[Diagnosis of allergy in asthma]. / Le diagnostic de l'allergie dans l'asthme.

Allergy is a hypersensitivity reaction induced by immunological mechanisms. In asthma, allergy has a complex role and is usually IgE mediated. Allergy must be evaluated during the work up but evidence of IgE sensitivity does not mean that allergens play a role in the pathophysiology of the disease. The clinical relevance of the sensitivity has to be considered. This paper describes current available tools to screen for IgE sensitivity, allergen exposure and their role in asthma.

Nonallergic airway hyperresponsiveness and allergen-specific IgE levels are the main determinants of the early and late asthmatic response to allergen.

BACKGROUND: Conflicting results have been reported in studies of predictive factors for airway responsiveness to allergens during bronchial challenges. OBJECTIVE: The aim of this study was to assess determinants of airway responsiveness to 3 different allergens during standardized bronchial challenges. METHODS: Data were collected from asthmatic patients who participated in allergen challenge trials between 2000 and 2006 (cat, n = 37; house dust mite [HDM], n = 35; grass pollen, n = 27). PD20 (provocative dose causing a 20% fall in forced expiratory volume in the first second) methacholine, PD20 allergen, allergen skin test endpoint, allergen-specific immunoglobulin (Ig) E levels, and late asthmatic response were analyzed for each allergen group. RESULTS: During the early asthmatic response, a significant relationship was found between PD20 allergen and PD20 methacholine (P < .01 for cat, HDM, and grass pollen), as well as between PD20 allergen and allergen-specific IgE levels (P < .05 for cat and HDM). No relationship was observed between PD20 allergen and allergen skin test endpoint (P > .05). Late asthmatic response was significantly more frequent after HDM challenge than after cat or grass pollen challenges (57.1% vs16.2% and 33.3%, P < .01). Dual responders during HDM challenges had significantly higher allergen-specific IgE levels (P < .05) and higher nonallergic airway responsiveness (P < .05). CONCLUSION: Nonallergic airway hyperresponsiveness and allergen-specific IgE levels were the main determinants of early and late asthmatic responses. HDM challenges were the most interesting model with regard to the occurrence of late asthmatic response. In contrast to previous publications and to the official statement on standardized challenge testing with sensitizing stimuli, skin sensitivity appears to be a poor predictor of the early asthmatic response.

Nonallergic Airway Hyperresponsiveness and Allergen-Specific IgE Levels Are the Main Determinants of the Early and Late Asthmatic Response to Allergen

Introducción: Hay una gran controversia sobre los posibles factores predictivos de la respuesta a la provocación bronquial con alérgenos. Objetivos: El objetivo del estudio fue analizar factores determinantes de la reactividad bronquial frente a tres diferentes alérgenos durante la provocación bronquial estandarizada. Métodos: Se estudiaron los datos de pacientes asmáticos participantes en diversos estudios de provocación con alérgenos, realizados entre los años 2000 al 2006 (gato, n=37, ácaros del polvo, n=35, polen de gramíneas, n=27). Se analizaron para cada grupo de alérgeno la PD20 metacolina, la PD20 alérgeno, la titulación a punto final de la prueba cutánea, los niveles de IgE específica y la respuesta asmática tardía. Resultados: En relación con la respuesta inmediata, se observaron correlaciones significativas entre la PD20 alérgeno y la PD20 metacolina (gato, ácaros del polvo, polen de gramíneas; p<0.01), y también entre la PD20 alérgeno y los niveles de IgE específica (gato y ácaros del polvo; p<0.05). No encontramos correlación entre la PD20 alérgeno y la titulación a punto final de la prueba cutánea. Se observaron respuestas tardías de significativamente mayor frecuencia tras la provocación bronquial con ácaros del polvo que las observadas tras la provocación con gato o polen de gramíneas (57.1% vs. 16.2% y 33.3%; p<0.01). Los pacientes que presentaron respuestas duales durante la provocación bronquial con ácaros del polvo presentaban niveles más elevados de IgE específica (p<0.05) junto con una mayor reactividad bronquial frente a metacolina (p<0.05). Conclusion: La reactividad bronquial no relacionada con alérgeno y los niveles de IgE específica frente al alérgeno fueron los principales determinantes de la respuesta asmática inmediata y tardía. La provocación bronquial con ácaros presentaba frecuencias mayores de respuestas tardías. En contra de lo referenciado en la literatura, incluyendo un protocolo oficial de estandarización de la provocación bronquial, la reactividad cutánea parece un pobre factor predictivo de la respuesta asmática inmediata (AU)

