Hj Sluiter

Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: A comparison between budesonide and terbutaline☆

We performed a double-blind crossover study to compare the effects of long-term treatment of inhaled budesonide and terbutaline on bronchial hyperreactivity in 17 patients with allergic asthma. Both drugs were administered for 4 weeks with a placebo-treatment period before and after each active-treatment period. To assess bronchial hyperreactivity, standardized inhalation provocation tests with histamine and propranolol were performed every 2 weeks. Before each inhalation provocation the drugs were withheld for at least 12 hours. Before the budesonide treatment the FEV1 value (percent predicted) was 85.3 +/- 4.1% (mean +/- SEM). After 2 and 4 weeks of treatment with this drug, the value increased significantly to 89.4 +/- 4.1% and 96.2 +/- 3.8%, respectively (p less than 0.05 and p less than 0.005). The histamine provocation concentrations causing a decrease in FEV1 of 20% (PC20) on the same days were 4.0, 7.2, and 9.5 mg/ml, respectively (both p less than 0.001). The PC20 values for propranolol, which were measured 1 hour after the histamine provocation, were 11.7, 13.3, and 14.0 mg/ml (ns). The FEV1 values before and after 2 and 4 weeks of treatment with terbutaline were 86.2 +/- 4.0%, 84.8 +/- 4.1%, and 87.0 +/- 4.6%, respectively. The histamine PC20 values on the same days were 4.7, 3.1 (p less than 0.05), and 3.8 mg/ml, respectively. The propranolol PC20 values were 14.2, 8.7, and 10.1 mg/ml (p less than 0.001 and p less than 0.05, respectively. We conclude that budesonide improves bronchial hyperreactivity, possibly by a dampening of late allergic reactions, whereas treatment with terbutaline may lead to a temporary increase of bronchial hyperreactivity, possibly as a result of beta-receptor desensitization.

A COMPARISON OF BRONCHODILATOR THERAPY WITH OR WITHOUT INHALED CORTICOSTEROID-THERAPY FOR OBSTRUCTIVE AIRWAYS DISEASE

BACKGROUND The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. METHODS In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. RESULTS Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group. CONCLUSIONS The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

Volumetric aerobiological survey of conidial fungi in the North-East Netherlands. II. Comparison of aerobiological data and skin tests with mould extracts in an asthmatic population.

A study was undertaken to see whether the principal airborne fungi in the North‐East Netherlands were also found to be the most reactive in skin testing. Atmospheric samples were taken weekly with the Andersen sampler, from April 1981, up to and including, June 1983, At the same time skin tests of 833 patients referred to the outpatient Departments of Pulmonology and Allergology, because of recurrent bronchial obstructive complaints and a suspected allergy, were studied for strongly positive skin reactivity to fungi. 4.6% of the patients reacted with a wheal of 10 mm diameter or more to one or more of the tested fungi. Almost three‐quarters of the airborne fungal “flora” was composed of seven genera, namely (in order of occurrence); 1) Cladosporium (42,6 %), 2) Botrytis (8.6 %), 3) Yeasts (7 %), 4) Penicillium (5.8%), 5) Basidiomycetes (5.7%), 6) Aspergillus (3.7%), and 7) Altenaria (0.9%), In skin‐testing, however, a different order of occurrence existed; namely: 1) Beauveria (6.8%), 2) Botrytis (6.1%), 3) Aspergillus (4.7%), 4) Mucor (3.8%), 5) Epicoccum (3%), 6) Cladosporium (2.3%), and 7) Altenaria (1.1%), It is concluded that the most prevailing airborne moulds are not necessarily the most potent allergens, at least in skin testing. Aspergillus and Botrytis showed a high sensitization rate, while Cladosporium and Altenaria did not. Botrytis deserves further study because of its frequent airborne occurrence and marked allergenic properties.

CLINICAL SIGNS IN SEVERE GUILLAIN-BARRE-SYNDROME - ANALYSIS OF 63 PATIENTS

Clinical data are presented of 63 artificially ventilated Guillain-Barré patients. About half of them had an antecedent event. In 57% the disease was heralded by sensory symptoms. The mean progressive phase lasted 12 days, the plateau 12 days and the recovery phase 568 days. In all patients one or more cranial nerves were involved, most often leading to facial palsy or difficulties in swallowing. Three-quarters of the patients had sensory signs, proprioceptive more often than superficial. Autonomic disturbances were common, especially hypertension and tachycardia. Twenty-two percent of the patients were severely confused in the first weeks of the disease. Laboratory examination showed atypical lymphocytes in the blood of 37% of patients and disturbed hepatic function tests in 79%. CSF protein level was elevated in all patients, with a mean value of 1.5 g/l.

VOLUMETRIC AEROBIOLOGICAL SURVEY OF CONIDIAL FUNGI IN THE NORTHEAST NETHERLANDS .1. SEASONAL PATTERNS AND THE INFLUENCE OF METEOROLOGICAL VARIABLES

In order to obtain actual data about the qualitative and quantitative occurrence of airborne fungi in The Netherlands, a viable‐volumetric sample survey with the Andersen sampler was undertaken. From April 1981 to the end of June 1983, one day a week samples were taken on the unobstructed rooftop of a hospital in the N‐E Netherlands. An average of 268 Colony Forming Units (CFU), per sample, per cubic metre of air were found. Almost three‐quarters of the total catch consisted of seven genera, Cladosporium predominating. Botrytis showed in surprisingly high numbers when compared with other surveys, while Alternaria occurred in very low concentrations. Most atmospheric airborne spora were found between May and September. Aspergillus and Penicillium prevailed in the autumn and winter months, although were present the year‐round. Momentary weather conditions seemed less important for the overall spore picture than the average meteorological characteristics for a whole season. The obtained aero‐mycological information may be useful in determining clinical strategies for skin testing and serological investigations in patients with suspected mould allergies.

INFLUENCE OF PLATINUM-INDUCED RENAL TOXICITY ON BLEOMYCIN-INDUCED PULMONARY TOXICITY IN PATIENTS WITH DISSEMINATED TESTICULAR-CARCINOMA

Pulmonary function tests, including T1CO, and renal function tests were performed and GFR and ERPF measured in 18 patients with disseminated testicular non-seminoma before and after remission induction according to the Einhorn regimen. We found a significant positive correlation between delta GFR and delta T1CO (p less than 0.05). No significance could be demonstrated between delta ERPF and delta T1CO. It is concluded that caution should be exercised in administrating bleomycin to patients with severely impaired renal function.

Changes in pulmonary function during and after bleomycin treatment in patients with testicular carcinoma

SummaryPulmonary function tests, including spirometry, transfer factor of the lungs for carbon monoxide (TlCO), and the two components of TlCO, the diffusing capacity of the alveolocapillary membrane (Dm) and pulmonary capillary blood volume (Vc), were carried out in a group of patients with testicular carcinoma during and after treatment with the Einhorn regimen. The lung function parameters of patients who developed bleomycin-induced pneumonitis were compared with those recorded in a group of patients who did not develop this syndrome.We suggest that bleomycin-induced damage to the pulmonary capillary vasculature can be monitored by measuring Vc and that ensuing fibrosis can be measured by recording Dm. The decrease in Dm is probably compensated for by an increase in Vc, leading to a smaller change in TlCO.

ENVIRONMENTAL AEROBIOLOGICAL STUDIES IN ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

An aerobiological pilot study was undertaken to measure airborne concentrations of Aspergillus spores in and around the dwellings of two patients with allergic broncho‐pulmonary aspergillosis (ABPA). The aim of the investigation was 1) to find a specific source of Aspergillus antigen, and 2) to find out whether disease activity, or exacerbation, paralleled Aspergillus spore prevalence. In the environment of the first patient heavy spore contaminated air was found in a cow‐shed, and the adjacent hayloft and scullery. The patient experienced no typical exacerbation during the study period, probably because she now scrupulously avoided this source. The environment of the second patient contained lower spore concentrations in and around the house, and the patient had no typical exacerbation, possibly due to low‐intensity exposure. Both patients, however, had increased bronchial obstruction during periods with high Aspergillus spore content in the outside air. The results suggest that avoidance of Aspergillus spore sources and low overall exposure may play a major role in preventing exacerbation of the disease.

Immunologic observations in sera of a patient with allergic bronchopulmonary aspergillosis by means of the enzyme-linked immunosorbent assay

Titers of IgG, IgA, and IgM antibodies against Aspergillus fumigatus were measured by ELISA in sera of a patient with allergic bronchopulmonary aspergillosis during an acute stage, remission, and exacerbation of the disease. Total IgE, specific IgE against A. fumigatus, and number of precipitation lines were also measured. ELISA IgG-, IgA-, and IgM-antibody titers were expressed in percentages of the titer of a strongly positive standard serum by use of the patients own serum as a standard. The fall in antibody concentration (in percent) and elevations during exacerbation appeared to be similar for these antibody classes and are related with the number of precipitates measured by double immunodiffusion. Furthermore, the changes in antibody titers were also similar to the elevations and decreases in both total IgE and specific-IgE antibodies (also expressed in percentages of a chosen standard serum). The ELISA IgG-antibody titers were higher compared with the ELISA IgA or IgM titers and demonstrated a continuous decline during a period of 2 yr after the acute phase of ABPA. Therefore, IgG-antibody titers are preferred as an indicator of disease activity in follow-up studies over longer time periods and are at least as sensitive as the measurement of concentrations of IgE antibodies.

PROTECTIVE EFFECT OF ORAL OXYPHENONIUM BROMIDE, TERBUTALINE AND THEOPHYLLINE AGAINST THE BRONCHIAL OBSTRUCTIVE EFFECTS OF INHALED HISTAMINE, ACETYLCHOLINE AND PROPRANOLOL

SummaryThe protective effects of oxyphenonium bromide, terbutaline and theophylline were compared in 8 asthmatic patients by determination of the degree of non-specific airway reactivity after 1 week of oral treatment according to a fixed dose scheme in a double-blind random order: oxyphenonium bromide 3×10 mg; terbutaline 3×5 mg; theophylline 2×300 mg and placebo. Controlled, standardized inhalation provocation tests were carried out with histamine, acetylcholine and propranolol. The study was monitored by measuring blood concentrations of the 3 drugs, and their effect on the plasma cAMP concentration was also determined. Significant protection by oxyphenonium bromide against the bronchial obstructive effects of acetylcholine and propranolol was observed, but not against the effect of inhaled histamine. The other two drugs provided no significant protection against the inhaled agents. The absence of any protective effect of terbutaline and theophylline might have resulted from too low a blood concentration. The observed differences in protection could not be explained by changes in pulmonary function. The study suggests dissociation between the bronchodilating effect of a drug and its protective effect against inhaled substances.