Asthmatic Patients Research Articles

Comparison of Budesonide/formoterol versus Fluticasone furoate/vilanterol as maintenance and reliever therapy for asthma control: a real-world observational study

BackgroundPrevious studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control.MethodsFrom October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment.ResultsA total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group.ConclusionsIn the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.

Associations Between Chronic Rhinosinusitis and the Development of Non–Cystic Fibrosis Bronchiectasis

BackgroundStudies have shown an association between chronic rhinosinusitis (CRS) and non-cystic fibrosis (CF) bronchiectasis. ObjectiveWe aimed to determine if CRS increases the risk of developing non-CF bronchiectasis. MethodsA retrospective analysis was conducted utilizing electronic medical records from an academic center. Patients with CRS without bronchiectasis, with at least one chest computed tomography (CT) performed after the diagnosis of CRS, were identified between January 2006 and December 2015. Charts were reviewed until May 2022. The control group was age, sex, and race matched, and included patients without CRS, asthma, or chronic obstructive pulmonary disease (COPD) who had at least one chest CT. Bronchiectasis was identified by chest CT radiology reports. The odds of developing bronchiectasis were analyzed in patients with CRS without asthma or COPD (Cohort 1) and patients with CRS with asthma or COPD (Cohort 2). ResultsThe odds of developing bronchiectasis were significantly higher in patients with CRS (139/1594, 8.7%) compared to patients in the control group (443/7992 [5.5%], OR 1.63 [1.34-1.99]). Furthermore, the odds of developing bronchiectasis were higher in Cohort 1 (63/863 [7.3%], OR 1.34 [1.02-1.76]) and Cohort 2 (76/731 [10.4%], OR 1.98 [1.53-2.55]) versus the control group. After adjusting for confounding diseases, the association was attenuated in Cohort 1 (OR 1.22 [0.92-1.61]) but remained significant in Cohort 2 (OR 1.78 [1.37-2.31]). ConclusionsCRS is associated with the future development of non-CF bronchiectasis. Patients with CRS, especially those with asthma or COPD, have a higher likelihood of developing bronchiectasis than patients without CRS.

Augmented type 2 inflammatory response in allergic rhinitis patients experiencing systemic reactions to house dust mite subcutaneous immunotherapy.

Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 μg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.

Severe Eosinophilic Asthma or Eosinophilic Granulomatosis With Polyangiitis: Potential Biomarkers for Novel Diagnostic Strategies

BackgroundSevere Eosinophilic Asthma (SEA) may be the prodromal phase of Eosinophilic Granulomatosis with Polyangiitis (EGPA). Nevertheless, few studies have tried to recognize EGPA in the early stages of the disease. ObjectivesTo identify a panel of clinical and biological markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA and crafting a strategy for diagnostic decision-making. Methods30 patients with EGPA and 49 with SEA were enrolled. A complete pulmonary, ear, nose and Throat (ENT) and rheumatologic assessment were made. Blood (eosinophil count, eosinophilic cationic protein-ECP, IL5, IL4, total-IgE, IgG4, anti-neutrophil cytoplasmic antibody (ANCA), sputum (eosinophils count, periostin, IL8 and GMCSF) and nasal smear (eosinophilia) biomarkers were assessed. Asthma Control Test, Short Form-36, SinoNasalOutcome Test-22, and Asthma Quality of Life Questionnaire were also used. ResultsSEA patients had poorer asthma control (p<0.001) and higher level of sputum eosinophils (p<0.002) while EGPA patients reported higher levels of blood eosinophils in the past. Sputum GMCSF was the only biomarker significantly increased in EGPA patients compared with SEA (p<0.0001). Among SEA patients, those with some suggestive but not diagnostic criteria of EGPA, particularly tissue eosinophilic infiltrates, presented higher levels of sputum GMCSF (p<0.0005), blood and sputum eosinophils (p<0.0006, p<0.011) in comparison with the other patients. ConclusionSputum GMCSF and eosinophils might be useful biomarkers to support early diagnosis and treatment choices in SEA patients, suspected of having EGPA

Evaluation of a Primary Care-Integrated Mobile Health Intervention to Monitor between-Visit Asthma Symptoms.

