Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 8.165
2.
Rev Paul Pediatr ; 42: e2023162, 2024.
Article En | MEDLINE | ID: mdl-38808869

OBJECTIVE: To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis. METHODS: Cross-sectional study on clinically stable children and adolescents with cystic fibrosis aged from six to 15 years. Participants underwent impulse oscillometry and spirometry evaluations before and 15 minutes after bronchodilator inhalation. The Kolmogorov-Smirnov test was applied to verify the sample distribution, and the Student's t-test and Wilcoxon test were used to compare the data before and after bronchodilator inhalation. RESULTS: The study included 54 individuals with a mean age of 9.7±2.8 years. The analysis showed a statistically significant improvement in impulse oscillometry and spirometry parameters after bronchodilator inhalation. However, according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommendations (2020 and 2021), this improvement was not sufficient to classify it as a bronchodilator response. CONCLUSIONS: The use of bronchodilator medication improved respiratory mechanics and pulmonary function parameters of children and adolescents with cystic fibrosis; however, most patients did not show bronchodilator response according to ATS/ERS recommendations.


Bronchodilator Agents , Cystic Fibrosis , Oscillometry , Spirometry , Humans , Cystic Fibrosis/physiopathology , Cystic Fibrosis/drug therapy , Child , Adolescent , Cross-Sectional Studies , Spirometry/methods , Female , Male , Oscillometry/methods , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/administration & dosage , Respiratory Mechanics/drug effects , Respiratory Mechanics/physiology , Respiratory Function Tests/methods
3.
BMJ Open Respir Res ; 11(1)2024 May 21.
Article En | MEDLINE | ID: mdl-38772900

BACKGROUND: Compared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score. This real-world study compared the effectiveness of switching patients with COPD in England from MITT to once-daily SITT with FF/UMEC/VI by evaluating rates of COPD exacerbation, healthcare resource use (HCRU) and associated direct medical costs. METHODS: Retrospective cohort pre-post study using linked primary care electronic health record and secondary care administrative datasets. Patients diagnosed with COPD at age ≥35 years, with smoking history, linkage to secondary care data and continuous GP registration for 12 months pre-switch and 6 months post-switch to FF/UMEC/VI were included. Index date was the first initiation of an FF/UMEC/VI prescription immediately following MITT use from 15 November 2017 to 30 September 2019. Baseline was 12 months prior to index, with outcomes assessed 6/12 months pre-switch and post-switch, and stratified by prior COPD exacerbation status. RESULTS: We included 2533 patients (mean [SD] age: 71.1 [9.9] years; 52.1% male). In the 6 months post-switch, there were significant decreases in the proportion of patients experiencing ≥1 moderate-to-severe (36.2%-28.9%), moderate only (24.4%-19.8%) and severe only (15.4%-11.8%) COPD exacerbation (each, p<0.0001) compared with the 6 months pre-switch. As demonstrated by rate ratios, there were significant reductions in exacerbation rates of each severity overall (p<0.01) and among patients with prior exacerbations (p<0.0001). In the same period, there were significant decreases in the rate of each COPD-related HCRU and total COPD-related costs (-24.9%; p<0.0001). CONCLUSION: Patients with COPD switching from MITT to once-daily SITT with FF/UMEC/VI in a primary care setting had significantly fewer moderate and severe exacerbations, and lower COPD-related HCRU and costs, in the 6 months post-switch compared with the 6 months pre-switch.


Benzyl Alcohols , Bronchodilator Agents , Chlorobenzenes , Drug Combinations , Nebulizers and Vaporizers , Primary Health Care , Pulmonary Disease, Chronic Obstructive , Quinuclidines , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Male , Retrospective Studies , Female , Aged , Middle Aged , Benzyl Alcohols/administration & dosage , Chlorobenzenes/administration & dosage , England , Administration, Inhalation , Bronchodilator Agents/administration & dosage , Quinuclidines/administration & dosage , Treatment Outcome , Muscarinic Antagonists/administration & dosage , Androstadienes
4.
Ther Adv Respir Dis ; 18: 17534666241232264, 2024.
Article En | MEDLINE | ID: mdl-38698565

What is this summary about?This summary describes the results of a clinical study called MANDALA that was published in the New England Journal of Medicine in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both albuterol and budesonide in a single inhaler (known as albuterol-budesonide, AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.


