Pediatr Pulmonol. 2025 Aug;60(8):e71230. doi: 10.1002/ppul.71230.

ABSTRACT

BACKGROUND: Medication adherence is essential in managing cystic fibrosis (CF). The role of socioeconomic factors for medication adherence in people with CF is poorly understood, and their differential impact across the life course is underexplored. This study investigates associations between measures of socioeconomic status (SES)-educational attainment, household income, and health insurance type-and adherence to CF medications across age groups.

METHODS: We conducted a cross-sectional analysis of data collected during the validation of the Daily Care Check-In, a measure of adherence barriers in people with CF. Adherence was measured as a composite medication possession ratio (cMPR) averaged across five CF-specific medications, with data collected from pharmacy records. Sociodemographic and clinical data were collected through self-report and medical record review.

RESULTS: A total of 405 participants completed the study, with an overall cMPR of 45.6%, lowest (38.5%) among young adults (aged 18-26 years) and highest (53.0%) among adolescents (aged 13-17 years). Lower household income and lack of college degree were associated with lower cMPR, more interference from adherence barriers, and decreased self-efficacy, as well as with increased depressive and anxiety symptoms. Similar associations, but less consistent, were observed for public health insurance. When stratified by age, associations between SES measures and adherence were most evident in adolescents, followed by adults, but absent in young adults, bringing into focus challenges with measuring SES in the 18-25 years age group.

CONCLUSION: Lower SES is associated with worse medication adherence, more interference from adherence barriers, and lower self-efficacy. Associations vary by SES measure and age group, calling for a nuanced approach to adherence interventions in this population.

PMID:40778648 | DOI:10.1002/ppul.71230

Pediatr Pulmonol. 2025 Aug;60(8):e71229. doi: 10.1002/ppul.71229.

ABSTRACT

Cystic fibrosis (CF) was once a fatal disease of childhood, but with advances in combination CFTR modulator therapies, life expectancy for persons with CF (PwCF) has increased. Despite remarkable improvements in life expectancy, CF is a chronic multiple organ system disease and comorbidities characterized by recurrent respiratory infections, pancreatic insufficiency, diabetes, liver disease, depression, anxiety, and bone disease resulting in exposure to many drugs. The Clinical Pharmacogenetics (PGx) Implementation Consortium (CPIC) publishes evidence-based guidelines for use of PGx to guide dosing for drug-gene interactions. This study aimed to assess the current use of PGx testing in CF care at CF Foundation-accredited care centers and affiliate programs (CFF-ACCAP) across the United States. A 14-item survey was distributed electronically to CF Foundation-accredited care centers and affiliate programs in the United States using the CF Foundation email exchange. Overall, 74 responses were received from a potential of the 287 CFF-ACCAP. Since each individual CFF-ACCAP may have had multiple team members who could have received and responded to the survey, it is possible that these responses include multiple respondents from a single center. Only eight (4%) respondents affirmed they were obtaining PGx testing beyond cystic fibrosis transmembrane conductance regulator (CFTR) and 66 (89%) respondents answered that they were not currently doing PGx for drug-gene pairs beyond CFTR. Based on this landscape survey, PGx is not commonly implemented in US CFF-ACCAP, but providers are open to using PGx to improve care in PwCF. Several barriers limit the implementation of PGx in CFF-ACCAP, which calls for guidance on how to effectively integrate PGx into CF clinical care.

PMID:40778643 | DOI:10.1002/ppul.71229

Pediatr Pulmonol. 2025 Aug;60(8):e71231. doi: 10.1002/ppul.71231.

ABSTRACT

INTRODUCTION: Medication adherence in cystic fibrosis (CF) has been shown to slow disease progression. Integrated pharmacy services can help increase medication access. The objective of this study was to compare the medication possession ratio (MPR) of dornase alfa between people with cystic fibrosis (PwCF) filling maintenance CF medications at one integrated health system specialty pharmacy (IHSSP) to those filling at multiple pharmacies.