Background: Conflicting results have been reported in studies of predictive factors for airway responsiveness to allergens during bronchial challenges. Objective: The aim of this study was to assess determinants of airway responsiveness to 3 different allergens during standardized bronchial challenges. Methods: Data were collected from asthmatic patients who participated in allergen challenge trials between 2000 and 2006 (cat, n=37; house dust mite [HDM], n=35; grass pollen, n=27). PD20 (provocative dose causing a 20% fall in forced expiratory volume in the first second) methacholine, PD20 allergen, allergen skin test endpoint, allergen-specific immunoglobulin (Ig) E levels, and late asthmatic response were analyzed for each allergen group. Results: During the early asthmatic response, a signifi cant relationship was found between PD20 allergen and PD20 methacholine (P<.01 for cat, HDM, and grass pollen), as well as between PD20 allergen and allergen-specific IgE levels (P<.05 for cat and HDM). No relationship was observed between PD20 allergen and allergen skin test endpoint (P>.05). Late asthmatic response was significantly more frequent after HDM challenge than after cat or grass pollen challenges (57.1% vs16.2% and 33.3%, P<.01). Dual responders during HDM challenges had significantly higher allergen-specific IgE levels (P<.05) and higher nonallergic airway responsiveness (P<.05). Conclusion: Nonallergic airway hyperresponsiveness and allergen-specifi c IgE levels were the main determinants of early and late asthmatic responses. HDM challenges were the most interesting model with regard to the occurrence of late asthmatic response. In contrast to previous publications and to the official statement on standardized challenge testing with sensitizing stimuli, skin sensitivity appears to be a poor predictor of the early asthmatic response (AU)

Indoor dust and air concentrations of endotoxin in urban and rural environments.

SIGNIFICANCE AND IMPACT OF THE STUDY: Rural dairy farming is associated with high exposure to indoor endotoxins as compared to rural nonfarming houses and urban houses. The time spent on the mattress (7 h for an adult) and of the proximity of the contaminated source should be taken into account with the other causes of exposure. Studies in European children from a farming background have shown that these children have a reduced risk of asthma and atopic sensitization compared to their urban counterparts. It has been suggested that this might be due to exposure to high levels of endotoxin in the farming environment. The aim of this study was to compare indoor endotoxin concentrations in air and dust samples from randomly selected urban and rural dwellings. In the rural area, endotoxins were analysed in farmhouses and nonfarmhouses as well as housing characteristics, lifestyle factors and agricultural practices likely to influence air and dust endotoxin levels. Endotoxin levels were significantly higher in floor (6600 ± 6100 vs 3600 ± 5600 and 3800 ± 17,000 ng g⁻¹; P < 0·001) and mattress dust (2900 ± 4100 vs 1100 ± 2400 and 800 ± 2600 ng g⁻¹; P < 0·001) from farmhouses compared to other rural and urban homes. However, no difference was observed between endotoxin concentrations in the air of urban and rural houses, and airborne endotoxin levels did not correlate to dust levels. Lack of ventilation and direct entry into the house were correlated with an increase in dust endotoxin levels. These results confirm that dairy farming is associated with high exposure to endotoxins in indoor dust samples. No difference was observed between indoor airborne concentrations between urban and rural houses. These results suggest that measuring endotoxin in dust is the most relevant method to assess endotoxin exposure.

[Respiratory allergens and asthma exacerbation]. / Facteurs déclenchants : allergènes respiratoires (usuels et professionnels).

INTRODUCTION: Asthma exacerbations are characterized by a progressive aggravation of respiratory symptoms such as dyspnea, cough, wheezing or chest tightness. BACKGROUND: The relationship between allergy and asthma exacerbations has been evaluated by epidemiological studies based on various criteria such as oral corticosteroid requirement, emergency room visits and hospital admission for asthma. Many studies have observed that deteriorating asthma can be related to increased exposure to allergens, particularly allergens from house dust mite, cockroach, cat, rodent, mold or pollen. Several studies have demonstrated that sensitization to respiratory allergens and allergen exposure increases the risk of exacerbation of asthma. When asthma exacerbations are work-related, occupational allergens may be implicated. CONCLUSIONS AND PERSPECTIVES: Most studies provide evidence that allergen exposure contributes to the risk of asthma exacerbations, but other precipitating factors, such as viruses, can interact and increase the risk.

[Relationships between indoor allergens, sensitization, and allergic asthma and rhinitis symptoms]. / Relation entre allergènes de l'environnement intérieur, sensibilisation et symptômes de rhinite et asthme allergiques.

