Randomized trial of a portable HEPA air cleaner intervention to reduce asthma morbidity among Latino children in an agricultural community

Background Data on pediatric asthma morbidity and effective environmental interventions in U.S. agricultural settings are few. We evaluated the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children. Methods Seventy-five children with poorly controlled asthma and living in non-smoking homes were randomly assigned to asthma education alone or along with HEPA air cleaners placed in their sleeping area and home living room. The Asthma Control Test (ACT) score, asthma symptoms in prior 2 weeks, unplanned clinical utilization, creatinine-adjusted urinary leukotriene E4 (uLTE4 [ng/mg]), and additional secondary outcomes were evaluated at baseline, six, and 12 months. Group differences were assessed using multivariable-adjusted generalized estimating equations. Incident rate ratios of ever experiencing the metrics of poorer asthma health during follow-up (suboptimal asthma management) were estimated using Poisson regression models in secondary analysis. Results Mean child age was 9.2 and 8.6 years in intervention and control groups, respectively, and two-thirds of participants were male. Primary analysis of repeated measures of ACT score did not differ between groups (HEPA group mean change compared to controls 10% [95% CI: − 12-39%]). A suggestion of greater decrease in uLTE4 (ng/mg creatinine) was observed (− 10% [95% CI: − 20 -1%]). Secondary analysis showed children with HEPAs were less likely to have an ACT score meeting a clinically defined cutoff for poorly controlled asthma using repeated measures (IRR: 0.45 [95% CI: 0.21–0.97]). In Poisson models, intervention participants had reduced risk of ever meeting this cutoff (IRR: 0.43 [95% CI: 0.21–0.89]), ever having symptoms in the past 2 weeks (IRR: 0.71 [95% CI: 0.52–0.98]), and lower risk of any unplanned clinical utilization (IRR: 0.35 [95% CI: 0.13–0.94]) compared to control participants. Discussion The HAPI study showed generally improved outcomes among children in the HEPA air cleaner group. However, primary analyses did not meet statistical significance and many outcomes were subjective (self-report) in this unblinded study, so findings must be interpreted cautiously. HEPA air cleaners may provide additional benefit for child asthma health where traditional asthmagens (traffic, tobacco smoke) are not prominent factors, but larger studies with more statistical power and blinded designs are needed. Trial registration ClinicalTrials.gov Identifier: NCT04919915. Date of retrospective registration: May 19, 2021.

Asthma Control during COVID-19 Lockdown in Patients with Severe Asthma under Biological Drug Treatment

Introduction: Coronavirus disease 2019 (COVID-19) has deeply affected the management of patients with severe asthma, treated with add-on biological therapies. Objective: In this study, severe asthmatic patients on treatment with one of three different biologics (omalizumab, mepolizumab, benralizumab) underwent a survey to evaluate the effects of COVID-19 on the management of their clinical condition, with regard to the changes caused by the limited access to health facilities during the pandemic period. Methods: In this prospective observational study, 28 severe asthmatic outpatients referring to the Respiratory Unit of Magna Graecia University Hospital, Catanzaro (Italy), were asked to answer a telephone survey from May to July 2021. This survey included the evaluation of demographic and clinical data, as well as the number of lung function tests performed, exacerbations, biologic doses administered at hospital, or at general practitioner office, or through self-administration. Adherence to biological therapies before and during the pandemic period was also assessed. Moreover, the most recent asthma control test (ACT) score and the last forced expiratory volume in the first second (FEV1) measurement, recorded during the pandemic phase, were compared to the pre-pandemic (baseline) period. Results: When comparing the pre-pandemic data with the pandemic observations, the mean ACT score and the exacerbation rate did not significantly change [ACT, 21.5 ± 2.8 to 23.0 ± 3.9 (p = 0.1); exacerbation rate, 0.3 ± 0.6 and 0.5 ± 1.5 (p = 0.3)]. When considering some variables related to disease management in the same periods, a statistically significant difference was detected with regard to the mean number of outpatient visits (5.2 ± 3.8 vs. 0.9 ± 2.5, p < 0.0001), as well as to the mean number of accesses to health facilities for the administration of biological drugs (from 7.0 ± 3.4 to 2.5 ± 3.9, p < 0.0001). None of the patients reported to have been infected with the SARS-CoV-2 virus and no adverse drug reactions (ADR) occurred during the study. Conclusions: The above results suggest that COVID-19 pandemic did not induce any significant change related to severe asthma control. Indeed, add-on treatment with biological drugs was regularly continued, despite the obvious limited access to health facilities.

