Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

Outdoor Mold and Respiratory Health: State of Science of Epidemiological Studies.

BACKGROUND: Fungal spores are the predominant biological particulates in outdoor air. However, in contrast to pollens or outdoor air pollution, little is known about their respiratory health risks. OBJECTIVES: The objectives were to conduct the first review of epidemiological studies on the short- and long-term effects of outdoor mold exposure on respiratory health in children and adults. METHODS: Health outcomes included asthma, lung function, and rhinitis. Cross-sectional and longitudinal epidemiological studies using quantitative measures of outdoor mold exposure (optical microscopy, culture-based methods) were selected, providing that important confounding factors including temporal trends or meteorological factors were accounted for. A systematic literature search was performed up to June 2020, leading to the selection of 37 publications. RESULTS: Most studies were longitudinal and investigated short-term effects. There is evidence of an association between outdoor fungal exposure and an increase in asthma exacerbation among children for total spores, 2 phyla (ascomycetes, basidiomycetes), and 2 taxa (Cladosporium, Alternaria). A few studies also suggested an association for Coprinus, Ganoderma, Aspergillus-Penicillium, Botrytis, and Epicoccum in children, but this needs to be confirmed. Some studies reported mold associations with rhinitis, lung function, and among adults, but these were few in number or inconsistent. DISCUSSION: Further ecological studies in different regions that measure exposure to all taxa over several years are required to better understand their impact on rhinitis, asthma exacerbations and lung function. Larger panel studies are necessary to identify threshold effects in susceptible individuals. Finally, further research should assess the long-term effects of outdoor mold.

Retrospective Study of the Upsurge of Enterovirus D68 Clade D1 among Adults (2014-2018).

Enterovirus D68 (EV-D68) has emerged as an agent of epidemic respiratory illness and acute flaccid myelitis in the paediatric population but data are lacking in adult patients. We performed a 4.5-year single-centre retrospective study of all patients who tested positive for EV-D68 and analysed full-length EV-D68 genomes of the predominant clades B3 and D1. Between 1 June 2014, and 31 December 2018, 73 of the 11,365 patients investigated for respiratory pathogens tested positive for EV-D68, of whom 20 (27%) were adults (median age 53.7 years [IQR 34.0-65.7]) and 53 (73%) were children (median age 1.9 years [IQR 0.2-4.0]). The proportion of adults increased from 12% in 2014 to 48% in 2018 (p = 0.01). All adults had an underlying comorbidity factor, including chronic lung disease in 12 (60%), diabetes mellitus in six (30%), and chronic heart disease in five (25%). Clade D1 infected a higher proportion of adults than clades B3 and B2 (p = 0.001). Clade D1 was more divergent than clade B3: 5 of 19 amino acid changes in the capsid proteins were located in putative antigenic sites. Adult patients with underlying conditions are more likely to present with severe complications associated with EV-D68, notably the emergent clade D1.

Burden and Characteristics of Severe Chronic Hypoxemia in a Real-World Cohort of Subjects with COPD.

BACKGROUND: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1<50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood. METHODS: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02<60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes). RESULTS: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02<60 mmHg and FEV1<50% (n=115, 13%), those with severe hypoxemia but FEV1≥50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification. CONCLUSION: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes. TRIAL REGISTRATION: 04-479.

NHP2 deficiency impairs rRNA biogenesis and causes pulmonary fibrosis and Høyeraal-Hreidarsson syndrome.

Telomeres are nucleoprotein structures at the end of chromosomes. The telomerase complex, constituted of the catalytic subunit TERT, the RNA matrix hTR and several cofactors, including the H/ACA box ribonucleoproteins Dyskerin, NOP10, GAR1, NAF1 and NHP2, regulates telomere length. In humans, inherited defects in telomere length maintenance are responsible for a wide spectrum of clinical premature aging manifestations including pulmonary fibrosis (PF), dyskeratosis congenita (DC), bone marrow failure and predisposition to cancer. NHP2 mutations have been so far reported only in two patients with DC. Here, we report the first case of Høyeraal-Hreidarsson syndrome, the severe form of DC, caused by biallelic missense mutations in NHP2. Additionally, we identified three unrelated patients with PF carrying NHP2 heterozygous mutations. Strikingly, one of these patients acquired a somatic mutation in the promoter of TERT that likely conferred a selective advantage in a subset of blood cells. Finally, we demonstrate that a functional deficit of human NHP2 affects ribosomal RNA biogenesis. Together, our results broaden the functional consequences and clinical spectrum of NHP2 deficiency.

Indoor exposure to particulate matter and volatile organic compounds in dwellings and workplaces and respiratory health in French farmers.

