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In this article a French working party critically review the international literature to revise the definition, pathophysiology, treatment and cost of exacerbations of adult asthma. The various guidelines do not always provide a consistent definition of exacerbations of asthma. An exacerbation can be defined as deterioration of clinical and/or functional parameters lasting more than 24 hours, without return to baseline, requiring a change of treatment. No single clinical or functional criterion can be used as an early marker of an exacerbation. Innate and acquired immune mechanisms, modified by contact with infectious, irritant or allergenic agents, participate in the pathogenesis of exacerbations, which are accompanied by bronchial inflammation. In 2010, mortality is related to progression of exacerbations, often occurring before the patient seeks medical attention. The objective of treatment is to control asthma and prevent exacerbations. However, many factors can trigger exacerbations and often cannot be controlled. The efficacy of inhaled corticosteroids has been demonstrated on reduction of the number of exacerbations and the number of asthma-related deaths. This treatment is cost-effective, especially in terms of reduction of exacerbations., (Copyright © 2010. Published by Elsevier Masson SAS.)

Therapeutic management of asthma is based on the key role of lower airway inflammation. New treatments and inhalation devices in conjunction with international recommendations have contributed to improve asthma management. The aim of asthma treatment is to avoid acute asthma and to reduce or suppress symptoms, to permit normal life (familial, scholar or professional) and to normalize lung function. The final goal is to improve patient quality of life and must also integrate the benefice/risk ratio of treatment. Asthmatic patients need to be regularly followed by a physician. Recently, French Anaes recommendations suggested to base the medical follow up on asthma control checking. Beside treatment of chronic asthma, acute asthma remains a potential emergency that needs to be rapidly identified and treated, following strict rules of clinical management.

Experts designated by the "référentiels" committee of the SRLF analyzed the numerous articles published after the French consensus conference on the severe acute asthma of 1988. From their work, a revision of this consensus conference has been performed. The pediatric specificity has been added in this revision. There is no severity score able to predict the severity of acute asthma on admission. In every case, the nebulization of beta-2 agonists represents the priority treatment. The nebulization of anticholinergic associated with the beta-2 agonists induces a moderate additional effect. In the absence of response to nebulizations, the usefulness of the beta-2 agonists associated intravenous. Administration is not demonstrated. Corticosteroids should be administered using a 1 to 2 mg per kg dosage, but their efficacy is delayed. In adult patients, aminophylline should not be prescribe, but it is still used by some pediatricians. Other associated treatments (adrenaline, magnesium sulfate, helium-oxygen mixture) did not demonstrate their efficacy as adjunctive therapies. The therapeutic response should be evaluated using the peak flow determination.

Background: To determine if the addition of ipratropium bromide in the emergency department (ED) for the treatment of childhood asthma reduces rates of hospitalization and relapses for moderate and severe exacerbations., Methods: Patients were given an oral corticosteroid treatment (2 mg/kg) and received every 20 minutes either three nebulizations with albuterol (0.15 mg/kg) and ipratropium bromide (250 micrograms) or six nebulizations with albuterol alone (control group). The primary end point was the need for hospitalization, additional nebulizations or a relapse during the following week. Secondary end point included the effect of age., Results: One hundred and forty three children, two to 15 years old, were randomized to ipratropium or control groups and 121 were evaluated on day seven. As a whole, the control group was less often hospitalized or in relapse than those treated with three nebulizations of albuterol and ipratropium (17.5% vs 37.9%, p < 0.02). The ipratropium group reached the same result after three additional albuterol nebulizations. The benefit of anticholinergic therapy was observed for children less than six years of age who had a similar rate of success (73.5 vs 75.7%)., Conclusion: The association of ipratropium bromide to the first three doses of the albuterol protocol for acute asthma did not act as well as six nebulizations of albuterol alone. The effect was age dependent and two to six years old children needed more attention. Nevertheless the hospitalization rate did not support the use of ipratropium compared with repeated albuterol nebulizations.

The value of educational measures in consideration of the asthmatic patient appeared at first twenty years ago to the eyes of clinical physicians, generalists or specialists. Round about the year 76 the first associations for asthmatic patients were born, under pressure from pneumologists, with the aim of clarifying their illness to asthmatics, to counsel them and especially to enable them to associate their symptoms with their treatment, to assure them of a ready availability of materials more or less onerous to test, aerosolizers, nebulizers, ionizers of the environment, peak flow meters, inhalation chambers, acaricides.... Twenty years after these pioneers of this education of the patient to these responsibilities, the associations devoted to asthma as well as schools of asthma have recently been instigated in order to complete the venture on the ground, often with only feeble means. It is hardly necessary to make an illusion: asthmatic patients, children or adults within these associations are always the same: it is those who are prepared to stir themselves to take part in meetings. There remains the great majority of asthmatics who necessarily need a particular treatment that is adapted to their personal case: it is the duo of physician-pharmacist which is and which constitutes always the best point of impact to devote the time necessary at the best appropriate moment. Such is the aim of this presentation which should not be considered as a return to the past, but an advance towards the individualized formulation of patients by benefitting from the former experiences of corporative formations.

