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Journal articlede Benedictis FM, Beasley R, Pavord I, et al., 2026,
50 years on: how inhaled corticosteroids have changed the treatment of asthma.
, Lancet Respir MedInhaled corticosteroids are the foundation of asthma therapy and now, 50 years on from their introduction, is an appropriate time to summarise some of the key studies that have progressed the field. We can now make better decisions in selecting the optimal inhaled corticosteroid-based regimens and identifying likely responders, based on biomarkers and patient characteristics. Inhaled corticosteroids reduce the risk of asthma attacks, but do not alter the course of the disease. Asthma remission, which is as yet an undefined therapeutic goal, is the aim, but the role of inhaled corticosteroids is unclear. High-dose inhaled corticosteroid therapy can cause systemic adverse events, suggesting that steps be taken to avoid this through the addition of long-acting β2-adrenergic agonists and the judicious use of biologics. Researchers will continue to learn more about the advantages and limitations of inhaled corticosteroids as they explore methods of disease prevention and remission in the future with new tools and treatments.
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Journal articleSory DR, Heyraud ACM, Jones JR, et al., 2026,
SiO2-CaOCME/Poly(Tetrahydrofuran)/Poly(Caprolactone) 3D-Printed Scaffolds Drive Human-Bone Marrow Stromal Cell Osteogenic Differentiation.
, Adv Healthc Mater, Vol: 15This article addresses the unmet clinical need of scaffolds for bone regeneration that can combine osteogenic properties, such as the promotion of bone marrow stem cell differentiation into osteoblasts, with the ability to withstand cyclic loading. In our previous study, we demonstrated that discs of SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) hybrids or their dissolution products can drive terminal osteogenic differentiation of human bone marrow stromal cells (h-BMSCs) in vitro. The current study shows that the 3D-printed hybrid scaffolds with physiologically relevant 3D architecture further promote h-BMSC osteogenesis. The 3D-printed scaffolds support spatially organized cell behavior in an environment mirroring conditions relevant to off-the-shelf implant applications. Primary cellular functions, including viability, adhesion, and proliferation, were maintained across 3D scaffold surfaces and within inter-strut regions. osteogenic commitment was evidenced by the upregulation of lineage-specific transcripts, hydroxyapatite deposition, and the organized assembly of extracellular matrix (ECM) proteins. Our results demonstrate that 3D-printed scaffolds drive osteogenesis by modulating cell metabolism, inducing osteogenic morphological transitions, and promoting the expression of osteocalcin and collagen type I alpha 1 chain, alongside hydroxyapatite matrix mineralization. Collectively, our findings highlight the SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) scaffold's strong osteogenic properties-driven by composition, surface architecture, and ion release - and its promise for clinical bone regeneration.
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Journal articleZheng Y, Li Y, Zeyneloglu C, et al., 2026,
Risk and Protective Factors for Infection, Severe Disease, and Mortality in Epidemic Respiratory Viruses.
, Allergy, Vol: 81, Pages: 1397-1432The post-COVID pandemic era has witnessed a concerning resurgence of respiratory viruses, driving a global increase in acute respiratory infections. This trend may stem from relaxed non-pharmaceutical interventions, waning herd immunity, immunological imprinting limiting heterosubtypic protection, or viral antigenic evolution. This review aims to identify and characterize risk and protective factors associated with infection, hospitalization, severe illness, and mortality, while elucidating the drivers of the rising incidence of respiratory virus infections post-pandemic. Evidence on SARS-CoV-2 sublineages, influenza, respiratory syncytial virus, rhinovirus, adenovirus, human metapneumovirus, human parainfluenza virus, human coronaviruses, and cytomegalovirus has been collected and identified. Identified risk factors include demographic characteristics such as pediatrics and older age, male sex, race (Black, Hispanic, American Indian or Alaska native), preterm birth, and HLA-DQA1, IFNAR2, ST6GAL, and B3GALT5 genetic susceptibility. Behavioral, socioeconomic (low socioeconomic status, crowded living conditions), environmental influences (cold seasons, pollution), smoking, obesity and malnutrition could also exacerbate the risk of infection and adverse outcomes. Comorbidities, such as chronic conditions and immunocompromised states, significantly increase the risk of severe disease and hospitalization. Laboratory indices linked to severe disease outcomes include neutrophilia or neutropenia, lymphopenia, eosinopenia, and elevated C-reactive protein. Viral subtypes, viral load kinetics, vaccination status, and antiviral therapies further delineate risk profiles. Epithelial barrier impairment and underlying chronic airway diseases characterized by type 2 immunity also play a detrimental role in the development and severity of respiratory viral infections. Our findings highlight the need for stratified prevention strategies, which combine universal measures targeting shar
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Journal articleWallace DV, Hossny EM, Levin M, et al., 2026,
Anaphylaxis Guidelines.
