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Open research questions in Asthma and respiratory diseases

80 unresolved questions extracted from the limitations and future-work sections of 895 Asthma and respiratory diseases papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • While anti-IL-5 therapy improves clinical outcomes in severe asthma, the cellular and molecular mechanisms underlying its effects on AR remain incompletely understood.

    IL-5 blockade restores the bronchial epithelium and attenuates airway remodelling in severe asthma · 2026 · DOI

  • The management of respiratory support in pediatric critical asthma has evolved signifi- cantly, with increasing emphasis on nonin- vasive strategies and refined approaches to MV when required. The fundamental princi- ple that MV strategies in asthma differs sig- nificantly from lung-protective strategies used in ARDS cannot be overemphasized. NRS is recommended as the first line of respiratory support for patients with critical asthma but when IMV is necessary, dynamic hyperinflation management takes precedence. With modern approaches, survival from asthma now exceeds 96%, underscoring the importance of evidence- based and physiology-guided care. editorial decisions. Long Xiang and Herng Lee Tan have no conflicts to declare.

    Respiratory Support in Pediatric Critical and Near-Fatal Asthma: A Narrative Review · 2026 · DOI

  • Looking ahead, future research should focus on validating and integrating biomarkers into clinical practice, optimizing early detection, and refining preventive strategies such as monoclonal antibody therapies and maternal vaccination. Additionally, further research is needed to identify which specific features of the preterm immune system most significantly contribute to increased susceptibility to severe RSV dis- ease and subsequent asthma.

    Letter to the Editor: 100-day window: Reframing early follow-up and parental guidance in recurrent wheezing · 2026 · DOI

  • These findings identify HDL-c, body composition, and symptom control as candidate correlates of pulmonary function, with potential sex-related differences warranting further investigation.

    Sex-Stratified Correlates of Pulmonary Function in Mexican Children and Adolescents (6–17 Years) with Asthma: An Exploratory Analysis of HDL Cholesterol, BMI, and Pubertal Stage · 2026 · DOI

  • Studies show anti–IL-5/5R biologics meaningfully reduce BEC; however, there are limited data describing the real-world effects of anti-IgE and anti–IL-4R biologics on BECs.

    Real-world effects of asthma biologics on blood eosinophil levels: data from the CHRONICLE study · 2026 · DOI

  • Future research should consider oscillometry‐defined SAD being incorporated as a key clinical outcome in phase 2 studies as new monoclonal antibodies are developed, such as bispecifics, especially both dual upstream (IL33/TSLP) or downstream blockade (IL4/5/13).

    Impact of Biologics on Oscillometry Defined Small Airway Dysfunction in Uncontrolled Asthma · 2026 · DOI

  • Data availability statement single-arm analysis without an untreated The absence of a concurrent control group and randomization are inherent limitations of this retrospective observational study. As comparator, a improvements over time may partially reflect regression to the mean or other unmeasured factors. Accordingly, the findings should be interpreted as descriptive of observed symptom trajectories rather than causal estimates of treatment effect. The within-person longitudinal design partially mitigates confounding by allowing each participant to serve as their own control. Mixedeffects models accounted for repeated measures and baseline heterogeneity, enabling estimation of population-level trends while preserving individual variability. However, residual confounding cannot be excluded. All outcomes were self-reported through voluntary surveys, introducing the possibility of reporting, recall, and social desirability bias (33). This may have influenced estimates of symptomatic improvement, medication use reduction, and treatment adherence. Adverse events, particularly mild and transient reactions, may also be under-reported in this setting. The symptom assessment instrument was developed for pragmatic use in a telemedicine context and has not undergone external validation. Missing data were addressed using a combination of last observation carried for descriptive summaries and likelihood-based mixed-effects and cumulative link mixed models for inferential analyses, which allow inclusion of all available observations and accommodate unbalanced longitudinal follow-up without requiring explicit imputation. Inspection of follow-up patterns did not suggest systematic dropout driven by observed symptom severity. Nonetheless, bias cannot be fully excluded if missingness depended on unmeasured outcomes or time-varying factors not captured in the models. forward (LOCF) logic This study reflects outcomes observed within a commercially operated real-world care model. The study was conducted using data collected through the Curex telemedicine platform; several authors were involved in the clinical operation and development of the platform and were affiliated with Curex Inc. during study conduct and manuscript preparation; and statistical analysis was performed independently by a third party engaged by Curex Inc. for biostatistical support. While these affiliations and relationships journal requirements, the are disclosed in accordance with potential biases associated with context the are acknowledged.

