Rosuvastatin treatment in stable chronic obstructive pulmonary disease (RODEO): a randomized controlled trial.

OBJECTIVES: The objective of this study was to examine whether statin therapy is associated with enhanced endothelium-dependent vascular function, improved pulmonary function and reduced systemic inflammation in patients with chronic obstructive pulmonary disease (COPD). DESIGN AND SETTING: This randomized, placebo-controlled, double-blind, parallel trial including patients with COPD was performed at two University hospitals in Norway. SUBJECTS, INTERVENTION AND MEASUREMENTS: Patients with stable COPD (n = 99) were assigned randomly to receive rosuvastatin 10 mg (n = 49) or matching placebo (n = 50) once daily for 12 weeks. The primary outcome measure was change in endothelium-dependent vascular function measured using peripheral arterial tonometry and expressed as the reactive hyperaemia index. Secondary end-points were change in pulmonary function, as assessed by forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC), and change in the circulating levels of the inflammatory markers interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP). RESULTS: In the overall study population, no significant between-group difference in change in endothelium-dependent vascular or pulmonary function was observed. Rosuvastatin therapy was associated with a reduction in hsCRP (-20% vs. 11%, P = 0.017) and an attenuation of the rise in IL6 concentration (8% vs. 30%, P = 0.028) compared with placebo. In a prespecified subgroup analysis of patients with a supra-median circulating hsCRP concentration (>1.7 mg L(-1) ), rosuvastatin was associated with improved endothelium-dependent vascular function (13% vs. 2%, P = 0.026). CONCLUSIONS: In stable COPD patients without the standard indications for statin therapy, rosuvastatin treatment is associated with a significant attenuation of systemic inflammation and improvement in endothelial-dependent vascular function in patients with evidence of systemic inflammation.

Lack of pro-inflammatory cytokine mobilization predicts poor prognosis in patients with acute heart failure.

AIMS: The aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients. METHODS AND RESULTS: Plasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n=22) on admission. Low levels of MCP-1, IL-1ß and a low IL-1ß/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1ß had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E' and inferior caval vein diameter, than patients with high levels. CONCLUSION: Immune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1ß and MCP-1 during AHF is associated with poor outcome.

Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Cardiovascular co-morbidities are common in chronic obstructive pulmonary disease (COPD). Retrospective studies on selected patients have indicated that cardiac troponin elevation is frequent during acute exacerbations of COPD (AECOPD), and that this is associated with poor survival. In the present prospective study the prevalence and prognostic value of elevated cardiac troponin T (cTnT) in unselected patients with AECOPD have been investigated, using a novel high-sensitivity assay (hs-cTnT assay). METHODS AND RESULTS: 99 patients hospitalised for AECOPD were included. They were followed until death or study termination. During a median follow-up time of 1.9 years, 57 patients (58%) died. 97 patients (98%) had measurable levels of hs-cTnT and 73 (74%) had hs-cTnT above the normal range (≥14.0 ng/l). The crude mortality rates in patients having hs-cTnT <14.0, 14.0-39.9 and ≥40 ng/l were 4.6, 30.2 and 58.3 per 100 patient-years, respectively. Adjusting for relevant covariables using an extended Cox regression analysis, the HRs (95% CI) for death were 4.5 (1.2 to 16) and 8.9 (2.4 to 32) among patients having hs-cTnT 14.0-39.9 and ≥40 ng/l, respectively, compared with patients with hs-cTnT <14.0 ng/l. The association between mortality and hs-cTnT was strongly modified by heart rate at admission (p<0.001)-that is, the association between mortality and hs-cTnT was stronger among patients with tachycardia. CONCLUSION: Elevated hs-cTnT during AECOPD is frequent, and it is associated with increased mortality. The effect is stronger among patients having tachycardia than among patients with normal heart rate.

Chest abnormalities in juvenile-onset mixed connective tissue disease: assessment with high-resolution computed tomography and pulmonary function tests.

