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1.
Allergy ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087443

RESUMO

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.

2.
Pediatr Allergy Immunol ; 35(8): e14208, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39087502

RESUMO

BACKGROUND: We investigated the individual and interaction effects of maternal plasma 𝛂- and ϒ-tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8-9. METHODS: Mother-child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second-trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self-reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother-child dyads) and tested for prespecified interaction terms. RESULTS: Median cholesterol-corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3-5.7) and 0.8 (0.7-0.9) (umol/mmol) for 𝛂- and ϒ-tocopherol, respectively. Associations between 𝛂-tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ-tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 𝛂-tocopherol levels, whereas this trend was not observed among those without a history of asthma (p-interaction = .05). CONCLUSION: We observed no associations for prenatal 𝛂- or ϒ-tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 𝛂-tocopherol and child asthma.


Assuntos
Asma , Efeitos Tardios da Exposição Pré-Natal , Sons Respiratórios , Vitamina E , Humanos , Asma/epidemiologia , Asma/sangue , Feminino , Gravidez , Criança , Masculino , Vitamina E/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , gama-Tocoferol/sangue , Estudos de Coortes , alfa-Tocoferol/sangue
3.
Sleep Breath ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088141

RESUMO

BACKGROUND: Asthma is a heterogeneous disorder. This study aimed to identify changes in gene expression and molecular mechanisms associated with moderate to severe asthma. METHODS: Differentially expressed genes (DEGs) were analyzed in GSE69683 dataset among moderate asthma and its controls as well as between severe asthma and moderate asthma. Key module genes were identified via co-expression analysis, and the molecular mechanism of the module genes was explored through enrichment analysis and gene set enrichment analysis (GSEA). GSE89809 was used to verify the characteristic genes related to moderate and severe asthma. RESULTS: Accordingly, 2540 DEGs were present between moderate asthma and the control group, while 6781 DEGs existed between severe asthma and moderate asthma. These genes were identified into 14 co-expression modules. Module 7 had the highest positive correlation with severe asthma and was recognized to be a key module by STEM. Enrichment analysis demonstrated that the module genes were mainly involved in oxidative stress-related signaling pathways. The expression of HSPA1A, PIK3CG and PIK3R6 was associated with moderate asthma, while MAPK13 and MMP9 were associated with severe asthma. The AUC values were verified by GSE89809. Additionally, 322 drugs were predicted to target five genes. CONCLUSION: These results identified characteristic genes related to moderate and severe asthma and their corresponding molecular mechanisms, providing a basis for future research.

4.
Iran J Public Health ; 53(7): 1651-1658, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39086401

RESUMO

Background: Asthma and allergic diseases are common chronic non-communicable conditions that can negatively impact the quality of life of patients. Psychological factors play a role in both the onset and progression of these conditions. The purpose of this study was to examine the relationship between handedness and emotion regulation and cognitive emotion regulation strategies in patients with asthma and allergies in Isfahan, central Iran. Methods: We employed a causal-comparative research design. The study population consisted of all patients visiting Asthma and Allergy Clinic in Isfahan. One hundred participants were selected through probability sampling. Data were collected using the Emotion Regulation Questionnaire and the Cognitive Emotion Regulation Strategies Questionnaire, and were analyzed using univariate analysis of variance (ANOVA). Results: Cognitive emotion regulation was significantly different between right-handed and left-handed patients with asthma and allergies (P=0.0001). A significant difference was also observed between the two groups in their emotion regulation strategies (P=0.031). The rate of positive and negative cognitive regulation strategies was higher in left-handed individuals with asthma and allergies, compared to right-handed individuals. Conclusion: Overall, handedness has a significant impact on the behavior and mental health of patients suffering from asthma and allergies. Therefore, handedness should be taken into consideration in interventions for emotion regulation.

