) and higher FEV1/FVC ratio (69.9 ± 11.5 vs 66.9 ± 12.4; p < 0.001) than patients without obesity. Obese asthmatics had lower blood eosinophilic count, and fractional exhaled nitric oxide (FeNO) levels than non-obese asthmatics. Asthma control test (ACT) was significantly poorer in obese patients (17, IQR 12-21) than other subgroups. Regarding treatment, overweight and obese patients were more likely to receive a GINA-Step 5 therapy (p 0.023), with more than 20 of obese asthmatics having frequent exacerbations requiring oral corticosteroid (OCS). Patients with severe asthma and obesity presented different characteristics that support the existence of distinct asthma phenotype in obese patients.

TRIAL REGISTRATION: Trial registry: ClinicalTrials.gov. ID: NCT06625216. Retrospectively registered October 3, 2024.

PMID:40458738 | PMC:PMC12127536 | DOI:10.1016/j.waojou.2025.101056