Sociodemographic profile and types of psychiatric patient care management in the Brussels area

The development of bronchial hyperresponsiveness (BHR) in asthma is considered to be caused by inflammation of the airway. In IgE-mediated allergy BHR is related to the occurrence of late phase reactions. We have previously shown that exposure to low doses of allergen can cause isolated late reactions. These findings are potentially of clinical importance, since exposure to low, subclinical allergen doses may lead to bronchial inflammation and increasing bronchial responsiveness without necessarily causing immediate bronchoconstriction. This study was performed to investigate whether repeated exposure to low doses of allergen could induce a change in BHR. The trial comprised two groups of five and eight patients with a history of allergic asthma. They were submitted to a series of allergen inhalations for 5-7 days. They were given the same low allergen dose (1-10 biological units) each day. Before and after the allergen exposure period histamine challenges were performed. After the week of allergen inhalation the bronchial responsiveness was increased in 11 of 13 patients.     

Pathophysiology and treatment of alpha 1-antitrypsin deficiency

The pathophysiology of alpha 1-antitrypsin (AAT) deficiency and the use of alpha 1-proteinase inhibitor therapy in the management of emphysema caused by AAT deficiency are described. AAT deficiency is the most common genetic cause of liver disease in children and emphysema in adults. However, not all patients with AAT deficiency develop hepatic or pulmonary involvement. Changes in the composition of the AAT molecule have been associated with AAT dysfunction in liver disease, whereas lung disease occurs when AAT concentrations are reduced. A definitive diagnosis can be made through serum AAT phenotype determination. Therapy for liver disease induced by AAT deficiency consists of supportive measures. Therapy for pulmonary disease due to AAT deficiency includes AAT augmentation therapy along with supportive measures. The available product, alpha 1-proteinase inhibitor, is derived from fractionated plasma and has similar biological activity to native serum AAT. Clinical trials have demonstrated a positive effect on serum and lung concentrations of AAT with few adverse events. Two recombinant forms of AAT have also been developed; however, few trials have been published evaluating their safety and efficacy in AAT-deficient patients. Many questions remain unanswered concerning AAT deficiency and replacement therapy. AAT augmentation therapy appears to reduce the progression of emphysema in some AAT-deficient patients.     

Acute hematogenous osteomyelitis in childhood--correlation of clinical aspects, diagnostic parameters, therapy and prognosis]

Airway inflammation particularly with eosinophil infiltration is an almost invariant feature of asthma, though it may not be exclusive to asthma. BHR and atopy are common phenomena in asthmatics but not invariably so. Allergen-induced late asthmatic responses can increase non-specific hyperresponsiveness and bronchial responsiveness in turn is, at least from some studies, correlated with the degree of airway inflammation. Atopy is a major risk factor for the development of asthma and its persistence from childhood into adulthood. Airway inflammation occurs very early in the natural history of asthma. No therapeutic intervention in established asthma has been shown to achieve a cure or even modify the natural history of the disease. Therefore, further studies are urgently required to identify whether strategies of early intervention to prevent the development of airway inflammation will modify the natural history of the disease.     

Patterns in children''s fruit and vegetable consumption by meal and day of the week