Albuterol , Asthma , Bronchodilator Agents , Budesonide , Drug Combinations , Nebulizers and Vaporizers , Humans , Asthma/drug therapy , Albuterol/administration & dosage , Administration, Inhalation , Bronchodilator Agents/administration & dosage , Budesonide/administration & dosage , Adult , Middle Aged , Male , Female , Treatment Outcome , Adolescent , Young Adult , Aged , Anti-Asthmatic Agents/administration & dosage
5.
BMJ Paediatr Open ; 8(1)2024 May 23.
Article En | MEDLINE | ID: mdl-38782483

OBJECTIVES: To review the efficacy of nebulised magnesium sulfate (MgSO4) in acute asthma in children. METHODS: The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO4 as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them. RESULTS: 10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO4/placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: -0.09; 95% CI: -0.2 to +0.02, I2=21%). Children in the MgSO4 group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I2=0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups. CONCLUSIONS: There is low-certainty evidence that nebulised MgSO4 as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO4 in paediatric acute asthma management. PROSPERO REGISTRATION NUMBER: CRD42022373692.


Asthma , Magnesium Sulfate , Nebulizers and Vaporizers , Humans , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/therapeutic use , Magnesium Sulfate/adverse effects , Asthma/drug therapy , Child , Acute Disease , Administration, Inhalation , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/adverse effects , Randomized Controlled Trials as Topic , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/adverse effects
6.
Ter Arkh ; 96(3): 246-252, 2024 Apr 16.
Article Ru | MEDLINE | ID: mdl-38713039

AIM: To determine and compare the work of breathing to overcome elastic resistance (Ael) in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) with similar changes in the elastic properties of the parenchyma in the same settings of ventilation disorders (grade 1). MATERIALS AND METHODS: Differences in the manifestations of similar changes in the elastic properties of the lungs in patients with BA and COPD were evaluated. To identify differences, a comparative study was conducted on Аel overcome in BA patients with positive bronchodilator (with salbutamol) and bronchoconstrictor (with methacholine) tests, with reduced and preserved bronchial conductance (groups 1 and 2, respectively), and in COPD patients with negative bronchodilator and bronchoconstrictor tests (group 3). All study patients showed a grade 1 lung ventilation disorder (a decrease in the one-second forced expiratory volume by 15-35%). The results were compared with each other and with the control group (group 4, healthy non-smokers). All study patients were comparable by age and sex. The respiration mechanics was studied using simultaneous registration of spirogram and transpulmonary pressure, and the parameters of bronchial conductance and ventilation were determined using body plethysmopressography using the Jager software and hardware system. RESULTS AND CONCLUSION: In COPD patients, Ael was significantly increased (p>0.05), whereas in both BA groups, it was unchanged. Increased elastic work of breathing in patients with COPD may be associated with the involvement of certain types of contractile elements, which are preserved in patients with BA at the initial stages of the disease.


Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Female , Asthma/physiopathology , Middle Aged , Work of Breathing/physiology , Lung/physiopathology , Adult , Elasticity , Respiratory Function Tests/methods , Bronchodilator Agents/pharmacology , Bronchodilator Agents/administration & dosage
7.
Int J Pharm ; 656: 124116, 2024 May 10.
Article En | MEDLINE | ID: mdl-38615803

Inhalation of pharmaceutical aerosol formulations is widely used to treat respiratory diseases. Spatially resolved thermal characterization offers promise for better understanding drug release rates from particles; however, this has been an analytical challenge due to the small particle size (from a few micrometers down to nanometers) and the complex composition of the formulations. Here, we employ nano-thermal analysis (nanoTA) to probe the nanothermal domain of a pharmaceutical aerosol formulation containing a mixture of fluticasone propionate (FP), salmeterol xinafoate (SX), and excipient lactose, which is widely used to treat asthma and chronic obstructive pulmonary disease (COPD). Furthermore, atomic force microscopy-infrared spectroscopy (AFM-IR) and AFM force measurements are performed to provide nanochemical and nanomechanical information to complement the nanothermal data. The colocalized thermal and chemical mapping clearly reveals the surface heterogeneity of the drugs in the aerosol particles and demonstrates the contribution of the surface chemical composition to the variation in the thermal properties of the particles. We present a powerful analytical approach for in-depth characterization of thermal/chemical/morphological properties of dry powder inhaler particles at micro- and nanometer scales. This approach can be used to facilitate the comparison between generics and reference inhalation products and further the development of high-performance pharmaceutical formulations.