This study aimed to evaluate implementation of a digital remote symptom monitoring intervention that delivered weekly symptom questionnaires and included the option to receive nurse callbacks via a mobile app for asthma patients in primary care. Research questions were structured by the NASSS (Nonadoption, Abandonment, Scale-up Spread, and Sustainability) framework. Quantitative and qualitative methods assessed scalability of the electronic health record (EHR)-integrated app intervention implemented in a 12-month randomized controlled trial. Data sources included patient asthma control questionnaires; app usage logs; EHRs; and interviews and discussions with patients, primary care providers (PCPs), and nurses. We included app usage data from 190 patients and interview data from 21 patients and several clinician participants. Among 190 patients, average questionnaire completion rate was 72.3% and retention was 78.9% (i.e., 150 patients continued to use the app at the end of the trial period). App use was lower among Hispanic and younger patients and those with fewer years of education. Of 1,185 nurse callback requests offered to patients. Thirty-three (2.8%) were requested. Of 84 PCP participants, 14 (16.7%) accessed the patient-reported data in the EHR. Analyses showed that the intervention was appropriate for all levels of asthma control; had no major technical barriers; was desirable and useful for patient treatment; involved achievable tasks for patients; required modest role changes for clinicians; and was a minimal burden on the organization. A clinically integrated symptom monitoring intervention has strong potential for sustained adoption. Inequitable adoption remains a concern. PCP use of patient-reported data during visits could improve intervention adoption but may not be required for patient benefits.

Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma Treated With Mepolizumab: The REMI-M Study

Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months. The REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period. Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months, based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastro-esophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent. This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.

A Review of the Latest Guidelines for Diagnosing and Managing Asthma in Children in the United States and Canada.

Globally, asthma remains the most widespread chronic respiratory condition in children, with a larger proportion of children being affected by the condition. Regardless of the higher prevalence rates, the outcomes of pediatric asthma have remained inadequate, even as there are numerous preventable deaths (approximately 300 children in the United States and 250 children in Canada, annually). The characteristic symptoms of pediatric asthma include wheezing, cough, and shortness of breath that are characteristically triggered by several potential stimuli. However, several diagnostic challenges exist and have resulted in either overdiagnosis or underdiagnosis, making pediatric asthma diagnosis and management problematic. Effective management of asthma in children entails a holistic approach that encompasses non-pharmacological and pharmacological management, alongside self-management and educational aspects. Working with pediatric asthma patients and their families/caregivers is vital to promoting and realizing better asthma diagnosis and management outcomes. Educational guidelines regarding the best ways for effective treatment, avoidance of triggers, modifiable risk factors, and the actions that should be taken during chronic asthma attacks through individualized action plans are vital. Thus, the objective of this systematic review is to provide an overview of the latest guidelines on pediatric asthma diagnosis and management. In this regard, this review presents several similarities in existing pediatric asthma diagnosis and management guidelines in the United States and Canada. For instance, most guidelines and studies reviewed have proposed the use of objective tests for confirmation of asthma diagnosis, particularly in symptomatic individuals. The peak flow variability measurement, bronchodilator reversibility testing, and spirometry have also been proposed by the guidelines and studies, even as the recommendations regarding the timing and hierarchy of the objective test substantially vary between the guidelines and studies. We hope that the present review will be helpful to physicians and healthcare service providers working within pediatric health contexts.

Inhibition of MARCKS phosphorylation attenuates of dendritic cell migration in a murine model of acute asthma

