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Background: An improved understanding of how severe asthma heterogeneity affects response could inform treatment decisions., Objectives: Characterize heterogeneity and benralizumab responsiveness in patients grouped by predefined Severe Asthma Research Program clusters using a multivariate approach., Methods: In post-hoc analyses of the randomized, double-blind, placebo-controlled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, patients with severe asthma who received benralizumab or placebo were assigned to clusters using an established discriminant function to analyze 11 clinical characteristics simultaneously. The annualized asthma exacerbation rate, exacerbation incidence, and lung function were analyzed across clusters., Results: Patients (n = 2,281) met criteria for four of five clusters: cluster 2 (early-onset moderate asthma, n = 393), cluster 4 (early-onset severe asthma, n = 386), cluster 3 (late-onset severe asthma, n = 641), and cluster 5 (late-onset severe, obstructed asthma, n = 861); no patients met cluster 1 criteria. Exacerbation rate reductions were significant in late-onset severe asthma (-48% [95% CI, -61% to -31%]; P < .0001) and late-onset severe, obstructed asthma (-50% [95% CI, -59% to -38%]; P < .0001), with nonsignificant reductions in early-onset clusters. These differences could not be fully explained by blood eosinophil count differences. Values for improvements in FEV 1 were significant in late-onset severe asthma (+133 mL [95% CI, 66-200]; P = .0001) and late-onset severe, obstructed asthma (+160 mL [95% CI, 85-235]; P < .0001) while maintaining acute bronchodilator responsiveness., Conclusions: Benralizumab reduced exacerbations and improved lung function, primarily in late-onset asthma clusters. This multivariate approach to identify subphenotypes, potentially reflecting pathobiological mechanisms, can guide therapy beyond univariate approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is a major public health concern due to its persistent inflammation of the airways. The intricate and widely variable epidemiology of asthma among nations and populations is a result of the interplay between genetic, environmental, and socioeconomic factors., Objective: This study aims to investigate whether VitD supplementation can reduce the frequency of exacerbations (including the frequency of exacerbations requiring systemic corticosteroids and the frequency of exacerbations necessitating trips to the hospital or emergency room, or both) and improve pulmonary function (clinical indicators such as the FEV1% predicted value)., Methods: Computers were used to search Pubmed, Medline, ISI Web of Science, Embase, Cachrane Library, CNKI, CBM, VIP, and the Wanfang Database. Asthma/asthma, VitD/VitD, lung function/lung function, retrieval time is from database setup to October 8, 2021, to search all randomized controlled trials (RCTs) on the effect of VitD on human asthma and to retroactively incorporate references to literature were all included in the search criteria. After rigorous screening, quality evaluation, and data extraction of the included literature by two reviewers independently, heterogeneity tests and sensitivity analyses were performed., Results: The findings show that a total of 12 relevant studies meeting the inclusion criteria were finally included, including 649 cases in the experimental group and 646 cases in the control group. VitD intervention reduced the number of asthma exacerbations, including the rate of exacerbations requiring systemic corticosteroid therapy and the rate of acute exacerbations requiring emergency department or hospital visits or both., Conclusions: In the outcome of lung function (FEV1% predicted value), it was shown that VitD supplementation improved lung function; in the outcome of serum 25-hydroxyVitD levels, it was shown that VitD supplementation increased serum 25-hydroxyVitD levels.

