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AbstractObjectiveMethodsResultsConclusionAsthma is a chronic respiratory disorder characterized by airway inflammation and narrowing often leading to acute exacerbations that necessitate a visit to the emergency department (ED). While life threatening cases usually require bronchodilator delivery by nebulizers, mild to moderate acute asthma exacerbations can be treated by bronchodilators delivered either by metered dose inhalers (MDI). Numerous studies have attempted to compare between the two modalities and have drawn similar conclusions in that both are comparable in efficacy with minimal differences. What is evident, however, is that physicians remain inclined to favor nebulizers in the majority of acute asthma exacerbations.In this questionnaire-based study, a survey was distributed to physicians who treat asthma exacerbations to examine demographics, knowledge, beliefs, and current practice in regard to bronchodilator therapy.The majority (90.8%) of physicians prefer short-acting beta agonists via nebulizer, with 9.2% favoring MDI + spacer. Participants include consultants, residents, and specialists across various emergency disciplines. While 90.1% find MDI + spacer equally effective as nebulizers, advantages cited include cost-effectiveness (49.6%), shorter ED stays (63.4%), quicker administration (67.9%), and ease of use (58.8%). Challenges include availability (66.4%) and ineffectiveness in younger patients (45%). Despite this, 65.6% are willing to switch to MDI for initial asthma management in the ED, while 34.4% are resistant.Concerns about availability and effectiveness in younger patients remain barriers. However, a significant number are willing to adopt MDIs with spacers, indicating potential for broader use with better availability and training. [ABSTRACT FROM AUTHOR]

BACKGROUND: High-flow nasal cannula (HFNC) systems employ different methods to provide aerosol to patients. This study compared delivery efficiency, particle size, and regional deposition of aerosolized bronchodilators during HFNC in neonatal, pediatric, and adult upper-airway and lung models between a proximal aerosol adapter and distal aerosol circuit chamber. METHODS: A filter was connected to the upper airway to a spontaneously breathing lung model. Albuterol was nebulized using the aerosol adapter and circuit at different clinical flow settings. The aerosol mass deposited in the upper airway and lung was quantified. Particle size was measured with a laser diffractometer. Regional deposition was assessed with a gamma camera at each nebulizer location and patient model with minimum flow settings. RESULTS: Inhaled lung doses ranged from 0.2-0.8% for neonates, 0.2-2.2% for the small child, and 0.5-5.2% for the adult models. Neonatal inhaled lung doses were not different between the aerosol circuit and adapter, but the aerosol circuit showed marginally greater lung doses in the pediatric and adult patient models. Impacted aerosols and condensation in the non-heated HFNC and aerosol delivery components contributed to the dispersion of coarse liquid droplets, high deposition (11-44%), and occlusion of the supine neonatal upper airway. In contrast, the upright pediatric and adult upper-airway models had minimal deposition (0.3-7.0%) and high fugitive losses (~24%) from liquid droplets leaking out of the nose. The high impactive losses in the aerosol adapter (56%) were better contained than in the aerosol circuit, resulting in less cannula sputter (5% vs 22%), fewer fugitive losses (18% vs 24%), and smaller inhaled aerosols (5 µm vs 13 µm). CONCLUSIONS: The inhaled lung dose was low (1-5%) during HFNC. Approaches that streamline aerosol delivery are needed to provide safe and effective therapy to patients receiving aerosolized medications with this HFNC system. [ABSTRACT FROM AUTHOR]

Introduction: Identifying factors influencing peak inspiratory flow (PIF) is essential for aerosol drug delivery in stable patients with chronic obstructive pulmonary disease. While a minimum PIF for dry powder inhalers (DPIs) is established, acute bronchodilator (BD) effects on PIF remain unknown. Materials and Methods: An inspiratory flow meter (In-Check™ DIAL) was used to measure PIF in stable patients during a 24-week observational cross-sectional study. Additionally, bronchodilator responsiveness (BDR) was determined using the In-Check DIAL device and spirometry. Patients received four puffs of albuterol, and pre- and post-BD PIF, forced expiratory volume in one second (FEV1), and forced vital capacity were measured. Sixty-three patients completed acute BDR data collection from July 31, 2019, to November 9, 2021. Primary endpoints were pre- and post-BD spirometry and PIF. Statistical analyses included PIF correlations with FEV1. BD change was assessed according to inhaler resistance and sex (subgroup analysis). Results: Median patient age was 64.8 years, 85.7% were non-Hispanic White, and 57.1% were female. The median increase in absolute PIF (In-Check DIAL) was 5.0 L/min, and the % PIF change was 8.9%. With albuterol, 57.1% experienced a PIF BD change >5.0%, whereas 49.2% experienced a change >10.0%. Similarly, 55.6% experienced an FEV1 BD change >5.0% and 28.6% had a >10.0% FEV1 BD change with albuterol. PIF was weakly correlated with FEV1 BD change (absolute; % PIF; r = 0.28 [p = 0.02]; r = 0.21 [p = 0.11]). Pre- and post-BD median PIF were 75.5 and 83.5 L/min for low-to-medium–resistance DPI and 45.0 and 52.0 L/min for high-resistance, respectively. The median increases in pre- and post-BD PIF were 9.0 L/min in males and 4.5 L/min in females. In contrast to when using the In-Check DIAL device, we observed no consistent bronchodilatory effects on PIF measured by spirometry. Conclusions: Using the In-Check DIAL device, ∼50% of patients experienced >10% PIF increase after acute BD, potentially enhancing medication lung deposition. Further research is required to understand PIF's impact on medication delivery. ClinicalTrials.gov Identifier: NCT04168775 [ABSTRACT FROM AUTHOR]

One of occupational illnesses is irritant-induced asthma (IIA), which IIA is a phenotype of asthma caused by the inhalation of irritant agents. The incidence of IIA is reported as 5-18% of occupational asthma cases. In some cases, it is challenging to differentiate IIA from work-exacerbated asthma (WEA) because no specific diagnostic tests can determine whether a person has asthma caused by exposure to irritants. In any case of suspected IIA, the diagnosis of asthma should be confirmed by spirometry demonstrating airflow limitation with significant bronchodilator response or nonspecific bronchial hyperresponsiveness (NSBHR) to methacholine/histamine. IIA Management is similar to asthma management, including bronchodilator therapy and inhaled and/or systemic corticosteroids. Several studies recommend treating asthma in adults and adolescents with short-acting beta-agonists (SABA), adding a controller in the form of inhaled corticosteroids (ICS) as needed to reduce the risk of severe exacerbations and to control symptoms. This type of controller can be given regularly every day, or ICS-formoterol can be given as needed to relieve symptoms in mild asthma. Prevention that can be done at IIA includes health promotion, special protection, early diagnosis and early treatment, limitation of disabilities, and rehabilitation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Optimal aerosol delivery methods for spontaneously breathing patients with a tracheostomy remain unclear. Thus, we aimed to assess the impact of nebulizer placement, flow settings, and interfaces on aerosol delivery by using a vibrating mesh nebulizer and a jet nebulizer in line with unheated humidification. METHODS: An 8.0-mm tracheostomy tube was connected to the lung model that simulates adult breathing parameters via a collecting filter. Albuterol sulfate (2.5 mg/3 mL) was administered via a vibrating mesh nebulizer and a jet nebulizer, which was placed in line with unheated humidification provided by a large-volume nebulizer, with FIO2 set at 0.28, with gas flows of 2 L/min versus 6 L/min. Nebulizers were placed in line distal and proximal to the lung model by using a tracheostomy collar and a T-piece. Conventional nebulization was tested using a vibrating mesh nebulizer and a jet nebulizer directly connected to the tracheostomy tube bypassing the humidification device. The drug was eluted from the collecting filter and assayed with ultraviolet spectrophotometry (276 nm). RESULTS: During in-line nebulizer placement with unheated humidification, the inhaled dose was 2-4 times higher with a gas flow of 2 L/min than 6 L/min, regardless of nebulizer type, placement, or interface (all P < .05). At 6 L/min, the inhaled dose was higher with proximal than distal placement when using both interfaces, but, at 2 L/min, the inhaled dose was lower with proximal placement. With a jet nebulizer, the tracheostomy collar generated a higher inhaled dose at proximal placement compared with the T-piece, whereas the T-piece resulted in a higher inhaled dose than the tracheostomy collar with distal placement, regardless of the flow settings. Compared with conventional nebulization using a vibrating mesh nebulizer, an in-line vibrating mesh nebulizer with a large-volume nebulizer at 2 L/min had a similar inhaled dose, regardless of nebulizer placement and interface. In contrast, the in-line jet nebulizer was influenced by both placement and interface. CONCLUSIONS: Aerosol delivery with an in-line vibrating mesh nebulizer and jet nebulizer with unheated humidification was affected by nebulizer placement, interface, and gas flow settings. [ABSTRACT FROM AUTHOR]

