[Neurofibromatosis as a cause of breathlessness]. / La neurofibromatose rend souvent essoufflé.

INTRODUCTION: Type 1 neurofibromatosis, also called "Recklinghausen's disease" is among the most frequent autosomal dominant genetic disorders, with an incidence of 1:3500 births. It mainly affects the skin and peripheral nervous system. However, in its less frequent manifestations, are tumors such as meningocele and skeletal dysplasias leading to severe clinical presentation. CASE REPORT: We report the case of a 55-year-old patient with type 1 neurofibromatosis and dyspnea due to a large left thoracic meningocele combined with a significant kyphoscoliosis, causing a severe restrictive ventilatory defect, complicated by chronic respiratory failure and pulmonary hypertension. Symptomatic treatment with non-invasive ventilation permitted an improvement of the clinical situation. CONCLUSIONS: Our observation shows the complexity of the therapeutic support of the neurofibromatosis of type 1. The contribution of non-invasive ventilation was illustrated by the arterial blood gas and clinical improvements as well as improved quality of life, with an acceptable level of inconvenience to the patient.

[E-cigarette use in university students and its relationship to cigarette smoking]. / Vapotage chez les étudiants à l'université et relation avec le tabagisme.

INTRODUCTION: There is concern that e-cigarette use could be a risk factor for subsequent cigarette smoking. METHODS: This survey included a group of 1220 students at Aix-Marseille University who attended a check-up visit and volunteered to participate to the survey. They answered a standardized questionnaire relating to e-cigarette use, smoking habits and the relationship between both habits. Mean age of participants was 19.9 years and 56% of them were female. RESULTS: All students invited to the check-up examination attended and agreed to participate in the survey. 13.3% of students answered they had already used e-cigarettes, a higher proportion of boys (17.5%) than girls (10.0%), starting at a mean age equal to 19.2 years. Forty-six percent of them had already smoked cigarettes, more girls (55.0%) than boys (45.0%). Among current cigarette smokers, e-cigarette use had induced giving up smoking in 12.6% and a decrease in the number of cigarettes smoked in 30.1%. Twenty percent said they begun to smoke cigarettes after using e-cigarettes. DISCUSSION: E-cigarette use is much less prevalent than smoking conventional tobacco cigarettes. There is a strong link between both. E-cigarette use had allowed a cessation or reduction in tobacco smoking in half of users. E-cigarette users may go on to start tobacco smoking but prospective surveys are needed to know how this will evolve over time. E-cigarette use could also be a means to prevent or postpone cigarette smoking.

[The feasibility of screening for COPD and asthma in the general population]. / Faisabilité du dépistage de l'asthme et de la BPCO en population générale.

INTRODUCTION: There are very few surveys devoted to the prevalence of asthma and COPD in the general population. The Motorola Health System has been developed to make such surveys easier. OBJECTIVES: The main objective was to assess the acceptability and efficacy of the Motorola Health system in collecting health data at home in the context of an epidemiological study of respiratory health. The secondary objective was to determine whether a home-based survey would lead to a higher participation rate than a hospital-based survey. METHODS: Four hundred and eighty-three individuals were selected from the electoral rolls of the 15th district of Marseille and randomly divided into two groups: home-based and hospital-based. The protocol included a questionnaire, several measurements: height, weight, blood pressure, spirometry and pulse oxymetry, and blood sampling. All data were transferred to a portable computer. RESULTS: Data acquisition and transfer worked well. Among the 232 subjects from the home-based survey, 62 (26.7%) participated, whereas only 36 (14.3%) of the 251 subjects from the hospital-based group did so (P<0.001). In an additional telephone survey, participants (13.6%) and non-participants (11.0%) had the same (P<0.9) prevalence of asthma. CONCLUSION: The Motorola Health System allowed accurate data acquisition and transfer in the context of an epidemiological survey of respiratory health. A home-based survey gave a higher participation rate than a hospital-based one.

Evaluation of the Aspergillus Western blot IgG kit for diagnosis of chronic aspergillosis.

