Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients.

The inhalation characteristics of patients when they use different dry powder inhalers.

BACKGROUND: The characteristics of each inhalation maneuver when patients use dry powder inhalers (DPIs) are important, because they control the quality of the emitted dose. METHODS: We have measured the inhalation profiles of asthmatic children [CHILD; n=16, mean forced expiratory volume in 1 sec (FEV1) 79% predicted], asthmatic adults (ADULT; n=53, mean predicted FEV1 72%), and chronic obstructive pulmonary disease (COPD; n=29, mean predicted FEV1 42%) patients when they inhaled through an Aerolizer, Diskus, Turbuhaler, and Easyhaler using their "real-life" DPI inhalation technique. These are low-, medium-, medium/high-, and high-resistance DPIs, respectively. The inhalation flow against time was recorded to provide the peak inhalation flow (PIF; in L/min), the maximum pressure change (ΔP; in kPa), acceleration rates (ACCEL; in kPa/sec), time to maximum inhalation, the length of each inhalation (in sec), and the inhalation volume (IV; in liters) of each inhalation maneuver. RESULTS: PIF, ΔP, and ACCEL values were consistent with the order of the inhaler's resistance. For each device, the inhalation characteristics were in the order ADULT>COPD>CHILD for PIF, ΔP, and ACCEL (p<0.001). The results showed a large variability in inhalation characteristics and demonstrate the advantages of ΔP and ACCEL rather than PIFs. Overall inhaled volumes were low, and only one patient achieved an IV >4 L and ΔP >4 kPa. CONCLUSION: The large variability of these inhalation characteristics and their range highlights that if inhalation profiles were used with compendial in vitro dose emission measurements, then the results would provide useful information about the dose patients inhale during routine use. The inhalation characteristics highlight that adults with asthma have greater inspiratory capacity than patients with COPD, whereas children with asthma have the lowest. The significance of the inhaled volume to empty doses from each device requires investigation.

Introducing the national COPD resources and outcomes project.

BACKGROUND: We report baseline data on the organisation of COPD care in UK NHS hospitals participating in the National COPD Resources and Outcomes Project (NCROP). METHODS: We undertook an initial survey of participating hospitals in 2007, looking at organisation and performance indicators in relation to general aspects of care, provision of non-invasive ventilation (NIV), pulmonary rehabilitation, early discharge schemes, and oxygen. We compare, where possible, against the national 2003 audit. RESULTS: 100 hospitals participated. These were typically larger sized Units. Many aspects of COPD care had improved since 2003. Areas for further improvement include organisation of acute care, staff training, end-of-life care, organisation of oxygen services and continuation of pulmonary rehabilitation. KEY POINTS: positive change occurs over time and repeated audit seems to deliver some improvement in services. It is necessary to assess interventions such as the Peer Review used in the NCROP to achieve more comprehensive and rapid change.

Determination of the relative bioavailability of salbutamol to the lungs following inhalation from dry powder inhaler formulations containing drug substance manufactured by supercritical fluids and micronization.

PURPOSE: The relative lung bioavailability of salbutamol sulfate particles produced using supercritical fluids (SEDS) and delivered by dry powder inhaler (DPI) was compared with the performance of a conventional micronized drug DPI using the same device design (Clickhaler, Innovata Biomed). MATERIALS AND METHODS: Twelve healthy volunteers and 11 mild asthmatic patients completed separate four-way randomised cross-over studies, assessing the relative bioavailability of salbutamol sulfate (urinary excretion method), formulated as SEDS particles (three batches) and micronized particles (Asmasal inhaler, UCB Pharma Ltd). Post-treatment improvements in patient lung function were assessed by measuring FEV(1). Physicochemical evaluation of the three SEDS batches revealed inter-batch differences in particle size and shape. RESULTS: There was no significant difference in the relative lung bioavailability of salbutamol and its bronchodilator response between the best performing SEDS formulation and the Asmasal inhaler in volunteers and patients, respectively. SEDS salbutamol sulfate showing wafer like morphology gave greater fine particle dose, relative lung bioavailability and enhanced bronchodilation compared to other SEDS batches containing elongated particles. CONCLUSIONS: Active Pharmaceutical Ingredient (API) manufactured using supercritical fluids and delivered by DPI can provide similar lung bioavailability and clinical effect to the conventional micronized commercial product. Product performance is however notably influenced by inter-batch differences in particle characteristics.

Survey of early discharge schemes from the 2003 UK National COPD Audit.

BACKGROUND: Early discharge for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has been shown to be effective by clinical trials. To evaluate its implementation and efficacy in clinical practice, data concerning early discharge schemes (EDS) from the 2003 National COPD Audit were collected and analysed. METHODS: All acute Trusts in the UK were surveyed in Autumn 2003 by two means: one a questionnaire relating to organisation of care and second an audit of 40 clinical cases admitted with AECOPD. RESULTS: Data were available for both organisation of care and clinical activity for 233 units, of which 103 (44%) had EDS. Models of care included admission prevention in the accident and emergency department (5%), rapid discharge in <48h (27%), assisted discharge occurring 2 days or more after admission (24%) and combinations of these (12%). There was wide variation in organisation of care overall. 30% of patients in units with EDS were discharged early from hospital. Units with EDS had an average LOS 1-day shorter with no increase in readmission rate (32% vs. 32%) as for those without an EDS and no increase in mortality. CONCLUSIONS: There is wide variation in the availability of EDS for AECOPD in the UK, with increasing implementation of schemes. Thirty percent of patients can effectively be put into EDS which is higher than the figure of 25% from randomised controlled trials (RCTs). Mortality and readmission rates are the same as for units where no EDS is available and similar to results reported in RCTs. EDS therefore appears to be effective in routine clinical practice.

Variability in the organisation and management of hospital care for COPD exacerbations in the UK.

Previous smaller UK audits have demonstrated wide variation in organisation, resources, and process of care for acute chronic obstructive pulmonary disease (COPD) admissions. Smallest units appeared to do less well. UK acute hospitals supplied information on (1) resources and organisation of care, (2) clinical data on process of care and outcomes for up to 40 consecutive COPD admissions. Comparisons were made against national recommendations. Eight thousand and thirteen admissions involved 7529 patients from 233 units (93% of UK acute Trusts). Twenty-six percent of units had at most one whole-time equivalent respiratory consultant while 12% had at least four. Thirty percent patients were admitted under a respiratory specialist and 48% discharged under their care whilst 28% had no specialist input at all. Variation in care provision was wide across all hospitals but patients in smaller hospitals had less access to specialist respiratory or admission wards, pulmonary rehabilitation programs, specialty triage or an early discharge scheme. Six percent of units did not have access to NIV and 18% to invasive ventilatory support. There remains wide variation in all aspects of acute hospital COPD care in the UK, with smaller hospitals offering fewest services. Those receiving specialist input are more likely to be offered interventions of proven effect. Management guidelines alone are insufficient to address inequalities of care and a clear statement of minimum national standards for resource provision and organisation of COPD care are required. This study provides a unique insight into the current state of care for patients admitted with COPD exacerbations in the UK.