Aerosols , Dry Powder Inhalers , Fluticasone , Lactose , Microscopy, Atomic Force , Particle Size , Powders , Salmeterol Xinafoate , Fluticasone/chemistry , Fluticasone/administration & dosage , Salmeterol Xinafoate/chemistry , Salmeterol Xinafoate/administration & dosage , Lactose/chemistry , Microscopy, Atomic Force/methods , Excipients/chemistry , Administration, Inhalation , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/chemistry , Spectrophotometry, Infrared/methods , Chemistry, Pharmaceutical/methods , Surface Properties
8.
Article En | MEDLINE | ID: mdl-38646606

Purpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany. Patients and Methods: Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015-31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period. Results: In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period. Conclusion: In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.


Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019. In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years. The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).


Adrenergic beta-2 Receptor Agonists , Bronchodilator Agents , Drug Combinations , Glycopyrrolate , Muscarinic Antagonists , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive , Humans , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Female , Retrospective Studies , Germany , Aged , Administration, Inhalation , Middle Aged , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , Glycopyrrolate/administration & dosage , Glycopyrrolate/adverse effects , Chlorobenzenes/administration & dosage , Chlorobenzenes/adverse effects , Quinuclidines/administration & dosage , Quinuclidines/adverse effects , Treatment Outcome , Benzyl Alcohols/administration & dosage , Benzyl Alcohols/adverse effects , Beclomethasone/administration & dosage , Beclomethasone/adverse effects , Formoterol Fumarate/administration & dosage , Drug Therapy, Combination , Time Factors , Aged, 80 and over
9.
AAPS J ; 26(3): 56, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38671158

Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate (FP) and salmeterol xinafoate (SX). However, the pharmacokinetics (PK) batch-to-batch variability of the reference-listed drug (RLD) hindered its generic product development. This work developed the PK models for inhaled FP and SX that could represent potential batch variability. Two batches each of the reference and the test product (R1, R2, T1, T2) of Advair Diskus (100 µg FP/50 µg SX inhalation) were administered to 60 healthy subjects in a 4-period, 4-sequence crossover study. The failure of the bioequivalence (BE) between R1 and R2 confirmed the high between-batch variability of the RLD. Non-linear mixed effect modeling was used to estimate the population mean PK parameters for each batch. For FP, a 2-compartment model with a sequential dual zero-order absorption best described the PK profile. For SX, a 2-compartment model with a first-order absorption model best fit the data. Both models were able to capture the plasma concentration, the maximum concentration, and the total exposure (AUCinf) adequately for each batch, which could be used to simulate the BE study in the future. In vitro properties were also measured for each batch, and the batch with a higher fraction of the fine particle (diameter < 1 µm, < 2 µm) had a higher AUCinf. This positive correlation for both FP and SX could potentially assist the batch selection for the PK BE study.


Bronchodilator Agents , Cross-Over Studies , Dry Powder Inhalers , Fluticasone-Salmeterol Drug Combination , Models, Biological , Therapeutic Equivalency , Humans , Administration, Inhalation , Male , Adult , Fluticasone-Salmeterol Drug Combination/pharmacokinetics , Fluticasone-Salmeterol Drug Combination/administration & dosage , Young Adult , Bronchodilator Agents/pharmacokinetics , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/blood , Female , Middle Aged , Fluticasone/pharmacokinetics , Fluticasone/administration & dosage , Salmeterol Xinafoate/pharmacokinetics , Salmeterol Xinafoate/administration & dosage , Healthy Volunteers
10.
Eur J Pediatr ; 183(6): 2637-2644, 2024 Jun.
Article En | MEDLINE | ID: mdl-38492031

