Single-inhaler triple therapy (SITT) combines an inhaled corticosteroid (ICS; for example, fluticasone furoate, budesonide, or beclometasone dipropionate), a long-acting β2-agonist (LABA; for example, vilanterol or formoterol fumarate), and a long-acting muscarinic antagonist (LAMA; for example, umeclidinium or glycopyrronium bromide) in one device. Triple pharmacological therapy reduces exacerbations in selected patients with chronic obstructive pulmonary disease (COPD), but its effects on mortality and cardiovascular outcomes remain uncertain. This structured narrative review summarizes randomized trials, observational comparative-effectiveness studies, target trial emulations, systematic reviews, and health technology assessments published between 2015 and 2026. We grouped the evidence by comparator: LABA/LAMA, ICS/LABA, multiple-inhaler triple therapy (MITT), and ICS continuation versus withdrawal, because each comparison addresses a different clinical question. Pivotal trials and evidence syntheses consistently showed fewer moderate-to-severe exacerbations with triple therapy, with reported rate ratios of approximately 0.69-0.93. Mortality signals from IMPACT and ETHOS are clinically important, but previous ICS use and ICS withdrawal among participants assigned to ICS-free comparators make these findings difficult to interpret. Observational cardiovascular findings are also uncertain because residual confounding, treatment selection, exposure misclassification, outcome misclassification, and differences in baseline disease severity limit causal interpretation. Compared with MITT, the main advantages of SITT are simpler treatment and possible improvements in adherence and persistence, not greater pharmacological potency. Treatment decisions should consider exacerbation history, repeated blood eosinophil counts, pneumonia risk, cardiovascular disease, previous ICS exposure and response, inhaler technique, device suitability, and patient preference. Trials in patients with documented absence of previous ICS use and well-designed target trial emulations are needed to determine whether the observed mortality and cardiovascular associations are causal.

Hematopoietic cell transplantation is a curative therapy for certain hematologic malignancies but is limited in use due to post-transplant complications such as graft-versus-host disease (GVHD), wherein donor cells mount an immune response against host tissues. GVHD is a major cause of post-transplant mortality, inspiring the development of prophylactic strategies to reduce GVHD severity. However, these involve administration of cytotoxic or immunosuppressive compounds into patients, increasing adverse side effects. To address this issue, we have developed a strategy to reduce GVHD through ex vivo graft conditioning. Previously we demonstrated that pretreatment of mouse grafts with a single compound, fluticasone propionate, dramatically reduced GVHD symptoms after allogeneic transplantation. Here, we condition grafts in a combination of fluticasone propionate, venetoclax, and IL-2 for 6 hours ex vivo prior to transplantation. We demonstrate that the preconditioning process increases the frequency of tolerogenic regulatory T cells pre- and post-transplant. Recipient mice receiving conditioned cells display reduced GVHD severity and increased overall survival in both fully mismatched and haploidentical models. This study highlights an alternative strategy to GVHD prophylaxis which reduces reliance on the administration of toxic compounds.

Intranasal corticosteroids (INS) are widely recommended as first-line therapy for pediatric upper airway disorders due to their potent local anti-inflammatory effects and favorable safety profile. This narrative review evaluates current evidence regarding the pharmacologic properties, clinical efficacy, and safety of INS in children with allergic rhinitis (AR), adenoid hypertrophy (ADH), obstructive sleep apnea (OSA) or sleep-disordered breathing (SDB), otitis media with effusion (OME), and rhinosinusitis (RS). A structured literature search of PubMed, EMBASE, and Cochrane databases (2015-2025) identified randomized controlled trials, observational studies, systematic reviews, and meta-analyses assessing indications, efficacy outcomes, and adverse events. Evidence consistently supports INS as the most effective pharmacologic therapy for pediatric AR, with significant improvements in symptom scores and quality of life. In ADH and mild OSA/SDB, INS may reduce nasal obstruction and decrease adenoid size, potentially lowering the need for surgical intervention. Data for OME are inconsistent, and routine use is not universally recommended. In acute and chronic RS, INS demonstrates benefit, particularly when allergic inflammation predominates. Pharmacokinetic differences among agents influence safety. Newer molecules such as fluticasone propionate, fluticasone furoate, and mometasone furoate exhibit low systemic bioavailability and high receptor affinity, minimizing hypothalamic-pituitary-adrenal axis suppression. Local adverse effects are generally mild and comparable to placebo. Epistaxis is a recognized local adverse effect, although pediatric data do not demonstrate a significant increase compared with placebo. Available data suggest minimal, clinically insignificant effects on growth velocity when recommended doses are used. Overall, INS remain a cornerstone of AR therapy, with well-established efficacy and a favorable safety profile when appropriately used. There is also supportive and clinically meaningful evidence for their use in selected children with ADH, although the available evidence is heterogeneous. In contrast, evidence for INS in OME, OSA/SDB, and pediatric CRS remains limited or inconsistent and does not currently support their routine use solely for these pediatric upper airway conditions, particularly in the absence of concomitant nasal allergic inflammation.

