Ventolin Diskus and Inspyril Turbuhaler: an in vitro comparison.

Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs), pulmonary deposition, and the biological effects depend on drug formulation and device and patient characteristics. The aim of this study was to measure, in vitro, the relationship between parameters of inhalation profiles recorded from patients, the TED and fine particle mass (FPM) of Diskus and Turbuhaler inhalers. Inhalation profiles (IPs) of 25 patients, a representative sample of a wide range of 1500 IPs generated by 10 stable asthmatics, 3 x 16 (mild/moderate/severe) COPD patients and 15 hospitalized patients with an exacerbation asthma or COPD, were selected for each device. These 25 IPs were input IPs for the Electronic Lung (a computerdriven inhalation simulator) to determine particle size distribution from Ventolin Diskus and Inspyril Turbuhaler. The TED and FPM of Diskus and FPM of Turbuhaler were affected by the peak inspiratory flow (PIF) and not by slope of the pressure-time curve, inhaled volume and inhalation time. This flow-dependency was more marked at lower flows (PIF < 40 L/min). Both the TED and FPM of Diskus were significantly higher as compared to those of the Turbuhaler [mean (SD) TED(_diskus) (%label claim) 83.5 (13.9) vs. TED(_turbuhaler) (72.5 (11.1) (p = 0.004), FPM(_diskus) (%label claim) 36.8 (9.8) vs FPM(_turbuhaler) (28.7 (7.7) (p < 0.05)]. The TED and FPM of Diskus and FPM of Turbuhaler were affected by PIF, the flow-dependency being greater at PIF values below 40 L/min. Lower PIFs occurred more often when using Turbuhaler than Diskus, since Turbuhaler have a higher resistivity, requires substantially higher pressure in order to generate the same flow as Diskus. TED, dose consistency and the FPM were higher for Diskus as compared to Turbuhaler. The flow dependency of TED and FPM was substantially influenced by inhalation profiles when not only profiles of the usual outpatient population were included but also the real outliers from exacerbated patients.

Asthma and chronic obstructive pulmonary disease: differences between workers with and without sick leave.

OBJECTIVE: Determinants of sick leave should be investigated before interventions to reduce sick leave can be designed. This cross-sectional study compares employees with asthma and chronic obstructive pulmonary disease (COPD) with and without sick leave. METHODS: One hundred and eighteen participants with asthma and 71 with COPD underwent a lung function test [one-second forced expiratory volume (FEV1), forced vital capacity (FVC)] and completed questionnaires on health complaints, work characteristics, demographic and psychosocial variables, and self-reported sick leave in the past 12 months. Backward multivariate logistic regression analyses, with sick leave (no/any) as dependent variable, were conducted for asthma, COPD, and the total group. RESULTS: Lung function measures were not significantly associated with sick leave in any group (P > 0.05). For asthma, psychosocial variables (spending all energy at work, OR 0.7) and health complaints (frequency of dyspnoea, OR 0.4 and breathing problems such as coughing, wheezing, OR 1.1) were associated with sick leave. In the COPD group, age (OR 0.9) was the only significant variable to be maintained in the model. In the total group, work characteristics (adjustment in work pace, OR 3.3), age (OR 0.9) and spending all energy at work (OR 0.7) were maintained in the final model. CONCLUSION: Severity of the disease, as measured by lung function, is not a determinant of sick leave in asthma and COPD. Different processes play a role in asthma and COPD. Interventions for reducing sick leave should aim more at psychosocial factors than at treating the severity of the disease.

Eccentric exercise training in patients with chronic obstructive pulmonary disease.

The oxygen cost of eccentric exercise is lower than that of concentric exercise at similar work-loads. In this study, the response to eccentric cycle exercise training (EET) in addition to general exercise training (GET) on exercise performance and quality of life was investigated in 24 patients with severe chronic obstructive pulmonary disease (COPD). All patients had a normal resting PaO2 and an arterial oxygen saturation (SaO2) below 90% at Wmax, achieved during a maximal incremental concentric cycle exercise test. The patients participated in a comprehensive inpatient pulmonary rehabilitation programme of 10 weeks. They were randomly assigned either to GET (GET group: mean FEV 38% predicted) or to GET and additional EET (GET/EET group: FEV1 45% predicted). During EET, the patients were able to cycle eccentrically for 15 min continuously at a mean of 160 (69%) of Wmax whereas the Borg dyspnoea score did not exceed 3.0 and SaO2 did not fall below 90%. Parameters of cardiocirculatory fitness and gas exchange improved in the GET/EET group but no further improvement in exercise capacity occurred compared to GET. It is concluded that eccentric cycle exercise is a safe and attractive training modality for patients with severe COPD and can be performed at a high intensity without the patient becoming out of breath or needing supplemental oxygen.

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients.

Medroxyprogesterone acetate (MPA) and acetazolamide (ACET) are two ventilatory stimulants which are used in hypoxic and hypercapnic patients with chronic obstructive pulmonary disease (COPD). In a double-blind randomised study, the effects of a 2-week treatment with MPA (30 mg b.i.d.) or ACET (250 mg b.i.d.), followed by a 2-week treatment with a combination of both drugs (MPA/ACET), on daytime and nocturnal ventilatory and blood gas parameters in 17 stable hypercapnic COPD patients were investigated. ACET, MPA and MPA/ACET treatment decreased mean daytime carbon dioxide tension in arterial blood by 0.4, 0.7 and 1.2 kPa, respectively. Minute ventilation was improved only with combined therapy, from 9.3 to 11.2 L x min(-1). With MPA/ACET therapy, the hypercapnic and hypoxic ventilatory responses significantly increased, from 3.7 to 5.8 L x min(-1) x kPa(-1) and from -0.13 to -0.40 L x min(-1) x %(-1), respectively. The mouth exclusion pressure response to hypoxia increased during combination therapy, from -0.01 to -0.03 kPa %(-1). Nocturnal end-tidal carbon dioxide tension decreased with MPA and MPA/ACET treatment, by 0.9 and 1.4 kPa, respectively. MPA/ACET significantly increased mean nocturnal arterial oxygen saturation values, from 85.5 to 90.2%. The authors conclude that short-term combined treatment with medroxyprogesterone acetate and acetazolamide has a more favourable effect on day and night-time blood gas values and chemical drive than single drug treatment.

Potential masking effect on dyspnoea perception by short- and long-acting beta2-agonists in asthma.

Asthma patients evaluate the effect of medication treatment through the degree of their asthma symptoms, which might be affected by their ability to perceive these symptoms. It has been suggested that beta2-agonists may mask the effects of an increase in airway inflammation. This study compared the perception of histamine-induced bronchoconstriction during monotherapy with short- or long-acting beta2-agonists. Asthmatic patients (68 male and 60 female, mean age 35+/-11 yrs, forced expiratory volume in one second (FEV1) 86+/-15% of the reference value, provocative concentration causing a 20% fall in FEV1 (PC20) geometric mean 0.97 mg x mL(-1) (95% confidence interval (CI): 0.73-1.30)) were selected and randomly allocated to use either a short-acting (salbutamol, n=41) or long-acting beta2-agonist (formoterol, n=46) or placebo (n=41) for 12 weeks. Perception of dyspnoea provoked by histamine-induced bronchoconstriction was measured at the start and every 4 weeks thereafter. Subjects quantified their sensation of breathlessness during the challenge tests on a modified Borg scale at the start of the study and every 4 weeks thereafter. The sensitivity to changes in FEV1 was analysed by the linear regression slope (alpha) Borg versus % fall in FEV1. The absolute perceptual magnitude (PS20) was determined by the perception score at the 20% fall in FEV1. Although the geometric mean PC20 decreased significantly within the group using short-acting beta2-agonists (in the group with initial PC20 > or = 2 mg x mL(-1) there was a drop from 5.26-1.94 mg x mL(-1); p=0.013), repeated measurement analysis showed no difference in the course of time of perception (both slope alpha and PS20) between the three medication groups. This study showed that chronic use of short- or long-acting beta2-agonists in asthmatics for a period of 12 weeks, did not significantly change the perception of histamine-induced bronchoconstriction compared with placebo. Further investigation is required to establish whether this suggests that these drugs do not mask a deterioration of asthma.