Effect of inhaled PGE2 on exercise-induced bronchoconstriction in asthmatic subjects

Previous studies have suggested that the endogenous release of inhibitory prostanoids limits the bronchoconstrictor response to repeated exercise. The aim of our study was to determine whether inhaled prostaglandin (PG)E2 attenuates exercise-induced bronchoconstriction or methacholine airway responsiveness in asthmatic subjects. Eight subjects with mild stable asthma and exercise bronchoconstriction were studied on 4 separate days, 48 h apart. Subjects inhaled PGE2 or placebo in a randomized, crossover, double-blind fashion, 30 min prior to an exercise challenge or a methacholine challenge. PGE2 inhalation significantly attenuated exercise bronchoconstriction. The mean maximal %fall in FEV1 after exercise was 26% (SEM 3.7%) after placebo, and was 9.7% (SEM 2.7%) after PGE2 (p < 0.001). PGE2 also significantly reduced the duration of exercise bronchoconstriction (p = 0.034). However, PGE2 did not significantly attenuate methacholine airway responsiveness. The geometric mean methacholine provocative concentration causing a 20% fall in FEV1 (PC20) was 0.77 (%SEM 1.48) after placebo day, and 1.41 (%SEM 2.20) after PGE2 (p = 0.30). These results demonstrate that inhaled PGE2 markedly attenuates exercise bronchoconstriction in asthmatic subjects and suggest that this effect is not occurring through functional antagonism of airway smooth muscle.     

Role of neutral endopeptidase in exercise-induced bronchoconstriction in asthmatic subjects

The membrane-bound metalloproteinase, neutral endopeptidase (NEP), is a degrading enzyme of both bronchoconstrictor and bronchodilator peptides within the airways. To examine the role of NEP in exercise-induced bronchoconstriction (EIB) in asthmatic subjects, we used inhaled thiorphan, a NEP inhibitor, as pretreatment to a 6-min standardized exercise challenge. Thirteen clinically stable asthmatic subjects participated in this double-blind, placebo-controlled, crossover study that was performed on 2 days separated by 48 h. Thiorphan was administered by two inhalations of 0.5 ml containing 1.25 mg/ml. Subsequently, exercise was performed on a bicycle ergometer at 40-50% of predicted maximal voluntary ventilation while inhaling dry air (20 degrees C, relative humidity 6%). The airway response to exercise was measured by forced expiratory volume in 1 s (FEV1) every 3 min, up to 30 min postexercise challenge, and was expressed both as the maximal percent fall in FEV1 from baseline and as the area under the time-response curve (AUC) (0-30 min). The acute effects of both pretreatments on baseline FEV1 were not different (P > 0.2), neither was there any difference in maximal percent fall in FEV1 between thiorphan and placebo (P > 0.7). However, compared with placebo, thiorphan reduced the AUC by, on average, 26% [AUC (0-30 min, +/-SE): 213.6 +/- 47.7 (thiorphan) and 288.6 +/- 46.0%fall.h (placebo); P = 0.047]. These data indicate that NEP inhibition by thiorphan reduces EIB during the recovery period. This suggests that bronchodilator NEP substrates, such as vasoactive intestinal polypeptide or atrial natriuretic peptide, modulate EIB in patients with asthma.     

Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0 +/- 0.8 yr) with a history of EIB participated in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo (0.9% saline) according to a double-blind, randomized, crossover design, and underwent an exercise challenge test 15 min after the pretreatment. Inhaled indomethacin significantly attenuated EIB. The mean maximal percent decrease in FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced the mean maximal decrease in arterial oxygen saturation after exercise (p = 0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in the airways may be a mechanism involved in the protective potency of inhaled indomethacin.     