METHODS: This retrospective study included PwCF < 18 years of age who were prescribed dornase alfa from January 1 to December 31, 2019. The primary endpoint was the MPR for dornase alfa. Subgroup analyses were performed for those with Medicaid and those with private insurance.

RESULTS: A total of 85 patients were included, with 29 (34.1%) filling all medications at IHSSP and 56 (65.9%) filling at multiple pharmacies. The median MPR of dornase alfa was 0.98 (IQR: 0.76-1) and 0.64 (IQR: 0.34-0.85), (p < 0.001), and ppFEV1 changed by -1% (IQR: -7% to 5%) compared to -5% (IQR: -10% to -1%), (p = 0.03) for the IHSSP group and multiple pharmacies groups, respectively. There was no difference in the number of hospitalizations or length of stay. Improved MPR for PwCF in the IHSSP group was sustained in the Medicaid and private insurance subgroups.

CONCLUSIONS: The MPR of dornase alfa was higher, and pulmonary function was maintained in PwCF who were able to use the IHSSP for CF medications. Some insurance policies require specific pharmacies for specialty medications, requiring PwCF to fill prescriptions at multiple pharmacies and potentially worsening adherence and clinical outcomes.

PMID:40778618 | DOI:10.1002/ppul.71231

Pediatr Pulmonol. 2025 Aug;60(8):e71222. doi: 10.1002/ppul.71222.

ABSTRACT

In 2024, important advances for people with cystic fibrosis (CF) were published. Important guidelines for newborn screening and care of infants diagnosed with CF transmembrane conductance regulator (CFTR)-Related Metabolic Syndrome/Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CRMS/CFSPID) were published alongside related key lessons from individual programs. Work continues to improve growth and nutrition and treat pulmonary exacerbations. New position papers on care delivery and the care team in the post-CFTR modulator era were developed next to continued information related to CFTR modulator use on treatment burden simplification and side effects, such as mental health and use during pregnancy. The aim of this review is to provide high-level information that may lead to changes in clinical care.

PMID:40778614 | DOI:10.1002/ppul.71222

bioRxiv [Preprint]. 2025 Jul 21:2025.07.21.666023. doi: 10.1101/2025.07.21.666023.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the CFTR gene, leading to epithelial dysfunction and progressive lung disease. Although CFTR modulators have transformed care, ∼10% of people with CF remain without effective therapy. Durable, mutation-agnostic approaches are urgently needed.

METHOD: We used a lentiviral (LV) vector to deliver wild-type CFTR to airway basal cells derived from 13 paediatric CF participants with a range of genotypes. Transduced cells were assessed for transgene expression, epithelial differentiation, and CFTR function using air-liquid interface (ALI) cultures. Separately, to evaluate regenerative capacity in vivo , LV GFP -transduced rabbit airway basal cells were transplanted into the denuded nasal septum of healthy New Zealand white rabbits using a biocompatible scaffold.

RESULTS: Transduced basal cells retained multilineage differentiation capacity, forming well-organized, pseudostratified epithelium with intact barrier function and ciliary activity. CFTR channel activity was restored to levels comparable to or exceeding those achieved with elexacaftor/tezacaftor/ivacaftor (ETI), including in individuals with nonsense mutations. Combined CFTR transduction plus ETI treatment showed additive benefit. In vivo , transplanted rabbit basal cells engrafted and differentiated to regenerate a mucociliary epithelium, with improved nasal potential difference and mucociliary clearance compared to scaffold-only controls.

CONCLUSION: Our study demonstrates that LV-mediated CFTR gene addition restores CFTR function in vitro across genotypes and supports epithelial regeneration in a clinically relevant animal airway model. This two-part platform offers a scalable path toward cell therapies for all people with CF and may have broader applications in upper airway epithelial repair.