Pediatric asthma is a common condition, and its exacerbations can be associated with significant morbidity and mortality. The role of nebulised magnesium as adjunct therapy for children with asthma exacerbations is still unclear. To compare clinical and functional outcomes for children with asthma exacerbation taking either nebulised magnesium sulfate added to standard medical therapy (SMT) versus SMT alone. PubMed, Embase, and Cochrane Library were systematically searched for randomised clinical trials (RCT) comparing the use of SMT with vs. without nebulised magnesium. The outcomes were respiratory rate, heart rate, % predicted peak expiratory flow rate (PEFR), % predicted forced expiratory volume (FEV1), peripheral O2 saturation, asthma severity scores, and need for intravenous (IV) bronchodilator use. Twelve RCTs and 2484 children were included. Mean age was 5.6 (range 2-17) years old, mean baseline % predicted FEV1 was 69.6%, and 28.66% patients were male. Children treated with magnesium had a significantly higher % predicted PEFR (mean difference [MD] 5.33%; 95% confidence interval [CI] 4.75 to 5.90%; p < 0.01). Respiratory rate was significantly lower in the magnesium group (MD -0.70 respirations per minute; 95% CI -1.24 to -0.15; p < 0.01). Need for IV bronchodilators, % predicted FEV1, heart rate, asthma severity scores, and O2 saturation were not significantly different between groups. CONCLUSION: In children with asthma exacerbation, treatment with nebulised magnesium and SMT was associated with a statistically significant, but small improvement in predicted PEFR and respiratory rate, as compared with SMT alone. WHAT IS KNOWN: • Magnesium sulfate has bronchodilating properties and aids in the treatment of asthma exacerbation when administered intravenously. • There is no significant evidence of benefit of nebulised magnesium as an adjunct therapy to the standard medical treatment for children with asthma exacerbations. WHAT IS NEW: • Our study suggests nebulised magnesium sulfate may have a statistically significant, but small benefit in respiratory rate and peak expiratory flow rate. The addition of nebulised magnesium does not seem to increase adverse events.


Asthma , Magnesium Sulfate , Nebulizers and Vaporizers , Humans , Asthma/drug therapy , Child , Magnesium Sulfate/administration & dosage , Adolescent , Bronchodilator Agents/administration & dosage , Administration, Inhalation , Child, Preschool , Randomized Controlled Trials as Topic , Treatment Outcome , Female , Anti-Asthmatic Agents/administration & dosage , Male
12.
Eur J Clin Pharmacol ; 80(6): 847-853, 2024 Jun.
Article En | MEDLINE | ID: mdl-38396308

INTRODUCTION: Long-acting muscarinic antagonists (LAMA) or beta-2 agonists (LABA) have been recommended for symptom control in group A COPD patients as a first-line bronchodilator treatment in GOLD guidelines. However, there is no mention of priority/superiority between the two treatment options. We aimed to compare the effectiveness of these treatments in this group. METHODS: The study cohort was formed of all subjects from six pulmonology clinics with an initial diagnosis of COPD who were new users of a LAMA or LABA from January 2020 to December 2021. Seventy-six group A COPD patients, in whom LABA or LAMA therapy had been started in the last 1 month as a first-line treatment, were included in our study. Participants were evaluated with spirometry, COPD Assessment Test (CAT), mMRC scale, and St. George Respiratory Questionnaire (SGRQ) for three times (baseline, 6-12th months). RESULTS: There were 76 group A COPD patients with LAMA (67.1%) and LABA (32.9%). The number of patients who improved in CAT score at the end of the first year was significantly higher in patients using LAMA than those using LABA (p = 0.022); the improvement at minimum clinically important difference (MCID) in CAT score of LAMA group at 1st year was also significant (p = 0.044). SGRQ total and impact scores were found to be statistically lower at 1st year compared to baseline in patients using LAMA (p = 0.010 and 0.006, respectively). Significant improvement was detected in CAT and SGRQ scores at the 6th month visit in the LAMA group having emphysema (p = 0.032 and 0.002, respectively). CONCLUSION: According to significant improvements in CAT and SGRQ score, LAMA may be preferred over LABA as a bronchodilator agent in group A COPD patients, especially in emphysema-dominant phenotype.


Adrenergic beta-2 Receptor Agonists , Muscarinic Antagonists , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Male , Female , Adrenergic beta-2 Receptor Agonists/therapeutic use , Adrenergic beta-2 Receptor Agonists/administration & dosage , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/therapeutic use , Aged , Middle Aged , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/administration & dosage , Treatment Outcome , Spirometry , Muscarinic Agonists/therapeutic use , Muscarinic Agonists/administration & dosage , Delayed-Action Preparations
14.
J Allergy Clin Immunol Pract ; 12(5): 1244-1253.e8, 2024 May.
Article En | MEDLINE | ID: mdl-38309696

BACKGROUND: Findings from CAPTAIN (NCT02924688) suggest that treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 inflammation markers in patients with moderate to severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management. OBJECTIVE: To investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting ß2-agonist combination FF/VI, or doubling the FF dose. METHODS: Prespecified and post hoc analyses of CAPTAIN data were performed using categorical and continuous variables of key baseline characteristics to understand their influence on treatment outcomes (lung function [trough FEV1], annualized rate of moderate/severe exacerbations, and asthma control [Asthma Control Questionnaire]) following addition of UMEC to FF/VI or doubling the FF dose in FF/VI or FF/UMEC/VI. RESULTS: Adding UMEC to FF/VI led to greater improvements in trough FEV1 versus doubling the FF dose across all baseline characteristics assessed. Doubling the FF dose was generally associated with numerically greater reductions in the annualized rate of moderate/severe exacerbations compared with adding UMEC, independent of baseline characteristics. Adding UMEC and/or doubling the FF dose generally led to improvements in Asthma Control Questionnaire scores irrespective of baseline characteristics. CONCLUSIONS: Unlike previous findings with type 2 biomarkers, lung function, bronchodilator reversibility, age and age at asthma onset do not appear to predict response to inhaled therapy.


Adrenal Cortex Hormones , Adrenergic beta-2 Receptor Agonists , Asthma , Benzyl Alcohols , Muscarinic Antagonists , Quinuclidines , Humans , Asthma/drug therapy , Asthma/physiopathology , Male , Female , Adult , Middle Aged , Benzyl Alcohols/therapeutic use , Benzyl Alcohols/administration & dosage , Quinuclidines/therapeutic use , Quinuclidines/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Adrenergic beta-2 Receptor Agonists/therapeutic use , Adrenergic beta-2 Receptor Agonists/administration & dosage , Muscarinic Antagonists/therapeutic use , Muscarinic Antagonists/administration & dosage , Chlorobenzenes/therapeutic use , Chlorobenzenes/administration & dosage , Administration, Inhalation , Treatment Outcome , Drug Combinations , Androstadienes/therapeutic use , Androstadienes/administration & dosage , Aged , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/administration & dosage , Young Adult
15.
J Asthma ; 61(6): 574-583, 2024 Jun.
Article En | MEDLINE | ID: mdl-38153316

OBJECTIVE: The aim of this pilot study was to assess the efficacy of doxofylline as an ICS-sparing agent in the treatment of Mexican children with asthma. METHODS: 10-week, open-label, crossover, pilot study, we examined the steroid-sparing effect of doxofylline in Mexican children with asthma. Patients aged 6-16 years treated with inhaled corticosteroids (ICS) for at least 8 wk before enrollment were divided randomly into two groups at the baseline visit. Group A (n = 31) received doxofylline (18 mg/kg/day) plus standard-dose budesonide (D + SDB) for the first 4-week period followed by doxofylline plus reduced-dose budesonide (D + RDB) for the second 4-week period. Group B (n = 30) received D + RDB followed by D + SDB. Clinical outcomes assessed included lung function (forced expiratory volume; in 1 s, FEV1), fractional exhaled nitric oxide (FeNO), asthma control, number of exacerbations and use of rescue medication (salbutamol). RESULTS: It was shown that combined use of doxofylline and ICS may allow children with asthma to reduce their daily dose of ICS while maintaining lung function and improving asthma control (p = 0.008). There were few asthma exacerbations and only one patient required treatment with systemic corticosteroids. Rescue medication use decreased significantly in patients receiving D + SDB during the first 4-week period. CONCLUSIONS: Our results suggest that doxofylline may be a steroid-sparing treatment in asthma, but longer-term, controlled studies are needed to confirm these observations.