Seasonal bronchial asthma causally connected with the exposure to pollen allergens is a chronic, eosinophilic mucosal inflammation of airway. This inflammation is the basis for the development of nonspecific bronchial hyperreactivity which is the most typical but mutable feature of asthma. Bronchial hyperreactivity often determines asthma intensity and the need of asthma treatment. The nonspecific bronchial hyperreactivity over two consecutive years was evaluated in 11 patients (2 women and 9 men) with seasonal bronchial asthma, sensitized to grass, remaining under the conditions of natural allergen exposure and out of this period. Bronchial reactivity to histamine was measured by Cockcroft's at all method. So called histamine threshold (PC20H) in mg/ml was assessed. The values of ventilatory parameters (FVC, FEV1) and asthma symptom scores were also measured. It was showed that nonspecific bronchial hyperreactivity significantly increased in subjects with seasonal bronchial asthma during natural pollen exposure. PC20H in two studies performed during this period decreased 3 and 6 times when compared to preseasonal values. The majority part of patients (80%) has the increased bronchial reactivity to histamine also beyond the of grass season when clinical symptoms of asthma and rhinitis are not observed. This postseasonal hyperreactivity could be the effect of the chronic inflammation process persisted from the period of natural allergen exposure. Continuous subthreshold, which means asymptomatic exposure to perennial allergens to which most of patients are sensitized, could be another reason of this hyperreastivity. The possibility of exposure to the activity of seasonal allergens the whole year in persons with asthma can not omitted, as the presence of pollens in the sample of the house dust in patient's flat is observed during the yield of pollen season. Nonspecific bronchial hyperreactivity in individual patients is fluctuated, which probably is not dependent on the intensity of natural allergen exposure.     

New drugs in asthma treatment. Leukotriene receptor blockers and leukotriene synthesis inhibitors

Asthma is an inflammatory airway disease. The patient is characterised by increased mucus secretion, mucosal oedema, bronchial obstruction of varying degree and bronchial hyperresponsiveness. Several cell types and a large number of mediators are involved in asthma-related inflammation and constriction of the airways. The leukotrienes constitute an important group of mediators in asthmatic inflammation. The study of specific leukotriene receptor antagonists and biosynthesis inhibitors has not only shed light on the underlying mechanisms in asthma, but also opened up the way to new treatment alternatives. As zafirlukast, a leukotriene receptor antagonist has just been licensed in Finland, it is a suitable opportunity to review the importance of leukotrienes in asthma and the use of agents that affect them.     

Methods of evaluating airway inflammation

Airway inflammation is a feature of bronchial asthma and can be quantified invasively with bronchial mucosal biopsy and bronchoalveolar lavage. The induction of sputum by the inhalation of hypertonic saline however is safer and more noninvasive when compared with such methods. Evidence of airway inflammation may be revealed by examining hypertonic saline-induced sputum for eosinophils, cytokines and eosinophil cationic protein. There is a clear need however to develop further noninvasive discriminant measurement of airway inflammation.     

The role of chemokines such as RANTES in allergic disease

Much attention has recently been focused on the role of allergic inflammatory reaction in asthma. Eosinophils are considered to be the major type of inflammatory cell involved in bronchial asthma, since eosinophil-specific granule proteins can damage bronchial mucosal cells. Chemokines related to the beta subfamily, the so-called platelet factor 4 (PF4) superfamily have been shown to stimulate human eosinophils or basophils, and are considered to be important mediators of inflammation. RANTES may be released from activated platelets and is considered to play an important role in various immune and allergic disorders. RANTES is a potent chemoattractant for various inflammatory cells such as eosinophils, as well as for memory T cells and monocytes, thus potentially recruiting these cells from the circulation to an inflamed focus. Involvement of eosinophils and T cells in bronchial asthma has also been reported. To extend our understanding of the participation of eosinophils, T cells, and RANTES in the pathogenesis of allergic disease, we demonstrated the important roles of chemokines such as RANTES in allergic disease.     

Serum matrix metalloproteinase-9:Tissue inhibitor of metalloproteinase-1 ratio correlates with steroid responsiveness in moderate to severe asthma

Asthma presents a variable clinical response to corticosteroids (CS). Because CS more likely act on inflammation than on tissue remodeling, the presence of bronchial structural changes in certain asthmatics may explain their limited clinical response to CS. Matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are, respectively, involved in tissue inflammatory processes and fibrogenic processes. Previous reports have suggested that MMP-9:TIMP-1 ratio may reflect the balance between these two processes in various diseases. This study evaluated the relation of this ratio and the response to CS in severe asthma. Twenty asthmatics with low baseline FEV1 (59 +/- 4% predicted) and >/= 30 % increase with beta2-agonist were recruited. Serum MMP-9 and TIMP-1 levels were measured and correlated with response to an oral CS trial (methylprenisolone 40 mg/d for 14 d). With oral CS, FEV1 changes (DeltaFEV1) ranged from -15 to +43%. The DeltaFEV1 closely correlated with the MMP-9:TIMP-1 ratios (rho = 0. 79, p = 0.0006). In conclusion, serum MMP-9: TIMP-1 ratio could predict the response of oral CS therapy in asthma. The low MMP-9:TIMP-1 ratio observed in subjects with little or no FEV1 improvement with CS supports the hypothesis that, in these asthmatic subjects, bronchial fibrogenesis predominates over inflammation.     

Respiratory pathology in the agricultural environment

Farmers are usually exposed to a wide variety of noxious organic or chemical substances. This explains why agriculture is probably one of the occupations where prevalences of respiratory diseases are the highest. Some diseases such as extrinsic allergic alveolitis, allergic asthma, silo filler's disease or pesticides-related fibrosis are classic and well described. Others, more recently identified although probably more frequent, remain often unrecognized. This is notably the case of agricultural chronic bronchitis and of organic dust toxic syndrome. Sometimes, these respiratory pathologies are intricate and lead to a complex presentation where signs of irritation or inflammation of the respiratory tract, bronchial hyperreactivity and chronic bronchial obstruction are mixed.     

A comparative assessment of the clinical efficacy of standard and low-volume plasmapheresis in treating patients with bronchial asthma and chronic bronchitis

21 patients with bronchial asthma and chronic obstructive bronchitis resistant to standard therapy have been exposed to discrete plasmapheresis. Changes in the bronchial tree inflammation measured by fibre bronchoscopy and activity of neuron-specific enolase (NSE) in bronchial wash-offs made it clear that low-volume plasmapheresis is not inferior in efficacy to the standard method. The trend in the fall of NSE activity as a marker of diffuse neuroendocrine system objectively reflects attenuating inflammation in bronchial mucosa in response to treatment of chronic obstructive diseases of the lungs using different techniques of plasmapheresis.     

Improving nursing education classroom environments

To study the characteristics of our outpatient clinic patients presenting with chronic cough as the sole symptom of bronchial asthma, and to evaluate the bronchial hyperreactivity of such patients in comparison with that of classic asthmatic patients with normal spirometry. For 3 years we studied 193 consecutive patients with chronic cough as the sole symptom, using the study protocol specified in the section on patients and methods. Sixty-three patients were diagnosed of bronchial asthma. Bronchial hyperreactivity was considered to be the cause of coughing based on reversibility testing or a positive methacholine test, along with response to specific antiasthmatic therapy. Forty-six (73%) of the 63 patients had unproductive cough and 28 (44%) coughed mainly at night. In 14 (22%) symptoms began with an upper respiratory tract infection. Wheezing could be heard in only 4 (6%). Diagnosis was based on reversibility in 11 (17%) and methacholine testing in 52 (83%). Mean PC20 was higher in patients diagnosed of variant cough. Unlike classic asthma, persistent and usually unproductive cough caused by asthma has few or no accompanying symptoms. The diagnostic yield of methacholine testing is high in such patients.     

Bronchial asthma: pathogenetic mechanisms and genetic aspects

At present there is a general consensus on the inflammatory nature of bronchial asthma. The main immunological features of the atopic state are represented by the ongoing expansion of Th2-like cells and production of IgE antibodies. IL-4 seems to represent the key factor for the differentiation of Th2-like cells, even though other cytokines have been recently proposed to play a some role. The possible genetic alterations which lead to the deregulated overexpression of IL-4 gene and of other genes of the same family in atopics are under active investigation. The existence of a polymorphism at level of IL-4 gene distal and proximal promoter has directly been shown. Even though IL-4 is required for the development and maintenance of atopic state, IL-5 certainly plays an essential role in the pathogenesis of bronchial inflammation in atopic, intrinsic and occupational asthma. On the basis of the findings emerged from new experimental models, it appears that there are different pathways by which T cell responses can develop bronchial eosinophilic inflammation but all the pathways have to lead to obligatory ongoing production of IL-5. The future research can be also addressed either to clarify the cytokines and/or other factors able to induce the differentiation and ongoing expansion of T cells prevalently producing IL-5, possibly involved in the pathogenesis of intrinsic asthma, either to understanding the nature of stimuli acting as etiologic factors. On the basis of the present acquisitions, IL-5 could represent the most important target of the new approaches to asthma therapy.     