Immunoprecipitin detection (IPD) is the current reference confirmatory technique for anti-Aspergillus antibody detection; however, the lack of standardization is a critical drawback of this assay. In this study, we evaluated the performance of the Aspergillus Western blot (Asp-WB) IgG kit (LDBio Diagnostics, Lyon, France), a recently commercialized immunoblot assay for the diagnosis of various clinical presentations of chronic aspergillosis. Three hundred eight serum samples from 158 patients with aspergillosis sensu lato (s.l.) were analyzed. More specifically, 267 serum samples were derived from patients with Aspergillus disease, including 89 cases of chronic pulmonary aspergillosis, 10 of aspergilloma, and 32 of allergic bronchopulmonary aspergillosis, while 41 samples were from patients with Aspergillus colonization, including 15 cystic fibrosis (CF) and 12 non-CF patients. For blood donor controls, the Asp-WB specificity was 94%, while the kit displayed a sensitivity for the aspergillosis s.l. diagnosis of 88.6%, with a diagnostic odds ratio (DOR) of 119 (95% confidence interval [CI], 57 to 251). The DOR values were 185.22 (95% CI,78.79 to 435.45) and 43.74 (95% CI, 15.65 to 122.20) for the diagnosis of Aspergillus disease and Aspergillus colonization, respectively. Among the patients, the sensitivities of the Asp-WB in the diagnosis of Aspergillus colonization were 100% and 41.7% in CF and non-CF patients, respectively. The Asp-WB yielded fewer false-negative results than did IPD. In conclusion, the Asp-WB kit performed well for the diagnosis of various clinical presentations of aspergillosis in nonimmunocompromised patients, with an enhanced standardization and a higher sensitivity than with IPD, which is the current reference method.

[The epidemiology of pollen allergy]. / Épidémiologie de l'allergie pollinique.

The prevalence of seasonal allergic rhinitis can be established through surveys performed in a sample of the general population. These surveys are based on a questionnaire, which could lead to an overestimate of prevalence rates, and on measurements of specific IgE, which need to be interpreted in the light of the responses to the questionnaire. Such surveys are few in France and need to be updated. Risk factors for seasonal allergic rhinitis are genetic, epigenetic and environmental. Relationships between exposure to pollen and health can be documented through ecological and panel surveys. Panel surveys may give information on threshold levels and dose-response relationships. In addition to pollen exposure, global warming and air pollutants act as cofactors. Monitoring of both pollen exposure and its health effects should be encouraged and strengthened.

Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite allergy.

OBJECTIVE: To establish the prevalence and serum levels of IgE to commercial Der p 1, Der p 2, Der p 10 and the carbohydrate MUXF3 in house dust-mite allergic patients. To compare individual vs. allergen microarray methods. METHODS: Prevalence and serum levels of IgE to Dermatophagoides pteronyssinus extract and components Der p 1, Der p 2, Der p 10 and MUXF3, specific IgG4 to D. pteronyssinus, total serum IgE levels, and clinical features (age, asthma, rhinitis and atopic dermatitis) were determined in 123 patients (64 children) with the ImmunoCAP® method. ImmunoCAP ISAC® was performed in 24 patients. RESULTS: All patients had serum IgE to D. pteronyssinus. Prevalences of serum IgE to commercial components were Der p 1 93%, Der p 2 77% (Der p 1 or Der p 2 94%), Der p 10 28% and MUXF3 25%. Levels of D. pteronyssinus IgE strongly correlated with Der p 1 and Der p 2 IgE (r = 0.89 and 0.85 respectively), but not Der p 10 and MUXF3. ImmunoCAP® and ImmunoCAP ISAC® were concordant, but the quantitative correlation was poor. No clinical implication for the prevalence, levels, or molecular IgE reactivity profile to house dust mite components was found. CONCLUSIONS AND CLINICAL RELEVANCE: Commercially available Der p 1 and Der p 2 strongly correlate with IgE D. pteronyssinus. The lack of Der p 1 and Der p 2 IgE may help with differential diagnosis. Der p 10 serum IgE prevalence and levels suggest different patterns in food and mite-related tropomyosin sensitization. Serum IgE to carbohydrate MUXF3, although unexpectedly prevalent, were low and did not modify D. pteronyssinus IgE levels. Follow-up may be best carried out with individual rather than microarrayed components.

Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics.

BACKGROUND: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. OBJECTIVES: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. METHODS: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. RESULTS: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. CONCLUSIONS: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma

[Exposure to fine air particles and occurrence of allergic diseases: results of ISAAC-France phase 2]. / Exposition aux particules atmosphériques fines et développement des maladies allergiques de l'enfant. Résultats épidémiologiques issus de l'étude des six villes (ISAAC-2 France).

To evaluate whether fine air particles could be involved in the occurrence of atopy and allergic diseases, we performed a cross-sectional epidemiological survey involving primary schoolchildren living in six French towns with contrasted air pollution levels. Air pollution was measured during a week in the school yards and by standard air monitoring networks. Children get an examination in school looking for atopic dermatitis and bronchial hyperresponsiveness assessed by a standardized run test. Besides, parents or guardians provided past medical history and environmental data, especially on passive smoking. Overall, 5,338 children, aged 10.4 (+/-0.7) years, coming from 108 different schools and 401 different classes were included in the survey. Taking into account potential confounders, high exposure to proximity PM(2.5) was linked to a higher point prevalence of atopic dermatitis and hyperresponsiveness, to a higher cumulative prevalence of allergic asthma and a higher sensitization rate to common indoor allergens. Thus, these data suggest that chronic exposure to urban fine particles could be a risk factor for atopy, hyperresponsiveness and asthma.

[Indoor volatile organic compounds: concentrations, sources, variation factors]. / Composés organiques volatils intérieurs: concentrations, sources, facteurs de variabilité.

INTRODUCTION: Volatile organic compounds (V.O.C.) are part of urban air pollution and are also generated indoors from cleaning and maintenance products. BACKGROUND: VOC measurements are, on average, 10 times higher within homes than outside. Results of the national survey led by the Observatoire National de la Qualité de l'Air Intérieur demonstrated that up to 25% of French homes have very high or high concentrations of VOC. Indoor levels depend mainly on indoor sources. Aldehydes are included in many everyday life products. VOC originate from various household decorating and cleaning products. Some products are less detrimental to the environment and health and have special labelling. Indoor VOC levels also depend on the rate of air exchange and on household characteristics such as indoor temperature and humidity, age of the building, presence of smokers, and communication with a garage. VIEWPOINTS: The public may participate in maintaining good indoor air quality and the authorities should also improve regulations. CONCLUSION: VOC are part of everyday air pollution. Their sources and concentrations should be better monitored.

Reported prevalence and co-morbidity of asthma, chronic bronchitis and emphysema: a pan-European estimation.

OBJECTIVE: Comparable population-based data exist at the European level for asthma but not for chronic obstructive pulmonary disease. Data from the World Health Organization's Large Analysis and Review of European Housing and Health Status Study conducted in random samples from eight European cities were used 1) to describe the prevalence of chronic bronchitis and emphysema (CBE) and asthma according to socio-demography, addictions, physical activities and body mass index; and 2) to identify the co-morbidities of these respiratory diseases. DESIGN: A total of 6915 adults filled out a standardised questionnaire on health outcomes, including major respiratory diseases and individual characteristics. RESULTS: Data showed that in the year preceding the survey, 3.3% of individuals had been diagnosed or treated for asthma and 6.2% for CBE. One per cent suffered simultaneously from both. Large variations were observed between cities. Physical activities and never smoking were inversely associated with CBE, independently of socio-cultural differences between the eight cities. Furthermore, both asthma and CBE were significantly related to several non-respiratory diseases, after adjustment for potential confounders. CONCLUSION: Population-based data from eight European cities show that there is a link between chronic respiratory diseases and various non-respiratory co-morbidities that needs further investigation.

[Environmental factors for asthma severity and allergy: results from the EGEA study]. / Facteurs environnementaux de l'asthme sévère et de l'allergie: résultats de l'étude EGEA.