BackgroundMARCKS (myristoylated alanine-rich C kinase substrates) serves as a substrate for protein kinase C, residing in the plasma membrane while acts as an actin filament crosslinking protein. This investigation aims to elucidate phosphorylated MARCKS (p-MARCKS) levels and activity in allergic asthma patients and explore the therapeutic potential of peptide inhibitors targeting p-MARCKS in an acute mouse model of allergic asthma. MethodsImmunohistochemistry and histology staining were employed on lung tissue slides to evaluate p-MARCKS expression and allergic asthma symptoms. Airway resistance was measured using invasive whole-body plethysmography. Flow cytometry detected lung dendritic cell migration, and migration/maturation assays were conducted on isolated murine bone marrow-derived dendritic cells (BM-DCs). ResultsElevated p-MARCKS expression was observed in both human asthmatic tissues and animal models immunized with ovalbumin or Alternaria alternata. Remarkably, asthmatic individuals showed elevated high p-MARCKS expression in lung tissues. Intraperitoneal injection of the peptide MPS, targeting the MARCKS phosphorylation site domain, before allergen challenged, effectively suppressed MARCKS phosphorylation in murine lung tissues. MPS inhibited both in vivo and in vitro migration and maturation of dendritic cells (BM-DCs) and reduced Th2-related lymphocyte activation in bronchoalveolar lavage fluid (BALF). MPS pretreatment additionally suppressed all symptoms associated with allergic airway asthma, including a reduction in inflammatory cell influx, airway mucous cell metaplasia, and airway hyperreactivity. ConclusionThese findings suggest that phosphorylated MARCKS occurs in asthmatic lung tissue, and the inhibition of MARCKS phosphorylation by the MPS peptide reduces dendritic cell migration and Th2-related lymphocytes in the lungs in a murine model of acute asthma.

Asthma Patients Satisfaction towards Nursing Management at Alshaab Teaching Hospital - Khartoum State 2023.

Asthma Patients Satisfaction towards Nursing Management at Alshaab Teaching Hospital - Khartoum State 2023.

Neighborhood Deprivation and Crime on Asthma Exacerbations and Utilization in Mild Adult Asthma

Social determinants of health (SDOH) have a significant impact on asthma outcomes, with factors such as income level and neighborhood environment playing crucial roles. This study aimed to assess the impact of Neighborhood Deprivation Index (NDI) and Total Crime Index (TCI) on acute asthma exacerbation (AAE) and asthma-related Emergency Department and urgent care (ED/UC) visits in adults with mild asthma. This retrospective cohort study utilized administrative data from Kaiser Permanente Southern California among 198,873 mild adult asthma patients between January 1, 2013, and December 31, 2018. Robust Poisson regression models, adjusted for age and sex, were employed to investigate the associations of NDI and TCI with AAE and asthma-related ED/UC visits. Data analysis included subgroup assessments by race and ethnicity and BMI categories to explore potential disparities in asthma outcomes. Among the cohort, 12,906 patients (6.5%) experienced AAE in one year, with Black patients having the highest AAE percentage (7.1%). Higher NDI quintiles were associated with increased AAE risk (aRRs: 1.11-1.27), with similar trends across BMI categories and race or ethnicity, except for Black patients. TCI showed weaker associations with AAE. Regarding ED/UC visits, 5.0% had such visits within one year. Higher NDI quintiles were associated with higher ED/UC visit risk (aRRs: 1.23-1.75), while TCI associations were weaker. Addressing socioeconomic disparities, as indicated by NDI, may be crucial in mitigating asthma exacerbations and reducing healthcare utilization, highlighting the importance of incorporating social determinants into asthma management strategies even in patients with mild asthma.

Real world prescription of beta-blockers in patients with asthma.

This study aimed to investigate the prescription of beta-blockers (β-blockers) for patients with asthma. In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, β-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a β-blocker and an asthma medication were co-prescribed in one billing statement or when separate β-blocker and asthma prescriptions had overlapping dates of use. In the 1027 patients with asthma who were prescribed non-selective β-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 β-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. β2-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. Carvedilol and propranolol accounted for half of all β-blockers prescribed to asthma patients. Prescribing β-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between β-blockers and co-prescribed asthma medications.

Development of a Digital Health Application Prototype among Adult Asthma Patients

Asthma is a chronic respiratory disease affecting more than 334 million people of all age groups globally. Although there are innumerable evidence-based guidelines and effective treatments for this disease, many patients with asthma still have uncontrolled symptoms. The effective control measures of chronic diseases primarily depend on the proper patient care in collaboration with healthcare providers. Currently, healthcare facilities are using the manual asthma action plan to customise each asthmatic patient to understand and manage asthma safely on their own. Thus, this article introduces a preliminary study of a digital health application prototype design based on the asthma action plan among adult asthma patients. The findings regarding the accessibility of this prototype among asthma patients will give a promising alternative tool to empower asthma patients to manage their asthma safely.