Corticosteroid reversibility in COPD is related to features of asthma

Eosinophilic inflammation has been observed in the airways of patients with chronic obstructive pulmonary disease (COPD). A subset of patients clinically diagnosed as having COPD show a reversibility of airflow obstruction when treated with corticosteroids, and may consist of patients with features of asthma including reticular basement membrane thickening and eosinophilic inflammation. Twenty-five unselected patients clinically diagnosed as having COPD received a daily oral dose of 1.5 mg/kg body weight of prednisolone for 15 d to assess the relationships between the functional response to corticosteroids and the presence of features of asthma. Eosinophilic inflammation was characterized before the course of corticosteroid therapy by enumerating eosinophils in peripheral blood, bronchoalveolar lavage fluid (BALF), and bronchial biopsies, using EG2 monoclonal antibody, and by measurement of eosinophil cationic protein (ECP) in BALF. A response to treatment was defined by an increase in FEV1 of at least 12% from baseline values and an absolute value of 200 ml measured at the end of the treatment. Twelve of 25 patients responded to the treatment. By comparison with nonresponders, responders had a significantly larger number of eosinophils (p < 0.015), and higher levels of ECP (p = 0.013) in their BALF. The responders had a thicker reticular basement membrane than the nonresponders (p < 0.04). These results indicate that a response to prednisolone in patients diagnosed as having COPD might occur more readily in a subset of patients presenting with features of asthma.     

Clinical value of evaluating "markers" of cellular inflammation in monitoring bronchial asthma

In the base of bronchial asthma is a chronic inflammatory process which takes place in bronchial mucous membrane. The main cells of allergic reaction are: mastocytes., basophils, eosinophiles and others. There are many factors released from them in various periods of allergic inflammation. Evaluation of a concentration of these factors may be very usefull in diagnostic and treatment of bronchial asthma.     

Chronic bronchitis--alterations of the bronchial mucosa

The mucociliary transport system is usually an important defense system which protects the body against a variety of noxious agents. Reactions of the bronchial mucosa to chronic infections are seen in the ciliated cells, the amount of globlet cells, in modifications of the basement membrane underlying the bronchial epithelium and an altered percentage of inflammatory cells. In ciliated cells the following atypia can be seen: thickening of the ciliar membrane, swollen cilia, formation of compound cilia, disarrangement of microtubules. Common alterations of the basement membrane are: increased diameter of the basement membrane zone, inhomogeneous staining pattern of the basement membrane zone, formation of cytoplasmatic protrusions, formation of double layers of the basement membrane and increased number of cytoplasmatic bound vesicles. Structural abnormalities of the basement membrane will lead to disturbances of the zone of transition and have to be interpreted as a sign of disregulation in the process of diffusion and resorption. The inflammatory response of the epithelium during chronic bronchitis and asthma shows many similarities. The bronchial epithelium has a specific reaction pattern which supports the response against different noxious agents. So all findings have to be interpreted as unspecific pathological changes. All alterations may show different degrees of severity and are dependent on individual pattern and the severity of chronic process. Electronmicroscopical examinations in combination with lightmicroscopical findings and immuno-histochemistry and seen in context with clinical data help to understand the mechanism of the inflammatory process.     

