The history of bronchial asthma from the Renaissance till the beginning of the twentieth century.

The aim of the paper is to give an overview of the history of knowledge on asthma from the Renaissance till the beginning of the 20th century. During this period the clinical picture of bronchial asthma and some etiological factors--like familiarity of the disease, the role of the pollen, psychological factors were cleared. The disease was relatively rare in these periods--the epidemiological explosion came only in the second half of the 20th century. Data on pediatric asthma, before all in Hungary are demonstrated mostly based on the works of Schoepf and Bókai senior in the first half of the 19th century.

The history of bronchial asthma from the ancient times till the Middle Ages.

The aim of the paper is to give an overview of the knowledge on asthma through the history of mankind. The text begins with ancient China and it is finished with the medicine of Middle Age. During this time, a lot of theories came and this appeared about the etiology and therapy of the disease. The paper is giving a short description of the changing medical views during this very long period including China, Egypt Greco-roman period, Mesopotamia, the Hebrews, the physicians of India, the pre-Columbian medicine in the America and the Arabic world, and partly the European medicine of the Middle Ages.

Relationship between the tumor necrosis factor system and the serum interleukin-4, interleukin-5, interleukin-8, eosinophil cationic protein, and immunoglobulin E levels in the bronchial hyperreactivity of adults and their children.

The aim of the study was to investigate the activation of inflammatory mediators interleukin (IL)-4, IL-5, and IL-8; immunoglobulin E (IgE); and eosinophil cationic protein (ECP) and to evaluate the regulatory role of the tumor necrosis system (TNF) system in bronchial hyperreactivity. Adults who had suffered from bronchial asthma in childhood but who had been symptom free for at least 3 years were examined together with their children who did not have asthma. The serum concentrations of TNF-alpha, soluble TNF receptor 1 (sTNF-R1), TNF-R2, IL-4, IL-5, IL-8, ECP, and IgE were studied in symptom-free adults (n = 22) and their children (n = 22) with bronchial hyperreactivity. Nonhyperreactive individuals with a similar medical history (adults, n = 17; children, n = 20) served as controls. Significantly elevated serum TNF-alpha (X +/- SD: 5.13 +/- 1.37 pg/mL versus 3.91 +/- 0.61 pg/mL; p < 0.0001), sTNF-R1 (X +/- SD: 1.37 +/- 0.28 ng/mL versus 1.16 +/- 0.13 ng/mL; p = 0.0002), and sTNF-R2 (X +/- SD: 0.78 +/- 0.42 ng/mL versus 0.43 +/- 0.41 ng/mL; p = 0.0001); IL-4 (X +/- SD: 4.05 +/- 1.02 pg/mL versus 3.34 +/- 0.84 pg/mL; p = 0.0016); IgE (X +/- SD: 390.1 +/- 361.4 KU/L versus 130.2 +/- 166.1 KU/L; p = 0.0001); and ECP (X +/- SD: 17.57 +/- 11.03 micrograms/L versus 10.65 +/- 6.01 micrograms/L; p = 0.0016) concentrations were measured in the subjects with bronchial hyperreactivity as compared with the nonhyperreactive group. Significant positive linear correlations were observed for the bronchial hyperreactive group between the concentrations of TNF-alpha and ECP, TNF-alpha and sTNF-R1, TNF-alpha and IL-8, sTNF-R1 and ECP, sTNF-R1 and IL-8, and sTNF-R2 and IL-8. Moreover, the TNF-alpha and sTNF-R2 levels correlated with the airway reactivity in the hyperreactive group. We suggest that the elevated cytokine levels indicate activation of the immune system in individuals who were previously asthmatic, but recovered, and are now symptom free and in their children with nonasthmatic bronchial hyperreactivity. The TNF system may play a key role in the pathomechanism of bronchial hyperreactivity.

Fluticasone propionate in asthma: a long term dose comparison study.

BACKGROUND: Few dose ranging studies have investigated optimal dosing with inhaled corticosteroids in children with asthma. AIMS: To compare the efficacy and tolerability of fluticasone propionate 100 or 200 microg twice daily in children with moderate to severe asthma for one year. METHODS: One year, randomised, double blind, parallel group, multicentre study. Children aged 4-11 years (n = 528) with moderate to severe asthma who had previously received high dose inhaled corticosteroids were given fluticasone propionate 100 or 200 microg twice daily for the 52 week treatment period. Efficacy (exacerbations, lung function, and symptoms) and tolerability (adverse events and cortisol levels) were measured. RESULTS: There was a non-significant decreased risk of experiencing an exacerbation at any time with fluticasone propionate 200 microg twice daily compared with fluticasone propionate 100 microg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 microg/day). Daily record card morning peak expiratory flow (PEF) in the total population improved significantly more with the higher dose of fluticasone propionate (between group difference, weeks 1-52: 11.4 l/min). Clinic visit mean PEF improved from baseline with both doses, but the response was significantly greater with the higher dose (between group difference, week 52: 17.8 l/min). Both doses were equally well tolerated and overnight urinary cortisol concentrations were unchanged or slightly increased during treatment with either dose. CONCLUSION: This long term dose comparison study shows that treatment with fluticasone propionate 200 micro g twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.

Role of TNF-alpha and its 55 and 75 kDa receptors in bronchial hyperreactivity.

The pathophysiological role of the tumour necrosis factor (TNF) system was studied in adults (n=37) and children (n=43) non asthmatic offspring of asthmatic parents with and without bronchial hyperreactivity proved by methacholine airway challenge test. SerumTNFalpha and its soluble receptors (sTNF-R1 and R2) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly elevated TNFalpha (adults: mean +/- SD=5.18 +/- 0.87 pg ml(-1), children: 5.08 +/- 1.78) vs. non-hyperreactives (adults: 4.12 +/- 0.43, P < 0.0001, children: 3.75 +/- 0.68, P=0.0084), sTNF-R1 (adults: 144 +/- 0.31 ng ml(-1), children: 1.30 +/- 0 25 vs. adults: 1.21 +/- 0.14, P=0.0305, children: 1.13+/-0.11 ng ml(-1), P=0.0042) and sTNF-R2 (adults: 0.85 +/- 0.40ng ml(-1), children: 0.70 +/- 0.46 vs. adults: 0.56 +/- 0.56 P=0.0084, children: 0.33 +/- 0.17, P=0.0048) and decreased sTNF-R1/R2 ratio (adults: mean +/- SD=0.96 +/- 0.73, children: 2.85 +/- 2.06 vs. adults: 4.82+/-3.40, P=0.0272, children: 4 42 +/- 2 30, P=0.0167) were measured in patients with bronchial hyperreactivityThe provocation doses of methacholine causing a 20% reduction (PD20) in forced expiratory volume in 1 sec (FEV1) were found to be in a significant negative linear correlation with TNFalpha sTNF-R1 and R2 levels in hyperreactive adults and with TNFalpha, sTNF-R2 in hyperreactive children. TNFalpha correlated significantly with its receptors both in hyperreactive adults and children and with the body mass index (BMI) values of adults. The TNF system may contribute to the pathophysiology of bronchial hyperreactivity Altered shedding of sTNF-R1 seems to occur in hyperreactive patients.

Complement activation in the nasal mucosa following nasal ragweed-allergen challenge.

The aim of this study was to explore complement activation in the nasal lavage following a nasal ragweed-allergen challenge. The study was carried out with 15 adolescents who were allergic to ragweed and with six non-allergic healthy volunteers. Following the baseline measurement after the symptoms were registered, subjects were given increasing doses of ragweed allergen. Lavage fluid was collected and tested for a complement-activation product (C3bBbP). The allergic patients responded to allergen provocation with an increase in C3bBbP formation compared to the initial lavage (p = 0.001). The C3bBbP level remained low in the lavage fluids of the non-allergic controls. We found a strong correlation between the threshold dose that induced symptoms and the dose where the maximum complement activation was detected (r = 0.78, p = 0.001). Our findings indicate that in allergic patients nasal challenge with ragweed allergen induces a rise in complement activation in the nasal lavage fluid. These results highlight the role of the complement system in the allergic inflammation on the nasal mucosal surface.

[Changes in the symptoms of bronchial asthma and associated allergic disorders from childhood to adult age]. / Az asthma bronchiale és a társuló allergiás tünetek alakulása gyermekkortól felnóttkorig.

The aim of the study was to determine the prognosis of bronchial asthma. 145 adults (96 men, 49 women) with bronchial asthma during childhood were examined above age of 28 years (mean age was 37.6, SD: 5.9 years). The patients filled out questionnaires about the asthmatic and accompanying allergic symptoms in their childhood, age at 18 years and at present. They all were physically examined and prick tested with 12 inhalant allergens. 43% of the patients became symptom-free but 57% still had intermittent or persisting asthmatic symptoms while growing up. More patients had intermittent asthmatic day (59%) and night (67%) symptoms than persisting ones (41 and 33%). The accompanying allergic diseases in childhood did not definitely affect the prognosis of bronchial asthma. These are more frequent in the females, regarding before all the atopic skin disorders. At the age of 18, the occurrence of allergic rhinitis was more frequent than in childhood. The frequency of other allergic disorders did not change significantly. Among patients with asthmatic symptoms, moulds and cat hair allergies were more frequent than in the symptom-free group. The long-term prognosis of childhood bronchial asthma is relatively good, however only less than 50% of the patients has become symptom-free. In most of the adult patients the complaints are relatively mild. The indoor allergens may contribute to the occurrence of asthmatic symptoms.

Higher serum eosinophil cationic protein levels in children with cow's milk allergy.

BACKGROUND: In the pathogenesis of cow's milk allergy, abnormal immunologically mediated reactions play a basic role. Eosinophil activation also participates in the development of several allergies. The purpose of this study was to characterize the degree of this activation by measuring the serum level of eosinophil cationic protein (sECP) and establishing whether it is a useful parameter in monitoring oral cow's milk allergy. METHODS: The sECP level of 35 patients with previously confirmed cow's milk allergy (mean age, 16 months) was evaluated using a fluoroimmunoassay before the cow's milk rechallenge test and at 2 hours and 24 hours after cow's milk challenge. RESULTS: Of the 35 children with previously confirmed cow's milk allergy, 10 had positive clinical reactions after the milk rechallenge test, whereas 25 children had no reaction. The median sECP level of all the patients before the challenge test was significantly higher (12.4 microg/L) than that of the control group (4.3 microg/L) (P < 0.05). Two hours after the challenge, the median sECP of all patients (9.4 microg/L) was lower than the starting values. The median sECP levels were higher in children with positive challenge test results at all time points. However, this difference was not statistically significant. CONCLUSIONS: The normalization of sECP level may indicate the cessation of the cow's milk allergy. Therefore, the measurement of sECP may be helpful in determining the optimal time in which to repeat the challenge test, when the result will more likely be negative. The significant decrease of the sECP level 2 hours after the beginning of milk challenge test may be explained by the fact that this protein is excreted into the intestinal lumen.

[Serum eosinophil cationic protein (sECP) level after cow's milk challenge test in allergic children]. / A szérum eosinophil kationos protein szintjének változása tehéntejterhelést követóen allergiás gyermekekben.

The eosinophil cationic protein (ECP) level in the sera is higher in allergic diseases. The change of the ECP level in the sera of patients with cow milk allergy was examined during the cow's milk challenge test after a long cow's milk free diet period. The sECP level of 35 milk sensitive patients was determined by a fluoroimmunoassay (Pharmacia CAP System ECP FEIA) before the milk challenge test, as well as 2 and 24 hours after it. The average age of the patients was 16 (6-49) months. The basic sECP level of cow's milk allergic patients was significantly higher (12.2 micrograms/l vs. 7.0 micrograms/l, p < 0.05) than that of the control group (n = 20). The sECP level significantly decreased 2 hours after the milk challenge test (12.2 micrograms/l vs. 9.2 micrograms/l, p = 0.01), 24 hours after the challenge it was again on the basic level (11.2 micrograms/l, p = 0.26). Out of the 35 allergic children ten had positive clinical reactions after the milk challenge test (positive group), while 25 had no reaction after it (negative group). Comparing the sECP level of these two groups, no significant difference was found in the sECP level either before the milk challenge test or after it. The significant decrease of the sECP level 2 hours after the beginning of milk challenge test might be explained by the fact that this toxic protein is secreted into the bowel.

[Current view on the etiology of childhood bronchial asthma]. / A gyermekkori asthma bronchiale kórokának korszerü szemlélete.

In the last decades atopic diseases and among them the incidence of atopic asthma has increased significantly worldwide, first of all in countries of higher technical civilization. In many places the incidence has doubled in 10-20 years compared to the previous period. The investigations have provided a lot of new data about genetic alterations in the background of the disease but the modifications in the genetic material cannot be responsible for the increased frequency of the disease in such a short time. It has become clear that sensibilization in connection with allergens begins in the fetus and continues in the early period after birth. Environmental allergens, especially indoor ones, the allergen burden in extrauterine life, the nutrition factors and later airway inflammations caused by virus--all contribute to the spread of atopy. The harms of civilization contribute to the dominance of T helper 2 cells and therefore to atopy in our immunosystem. It seem, that otherwise useful components like the decrease of infective diseases, vaccinations, better hygienic conditions and "western" lifestyle also manipulate our immunosystem in the direction of atopy. Our existing knowledge can provide profilactic tasks against unfavourable processes only to a very small extent.

Is it possible to prevent asthma?

Atopic diseases and among them bronchial asthma seem to be the worldwide epidemic of the end of the 20th century and this tendency may continue even in the 3rd millenium. The main factors and periods which are important in the genesis of bronchial asthma are the following: genetic influences; intrauterine sensitization; factors in the perinatal life; influences in infancy; environmental factors in childhood; bronchial asthma and "western lifestyle"; prevention of further developing of atopic diseases.

[Multicenter studies of terfenadine-containing suspensions in children with hayfever]. / Multicentrikus vizsgálat terfenadin tartalmú szuszpenzióval szénanáthás gyermekeken.

Authors treated 50 seasonal allergic rhinitis ragweed sensitive patients with a second generation antihistamine, terfenadine containing suspension given twice/day for two weeks in the weeds season of 1996. Nasal (rhinorrhoea, stuffed nose, sneezing, itching) and eye symptoms (hyperaemia, itching, tearing), noted by the physicians and by the patients' diary, blood count, liver function, kidney function and ECG were examined. There was no meaningful difference between the symptoms registrated by the physicians and the patients. It was pointed out that according to both notes at all symptoms there was an improvement already on the 7th day of the treatment, which developed further for the 14th day. The only exception was rhinorrhoea which ameliorated only for the 14th day. ECG deviation related to the terfenadine treatment was not found. Repeated vomiting was experienced at one child. Transitional, slight SGOT, SGPT activity increase appeared in 4 children, the same was observed at two children in se kreatinine and carbamid nitrogen level. Nine patients needed (from the 7th day) supplementary local treatment (cromoglycate eyedrops or nasal spray).

Nasal immunotherapy in pollen-sensitive children.

UNLABELLED: Subcutaneous specific immunotherapy has a considerable risk of side effects, including severe life-threatening ones or even death. The disadvantages and problems of this kind of therapy gave rise to looking for new ways of hyposensitization. In allergic rhinitis the local (nasal) immunotherapy may be effective. We studied the efficacy of local nasal immunotherapy (Allerkin) in grass and ragweed allergic children suffering from seasonal atopic rhinitis. PATIENTS: 36 children (12 with grass pollen, 12 with ragweed pollen immunotherapy, 12 controls). METHODS: nasal provocation tests with increasing doses of Allerkin, skin prick test, diary cards. Schedule of the investigations: enrollment of the patients and nasal provocation tests; grass pollen and ragweed pollen preseasonal immunotherapy with increasing doses of Allerkin; during pollen season registration by symptoms and drug consumption; after the season nasal provocation tests. RESULTS: grass immunotherapy: nasal provocation threshold increased (P < 0.01), symptoms became fewer (P < 0.01) and drug consumption was less in the active group compared to control. Similar but less expressed tendencies were seen in the ragweed group. After the second year of immunotherapy the need for steroid treatment was significantly (P < 0.05) fewer in the immunotherapy group than in the control group. No side effects appeared during the course of immunotherapy, but some patients suffered from mild sneezing or nasal discharge after the Allerkin application. CONCLUSION: local (nasal) immunotherapy is an effective, safe and not troublesome alternative to systemic immunotherapy.

[Seasonal allergic rhinitis and pollen count (a 5-year survey in Budapest)]. / Szezonális allergiás rhinitis és pollenszám (Otéves felmérés Budapesten).

The authors compared the seasonal symptoms and the pollen allergen spectrum of pollen allergy with the 5-year aeropalynological data in Budapest. They summarized the average of symptom scores based on the diaries of 105 pollen allergic patients (mainly children) suffering from seasonal allergic rhinoconjunctivitis. The pollen allergen spectrum of the patients was defined. They constructed a local pollen calendar on the basis of the first regular pollen counting in Budapest, which had been done by them for 5 years. The symptom scores grew parallel with the increasing number of grass and ragweed pollen. Tree pollen allergy was found in 7.6 per cent of the patients. In spite of the high number of three pollen in the air in March and April the patients did not have too many complaints according to their symptom scores. Grass pollen allergy was found in 67.6 per cent of the patients and in the grass pollen season (May-July) the characteristic clinical symptoms were expressed. Weeds (in 64.8 per cent of the patients), especially ragweed (in 59.0 per cent of the patients) caused the most significant complaints in the late summer--autumn (August, September and partly October) period. Ragweed and other weeds play an important role in the etiology of seasonal allergic diseases in Hungary. The authors call the attention to the necessity of measures taken against the spread of ragweed.

[Effect of a mite-killing agent on house dust and on symptoms of house dust allergy]. / Atkaölö szer hatása a háziporra és a házipor allergiások tüneteire.

UNLABELLED: The efficacy of acaricid benzyl-benzoate (Acarosan) has been followed in an open study for one year in patients with house dust mite allergy; the clinical signs and the mite allergen level have been considered. METHODS: the furniture (beds, upholstered pieces, carpets) of 17 house dust mite allergic patients suffering from bronchial asthma and/or allergic rhinitis has been investigated. The mite content of the dust gained from the furniture has been determined with the help of the semiquantitative Acarex test. This test has been done before the mite elimination and 3, 6, 9 and 12 months after it. The registered clinical signs of the patients: symptoms, drug consumption, expiratory peak flow values have been measured twice a day. RESULTS: 9/17 beds have become free from mites, 6/17 beds have had less mites than before, 1/17 no change, 1/17 augmentation of mite content. The proportion of days free from complaints has been 26.8% at the beginning of the trial and 47.1% after 12 months, the drug consumption has diminished meanwhile. At the beginning of the trial 6 children had pathologic lability index based on peak-flow measurements, they improved significantly. The information about the mite content of the furniture gives help for the elimination measures. The chemical mite elimination reduces the mite content of the flat and results in clinical improvement of house dust mite allergic patients.

Use of beta 2-adrenergic drugs in obstructive respiratory tract diseases of childhood.

The chemical structure and clinical application of beta 2-mimetic drugs used currently in obstructive respiratory tract diseases of childhood have been discussed. It has been pointed out that these drugs may be used as bronchodilators in manifesting obstruction and as prophylactic agents in chronic forms of such obstructive diseases. The aerosol forms of these compounds are the most effective but this route of administration meets some technical difficulties and cannot be used in children younger than 5-6 years. In the treatment of this age group, besides the tablet and elixir forms, the aerosol inhalation is the most useful. Selective slow-release beta 2-mimetics introduced about 25 years ago are successfully used in form of monotherapy or combination therapy in respiratory tract obstructions.

[Incidence of obstructive respiratory diseases in 1839-1850 at the Hospital for Poor Children in Pest]. / Légúti obstruktív megbetegedések elöfordulása 1839-1850 között a Pesti Szegény-Gyermek Kórházban.

According to the observations of several authors the number of obstructive respiratory diseases kept rising during the past decades, at the same time this disease was infrequent in the last century as indicated by the sporadically detectable data pertinent to adult patients. The 1st Pediatric Department of the Semmelweis University of Medicine, legal successor of the Poor-Children's Hospital of Pest is in possession of the complete case reports of 5050 out-patients of the period between 1839-1850. It can be established on the basis of these records that the diseases of the lower respiratory tract were frequent. Approximately 7 disease forms were distinguished with 323 children who suffered from bronchopathies. Of them only 13 (0.26% of the total patient material) were spasmodic bronchitis. Agoston Schopf, director of the hospital wrote at this period his book on Pediatrc. This work as well as the preparatory material of further tomes show clearly that the doctors of the hospital were well acquainted with the method of physical diagnostics and were capable to diagnose obstructive respiratory diseases. These case records are assumably the only pediatric patient material of this period not only in Hungary but also in Europe. Data confirm that obstructive respiratory diseases were infrequent at this period in children.

[Clinical considerations on exercise-induced bronchoconstriction]. / Klinische Betrachtungen zum belastungsinduzierten Bronchospasmus.

With 378 children suffering from asthma authors performed three types of physical exercises. The correlation between the exercise induced bronchospasm and the clinical symptoms of asthmatics, first of all the severity of asthma, has been investigated. No significant correlation was found between the EIB and age, sex, somatic development, start and duration of asthma and frequent respiratory infections. The seriously ill patients had more serious and frequent EIB. As practical conclusion it can be established that the examination of asthmatic children with exercise induced bronchospasm is important from the point of view of sports, but also in judging the severity of asthma.