Stable Asthma Research Articles

Comparative Study of Inhaled Corticosteroids and Leukotriene Receptor Antagonists As Controller Options for Mildly to Moderately Persistent, Stable Asthma

Comparative Study of Inhaled Corticosteroids and Leukotriene Receptor Antagonists As Controller Options for Mildly to Moderately Persistent, Stable Asthma

Reliability of 24-hours measurement of physical activity, sleep and sedentary time in adult patients with asthma using a triaxial accelerometer

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. Adult patients with stable asthma were asked to wear a triaxial accelerometer for at least four days, with at least 22.5 hours 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. 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. 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.

Relationship between Serum Vitamin D Levels and Asthma Control in Adult Patients

Asthma is a heterogeneous disease characterized by respiratory symptoms that vary both over time and in intensity, along with limited expiratory airflow. This heterogeneity is related to the patient's genetic and environmental phenotype. Vitamin D levels can affect the severity of asthma and the success of asthma treatment. Vitamin D can also influence the effectiveness of glucocorticoid therapy as an anti-inflammatory. This study aimed to determine the relationship between serum vitamin D levels and asthma control, severity, obstruction, and exacerbation levels. This research was a descriptive cross-sectional study on asthma patients at Wahidin Sudirohusodo Hospital and its network for the period October–December 2023. Each research subject had a venous blood sample taken and then checked vitamin D levels at the Hasanuddin University Teaching Hospital Research Laboratory. This research involved 72 research subjects. Most of the research subjects were female (61.1%), aged <45 years (52.8%), worked as housewives (29.2%), had overweight BMI (33.3%), and had a history of atopy (59.7%). The degree of airway obstruction in the study subjects was mostly mild (66.7%) and the degree of severity was intermittent, persistent, and the degree of exacerbation in the same sample (33.3%). The results of the study showed a relationship between vitamin D levels and nutritional status, history of atopy, degree of asthma control using the ACT questionnaire, degree of stable asthma, and exacerbations where p<0.05. Also, it is found that a weakly positive connection (R: 0.2–0.4) between vitamin D levels and ACT, FEV1, FEV/FVC. There is a relationship between vitamin D levels and nutritional status, history of atopy, degree of asthma control using the ACT questionnaire, degree of stable asthma, and exacerbations. There was a relationship between vitamin D levels and the degree of obstruction assessed by spirometry in this study.

Exposure to toluene diisocyanate induces dysbiosis of gut-lung homeostasis: Involvement of gut microbiota

Toluene diisocyanate (TDI) is a major industrial compound that induces occupational asthma with steroid-resistant properties. Recent studies suggest that the gastrointestinal tract may be an effective target for the treatment of respiratory diseases. However, the alterations of the gut-lung axis in TDI-induced asthma remain unexplored. Therefore, in this study, a model of stable occupational asthma caused by TDI exposure was established to detect the alteration of the gut-lung axis. Exposure to TDI resulted in dysbiosis of the gut microbiome, with significant decreases in Barnesiella_intestinihominis, Faecalicoccus_pleomorphus, Lactobacillus_apodemi, and Lactobacillus_intestinalis, but increases in Alistipes_shahii and Odoribacter_laneus. The largest change in abundance was in Barnesiella_intestinihominis, which decreased from 12.14 per cent to 6.18 per cent. The histopathological abnormalities, including shorter length of intestinal villi, thinner thickness of muscularis, reduced number of goblet cells and inflammatory cell infiltration, were found in TDI-treated mice compared to control mice. In addition, increased permeability (evidenced by significantly reduced levels of ZO-1, Occludin and Claudin-1) and activation of TLR4/NF-κB signaling were observed in the intestine of these TDI-exposed mice. Concurrently, exposure to TDI resulted in airway hyperresponsiveness, overt cytokine production (e.g., IL-4, IL-5, IL-13, IL-25, and IL-33), and elevated IgE level within the respiratory tract. The expression of tight junction proteins is reduced and TLR4/NF-κB signaling is activated in the lung following TDI treatment. In addition, correlation analyses showed that changes in the gut microbiota were correlated with TDI exposure-induced airway inflammation. In conclusion, the present study suggests that the immune gut-lung axis may be involved in the development of TDI-induced asthma, which may have implications for potential interventions against steroid-resistant asthma.

