Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial

2021 ◽  
pp. 2102184
Author(s):  
Lata Jayaram ◽  
Alain C. Vandal ◽  
Catherina Chang ◽  
Chris Lewis ◽  
Cecilia Tong ◽  
...  
Keyword(s):  
Lung Function ◽  
Crossover Trial ◽  
Airflow Limitation ◽  
Smoking History ◽  
Double Blind ◽  
Intention To Treat ◽  
History Of ◽  
Long Acting ◽  
Anticholinergic Bronchodilator ◽  
Event Based

Tiotropium via HandiHaler® is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with COPD. We hypothesized that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. In a randomised, double-blind, 2-period crossover trial, we recruited adult patients from 3 hospitals in New Zealand. Patients were excluded if they had a smoking history of more than 20 pack years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18mcg via the HandiHaler® device daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary endpoint was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. Ninety patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations under the tiotropium treatment was 2.17 y−1 and 2.27 y−1 under placebo (rate ratio 0.96, 95% CI 0.72–1.27; p=0.77). Tiotropium, as compared with placebo, improved FEV1 by 58 mL (95% CI 23–92; p=0.002). Adverse events were similar under both treatments. Tiotropium via HandiHaler® over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

scholarly journals Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD)

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 783 ◽  
Author(s):  
Ozretić ◽  
da Silva Filho ◽  
Catalano ◽  
Sokolović ◽  
Vukić-Dugac ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Minor Allele ◽  
Fine Tuning ◽  
Airflow Limitation ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Impact

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients’ overall survival was analyzed with the Kaplan–Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

scholarly journals Lung function, pharmacokinetics, and tolerability of inhaled indacaterol maleate and acetate in asthma patients

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
David Miller ◽  
Soniya Vaidya ◽  
Juergen Jauernig ◽  
Brian Ethell ◽  
Kristina Wagner ◽  
...  
Keyword(s):  
Lung Function ◽  
Systemic Exposure ◽  
Forced Expiratory Volume ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Electronic Diary ◽  
Double Blind ◽  
Once Daily ◽  
Long Acting ◽  
Salt Forms

Abstract Background Indacaterol maleate delivered with the Breezhaler® inhalation device is a long-acting β2-agonist approved for chronic obstructive pulmonary disease. In the development of a once daily, inhaled fixed dose combination (FDC) of indacaterol, glycopyrronium bromide (a long-acting muscarinic antagonist), and mometasone furoate (an inhaled corticosteroid [ICS]) for the treatment of patients with asthma, the acetate salt of indacaterol is used instead of the maleate salt. Here, we investigated the lung function, pharmacokinetics (PK) and safety of indacaterol maleate 150 μg once daily (o.d.) and indacaterol acetate 150 μg o.d. in comparison with placebo. Methods This was a randomised, double-blind, three-period crossover study (ClinicalTrials.gov identifier, NCT03257995) in patients with asthma on background ICS therapy. Patients with percent predicted pre-bronchodilator forced expiratory volume per second (FEV1) ≥50% and ≤ 90% were included in the study. Patients received indacaterol maleate 150 μg o.d., indacaterol acetate 150 μg o.d., or placebo on top of stable background ICS in randomised sequence. Trough FEV1 was assessed after 14 days of treatment. PK of indacaterol salts were assessed at steady state after 14 days of treatment; peak expiratory flow (PEF) rate and rescue medication use were collected with a combined PEF-meter/electronic diary throughout the study. Results Of the 54 adult patients (median age of 48 years), 51 patients completed the study. Both indacaterol salts demonstrated statistically significant improvements in trough FEV1 of 186 mL (maleate) and 146 mL (acetate) compared with placebo (both P < 0.001). FEV1 AUC0-4h improved by 248 mL (maleate) and 245 mL (acetate), and PEF by 33 L/min (maleate) and 30.8 L/min (acetate) versus placebo. Systemic exposure of indacaterol (AUC0-24h,ss and Cmax,ss on Day 14) was comparable after administration of both salt forms. Both salt forms demonstrated a good safety profile and were well tolerated, with a difference in the reporting frequency of AEs of coughing (maleate, 23.5%; acetate, 0%). Conclusions In patients with asthma, indacaterol maleate and acetate elicited comparable and significant improvements in lung function compared with placebo and achieved comparable systemic exposure. Both indacaterol salts were safe and well tolerated. Trial registration ClinicalTrials.gov NCT03257995 June 06, 2017

scholarly journals Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Claus F. Vogelmeier ◽  
Paul W. Jones ◽  
Edward M. Kerwin ◽  
Isabelle H. Boucot ◽  
François Maltais ◽  
...  
Keyword(s):  
Lung Function ◽  
Rescue Medication ◽  
Inhaled Corticosteroids ◽  
Full Range ◽  
Medication Use ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Double Blind ◽  
Once Daily ◽  
Post Hoc

