Predicting positive food challenges at the introduction of nuts in sensitised children

Rationale: Children with atopic diseases in early life are frequently found with positive IgE tests to nuts, without a history of previous ingestion. We aimed to identify risk factors for reactions to nuts at their first introduction. Methods: A detailed retrospective case note and database analysis was performed. Inclusion criteria were: patients aged 3 to 16 years who had had a standardized food challenge to peanut and/or tree nuts due to primary sensitisation to the nut (positive specific IgE or SPT). A detailed assessment was performed of factors relating to food challenge outcome with univariate and multivariate logistic regression analysis. Results: There were 98 food challenges (48% peanut, 52% tree nut) with 29 positive, 67 negative and 2 inconclusive challenges. A positive maternal history and a specific IgE > 2 kU/l were strongly associated with a significantly increased risk of a positive food challenge (OR 3.54; 95% CI 1.28 to 9.81; and OR 4.82; 95% CI 1.57 to 14.86; respectively). There was no significant association between the type of nut, age, presence of other food allergies, paternal or sibling atopic history, other atopic conditions or severity of previous reaction to other foods. Conclusions: We have demonstrated an association between the presence of a maternal atopic history and a specific IgE > 2 kU/l, and a significant increase in the likelihood of a positive food challenge in children with primary sensitisation to nuts. Although requiring further prospective validation we suggest these easily identifiable components should be considered when deciding the need for a nut challenge.

Immunotherapy reduces allergen-mediated CD66b expression and myeloperoxidase levels on human neutrophils from allergic patients.

CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation. RESULTS CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p<0.001). Myeloperoxidase activity in nasal lavage fluid was also significantly reduced by immunotherapy, as were the neutrophil cell-surface expression of CD66b and myeloperoxidase (p<0.001). Interestingly, CD66b expression was higher in neutrophils from nasal lavage fluid than those from peripheral blood, and immunotherapy reduced the number of CD66+MPO+ cells in nasal lavage fluid. Thus, immunotherapy positive effects might, at least in part, be mediated by the negative regulation of the CD66b and myeloperoxidase activity in human neutrophils.

Allergo-immunologie. 2 : Les réactions allergiques aux anti-inflammatoires non stéroïdiens [Allergic reactions to nonsteroidal anti-inflammatory drugs]

Allergy to nonsteroidal antiinflammatory drugs (NSAIDs) is a very common affliction, especially among patients with asthma and chronic urticaria. These reactions are most often of a non-immunological nature but related to pharmacologic intolerance and linked to arachidonic acid metabolism and leukotriene release. Therefore, crossed reactions implying all non-selective and semi-selective NSAIDs constitute the rule, especially during respiratory reactions to NSAIDs and for patients with chronic urticaria. In isolated acute urticaria, crossed reactions are difficult to predict so caution is necessary. Tolerance induction is possible, especially when aspirin has to be administered in small doses as antiplatelet agent. Finally, acetaminophen and selective NSAIDs as celecoxib are well tolerated by most of these patients. L'allergie aux anti-inflammatoires non stéroïdiens (AINS) est très fréquente, en particulier chez les asthmatiques ou dans l'urticaire chronique. Il s'agit en général de réactions non immunologiques, mais dues à une intolérance pharmacologique liée au métabolisme de l'acide arachidonique et à la formation de leucotriènes. Ainsi, les réactions croisées impliquant tous les AINS non sélectifs et semi-sélectifs sont la règle, surtout lors de réactions respiratoires aux AINS et dans l'urticaire chronique. Lors d'urticaire aiguë isolée, les réactions croisées sont difficiles à prédire, ainsi la prudence s'impose. Une induction de tolérance est possible, en particulier lorsque l'aspirine est nécessaire à dose faible, comme antiagrégant plaquettaire. Enfin, le paracétamol et les AINS sélectifs sont supportés par la grande majorité de ces patients.

Quality of life in patients with respiratory allergy is influenced by the causative allergen.