, Immunol Allergy Clin North Am, Vol: 46, Pages: 233-256This article compares 12 national and international anaphylaxis guidelines published between 2006 and 2025, highlighting evolving methodological frameworks, diagnostic criteria, and treatment approaches. While consensus supports prompt epinephrine use, differences remain in definitions, risk stratification, and post-acute care. Gaps in education, early childhood care protocols, and global harmonization continue to exist. The analysis emphasizes the shift from crisis-based to proactive anaphylaxis management and underscores the need for equity-focused, evidence-based interventions.
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Journal articleJenkins RG, 2026,
Developing a vaccine strategy to prevent the progression of pulmonary fibrosis.
, Nat Immunol, Vol: 27, Pages: 890-891 -
Journal articleBush A, 2026,
Update in childhood asthma.
, Allergol IntThe areas covered represent a personal selection in the field. Asthma is defined in this manuscript as a clinical syndrome of wheeze, breathlessness and chest tightness, sometimes with excess cough. No assumptions are made about underlying pathology, and asthma thus becomes a clinical description, not a diagnosis. The areas covered include the need never to forget the importance of getting the basics right, including correct diagnosis and appropriate management; most children with asthma do not need biologics. Recent advances in preschool wheeze are covered next, especially the beginnings of phenotype-driven treatment, and the difficult issue of understanding non-eosinophilic wheezing. It is becoming clearer that infection likely plays a big role, but management is very difficult with no evidence base. We are now coming to realize the importance of phenotyping acute asthma attacks; one size does not fit all, but whereas many are eosinophilic, some are infection driven and are non-eosinophilic, especially in the preschool years. A phenotypic approach may allow us to reduce the burden of repeated oral corticosteroid bursts. Furthermore, we need to move beyond mere cell counting to assessing functional status. We are increasingly appreciating the importance of replacing short-acting β-2 agonist reliever therapy with combined inhaled corticosteroid and a fast acting short- and especially long-acting β-2 agonists. Finally, the use of biologicals in severe asthma is discussed. The possibility that early use of biologics may induce remission or even cure asthma.
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Journal articleKlimek L, Mullol J, Reitsma S, et al., 2026,
Correspondence: The First Biosimilar for Biologics in Allergy: CT-P39 (Omlyclo-Omalizumab-Igec) Is Available for Asthma, Chronic Spontaneous Urticaria, and Chronic Rhinosinusitis With Nasal Polyps.
, Allergy -
Journal articleSafavi S, Smith S, Jahnke N, et al., 2026,
Lung transplant in people with cystic fibrosis and nontuberculous mycobacteria infection.
, Cochrane Database Syst Rev, Vol: 4RATIONALE: Cystic fibrosis (CF) is an inherited multi-organ disorder. People with CF (pwCF) experience recurrent and chronic lung infections and a progressive loss of lung function. PwCF with poor and rapidly declining lung function may be considered for lung transplantation (LTx), which may improve their quality of life and survival. Nontuberculous mycobacteria (NTM) can cause pulmonary disease in pwCF, and NTM infection is a poor prognostic factor in LTx. Guidelines recommend NTM infection should not automatically preclude LTx. It is important to evaluate the evidence base for LTx in pwCF and NTM pulmonary disease. OBJECTIVES: To evaluate clinical outcomes in pwCF and with NTM infection (NTM infection alone or with NTM pulmonary disease) who undergo LTx by comparing: 1. pwCF with current NTM lung infection who undergo LTx versus those with NTM infection who do not undergo LTX; 2. pwCF with current NTM lung infection who undergo LTx versus those without NTM undergoing LTx. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, CENTRAL, MEDLINE, Embase, and PubMed as well as two ongoing trials registries. We checked references. The latest search date was 17 February 2026. ELIGIBILITY CRITERIA: We considered non-randomised studies of pwCF (any age) with or without NTM lung infection or disease being considered for LTx as well as studies of pwCF and NTM who either did or did not undergo LTx. OUTCOMES: Our critical outcomes were mortality, disseminated NTM infection post-LTx, time to chronic lung allograft dysfunction (CLAD), and quality of life at any time points reported. We additionally planned to report lung function, hospitalisations for pulmonary exacerbations, and nutritional parameters in the review. RISK OF BIAS: We assessed the risk of bias in three studies using ROBINS-I and in one study using the Joanna Briggs Institute checklist for case series. SYNTHESIS METHODS: We could only report results narratively. We used GRADE to assess the cert
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Journal articleScheire S, Lourijsen E, Blauwblomme M, et al., 2026,
Meta-Analysis on the Harm of Systemic Glucocorticosteroids in Inflammatory Upper Airway Disease and Asthma: An EAACI Task Force.