Abstract The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83–0.94; p

Abstract Background Salbutamol and hyoscine butylbromide (HBB) are commonly used bronchodilators in horses with severe asthma (SA). Objective To compare the bronchodilation potency, duration, and adverse effects of salbutamol and HBB in SA. Animals Six horses in exacerbation of SA. Methods The effects of inhaled salbutamol (1000 μg) and HBB (150 mg, IV) were compared in a randomized, blinded, crossover experiment. Lung function, intestinal borborygmi and heart rate were assessed before and sequentially until 180 minutes after drug administration, and analyzed with 2‐way repeated‐measures ANOVA and Dunnett's multiple comparison tests. Results Both treatments caused a similar improvement in lung function. Pulmonary resistance and reactance returned to baseline values within 30 minutes after HBB administration, whereas salbutamol improved reactance until 180 minutes (mean improvement at 180 minutes of 0.040 Kpa/L/s, 95% CI = 0.004 to 0.076; P = .02 for salbutamol and of 0.009 Kpa/L/s, 95% CI = −0.028 to 0.045; P = .98 for HBB for the resistance at 3 Hz and of 0.040 Kpa/L/s, 95% CI = 0.007 to 0.074; P = .01 for salbutamol and of 0.009 Kpa/L/s, 95% CI = −0.024 to 0.042; P = .97 for HBB for the reactance at 7 Hz). From 5 to 30 minutes after HBB administration, the heart rate accelerated (mean increase of 3.3 beats per minute, 95% CI = −6.6 to 13.1; P = .92 for salbutamol, and of 13.0 beats per minute, 95% CI = 3.6 to 22.4; P = .002 for HBB at 30 minutes) and the gut sounds decreased (mean reduction of 1.3, 95% CI = −0.1 to 2.8; P = .09 for salbutamol and of 2.8 for the gastrointestinal auscultation score, 95% CI = 1.4 to 4.3; P

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83–0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD. [ABSTRACT FROM AUTHOR]

Asthma exacerbations are a frequent reason for pediatric emergency medical services (EMS) encounters. The objective of this study was to examine the implementation of evidence-based treatments for pediatric asthma in a regional consortium of EMS agencies. This retrospective study applied the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) implementation framework to data from an EMS agency consortium in the Cincinnati, Ohio region. The study analyzed one year before an oral systemic corticosteroid (OCS) option was added to the agencies' protocol, and five years after the protocol change. We constructed logistic regression models for the primary outcome of Reach, defined as the proportion of pediatric asthma patients who received a systemic corticosteroid. We modeled Maintenance (Reach measured monthly over time) using time series models. A total of 713 patients were included, 133 pre- and 580 post-protocol change. In terms of Reach, 3% (n = 4) of eligible patients received a systemic corticosteroid pre-OCS versus 20% (n = 116) post-OCS. Multivariable modeling of Reach revealed the study period, EMS transport time, months since implementation of OCS, and number of bronchodilators administered by EMS as significant covariates for the administration of a systemic corticosteroid. For Maintenance, it took approximately two years to reach maximal administration of systemic corticosteroids. Indicators of asthma severity and time since the protocol change were significantly associated with EMS administration of systemic corticosteroids to pediatric asthma patients. The two-year time for maximal Reach suggests further work is required to understand how to best implement evidence-based pediatric asthma treatments in EMS. [ABSTRACT FROM AUTHOR]

Background: Salbutamol and hyoscine butylbromide (HBB) are commonly used bronchodilators in horses with severe asthma (SA). Objective: To compare the bronchodilation potency, duration, and adverse effects of salbutamol and HBB in SA. Animals: Six horses in exacerbation of SA. Methods: The effects of inhaled salbutamol (1000 μg) and HBB (150 mg, IV) were compared in a randomized, blinded, crossover experiment. Lung function, intestinal borborygmi and heart rate were assessed before and sequentially until 180 minutes after drug administration, and analyzed with 2‐way repeated‐measures ANOVA and Dunnett's multiple comparison tests. Results: Both treatments caused a similar improvement in lung function. Pulmonary resistance and reactance returned to baseline values within 30 minutes after HBB administration, whereas salbutamol improved reactance until 180 minutes (mean improvement at 180 minutes of 0.040 Kpa/L/s, 95% CI = 0.004 to 0.076; P =.02 for salbutamol and of 0.009 Kpa/L/s, 95% CI = −0.028 to 0.045; P =.98 for HBB for the resistance at 3 Hz and of 0.040 Kpa/L/s, 95% CI = 0.007 to 0.074; P =.01 for salbutamol and of 0.009 Kpa/L/s, 95% CI = −0.024 to 0.042; P =.97 for HBB for the reactance at 7 Hz). From 5 to 30 minutes after HBB administration, the heart rate accelerated (mean increase of 3.3 beats per minute, 95% CI = −6.6 to 13.1; P =.92 for salbutamol, and of 13.0 beats per minute, 95% CI = 3.6 to 22.4; P =.002 for HBB at 30 minutes) and the gut sounds decreased (mean reduction of 1.3, 95% CI = −0.1 to 2.8; P =.09 for salbutamol and of 2.8 for the gastrointestinal auscultation score, 95% CI = 1.4 to 4.3; P <.0001 for HBB at 30 minutes). Conclusions and Clinical Importance: Both drugs have a similar bronchodilator potency but with a longer duration for salbutamol. Gastrointestinal and cardiovascular effects were noted only with HBB, suggesting the preferential use of salbutamol to relieve bronchoconstriction in horses with asthma. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this review is to summarize the management of asthma in children and to highlight different guideline-based approaches. This review also discusses literature regarding the use of corticosteroids, both inhaled and systemic, as well as biologic agents, in asthma management. Summary Asthma is a common chronic respiratory condition in the pediatric population and has evolved into a highly patient-specific disease. Of the 2 main asthma guidelines, one developed by the National Asthma Education and Prevention Program was recently published as a focused update in 2020. The other, from the Global Initiative for Asthma, focuses on a global strategy for management and prevention, with the most recent update in 2023. Both reports discuss diagnosis, assessment, and treatment of asthma in adults and children. Treatment is designed as a stepwise approach in both reports, although there are key differences. This article focuses on gaps in these guidelines, including the use of bronchodilators and inhaled corticosteroids with single maintenance and reliever therapy and long-acting muscarinic antagonists in children. It also reviews treatment in children under 5 years of age, although recommendations are limited due to a lack of evidence in this age group. Finally, this review discusses considerations for emerging treatments, including biologics, for patients who are difficult to treat. Conclusion New treatment strategies and agents have emerged in the treatment of pediatric asthma. Pharmacists play a key role in providing education about, dispensing, and recommending the newest evidence-based treatment options for children. [ABSTRACT FROM AUTHOR]

