Indacaterol once-daily is equally effective dosed in the evening or morning in COPD.

UNLABELLED: Indacaterol is a novel, inhaled, long-acting ß(2)-agonist providing 24-h bronchodilation with once-daily (o.d.) dosing in patients with COPD. In this double-blind, incomplete block crossover study, patients with moderate-to-severe COPD were randomised to receive three treatment cycles from: indacaterol 300 µg o.d. dosed PM or AM, salmeterol 50 µg twice daily or placebo, each for 14 days. Trough FEV(1) was measured 24 h after indacaterol, and 12 h after salmeterol. Ninety-six patients (mean age: 64 years; post-bronchodilator FEV(1) 57% predicted, FEV(1)/FVC 55%) were randomised; 83 completed. After 14 days, the difference vs. placebo in trough FEV(1) for PM indacaterol was 200 mL (p < 0.001 [primary analysis]) and for AM indacaterol was 200 mL (p < 0.001). Compared with salmeterol, trough FEV(1) for PM indacaterol was 110 mL higher (p < 0.001), and for AM indacaterol was 50 mL higher (p = NS). Over 14 days, vs. placebo, both PM and AM indacaterol improved the % of nights with no awakenings (by 11.9 and 8.1 points; p < 0.01); the % of days with no daytime symptoms (by 6.7 and 5.5 points; p < 0.05); and the % of days able to perform usual activities (by 6.7 and 7.8 points; p < 0.05). Indacaterol provided 24-h bronchodilation and improvement in symptoms regardless of whether taken regularly in the morning or evening. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00615030.

Sustained 24-h efficacy of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients.

NVA237 is a once-daily inhaled long-acting muscarinic antagonist in development for the treatment of COPD. This randomized, double-blind, placebo-controlled, four-period, incomplete block crossover study, with open-label active comparator (tiotropium), assessed the efficacy and safety of NVA237. Patients (>or=40 years; smoking history >or=10 pack-years) with stable moderate-to-severe COPD (post-bronchodilator FEV(1) >or= 30% and <80% predicted, FEV(1)/FVC < 0.7) received NVA237 12.5, 25, 50 or 100 microg, placebo, or tiotropium 18 microg once-daily for 7 days. The primary endpoint was mean trough (23-24 h post-dose) FEV(1) on Day 7. Secondary endpoints included mean trough FEV(1) on Day 1, and FEV(1) and FVC at individual time points post-dose on Days 1 and 7. 83 patients (mean age 64.4 years; male 83.1%; mean COPD duration 6.7 years; mean post-bronchodilator FEV(1) 1.5 L/52.7% predicted) were randomized; 78 completed. Mean trough FEV(1) on Day 7 and Day 1 was significantly higher with all active treatments versus placebo (p < 0.05). NVA237 50 microg, 100 microg and tiotropium showed clinically relevant improvements versus placebo on Day 7 (differences of 131, 142 and 127 mL, respectively; p < 0.0001) and 1 (differences of 121, 135 and 112 mL, respectively; p < 0.0001). On Day 1, but not Day 7, FEV(1) was significantly higher (p < 0.05) with NVA237 50 and 100 microg versus tiotropium from 5 min up to 2 and 4 h post-dose, respectively. All doses of NVA237 and tiotropium were well tolerated. NVA237 once-daily was effective and well tolerated versus placebo, and demonstrated rapid and sustained 24-h bronchodilation. (ClinicalTrials.gov Identifier: NCT00501852).

Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients.

