Journal of Allergy and Clinical Immunology

BackgroundPathway-based approaches may effectively dissect the polygenic architecture of complex diseases. We conducted a semi-explorative interaction study between genome-wide and pathway-specific polygenic risk scores (PRS) and occupational asthmagens (i.e., cleaning agents) on adult asthma. MethodsThis study included 2615 adults from the Personalized Environment and Genes Study (PEGS) in North Carolina, with comprehensive questionnaire-based health and exposure data and whole genome sequenci...

Asthma is one of the most common chronic diseases globally. There are various risk factors for asthma, including respiratory infections, like rhinovirus and respiratory syncytial virus infections. Nevertheless, impacts from non-respiratory tract infections on asthma remain unresolved. Globally, enteric infections are the most common infections. Their target organ, the intestinal system, shares the same embryonic origin, the endoderm, as the respiratory tract. These led us to inspect the potentia...

Biologic monoclonal antibody therapies for severe asthma target the Type 2 endotype through blockade of the IgE, IL-5/eosinophil, or IL-4/13 pathways, which represents at least two-thirds of patients, and have led to significant clinical benefits in severe asthma management. However, studies show that 10-20% of patients may be non-responders and require a change in therapy. There is also the emerging concept that a significant percentage of patients may enter clinical remission, with a very hig...

RationaleAsthma is a chronic airway disease driven by multiple immunologic pathways that determine the clinical response to therapy. Current diagnostic methods are incapable of discriminating subtypes of asthma and guiding targeted treatment. We hypothesized that sputum cytokine profiles could help to identify immunologically-defined disease subtypes and individualize therapy in patients with severe asthma. ObjectivesDefine asthma subtypes associated with sputum alarmin and cytokine levels. Me...

BackgroundChronic rhinosinusitis (CRS) is characterized by persistent nasal and paranasal sinus mucosa inflammation. It comprises two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies. ObjectiveThis study investigated the phenotypic...

The prevalence, inter-relationships, and longitudinal behavior of type 1 (T1) and type 2 (T2) immune responses in asthma are uncertain, as is the role of viruses as determinants of these responses. Here, we performed whole transcriptome network analysis on sputum cells collected from Severe Asthma Research Program (SARP)-3 patients before and after treatment with intramuscular corticosteroid and again at 1 and 3-year follow-up visits. We used network analysis to analyze whole-transcriptome gene ...

BackgroundEffective initial asthma treatment in primary care requires a comprehensive assessment of airway inflammation and lung function impairment, including small airway dysfunction (SAD). We investigated the prevalence of type 2 (T2) inflammation and SAD in treatment-naive patients with uncontrolled asthma who received primary care, and assessed the utility of the Asthma Control Questionnaire-5 (ACQ-5) as a potential indicator of these factors. MethodsThis single-center retrospective study ...

BackgroundMepolizumab is a therapy for severe asthma. However, studies on mepolizumab with external validity and diverse population from the US are lacking. There is little knowledge of the characteristics of people that discontinue mepolizumab in clinical care. ObjectiveTo investigate the real-world efficacy and time to clinical discontinuation of mepolizumab, we evaluated individuals with asthma started on mepolizumab at the Cleveland Clinic. We hypothesized that there are characteristics tha...

Biologic treatment options have expanded considerably for severe asthma, transforming patient management, but only ~70% of patients respond to the treatment following standard criteria. This preliminary study utilized data collected in the Wessex AsThma CoHort of difficult asthma (WATCH) study. DNAm was measured in n=15 severe asthma patients at baseline, i.e., before mepolizumab (MEPO), an interleukin-5 receptor antagonist, was administered and the response to MEPO was analyzed. We aimed to as...

BackgroundTrials have not directly compared biologics for the treatment of asthma. ObjectiveTo comparative the relative efficacy of biologics in asthma. MethodsWe searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to May 31, 2022, for randomized trials addressing biologic therapies for asthma. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist network meta-analysis and assessed the certai...

This study explores the potential of nasal secretions to serve as a source of biomarkers for diagnosing respiratory conditions. A total of 40 inflammatory biomarkers were detected and quantified in participants with upper respiratory diseases, including chronic rhinosinusitis (CRS), allergic rhinitis, and viral and bacterial infections. The different expression levels of various biomarkers could distinguish CRS participants with and without nasal polyps (i.e. CRP, GzmB, IL-4, MMP-1, MMP-8, SAA a...

BackgroundAmong the members of the Transient Receptor Potential (TRP) family, TRPV1 is distinguished as the primary receptor involved in thermal pain perception, closely associated with temperature changes. Acting as a critical nociceptor and thermosensitive receptor, TRPV1 is pivotal in the domain of allergic diseases. Despite its significance, there is a discernible lack of comprehensive reviews exploring the interactions between TRPV1 and allergic conditions in the academic literature. This s...

BACKGROUNDPatients with severe asthma often suffer from comorbidities whose impact on the course of biological therapy has not been elucidated yet. OBJECTIVETo evaluate real-life effectiveness and the presence/absence of predictors of treatment response in patients with one or more comorbidities who received mepolizumab (MEPO) for the treatment of severe eosinophilic asthma (EA). METHODSHealth records of 31 patients were retrospectively analyzed. Asthma control test (ACT) score, blood eosinoph...

RationaleNon-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined. ObjectivesTo investigate the dynamics of nasal mediators during ASA provocation in N-ERD patients before and twenty-four weeks after therapy with the IL-4 recep...

BackgroundPatients with severe asthma may have a greater risk of dying from COVID-19 disease caused by SARS-CoV-2 virus. Angiotensin converting enzyme 2 (ACE2) receptor and enzyme proteases, transmembrane protease, serine 2 (TMPRSS2) and furin are needed for the attachment and invasion of the virus into host cells. We determined whether their expression in the airways of severe asthma patients is increased. MethodWe examined the microarray mRNA expression of ACE2, TMPRSS2 and furin in the sputu...

IntroductionWhile reliable, quantitative in vitro testing for sensitivity to aeroallergens has been available for decades, if and how asthma severity markers might be predictably expressed in clusters matched for comparable multiple sensitizations is unknown. ObjectiveOur aim is to use machine learning techniques to explore how allergic poly-sensitization (APS) clusters may serve as precision markers in adult urban patients with moderate to severe asthma. MethodsWe constructed a database of se...

BackgroundAsthma has been associated with impaired interferon responses. Multiple cell types have been implicated in these impaired responses and may be responsible for increased exacerbations and immunopathology of asthma. ObjectiveCharacterize the single-cell response to Poly I:C of peripheral blood mononuclear cells (PBMCs) of patients with severe asthma (SA). MethodsTwo complementary single-cell methods, DropSeq for single-cell RNA sequencing (scRNA-Seq) and mass cytometry (CyTOF), were us...

Exposure to respiratory syncytial virus (RSV) during childhood is nearly ubiquitous by age two, and infants who develop severe RSV bronchiolitis are more likely to develop asthma later in life. In the Factors Influencing Pediatric Asthma (FIPA) study including 319 children from a Northern Plains American Indian community, we found 73% of children to have high concentrations of RSV-specific IgG (>40 IU/mL). High concentration of RSV-specific IgG was associated with increased exposure to second-ha...

BackgroundAsthma is an umbrella diagnosis encompassing distinct pathophysiological mechanisms. While a global problem, our understanding of the interplay between respiratory microbiology and airway inflammation is largely from populations in high income settings. As a result, treatment approaches align poorly with asthma characteristics in less studied populations. ObjectiveTo identify conserved and geographically distinct relationships between airway inflammation and microbiota characteristics...

IntroductionIL-4 receptor (IL-4R)-mediated alternative activation of macrophage drives type 2 airway inflammation. Cadherin-26 (CDH26) upregulates epithelial type II IL-4R signaling in asthma. However, whether CDH26 contributes to type I IL-4R-mediated macrophage activation and the mechanism by which CDH26 upregulates IL-4R expression remains unknown. MethodsCDH26 expression in bronchoalveolar lavage cells of asthma patients was examined using quantitative PCR and immunostaining. Airway inflamm...