Journal of Asthma最新文献

Objective: It is well-known that children who suffer from obesity and asthma may also have exercise-induced bronchospasm. Exhaled nitric oxide is an indicator of airway inflammation, and could be affected by exercise. This study looked at how exercise, which is a typical cause of acute airway obstruction, affects the levels of FeNO and spirometric parameters in obese and asthmatic children.

Materials and methods: Seventy children between the ages of 6 and 18 were divided into four groups: healthy children, obese children with asthma, obese children without asthma, and normal-weight asthmatic children. FeNO and spirometric parameters were assessed before and after exercise. Their heart rate was raised to 160-170 beats per minute by walking on a flat surface.

Results: The highest mean FeNO was seen in the asthmatic-obese group, while the lowest mean FeNO was found in the healthy group. MEF25-75 increased with exercise in the obese non-asthmatic group. FEV1/FVC was the lowest in the asthmatic-obese group.

Conclusions: FeNO and FEV1/FVC have a strong association with asthma. The highest values of FeNO found in asthma-obesity combined. It was seen that obesity increased inflammation but exercise did not affect FeNO values. FeNO and FEV1 values were found to be higher in obese patients with and without asthma than normal weight and overweight asthmatics and non-asthmatics.

Objective:Severe asthma burdens patients and presents clinical management challenges for healthcare professionals. Biologics are crucial interventions for severe type two (T2) patients with high eosinophil counts. We conducted a Delphi consensus in seven developing or typically underrepresented countries to understand expert agreement on managing severe asthma with type two (T2) inflammation.

Methods:The study comprised two online survey rounds and a participant meeting, involving 21 and 20 respiratory experts in the first and second survey, respectively. We developed a 70-statement questionnaire after literature review. Responses were recorded on a Likert scale (0-9) with 75% consensus threshold.

Results:Consensus was reached on 37/60 closed-ended questions, including subtypes, in survey-1 and 20/47 closed-ended questions in survey-2. 95% of participants agreed on biomarker use for biologic treatment selection. 100% agreed timely biologic treatment leads to improvement in patients with severe asthma and an eosinophilic phenotype. 90% agreed to avoid maintenance oral corticosteroids (OCS) and start biologic therapy directly. Experts defined clinical remission on treatment as no exacerbations, no OCS use, Asthma Control Questionnaire (ACQ)-5 score < 1.5, and lung function optimization (forced expiratory volume in one second [FEV₁] ≥ 80% of predicted or pre-bronchodilator FEV₁ increase ≥ 100 mL from baseline). In survey-1, 81% agreed these outcomes are achievable in practice. All referral statements achieved consensus.

Conclusions:This Delphi study focused on understanding patients with severe asthma and T2 inflammation in developing/underrepresented countries. Appropriately utilizing biomarkers, timely treatment interventions for best outcomes, expert consensus on clinical remission, and referral are crucial for improving patient management.

Introduction: Asthma attacks are set off by triggers such as pollutants from the environment, respiratory viruses, physical activity and allergens. The aim of this research is to create a machine learning model using data from mobile health technology to predict and appropriately warn a patient to avoid such triggers.

Methods: Lightweight machine learning models, XGBoost, Random Forest, and LightGBM were trained and tested on cleaned asthma data with a 70-30 train-test split. The models were measured on Precision Score, Accuracy Score, Recall Score, F1 Score and model speed.

Results: The best model, XGBoost, obtained an Accuracy score of 0.902, Recall score of 0.904, Precision score of 0.835, and F1 score of 0.860 and a model training speed of 14 s.

Conclusion: As proved by the XGBoost model, predicting asthma triggers can be a viable option for asthma control using machine learning. In addition, the actionable information of triggers, allows patients to make behavior changes. However there will still need to be work testing the system in a mobile health system.

Objective: Although the efficacy of mepolizumab in reducing exacerbations and oral corticosteroid (OCS) use in severe asthma is well-established, real-world long-term effectiveness data are limited. This study evaluated the real-world impact of mepolizumab treatment in patients with severe asthma over a 4-year follow-up period.

Methods: This was a retrospective cohort study of patients with asthma initiating mepolizumab (index date: first claim, November 2015-September 2019) using the Merative MarketScan Commercial and Medicare Databases. Outcomes included asthma exacerbations, OCS use, and exacerbation-related healthcare resource utilization (HCRU) and costs, assessed 12-months pre-index (baseline) and annually during the 4-year follow-up period.

Results: Among 189 eligible patients, mean asthma exacerbation rate (AER) declined progressively from baseline during follow-up: AER decreased by 53.8% at Year 1 and 73.8% by Year 4 (p < 0.001). The annual OCS prescription rate reduced from baseline by 41.1% at Year 1 and 62.2% at Year 4 (p < 0.001). The proportion of patients with both no exacerbations and no OCS use progressively increased from 6.4% at baseline to 18.5% at Year 1 and 41.8% at Year 4. Exacerbation-related HCRU including inpatient, emergency room, and outpatient office visits decreased from baseline (9.0%, 21.7%, and 78.8%, respectively), at Year 1 (3.2%, 12.2%, and 49.2%), and Year 4 (0.0%, 4.8%, and 31.8%). Exacerbation-related healthcare costs declined from $4,635 at baseline to $1,487 at Year 1 and $217 at Year 4 (p < 0.001).