Iraqi patients with a single-nucleotide polymorphism of interleukin-10 -1082G/A and interleukin-6 -174G/C susceptibility to asthma

The effects of genetic variations in the IL-10 -1082G/A gene and IL-6 -174G/C gene, as well as the genotypes and alleles linked to the prevalence of asthma disease, were investigated using a molecular and immunological study. Between October 2018 and the end of July 2020, 40 healthy individuals (20 females and 20 males) served as a control group for the study, which involved 50 asthmatic patients (31 females and 19 males) at the Allergy Centre, Al-Anbar Teaching Hospital, in Al-Anbar City. The study used the Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) technique to show that the single nucleotide polymorphisms IL-10 -1082G/A and IL-6 -174G/C had a considerably high prevalence rate (P&lt;0.05) among asthma case and that there was an association between the polymorphism and the asthma risk. The findings indicate that asthma patients had considerably higher (P&lt;0.05) IL-10 A alleles and heterozygous GA genotypes (1082G/A) compared to the control group. Genetic variations affecting IL-10 production and the genotypes affecting IL-10 serum levels are associated with the occurrence of asthma and are attributed to the IL-10 -1082G/A promoter gene polymorphism. There was a strong correlation between cytokine levels, of disease development, and the genotypes of the AA and AG genes, indicating that IL-10 -1082A/G predisposition to asthma may be influenced by the gene promoter polymorphism. Asthma development and immunological markers (IL-10) are substantially correlated. One theory links allergic rhinitis to both the development of asthma and its risk. Inducing long-term immunological and clinical tolerance in patients was a good use of HDM immunotherapy. The current study's findings indicate a substantial difference between the asthma patients and the control group in terms of gene type and allele frequency of the IL-6 -174G/C polymorphism. The patients exhibited a higher prevalence of the G allele and the GG homozygous genotype than the control group. Therefore, it was shown that those with GG genotypes had a 2-fold increased probability of having asthma, indicating that patients were more prone to the condition.

Is Botulinum Toxin Type A Safe for Gummy Smile Treatment in Bronchial Asthma Patients? A Case Report

Background and Aim: The increasing demand for aesthetic enhancements has led to the widespread use of Botox for various facial concerns, including gummy smiles. While its efficacy in treating gummy smiles is established, the safety profile of Botox in patients with underlying medical conditions, such as asthma, remains relatively unexplored. This case report presents a patient with asthma who underwent Botox treatment to correct excessive gingival display. The study aims to demonstrate the potential of Botox for aesthetic improvement in this patient population while emphasizing the need for further research to assess its safety profile. Results: A two-week Botox treatment course successfully eliminated the patient's gummy smile without inducing any asthma-related complications or adverse effects. Conclusion: Although this case suggests the potential of Botox for treating gummy smiles in patients with asthma, it is essential to conduct larger studies to establish its safety and efficacy. A comprehensive medical evaluation is crucial before considering Botox treatment for individuals with underlying health conditions.

Terapi &lt;i&gt;Montelukast &lt;/i&gt;pada Asma

Asthma is a chronic inflammatory respiratory condition caused by various inflammatory mediators, including those from the arachidonic acid pathway, which serves as a precursor for leukotrienes and prostaglandins. Leukotriene receptor antagonists (LTRAs) have been approved since 1998 as a treatment for asthma. Montelukast is one of the LTRAs that is useful for asthma control, including cases that accompanied by allergic rhinitis. A daily dose of 5-10 mg is recommended for persistent asthma as the preferred controller. LTRAs are not recommended for acute asthma exacerbation due to their relatively slow onset, but they are beneficial in preventing exacerbations. They are also indicated for exercise-induced asthma (EIA), and can be taken 2 hours prior to exercise. Montelukast can be administered as monotherapy or added to LABA-ICS therapy. It is suitable for adults, children, and infants over 1 year of age, preferably taken at night to prevent symptoms in the early morning. Possible side effects include respiratory tract infections, abdominal pain, diarrhea, and neuropsychiatric disorders. Montelukast is considered safe for use during pregnancy and breastfeeding. Physicians should provide comprehensive education for patients regarding medication compliance and the potential risks of side effects. Regular daily use of montelukast is beneficial in preventing acute exacerbations in asthma patients.