PMID:40777307 | PMC:PMC12330628 | DOI:10.1101/2025.07.21.666023

Pathology. 2025 Jul 10:S0031-3025(25)00219-3. doi: 10.1016/j.pathol.2025.05.006. Online ahead of print.

NO ABSTRACT

PMID:40774858 | DOI:10.1016/j.pathol.2025.05.006

Chronic Obstr Pulm Dis. 2025 Aug 1. doi: 10.15326/jcopdf.2025.0611. Online ahead of print.

NO ABSTRACT

PMID:40774292 | DOI:10.15326/jcopdf.2025.0611

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Aug 6;56:101595. doi: 10.1016/j.cbd.2025.101595. Online ahead of print.

ABSTRACT

Soil salinization is an increasingly critical global issue for which fishery-based utilization has emerged as a promising mitigation strategy. Penaeus vannamei is an ideal species for aquaculture in saline-alkali waters; however, the differences in alkali tolerance among various families and their underlying mechanisms remain largely unexplored. In this study, alkali-tolerant families were identified through median lethal time (LT50) assays under high alkalinity and elevated pH. Comparative analyses with wild-type family revealed that alkali-tolerant families showed significant differences in energy metabolism and ion transport (Na+/K+-ATPase (NKA), carbonic anhydrase (CA), and cystic fibrosis transmembrane conductance regulator (CFTR)) Transcriptomic analysis showed that alkali-tolerant families had pathways related to cytoskeletal remodeling, including actin cytoskeleton organization (GO:0030029) and myosin complex (GO:0016459). KEGG analysis further revealed enrichment in cardiac muscle contraction (ko04260) and adrenergic signaling in cardiomyocytes (ko04261). We propose that CaCO3 precipitation reduces extracellular Ca2+ levels and disrupts the carbonate buffering system under high pH and alkalinity. In response, alkali-tolerant families mitigate pH and alkalinity stress by enhancing ion regulation and energy efficiency while simultaneously downregulating high-energy Ca2+ regulatory pathways and remodeling gill microstructures. Collectively, these findings provide novel insights into the alkali adaptation mechanisms of P. vannamei and support selective breeding strategies to improve stress resilience in saline-alkali aquaculture.

PMID:40774072 | DOI:10.1016/j.cbd.2025.101595

J Clin Invest. 2025 Aug 7:e191824. doi: 10.1172/JCI191824. Online ahead of print.

NO ABSTRACT

PMID:40773289 | DOI:10.1172/JCI191824

Ann Am Thorac Soc. 2025 Aug 7. doi: 10.1513/AnnalsATS.202501-007RL. Online ahead of print.

NO ABSTRACT

PMID:40772887 | DOI:10.1513/AnnalsATS.202501-007RL

mSphere. 2025 Aug 7:e0082024. doi: 10.1128/msphere.00820-24. Online ahead of print.

ABSTRACT

The intestinal epithelium serves as a critical interface between the external environment and internal tissues, coordinating nutrient absorption, immune defense, and barrier integrity. Discerning the processes that maintain gut homeostasis has been challenging due to the complexity of the intestinal microenvironment and the difficulty in accessing human tissue. The advent of human intestinal organoid technology has transformed the field by providing relevant in vitro models that recapitulate the cellular diversity and function of the gut epithelium. A recent advance involves the integration of immune cells into organoid cultures, enabling the study of epithelial-immune cell interactions in both health and disease. Furthermore, the application of cutting-edge multi-omics approaches, including transcriptomics, proteomics, and metabolomics, has enabled a deeper understanding of intestinal cell signaling, niche factors, and host-microbe dynamics. These innovations have led to breakthroughs in translational research, particularly in the field of precision medicine. This minireview highlights how intestinal organoids derived from human tissue stem cells, coupled with high-resolution omics technologies, are advancing our knowledge of intestinal physiology, host responses, and disease mechanisms. It also describes the emergence of patient-derived organoids as tools to guide personalized therapeutic strategies for conditions such as inflammatory bowel disease and cystic fibrosis. As organoid models continue to evolve, the integration of additional tissue components-such as diverse immune cell lineages, stromal elements, vasculature, neural cells, and microbiota-will more accurately replicate the intricate nature of human physiology and broaden their translational potential.

