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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 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 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 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 articleCustovic D, Custovic A, Gern J, et al., 2026,
Reply.
, J Allergy Clin Immunol -
Journal articleAnanth S, Aerts J, Chotirmall SH, et al., 2026,
Find your career: the ERS "My Career Path" series.
, Breathe (Sheff), Vol: 22, ISSN: 1810-6838The ERS "My Career Path" series provides an excellent insight into different subspecialties in respiratory medicine. All episodes can be found on the ERS Respiratory Channel. https://bit.ly/4sADqiS.
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Journal articleSousa-Pinto B, Bousquet J, Vieira RJ, et al., 2026,
Allergic Rhinitis and Its Impact on Asthma (ARIA)-EAACI Guidelines-2024-2025 Revision: Part I-Guidelines on Intranasal Treatments.
, Allergy, Vol: 81, Pages: 954-976BACKGROUND: Allergic rhinitis (AR) impacts quality of life, work and school productivity. Over the last years, an important body of evidence resulting from mHealth data has led to a better understanding of AR. Such advances have motivated an EAACI-endorsed update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (ARIA 2024-2025). This manuscript presents the ARIA 2024-2025 recommendations for intranasal treatments, one of the mainstays for AR management. METHODS: The ARIA 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgments and recommendations, including systematic reviews, evaluation of mHealth and pharmacovigilance data, as well as a survey of experts on costs. RESULTS: Eleven guideline questions concerning intranasal treatments for AR were prioritized, leading to recommendations. Overall, these questions concern the choice between different classes of intranasal medications-most notably, intranasal corticosteroids (INCS), antihistamines (INAH), fixed combinations of INAH+INCS and decongestants-or between different individual medications within each class. Four questions had not been evaluated in previous ARIA guidelines, while for the other three there was a change in the strength or directionality of recommendations. Overall, recommendations point to the suggested use of INAH+INCS over INAH or INCS and INCS over INAH. CONCLUSION: This ARIA 2024-2025 article supports patients, their caregivers, and healthcare professionals in choosing an intranasal treatment. However, decisions on AR treatment should consider the clinical variability of the disease, patients' values, and the affordability of medications.
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Journal articleKarp T, Merid SK, Kermani NZ, et al., 2026,
Nasal gene expression shows a distinct signature in type 2-high asthma but not in type 2-low disease.
, J Allergy Clin Immunol, Vol: 157, Pages: 879-889BACKGROUND: Type 2 (T2)-low asthma is defined by low levels of T2 inflammation and is associated with resistance to inhaled corticosteroids. Its molecular mechanisms are mostly unknown, and treatment options are limited. We previously showed that nasal brush transcriptomes differ between asthma and controls, reflecting disease-relevant biology. OBJECTIVE: We explored nasal gene expression related to T2-low asthma in the ATLANTIS cohort. METHODS: We compared nasal brush RNA sequencing data between 82 T2-low and 63 T2-high asthma patients and 57 controls. T2-low asthma was defined as blood eosinophil counts < 0.15 × 109/L and Feno < 25 ppb and T2-high as blood eosinophil counts > 0.3 × 109/L and Feno > 25 ppb. Weighted gene coexpression network analysis (WGCNA) was applied to identify gene modules associated with T2-low asthma. The BAMSE and U-BIOPRED cohorts were used for replication analyses. RESULTS: Although differentially expressed genes were found in patients with T2-high asthma across all 3 cohorts, no differentially expressed genes were observed in individuals with T2-low disease compared to controls in ATLANTIS, nor consistently across other cohorts. Our assessment of molecular heterogeneity could not attribute this result to greater intersample variability within the T2-low group. WGCNA in ATLANTIS identified "black" and "purple" gene modules linked to T2-low asthma, with genes enriched in T-cell immunity and ribosomal RNA biology pathways, respectively. The "black" module was replicated in U-BIOPRED and showed the same direction in BAMSE. CONCLUSION: T2-high asthma shows a distinct nasal gene expression signature compared to healthy controls, while patients with T2-low asthma exhibit no consistent changes. Future studies should explore T-cell immunity in T2-low asthma and integrate lower airway multiomics data.
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Journal articleFreeman A, Rink S, Bansal AT, et al., 2026,
Multimorbidity phenotypes and associated characteristics in severe asthma: an observational study of European severe asthma registries.