INTRODUCTION: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article. METHODS AND RESULTS: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis. CONCLUSIONS: New hypothesis will be tested in the near future from the second stage of this survey.

Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A double-blind, placebo-controlled study.

BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens. METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were randomized to receive immunotherapy or a matched placebo. Specific immunotherapy was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point score. RESULTS: Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001; 14 in each group completed year 2002. A statistically significant improvement (41%, p < 0.02) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was not significant. This significant improvement was greater at the peak of the 2002 pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly validates the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted.

Twenty five year mortality and air pollution: results from the French PAARC survey.

AIMS AND METHODS: Long term effects of air pollution on mortality were studied in 14,284 adults who resided in 24 areas from seven French cities when enrolled in the PAARC survey (air pollution and chronic respiratory diseases) in 1974. Daily measurements of sulphur dioxide, total suspended particles, black smoke, nitrogen dioxide, and nitric oxide were made in 24 areas for three years (1974-76). Cox proportional hazards models controlling for individual confounders (smoking, educational level, body mass index, occupational exposure) were applied, and frailty models used to take into account spatial correlation. Indicators of air pollution were the mean concentration. RESULTS: Models were run before and after exclusion of six area monitors influenced by local traffic (NO/NO2 >3 in ppb). After exclusion of these areas, analyses showed that adjusted risk ratios (95% CI) for TSP, BS, NO2, and NO for non-accidental mortality were 1.05 (1.02 to 1.08), 1.07 (1.03 to 1.10), 1.14 (1.03 to 1.25), and 1.11 (1.05 to 1.17) for 10 microg/m3 respectively. Consistent patterns for lung cancer and cardiopulmonary causes were observed. CONCLUSIONS: Urban air pollution assessed in the 1970s was associated with increased mortality over 25 years in France.

Air pollution and atopy.

Relationships between air pollutants and atopy can be studied within 3 different settings. In vitro, exposure of pollen to air pollutants induce morphological changes and seems to facilitate extrusion on allergenic material out of the pollen grain. In animal as well as in human experiments, air pollutants, especially diesel exhaust particulates, are able to trigger an IgE-response. Epidemiological surveys also show that air pollutants trigger symptoms in patients. In contrast, whether or not air pollutants can induce de novo allergic diseases is still a matter of debate. Some surveys suggest that, in humans also, air pollutants, especially diesel-exhaust particulates, could trigger allergic sensitization and development of atopic diseases. At home, other pollutants can be involved: volatile organic compounds have pro-inflammatory properties and favour T-cell sensitization. Relationship between exposure to secondhand tobacco smoke or occupational hazards and atopic sensitization have led to discordant results.

Increased prevalence of asthma and allied diseases among active adolescent tobacco smokers after controlling for passive smoking exposure. A cause for concern?

BACKGROUND: Whereas effects on allergic and respiratory health have been established for passive tobacco smoking, contradictory results still exist for active tobacco smoking. OBJECTIVE: Whether adolescents with asthma and allied diseases have higher rates of active smoking compared with adolescents without asthma was assessed after controlling for environmental tobacco smoking exposure. METHODS: A population-based sample of 14,578 adolescents was enrolled in an epidemiological survey on allergies in France. RESULTS: After controlling for age, sex, geographic region, familial allergy and passive smoking, current (in the past year) wheezing (12.4%), current asthma (5.6%), lifetime asthma (12.3%), current rhinoconjunctivitis (13.9%), lifetime hayfever (14.4%) and current eczema (9.3%) but not lifetime eczema (22.5%) were all significantly related to active smoking (>1 cigarette/day) (9.3%). A higher risk of current wheezing, current and lifetime asthma or current eczema was seen in smokers exposed to passive smoking compared with smokers not exposed to it using a polychotomous logistic regression model, in which the different modalities of exposure to active and passive smoking constituted the response variable. Passive smoking was significantly associated only with current diseases. Active smoking was also highly related to both severe asthma (OR=4.02; 95% confidence interval: 1.37, 11.79) and severe rhinoconjunctivitis (OR=2.95; 1.58, 5.49). The highest rate of adolescents suffering from the co-morbidity of lifetime asthma and hayfever (3.6%) was also seen in active smokers compared with passive and non-smokers (5.5% vs. 3.6% and 3.1%, respectively; P=0.001). CONCLUSIONS: Being asthmatic or allergic does not seem to act as a deterrent towards starting active smoking or continuing to smoke in adolescence. Results suggest the need for considering individual allergic status in programming health educational activities aimed at reducing smoking among adolescents.

