Inhalation in Asthma and COPD With Spiromax and Turbuhaler
This was a randomised, open-label, cross-over study involving five groups of participants: children with asthma, adolescents with asthma, adults with asthma, adults with COPD and healthy adult volunteers. The study was conducted at four centres in the United Kingdom, with recruitment from 1 November 2010 until 2 March 2011. Local research ethics committee approval was obtained (Bradford Research Ethics Committee 09/H1302/64), in addition to Research and Development approval from each participating centre. The study was conducted in accordance with good clinical practice and the declaration of Helsinki. All study participants, and parents/guardians of participants aged ≤17 years, provided signed informed consent.
One hundred asthma patients were recruited as follows: children (age range 6–11 years, n = 23); adolescents (age range 12–17 years, n = 27); adults (age range 18–45 years, n = 50). Inclusion criteria for these patients were: stable asthma with no other respiratory conditions, and use of inhaled asthma medication for ≥4 weeks before study enrolment. Patients with an asthma exacerbation or who required oral prednisolone therapy during the 4 weeks preceding enrolment were excluded. Adult COPD patients (age >50 years, n = 50) were recruited, provided they had been taking inhaled COPD medication for ≥4 weeks before study enrolment. Exclusion criteria for COPD patients were asthma or other clinically relevant pulmonary disease, and an exacerbation of COPD or oral prednisolone therapy during the 4 weeks before enrolment.
Participants completed the study during a single clinic visit (Figure 2). Demographic data were recorded and lung function (peak expiratory flow rate [PEFR], forced expiratory volume in 1 second [FEV1]) was assessed by spirometry. Disease status was assessed in patients with asthma or COPD using the Asthma Control Questionnaire (ACQ; six domains, each with a scale from 0 [minimal impairment] to 6 [severe impairment]) or Baseline Dyspnoea Index (BDI; three categories, each with a symptom severity scale from grade 1 [minimal impairment] to grade 5 [severe impairment]), respectively.
(Enlarge Image)
Figure 2.
Study design.
Both the Spiromax (Teva Pharmaceuticals) and the Turbuhaler (AstraZeneca) were provided by the manufacturers as empty devices, containing neither active drug nor powder vehicle but otherwise unmodified.
Randomisation was performed to determine which of the two devices would be used first. Training to use each DPI was provided verbally by a highly trained researcher, with instructions as per the patient information leaflet (obtained from the manufacturers of both devices). Two consecutive inhalation manoeuvres were then performed with each device.
Study participants subsequently underwent enhanced training using an In-Check Dial™ (Clement Clarke International) with the device set to the resistance of a Turbuhaler. This training was provided by a highly trained researcher, who also made the inhalation manoeuvre measurements. Participants were shown their PIF and encouraged to improve it by inhaling more quickly, particularly from the start of their inhalation. Inhalation parameters for two manoeuvres performed using the faster inhalation technique were then measured in the same way as before enhanced training.
A probe (ensuring an airtight seal) was placed into the inhalation channel of each inhaler distal from the opening of the mouthpiece. The probe was connected to PR3202 low differential pressure sensors (Applied Measurements Ltd, Reading, UK). The resistance of the DPI was measured before and after the insertion of the probe to ensure no changes and that an airtight seal was present. During each inhalation, the change in pressure (in mbar) with time (in milliseconds) that occurred in the inhalation channel of the device, was downloaded into an EXCEL spreadsheet.
The pressure changes were converted to inhalation flow as recommended by Clark and Hollingworth. From the pressure-time readings and the corresponding inhalation flow readings the following parameters were obtained: PIF (in L min), the time to PIF (Tmax), the maximum pressure change that occurred inside the DPI (ΔP; in kPa), the initial acceleration of the inhalation flow (ACCEL; in kPa sec), the inhalation volume (IV; in litres), and the duration of the inhalation (Ti; in seconds). The internal resistance of each device was measured using the technique of Clark and Hollingworth.
For each pair of manoeuvres, the profile with the highest PIF was selected for analysis. Descriptive statistics were calculated for each parameter, and results are presented as mean and standard deviation. The percentage improvement in each inhalation parameter following training was calculated for each subject; the mean percentage improvement and standard deviation are presented.
The paired t-test was used to determine whether there were statistically significant differences between the Spiromax and Turbuhaler devices, both pre- and post-training. The paired t-test was also used to examine whether differences between values post- and pre-training were statistically significant. The statistical analysis was performed using SPSS version 17/18.