, AllergySystemic glucocorticosteroids (sGCS) are widely used in the treatment of chronic inflammatory airway diseases such as rhinitis, rhinosinusitis and asthma. It is well-known that systemic use is linked to multiple adverse effects (AEs) both in the short- and the long-term. However, less is known about the safety of multiple short courses of sGCS. Currently there is no established agreement on the acceptable cumulative exposure to sGCS, considering the potential for various AEs. This systematic review and meta-analysis evaluated sGCS-related AEs in both upper and lower inflammatory airway disease, with a particular focus on short- and long-term risks. We further evaluated whether a dose-response relationship existed between the daily and cumulative dosages of sGCS and the occurrence of those AEs. Our meta-analysis confirmed that cumulative dosages between 500 mg and 1 g prednisolone-equivalent significantly increase the risk of most AEs, with risks increasing with incremental dose. These findings underscore the importance of: (a) judicious sGCS prescription and need for steroid stewardship, due to their potential for short- and long-term complications, occurring even with repeated short courses, and (b) prioritization of steroid-sparing approaches (e.g., biologicals) to avoid reaching a cumulative dose of 500 mg.
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Journal articleMohammed Abdul Wajid L, Saglani S, Nagakumar P, et al., 2026,
Exploring health professional views of management for preschool wheeze: a qualitative study.
, Arch Dis Child, Vol: 111, Pages: 444-448OBJECTIVE: This study aimed to explore health professionals' perspectives on the management of preschool wheeze, including their views on using tests to guide treatment for children with recurrent wheeze. DESIGN: Purposive and snowball sampling were used in this qualitative study to recruit health professionals with experience of managing children with pre-school wheeze from primary and secondary care settings across England. Semi-structured interviews were conducted via Microsoft Teams. Transcripts were analysed thematically, supported by the use of NVivo software, to identify key themes. RESULTS: 14 health professionals participated: four general practitioners, four general paediatricians, four hospital asthma nurses, one tertiary respiratory paediatrician and one primary care nurse. Participants agreed that preschool wheeze remains a significant disease. Thematic analysis identified four key themes: (1) challenges with diagnostic terminology, where a lack of consistent terminology was considered to impact communication and management; (2) diagnostic uncertainty, where the absence of objective tests for early asthma diagnosis negatively contributed to management plans; (3) current practice of investigating children with preschool wheeze, where participants described a lack of infrastructure and approach to performing tests in primary and secondary care; and (4) treatment considerations in which parents' medication beliefs were thought to influence adherence to prescribed treatments. There were differences in the views regarding the management of preschool wheeze between primary and secondary care professionals. CONCLUSION: Health professionals' views highlight inconsistent use of diagnostic terminology for preschool wheeze, contributing to variation in management. Integrated care pathways and infrastructure are urgently needed to improve outcomes for children with preschool wheeze.
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Journal articleMakuyana N, Seldeslachts L, Michiels L, et al., 2026,
Gene delivery of immunomodulatory cytokines to the lung preserves respiratory function during inflammatory challenge.
