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Summary Background Few studies have assessed the safety and efficacy of potential asthma medications in children younger than 5 years. We descriptively assessed the safety and efficacy of tiotropium, a long-acting anticholinergic drug, in children aged 1–5 years with persistent asthmatic symptoms. Methods This exploratory 12-week, randomised, double-blind, placebo-controlled, parallel-group, phase 2/3, regulatory multicentre trial was done at 32 hospitals, clinics, and clinical research units in 11 countries in Asia, Europe, and North America. Children aged 1–5 years with at least a 6-month history of persistent asthmatic symptoms and a need for inhaled corticosteroids were eligible. Patients were randomly allocated using an interactive voice or web-based response system to receive once-daily tiotropium 2·5 μg, tiotropium 5 μg, or placebo as an add-on to inhaled corticosteroids with or without additional controller medication. Patients and investigators were masked to study group assignment. Tiotropium was given via the Respimat inhaler once daily as two puffs of 1·25 μg in the 2·5 μg group, two puffs of 2·5 μg in the 5 μg group, or two puffs of placebo. The primary outcomes were safety, which was assessed by comparing adverse events between the tiotropium and placebo groups, and efficacy, which was measured as the change in weekly mean combined daytime asthma symptom score from baseline to week 12. Statistical analyses of treatment effects were exploratory; although endpoints were defined, they were used for descriptive analyses only. The safety and primary analyses were done in all patients who received at least one dose of their assigned treatment. This study is registered with ClinicalTrials.gov ( NCT01634113 ), and is completed. Findings Between July 26, 2012, and Dec 4, 2014, 102 children were randomly assigned to the three treatment groups (36 to receive tiotropium 2·5 μg, 32 to receive tiotropium 5 μg, and 34 to receive placebo). 101 children completed the study and were included in the analyses. The changes in adjusted weekly mean combined daytime asthma symptom scores between baseline and week 12 were not significantly different between any of the groups. The adjusted mean difference between the tiotropium 2·5 μg group and placebo group was −0·080 (95% CI −0·312 to 0·152) and the difference between tiotropium 5 μg and placebo group was −0·048 (−0·292 to 0·195). Adverse events were less frequent with tiotropium treatment than with placebo (20 [56%] of 36 children with tiotropium 2·5 μg, 18 [58%] of 31 with tiotropium 5 μg, and 25 [74%] of 34 with placebo), although no formal statistical comparison between groups was performed. A greater proportion of children reported asthma exacerbations as adverse events in the placebo group (ten [29%] of 34) than in the tiotropium groups (five [14%] of 36 in the 2·5 μg group and two [6%] of 31 in the 5 μg group). Serious adverse events were reported in three patients (all of whom received placebo); no adverse events led to discontinuation of treatment or death. Interpretation To our knowledge, our small study is the first to assess the safety and efficacy of tiotropium in children aged 1–5 years with persistent asthmatic symptoms. Tolerability of tiotropium was similar to that of placebo, which is consistent with previous findings in older populations. Although mean daytime asthma symptom scores were not significantly different between groups, tiotropium showed the potential to reduce asthma exacerbation risk compared with placebo. The findings of the study are limited by the small sample size and descriptive statistical analyses. Additional well powered trials are needed to further assess the safety and efficacy of tiotropium in young children. Funding Boehringer Ingelheim. [ABSTRACT FROM AUTHOR]

Background Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma. Objective We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma. Methods In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. Results Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV 1 within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, −28 to 99; P = .27]), and the key secondary end point, trough FEV 1 (5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, −48 to 85; P = .59]). The safety and tolerability of tiotropium were comparable with those of placebo. Conclusions Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma. [ABSTRACT FROM AUTHOR]

Background The Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) are widely used in asthma research; however, in studies of newer asthma treatments, mean improvements in these measures compared with placebo arms do not exceed the minimal important difference (MID), particularly when a new treatment is added to current treatment. Objective We performed a systematic review and network meta-analysis to examine the magnitude of AQLQ and ACQ responses achieved with commonly used asthma drugs and factors influencing these end points in clinical trials. Methods A systematic literature search was conducted to identify blinded randomized controlled trials reporting AQLQ or ACQ results. Mixed treatment comparisons, combined with meta-regression, were then performed. Results Of the 64 randomized controlled trials (42,527 patients) identified, 54 included the AQLQ and 11 included the ACQ as end points. The presence of a run-in period, the nature of treatment during the run-in period, concurrent treatment during the treatment period, and instrument version significantly influenced the change in AQLQ score from baseline and whether it exceeded the MID. When compared with placebo, only inhaled corticosteroids (ICSs), with or without a long-acting β-agonist, achieved the MID. The ACQ results were comparable with those of the AQLQ: no differences from placebo exceeded the MID, and ICS-based treatments provided the greatest improvements. Conclusion The established within-patient MID for the ACQ and AQLQ is not achievable as a group-wise efficacy threshold between treatment arms in clinical studies in which controllers are added to ICS treatment. Thus in addition to reporting mean changes of the instruments, other measurement criteria should be considered, including responder analyses. [ABSTRACT FROM AUTHOR]

Summary Background In patients with severe asthma, tiotropium improves lung function and exacerbation risk when added to high-dose inhaled corticosteroids plus long-acting β 2 agonists. We aimed to assess the safety and efficacy of tiotropium in patients with moderate asthma who were symptomatic despite treatment with medium-dose inhaled corticosteroids. Methods We did two 24-week, replicate, randomised, double-blind, placebo-controlled, parallel-group, active-comparator trials at 233 sites in 14 countries. Eligible patients were aged 18–75 years with symptomatic asthma and a pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) of 60–90% predicted despite use of medium-dose inhaled corticosteroids, and had never smoked or were ex-smokers for 1 year or more with 10 pack-years or less. Patients were randomly assigned (1:1:1:1), with computer-generated pseudorandom numbers, to receive once-daily tiotropium 5 μg or 2·5 μg, twice-daily salmeterol 50 μg, or placebo, while maintaining inhaled corticosteroids. Patients and study investigators were masked to treatment allocation. Prespecified co-primary endpoints, assessed at week 24 in the full analysis set, were peak FEV 1 response, measured within the first 3 h after evening dosing; trough FEV 1 response; and responder rate assessed according to the seven-question Asthma Control Questionnaire (ACQ-7). These studies are registered with ClinicalTrials.gov , numbers NCT01172808 and NCT01172821 . Findings Between Aug 24, 2010, and Nov 13, 2012, we randomly assigned 2103 patients to the tiotropium 5 μg group (n=519), the tiotropium 2·5 μg group (n=520), the salmeterol group (n=541), or the placebo group (n=523); 1972 (94%) patients completed the study. Peak and trough FEV 1 responses were significantly greater with tiotropium and salmeterol than with placebo and were similar in both studies. With pooled data, difference versus placebo in peak FEV 1 was 185 mL (95% CI 146–223) in the tiotropium 5 μg group, 223 mL (185–262) in the tiotropium 2·5 μg group, and 196 mL (158–234) in the salmeterol group (all p<0·0001); difference in trough FEV 1 was 146 mL (95% CI 105–188), 180 mL (138–221), and 114 mL (73–155; all p<0·0001), respectively. There were more ACQ-7 responders in the tiotropium 5 μg (OR 1·32, 95% CI 1·02–1·71; p=0·035) and 2·5 μg (1·33, 1·03–1·72; p=0·031) groups, and the salmeterol group (1·46, 1·13–1·89; p=0·0039), than in the placebo group. 48 (2%) of 2100 patients had serious adverse events (tiotropium 5 μg n=11, tiotropium 2·5 μg n=12, salmeterol n=11, placebo n=14). Interpretation Once-daily tiotropium add-on to medium-dose inhaled corticosteroids reduces airflow obstruction and improves asthma control in patients with moderate symptomatic asthma. Patterns of response with both tiotropium doses were similar to those of salmeterol, and all active compounds had good safety and tolerability. Tiotropium is a safe and effective bronchodilator, and an alternative to salmeterol in this patient population. Funding Boehringer Ingelheim. [ABSTRACT FROM AUTHOR]

Background: To determine the safety and efficacy of BEA2180, an anticholinergic agent in patients with chronic obstructive pulmonary disease (COPD). Methods: Smokers or ex-smokers ≥40 years with COPD and a postbronchodilator forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≤70% participated in this multinational, randomised, double-blind, parallel study. Patients received BEA2180 (50, 100 or 200 µg), tiotropium (5 µg) or placebo once daily via Respimat® Soft Mist™. The primary endpoint was trough FEV1 after 24 weeks. Secondary endpoints included Transition Dyspnoea Index (TDI) focal score, St George's Respiratory Questionnaire (SGRQ) total score, exacerbations and adverse events. Results: Patients (n = 2080, 64.5% male) had a mean age of 64.2 years and a baseline FEV1 of 1.2 L. Trough FEV1 at 24 weeks with all BEA2180 doses (0.044-0.087 L) and tiotropium 5 µg (0.092 L) was significantly higher (p < 0.0001) than placebo (-0.034 L) and BEA2180 (200 µg) was noninferior to tiotropium. Mean TDI focal scores were higher with BEA2180 (1.43-1.48) or tiotropium (1.46) versus placebo (0.94; p ≤ 0.01 for all). Mean SGRQ total scores also improved with BEA2180 (40.1-40.7) or tiotropium (39.5) compared with placebo (43.0, p < 0.01 for all). COPD exacerbation rates were reduced for all active treatments, reaching statistical significance for BEA2180 (50 and 200 µg) (p < 0.05, for both). Conclusion: All study doses of BEA2180 improved lung function, reduced symptoms and exacerbations, and improved health status in COPD; all treatments were well tolerated. Clinical trial identifier: NCT00528996. [ABSTRACT FROM AUTHOR]

The article presents the authors' reply to comments on their study about bronchodilator reversibility and cardiac considerations with use of tiotropium.

The article focuses on the research study conducted to analyse the use of Tiotropium or salmeterol as an add-on therapy in case of patients suffering with moderate symptomatic asthma, and mentions that till date there are no anti-inflammatory effects of Tiotropium in human beings.