Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.     

A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.     

Physiological changes during symptom recovery from moderate exacerbations of COPD.

Acute exacerbations of chronic obstructive disease (AECOPD) are characterised by worsening dyspnoea that is variably prolonged. In this study, physiological changes during moderate AECOPD were examined and the factors associated with dyspnoea resolution over time were determined. In total, 20 patients experiencing an AECOPD were evaluated within 72 h of initial worsening of symptoms (day 0) with pulmonary function testing, metabolic testing and symptom assessment using the dyspnoea domain of the Chronic Respiratory Disease Questionnaire (CRQ). Treatment was optimised and testing was repeated after 7, 14, 30 and 60 days. At day 0, patients were very short of breath (CRQ-dyspnoea mean+/-SEM 2.4+/-0.3) and showed significant airflow obstruction (forced expiratory volume in one second (FEV1) 41+/-3% predicted) and lung hyperinflation (forced residual capacity (FRC) 164+/-7% pred). By day 60 CRQ-dyspnoea improved to 4.6+/-0.5 (some shortness of breath); FRC and residual volume decreased by 5 and 11%, respectively; inspiratory capacity (IC) and slow vital capacity increased by 18 and 17%, respectively; and FEV1 increased by 18% with no change in FEV1/FVC. Total lung capacity did not change during AECOPD, and thus, changes in IC reliably reflected changes in end-expiratory lung volume. In conclusion, moderate acute exacerbation of chronic obstructive pulmonary disease is characterised by worsening airflow obstruction and lung hyperinflation. Improvement of dyspnoea following acute exacerbations of chronic obstructive pulmonary disease was associated with reduction in lung hyperinflation and consequent increase in expiratory flow rates.     

Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium.

Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in chronic obstructive pulmonary disease (COPD) patients. Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18 microg once daily (n=356) compared with ipratropium 40 microg q.i.d. (n=179). Screening forced expiratory volume in one second (FEV1) were 1.25+/-0.43 L (41.9+/-12.7% of the predicted value) (tiotropium) and 1.18+/-0.37 L (39.4+/-10.7% pred) (ipratropium). Trough FEV1 at 1 yr improved by 0.12+/-0.01 L with tiotropium and declined by 0.03+/-0.02 L with ipratropium (p<0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p<0.01). Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalization for a COPD exacerbation (p<0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments. Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.     

Improvements with tiotropium in COPD patients with concomitant asthma

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have different diagnostic criteria and treatment paradigms. Both are common and can occur in the same patient. We sought to determine the spirometric effects of tiotropium in COPD patients with concomitant asthma. METHODS: A 12-week randomized, double-blind, placebo-controlled, parallel group trial with tiotropium 18 mcg daily was performed. Patients continued usual respiratory medications except for inhaled anticholinergics. Inclusion criteria: Physician diagnosis of COPD and asthma, age >or= 40 years, smoking >10 pack years, post-bronchodilator forced expiratory volume in 1s (FEV(1))<80% predicted, FEV(1)/forced vital capacity (FVC)<70%, >or= 12%, and >or= 200 ml increase in FEV(1) following inhaled bronchodilator, treatment with inhaled steroids >or= 1 year. Spirometry was measured serially for 6h on days 1, 29 and 85. RESULTS: Four hundred and seventy-two patients were randomized. Baseline characteristics were balanced. Mean age=59.6 years, 61.4% were men, and FEV(1)=1.55l (53.0% predicted). Improvements at 12 weeks with tiotropium were observed for the primary endpoint FEV(1) area under the curve (AUC) from 0 to 6h (difference=186+/-24 ml, p<0.001) and for morning pre-dose FEV(1) (difference=98+/-23 ml, p<0.001). Significant differences in favor of tiotropium were observed for pre-dose FVC (difference=128+/-34 ml, p<0.001) and FVC AUC 0-6h (difference=232+/-35 ml, p<0.001). Compared to baseline, the mean weekly number of daily puffs of prn salbutamol was reduced by 0.05+/-0.12 puffs/day in the placebo group and by 0.50+/-0.12 puffs/day in the tiotropium group at week 12 (p<0.05). CONCLUSIONS: Patients with COPD and concomitant asthma achieve spirometric improvements with tiotropium along with symptomatic benefit as seen by reduced need for rescue medication.     

Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease.

Lung function in chronic obstructive pulmonary disease (COPD) can be improved acutely by oral corticosteroids and bronchodilators. Whether clinical improvement can be maintained by subsequent inhaled therapy is unknown. COPD patients (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1) 36% predicted) initially received formoterol (9 microg b.i.d.) and oral prednisolone (30 mg o.d.) for 2 weeks. After this time, patients were randomised to b.i.d. inhaled budesonide/formoterol 320/9 microg, budesonide 400 microg, formoterol 9 microg or placebo for 12 months. Postmedication FEV1 improved by 0.21 L and health-related quality of life using the St George's Respiratory Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving budesonide/formoterol withdrew from the study than those receiving budesonide, formoterol or placebo. Budesonide/formoterol patients had a prolonged time to first exacerbation (254 versus 96 days) and maintained higher FEV1 (99% versus 87% of baseline), both primary variables versus placebo. They had fewer exacerbations (1.38 versus 1.80 exacerbations per patient per year), had higher prebronchodilator peak expiratory flow, and showed clinically relevant improvements in SGRQ versus placebo (-7.5 units). Budesonide/formoterol was more effective than either monocomponent in both primary variables. Budesonide/formoterol in a single inhaler (Symbicort) maintains the benefit of treatment optimisation, stabilising lung function and delaying exacerbations more effectively than either component drug alone or placebo.     

Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma

This double-blind, placebo-controlled, randomized, parallel-group, multicenter study was conducted in 302 children aged 6-11 years with asthma not optimally treated with inhaled corticosteroids alone. Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo, formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered via Turbuhaler). Terbutaline was available as reliever medication. The primary efficacy variable was change from baseline in morning peak expiratory flow (PEF); secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)), serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF and FEV(1) were also significantly increased compared with placebo, with no statistically significant difference between formoterol doses. Lung-function improvements compared with placebo were greater in the middle of the day. Twelve-hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39 l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in the formoterol 4.5-microg group. The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group, indicating that formoterol may have the potential to improve exacerbation control in children. Both formoterol doses were well-tolerated, and tolerance to the drug's bronchodilator effect was not observed. Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone.     

Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD.

AIMS: Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted). METHODS: In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1). RESULTS: Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar. CONCLUSION: Compared with placebo, tiotropium improved lung function in patients with mild COPD.     

Addition of inhaled salmeterol to inhaled corticosteroids in patients with poorly controlled nocturnal asthma

The effect of adding inhaled salmeterol to inhaled corticosteroids was studied in patients with poorly controlled nocturnal asthma. In a double-blind, cross-over study, 20 patients were randomized to receive either salmeterol 50 micrograms twice daily or placebo via a Diskhaler after a 1-week run-in period. After 4 weeks of treatment, patients were subsequently crossed over to receive the other treatment for a further 4 weeks with a 2-week wash-out period in between. The response to treatment was assessed by peak expiratory flow rates (PEF) measured in the morning and evening, symptom scores of asthma, number of bronchodilators used, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at regular intervals. Patients' preference for the Diskhaler or metered-dose inhaler was assessed at the last visit. The results showed that morning PEF was significantly higher while on salmeterol than on placebo (296.9 +/- 70.2 vs 274.6 +/- 77.4 L/min). Evening PEF showed a trend towards a higher value while on salmeterol than on placebo (321.1 +/- 73.4 vs 288.7 +/- 79.4 L/min), but the difference was not significant. There was no statistically significant improvement in symptom scores, number of rescue bronchodilators used and FEV1 or FVC between the two treatment groups. The occurrence of side effects in terms of tremors and palpitations between treatment and placebo were similar. There were more patients who preferred Diskhaler to metered-dose inhaler (70% vs 30%). We conclude that salmeterol 50 micrograms twice daily produces significant improvement in morning PEF and is well tolerated in patients with nocturnal asthma. Diskhaler is a device which is easy to use and preferred to a metered-dose inhaler.     