, Sci Immunol, Vol: 11Respiratory infections that result in severe and life-threatening immune-mediated respiratory decline are a major public health issue. Controlling local respiratory immune reactions without the use of systemic immunosuppressants remains an unmet clinical challenge. We developed a gene delivery system to express anti-inflammatory cytokines in the lung, which reestablishes local immune homeostasis without triggering systemic effects. Using an adeno-associated vector cargo system (AAV6.2-CC10), we induced production of interleukin-2 (IL-2), IL-1 receptor antagonist (IL-1RA), and IL-10 in situ in the lung microenvironment, with no detectable expression or immunological deviation in the peripheral immune system. We demonstrate the effective potential of IL-2, IL-1RA, and IL-10 as immunomodulatory cargos in severe infectious challenge, which reduced respiratory pathology after influenza-associated pulmonary aspergillosis. Thus, the AAV6.2-CC10 platform enables targeted delivery of biologics to the lung, modulates the lung environment, and improves pathology without inducing systemic immune reactions.
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Journal articleCanizales J, Schofield S, Shamji MH, et al., 2026,
Patterns of Mouse Allergen-Specific IgE and IgG4 in Contemporary Animal Research Environments.
, Clin Exp Allergy -
Journal articlePeter J, Jindal A, Del Giacco S, et al., 2026,
Urticaria and Angioedema: When East Meets West-and the Middle.
, Allergy -
Journal articleKaenmuang P, Barnett JL, Maher TM, et al., 2026,
Association of bronchoalveolar lavage cellular analysis and radiological findings in fibrotic interstitial lung diseases
, BMJ Open Respiratory Research, ISSN: 2052-4439Background and aims: Inflammation may play a role in driving interstitial lung diseases (ILD). Radiological ground-glass opacity (GGO) may not reliably distinguish fine intralobular fibrosis from inflammatory processes in fibrotic ILD. We therefore investigated the relationship between GGO, fibrosis and leukocytes in bronchoalveolar lavage (BAL).Methods: We recruited patients with fibrotic ILD at a single centre between May 2014 and February 2018. The extent of GGO and fibrosis were evaluated by two radiologists. Linear regression examined the association between leukocyte numbers in BAL obtained from the right middle lobe (RML) and GGO/fibrosis extent in whole lung, adjusting for age, sex, and smoking. Z-test was used to compare the association between BAL and GGO/fibrosis.Results: 316 patients were included. Adjusting analyses for covariates, only BAL eosinophil and eosinophil-to-macrophage ratio were positively associated with GGO involvement (0.23 [95%CI 0.03 to 0.42] p = 0.023 and 11.21[1.33, 21.08] p = 0.026). Lymphocyte percentages (fibrosis -0.17 vs. GGO -0.02 p = 0.046); neutrophil percentages (fibrosis 0.38 vs. GGO 0.06 p 0.002); neutrophil-to-lymphocyte ratio (fibrosis 0.63 vs. GGO -0.05 p 0.027); neutrophil-to-macrophage ratio (Fibrosis 14.08 vs. GGO 2.57 p = 0.015), and neutrophilia (fibrosis 6.81 vs. GGO -0.31 p = 0.002) all demonstrated a significantly stronger associations with fibrosis than GGO. Conclusions: Lack of relationships between radiological GGO and BAL leukocyte counts in fibrotic lung disease indicates that GGO may not always be inflammatory in nature. Higher levels of neutrophil were associated with more extensive fibrosis.
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Journal articleGardiner LE, Lozano-Rojas D, Smith N, et al., 2026,
Investigating prognostic classifications of preexisting multiple long-term conditions for health outcomes 1 year after COVID-19 hospitalization: A UK prospective observational study.