Rationale: A COPD Foundation working group sought to identify measures of exercise endurance, a meaningful aspect of physical functioning in everyday life among patients with chronic obstructive pulmonary disease (COPD) that is not fully accepted in regulatory decision making, hampering drug development. Objectives: To demonstrate, as we previously asserted (Casaburi COPD 2022;9:252), that constant work rate cycling endurance time is an appropriate exercise endurance measure in patients with COPD. Methods: To validate this assertion, we assembled an integrated database of endurance time responses, including 8 bronchodilator (2,166 subjects) and 15 exercise training (3,488 subjects) studies (Casaburi COPD 2022;9:520). Results: Construct validity was demonstrated: 1) peak physiologic and perceptual responses were similar for constant work rate and incremental cycling; 2) after bronchodilator therapy, there were greater increases in endurance time in patients with more severe airflow limitation; 3) after exercise training, endurance time increases were similar across airflow limitation severities; and 4) there were correlations between changes in endurance time and changes in mechanistically related physiologic and perceptual variables. Test–retest reliability was demonstrated, with consistency of changes in endurance time at two time points after the intervention. Responsiveness was confirmed, with significant increases in endurance time after active (but not placebo) bronchodilator therapy, with greater increases seen with more severe airflow limitation and after exercise training. On the basis of regression analysis using multiple anchor variables, the minimum important difference for endurance time increase is estimated to be approximately 1 minute. Conclusions: Constant work rate cycling endurance time is a valid exercise endurance measure in COPD, suitable for contributing to the evaluation of treatment benefit supporting regulatory decision making and evidence-based therapeutic recommendations. [ABSTRACT FROM AUTHOR]

Measles is an acute respiratory infectious disease caused by the measles virus. It leads to respiratory involvement with manifestations such as pneumonia, laryngobronchitis, pneumonitis, etc. It can also cause secondary bacterial and fungal infections. Aminophylline is a methylxanthine bronchodilator composed of theophylline and ethylenediamine. Airway blockage is reversed by bronchial smooth muscle relaxation, increased myosin light chain kinase activity, and decreased intracellular calcium concentration. It relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels, reducing airway responsiveness to histamine, methacholine, adenosine, and allergens. Allergic skin reactions secondary to aminophylline administration have been rarely seen. Aminophylline can be given orally as well as intravenously. A seven-month-old male infant presented with a lower respiratory tract infection and a maculopapular rash involving the face and trunk. A history of contact with measles was present. Intravenous aminophylline was administered for persistent wheezing. The infant developed a generalised erythematous papular rash with a more widespread distribution than before within one hour of administration. The child was treated with antihistamines for the same. After a detailed physical examination, looking at the pattern of the rash and excluding other causes like environmental factors and drug history, the diagnosis of an allergic reaction to aminophylline was made. Early identification of allergic reactions is paramount, as prompt cessation of the offending agent and initiation of appropriate medical interventions can significantly mitigate the severity of the reaction and prevent potential life-threatening complications.

BackgroundBronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.Research questionIs consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD?Study design and methodsWe retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEV1 (FEV1-BDR), change in FVC (FVC-BDR), and change in in FEV1, FVC or both (ATS-BDR). Using generalized linear models adjusted for demographics, smoking history, FEV1 % predicted after bronchodilator administration, and number of visits that the participant completed, we assessed the association of BDR group: (1) consistent BDR, (2) inconsistent BDR, and (3) never BDR with asthma, CT scan features, blood eosinophil levels, and FEV1 decline in participants without COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) and the entire cohort (participants with or without COPD).ResultsBoth consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEV1-BDR and FVC-BDR definitions. Eosinophils did not vary consistently among BDR groups. Consistent BDR was associated with FEV1 decline over time relative to never BDR in the entire cohort. In participants with GOLD stage 0 disease, both the inconsistent ATS-BDR group (OR, 3.20; 95% CI, 2.21-4.66; P < .001) and consistent ATS-BDR group (OR, 9.48; 95% CI, 3.77-29.12; P < .001) were associated with progression to COPD relative to the never ATS-BDR group.InterpretationDemonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease.

Background Oral bronchodilators may be used as an adjunctive treatment, especially in patients with uncontrolled asthma or poor inhaler technique. This study aimed to determine the differences in asthma symptoms and bronchodilator effect between oral doxofylline and oral procaterol in adults with asthma. Methods A crossover randomized controlled trial was conducted. Asthmatic patients aged 18 years or older with stable inhaled corticosteroids and long-acting beta2-agonists (ICS/LABA) treatment were included. Each patient received 2 weeks of treatment with either doxofylline or procaterol followed by a 1-week washout period and 2 weeks of treatment with the other drug. Asthma symptoms were assessed using the Asthma Control Questionnaire-5 (ACQ-5) scores, pulmonary function was assessed by spirometry with bronchodilator testing, and adverse events were recorded. Results A total of 21 patients were randomly allocated to either the doxofylline or procaterol groups. The mean age of the patients was 53.0±14.8 years. ACQ-5 scores were 1.4±1.1. After two weeks of treatment, the ACQ-5 scores and all pulmonary function parameters were not significantly different between the two groups ( P>0.05). However, significant improvements in ACQ-5 scores were found in both groups (mean change: -0.381± 0.740, P=0.029 and -0.476± 0.873, P=0.021 for the doxofylline and procaterol groups, respectively). None of the patients experienced asthma exacerbations. Conclusions Doxofylline and procaterol can improve asthma symptoms, although they cannot enhance lung function. These oral bronchodilators might be used as an add-on therapy in asthmatic patients with persistent symptoms despite treatment with an ICS/LABA combination.

ABSTRACTBackground The criteria for significant bronchodilator responsiveness (BDR) were published in 2005 by the European Respiratory Society/American Thoracic Society, which were revised in 2021, however, data on the agreement between these two recommendations in untreated patients with airflow limitation are missing.Aims We aimed to study BDR to salbutamol (SABA) or ipratropium bromide (SAMA) in patients with suspected bronchial asthma or COPD at initial clinical presentation using the 2005 and 2021 criteria and explore clinical factors associated with BDR+.Methods Symptomatic, treatment-naïve patients with expiratory airflow limitation (n = 105, 57 men, age (mean ± standard deviation): 65 ± 10 years) underwent BDR testing with 400 mcg salbutamol (day 1) or 80 mcg ipratropium bromide (day 2) and BDR was measured after 15 and 30 minutes. Clinical factors with risk for BDR+ were assessed with binomial logistic regression analysis.Results We found a good agreement between the number of 2005-BDR+ and 2021-BDR+ patients at 15 and 30 minutes post-salbutamol and post-ipratropium (88.6–94.8%). More patients showed BDR+ after 30 minutes than following 15 minutes using either criterion. When results at 30 minutes are considered, the number of patients with 2005-BDR+ (82%) was higher than that of 2021-BDR+ (75%), with the proportion of SAMA+ patients being higher than that of SABA+ (2005: 70% vs. 49%, Fisher exact p

IntroductionThe COPD Biomarkers Qualification Consortium (CBQC) was formed under COPD Foundation management, with the goal of qualifying biomarkers and clinical outcome assessments through established regulatory processes for chronic obstructive pulmonary disease (COPD). Within CBQC, a working group evaluated opportunities for qualification of an exercise endurance measure. In a recent publication (Chronic Obstr Pulm Dis. 2022; 9[2]:252-265), we described a conceptual framework establishing exercise endurance's direct relationship to an individual with COPD's experience of physical functioning in daily life, and that increase in exercise endurance is a patient-centered, meaningful treatment benefit. We further proposed endurance time during constant work rate cycle ergometery (CWRCE) as a useful efficacy endpoint in clinical therapeutic intervention trials. In this current publication, we describe the process of assembling an integrated database of endurance time responses to interventions in COPD.MethodsWe sought participant-level data from published studies incorporating CWRCE as an outcome measure. A literature search screened 2993 publications and identified 553 studies for assessment. Two interventions had sufficient data across studies to warrant data extraction: bronchodilators and rehabilitative exercise training. Investigators were contacted and requested to provide participant-by-participant data from their published studies.ResultsThe final dataset included data from 8 bronchodilator studies (2166) participants and 15 exercise training studies (3488 participants). The database includes 71 variables per participant, comprising demographic, pulmonary function, and detailed physiologic response data. This paper provides a detailed description of the analysis population, while analysis supporting the validation/qualification process and addressing other scientific questions will be described in subsequent publications.