Tiotropium improves FEV1 in patients with COPD irrespective of smoking status

This study evaluated whether the effect of tiotropium on the change in trough forced expiratory volume in 1s (FEV1), vs. placebo, is affected by smoking status. In a 3-month, double-blind study in 31 centres in Portugal, 311 (289 completed) patients were randomised to tiotropium 18 microg once daily or placebo. Baseline mean (standard deviation (SD)) FEV1 was 1.11 (0.39) l in the tiotropium group and 1.13 (0.39) l in the placebo group. Patients had an average smoking history of 55 (25.7) pack-years; 80 (26%) were smokers and 224 (74%) were ex-smokers. The primary end-point was change in morning pre-dose (i.e. trough) FEV1 after 12 weeks. Trough FEV1 at 12 weeks was significantly improved with tiotropium vs. placebo: the difference in means was 102 ml, P=0.0011, 95% confidence interval (CI) (41, 164). The difference in means in smokers was 138 ml, P=0.0105, CI (32, 244); in ex-smokers it was 66 ml, P=0.0375, CI (3, 129). The difference between smokers and ex-smokers was not statistically significant (P=0.6982) and may be due to greater variability and differences in disease severity. The significant improvement in lung function in patients treated with tiotropium vs. placebo in both smokers and ex-smokers suggests that tiotropium is an effective and well-tolerated therapy in chronic obstructive pulmonary disease (COPD), regardless of smoking status.     

Randomized comparison of ciclesonide 160 and 640 microg/day in severe asthma

OBJECTIVE: Demonstrating clinical benefit of higher doses of inhaled corticosteroids in asthma is frequently problematic owing to their relatively flat dose-response curve in this condition. In this study we compared the efficacy and safety of a fourfold difference in the dose of ciclesonide-ciclesonide 320 microg twice daily (CIC640) versus ciclesonide 160 microg once daily (CIC160)-in patients with severe persistent asthma. METHODS: Patients with bronchial asthma (6 months) were included in this randomized, double-blind study. After receiving fluticasone propionate 250 microg twice daily during run-in, patients were randomized to CIC160 (n=339) or CIC640 (n=341) for 12 weeks. Primary endpoints were time to first asthma exacerbation and forced expiratory volume in 1s (FEV(1)). Secondary endpoints included other lung function variables, asthma symptom scores and rescue medication use (RMU). RESULTS: Asthma exacerbations occurred in 12.7% of patients receiving CIC160 and 6.7% receiving CIC640. CIC640 was superior for time to first exacerbation (p=0.0050, one-sided). FEV(1) increased significantly with CIC160 and CIC640 (least squares mean+/-SE of mean: 269+/-31 and 332+/-31 mL, respectively; p<0.0001), with no significant difference between groups. Change in % predicted FEV(1) and morning peak expiratory flow (PEF) were significantly higher with CIC640 (p<0.05). Asthma symptom score sums and RMU decreased in both groups; CIC640 was statistically superior (p=0.0108 and 0.0005, respectively). No unexpected adverse events were reported in either group and the majority of the events reported were mild or moderate in intensity. No significant changes in serum cortisol were observed from the baseline to the study end. Small decreases in creatinine-adjusted 24h urine cortisol levels from baseline were seen in both the treatment groups, which, due to the large patient numbers, were statistically significant (p<0.05); however, no dose-response effect was seen and the difference between groups was not significant (p=0.7892). CONCLUSION: CIC640 was superior to CIC160 for time to first exacerbation, % predicted FEV1, morning PEF, asthma symptom score sum and RMU in patients with severe asthma; both doses had similar tolerability profiles and no significant changes in serum cortisol were seen in either treatment group.     

Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with worse health and increased healthcare utilisation. The Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE) study in COPD showed a 26% reduction in the yearly rate of exacerbations in patients treated with fluticasone propionate (FP) compared to placebo, but did not indicate which patients showed greatest benefit. In this study the patients were stratified into mild and moderate-to-severe COPD using the American Thoracic Society criterion of forced expiratory volume in one second (FEV1) 50% predicted, and the total number of exacerbations and those requiring treatment with oral corticosteroids were examined. There were 391 (195 FP) patients with mild COPD and 359 (180 FP) patients with moderate-to-severe disease. The exacerbation rate was highly skewed in mild disease, but more normally distributed in moderate-to-severe disease. FP reduced the overall exacerbation rate in moderate-to-severe disease (FP median rate 1.47 yr(-1), placebo 1.75 yr(-1)), but not in mild disease (FP 0.67 yr(-1), placebo 0.92 yr(-1)). FP use was associated with fewer patients with > or = 1 exacerbation x yr(-1) being treated with oral corticosteroids (mild: FP 8%, placebo 16%; moderate-to-severe: FP 17%, placebo 30%). Effects of fluticasone propionate on exacerbations were seen predominantly in patients with a postbronchodilator forced expiratory volume in one second <50% predicted. These data support recommendations in the Global Initiative for Chronic Obstructive Disease treatment guidelines that inhaled corticosteroids should be considered in patients with moderate-to-severe chronic obstructive pulmonary disease who experience recurrent exacerbations.     

Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD.

Chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations demonstrate increased stable-state airway inflammation. Tiotropium has been shown to reduce exacerbation frequency, but its effect on airway inflammation is unknown. The aim of the present study was to investigate the effect of tiotropium on sputum inflammatory markers and exacerbation frequency. Patients (n = 142) were randomised to receive tiotropium or placebo in addition to their usual medication for 1 yr. Sputum and serum cytokines were assayed by ELISA and exacerbation frequency calculated using a symptom-based diary. There was no difference in the area under the curve for sputum interleukin (IL)-6 or myeloperoxidase between the groups, but sputum IL-8 level was increased in the tiotropium arm. There was no difference between start and end of study in serum IL-6 or C-reactive protein level. Tiotropium was associated with a 52% reduction in exacerbation frequency (1.17 versus 2.46 exacerbations.yr(-1)). Of patients on tiotropium, 43% experienced at least one exacerbation, compared with 64% on placebo. The total number of exacerbation days was reduced compared with placebo (17.3 versus 34.5 days). Tiotropium reduces exacerbation frequency in chronic obstructive pulmonary disease, but this effect does not appear to be due to a reduction in airway or systemic inflammation.     

A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium

AZD9668 is a fully reversible, selective, oral inhibitor of neutrophil elastase, a protease implicated in chronic obstructive pulmonary disease (COPD). Efficacy, safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb trial (NCT00949975: approved by an Investigational Review Board), in patients with symptomatic COPD receiving maintenance tiotropium. The primary endpoint was pre-bronchodilator forced expiratory volume in 1 second (FEV?). Secondary endpoints included forced vital capacity and inspiratory capacity, peak expiratory flow, Breathlessness, Cough and Sputum Scale score, exercise capacity, quality of life (QoL), exacerbation assessments, safety and pharmacokinetics. Exploratory endpoints included inflammatory and tissue degradation biomarkers. A total of 838 patients were randomised to AZD9668 5 mg bid (212 patients), 20 mg bid (206 patients), 60 mg bid (202 patients) or placebo (218 patients). AZD9668 showed no effect on lung function, respiratory signs and symptoms, QoL or biomarkers. At end of treatment, the change in mean pre-bronchodilator FEV? for AZD9668 60 mg bid compared with placebo was 0.00L (95% confidence interval: -0.05, 0.04; p = 0.873). Overall, AZD9668 was well tolerated; the numbers of patients with adverse events (AEs), serious AEs and AEs leading to discontinuation were similar in each of the four study groups. AZD9668 60 mg bid showed no clinical benefit and no effect on biomarkers of inflammation or tissue degradation when added to tiotropium in patients with COPD. These results raise important questions for future investigation of anti-inflammatory and disease-modifying agents in patients with COPD.     

Pharmacodynamic steady state of tiotropium in patients with chronic obstructive pulmonary disease.

Tiotropium (Spiriva) is a new once-daily inhaled anticholinergic that has its effect through prolonged muscarinic (M)3 receptor antagonism. It has a clinically documented, long duration of action with once-daily dosing in chronic obstructive pulmonary disease (COPD). A single-centre, double-blind, ipratropium-controlled study was conducted in order to characterize the onset of pharmacodynamic steady state of tiotropium in patients with COPD. Thirty-one patients (25 male, six female) with a mean age of 62 yrs and a mean forced expiratory volume in one second (FEV1) of 1.13 L (38% of predicted) were randomly assigned to receive either tiotropium 18 microg once-daily from a dry-powder inhaler (HandiHaler, 20 patients), or ipratropium 40 microg four-times daily from a pressurized metered-dose inhaler (11 patients) for a period of 1 week. FEV1 and forced vital capacity (FVC) were measured 1 h prior to, and just before inhalation (mean value of the two measurements on test-day 1 was the baseline value, while on all other test days it was the trough value), and 0.5, 1, 2, 3, 4, 5, and 6 h after inhalation of the morning dose of the study drug (one capsule and two puffs) on days 1, 2, 3, and 8. Trough FEV1 following 8 days of tiotropium was 0.19 L (18%) above baseline. Approximately 90% of this increase was achieved within 24 h of the first dose (0.17 L, 16%). Trough FVC increased 0.67 L (27%) on test-day 8. Approximately 70% of the improvement was observed after two tiotropium doses (0.47 L, 19%). Achievement of FVC steady state was delayed compared to FEV1. Ipratropium performed typically with an onset of action within 30 min, a peak response between 1-2 h postdosing and a duration of action of approximately 4 h. It was concluded that forced expiratory volume in one second steady state with tiotropium is reached within 48 h, while continued improvements in forced vital capacity can be expected over or beyond the first week of therapy. The continued increases in forced vital capacity beyond 48 h suggests that maintenance bronchodilator therapy is required to achieve maximal changes in hyperinflation.     

Long-acting inhaled anticholinergic therapy improves sleeping oxygen saturation in COPD.

Oxygen desaturation occurs during sleep in severe chronic obstructive pulmonary disease (COPD), especially during rapid eye movement (REM) sleep, due to hypoventilation and ventilation-perfusion mismatching, but the possible contribution of airflow limitation is unclear. In a randomised, placebo-controlled, double-blind study of severe, stable COPD patients, the authors compared 4 weeks treatment with a long-acting inhaled anticholinergic agent (tiotropium), taken in the morning (tiotropium-AM), or in the evening (tiotropium-PM), on sleeping arterial oxygen saturation (Sa,O2) and sleep quality. Overnight polysomnography was performed at baseline and after 4 weeks treatment. A total of 95 patients with awake resting arterial oxygen tension < or = 9.98 kPa (75 mmHg) were randomised, with a mean age of 66.4 yrs and mean forced expiratory volume in one second (FEV1) of 32% predicted. A total of 80 patients completed the study, of which 56 fulfilled the polysomnographic criterion of at least 2 h sleep in both sleep study nights and represent the group analysed. Tiotropium significantly improved spirometry compared with placebo. Both tiotropium-AM and tiotropium-PM groups had higher Sa,O2 during REM than placebo (+2.41% and +2.42%, respectively, and both pooled and tiotropium-PM groups had higher Sa,O2 during total sleep time (+2.49% and +3.06%, respectively). End-of-treatment FEV1 correlated with Sa,O2 during REM sleep, however, tiotropium did not change sleep quality. Sustained anticholinergic blockade improves sleeping arterial oxygen saturation without affecting sleep quality.     