PMID:40772719 | DOI:10.1128/msphere.00820-24

Microbiol Spectr. 2025 Aug 7:e0068225. doi: 10.1128/spectrum.00682-25. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa causes acute and chronic infections, such as those that occur in the lungs of people with cystic fibrosis (CF). In infection environments, oxygen (O2) concentrations are often low. The transcription factor Anr (anaerobic regulation of arginine deiminase and nitrate reduction) responds to low O2 by upregulating genes necessary for P. aeruginosa fitness in microoxic and anoxic conditions. Anr regulates Dnr (dissimilative nitrate respiration regulator), a gene encoding a transcriptional regulator that promotes the expression of genes required for using nitrate as an alternative electron acceptor during denitrification. In CF sputum, transcripts involved in denitrification are highly expressed. While Dnr is necessary for the anoxic growth of P. aeruginosa in CF sputum and artificial sputum media (ASMi), the contribution of denitrification to P. aeruginosa fitness in oxic conditions has not been well described. Here, we show that P. aeruginosa requires dnr for fitness in ASMi, and the requirement for dnr is abolished when nitrate is excluded from the media. Additionally, we show that P. aeruginosa consumes nitrate in lysogeny broth (LB) under microoxic conditions. Furthermore, strains without a functioning quorum sensing regulator LasR, which leads to elevated Anr activity, consume nitrate in LB even in normoxia. There was no growth advantage for P. aeruginosa when nitrate was present at concentrations from 100 to 1,600 µM. However, P. aeruginosa consumption of nitrate in oxic conditions created a requirement for Dnr and Dnr-regulated NorCB, likely due to the need to detoxify nitric oxide. These studies suggest that Anr- and Dnr-regulated processes may impact P. aeruginosa physiology in many common culture conditions.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen commonly isolated from low-oxygen environments such as the lungs of people with cystic fibrosis. While the importance of P. aeruginosa energy generation by denitrification is clear in anoxic environments, the effects of denitrification in oxic cultures are not well understood. Here, we show that nitrate is consumed in microoxic environments and, in some strains, in normoxic environments. While nitrate does not appear to stimulate microoxic growth rate or yield, it does impact physiology. We show that the regulators Anr (anaerobic regulation of arginine deiminase and nitrate reduction) and Dnr (dissimilative nitrate respiration regulator), which are best known for their roles in anoxic conditions, contribute to P. aeruginosa fitness in common laboratory media in the presence of oxygen.

PMID:40772714 | DOI:10.1128/spectrum.00682-25

Clin Ther. 2025 Aug 5:S0149-2918(25)00244-9. doi: 10.1016/j.clinthera.2025.07.008. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to evaluate the effects of azithromycin on lung function in children with cystic fibrosis (CF) through a systematic review and meta-analysis of randomized controlled trials (RCTs). The study primarily focuses on its impact on FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), and the progression of lung function decline.

METHODS: Electronic searches were conducted across PubMed,Cochrane Central, Embase, Web of Science, and China National Knowledge Infrastructure databases, including studies published up to November 1, 2024. Inclusion criteria required RCTs involving children with CF, azithromycin as the intervention, and placebo controls. Meta-analyses were performed using random-effects models, and heterogeneity was assessed using the I² statistic. Sensitivity analyses were conducted to ensure the robustness of results.