INTRODUCTION: Few investigations have related objective assessments of indoor air pollutants to respiratory health in farmers, in spite of the many rural environmental hazards to which they are exposed. Chemical air pollution has been particularly neglected. OBJECTIVE: We investigated the relationships of indoor exposure to particulate matter (PM) and volatile organic compounds (VOCs) to respiratory health in farmers. METHODS: Nineteen VOCs (5 families) and PM (from ultrafine to total suspended particles (TSP)) were objectively assessed in dwellings and workplaces in 109 French farmers during a week. To take into account multiple exposures, scores of exposure were computed for total VOCs and VOCs families. Individuals filled a standardized questionnaire and underwent spirometry with bronchodilation test. RESULTS: On average, VOCs concentrations were higher in dwellings than in workplaces. The reverse was observed for PM. When considering the mean concentrations of air pollutants for the whole farm (dwellings + workplaces), asthma (9.3%) was positively associated with elevated exposure to benzene (adjusted odds-ratio (ORa) = 6.64, 95%CI: 1.56-28.27), trichloroethylene (4.80, 1.00-23.30) and halogenated hydrocarbons score (2.9, 95% 1.3-6.8). Early airway obstruction (FEF25-75 < 80%, with normal FEV1 and FVC and FEV/FVC ≥ 70%) (29.8%) was related to elevated exposure to 2-butoxyetylacetate (11.49, 1.55-85.37) and glycol ethers score (2.0; 1.0-4.1) in the whole farm and to PM2.5 (ORa = 5.26, 95% CI: 1.09-25.28) in the granary/stable. The risk of Chronic Obstructive Pulmonary Diseases (FEV/FVC < 70%) (COPD) (4.26%) was found to be larger with elevated exposure to aldehydes (OR = 3.95, 1.09-14.26). CONCLUSION: Indoor chemical air pollution is detrimental to farmers' respiratory health. More epidemiological investigations with detailed exposure assessments and clinical measures of respiratory effects are needed in rural settings to corroborate these findings.

A TUG Value Longer Than 11 s Predicts Fall Risk at 6-Month in Individuals with COPD.

Risk of a fall is increased in individuals with chronic obstructive pulmonary disease (COPD), and is usually evaluated using the Berg Balance Scale (BBS), but this is difficult to perform in everyday clinical practice. We aimed to prospectively predict short-term fall recurrence in COPD patients using a predetermined cut-off value of the Timed Up and Go test (TUG). In stable COPD patients, we collected self-reported records of the number of falls in the previous year, and measured TUG and BBS scores for each individual. Records of fall recurrence were obtained prospectively at 6-months after the initial evaluation. Among the 50 patients recruited, 23 (46%) had at least one fall during the past year. The optimal diagnosis value for the TUG to detect a fall was 10.9 s with a sensitivity of 100% and a specificity of 97%. A cut-off of 11 s predicted fall recurrence with high sensitivity and specificity (93% and 74%, respectively). The TUG as well as the BBS score detected fallers, and a cut-off value of 11 s predicted fall recurrence. TUG could be easily incorporated into the scheduled functional evaluations of COPD patients, could predict the risk of a fall and when appropriate, could guide specific balance training exercises to prevent fall.

Exposure to Cypress Pollens and Subsequent Symptoms: A Panel Study.

OBJECTIVE: The objective of this panel study was to document the relationship between exposure to cypress pollen and allergic symptoms. METHODS: The study group included 47 patients with allergy to cypress pollen who completed a daily diary and a weekly evaluation of quality of life (QoL) during the cypress pollen season. Different patients were included in three consecutive pollen seasons: 2014-2015, 2015-2016, and 2016-2017. Daily cypress pollen counts were obtained from the National Aerobiological Network. Air pollution and meteorological data were recorded on a daily basis. The pollen-symptoms relationship was quantified by calculating odds ratios for an increase of 1 log of grains of pollen/m3, taking into account potential confounding factors. The QoL score was expressed with a beta coefficient that increased with 1 grain of pollen/m3. RESULTS: There was a marked increase in rhinitis and ocular symptoms during the pollen season, with a plateau effect at high levels of exposure, but no relationship with bronchial symptoms. The QoL score had a linear and significant relationship with the cypress pollen count. We did not detect any threshold level. CONCLUSION: This panel study demonstrated a significant association between exposure to cypress pollens and allergic symptoms, with a plateau effect for high exposures.

Relationship between gender and survival in a real-life cohort of patients with COPD.