NVA237 is a novel once-daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and bronchodilator efficacy of two doses of NVA237 (100 and 200 microg), versus placebo, in patients with moderate-to-severe COPD (forced expiratory volume in 1s [FEV(1)]>or=30% and <80% predicted and FEV(1)/forced vital capacity [FVC]<0.7, 30 min after inhalation of 80 microg ipratropium bromide). After appropriate washout periods, patients were randomized to treatment with NVA237 100 microg (n=92), NVA237 200 microg (n=98) or placebo (n=91) for 28 days. The primary objective was evaluation of safety, with efficacy measures included as secondary objectives. NVA237 was generally well tolerated and associated with a frequency and distribution of adverse events similar to placebo. Serious adverse events were uncommon and there was no evidence of adverse cardiovascular effects or unexpected events. Trough FEV(1) was significantly higher in those receiving NVA237 compared with placebo. For NVA237 100 microg the differences were 131 and 161 mL on Days 1 and 28, respectively (p<0.05), and for NVA237 200 microg the differences were 146 and 151 mL on Days 1 and 28, respectively (p<0.05). Peak FEV(1), FEV(1) at all timepoints up to 24h after dosing, and FEV(1) area under the curve during 5 min-5 h post-dosing were also significantly higher in both NVA237 groups, compared with placebo. Patients receiving NVA237 required fewer daily puffs of rescue medication and had a higher percentage of days on which rescue medication was not required. Overall, the present study provides further evidence of the safety, tolerability and bronchodilator efficacy of once-daily treatment with NVA237 100 and 200 microg in patients with moderate-to-severe COPD.

Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD.

Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL). This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 microg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD. HRQoL was assessed using the St. George's Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated. The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9). Mean +/- SD baseline SGRQ total score was 47.4 +/- 18.1. Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029). Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 +/- 0.02 L vs 0.01 +/- 0.02 L; between-group difference: 0.10 +/- 0.03 L, p = 0.0001) and reduced exacerbations vs placebo. Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ.

The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation. OBJECTIVE AND METHODS: To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 mug once daily or placebo for 12 weeks. RESULTS: Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 +/- 0.08 liters) and 84 (0.20 +/- 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 +/- 0.07 liters) and 84 (0.15 +/- 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 +/- 12 (day 42) and 36 +/- 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George's Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living. CONCLUSION: Tiotropium 18 mug once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.

[Asthma in the elderly]. / L'asthme du sujet âgé.

INTRODUCTION: Asthma in the elderly is a growing clinical problem. It affects 6 to 7% of this age-group, but making the distinction between asthma and chronic obstructive pulmonary disease is more difficult as patients get older. STATE OF THE ART: This difficulty is due to a number of factors: the confounding role of smoking, and also the physiological effects of ageing on the airways which renders airway obstruction more resistant to bronchodilation. Elderly asthmatics can be divided on clinical grounds into two arbitrary groups: "ageing asthmatics" who have had asthma since childhood or adolescence and "late-onset asthmatics" who may present following an infective episode. Certain features of asthma in the elderly include: poor perception of breathlessness, technical difficulties in making reliable pulmonary function measurements and the extrapulmonary manifestations (impact on quality of life). PERSPECTIVES: The therapeutic strategy is much the same as for younger asthmatics but certain aspects take on greater importance: concerns about osteoporosis with long-term corticosteroid therapy (both oral and inhaled), the risk of arrhythmias with beta-2 adrenergic drugs and the significant side-effects of theophylline justifies, in difficult cases, consideration of anticholinergic and/or anti-leukotriene therapy. CONCLUSION: Most importantly, for elderly asthmatics it is a treatment regimen that is as simple as possible and is backed up by a written self-management plan that will improve outcomes.

[Asthma in the elderly]. / L'asthme du sujet âgé

INTRODUCTION: Asthma in the elderly is a growing clinical problem. It affects 6 to 7% of this age-group, but making the distinction between asthma and chronic obstructive pulmonary disease is more difficult as patients get older. STATE OF THE ART: This difficulty is due to a number of factors: the confounding role of smoking, and also the physiological effects of ageing on the airways which renders airway obstruction more resistant to bronchodilation. Elderly asthmatics can be divided on clinical grounds into two arbitrary groups: "ageing asthmatics" who have had asthma since childhood or adolescence and "late-onset asthmatics" who may present following an infective episode. Certain features of asthma in the elderly include: poor perception of breathlessness, technical difficulties in making reliable pulmonary function measurements and the extra-pulmonary manifestations (impact on quality of life). PERSPECTIVES: The therapeutic strategy is much the same as for younger asthmatics but certain aspects take on greater importance: concerns about osteoporosis with long-term corticosteroid therapy (both oral and inhaled), the risk of arrhythmias with beta-2 adrenergic drugs and the significant side-effects of theophylline justifies, in difficult cases, consideration of anti-cholinergic and/or anti-leukotriene therapy. CONCLUSION: Most importantly, for elderly asthmatics it is a treatment regimen that is as simple as possible and is backed up by a written self-management plan that will improve outcomes.