, Lancet Reg Health Eur, Vol: 63BACKGROUND: The phenotypic nature of multimorbidity in severe asthma is poorly understood. Our aims in this study were to define multimorbidity phenotypes and their characteristics in severe asthma across Europe by identifying and characterising co-aggregation of comorbidities. METHODS: Cross-sectional patient data were analysed from the pan-European Severe Heterogenous Asthma Research Collaboration: Patient Centred (SHARP) Central database of national severe asthma registries. Patients were grouped by four European regions (North, South, East, and West). Hierarchical clustering of comorbidities was applied to characterise the correlation structure of the ten commonest comorbidities within these geographical regions. Subsequent multimorbidity phenotypes (MMP) and their clinical features were then defined. FINDINGS: Data were available for 2690 severe asthma patients and 23 comorbidities from 11 countries. Three comorbidity clusters were consistently seen across the four European regions: 1) osteoporosis plus steroid-induced weight gain, 2) eczema plus rhinitis, and 3) chronic sinusitis plus nasal polyps. Four further comorbidities (obesity, bronchiectasis, gastro-oesophageal reflux disease, psychological factors) showed variable clustering. Multimorbidity was ubiquitous. Patients were assigned multimorbidity phenotypes (MMP) according to comorbidity cluster alignment. MMP sn (sinonasal-associated) and MMP u (no specific cluster alignment) were commonest. MMP ster (steroid-associated multimorbidity) had highest maintenance oral steroid (m-OCS) use, and Body Mass Index, plus worst lung function, asthma control, and asthma exacerbation frequency. MMP max (maximal multimorbidity) showed high prevalence of variably assigned comorbidities, higher m-OCS and biologic treatment needs. INTERPRETATION: Multimorbidity is common in severe asthma and can be classified into replicable novel phenotypes with characteristic clinical traits and outcomes. Recognising these phenotypes c
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Journal articleBush A, 2026,
Childhood Environmental Exposures and Adult Disease.
, Pediatr Pulmonol, Vol: 61The association of early life adverse events with worse adult outcomes was first proposed by David Barker, the Developmental Origins of Health and Disease (DOHaD). Subsequently we have learned that adverse exposures are not merely important during pregnancy, but also exert transgenerational effects. Most of our knowledge derives from studies of nicotine and tobacco exposure. Adverse intrauterine exposures lead to low birth weight and premature delivery; altered airway and parenchymal structure; altered immune function; sensitization to later adverse exposures; and premature aging manifest by premature telomere shortening. Impaired spirometry for most tracks from birth to late middle age, and especially a low forced vital capacity, is associated with premature respiratory and all cause morbidity and mortality. Childhood exposure to passive smoking exacerbates antenatal effects on lung function, as does pollution. Pollution also increases the risk of early life respiratory infection which are a cause of impaired lung function in at least some studies, and also are associated with premature mortality. Diseases traditionally thought of as arising in adult life, including late-onset and occupational asthma, chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis all have their roots in early life adverse exposures, especially childhood onset smoking. Smoking provides proof of concept that prevention of adult disease must start earlier than adult life if it is to be effective. It is also likely that other early adverse exposures contribute to adult disease. Political action is needed to counteract the view that children "just grow out of it". They do not.
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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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Journal articleOgbogu PU, Roufosse F, Akuthota P, et al., 2026,
Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial.
, Nat MedBenralizumab, an eosinophil-depleting anti-IL-5 receptor α antibody, has demonstrated efficacy in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis and shown promising results in hypereosinophilic syndrome (HES). NATRON was a randomized, double-blind placebo-controlled phase 3 study evaluating the efficacy and safety of benralizumab in FIP1L1::PDGFRA-negative HES. The primary endpoint was time to first HES flare. In total, 133 patients (median (range) age 51 (14-87) years, 62% female) were randomized (1:1) to receive benralizumab 30 mg every 4 weeks or placebo for 24 weeks, in addition to background therapy. Benralizumab significantly reduced the risk of first flare versus placebo (hazard ratio 0.35, 95% CI 0.18 to 0.69, P = 0.0024). Adverse events occurred in 64.2% and 66.7% of benralizumab- and placebo-treated patients, respectively. Benralizumab's safety was consistent with its known profile. These results demonstrate the efficacy and safety of add-on benralizumab in the treatment of HES. ClinicalTrials.gov identifier: NCT04191304 .
