Søren Pedersen

Errors in Inhalation Technique and Efficiency in Inhaler Use in Asthmatic Children

256 asthmatic children receiving regular inhalation therapy demonstrated how they used their inhalers. Pulmonary function measurements (PFM) were made before and after the demonstrations, and errors in technique were recorded. 242 children had revisable airway obstruction on the day of study. In only 109 (45 %) did die inhalation technique in an increase in FEV1≥ 15% (efficient technique). An efficient inhalation technique was found in 46% of children who demonstrated a pressurized aerosol, 59% who demonstrated a rotahaler, and 46% who demonstrated. a rotahaler, and the frequency of technique varied from 17 % to 84% between six different groups of instructors. 87 % of children controlled and 25% not controlled with PFM at the time of prescription had an efficient technique. Children under 6 years had a more inefficient and a more faulty technique than older children, but otherwise age did influence the result. Neither was time since instruction of any importance for efficiency or number of errors. The errors recorded that seem to influence efficiency most were: coordination problems, rapid inspirations, ceasing to inspire when the aerosol was fired, and inhalation through the nose. The results emphasize the paramount importance of clear instructions and control of inhalation technique at the time the treatment is prescribed.

Persistent subcutaneous nodules in children hyposensitized with aluminium-containing allergen extracts.

A follow‐up study of 202 children who had received hyposensitization with aluminium‐containing allergens showed that 1–3 years after cessation of hyposensitization 13 children still had severely pruiginous treatment‐resistant subcutaneous nodules in their forearms. Because of their long persistence the nodules of six children were studied in detail. Histologically, the nodules showed infiltration with lymphocytes (forming germinal centres), macrophages, plasma cells, mast cells and a few cosinophils. In five patients aluminium crystals were found scattered between the cells and, in addition, the phagosomes of the macrophages contained aluminium. Patch tests for aluminium were positive in four of the six patients. It is concluded that persisting nodules during hyposensitization with aluminium‐containing allergens may indicate development of aluminium hypersensitivity, and if this is confirmed hyposensitization should be discontinued.

Influence of Food on the Absorption Rate and Bioavailability of a Sustained Release Theophylline Preparation

Six children and six adults were given a single dose of a sustained release theophylline preparation (Nuelin Retard®) after an overnight fast and later after a standardized breakfast. Food significantly reduced the absorption rate of theophylline whereas the extent of absorption of theophylline was unaffected by food. Under steady state treatment the fluctuations in the serum levels of theophylline were small when the tablets were taken after meals twice a day showing that this dose regimen was sufficient. No characteristic absorption or elimination phases were seen during the steady state dose interval, and the time to peak serum theophylline level showed great variation. Serum theophylline control about 4 h after fasting intake of the tablet is recommended.

Treatment of Acute Bronchoconstriction in Children with Use of a Tube Spacer Aerosol and a Dry Powder Inhaler

In a double blind cross‐over study 24 children suffering from acute bronchoconstriction were treated with either placebo, or terbutaline delivered by a pressurized aerosol with a tube spacer (TS), or salbutamol from a dry powder inhaler (Rotahaler = RO). Both active treatments resulted in a significant increase in FEV1 as compared with placebo (P < 0.001). Furthermore, TS treatment resulted in significantly greater improvement in FEV1 than treatment with the RO (P < 0.05). Under the conditions of marked airways obstruction problems with correct handling of the RO (loading and breaking the capsule) were prevalent and many children were unable to empty the RO capsule. These difficulties seemed to account for the smaller bronchodilation after RO treatment and were not seen under quiet circumstances. It is recommended that inhalation therapy in children is supervised by an adult during periods of marked airways disease.

Nasal Inhalation as a Cause of Inefficient Pulmonal Aerosol Inhalation Technique in Children

In order to evaluate whether children can be taught the efficient use of a pressurized terbutaline aerosol with a tube spacer 71 children were given careful instruction in aerosol inhalation technique according to the manufacturers instructions. Inhalation technique, was assessed as being efficient when a child achieved an increase of more than 19% in FEV1 10 min after taking two puffs of terbutaline (each puff = 0.25 mg). After instruction about 37% of children aged 5–7 years and about 80% of children over 7 year were efficient in inhalation technique. Inhalation through the nose after actuation into the mouth accounted for about 50% of treatment failures, with the problem being more frequent in the younger age group. When this error was corrected about 83% of the children were efficient in the technique. Coordination problems and too rapid inspiration after actuation were also common errors. The findings stress the importance of checking all childrens inhalation technique before prescribing inhalation therapy. Careful instruction was not enough. The possibility of nasal inhaling should be borne in mind when looking for causes of treatment failure.

The importance of a pause between the inhalation of two puffs of terbutaline from a pressurized aerosol with a tube spacer

In a double-blind crossover study, 16 children with asthma were treated with two puffs of terbutaline (0.25 mg per puff)/placebo from a pressurized aerosol with a tube spacer. The puffs of terbutaline were taken either immediately after each other (TT) or with a pause of 3 minutes (3TT) or 10 minutes (10TT) between the two puffs. All active treatments compared with placebo resulted in a significant bronchodilation, both under normal day-to-day conditions and during acute attacks of bronchoconstriction (p less than 0.01). Under basic conditions there was no statistically significant difference in increase in FEV1 after TT, 3TT, and 10TT treatments (22%, 24%, and 25%, respectively). During attacks of acute wheeze, however, a pause between the two puffs of terbutaline improved bronchodilation significantly from 49% (TT), to 68% (3TT), and 78% (10TT) (p less than 0.01). There was no statistically significant difference between 3TT and 10TT treatments. It is concluded that pauses between the doses of inhaled terbutaline is likely to improve bronchodilation during episodes of wheeze or poor control of symptoms, whereas there appears to be no need to recommend pauses between the puffs in the routine day-to-day management of children with moderate asthma.

Cathodic trypsin-like immunoreactivity in serum: influence of sex, age, renal function, food and diurnal variation

Radioimmunologically determined cathodic trypsin-like immunoreactivity (TLI) in serum was positively correlated with age (Spearmans rho = 0.40, p less than 0.001) and negatively correlated with estimated creatinine clearance (Spearmans rho = -0.31, p less than 0.01) in healthy adults (37 women, 27 men) under standard conditions. Women had higher TLI concentrations than men (median value 358 micrograms trypsin standard/l compared with 283 micrograms trypsin standard/l, p less than 0.02). A clinically significant uptake of cathodic trypsin from the intestine to the blood is not likely because no change was found in serum concentrations of TLI and the two major protease inhibitors (alpha 1-antitrypsin and alpha 2-macroglobulin) one hour after a standard meal. No diurnal variation of TLI in serum was found in a group of 12 healthy subjects. The results indicate that due consideration must be given to sex, age and renal function of the persons used in reference groups for TLI determination.

Cumulative dose response relationship of terbutaline delivered by three different inhalers.

In a controlled, open cross‐over study 15 asthmatic children received increasing doses of terbutaline (0.125 mg + 0.125 mg + 0.25 mg + 0.5 mg + 0.I mg) delivered by a pressurized aerosol alone or with a tube spacer or a nebuhaler attached. At no time was there any significant difference in measured FEV1 or percent increase in FEV1 between the three inhalers. However, when eight patients with bronchodilation > 50% on all tests days were studied separately, a significantly greater improvement in FEV1 was seen after the first three inhalations of terbutaline when a nebuhaler or a tube spacer was used compared with the response after the pressurized aerosol (P < 0.05) Bronchodilation measurements did not differ after use of the two spacers. There was no statistically significant difference in side effects between the three inhalers, but there was a trend towards a higher occurrence of side effects when the pressurized aerosol was used alone.

Food and Fasting Absorption of a Single Dose of a Sustained Release Theophylline Sprinkle Formulation in Children

The bioavailability and absorption pattern of theophylline from a single dose of a slow release theophylline sprinkle product (Somophyllin®) were investigated in 10 asthmatic children both in Fasting conditions and after a standerdized breakfast. Theophylline given intravenously was used as a reference. The fasting absorption of. Somophyllin was rather fast with peak serum theophylline levels 3–5 h (mean 3.7 h) after dosing. Food produced a small bin statistically significant reduction in the rate of absorption of theopylline. so that the mean time to peak serum theophyllne level was 5.6 h (range 4–8 h) after food. In no case was there any important difference between the absorption) profiles on the test days, and the bioavailability was complete after both fasted and fed intake of the product (92.5% and 105%, respectively). It is suggested hat to obtain the optimum absorption profile children should take Somophyllin with food rather than between meals.

Absorption of Theo-Dur Sprinkle with food: importance of types of meals and medication times.

The bioavailability and absorption pattern of theophylline from Theo-Dur Sprinkle were investigated in adults both in fasting conditions and after two different meals. Theophylline administered intravenously was used as a reference. Furthermore, the importance of the time of medication in relation to the meal consumption for the effect of food on absorption was studied. The preparation was well absorbed under fasting conditions. A high water-content meal (apple sauce) delayed the absorption of theophylline slightly but did not influence the extent of absorption (bioavailability, 83%). A dry meal (corn flakes and bread) markedly affected both absorption pattern and bioavailability. Long delays in absorption and periods of rapid absorption of theophylline were found, and the bioavailability was reduced from 92% (fasting) to 65% (p less than 0.05). Substantial interindividual variations in absorption were observed. Taking the preparation 5 minutes before the dry meal instead of immediately after markedly reduced the effect of food on absorption. Bioavailability increased to about 84%, and the absorption profiles became much more reliable.