tiotropium-bromide and Respiratory-Tract-Infections

Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing.. This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland. Children aged 6 to 35 months with 2 to 4 physician-confirmed episodes of wheeze and/or shortness of breath were considered eligible. Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 27), twice-daily fluticasone propionate 125 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 25), or as-needed albuterol sulfate 0.2 mg alone (n = 28). The primary outcome was efficacy, assessed as intention-to-treat by comparing the proportion of episode-free days (the days lacking symptoms or treatments) between the treatment groups.. The proportion of episode-free days was higher in those receiving intermittent tiotropium bromide (median 97% [interquartile range, 93% to 99%]) than in those receiving intermittent fluticasone propionate (87% [78% to 93%], P = .002), or with as-needed albuterol sulfate alone (88% [79% to 95%], P = .003). Adjustment with allergic sensitization, the baseline number of physician-confirmed episodes of wheeze and/or shortness of breath, or short-course glucocorticoid treatment in the 2 weeks before the enrollment, did not affect the result. Intervention-related adverse events were not seen.. Intermittent tiotropium bromide treatment may be an effective alternative to current therapies for episodic wheezing. Before implementation of use, further research on safety and efficacy is indicated.

Topics: Albuterol; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Dyspnea; Fluticasone; Humans; Respiratory Sounds; Respiratory Tract Infections; Tiotropium Bromide; Treatment Outcome

Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI).. This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µg maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for ≤7 days. Patients received standard care for AECOPD and RTI. Due to under-recruitment, the trial ended early and hence was underpowered to detect treatment differences. Data were pooled and exacerbation recovery patterns examined by using the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT), forced expiratory volume in 1 second, rescue medication use, COPD Assessment Test™, Functional Assessment of Chronic Illness Therapy-Short Form, and Work Productivity and Activity Impairment Questionnaire: Respiratory Symptoms.. Of 140 patients, 73.6% had a prior COPD diagnosis without maintenance therapy; 80.0% had moderate-to-severe airflow obstruction. In addition to study drug, 40.0% were prescribed pharmacologic therapy (corticosteroids [34.3%], antibiotics [16.4%], and short-acting β. A substantial portion of newly diagnosed or maintenance treatment-naïve patients with COPD experience relapse or persistent symptoms following a clinic visit for AECOPD with symptoms of RTI. Whether initiating maintenance therapy could improve outcomes and reduce exacerbation risk requires further study.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Early Termination of Clinical Trials; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Respiratory Tract Infections; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Tiotropium Bromide; Treatment Outcome; United States; Work Capacity Evaluation

The use of long-acting bronchodilators is an essential component of the management of chronic obstructive pulmonary disease (COPD). The GOLDEN 5 Phase III, randomized, active-controlled, open-label study was conducted to evaluate the long-term safety and tolerability of a nebulized glycopyrrolate formulation (SUN-101) delivered via the investigational eFlow. Subjects were randomized in a 4:3 ratio to nebulized glycopyrrolate 50 μg twice daily (BID) or tiotropium 18 μg once daily (OD) and treated for 48 weeks. Subjects represented the general COPD population with real-world characteristics including severe disease, presence of comorbidities, and receiving background COPD therapy. Primary endpoints were the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Secondary endpoints included the number of subjects with major adverse cardiovascular events (MACE); change from baseline in trough forced expiratory volume in 1 s (FEV. 1086 subjects received at least one dose of study drug. The overall incidence of TEAEs was comparable for subjects treated with glycopyrrolate (69.4%) or tiotropium (67.0%). Serious TEAEs occurred at similar rates in both treatment groups (glycopyrrolate, 12.3%; tiotropium, 10.5%). The most frequent TEAEs were COPD exacerbation/worsening and cough. Discontinuation due to TEAEs was higher in the glycopyrrolate group (10.0%) than the tiotropium group (2.8%) and related, in part, to the open-label study design, prior use of long-acting muscarinic antagonists and aerosol-airway interactions. Fewer subjects in the glycopyrrolate group experienced MACE (glycopyrrolate, n = 3 [0.5%]; tiotropium, n = 8 [1.7%]). Nebulized glycopyrrolate treatment resulted in improvements in trough FEV. Treatment with nebulized glycopyrrolate was well tolerated over 48 weeks with the most common adverse events being COPD worsening and cough. The overall and cardiac safety and tolerability profile and improvements in pulmonary function and patient-reported health outcomes support the use of nebulized glycopyrrolate as a maintenance treatment for moderate-to-very-severe COPD.. NCT02276222.

Topics: Administration, Inhalation; Aged; Bronchodilator Agents; Cough; Female; Forced Expiratory Volume; Gastrointestinal Diseases; Glycopyrrolate; Headache; Humans; Male; Middle Aged; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Severity of Illness Index; Tiotropium Bromide; Vital Capacity

Patients with postinfectious bronchiolitis obliterans (PIBO) usually have severe airflow obstruction and respond poorly to β-adrenergic drugs. However, the bronchodilator response to an anticholinergic agent such as tiotropium bromide is not known. We studied the acute bronchodilator response to tiotropium for up to 24 h in children with PIBO using spirometric and plethysmographic criteria.. A randomized, double-blind, placebo-controlled, crossover, prospective study was performed in patients with stable PIBO, 6 to 16 years of age. Standard spirometry and plethysmography were performed before and at 30, 60, 120, and 180 min and 24 h after inhalation of 18 μg of tiotropium or a placebo. After 7 to 14 days, the drugs were inverted, and the procedures were repeated. The changes in lung function parameters at each time point were compared with the baseline by analysis of variance and Tukey posttest, and the differences in all time points assessments vs baseline in tiotropium vs placebo groups were compared using the Friedman test.. A total of 30 patients were enrolled in the study (23 boys, seven girls; aged 10.9 ± 2.8 years) with baseline lung function values (% predicted) of FVC, FEV1, FEV1/FVC, forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), total lung capacity (TLC), residual volume (RV), RV/TLC, airway resistance (Raw), and specific airway conductance (sGaw) of 75 ± 15, 48 ± 14, 59 ± 11, 22 ± 11, 120 ± 19, 281 ± 101, 49 ± 13, 250 ± 65, and 23 ± 9, respectively. Statistically significant differences were observed after tiotropium inhalation in the following parameters compared with baseline: FVC at 60, 120, and 180 min and 24 h; FEV1 at 30, 60, 120, and 180 min; FEV1/FVC at 60, 120, and 180 min; FEF25%-75% at 60, 120, and 180 min; RV at 30, 60, 120, and 180 min; TLC at 30, 120, and 180 min; RV/TLC at 30, 60, 120, and 180 min; Raw at 30, 60, 120, and 180 min and 24 h; and sGaw at 30, 60, 120, and 180 min and 24 h. For the placebo group, no significant differences were observed in any lung function parameters at any time. The differences in the main functional measurements between the tiotropium and placebo groups were statistically significant.. Tiotropium acutely decreased airway obstruction and air trapping for up to 24 h in children with PIBO.

Topics: Administration, Inhalation; Bronchiolitis Obliterans; Bronchoconstriction; Bronchodilator Agents; Child; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Plethysmography; Prospective Studies; Respiratory Function Tests; Respiratory Tract Infections; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Vital Capacity