Comorbid Asthma Research Articles

Increased di-(2-ethylhexyl) phthalate exposure poses a differential risk for adult asthma clusters

BackgroundDEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are “non-atopic”, lacking a clear etiology.MethodsIn a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman’s rank correlation coefficients, multiple logistic regression, and multinomial logistic regression.ResultsAsthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified.ConclusionThe current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.

Analysis of the potential molecular mechanisms of asthma and gastroesophageal reflux disease

Objective Asthma and gastroesophageal reflux disease (GERD) often occur simultaneously, with GERD being a comorbidity of asthma. This study aimed to explore the biological markers related to asthma and GERD by bioinformatics analysis. Methods Initially, gene expression datasets for asthma and GERD were obtained from the Gene Expression Omnibus database, and subsequent differential expression analysis yielded 620 differentially expressed genes (DEGs) for asthma and 2367 DEGs for GERD. The intersection of these two gene sets yielded a total of 84 DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these genes may be involved in steroid hormone secretion and cellular stress response. Five hub genes (PTGDR2, CPA3, FCER1A, TPSAB1, and IL1RL1) were identified by a protein–protein interaction (PPI) network analysis and topological algorithm. Results Enrichment analysis results indicated that hub genes may be involved in hormone secretion and disease development, particularly in regulating the renin–angiotensin system and systemic arterial blood pressure. PTGDR2, CPA3, TPSAB1, and IL1RL1 were upregulated in both asthma and GERD patient groups, while FCER1A was upregulated in asthma patients but downregulated in GERD patients. Through drug prediction, 22 drugs targeting hub genes PTGDR2, FCER1A, and TPSAB1 were identified. By constructing a transcription factor (TF)-target gene network, we found that eight TFs may regulate the expression of PTGDR2, FCER1A, and IL1RL1. Conclusion Hence, Asthma and GERD were related to steroid hormone secretion and the renin–angiotensin system.

Comparison of the yield of two tuberculosis screening approaches among household contacts in a community setting of Silti Zone, Central Ethiopia: a prospective cohort study

BackgroundHousehold contacts of tuberculosis (TB) patients are at a greater risk of infection and developing TB as well. Despite recommendations to actively screen such high-risk groups for TB, it is poorly implemented in Ethiopia. A community-based household contact screening was conducted to compare the yield of two different screening approaches and to identify factors associated with TB occurrence.MethodsSmear-positive pulmonary TB index cases from six health facilities in six districts of Silti Zone were identified and enrolled prospectively between September 2020 and December 2022. Trained healthcare workers conducted house visits to screen household contacts for TB. WHO (World Health Organization) recommended symptom-based screening algorithms were used. The yield of screening was compared between a two-time screening at study site I and a single baseline screening at study site II, which is the current programmatic approach. Generalized estimating equation was used to run multivariate logistic regression to identify factors associated with TB occurrence.ResultsA total of 387 index TB cases (193 at site I and 194 at site II) with 1,276 eligible contacts were included for analysis. The TB yield of repeat screening approach did not show a significant difference compared to a single screening (2.3% at site I vs. 1.1% at site II, p < 0.072). The number needed to screen was 44 and 87 for the repeat and single screening, respectively, indicating a high TB burden in both settings. The screening algorithm for patients with comorbidities of asthma and heart failure had a 100% sensitivity, 19.1% specificity and a positive predictive value of 5.6%. Cough [AOR: 10.9, 95%CI: 2.55,46.37], fatigue [AOR: 6.1, 95%CI: 1.76,21.29], daily duration of contact with index case [AOR: 4.6, 95%CI; 1.57,13.43] and age of index cases [AOR: 0.9, 95%CI; 0.91–0.99] were associated with the occurrence of TB among household contacts.ConclusionOur study showed that the yield of TB was not significantly different between one-time screening and repeat screening. Although repeat screening has made an addition to case notification, it should be practiced only if resources permit. Cough, fatigue, duration of contact and age of index cases were factors associated with TB. Further studies are needed to establish the association between older age and the risk of transmitting TB.