OBJECTIVE We aimed to analyze health-related quality of life (HRQOL) in adults with newly diagnosed respiratory allergy according to the sensitization profile for relevant aeroallergens in their usual area of residence. METHODS We performed a cross-sectional, epidemiological, observational, descriptive, multicenter study in allergy clinics in Spain. The sample comprised adults diagnosed with rhinitis, asthma, or both caused by significant allergens in their residential area (olive and/or grass pollen or house dust mite). Allergic rhinitis was classified according to the Allergic Rhinitis and its Impact on Asthma guidelines; asthma was classified according to the Guía Españiola para el Manejo del Asma (Spanish Guideline on the Management of Asthma). HRQOL was studied according to the ESPRINT-15 questionnaire and Mini Asthma Quality of Life Questionnaire. Control of asthma was measured using the Asthma Control Questionnaire 5. RESULTS We studied 1437 patients. Rhinitis was the most common respiratory disease. The HRQOL of rhinitis patients was lower in those sensitized to olive pollen only and in those with combined sensitization to olive and grass pollens. HRQOL associated with rhinitis was worse in patients diagnosed with both rhinitis and asthma than in patients diagnosed with rhinitis only. Asthma patients sensitized to olive pollen or olive and grass pollens had worse HRQOL. CONCLUSIONS In our study population, the HRQOL of patients with respiratory allergies varied with the allergen responsible for symptoms. In patients with rhinitis, the presence of asthma significantly worsened rhinitis-associated HRQOL.

Allergens Induce the Release of Lactoferrin by Neutrophils from Asthmatic Patients.

BACKGROUND Despite the evidence that Lactoferrin (Lf) is involved in allergic asthma processes, it is unknown whether neutrophils can be one of the main cellular sources of this key inflammatory mediator directly in response of an IgE mediated stimulus. The present study was undertaken to analyze this question. METHODS Neutrophils from healthy subjects (n = 34) and neutrophils from allergic asthmatic patients (n = 102) were challenged in vitro with specific allergens to which the patients were sensitized, PAF, or agonist mAbs against IgE-receptors, and the levels of Lf were measured in the culture supernatant. The levels of serum IgE together with the severity of symptoms were also analyzed. RESULTS Lf was released into the culture supernatant of neutrophils from allergic asthmatic patients in response to allergens and PAF. This response was highly allergen-specific, and did not happen in neutrophils from healthy donors. Allergen effect was mimicked by Abs against FcεRI and galectin-3 but not by FcεRII. The levels of released Lf correlated well with the levels of serum specific IgE and severity of asthma symptoms. These observations represent a novel view of neutrophils as an important source of Lf in allergic asthma. Importantly, the levels of released Lf by neutrophils could therefore be used to evaluate disease severity in allergic asthmatic patients.

The "Squeeze and Wheeze" Sign: A Useful Clinical Sign in Lung Sounds Analysis of Children With Acute Cough.

Cough is a very frequent symptom in children. Different reviews have tried to delineate the best approach to pediatric cough.1 Clinical evaluation remains the most important diagnostic initial step. Although the relations between cough and asthma are not straightforward,2 wheeze should be considered as a physical sign of increased resistance to air flow. Lung function testing is the gold standard for analyzing pulmonary resistance to air flow but has a limited practical value in young children. The clinical evaluation of the presence or absence of wheeze thus remains a primary clinical step in coughing children. Young children do not necessarily breathe deeply in and out when asked to. For years, the author has used a so-called "squeeze and wheeze" maneuver (SWM, see Methods section for definition) to elicit chest signs in young children. The basic idea is to increase expiratory flows in children who do not cooperate adequately during their lung sounds analysis. This study was realized to communicate the author's experience of a yet unreported physical sign and to study its prevalence in young children cared for in a general pediatrics practice.

IL-6 activated integrated BATF/IRF4 functions in lymphocytes are T-bet-independent and reversed by subcutaneous immunotherapy.

IL-6 plays a central role in supporting pathological TH2 and TH17 cell development and inhibiting the protective T regulatory cells in allergic asthma. TH17 cells have been demonstrated to regulate allergic asthma in general and T-bet-deficiency-induced asthma in particular. Here we found an inverse correlation between T-bet and Il-6 mRNA expression in asthmatic children. Moreover, experimental subcutaneous immunotherapy (SIT) in T-bet((-/-)) mice inhibited IL-6, IL-21R and lung TH17 cells in a setting of asthma. Finally, local delivery of an anti-IL-6R antibody in T-bet((-/-)) mice resulted in the resolution of this allergic trait. Noteworthy, BATF, crucial for the immunoglobulin-class-switch and TH2,TH17 development, was found down-regulated in the lungs of T-bet((-/-)) mice after SIT and after treatment with anti-IL-6R antibody, indicating a critical role of IL-6 in controlling BATF/IRF4 integrated functions in TH2, TH17 cells and B cells also in a T-bet independent fashion in allergic asthma.