Abstract Background In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids. Methods The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV1) of ≥ 12% and ≥ 200 mL 10−30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV1 and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21–24, and rescue medication use (puffs/day) over Weeks 1–24. Analyses were conducted across the full range of reversibility (−850–896 mL); however, results are presented for the range −100–400 mL because there were few participants with values outside this range. Results The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV1, SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV1 and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range. Conclusions FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.

scholarly journals The Impact of Changes in the Intake of Fiber and Antioxidants on the Development of Chronic Obstructive Pulmonary Disease

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 580
Author(s):  
Young Ju Jung ◽  
Se Hee Lee ◽  
Ji Ho Chang ◽  
Hye Seung Lee ◽  
Eun Hee Kang ◽  
...  
Keyword(s):  
Folic Acid ◽  
Lung Function ◽  
Vitamin C ◽  
Airflow Limitation ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Age Related ◽  
The Impact

Diet is a health-related factor that can modify lung function. This study hypothesized that the change in age-related dietary intake affects lung function. The subjects who undertook a dietary assessment and spirometry in 2012 and 2017, were retrospectively collected in a health screening center. Dietary intakes were directly evaluated using food frequency questionnaires (FFQ) administered by trained dietitians and were compared at the baseline (2012) and 5-year follow-up (2017). A forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) value below 0.70 was defined as airflow limitation. Logistic regression models were used to estimate the odds ratio (ORs) adjusted for potential confounders. A total of 1439 subjects with normal spirometry were enrolled. New airflow limitations were detected in 48 subjects (3.3%) at the 5-year follow-up, including 41 (85.4%) men and 11 (22.9%) current smokers. After adjusting for age, sex, smoking history, and baseline FEV1/FVC, the odd ratios (OR) for new airflow limitation in fiber, vitamin C, and folic acid per 10% decrease in daily recommended requirement were 2.714 (95% confidence interval (CI), 1.538–4.807; p = 0.001), 1.083 (95% CI: 1.020–1.149; p = 0.007), and 1.495 (95% CI: 1.172–1.913; p = 0.001), respectively. A decreased intake of dietary fiber, vitamin C, and folic acid is associated with a newly developed airflow limitation.

scholarly journals Evidencia de Tiotropio en asma.

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Stephanie Veronica Yagua Velasquez ◽  
Luis Diego Solano Vega
Keyword(s):  
Asthma Management ◽  
Good Control ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
High Quality ◽  
Obstructive Pulmonary Disease ◽  
Significant Difference ◽  
Gina Guidelines ◽  
Long Acting ◽  
Anticholinergic Bronchodilator

Asthma is a chronic disease with a significant disease burden and many patients fail to control the disease despite recommended medical therapy.19 The long-term goals of asthma management include achieving good control of symptoms, minimizing risk asthma exacerbations, reduce hospitalizations, use of rescue medication, airflow limitation and side effects, as well as allow normal levels of activity.29 According to the Global Initiative for Asthma (GINA) guidelines , asthma management is based on a cornerstone of inhaled corticosteroid therapy (ICS), supplemented with complementary therapies for those with poor or deteriorating disease control.1 Tiotropium, a long-acting anticholinergic bronchodilator that is administered once a day, it is indicated for the treatment of chronic obstructive pulmonary disease (COPD) for more than a decade and has recently been approved in several countries for the treatment of asthma.18 In this review, we summarized the significant effect of tiotropium for the treatment of moderate-to-severe asthma, mainly in increasing morning PEF, evening PEF, peak FEV and trough FEV based on high-quality RCTs. Nevertheless, no significant difference in peak FVC, trough FVC, AE and serious AE was found between the 2 groups. A close comparison of the 2 groups revealed that more high-quality larger-sample RCTs are needed to gather more strong evidence on the therapeutic efficacy and safety of tiotropium for clinical practice.

