Journal of Asthma

Background: Clinical studies involving observation have uncovered a mutual relationship between allergic disorders and diabetes, yet the precise causal link remains undetermined. Methods: We conducted two-sample bidirectional Mendelian randomization analyses using single nucleotide polymorphisms (SNPs) associated with allergic conditions (asthma, allergic rhinitis, atopic dermatitis) from genome-wide studies and SNPs related to type 2 diabetes from FinnGen. Initially, we evaluated the causal link between allergic disorders and type 2 diabetes through a univariate Mendelian randomization study, incorporating inverse variance weighting, MR-Egger, and the weighted median estimator. To address potential confounding, we employed multivariate Mendelian randomization. Finally, we validated mediators influencing the correlation between asthma and type 2 diabetes. Results: The Inverse variance weighte method showed that asthma genetically increased the risk of type 2 diabetes (Asthma- type 2 diabetes: β(95%CI)＝0.892(0.152～1.632), P = 0.018). Allergic rhinitis and type 2 diabetes exhibit a mutual protective effect: β(95% CI)＝-1.333(-2.617 to -0.049), P = 0.042；type 2 diabetes - Allergic rhinitis: β(95%CI)＝-0.002(-0.004 to -0.000), P = 0.018). The Multivariable Mendelian randomization study results showed that after after excluding confounding factors, asthma still demonstrates statistical significance in relation to type 2 diabetes. Through mediation analysis, it was discovered that lung function and the percentage of monocytes in leukocytes exert an inhibitory effect on the mediation between asthma and type 2 diabetes. Conclusion: The Multivariable Mendelian randomization study indicates asthma as a risk factor for type 2 diabetes.Lung function, and the percentage of monocytes in leukocytes, play an inhibitory role in asthma and type 2 diabetes mediating effects.

Objective: This study aimed to assess the causality of allergic diseases and celiac disease. Methods: We collected summary-level data from publicly available genome-wide association studies to conduct our bidirectional two-sample and multivariable Mendelian randomization analysis. Furthermore, a series of sensitivity analyses were applied to validate our findings. Results: In bidirectional two-sample MR analyses, we found a significant causal effect of atopic dermatitis (AD) on CD (Inverse-variance weighted (IVW): odds ratio [OR] = 1.302, 95% confidence interval [CI] = 1.152-1.471, P < 0.001). We also found a significant causal effect of allergic rhinitis (AR) on CD (IVW: OR = 4.181, 95% CI = 1.495-11.697, P = 0.006). However, the MR-Egger method indicated a different causal effect direction compared to the IVW and weighted median method. After Bonferroni correction, the result of asthma on CD is suggestive of a causal effect (IVW: OR = 1.186, 95% CI = 1.021-1.378, P = 0.026). No causal effects were found when CD was considered as an exposure variable. In MVMR analyses, after separately and jointly adjusting for the influence of smoking and BMI, the causal effect of AD on CD remained robust. Conclusions: Our study suggests that AD is a risk factor for CD and it is considered suggestive of a causal relationship between asthma and CD. Further research is needed to explore the potential mechanisms underlying this causal effect.

Background: Oxidative stress plays a crucial role in the development of multiple chronic respiratory diseases. Oxidative Balance Score (OBS) composing of 16 dietary factors and 4 lifestyle factors has been developed to evaluate the effect of oxidants/antioxidants produced by dietary intake and lifestyle habits on the overall oxidative balance. However, the relationships between OBS with asthma, COPD, and asthma-COPD overlap (ACO) are still unclear. Methods: A total of 10,942 adults aged 20 years and older from the 2013-2018 National Health and Nutrition Examination Survey were included in the analyses. ANOVA and chi-square tests were used to compare characteristics between different OBS subgroups. Multiple multivariate logistic regression was used to analyze the associations between OBS and asthma, COPD, and ACO.RCS curves were used to describe the dose-response effect of the associations. Subgroup analyses and interaction effects were employed to reflect the stability of the associations. Results: In the fully adjusted models, OBS was found to be negatively associated with asthma, COPD, and ACO. OBS at Q2, Q3, and Q4 (OR: 0.66, 95% CI: 0.46-0.97) were negatively associated with the risk of asthma. OBS at Q2 and Q4 were negatively associated with the risk of COPD. OBS at Q2 and Q4 were negatively associated with the risk of ACO. The RCS curves reflected the negative dose-response trend of association. Moreover, the associations were stable in various subgroups. Conclusion: The negative associations between OBS and asthma, COPD, and ACO were found in American adults, providing evidence for dietary and lifestyle prevention.