Half of the life of children is spent in schools. Emergencies may occur, due to food anaphylaxis or other allergic causes. Main clinical pictures are anaphylactic shock, laryngeal angioedema, acute asthma. Lethality is a risk. Recent French rules go into more details about the management of emergency cases and the need of training for teachers and other members of the educational staff. The need to use injectable i.m. adrenaline is underlined in a protocol with consents of parents and agreement of all parties. Eviction diets are not yet guaranteed so that parents are allowed to provide their children with suitable meals. The authors debate about the indications of such protocols.

We report a case of severe asthma initially considered as cortico-resistant. Clinical analysis of dyspneic attacks demonstrated they were atypical, sometimes associated with dysphonia and syncopes. Severity of clinical presentation was discordant with lung function tests. The diagnosis of vocal cord dysfunction was confirmed by ENT specialized examination. It showed paradoxal inspiratory adduction of the vocal cords triggered by exercise. Treatment remained however difficult, based on speech therapy, relaxation and psychotherapy. This observation underlines the influence of searching a vocal cord dysfunction in cortico-dependent asthma, especially if clinical presentation is atypical. Treatment of this condition may allow to decrease steroid treatment in such patients.

Three modes of inhaled therapy are available for the administration of bronchodilators in acute respiratory diseases in children: spacer devices, nebulizers, inhaled powders. Principles, medications available in France, and dosages, are presented. Acute asthma is the main indication.

This study investigated the efficacy of a system for continuous nebulization of terbutaline sulphate in the treatment of acute asthmatic crises in children. The equipment consisted of a condensation nebulizer attached to a 40 liter acrylic tent placed around the patient's head. A prospective, randomized and open clinical trial was conducted. Twenty eight children, 2 to 5 year-old, in acute asthmatic crises were selected. Fourteen were nebulized with terbutaline sulphate while in the control group the aerosolization was proceeded only with half diluted physiologic serum. All patients were administered aminophyline intravenously. The parameter used to evaluate the efficacy of the terbutaline sulphate nebulizing system was clinical improvement measured by the Wood-Downes Score. Two additional parameters indicating terbutaline sulphate absorption were used: reduction of potassium seric levels and positive chronotropic effect. The group treated with terbutaline sulphate showed greater clinical improvement than control group at the 12 hour protocol evaluation as well as lower seric potassium level. A positive chronotropic effect was also observed at the final protocol evaluation. The data showed, preliminarily, that (a) the system for continuous nebulization of terbutaline sulphate was effective in treatment of children's acute asthmatic crises, and (b) there was evidence attesting to the absorption of terbutaline sulphate by the children treatment with it.

Skeletal muscle myopathy is one of the main side-effects of systemically administered corticosteroids, and involves respiratory as well as peripheral muscles. After prolonged treatment with moderate doses of either fluorinated or non-fluorinated corticosteroids, chronic myopathy may occur. In patients, such myopathy is characterized by the gradual onset of proximal limb muscle weakness and a sudden increase in creatine excretion in 24h urine. This myopathy is associated with a generalized fiber atrophy of the quadriceps in which myopathic changes are present. Since these changes were also observed in animal models, it was concluded that steroid treatment was responsible for them. After cessation of treatment, recovery of muscle force occurs but may be protracted. The severity of corticosteroid-induced myopathy appears to depend upon the type of steroid used, the treatment duration, the dose and the treatment regimen where repetitive burst treatment effects are worse than those obtained with continuous treatment with the same dose. During short-term treatment with massive doses of corticosteroids as frequently used to treat status asthmaticus, acute myopathy may develop and is characterized by generalized fiber necrosis and rhabdomyolysis. Because such necrosis was not observed in animal studies, it was suggested that the necrosis may result from the combined effect of corticosteroids with other agents such as aminoglycoside antibiotics and/or muscle relaxants.

We report a case of spontaneous rupture of oesophagus revealed by a severe asthma attack, in a 78-year-old woman, with continuous dyspneic asthma treated with corticosteroids. We discuss the diagnostic difficulties in spontaneous oesophageal rupture, and emphasize the necessity for always looking for a triggering factor in case of severe attacks of asthma not responding to treatment.

Moderate asthma is a frequent disorder in general medicine. In 1990, the British Thoracic Society published their first guidelines on the management of asthma. Three years later, we have studied, using a questionnaire, the diagnosis and therapeutic criteria of moderate asthma used by general physicians, and comparing these to the guideline recommendations. Out of 46 physicians questioned in Bordeaux, 40 (87 per cent) agreed to participate in the study. Thirty two physicians (80 per cent) described as moderate an asthma which was mild according to the guidelines; eight physicians (20 per cent) described a moderate asthma according to the guidelines; twenty five (63 per cent) considered as severe a moderate asthma according to the recommendations, although eleven (28 per cent) considered it as moderate and four (10 per cent) did not give an opinion. In total, four (10 per cent) judged asthma severity according to the guidelines (Group R), twenty one (52 per cent) over-estimated the severity of moderate asthma (Group S), and fifteen (37 per cent) gave an inconsistent assessment (Group 1). Twenty six (65 per cent) prescribed an association of beta-2-agonists and inhaled corticosteroids for moderate asthma. Although most of the questioned physicians gave an appropriate treatment for moderate asthma treatment adapted to the severity of the situation, their therapeutic approach did not seem to be based upon the same criteria than that recommended in the guidelines.

Acute myopathy occurred in a 49-year-old woman hospitalized in the intensive care unit for status asthmaticus. She was given high-dose intravenous steroid therapy and intubated. Pancuronium bromide was used for prolonged curarization. Flaccid quadriplegia developed with preservation of the deep tendon reflexes. Muscle biopsy showed a myogenic process with disorganized myofibrils and selective loss of thick myosin filaments. This mainly myogenic process would result from the toxic effect of corticosteroids favored by prolonged curarization although the effect of other factors still remains unknown.

Ipratropium bromide is a synthetic derivative of atropine with little absorption when used in inhalation, and therefore little secondary effects. The authors review its pharmacological properties and therapeutic efficacy in the treatment of asthma in children. Combined nebulized inhalation of ipratropium bromide and beta 2 sympathomimetic results in a more efficient and more sustained bronchodilatation than beta 2 sympathicomimetic alone in the treatment of acute asthma in children. Ipratropium bromide should be usefully introduced in the therapeutic scheme of acute asthma in children. Further studies will be necessary in order to determine its efficacy and tolerance in infants.

Acute asthma can sometimes be severe and potentially life threatening. International guidelines have defined both characteristics of these severe attacks and the associated therapeutic instructions. The efficacy and feasibility of these recommendations were evaluated in 15 asthmatic patients who were admitted to hospital because a severe asthma attack. These patients fulfilled the criteria of severity defined by a British experts conference in the international guidelines published in 1990 in the British Medical Journal. A first line treatment was given to all the patients and included both systemic corticosteroids and inhaled beta 2-agonists. In case of failure, beta 2-agonists were given intravenously and oxygen was administered as required. Monitoring was carried out between the admission and the 8th hour using the following criteria: peak expiratory flow (DP), respiratory frequency (FR), and heart rate (FC). Both DP and FR significantly improved from 196 +/- 79 to 292 +/- 104 l/min (p < 0.01) and from 27.5 +/- 5.5 to 23.7 +/- 5.6 (p < 0.02), respectively. FR remained unchanged (97 +/- 13 vs 98 +/- 13; ns). There was a favourable outcome in all cases. beta 2-agonists administered intravenously were only necessary in two patients for whom no predictive factor could be determined. It is concluded that international guidelines are applicable to severe acute asthma. Inhaled route for beta 2-agonist is sufficient for the majority of patients presenting with the criteria defining severe acute asthma unless life threatening symptoms are present.

A female patient treated by mechanical ventilation with high doses of pancuronium and methylprednisolone for status asthmaticus presented with acute total areflexic and severe amyotrophic tetraplegia; she died after multiple organ failure. Muscle biopsy confirmed the clinical diagnosis of "acute corticosteroid myopathy", precipitated by a corticosteroid "disuse hypersensitivity" after pancuronium. The electromyogram showed a critical illness polyneuropathy, secondary to multiple organ failure. Nerve biopsy was normal. The respective parts played by corticosteroids, curare-like derivatives and intensive care in the genesis of unexplained difficulty in weaning from the ventilator are discussed.