Conclusion: Patients treated with mepolizumab demonstrated progressive and sustained long-term, real-world reductions in exacerbation frequency, OCS dependency, and exacerbation-related HCRU and costs over 4 years.

Introduction: Asthma imposes a critical economic burden on health systems, especially with the incorporation of new drugs. Recently, mepolizumab has been approved to prevent exacerbations in patients with eosinophilic asthma, however their high cost constitutes a barrier for their use, especially in middle- and low-income countries. This study aimed to estimate the economically justifiable price of mepolizumab for preventing exacerbations in patients with severe asthma in Colombia.

Materials and methods: A model was developed using the microsimulation to estimate the quality-adjusted costs and life years of two interventions: mepolizumab versus not applying standard treatment without mepolizumab. This analysis was made during a lifetime horizon and from a third-payer perspective. We analyzed the economically justifiable price using two recent willingness to pay (WTP) estimates in Colombia ($4,828 and $5,128) and $19,992, equivalent to up to three times the GDP per capita, as previously used in conjunction with the two estimates mentioned above.

Results: At current costs of US$781 per dose of 100 mg of mepolizumab, this drug is not cost-effective using a WTP of U$4828, U$ 5128, and U$19 992 per QALY. Based on the thresholds of $4,828, $5,128, and $19,992 per QALY assessed in this study, the economically justifiable costs of mepolizumab were determined to be $147, $165, and $691 per dose, respectively.

Conclusion: The economically justifiable cost for mepolizumab in Colombia is between $147 and $691 per dose, depending on the WTP used. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

Introduction: Asthma is one of the severe respiratory diseases and affects the health of people globally. Animal studies have found that the mucin 5ac (Muc5ac) levels in the lung are associated with asthma. This paper aimed to systematically evaluate the relationship between Muc5ac levels in lung and asthma by extracting relevant data from animal experiments.

Methods: Literatures published before September 2022 in PubMed, Web of Science, Embase and Cochrane databases were collected. Literatures screening and data extraction were performed according to the criteria and the risks of bias were assessed for the included literatures according to the SYRCLE tool. Type 2 inflammatory asthma model was applied in this paper. Meta-analysis was performed using Stata 16.0 software.

Results: A total of 40 publications containing 347 control mice and 337 mice with asthma were included in this study. Meta-analysis results showed the levels of Muc5ac in BALF of mice in asthma group were significantly higher than that in control group [SMD = 3.50, 95%CI(1.45, 5.54)], and the heterogeneity test results showed I2 = 93.0%, p < 0.05. The mRNA expression levels of Muc5ac in lung tissue of mice in asthma group showed a higher level than that in control group [SMD = 4.46, 95%CI (3.38, 5.55)], and the heterogeneity test results showed I2 = 84.3%, p < 0.01. The protein expression levels of Muc5ac in lung tissue of mice in asthma group were significantly higher than those in control group [SMD = 5.70, 95%CI (4.09,7.31)], and the heterogeneity test results showed I2 = 89.7%, p < 0.01.

Conclusion: The meta-analysis clarified the positive relationship between Muc5ac in lung and asthma.

Objective: It remains unclear whether baseline FeNO levels can predict response to anti-IL5/5R biologic treatment in patients with severe asthma.

Methods: We recruited 104 patients with severe eosinophilic asthma treated with anti-IL5/anti-IL5R for at least one year who had measured FeNO values before the beginning of anti-eosinophilic treatment. Population was divided into subjects with FeNO < 25 and ≥25 ppb. In each group we evaluated the changes in pulmonary function (FEV₁% and FEF_25-75%), clinical (ACT and exacerbations) and steroid-sparing effect, expressed as the modification of daily dosage of inhaled corticosteroids (ICS) and oral corticosteroids (OC), after anti-IL5/anti-IL5R.

Results: FEV₁ changes after treatment were 3.34 ± 15,97% in subjects with low baseline FeNO, whereas 11.2 ± 16.1% in individuals with FeNO ≥ 25 ppb (p = 0.012). Also, FEF_25-75% variations after treatment were different in the two groups: 2.1 ± 10.7% vs 9.6 ± 18% in individuals with FeNO < 25 and ≥25 respectively (p = 0.05). Conversely, ACT (4.4 ± 4.2 vs 5.9 ± 4.6; p = 0.147), exacerbation changes (-2.46 ± 1.5 vs -2.9 ± 1.6; p = 0.137) after treatment were similar in both groups where ICS dosages reduction was alike. On the contrary, the percentage of subjects that reduced/stopped OC treatment after anti-IL5/anti-IL5R was 71.7% in the group with FeNO < 25 ppb whereas 94.1% in individuals with FeNO ≥ 25 (p = 0.06). Multivariate analysis adjusted for all confounding factors also confirmed the relationship between FeNO ≥ 25 and improvement in FEV₁%/FEF_25-75% (β = 8.372, p = 0.013 and β = 8.883; p = 0.062 respectively) and the increased probability of discontinuing/reducing OC use (OR:17.838 [95%CI:3.159-100.730]; p = 0.001) in the high FeNO group.

