Dupilumab Treatment for Aspirin-Exacerbated Respiratory Disease in a Real-World Setting: Impact on Quality of Life and Healthcare Utilization.

Background: Patients with aspirin-exacerbated respiratory disease (AERD) have difficult-to-treat asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and often require treatment with biologic therapy for asthma or CRSwNP. Healthcare utilization in patients with AERD has not been well described since the advent of respiratory biologics.

Objective: To determine real-world healthcare utilization and quality of life among patients with AERD and to understand the impact of dupilumab, a monoclonal antibody targeting the interleukin 4 receptor, on patient-reported health outcomes and healthcare utilization.

Dupilumab rapidly improves eustachian tube dysfunction and otologic symptoms in aspirin-exacerbated respiratory disease.

Patients with aspirin-exacerbated respiratory disease (AERD) frequently experience symptoms consistent with eustachian tube dysfunction (ETD), which can substantially impair patient quality of life. We analyzed a cohort of 98 adult patients with AERD who participated in a longitudinal, survey-based study. By assessing data over 1 year, we established that, in patients with AERD, the ear/facial subdomain of the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire could predict performance on the 7-item Eustachian Tube Dysfunction Questionnaire, a validated instrument for the diagnosis of ETD.

Effect of Tezepelumab on Sino-Nasal Outcome Test (SNOT)-22 Domain and Symptom-Specific Scores in Patients with Severe, Uncontrolled Asthma and a History of Chronic Rhinosinusitis with Nasal Polyps.

Introduction: Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2 years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes.

Determinants of persistence and recovery of chronic coronavirus disease 2019 chemosensory dysfunction.

Background: In 2% to 4% of patients, coronavirus disease 2019 (COVID-19) chemosensory dysfunction (CSD) persists beyond 6 months, accounting for up to 4 million people in the United States. The predictors of persistence and recovery require further exploration.

Objective: We sought to define the predictors of recovery and assess the quality of CSD in registry subjects with self-reported persistent smell and taste dysfunction after COVID-19.

Peanut-specific IgG subclasses as biomarkers of peanut allergy in LEAP study participants.

Antigen-specific IgG2 and IgG3 are rarely measured in food allergy clinical trials despite known function in preventing mast cell and basophil activation. Our objective was to determine whether measuring peanut-specific IgG2 and IgG3 levels would correlate with peanut allergy status. Peanut-specific IgG subclasses were measured via ELISA assays in Learning Early About Peanut allergy (LEAP) trial participants at 5 years of age and were correlated with peanut allergy vs peanut sensitization vs non-peanut allergic and peanut consumption vs peanut avoidance.

Nasal brushing molecular endotyping distinguishes patients with chronic rhinosinusitis with nasal polyps with better response to dupilumab.

Background: There is evidence of pathophysiologic diversity in chronic rhinosinusitis with nasal polyps (CRSwNP), but data characterizing the molecular endotypes of CRSwNP and their association with treatment are lacking.

Objective: This study aimed to identify gene signatures associated with CRSwNP endotypes, clinical features, and dupilumab treatment response.

Methods: Nasal brushing samples were collected from 89 patients randomized to dupilumab 300 mg every 2 weeks or placebo in the SINUS-52 trial (NCT02898454).

Follow-up to Adolescence after Early Peanut Introduction for Allergy Prevention.

Background: A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption.

Ratio of plasma IL-13/TNF- ∝ and CXCL10/CCL17 predicts mepolizumab and omalizumab response in asthma better than eosinophil count or immunoglobulin E level.

To date, most studies to identify biomarkers associated with response to the anti-interleukin 5 agent, mepolizumab, and to the anti-immunoglobulin E agent, omalizumab have focused on clinically available biomarkers, such as the peripheral blood eosinophil counts (BEC) and total immunoglobulin E (IgE). However, these biomarkers often have low predictive accuracy, with many patients with eosinophilic or allergic asthma failing to demonstrate clinical response to mepolizumab or omalizumab respectively. In this study, we evaluated the association of baseline pre-biologic plasma levels of 26 cytokines and chemokines, including T-helper 1 (Th1)-, Th2-, Th17-related cytokines, and their ratios with subsequent clinical response to mepolizumab or omalizumab.