Degree of Airway Obstruction and Contributing Factors, Exploring Potential Mismatches and Pitfalls

BACKGROUND: The study investigates asthma, a chronic inflammatory respiratory condition that poses diagnostic challenges due to its variable symptoms, highlighting the importance of accurate documentation and interpretation. It aims to explore the demographic and clinical profiles of asthma patients, particularly focusing on the relationships among airway obstruction severity, spirometric measurements, atopic history, and family history to reveal the complex factors influencing asthma. AIMS: Employing a retrospective descriptive-analytic design, the research analyzes medical records of 107 patients treated at the Outpatient Installation of the Lung Polyclinic at Wlingi General Hospital in Blitar Regency from 2021 to 2022. The analysis incorporates descriptive statistics for demographic and clinical variables alongside Spearman correlation tests. METHOD: Results indicate a significant prevalence of smoking history among asthma patients, with 22.4% being active smokers and 52.3% passive smokers; however, no significant correlation with asthma control was found. Environmental risk factors such as dust and cold air were common but did not consistently correlate with asthma exacerbations. Spirometric analysis revealed a significant relationship between airway obstruction severity and parameters like FEV1, FVC, FEV1/FVC, PEF, FEF 25, FEF 50, and FEF 75, emphasizing the link between airflow obstruction and reduced lung function. Furthermore, no significant correlation was observed between stable asthma diagnosis and atopic or family history, suggesting that asthma control is influenced by various complex factors. CONCLUSION: Our research reveals critical pitfalls in the current understanding of asthma, advocating for a comprehensive evaluation of all contributing factors to enhance diagnostic accuracy and treatment efficacy. Recognizing these complexities is essential for improving asthma management and ensuring better health outcomes for patients.

Fixed Airflow Obstruction in Asthma Can Be Identified Early by Low FEF25-75% and is Associated with Environmental Exposure.

This study aimed to identify environmental risk factors associated with asthmatic fixed airflow obstruction (FAO) and assess the relationship between small airway abnormalities defined by forced expiratory flow at 25-75% (FEF25-75%) and FAO. We analyzed data from 312han Chinese patients with stable asthma on standard treatment. Low FEF25-75% was defined as post-bronchodilator FEF25-75% z-score <-0.8435, and FAO as post-bronchodilator FEV1/FVC z-score <-1.645. Exposure levels were retrospectively analyzed in relation to FAO risk in asthmatics. Asthmatics were grouped by low FEF25-75% and FAO, and lung function, environmental exposure, daily symptoms, and exacerbations in the previous year were compared cross-sectionally across groups. In retrospective analyses, pack-years of smoking in male patients (adjusted odd ratio [95% confidence interval] 1.05 [1.03-1.07], P<0.001), biomass exposure for >20 years (2.65 [1.13-6.43], P=0.027), occupational exposure for >10 years (2.01 [1.06-3.86], P=0.035) and occupational exposure for >20 years (2.67 [1.24-5.91], P=0.013) were associated with asthmatic FAO. In cross-sectional analyses, compared with the normal FEF25-75%/ asthmatics without FAO (NON-FAO) group, the low FEF25-75%/ asthmatics with FAO (FAO) group had lower FEV1 z-scores and FEV1/FVC z-scores, more pack-years and years of biomass and occupational exposure, higher Asthma Control Questionnaire-5 and Chronic Obstructive Pulmonary Disease Assessment Test scores, and more frequent exacerbations. The low FEF25-75%/NON-FAO group showed the same trend, but to a lesser extent. Chronic airway inflammation is not the only driver of asthmatic FAO, and management and treatment targeting environmental risk factors (smoking and biomass and occupational exposures) may slow FAO progression in asthmatics. The FEF25-75% determined by the z-score is a reliable marker of small airway abnormalities, and patients with low FEF25-75% are at greater risk for FAO, requiring more frequent follow-up.