FINDINGS: Eight RCTs were included, covering a total of 625 participants. Meta-analysis revealed that azithromycin significantly improved FEV1 compared to the control group, with a standardized mean difference (SMD) of 0.58 (95% CI: 0.03-1.14), though substantial heterogeneity was observed (I² = 82.8%). However, no statistically significant improvement in FVC was detected (SMD: 0.62, 95% CI: -0.04 to 1.29, I² = 85.4%). Additionally, azithromycin reduced the relative risk of lung function decline (RR: 0.79, 95% CI: 0.62-1.00), with moderate heterogeneity (I² = 45.5%). Sensitivity analyses confirmed the stability of these results.

IMPLICATIONS: Azithromycin shows potential in improving FEV1 and slowing lung function decline in children with cystic fibrosis, likely through its anti-inflammatory and immunomodulatory effects. Further large-scale studies are warranted to confirm its long-term efficacy, evaluate safety, and optimize treatment strategies, including potential combination therapies.

PMID:40769868 | DOI:10.1016/j.clinthera.2025.07.008

Clin Chest Med. 2025 Sep;46(3):559-567. doi: 10.1016/j.ccm.2025.04.014. Epub 2025 Jul 1.

ABSTRACT

This article provides an overview of remote or home spirometry. It includes discussions about the types of devices available, their accuracy, and pitfalls. It also summarizes the data available for the use of home spirometry in specific pulmonary diseases such as lung transplant, cystic fibrosis, neuromuscular disease, and obstructive lung disease.

PMID:40769599 | DOI:10.1016/j.ccm.2025.04.014

Eur Respir Rev. 2025 Aug 6;34(177):240255. doi: 10.1183/16000617.0255-2024. Print 2025 Jun.

ABSTRACT

Great strides have been made in pre-clinical research in recent decades using animal models and cell lines. However, traditional models may fail to translate to humans, resulting in substantial failure rates in drug development. Recent three-dimensional organoid models have borne a good resemblance to the architecture, development and function of tissues, especially for organs with complex cell interactions and dynamics such as the lungs. In 2022, the role of organoids as alternative to animal testing was recognised by the US Food and Drug Administration. We searched Medline and ClinicalTrials.gov for studies on the experimental use of lung organoids to model disease pathogenesis and test treatments for paediatric and neonatal respiratory diseases. We comprehensively review the translational value of organoids for paediatric and neonatal respiratory conditions, with current limitations and future expectations, while glancing at other in vitro respiratory models. Combinations of organoid models varying in derivation and differentiation have been used to test interventions for conditions such as infectious/inflammatory diseases, abnormalities of the lung vasculature, surfactant deficiency and genetic diseases. Even multifactorial diseases such as congenital diaphragmatic hernia and bronchopulmonary dysplasia are benefiting from new options for patient-specific sampling and organoid derivation. Microscale technologies and engineering contribute to further advancements in lung-on-chip and microfluidic environments. Overall, organoids show great potential as a bridge between basic research and clinical applications, with versatile adaptability to research purposes. Patient-derived organoids carry exciting possibilities for both personalised medicine and clinical research. Rapid advances in regenerative medicine and engineering have opened up new avenues for neonatology and paediatric respiratory medicine.

PMID:40769535 | DOI:10.1183/16000617.0255-2024

Cell Host Microbe. 2025 Jul 31:S1931-3128(25)00281-1. doi: 10.1016/j.chom.2025.07.009. Online ahead of print.

ABSTRACT

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve the physiological defect causing cystic fibrosis, but the lungs of most people remain infected and inflamed. A leading hypothesis implicates damaged segments as the cause of persistent infection and predicts that mildly diseased segments within an individual's lungs will clear after treatment, whereas severely diseased segments will not. Our findings contradict this hypothesis. We used bronchoscopy to sample the least- and most-damaged lung segments in Pseudomonas aeruginosa (Pa)-infected individuals before modulators and returned to these same segments after 1.5 years. Surprisingly, we find an "all-or-none" infection clearance response: the most-diseased segments clear if any other lung segment in that person clears, and the least-diseased segments remain infected if others in that person do. Furthermore, neutrophilic inflammation completely resolves where Pa clears but remains elevated where Pa persists. These data indicate that post-modulator infections are not limited to severely diseased segments and that Pa infections drive persistent lung inflammation after modulators.