    Real-world outcomes of personalized sublingual immunotherapy for environmental allergies delivered through a telemedicine platform: a retrospective longitudinal cohort study · 2026 · DOI

  • While +46 A>G has been widely studied for its association with asthma susceptibility, severity, and pharmacogenetics across various ethnic groups, including Indian cohorts, the pathological significance of +79 C>G remains unexplored in Indian asthmatics, particularly among the South Indian population.

    Lack of association between ADRB2 (Gln27Glu) variant with susceptibility, severity and salbutamol response in South Indian asthmatics · 2026 · DOI

  • This study boasts several significant strengths that enhance its importance. Firstly, this pioneering economic evaluation compares mepolizumab’s costs and outcomes for severe asthma in Chinese patients. Using a Chinese societal perspec- tive and long-term horizon, the study assesses its effects on medical expenses, productivity, and quality of life, addressing a critical gap in the literature with insightful findings. Secondly, the study’s strength lies in its evaluation of cost- effectiveness across diverse subgroups, offering a nuanced understanding of how mepolizumab treatment affects various populations and demographic traits. This detailed analysis is essential for decision-makers, policymakers, and healthcare providers in optimizing resource allocation and treatment choices. Thirdly, the study meticulously incorporates the impact of AEs into the model, considering their implications on health state utilities and additional treatment costs, thereby ensuring a robust and reliable cost-effectiveness analysis. This study also faces several limitations. Firstly, the CSEs rate was derived from the MENSA trial, which may inher- ently introduce biases due to the trial’s specific design. Despite this, our sensitivity analysis has confirmed the stability of our results, with the ICER for mepolizumab consistently below the lower limit of the predefined WTP threshold range, even with substantial changes in CSEs rate-related parameters. Secondly, we have relied on health state utilities and cost parameters sourced from international literature, but the DSA has shown that potential variations in these parame- ters would not significantly impact the model’s ICER, implying that our conclusions would likely remain unchanged with PLOS One | https://doi.org/10.1371/journal.pone.0348955 May 13, 2026 9 / 13 more accurate utility and cost data (see Fig 2 and S9 Table for DSA results). Thirdly, the subgroup analysis should be interpreted with caution, given our assumption of a uniform CSEs rate across all subgroups in the placebo arm. Future studies incorporating subgroup-specific CSEs rate data would help optimize our findings. Fourthly, although our Markov model with a 14-day cycle length is grounded in empirical evidence, it may not fully capture the individual variability in exacerbation durations. Fifthly, our study failed to consider the potential impact of exacerbation history on the CSEs rate, a critical factor for predicting future exacerbations [42]. This oversight is due to the absence of direct empirical data in the Chinese context linking exacerbation history with CSE. Nonetheless, our sensitivity analysis has validated the consistency of our conclusions despite variations in CSEs rate-related parameters. Sixthly, we employed the human capital approach to quantify indirect costs attributable to asthma-related productivity loss, given its widespread use in cost-effectiveness research [43,44]. Although this method has inherent limitations, our deterministic sensitivity analysis demonstrated that fluctuations in key related parameters exerted minimal impact on the core outcomes of our model (see Fig 2 and S9 Table for DSA results). In summary, while our study is not without its limitations, the robustness of our findings, as evidenced by sensitivity analysis, indicates that our key conclusions are well-founded and reliable.

    Cost-effectiveness analysis of mepolizumab among patients with severe asthma from the Chinese societal perspective · 2026 · DOI

  • In the future of asthma Chrono pharmacology, it will be involved in integrating circadian biology and the latest technology and personalized treatments. Prospective research will enhance patient outcomes and clinical quality. Recent studies examine wearable AI-optimized dosing, clock genetargeted including therapy, and novel chronodelivery, nanoparticle technologies with precise nocturnal delivery. The use of gene-clock relationships with severe asthma and potential Chrono pharmacokinetics of biologics (e.g. anti-IL- 5 administered at the time of inflammatory peaks) is increasingly popular in research.64 Efforts to integrate evening ICS/LABA in GINA/BTS guidelines require large RCTs that affirm evening ICS/LABA superiority and utilize technological adherence. Training clinicians on rhythm profiling and shift workers adaptation will stimulate adoption as the practice will shift to non-uniform practices but timesensitive practices.45 Chronotherapy can enhance the normal functioning of the body, enhance sleep, reduce nocturnal symptoms and reduce exacerbation by thirty to fifty percent. Being one of the main elements of precision respiratory care, it enhances the general quality of life, adherence, and control of asthma because of its customization via applications and biomarkers.65 As the existing literature employs drug delivery technology, molecular chronobiology and custom medicine to apply the basic knowledge into clinical practice, the field of chronopharmacology in asthma is promising.