INTRODUCTION: There is a strong and consistent association between immediate hypersensitivity, asthma and exposure to allergens. However, the role that the inhaled allergen plays and the timing of events related to sensitization are still controversial. BACKGROUND: Information obtained by studies of the follow-up of cohorts underlines the fact that there is no continuum between specific IgE responses and the development of childhood asthma. Allergic rhinitis and asthma result from a complex and multifactorial interaction between genetic factors, exposure to allergens, and many biological or chemical co-factors. However, when the child is exposed to an allergen, sensitization to the allergen is a risk factor for childhood asthma and severity of the disease. CONCLUSIONS AND VIEWPOINTS: Despite numerous epidemiological studies, the association and links between atopy, allergens, environment, sensitization and allergic rhinitis and/or asthma remain difficult to evaluate and poorly understood. Complementary studies are also necessary for the standardization of therapeutic strategies.

[Health effects of domestic volatile organic compounds]. / Effets sur la santé des composés organiques volatils de l'habitat.

INTRODUCTION: Most human environments are characterised by the presence of a large number of chemical substances which belong, for the most part, to the group of volatile organic compounds (VOC). BACKGROUND: The first epidemiological transverse studies have revealed that respiratory symptoms could be related to high domestic exposure to VOC. More recently, the results of longitudinal studies have suggested a possible influence of VOC exposure on the immune status of the newborn child after maternal exposure, the enhancement of sensitisation and the risk of asthma or respiratory symptoms. VIEWPOINT AND CONCLUSIONS: Further studies are needed to understand the mechanisms underlying the health effects of VOC. These should rely on greater knowledge of the individual exposure concentrations of these compounds and their sources. Proposals to improve the indoor environment could be made to reduce exposure and prevent the health effects of VOC.

Inhaled formaldehyde exposure: effect on bronchial response to mite allergen in sensitized asthma patients.

BACKGROUND: Formaldehyde, an indoor air pollutant, is known to be an irritant and an etiologic factor in occupational asthma. An epidemiologic study suggests that it may also increase the risk of childhood asthma for concentrations above 60 microg/m(3). AIM: To evaluate the influence of pre-exposure to low-dose formaldehyde (100 microg/m(3) in 30 min according to the World Health Organization's recommended maximum value for indoor environments) on bronchial response to Dermatophagoides pteronyssinus. METHOD: Nineteen asthmatic subjects were included. Each subject underwent a mite allergen bronchial challenge test immediately after a standardized exposure in a chamber to formaldehyde or air (random order). Induced sputum were collected 24 h before and after mite challenge. RESULTS: After formaldehyde inhalation, patients developed an immediate bronchial response at a significantly lower dose of mite allergen than after air exposure (the geometric mean PD(20) for Der p 1 was 34.3 ng after formaldehyde and 45.4 ng after placebo, P = 0.05). The late-phase reaction, expressed as the maximum fall in forced expiratory volume in 1 s (FEV(1)) from baseline, was significantly higher after formaldehyde (15%vs 11%, P = 0.046). CONCLUSION: Our study demonstrated that exposure to low levels of formaldehyde significantly enhanced bronchial responsiveness to mite allergen in mite-sensitized subjects with asthma.

Low-dose endotoxin in allergic asthmatics: effect on bronchial and inflammatory response to cat allergen.

BACKGROUND: Endotoxin was proposed to increase the severity of asthma. Endotoxin levels greatly differ according to settings. In domestic environments, airborne concentrations may be dramatically low compared with levels reported in occupational settings. OBJECTIVE: Our first objective was therefore to assess the effect of inhalation of low-level lipopolysaccharide (LPS) on the immediate and late-phase asthmatic bronchial response. Our second objective was to evaluate the effect of exposure to LPS on the local and systemic inflammatory response. METHODS: Nineteen asthmatics sensitized to cat underwent on two separate occasions a bronchial challenge test to cat allergen (cat BCT) preceded randomly by a pre-exposure to either saline or LPS (2 microg). Methacholine challenge test was performed 24 h before exposure to LPS or saline. The Borg scale for dyspnoea and lung function were recorded before and after exposure to LPS or saline, and before and after cat BCT. Induced sputum and blood samples were collected before and after cat BCT, and analysed for cell counts and eosinophil cationic protein (ECP) levels. RESULTS: Inhalation of 2 microg LPS did not induce any changes in forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), FEF 25-75 and Borg scale of dyspnoea. It neither modified Fel d 1 PD20 (45.03 ng as compared with 87.03; P=0.42). As well, there was no significant difference in late-phase reaction. Pre-exposure to LPS did not influence eosinophil counts or ECP levels in blood and sputum. CONCLUSION: Our study demonstrated that pre-exposure to LPS at low levels, which may be encountered in domestic environment, had no significant effect on the immediate and late-phase bronchial response to cat allergen. It neither modified local and systemic eosinophilic inflammation.