Mepolizumab Is an Effective Option in Severe Eosinophilic Asthma Regardless of Baseline Features: Single-Center Real-Life Data

<b><i>Background:</i></b> Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response. <b><i>Methods:</i></b> The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month. <b><i>Results:</i></b> A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/μL to 89/μL and 85/μL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations. <b><i>Conclusion:</i></b> Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings.

TGF-β gene polimorphisms as risk factors for asthma control among clinic patients

Background TGF-β and its receptors play a crucial role in asthma pathogenesis, bronchial hyperreactivity, and bronchial remodeling. Expression of isoforms 1–3 of TGFβ cytokine is influenced by tagging polymorphisms in the TGFβ1, TGFβ2 and TGFβ3 gene, and these SNPs may be associated with the risk of asthma development and severity as well as with other diseases. Polymorphic forms of TGF-β1, TGF-β2 and TGF-β3 genes regulate the degree of bronchial inflammation, deterioration of lung functional parameters in spirometry and elevated level of total IgE. All this results in intensification of disease symptoms. According to current GINA 2020 guidelines, the Asthma Control Test (ACT™) should be applied to assess asthma symptoms. Methods An analysis of polymorphisms localized in TGF-β1, TGF-β2 and TGF-β3 genes was conducted on 652 DNA samples with an application of the MassARRAY® system using the mass spectrometry technique MALDI TOF MS. The degree of asthma control was evaluated with ACT™. Results The occurrence of the T / C genotype in rs8109627 (p = 0.0171) in the TGF-β1 gene is significantly associated with a higher ACT result (controlled asthma) in a multivariate linear regression analysis model after using backward stepwise selection of variables. In addition, in the linear model for prediction of ACT score we showed SNP rs8109627 (p = 0.0497) in the TGF-β1 gene (improvement of the disease control - controlled asthma) and rs2796822 (p = 0.0454) in the TGF-β2 gene (deterioration of the diseases control - uncontrolled asthma) significantly modify the degree of asthma control. Discussion We described clinical significance of two SNPs in two genes TGF-β1 and TGF-β2, as yet unknown. We proved that the use of both genotypes and MAC allows to create a moderately correct prognostic model which is about 70% efficient on the entire set of analyzed SNPs in TGF-β1, TGF-β2, and TGF-β3 genes.

The impact of using a mobile application to improve asthma patients’ adherence to medication in Jordan

The main aim of this study is to assess the effectiveness of using a developed asthma mobile application to enhance medication adherence in Jordan. Asthma patients visiting outpatient respiratory clinics and using inhalers were recruited. Patients were assigned into two groups: intervention and control. The intervention group was instructed to download and use the application. Asthma control was assessed using Asthma Control Test (ACT) at baseline and at follow-up of 3 months for both groups. A total of 171 patients (control, n = 83, and intervention, n = 88) participated in the study. After 3 months of usage, patients in the intervention group achieved a significant improvement in ACT score compared to control ( p-value <0.05), and reported a significant satisfaction of the application use. Therefore, the asthma mobile application is found as an effective tool to enhance medication adherence in asthma patients.

Randomized Trial of a Portable HEPA Air Cleaner Intervention to Reduce Asthma Morbidity among Latino Children in an Agricultural Community