    Chronopharmacology in asthma: Role of biological rhythms in optimizing therapy · 2026 · DOI

  • Airway measurements were standardized to predefined segmental bronchi (RB1, RB10, and LB10), representing proxy measurements rather than comprehensive assessment of airway remodeling throughout the entire bronchial tree.

    CT imaging in children with non-severe asthma and cough-variant asthma: functional spasm or structural remodeling? · 2026 · DOI

  • School-supervised asthma therapy improves asthma outcomes for up to 15 months for underrepresented minority children, but little is known about whether these benefits are sustained over time.

    School-supervised Asthma Therapy is Associated with Improved Long-Term Asthma Outcomes for Underrepresented Minority Children · 2022 · DOI

  • BACKGROUND: There is inconclusive evidence on the role of nebulized magnesium sulphate (MgSO4) in the management of acute asthma in paediatric population.

    Nebulized Salbutamol with or without Magnesium Sulphate in the Management of Acute Asthma in Children in India: A Randomized Controlled Trial · 2022 · DOI

  • The wide prevalence range of ACO (0.3% to 5% in general population; 3.2% to 51.4% in asthma patients; 12.6% to 55.7% in COPD patients) indicates inconsistent diagnostic criteria and methodology across studies.

    Aspergillus fumigatus sensitization among asthma COPD overlap patients · 2021 · DOI

  • Treatment specifically targeted at ACO phenotype is noticeably lacking because patients with ACO are often precluded in clinical trials of novel medications for asthma and COPD.

    Aspergillus fumigatus sensitization among asthma COPD overlap patients · 2021 · DOI

  • Analysis of Gln27Glu polymorphism gene Gln27Glu ADRB2 connection at risk and severity of BA showed mixed results, which can be explained by the existence of the possible for each population specific set of candidate genes.

    Relations Gln27Glu polymorphism β2-adrenoceptor gene with bronchial asthma · 2016 · DOI

  • However, it was not clear whether this observation was limited to asthma or depended on the type of microvascular cell and collagen IV used as a base.

    Blocking of α1β1 and α2β1 adhesion molecules inhibits eosinophil migration through human lung microvascular endothelial cell monolayer · 2014 · DOI

  • BACKGROUND AND OBJECTIVE: While paracetamol exposure in pregnancy and early infancy has been associated with asthma, it remains unclear whether this is confounded by respiratory tract infections, which have been suggested as an alternative explanation.

    Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis · 2014 · DOI

  • Studies have shown that pediatric asthma is associated with psychiatric disorders, but the specificity and temporality of these relations is not well known.

    Childhood Asthma, Chronic Illness, and Psychiatric Disorders · 2002 · DOI

  • Introduction Patient-reported outcome measures are widely used to assess symptom burden in respiratory disease, yet the extent to which symptom severity reflects underlying mucosal biology remains incompletely understood.

    Exploring associations between nasal fluid inflammatory proteins and patient-reported symptom burden in respiratory disease · 2026 · DOI

  • While genetic variations in these cytokines are known to influence asthma pathogenesis, their specific impacts on clinically relevant phenotypes remain to be fully elucidated.

    IL5 rs2069812 and IL13 rs1800925 Genetic variants as key determinants of clinically relevant asthma phenotypes · 2026 · DOI

  • Background: Clinical guidelines recommend objective tests to diagnose asthma in school-age children, but their availability and use in routine practice remain uncertain.

    Asthma diagnosis in school-age children: a survey among Swiss physicians · 2026 · DOI

  • Systemic inflammation, oxidative stress, and nasal microbiome alterations were identified as internal mediators linking exposures to allergic phenotypes, though mechanistic pathways remain incompletely defined.

    Exposome and Respiratory Allergic Diseases: A Structured Narrative Review · 2026 · DOI

  • While the association between higher ACEs and higher odds of developing asthma are established in the literature, PCEs and asthma remain understudied, particularly among Tennesseans (Sandberg et al.

    Breathing Room: Associations Between Positive Childhood Experiences, Adverse Childhood Experiences, and Asthma throughout the Lifespan in Tennessee · 2026

  • The retrospective design, relatively small cohort size, and restriction of imaging analysis to selected segmental airways using limited morphometric indices may reduce the ability to detect structure–function relationships.

    CT imaging in children with non-severe asthma and cough-variant asthma: functional spasm or structural remodeling? · 2026 · DOI

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