Innate immune responses are increased in children with acute asthma exacerbation.

BACKGROUND: Little is known about the immune responses during acute asthma exacerbation. In this study, we examined immune responses in children following an acute asthma exacerbation. METHODS: We evaluated pro-inflammatory cytokine levels and gene expression profiles in blood samples from pediatric patients admitted for acute asthma exacerbation. Viral PCR was performed to differentiate between viral or non-viral-associated exacerbations. RESULTS: Following informed consent, clinical data were obtained from 20 children with asthma (median [interquartile range, IQR]: age 11.5 [8.0, 14.2]) years and 14 healthy age-matched controls (10.5 [7.0, 13.0]). Twelve had positive nasopharyngeal Polymerase chain reaction (PCR) for viral infection (11 rhinoviruses and 1 respiratory syncytial virus (RSV)). Nine were in the pediatric intensive care unit (PICU) and among them five required continuous positive airway pressure (CPAP). Mean (±SD) days on systemic steroids before drawing blood sample were 2.5 ± 1.6. Twelve had history of environmental allergies with 917 (274, 1396) IU/mL total IgE (median (IQR)). Compared with controls, IL-1RA and IL-10 levels were significantly increased and TNF-α significantly decreased in asthma subjects (p < .05 for all). RNA-seq analysis revealed 852 differentially expressed genes in subjects with asthma. Pathway analysis found upregulated genes and pathways involved in innate immune responses in subjects with asthma. Significantly reduced genes included pathways associated with T helper cell differentiation and activation. CONCLUSIONS: In acute asthma exacerbation, innate immune pathways remained increased while adaptive immune responses related to T helper cells are blunted and are independent of trigger or asthma severity. Our novel findings highlight the need to identify new therapies to target persistent innate immune responses to improve outcomes in acute asthma.

Predictors of recurrent wheezing in late preterm infants.

INTRODUCTION: Premature infants have an increased risk of respiratory morbidity, including the development of recurrent wheezing. We sought to determine perinatal factors in late preterm infants associated with an increased risk of recurrent wheezing in the first 3 years of life. METHODS: A retrospective chart review of infants born between 32 and 36 weeks gestational age at a tertiary hospital from 2013 to 2016 was performed. Infants with any co-morbid medical conditions were excluded. Recurrent wheezing was identified by two or more visit diagnoses for reactive airway disease, wheezing-associated respiratory infection, wheezing, or asthma during the first 3 years of life. Those with recurrent wheezing were compared to matched preterm infants who did not develop wheezing. RESULTS: Three hundred and fourteen late preterm infants were included in this study; 210 infants developed recurrent wheezing while 104 did not. Gender, sex, and race were comparable between both groups. Development of wheezing was associated with positive family history of asthma (p = .014), receiving antibiotics during the neonatal period (p < .001), requiring continuous positive airway pressure for <24 h (p = .019), and receiving supplemental oxygen during the newborn period (p = .023). CONCLUSION: This study retrospectively identified risk factors associated with development of wheezing in late preterm infants. Prospective studies are needed to determine whether these factors will predict recurrent wheeze in this patient population.

The 80th anniversary of Annals of Allergy, Asthma & Immunology (1943-2023).

The year 2023 marks the 80th year of publication of Annals of Allergy, Asthma & Immunology. To celebrate this important milestone, we look back on the history of the journal from its inception to the present day. This special article explores the rationale and people involved in creating the journal and highlights major advances in Annals history. Our celebration of Annals' 80th year of publication concludes with a glimpse into the potential future of Annals.

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Sterols and immune mechanisms in asthma.

The field of sterol and oxysterol biology in lung disease has recently gained attention, revealing a unique need for sterol uptake and metabolism in the lung. The presence of cholesterol transport, biosynthesis, and sterol/oxysterol-mediated signaling in immune cells suggests a role in immune regulation. In support of this idea, statin drugs that inhibit the cholesterol biosynthesis rate-limiting step enzyme, hydroxymethyl glutaryl coenzyme A reductase, show immunomodulatory activity in several models of inflammation. Studies in human asthma reveal contradicting results, whereas promising retrospective studies suggest benefits of statins in severe asthma. Here, we provide a timely review by discussing the role of sterols in immune responses in asthma, analytical tools to evaluate the role of sterols in disease, and potential mechanistic pathways and targets relevant to asthma. Our review reveals the importance of sterols in immune processes and highlights the need for further research to solve critical gaps in the field.

Low-Dose Lipopolysaccharide Protects from Lethal Paramyxovirus Infection in a Macrophage- and TLR4-Dependent Process.

Respiratory diseases are a major public health burden and a leading cause of death and disability in the world. Understanding antiviral immune responses is crucial to alleviate morbidity and mortality associated with these respiratory viral infections. Previous data from human and animal studies suggested that pre-existing atopy may provide some protection against severe disease from a respiratory viral infection. However, the mechanism(s) of protection is not understood. Low-dose LPS has been shown to drive an atopic phenotype in mice. In addition, LPS has been shown in vitro to have an antiviral effect. We examined the effect of LPS treatment on mortality to the murine parainfluenza virus Sendai virus. Low-dose LPS treatment 24 h before inoculation with a normally lethal dose of Sendai virus greatly reduced death. This protection was associated with a reduced viral titer and reduced inflammatory cytokine production in the airways. The administration of LPS was associated with a marked increase in lung neutrophils and macrophages. Depletion of neutrophils failed to reverse the protective effect of LPS; however, depletion of macrophages reversed the protective effect of LPS. Further, we demonstrate that the protective effect of LPS depends on type I IFN and TLR4-MyD88 signaling. Together, these studies demonstrate pretreatment with low-dose LPS provides a survival advantage against a severe respiratory viral infection through a macrophage-, TLR4-, and MyD88-dependent pathway.

Immunopathology of Differing Viral Infection in Allergic Asthma Disease.

The pathophysiology of asthma development is heterogenous. Although complex interactions between factors are present in any one individual, early life viral infections have been shown to play a major role through induction of epithelial damage as well as various innate and adaptive immune responses. The cytokine profile that results from epithelial damage leads to Th2 skewing of the adaptive immune response. Most asthma exacerbations in children and up to half of adults are related to viral infections that also induce epithelial damage and an acute predominately Th2 inflammatory response, leading to acute symptoms and chronic airway remodeling.