Asthma , Budesonide , Cross-Over Studies , Drug Therapy, Combination , Theophylline , Theophylline/analogs & derivatives , Humans , Child , Asthma/drug therapy , Male , Female , Adolescent , Mexico , Theophylline/therapeutic use , Theophylline/administration & dosage , Pilot Projects , Budesonide/administration & dosage , Budesonide/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Administration, Inhalation , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/administration & dosage , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Treatment Outcome , Forced Expiratory Volume/drug effects
16.
Int J Chron Obstruct Pulmon Dis ; 18: 1091-1102, 2023.
Article En | MEDLINE | ID: mdl-37313498

Purpose: Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM). Materials and Methods: This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 µg) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O. Results: Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline. Conclusion: Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD.


Bronchodilator Agents , Pulmonary Disease, Chronic Obstructive , Aged , Female , Humans , Male , Middle Aged , Bronchodilator Agents/administration & dosage , Cluster Analysis , Multicenter Studies as Topic , Pulmonary Disease, Chronic Obstructive/drug therapy , Randomized Controlled Trials as Topic , Dose-Response Relationship, Drug
17.
J Aerosol Med Pulm Drug Deliv ; 36(4): 181-188, 2023 08.
Article En | MEDLINE | ID: mdl-37219899

Background: A pressurized metered dose inhaler combined with a valved holding chamber (pMDI+VHC) is used to prevent upper airway complications and improve the efficiency of inhaled drug delivery; however, the aerodynamic behavior of the released particles has not been well investigated. This study aimed at clarifying the particle release profiles of a VHC using simplified laser photometry. Methods: An inhalation simulator comprised a computer-controlled pump and a valve system that withdrew aerosol from a pMDI+VHC using a jump-up flow profile. A red laser illuminated the particles leaving VHC and evaluated the intensity of the light reflected by the released particles. Results: The data suggested that the output (OPT) from the laser reflection system represented particle concentration rather than particle mass, and the latter was calculated as OPT × instantaneous withdrawn flow (WF). Summation of OPT hyperbolically decreased with flow increment, whereas summation of OPT × instantaneous flow was not influenced by WF strength. Particle release trajectories consisted of three phases, namely increment with a parabolic curve, flat, and decrement with exponential decay phases. The flat phase appeared exclusively at low-flow withdrawal. These particle release profiles suggest the importance of early phase inhalation. The hyperbolic relationship between WF and particle release time revealed the minimal required withdrawal time at an individual withdrawal strength. Conclusions: The particle release mass was calculated as laser photometric output × instantaneous flow. Simulation of the released particles suggested the importance of early phase inhalation and predicted the minimally required withdrawal time from a pMDI+VHC.


Aerosols , Inhalation Spacers , Metered Dose Inhalers , Administration, Inhalation , Aerosols/analysis , Bronchodilator Agents/administration & dosage , Equipment Design , Photometry/methods , Pressure , Lasers
18.
Curr Opin Pulm Med ; 29(3): 209-214, 2023 05 01.
Article En | MEDLINE | ID: mdl-36994505

PURPOSE OF REVIEW: Asthma is the most common chronic respiratory disorder, characterized by recurring, reversible airflow obstruction due to inflammation and airway hyperresponsiveness. Although biologics have provided significant advances in the treatment of asthma, they are expensive, and their use remains restricted to more severe asthma. Additional approaches in the management of moderate-to-severe asthma are necessary. RECENT FINDINGS: ICS-formoterol as maintenance and reliever therapy in asthma and its effect on improved asthma control has been demonstrated in multiple cohorts of asthma. Although ICS-formoterol as maintenance and reliever therapy has been widely validated, there are significant design considerations including the requirement for exacerbation and bronchodilator response and the lack of evidence for effectiveness in patients who use nebulized reliever therapies, which may limit the use of this therapy in selected populations. More recent trials of as-needed ICS have demonstrated effectiveness in reducing asthma exacerbations and improvements in asthma control and may provide an additional therapeutic strategy for individuals with moderate-to-severe asthma. SUMMARY: Both ICS-formoterol as a maintenance and a reliever as well as as-needed ICS have demonstrated significant improvements in the control of moderate-to-severe asthma. Future investigational work will be necessary to elucidate whether a strategy of ICS-formoterol as maintenance and reliever therapy or an as-needed ICS strategy demonstrates superiority in asthma control in the context of the cost to individual patients and health systems.