Methods
This was a randomised, open-label, cross-over study involving five groups of participants: children with asthma, adolescents with asthma, adults with asthma, adults with COPD and healthy adult volunteers. The study was conducted at four centres in the United Kingdom, with recruitment from 1 November 2010 until 2 March 2011. Local research ethics committee approval was obtained (Bradford Research Ethics Committee 09/H1302/64), in addition to Research and Development approval from each participating centre. The study was conducted in accordance with good clinical practice and the declaration of Helsinki. All study participants, and parents/guardians of participants aged ≤17 years, provided signed informed consent.
Inclusion/Exclusion Criteria
One hundred asthma patients were recruited as follows: children (age range 6–11 years, n = 23); adolescents (age range 12–17 years, n = 27); adults (age range 18–45 years, n = 50). Inclusion criteria for these patients were: stable asthma with no other respiratory conditions, and use of inhaled asthma medication for ≥4 weeks before study enrolment. Patients with an asthma exacerbation or who required oral prednisolone therapy during the 4 weeks preceding enrolment were excluded. Adult COPD patients (age >50 years, n = 50) were recruited, provided they had been taking inhaled COPD medication for ≥4 weeks before study enrolment. Exclusion criteria for COPD patients were asthma or other clinically relevant pulmonary disease, and an exacerbation of COPD or oral prednisolone therapy during the 4 weeks before enrolment.
Study Design, PIL Training and Enhanced Training
Participants completed the study during a single clinic visit (Figure 2). Demographic data were recorded and lung function (peak expiratory flow rate [PEFR], forced expiratory volume in 1 second [FEV1]) was assessed by spirometry. Disease status was assessed in patients with asthma or COPD using the Asthma Control Questionnaire (ACQ; six domains, each with a scale from 0 [minimal impairment] to 6 [severe impairment]) or Baseline Dyspnoea Index (BDI; three categories, each with a symptom severity scale from grade 1 [minimal impairment] to grade 5 [severe impairment]), respectively.
(Enlarge Image)
Figure 2.
Study design.
Both the Spiromax (Teva Pharmaceuticals) and the Turbuhaler (AstraZeneca) were provided by the manufacturers as empty devices, containing neither active drug nor powder vehicle but otherwise unmodified.
Randomisation was performed to determine which of the two devices would be used first. Training to use each DPI was provided verbally by a highly trained researcher, with instructions as per the patient information leaflet (obtained from the manufacturers of both devices). Two consecutive inhalation manoeuvres were then performed with each device.
Study participants subsequently underwent enhanced training using an In-Check Dial™ (Clement Clarke International) with the device set to the resistance of a Turbuhaler. This training was provided by a highly trained researcher, who also made the inhalation manoeuvre measurements. Participants were shown their PIF and encouraged to improve it by inhaling more quickly, particularly from the start of their inhalation. Inhalation parameters for two manoeuvres performed using the faster inhalation technique were then measured in the same way as before enhanced training.
Measurement of Inhalation Characteristics
A probe (ensuring an airtight seal) was placed into the inhalation channel of each inhaler distal from the opening of the mouthpiece. The probe was connected to PR3202 low differential pressure sensors (Applied Measurements Ltd, Reading, UK). The resistance of the DPI was measured before and after the insertion of the probe to ensure no changes and that an airtight seal was present. During each inhalation, the change in pressure (in mbar) with time (in milliseconds) that occurred in the inhalation channel of the device, was downloaded into an EXCEL spreadsheet.
The pressure changes were converted to inhalation flow as recommended by Clark and Hollingworth. From the pressure-time readings and the corresponding inhalation flow readings the following parameters were obtained: PIF (in L min), the time to PIF (Tmax), the maximum pressure change that occurred inside the DPI (ΔP; in kPa), the initial acceleration of the inhalation flow (ACCEL; in kPa sec), the inhalation volume (IV; in litres), and the duration of the inhalation (Ti; in seconds). The internal resistance of each device was measured using the technique of Clark and Hollingworth.
Statistical Analysis
For each pair of manoeuvres, the profile with the highest PIF was selected for analysis. Descriptive statistics were calculated for each parameter, and results are presented as mean and standard deviation. The percentage improvement in each inhalation parameter following training was calculated for each subject; the mean percentage improvement and standard deviation are presented.
The paired t-test was used to determine whether there were statistically significant differences between the Spiromax and Turbuhaler devices, both pre- and post-training. The paired t-test was also used to examine whether differences between values post- and pre-training were statistically significant. The statistical analysis was performed using SPSS version 17/18.
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