Mechanisms of persistent airway inflammation in asthma. A role for T cells and T-cell products

The role of T cells in human allergic inflammation is just beginning to be understood. However, the data presented indicate how the T cell may be a pivotal cell to direct features of allergic inflammation in asthma, how the T cell may be able to transfer hyperresponsiveness, which is a feature of bronchial asthma, what some of the genetic factors are that may determine this process, and how an important precipitant of asthma, viral respiratory infections, may participate in this process. Its cells are isolated from patients with asthma and studied for their ability to generate proinflammatory failure. An expanded understanding of the chronic, persistent nature of asthma will become apparent.     

Aberrant functional organization in schizophrenia: analysis of EEG coherence during rest and photic stimulation in drug-naive patients

Participation in bronchial asthma pathogenesis of the epithelium, bronchial wall, effector cells of inflammation at various periods of the disease are described. Morphology of the bronchi between the attacks, at the height of the attack and at the experimental model of the bronchospasm is presented. The hypotheses of the bronchospasm and respiratory tract obstruction are discussed.     

Prolonged peribulbar anaesthesia with indwelling catheter: a preliminary report of 217 cases

Epidemiological aspects of attacks of bronchial asthma related to drugs are prospectively studied in inpatients of three teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM)-programme. Results are based on 34,840 individual patients (among 48,005 consecutive admissions) in the years 1974-1993. Between 1974 and 1993, every patient admitted to any of the three medical clinics in the CHDM programme was monitored for any suspicion of an adverse drug reaction (ADR); every drug exposure period during hospital stay was registered. Nineteen patients (0.05% of the 34,840 individual patients) had at least one attack of bronchial obstruction during hospitalisation, considered as probable or definite ADR. The frequency related to exposure periods in response to penicillins is 0.014%, to non-steroidal anti-inflammatories (NSAIDs) 0.0145, to acetyl salicylic acid (ASA) 0.018%, to paracetamol 0.008% and to beta-adrenoceptor blockers 0.26%. Of the 12 patients reacting to a drug with an allergic or idiosyncrasy/intolerance type of bronchial obstruction, 7 had a history of bronchial asthma (extrinsic or intrinsic), and 3 had the diagnosis chronic obstructive pulmonary disease (COPD). A history of bronchial asthma or COPD is confirmed to be a risk factor for this particular ADR. Of the seven patients with a bronchial obstruction to beta-adrenoceptor blockers, five were diagnosed with COPD, while two had neither COPD nor bronchial asthma. The relative risk for this pharmacological reaction in COPD patients was 96 (95% confidence interval 45-208) compared with non-COPD patients in the group of 3244 exposed to beta-adrenoceptor blockers.     

The Conconi test

Our purpose was to determine if the study of rhinitis is useful in the diagnosis of asthma. We formulated the hypothesis that the inflammation of the upper airway reflects the inflammation of the lower airway. It was found that there are allergens that produce rhinitis more frequently than asthma, and vice versa. This can be explained by size. This explanation, however, is questionable as the allergic proteins are extracted from the carrying agent, and through the lymphatic route or the blood, reach the entire human organism. It was also found that with bronchoalveolar lavage in allergic asthma it is possible to obtain the same results for eosinophils as with a nasal wash or using Citospyn. However, the results in the late phase are questionable. In the immediate phase and in the late phase, eosinophil cationic protein (ECP) was detected in the blood (in asthma) and in nasal washes (in rhinitis). In the immediate response tryptase was detected from the mast cells. The role of leukotrienes in asthma and rhinitis is well established in the early and late response. The use of leukotriene inhibitors guarantee their importance in the airway. Platelet-activating factor (PAF) has been demonstrated to increase vascular permeability and the use of antagonists were the best nasal feature. The inhalation of histamine caused bronchospasm, while instillation of histamine in the nasal passages increased resistance. With this information it seems that our hypothesis has been confirmed. Rhinitis and BHR together are equivalent to asthma, although the PFER decreases during the course of nasal provocation test (NPT) in nonasthmatic patients. In pure rhinitis patients, however, we find decreases in PFER due to effort. All this suggests that the study of nasal inflammation is still unclear with regard to bronchial inflammation.     

Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma

Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.