Background and Objective: Theophylline has been used for decades to treat both acute and chronic asthma. Despite its longevity in the practitioner's formulary, no detailed meta-analysis has been performed to determine the conditions, including concomitant medications, under which theophylline should be used for acute exacerbations of asthma. We aimed to quantify the usefulness and side effects of theophylline with or without ethylene diamine (aminophylline) in acute asthma, with particular emphasis on patient subgroups, such as children, adults, and concomitant medications., Methods: We searched PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, and the WHO Clinical Trials Registry for randomized, controlled clinical trials. We planned a priori subgroup analyses by time post-medication, concomitant medication, control type, and age., Results: We included 52 study arms from 42 individual trials. Of these, 29 study arms included an active control, such as adrenaline, beta-2 agonists, or leukotriene receptor antagonists, and 23 study arms compared theophylline (with or without ethylene diamine) with placebo or no drug. Theophylline significantly reduced heart rate when compared with active control ( p =0.01) and overall duration of stay ( p =0.002), but beta-2 agonists were superior to theophylline at improving forced expiratory volume in one second (FEV1) ( p =0.002). Theophylline was not significantly different from other drugs in its effects on respiratory rate, forced vital capacity (FVC), peak expiratory flow rate, admission rate, use of rescue medication, oxygen saturation, or symptom score. Closer examination of the data revealed that the medications given in addition to theophylline or control significantly changed the effectiveness of theophylline (subgroup difference: p <0.00001)., Conclusion: Given the low cost of theophylline, and its similar efficacy and rate of side effects compared with other drugs, we suggest that theophylline, when given with bronchodilators with or without steroids, is a cost-effective and safe choice for acute asthma exacerbations., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Ethnopharmacological Relevance: Over the past few decades, there have been significant scientific advances leading to improved understanding of asthma as a disease and treatment providing immediate relief. However, prevention of recurrent attacks, exacerbations and disease cure remains a challenge. Ayurveda refers to bronchial asthma as Tamaka Swasa and it is well explained in Charaka Samhita. Management of asthma in Ayurveda includes removal of vitiated Kapha through Shodhana, Shamana procedures, herbal and herbomineral formulations in addition to advising a healthy lifestyle and diet. Several clinical trials on Ayurvedic formulations for treatment of asthma are reported, however, whole system management of asthma has rarely been studied in the manner in which it is actually being practiced. Ayurveda therapeutics provides Dosha specific approaches, which needs biological investigation., Aim of the Study: The objective of our study was to investigate lung functions and cytokine changes in Asthmatic individuals in response to Ayurvedic intervention., Methods: The study design was approved by the Institutional Ethics Committee of Tilak Ayurveda Mahavidyalaya (TAMV) & Sheth Tarachand Ramnath Charitable Ayurveda Hospital and followed guidelines of the Declaration of Helsinki and Tokyo for humans. It was conducted as a whole system individualized pragmatic clinical trial and written consent of patients was collected before enrollment. One hundred and fifteen patients with mild-to-moderate asthma were divided into 2 sub-groups depending on their disease subsets and administered phenotype specific ayurvedic interventions. Seventy six asthma patients completed the treatment. Serum IgE levels, blood eosinophil counts, spirometry and blood cytokine levels were measured before the start of treatment and six months at the end of treatment. Age and sex matched healthy participants (n=69) were recruited in the study for comparison of cytokines levels., Results: Significant improvements in FEV1(% predicted) (p<0.0001) and FVC (% predicted) (p=0.0001) was observed in asthmatic patients who underwent Ayurvedic treatment. Circulating levels of IgE (p<0.03) and eosinophil numbers (p=0.001) reduced significantly in the asthmatics after Ayurvedic treatment. This was associated with significant reduction in levels of circulating cytokines. Levels of Th2, Th1 and inflammatory cytokines in the peripheral blood were higher than healthy control participants at baseline (p values <0.0001) and reduced significantly after ayurvedic intervention., Conclusion: This proof of concept study highlights the potential benefits and possible mechanism of Ayurvedic interventions in patients with mild-to-moderate asthma. The interventions significantly reduced IgE and eosinophil count, also improved lung function and reduced levels of circulating Th2 cytokines., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of the work presented here was to determine the role of dry powder inhaler (DPI) counselling on inhalation technique and lung function test scores of the asthmatic patients. To decrease variability, asthmatic patients using an Aerolizer were enrolled in