Isabel Urrutia

Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II)

BACKGROUND The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. METHODS We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study centre. FINDINGS A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4, 1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2, 1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. INTERPRETATION Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.

Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study

BACKGROUND Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population. METHODS We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow-up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4-6 years in the Tucson Childrens Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function. FINDINGS After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV1 at baseline, we found an inverse association between CC16 concentration and decline in FEV1 in adults in TESAOD (4·4 mL/year additional FEV1 decline for each SD decrease in baseline CC16 concentration, p=0·0014) and ECRHS-Sp (2·4 mL/year, p=0·023); the effect in SAPALDIA was marginal (4·5 mL/year, p=0·052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV1 to forced expiratory volume [FEV1/FVC] less than 70% plus FEV1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV1 deficit of 68 mL up to age 16 years (p=0·0001), which was confirmed in children who had never smoked by age 16 years (-71 mL, p<0·0001). INTERPRETATION Low concentrations of CC16 in serum are associated with reduced lung function in childhood, accelerated lung function decline in adulthood, and development of moderate airflow limitation in the general adult population. FUNDING National Heart, Lung, and Blood Institute and European Union Seventh Framework Programme.

The occupational contribution to severe exacerbation of asthma.

The goal of this study was to identify occupational risk factors for severe exacerbation of asthma and estimate the extent to which occupation contributes to these events. The 966 participants were working adults with current asthma who participated in the follow-up phase of the European Community Respiratory Health Survey. Severe exacerbation of asthma was defined as self-reported unplanned care for asthma in the past 12 months. Occupations held in the same period were combined with a general population job-exposure matrix to assess occupational exposures. 74 participants reported having had at least one severe exacerbation event, for a 1-yr cumulative incidence of 7.7%. From regression models that controlled for confounders, the relative risk (RR) was statistically significant for low (RR 1.7, 95% CI 1.1–2.6) and high (RR 3.6, 95% CI 2.2–5.8) biological dust exposure, high mineral dust exposure (RR 1.8, 95% CI 1.02–3.2), and high gas and fumes exposure (RR 2.5, 95% CI 1.2–5.5). The summary category of high dust, gas, or fumes exposure had RR 3.1 (95% CI 1.9–5.1). Based on this RR, the population attributable risk was 14.7% among workers with current asthma. These results suggest occupation contributes to approximately one in seven cases of severe exacerbation of asthma in a working population, and various agents play a role.

Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II

Occupational exposure is a well-recognised modifiable risk factor for asthma, but the relationship between occupational exposure and asthma control has not been studied. We aimed to study this association among working-age adults from the European Community Respiratory Health Survey (ECRHS). Data were available for 7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and 1210 with current asthma). Associations between occupational exposure to specific asthmagens and asthma control status (33% with uncontrolled asthma, based on the Global Initiative for Asthma guidelines) were evaluated using logistic and multinomial regressions, adjusted for age, sex and smoking status, with study areas included as a random effect. Statistically significant positive associations were observed between uncontrolled adult-onset asthma and both past 12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6 (1.0–2.40) and 1.7 (1.2–2.5), respectively); high (1.7 (1.0–2.8) and 1.9 (1.3–2.9), respectively) and low (1.6 (1.0–2.7) and 1.8 (1.2–2.7), respectively) molecular weight agents; and cleaning agents (2.0 (1.1–3.6) and 2.3 (1.4–3.6), respectively), with stronger associations for long-term exposures. These associations were mainly explained by the exacerbation domain of asthma control and no associations were observed between asthmagens and partly controlled asthma. These findings suggest that occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma. Occupational risk factors should be quickly identified to prevent uncontrolled asthma. Occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma in ECRHS II http://ow.ly/reN8g

Absolute values of lung function explain the sex difference in breathlessness in the general population

Activity-related breathlessness is twice as common among females as males in the general population and is associated with adverse health outcomes. We tested whether this sex difference is explained by the lower absolute forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) in females. This was a cross-sectional analysis of 3250 subjects (51% female) aged 38−67 years across 13 countries in the population-based third European Community Respiratory Health Survey. Activity-related breathlessness was measured using the modified Medical Research Council (mMRC) scale. Associations with mMRC were analysed using ordered logistic regression clustering on centre, adjusting for post-bronchodilator spirometry, body mass index, pack-years smoking, cardiopulmonary diseases, depression and level of exercise. Activity-related breathlessness (mMRC ≥1) was twice as common in females (27%) as in males (14%) (odds ratio (OR) 2.21, 95% CI 1.79−2.72). The sex difference was not reduced when controlling for FEV1 % predicted (OR 2.33), but disappeared when controlling for absolute FEV1 (OR 0.89, 95% CI 0.69−1.14). Absolute FEV1 explained 98−100% of the sex difference adjusting for confounders. The effect was similar within males and females, when using FVC instead of FEV1 and in healthy never-smokers. The markedly more severe activity-related breathlessness among females in the general population is explained by their smaller spirometric lung volumes. The sex difference in breathlessness is explained by absolute FEV1 or FVC http://ow.ly/TXoI308DZO3

Asociación entre el cociente FEF25-75%/FVC y la hiperreactividad bronquial

Objetivo: La desproporcion entre el calibre de la via aerea y el parenquima pulmonar tiene una relacion negativa con la presencia de hiperreactividad bronquial (HRB). El objetivo del presente estudio es medir la asociacion entre el calibre de la via aerea relativa a la talla pulmonar, expresado por el cociente entre el flujo mesoespiratorio entre el 25 y el 75% de la capacidad vital forzada dividido por la capacidad vital forzada (FEF25-75%/FVC), con la HRB medida por el test de metacolina, ajustando por edad, altura, sexo, consumo de tabaco, area geografica, sintomas respiratorios y volumen espiratorio forzado en el primer segundo previo. Material y metodos: Estudio multicentrico transversal sobre poblacion general espanola (2.647 sujetos) del Estudio de Salud Respiratoria de la Comunidad Europea (ECRHS-I). Se aplico un cuestionario llamado ECRHS, se determino la inmunoglobulina E total y especifica, y se realizaron pruebas cutaneas, espirometria y test de metacolina. Resultados: Se presenta la relacion entre las diferentes variables sociodemograficas y clinicas con los 2 parametros de positividad del test de metacolina. Hay aumento del riesgo de HRB a menor cociente FEF25-75%/FVC ajustado por diferentes variables (odds ratio = 0,09; intervalo de confianza del 95%, 0,04-0,18, para PC20, y odds ratio = 0,06; intervalo de confianza del 95%, 0,03-0,12 para PD20). Conclusiones: El cociente FEF25-75%/FVC esta asociado significativamente a la HRB, independientemente de la edad, la existencia de atopia, el consumo de tabaco, el area geografica, los sintomas respiratorios y el volumen espiratorio forzado en el primer segundo.

Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction

Rationale: Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long‐term consequences of cleaning agents on respiratory health are, however, not well described. Objectives: This study aimed to investigate long‐term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction. Methods: The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population‐based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders. Measurements and Main Results: As compared with women not engaged in cleaning (&Dgr;FEV1 = −18.5 ml/yr), FEV1 declined more rapidly in women responsible for cleaning at home (−22.1; P = 0.01) and occupational cleaners (−22.4; P = 0.03). The same was found for decline in FVC (&Dgr;FVC = −8.8 ml/yr; −13.1, P = 0.02; and −15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV1 decline (−22.0, P = 0.04; and −22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV1/FVC decline or airway obstruction. Conclusions: Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long‐term respiratory health.

Predictors of respiratory sickness absence: an international population-based study.

BACKGROUND Respiratory tract-related occupational disability is common among adults of working age. We examined occupational vapors, gas, dust, or fume (VGDF) exposure as a predictor of disability, based on respiratory sickness absence among the actively employed, at an early point at which prevention may be most relevant. METHODS Currently employed European Community Respiratory Health Survey II participants (n = 6,988) were classified into three mutually exclusive, condition/symptom-based categories: physician-diagnosed asthma, self-reported rhinitis, and wheeze/breathlessness (n = 4,772). Logistic regression analysis estimated the odds of respiratory sickness absence (past 12 months) by VGDF exposure. RESULTS In the condition/symptom groups, 327 (6.9%) reported respiratory sickness absence. Exposure to VGDF was associated with increased odds of respiratory sickness absence: asthma odds ratio [OR] 2.0 (95% confidence interval [CI] 1.1-3.6), wheeze/breathlessness OR 2.2 (95% CI 1.01-4.8); rhinitis OR 1.9 (95% CI 1.02-3.4). CONCLUSION One in 15 currently employed with asthma, breathlessness, or rhinitis reported respiratory sickness absence. VGDF exposure doubled the odds of respiratory sickness absence, suggesting a focus for disability prevention.

Association Between the Forced Midexpiratory Flow/Forced Vital Capacity Ratio and Bronchial Hyperresponsiveness

OBJECTIVE A long-standing hypothesis is that a low ratio of airway caliber to lung size is associated with bronchial hyperresponsiveness (BHR). The aim of our study was to measure the association between airway caliber relative to lung size (expressed as the ratio between forced expiratory flow, midexpiratory phase, divided by forced vital capacity [FEF(25%-75%)/FVC]) and BHR measured by a methacholine challenge test, adjusting for age, height, sex, smoking history, geographic area, respiratory symptoms, and baseline forced expiratory volume in 1 second (FEV1). MATERIAL AND METHODS We carried out a multicenter cross-sectional study of the general Spanish population in 2647 subjects from the European Community Respiratory Health Survey (ECRHS I). The ECRHS questionnaire was administered, total and specific immunoglobulin E were measured, and skin tests, spirometry, and a methacholine challenge test were performed. RESULTS We show the relationship of the various clinical and sociodemographic variables with the 2 parameters indicative of a positive methacholine test. The lower the FEF(25%-75%)/FVC ratio was, the greater the risk of HRB, after adjustment for variables (odds ratio [OR]=0.09; 95% confidence interval [CI], 0.04-0.018 for the concentration provoking a 20% decrease in FEV1, and OR=0.06; 95% CI, 0.03-0.12 for the dose provoking a 20% decrease in FEV1). CONCLUSIONS There is a significant association between the FEF(25%-75%)/FVC ratio and BHR after adjustment for age, atopy, smoking, geographic area, respiratory symptoms, and initial FEV1.

Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey

Background Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey. Methods General population samples aged 20–44 were randomly selected in 1991–1993 and followed up 20 years later (2010–2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework. Findings 3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%. Interpretation These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD.