Real-Life Response to Biologics in Severe Asthma with Nasal Polyposis: Insights from the Belgian Severe Asthma Registry.

BACKGROUND: Nasal polyposis (NP) is a comorbidity of type 2 severe asthma (SA) which could influence response to SA biologics. METHODS: We evaluated (super-) response in SA patients with (NP +) and without NP (NP-) enrolled in the Belgian Severe Asthma Registry (BSAR). RESULTS: 914 patients, of whom 31% NP + , were included. At enrollment, NP + patients had higher annual exacerbation rates, higher number of emergency room visits and more elevated type 2 biomarkers. In the longitudinal subanalysis of 104 patients, both groups had significant and similar asthma responses to asthma biologics, except for a greater increase in FEV1 in the NP + group. Super-response was achieved in 33 patients (32%), irrespective of NP status or type of biologic. CONCLUSION: In conclusion, both NP + and NP - patients had positive treatment responses, with some able to achieve super-response. In SA patients with NP, a greater FEV1 improvement as compared to SA patients without NP was observed.

Sodium houttuyfonate modulates the lung Th1/Th2 balance and gut microbiota to protect against pathological changes in lung of ovalbumin-induced asthmatic mice.

OBJECTIVE: The gut-lung axis involves microbial and product interactions between the lung and intestine. Antibiotics for chronic asthma can cause intestinal dysbiosis, disrupting this axis. Sodium houttuyfonate (SH) has diverse biological activities, including modifying gut microbiota, antibacterial, and anti-inflammatory. This study aims to explore the relationship between SH, CD4+ T cells, and gut microbiota. METHODS: Allergic asthma was experimentally induced in mice through injection and inhalation of ovalbumin. After the administration of different amounts of SH, ELISA was utilized to ascertain the levels of inflammatory cytokines in the serum, flow cytometry was used to examine the levels of Th1/Th2 cytokines in CD4+ cells from lung tissues. The expression of T-bet and GATA3 in lung tissue was determined by Western blotting and quantitative real-time PCR assay. Gut microbiota was determined by 16S rRNA gene sequencing. RESULTS: The results showed that SH can alleviate pulmonary injury in asthmatic mice, reducing serum levels of IL-4, IL-5, and IL-13 while simultaneously increasing IFN-γ. Furthermore, SH has been observed to modulate the balance of Th1/Th2 cells by up-regulating the mRNA and protein expression of T-bet but down-regulating GATA3 in the lung tissues of asthmatic mice, thereby promoting the differentiation of Th1 cells. Additionally, SH can regulate the variety and composition of gut microbiota especially genus Akkermansia in asthmatic mice. CONCLUSION: SH can alleviate asthma through the regulation of Th1/Th2 cells and gut microbiota.

Use of oral moist tobacco (snus) in puberty and its association with asthma in the population-based RHINESSA study.

OBJECTIVES: To investigate the association of early snus use initiation (≤15 years of age) with asthma and asthma symptoms. DESIGN: Cross-sectional analysis of a population-based cohort. SETTING: Study centres in Norway, Sweden, Iceland, Denmark and Estonia, from 2016 to 2019. PARTICIPANTS: 9002 male and female participants above 15 years of age of the Respiratory Health in Northern Europe, Spain and Australia study. MAIN OUTCOME MEASURES: Current asthma and asthma symptoms. RESULTS: The median age of study participants was 28 years (range 15-53) and 58% were women. 20% had used snus, 29% men and 14% women. Overall, 26% of males and 14% of females using snus started ≤15 years of age. Early snus use initiation was associated with having three or more asthma symptoms (OR 2.70; 95% CI 1.46 to 5.00) and a higher asthma symptom score (ß-coefficient (ß) 0.35; 95% CI 0.07 to 0.63) in women. These associations were weak in men (OR 1.23; 95% CI 0.78 to 1.94; ß 0.16; 95% CI -0.06 to 0.38, respectively). There was evidence for an association of early snus initiation with current asthma (OR 1.72; 95% CI 0.88 to 3.37 in women; OR 1.31; 95% CI 0.84 to 2.06 in men). A sensitivity analysis among participants without smoking history showed stronger estimates for all three outcomes, in both men and women, statistically significant for three or more asthma symptoms in women (OR 3.28; 95% CI 1.18 to 9.10). Finally, no consistent associations with asthma outcomes were found for starting snus after age 15 years. CONCLUSIONS: Snus initiation in puberty was associated with higher likelihood of asthma and asthma symptoms, with the highest estimates in females and those without smoking history. These results raise concerns about the health adversities of early snus initiation and emphasise the need for public health initiatives to protect young people from this tobacco product.