, Int J Infect Dis, Vol: 168BACKGROUND: Preexisting multiple (two or more) long-term conditions (MLTCs) may negatively affect recovery after COVID-19. We investigated how preexisting MLTCs, including different categorization and patterns of MLTCs, affect 1-year health outcomes after severe COVID-19. METHODS: Adults post-hospitalization after COVID-19 were recruited during 2020-2021. We compared recovery at 1 year after discharge using adjusted multivariable logistic regression in 1:1 propensity-matched adults (for age, sex, ethnicity, social deprivation, obesity, and smoking history) with and without preexisting MLTCs. In adults with MLTCs, different categorization such as number of conditions, number and types of body systems involved (e.g. respiratory, cardiovascular), and latent class analysis-derived patterns of condition co-occurrence were assessed for their association with recovery at 1 year. RESULTS: A total of 647 adults with MLTCs were matched with 647 adults without MLTCs (n = 1294; 61.9% male, 79.6% of White ethnicity, median age 59 [interquartile range 52-67] years). The presence of MLTCs was associated with lower odds of feeling fully recovered (odds ratio 0.66 [95% confidence interval 0.51-0.85], P = 0.001). In those with MLTCs, recovery was negatively affected by number and type of body systems involved (e.g. respiratory [odds ratio 0.49 (95% confidence interval 0.34-0.69), P <0.001]) but not by the number of conditions (P >0.1). Four latent classes of MLTC co-occurrence were estimated with different risks of recovery (P <0.01). CONCLUSION: Adults with preexisting MLTCs were 34% less likely to feel fully recovered at 1 year after COVID-19 hospitalization than adults without MLTCs. We describe prognostic classifications of MLTCs, with future work needed to understand whether they have prognostication in broader post-acute infection sequalae.
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Journal articleWu Z, Yazbeck L, Smith DJF, et al., 2026,
Characterising cough and its response to therapy in hypersensitivity pneumonitis.
, ChestBACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) driven by repeated antigen exposure in susceptible individuals. Cough is a prominent but poorly characterised symptom, especially in relation to objective measures and treatment response. RESEARCH QUESTION: What are the clinical predictors of cough severity in HP, and how does cough respond to corticosteroid therapy based on subjective and objective assessments? STUDY DESIGN AND METHODS: A prospective cohort of patients with fibrotic HP diagnosed per ATS/JRS/ALAT guidelines was recruited. Baseline assessments included cough visual analogue (VAS) and the Leicester cough Questionnaire (LCQ). Cough frequency was assessed using the VitaloJAK cough monitor in a subset of patients. Multivariable models evaluated predictors of cough severity, and in incident cases, changes in cough outcomes were evaluated after three months of corticosteroid therapy. RESULTS: A total of 101 patients were recruited (41 male; mean age 65 years). The median cough VAS was 35 mm (IQR 14-50 mm) and the median LCQ was 15.2 (IQR 13.2-17.4). The median cough count was 8.7/hr (range 0.2-32.1/hr, n=28). Subjective cough scores correlated with objective cough frequency (cough VAS ρ = 0.69, P < 0.001 and LCQ ρ=-0.555, P = 0.002). Female sex, reduced forced vital capacity (FVC), and higher bronchoalveolar lavage (BAL) lymphocyte fractions were independent predictors of worse cough severity, as measured by cough VAS. Corticosteroids significantly improved cough subjectively (cough VAS -13.7 mm, P = 0.002 and LCQ +1.9, P < 0.001; n = 44) but did not significantly reduce objective cough frequency (n=16). Lung function remained unchanged at three months. INTERPRETATION: Cough is a major symptom for patients with HP. While corticosteroids improved subjective cough, there was no impact on objective cough count. Randomised controlled trials are required to validate these findings and provide eviden
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Journal articleJenkins G, 2026,
A statistical model for lung function trajectory and mortality in patients with fibrotic interstitial lung disease
, American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449XBackground. Fibrotic interstitial lung diseases (ILDs) cause loss of forced vital capacity (FVC) and increased risk of death over time. Most clinical trials aim to slow FVC decline and reduce mortality. However, the association of lower FVC with higher mortality will bias simple estimates of differences in FVC progression between groups. Therefore, both the time-dependent decline in FVC and increase in mortality should be jointly modelled.Methods. We developed a Bayesian, joint mixed effects disease progression model (DPM), using minimally informative prior distributions, for FVC trajectory and the hazard for ILD-related mortality over time. This model minimizes bias due to mortality in estimating differences in the rate of FVC decline and is suitable for use when characterizing populations or in estimating a treatment effect in a clinical trial. The DPM was applied to individual patient data from prospective cohort studies of fibrotic ILD.Results. The DPM yields a higher estimated rate of FVC decline (6.0 vs 4.7%/year) and a more precise fit than a linear mixed model of FVC alone, and replicates the non-linear pattern in the observed data. By modelling the full FVC trajectory rather than only the change from baseline at a given time point, the DPM increases the information from each patient and reduces both the time to information and the effect of variability in baseline FVC measurements on the estimation of treatment effects.Conclusions. The joint DPM provides an integrated approach to minimizing bias in the estimation of treatment effects in clinical trials in fibrotic ILDs.