the study, as this was the most commonly prescribed DPI in outpatient clinics of Beni Suef University hospital. Each patient was subjected to three visits separated by 1 month each. In each visit, patient inhalation technique from the DPI was checked, and the number of mistakes was identified and corrected. Also, patients' peak expiratory flow (PEF) and forced expiratory volume in one second (FEV) presented as a percentage of the forced vital capacity (FVC) were checked. As the number of visits increased, the mean number of observed mistakes was significantly decreased ( p < 0.001). The most common repeated mistakes were 'To inhale fast' and 'To maintain a fast inhalation rate until the lungs are full'. In all age groups, there was a significant increase ( p < 0.001) in the pulmonary function test after the period of counselling. To improve and maintain the recommended inhalation technique of DPI and possibly improve patients' lung function test scores, counselling on proper DPI technique should be repeated at every possible opportunity. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1 s (FEV) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24 h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV, and sex. Age and height were found to have significant effects on the mean FEV level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV occurred in the early morning and maximum FEV occurred in the early afternoon, with a population mean fluctuation of 170 mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to describe the time course of the placebo effect in asthma and quantitatively investigate the affective factors of the placebo effect for the placebo response simulation during the asthma clinical study design. Methods: We conducted a systemic search of public data sources for the study-level forced expiratory volume in 1 second (FEV) to build the placebo effect model for studies by oral or inhaled administrations simultaneously. The administration routes, types of inhalation device, mean patient age, mean male proportion, baseline FEV, disease severity, year of publication, inhaled corticosteroid status during the treatment, and dropout rate were tested as covariates. Results: There are 34 literature sources containing 178 mean values for FEV presenting the individual observations from about 3,703 patients. The exponential models adequately described the time course of placebo effect with the typical value of the maximum placebo effect (P) of 0.060 L. Dropout rate incorporated in the residual error model and the disease severity (mild to moderate and moderate to severe) at baseline were covariates that remained in the final model. Conclusions: The placebo effect is adequately described by an exponential model over time. By incorporating the dropout rate in the residual error model, the estimation precision was improved. The model could predict the placebo response profile in mild to severe asthmatic patients for the asthma clinical study design and could also be a structure model of the placebo effect for the pure drug effect evaluation in the asthma clinical trials. [ABSTRACT FROM AUTHOR]

Background: Adenosine receptor stress agents for myocardial perfusion imaging (MPI) may cause A and/or A receptor-mediated bronchoconstriction, of particular concern to physicians testing patients with asthma or chronic obstructive pulmonary disease (COPD). Methods: A Phase 4, randomized, double-blind study (NCT00862641) assessed the safety of the selective A receptor agonist, regadenoson, compared with placebo in subjects with asthma or COPD who represented likely candidates for MPI. Results: Overall, 356 and 176 subjects with asthma and 316 and 151 subjects with COPD received regadenoson and placebo, respectively. The percentage of subjects experiencing a >15% decrease in FEV from baseline to any assessment up to 24 hours post-baseline was not statistically significantly different between the regadenoson and the placebo groups in the asthma or COPD stratum. Dyspnea, the most frequent respiratory adverse event, occurred with higher incidence ( P < .0001) in the regadenoson group than the placebo group in the asthma (10.7% vs 1.1%) and COPD (18.0% vs 2.6%) strata. No subjects experienced severe bronchoconstriction, although the occurrence of such reactions with adenosine receptor agonists cannot be ruled out, such that caution is advised. Conclusions: This information may be helpful to physicians selecting a pharmacologic stress agent for MPI in patients with asthma or COPD. [ABSTRACT FROM AUTHOR]

The objective of this double-blind cross-over study was to evaluate montelukast for the prevention of exercise-induced bronchoconstriction (EIB). Sixty-two patients with EIB (post-exercise decrease in forced expiratory volume in 1 second (FEV1) ≥ 20% at pre-randomization) were randomized to montelukast 10 mg or placebo, followed by exercise-challenge 2, 12, and 24 hours postdose. The primary endpoint was the maximum percent-fall in FEV1 (from pre-exercise FEV1) during 60 minutes after exercise-challenge at 2 hours postdose. This endpoint was improved after montelukast (mean ± SD = 11.7% ± 10.8) versus placebo (17.5% ± 13.8) (p ≤ 0.001); numerically greater improvements were seen at 12 hours and 24 hours. A quicker time to recovery after challenge (p ≤ 0.001) and a smaller area under the curve for percent-fall in FEV1 during 60 minutes after challenge (p ≤ 0.01) were seen with montelukast at 2 hours. At this timepoint, more patients taking montelukast (45/54) than taking placebo (37/54) were protected against EIB (p = 0.039). We concluded that montelukast provided significant protection against EIB at 2 hours after a single dose. [ABSTRACT FROM AUTHOR]