Objective: Physical activity (PA), sleep, and sedentary time (SST) are important outcomes to monitor and to improve as part of patients' asthma management. This study aimed to assess the number of measurement days needed to reliably measure PA and SST. Secondly, the influence of external factors on the reliability of measuring PA and SST was studied. Methods: Adult patients with stable asthma were asked to wear a triaxial accelerometer for at least four days, with at least 22.5 h of wear time per day. The Intraclass Correlation Coefficients (ICCs) between different number of measurement days were used to determine reliability. Values ≥0.75 indicated good reliability. Results: Data from 452 patients were analyzed (63% women; age: 49 ± 16 years; FEV1: 87 ± 17% predicted). PA could reliably be measured with four valid measurement days (ICC 0.761). For SST, three days were needed (ICC 0.778). In summer and autumn, three days were needed to reliably measure PA, in winter four, in spring six. For SST, five days were needed in spring for good reliability, and two in all other seasons. Conclusion: Based on data from four valid days, PA and SST can reliably be measured with an accelerometer in patients with asthma. Seasonal influences are present, especially during spring. When measuring for four days, using only weekdays or three weekdays and one weekend day is recommended. The degree of asthma control, dyspnea or spirometric values did not influence the reliability.

Objective: Mepolizumab, an anti-IL-5 monoclonal antibody, has shown promise in reducing exacerbations and steroid dependency in severe eosinophilic asthma. This study aims to evaluate the effectiveness of mepolizumab in achieving clinical remission in asthma over 12 months and explore Vitamin D levels as a predictor of response. Method: We assessed Asthma Control Questionnaire (ACQ) scores, spirometry, number of exacerbations, oral corticosteroid (OCS) use, and inhaled corticosteroid (ICS) use in 32 patients, observing significant clinical improvements. Data were collected 1 year prior to starting mepolizumab and one year after starting mepolizumab. Nasal polyps were not seen in all the patients, and computed tomography of para-nasal sinuses are not available for all the patients, so nasal polyps status are not evaluated to avoid any bias. Result: Our results indicate that 12 patients achieved clinical remission after starting mepolizumab, with a strong correlation between higher Vitamin D levels and positive treatment outcomes. This suggests that optimizing Vitamin D levels could enhance the response to mepolizumab in asthma patients, and help in achieving better asthma control. Conclusion: Mepolizumab is an effective treatment for severe eosinophilic asthma, significantly improving clinical outcomes and reducing corticosteroid use. This study highlights the importance of Vitamin D as a predictor of response to mepolizumab, suggesting that higher Vitamin D levels may enhance treatment efficacy.

Background: Recurrent respiratory tract infections (RRTIs) in children represent a significant clinical challenge. Although some studies have identified potential risk factors, a comprehensive and systematic overview is lacking. Objective: This analysis is carried out to provide more advanced evidence to guide future prevention and health care. Methods: This study (PROSPERO: CRD42024576464) was conducted in accordance with PRISMA guidelines. PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant studies published in English. Subgroup analysis, sensitivity analysis, and publication bias assessments were performed. Data analysis was conducted using Stata 17, and GRADE was employed to assess the quality of evidence. The risk factors identified in the positive results were discussed qualitatively. Results: A total of 29 studies covering 639,078 children were included. Some risk factors: asthma (OR = 3.08, 2.06-4.62), breastfeeding <6 months (OR = 1.26, 1.04-1.52), DCC: day care center (OR = 1.50, 1.16-1.93), have siblings (OR = 1.26, 1.00-1.59), ETS: Environmental tobacco smoke (OR = 1.13, 1.00-1.27), snoring (OR = 1.49, 1.16-1.93) got positive result. Conclusion: This analysis identifies several key risk factors for RRTIs in children, providing enhanced evidence for prevention and management strategies. In particular, asthma warrants closer attention, given its strong association with respiratory infections in pediatrics.