Morphological changes induced by extensive endobronchial electrocautery.

Due to recent improvements of safety conditions for therapeutic devices, electrocautery is being considered with renewed interest in the field of therapeutic bronchoscopy. The efficiency of this technique for destructing intraluminal tumours is well documented and makes it an attractive alternative to Yttrium aluminium garnet (YAG) laser photo-coagulation. Little is known, however, about the morphologic changes induced by electrocautery within the bronchial wall structures. This information is, however, important since electrocautery has been proposed as an alternative to other techniques to treat superficial tumours of the bronchial wall. Soft coagulation, with autostop, using two different power setting (40 and 120 W), produced by a new generation of high frequency voltage regulated generators was applied circumferentially to the trachea or left main bronchus, in a series of 52 piglets. Early (48 h) and late effects (6 weeks) were assessed through gross examination (bronchoscopy and autopsy) and light microscopy. Early effects of electrocautery included coagulation necrosis of the mucosa only and intense acute inflammation extending deep into the bronchial structure. The inflammatory phase progressively resolved while extensive transmural fibrosis and deterioration of the cartilage plates developed. The nature and extent of these lesions did not depend upon the energy delivered (40 W versus 120 W). Retractile scar formation and loss of cartilaginous support then produced iatrogenic secondary stenoses. These results do not question the use of electrocautery to palliate endoluminal tumours but should make operators careful when treating extensive infiltration of the bronchial wall.

Multidisciplinary approach to management of postintubation tracheal stenoses.

The optimal management of postintubation tracheal stenosis is not well defined. A therapeutic algorithm was designed by thoracic surgeons, ear, nose and throat (ENT) surgeons, anaesthetists and pulmonologists. Rigid bronchoscopy with neodymium-yttrium aluminium garnet (Nd-YAG) laser resection or stent implantation (removable stent) was proposed as first-line treatment, depending on the type of stenosis (web-like versus complex stenosis). In patients with web-like stenoses, sleeve resection was proposed when laser treatment (up to three sessions) failed. In patients with complex stenoses, operability was assessed 6 months after stent implantation. If the patient was judged operable, the stent was removed and the patient underwent surgery if the stenosis recurred. This algorithm was validated prospectively in a series of 32 consecutive patients. Three patients died from severe coexistent illness shortly after the first bronchoscopy. Of the 15 patients with web-like stenosis, laser resection was curative in 10 (66%). Among the 17 patients with complex stenoses, three remained symptom-free after stent removal. Bronchoscopy alone was thus curative in more than one-third of the patients. Six patients underwent surgery, two after failure of laser resection and four after failure of temporary stenting. Surgery was always performed with the patient in good operative condition. Palliative stenting was the definitive treatment in nine cases. Tracheostomy was the definitive solution in two cases. This approach, including an initial conservative treatment, depending on the type of the stenosis, appears to be applicable to almost all patients and allows secondary surgery to be performed with the patient in good condition.

[Post-intubation tracheal stenosis]. / Sténoses trachéales post-intubation.

Post intubation tracheal stenosis (STPI) is a rare but serious complication of tracheal intubation and/or tracheotomy. The epidemiology has changed over the last twenty years. The diagnosis is sometimes difficult to establish on clinical grounds alone. Flexible bronchoscopy is often necessary to confirm the diagnosis and to influence treatment. The ideal curative treatment is surgical resection of the stenosis with end-to-end tracheal anastomosis. In patients presenting with definitive or transitory contraindications to this treatment there is a place for interventional endoscopy. Rigid bronchoscopy enables mechanical dilatation of the STPI which can be associated with Nd-Yag laser ortracheal endoprostheses. In certain cases interventional bronchoscopy may be curative. However in all cases the management of such lesions remains multi-disciplinary involving pulmonologists, thoracic surgeons, otolaryngologists and anaesthetists.