Adult-onset asthma, allergy, and aspirin hypersensitivity associate with self-reported food avoidance.

Background: The adoption of avoidance diets by adult-onset asthmatics has not previously been studied. We hypothesized that avoidance diets would associate with adult-onset asthma, allergy, and aspirin-exacerbated respiratory disease (AERD).

Methods: A total of 1247 subjects with adult-onset asthma (age range: 31-91) from the Finnish national registry, and age- and sex-matched controls ( = 1970) participated in a questionnaire study in 1997.

IL-4Rα signaling promotes barrier-altering oncostatin M and IL-6 production in aspirin-exacerbated respiratory disease.

Background: Aspirin-exacerbated respiratory disease (AERD) is a severe disease involving dysregulated type 2 inflammation. However, the role other inflammatory pathways play in AERD is poorly understood.

Objective: We sought to broadly define the inflammatory milieu of the upper respiratory tract in AERD and to determine the effects of IL-4Rα inhibition on mediators of nasal inflammation.

TCF1-LEF1 co-expression identifies a multipotent progenitor cell (T2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (T2) cells with co-expression of TCF7 and LEF1, and features of chronic activation.

A nasal cell atlas reveals heterogeneity of tuft cells and their role in directing olfactory stem cell proliferation.

The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. Among them, microvillous cells (MVCs) are strategically positioned at the apical surface, but their specific functions are enigmatic, and their relationship to the other specialized epithelial cells is unclear.

Lung function trajectories in a cohort of patients with moderate-to-severe asthma on mepolizumab, omalizumab, or dupilumab.

Background: Lung function is an independent predictor of mortality. We evaluated the lung function trajectories of a cohort of patients with asthma receiving biologic therapy.

Methods: We identified 229 monoclonal antibody-naïve adult patients with moderate-to-severe asthma who initiated omalizumab, mepolizumab, or dupilumab between 2010 and 2022 in a large healthcare system in Boston, MA.

Validation of a questionnaire assessing smell loss in an international aspirin-exacerbated respiratory disease population.

Olfactory dysfunction (OD) and smell loss affects aspects of patients' everyday life and lowers their quality of life. OD questionnaires are considered one of the core-outcome measures in chronic rhinosinusitis, but many existing smell loss questionnaires contained pandemic-prohibitive questions on social gatherings or restaurant visits, were too culture specific or gender specific, or were overly long and cumbersome. We aimed to develop a new brief questionnaire to assess the impact and consequences of smell loss and its burden on daily life.

Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

Background: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs.

Objective: We assessed the association between reported NSAID ADRs and postpartum opioid utilization.

Increased epithelial mTORC1 activity in chronic rhinosinusitis with nasal polyps.

Background: The airway epithelium plays a central role in the pathogenesis of chronic respiratory diseases such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), but the mechanisms by which airway epithelial cells (EpCs) maintain inflammation are poorly understood.

Objective: We hypothesized that transcriptomic assessment of sorted airway EpCs across the spectrum of differentiation would allow us to define mechanisms by which EpCs perpetuate airway inflammation.

Methods: Ethmoid sinus EpCs from adult patients with CRS were sorted into 3 subsets, bulk RNA sequenced, and analyzed for differentially expressed genes and pathways.

Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis.

Should Biologics Be Used Before Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease?

There has been a paradigm shift in the management of aspirin-exacerbated respiratory disease (AERD). It started in 2015 when the first biologic was Food and Drug Administration (FDA) approved for severe eosinophilic asthma. Thus, there emerged a new era in the treatment of patients with type 2-mediated airway diseases.