Can all patients with COPD use the correct inhalation flow with all inhalers and does training help?

The inhalation rate is important when patients use an inhaler. Dry powder inhalers (DPIs) require an inhalation rate >30 L min(-1) whereas metered dose inhalers (MDIs) should be used at <90 L min(-1). Within the setting of a routine clinic, we have measured peak inhalation flows (PIF) of COPD patients when they used a Diskus (SDSK), Turbuhaler (STBH), Handihaler (SHAND) and MDI. Subjects were then randomised into trained (VT) and non-trained (NT) groups. One hundred and sixty-three patients with a mean (S.D.) age and % predicted FEV(1) of 72.5 (9.9) years and 47.8 (22.2)% completed the study. Of the patients, 4.9%, 14.2% and 57.0% inhaled <30 L min(-1) through SDSK, STHB and SHAND, respectively and 59.5% inhaled >90 L min(-1) with the MDI. Generally, the more severe the COPD, the slower was their PIF with all inhalers. The MDI PIF values in the VT group (n=84) post-training were significantly (p<0.001) slower but there was no change for the DPIs. Of the 55 VT patients inhaling >90 L min(-1) through the MDI only 7 (p<0.001) inhaled too fast post-training. Pre-training 3, 15 and 46 VT subjects inhaled <30 L min(-1) through the SDSK, STBH and SHAND and after training none, 5 and 26 did not inhale faster than this minimum required rate. Some COPD patients have problems achieving required PIFs through DPIs but training is useful to help some exceed the minimum required rate despite only small improvements. The patients found it easier to slow their PIF through the MDI.

The potential of a 2Tone Trainer to help patients use their metered-dose inhalers.

BACKGROUND: Many patients have problems using the correct inhalation technique when they use their metered-dose inhalers (MDIs). We have investigated whether a training aid (2Tone Trainer [2T]; Canday Medical Ltd; Newmarket, UK) helps to maintain the correct inhaler technique after patients leave the clinic METHODS: Ethics committee approval was obtained, and patients gave consent. Asthmatic patients who had been prescribed an MDI had their inhalation technique assessed. Their peak inhalation flow (PIF) when using their MDI, FEV(1), and the Juniper asthma quality of life questionnaire (AQLQ) score were measured. Those patients using the recommended MDI technique were the good-technique (GT) group. The remainder were randomized to receive verbal training (VT) or VT plus the 2T to improve their MDI technique. All patients returned 6 weeks later. RESULTS: There were 36, 35, and 36 asthmatic patients, respectively, who completed the GT, VT, and 2T procedures. FEV1 did not change within all groups between visit 1 and 2. PIF and AQLQ score did not change in the GT group. In the VT and 2T groups, the AQLQ score increased by mean differences of 0.33 (95% confidence interval [CI], 0.14 to 0.53; p < 0.001) and 0.74 (95% CI, 0.62 to 0.86; p < 0.001). At visit 1, all patients in the VT and 2T groups inhaled > 90 L/min decreasing to 12 patients and 1 patient, respectively, at visit 2 (p < 0.001 both groups). The overall changes in the 2T group for PIF and AQLQ score, between visits 1 and 2, were significantly (p < 0.001) greater than the corresponding changes in the VT group. CONCLUSION: The 2T helps patients to maintain the recommended MDI technique posttraining with improvements in AQLQ score.

A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma.

OBJECTIVE: The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence-based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc. METHODS: Forty-five patients were randomized to receive low-dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single-breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores. An intent-to-treat statistical analysis was performed. RESULTS: At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty-two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non-trial-related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between-group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified. CONCLUSION: This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.

Emitted dose estimates from Seretide Diskus and Symbicort Turbuhaler following inhalation by severe asthmatics.

The dose emitted from dry powder inhalers may be inhalation flow-dependent. Using an ex vivo method, the Electronic Lung, we have measured the aerodynamic characteristics of the emitted dose for both active constituents from Seretide Diskus (salmeterol xinafoate 50 mcg; fluticasone propionate 500 mcg) and Symbicort Turbuhaler (formoterol 6 mcg; budesonide 200 mcg). Electronic inhalation profiles were collected from 20 severe asthmatics (mean PEFR 53% predicted) when they inhaled using a placebo Seretide Diskus and a placebo Symbicort Turbuhaler. These were replayed in the Electronic Lung with the respective active inhaler in situ. Mean(S.D.) peak inhalation flow rates (PIFR) through the Diskus and Turbuhaler were 94.7(32.9) and 76.8(26.2) l min(-1), respectively. From the Electronic Lung the Diskus inhalation profiles provided a mean(S.D.) fine particle dose (FPD) for fluticasone propionate and salmeterol of 20.4(4.8) and 18.4(4.4)% labelled dose. For Turbuhaler inhalation profiles the FPD was 23.1(12.9) and 20.7(11.1)% labelled dose for budesonide and formoterol, respectively. The linear (p < 0.001) relationships between FPD against PIFR for budesonide and formoterol were 3 (p = 0.002) and 2.8 (p = 0.007) times steeper than fluticasone propionate and salmeterol, respectively. The results highlight a more significant effect of inspiratory flow on variable dosage emission when using the Symbicort Turbuhaler compared with the Seretide Diskus.

A randomized controlled trial to assess the optimal dose and effect of nebulized albuterol in acute exacerbations of COPD.

STUDY OBJECTIVES: Despite the widespread use of short-acting, inhaled beta(2)-agonists in acute exacerbations of COPD (AECOPDs), little is known about their optimal dose. The aims of this study are to compare the bronchodilator response to incremental doses of inhaled albuterol during and after recovery from an AECOPD, and to compare the effects of regular nebulized albuterol, 2.5 mg and 5 mg, on the speed of recovery. METHODS: Eighty-six patients admitted with an AECOPD were recruited. Each patient was administered incremental doses of inhaled albuterol on hospital admission and following recovery. Dose-response curves were constructed based on FEV(1) and peak expiratory flow rate (PEFR) recorded after each incremental dose. Patients were then randomized in a double-blind fashion to receive 2.5 mg or 5 mg of nebulized albuterol q4h until recovery. Twice-daily PEFR, the number of extra doses of bronchodilators, and side effects reported were recorded. RESULTS: Maximal bronchodilation (Emax) FEV(1) (maximal bronchodilatory response to albuterol) increased from 0.64 +/- 0.27 L/min during the exacerbation to 0.94 +/- 0.38 L/min during recovery (p < 0.001). The Emax PEFR increased from 147.53 +/- 62.46 L/min to 222.94 +/- 73.82 L/min after recovery (p = < 0.001). There was no significant difference in rate of recovery of PEFR (p = 0.684), duration of hospital stay (p = 0.084), or side effects (p = 0.506) between the groups receiving 2.5 mg or 5 mg of nebulized albuterol. CONCLUSIONS: There was significant improvement in Emax to inhaled albuterol as the COPD exacerbation resolved. There was no significant difference in outcomes including length of hospital stay or recovery of lung function between patients treated with regular 2.5 mg vs 5 mg of nebulized albuterol during an AECOPD.