Comparison of Pulmicort pMDI plus Nebuhaler and Pulmicort Turbuhaler in asthmatic patients with dysphonia.

BACKGROUND: Dysphonia is a known local adverse effect of inhaled corticosteroids. This symptom was investigated by laryngoscopy and assessment in a voice laboratory. The effects of changing the treatment of patients with dysphonia, reported whilst using the pMDI, to pMDI plus Nebuhaler or Tubuhaler was also assessed. METHODS: Seventy-two patients reporting dysphonia and taking inhaled steroids from a pMDI entered a 12-week, open, parallel group study. Fifty-one completed the study per protocol; 26 in the Nebuhaler group [21 female, mean age 57 years (22-77)] and 25 in the Turbuhaler group [18 female, mean age 58 years (21-81)]. A dysphonia diary card was completed weekly. Voice laboratory assessments and laryngoscopy were performed on entry and at 12 weeks. RESULTS: There were no differences in voice laboratory data, laryngoscopic evidence of disordered glottic closure and diary data between the two groups at 12 weeks. At study entry laryngoscopic appearances were normal in almost half the patients. Vocal cord bowing was rarely seen. Glottic closure changed in nine patients during the study period, but there was no correlation with voice symptoms. The trend of symptomatic improvement of voice status in the Turbuhaler group did not correlate with voice laboratory assessments and laryngoscopic evidence of disordered glottic closure. After 4 weeks, 40% of patients using Turbuhaler and 8% in the Nebuhaler group scored their voice status as better (P < 0.02) but there was no significant difference between the two groups at 12 weeks (Turbuhaler 52%, Nebuhaler 23%, P=0.08). CONCLUSION: This study does not support the view that dysphonia in asthmatics inhaling corticosteroids is usually caused by myopathic bowing of the vocal cord muscles.

Bambuterol: effective in nocturnal asthma.

Bambuterol was compared with placebo in 28 patients with nocturnal asthma in a randomized, double-blind cross-over study. All patients were symptomatic despite taking inhaled beta 2-agonists, inhaled corticosteroids (in 26 patients the median daily dose was 1500 micrograms) and oral corticosteroids (in eight patients the median daily dose was 10 mg). Patients demonstrated > or = 20% overnight fall in peak expiratory flow (PEF) for at least half of the 14-day run-in period. They then entered two treatment periods lasting 14 days when bambuterol 20 mg nocte and placebo were given in random order. Compared to placebo, bambuterol produced a 16% improvement in mean PEF on waking (271 l min-1 vs. 239 l min-1 P = 0.0002) and a 10% improvement in evening PEF measured 24 h after drug intake (318 l min-1 vs. 296 l min-1 P = 0.01). Bambuterol significantly reduced frequency of nocturnal awakening from 1.1 to 0.7 per night (P = 0.01) and nocturnal beta 2-agonist use from 2.7 to 2.1 puffs (P = 0.0004). Other nocturnal symptoms: cough, wheeze and dyspnoea were also significantly reduced during bambuterol treatment and patients quality of sleep was improved. The results indicate bambuterol (20 mg nocte) provides effective nocturnal bronchodilation with sustained effect for 24 h and may have a useful therapeutic role in the control of symptomatic nocturnal asthma.

Further studies on the control of arachidonic acid turnover in guinea-pig endometrium in relation to prostaglandin production.

The amounts of phospholipids in the guinea-pig endometrium were phosphatidylcholine (PC) greater than phosphatidylethanolamine (PE) = sphingomyelin (Sph.) greater than phosphatidylserine (PS) + phosphatidylinositol (PI). There were no significant differences in the amounts of any of these phospholipids in endometrium between Days 7 and 15 of the cycle. The de novo synthesis of PC was 5- to 10-fold higher than the synthesis of PC from PE in guinea-pig endometrium. There were no differences in the amounts of PC formed by either pathway, and in the amounts of PI synthesized by guinea-pig endometrium between Days 7 and 15 of the cycle during a 6 h culture period. The increased incorporation of arachidonic acid into phospholipids of guinea-pig endometrium on Day 15 compared to Day 7 cannot be accounted for by an increase in phospholipid content or increased phospholipid synthesis on the former day. Following a 24 h labelling period of endometrial lipids with [3H] arachidonic acid (3H-AA), there was a significant decrease in the amount of 3H-AA in PC and PE on Day 15, but not on Day 7, following a further 48 h culture period. Progesterone, oestradiol and A23187 did not affect the amounts of 3H-AA released from the various lipid classes in guinea-pig endometrium during the time periods of culture studied. It is concluded that PC and PE may be the source of arachidonic acid for increased PGF2 alpha synthesis by guinea-pig endometrium after Day 11 of the oestrous cycle. The lack of changes in PI content and PI synthesis between Days 7 and 15 of the cycle indicates that stimulation of the PI cycle is not involved in the biochemical processes which lead to increased AA release and PGF2 alpha synthesis in guinea-pig endometrium after Day 11 of the cycle.

Arachidonic acid uptake into and release from guinea-pig endometrium in vitro on days 7 and 15 of the oestrous cycle.

Endometrium from guinea-pigs on Days 7 and 15 of the oestrous cycle (days of low and high endometrial prostaglandin F2 alpha production, respectively) was maintained in tissue culture for periods up to 24 h (uptake experiments) or 48 h (release experiments). Tritiated arachidonic acid (3H-AA) was incorporated into endometrial phospholipids and neutral lipids in a time-dependent manner. After 24 h of culture, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were the major phospholipids, and triglyceride (TG) was the major neutral lipid which had incorporated 3H-AA. PC, PE and phosphatidylserine/phosphatidylinositol (PS/PI) incorporated significantly more 3H-AA on Day 15 than on Day 7. TG also incorporated more 3H-AA on Day 15 than on Day 7, but the increase was not statistically significant. Tritiated oleic acid (3H-OA) was incorporated into endometrial phospholipids and neutral lipids in a time-dependent manner. No increase in uptake of 3H-OA occurred on Day 15 compared to Day 7. There appears to be a specific stimulation of the mechanisms involved in the uptake of arachidonic acid into guinea-pig endometrium (particularly into the phospholipids) at the end of the oestrous cycle. There was little apparent release of 3H-AA from any endometrial lipid class, except diglyceride (DG) and monoglyceride (MG), on Day 7. In contrast, there was an apparent 50 to 80% decrease in the 3H-AA content of several endometrial lipid classes, particularly PC, PE and TG, on Day 15. Overall, the uptake and release studies suggest that PC, PE and possibly TG form the source of free arachidonic acid for PGF2 alpha synthesis by the guinea-pig endometrium.

Breath-actuated inhalers in chronic asthma: comparison of Diskhaler and Turbohaler for delivery of beta-agonists.

An open, randomized, cross-over study was performed to compare the efficacy and acceptability of two breath-actuated inhalers, the Turbohaler (T) and Diskhaler (D), for delivery of beta-agonists. Thirty six adults with chronic asthma requiring beta-agonists four times daily were treated with terbutaline 500 micrograms via T and salbutamol 400 micrograms via D four times daily, each period lasting four weeks. Additional bronchodilator via pressurized aerosol was permitted as required. Peak expiratory flow (PEF) was recorded in the morning (before and after beta-agonist) and in the evening. The mean morning PEF was higher during the first two weeks using T (295 l.min-1) than whilst using D (281 l.min-1, p < 0.01), but this difference did not persist during the second two weeks and there were no differences in post-bronchodilator PEF or rescue beta-agonist use. After four weeks, > 90% of patients used both inhaler devices efficiently and they were equally acceptable in terms of ease of use and convenience to carry. The Diskhaler and Turbohaler achieve similar clinical efficacy for delivery of beta-agonists.

Peak inspiratory flow through Turbuhaler in acute asthma.

Efficient use of dry powder inhalers, such as Turbuhaler, is dependent on the generation of adequate inspiratory flow. It is not clear whether patients with acute asthma are able to generate adequate flow. Peak inspiratory flow (PIF) was measured through an empty Turbuhaler, and without this device, in 99 adults presenting to hospital with acute exacerbations of asthma. Where possible, patients were studied prior to nebulized bronchodilator therapy. Mean (SD) forced expiratory volume in one second (FEV1) was 1.2 (0.7) L, forced vital capacity (FVC) 2.1(1.0) L and peak expiratory flow (PEF) 199 (92) L.min-1. PIF without Turbuhaler was 152 (77) L.min-1 and correlated with PEF (r = 0.69). PIF through Turbuhaler was 60 (20) L.min-1 and weakly correlated with PEF (r = 0.35), and with PIF without Turbuhaler (r = 0.43). Two patients failed to generate the minimum inspiratory flow (30 L.min) required for efficient use of Turbuhaler; both recorded 26 L.min-1. Acute asthma is associated with considerable inspiratory, as well as expiratory airflow limitation. The relationship between inspiratory and expiratory airflow is not strong enough to predict whether patients with severe acute asthma will have difficulty using dry powder inhalers efficiently. Despite this, 98% of patients in this study generated inspiratory flow through Turbuhaler which would allow a therapeutically active amount of bronchodilator drug to be delivered to the airways.