Disability and long-term breathlessness: a cross-sectional, population study.

INTRODUCTION: Disability, resulting from altered interactions between individuals and their environment, is a worldwide issue causing inequities and suffering. Many diseases associated with breathlessness cause disability but the relationship between disability and the severity of breathlessness itself is unknown.This study evaluated associations between disability using the WHO's Disability Assessment Schedule (WHODAS) 2.0 and levels of long-term breathlessness limiting exertion. METHODS: This population-based, cross-sectional online survey (n=10 033) reflected the most recent national census (2016) by age, sex, state/territory of residence and rurality. Assessments included self-reported disability (WHODAS 2.0 12-item (range 12 (no disability) to 60 (most severe disability)) assessed in 6 domains) and long-term breathlessness limiting exertion (modified Medical Research Council (mMRC) breathlessness scale; 0-4 (4-most severe)). Days in the last month affected by breathlessness were reported. RESULTS: Of respondents (52% women; mean age 45), mean total disability score was 20.9 (SD 9.5). 42% (n=4245) had mMRC >0 (mMRC1 31% (n=3139); mMRC2 8% (n=806); mMRC3,4 3% (n=300)). Every level of long-term breathlessness limiting exertion was associated with greater levels of disability (total p <0.001; each domain p <0.001). The most compromised domains were Mobility and Participation.In the last 30 days, people with severe breathlessness (mMRC 3-4): experienced disability (20 days); reduced activities/work (10 days); and completely forwent activities (another 5 days). CONCLUSIONS: Disability should be in the definition of persistent breathlessness as it is systematically associated with long-term breathlessness limiting exertion in a grade-dependent, multidimensional manner. Disability should be assessed in people with long-term breathlessness to optimise their social well-being and health.

Neighborhood Socioeconomic Context Predicts Pediatric Asthma Exacerbation.

Causes of asthma exacerbation in children have been studied extensively at the individual level, but contributions of neighborhood-level factors are less explored. We test which distinctive residential characteristics produce variation in uncontrolled asthma among pediatric patients. We extracted electronic medical record data from pediatric patients living in Southern California and used multilevel modeling techniques to isolate which neighborhood characteristics drive inequitable asthma control. Above and beyond the individual-level factors known to predict inadequate disease control, neighborhoods with greater concentration of non-Hispanic black residents (odds ratios [OR] = 1.02; 95% confidence interval [CI]: 0.99-1.03; P < .05), higher proportions of female-headed households (OR = 1.01; 95% CI: 0.99-1.01; P < .05), and higher levels of ambient air pollution (OR = 1.05; 95% CI: 1.01-1.10; P < .001) associate with greater odds of asthma exacerbation. The interplay between community characteristics and asthma management during childhood is complex, and place-based initiatives are needed to narrow the gap in asthma exacerbation.

A critical analysis of the effect of OM-85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta-analysis.

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

Emollient application from birth to prevent eczema in high-risk children: the BEEP RCT.

Background: Atopic eczema is a common childhood skin problem linked with asthma, food allergy and allergic rhinitis that impairs quality of life. Objectives: To determine whether advising parents to apply daily emollients in the first year can prevent eczema and/or other atopic diseases in high-risk children. Design: A United Kingdom, multicentre, pragmatic, two-arm, parallel-group randomised controlled prevention trial with follow-up to 5 years. Setting: Twelve secondary and four primary care centres. Participants: Healthy infants (at least 37 weeks' gestation) at high risk of developing eczema, screened and consented during the third trimester or post delivery. Interventions: Infants were randomised (1 : 1) within 21 days of birth to apply emollient (Doublebase Gel®; Dermal Laboratories Ltd, Hitchin, UK or Diprobase Cream®) daily to the whole body (excluding scalp) for the first year, plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). Families were not blinded to allocation. Main outcome measures: Primary outcome was eczema diagnosis in the last year at age 2 years, as defined by the UK Working Party refinement of the Hanifin and Rajka diagnostic criteria, assessed by research nurses blinded to allocation. Secondary outcomes up to age 2 years included other eczema definitions, time to onset and severity of eczema, allergic rhinitis, wheezing, allergic sensitisation, food allergy, safety (skin infections and slippages) and cost-effectiveness. Results: One thousand three hundred and ninety-four newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in the emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months. At 2 years, eczema was present in 139/598 (23%) in the emollient group and 150/612 (25%) in controls (adjusted relative risk 0.95, 95% confidence interval 0.78 to 1.16; p = 0.61 and adjusted risk difference -1.2%, 95% confidence interval -5.9% to 3.6%). Other eczema definitions supported the primary analysis. Food allergy (milk, egg, peanut) was present in 41/547 (7.5%) in the emollient group versus 29/568 (5.1%) in controls (adjusted relative risk 1.47, 95% confidence interval 0.93 to 2.33). Mean number of skin infections per child in the first year was 0.23 (standard deviation 0.68) in the emollient group versus 0.15 (standard deviation 0.46) in controls; adjusted incidence rate ratio 1.55, 95% confidence interval 1.15 to 2.09. The adjusted incremental cost per percentage decrease in risk of eczema at 2 years was £5337 (£7281 unadjusted). No difference between the groups in eczema or other atopic diseases was observed during follow-up to age 5 years via parental questionnaires. Limitations: Two emollient types were used which could have had different effects. The median time for starting emollients was 11 days after birth. Some contamination occurred in the control group (< 20%). Participating families were unblinded and reported on some outcomes. Conclusions: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children. Emollient use was associated with a higher risk of skin infections and a possible increase in food allergy. Emollient use is unlikely to be considered cost-effective in this context. Future research: To pool similar studies in an individual patient data meta-analysis. Trial registration: This trial is registered as ISRCTN21528841. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/67/12) and is published in full in Health Technology Assessment; Vol. 28, No. 29. See the NIHR Funding and Awards website for further award information.

Eczema is a troublesome itchy skin condition affecting 1 in 5 children and 1 in 10 UK adults. There is no cure and affected children are more likely to develop food allergies. We wanted to see if we could prevent eczema by protecting the skin of babies at higher risk of developing eczema (with an immediate relative with eczema, asthma or hay fever) with moisturisers used to treat dry skin. Previous research suggested that protecting the skin barrier might also prevent food allergy. One thousand three hundred and ninety-four families took part in a study; half of them were asked to apply moisturiser every day to their newborn baby for the first year and half to look after their baby's skin in the normal way. At the age of 2 years, we did not see any difference in how common eczema was between the two groups: 23% had eczema in the moisturiser group and 25% in the normal care group. It did not matter how we defined eczema ­ whether examined by a researcher or parent report. We did not find any differences in related conditions like asthma or hay fever either. We found that children using moisturisers had seen their doctor slightly more often for mild skin infections. There was a hint that food allergy might have been increased in the moisturiser group, but there was not enough data to be sure. We followed up the children to age 5 years, but we still did not find any benefits from using moisturisers in early life. Since this study, other similar research has been done using newer types of moisturisers, but their results are the same. This study shows that using daily moisturisers on healthy babies with a high risk of eczema does not prevent eczema. It is one less thing for busy families to worry about.

Combining Federated Machine Learning and Qualitative Methods to Investigate Novel Pediatric Asthma Subtypes: Protocol for a Mixed Methods Study.