Total extract of Tephrosia purpurea (T. purpurea) expressed potent ex-vivo bronchodilator effect in isolated Guinea pigs’ tracheal muscles. Fractionation of T. purpurea total extract (TPTE) using liquid–liquid technique followed by ex-vivo bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl3) soluble fraction. Phytochemical study of the CHCl3 fraction guided by ex-vivo bronchodilator activity led to the isolation of 7 active flavones of which compounds 1 (epi-Tephroapollin G), 3 (Acetyltephroapollin C), 4 (4′’-Dehydroxytephroapollin E), and 5 (epi-Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds 1, 3, 4 and lanceolatin A (6) behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K+)-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G (2) selectively inhibited CCh-mediated contractions but was not found active against high K+. epi-Tephroapollin F (5) and (-)-Pseudosemiglabrin (7) in contrast were significantly more potent to abolish CCh induced contraction when compared with high K+ similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca++ ion inhibitory activities of 1, 3, 4 and 6 were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca++ inhibitory effect of 1 and 3–7 was confirmed by the rightward deflection of Ca++ concentration–response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds 2, 5 and 7 at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the TPTE, CHCl3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo.

Measles is an acute respiratory infectious disease caused by the measles virus. It leads to respiratory involvement with manifestations such as pneumonia, laryngobronchitis, pneumonitis, etc. It can also cause secondary bacterial and fungal infections. Aminophylline is a methylxanthine bronchodilator composed of theophylline and ethylenediamine. Airway blockage is reversed by bronchial smooth muscle relaxation, increased myosin light chain kinase activity, and decreased intracellular calcium concentration. It relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels, reducing airway responsiveness to histamine, methacholine, adenosine, and allergens. Allergic skin reactions secondary to aminophylline administration have been rarely seen. Aminophylline can be given orally as well as intravenously. A seven-month-old male infant presented with a lower respiratory tract infection and a maculopapular rash involving the face and trunk. A history of contact with measles was present. Intravenous aminophylline was administered for persistent wheezing. The infant developed a generalised erythematous papular rash with a more widespread distribution than before within one hour of administration. The child was treated with antihistamines for the same. After a detailed physical examination, looking at the pattern of the rash and excluding other causes like environmental factors and drug history, the diagnosis of an allergic reaction to aminophylline was made. Early identification of allergic reactions is paramount, as prompt cessation of the offending agent and initiation of appropriate medical interventions can significantly mitigate the severity of the reaction and prevent potential life-threatening complications. [ABSTRACT FROM AUTHOR]

Weimin Li,1 Sami Z Daoud,2 Roopa Trivedi,3 Pradeep B Lukka,4 Eulalia Jimenez,5 Eduard Molins,5 Catherine Stewart,6 Pranob Bharali,3,7 Esther Garcia-Gil8 1Clinical Trial Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 3Late Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Durham, NC, USA; 4Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA; 5Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Barcelona, Spain; 6Statistics, Phastar, Chiswick, London, UK; 7BioPharmaceuticals R&D Late-Stage Development, AstraZeneca India Pvt Ltd., Bangalore, Karnataka, India; 8Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Barcelona, SpainCorrespondence: Sami Z Daoud, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA, Tel +1 302-598-8614, Email Sami.Daoud@astrazeneca.comPurpose: To date, aclidinium pharmacokinetic (PK) studies have focused on Caucasian populations, and no data are available for Chinese populations. We aimed to characterize the PK and safety profile of aclidinium and its metabolites (LAS34823 and LAS34850) following single and multiple (twice-daily; BID) dosing in healthy Chinese participants, and to compare PK data between Chinese and Caucasian populations.Materials and methods: In this Phase I, open-label study (NCT03276052), healthy participants from a single site in China received aclidinium bromide 400 μg via a dry powder inhaler. The Day 1 single dose was followed by a washout period of 96 hours. On Days 5 through 8, participants received BID doses.Results: Twenty healthy Chinese participants, aged 18– 45 years, were enrolled. Aclidinium absorption was rapid (median time to maximum concentration [tmax] 0.08 hours post-dose following single/multiple doses). LAS34823 had a similar median tmax of 0.08 hours, whereas LAS34850 tmax occurred later (median 2.50– 3.00 hours). Aclidinium, LAS34823, and LAS34850 concentrations declined in a bi-phasic manner; geometric mean half-life was 13.5 hours (single dosing) and 21.4 hours (multiple dosing), while steady state was generally achieved after 5 days’ continuous dosing. Area under the concentration–time curve during a dosage interval (AUCτ) metabolite to parent ratios for LAS34823 were 2.6 (Day 1) and 2.9 (Day 9), while LAS34850 had ratios of 136.0 and 94.8, respectively. Aclidinium accumulation occurred after 5 days of BID dosing (LS mean accumulation ratio for AUCτ Day 9/Day 1: 214.1% [90% CI, 176.5, 259.6]); LAS34823 accumulation was similar, while LAS34850 accumulation was lower. Between-participant exposure variability was moderate to high for aclidinium and LAS34823, and low for LAS34850.Conclusion: Single and multiple doses of aclidinium were well tolerated in healthy Chinese participants. The safety profile of and exposure to aclidinium was consistent with previous studies conducted in Caucasian populations.Keywords: aclidinium bromide, bronchodilator, China, chronic obstructive pulmonary disease, pharmacokinetics, safety

The purpose of this study was to explore the relationships between heart rate variability (HRV) and various phenotypic measures that relate to health and functional status in chronic obstructive pulmonary disease (COPD), and secondly, to demonstrate the feasibility of ascertaining HRV via a chest-worn wearable biosensor in COPD patients. HRV analysis was performed using SDNN (standard deviation of the mean of all normal R-R intervals), low frequency (LF), high frequency (HF), and LF/HF ratio. We evaluated the associations between HRV and COPD severity, class of bronchodilator therapy prescribed, and patient reported outcomes. Seventy-nine participants with COPD were enrolled. There were no differences in SDNN, HF, and LF/HF ratio according to COPD severity. The SDNN in participants treated with concurrent beta-agonists and muscarinic antagonists was lower than that in other participants after adjusting heart rate (beta coefficient -3.980, p = 0.019). The SDNN was positively correlated with Veterans Specific Activity Questionnaire (VSAQ) score (r = 0.308, p = 0.006) and handgrip strength (r = 0.285, p = 0.011), and negatively correlated with dyspnea by modified Medical Research Council (mMRC) questionnaire (r = -0.234, p = 0.039), health status by Saint Georges Respiratory Questionnaire (SGRQ) (r = -0.298, p = 0.008), symptoms by COPD Assessment Test (CAT) (r = -0.280, p = 0.012), and BODE index (r = -0.269, p = 0.020). When measured by a chest-worn wearable device, reduced HRV was observed in COPD participants receiving inhaled beta-sympathomimetic agonist and muscarinic antagonists. HRV was also correlated with various health status and performance measures.