Profile of Urticaria and Angioedema Patients at Dr. Moewardi General Hospital Surakarta, Indonesia

Background: Urticaria is a heterogeneous inflammatory skin disease that results from the activation and degranulation of cutaneous mast cells, followed by the release of histamine and other mediators that cause sensory nerve activation, vasodilation, plasma extravasation, and recruitment of immune cells. The prevalence and incidence of urticaria and angioedema have been extensively studied worldwide, but there is still limited data in Indonesia, especially regarding the profile of urticaria and angioedema patients. The purpose of this study was to determine the profile of urticaria and angioedema patients at Dr. Moewardi General Hospital for the period January 1st, 2020 - December 31st, 2022.&#x0D; Methods: This study is a cross-sectional retrospective study with secondary data derived from medical records of urticaria and angioedema patients.&#x0D; Results: There were 152 patients with urticaria, most of whom were in the age group &gt;60 years (20.39%), female with a male to female ratio of 1:1.92, and worked as housewives (17.76%) and students (16.45%). Most cases were diagnosed with urticaria (86.84%) with some patients having angioedema (13.16%). The most common comorbidities rhinoconjunctivitis (2.63%), atopic dermatitis (1.97%) and asthma (1.32%). The dominant symptoms were itching and bumps (100%). The main treatment received by patients was single AH1 (71.71%) followed by combination therapy of AH1 and systemic corticosteroids (14.47%), combination therapy of AH1 and topical corticosteroids (10.53%), and the rest received combination therapy of AH1, topical corticosteroids, and systemic corticosteroids (3.29%). The skin prick test was positive in 16 patients (35.56%), with the most common allergens found being peanut (37.5%), egg yolk (37.5%), and tomato (37.5%).&#x0D; Conclusion: The characteristics of urticaria patients were dominated by elderly patients, female gender, and working as housewives or not working. Patients were predominantly diagnosed with urticaria with the most common comorbidities being diabetes mellitus. The main treatment received was AH1 class drugs. The most common types of allergens identified were peanuts, egg yolks, and tomatoes.

Comorbidities associated with adult asthma: a population-based matched cohort study in Finland

BackgroundAsthma is a common chronic disease characterised by variable respiratory symptoms and airflow limitation, affecting roughly 4%–10% of the adult population. Adult asthma is associated with higher all-cause mortality compared...

Proteomic and metabolomic proof of concept for unified airways in chronic rhinosinusitis and asthma

BackgroundThe pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) with comorbid asthma remains unclear. ObjectiveTo assess upper and lower airway unity and identify a possible common pathogenesis in CRSwNP with asthma. MethodsThis study analyzed the expression of proteins and metabolites in nasal lavage fluid cells (NLFCs) and induced sputum cells (ISCs). Differentially expressed proteins and their function-related metabolites in the upper and lower airways of patients having CRSwNP with or without asthma were identified; relevant signaling pathways were analyzed, and key pathway-related proteins were identified. Parallel reaction monitoring was used to verify these target proteins. ResultsProtein or metabolite expression between NLFCs and ISCs was highly correlated and conservative on the basis of expression profiles and weighted gene coexpression network analysis. There were 17 differentially coexpressed proteins and their function-related 13 metabolites that were identified in the NLFCs and ISCs of CRSwNP, whereas 11 proteins and 11 metabolites were identified in CRSwNP with asthma. An asthma pathway was involved in the copathogenesis of upper and lower airways in whether CRSwNP or CRSwNP with asthma. The asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase, as the core of the protein-metabolism interaction networks between the upper and lower airways, were both highly coexpressed in NLFCs and ISCs in patients having either CRSwNP or CRSwNP with asthma by parallel reaction monitoring validation. ConclusionProteomics and metabolomics reveal upper and lower airway unity. Asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase from the upper airway could be used to assess the potential risk of lower airway dysfunction in CRSwNP.

Discovery of common molecular signatures and drug repurposing for COVID-19/Asthma comorbidity: ACE2 and multi-partite networks