scholarly journals Comparison of Intramuscular Betamethasone and Oral Pprednisone in the Prevention of Relapse of Acute Asthma

2001 ◽  
Vol 8 (3) ◽  
pp. 147-152 ◽  
Author(s):  
John S Chan ◽  
Robert L Cowie ◽  
Gerald C Lazarenka ◽  
Cinde Little ◽  
Sandra Scott ◽  
...  
Keyword(s):  
Relapse Rate ◽  
Intramuscular Injection ◽  
Inhaled Corticosteroids ◽  
Acute Asthma ◽  
Oral Prednisone ◽  
Double Blind ◽  
Intention To Treat ◽  
Single Intramuscular Injection ◽  
Acute Exacerbations ◽  
Long Acting

OBJECTIVE: To compare the relapse rate after a single intramuscular injection of a long acting corticosteroid, betamethasone, with oral prednisone in patients discharged from the emergency department (ED) for acute exacerbations of asthma.PATIENTS AND METHODS: Patients with acute exacerbations of asthma who were suitable for discharge from the ED were enrolled in a double-blind, randomized, placebo controlled pilot study. At discharge, patients were randomly assigned to receive either intramuscular betamethasone 12 mg and placebo capsules, or a placebo intramuscular injection and prednisone 50 mg daily for seven days. At days 7 and 21, patients were contacted by telephone to determine relapse. Relapse was defined as an unscheduled visit to a physician for treatment of continuing or worsening symptoms of asthma.RESULTS: One hundred and seventy-one patients were enrolled, of whom 87 were randomly assigned to the betamethasone group and 84 to the prednisone group. Baseline char- acteristics were matched evenly between the groups, with the exception of asthma duration (15.5 versus 21.2 years, respectively) and use of inhaled corticosteroids (46% versus 64.3% respectively) (P<0.05). Using intention-to-treat analysis, the relapse rates for betamethasone and prednisone at day 7 were 14.9% (13 of 87 patients) and 25% (21 of 84 patients), respectively (P=0.1), and at day 21, the rates were 36.8% (32 of 87 patients) and 31% (26 of 84 patients), respectively (P=0.4). There were no differences in symptom score, peak flows and adverse effects between the two groups at days 7 and 21.CONCLUSIONS: A single dose of intramuscular betamethasone 12 mg was safe and as efficacious as prednisone in preventing the relapse of acute asthma. There was a trend toward a reduced relapse rate at seven days. In select ED patients discharged for acute asthma, intramuscular betamethasone may be an effective alternative to prednisone.

scholarly journals Impact of long-term treatment with inhaled corticosteroids and bronchodilators on lung function in a patient with post-infectious bronchiolitis obliterans

2016 ◽  
Vol 42 (3) ◽  
pp. 228-231 ◽  
Author(s):  
Cecilia Calabrese ◽  
Nadia Corcione ◽  
Gaetano Rea ◽  
Francesco Stefanelli ◽  
Ilernando Meoli ◽  
...  
Keyword(s):  
Lung Function ◽  
Bronchiolitis Obliterans ◽  
Airflow Limitation ◽  
Term Therapy ◽  
Small Airways ◽  
Close Monitoring ◽  
Long Term Treatment ◽  
Long Acting ◽  
Post Infectious

ABSTRACT Post-infectious bronchiolitis obliterans (PIBO) is a small airways disease characterized by fixed airflow limitation. Therefore, inhaled bronchodilators and corticosteroids are not recommended as maintenance therapy options. The management of PIBO currently consists only of close monitoring of affected patients, aimed at the prevention and early treatment of pulmonary infections. In recent years, there has been an increase in the incidence of PIBO in the pediatric population. Patients with PIBO are characterized by a progressive decline in lung function, accompanied by a decrease in overall functional capacity. Here, we report the case of a relatively young man diagnosed with PIBO and followed for three years. After short- and long-term therapy with an inhaled corticosteroid/long-acting 2 agonist combination, together with an inhaled long-acting antimuscarinic, the patient showed relevant improvement of airway obstruction that had been irreversible at the time of the bronchodilator test. The lung function of the patient worsened when he interrupted the triple inhaled therapy. In addition, a 3-week pulmonary rehabilitation program markedly improved his physical performance.

scholarly journals Asthma is not a common cause of severe chronic respiratory failure in non-smokers: ALOT study

2005 ◽  
Vol 63 (2) ◽  
Author(s):  
G. Caramori ◽  
M. Fabbri ◽  
D. Paioli ◽  
F. Falcone ◽  
C. Severino ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Oxygen Therapy ◽  
Chronic Respiratory Failure ◽  
Airflow Limitation ◽  
Smoking History ◽  
Chronic Lung Diseases ◽  
Arterial Blood ◽  
History Of ◽  
Long Term Oxygen Therapy

Background. Little is known about the long-term natural history of asthma and the long-term clinical and functional consequences in non-smoking patients. From a functional point of view, non-smoking asthmatic patients may have a significantly greater decline in forced expiratory volume in one second (FEV1) compared with nonasthmatic subjects and may develop chronic irreversible (fixed) airflow limitation. This has been related to the physiological consequences of chronic airway inflammation causing airway remodeling. However these lesions are all potentially reversible and there is little radiological evidence indicating lung destruction (pulmonary emphysema), which is potentially irreversible, in non-smoking asthmatics. Severe chronic respiratory failure is the major cause of mortality in patients with severe chronic lung diseases. Domiciliary long-term oxygen therapy (LTOT) is an accepted treatment for patients with severe chronic respiratory failure. Our reasoning, therefore, was that if asthma is a cause of severe chronic respiratory failure in nonsmokers we should be able to find non-smoking asthmatics within a large population of patients on LTOT. The aim of our study (Asthma and Long-term Oxygen Therapy, “ALOT”) was to investigate the prevalence of non-smoking asthmatics in patients on LTOT in a multicentre, cross-sectional study. Methods. Between June and September 2003 we screened all subjects on long-term domiciliary oxygen therapy in three different hospitals in the North-East area of Italy (within the provinces of Ferrara and Bologna). Taken collectively, we have found one-hundred and eighty-four patients on LTOT. We have reviewed their clinical data (age, sex, smoking, history and physical examination, arterial blood gas analysis, pulmonary function). Results. 114 patients (all smokers) fulfilled the diagnostic criteria for COPD. Seventy patients (all smokers) had other diseases. We were unable to find any non-smokers in our screened population of subjects on long-term domiciliary oxygen therapy. Furthermore, there was no past history of asthma and/or acute wheezing episodes in either of the patient groups. Conclusions. This data suggests that asthma is an uncommon cause of severe chronic respiratory failure necessitating long-term domiciliary oxygen therapy in nonsmokers and supports the current consensus that asthma and COPD are different diseases with differing stages of severity and the concept that long-term avoidance of active smoking is fundamental for the prevention of severe chronic respiratory failure.

A Double Blind Trial of Lithium Carbonate and Haloperidol in Huntington's Chorea

1975 ◽  
Vol 9 (2) ◽  
pp. 115-118 ◽  
Author(s):  
D. P. Leonard ◽  
M. A. Kidson ◽  
J. G. E. Brown ◽  
P. J. Shannon ◽  
S. Taryan
Keyword(s):  
Family History ◽  
Crossover Trial ◽  
Lithium Carbonate ◽  
Double Blind Trial ◽  
Huntington's Chorea ◽  
Double Blind ◽  
Psychological Variables ◽  
Blind Trial ◽  
History Of ◽  
Depression Ratings

Six patients with a family history of Huntington's chorea (HC) participated in a double blind crossover trial involving four treatments— lithium carbonate, haloperidol, lithium carbonate and haloperidol, and placebo. Each treatment was administered for three weeks and, at the end of each treatmeat period, assessments were made of chorea and a rumber of psychological variables. None of the treatments significantly affected chorea measurements. With regard to the psychclog.cal variables, the levels of irritability, the frequency of angry outbursts and depression did appear to be affected in some patients by the treatment. Three patients improved on a combination of lithium carbonate and haloperidol while the remaining three did not. Haloperidol alone significantly raised depression ratings above levels for other treatments including placebo. It is suggested that lithium carbonate and haloperidol together should be seriously considered in the treatment of HC when patients are excessively irritable and impulsive.

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