BACKGROUND: Pediatric asthma is a heterogeneous disease; however, current characterizations of its subtypes are limited. Machine learning (ML) methods are well-suited for identifying subtypes. In particular, deep neural networks can learn patient representations by leveraging longitudinal information captured in electronic health records (EHRs) while considering future outcomes. However, the traditional approach for subtype analysis requires large amounts of EHR data, which may contain protected health information causing potential concerns regarding patient privacy. Federated learning is the key technology to address privacy concerns while preserving the accuracy and performance of ML algorithms. Federated learning could enable multisite development and implementation of ML algorithms to facilitate the translation of artificial intelligence into clinical practice. OBJECTIVE: The aim of this study is to develop a research protocol for implementation of federated ML across a large clinical research network to identify and discover pediatric asthma subtypes and their progression over time. METHODS: This mixed methods study uses data and clinicians from the OneFlorida+ clinical research network, which is a large regional network covering linked and longitudinal patient-level real-world data (RWD) of over 20 million patients from Florida, Georgia, and Alabama in the United States. To characterize the subtypes, we will use OneFlorida+ data from 2011 to 2023 and develop a research-grade pediatric asthma computable phenotype and clinical natural language processing pipeline to identify pediatric patients with asthma aged 2-18 years. We will then apply federated learning to characterize pediatric asthma subtypes and their temporal progression. Using the Promoting Action on Research Implementation in Health Services framework, we will conduct focus groups with practicing pediatric asthma clinicians within the OneFlorida+ network to investigate the clinical utility of the subtypes. With a user-centered design, we will create prototypes to visualize the subtypes in the EHR to best assist with the clinical management of children with asthma. RESULTS: OneFlorida+ data from 2011 to 2023 have been collected for 411,628 patients aged 2-18 years along with 11,156,148 clinical notes. We expect to complete the computable phenotyping within the first year of the project, followed by subtyping during the second and third years, and then will perform the focus groups and establish the user-centered design in the fourth and fifth years of the project. CONCLUSIONS: Pediatric asthma subtypes incorporating RWD from diverse populations could improve patient outcomes by moving the field closer to precision pediatric asthma care. Our privacy-preserving federated learning methodology and qualitative implementation work will address several challenges of applying ML to large, multicenter RWD data. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57981.

Role of Thymic Stromal Lymphopoietin in the Pathophysiology of Asthma and Clinical and Biological Effects of Blockade With Tezepelumab.

BACKGROUND: The airway epithelium is the first line of defense of the respiratory system against the external environment. It plays an active role in the initiation of immune and allergic responses against potential hazards. Among the various specialized cells and cytokines that participate in epithelium-induced responses, alarmins are particularly interesting, given their ample role in mediating T2 and non-T2 inflammatory mechanisms involved in the pathogenesis of asthma. Thymic stromal lymphopoietin (TSLP) is an alarmin with broad effects in asthma that result from its widespread action on multiple cell types, including eosinophils, mast cells, dendritic cells, and group-2 innate lymphoid cells. Its role in allergy-mediated responses, eosinophilic inflammation, airway hyperresponsiveness, mucus hyperproduction, viral tolerance, and airway remodeling is of the utmost importance, as more comprehensive asthma assessments have been developed to explore these pathogenic features. Therefore, blockade with targeting molecules, such as monoclonal antibodies, has emerged as a promising therapeutic option, particularly in patients with multiple pathogenic pathways. In this review, we examine the roles of alarmins (mainly TSLP) in the pathogenesis of asthma and clinical expression and discuss the effects of inhibiting TSLP on several inflammatory and clinical outcomes. We also review the literature supporting treatment with anti-TSLP biologics and the unanswered questions and unmet needs associated with targeting alarmins in asthma.

Association of food folate with asthma in US children and adolescents: a cross-sectional study.

BACKGROUND: Asthma is a chronic inflammatory disease. Currently, contradictory findings exist regarding the association between food folate and asthma. Therefore, we hypothesize a positive correlation between food folate and asthma. PURPOSE: To investigate the possible relationship between food folate intake and the development of asthma in children and adolescents in the United States. METHODS: Data from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018 were analyzed cross-sectionally by covariate adjustment using multivariate logistic regression, restricted triple spline curves, threshold effects, and stratified analyses. RESULTS: There were 8,821 participants, of whom 1,697 (19.2%) self-reported having received a diagnosis of asthma from a physician or other health professional. After accounting for potential confounders, the adjusted odds ratios (ORs) for asthma in the second (T2, 111-178 µg/day) and third (T3, >178 µg/day) groups were 1.15 (1-1.33) and 1.23 (1.04-1.46), respectively, compared with the group with the lowest food folate intake (T1, <111 µg/day). In addition, the association between food folate intake and asthma showed an inverse L-shaped curve (non-linear relationship, p = 0.003), and stratified analysis further validated the robustness of the results. The OR of asthma in subjects with food folate intake less than 263.9 µg/day was 1.002 (1.001-1.004). CONCLUSION: In children and adolescents in the United States, there is a non-linear association (inverted "L" shape) between food folate intake and asthma, with an inflection point at 263.9 micrograms per day.

Indeno[1,2,3-cd]pyrene enhances the sensitivity of airway epithelial cells to ferroptosis and aggravates asthma.