Assessing airway function during exercise provides useful information regarding mechanical properties of the airways and the extent of ventilatory limitation in COPD. The primary aim of this study was to use impulse oscillometry (IOS) to assess dynamic changes in airway impedance across a range of exercise intensities in patients with GOLD 1-4, before and after albuterol administration. A secondary aim was to assess the reproducibility of IOS measures during exercise. Fifteen patients with COPD (8 males/7 females; age = 66 ± 8 yr; prebronchodilator FEV1 = 54.3 ± 23.6%Pred) performed incremental cycle ergometry before and 90 min after inhaled albuterol. Pulmonary ventilation and gas exchange were measured continuously, and IOS-derived indices of airway impedance were measured every 2 min immediately preceding inspiratory capacity maneuvers. Test-retest reproducibility of exercise IOS was assessed as mean difference between replicate tests in five healthy subjects (3 males/2 females). At rest and during incremental exercise, albuterol significantly increased airway reactance (X5) and decreased airway resistance (R5, R5-R20), impedance (Z5), and end-expiratory lung volume (60% ± 12% vs. 58% ± 12% TLC, main effect P = 0.003). At peak exercise, there were moderate-to-strong associations between IOS variables and IC, and between IOS variables and concavity in the expiratory limb of the spontaneous flow-volume curve. Exercise IOS exhibited moderate reproducibility in healthy subjects which was strongest with R5 (mean diff. = -0.01 ± 0.05 kPa/L/s; ICC = 0.68), R5-R20 (mean diff. = -0.004 ± 0.028 kPa/L/s; ICC = 0.65), and Z5 (mean diff. = -0.006 ± 0.021 kPa/L/s; ICC = 0.69). In patients with COPD, exercise evoked increases in airway resistance and decreases in reactance that were ameliorated by inhaled bronchodilators. The technique of exercise IOS may aid in the clinical assessment of dynamic airway function during exercise.NEW & NOTEWORTHY This study provides a novel, mechanistic insight into dynamic airway function during exercise in COPD, before and after inhaled bronchodilators. The use of impulse oscillometry (IOS) to evaluate airway function is unique among exercise studies. We show strong correlations among IOS variables, dynamic hyperinflation, and shape-changes in the spontaneous expiratory flow-volume curve. This approach may aid in the clinical assessment of airway function during exercise.

Abstract In recent years, emphasis has shifted from preventing and treating chronic obstructive pulmonary disease (COPD) to early prevention, early treatment, and disease stabilization, with the main goal of improving patients’ quality of life and reducing the frequency of acute exacerbations. This review summarizes pharmacological therapies for stable COPD.

Rationale: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis and access to affordable interventions. There are no previous reports describing therapeutic needs of populations with COPD in LMICs who were identified through screening. Objectives: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. Methods: We compared interventions recommended by the international Global Initiative for Chronic Obstructive Lung Disease COPD strategy document, with that received in 1,000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru, and Uganda. We calculated costs using data on the availability and affordability of medicines. Measurement and Main Results: The greatest unmet need for nonpharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%), and advice on biomass smoke exposure (26%). Ninety-five percent of the cases were previously undiagnosed, and few were receiving therapy (4.5% had shortacting β-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable, with 30 days of treatment costing more than a low-skilled worker's daily average wage. Conclusions: We found a significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Although there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis combined with access to affordable interventions could translate to immediate benefit. [ABSTRACT FROM AUTHOR]

The present involves the development of an accurate, specific, and precise high‐performance thin‐layer chromatographic method for the identification and quantification of three markers apigenin, oleanolic acid, and β‐sitosterol in Clerodendrum serratum (Bharangi) root extract. The thin layer chromatographic development was carried out using an aluminum plate, pre‐coated with silica gel 60 F254 with toluene–chloroform‐ethyl acetate‐formic acid (5:4:1:0.1 v/v/v/v) as the mobile phase. Densitometric quantification was performed at 334 nm for apigenin and 662 nm for oleanolic acid and β‐sitosterol after derivatization with anisaldehyde‒sulfuric acid reagent. The optimized mobile phase resulted in chromatographic separation of apigenin, oleanolic acid, and β‐sitosterol bands at Rf of 0.19, 0.50, and 0.63, respectively. The method was found to be linear in the concentration range of 200–1200 ng/band for apigenin, and 400–2400 ng/band for oleanolic acid and β‐sitosterol, respectively. The recoveries were found to be 99.34%–99.92% for apigenin, 99.38%–99.81% for oleanolic acid, and 99.49%–99.66% for β‐sitosterol. The optimized method was found to be accurate, reproducible, robust, and specific and it was applied for the quantification of apigenin, oleanolic acid, and β‐sitosterol in hydroalcoholic root extract of Clerodendrum serratum. [ABSTRACT FROM AUTHOR]

Asthma is a heterogeneous chronic airway disease with an unmet need for improved therapeutics in uncontrolled severe disease. The calcium-sensing receptor (CaSR) is a G protein–coupled receptor upregulated in asthma. The CaSR agonist, spermine, is also increased in asthmatic airways and contributes to bronchoconstriction. CaSR negative allosteric modulators (NAMs) oppose chronic airway inflammation, remodeling, and hyperresponsiveness in murine and guinea pig asthma models, but whether CaSR NAMs are effective acute bronchodilators compared with standard of care has not yet been established. Furthermore, the ability of different classes of NAMs to inhibit spermine-induced CaSR signaling or methacholine (MCh)-induced airway contraction has not been quantified. Here, we show CaSR NAMs differentially inhibit spermine-induced intracellular calcium mobilization and inositol monophosphate accumulation in HEK293 cells stably expressing the CaSR. NAMs reverse MCh-mediated airway contraction in mouse precision-cut lung slices with similar maximal relaxation compared with the standard treatment, salbutamol. Of note, the bronchodilator effects of CaSR NAMs are maintained under conditions of β2-adrenergic receptor desensitization when salbutamol efficacy is abolished. Furthermore, overnight treatment with some, but not all, CaSR NAMs prevents MCh-mediated bronchoconstriction. These findings further support the CaSR as a putative drug target and NAMs as alternative or adjunct bronchodilators in asthma. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the ocular surface, intraocular pressure, and lens condition in bronchodilator- and steroid-treated chronic pulmonary disease patients. Methods: In this cross-sectional clinical study, 101 patients with chronic pulmonary disease were treated with an inhaler and/or nebulized therapy for bronchodilatation. The patients were evaluated in 2 groups namely chronic obstructive pulmonary disease and asthma. We investigated the effects of patient demographic characteristics, smoking, and medications on the presence of dry eye disease (DED), intraocular pressure, and cataract. Results: Patients had a mean age of 66.4 ± 11.9 years, and 46.5% (n = 47) were female. A unit increase in the length of inhaled corticosteroids (ICS) and long-acting β-agonists (LABA) combination use was associated with a 1.02-fold increase in cataract risk (OR: 1.02, CI: 1.01–1.04, p = 0.016), and current smokers had 10.8 times as many cataracts (OR: 10.79, CI: 1.70–68.30, p = 0.011). Patients who used a nebulized corticosteroid had a 9.15 times higher risk of developing dry eyes than those who did not (OR: 9.15, CI: 2.34–35.75, p = 0.001). In patients using ICS-LABA, in comparison to formoterol beclomethasone, salmeterol fluticasone was found to increase the risk 7.49-fold for DED (OR: 7.49, CI: 1.48–35.75, p = 0.015). Conclusions: Nebulizer delivery of steroids is associated with dry eyes and cataracts. Smoking, aging, and long-term inhaled steroid use have all been linked to an increased risk of cataracts. Longitudinal and larger sample size studies are needed to explore cause-effect relationships. [ABSTRACT FROM AUTHOR]

Richard N van Zyl-Smit,1 Kenneth R Chapman,2 Huib AM Kerstjens,3 Christian Gessner,4 Hironori Sagara,5 Ana-Maria Tanase,6 Motoi Hosoe,6 Abhijit Pethe,7 David Lawrence,6 Hanns-Christian Tillmann,8 Peter D’Andrea7 1Division of Pulmonology and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; 2Division of Respiratory Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 3Department of Pulmonology, University of Groningen, University Medical Center Groningen, and Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands; 4Universitätsklinikum Leipzig, Germany POIS Leipzig GbR, Leipzig, Germany; 5Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, Tokyo, Japan; 6Novartis Pharma AG, Basel, Switzerland; 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 8Novartis Institutes for BioMedical Research, Translational Medicine, Basel, SwitzerlandCorrespondence: Ana-Maria Tanase, Novartis Pharma AG, Fabrikstrasse 4, Novartis Campus, Basel, Switzerland, Tel +41 79 899 98 22, Email ana-maria.tanase@novartis.comBackground: Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler® have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment.Objective: Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies.Methods: The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations.Results: Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study.Conclusion: These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.Keywords: mometasone/indacaterol/glycopyrronium, mometasone/indacaterol, fluticasone/salmeterol, tiotropium, bronchodilator, lung function, asthma control, exacerbation

Asthma medication adherence is of crucial importance for successful disease management. The aim of this study was to identify and rank factors associated with medication adherence among adults with asthma in the general population. We used data on physician-diagnosed asthma, medication adherence, and factors associated with asthma medication adherence from the Danish General Suburban Population Study using a cross-sectional study design. We ranked factors associated with asthma medication adherence based on the magnitude of odds ratios, and the population attributable fractions. Among 20,032 individuals from the general population, 1,128 (6%) suffered from asthma and 822 (73%) of these were adherent to asthma medications. Based on odds ratios, the three top-ranked factors associated with asthma medication adherence were asthma attacks within the past year (4.0; 95% CI: 2.9–5.5), allergy medication use (3.8; 2.6–5.6), and age above median (3.4; 2.4–4.7), followed by asthma severity markers like airway obstruction, and coughing with mucus. Based on population attributable fractions, the three top-ranked factors associated with adherence to asthma medications were asthma attacks within the past year (70%), age above median (57%), and use of allergy medication (49%). The study showed that in the general population recent asthma attacks, higher age, and taking allergy medication were the three most important factors associated with asthma medication adherence. The importance of maintaining adherence to asthma medications even in the absence of severe disease or expressed asthma symptoms should be better communicated to the general population. [ABSTRACT FROM AUTHOR]

Precision cut lung slices (PCLS) have emerged as powerful experimental tools for respiratory research. Pioneering studies using mouse PCLS to visualize intrapulmonary airway contractility have been extended to pulmonary arteries and for assessment of novel bronchodilators and vasodilators as therapeutics. Additional disease-relevant outcomes, including inflammatory, fibrotic, and regenerative responses, are now routinely measured in PCLS from multiple species, including humans. This review provides an overview of established and innovative uses of PCLS as an intermediary between cellular and organ-based studies and focuses on opportunities to increase their application to investigate mechanisms and therapeutic targets to oppose excessive airway contraction and fibrosis in lung diseases. [ABSTRACT FROM AUTHOR]

Background: Little has been reported in terms of clinical outcomes to confirm the benefits of nebulized bronchodilators during mechanical ventilation (MV). Electrical Impedance Tomography (EIT) could be a valuable method to elucidate this gap. Objective: The purpose of this study is to evaluate the impact of nebulized bronchodilators during invasive MV with EIT by comparing three ventilation modes on the overall and regional lung ventilation and aeration in critically ill patients with obstructive pulmonary disease. Method: A blind clinical trial in which eligible patients underwent nebulization with salbutamol sulfate (5 mg/1 mL) and ipratropium bromide (0.5 mg/2 mL) in the ventilation mode they were receiving. EIT evaluation was performed before and after the intervention. A joint and stratified analysis into ventilation mode groups was performed, with p < 0.05. Results: Five of nineteen procedures occurred in controlled MV mode, seven in assisted mode and seven in spontaneous mode. In the intra-group analysis, the nebulization increased total ventilation in controlled (p = 0.04 and ⅆ = 2) and spontaneous (p = 0.01 and ⅆ = 1.5) MV modes. There was an increase in the dependent pulmonary region in assisted mode (p = 0.01 and ⅆ = 0.3) and in spontaneous mode (p = 0.02 and ⅆ = 1.6). There was no difference in the intergroup analysis. Conclusions: Nebulized bronchodilators reduce the aeration of non-dependent pulmonary regions and increase overall lung ventilation but there was no difference between the ventilation modes. As a limitation, it is important to note that the muscular effort in PSV and A/C PCV modes influences the impedance variation, and consequently the aeration and ventilation values. Thus, future studies are needed to evaluate this effort as well as the time on ventilator, time in UCI and other variables. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines based on scientific evidence from testing and therapeutic interventions are needed to improve control of asthma. The latest asthma treatment paradigm shift is discussed as presented in recent guidelines from the Global Initiative for Asthma and the National Asthma Education and Prevention Program. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spirometry tests with a bronchodilator response (BDR) in FEV1, a methacholine concentration that produces a 20% drop in FEV1 (PC20) ≤ 2 mg/mL, and a positive exercise test have high specificity for the diagnosis of asthma in children. However, the value of forced expiratory flow during the middle half of the FVC maneuver (FEF25-75) in spirometry has been questioned. The objective of this study was to relate the BDR in FEF25-75 of spirometry tests with normal FEV1 and FEV1/FVC to airway hyper-responsiveness (AHR) to methacholine or exercise in children age 5-15 y with clinical suspicion of asthma. METHODS: This was a cross-sectional study of spirometry tests performed between January 2017-December 2019 in children age 5-15 y with diagnostic suspicion of asthma who had a methacholine and/or exercise testing within a period not exceeding 60 d between exams. RESULTS: The mean (± SD) age of the children was 9.04 ± 2.67 y, with a range of 5-15 y, and 56.17% were male. Of the 324 spirometry tests with normal FEV1 and FEV1/FVC, 66 (20.4%) tests showed BDR in FEF25-75. A total of 46.9% and 33.3% of the children with and without BDR in FEF25-75, respectively, had a PC20 value ≤ 2 mg/mL and/or a positive exercise testing (P = .039). CONCLUSIONS: Children with suspected asthma and normal spirometry, other than BDR in FEF25-75, had greater AHR than those without BDR in FEF25-75. BDR in FEF25-75 was not always accompanied by AHR to confirm the diagnosis of asthma, so this study suggests that assessment of FEF25-75 alone is not always reliable for ruling in or ruling out AHR in the setting of otherwise normal spirometry results in children with suspected asthma. [ABSTRACT FROM AUTHOR]

TAS2Rs (bitter taste receptors) are GPCRs (G protein-coupled receptors) expressed on human airway smooth muscle (HASM) cells; when activated by receptor agonists they evoke marked airway relaxation. In both taste and HASM cells, TAS2Rs activate a canonical Gβγ-mediated stimulation of Ca2+ release from intracellular stores by activation of PLCβ (phospholipase Cβ). Alone, this [Ca2+]i signaling does not readily account for relaxation, particularly since bronchoconstrictive agonists acting at Gq-coupled receptors also increase [Ca2+]i. We established that TAS2R14 activation in HASM promotes relaxation through F-actin (filamentous actin) severing. This destabilization of actin was from agonist-promoted activation (dephosphorylation) of cofilin, which was pertussis toxin sensitive. Cofilin dephosphorylation was due to TAS2R-mediated deactivation of LIM domain kinase. The link between early receptor action and the distal cofilin dephosphorylation was found to be the polarity protein partitioning defective 3 (Par3), a known binding partner with PLCβ that inhibits LIM kinase. The physiologic relevance of this pathway was assessed using knock-downs of cofilin and Par3 in HASM cells and in human precision-cut lung slices. Relaxation by TAS2R14 agonists was ablated with knock-down of either protein as assessed by magnetic twisting cytometry in isolated cells or intact airways in the slices. Blocking [Ca2+]i release by TAS2R14 inhibited agonist-promoted cofilin dephosphorylation, confirming a role for [Ca2+]i in actin-modifying pathways. These results further elucidate the mechanistic basis of TAS2R-mediated HASM relaxation and point toward nodal points that may act as asthma or chronic obstructive pulmonary disease response modifiers or additional targets for novel bronchodilators. [ABSTRACT FROM AUTHOR]

BackgroundSmoking is a major risk factor for COPD and may impact the efficacy of COPD treatments; however, a large proportion of COPD patients continue to smoke following diagnosis.MethodsThis post-hoc analysis of pooled data from the replicate 12-week, placebo-controlled GEM1 and GEM2 studies assessed the impact of smoking status on the efficacy and safety of glycopyrrolate 15.6 μg twice daily vs placebo in patients with moderate-to-severe COPD. Data from 867 patients enrolled in GEM1 and GEM2 were pooled for analysis and grouped by smoking status (57% current smokers, 43% ex-smokers). Forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 12 h, trough FEV1, forced vital capacity, St George's Respiratory Questionnaire (SGRQ) total score, COPD assessment test (CAT) score, transition dyspnea index (TDI) focal score, daily symptom scores, and rescue medication use were assessed in current smokers and ex-smokers. Incidences of adverse events (AEs) and serious AEs (SAEs) were also assessed.ResultsTreatment with glycopyrrolate resulted in significant improvements in all lung function measures, independent of smoking status. In both current and ex-smokers, changes from baseline in trough FEV1 were less marked in patients taking inhaled corticosteroids (ICS) than those not receiving ICS. Changes from baseline in SGRQ total score and rescue medication use were significantly greater with glycopyrrolate compared with placebo, regardless of smoking status. Changes in the CAT score, TDI focal score, and daily symptom scores significantly improved versus placebo, but only in current smokers. Improvements in patient-reported outcomes (PROs) with glycopyrrolate relative to placebo were numerically greater in current smokers than ex-smokers. The incidences of AEs and SAEs were similar regardless of smoking status.ConclusionsIn this post-hoc analysis of GEM1 and GEM2, glycopyrrolate use led to significant improvements in lung function, independent of baseline smoking status; improvements were less marked among patients receiving background ICS, regardless of baseline smoking status. Improvements in PROs were greater with glycopyrrolate than placebo, and the magnitude of changes was numerically greater among current smokers. The safety profile of glycopyrrolate was comparable between current smokers and ex-smokers.

Abstract Background The benefit of prompt vs delayed treatment initiation with inhaled long-acting bronchodilators in reducing exacerbations in chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate if long-acting bronchodilator therapy initiation within 30 days of COPD diagnosis reduces exacerbation risk in patients with COPD. Methods This was a retrospective cohort study of patients with COPD based on claims and electronic medical records data extracted from the Real World Data database. The index date (day 0) was the date of the first confirmed inpatient or outpatient COPD diagnosis between January 1, 2005, and December 31, 2018. Patients with COPD without an asthma diagnosis and aged ≥ 40 years at the index date were included. Patients who initiated inhaled long-acting bronchodilator therapy within the first 30 days (day 0 to day 29) were categorized into the “prompt therapy” group and the rest into the “delayed therapy” group. Time from day 30 post-diagnosis to the first exacerbation and annual exacerbation rate (AER) were evaluated for the overall population and those stratified by COPD phenotype, including chronic bronchitis (CB) and emphysema. Results Compared with the delayed therapy group (n = 1516), time to first exacerbation was prolonged (hazard ratio 0.78; 95% confidence interval [CI] [0.70, 0.87]) and annual rates of moderate or severe exacerbations were lower (rate ratio 0.74; 95% CI [0.65, 0.84]) in the prompt therapy group (n = 1466). Similarly, time to first exacerbation was prolonged and AERs were lower in the prompt therapy group in the subgroups of patients with CB or emphysema. Conclusions This is the first study to demonstrate a prolonged time to first exacerbation upon initiation of long-acting bronchodilators within 30 days of COPD diagnosis. A beneficial effect was also observed in patients with CB and emphysema. Our data support advising patients to initiate long-acting bronchodilators soon after COPD diagnosis.

Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults. Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods. Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only. Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer. [ABSTRACT FROM AUTHOR]

Precision cut lung slices (PCLS) have emerged as powerful experimental tools for respiratory research. Pioneering studies using mouse PCLS to visualize intrapulmonary airway contractility have been extended to pulmonary arteries and for assessment of novel bronchodilators and vasodilators as therapeutics. Additional disease-relevant outcomes, including inflammatory, fibrotic, and regenerative responses, are now routinely measured in PCLS from multiple species, including humans. This review provides an overview of established and innovative uses of PCLS as an intermediary between cellular and organ-based studies and focuses on opportunities to increase their application to investigate mechanisms and therapeutic targets to oppose excessive airway contraction and fibrosis in lung diseases.

Introduction. According to modern data, bronchial asthma (BA) is an independent risk factor for the development of cardiac arrhythmias (CA), and the use of long-acting β2-agonists (LABA) in basic therapy may further increase the risks of CA.Aim. To study the structure and risk factors of cardiac arrhythmias in patients with bronchial asthma. Materials and methods. A retrospective study included 181 patients aged 69.4 ± 0.8 years, hospitalized for asthma, with the presence a CA in medical documentation.Results. Among BA patients with CA, supraventricular CA were found in 71.3% (129) patients, ventricular CA in 16.6% (30), combined CA in 12.2% (22). In 52.5% (95) patients, supraventricular extrasystole was detected, in 35.9% (65) – atrial fibrillation, in 28.7% (52) – ventricular extrasystole, in 1.1% (2) – paroxysmal supraventricular tachycardia, in 0.6% (1) – paroxysmal ventricular tachycardia. It was found that supraventricular CA was significantly more frequent among women (χ2 = 5.974, p = 0.05). The severity of BA and the level of control are not related to the type of observed CA (χ2 = 0.755, p = 0.685 and χ2 = 3.003, p = 0.557, respectively).Discussion. The use of a combination of ICS and LABA in basic BA therapy versus the use of ICS alone does not have a significant effect on the frequency and structure of cardiac arrhythmias (χ2 = 1.172, p = 0.556).Conclusion. In hospitalized BA patients, supraventricular cardiac arrhythmias are most often detected, among which supraventricular extrasystole and atrial fibrillation take the main place.

The plant kingdom comprises medicinally useful plants that have provided many new drugs used to treat various diseases. In our search for bronchodilator secondary metabolites from plants growing in Saudi Arabia, the total extract of Rhazya stricta showed activity against carbamylcholine- (CCh) induced bronchoconstriction in guinea pig tracheal muscles used as an ex vivo model. The fractions obtained from liquid–liquid extraction process were tested for bronchodilator effects. The most active ethyl acetate fraction (RS-E) and aqueous fraction (RS-H) were subjected to biologically guided phytochemical study using different stationary phases and chromatographic techniques to isolate the pure secondary metabolites. Five known compounds were isolated from the active fractions. Three alkaloids namely; (-)-quebrachamine (1), (+)-eburenine (2), (+)-stemmadenine (3) as well as the two iridoid glycosides loganic acid (4) and loganine (5) were identified by various spectroscopic methods. Among the isolated compounds 1 and 5 were the only active as bronchodilators in the plant. It is worth to mention that iridoid glycosides are isolated for the first time from R. stricta. [ABSTRACT FROM AUTHOR]

Inhaled bronchodilators (alone or in combination) are the cornerstone of treatment for symptomatic patients with COPD, either as initial/first-line treatment or for second-line/treatment escalation in patients who experience persistent symptoms or exacerbations on monotherapy. The Global Initiative for Chronic Obstructive Lung Disease 2022 report recommends initial pharmacological treatment with a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA) as monotherapy for most patients, or dual bronchodilator therapy (LABA/LAMA) in patients with more severe symptoms, regardless of exacerbation history. The recommendations for LABA/LAMA are broader in the American Thoracic Society treatment guidelines, which strongly recommend LABA/LAMA combination therapy over LAMA or LABA monotherapy in patients with COPD and dyspnea or exercise intolerance. However, despite consistent guideline recommendations, real-world prescribing data indicate that LAMA and/or LABA without an inhaled corticosteroid are not the most widely prescribed therapies in COPD. This article reviews global and regional/national guideline recommendations for the use of LABA/LAMA in COPD, examines the evidence for the effectiveness and safety of LABA/LAMA versus other therapies and offers a practical guide for clinicians to help ensure appropriate use of LABA/LAMA therapy. [ABSTRACT FROM AUTHOR]

The bronchodilator effect of the Achillea fragrantissima essential oil (AFO) was studied in guinea pigs' tracheas and the influence of drying on the quantity and composition of AFO was studied using GC-MS and GC analyses. AFO produced a complete and potent relaxation against carbachol (CCh), while lower potency and partial efficacy were observed against high K+ (80 mM), thus producing dual inhibitory effects similar to dicyclomine. The anticholinergic-like action was further confirmed when pre-incubation tracheal tissues were used at lower concentrations with AFO displacing the CCh concentration-response curves (CRCs) to the right in a competitive manner similar to atropine. However, non-parallel shifts in CCh CRCs were observed with higher doses, similar to dicyclomine. Further confirmation of the CCB-like effect was obtained from the non-specific deflection of Ca++ CRCs toward the right using the pre-incubated tissues with AFO in Ca++ free medium, similar to verapamil. When AFO was tested against low K+-mediated contractions to explore the possible involvement of additional antispasmodic mechanism(s), AFO interestingly showed a complete inhibition with a higher potency. This inhibition was found to be sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP), whereas glibenclamide (Gb) remained inactive. These results show that AFO possesses bronchodilator effects predominantly from its anticholinergic and K+ channel activation followed by weak Ca++ channels inhibition. [ABSTRACT FROM AUTHOR]

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Background: Acute bronchiolitis is an inflammatory process affecting small airways. Although most cases are self-limiting, it is still one of the most common causes of hospitalization below 24 months of age. Treatment is mainly supportive. The purpose of this narrative review was to look for recent evidence in the management of bronchiolitis. Methods: PubMed, EMBASE, Global Health, MEDLINE, SCOPUS, and Cochrane database searches were performed using keywords such as bronchiolitis, management, bronchodilators, nebulized epinephrine, corticosteroids, and hypertonic saline. Systematic reviews, original articles, and clinical practice guidelines with evidence for bronchiolitis management were included during our search. We excluded guidelines and clinical trials which solely focused on high-risk children, articles by a single author, and trials that are not part of a clinical practice guideline. Discussion: The safety and efficacy of various therapies for bronchiolitis such as bronchodilators, epinephrine, hypertonic saline, and corticosteroid were analyzed. Bronchodilators have not shown consistent benefits in bronchiolitis and may be tried in the selected population. Current evidence does not suggest routine use of nebulized epinephrine in bronchiolitis except as rescue therapy in selected cases. Hypertonic saline showed positive results in some studies but questions still remain regarding its effectiveness in all. Recent trials also do not support the use of systemic or inhaled corticosteroids in bronchiolitis. Conclusion: In conclusion, there is no strong evidence to routinely recommend the use of bronchodilator, epinephrine, hypertonic saline, or corticosteroids in acute bronchiolitis. Supportive care still remains the mainstay of therapy for bronchiolitis.

BACKGROUND:The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment. METHODS:The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients. RESULTS:A total of 404 patients received treatment, with 165 participating in the ESWT substudy. A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% ( p = 0.02)] but not with tiotropium/olodaterol 2.5/5 µg [9% ( p = 0.14)] versus placebo. In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 µg [21% ( p = 0.055)] and tiotropium/olodaterol 2.5/5 µg [21% ( p = 0.056)] versus placebo. CONCLUSION:Tiotropium/olodaterol 5/5 µg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time. [ ClinicalTrials.gov identifier: NCT01525615.].

Mohammed A Almeshari,1,2 Nowaf Y Alobaidi,1,3 Elizabeth Sapey,1,4 Omar Usmani,5 Robert A Stockley,6 James A Stockley7 1Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK; 2Rehabilitation Health Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 3Respiratory Therapy Department, King Saud Bin Abdulaziz University for Health Sciences, Alahsa, Saudi Arabia; 4Acute Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW, UK; 5Imperial College of London, London, UK; 6Department of Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 7Lung Function & Sleep Department, Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UKCorrespondence: Mohammed A AlmeshariRehabilitation Health Science Department, College of Applied Medical Sciences, King Saud University, P. Box 145111,, Riyadh, ZIP 4545, Saudi ArabiaTel +966 50 8033 880Email malmeshari@ksu.edu.saBackground: Bronchodilator responsiveness (BDR) is commonly used in the diagnosis of lung disease. Although small airways dysfunction is a feature of asthma and COPD, physiological tests of small airways are not included in guidelines for BDR testing. This systematic review assessed the current evidence of BDR using small airways function in asthma and COPD.Methods: The systematic review used standard methodology with the protocol prospectively registered on PROSPERO (CRD42020164140). Electronic medical databases (EMBASE and Medline) were searched using related keywords. Abstracts and full texts were screened independently by two reviewers. Studies that reported the change of physiological small airways function and FEV1 were included in the review. The revised Cochrane risk of bias tool for RCT and NIH quality assessment tool for cohort and cross-sectional studies were used to evaluate the studies.Results: A total of 934 articles were identified, with 12 meeting the inclusion criteria. Ten studies included asthma patients, 1 study included COPD patients and 1 study included both asthma and COPD. A total of 1104 participants were included, of whom 941 were asthmatic, 64 had COPD and 109 were healthy controls. Studies were heterogeneous in design including the device, dose and time intervals for BDR assessment. A small airway BDR was seen for most tests in asthma and COPD, including oscillometry (R5-20, reactance (X5), area of reactance (AX) and resonant frequency (Fres)) and Maximal Mid Expiratory Flow.Conclusion: There is a measurable BDR in the small airways. However, with no consensus on how to assess BDR, studies were heterogeneous. Further research is needed to inform how BDR should be assessed, its clinical impact and place in routine clinical practice.Keywords: asthma, COPD, bronchodilator, reversibility, small airways function

Abstract Background Blood cleansing, purification, detoxification or strengthening is an ancient folkloric East African practice without any validated scientific underpinnings. This study was undertaken to retrieve ethnobotanical information and reported bioactivities of plants claimed to be blood purifiers, cleansers, detoxifiers and tonics in Eastern Africa and correlate their claimed use with scientific studies to find out whether there is any justification for their use in this ancient practice. Method An elaborate review was performed in electronic databases (PubMed, Science Direct, Scopus, Springer Link, Wiley Online Library, Taylor & Francis Online, SciFinder, Google Scholar, Web of Science) and the Google search engine to retrieve information on ethnomedicinal plants used in East Africa in blood purification, detoxification, cleansing or strengthening and their investigated bioactivities related to their use in this traditional practice. Results The search retrieved 74 plant species from 45 families distributed among 66 genera with some documented bioactivities, though, with little correlation with their traditional utilization in blood purification, cleansing, detoxification and strengthening. Some justification of the link between blood purification, cleansing, detoxification and strengthening and the use of the plants as antiplatelet aggregation, vasorelaxant, bronchodilatory, antihyperlipidaemic, cardioprotective, antiatherosclerotic and immunomodulatory agents were evident, but majorly antimicrobial activity has been investigated in most species. Thus, only 15 (20.2%) of the plant species (Allium sativum, Moringa oleifera, Olea capensis, Clausena anisata, Centella asiatica, Nasturtium officinale, Solanum nigrum, Withania somnifera, Rubus apetalus, Delonix elata, Persia americana, Aloe vera, Azadirachta indica, Echinacea angustifolia and Dioscorea bulbifera) could be directly correlated with studies pertaining to blood health. Conclusion Medicinal plants used in blood purification, cleansing, detoxification and strengthening in East Africa play a holistic role in rejuvenation of overall human health. Few studies have examined their bioactivities pertaining to blood health. Thus, bioactivities and pharmacological activities (such as blood thinning, hypolipemic, cardioprotective, immunomodulatory, tonic and renoprotective properties) and phytochemicals of the claimed plants warrant further research as these could lead to discovery of chemical scaffolds of lead compounds that can be used in modern blood purification.