Single-cell and spatial omics offer unprecedented opportunities to decipher the mechanisms of disease, however, this process requires teams of experts, iterative trial-and-error and reasoning across modalities. Here we present LungChat (https://chat.lungmap.net), a conversational system for integrated multi-omics analysis and biomedical discovery, deployed as a hierarchical multi-agent architecture in which a supervisor decomposes natural-language questions into parallel, tool-grounded tasks spanning single-cell and spatial analyses, literature and clinical-trial synthesis, and drug repurposing. To predict new therapeutics, LungChat implements Direction-Aware Repurposing and Targeting (DART) to distinguish perturbations that reverse disease transcriptional programs from those that reinforce them, at the cell-type level, for safety prediction. Controlled architecture ablations showed that hierarchical orchestration improved grounded abstention and token efficiency and preserved strong performance on complex multi-step tasks. In pulmonary disease case studies, LungChat independently prioritized saracatinib for IPF through drug-connectivity screening, followed by DART-based cell-type analysis; the same compound has been evaluated in the STOP-IPF clinical trial (NCT04598919). The system also recovered fluticasone propionate, an established COPD therapy, through a single orchestrated analysis. This tissue-agnostic system provides a blueprint for verifiable agentic AI systems that support reproducible scientific discovery.

While short-acting beta-agonists have been a mainstay of therapy during acute asthma exacerbations and for patients with intermittent asthma, there is increasing evidence that the use of combination inhalers, containing both an inhaled corticosteroid and a fast-acting bronchodilator, lead to improvement in symptom control, reduction in severe asthma exacerbations, and increased adherence to medications. These combination inhalers may be used in the form of stand-alone anti-inflammatory reliever therapy or as single maintenance and reliever therapy.

Background/Objectives: Biologic therapies are the cornerstone of severe asthma management. However, evidence regarding switching between biologics in children with severe asthma remains limited. Methods: Retrospective observational study including patients aged 6-17 years with severe asthma, followed at our tertiary referral center, who switched biologic therapy. Clinical, laboratory, and lung function data were collected at the initiation of the second biologic (T0) and after 4 (T1) and 12 months (T2). Changes in asthma control, exacerbation rate, inhaled corticosteroid dose, FeNO and lung function were evaluated. Results: Eight patients who switched and had been treated with a second biologic for at least 12 months were included. Switching occurred from omalizumab to dupilumab (n = 1), mepolizumab to dupilumab (n = 5), and mepolizumab to omalizumab (n = 2). The main reason for switching was inadequate asthma control, while one patient switched because of poorly controlled comorbidity. At T2, exacerbations significantly decreased (p = 0.03), with significant improvements in FEV1 (p = 0.002) and FEV1/FVC (p = 0.015). The daily fluticasone-equivalent dose decreased from a median of 500 μg to 425 μg. Conclusions: In this cohort, switching biologic therapy was associated with improved clinical and functional outcomes, with a significant response already detectable after 4 months. These findings highlight the importance of close clinical and functional monitoring to identify children who may benefit from a change in biologic therapy. Larger prospective studies are needed to define standardized criteria and optimal timing for biologic switching in pediatric severe asthma.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus, with increasing prevalence and incidence, characterized by eosinophilic infiltration of the mucosa, and frequently associated with asthma and atopic predisposition. We report the case of a 13-year-old female patient with poorly controlled moderate persistent asthma, admitted for recurrent vomiting over the past year, complicated by the sudden onset of hematemesis, associated with fever and clinical deterioration. On admission, the patient presented with tachycardia, hypoxemia, and acute respiratory distress associated with an asthma exacerbation. An emergency esophagogastroduodenoscopy revealed EoE, with histopathology demonstrating dense eosinophilic infiltration (>15 eosinophils/high-power field). Allergy testing revealed food sensitization to prawns. Treatment with oral fluticasone (250 μg twice daily) combined with double-dose proton pump inhibitors resulted in rapid clinical remission and complete histological normalization at 10 months. This case highlights the need to systematically consider EoE in the presence of any acute gastrointestinal symptoms in a patient with atopic predisposition, and the importance of early management.