Active and passive smoking: hazards for children

In 1995 the Sainsbury Centre for Mental Health commissioned a major review of all specialist mental health training. The current, largely uni-disciplinary approach to training was felt to be failing to equip professionals with the necessary skills for today's multi-disciplinary, integrated, community-based service, where users and their carers expect an equal partnership and sharing of information. Kevin Gournay and Susannah Strong outline the findings and recommendations of the review, and its implications for mental health nurse education, which make a case for its separation from the rest of the nursing profession.     

Incidence of exercise-induced asthma in children

The incidence of exercise-induced asthma (EIA) was studied in 134 asthmatic and 102 nonasthmatic atopic children and compared to that in 56 nonatopic children. Pulmonary function tests measuring forced vital capacity (FVC) and 1-sec forced expiratory volume (FEV1) were performed on each child prior to and serially for 20 min following free running exercise. The incidences of EIA among the asthmatic and atopic nonasthmatic children were 63% and 41%, respectively. This phenomenon is widespread among allergic children and cannot be accurately predicted from the history. A simple and easily performed outpatient procedure is described for the diagnosis of EIA.     

Effects of acute cigarette smoking on endothelium-dependent arterial dilatation in normal subjects

The effects of acute cigarette smoking on endothelial function were evaluated in the brachial artery of 10 nonsmoking healthy subjects. Endothelial dysfunction observed after cigarette smoking is a phenomenon lasting at least 60 minutes and does not appear to be attenuated with repeat exposure.     

Health effects of passive smoking. 3. Parental smoking and prevalence of respiratory symptoms and asthma in school age children

BACKGROUND: A systematic quantitative review of the evidence relating parental smoking to the prevalence of asthma and respiratory symptoms was conducted amongst school age children. METHODS: Sixty relevant studies were identified after consideration of 1593 articles selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997 and identified 25 studies of asthma, 41 of wheeze, 34 of chronic cough, seven of chronic phlegm and six of breathlessness which were included in a quantitative overview. RESULTS: The pooled odds ratios for either parent smoking were 1.21 (95% CI 1.10 to 1.34) for asthma, 1.24 (95% CI 1.17 to 1.31) for wheeze, 1.40 (95% CI 1.27 to 1.53) for cough, 1.35 (95% CI 1.13 to 1.62) for phlegm, and 1.31 (95% CI 1.08 to 1.59) for breathlessness. Adjustment for confounding had little effect. Evidence of heterogeneity between studies appeared largely explicable by publication bias with a superfluity of small studies with large odds ratios. However, excluding these had little effect on the pooled odds ratios. The prevalence of all symptoms increased with the number of parents who smoked. While maternal smoking had a greater effect than paternal smoking, the effect of father only was clearly significant. CONCLUSIONS: The relationship between parental smoking and respiratory symptoms seems very likely to be causal given statistical significance, robustness to adjustment for confounding factors, consistency of the findings in different countries, and evidence of dose response. The raised risk in households where the father, but not the mother, smoked argues for a postnatal effect.     

Rebox effect on exercise-induced acute inflammation in human muscle

BACKGROUND: The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens. OBJECTIVE: To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children. METHODS: Serum samples from 33 cat allergic asthmatic children, 7-17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0. 13 microg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles. RESULTS: Fel d 1 was detected (0.15-1.8 microg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC. CONCLUSION: Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.     

Progressive bronchial obstruction during the acute stage of respiratory tract infection in asthmatic children

To study the time-course of infectious asthma, we retrospectively examined FEV1 from 5 days before to 10 days after the onset of illness in 31 asthmatic children (20 boys and 11 girls), aged 8 to 12 years. Infections were confirmed by a rise of at least fourfold in serum compliment fixation titers (respiratory syncytial virus, adenovirus, and Mycoplasma pneumoniae) and hemoagglutination inhibition titers (parainfluenza virus types 1, 2, and 3). All the patients had 20 percent or more fall in FEV1 from baseline value during acute phase, but were clinically tolerable and required minimum or no bronchodilators. Regardless of infectious agent, FEV1 began to fall on the first disease day or the previous day, and deteriorate for the first few days. Mean(SD) maximum fall in FEV1 ranged from 39(12) percent to 45(20) percent. Thereafter, FEV1 began to improve and returned to the preillness level by the seventh to tenth day. These results suggest that progressive bronchial obstruction may be inevitable during the acute stage of any infectious asthma.     