BackgroundData on pediatric asthma morbidity and effective environmental interventions in agricultural settings are few.ObjectivesTo evaluate the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children.MethodsSeventy-five children with poorly controlled asthma and residing in non-smoking homes were randomly assigned to asthma education alone or along with HEPA air cleaners placed in their sleeping area and home living room. Asthma Control Test (ACT) score, asthma symptoms in prior two weeks, unplanned clinical utilization for asthma, creatinine-adjusted urinary leukotriene E4 (uLTE4 [ng/mg]), and other secondary asthma outcomes were assessed at baseline, six and 12 months later. Multivariable-adjusted generalized estimating equations examined differences between groups based on repeated measures. Incident rate ratios of ever experiencing the metrics of poorer asthma health during follow-up (suboptimal asthma management) were estimated using Poisson regression models.ResultsMean intervention group child age was 9.2 years, control mean age was 8.6, and two-thirds of participants were male. In repeated measures analysis, intervention participants were less likely to have an ACT score representing poorly controlled asthma (IRR: 0.45 [95% CI: 0.21–0.97]). In Poisson models, intervention participants had reduced risk of ever experiencing an ACT score representing poorly controlled asthma (IRR: 0.43 [95% CI: 0.21–0.89]), ever having any asthma symptoms in the past two weeks (IRR: 0.71 [95% CI: 0.52–0.98]), and lower risk of any unplanned clinical utilization over the year of follow-up (IRR: 0.35 [95% CI: 0.13–0.94]) compared to control participants. There was a suggestion of greater decrease in uLTE4 (ng/mg creatinine) levels among intervention participants (-10% [95% CI: -20% -1%]).DiscussionHEPA air cleaners may provide additional benefit for child asthma health even in settings with strong asthma education programs and in areas where traditional asthmagens (traffic, tobacco smoke) are not prominent factors.Trial RegistrationClinicalTrials.gov Identifier: NCT04919915. Date of retrospective registration: May 19, 2021.

The Impact of Student Choice to Engage in Cooperative Learning on the Final Exam While Controlling for Early Exam Performance and ACT in Introduction to Psychology

Background: Researchers suggest benefits for cooperative learning, but often fail to control for choosing to engage cooperatively, ACT scores or early course performance. Objective: To observe the effects of choosing cooperative work on exam performance in an Introduction to Psychology Course, while controlling for early exam performance and ACT. Method: Data from 261 students assessed the interaction between choice to work cooperatively, alone or being required to work alone while controlling for ACT Score and performance on early tests, respectively. Results: We observed an interaction between Group and ACT on final exam scores, indicating students who worked cooperatively showed the greatest exam benefits at lower ACT scores. Additionally, a trend toward a significant interaction was found between group and early exam performance, indicating a possible benefit for choosing to work cooperatively for low performers. Conclusion: Choosing to engage in cooperative learning may decrease ACT-indicated skill differences and early exam success on final exam performance. Teaching Implications: To decrease the impact of ACT-influenced effects on exam scores, choice to complete cooperative learning activities should be offered in Introduction to Psychology courses.

Real-life cost-effectiveness of benralizumab in patients with severe asthma

Background Availability of clinically effective and cost-effective treatments for severe asthma would be beneficial to patients and national healthcare systems. The aim of this study was to evaluate clinical outcomes and healthcare expenditure after incorporating benralizumab into the standard treatment of refractory eosinophilic asthma. Methods This was a cross-sectional multicentre study of consecutive patients with refractory eosinophilic asthma who received treatment with benralizumab during at least 12 months. Patient follow-up was performed in specialised severe asthma units. The main effectiveness parameters measured were: the avoidance of one asthma exacerbation, a 3-point increase in the asthma control test (ACT) score, and the difference in utility scores (health-related quality of life) between a 1-year baseline treatment and 1-year benralizumab treatment. The health economic evaluation included direct costs and incremental cost-effectiveness ratios (ICERs). Results After 1 year of treatment with benralizumab, patients with refractory eosinophilic asthma showed an improvement in all the effectiveness parameters analysed: improvement of asthma control and lung function, and decrease in the number of exacerbations, oral corticosteroid (both as corticosteroid courses and maintenance therapy), and inhaled corticosteroid use. The total annual cost per patient for the baseline and benralizumab treatment periods were €11,544 and €14,043, respectively, reflecting an increase in costs due to the price of the biological agent but a decrease in costs for the remaining parameters. The ICER was €602 per avoided exacerbation and €983.86 for every 3-point increase in the ACT score. Conclusions All the pharmacoeconomic parameters analysed show that treatment with benralizumab is a cost-effective option as an add-on therapy in patients with refractory eosinophilic asthma.

Prevalence of Suppressed Morning Serum Cortisol and Its Relationship With Cumulative Glucocorticoid Exposure in a Moderate-Severe Asthma Patient Cohort

The extent to which inhaled glucocorticoid exposure (ICS) contributes to risk of adrenal insufficiency (AI) is not fully understood. The aim of this study was to establish the relative contribution of both oral (OCS) and inhaled (ICS) glucocorticoid exposure to risk of AI.82 patients with severe asthma treated with fluticasone propionate (FP) who participated in a 32-week prospective randomised trial INCA SUN, (NCT02307669) were studied. Cumulative ICS exposure was calculated using a unique digital device, which creates an acoustic recording of inhaler adherence and technique. Analysis of this data provides an exact measure of the ICS dose received by each patient. Morning serum samples collected during the final study visit (week 32) were analysed for serum cortisol concentration (cortisol) using Roche Elecsys Cortisol II immunoassay. Participants were then stratified into three groups based on cortisol concentration to predict risk of AI; cortisol &lt; 100nmol/l (high risk), 100–315 nmol/l (indeterminate risk) and &gt; 315 nmol/l (low risk) based on locally derived reference ranges. 21% participants were classified as low risk, 18% as high risk and the remaining 61% at indeterminate risk of AI. Median morning cortisol in the low risk group was ten-fold higher than those in the high risk group (380 vs 38.5 nmol/l, p=0.001). OCS exposure was a significant predictor of risk of AI (OR 1.1 [1.03–1.17] per mg/kg increase in prednisolone exposure, p=0.004)). Participants at high risk were more likely to be on maintenance OCS (33% vs 0%, p=0.015) and had a greater median cumulative OCS exposure over the study period (7.55 vs 0.66 mg/kg prednisolone, p=0.002). ICS exposure was also associated with risk of AI. Participants at high risk AI had a greater adherence to ICS therapy (78% vs 62%, p=0.049) and greater cumulative received ICS dose over the study duration than those at low risk AI (178.2 vs 127.9 mg, p=0.036). ICS exposure remained a significant predictor of AI even when OCS exposure is controlled for (OR 2.49 [1.06–5.82] per 1mg/kg increase in FP exposure). Both the asthma control test (ACT) & asthma quality of life questionnaire (AQLQ) scores correlate with morning cortisol concentration (ACT r=0.2, p=0.068, AQLQ r=0.26, p=0.019). Interestingly, participants with cortisol &lt; 100nmol/l reported worse asthma control (ACT score 16 vs 20, p=0.07) and a lower AQLQ score (4.1 vs 5.8, p=0.02) than the low risk group despite objectively better lung function (FEV1 90.6 vs 77.6% predicted). Our data suggests that both cumulative oral and inhaled glucocorticoid exposure contribute independently to cortisol suppression and risk of AI. The discrepancy between objective (FEV1) and more subjective measures of asthma control (ACT score) in the high risk group suggests that undiagnosed AI, as well as other non-airway co-morbidities, may contribute to the symptom burden experienced by these patients.

Effectiveness of Personalized Low Salicylate Diet in the Management of Salicylates Hypersensitive Patients: Interventional Study

Salicylic acid and its derivatives (including acetylsalicylic acid/aspirin) are popular in medicine. They also occur naturally in many food products. The aim of the study was to investigate the effect of the personalized low salicylate diet (PLSD) on the reduction of asthma, rhinosinusitis and urticaria symptoms in patients with hypersensitivity to aspirin (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs). To achieve the research goal, a prospective, nonrandomized, baseline-controlled intervention study was conducted. Thirty patients diagnosed with NSAIDs hypersensitivity, who despite pharmacotherapy had symptoms of hypersensitivity, were included in the study. The PLSD was recommended for all participants for a period of two to four weeks. The intensity of subjectively declared symptoms of asthma, rhinosinusitis and urticaria were measured before and after dietary intervention, using, respectively, the asthma control test (ACT), the sino-nasal outcome test (SNOT-22) and the four-item itch questionnaire (FIIQ). Diet adherence and salicylate intake were measured by a 3-day food record. The severity of symptoms improved significantly after the intervention. The median of the ACT score was 24 scores before and 25 after the dietary intervention (p < 0.002), the median of the SNOT-22 score was 25 before and 13 after a dietary intervention (p < 0.0002) and the median of the FIIQ score was 5 before and 0 after a dietary intervention (p < 0.0002). The intake of salicylates decreased from 0.79 mg/day (before intervention) to 0.15 mg/day (p < 0.001) (during intervention). Although the usefulness of a low salicylate diet in the treatment of salicylate hypersensitivity is controversial, the results of our study indicate that the PLSD may have a positive effect in reducing symptoms of salicylate hypersensitivity and could be an additional tool supporting the therapy of these patients.