Objectives: Current variations in asthma prevalence and clinical characteristics suggest that lifestyle choices including dietary habits, may affect the pathogenesis and/or clinical expression of the disease. The purpose of this study is to evaluate the association between adherence to Mediterranean diet (MD) and asthma control, considering disease severity. Methods: Adherence to MD was assessed through a questionnaire, the MD Adherence Screener (MEDAS), previously validated in Mediterranean populations. Each participant received a score ranging from 0 to 14. A score higher than 10 indicates high MD adherence. The level of asthma control was assessed by the Asthma Control Test and two groups were formed (controlled vs. partly controlled/uncontrolled). Results: The study sample included 105 participants (34% males). About 45% of participants were severe asthmatics. Adherence to MD was associated with 14% higher, though not statistically significant, probability of controlled asthma in the overall study sample (OR = 1.14; 95% CI = 0.46-2.81) and 60% higher probability of controlled asthma among severe asthmatics (OR = 1.60, 95% CI = 0.46-5.59). Conclusions: These results indicate a possible association between adherence to MD and asthma control, but findings are restricted by the study's small sample size which does not allow asserting the inference.

Objective: This meta-analysis aims to evaluate the efficacy and safety of montelukast combined with levocetirizine in the treatment of allergic rhinitis with asthma, and to provide objective and effective evidence-based medical evidence for clinical use. Data sources: Pubmed, Web of Science, Cochrane Library, WANFANG DATA, CNKI, and Chinese BioMedical Literature Database were retrieved to identify records related to Montelukast combined with levocetirizine in the treatment of allergic rhinitis with asthma. Study selections: First, the eligibility criteria were employed to screen search results. Then, two investigators independently assessed titles, abstracts, and the full text of all retrieved references to identify potentially eligible studies. Results: As of 2024-02-03, a total of 6 articles were included in this meta-analysis, covering 2950 patients with allergic rhinitis with asthma. The meta-analysis results exhibited a pooled NSS of -1.28 (95%CI: -1.64 to -0.92), suggesting that the combination of montelukast and levocetirizine was effective in the treatment of nasal symptoms of allergic rhinitis complicated with asthma. The meta-analysis of controlled trials showed that the SMD of NSS in the group of Montelukast combined with levocetirizine was -2.56 (95%CI: -2.77 to -2.35). The result indicated that compared with the control group, the combination of montelukast with levocetirizine significantly improved the symptoms of allergic rhinitis. Conclusion: In summary, this meta-analysis demonstrated the efficacy of montelukast combined with levocetirizine in the treatment of nasal symptoms in AR with asthma, indicating that the combination of montelukast with levocetirizine is more effective in improving symptoms of allergic rhinitis than monotherapy and has good safety.

Background: Severe asthma, which differs significantly from typical asthma, involves specific molecular biomarkers that enhance our understanding and diagnostic capabilities. The objective of this study is to assess the biological processes underlying severe asthma and to detect key molecular biomarkers. Methods: We used Weighted Gene Co-Expression Network Analysis (WGCNA) to detect hub genes in the GSE143303 dataset and indicated their functions and regulatory mechanisms using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) annotations. In the GSE147878 dataset, we used Gene Set Enrichment Analysis (GSEA) to determine the regulatory directions of gene sets. We detected differentially expressed genes in the GSE143303 and GSE64913 datasets, constructed a Least Absolute Shrinkage and Selection Operator (LASSO) regression model, and validated the model using the GSE147878 dataset and real-time quantitative PCR (RT-qPCR) to confirm the molecular biomarkers. Results: Using WGCNA, we discovered modules that were strongly correlated with clinical features, specifically the purple module (r = 0.53) and the midnight blue module (r = -0.65). The hub genes within these modules were enriched in pathways related to mitochondrial function and oxidative phosphorylation. GSEA in the GSE147878 dataset revealed significant enrichment of upregulated gene sets associated with oxidative phosphorylation and downregulated gene sets related to asthma. We discovered 12 commonly regulated genes in the GSE143303 and GSE64913 datasets and developed a LASSO regression model. The model corresponding to lambda.min selected nine genes, including TFCP2L1, KRT6A, FCER1A, and CCL5, which demonstrated predictive value. These genes were significantly upregulated or under expressed in severe asthma, as validated by RT-qPCR. Conclusion: Mitochondrial abnormalities affecting oxidative phosphorylation play a critical role in severe asthma. Key molecular biomarkers like TFCP2L1, KRT6A, FCER1A, and CCL5, are essential for detecting severe asthma. This research significantly enhances the understanding and diagnosis of severe asthma.