The drugs used in asthmatic attacks must act on the two major mechanisms of the disease: bronchial obstruction and inflammation of the airways. Two main classes of drugs are available to reach these targets: bronchodilators, headed by beta 2-stimulants, and anti-inflammatory drugs of the corticosteroid family. Bronchodilatation obtained with beta 2-stimulants is the first and most effective treatment of the attack. These drugs are usually administered by inhalation: metered-dose aerosols with or without inhalation chambers, or nebulization for severe attacks. Very high doses can be used without fear of side-effects, the principal objective of this treatment being to relieve bronchial obstruction. In the absence of rapid and lasting improvement bronchodilators must always be combined with corticosteroids. In all cases medical supervision immediately after the attacks is necessary and the patient should subsequently be put under care of pneumologists.

After setting the essential rules of the emergency prescription in the dental office, the authors consider successively from a standpoint of properties, indications, contra-indications, danger of associating medications, presentation, use and posology. The medicines used in order to treat the different emergency situations that can arise in a dental practice.

A patient, treated by mechanical ventilation with pancuronium or atracurium and with intravenously administered corticosteroid for status asthmaticus, presented with rhabdomyolysis (severe amyotrophy and marked of creatine kinase activity) and acute flacid and areflexic quadriplegia, involving the proximal and distal muscles but sparing the cephalic musculature. After review of the investigations (biochemistry, electromyogram, muscle biopsy), the diagnostic of acute corticosteroid myopathy following status asthmaticus was suggested, and a pancuronium neuromuscular complication or a critically ill polyneuropathy excluded. The non-inflammatory rhabdomyolysis concerned all the fiber types. Predominantly distal weakness resolved six months after the insult, in spite of the laboratory recurrence of the rhabdomyolysis at the time of a new status asthmaticus briefly treated with corticosteroid.

Systemic corticosteroids are misused in children with acute asthma. Their misuse is one of the factors responsible for the recent increase in asthma mortality. Since 1980, 10 of 12 double blind randomized clinical trials have shown the beneficial effects of corticosteroids in acute asthma incompletely responsive to bronchodilatators. The value of early course-high dose-short term corticosteroid therapy is emphasized. The side effects of such short corticosteroid courses are minimal and transient. Management of asthma should be reconsidered if steroid courses are too frequent.

Although abnormal blood gases are unusual in status asthmaticus, hypercapnia indicates a considerable increase in bronchial resistance. The authors report their experience of 106 personal cases of acute severe asthma. Emergency management of acute respiratory failure consisted in symptomatic therapy (low rate oxygen or mechanical ventilation after nasal intubation). Corticosteroids, rehydration, antibiotics and beta-2 adrenergic agents were associated. Mechanical ventilation was necessary in patients who developed alterations of consciousness or PaCO2 above 60 mm Hg (8 kPa). In respirator-patients, sedative drugs were needed. Terbutaline and salbutamol were occasionally beneficial but epinephrine remains the drug of choice. In our series of 106 cases (79 with hypercapnia) the overall mortality was 3.8 p. 100. Of the 33 cases who underwent mechanical ventilation, there were 4 deaths (12 p. 100). A review of the literature showed a much higher mortality in other series.

The treatment of status asthmaticus remains poorly defined. Even the definition of the condition is controversial. We have therefore attempted to define a therapeutic protocol consisting of a combination of terbutaline, aminophylline and hydrocortisone administered parenterally. We have conducted a prospective evaluation of the effectiveness and tolerance of this protocol. 44 consecutive patients with status asthmaticus (defined as an abnormally severe episode of asthma with early or marked alveolar hypoventilation: PaCO2 greater than or equal to 5.20 kPa) were entered into the study over a period of 56 months. The effectiveness of this combination is reflected by the rapid improvement in the clinical and blood gas parameters, the relatively rare use of mechanical ventilation (of brief duration) and the low mortality. The tolerance proved to be excellent, as the terbutaline only had to be stopped in 1 case (permanently) and the aminophylline in one other case (temporarily). These initial results encourage us to a more aggressive approach in the early treatment of status asthmaticus with particular attention to the associated metabolic acidosis.

The fact that 1% of pregnant women are asthmatic raises the question of possible interactions between asthma and pregnancy. The effects of pregnancy on respiratory physiology are studied in a first chapter, while the second chapter is devoted to the effects of pregnancy on asthma. In round figures, 1/3 of the patients get worse, 1/3 are improved and 1/3 remain stable. The patients who deteriorate are those with very severe asthma and high IgE On the other hand, well-treated asthmas have no influence on pregnancy or foetal growth. All drugs classically used in asthma (theophyllines, beta-adrenergic stimulants [at a distance of delivery], atropine-like compounds and cortico-steroids) may be used by pregnant asthmatic women and should be prescribed in effective doses.

The treatment of childhood asthma should be considered with respect to age, severity and aetiology. Treatment should be instituted early from the first crisis in order to avoid progression to a more severe form. It consists of two aspects: the treatment of the acute episode and the chronic treatment. The treatment of the acute episode consists of using bronchodilators (BD) (rapid release Theophylline and/or beta agonists) to which one might add corticosteroids if the crisis lasts for more than a few hours or seems severe at the outset, an antibiotic should also be used as infection is often a trigger factor in infants. Maintenance treatment is necessary in asthmatics with frequent exacerbations. It should be tailored to the symptomatology and aetiology. The symptomatic treatment consists of a bronchodilator (slow release Theophylline or an atropine-like pharmacological derivative) to which one may add, in severe cases, corticosteroids which may be in the form of aerosol, or as rarely as possible by mouth. The second aspect of treatment relating to the aetiology is the most difficult to apply as childhood asthma is often multi-factorial: in allergic asthma the avoidance of allergens, disodium cromoglycate, ketotifen, and if necessary specific desensitization. In non-allergic asthma, physiotherapy, treatment of infectious foci, particularly ENT (ORL), and attention to psychosomatic features. When asthma is diagnosed and treated early the prognosis is transformed and progress towards chronicity is avoided.

Intravenous infusions of aminophylline expose the patient to the risk of overdosage related to the narrow safety margin of the therapeutic concentrations and to the great individual variability of its excretion. The aim of this study was to evaluate a simplified protocol designed to determine the optimal dose of theophylline based on total body clearance. Forty-four patients (average age: 63 years) admitted with decompensation of chronic respiratory failure (N = 33) or with status asthmaticus (N = 11) were studied. Theophylline was administered initially at a constant rate R0 (mg/kg/h) depending on serum theophylline concentrations on admission T0 (mg/l): R0 = 0.75 - 0.75 T0/20. Serum theophylline concentrations were measured at the 6th and 12th hours (T6 and T12) for calculation of clearance (Chiou et al. J. Pharmacokinet. Biopharm., 1978, 6, 135-151) and for adjusting dosage R. After 48 hours of treatment at this infusion rate, serum theophylline was again measured (T48) to check the adjustment of the dosage and recalculate clearance. In 11 patients T0 was greater than 15 mg/l (max = 44) and T12 was 10.5 +/- 6.4 mg/l. Theophylline was withdrawn in 6 patients with initial clearances less than 5 ml/kg/h (zero in 5 cases). T48 was within therapeutic values (10-20 mg/l) in 55 p. 100 of cases (21/38). Twelve patients had T48 less than 10 mg/l due to an increase in theophylline clearance (+ 80 p. 100 on average) related to improved right ventricular function in 7 cases. In 5 patients T48 was greater than 20 mg/l (max = 27.5) due to a fall in clearance (average -47 p. 100) which could have been caused by administration of erythromycin in 1 case and by dose-dependent kinetics in 2 cases. This protocol which is simple to carry out in practice allows early adjustment of dosage to give effective serum theophylline concentrations in over 50 p. 100 of cases. No serious cases of overdosage were observed, even in patients with high T0 and/or low initial clearances. Under-dosage and overdosage are related to large individual variations in theophylline clearance.

Thirty-two children were treated with nebulized salbutamol for acute asthma. Seventy-five per cent of the treatments were efficient, either after a first nebulization at 0.15 mg/kg (47% = group I), or after a second nebulization 45 min later, at 0.05 mg/kg (27% = group II). Twenty-five per cent of the treatments (group III) were inefficient or only partly efficient. The clinical tolerance was good except in two children. Group I and II presented differences only for the auscultation score. Children from group I and II were older and had less severe asthma than those from group III. On the basis of this study, nebulized salbutamol appears to be an affective and safe treatment for acute asthma. The repeated administration of low doses, shortly after the first nebulization increases the quality of the response.

A case is reported of a 56 year old woman admitted for status asthmaticus. She had no known history of cardiovascular disease. During the infusion of salbutamol, there appeared signs of myocardial infarction on the ECG trace. The patient did not complain of any symptoms suggestive of myocardial infarction. Closer cardiac examination and ultrasound revealed features of hypertrophic cardiomyopathy. The first ECG carried out on admission was in fact in favour of this diagnosis. The pathogenesis of this myocardial infarction is discussed: the long lasting hypoxaemia and the tachycardia induced by the salbutamol simulated hard exercise, poorly tolerated by patients suffering from hypertrophic cardiomyopathy. Also, this type of cardiomyopathy is known to be associated with impaired myocardial vasodilator reserve and small vessel coronary artery disease.