Conclusion: Pre-biologic FeNO might predict a greater response to treatment with anti-IL-5/5R especially in terms of lung function and OC sparing in subjects with severe eosinophilic/allergic asthma. This could likely be a biomarker that can better guide in choosing an anti-IL5/5R in severe overlapping asthma (eosinophilic/allergic) to maximize treatment effects.

Objectives: Patient perception of treatment effectiveness is key to optimizing adherence. This is potentially impacted by color, yet no such studies have been conducted in asthma. This study assessed the influence of pink vs. white pressurized metered-dose inhaler (pMDI) actuators on asthma symptoms perception.

Methods: In this double-blind, randomized, multicenter, crossover study, adults with moderate-to-severe asthma received extrafine formulation beclomethasone dipropionate/formoterol furoate (BDP/FF) pMDI for a 2-week run-in. During two, 2-week treatment periods they received BDP/FF pMDI, white in one, pink in the other, using an 'authorized deception' approach (patients were told the inhalers contained the same active ingredients, but device characteristics differed). Endpoints included patient-reported asthma symptoms and psychopharmacological aspects (prior to use: did patients expect an improvement; after use: did they think there had been an improvement; both on 100-point visual analog scales [VAS]).

Results: Of 74 patients analyzed, 72 completed the study. There were no statistically significant differences between inhalers for asthma symptoms, with minimal changes from baseline. Patients were numerically more likely to expect symptoms improvement with the white than pink inhaler (mean VAS 64.5 vs. 60.8). Perceived improvements were lower than expected with both, numerically favoring the pink inhaler (mean VAS 41.1 vs. 44.6); 46.6% believed a change had been made, 51.9% of whom believed this impacted symptoms.

Conclusions: Changing inhaler color had no impact on asthma symptoms, but did have a numerical impact on patients' expectations of subsequent treatment effect. This emphasizes the importance of communication between patients and healthcare practitioners when changing inhalers.

Objective: Exacerbations and suboptimal disease control are common in severe asthma with an eosinophilic phenotype (SAep). Mepolizumab, an anti-interleukin-5 monoclonal antibody, has demonstrated efficacy and safety in randomized controlled trials (RCTs). We aimed to strengthen the real-world evidence base for mepolizumab in SAep.

Methods: We analyzed data from Italian participants of REALITI-A, a global, real-world, prospective, observational study (primary outcome: rate of clinically significant exacerbations [CSEs]). Using these data and those from Italian real-world studies of mepolizumab (identified by systematic literature review), we performed a meta-analysis.

Results: In the Italian cohort of REALITI-A (n = 244), mean CSE rate was lower 12 months post-mepolizumab initiation versus 12 months pre-mepolizumab (0.67 vs. 3.74 CSEs/patient/year; relative risk [RR], 0.18; 95% confidence interval (CI), 0.15-0.22; p < .001). The meta-analysis included 863 patients. Mean CSE rate decreased from 4.2/patient/year at baseline to 0.71/patient/year post-mepolizumab initiation. Mean oral corticosteroid (OCS) dose reduced by 8.66 mg/day (95% CI, 6.17-11.16 mg/day; p < .0001) from baseline (10.0 mg/day). The RR for OCS maintenance, post- versus pre-mepolizumab, was 0.37 (95% CI, 0.27-0.52; p < .0001). A mean increase in Asthma Control Test score of 6.50 (95% CI, 5.67-7.33; p < .00001) was observed. Proportions of patients reporting adverse events were low.

Conclusions: Real-world experience in this unified health care system identifies that mepolizumab has a low adverse event rate and provides consistent clinical benefits. Mepolizumab represents an important treatment option for patients with SAep.

Background: Studies have suggested associations between montelukast and increased risks of sleep disorders, including overall sleeping problems and insomnia. However, the results of observational studies are not consistent. Understanding these associations is crucial, particularly in patients solely diagnosed with allergic rhinitis, where montelukast use remains prevalent.

Objective: This study aimed to assess whether montelukast exposure is associated with sleep disorders and elucidate the possible molecular mechanism.

Method: We conducted a cross-sectional study of 16,520 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Multivariable regression was used to evaluate the association between montelukast exposure and sleep disorder. Network pharmacology was conducted to identify the mechanisms of montelukast on sleep disorders.

Results: Montelukast exposure had a higher prevalence of sleep disorders (25.28%). In a multivariable logistic regression model adjusted for sociodemographic, behavioral, and health characteristics, montelukast exposure was associated with sleep disorders (odds ratio [OR]: 1.72; confidence interval [CI]: 1.32-2.26). Network pharmacology was identified 39 intersection targets and 17 core targets of montelukast on sleep disorders. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested montelukast mainly works through multiple pathways in chemical carcinogenesis-receptor activation, cancer, estrogen signaling pathway, etc.

Conclusions: The study implies a potential positive association between long-term montelukast exposure and sleep disorders through multi-faceted mechanisms. It is suggested that attention be given to the possibility of sleep disorders in patients undergoing prolonged montelukast therapy.