Capacité de travail en cas d'affections pulmonaires

This short review begins by defining some basic medico-legal concepts such as "impairment" and "disability" and gives the corresponding terms in French and German. It is then shown how, in stable obstructive and restrictive respiratory diseases such as COPD and lung fibrosis, the degree of impairment can be assessed on the basis of FEV1 and indices of gas exchange. In the case of bronchial asthma, however, with its typically variable degree of airflow limitation, the amount of reversibility and treatment necessary to achieve optimum bronchodilatation must be taken into account. This can best be done using a score system. Impairment represents a base but in no way equals the final percentage of disability pension or compensation, which are always assessed by the competent administrative authority. However, it is the physician who specifies the amount and type of work an individual patient, with his or her particular degree of disability, can or cannot be expected to do.

Le choc anaphylactique [Anaphylactic shock]

Anaphylactic shock is an unexpected, sudden and sometimes deadly event that attacks the patient in 75% of the cases without pre-existent history of allergy. In general, drugs, hymenopteric poisons and nutrients (according to the recent concept) are responsible. Beside the classical IgE-mediated anaphylactic shock there exists another anaphylactic shock, identical in its clinical picture and treatment but not in the mechanism of development. Epinephrine is the only effective drug in case of respiratory (bronchial asthma, laryngeal edema) or cardiovascular (hypotension, arrhythmias, hypovolemic shock) manifestation. It has to be administered as rapidly as possible

De nouvelles méthodes pour relier le déclenchement des symptômes respiratoires à l'exposition aux moisissures

Un nombre de plus en plus important d'études proposent l'exposition aux moisissures de l'environnement intérieur comme un facteur majeur dans l'apparition de symptômes respiratoires chez l'adulte et dans le développement de l'asthme chez l'enfant. Afin de contrôler l'incidence de telles pathologies dans la population générale, il est indispensable premièrement, de déterminer le niveau d'exposition aux particules fongiques qui déclenche les symptômes et deuxièmement d'identifier un marqueur environnemental associé de manière significative au tableau clinique. La première étude, choisie dans le cadre de cette note, s'inscrit dans le premier volet. Elle explore la relation entre la colonisation par des moisissures des voies aériennes de personnes asthmatiques et la concentration en spores de ces espèces fongiques dans l'air des habitations. La deuxième étude répond à la deuxième problématique en montrant qu'un marqueur environnemental, la fraction de (1-3)-beta-D-glucanes présente à la surface des particules fongiques, est corrélée au tableau des symptômes cliniques.

Desarrollo y validación de ensayos rápidos para la detección de aeroalérgenos ocupacionales/ambientales: soja i proteinas séricas de paloma

Tanto el asma ocupacional como la neumonitis por hipersensibilidad, como es el pulmón del cuidador de aves, son patologías respiratorias que se pueden prevenir o disminuir su aparición mediante la evitación de la fuente antigénica. Para poder actuar de forma preventiva es de utilidad el disponer de ensayos rápidos que sean capaces de estimar la presencia de alérgeno de forma inmediata. En el marco de este proyecto de dos años de duración tenemos por objeto el desarrollar y estandarizar dos métodos rápidos, inmunocromatográficos, para la determinación de alérgenos de soja y de proteínas séricas de paloma. Alérgenos que han sido seleccionados por su importancia en el medio como agentes causales de asma y neumonitis por hipersensibilidad, respectivamente. También tenemos por objeto determinar la carga de alérgeno de soja en la fracción de partículas menores de 10 micrómetros (PM10) en los alrededores del puerto de Barcelona y comprarla con los niveles en los filtros de partículas suspendidas totales (TSP). Como pasos previos al desarrollo de los ensayos rápidos se han producido anticuerpos específicos frente al extracto de cáscara de soja de bajo peso molecular y frente al suero de paloma, se ha desarrollado un ELISA tipo sándwich para cada alérgeno y parte de los anticuerpos se ha conjugado con oro coloidal. El ensayo inmunocromatográfico para la soja presenta un límite de detección de 6.25ng/ml y ha sido validado mediante el análisis de 119 muestras ambientales, presentando una elevada especificidad y sensibilidad. El ensayo inmunocromatográfico para la determinación de antígenos séricos de paloma requiere ser validado. Mediante un métodos de ELISA de inhibición se han determinado los niveles de alérgeno de soja en filtros PM10 y TSP. A pesar de la buena correlación entre los niveles de alérgeno en ambos filtros, se observó una amplia variación en la proporción PM10/TSP entre días.