Inspiratory capacity and forced expiratory volume in the first second in exacerbation of chronic obstructive pulmonary disease

Object: Periodic exacerbations of symptoms are the major cause of morbidity, mortality and health care costs in patients with chronic obstructive pulmonary disease (COPD). Dyspnea is the major factor affecting the comfort of patients in the exacerbation of COPD. In this study, we aimed to compare the value of forced expiratory volume in the first second (FEV₁) and inspiratory capacity (IC) measured before and after treatment in exacerbations and in the improvement in dyspnea. Methods: Eighty‐seven patients (male/female, 80/7; mean age, 63 ± 7) with COPD exacerbation were included in this study. All subjects underwent spirometric tests on the first day and at the end of treatment. The subjects were asked to quantify the sensation of dyspnea that was described to them as a nonspecific discomfort associated with the act of breathing. The patients quantified dyspnea by pointing to a score on a large Borg scale from 0 to 10 arbitrary units. In the beginning and at the end of treatment, forced vital capacity (FVC), FEV₁, forced expiratory flow rate between 25% and 75% of FVC (FEF25–75), peak expiratory flow rate (PEF), IC and Borg score (BS) values were compared. Results: After treatment of COPD exacerbations, FEV₁, FEF25–75, PEF and IC significantly increased, and the BS significantly decreased compared to the initial values. The increase in IC was more significantly correlated with the improvement in BS compared with FEV₁. Admission and discharge day BS was negatively correlated with FEV₁, FEF25–75 and IC. Conclusion: We have shown a more dramatic improvement in IC compared with FEV₁ in patients treated as a result of acute exacerbation of COPD. These data suggest that IC may be more useful than FEV₁ during acute exacerbation of COPD. Moreover, IC better reflects the severity of dyspnea in these patients. Please cite this paper as: Yetkin O and Gunen H. Inspiratory capacity and forced expiratory volume in the first second in exacerbation of chronic obstructive pulmonary disease. The Clinical Respiratory Journal 2008; 2: 36–40.     

Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD.

This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD). A total of 71 COPD patients (mean forced expiratory volume in one second (FEV1) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 microg q.d., formoterol 12 microg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV1, forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety. Compared with baseline (FEV1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV1 (0-12 h) than formoterol (127 versus 86 mL), while average night-time FEV1 (12-24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81 puffs.day(-1), tiotropium 2.41 puffs x day(-1), formoterol 2.37 puffs x day(-1)). All treatments were well tolerated. In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.     

茚达特罗与噻托溴铵对强迫振荡技术测定慢阻肺患者呼吸力学参数的影响对比

目的评估并比较茚达特罗和噻托溴铵单药治疗对慢性阻塞性疾病(简称"慢阻肺")患者气流限制和呼吸阻抗的影响。方法选取2014年3月至2015年1月于我院诊断为慢阻肺患者78例(平均年龄为72.4岁,平均FEV1预计值为61.6%),随机分为两组,每组各39例,分别接受茚达特罗或噻托溴铵治疗。在药物治疗开始及治疗8周后,对患者进行肺功能测试、慢阻肺评估测试(CAT)和多频强迫振荡技术测试。在全呼吸、吸气和呼气阶段测定5 Hz和20 Hz振动频率时的粘性阻力(R_5和R-20),5 Hz时电抗(X——5)和共振频率(Fres)及低频电抗面积(ALX)。结果茚达特罗与噻托溴铵均可改善慢阻肺患者的气流受限情况,平均FEV1值分别提高170 m L和90 m L。患者接受茚达特罗药物治疗后CAT得分由11.2±4.3降为7.5±2.3,治疗前后具有显著性差异(P0.001)。与噻托溴铵相比,茚达特罗可明显改善患者的FEV1值,FEV1百分比预计值及CAT得分(P分别为0.042,0.008和0.027)。对于呼吸阻抗,两种药物在全呼吸、吸气和呼气阶段都可改变患者的R_5、X_5、Fres及ALX值。茚达特罗组R_5、R_5-R_20、X_5、Fres及ALX值的变化与FEV1变化显著相关。结论茚达特罗可显著改善慢阻肺患者的气流受限情况和症状。对于呼吸阻抗,茚达特罗和噻托溴铵两种支气管扩张药物改善强迫振荡技术参数的程度相似,均可用于慢阻肺患者的临床治疗。