Particulate matter of aerodynamic diameter ≤2.5 µm (PM2.5) exposure induces oxidative stress in lung tissues. Ferroptosis is a form of regulated cell death based on oxidative damage and lipid peroxidation. Whether PM2.5 exposure-induced oxidative stress can promote ferroptosis to aggravate asthma is not known. To investigate if PM2.5 exposure induces oxidative stress to promote ferroptosis and influence asthma development, a cockroach extract-induced asthma model in mice was used for in vivo studies. Airway epithelial cell (AEC) ferroptosis was detected by assays (CCK8, malonaldehyde, and 4-hydroxynonenal). Molecular mechanisms were investigated by real-time reverse transcription-quantitative polymerase chain reaction, western blotting, flow cytometry, liquid chromatography-tandem mass spectrometry, and chromatin immunoprecipitation. We found that exposure to PM2.5 and Indeno[1,2,3-cd] pyrene (IP; one of the prominent absorbed polycyclic aromatic hydrocarbons in PM2.5) enhanced the sensitivity of AECs to ferroptosis to aggravate asthma, whereas ferroptosis inhibitors and cytosolic phospholipase A2 (cPLA2) inhibitors reversed this augmented inflammatory response in mice suffering from asthma. IP treatment enhanced cPLA2 expression/activation through aryl hydrocarbon receptor (AhR) genomic and non-genomic pathways, resulting in arachidonic-acid release to promote the sensitivity of AECs to ferroptosis. IP exposure enhanced the release of leukotriene-B4 from lung macrophages, resulting in enhanced expression of acyl-coA synthetase long chain family member4 (ACSL4) and the sensitivity of AECs to ferroptosis. This finding suggests that exposure to PM2.5 and IP promote ferroptosis sensitivity in AECs to aggravate asthma, which may provide new targets for the prevention and treatment of asthma.

Sex differences in airway disease: estrogen and airway surface liquid dynamics.

Biological sex differences exist for many airway diseases in which females have either worse or better health outcomes. Inflammatory airway diseases such as cystic fibrosis (CF) and asthma display a clear male advantage in post-puberty while a female benefit is observed in asthma during the pre-puberty years. The influence of menstrual cycle stage and pregnancy on the frequency and severity of pulmonary exacerbations in CF and asthma point to a role for sex steroid hormones, particularly estrogen, in underpinning biological sex differences in these diseases. There are many ways by which estrogen may aggravate asthma and CF involving disturbances in airway surface liquid (ASL) dynamics, inappropriate hyper-immune and allergenic responses, as well as exacerbation of pathogen virulence. The deleterious effect of estrogen on pulmonary function in CF and asthma contrasts with the female advantage observed in airway diseases characterised by pulmonary edema such as pneumonia, acute respiratory distress syndrome (ARDS) and COVID-19. Airway surface liquid hypersecretion and alveolar flooding are hallmarks of ARDS and COVID-19, and contribute to the morbidity and mortality of severe forms of these diseases. ASL dynamics encompasses the intrinsic features of the thin lining of fluid covering the airway epithelium which regulate mucociliary clearance (ciliary beat, ASL height, volume, pH, viscosity, mucins, and channel activating proteases) in addition to innate defence mechanisms (pathogen virulence, cytokines, defensins, specialised pro-resolution lipid mediators, and metabolism). Estrogen regulation of ASL dynamics contributing to biological sex differences in CF, asthma and COVID-19 is a major focus of this review.

Sex differences exist in many airway diseases in which females have either worse or better health outcomes. These include cystic fibrosis (CF) and asthma where females post-puberty have more frequent lung exacerbations and higher mortality. Lung infections and difficulty in breathing become worse in post-puberty in females and during the ovulation period of the menstrual cycle, and in pregnancy, indicating a role for sex hormones in underpinning sex differences in CF and asthma. Evidence also exists for sex differences with a female advantage in airway diseases which are characterised by flooding of the airways, as in pneumonia and COVID-19, where females have better lung function and lower risk of death than males. The female sex hormone estrogen plays an important role in determining the role of sex biology in airway disease severity and mortality. Estrogen can control the movement of salt and water in and out of the lung airway tubes and dehydrate the lung surface to make it more sticky with mucus, as observed in CF and asthma, thus worsening the condition. In contrast, estrogen can have beneficial effects in lowering the volume of water in the lungs in COVID-19 thus alleviating flooding of the airways. This review focusses on the biology of sex differences in CF, asthma and COVID-19, and the cellular mechanisms by which estrogen can have either detrimental or beneficial effects in these diseases.