BACKGROUND: Although COPD affects both men and women, its prevalence is increasing more rapidly in women. Disease outcomes appear different among women with more frequent dyspnea and anxiety or depression but whether this translates into a different prognosis remains to be determined. Our aim was to assess whether the greater clinical impact of COPD in women was associated with differences in 3-year mortality rates. METHODS: In the French Initiatives BPCO real-world cohort, 177 women were matched up to 458 menon age (within 5-year intervals) and FEV1 (within 5% predicted intervals). 3-year mortality rate and survival were analyzed. Univariate and multivariate logistic regression analyses were performed. RESULTS: For a given age and level of airflow obstruction, women with COPD had more severe dyspnea, lower BMI, and were more likely to exhibit anxiety. Nevertheless, three-year mortality rate was comparable among men and women, respectively 11.2 and 10.8%. In a multivariate model, the only factors significantly associated with mortality were dyspnea and malnutrition but not gender. CONCLUSION: Although women with COPD experience higher levels of dyspnea and anxiety than men at comparable levels of age and FEV1, these differences do not translate into variations in 3-year mortality rates. TRIAL REGISTRATION: 04-479.

Predictors in routine practice of 6-min walking distance and oxygen desaturation in patients with COPD: impact of comorbidities.

Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as <350 m. EID was defined by a minimum pulse oxygen saturation (SpO2)<90% and delta SpO2≥4% from baseline. Multivariate logistic regression analyses assessed the influence on 6MWD and EID of age, sex, obesity (body mass index, BMI >30 kg/m2), low BMI (BMI <18.5 kg/m2), modified Medical Research Council (mMRC) dyspnea scale, FEV1% pred, FVC % pred, hyperinflation and comorbidities including cardiovascular diseases. Results: Among 440 patients with available 6MWT data, a 6MWD <350 m was found in 146 patients (33%), which was positively associated in multivariate analyses with age and mMRC and negatively with resting SpO2 and FVC % pred (rescaled r2=0.34), whereas no comorbidity was associated with a low 6WMD. EID was found in 155 patients (35%). This was positively associated with hypertension and negatively with age, obesity, FEV1% pred and resting SpO2 (rescaled r2=0.37). Conclusion: 6MWD and EID exhibit different determinants in COPD with a minor impact of comorbidities limited to hypertension in EID and to obesity, which was unexpectedly associated with less EID. Other variables including age, routine resting lung function and SpO2 were weakly associated with 6MWD and EID. Altogether, these results suggest that 6MWT performance remains difficult to predict with routine clinical/functional parameters.

Indoor mould exposure, asthma and rhinitis: findings from systematic reviews and recent longitudinal studies.

Starting from the Institute of Medicine (IOM) and World Health Organization (WHO) reports, this review provides an overview of the literature published from 2006 to 2017 on the associations between indoor mould exposure and asthma and rhinitis separately in children and adults with a focus on longitudinal epidemiological studies.A systematic search of peer-reviewed literature was performed, including systematic reviews and meta-analyses, longitudinal, incident case-control and panel studies. 61 publications were identified reporting visible mould or mould odour or quantitative assessment of culturable fungi or mould species.In children, visible mould and mould odour were associated with the development and exacerbations of asthma, providing sufficient evidence of a causal relationship. Results from population-based studies in adults were too few and divergent to conclude at more than a limited level of evidence. Exposure to mould in a work building was associated with the incidence and exacerbations of occupational asthma, and we concluded at a sufficient evidence for an association. Systematic reviews, meta-analyses and longitudinal studies on the relationships between mould exposure and allergic rhinitis provide sufficient evidence of an association.This review extended the conclusions of the IOM and WHO reports, and highlighted the need for further longitudinal studies on asthma in adults, and on rhinitis.

Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD.

In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations. To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels. The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications. Three-year survival between groups was compared using Kaplan-Meier analysis. Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos. Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%). For all cutoffs, there was no difference between Eos+ and Eos- groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories). In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival. In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis. These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping.

Serum cytokine levels related to exposure to volatile organic compounds and PM2.5 in dwellings and workplaces in French farmers - a mechanism to explain nonsmoking COPD.

Although French farmers smoke less on average than individuals from the general population, they suffer more from COPD. Exposure to biological and chemical air pollutants in the farm may be the cause of these higher COPD rates. This study investigates the role of bio-contaminants, including the relationship of exposure to volatile organic compounds (VOCs) and fine particulate matter (of diameter of 2.5 µm [PM2.5]) objectively measured in the farm settings (dwellings and workplaces) to serum cytokines involved in COPD, in a sample of 72 farmers from 50 farms in the Auvergne region, France. Mean concentrations of VOCs were highest inside the home, while levels of PM2.5 were highest in workplaces (stables and granaries). After adjusting for confounders, high exposure to PM2.5 was significantly associated with a decreased level of serum cytokines (among others, IL13: ß: -0.94, CI: -1.5 to -0.2, P-value =0.004; IL8: ß: -0.82, CI: -1.4 to -0.2, P-value =0.005) and high exposure to VOCs according to a VOC global score with a decreased IL13 level (ß: -0.5, CI: -0.9 to -0.1, P-value =0.01). Moreover, respiratory symptoms and diseases, including COPD, were associated with a decreased level of serum cytokines significantly in the case of IL5. An alteration of immune response balance in terms of cytokine levels in relation to indoor chemical air pollution exposure may contribute to respiratory health impairment in farmers.