Increased level of GATA3-AS1 long non-coding RNA is correlated with the upregulation of GATA3 and IL-4 genes in multiple sclerosis patients.

Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies.

Demographic and Asthma-Related Characteristics of Asthmatics Using Pressurized Metered Dose Inhalers and Dry Powder Inhalers.

Background: Asthma controller medications can be delivered via pressurized metered dose inhaler (pMDI) or dry powder inhaler (DPI) devices. Objective: This study aimed to evaluate the frequency of exacerbations and satisfaction rate with device use in asthmatics using pMDIs or DPIs. Methods: A multicenter, cross-sectional study was conducted in adults who used pMDIs or DPIs with correct inhaler technique and good adherence for asthma treatment. Demographic and asthma-related characteristics of the subjects and data regarding device satisfaction were collected through a face-to-face interview in the outpatient clinic. Rates of pMDI and DPI users and the data were compared between the two groups. Results: The study included 338 patients (mean age: 48.6 ± 14.5 years, 253 [74.9%] women). Among participants, 96 (28.4%) were using pMDI and 242 (71.6%) were using DPI. The age of patients using pMDI were significantly lower compared with DPI users. No significant difference was observed in terms of device satisfaction and clinical outcomes of asthma between pMDI and DPI users with good inhaler technique and good adherence. Conclusion: More asthmatics use DPIs, however, pMDIs are used in younger asthmatic patients. No significant difference in terms of device satisfaction and clinical outcomes of asthma was observed between pMDI and DPI users.

Soluble E-Cadherin Contributes to Airway Inflammation in Severe Asthma.

Impaired airway epithelial barrier and decreased expression of E-cadherin are key features of severe asthma. As a gatekeeper of the mucosa, E-cadherin can be cleaved from the cell surface and released into the apical lumen as a soluble form (sE-cadherin).This study was aimed to investigate the role of sE-cadherin in severe asthma.Induced sputum was obtained from healthy subjects and patients with asthma. Two murine models of severe asthma were established using either TDI (toluene diisocyanate) or OVA (ovalbumin)/CFA (complete Freund's adjuvants). The role of sE-cadherin in severe asthma was evaluated by intraperitoneal injection of DECMA-1, a neutralizing antibody against sE-cadherin. Mice or THP-1-derived macrophages were treated with recombinant sE-cadherin to explore the pro-inflammatory mechanism of sE-cadherin.Severe asthma patients had a significantly higher sputum sE-cadherin level than the health subjects with mild to moderate asthma, which were positively correlated with sputum HMGB1 level and glucocorticoid dosage required for daily control. Allergen exposure markedly increased sE-cadherin level in the bronchoalveolar lavage fluid in mice. Treatment of DECMA-1 significantly attenuated allergen-induced airway inflammation and hyperresponsivenes in both models of severe asthma. While exposure to recombinant sE-cadherin dramatically up-regulated VEGF expression in THP-1-derived macrophages, and increased neutophlil and eosinophil infiltration into the airway as well as the release of VEGF and IL-6 in mice, both of which can be suppressed by pharmacological inhibition of ERK signaling.Taken together, our data indicated that sE-cadherin contributed to the airway inflammation of severe asthma in an ERK-depedent pathway.

House dust mite-induced asthma exacerbates Alzheimer’s disease changes in the brain of the AppNL-G-F mouse model of disease

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal death. Besides aging, various comorbidities increase the risk of AD, including obesity, diabetes, and allergic asthma. Epidemiological studies have reported a 2.17-fold higher risk of dementia in asthmatic patients. However, the molecular mechanism(s) underlying this asthma-associated AD exacerbation is unknown. This study was designed to explore house dust mite (HDM)-induced asthma effects on AD-related brain changes using the AppNL-G-F transgenic mouse model of disease. Male and female 8–9 months old C57BL/6J wild type and AppNL-G-F mice were exposed to no treatment, saline sham, or HDM extract every alternate day for 16 weeks for comparison across genotypes and treatment. Mice were euthanized at the end of the experiment, and broncho-alveolar lavage fluid (BALF), blood, lungs, and brains were collected. BALF was used to quantify immune cell phenotype, cytokine levels, total protein content, lactate dehydrogenase (LDH) activity, and total IgE. Lungs were sectioned and stained with hematoxylin and eosin, Alcian blue, and Masson’s trichrome. Serum levels of cytokines and soluble Aβ1-40/42 were quantified. Brains were sectioned and immunostained for Aβ, GFAP, CD68, and collagen IV. Finally, frozen hippocampi and temporal cortices were used to perform Aβ ELISAs and cytokine arrays, respectively. HDM exposure led to increased levels of inflammatory cells, cytokines, total protein content, LDH activity, and total IgE in the BALF, as well as increased pulmonary mucus and collagen staining in both sexes and genotypes. Levels of serum cytokines increased in all HDM-exposed groups. Serum from the AppNL-G-F HDM-induced asthma group also had significantly increased soluble Aβ1-42 levels in both sexes. In agreement with this peripheral change, hippocampi from asthma-induced male and female AppNL-G-F mice demonstrated elevated Aβ plaque load and increased soluble Aβ 1–40/42 and insoluble Aβ 1–40 levels. HDM exposure also increased astrogliosis and microgliosis in both sexes of AppNL-G-F mice, as indicated by GFAP and CD68 immunoreactivity, respectively. Additionally, HDM exposure elevated cortical levels of several cytokines in both sexes and genotypes. Finally, HDM-exposed groups also showed a disturbed blood–brain-barrier (BBB) integrity in the hippocampus of AppNL-G-F mice, as indicated by decreased collagen IV immunoreactivity. HDM exposure was responsible for an asthma-like condition in the lungs that exacerbated Aβ pathology, astrogliosis, microgliosis, and cytokine changes in the brains of male and female AppNL-G-F mice that correlated with reduced BBB integrity. Defining mechanisms of asthma effects on the brain may identify novel therapeutic targets for asthma and AD.

Cost-effectiveness analysis of budesonide/formoterol SMART therapy versus salmeterol/fluticasone plus as-needed SABA among patients ≥12 years with moderate asthma from the Chinese societal perspective

Objectives To evaluate the cost-effectiveness of budesonide/formoterol reliever and maintenance therapy compared with salmeterol/fluticasone plus salbutamol as reliever therapy for asthma patients ≥12 years from the societal perspective in China. Methods A Markov model was developed with three health states (non-exacerbation, exacerbation, and death) with a lifetime horizon. The exacerbation rates were obtained from a prospective cohort study conducted in Chinese asthma patients. Healthcare resources utilization data were estimated based on current clinical asthma management guidelines. Asthma-related mortality, cost input and utility values were derived from public database and literature. Model robustness was assessed with one-way sensitivity and probabilistic sensitivity analyses. Results Compared with salmeterol/fluticasone plus salbutamol, budesonide/formoterol reliever and maintenance therapy led to fewer exacerbation events (13.6 vs. 15.9) and 0.0077 quality-adjusted life years (QALY) gain at an additional cost of ¥196.38 over lifetime. The base case incremental cost-effectiveness ratio (ICER) was ¥25,409.98 per QALY gained. The variables that had most impact on the model output included drug costs and medication adherence. At a willingness-to-pay threshold of ¥257,094/QALY (3 times of gross domestic product per capita in China in 2022), the probability of budesonide/formoterol maintenance and reliever therapy being cost-effective versus salmeterol/fluticasone plus as-needed salbutamol was 83.00%. Conclusion From the societal perspective, budesonide/formoterol reliever and maintenance therapy is likely to be a cost-effective option compared with salmeterol/fluticasone plus as-needed salbutamol for Chinese asthma patients ≥12 years.