Distinguishing Childhood Asthma Exacerbations from Stable Asthma: The Utility of Inflammatory White Blood Cell Biomarkers.

Asthma is a chronic inflammatory condition characterized by episodes of acute asthma exacerbations (AAEs), in addition to chronic airway inflammation, which has a huge impact on both the affected patients and their parents. The main objective of this study was to explore the utility of available white-blood-cell-derived inflammatory markers in diagnosing AAEs and identifying children at risk for severe exacerbations requiring admission to the pediatric intensive care unit (PICU). This study was a retrospective cohort study. The medical records of 128 children diagnosed with asthma exacerbation and 131 children with stable asthma between the ages of 2 and 12 years were reviewed. A total of 259 participants were enrolled. Children with AAE demonstrated significantly higher white blood cell counts (WBC: 10.0 ± 4.2 × 103/μL vs. 7.1 ± 2.2 × 103/μL, p < 0.001), absolute neutrophil counts (ANC: 7398.5 ± 4600 cells/μL vs. 2634.8 ± 1448 cells/μL, p < 0.001), and neutrophil-to-lymphocyte ratios (NLR: 7.0 ± 6.8 vs. 0.9 ± 0.7, p < 0.001) but significantly lower absolute lymphocyte counts (ALC: 1794.1 ± 1536 × 103/μL vs. 3552.9 ± 1509 × 103/μL, p < 0.001). Interestingly, blood eosinophil count displayed an opposite trend: children with stable asthma had significantly more eosinophils compared to those experiencing an exacerbation (370.1 ± 342.7 cells/mm3 vs. 0.9 ± 1.9 cells/mm3, p < 0.001). Two criteria that are indicative of AAE were identified: NLR values greater than 1.2, with good discriminative ability (area under the curve [AUC] 0.90; 95% confidence interval [CI] 0.85-0.94; sensitivity 82.5%; specificity 79.5%), and ANC values exceeding 3866, with moderate discriminative ability (AUC 0.86; 95% CI 0.81-0.91; sensitivity 75.0%; specificity 82.3%). Moreover, a comparative analysis of these markers (NLR, ANC, PLR, WBC, AEC, and ALC) in patients with AAE did not demonstrate significant differences between those requiring PICU admission and those who did not require it. This study contributes two major findings. The first is that NLR, ANC, WBC, and PLR are significantly higher in AAE patients compared to those with stable asthma. The second is that children with stable asthma have higher AEC and ALC levels compared to those with AAE. Furthermore, this study has revealed that the studied markers (NLR, ANC, PLR, WBC, AEC, and ALC) did not differentiate between AAE patients requiring PICU admission and those managed in the general ward, suggesting a need for alternative predictive factors.

Exercise to Improve Asthma Control and Lung Function in Stable Asthma: An Evidence-based Case Report

Exercise to Improve Asthma Control and Lung Function in Stable Asthma: An Evidence-based Case Report

Evaluation of Eosinophil-Derived Neurotoxin Level and Asthma Severity in Isolated Asthma in Comparison to Asthma with Allergic Comorbidity