Background: The house dust mite Blomia tropicalis (B. tropicalis ) was found to be the most prevalent domestic mite in Singapore. However, its pathogenicity in allergic airway diseases remains to be investigated. Methods: Twenty adults with persistent allergic rhinitis (PAR) were studied. Five had a history of asthma, and all were asymptomatic except one who was under treatment with low-dose inhaled corticosteroid. Nasal challenge was carried out by nasal spray with phosphate-buffered saline (PBS) and with increasing concentrations of crude B. tropicalis extracts (0.6, 6.0 and 60 µg/ml) at 15 min intervals. Subjective symptom scores and absolute number of sneezes were recorded together with objective measurements of spirometry (forced expiratory volume in 1 s, FEV1 ) and acoustic rhinomanometry (volume of the nasal cavity). These were performed at baseline, 5 min after each incremental challenge, and 30 min, 1 h, 3 h, 5 h and 7 h after the last challenge. Meanwhile, concentrations of mediators in nasal secretions (tryptase, leukotriene C4 (LTC4 ) and eosinophil cationic protein (ECP)) were measured in nasal aspirate samples at similar time intervals. An identical (control) challenge procedure with PBS alone was repeated in seven patients after a washout period of at least 2 weeks. Results: Significant increases in the subjective and objective nasal symptoms, together with a significant increase of tryptase and LTC4 concentrations in nasal secretion, were found 5 min after each challenge with B. tropicalis, but not with PBS. There was no definitive pattern of the late-phase nasal response in either subjective symptoms or objective measurements. Three patients (3/5) with a history of asthma showed a fall in FEV1 readings (33%, 22% and 11% from baseline, respectively) at 7 h post challenge with concomitant mild wheezing in the night. Conclusions: Our study demonstrates direct evidence of allergic nasal... [ABSTRACT FROM AUTHOR]

Objective: International consensus guidelines suggest that in asthma and chronic obstructive pulmonary disease (COPD), measurements of FEV1 and PEF are equivalent in the assessment of the degree of airflow obstruction when expressed as the per cent of predicted values. Methodology: In this retrospective study, 2587 paired measurements of PEF and FEV1 performed by 101 adult patients with asthma (n = 56) and COPD (n = 45) attending an outpatient chest clinic were obtained. The mean differences between FEV1 and PEF measurements when expressed as the percentage of predicted values was determined. The level of agreement between the two measurements in the classification of asthma severity (life-threatening, severe, moderate and mild asthma determined by PEF or FEV1 measurements of <30%, 30–60%, 60–80%, and >80% of the predicted values, respectively) was determined. Results: There was considerable variability between measurements of FEV1 and PEF when expressed as % predicted values. In both asthma and COPD, the FEV1 % predicted was smaller than the PEF % predicted, with the mean difference being –10.9% (95% CI, –12.8% to –8.9%) with limits of agreement of –35.4% to +13.6%. The weighted Kappa statistic for agreement was 0.59 (95% CI, 48–70%) in the classification of the severity of airflow obstruction. Conclusion: When expressed as percentage of predicted values, PEF and FEV1 values are not equivalent. We recommend that guidelines be modified to state that across the spectrum of the severity of airflow obstruction there is considerable variability between measurements of FEV1 and PEF when expressed as % predicted such that the FEV1 may be as much as 35% lower or up to 15% higher than the PEF for patients with obstructive lung diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the relevance of immunoinflammatory markers on the response to short acting β[sub 2] -agonist in acute asthma exacerbation. Thus, we measured serum eosinophil cationic protein (ECP) levels and sIL-2R at acute exacerbation in 52 adult patients with atopic asthma, and assessed forced expiratory volume in 1 s (FEV[sub 1] ) before and after the administration of aerosolized salbutamol. After a cumulative dose of salbutamol causing a 10% improvement in FEV[sub 1] from baseline [CD10, i.e. cumulative doses of salbutamol (800 μg) causing an improvement in FEV[sub 1] from baseline to 10%] the patients were divided into two groups: group A with CD <10 and group B with CD >10. The bronchodilator response, as defined by a ΔFEV[sub 1] (percentage of predictive value of FEV[sub 1] ) of ≥10 predictive value, was shown by 40% of the patients. After 200, 400 and 800 μg of salbutamol, significant differences of FEV[sub 1] with respect to baseline values were, respectively, p = 0.049, 0.0039 and 0.0014. In contrast, no significant difference of the means of FEV[sub 1] between the doses of salbutamol was observed. Significant differences of ΔFEV[sub 1] between 200 