Effect of erythromycin on theophylline clearance in asthmatic children

Fifteen asthmatic children (mean age = 14.5 years) who required daily theophylline therapy were studied for effect of erythromycin ethyl-succinate on theophylline clearance. After a one week course of EES, there was 25.8 +/- 18.4% reduction in theophylline clearance rate (P less than 0.001), and a concomitant elevation in steady-state serum theophylline concentration of 40.0 +/- 35.3% (P less than 0.01). Three subjects reached serum theophylline concentrations greater than 20 micrograms/ml. Patients receiving therapeutic doses of theophylline are at considerable risk of theophylline toxicity if EES is co-administered.     

Prevalence and characteristics of exercise-induced asthma in children

We have evaluated the prevalence and the characteristics of exercise-induced asthma (EIA) in a group of 71 patients with a prior history of mild, moderate or severe asthma (42 males and 29 females), aged 6-16 years-old. Measurements of the forced expiratory volume in 1 second (FEV1) were obtained before and at regular intervals up to 8 hours following exercise. As a control, the same patients were evaluated at similar time intervals on another day when they had not been submitted to an exercise challenge. Using pre-exercise FEV1 values as the reference, 32 patients (45.1%) had a positive exercise challenge, defined as a fall in FEV1 value equal to or greater than 15% from baseline following exercise. Among the patients with a positive exercise challenge, the majority (23/32, 71.8%) had an immediate response alone, with no significant changes in FEV1 within the 8-hour follow-up. However, a subgroup of patients (9/32, 28.1%) had both an immediate and a late-phase response to exercise. During the control day, no significant fall in FEV1 were observed. In keeping with previous investigations, no correlation was found between a history of EIA and a positive exercise challenge in the present study. Positive exercise challenges were found more frequently among patients with moderate and severe asthma than patients with mild asthma.     

Overnight protection by inhaled salmeterol on exercise-induced asthma in children

The main aim of the present study was to evaluate whether inhaled salmeterol given in the evening protected against exercise-induced asthma the next morning. Twenty three children (12 males and 11 females) with a mean age of 11 yrs and with exercise-induced asthma participated in a double-blind, randomized, placebo-controlled study. The children inhaled salmeterol 25 micrograms, salmeterol 50 micrograms and placebo by Diskhaler at 10 p.m. on 3 separate days. Next morning, half of the children ran on a motor-driven treadmill for 6 min at submaximal load at 8 a.m. and the remainder at 10 a.m. Lung function was measured by maximal expiratory flow-volume loops before running, immediately after, and 3, 6, 10 and 15 min after running. The mean maximum reduction in forced expiratory volume in one second (FEV1) after treadmill run was 34% before inclusion in the study. Mean maximum fall in FEV1 was significantly greater after placebo: 30% (23-36) 95% confidence interval) than after salmeterol 25 micrograms: 19% (12-23) or salmeterol 50 micrograms: 18% (12-25). In addition to the reduced postexercise bronchoconstriction, pre-exercise lung function (FEV1) was significantly higher both after salmeterol 25 micrograms: 2.4 L.s-1 (2.1-2.7) and salmeterol 50 micrograms: 2.5 L.s-1 (2.2-2.8) than after placebo: 2.2 L.s-1 (1.9-2.5). No significant differences in pre- and postexercise lung function were found between children tested at 8 or 10 a.m., or in relation to salmeterol dosage. Thus, inhaled salmeterol 25 and 50 micrograms offered similar overnight protection against exercise-induced asthma and improved baseline lung function in the morning as compared to placebo.     

Spontaneous IgE production in asthmatic children

In this study, we demonstrated spontaneous IgE production by peripheral blood mononuclear cells of asthmatic children. In 26 asthmatic children, the level of spontaneous IgE ranged 0.1-15.0 IU/ml and in 5 healthy normal children showed under 0.051 IU/ml. In 5 of asthmatic children, specific antibody of Dermatophagoides farinae was detected from PBMC by CAP RAST. In healthy normal children, specific antibody of Df was not detected. Spontaneous IgE production by PBMC and serum IgE level showed well correlation (gamma = 0.835, p < 0.001). Spontaneous IgE production and specific antibody of Df by PBMC also showed well correlation (gamma = 0.717, p < 0.001) IgE production of asthmatic children was inhibited by IFN-gamma.     

Endotoxin exposure and symptoms in asthmatic children

Osteoporosis is not an inevitable accompaniment of aging. Rather, it evolves silently over a lifetime, with its attendant morbidities occurring late in life. It is no longer the standard of care to wait until the primary morbidity strikes to begin therapy. A better outcome is always achieved when the individuals at risk are identified early, lessening or even preventing morbidity such as osteoporotic fractures. Recent surveys show a reluctance on the part of many physicians to diagnose or treat osteoporosis in their patients. A second level of resistance is often seen even after fractures occur. Either scenario is particularly unfortunate as therapies currently exist that can significantly reduce future morbidity and probably mortality. Physicians must recognize that patients who have had one fracture are at significantly greater risk to sustain more fractures and are more likely to suffer chronic debilitating musculoskeletal failure. Therefore, in the elderly fracturing patient, even more intensive intervention (fracture prevention) is required.     

Effectiveness of nedocromil sodium in preventing exercise-induced asthma in children

Exercise-induced asthma is a well-known phenomenon, particularly affecting children, with an important social impact. In order to assess the usefulness of nedocromil sodium in the prevention of exercise-induced asthma, we studied 49 (15 females, 34 males) children who suffered from asthma; their mean +/- SD age was 9.2 +/- 3.0 (range: 3.3-19.1) years. On the first day respiratory function was evaluated by spirometry, basally and after 6 minutes. The inhalation of nedocromil sodium had a great influence on post-exercise lung function measurements; in fact on the day of nedocromil sodium pretreatment, our patients showed an increase of respiratory function, significantly different from the parameters recorded during the first day. Our findings suggest that nedocromil sodium is effective in the prevention of exercise-induced asthma, in pediatric age.     

Effects of intense exercise training on endothelium-dependent exercise-induced vasodilatation

To analyse the accuracy of the conversion formulae for estimation of glycohaemoglobin (GHb) measured by different methods, we analysed 210 samples for HbA1c using HPLC. Fifty of these specimens were analysed by micro-column chromatography (MC), 43 by electrophoresis (EP), 50 by IMX system (Abbott Laboratories), 38 by Primus HPLC and 29 by Diamat HPLC. Regression analyses were performed and the equations were used to estimate HbA1c values (HbA1c calc) for the five methods. The 95% limits of agreement between HPLC and the converted results were -1.77 to 1.71%, -1.54 to 1.54%, -0.92 to 0.88%, -0.46 to 0.56%, and -0.39 to 0.41% for MC, EP, IMX, Primus and Diamat equations, respectively. The mean relative errors were 3.4 (-28.2 to 35%), 1.3 (-22.9 to 25.5%), 0.4 (-14.6 to 15.0%), 0.51 (-6.55 to 7.57%), -0.20 (-5.8 to 5.4%), for MC, EP, IMX, Primus and Diamat, respectively. These results show that conversion formulae based on methods that do not measure HbA1c (MC, EP and IMX) are inaccurate and can mask a clinically relevant variation of HbA1c. However, GHb results obtained by HPLC methods could be interchangeably converted with an absolute variation of less than 1%. Converted HbA1c results from non-standardized methods should be interpreted with caution.