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Journal articleCustovic D, Custovic A, Gern J, et al., 2026,
Reply.
, J Allergy Clin Immunol -
Journal articleBonner KL, Fontanella S, Gore M, et al., 2026,
Lower airway immunophenotyping in severe preschool wheeze reveals distinct clusters described by heterogeneity in neutrophil phenotypes.
, Am J Respir Crit Care Med, Vol: 212, Pages: 733-745RATIONALE: Recurrent preschool wheeze accounts for most childhood hospitalizations for asthma and often responds poorly to inhaled corticosteroids (ICSs). OBJECTIVE: To relate lower airway immune cell composition in children with recurrent severe wheeze (RSW) to infection, allergic sensitization, and prescribed treatments. METHODS: Children with RSW aged 1 to 5 years underwent clinical phenotyping, bronchoscopy, multiparameter flow cytometry of blood and bronchoalveolar lavage (BAL) to characterize leukocytes, and assessments of lower airway bacterial and viral infection. An unsupervised analysis was undertaken to uncover clusters of airway inflammation. MEASUREMENTS AND MAIN RESULTS: Of 106 children (median age 36.5 months), 32% had allergic sensitization. Lower airway immune cells were similar in type and abundance in sensitized and nonsensitized children. However, significantly more nonsensitized wheezers had positive BAL bacterial culture. Bacterial infection was associated with neutrophils with low CD62L and CXCR2 expression. Children without airway bacterial infection also had up to 50% neutrophils but with high CD62L and CXCR2 expression. The data-driven analysis revealed 3 clusters: cluster 1, airway infection predominant with CD62Llo neutrophils; cluster 2, eosinophil/lymphocyte rich with CD62Lhi neutrophils; and cluster 3, low infection rate with CD62Lhi neutrophils. The clusters were independent of clinical features, prescribed ICSs, antibiotics, and allergic sensitization. CONCLUSIONS: Airway inflammation in RSW is heterogeneous. A subgroup had airway neutrophilia but with distinct neutrophil subtypes. Those with bacterial infection had CD62Llo neutrophils (cluster 1). Others had CD62Lhi neutrophils (clusters 2 and 3). Intervention trials stratifying using these clusters may provide a novel management approach.
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Journal articleGonzalez-Estrada A, Estrada-Mendizabal RJ, Ansotegui IJ, et al., 2026,
World Allergy Organization survey on the diagnosis and management trends of perioperative anaphylaxis.
, World Allergy Organ J, Vol: 19, ISSN: 1939-4551BACKGROUND: Perioperative anaphylaxis (POA) is a life-threatening condition with substantial variability in evaluation and management practices. OBJECTIVE: To assess current practices, perceived barriers, and regional differences in POA management among allergists worldwide. METHODS: A cross-sectional online survey was distributed to World Allergy Organization (WAO) members from March to June 2024. The 39-question survey addressed demographics, clinical practices, diagnostic tools, perceived challenges, and future needs. RESULTS: A total of 249 respondents from 50 countries completed the survey (median age 49 years, 49% female, 94% allergists, and 57% with >15 years of clinical experience). While 70% had access to acute serum tryptase (sAT), only 46% obtained it within the recommended 2-h window. Guideline adherence was low: 63% did not perform skin testing 4-6 weeks post-reaction, and fewer than half routinely tested for latex or chlorhexidine. Regional differences were observed: routine latex and chlorhexidine testing was most common in Europe and United States/Canada and least frequent in Africa and Asia (p = 0.0001); tryptase availability was lower in Africa and Latin America. Most respondents identified a culprit in <65% of cases, with antibiotics reported most frequently in Europe and United States/Canada, followed by neuromuscular blocking agents and non-steroidal anti-inflammatory drugs (NSAIDs). Major barriers included limited access to anesthesia records, testing reagents, and resource-related contrainsts in low-income regions. Respondents expressed the need for guidelines on alternative agents and validated non-irritating skin test concentrations. CONCLUSIONS: This international survey highlights substantial regional differences and global barriers in POA evaluation. Improving access to diagnostic resources, enhancing interdisciplinary collaboration, and providing clear guidance on alternative agents and standardized testing methods are essential to
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