Circulating innate lymphoid cells (cILCs): Unconventional lymphocytes with hidden talents.

Innate lymphoid cells (ILCs) are a group of lymphocytes that are devoid of antigen-specific receptors and are mainly found in tissues. The subtypes ILC1, 2, and 3 mirror T-cell functionality in terms of cytokine production and expression of key transcription factors. Although the majority of ILCs are found in tissue (tILCs), they have also been described within the circulation (cILCs). As a result of their better accessibility and putative prognostic value, human cILCs are getting more and more attention in clinical research. However, cILCs are in many aspects functionally distinct from their tILC counterparts. In fact, from the 3 ILC subsets found within the circulation, only for cILC2s could a clear functional correspondence to their tissue counterparts be established. Indeed, cILC2s are emerging as a major driver of allergic reactions with a particular role in asthma. In contrast, recent studies revealed that cILC1s and cILC3s are predominantly in an immature state and constitute progenitors for natural killer cells and ILCs, respectively. We provide an overview about the phenotype and function of the different cILC subtypes compared to tILCs in health and disease, including transcriptomic signatures, frequency dynamics, and potential clinical value. Furthermore, we will highlight the dynamics of the NKp44+ ILC3 subset, which emerges as prognostic marker in peripheral blood for inflammatory bowel disease and leukemia.

Mapping the Periostin splice isoforms in atopic dermatitis and an in vitro asthma model - A multi-platform analysis using mass spectrometry and RT-qPCR.

Periostin is a matricellular protein known to be alternatively spliced to produce ten isoforms with a molecular weight of 78-91 kDa. Within the extracellular matrix, periostin attaches to cell surfaces to induce signaling via integrin-binding and actively participates in fibrillogenesis, orchestrating the arrangement of collagen in the extracellular environment. In atopic diseases such as atopic dermatitis (AD) and asthma, periostin is known to participate in driving the disease-causing type 2 inflammation. The periostin isoforms expressed in these diseases and the implication of the alternative splicing events are unknown. Here, we present two universal assays to map the expression of periostin isoforms at the mRNA (RT-qPCR) and protein (PRM-based mass spectrometry) levels. We use these assays to study the splicing profile of periostin in AD lesions as well as in in vitro models of AD and asthma. In these conditions, periostin displayed overexpression with isoforms 3 and 5 standing out as highly overexpressed. Notably, isoforms 9 and 10 exhibited a divergent pattern relative to the remaining isoforms. Isoforms 9 and 10 are often overlooked in periostin research and this paper presents the first evidence of their expression at the protein level. This underlines the necessity to include isoforms 9 and 10 in future research addressing periostin splice isoforms. The assays presented in this paper hold the potential to improve our insight into the splicing profile of periostin in tissues and diseases of interest. The application of these assays to AD lesions and in vitro models demonstrated their potential for identifying isoforms of particular significance, warranting a further in-depth investigation.

The Burden of Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease: Interplay Between Quality of Life and Economic Implications.

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) presents a significant challenge in clinical management owing to recalcitrant disease with accompanying profound impacts on patient quality of life. Although asthma represents a significant component of this disease, quality of life disruptions are driven primarily by recalcitrant sinonasal problems, olfactory dysfunction, and the associated psychosocial and dietary implications. This review delves into specific quality of life metrics used to assess NSAID-ERD and the associated health care burden and financial implications of this disease, offering insights into the comparative challenges in chronic rhinosinusitis with nasal polyps when available. The article reviews the associated costs and cost-effectiveness of NSAID-ERD-directed therapies, including endoscopic sinus surgery, aspirin desensitization, and biologic therapy. Although some of these emerging treatment approaches show promise, they also present numerous unanswered questions, reflecting the dynamic nature of this field. As the landscape of NSAID-ERD management continues to evolve, this review provides insights into the challenges faced by clinicians and underscores the need for further research to optimize patient care and quality of life outcomes.

Relationship between fraction of exhaled nitric oxide and peripheral eosinophilia in asthma.