ABSTRACT Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global coronavirus disease-2019 (COVID-19) pandemic. This study aimed to elucidate potential therapeutic avenues by scrutinizing approved drugs through the identification of the genetic signature associated with SARS-CoV-2 infection in individuals with asthma. This exploration was conducted through an integrated analysis, encompassing interaction networks between the ACE2 receptor and common host (co-host) factors implicated in COVID-19/asthma comorbidity. The comprehensive analysis involved the identification of common differentially expressed genes (cDEGs) and hub-cDEGs, functional annotations, interaction networks, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and module construction. Interaction networks were used to identify overlapping disease modules and potential drug targets. Computational biology and molecular docking analyzes were utilized to discern functional drug modules. Subsequently, the impact of the identified drugs on the expression of hub-cDEGs was experimentally validated using a mouse model. A total of 153 cDEGs or co-host factors associated with ACE2 were identified in the COVID-19 and asthma comorbidity. Among these, seven significant cDEGs and proteins – namely, HRAS, IFNG, JUN, CDH1, TLR4, ICAM1, and SCD—were recognized as pivotal host factors linked to ACE2. Regulatory network analysis of hub-cDEGs revealed eight top-ranked transcription factors (TFs) proteins and nine microRNAs as key regulatory factors operating at the transcriptional and post-transcriptional levels, respectively. Molecular docking simulations led to the proposal of 10 top-ranked repurposable drug molecules (Rapamycin, Ivermectin, Everolimus, Quercetin, Estradiol, Entrectinib, Nilotinib, Conivaptan, Radotinib, and Venetoclax) as potential treatment options for COVID-19 in individuals with comorbid asthma. Validation analysis demonstrated that Rapamycin effectively inhibited ICAM1 expression in the HDM-stimulated mice group (p < 0.01). This study unveils the common pathogenesis and genetic signature underlying asthma and SARS-CoV-2 infection, delineated by the interaction networks of ACE2-related host factors. These findings provide valuable insights for the design and discovery of drugs aimed at more effective therapeutics within the context of lung disease comorbidities.

Unraveling the Link between Ιnsulin Resistance and Bronchial Asthma.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has proven to be a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

Comparison between upper and lower airway microbiome profiles in chronic rhinosinusitis patients.

Dysregulation of the airway microbiota is thought to contribute to airway inflammation in both chronic rhinosinusitis (CRS) and asthma. However, the relationship between the upper and lower airway microbiome remains unclear. Sinus and lung brushes were collected from 29 CRS participants undergoing sinus surgery. DNA was extracted and submitted for 16s rRNA microbiome sequencing. Alpha and beta diversity metrics, taxonomic composition, and differences between individual taxa were compared for paired sinus and bronchial samples. Twenty-three out of 29 participants had sufficient samples for analysis. The mean (standard deviation) age was 51.59 (14.57) years, and 10 (44%) patients were female. Twelve (52%) patients had comorbid asthma. Sinus brushes had significantly higher alpha diversity indexes (Shannon and Faith) compared to bronchial brushes (p<0.001). Beta diversity metrics were significantly different between the sinus and bronchial samples. Principal coordinate analysis showed no clustering of paired nasal and bronchial samples. Sinus brushes had significantly more Lawsonella, Corynebacterium, and Staphylococcus compared to bronchia brushes, while the latter were enriched in Tropheryma and Sphingomonas, among others (false discovery rate [FDR]-adjusted p<0.01). Finally, CRS patients with comorbid asthma had significantly higher Pseudomonas and Peptoniphilus in sinus brushes and lower Prevotella in bronchial brushes when compared to non-asthmatics (FDR-adjusted p<0.01). The sinus and bronchial bacterial microbiomes differ in important ways. Our study suggests that migration of bacteria from the sinus into the lower airways is unlikely in patients with CRS.

Investigation of the Comorbidity of Bronchial Asthma and Allergic Rhinitis in Children

Today there is an increasing tendency for all allergic diseases, including a high prevalence of bronchial asthma (BA), as well as an increasing number of patients with co-morbidities. Allergic rhinitis leads in frequency of occurrence with bronchial asthma. In the last decade, the term comorbidity has often been used to define the interrelation as well as the mutual influence of 2 or more syndromes, diseases in one patient. The aim of the research was to study the comorbidity of bronchial asthma and allergic rhinitis in children in the Department of Pulmonology. The retrospective study included an analysis of 51 case histories of children diagnosed with atopic bronchial asthma. Of the 51 patients, 28 children (54.9±7%) were diagnosed with allergic rhinitis after examination by an ENT specialist.

Editorial: Treatment of comorbidities of asthma and its safety

Editorial: Treatment of comorbidities of asthma and its safety

Exploring the association between asthma and chronic comorbidities: impact on clinical outcomes.