Climate and Allergic Sensitization to Airborne Allergens in the General Population: Data from the French Six Cities Study.

BACKGROUND: The results of international epidemiological surveys show large geographical variations in skin test reactivity but do not provide a rationale for such variations. OBJECTIVE: To assess the relationship between climate and allergic sensitization in schoolchildren. METHODS: In the present study, we analyzed data from a multicenter, epidemiological survey that included 6,461 schoolchildren, aged 9-11 years, living in 6 French cities scattered around France. The protocol also included a battery of skin prick tests to common airborne allergens. The crude prevalence of sensitization to each allergen was estimated for each city and then adjusted for potential confounding factors. This analysis was repeated for monosensitization and for allergens grouped into 2 categories: indoor allergens, i.e., house dust mite (HDM), cat, and cockroach allergens, and outdoor allergens, i.e., birch pollen, grass pollen, and Alternaria. We also grouped cities according to their location on the coast, i.e., Marseille and Bordeaux, or inland, i.e., Créteil, Clermont-Ferrand, Reims, and Strasbourg. RESULTS: A difference in prevalence of sensitization to each airborne allergen or allergens grouped into indoor and outdoor categories was found between cities, even after adjusting for potential confounding factors. Also, a higher prevalence of sensitization to HDM, cat dander, and, broadly speaking, indoor allergens, was found in children living on the coast than in those living inland, whereas they showed a lower prevalence of sensitization to birch pollen. Between-city differences in the prevalence of monosensitization were also statistically significant. Children living in coastal cities had a higher rate of monosensitization to indoor allergens and a lower prevalence of sensitization to birch pollen. The higher prevalence of allergic sensitization in children from coastal cities is most likely due to climatic conditions, such as proximity from sea and humidity. Differences in sensitization to birch allergens could be due to differential exposure to these pollen. CONCLUSION: These results indicate a role of environmental exposure in sensitization to perennial as well as seasonal allergens.

Changes in body mass index during childhood and risk of various asthma phenotypes: a retrospective analysis.

BACKGROUND: It is known that asthma is related to obesity but also to small birthweight. The objective of this study was to clarify this issue by assessing the putative relationship between the changes in corpulence between birth and childhood as assessed by body mass index (BMI) and asthma phenotypes. METHODS: The following status in corpulence was assessed in 7781 schoolchildren using quartile of BMI at birth and at around 10 (9-11 years): underweight at birth and at around 10, underweight at birth and overweight at around 10, overweight at birth and underweight at around 10, overweight at birth and at around 10, and the reference group constituted by all the other children in whom corpulence changes were not extreme. Determination of asthma phenotypes (allergic, non-allergic, and exercise-induced asthma) was based on a clinical examination including skin prick tests, an exercise challenge test, and a questionnaire. RESULTS: The risk of allergic asthma was higher in children with persistent underweight, children with persistent overweight, and children becoming markedly more corpulent. In boys, the risk of allergic asthma was significantly higher for the less corpulent children at birth, regardless of whether they remained so or become overweight. In girls, the risk of allergic asthma was significantly higher in those with persistent overweight. There were no significant associations between BMI changes and non-allergic and exercise-induced asthma. CONCLUSIONS: We observed that some extreme changes in BMI, persistent underweight, and persistent overweight in childhood increased the risk of allergic asthma.

Impact of current cough on health-related quality of life in patients with COPD.

BACKGROUND: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD. METHODS: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities. RESULTS: One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]). In univariate analyses, health-related quality of life (Saint George's respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54). CONCLUSION: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.

Identification of Antigenic Proteins from Lichtheimia corymbifera for Farmer's Lung Disease Diagnosis.

The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis.

Prevalence and association of asthma and allergic sensitization with dietary factors in schoolchildren: data from the french six cities study.

BACKGROUND: The prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study. METHODS: Cross-sectional studies were performed among 7432 schoolchildren aged 9-11 years in Bordeaux, Clermont-Ferrand, Créteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions. RESULTS: Asthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56-0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07-2.05]) and having lunch at the canteen 1-2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52-0.96]), lifetime asthma (0.76 [0.60-0.96]) and allergic sensitization (0.80 [0.67-0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50-0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47-3.93] and 1.51 [1.17-2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43-0.87]. None of the dietary factors was associated with BHR. CONCLUSIONS: Diet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy.