Short-term effect of outdoor mould spore exposure on prescribed allergy medication sales in Central France.

BACKGROUND: Outdoor moulds are classically associated with exacerbations of asthma. OBJECTIVE: The aim of this paper was to examine nasal allergy morbidity by studying the short-term relationship between mould spore exposure and daily sales of reimbursable anti-allergic treatment in central France. METHODS: The relationship between daily changes in mould concentrations and daily sales obtained from the national healthcare database was analysed with generalized additive models, taking into account confounding factors such as air pollution, weather conditions, pollen counts, and days of the week. RESULTS: During the study, the average total yearly number of treated people was around 10 000 over approximately 230 000 surveyed. The relative risk (95% CI confidence interval) of sales of oral antihistamines with topical treatment associated with an interquartile increase in mould concentration was significant for Cladosporium 1.079 [1.019-1.142] and Aspergillus-Penicillium (Asp-Pen) 1.051 [1.021-1.082] in the whole population. When the influence of age and sex was considered, the relationship was significant only in male children aged 0-12 years and those aged between 13 and 49 years for Cladosporium: 1.256 [1.081-1.460] and 1.151 [1.063-1.245], respectively. The relationship was also significant for Asp-Pen: 1.038 [1.003-1.075] for those aged between 13 and 49 years and 1.056 [1.007-1.108] for adults over 50 years of age. CONCLUSION: The association between prescribed daily sales of oral antihistamines with topical treatment sales is associated with temporal changes to Cladosporium and Aspergillus-Penicillium in the whole population. When the influence of age and sex was considered, these two moulds contributed to prescribed medication sales only in the male general population.

Airborne pollen levels and drug consumption for seasonal allergic rhinoconjunctivitis: a 10-year study in France.

BACKGROUND: Few time-series studies, and none lasting longer than 4 years, have investigated the etiology of treated seasonal allergic rhinoconjunctivitis (SAR) on the basis of anti-allergic medication prescriptions. The aim of this article was to study the short-term relationship between pollen exposure and drug-treated SAR over 10 years in an urban area in central France. METHODS: A SAR case was defined as the association between an oral antihistamine and a local anti-allergic drug on the same prescription. The relationship between daily changes in pollen concentrations and daily changes in the number of treated SAR cases was analysed using generalized additive models, taking into account confounding factors such as air pollution, weather and days of the week. RESULTS: Between 2003 and 2012, the total yearly number of treated SAR cases rose from 7265 to 11 315. The relative risk of treated SAR associated with an interquartile increase in pollen concentration increased significantly for Fraxinus, Betula, Carpinus, Platanus, Poaceae and Urticaceae for the whole pollen season, and for Urticaceae in the first semester. CONCLUSIONS: The prevalence of treated SAR cases rose by about 55% in 10 years. The study not only confirmed the highly allergenic role of Fraxinus, Betula and Poaceae pollens but also showed a relatively unknown association between treated SAR and Carpinus and Platanus pollens, despite their pollen counts being <1% of overall pollen concentration. It also showed robust correlations with Urticaceae pollens, especially during the first semester, suggesting a potential allergenic role of Parietaria pollination in this non-Mediterranean area.

Short-term effects of airborne ragweed pollen on clinical symptoms of hay fever in a panel of 30 patients.

OBJECTIVES: Ragweed, Ambrosia artemisiifolia, is a highly allergenic annual herbaceous plant that is spreading quickly across the globe. Few studies have investigated the relationship between ragweed pollen counts and hay fever symptoms. We investigate the dose-response relationship between ragweed exposure in patients sensitized to ragweed and daily hay fever symptoms. METHOD: A panel study was conducted among 31 adult patients sensitized to A artemisiifolia in France and Switzerland. Rhinitis, conjunctivitis, and bronchial symptoms were recorded daily, as well as daily pollen counts of ragweed, air pollutants, and meteorological data over 2 successive years. Data were analyzed with generalized estimating equation models to quantify effects of ragweed pollen whilst controlling for confounders. RESULTS: The relationship between ragweed pollen and the percentage of patients with nasal, ocular, and bronchial symptoms was linear. For every increase of 10 grains/m3, the odds ratio (OR) (95% confidence interval) for nasal symptoms was, in 2009, 1.18 [1.04-1.35] on weekdays and 1.43 [1.16-1.75] at weekends, and in 2010, 1.04 [1.00-1.07] on weekdays and 1.25 [1.06-1.46] at weekends.The OR for ocular symptoms was 1.32 [1.16-1.56] in 2009 and 1.05 [1.02-1.07] in 2010. Finally, the OR for bronchial symptoms was 1.14 [1.03-1.25] in 2009 and 1.03 [0.97-1.08] in 2010. CONCLUSION: There is a statistically significant linear relationship between ragweed pollen counts and hay fever symptoms. Our study shows that nasal symptoms differ on weekdays and at weekends.

Could past Chlamydial vascular infection promote the dissemination of Chlamydia pneumoniae to the brain?

Chlamydia pneumoniae, a pathogen responsible for respiratory tract infections, has been associated with atherosclerosis which, along with hypertension, hyperlipidemia, cardiovascular and/or cerebrovascular ischemia and stroke, is a risk factor for chronic neurological disorders. Several studies have demonstrated the ability of C. pneumoniae to disseminate from lungs to arteries through peripheral blood mononuclear cells. Once inside the vascular tissue, C. pneumoniae infection may disseminate via peripheral monocytes to the brain over the intact blood-brain barrier, and contribute to the development of chronic neurological disorders. The aim of our study was to evaluate whether past C. pneumoniae vascular infection may promote the dissemination of this microorganism to the brain, therefore we investigated the presence of C. pneumoniae in post-mortem brain tissue specimens of patients with past chlamydial vascular infection. Seventy six post-mortem brain tissue specimens from 19 patients with past chlamydial vascular infection were investigated for the presence of C. pneumoniae by immunohistochemistry, polymerase chain reaction, in situ polymerase chain reaction and in situ reverse transcription polymerase chain reaction. As control, 28 brain tissue specimens were taken from 7 age and sex matched subjects without chlamydial infection. C. pneumoniae was detected in 16 (84.2%) out of 19 patients with chlamydial vascular infection whereas it was not detected in control subjects (p= 0.0002). In conclusion, the main result of our study is the evidence that a chlamydial vascular infection can disseminate to the brain. It will be important for current and future researches to perform large-scale prospective studies on cardiovascular patients with chlamydial vascular infection in order to evaluate the long-term pathological alterations of the brain.

[Mortality study among veterans with dosimeter monitoring during the French nuclear tests in the Pacific]. / Étude de mortalité des vétérans ayant bénéficié d'une surveillance dosimétrique lors des essais nucléaires français dans le Pacifique.

BACKGROUND: A mortality study was carried out in a cohort of veterans present on the sites of the French nuclear experiments center in the Pacific (CEP) from 1966 to 1996, and for whom external dosimeter monitoring recordings were available. METHODS: The cohort included 32,550 veterans having had at least one dosimetry recording. Current vital status was collected from the National Register of Identification of Physical People and causes of death data from the national causes of death database. Total mortality and mortality by cause were compared with mortality of the French population using standardized mortality ratios (SMR). To test the effect of a dosimeter recording higher than the threshold (0.2 mSv), i.e., no null dosimetry, the mortality of veterans was compared inside the cohort, using standardized ratios and Poisson regression models. RESULTS: The mortality analysis was performed among 26,524 men, of whom 8% had had at least one non-null dosimeter. Five thousand four hundred and ninety-two (21%) veterans died before December 31, 2008 and causes were available for nearly 97% of these deaths. Comparing the mortality between the cohort and the French population highlighted a deficit of mortality, for all causes, by cancer and for radiation-induced pathologies; these results were related to the "healthy worker effect". The data showed that all causes mortality and cancer mortality of the cohort of veterans with no null dosimeter were not different from those of other veterans, but also showed an excess of hematological malignancies in this sub-population: this excess was significant in the regression model (RR=1.82; CI 95% [1.6-2.0]). CONCLUSION: Among veterans with an external dosimeter monitoring recording, presence on the sites of CEP from 1966 to 1996 does not constitute a factor of increased mortality compared with the national population. However, an increased risk was observed for mortality by hematological malignancies among veterans with no null dosimetry. This result is in line with studies on veterans present during nuclear experiments abroad.

Endotoxin concentration in poultry houses for laying hens kept in cages or in alternative housing systems.

Endotoxins as components of organic dust may have adverse effects on the respiratory health of workers in poultry buildings. The move towards more welfare-friendly housing systems for layers may increase worker exposure to air contaminants due to the use of litter. The endotoxin concentrations in the inhalable fraction of airborne dust (below 100 µm) from cage and alternative system houses (on-floor, free range and aviaries) were compared under both experimental and commercial conditions. The endotoxin concentration was higher in experimental aviaries (median: 565 EU/m³, range: 362-1491 EU/m³) than in cage housing (98 EU/m³ (51-470)). In field conditions, the endotoxin concentration in the air of 13 alternative houses was higher (35 to 3156 EU/m³) than in cage system buildings (n = 8, 78-576 EU/m³). It was correlated to the respirable dust concentration (fraction below 5 µm) and to the temperature inside the hen house but no seasonal variation was observed. The present study emphasises that considerable worker exposure to endotoxins may occur in laying houses, especially in alternative systems.

Short-acting ß2-agonists (SABA) bronchodilator sales and outdoor mould in central France.

BACKGROUND: Temporal ecological studies have shown that outdoor moulds are associated with severe asthma exacerbations, as emergency department visits or hospitalisations. The aim of this was to assess the associations between daily sales of short-acting ß2-agonists (SABA), a specific and frequent treatment for control of mild asthma exacerbations in children and young adults, and outdoor mould concentrations in the central France area over a 5 year period. METHODS: The relationship between daily changes in mould (25 species) concentrations and daily SABA sales within a population of patients aged 6 to 39 years in a middle-size town of central France (approximately 127,000) was obtained from social security database and analysed with generalized additive models, taking into account confounding factors (air pollution, weather conditions, pollen counts and trend). RESULTS: Daily SABA sales (mean, SD) rose from 17.3 (9.7) in 2010 to 22.7 (12) in 2015. The relative risk (RR [95% CI]) of SABA sales associated with an interquartile increase in mould concentration was significant in the whole population for Alternaria 1.06 [1.002-1.12]. When the influence of age and sex was accounted for, the relationship was significant only in 6-12 years old males for Alternaria 1.21 [1.04-1.41] and Aspergillus-Penicillium 1.08 [1.04-1.12]. CONCLUSIONS: Daily SABA sales are positively associated with Alternaria spores in the general population of children and young adults. The association between daily SABA sales and temporal changes to Alternaria and Aspergillus-Penicillium in male children indicate that outdoor moulds contribute to asthma morbidity.

Tumor progression and oxidant-antioxidant status.

We previously reported on a paradoxical oxidant-antioxidant status in breast cancer patients, more so in pre-menopausal than menopausal women. In this study, measurements were performed on 146 patients with various carcinomas. Vitamin E/total cholesterol increased and plasma malondialdehyde decreased with tumor size and progression. To investigate the difference between young pre-menopausal and aged menopausal breast cancer patients, the same measurements were performed in 365 breast cancer patients according to pathology, tumor size and estrogen receptors. The oxidant-antioxidant status varied with these prognosis factors in the same pattern, and was more pronounced in young than aged women.

Aging and cancer: plasma antioxidants and lipid peroxidation in young and aged breast cancer patients.

The relationship between aging and cancer is complex because the intrication takes place at the cell, the organism and the environment levels. On the other hand, carcinogenesis is a multi-step process, and different mechanisms may be involved in each step. For example, oxidants and antioxidants may play a different role depending upon the phase considered. Tumors in older patients are generally described as slow growing. The difference in tumor aggressiveness between young and older patients is especially obvious in breast cancer patients. The age specificity of some breast risk factors suggests that breast cancer which has been diagnosed in an aged woman was induced late in her life. We address the question whether the characteristics of a senescent organism with regards to oxidant-antioxidant status could be causally related to the slow evolution of tumors in old patients.

Peak expiratory flow rate variability in population surveys. Does the number of assessments matter?

We investigated the effect of reducing the number of daily peak expiratory flow (PEF) measurements on (1) the amplitude of PEF variability and (2) the relationships of this amplitude to bronchial reactivity to methacholine. One hundred seventeen workers (mean age = 38.7 years +/- 9.5; men = 86.3%) recorded their highest of three PEF measurements, every 3 waking hours, ie, 5 times a day, for 7 days, each using a newly purchased peak flowmeter (Vitalograph), and underwent methacholine challenge tests. The variability of PEF of each subject was expressed using the three sets of indices: amp%mean, ie, highest of the daily measurements considered minus the lowest/mean x 100, averaged over 6 days from the second to the seventh, amp%highest (same as amp%mean, but with the highest daily measurements as denominators) and SD%mean (calculated initially as single measures using the data of the 6 days considered, with standard deviation (SD) of each subject's PEF measurements). For each set, we used the indices constructed with the five daily measurements of each day (gold standard), with the first, third, fourth, and fifth, the first, third, and fourth, the first and third, and the first and fourth. The PEF variability was significantly reduced when reducing the number of daily measurements, only when the amp%mean and the amp%highest sets were used. No decrease was observed with the SD%mean set of indices, and SD%mean constructed with the first, third, fourth, and fifth daily measurement was satisfactory. Whatever the sort of index used, three daily measurements were sufficient to identify the group of subjects with excessive variability in relation to methacholine reactivity.

Relationship of serum cholesterol, dietary and plasma beta-carotene with lung cancer in male smokers.

It has been hypothesized that beta-carotene mediates the association between low serum cholesterol levels and increased risk of lung cancer. It follows from this assumption that this association should be greater in population strata with a low intake of beta-carotene than in with those with a high intake. To investigate this hypothesis, we analysed dietary beta-carotene, plasma beta-carotene and serum cholesterol levels in 20 male smokers with lung cancer and 103 male smoking controls, a subsample taken from a larger case-control study on oxidant-antioxidant status. As predicted, we found that the association between low serum cholesterol levels and lung cancer risk was greater in subjects with low plasma beta-carotene. Controlling for plasma beta-carotene decreased but did not negate the magnitude of the inverse association between serum cholesterol and lung cancer. A low serum cholesterol level tended to increase the risk associated with low plasma beta-carotene. Our data suggest that a low plasma beta-carotene does not totally explain the association between serum cholesterol and lung cancer.

Air pollution and health: correlation or causality? The case of the relationship between exposure to particles and cardiopulmonary mortality.

Many epidemiologic studies have observed, in different contexts, a slight short-term relationship between particles in air and cardiopulmonary mortality, even when air quality standards were respected. The causality of this relationship is important to public health because of the number of people exposed. Our aim was to make a critical assessment of the arguments used in 15 reviews of published studies. We explain the importance of distinguishing validity from causality, and we systematically analyze the various criteria of judgment within the context of ecologic time studies. Our conclusion is that the observed relationship is valid and that most of the causality criteria are respected. It is hoped that the level of exposure of populations to these particles be reduced. In Europe, acting at the root of the problem, in particular on diesel emissions, will also enable the reduction of levels of other pollutants that can have an impact on health. In the United States, the situation is more complicated, as particles are mainly secondary. It is also essential to continue with research to become better acquainted with the determinants of personal global exposures and to better understand the toxic role of the various physicochemical factors of the particles.

[Odors and health: a descriptive epidemiological study around a wastewater treatment plant]. / Odeurs et santé: enquête épidémiologique descriptive autour d'une usine d'épuration.

BACKGROUND: Following community concern regarding potential health effects associated with odors of a wastewater treatment plant, a descriptive epidemiological study was conducted to assess the complaints and the health status of the community and to identify potentially more susceptible groups. METHODS: Questionnaires were administered by telephone to nearly 3.000 subjects, randomly selected in the 8 nearby towns, using a geographical Information System. Residents of three areas were compared, according to the distance from the site: 0-1.5 km (high exposed group), 1.5-3 km (moderate exposed group) and 3-4.5 km (low exposed group). Questions measured demographic characteristics, concerns, perceived environmental risk and health effects (symptoms in the past 1 month and in the past 1 year). Multivariate logistic models study the relationships of complaints and health effects, with area and susceptibility factors. RESULTS: Two thousand eight hundred and sixty seven eligible adults participated in an interview. Taking in account confounding factors, population of high and moderate exposed groups reported more odor complaints than the low exposed group, with adjusted odds ratio (OR) of 4.73 (CI95%: 3.63-6.14) and 2.06 (CI95%: 1.59-2.66) respectively. But these 2 groups did not report more frequent health effects compared to the low exposed group. Several health effects were significantly more frequent in persons with self-reported chemical intolerance and in persons considering malodor in terms of health threat. In this last sub-group of population, rhinitis were significantly more frequent in the high exposed group compared to low exposed group, whereas respiratory infections and asthma attacks showed the same non significant patterns. CONCLUSION: If 24,2% of the total sample complaints from odors of the site, this study did not show a higher frequency of health effects in people living near the site (high exposed group). But 2 susceptible groups (with a higher frequency of symptoms potentially related to odors) were identified: persons with self-reported chemical intolerance, among those, many allergic and asthmatic subjects, and persons considering malodor in terms of health threat.

Short-term effects of low-level winter pollution on respiratory health of asthmatic adults.

We studied the short-term effects of Paris winter air pollution (i.e., sulfur dioxide, Black Smoke, suspended particulates with an aerodynamic diameter close to 10 microm, and nitrogen dioxide) in 40 nonsmoking mild to moderate asthmatics (52% male; mean age = 46 y; 90% treated with inhaled steroids). During a 6-mo period, subjects recorded asthma symptoms and three daily peak expiratory flow measurements. Statistical analysis (i.e., generalized estimating equation models that accounted for autocorrelation of responses, weather data, and time trends) revealed consistent and significant associations between the pollutants and asthma attacks and symptoms in the entire study group, especially in the subgroup of individuals who took inhaled beta2 agonists as needed. Pollutants correlated negatively with morning peak expiratory flow in the subgroup that took inhaled beta2 agonists as needed, and they correlated positively with daily variability in asthmatics who received regularly scheduled inhaled beta2 agonists. The effects lingered several days after exposure occurred. Low-level pollution has consistent measurable effects on nonsmoking adults who have well-treated mild or moderate asthma.

[Mortality related to asthma. Trends in France from 1970 to 1987]. / Mortalité rapportée à l'asthme. Tendances pour la France de 1970 à 1987.

An increase in mortality related to asthma has been observed in a great number of countries during the last decade. The purpose of this work is to study this evolution in France from 1970 to 1987. Numbers of deaths were obtained from INSERM, by sex and age groups and the corresponding populations from INSEE. Data were interpreted from crude rates and with the computation of age adjusted and age specific rates. In men, we observed a decrease in mortality from 1972 to 1979, then an increase from 1980 to 1987. In women, the decrease stopped as early as 1974 and we observed an increase from 1975 to 1987. On the other hand their crude and age-adjusted rates become higher than men's rates as early as 1977.

[Asthma in private pneumology practice]. / Asthme en pneumologie libérale.

We assessed asthma severity in patients attending private practice chest specialists, studied the factors related to classification by physicians, and described medications prescribed. 545 chest specialists scattered throughout France, included the patients examined from 3 to 28 May 1993 (N = 14,865). Besides a classification of asthma severity in four classes (mild, moderate, moderately severe, and severe), questionnaires included 20 questions on the history and characteristics of asthma, lung function level and medications prescribed. The proportion of mild asthmatics was 55% among the 3,620 children (aged 6 to 15 years), 42% among the 6,479 young adults (aged 16 to 45 years), and 18% among the 4,766 older adults (aged 46 to 75 years). Followed-up patients were considered more severe than new patients among adults, but not among children. The factors related to asthma severity were impaired FEV1, history of hospitalization, critical care and emergency visits for asthma, limitation of physical activities, and, to a latter extent, symptoms between exacerbations, frequent asthma attacks and daily use of beta 2-agonists. Anti-inflammatory drugs were prescribed to practically all patients from grade 2 (moderate): steroids increased whereas sodium cromoglycate and nedocromil decreased with increasing severity. This study provides a valuable estimate of the classification and medications prescribed to asthmatic patients examined by 50% of private practice chest specialists in France.

[Factors predicting the severity and the degree of symptom control of asthma in a recently diagnosed cohort of adult patients (A.S.M.A study)]. / Facteurs liés à la sévérité et au contrôle de l'asthme récemment diagnostiqué dans une cohorte de patients adultes.

INTRODUCTION: The aim of this cohort study was to describe the evolution of recently diagnosed (<12 months) asthma, and to identify outcome predictive factors. This paper describes the evolution of an adult cohort and the factors related to asthma severity and control. METHODS: In 1995, 251 chest specialists from throughout France, recruited 347 asthmatic adults (subjects with severe asthma were excluded). 220 eligible patients were examined every four months over a three year period. Data (socio-demographic characteristics, asthma history, results of atopy testing and lung function tests, treatment, drug compliance, respiratory infections, changes in lifestyle and environment, and major life events) were collected by means of detailed standardised questionnaires completed by physicians. Asthma severity, recorded one year after study inclusion, and asthma control, assessed at each follow-up visit in the second and third year, were defined according to the international guidelines. RESULTS: The clinical status of these adult patients generally improved rapidly. Asthma severity correlated closely with allergy, with a history of childhood asthma and with sensitisation to indoor allergens. After adjusting for severity, poor asthma control was associated with poor compliance, with respiratory infections, and, to a lesser extent, with animals inside the home. CONCLUSIONS: This cohort study highlights the association of asthma severity with allergy, and of poor asthma control with poor compliance and respiratory infections.

[Epidemiology of the cardiorespiratory effects of particulates]. / Epidémiologie des effets cardio-respiratoires des particules.

This review summarises the epidemiology of cardio-pulmonary effects of air pollution particles. The published studies that are reviewed here, were published between 1990 and 2000. First, the study designs, used in air pollution epidemiology, are defined. Second, the health effects of acute exposure are related, such as mortality, respiratory effects, effects on allergy and asthma and cardio-vascular effects. Third, the effects of chronic exposures are described, with also mortality, respiratory effects, effects on allergy and asthma, cardio-vascular effects, and effects on cancer incidence. Finally, the numerous studies published this last ten years, highlight a coherent cascade of cardio-pulmonary effects in relation to particles air pollution.

[Health impact of exposure to pollens: A review of epidemiological studies]. / Impact sanitaire des pollens : revue des études épidémiologiques.

The aim of this review is to describe the health impact of exposure to pollen based on recently published epidemiological studies. The methodology chapter, describes a review of the literature and outlines important elements of these studies: measurement of exposure to pollens, study types used, study populations and the health indicators related to pollen exposure. In this review, two types of studies have been used to assess the epidemiological evidence of short-term links between pollen exposure and hay fever or asthma. Ecological time-series studies use daily indicators of asthma exacerbations (emergency room admissions or hospitalizations), consultations for rhinitis or conjunctivitis, or anti-allergic drug consumption within general population. Panel studies relate measurements of pollen grain concentrations to nasal, ocular and bronchial symptom severity in a group of subjects sensitized to a specific pollen, monitored during the pollen season. In both cases, the studies show a relationship on a day-to-day basis between health indicators and daily rates of atmospheric pollen collected by a pollen trap. These studies take into account confounding factors, such as air pollution, weather factors and sometimes exposure to outdoor molds. Unlike earlier studies, more and more studies focus on the shape of the dose-response relationship and the lag between pollen exposure and symptoms. Only rarely, individual susceptibility factors, the clinical phenomenon of priming and polysensitization are reported. Thus, ecological time-series studies and panel studies assess respectively the impact of pollen exposure in the general population and in groups of sensitized patients. Using appropriate statistical tools, these studies provide insight into the shape of the dose-response relationship, with a potential threshold below which symptoms are absent, then a linear relationship for nasal, ocular and bronchial symptoms and a plateau where the symptoms do not increase despite the continued increase in pollen.