Triggers in intrinsic asthma in the EGEA study.

The objective of the study was to compare triggers for asthma attacks in a group of intrinsic (IA) and extrinsic asthmatic (EA) subjects. We included 205 asthmatic patients divided, according to skin-prick tests, in a group (n = 63) of IA and a group (n = 142) of EA. The questionnaire provided information on associated conditions (nasal polyps and intolerance to aspirin) as well as on allergenic and nonallergenic triggers. Data analysis demonstrated that in IA, some airborne nonallergenic factors were significantly more often involved. In addition, this association did hold true when comparing subgroups of patients with normal baseline FEV1 values. For those subjects, PC20 and the slopes of the dose-response curves to metacholine were comparable. In conclusion, the higher sensitivity of a group IA subjects to some nonallergenic factors is not related to a lower baseline spirometric value in this subgroup. It may be hypothesized that, in these patients, sensitivity of airways irritant receptors might be increased.

Long-term mortality among adults with or without asthma in the PAARC study.

The Pollution Atmosphérique et Affections Respiratoires Chroniques (PAARC; Air Pollution and Chronic Respiratory Diseases) study provided the opportunity to examine the 25-yr mortality of 940 asthmatic adults drawn from a large population-based sample of 14,267 adults investigated during 1974-1976 in seven French cities. Vital statistics were collected in 2001 for the whole population. Multivariate survival analysis was used to assess exact survival rates in asthmatics and nonasthmatics taking relevant confounders into account. On average, the mortality rates obtained were 10.4 and 6.9 deaths 1,000 person-yrs-in asthmatics and nonasthmatics, respectively. On univariate analysis, asthma increased the relative risk (RR) of death by 1.48 (95% confidence interval (CI) 1.29-1.69). The association between asthma and death had an RR of 1.16 (95% CI 0.99-1.37) when age, sex, educational level, smoking habits, occupational exposure and forced expiratory volume in one second (FEV1) were taken into account. FEV1 was an important contributive factor causing increased risk of death in both smokers and nonsmokers. For instance, in asthmatics, the numbers of deaths due to respiratory disease and cancer appeared excessive. The present study suggests that asthmatics exhibit a higher risk of mortality.

[Factors associated with smoking in sixth grade (11-13 years old)]. / Facteurs associés au tabagisme en classe de sixième.

Because smoking begins most often in adolescence it is important to define clearly, with a view to prevention, the motivation of an adolescent to smoke. The role of the social group is well known. The aim of this study was to evaluate the potentially preventative role of knowledge in the field of respiration and the effects of cigarette smoke on one hand and of involvement in activities involving breathing on the other. The group studied was made up of 1,802 pupils at state schools, randomly selected, in the city of Marseilles. These pupils filled in an anonymous questionnaire in the classroom. The overall percentage of non-responders was very small. Overall 10.5% if the children declared that they had already smoked, more often boys (13.1%) than girls (8.1%). In contrast to smoking by the father, smoking by the mother and siblings significantly influenced smoking in the child. The child was not influenced by smoking by a sibling of the same sex. The proportion of children having already smoked increased progressively in proportion to the number of smokers in the household. Using a logistical regression analysis the following were predictive of smoking: being a boy, having a best friend who smoked, and the number of smokers in the family. On the other hand a history of allergy, an understanding of the effects of the environment on the respiratory system, knowledge of the effects of cigarettes, and finally involvement in sport, playing a wind instrument or singing in a choir were not associated with a lower incidence of smoking. These results call into question the effectiveness of the standard preventative methods and of anti-smoking programmes that are based on such strategies.