Asthma remains a significant global health challenge. While both the incidence and mortality rates have shown a decline, older individuals with asthma exhibit not just more severe symptoms but also demonstrate an elevated mortality rate. This phenomenon could be attributed to the presence of chronic comorbidities that exert an influence on clinical outcomes among adult patients with asthma. This review aims to present various aspects of asthma comprehensively, including the prevalence, incidence, mortality rates, and causes of death in adult patients with asthma. Additionally, this review delves into the impact of chronic comorbidities that contribute to the morbidity and mortality of patients with asthma on a global scale, encompassing conditions such as chronic kidney disease, diabetes mellitus, lung cancer, obesity, and cardiovascular disease, concerning asthma. Furthermore, the manuscript reviews the distinctions between asthma and asthma chronic obstructive pulmonary disease overlap and adds perspective on asthma as an occupational lung disease. Thus, this review aims to enhance clinicians' awareness of the significance of chronic comorbidities in the management of patients with asthma. It seeks to provide insights that contribute to a more comprehensive approach to managing patients with asthma who also have comorbid conditions.

Analysis of risk factors for acute attacks complicated by respiratory failure in children with asthma.

To describe the proportion and clinical characteristics of hospitalized children with acute asthma attacks complicated by respiratory failure and to analyze the risk factors. This retrospective study analyzed hospital admissions of children and adolescents with acute asthma attacks between January 2016 and December 2021. Inclusion criteria were used to identify eligible cases, and demographic information and disease characteristics were collected. Patients were categorized into respiratory failure group and the other group based on the result of artery blood gas analysis. Multivariate logistic regression was utilized to investigate the risk factors associated with respiratory failure resulting from acute asthma attacks. The data were analyzed using SPSS 22.0, and significance was considered at P < 0.05. Our research involved 225 participants, with 18.7% diagnosed with respiratory failure. The respiratory failure group was found to be younger and have higher percentage of male, while birth weight, nationality, and type of residence did not differ between the two groups. In the respiratory failure group, a significant difference was observed in emergency hospitalization, ICU treatment, severe to critical attack, dyspnea and allergy history. The two groups did not differ in admission season, first asthma diagnosis, respiratory infection and comorbidity. The respiratory failure group exhibited a higher proportion of atopy-only asthma and a lower proportion of T2-high asthma. The eosinophil count, and eosinophil percentage were lower in the respiratory failure group, while neutrophil count was higher. Having a history of allergies (OR = 2.46, 95% CI: 1.08-5.59) and neutrophil count (OR = 1.10, 95% CI: 1.00-1.21) were the risk factors for respiratory failure in children with asthma. There also existed that the risk of respiratory failure increases with decreasing age of the children (OR = 0.85, 95% CI: 0.73-0.99). Notably, risk factors for respiratory failure in hospitalized asthma children include age, having a history of allergies, and neutrophil count. The identification of the above factors and the implementation of timely intervention can optimize the treatment of asthma in children.

Allergic rhinitis and other comorbidities associated with asthma control in Thailand.

Asthma and allergic rhinitis (AR) can coexist and cause disabilities. This study aimed to assess the association between AR, asthma control, asthma-related quality of life, and other comorbidities. A cross-sectional study was conducted in adults with asthma in six hospitals in Thailand. The outcomes were association of asthma control assessed by the asthma control test (ACT), AR, and asthma comorbidities. Not-well-controlled asthma was defined as ACT scores ≤22. The severity of AR was determined by visual analog scale (VAS). Severe AR was defined as VAS ≥5. Asthma-related quality of life (AQLQ), comorbidities, and total IgE were recorded. A total of 682 asthmatic patients were included. Median (IQR) age was 58.0 (47.0-64.0) years. 69.9% were female. Not-well-controlled asthma was present in 44.7%. The prevalence of AR was 86.1%. Moderate/severe persistent AR was diagnosed in 21.7% and severe AR was diagnosed in 30.2% of the patients. Inhaled corticosteroid-containing regimens were prescribed in 97.7% of patients. Intranasal corticosteroid and antihistamine were prescribed in 65.7 and 31.7%, respectively. Patients with not-well-controlled asthma had higher body mass index, VAS scores, proportions of pollution exposure, aeroallergen sensitization, severe AR, nasal polyp, urticaria, food allergy, gastroesophageal reflux disease, depression and anxiety, peptic ulcer, and asthma exacerbations, but younger age, lower AQLQ scores, and lower FEV1. Correlation was found between AR severity and ACT (r = -0.461, p < 0.001), AQLQ (r = -0.512, p < 0.001), and total IgE (r = 0.246, p < 0.023). Multiple regression analysis revealed that ACT, AQLQ, and percentage of FEV1/FVC were significantly associated with severe AR. Allergic rhinitis is prevalent in Thai asthmatic patients. AR severity is associated with asthma control, quality of life, and pulmonary function. Comprehensive care is essential for patients with uncontrolled asthma, particularly when coexisting with conditions.