5.
J Asthma ; : 1-11, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087774

RESUMO

OBJECTIVE: The observational association between blood metabolites and asthma has been extensively studied. However, it is still unclear whether this association is causal. In this study, we aimed to investigate the causal relationship between blood metabolites and asthma using a bidirectional Mendelian randomization (MR) analysis. Additionally, we aimed to explore the potential mechanisms underlying this relationship. METHODS: The study design involved the use of genetic instruments as instrumental variables (IVs) to fulfill the assumptions of MR analysis. The data on 1,091 metabolites and 309 metabolite ratios were obtained from the Canadian Longitudinal Study on Aging (CLSA), while the data on asthma were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS Project. Utilizing the inverse variance-weighted (IVW) method as the primary MR analysis approach, sensitivity tests were conducted to assess the reliability of the findings, which involved employing Cochran's Q and the MR-Egger intercept. Furthermore, Bayesian weighted MR was used to further test the robustness of the results. Additionally, pathway analysis was conducted to explore the metabolic explanations underlying asthma. RESULT: In our study, a comprehensive MR Analysis identified 10 metabolites and 6 metabolite ratios significantly associated with the development of asthma (FDR < 0.05). The metabolites included glycerophosphocholines(GPCs), glycerophosphoethanolamines(GPEs), and an unknown metabolite. Of these, 1-arachidonoyl-GPC, 1-myristoyl-2-arachidonoyl-GPC, 1-palmitoyl-2-arachidonoyl-GPC, and 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC were associated with an increased risk of asthma, whereas 1,2-dilinoleoyl-GPC, 1-palmitoyl-2-linoleoyl-GPC, 1,2-dilinoleoyl-GPE, 1 - oleoyl - 2 - linoleoyl - GPE, 1-palmitoyl-2-linoleoyl-GPE, and X-21470 were found to have a protective effect. No heterogeneity and pleiotropy were observed in the significant metabolites (p > 0.05), and each metabolite exhibited a consistent effect direction across all five methods. BWMR analysis results confirmed the significance and direction of effects across exposures, except for Cholesterol to linoleoyl-arachidonoyl-glycerol ratio(p = 0.673). Pathway analysis suggests that glycerophospholipid metabolism may potentially be a mechanism underlying the development of asthma. CONCLUSION: Our MR findings suggest that the identified metabolites and pathways can serve as biomarkers for clinical asthma screening and prevention, while also providing new insights for future mechanistic exploration and drug target selection.

6.
Anaesth Crit Care Pain Med ; : 101414, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39089455

RESUMO

BACKGROUND: Asthma is a common chronic respiratory disease affecting 1-29% of the population in different countries. Exacerbations represent a change in symptoms and lung function from the patient's usual condition that requires emergency department (ED) admission. Recently, the use of a High-Flow Nasal Cannula (HFNC) plus an in-line vibrating mesh nebulizer (VMN) for aerosol drug delivery has been advocated in clinical practice. Thus, this pilot observational study aims to investigate the feasibility of HFNC treatment with VMN for in-line bronchodilator delivery in patients with severe asthma. METHODS: This study was conducted from May 2022 to May 2023. Subjects ≥ 18 years old with a previous diagnosis of asthma who were admitted to the ED during severe exacerbation were included. The primary endpoint was the change in peak expiratory flow ratio (PEFR) after 2-h of treatment with bronchodilator delivered by HFNC with in-line VMN. Additional outcomes were changes in forced expiratory volume in 1 second (FEV1) and clinical variables before treatment. RESULTS: 30 patients mean age of 43 (SD ± 16) years, mostly female (67%) were studied. A significant change in PEFR (147 ± 31 L/m vs. 220 ± 38 L/m; p < 0.001) was observed after treatment with HFNC and in-line VMN with significant improvement in clinical variables. And no subjects required invasive mechanical ventilation (IMV) during the study. CONCLUSIONS: HFNC treatment with in-line VMN for bronchodilator delivery appears feasible and safe for patients with severe asthma exacerbation. These preliminary promising results should be confirmed with appropriately large-designed studies.