Anti-Asthmatic Agents , Asthma , Formoterol Fumarate , Glucocorticoids , Humans , Administration, Inhalation , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Budesonide/adverse effects , Drug Therapy, Combination , Formoterol Fumarate/administration & dosage , Formoterol Fumarate/therapeutic use , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use
19.
Allergol. immunopatol ; 51(2): 1-10, 01 mar. 2023. tab, graf
Article En | IBECS | ID: ibc-216793

Background and aim: A precise scaling system of acute asthma leads to an accurate assessment of disease severity. This study aimed to compare the accuracy of the Buddhasothorn Asthma Severity Score (BASS) with the Wood–Downes–Ferrés Scale (WDFS) to recognize the severity level of acute asthma. Materials and methods: A cross-sectional study was conducted comprising Thai children aged 2–15 years with acute asthma. The BASS and WFDS were rated once in the emergency department. The degree of severity was determined by frequency and type of nebulized bronchodilator administrations at the time of initial treatment. The optimum cutoff points for the area under the curve (AUC) were established to predict severe asthma exacerbations. Results: All 73 episodes of asthma exacerbations (EAEs) in 35 participants were analyzed. Fifty-nine (80.8%) EAEs were classified as severe. Both scales had good significance to recognize the selection of nebulized bronchodilator treatments by AUC of 0.815 (95% Confidence Interval [CI]: 0.680–0.950) in case of BASS, and AUC of 0.822 (95% CI: 0.70–0.944) in case of WDFS. Cutoff points of BASS ≥ 8 had sensitivity 72.9%, specificity 64.3%, positive predictive value (PPV) 89.6%, negative predictive value (NPV) 36.0% at an AUC of 0.718 (95% CI: 0.563–0.873) for severe exacerbations. These results were consistent for cutoff points of WDFS ≥ 5 with sensitivity 78.0%, specificity 50.0%, PPV 86.8%, NPV 35.0% at an AUC of 0.768 (95% CI: 0.650–0.886) for predicting severe exacerbations. There was no significant difference between the AUCs of both scales. Conclusions: Both the BASS and WDFS were good and accurate scales and effective screening tools for predicting severe asthma exacerbations in pediatric patients by optimal cutoff points (AU)


Humans , Male , Female , Child, Preschool , Child , Adolescent , Symptom Flare Up , Bronchodilator Agents/administration & dosage , Asthma/drug therapy , Asthma/classification , Severity of Illness Index , Cross-Sectional Studies
20.
Allergol. immunopatol ; 51(1): 74-76, ene. 2023. tab
Article En | IBECS | ID: ibc-214040

Background: The Pediatric Respiratory Assessment Measure (PRAM) score is a useful tool for the assessment of asthma exacerbations in children. This study aimed to estimate the risk of hospitalization in children, assessed with the PRAM score and having mild–moderate asthma exacerbation, who were treated with salbutamol delivered via a metered-dose inhaler and spacer (MDI/S). Methods: The study population consisted of children aged 3–16 years with mild–moderate asthma exacerbations. All children received 1mg/kg prednisolone p.o. (max 40 mg) and 4–6 puffs of salbutamol via MDI/S. Results: Fifty patients participated in the study. Admission was associated positively with the initial PRAM score (OR: 18.91, CI: 2.42–123.12, P = 0.005) and negatively with the improvement in PRAM score (OR: 0.52, CI: 0.01–0.78, P = 0.032). Conclusion: PRAM is a reliable tool that can be used effectively to estimate the asthma exacerbation severity (AU)


Humans , Male , Female , Child, Preschool , Child , Adolescent , Albuterol/administration & dosage , Bronchodilator Agents/administration & dosage , Asthma/drug therapy , Anti-Asthmatic Agents/administration & dosage , Emergency Medical Services
...