[The bronchial response to inhaled formaldehyde]. / Le formaldéhyde inhalé et la réponse bronchique.

INTRODUCTION: Formaldehyde is an ubiquitous indoor chemical polutant. Occupational exposure to high concentrations has revealed its irritant and allergenic potential. Nevertheless, domestic exposure to low concentrations may also have an effect on respiratory health in a non-specific way, just as has been found for other pollutants. STATE OF KNOWLEDGE: Potentiation of the response to allergens has been observed in animals and children. This effect has also been found on respiratory symptoms, with a 39% increase in the risk of asthma for a domiciliary exposure of more than 60 microgrammes.m(-3). We have recently been able to show, in a study with asthmatics sensitised to house dust mite, that the response to allergen provocation was increased following a 30 minutes exposure to 100 microgrammes.m(-3) formaldehyde. VIEWPOINT AND CONCLUSIONS: All the data show that mild exposure to formaldehyde in the home is sufficient to provoke sensitisation and also an aggrevation of symptoms in patients with allergic asthma. Taking into account the published evidence it is advisable that the concentrations of formaldehyde in domestic products should be made known in order to improve domiciliary air quality.

[IgE and respiratory disease]. / Immunoglobuline E et maladies respiratoires.

INTRODUCTION: IgE is known to provide the biological basis for allergy and immediate hypersensitivity. However, recent data provide some evidence that IgE responses are involved in other inflammatory processes apart from allergy, including several respiratory diseases. STATE OF THE ART: IgE binds to mast cells and basophils but also to other inflammatory cells, which are involved in non-allergic processes. IgE has a role in antigen presentation and is implicated in a number of other immune mechanisms. In the airways, IgE plays an important role in bronchial hyperactivity, even in the absence of an allergen. Epidemiological studies have demonstrated that IgE response is related not only to allergy but also to asthma symptoms, in the presence or absence of atopy, as well as exposure to cigarette smoke. IgE response is altered in several respiratory diseases including extrinsic and intrinsic asthma and allergic bronchopulmonary aspergillosis. CONCLUSION AND PERSPECTIVES: Since anti-IgE monoclonal antibodies are now available for administration to humans, a better understanding of the IgE response may allow the identification of novel therapeutic targets in the field of respiratory disease.

[Pharmacists' role in the management of asthma: a survey of 120 pharmacists in Bas-Rhin]. / Prise en charge de l'asthme à l'officine: enquête auprès de 120 pharmaciens du Bas-Rhin.

INTRODUCTION: The pharmacist plays an essential role in the management of the asthmatic patients on account of their frequent visits to the pharmacy to obtain their medication. METHODS: In order to evaluate the practice and knowledge of asthma among the pharmacists of the department of Bas-Rhin, 120 pharmacists were selected at random to reply to a standardised questionnaire. RESULTS: The 86 pharmacists who replied to the questionnaire had a good general understanding of asthma and its treatment. However, only 26.4% knew all the criteria of the severity of an attack of asthma. Among the 57 pharmacists who gave a demonstration of the use of inhaler devices, 16.3% showed all the steps in the use of a metered dose aerosol. These results are comparable to those of non-specialist doctors and nurses in whom poor techniques were found in 63-100% and 65-96% respectively. The mean scores of the pharmacists were 10.5/12 (+/- 1.2) steps for metered dose aerosols, 10.4/11 (+/- 1.0) for the Tubuhaler, 9.3/12 (+/- 1.7) for the Autohaler and 8.1/9 (+/- 0.9) for the Volumatic spacer. The asthmatic patient's main expectation of the pharmacist concerned the use of the prescribed systems (87.2%), underlining the lack of information received by the patient at the time of prescription. CONCLUSIONS: An improvement in the knowledge of the signs of severity of asthma and the use of inhaled devices could usefully be one of the objectives in the training of a dispensing pharmacist.

[Critical analysis of hypotheses explaining the increase in respiratory allergens]. / Etude critique des hypothèses explicatives de l'augmentation des allergies respiratoires.

There are three hypotheses to explain the relation between allergens and other factors and the onset of atopy: the hygiene hypothesis, the TH2 like hypothesis and the allergenic hypothesis. None of them have been confirmed. It seems necessary to wait for the results of prospective studies before giving recommendations for primary prevention of respiratory allergic diseases. In contrast, tertiary prevention appears as an essential method for treatment of allergic diseases.