Abstract Background Asthma and associated type 2 inflammation are observed in 50–70% of patients with asthma and eosinophilic inflammation is a common feature in many asthma patients, and is associated with a higher risk of a more severe disease. Esinophilic Derived Neurotoxin (EDN) it’s useful as a clinical biomarker for the diagnosis and monitoring of asthma. High levels of EDN have been observed in patients with asthma, with higher levels measured during asthma exacerbations than in those with stable asthma. Objective To compare the association of the level of Esinophilic Derived Neurotoxin and burden of asthma in patients with asthma with Allergic comorbidities such as rhinitis and / or eczema compared to patients with asthma alone. Methods A cross sectional study included 100 adult patients, 50 patients diagnosed as asthma according to GINA guidelines and 50 patients diagnosed as asthma with allergic comorbidity such as Allergic rhinitis and/or eczema were selected from those who presented to the Allergy and clinical immunology clinics at Ain Shams University Hospitals during the period between January to July 2022. Results 50% of the studied population had bronchial asthma alone while the remaining had asthma with allergic comorbidities with most of them had asthma with allergic rhinitis and Most of the patients with allergic rhinitis had mod/severe persistent AR. 77% of total patients had positive SPT and 23% had negative SPT. Most of the patients had positive result for dust mites (Dermatophagoides farina 35% and Dermatophagoides pteronyssinus 30%) followed by pollens (mugwort 27%, rye grass 26% and tobacco 13%) and Animal dander (horse hair 15%, sheep wool 14%, cat hair 13% and dog hair 12%). The Median (IQR) of absolute eosinophil count and total IgE were higher in patients with asthma with Allergic comorbidities [0.68 (0.58 – 0.83) cells/mm3 and 155 (120 – 350) IU/ml respectively] while patients with asthma alone were 0.25 (0.12 – 0.45) cells/mm3 and 68.5 (29 – 123) IU/ml respectively. Our study showed the Median (IQR) of Serum EDN level was higher in patients with asthma with Allergic comorbidities [34 (28 – 40) ng/ml] compared to the patients with asthma alone [15(11 – 18) ng/m]. The quality of life and asthma control test was poor in asthmatic patients with allergic comorbidities compared to patients with asthma alone. Conclusion Serum EDN, Absolute Eosinophilis and total IgE can be used as a marker of T2 inflammation of air ways as their levels were higher in asthma with Allergic comorbidities. Asthma with comorbidities has more symptom burden with poorer quality of life and lower asthma control test than asthma alone; with more concern to be taken for those patients with asthma comorbidities as they have more severe asthma and poorer quality of life

A study on viruses and bacteria with particular interest on Mycoplasma pneumoniae in children with exacerbation of asthma from a tertiary care hospital in Sri Lanka.

Asthma is a significant public health concern, particularly in children with severe symptoms. Exacerbation of asthma (EOA) is life-threatening, and respiratory infections (RIs) play a crucial role. Though viruses play a significant role in EOA, patients are empirically treated with antibiotics, contributing to antibiotic resistance development. Although there are widely reported associations of EOA with viral or Mycoplasma pneumoniae infections, there are no published data for Sri Lanka. The present study aimed to identify the association of common respiratory viruses, typical respiratory bacterial pathogens and M. pneumoniae in children with EOA and relate them with the compatibility of antimicrobial use. A case-control study was conducted in the paediatric unit of North Colombo Teaching Hospital, Sri Lanka, involving two groups of children between 5 and 15 years of age. Group 1 is children with EOA and Group 2 is children with stable asthma (SA). Each group consisted of 100 children. Sputum/throat swabs were tested for common respiratory viruses using virus-specific fluorescein isothiocyanate-labelled monoclonal antibodies (MAbs), bacteria by routine culture, and M. pneumoniae by real-time polymerase chain reaction. Macrolide resistance in M. pneumoniae was detected using conventional PCR and sequencing specific genetic mutations in the 23S rRNA gene. M. pneumoniae was genotyped using nested multilocus sequence typing, which targeted eight housekeeping genes (ppa, pgm, gyrB, gmk, glyA, atpA, arcC and adk). There was no significant difference in age, gender, demographic or geographical location between the two groups. In children with EOA, antibiotics were used in 66 % (66/100) and macrolides in 42 % (42/100). Samples comprised 78 % (78/100) sputum and 22 % (22/100) throat swabs. Adenovirus was the most common virus identified, and it was significantly higher in children with EOA compared to those with SA. Still, the two groups had no significant difference in typical bacteria findings. M. pneumoniae was detected in one patient with EOA, but none was detected in the SA group. The M. pneumoniae was macrolide-sensitive and ST14 by multilocus sequence typing. This study showed that the empiric use of antibiotics in children with asthma might be better targeted with prior pathogen screening to inform appropriate treatment to minimize antibiotic resistance.