and 400 μg (p = 0.0002) and between 200 and 800 μg (p < 0.0001) were observed, but not between 400 and 800 μg of salbutamol. There were significant correlations between baseline values of predictive FEV[sub 1] and serum ECP levels (rho = –0.60, p < 0.0001) and sIL-2R levels (rho = –0.35, p = 0.01) respectively. Besides, a correlation between ΔFEV[sub 1] and serum ECP levels (rho = –0.53, p < 0.0001) was observed, whereas no correlation was found between ΔFEV[sub 1] and sIL-2R. By analyzing differences between the two groups (A and B) for serum ECP levels, sIL-2R and blood eosinophil count, a significant difference was found for serum ECP levels. We conclude that subjects with acute exacerbation of asthma show high serum levels of ECP and sIL-2R and, more interestingly, that the response to brochodilator was higher in patients with lower serum ECP levels.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between ibuprofen use and pulmonary function in children with Asthma. Methods: Ninety 9- to 10-year-old children were classified into 3 groups: Study group, mild to moderate stable asthmatic children with self-reported aspirin allergy and no history of anaphylaxis; Allergy control group: atopic children (allergic rhinitis/atopic dermatitis); Healthy control group: non-atopic healthy children. None of the participants in the atopic and healthy control groups had a history of aspirin allergy. All received ibuprofen 4 times a day for 3 consecutive days. Forced expiratory volume in the first second (FeV) and fractional exhaled nitric oxide (FeNO) measurements were performed before and after ingestion of ibuprofen daily for 3 days. Results: In the study group, a decrease in FeV and increase in FeNO levels were observed after taking ibuprofen for 2 days. The atopic control group showed only an increase in FeNO but not FeV. In the healthy control group, both FeV and FeNO were unchanged from baseline. Conclusion: The results showed that cross-reactive non-steroidal anti-inflammatory drug hypersensitivity may exist between ibuprofen and aspirin. This raises the possibility that asthma exacerbation could be mediated by ibuprofen ingestion. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have shown a high prevalence of respiratory symptoms in farming communities and that storage mites constitute important allergens. We examined risk factors associated with asthma and rhinoconjunctivitis among Swedish farmers. Methods: A population of 1015 small‐scale dairy farmers was part of an epidemiologic survey. After selection based on symptom reports in a questionnaire, 461 of the farmers attended a medical examination, which comprised SPT, RAST analyses, and lung‐function measurements. Risk factors for sensitization to different allergens, and development of asthma and rhinoconjunctivitis were assessed by multiple logistic regression. Results: The prevalence of atopy was 26.7% among the farmers. For both asthma and rhinoconjunctivitis, sensitization to mites (OR=5.8 vs OR=3.8) and pollens (OR=10.3 vs OR=5.8) was a significant risk factor. There was a significant relationship between sensitization to mites and working time (OR=5.2). Environmental tobacco smoke and exposure to different animal species at the farm did not appear to affect the risk of allergen sensitization or respiratory symptoms. Farmers smoked less than the general population, but they more frequently had reduced FEV1. Conclusions: Allergen sensitization, especially to mites and pollens, was significantly associated with asthma and rhinoconjunctivitis in a farming community. The results point to allergen avoidance as a major goal for the prevention of occupational respiratory diseases among the farming population. [ABSTRACT FROM AUTHOR]

Background Exposure to house dust mite (HDM) allergens often results in worsening of asthma. Therefore, avoidance of exposure to HDM allergens is often proposed. Unfortunately, the most effective and feasible avoidance strategy is still not completely assessed. Consequently, we investigated the effects of a combined HDM avoidance strategy on HDM allergen concentrations and clinical condition of allergic, mild asthmatic, patients using no inhaled steroids. Methods Asthmatic patients, allergic to HDM, using no inhaled corticosteroids, were randomly allocated to an active (n = 76) or a placebo allergen-avoidance group (n = 81). Avoidance measures consisted of applying Acarosan® (placebo: water) to the living room and bedroom floors, and the use of HDM-impermeable covers for mattresses and bedding (placebo: cotton covers for mattresses only). Effects on allergen concentrations (Der p 1), FEV1, bronchial hyperresponsiveness, peak flow parameters and asthma symptom scores were studied during 20 weeks and controlled for the allergic status of the patients. Results The active covers reduced Der p 1 concentrations to 9.4% (P = 0.0001), and were always significant lower than in the placebo group (P = 0.0002). Acarosan® resulted in slight but significant decreases (twofold, P = 0.0001), both on living room and bedroom floors, but concentrations were never significantly lower than the placebo group. Although the combined avoidance strategy resulted in a considerable reduction in allergen load in the active group, no differences were seen between the two groups in any of the clinical parameters during the follow-up period in this group of allergic asthmatics, using no inhaled corticosteroids. Corrections for the allergic status did not alter these results. Conclusions The combined avoidance strategy was effective in reducing HDM allergen concentration. This was especially achieved by the allergen-impermeable covers, while the... [ABSTRACT FROM AUTHOR]

