Dan Norbäck

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.

Asthmatic symptoms and volatile organic compounds, formaldehyde, and carbon dioxide in dwellings.

OBJECTIVES--As a part of the worldwide European Community respiratory health survey, possible relations between symptoms of asthma, building characteristics, and indoor concentration of volatile organic compounds (VOCs) in dwellings were studied. METHODS--The study comprised 88 subjects, aged 20-45 years, from the general population in Uppsala, a mid-Swedish urban community, selected by stratified random sampling. Room temperature, air humidity, respirable dust, carbon dioxide (CO2), VOCs, formaldehyde, and house dust mites were measured in the homes of the subjects. They underwent a structured interview, spirometry, peak expiratory flow (PEF) measurements at home, methacholine provocation test for bronchial hyperresponsiveness, and skin prick tests. In addition, serum concentration of eosinophilic cationic protein (S-ECP), blood eosinophil count, and total immunoglobulin E (S-IgE) were measured. RESULTS--Symptoms related to asthma were more common in dwellings with house dust mites, and visible signs of dampness or microbial growth in the building. Significant relations were also found between nocturnal breathlessness and presence of wall to wall carpets, and indoor concentration of CO2, formaldehyde, and VOCs. The formaldehyde concentration exceeded the Swedish limit value for dwellings (100 micrograms/m3) in one building, and CO2 exceeded the recommended limit value of 1000 ppm in 26% of the dwellings, showing insufficient outdoor air supply. Bronchial hyperresponsiveness was related to indoor concentration of limonene, the most prevalent terpene. Variability in PEF was related to two other terpenes; alpha-pinen and delta-karen. CONCLUSION--Our results suggest that indoor VOCs and formaldehyde may cause asthma-like symptoms. There is a need to increase the outdoor air supply in many dwelling, and wall to wall carpeting and dampness in the building should be avoided. Improved indoor environment can also be achieved by selecting building materials, building construction, and indoor activities on the principle that the emission of volatile organic compounds should be as low as reasonably achievable, to minimise symptoms related to asthma due to indoor air pollution.

Early life origins of chronic obstructive pulmonary disease

Background: Early life development may influence subsequent respiratory morbidity. The impact of factors determined in childhood on adult lung function, decline in lung function and chronic obstructive pulmonary disease (COPD) was investigated. Methods: European Community Respiratory Health Survey participants aged 20–45 years randomly selected from general populations in 29 centres underwent spirometry in 1991–3 (n = 13 359) and 9 years later (n = 7738). Associations of early life factors with adult forced expiratory volume in 1 s (FEV1), FEV1 decline and COPD (FEV1/FVC ratio <70% and FEV1 <80% predicted) were analysed with generalised estimating equation models and random effects linear models. Results: Maternal asthma, paternal asthma, childhood asthma, maternal smoking and childhood respiratory infections were significantly associated with lower FEV1 and defined as “childhood disadvantage factors”; 40% had one or more childhood disadvantage factors which were associated with lower FEV1 (men: adjusted difference 95 ml (95% CI 67 to 124); women: adjusted difference 60 ml (95% CI 40 to 80)). FEV1 decreased with increasing number of childhood disadvantage factors (⩾3 factors, men: 274 ml (95% CI 154 to 395), women: 208 ml (95% CI 124 to 292)). Childhood disadvantage was associated with a larger FEV1 decline (1 factor: 2.0 ml (95% CI 0.4 to 3.6) per year; 2 factors: 3.8 ml (95% CI 1.0 to 6.6); ⩾3 factors: 2.2 ml (95% CI −4.8 to 9.2)). COPD increased with increasing childhood disadvantage (1 factor, men: OR 1.7 (95% CI 1.1 to 2.6), women: OR 1.6 (95% CI 1.01 to 2.6); ⩾3 factors, men: OR 6.3 (95% CI 2.4 to 17), women: OR 7.2 (95% CI 2.8 to 19)). These findings were consistent between centres and when subjects with asthma were excluded. Conclusions: People with early life disadvantage have permanently lower lung function, no catch-up with age but a slightly larger decline in lung function and a substantially increased COPD risk. The impact of childhood disadvantage was as large as that of heavy smoking. Increased focus on the early life environment may contribute to the prevention of COPD.