BACKGROUND: Mixed connective tissue disease (MCTD) is associated with several chest manifestations. Only a few studies have focused on chest manifestations in juvenile-onset MCTD (jMCTD), and the true prevalence of pulmonary abnormalities on high-resolution computed tomography (HRCT) in these patients is unknown. PURPOSE: To investigate the occurrence of pulmonary abnormalities in jMCTD with particular reference to interstitial lung disease (ILD), and to evaluate a possible association between pulmonary findings and disease-related variables. MATERIAL AND METHODS: Twenty-four childhood-onset MCTD patients with median disease duration of 10.5 years (range 1-21 years) were investigated in a cross-sectional study by means of HRCT, pulmonary function tests (PFT), and clinical assessment. RESULTS: Discrete ILD was identified in six patients (25%). Median extent of ILD was 2.0%, and all except one of the patients had very mild disease in which 5% or less of the parenchyma was affected. The CT features of fibrosis were mainly microcystic and fine intralobular. The most frequently abnormal PFT was carbon monoxide uptake from the lung, which was abnormal in 33% of the patients. PFT and disease duration were not significantly associated with HRCT findings of ILD. CONCLUSION: The prevalence of ILD in childhood-onset MCTD patients was lower than previously believed. In most of the patients with ILD, the findings were subtle and without clinical correlation. The results suggest a low extent of ILD in childhood-onset MCTD, even after long-term disease duration.

Quantitative and qualitative assessment of exposure among employees in Norwegian smelters.

OBJECTIVES: To generate a job exposure matrix (JEM) for dust exposure in Norwegian smelters to be used in an epidemiologic study of respiratory diseases and to identify determinants of exposure. METHODS: The arithmetic mean and geometric mean (GM) of 2619 personal dust exposure measurements were applied in constructing the JEM, which was assigned to 2620 employees participating in a respiratory survey including yearly spirometry and a respiratory questionnaire. A qualitative exposure classification was constructed: (i) line operators were those employed full time in the production line, (ii) non-exposed employees were those who did not work in production and (iii) the remainder were classified as non-line operators. RESULTS: In the ferrosilicon alloy and silicon metal production group (FeSi/Si-metal), the median GM of dust exposure was 2.3 mg m(-3) (0.04-5.6) (10-90% percentiles) compared with 1.6 mg m(-3) (0.02-2.3) in the silicomanganese, ferromanganese and ferrochromium production group (SiMn/FeMn/FeCr). Multivariate analyses showed that dust exposure concentration levels decreased significantly with increasing age (FeSi/Si-metal), was significantly lower in females than in males and was significantly higher in current smokers than in never-smokers. Dust exposure concentration levels were also higher in employees reporting previous exposure to dust, fumes and gases than in employees without such previous exposure, though, significant only in the FeSi/Si-metal production group. CONCLUSION: The dust exposure levels of the employees were higher in the FeSi/Si-metal production group than in the SiMn/FeMn/FeCr production group. Age, gender, smoking status and previous exposure were significant determinants of dust exposure and should be evaluated in future analyses of the relationship between health outcomes and dust exposure in this industry.

Decreased lung function among employees at Norwegian smelters.

BACKGROUND: In the smelting industry airborne pollutants are emitted into the workplace atmosphere during the production process. Our aim in this study was to investigate the relationship between production and lung function among employees at Norwegian smelters. METHODS: Spirometry was performed on 3,924 employees, who also completed a standardized questionnaire. The employees were classified by job functions: (i) line operators were employed full-time on the production line, (ii) non-exposed employees did not work in production, and (iii) the remainder of the employees were classified as non-line operators. RESULTS: The mean age of the participants was 38.6 (range 20.0-55.0) years, 88.5% were males. The multivariate analyses showed that, compared to the forced expiratory volume in one second (FEV(1)) in non-exposed employees, the FEV(1) (95% confidence interval) was 87 (33-141) ml and 65 (12-118) ml lower in line and non-line operators, respectively. The prevalence of airflow limitation (FEV(1)/forced vital capacity (FVC) below the 5th percentile of the predicted value) was 4.7% in non-exposed employees, 7.5% in non-line operators and 8.3% in line operators. CONCLUSION: Compared with non-exposed employees, impairment of lung function among employees at Norwegian smelters was significantly related to the job categories of line operator and non-line operator.

Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease, exacerbations of which increase strain on the heart. The prognostic value of elevated circulating levels of cardiac Troponins seen during COPD exacerbations has been investigated. From the Akershus hospital database, 897 patients discharged after treatment for COPD exacerbation in the period 2000-2003 were identified and followed-up until June 30, 2005. Median observation time was 1.9 yrs. In 396 patients, measurements of cardiac-specific troponin T (cTnT) were available. Levels of cTnT >/=0.04 mug.L(-1) were considered elevated. Clinical data were retrieved from patient records and date of death was obtained from the Norwegian National Registry. In order to balance the nonrandomised nature of available cTnT measurements, an exposure propensity score (EPS) for cTnT sampling was calculated and used in regression analyses. After adjusting for EPS in Cox regression analyses, elevated cTnT was significantly associated with increased all-cause mortality in the observation period, with a hazard ratio of 1.64 (95% confidence interval 1.15-2.34). In conclusion, chronic obstructive pulmonary disease patients with elevated cardiac-specific Troponin T during exacerbation are at increased risk of death after discharge.