Electronic nose based analysis of exhaled volatile organic compounds spectrum reveals asthmatic shifts and consistency in controls post-exercise and spirometry

Analyzing exhaled volatile organic compounds (VOCs) with an electronic nose (e-nose) is emerging in medical diagnostics as a non-invasive, quick, and sensitive method for disease detection and monitoring. This study investigates if activities like spirometry or physical exercise affect exhaled VOCs measurements in asthmatics and healthy individuals, a crucial step for e-nose technology’s validation for clinical use. The study analyzed exhaled VOCs using an e-nose in 27 healthy individuals and 27 patients with stable asthma, before and after performing spirometry and climbing five flights of stairs. Breath samples were collected using a validated technique and analyzed with a Cyranose 320 e-nose. In healthy controls, the exhaled VOCs spectrum remained unchanged after both lung function test and exercise. In asthmatics, principal component analysis and subsequent discriminant analysis revealed significant differences post-spirometry (vs. baseline 66.7% cross validated accuracy [CVA], p < 0.05) and exercise (vs. baseline 70.4% CVA, p < 0.05). E-nose measurements in healthy individuals are consistent, unaffected by spirometry or physical exercise. However, in asthma patients, significant changes in exhaled VOCs were detected post-activities, indicating airway responses likely due to constriction or inflammation, underscoring the e-nose’s potential for respiratory condition diagnosis and monitoring.

Exploratory analysis of gut microbiota differences in patients with bronchial asthma of different inflammatory types

Objective: To observe the characteristics and differences of gut microbiota in asthma patients with different inflammatory types through metagenomic analysis. Methods: Adults aged ≥18 years who visited the Respiratory Clinic of Peking University Third Hospital from August 1, 2021 to August 31, 2022 and were primarily diagnosed with asthma were selected as the study subjects. Finally, 29 patients with stable asthma were included. Fresh fecal samples were collected and the fecal DNA was extracted for high-throughput 16sRNA sequencing of gut microbiota. The diversity and community structure of gut microbiota in different groups of asthma patients were compared, and the species differences were analyzed through random forest and LEfSe analysis. Results: There were sex-based differences in asthma patients with different types of inflammation, and the proportion of female patients was higher in neutrophilic asthma patients (χ2=4.14, P=0.042). There was no significant intergroup difference in the alpha diversity of gut microbiota among asthma patients with different inflammatory types, but there were significant differences in the microbiome. Patients with neutrophilic asthma had higher relative abundance of Bacillales (P=0.029) and Oscillospiraceae (P=0.015). In species LEfSe analysis, patients with eosinophilic asthma had a higher relative abundance of fungi. Conclusion: There are intergroup differences in the gut microbiota of asthma patients with different inflammation types, and fungi are biomarkers that distinguish the differences in gut microbiota between patients with eosinophilic asthma and neutrophilic asthma.

The role of 14-3-3β in acute asthma in children and analysis of the risk factors for asthma exacerbation

Objective To investigate the role of 14-3-3β in acute asthma exacerbations in children and analyze the risk factors for asthma exacerbations. Methods This study recruited 101 children with acute asthma exacerbations, 101 children with stable asthma, and 65 healthy children. Serum 14-3-3β was compared among the three groups. Factors such as asthma family history, skin prick test, serum-specific IgE test, coinfections, and clinical indicators (FeNO, FEV1, white blood cells, eosinophils, and serum IgE level) were compared between the asthma groups. Risk factors associated with acute asthma exacerbations were identified using multivariate logistic regression models. ROC curve was drawn to determine the diagnostic sensitivity and specificity of 14-3-3β. Results Serum 14-3-3β was significantly greater in the acute asthma group than in the stable asthma and control groups. Serum 14-3-3β was higher in severe acute asthma group than in mild-moderate asthma group. There were no significant differences in serum 14-3-3β levels between stable asthma and control groups (p > .05). Multivariate logistic regression analysis revealed that serum 14-3-3β level, FeNO, coinfection, and FEV1 z-score significantly increased the odds of acute asthma exacerbations in children. The optimal 14-3-3β cutoff value (39.79 ng/mL), had a sensitivity of 69.3% and specificity of 94.1% for predicting acute asthma exacerbations. Conclusions 14-3-3β is elevated in children with acute exacerbations of asthma, and increases with exacerbation severity. 14-3-3β, FeNO, FEV1, and coinfection could be independent risk factors for predicting asthma exacerbations. The optimal 14-3-3β cutoff value for predicting asthma exacerbations was 39.79 ng/mL.

Correlating Cyberchondria and Health Anxiety: Demographic Insights from Stable Asthma Patients

Objective: With the increasing ubiquity of internet, the phenomenon of cyberchondria is becoming progressively widespread in today's digital society. This study investigates the correlation between health anxiety and cyberchondria severity and evaluates the influence of demographic factors in stable asthma patients. Methods: This cross-sectional study incorporated a sample of 51 patients with stable asthma. Sociodemographic data were systematically documented, and participants completed the Health Anxiety Inventory (HAI) and Cyberchondria Severity Scale-12 (CSS-12). Data analyses were performed using IBM SPSS Statistics v.22, Pearson and Spearman correlation analyses were employed to investigate relationships between variables, and multivariate linear regression was used to identify potential predictors of health anxiety. Results: The sample primarily consisted of female (76.5%) and married (74.5%) individuals with a mean age of 41.47 years (SD:12.92). Smokers reported higher median scores in health anxiety compared to non-smokers, with a significant difference (p=0.023), while no significant difference in cyberchondria severity was seen across smoking statuses (p=0.380). A moderate positive correlation between health anxiety and cyberchondria severity scores was also identified (r=0.415, p=0.002). The regression analysis indicated that together, cyberchondria severity, smoking status, and education level accounted for a significant proportion of the variance in health anxiety scores (Adjusted R^2:0.374, p&lt;0.001). Conclusion: The study establishes a connection between health anxiety and cyberchondria severity in patients with stable asthma. The results suggest that health interventions targeting modifiable factors could be beneficial in reducing health anxiety within this patient group.

The effect of manual therapy on diaphragm function in adults with asthma: Protocol for a randomized controlled trial.

Diaphragm dysfunction is prevalent among individuals with asthma due to lung hyperinflation and hyperventilation in asthma paroxysm. This study was designed to evaluate the effect of the manual diaphragm release technique (MDRT) on diaphragm function in individuals with asthma. Adults with diagnosed stable asthma (n = 24), will be recruited from the General Hospital of Kifissia "Agioi Anargyroi" in Athens, Greece. The volunteers who meet the inclusion criteria will be randomly allocated to two groups: (a) the experimental group (n = 12) that will receive 12 sessions of MDRT in conjunction with breathing retraining exercises (BRE), and (b) the control group (n = 12) that will receive 12 sessions of BRE. Measurements will occur at three time points: before the initiation of treatment sessions (week 0), followed by 12 treatment sessions (week 6), and three months from the beginning of the trial (week 12). The main outcomes will be the diaphragm excursion (ultrasonography) and chest expansion (inch tape), with secondary outcomes the maximal respiratory pressures (digital pressure manometer), dysfunctional breathing (Nijmegen questionnaire), asthma control (ACT), dyspnea (Borg scale) and quality of life (SF-12v2). The proposed protocol is the first to examine the effectiveness of MRDT on diaphragm's function in individuals with asthma. Manual Therapy (MT) is a low-cost alternative and supplementary therapy to standard treatment procedures that might improve the biomechanics of respiration in pulmonary rehabilitation. Registered on Clinical Trials.gov (ID: NCT05709054). 29/09/2023.