PMID:40769150 | DOI:10.1016/j.chom.2025.07.009

Respir Med Res. 2025 Jun 16;88:101186. doi: 10.1016/j.resmer.2025.101186. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) patients often undergo treatment with CFTR modulators, which have demonstrated high efficacy but also potential involvement in drug interactions. Inquiries regarding the risks of drug interactions with complementary and alternative medicine products (CAMp) and self-medication drugs have become frequent among patients and prescribers at Toulouse University Hospital. Currently, there is lack of literature on these practices within CF patients, particularly in France, and more so since the advent of CFTR modulators.

METHODS: This observational monocentric study (MUCAUTOMED) aimed to characterize and quantify the prevalence of CAMp utilization among CF patients under our hospital's care. A secondary objective was to assess and describe the prevalence of self-medication practices. Surveys were administered to outpatients during visits from January 10 to June 6, 2022.

RESULTS: Out of 171 included patients, responses from 64 adults and 69 children were analyzed (response rate 133/171 = 77.8 %). CAMp usage was reported by 56.3 % of adults and 46.4 % of children. Most patients use CAMp for enhancing wellness, addressing digestive concerns, and managing respiratory issues. Remarkably, 71.4 % of participants were unaware of potential drug interactions with CAMp, and 48.9 % initiated such use without consulting healthcare professionals. Notably, a significant correlation between CAMp utilization and self-medication was identified within the pediatric population.

CONCLUSION: Our investigation underscores a notably high prevalence of CAMp use among the CF population. Given these findings, it is imperative to routinely discuss CAMp utilization and self-medication practices when initiating CFTR modulator therapy. A multidisciplinary approach is recommended to address potential interactions that may impact overdosing and underdosing, ensuring patients and families are informed of associated risks. Registration number 2021-A02593-38.

PMID:40768781 | DOI:10.1016/j.resmer.2025.101186

Proc Natl Acad Sci U S A. 2025 Aug 12;122(32):e2506821122. doi: 10.1073/pnas.2506821122. Epub 2025 Aug 6.

ABSTRACT

The emergence of immune-evasive SARS-CoV-2 Omicron subvariants highlights the need to develop a mucosal SARS-CoV-2 vaccine that can provide broad protection against virus infection and transmission. Here, we developed an intranasal monovalent SARS-CoV-2 vaccine expressing the six-proline-stabilized prefusion spike proteins (preS-6P) of Omicron XBB.1.5 based on the attenuated mumps virus (MuV) Jeryl Lynn (JL1) vaccine strain. We also developed an intranasal trivalent vaccine expressing the preS-6P of ancestral SARS-CoV-2 WA1 and two Omicron subvariants, BA.1 and XBB.1.5, using the attenuated measles virus (MeV) and MuV-JL1 and JL2 vaccine strains, respectively. Intranasal immunization of hamsters with the monovalent rMuV-JL1-XBB.1.5 or the trivalent vaccine induced high levels of neutralizing antibodies (NAbs) that efficiently neutralized Omicron subvariants XBB.1.5, EG.5, and JN.1, providing complete protection against these Omicron subvariants. Similar levels of Omicron XBB.1.5 NAbs were detected in monovalent rMuV-JL1-XBB.1.5 and trivalent vaccine groups even when hamsters had been preimmunized with the rMuV-JL2-WA1 vaccine, suggesting that both intranasal vaccines are effective in the presence of immune imprinting induced by the spike of SARS-CoV-2 WA1. Intranasal, but not subcutaneous, immunization generated high levels of S-specific mucosal IgA antibodies as well as lung-resident memory T cells in IFNAR1-/- mice. Finally, intranasal immunization with the trivalent vaccine efficiently blocked transmission of SARS-CoV-2 WA1 and Omicron XBB.1.5 among hamsters in a direct contact transmission setting. In summary, we have developed intranasal MeV and MuV-based trivalent vaccines that induce broad NAbs, robust mucosal immunity, and strong protection against both virus challenge and virus transmission.

PMID:40768351 | DOI:10.1073/pnas.2506821122

Phytother Res. 2025 Aug 6. doi: 10.1002/ptr.8367. Online ahead of print.

ABSTRACT

The increasing prevalence of inflammatory diseases in the respiratory tract worldwide has raised concerns, and due to its high prevalence and poor prognosis, it remains a clinical focus and research hotspot. These inflammatory diseases include airway inflammation, asthma, bacterial antigens-induced tonsil epithelial inflammation, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), COVID-19, acute lung injury, and lung cancer. This review summarizes the relevant molecular mechanisms of inflammatory diseases in the respiratory tract and the progress of natural bioactive components in inflammatory diseases in the respiratory tract. The natural bioactive components have good therapeutic or intervention effects on inflammatory airway diseases in vitro, in vivo, and in clinical trials. The information on inflammatory diseases in the respiratory tract and natural bioactive ingredients in anti-inflammatory diseases were collected from famous literature databases such as Web of Science, PubMed, and Google Scholar, with keywords including bioactive components, inflammatory diseases, respiratory tract, and so forth. The bioactive phytochemicals, such as curcumin, ginsenoside, safranal, melatonin, could improve inflammatory diseases through the regulation of PI3K/Akt, NF-κB, NRF2/HO-1, MAPK, cAMP-PKA, and MEK/ERK Signaling pathways. Further high-quality studies are still needed to firmly establish the clinical efficacy of bioactive ingredients. This review provides new insight for future research on functional food or drug-lead compound development on natural products improving inflammatory diseases in the respiratory tract.

PMID:40767628 | DOI:10.1002/ptr.8367

J Asthma. 2025 Aug 6:1-12. doi: 10.1080/02770903.2025.2494233. Online ahead of print.

ABSTRACT

OBJECTIVE: Age of asthma onset is critical for determining heterogeneous asthma phenotypes. How onset and duration affect therapeutic response is not well understood. Phase 3 QUEST (NCT02414854) and open-label extension TRAVERSE (NCT02134028) studies demonstrated dupilumab's efficacy up to three years in patients ≥12 years with uncontrolled, moderate-to-severe asthma. We assessed how age of asthma onset and asthma duration affect clinical efficacy of dupilumab in patients with moderate-to-severe type 2 inflammatory asthma.

METHODS: This post hoc analysis included patients with type 2 asthma from QUEST who enrolled in TRAVERSE. Annualized severe exacerbation rates (AER), change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 s (FEV1), and five-item Asthma Control Questionnaire (ACQ-5) score were assessed according to asthma age of onset (<18 years, 18-40 years, >40 years) and duration (<20 years, ≥20 years).

RESULTS: In all subgroups, treatment with dupilumab through QUEST and TRAVERSE progressively reduced AER (TRAVERSE Week 48-96 range, 0.160-0.333), increased pre-bronchodilator FEV1 (TRAVERSE Week 96 change from PSBL range, 0.20-0.44 L), and reduced ACQ-5 scores (TRAVERSE Week 48 change from PSBL range, -1.63 to -1.84). In patients who received placebo during QUEST, treatment with dupilumab in TRAVERSE improved AER, FEV1, and ACQ-5 in all subgroups.

CONCLUSIONS: In patients with uncontrolled, moderate-to-severe type 2 asthma, treatment with dupilumab provides sustained, long-term exacerbation rate reductions and improvements in lung function and asthma control, across all subgroups, with higher reductions in AER and improvements in pre-bronchodilator FEV1 seen in patients with later onset or longer duration.

PMID:40767333 | DOI:10.1080/02770903.2025.2494233