Asthma among secondary schoolchildren in relation to the school environment

Background Poor indoor air quality has been suggested to be related to the increase in the prevalence of asthma that has occurred in the western world, especially among children and young persons. Apart from the home, school is the most important indoor environment for children.

Volatile organic compounds, respirable dust, and personal factors related to prevalence and incidence of sick building syndrome in primary schools.

Possible relations between incidence and prevalence of sick building syndrome (SBS), indoor exposures, and personal factors were studied in a four year longitudinal study among personnel (n = 129) in six primary schools. The mean concentration of carbon dioxide was above the recommended value of 0.08 microliter/l (800 ppm) in all schools, indicating a poor outdoor air supply. Indoor concentration of volatile hydrocarbon (VOC) was enhanced at high room temperatures. Respirable dust, but not concentration of VOC was enhanced at lower ventilation rates and high air humidity. Chronic SBS was related to VOC, previous wall to wall carpeting in the schools, hyper-reactivity, and psychosocial factors. Incidence of new SBS was related to concentration of respirable dust, current smoking, and the psychosocial climate. Remission of hyperreactivity, decrease in sick leave owing to airway illness, removal of carpeting in the schools, and moving from new to old dwellings resulted in a decrease in SBS score. It is concluded that SBS is of multifactorial origin, related to a variety of factors and exposures. The total concentration of hydrocarbons is a simple and convenient measure of exposure, which also seems to be a predictor of chronic symptoms. Further investigations on the effect of temperature, ventilation, and air humidity on SBS should consider how these factors may influence the chemical composition of the air. Because poor air quality in schools could also affect the children, it may have implications for the state of health of a large proportion of the population.

Carpal tunnel syndrome (CTS) and exposure to vibration, repetitive wrist movements, and heavy manual work: a case-referent study.

Possible connections between carpal tunnel syndrome (CTS) and exposure to vibrating handheld tools, repetitive wrist movements, and heavy manual work were examined in a case-referent study. The cases were 38 men operated on for CTS between 1974 and 1980. For each case, two referents were drawn from among other surgical cases (hospital referents) and two further referents from the population register and telephone directory, respectively (population referents). Thirty four of 38 cases (89%) and 143 of 152 referents (94%) were interviewed by telephone. An increased prevalence of obesity, rheumatoid disease, diabetes, or thyroid disease was observed among the cases but most did not suffer from any of these disorders. CTS was significantly correlated with exposure to vibration from handheld tools and to repetitive wrist movements but showed a weaker correlation with work producing a heavy load on the wrist. A cause-effect relation between CTS and exposures to handheld vibrating tools and to work causing repetitive movements of the wrist seems probable. Some differences between hospital and population referents indicate that a case-referent study of this type could be biased by inappropriate selection of referents.

Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms

Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5–10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults.

Environmental, occupational, and personal factors related to the prevalence of sick building syndrome in the general population.