A phase I clinical trial assessing the safety, tolerability, and pharmacokinetics of inhaled ethanol in humans as a potential treatment for respiratory tract infections.

Current treatments for respiratory infections are severely limited. Ethanol's unique properties including antimicrobial, immunomodulatory, and surfactant-like activity make it a promising candidate treatment for respiratory infections if it can be delivered safely to the airway by inhalation. Here, we explore the safety, tolerability, and pharmacokinetics of inhaled ethanol in a phase I clinical trial. The study was conducted as a single-centre, open-label clinical trial in 18 healthy adult volunteers, six with no significant medical comorbidities, four with stable asthma, four with stable cystic fibrosis, and four active smokers. A dose-escalating design was used, with participants receiving three dosing cycles of 40, 60%, and then 80% ethanol v/v in water, 2 h apart, in a single visit. Ethanol was nebulised using a standard jet nebuliser, delivered through a novel closed-circuit reservoir system, and inhaled nasally for 10 min, then orally for 30 min. Safety assessments included adverse events and vital sign monitoring, blood alcohol concentrations, clinical examination, spirometry, electrocardiogram, and blood tests. No serious adverse events were recorded. The maximum blood alcohol concentration observed was 0.011% immediately following 80% ethanol dosing. Breath alcohol concentrations were high (median 0.26%) following dosing suggesting high tissue levels were achieved. Small transient increases in heart rate, blood pressure, and blood neutrophil levels were observed, with these normalising after dosing, with no other significant safety concerns. Of 18 participants, 15 completed all dosing cycles with three not completing all cycles due to tolerability. The closed-circuit reservoir system significantly reduced fugitive aerosol loss during dosing. These data support the safety of inhaled ethanol at concentrations up to 80%, supporting its further investigation as a treatment for respiratory infections.Clinical trial registration: identifier ACTRN12621000067875.

Paradoxical eosinophilic and cytokine responses to oral corticosteroid treatment in patients with asthma exacerbations

BackgroundThymic stromal lymphopoietin (TSLP) orchestrates eosinophilic inflammation, which may increase in asthma exacerbations. On the contrary, miR-1 inhibits TSLP-mediated eosinophil trafficking in lung endothelium. Whether the balance of TSLP and miR-1 levels determines the response to oral corticosteroids during the treatment of asthma exacerbations remains unknown. ObjectiveTo investigate the involvement of TSLP/miR-1 axis in inflammatory response to OCS treatment for asthma exacerbations. MethodsWe measured the concentrations of TSLP and other inflammatory cytokines and miR-1 expression during acute asthmatic exacerbations treated with standard oral corticosteroids (OCS) in a real-life setting. Twenty eight consecutive patients with acute asthma exacerbations treated with OCS for 1 week at the Emergency Department (ED) were studied prospectively. Steroid responders (SR) were identified by a significant reduction in blood eosinophils, whereas paradoxical responders (PR) showed no markedly decreased or even increased absolute blood eosinophil counts after OCS treatment. Differential white blood cell counts, blood cytokine levels and miR-1 expression within and between groups were compared before and after OCS treatment. The baseline cytokine concentrations in both groups were compared with those of stable asthmatics (SA). ResultsOCS treatment significantly reduced TSLP levels in steroid responders whereas this effect did not occur in paradoxical responders (P = 0.006 and P = 0.742, respectively). In contrast, miR-1 expression was unchanged in steroid responders in response to OCS, whereas it was markedly reduced in the paradoxical responders, despite higher expression at baseline compared with stable asthmatics, which may account for slower resolution of the exacerbation. ConclusionsIn some asthmatic patients with acute exacerbations who do not suppress eosinophils after a course of OCS, there is a paradoxical decrease in plasma miR-1 and increase in TSLP compared with steroid responders, which may result in slower clinical recovery.

Involvement of the Constitutive Photomorphogenesis 9 Signalosome Subunit 5 With Programmed Cell Death Protein 1 Ligand in Asthma.