Production of silicon alloys is associated with respiratory symptoms among employees in Norwegian smelters.

OBJECTIVES: To develop a qualitative exposure classification of employees in Norwegian smelters and to investigate the relationship between respiratory symptoms and occupational exposure using this classification. METHODS: The 3,924 participants completed a standardised questionnaire including questions of respiratory symptoms, familial asthma, allergy, doctor-diagnosed asthma, smoking habits, previous exposure and occupation. The employees were classified according to their current job function: (1) line operators were employed full time on the production line, (2) non-exposed employees did not work in production, (3) the remaining employees were classified as non-line operators. The association between the prevalence of respiratory symptoms and job category was examined using multivariate logistic regression. RESULTS: The mean age of the participants was 38.6 years (standard deviation 9.2 years), 88.5% were males. The odds ratios (OR) (95% confidence intervals in parenthesis) for dyspnoea, cough and phlegm regarding previous exposure compared with no previous exposure were 1.4 (1.1-1.7), 1.4 (1.2-1.8) and 1.3 (1.0-1.7), respectively. The OR in line operators compared with non-exposed employees was 1.2 (0.9-1.7) for dyspnoea, 1.3 (1.0-1.8) for cough and 1.9 (1.4-2.7) for phlegm. The OR for respiratory symptoms was higher in relation to previous exposure than current job function except for phlegm. CONCLUSION: In Norwegian smelters respiratory symptoms appear to be positively related to both current job function and previous exposure. Previous exposure appears to be more important than current job function.

Statin use is associated with reduced mortality in COPD.

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of ischaemic heart disease (IHD). Statins reduce mortality and morbidity in IHD. It has been hypothesised that statin treatment is associated with reduced long-term mortality in patients with COPD. Using a retrospective cohort design, 854 consecutive patients (mean age 70.8 yrs; 51.5% female) with a diagnosis of COPD exacerbation were included in the study at discharge from a Norwegian teaching hospital. Median follow-up was 1.9 yrs, during which 333 patients died. The crude mortality rate per 1,000 person-yrs was 110 in patients treated with statins, and 191 in patients not treated with statins. After adjustment for sex, age, smoking, pulmonary function and comorbidities, the hazard ratio (HR) for statin users versus statin nonusers was 0.57 (95% confidence interval 0.38-0.87). When subdividing statin users and statin nonusers into groups according to concomitant treatment with inhaled corticosteroids (ICS) the following HRs were found: 0.75 (0.58-0.98) for ICS only; 0.69 (0.36-1.3) for statins only; and 0.39 (0.22-0.67) for the combined treatment with statin and ICS compared with no such treatment. Treatment with statins was associated with improved survival after chronic obstructive pulmonary disease exacerbation, while inhaled corticosteroids appeared to increase the survival benefit associated with statin use.

Respiratory symptoms and 30 year mortality from obstructive lung disease and pneumonia.

BACKGROUND: As little is known about the long term relationship between respiratory symptoms and mortality from non-malignant respiratory diseases, a study was undertaken to investigate the predictive value of respiratory symptoms and symptom load for mortality from obstructive lung disease (OLD) and pneumonia in the long term in a Norwegian population. METHODS: In 1972, 19 998 persons aged 15-70 years living in Oslo were randomly selected for a respiratory survey. The response rate was 89%. All were followed for 30 years. The association between cough, asthma-like symptoms, two levels of dyspnoea on exercise, a symptom score, and mortality from OLD and pneumonia were investigated separately for men and women by multivariable analyses, with adjustment for age, occupational exposure to air pollution, and smoking habits. RESULTS: OLD accounted for 43% and pneumonia for 50% of all deaths from respiratory causes. In men the hazard ratio for mortality from OLD varied from 4.0 (95% confidence interval (CI) 2.4 to 6.5) for cough to 9.6 (95% CI 5.1 to 18.3) for severe dyspnoea, and in women from 5.1 (95% CI 2.3 to 11.3) for moderate dyspnoea to 13.0 (95% CI 6.0 to 28.3) for severe dyspnoea. The symptom score was strongly predictive of death from OLD in a dose-response manner. CONCLUSIONS: There is a significant, positive, strong association between respiratory symptoms and 30 year mortality from OLD. The association between respiratory symptoms and mortality from pneumonia is weaker and not significant.