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Journal articleMassenet T, Bosman P, Schleich F, et al., 2026,
Evaluating off-line exhaled breath sampling techniques: a comparative study of practices for clinical implementation.
, J Breath Res, Vol: 20Exhaled breath analysis represents a promising non-invasive approach for disease monitoring through volatile organic compounds (VOCs) detection. However, the lack of standardized sampling methods do not enable direct clinical translation. This study compared three widely used offline breath sampling techniques (Tedlar® bags, BioVOC-2®, and ReCIVA®) using the established peppermint benchmarking protocol and comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC × GC-MS). Seven healthy participants completed the peppermint experiment, with breath samples collected at multiple time points following capsule ingestion. Washout curves for targeted terpenoid compounds were analyzed to assess analytical performance, reproducibility, and background contamination across devices. Clinical feasibility was evaluated through focus groups with clinicians, researchers, and study participants. Tedlar® bags demonstrated reliable performance with lowest overall pooled relative standard deviations, though sensitive to exogenous contamination. ReCIVA® showed higher overall variability, superior selectivity and reduced background interference compared to Tedlar® bags (p< 0.01). However, ReCIVA® showed higher complexity, cost, reduced comfort and potential for saliva contamination during extended sampling. BioVOC-2® offered operational simplicity but was limited by small sampling volume (129 ml) reducing its sensitivity and manual handling variability. No single device emerged as universally optimal. Tedlar® bags, when accompanied by rigorous standard operating procedures, remain most suitable for large-scale studies, BioVOC-2® for rapid targeted screening, and ReCIVA® for controlled research requiring high selectivity. Successful clinical implementation will require balancing analytical performance with practical considerations including patient comfort, cost-effectiveness, and workflow integration. These fin
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Journal articleWu Z, Moor K, Wijsenbeek M, et al., 2026,
The impact of disease severity and symptoms on anxiety and depression in individuals with idiopathic pulmonary fibrosis.
, ChestBACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating, life-limiting fibrotic lung disease. Symptoms including breathlessness, cough, and fatigue, together with disease severity, contribute to psychological burden, yet the relationship between these factors and anxiety and depression remains unclear. RESEARCH QUESTION: We investigated the prevalence and severity of anxiety and depression, and their association with symptoms and disease severity, in patients with IPF using Hospital Anxiety and Depression Scales (HADS). STUDY DESIGN AND METHODS: This observational study prospectively recruited incident IPF patients. HADS, Dyspnoea-12, Leicester Cough Questionnaires (LCQ), cough visual analog scales (VAS), and lung function data were collected at baseline and 12 months. RESULTS: 269 IPF patients were recruited; 157 completed follow-up. Mean age was 73.5 years; 81% were male. Mean ± standard deviation forced vital capacity (FVC) percent predicted was 79% ± 14.7%. At baseline, the prevalence of anxiety and depression (HADS >8) was 27.5% and 28.2%, respectively. On multivariate analysis, worse baseline Dyspnoea-12 and poorer Living with IPF (L-IPF) energy were independent factors for both anxiety and depression at baseline; younger age was for anxiety. Baseline lung function did not correlate with either HADS-anxiety or HADS-depression. At follow-up, there was a numerical increase in HADS-anxiety scores, which was below reported minimal clinically important difference values, and no notable change in HADS-depression scores. Younger age, higher Dyspnoea-12 scores, and poorer L-IPF energy were associated with greater increases in anxiety. Moderate or weak correlations were observed between changes in HADS and longitudinal changes in patient-reported outcomes (worsening breathlessness, cough, and energy levels). Changes in FVC% predicted did not correlate with HADS. INTERPRETATION: Anxiety and depression are common in patients with IPF and are as
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Journal articleMarques-Mejias A, Bartha I, Ciaccio CE, et al., 2026,
Corrigendum to 'Skin as the target for allergy prevention and treatment' [Annals of Allergy, Asthma & Immunology, Volume 133, Issue 2 (2024) 133-143].
, Ann Allergy Asthma Immunol -
Journal articleZheng Y, Li Y, Zeyneloglu C, et al., 2026,
Risk and Protective Factors for Infection, Severe Disease, and Mortality in Epidemic Respiratory Viruses.
, AllergyThe 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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