BACKGROUND: Achieving disease control is the goal of asthma management. Serum or sputum eosinophil counts have been known traditional means of assessing eosinophilic airway inflammation in asthma, which is vital in predicting response to corticosteroid therapy which ultimately promotes control of the disease. Evidence suggests that fraction of exhaled nitric oxide (FeNO) may be a more useful non-invasive surrogate biomarker for the assessment of eosinophilic airway inflammation and could help with the timely adjustment of inhaled corticosteroid therapy in the uncontrolled asthma patient. The relationship between FeNO and other markers of airway inflammation has been variable in literature, with limited data in sub-Saharan Africa where FeNO testing is very sparse. We sought to define the relationship between FeNO levels, serum eosinophil counts, spirometry measures and symptom control among asthma patients. MATERIALS AND METHODS: The study was conducted at the Asthma Clinic of a large tertiary hospital. This study included 82 patients with physician-diagnosed asthma being regularly managed at the clinic. All participants were taken through the asthma control test (ACT), had FeNO and spirometry measurements taken according to the American Thoracic Society (ATS) guidelines. Blood samples were obtained from all participants for serum eosinophil counts. Correlation coefficient was used to ascertain the relationship between FeNO levels and serum eosinophil counts, ACT scores, and spirometry measurements. Logistic regression was used to examine the association between high FeNO and abnormal FEV1 percentage predicted (<80%) with adjustments for age, sex, and BMI. RESULTS: A total of 82 patients with asthma were included in the study, with higher prevalence of females (72%). Majority (40.2%) of the patients were found in the 60 and above age category. The median FeNO level and ACT score was 42.00 (26.00-52.50) parts per billion (ppb) and 20.0 (18-23) respectively. The median serum eosinophil counts was 0.25(0.90-0.38) × 109/L. The median FeNO levels were significantly higher in patients with partly and very poorly controlled asthma than in the well-controlled group (p < 0.001). A total of 47(57%) of the patients were classified as having well controlled asthma and 35 (42%) uncontrolled. FeNO correlated with serum eosinophil counts (r = 0.450, p < 0.001), ACT (r = -0.648, p < 0.001), and FEV1 percentage predicted (r = -0.353, p = 0.001). High FeNO (>50 ppb) was associated with an over fivefold increased risk of having an abnormal FEV1 percentage predicted. CONCLUSION: FeNO levels significantly correlated with the ACT scores, serum eosinophil counts and FEV1% predicted among the asthma patients who were on inhaled corticosteroid therapy. High FeNO was significantly associated with abnormal FEV1 percentage predicted. We suggest that the point of care assessment of FeNO is a reliable marker of eosinophilic inflammation in our cohort of patients and together with 'ACT scores' in our asthma clinics could increase asthma control rates.

Influence of Climatic Changes on Respiratory Health in a Teaching Herd of Outdoor-Housed Horses.

Horses maintained outdoors may experience a lower-allergenic environment compared to their stabled counterparts. This study hypothesizes that climatic changes in southern Brazil can influence respiratory status. To test this hypothesis, we evaluated the lower airways of 17 horses from a teaching herd in southern Brazil, maintained outdoors, during winter, spring, and summer. Except for one mare with a history of severe asthma, all horses were considered healthy and underwent a physical examination. Airway endoscopic evaluation included scoring for tracheal mucus (0-5) and bronchial septum thickness (1-5). Bronchoalveolar lavage fluid (BALF) was collected at three time points, while bronchial septum biopsies were performed during spring and summer for airway epithelial investigation. Data analysis involved repeated measures ANOVA and Wilcoxon tests (p < 0.05). Tracheal mucus score and septal thickness did not differ across investigation periods. In BALF cytology, the mean percentage of neutrophils was higher in spring than summer (7.9 ± 13.4% vs. 4.5 ± 11.7%, P = 0.037), and eosinophil count was higher in winter than spring (0.64 ± 1.29% vs. 0.03 ± 0.13%, P = 0.034) and summer (0.64 ± 1.29% vs. 0.14 ± 0.60%, P = 0.023). Histopathological observations showed no differences between time points, and no correlations were observed with BALF analyses (P > 0.05). This study demonstrates that, even in an outdoor environment, horses' airways exhibit cytological modifications associated with different seasons, indicating a need for deeper investigation; endobronchial biopsy did not contribute to the clinical diagnosis.