7.
Pharmacoepidemiol Drug Saf ; 33(8): e5806, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39090769

RESUMO

PURPOSE: This study aimed to investigate the prescription of beta-blockers (ß-blockers) for patients with asthma. METHODS: In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, ß-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a ß-blocker and an asthma medication were co-prescribed in one billing statement or when separate ß-blocker and asthma prescriptions had overlapping dates of use. RESULTS: In the 1027 patients with asthma who were prescribed non-selective ß-blockers (non-SBs), 3087 non-SB prescriptions were identified, of which 62.3% and 37.3% were for carvedilol and propranolol, respectively. Of the 906 patients with asthma prescribed selective ß-blockers (SBs), 2942 SB prescriptions were identified, of which 48.5%, 28.3%, and 20.3% were for bisoprolol, atenolol, and nebivolol, respectively. Overall, 2149 non-SB and 2124 SB prescriptions with overlapping use dates with asthma medications were identified, which were prescribed to 726 and 657 patients, accounting for 70.7% and 72.5% of the patients receiving non-SBs and SBs, respectively. ß2-agonists accounted for 39.9% of the concomitant asthma medications with overlapping dates of use with non-SBs. Co-prescribing of bronchodilators occurred at a rate of 38.7% and 45.1% for the 3087 non-SB prescriptions and 2942 SB prescriptions, respectively. CONCLUSIONS: Carvedilol and propranolol accounted for half of all ß-blockers prescribed to asthma patients. Prescribing ß-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between ß-blockers and co-prescribed asthma medications.


Assuntos
Antagonistas Adrenérgicos beta , Asma , Humanos , Asma/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Estudos Retrospectivos , Estudos Transversais , Masculino , Feminino , República da Coreia , Pessoa de Meia-Idade , Adulto , Idoso , Prescrições de Medicamentos/estatística & dados numéricos , Adulto Jovem , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos , Adolescente
8.
Pediatr Allergy Immunol ; 35(8): e14199, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39092605

RESUMO

BACKGROUND: The coexistence of childhood asthma and mental health (MH) conditions can impact management and health outcomes but we need to better understand the etiology of multimorbidity. We investigated the association between childhood asthma and MH conditions as well as the determinants of their coexistence. METHODS: We used data from the Canadian Health Survey of Children and Youth 2019 (3-17 years; n = 47,871), a cross-sectional, nationally representative Statistics Canada dataset. Our primary outcome was condition status (no asthma or MH condition; asthma only; MH condition only; both asthma, and a MH condition (AMHM)). Predictors of condition status were assessed using multiple multinomial logistic regression. Sensitivity analyses considered individual MH conditions. RESULTS: MH condition prevalence was almost two-fold higher among those with asthma than those without asthma (21.1% vs. 11.6%, respectively). There were increased risks of each condition category associated with having allergies, other chronic conditions, and family members smoking in the home while there were protective associations with each condition status category for being female and born outside of Canada. Four additional variables were associated with AMHM and MH condition presence with one additional variable associated with both AMHM and asthma. In sensitivity analyses, the associations tended to be similar for most characteristics, although there was some variability. CONCLUSION: There are common risk factors of asthma and MH conditions along with their multimorbidity with a tendency for MH risk factors to be associated with multimorbidity. MH condition presence is common and important to assess among children with asthma.


Assuntos
Asma , Multimorbidade , Fatores de Proteção , Humanos , Asma/epidemiologia , Canadá/epidemiologia , Feminino , Criança , Masculino , Estudos Transversais , Adolescente , Fatores de Risco , Pré-Escolar , Prevalência , Inquéritos Epidemiológicos , Saúde Mental , Transtornos Mentais/epidemiologia
10.
Ital J Pediatr ; 50(1): 140, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090673

RESUMO

Pediatric asthma management is a compelling challenge for every pediatrician. Different aspects require attention and definition. The present Intersocietal Survey aimed to collect real-world experiences from a sample of Italian pediatricians. A web platform was used to collect anonymous answers to the survey questions.Four hundred four pediatricians participated in this initiative promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP), the Society of Preventive and Social Pediatrics (SIPPS), and the Federation of Italian Pediatricians (FIMP).The results showed an extensive participation of primary care pediatricians (72%). There was a large consensus about diagnostic criteria and medication choice. However, treatment duration and device choice were various. Adherence to guidelines on general aspects of practical clinical management was high.In conclusion, the present Intersocietal Survey confirmed that pediatric asthma management is rather satisfactory, even if further improvement should concern a more widespread use of ICS for acute asthma/wheezing attacks, a better definition of the duration of ICS and bronchodilator use, and hospital-primary care integration.