Effects of biological therapies on patients with Type-2 high asthma and comorbid obesity.

Over 20 million adults and 6 million children in the United States (US) have asthma, a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, and mucus hypersecretion. Obesity, another highly prevalent disease in the US, is a major risk factor for asthma and a significant cause of diminished asthma control, increased submucosal eosinophilia, and reduced quality of life. A large subgroup of these patients experiences severe symptoms and recurrent exacerbations despite maximal dosage of standard asthma therapies. In the past two decades, the development of biological therapies has revolutionized the field and advanced our understanding of type 2 inflammatory biomarkers. However, patients with obesity and comorbid asthma are not principally considered in clinical trials of biologics. Large landmark cluster analyses of patients with asthma have consistently identified specific asthma phenotypes that associate with obesity but may be differentiated by age of asthma onset and inflammatory cell profiles in sputum. These patterns suggest that biologic processes driving asthma pathology are heterogenous among patients with obesity. The biological mechanisms driving pathology in patients with asthma and comorbid obesity are not well understood and likely multifactorial. Future research needs to be done to elicit the cellular and metabolic functions in the relationship of obesity and asthma to yield the best treatment options for this multiplex condition. In this review, we explore the key features of type 2 inflammation in asthma and discuss the effectiveness, safety profile, and research gaps regarding the currently approved biological therapies in asthma patients with obesity.

IL-1β and iNOS can drive the asthmatic comorbidities and decrease of lung function in perennial allergic rhinitis children.

Allergic asthma and rhinitis (AR) are closely linked, with a significant proportion of AR patients developing asthma. Identification of the early signs of comorbidity of AR and asthma can enable prompt treatment and prevent asthma progression. This study investigated the role of interleukin-1β (IL-1β), a pro-inflammatory cytokine, and inducible nitric oxide synthase (iNOS) in the comorbidity of AR and asthma and lung function in Korean children with perennial AR (PAR). A cohort of 240 subjects (6 to 10 years old) with PAR (PAR alone: 113 children, PAR and asthma: 127 children) was analyzed for various biomarkers, including IL-1β, iNOS, and epithelial-mesenchymal transition (EMT) markers in serum. The blood levels of eosinophils and immunoglobulin E (IgE) were examined. IL-1β, CCL-24, E-cadherin, and vimentin were measured by enzyme-linked immunosorbent assay (ELISA). Epithelial iNOS was measured by the NOS kit. Elevated levels of IL-1β, iNOS, and vimentin in the serum were identified as significant indicators of the likelihood of comorbidity of PAR and asthma in children. Furthermore, higher concentrations of IL-1β, iNOS, and vimentin have been linked to reduced lung function in PAR children. Notably, IL-1β expression shows a relationship with the levels of E-cadherin, vimentin, and CCL-24. However, no correlation was found between IL-1β and iNOS expressions. This study suggests that IL-1β and iNOS can be biomarkers in the progression of PAR and asthma and decreased lung function, suggesting potential targets for early intervention and treatment.

Asthma: a respiratory pathology with a high risk for mental health

The subjective experience of asthma can be accompanied by significant emotional suffering. The presence of psychiatric comorbidities in asthma is common and worsens the prognosis of asthma. Bidirectional relationships between psychiatric disorders and asthma via inflammatory mechanisms are highlighted. Systematic screening for the most common psychiatric comorbidities such as depression, anxiety disorders and post-traumatic stress disorder is recommended. A multidisciplinary collaboration with a mental health specialist in the presence of psychiatric comorbidity has proven necessary to improve the quality of life and both the somatic and psychiatric prognosis of patients suffering from asthma.

Clinical Utility of Machine Learning Methods Using Regression Models for Diagnosing Eosinophilic Chronic Rhinosinusitis.

