Shozo Maeda

Relationship between ultrasonically nebulized distilled water–induced bronchoconstriction and acetic acid–induced cough in asthmatic children

BACKGROUND Although wheezing and cough are the most common complaints in asthmatic persons, the mechanisms of hyperresponsiveness to bronchoconstriction and cough are nevertheless still unclear. OBJECTIVE To investigate the common mechanisms between them, we studied the relationship between ultrasonically nebulized distilled water (UNDW) inhalation challenge and acetic acid (AA) inhalation challenge. In addition, we evaluated the effect of inhaled furosemide on both provocation tests by means of a placebo-controlled study. METHOD In study 1 the UNDW, AA, and histamine inhalation challenges were performed in 40 asthmatic children (26 boys, aged from 7 to 16 years; mean +/- SD, 11.2 +/- 2.0 years). In study 2, 12 of the study 1 subjects (9 boys, 11.3 +/- 2.4 years) were subjected to each challenge test after inhalation of furosemide (10 mg/body square meters), or placebo (0.9% saline solution) on separate days. RESULTS There was a good correlation between the provocative dose causing a 20% fall in forced expiratory volume in 1 second in the UNDW inhalation challenge (UNDW-PD20) and threshold dose causing cough in the AA inhalation challenge (R = 0.527; p < 0.001). There was no relationship either between UNDW-PD20 and the provocative concentration causing a 20% fall in the histamine inhalation challenge (histamine-PC20)(R = 0.384; p > 0.1), or between histamine-PC20 and the cough threshold (R = 0.308; p > 0.05). In study 2 neither bronchoconstriction nor bronchodilation after inhalation of furosemide was observed. Inhaled furosemide exerted a protective effect on UNDW-PD20 and cough threshold of the AA inhalation challenge (p < 0.01 and p < 0.01, respectively), but did not attenuate histamine-PC20 (p > 0.1). CONCLUSION These data suggest that a common mechanism may cause hyperresponsiveness against both UNDW-induced bronchoconstriction and AA-induced cough in asthmatic children.

The concentration of bovine IgG in human breast milk measured using different methods.

The bovine IgG concentration in human breast milk was measured using three different methods: competition radioimmunoassay (RIA), competition enzyme‐linked immunosorbent assay (ELISA) and sandwich ELISA. In 36 samples of human breast milk taken from mothers on diets including cows milk, the concentration of bovine IgG was significantly higher when measured by either competition RIA or ELISA (mean 324.9 ± 97.4 ng/ml and 396.7 ± 58.7 ng/ml, respectively) than by sandwich ELISA (3.44 ± 0.48 ng/ml). In 7 samples of human breast milk taken from mothers on cows‐milk‐free diets of more than one month, the concentration of bovine IgG was still within a detectable range (112.3±41.4 ng/ml) using competition ELISA, whereas it was not detected when using sandwich ELISA, suggesting that competition ELISA might measure some unknown substances in addition to bovine IgG. Gel filtration of pooled human breast milk revealed three large fractions. The concentration of bovine IgG in every fraction was significantly higher using competition compared with sandwich ELISA, suggesting that the difference between these assays does not result from measuring different quantities of bovine IgG, or of fragments of this protein. The time course of the bovine IgG level was different between each human breast milk sample after taking cows milk. We showed that human breast milk contains bovine IgG at a concentration of approximately 3 ng/ml when analysed using sandwich ELISA. This level is comparable to the quantity of either casein or of 8‐lactoglobulin in human breast milk. Bovine IgG might be an important allergen in cows milk allergy due to the quantity in human breast milk.

Roxithromycin Attenuates Acid-Induced Cough and Water-Induced Bronchoconstriction in Children with Asthma

In the present study, we evaluated the effect of roxithromycin, a semisynthetic macrolide antibiotic, on the cough response to inhaled acetic acid (AA) and on the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma. Ten hospitalized asthmatic children (8 boys and 2 girls, mean +/- SEM age 12.6 +/- 0.4 years) were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. All the patients underwent AA inhalation challenge before and 2, 4, and 8 weeks after the administration of roxithromycin. Seven of the 10 patients, who had a fall in FEV1 of at least 20% after UNDW inhalation, underwent UNDW inhalation challege at the same time. The cough threshold values, the lowest concentrations of AA eliciting coughs, and UNDW provocative dose producing a 20% fall in FEV1 (UNDW PD20) values 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05). No significant change was observed in baseline FEV1 or serum theophylline concentrations throughout the study. These results support the notion that administration of roxithromycin may have favorable results in the treatment of childhood asthma.

Diurnal variation of peak expiratory flow in children with cough variant asthma.

Cough variant asthma (CVA) is thought to be a variant form of asthma in which cough is the sole clinical manifestation of airways hyperresponsiveness, a characteristic feature of asthma. Another characteristic feature of asthma includes an increased diurnal variation of peak expiratory flow (PEF) compared to normal subjects. To examine whether diurnal variation of PEF might also increase in children with CVA, we have examined the degree of diurnal variation of PEF in these children (n = 7) by measuring peak flow serially for a week, and compared it with those in mild to moderate asthma (n = 17) and in control children without cough (n = 8). In control children without cough, the average value of the mean diurnal variation of PEF was 10.4 +/- 0.8%. In both groups of children with asthma and with CVA, there was a significant increase in the value (20.5 +/- 1.3% and 23.6 +/- 3.6%, respectively) compared to that in control children (p < 0.01 in both groups), although there was no significant difference between these 2 groups. These results show that mild, but significant airway obstruction is occurring in children with CVA, although clinical wheezing is not recognized. Serial measurements of diurnal variation of PEF may be helpful for the diagnosis of CVA in children.

Relation between Theophylline and Circulating Vitamin Levels in Children with Asthma

We investigated the effect of theophylline administration on circulating vitamin levels in children with asthma. Twenty-three asthmatic children, ranging in age from 7 to 15 with a mean of 10.8 years and including 16 patients who were treated with slow-release theophylline and 7 patients not receiving any type of theophylline preparation, were enrolled in this study. They all were inpatients who had been hospitalized for the control of asthma. Steady-state serum theophylline and vitamin A, B1, B2, B6, B12 and C levels were evaluated in these patients. Circulating vitamin B1 and B6 levels were depressed in asthmatic children treated with theophylline compared to those not receiving the agent (38.4 +/- 1.6 (mean +/- SEM) vs. 46.4 +/- 3.5 ng/ml and 7.1 +/- 0.5 vs. 11.8 +/- 2.1 ng/ml, respectively, p < 0.05). A significant negative correlation between theophylline and circulating levels of vitamin B6 was demonstrated in the subjects of this study (rs = -0.657, p < 0.001). In contrast, no relationship was noted between theophylline and circulating vitamin B1 levels. Theophylline did not affect circulating vitamin A, B2, B12 or C levels. We conclude that theophylline induces depression of circulating vitamin B1 and B6 levels in asthmatic children, although a dose-dependent interaction between theophylline and vitamin B1 would be unlikely.

Effect of Theophylline on Serum Uric Acid Levels in Children with Asthma

This study was undertaken to investigate the effect of theophylline on serum uric acid levels in children with asthma. Twenty-seven asthmatic children, including 21 patients who were treated with slow-release theophylline and 6 patients not receiving any type of theophylline preparation, were enrolled in this study. Serum uric acid levels were increased in the asthmatic children treated with theophylline compared to those not receiving this agent (6.28 +/- 0.29 mg/dl, mean +/- SEM, vs. 4.82 +/- 0.52 mg/dl, p < 0.05). A significant positive correlation between the serum levels of uric acid and theophylline was demonstrated in the patients of this study (rs = 0.596, p < 0.01). All the patients in whom theophylline administration was stopped showed significant decreases in serum uric acid levels (p < 0.05). From these results, we conclude that theophylline increases serum uric acid levels in children with asthma, just as it does in adult asthmatics.