Assuntos
Asma , Humanos , Asma/terapia , Asma/tratamento farmacológico , Itália , Criança , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Feminino , Inquéritos e Questionários , Antiasmáticos/uso terapêutico , Fidelidade a Diretrizes
11.
Front Med (Lausanne) ; 11: 1332664, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091286

RESUMO

Background: Type 2 diabetes (T2D) frequently co-occurs with respiratory system diseases such as chronic obstructive pulmonary disease (COPD), bronchial asthma, lung cancer, interstitial lung disease, and pulmonary tuberculosis. Although a potential association is noted between these conditions, the available research is limited. Objective: To investigate the causal relationship between patients with T2D and respiratory system diseases using two-sample Mendelian randomization analysis. Methods: Causal relationships were inferred using a two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies. We employed the variance inverse-weighted method as the primary analytical approach based on three key assumptions underlying MR analysis. To bolster the robustness and reliability of our results, we utilized MR Egger's intercept test to detect potential pleiotropy, Cochran's Q test to assess heterogeneity, funnel plots to visualize potential bias, and "leave-one-out" sensitivity analysis to ensure that our findings were not unduly influenced by any single genetic variant. Result: The inverse variance weighted (IVW) analysis indicated a causal relationship between T2D and COPD [Odds Ratio (OR) = 0.87; 95% Confidence Interval (CI) = 0.82-0.96; p < 0.05]. No significant heterogeneity or pleiotropy were observed through their respective tests (p > 0.05), and the statistical power calculations indicated that the results were reliable. The IVW analysis showed a negative causal relationship between T2D and bronchial asthma [OR = 0.85; 95% CI = 0.81-0.89; p < 0.05]. However, the IVW under the random-effects model indicated heterogeneity (p < 0.05), suggesting instability in the results and requiring cautious interpretation. The study found a positive causal relationship between T2D and pulmonary tuberculosis (OR = 1.24, 95% CI = 1.05-1.45, p < 0.05). However, they exhibited pleiotropy (p < 0.05), indicating their instability. No correlation between T2D and interstitial lung disease or lung cancer was observed. Conclusion: T2D is negatively associated with COPD, suggesting that T2D may reduce the risk of developing COPD. A negative causal relationship between T2D and bronchial asthma has been observed, but the results exhibit heterogeneity. There is a positive causal relationship between T2D and pulmonary tuberculosis, yet the findings suggest the presence of pleiotropy. No significant causal relationship between T2D and lung cancer or interstitial lung disease was observed.

13.
Front Immunol ; 15: 1423764, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091502

RESUMO

Background: Sputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma. Methods: This study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation. Results: The levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%). Conclusion: This study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.


Assuntos
Asma , Eosinófilos , Imunoglobulina G , Escarro , Humanos , Asma/imunologia , Asma/diagnóstico , Feminino , Masculino , Imunoglobulina G/imunologia , Pessoa de Meia-Idade , Escarro/imunologia , Adulto , Eosinófilos/imunologia , Biomarcadores , Índice de Gravidade de Doença , Peroxidase de Eosinófilo/metabolismo , Peroxidase de Eosinófilo/imunologia , Estudos de Casos e Controles
14.
World Allergy Organ J ; 17(7): 100934, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39091592

RESUMO

Background: Few studies have evaluated the comparative efficacy of biologics for asthma. This network meta-analysis aimed to compare the efficacy of biologics. Methods: This study included randomized controlled trials (RCTs) evaluating the efficacy of a biologic compared to a placebo or another biologic in patients with inadequately controlled asthma despite high-intensity treatment, published by January 6, 2022. Two researchers independently searched the PubMed, Embase, Web of Science, and Scopus and assessed the risk of bias using the Cochrane tool. The outcomes of interest were the annual asthma exacerbation rate (AER), forced expiratory volume per second before bronchodilator use (preBD FEV1), the asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ) results. A frequentist network meta-analysis was conducted, and a random effects model was used to draw pooled incidence rate ratio or standardized mean differences. Results: Twenty-three RCTs with 8376 participants were retrieved. All biologics included in this study were associated with significantly better effects than placebo in AER, preBD FEV1, and ACQ outcomes. Although there were no significant differences between the biologics in the overall study population, patients with eosinophil levels ≥300 cells/µL or eosinophilic asthma showed that dupilumab and tezepelumab were significantly better than anti-IL-5 biologics in improving preBD FEV1. Additionally, in patients with eosinophil levels ≥300 cells/µL, benralizumab, unlike reslizumab, performed significantly better than placebo in improving ACQ and AQLQ outcomes. Conclusion: The comparative effects of biologics can be considered with phenotypes and biomarkers to help clinicians select an appropriate treatment for inadequately controlled asthma.