Objective This review aims to present existing evidence on the impact of pioglitazone, a thiazolidinedione class anti-diabetic drug, on asthma control and lung function, providing a comprehensive understanding of its potential as a treatment for asthma. Data Sources The review draws upon data from preclinical animal studies and clinical trials investigating the effects of pioglitazone on asthma, focusing on its role in reducing airway inflammation, hyperreactivity, and remodeling, and its impact on pulmonary function. Study Selections Relevant studies were selected based on their examination of pioglitazone’s therapeutic effects in asthma, including both animal models and clinical trials involving human asthma patients. Results Animal studies have suggested that pioglitazone could alleviate inflammation, airway hyperreactivity, and airway remodeling, thereby improving pulmonary function in asthma. However, clinical trials have not demonstrated significant therapeutic benefits, with minimal improvements observed in asthma control and lung function, and the presence of notable side effects. Conclusion Despite promising preclinical data, the efficacy of pioglitazone in treating human asthma remains unproven, with safety concerns and limited clinical benefits observed in trials. Further research is needed to assess the safety and effectiveness of pioglitazone in asthma treatment and to explore its impact on other inflammatory mechanisms.

Background: There is limited information on the discrepancy between the spirometric values calculated with diverse spirometric prediction equations in normal children. Objective: To determine the differences in percentage predicted (PP) values calculated through thirteen prediction equations (PEs) in healthy Chilean children. Methods: We compared the PP values for FVC, FEV1, FEF25-75% and FEV1/FVC obtained by applying thirteen PEs, using GLI-2012 as a gold standard reference equation and including race neutral GLI-2022 in the analysis; PP values are from a group of 208 healthy Chilean children aged 7 to 17 years. Results: In boys, the range of differences for FVC between PEs compared to the reference group went from -5.47% to 20.82% and from -6.4% to 19.74% in girls. For FEV1, in girls, the range of differences went from -5.96% to 18.01% and from -5,04% to 20.67% in boys. Significant differences between GLI-2012 PPs and the other PEs were observed more frequently in girls than in boys (p < 0.001). Conclusions: There is a wide difference between the spirometric PPs values by different PEs, including race neutral GLI-2022. Our findings, especially given the potential interpretative and clinical implications, might suggest the need for conducting standardized, multicenter studies in Latin America to determine which PEs would better fit pediatric populations in this region.

Objective: The study objective was to investigate the factors associated with the physical and psychological wellness of United States (US) adults with asthma.Methods: This cross-sectional analysis used a sample of 2329 US adults with asthma in the 2021 Medical Expenditure Panel Survey data. A logistic regression model investigated the association of the following factors and the dependent variables (physical wellness and psychological wellness): age, sex, race, ethnicity, education, employment, healthcare provision, marriage, income, regular physical activity, current smoker, pain, and limitations. Nationally representative estimates were produced through a weighted analysis. The data structure was maintained using cluster and strata variables. The alpha limit was 0.05.Results: Factors associated with higher odds of reporting good physical wellness included: private (versus no) healthcare provision (odds ratio [OR] = 2.63, 95% confidence interval [CI] = 1.10-6.26), good (versus poor) psychological wellness (OR = 6.83, 95% CI = 4.35-10.72), regular (versus no regular) physical activity (OR = 2.18, 95% CI = 1.42-3.34), little/moderate (versus quite a bit/extreme) pain (OR = 3.51, 95% CI = 2.38-5.15) and no (versus any) limitation (OR = 3.73, 95% CI = 2.30-6.06). In the psychological wellness model, those aged ≥70 (OR = 6.18, 95% CI = 2.72-14.07), 60-69 (OR = 4.64, 95% CI = 2.13-10.10), and 50-59 (OR = 4.96, 95% CI = 2.24-11.02) versus those aged 18-29, and good (versus poor) physical wellness (OR = 6.89, 95% CI = 4.34-10.94) were associated with higher odds of reporting good versus poor psychological wellness.Conclusion: These results may be helpful at targeting resources to optimize the wellness of US adults with asthma. Additional studies are needed to determine any temporal associations between these findings.

Objective: To evaluate the feasibility of a novel intervention of health literacy-informed, telemedicine-enhanced asthma education and home management support for hospitalized children and caregivers, and assess caregiver perspectives of the intervention. Methods: We conducted a pilot randomized trial of the Telehealth Education for Asthma Connecting Hospital and Home (TEACHH) intervention vs. standardized care (SC) for children (5-13 yrs) hospitalized with asthma. Participants in TEACHH received health literacy-informed teaching prior to discharge, including pictorial materials (e.g. flipchart, action plan), color- and shape-coded medication labels, and medication demonstration. Two Zoom-based follow-up teaching visits were completed within 1-month of discharge. Feasibility was assessed by tracking visit completion, and we measured preliminary outcomes using health records (i.e. total asthma-related acute healthcare visits) and blinded surveys of caregivers 2-, 4-, and 6-months post-discharge (i.e. symptom-free days, quality of life). We interviewed caregivers about their perceptions of TEACHH. Transcripts were coded inductively. Results: We enrolled 26 children and interviewed 14 caregivers (9 TEACHH, 5 SC). All inpatient sessions were completed, as were 77% of virtual visits. Both groups experienced improved symptoms and quality of life over time. Caregivers valued the teaching, involvement of children, visual tools, and color-coded information of TEACHH. They described child-specific benefits, greater support after discharge, and improved asthma-related communication, and indicated that other families would benefit from similar teaching. Conclusions: A novel program of patient-centered asthma education was feasible in both hospital and home settings and well received by caregivers. A larger study is needed to assess the impact of TEACHH on childhood asthma morbidity. Clinicaltrials.gov identifier: NCT04995692 (Registration date 8/9/2021).

Objective: The aim of the present study was to determine the cost-utility of single inhaler combination inhaled corticosteroid and a long-acting β2-agonist (ICS/LABAs) as both maintenance and reliever (SMART) compared with a step-up maintenance treatment with a fixed medium to high dose of ICS combined with LABA and a short-acting β2-agonist (SABA) as reliever (ICS-LABA maintenance plus SABA) among patients aged 12 years or more with poorly controlled asthma in Colombia. Methods: A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The main effectiveness data were obtained from a recent meta-analysis. The main outcome was the variable ''quality-adjusted life-years'' (QALYs). Results: The base-case analysis showed that the budesonide/formoterol (BUD/FORM) SMART strategy was associated with lower overall treatment costs (US $3,062.37 vs.$4,462.02 average cost per patient over 12 months) and the greatest gain in QALYs (0.8511 vs. 0.8258 QALYs on average per patient over 12 months) compared with ICS-LABA maintenance plus SABA at step 4, thus leading to dominance. Conclusions: In patients aged 12 years or more with uncontrolled asthma at GINA step 3 or 4, the BUD/FORM SMART strategy at either step 3 or 4 is cost-effective compared with the ICS-LABA maintenance plus SABA at step 4 strategy, because it shows a greater gain in QALYs at lower total treatment costs.

Introduction: Personalised Asthma Action Plans (AAPs) are a cornerstone of paediatric asthma management. We aimed to assess parental knowledge and perceptions of the use of AAPs in managing their child's asthma. Methods: In 2023 we conducted a cross-sectional survey to assess knowledge and perceptions of AAPs in parents/caregivers of children aged 0-17 years with asthma who had an AAP and attended respiratory clinics at Sydney Children's Hospital, Randwick. The questionnaire included parental perceptions on the utility of AAPs, parental asthma management self-efficacy (PAMSE), and an adapted version of the Asthma Action Plan Knowledge Interview tool (AAPKI). Descriptive statistics and regression analyses were used to assess associations between AAPKI, PAMSE and other outcomes. Results: Seventy-one parents completed the survey. Mean PAMSE score was 4.2/5 (SD 0.5). Median AAPKI score was 70.2% out of 100% (IQR 20.4%). Most parents (80.0%, n = 56) were satisfied/very satisfied with using AAPs to manage their child's asthma. Most agreed/strongly agreed that AAPs were helpful in knowing when to seek medical attention for their child's asthma (81.7%, n = 58), helped their understanding of asthma severity (81.7%, n = 58), and increased their confidence in asthma management (76.0%, n = 54). Over half of parents (55.7%, n = 39) would prefer AAPs digitally and majority (78.6%, n = 55) would like colour-coded AAPs. Conclusion: High levels of AAP knowledge and self-efficacy scores were demonstrated. Most parents expressed understanding of the benefits of AAPs. Our findings suggest parents of children with asthma prefer AAPs in colour and in digital version which may help guide standardisation of AAPs across Australia.

Objective: Existing research suggests that emotion plays an important role in airway inflammation and asthma symptom control. The objective of this study was to determine whether difficulties regulating emotion were associated with overuse of short-acting inhaled medications and acute medical care usage in adults with asthma. Methods: The sample included 401 adults with asthma recruited from an online panel of adults with chronic respiratory disease. Sequential binary logistic regression models were used to examine the associations of emotion regulation with short-acting inhaled medication use and acute medical care use, controlling for patient characteristics and comorbid mental health conditions. Results: Greater difficulties with emotion regulation were significantly associated with greater odds of short-acting inhaler medication overuse (p < 0.001), emergency department visits (p < 0.001), and hospitalizations (p = 0.001). Conclusions: Emotion dysregulation may play an important role in asthma management. Evidence-based interventions to reduce difficulties in emotion regulation may help improve problematic patterns of short-acting medication overuse and acute service use. The current findings should be interpreted in the context of several limitations, including the use of self-report measures. Future research should use electronic medical records or metered dose inhalers to objectively assess short-acting inhaler overuse and acute medical care use.

Background and aims: To construct a set of scientific and effective quality evaluation indicators of continuing care for children with asthma, and to promote the development of continuing care for children with asthma toward a more specialized and standardized direction. Methods: Through literature research and semi-structured interview, the item pool of evaluation index was drawn up, and the first draft of expert inquiry questionnaire was formed based on the three-dimensional quality theoretical model of structure-process-result, and the construction of quality evaluation index was completed through two rounds of expert inquiry and analytic hierarchy process. Results: The effective recovery rate was 94.44% in the first round and 100.00% in the second round, the expert authority coefficient was 0.852 and 0.863, and the Kendal coordination coefficient was 0.129 and 0.126, respectively (p < 0.01). Finally, the evaluation index of continuing care quality for children with asthma was formed, including 3 first-level indicators, 9 s-level indicators and 36 third-level indicators, and then the weight and combination weight of each index were obtained by AHP. Conclusions: The evaluation index of continuing care quality for children with asthma is scientific and specific, which is of great significance to the improvement of continuing care quality for children with asthma.

Background: Asthma is a common chronic condition with increasing prevalence. Diet, including dried fruit consumption, has been linked to asthma risk, but the mechanisms remain unclear. This study investigates how dried fruit consumption affects asthma risk, focusing on acetate as a potential mediator. Methods: We used Mendelian Randomization (MR) to analyze the relationships between dried fruit intake, acetate levels, and asthma. We applied three MR methods-Inverse-Variance Weighted (IVW), Weighted Median (WM), and MR-Egger-to determine causal effects. Results: Dried fruit intake was inversely associated with asthma risk (IVW: β = -0.506, p = 0.0135) and positively associated with acetate levels (IVW: β = 0.269, p < 0.0001). Higher acetate levels were also linked to lower asthma risk (IVW: β=-0.361, p < 0.0001). Mediation analysis showed that acetate mediates approximately 19.22% of the effect of dried fruit on asthma risk. Conclusion: Dried fruit consumption reduces asthma risk, partly through increasing acetate levels. This acetate-mediated pathway accounts for about 20% of the effect, suggesting potential for dietary strategies in asthma prevention and management. Further research could enhance the understanding and applicability of these findings.