The constitutive photomorphogenesis 9 signalosome (CSN) is a highly conserved protein complex comprised of eight subunits, each of which play crucial roles in diverse cellular processes, such as signal transduction, gene transcription, angiogenesis, and cell proliferation. In the context of asthma, a potential emerging target is the programmed death-ligand 1 (PD-L1)-mediated pathway, which serves as a significant immune checkpoint inhibitor in this condition. However, the precise involvement of CSN subunit 5 (CSN5) in bronchial asthma and the interplay between CSN5 and PD-L1 in asthma remain poorly understood. The potential association between CSN5 and bronchial asthma was explored in a mouse model of ovalbumin (OVA)-induced asthma. Samples were obtained from human lung microvascular endothelial cell (HMVEC-L) treated with Dermatophagoides pteronyssinus (Der p 1) and CSN5 small interfering RNA. The expression of nuclear factor (NF)-κB, IκBα, inhibitor of κB kinase β (IKKβ), PD-L1, and CSN5 was assessed. Additionally, plasma CSN5 levels in asthma patients, both in stable and exacerbated states, were examined. Plasma levels of CSN5 were elevated in patients with exacerbated asthma (n = 19) compared to both healthy controls (n = 10) and patients with stable asthma (n = 19). The CSN5 level demonstrated a correlation with lung function in individuals with asthma. Silencing CSN5 in HMVEC-L led to a reduction in NF-κB protein levels at 4 hours and PD-L1 levels at 4, 8, and 24 hours after Der p 1 treatment. In OVA-sensitized/challenged mice, goblet cell hyperplasia, lung fibrosis, and the levels of CSN5, PD-L1, interleukin-13, interferon-γ, phospho (p)-NF-κB, p-IκBα, and p-IKKβ proteins increased at 33 and 80 days compared to control mice. However, these changes were mitigated by treatment with a PD-L1 inhibitor. These findings suggest that CSN5, along with PD-L1, could serve as a promising target for the treatment of asthma.

Safety and efficacy of Ayurveda compound formulations (Kantakaryavaleha and Eladi gutika) in the management of mild stable bronchial asthma (Tamaka shwasa) – A prospective, open-label, multicentric clinical trial

Safety and efficacy of Ayurveda compound formulations (Kantakaryavaleha and Eladi gutika) in the management of mild stable bronchial asthma (Tamaka shwasa) – A prospective, open-label, multicentric clinical trial

Aberrant characteristics of peripheral blood innate lymphoid cells in COPD, independent of smoking history.

Distinguishing asthma and COPD can pose challenges in clinical practice. Increased group 1 innate lymphoid cells (ILC1s) have been found in the lungs and peripheral blood of COPD patients, while asthma is associated with elevated levels of ILC2s. However, it is unclear whether the inflammatory characteristics of ILC1s and ILC2s differ between COPD and asthma. This study aims to compare peripheral blood ILC subsets and their expression of inflammatory markers in COPD patients, asthma patients and controls. The study utilised multi-colour flow cytometry to analyse peripheral blood ILC populations in clinically stable COPD patients (n=38), asthma patients (n=37), and smoking (n=19) and non-smoking (n=16) controls. Proportions of peripheral blood inflammatory CD4+ ILC1s were significantly higher in COPD patients than in asthma. Proportions of CD4- ILC1s were increased in COPD patients compared to asthma patients and smoking controls. Frequencies of CD117- ILC2s were significantly reduced in COPD patients compared with asthma patients. In contrast, the fraction of inflammatory CD45RO+ cells within the CD117- ILC2 population was significantly increased. Principal component analyses showed that combined features of the circulating ILC compartment separated COPD patients from asthma patients and both control groups. Our in-depth characterisation of ILC1 and ILC2 populations in peripheral blood revealed significant differences in their phenotypes between COPD and asthma patients and smoking or non-smoking controls. These findings suggest a role for both ILC subsets in COPD disease pathology, independent of smoking history, and may have implications for patient stratification and therapy development.