15.
Clin Case Rep ; 12(8): e9137, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39091622

RESUMO

A 46-year-old male developed respiratory distress due to asthma-chronic obstructive pulmonary disease overlap and experienced severe tremor caused by beta2 agonist inhalant. We present our successful experience with tizanidine administration.

16.
J Allergy Clin Immunol Glob ; 3(3): 100255, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39092213

RESUMO

House dust mite (HDM) allergen immunotherapy (AIT) has an established role in the treatment of perennial allergic rhinitis (AR) and allergic asthma (AA) triggered by HDM sensitization. We aimed to identify all double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AR and AA in humans and to summarize the evidence for AIT products that are currently manufactured and available for clinical use. A total of 56 eligible double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AA and/or AR in humans fit the inclusion criteria and investigated a total of 14 commercial AIT products; together, the 56 studies enrolled a total of 14,619 patients. Of the 56 studies, 39 studies investigated the current manufacturer-recommended maintenance dose (MRMD) of the product, and 17 investigated other doses. We identified 39 studies (12,539 patients randomized) for 8 sublingual immunotherapy (SLIT) products and 17 studies (2,080 patients randomized) for subcutaneous immunotherapy products. For AR, 3 products, the ALK 12 standardized-quality (SQ-HDM) SLIT tablet, the ALK 6 SQ-HDM tablet, and the SG 300 index of reactivity SLIT tablet, had both dose-finding studies (DFSs) and phase III definitive studies (DSs) to demonstrate efficacy of the MRMD of the product. For AA, 2 products, the ALK 12 SQ-HDM SLIT tablet and the ALK 6 SQ-HDM tablet, had both DFSs and DSs for the MRMD. No subcutaneous immunotherapy product had a paired DFS and DS supporting the MRMD. A total of 30 studies of products no longer commercially manufactured were excluded. This study will help to inform clinical care and product selection for the treatment of HDM-induced AR and AA.

17.
Artigo em Inglês | MEDLINE | ID: mdl-39097197

RESUMO

BACKGROUND: Mepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. OBJECTIVE: Our study aimed to explore the corticosteroid-responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway. METHOD: The MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for SEA. We analysed paired sputum (n=16) and plasma (n=25) samples from the MAPLE trial using high-throughput Olink® proteomics. We also analysed additional sputum proteins using ELISA. RESULTS: In patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type-2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated. Type-2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. CONCLUSION: At stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations.

18.
Biomedica ; 44(2): 217-229, 2024 05 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39088529

RESUMO

Introduction. Asthma is a chronic disease affecting millions of people around the world. Air quality is a major factor in triggering asthma symptoms. Objective. To analyze air quality and asthma in high-altitude residents of La Paz, Bolivia. Materials and methods. In this analytical, descriptive, and retrospective study, we collected data from patients diagnosed with asthma at the Instituto Nacional del Tórax and the Instituto Boliviano de Biología de Altura. In addition, air quality monitoring of particulate matter was carried out at the stations of the Red de Monitoreo de la Calidad del Aire. Results. Women represented 56.9% of cases at the Instituto Nacional del Tórax and the Instituto Boliviano de Biología de Altura. In both institutions, the average age was 47 years and patients were overweight or obese. Increases in PM2.5 were recorded in autumn, winter and spring from 2014, 2016 to 2019 and 2015 in all four seasons. PM10 showed increases in autumn and winter from 2014 to 2020 within the established limits. We observed a positive and significant association between PM2,5 concentration and the spirometry parameters of forced vital capacity, peak expiratory flow, and "reversibility percentage" or "bronchodilator response percentage". The association of PM10 and forced vital capacity, forced expiratory volume in the first second, and peak expiratory flow, was also statistically significant. Conclusion. Asthma cases occur on average at 47 years of age in overweight or obese people. We observed a positive association between particles PM2,5 and PM10 with spirometric parameters, stronger with particulate matter PM2,5.


Introducción. El asma es una enfermedad crónica que afecta a millones de personas en todo el mundo. La calidad del aire es uno de los factores clave que puede desencadenar los síntomas del asma. Objetivo. Analizar la calidad del aire y su relación con el asma en habitantes de grandes altitudes en La Paz (Bolivia). Materiales y métodos. Se desarrolló un estudio analítico, descriptivo y retrospectivo. Se recolectaron datos de pacientes con diagnóstico de asma en el Instituto Nacional del Tórax y en el Instituto Boliviano de Biología de Altura. Además, se monitoreó la calidad del aire y su material particulado en las estaciones de la "Red de monitoreo de la calidad del aire". Resultados. El 56,9 % de los casos fueron mujeres del Instituto Nacional del Tórax y el 45,7 % del Instituto Boliviano de Biología de Altura. En ambas instituciones, la media de edad fue de 47 años y los pacientes presentaban sobrepeso u obesidad. Se registraron incrementos de material particulado fino (PM2,5) en otoño, invierno y primavera, en 2014, 2016-2019 y en las cuatro estaciones del 2015. El material particulado inhalable grueso (PM10) se incrementó en otoño e invierno del 2014 al 2020, dentro de los límites establecidos. Se observó una asociación positiva y significativa entre la concentración de material particulado PM2,5 y los parámetros espirométricos de capacidad vital forzada, flujo espiratorio máximo y el porcentaje de reversión. La relación de partículas PM10 y los parámetros espirométricos de capacidad vital forzada, volumen espiratorio máximo en el primer segundo y flujo espiratorio máximo, también fue estadísticamente significativa. Conclusión. Los casos de asma se presentaron en promedio a los 47 años y en personas con sobrepeso u obesidad. Se observó una asociación positiva entre el material particulado, PM2,5 y PM10, con los parámetros espirométricos, la cual fue más marcada con las partículas PM2,5.


Assuntos
Poluição do Ar , Altitude , Asma , Material Particulado , Humanos , Asma/epidemiologia , Bolívia/epidemiologia , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Material Particulado/análise , Material Particulado/efeitos adversos , Masculino , Adulto , Poluição do Ar/análise , Poluição do Ar/efeitos adversos , Estações do Ano , Idoso
19.
BMC Pulm Med ; 24(1): 380, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095773

RESUMO

BACKGROUND: Dry powder inhalers (DPIs) rely on both internal resistance and patients' inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity. METHODS: The accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland-Altman graphical analysis. RESULTS: PF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland-Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients. CONCLUSIONS: In-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.


Assuntos
Inaladores de Pó Seco , Capacidade Inspiratória , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Reprodutibilidade dos Testes , Desenho de Equipamento , Adulto Jovem , Administração por Inalação , Capacidade Vital , Voluntários Saudáveis
20.
J Sch Health ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39098995

RESUMO

BACKGROUND: Asthma reliever medication access is critical, especially in schools. Policies that "stock" reliever inhalers in schools provide failsafe medication access. This research aims to understand barriers and facilitators to Illinois stock inhaler policy implementation. METHODS: We conducted 18 semi-structured interviews in 2021-2022 with key school-based and non-school-based partners (school administrators, nurses, governmental agencies, and advocacy leaders). Through Atlas.ti, code frequencies compared (Fisher's exact test), and a thematic analysis performed. RESULTS: Four themes emerged: facilitators, barriers, program rationale, and process considerations. The common facilitators were "Finding a provider," having a "Champion," and "Funding". Barriers included "Not enough school nurses," "Pharmacy refusal to fill prescriptions," and "Feeling overwhelmed." All were supportive of the rationale for stock inhalers. Non-school-based informants (p < .01) were more likely to mention medication donations, while school staff reported having enough nurses as a facilitator (p < .01). School staff reported concerns about children with asthma not having their medication significantly more than other partners (p = .02). IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Our analysis revealed that school partners recognize the value of stock inhalers. Barrier mitigation to support the funding, prescription access and processing, and training are essential to success of stock inhaler programming. Multilevel collaborative efforts through coalitions could be a potential solution.

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