Possible relations between prevalence of sick building syndrome (SBS) and environmental, occupational, and personal factors were studied in a random sample (0.1%) of the general population aged 20-65 in a three county region in middle Sweden. Childhood exposure to environmental tobacco smoke from smoking mothers and a childhood in urban areas was related to SBS symptoms. Current urban residency, fresh paint, and preschool children in the dwelling were also related to symptoms. Other residential factors such as age of building, type of building, degree of crowding, mechanical ventilation, or signs of moisture or mould growth were not related to symptoms. Other factors related to symptoms were history of atopy, allergy to nickel, proneness to infection, hyperreactivity, static electricity, work with video display units (VDU), work satisfaction, and climate of cooperation at work. Age, sex, marital state, education level, work stress, obesity, current or earlier smoking, regular physical exercise, or occupational exposure to chemicals did not correlate with symptoms. Women had a higher proportion of symptoms than men but these differences were not significant when adjusting for differences in allergy to nickel, hyperreactivity, and proneness to infection. Maternal smoking was related to a twofold increase of both atopy and allergy to nickel in the adult offspring. Eye symptoms were most common in administrative, managerial, and service work. Airway symptoms were most common in transport and communication work. Dermal symptoms were most common in professional and technical and related work. General symptoms were most common in service, health, hospital, and social work. The lowest prevalence of symptoms was found in agricultural, forestry, and sales work. Women and subjects allergic to nickel worked more often in occupations without exposure to chemicals, but no evidence was found for selection mechanisms causing sensitive persons to move from exposed to unexposed occupations. It was concluded that symptoms included in SBS are common in the general population, and of multifactorial origin related to both personal, occupational, and residential factors, and certain environmental exposures such as maternal smoking, the urban environment, VDU work, and volatile organic hydrocarbons from newly painted dwellings.

Comparison of oxidative properties, light absorbance, total and elemental mass concentration of ambient PM2.5 collected at 20 European sites

Objective It has been proposed that the redox activity of particles may represent a major determinant of their toxicity. We measured the in vitro ability of ambient fine particles [particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5)] to form hydroxyl radicals (•OH) in an oxidant environment, as well as to deplete physiologic antioxidants (ascorbic acid, glutathione) in the naturally reducing environment of the respiratory tract lining fluid (RTLF). The objective was to examine how these toxicologically relevant measures were related to other PM characteristics, such as total and elemental mass concentration and light absorbance. Design Gravimetric PM2.5 samples (n = 716) collected over 1 year from 20 centers participating in the European Community Respiratory Health Survey were available. Light absorbance of these filters was measured with reflectometry. PM suspensions were recovered from filters by vortexing and sonication before dilution to a standard concentration. The oxidative activity of these particle suspensions was then assessed by measuring their ability to generate •OH in the presence of hydrogen peroxide, using electron spin resonance and 5,5-dimethyl-1-pyrroline-N-oxide as spin trap, or by establishing their capacity to deplete antioxidants from a synthetic model of the RTLF. Results and Conclusion PM oxidative activity varied significantly among European sampling sites. Correlations between oxidative activity and all other characteristics of PM were low, both within centers (temporal correlation) and across communities (annual mean). Thus, no single surrogate measure of PM redox activity could be identified. Because these novel measures are suggested to reflect crucial biologic mechanisms of PM, their use may be pertinent in epidemiologic studies. Therefore, it is important to define the appropriate methods to determine oxidative activity of PM.

Asthmatic symptoms and indoor levels of micro‐organisms and house dust mites

As a part of a worldwide investigation on the prevalence of respiratory symptoms, we have performed a study on the relationship between the indoor environment and asthma‐like symptoms in the population of a central Swedish municipality. The study comprised 88 individuals, aged 20–45 years who underwent a structured interview, spirometry, a methacholine provocation test, skin‐prick tests and blood samples for measurements of serum concentrations of eosinophil cationic protein (S‐ECP), blood eosinophil count and total immunoglobulin E (S‐IgE). In the homes, the room temperature, air humidity, respirable dust, house dust mites (HDM) and airborne micro‐organisms were measured. The relative humidity in all the homes was found to be above 33%. HDM were found in 13% of homes. In the homes of the 47 subjects with asthma related symptoms, significantly higher total levels of bacteria and mould (P<0.05) and a higher proportion of detected HDM (OR = 5.3) was found than in subjects with no asthma related symptoms, after adjustment for age, sex, smoking, indoor temperature and air humidity. HDM were found to be an independent risk factor for asthma related symptoms (OR = 7.9) and nocturnal breathlessness (OR = 6.2) (P<0.05), while the total level of bacteria was a risk factor for asthma related symptoms and wheezing (P<0.05). We conclude that although HDM is relatively infrequently found in the homes of central‐Sweden, the presence of HDM is related to asthmatic symptoms. A relation between levels of airborne bacteria and asthma related symptoms was also found.