BackgroundInternational guidelines recommend that, in addition to symptoms and medication requirements, measurements of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) are necessary for the objective assessment of asthma severity. The guidelines suggest that parity exists between measurements of FEV1 and PEF when expressed as percentage of predicted normal values, and that asthma severity can be classified as mild, moderate or severe on the basis of FEV1 and PEF measurements of > 80%, 60–80% and < 60% of predicted values, respectively. ObjectiveTo determine the relationship between measurements of FEV1 and PEF when expressed as percentage predicted values. MethodsA total of 1198 paired measurements of FEV1 and PEF were obtained from the medical records of a random sample of 25 adult asthmatic patients attending a hospital-based chest clinic. Measurements of lung function were expressed as a percentage of predicted normal values, using the European Respiratory Society prediction equations for PEF and FEV1. For the individual paired measurements, the mean differences between PEF and FEV1 percentage predicted were calculated. Measurements of lung function were used to determine asthma severity with < 60%, 60–80%, and > 80% predicted FEV1 and PEF values representing severe, moderate and mild asthma, respectively. The proportion of paired measurements in which differences in classification resulted from the use of FEV1 or PEF percentage predicted values was then calculated. ResultsIn asthma of differing severity, there was considerable variability between measurements of FEV1 and PEF when expressed as percentage predicted values; calculation of the FEV1% predicted resulted in lower values than those of the PEF percentage predicted, with a mean difference of -17.2% (95% CI -16.3%, -18.1%). There was... [ABSTRACT FROM AUTHOR]

The bronchial effects of prenalterol, a selective inotropic β-adrenoceptor agonist, were examined to see whether β-adrenoceptor stimulation would produce bronchodilatation, or whether β-adrenoceptor blockade could be demonstrated. In a first investigation 8 asthmatic patients were studied under standardized conditions in a double-blind, randomized, crossover comparison between i.v. doses of prenalterol and saline infusions. After the fourth dose of prenalterol/saline, 4 intravenous doses of terbutaline were given. All medication was given at 30 min intervals. In a second study in 7 of the previously studied patients, 5 increasing doses of prenalterol or saline were inhaled from a Bird ventilator, and after the last dose 4 i.v. doses of terbutaline were given as before. Prenalterol and saline caused no change in FEV during the intravenous study. Terbutaline infusion produced a dose dependent increase in FEV which was not significantly altered after prenalterol treatment. In the inhalation study, in which a much larger dose was applied to the bronchial tree, there was no significant difference in FEV, between the saline and prenalterol inhalations. However, prenalterol did show β-blocking property, as the dose response curve of terbutaline was shifted to the right. The heart rate increased significantly and to the same degree during both the i.v. and inhaled prenalterol treatments. Thus, this study revealed no significant β-blocking effect of therapeutic doses of i.v. prenalterol. However, when the drug was inhaled in a much higher dose, a β-blocking effect on FEV was recorded. No significant β-adrenoceptor-mediated bronchodilator effect of prenalterol could be demonstrated. [ABSTRACT FROM AUTHOR]

This double-blind, randomised, within patient, placebo-controlled study set out to investigate the effect of a cardioselective beta-blocker, atenolol, at different oral doses (50, 100 and 200 mg) and a non-selective agent, propranolol (40 mg), upon 1. airways resistance (forced expiratory volume at one second=FEV) and 2. the bronchodilator action of increasing doses of inhaled isoprenaline, in patients with co-existent hypertension and reversible airways obstruction. In 10 patients, two hours after drug administration, the 3 doses of atenolol caused a significantly greater ( P<0.05) degree of B-blockade than propranolol. In contrast the 3 doses of atenolol caused significantly less ( P<0.05 to 0.01) B-blockade as evidenced by a smaller fall in FEV. The isoprenaline FEV dose response curves were displaced progressively to the right of the placebo curve with increasing doses of atenolol, but the greatest displacement was with propranolol. It was concluded that patients with reversible airways obstruction who require beta-blockade should be given a low dose of a cardioselective agent in conjunction with, if required, a beta stimulant such as isoprenaline. Such a treatment will be less likely to cause a troublesome increase in airways resistance and the bronchodilator action of the beta stimulant will be almost fully preserved. [ABSTRACT FROM AUTHOR]