Machine learning methods using regression models can predict actual values of histological eosinophil count from blood eosinophil levels. Therefore, these methods might be useful for diagnosing eosinophilic chronic rhinosinusitis, but their utility still remains unclear. We compared 2 statistical approaches, and investigated the utility of machine learning methods for diagnosing eosinophilic chronic rhinosinusitis. Retrospective study. Medical center. Data, including eosinophilic levels, obtained from blood and sinonasal samples of 264 patients with chronic rhinosinusitis (257 with and 57 without nasal polyps) were analyzed. We determined factors affecting histopathological eosinophil count in regression models. We also investigated optimal cutoff values for blood eosinophil percentages/absolute eosinophil counts (AECs) through receiver operating characteristic curves and machine-learning methods based on regression models. A histopathological eosinophil count ≥10/high-power field was defined as eosinophilic chronic rhinosinusitis. Blood eosinophil levels, nasal polyp presence, and comorbid asthma were factors affecting histopathological eosinophil count. Cutoffs between the 2 statistical approaches differed in the group with nasal polyps, but not in one without nasal polyps. Machine-learning methods identified blood eosinophil percentages ≥1% or AEC ≥100/μL as cut-offs for eosinophilic chronic rhinosinusitis with nasal polyps, while ≥6% or ≥400/μL for one without nasal polyps. Cut-offs of blood eosinophil levels obtained by machine-learning methods might be useful when suspecting eosinophilic chronic rhinosinusitis prior to biopsy because of their ability to adjust covariates, dealing with overfitting, and predicting actual values of histological eosinophil count.

Eosinophilia, asthma, NERD and the use of oral corticosteroids predict uncontrolled chronic rhinosinusitis with nasal polyps after surgery.

Severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging condition to treat. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) has the following criteria when considering biological therapy for severe uncontrolled CRSwNP: eosinophilia, need for oral corticosteroids (OCS), symptom score, loss of sense of smell and co-morbid asthma. This study aimed at finding associations of baseline factors with uncontrolled CRSwNP after endoscopic sinus surgery (ESS). Electronic health record data of CRSwNP patients (N = 137) undergoing ESS in 2002-17 were used. Endpoints of uncontrolled CRSwNP were revision ESS, purchased OCS and antibiotic courses during follow up. Baseline factors were chosen based on EPOS2020 and the data available: nasal polyp (NP) eosinophilia, peripheral blood eosinophilia, co-existing asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD), need for OCS during the previous year, previous ESS, endoscopic NP score, and Lund-Mackay score of sinus computed tomography scans. During the follow-up of 10.1 ± 3.1 (mean ± standard deviation) years, 35 (25.5%) individuals underwent revision ESS. The best predictive model was obtained by a sum of baseline (1) blood eosinophilia ≥ 250 cells/≥l and/or NP eosinophilia ≥ 30% (Eos), (2) asthma/NERD, and (3) ≥ 1 OCS/year. It was significantly associated with revision ESS, purchased doctor-prescribed OCS and antibiotic courses during follow-up. We identified similar predictive variables for uncontrolled CRSwNP that are used in the EPOS2020 indications of biological therapy, thus suggesting that these estimates are usable in clinical practice.

Does Comorbid Food Allergy Affect Response to Omalizumab in Patients with Asthma?

The intrinsic link between food allergy and asthma is well-established, and comorbidity can exacerbate both conditions. Omalizumab, an anti-immunoglobulin E (IgE) antibody, has the biological plausibility to manage both conditions, but only a few small studies have assessed omalizumab in patients with comorbid asthma and food allergy. We conducted a post hoc analysis of placebo-controlled, randomized clinical trials (IA05 in children and 008/009 in adolescents/adults) and real-world observational studies (EXCELS and PROSPERO). For each study, patients with asthma were stratified by whether they had physician-reported food allergy, as per baseline characteristics data. For patients with comorbid food allergy, there was evidence for increased atopy at baseline (numerically higher total IgE levels and atopic comorbidities). The collective body of evidence found that omalizumab consistently improved general and asthma-specific patient-centered outcomes (food allergy-specific outcomes were not available). For patients with asthma, omalizumab improved healthcare resource use (emergency room visits, hospitalizations, unscheduled doctor visits), quality of life (asthma-specific Asthma Quality of Life Questionnaire), productivity (missed work/school days and the Work Productivity and Activity Impairment: Asthma), and asthma outcomes (asthma exacerbations and Asthma Control Test score) regardless of comorbid food allergy. There was no loss of omalizumab efficacy even though patients with both asthma and food allergy appeared to be generally more atopic. Omalizumab may be a viable management option for patients with these comorbidities. NCT00079937; NCT01922037; NCT00252135.