Passive smoking in babies: The BIBE Study (Brief Intervention in babies. Effectiveness)

Background: There is evidence that exposure to passive smoking in general, and in babies in particular, is an important cause of morbimortality. Passive smoking is related to an increased risk of pediatric diseases such as sudden death syndrome, acute respiratory diseases, worsening of asthma, acute-chronic middle ear disease and slowing of lung growth.The objective of this article is to describe the BIBE study protocol. The BIBE study aims to determine the effectiveness of a brief intervention within the context of Primary Care, directed to mothers and fathers that smoke, in order to reduce the exposure of babies to passive smoking (ETS).Methods/DesignCluster randomized field trial (control and intervention group), multicentric and open. Subject: Fathers and/or mothers who are smokers and their babies (under 18 months) that attend pediatric services in Primary Care in Catalonia.The measurements will be taken at three points in time, in each of the fathers and/or mothers who respond to a questionnaire regarding their baby's clinical background and characteristics of the baby's exposure, together with variables related to the parents' tobacco consumption. A hair sample of the baby will be taken at the beginning of the study and at six months after the initial visit (biological determination of nicotine). The intervention group will apply a brief intervention in passive smoking after specific training and the control group will apply the habitual care.Discussion: Exposure to ETS is an avoidable factor related to infant morbimortality. Interventions to reduce exposure to ETS in babies are potentially beneficial for their health. The BIBE study evaluates an intervention to reduce exposure to ETS that takes advantage of pediatric visits. Interventions in the form of advice, conducted by pediatric professionals, are an excellent opportunity for prevention and protection of infants against the harmful effects of ETS.

Smoking, prevalence of disease and health service utilization among the Swiss population.

The data of the 1981-83 Swiss National Health Survey "SOMIPOPS", based on a randomly selected sample of 4,235 individuals aged 20 or over representative of the whole Swiss population, were used to investigate the relation between smoking, prevalence of disease and frequency of health care utilization. The risks of several conditions, including hypertension, myocardial infarction and other heart diseases, asthma, tuberculosis and kidney disease were elevated among ex-smokers. The diseases showing elevated risks among current smokers and significantly positive dose-risk trends included acute bronchitis (relative risk, RR = 3.2 for heavy cigarette smokers vs never smokers), chronic bronchitis or lung emphysema (RR = 2.0), gastro-duodenal ulcer (RR = 1.8) and bone fractures (RR = 1.6). For respiratory conditions, the risk of pipe or cigar smokers was comparable to that of moderate cigarette smokers, whereas for ulcer (RR = 4.1) or fractures (RR = 2.0) the point estimates were even higher than for heavy cigarette smokers. Smokers tended to consult more frequently general practitioners, used more other outpatients services, and were more frequently admitted to hospital during the year preceding the interview. These effects were consistent across strata of age, socio-economic indicators, and persisted after allowance for major identified potential distorting factors. Thus, the results of this survey confirm that smoking is an important cause of morbidity and a major contributory factor to the use of health services.

Allergo-immunologie [Allergie rhinoconjunctivitis and immunotherapy: an uptodate]

Rhinitis and allergic conjunctivitis are frequent and may have severe impact on quality of life. Moreover risks of evolution of rhinitis to asthma are high, whereas conjunctivitis may either lead to eye-related complications when some topical drugs (such as steroids) are used, or when severe ailments are belatedly diagnosed. This article enables to review the treatment of allergic rhino-conjunctivitis. It also presents recent progress realized in the domain of allergen specific immunotherapy. In particular, this review underlines the search for hypoallergenic formulations that may minimize the risk of systemic allergic side effects as well as the use of new adjuvants to improve the efficiency of treatment and reduce its duration.

Prise en charge du patient avec bronchopneumopathie obstructive: ambulatoire ou hospitalière [Management of the patient with COPD: home case or hospitalization].

Acute exacerbation of COPD is one of the most common causes of hospital admission in patients affected with this disease. In most cases, consideration of differential diagnoses and assessment of important comorbidities will allow to make the decision whether or not the patient needs to be hospitalized. A decision to hospitalize will be based on specific symptoms and signs, as well on the patient's history. Contrary to bronchial asthma, a systematic action plan strategy is lacking for COPD. However, a disease management plan involving all the health care providers may have the potential to improve the patient's well being and to decrease costs related to these exacerbations.