Respiratory symptoms as predictors of all-cause mortality in an urban community: a 30-year follow-up.

OBJECTIVE: We investigated the relationship between respiratory symptoms and mortality from all causes in a large Norwegian population. We also examined mortality during separate periods of follow-up. DESIGN: Population-based, prospective cohort study. SETTING AND SUBJECTS: A total of 19,998 men and women were randomly selected from the general population of Oslo. They received a postal respiratory questionnaire. The response rate was 88%. MAIN OUTCOME MEASURES: The relationship between 11 respiratory symptoms and 30 years of total mortality was investigated separately for men and women by multivariate analyses with adjustment for age, smoking habits and occupational exposure to air pollution. RESULTS: The relative mortality risk in comparison with asymptomatic subjects varied from 1.36 (95% confidence interval 1.25-1.48) for cough symptoms to 2.46 (2.13-2.85) for severe dyspnoea amongst men; the corresponding rates amongst women were 1.28 (1.16-1.40) and 1.52 (1.31-1.75), respectively. The relative risk of mortality in individuals with 1-3, 4-6 and 7 or more symptoms was 1.20, 1.60 and 2.53 (P for trend 0.000) in men and 1.14, 1.47 and 1.84 (P for trend 0.000) in women. Except for cough, the mortality rates associated with respiratory symptoms decreased significantly during follow-up. The positive association between respiratory symptoms and mortality was observed in people with and without cardiopulmonary diseases. CONCLUSIONS: Respiratory symptoms were significant predictors of mortality from all causes over 30 years, decreased during follow-up and were still increased after 30 years.

[The chain that saves life. Prehospital treatment of myocardial infarction]. / Kjeden som redder liv. Prehospital behandling av hjerteinfarkt.

A 53-year old woman living in a rural area 220 km from the nearest hospital experienced an acute myocardial infarction. The local doctor contacted the emergency service and requisitioned an air ambulance. 29 minutes later the physician-manned helicopter arrived, and thrombolytic treatment was started after 15 minutes. The patient arrived at the county hospital 35 minutes later, after having been electroconverted three times because of ventricular fibrillation. The patient was discharged from hospital ten days later with no cerebral sequelae, and left ventricular ejection fraction 49%. This example shows that active use of emergency communications systems and air ambulances enables both prompt thrombolytic treatment and the effective treatment of complications associated with myocardial infarction to be accomplished.

[Occurrence of asthma among school children in Norway during the period 1985-94]. / Forekomsten av astma blant skolebarn i Norge i perioden 1985-94.

Several comparable surveys of childhood as have been performed in Norway. This article describes the prevalence among children, 6-13 years old, during the period 1985-94, and how this prevalence is influenced by the operational definition of asthma. Questionnaires were administered in eight areas; Troms/Finnmark (1985), Nordland (1985), Ardal/Laerdal (1989/92), Sør-Varanger (1992), Oslo (1994), Hallingdal (1994) and Odda (1994). The response rates varied from 85 to 96%. The parent-reported lifetime prevalences were lowest in the areas where the studies took place in 1985, the earliest year of study; Nordland 7.2% (95% CI 6.5-7.9), Troms/Finnmark 8.1% (7.4-8.8). The prevalence increased up to 1994, with the highest prevalence in Oslo 13.7% (12.0-15.4). The prevalence of current asthma was about half the lifetime prevalence; Oslo 5.7% (4.6-6.8) compared with 10.1% (8.5-11.6). When respiratory symptoms the estimates were doubled in some areas and regional differences were reduced. The prevalence increased during the study period and seemed to be highest in northern Norway. Regions classified as polluted did not have a higher prevalence.

Relation between decline in FEV1 and exposure to dust and tobacco smoke in aluminium potroom workers.

OBJECTIVES: To investigate the relation between pulmonary function and occupational exposure in aluminium pot operators. METHODS: 2795 observations were obtained in 630 workers over six years of follow up. An autoregressive method of analysis was used. RESULTS: After adjustment for FEV1 in the three previous years, the effect of smoking v no smoking on FEV1 was -43.1 ml, 95% confidence interval (95% CI) -72.3 to -13.9. Similarly, an increase in the exposure to particulates by 1 mg/m3 corresponded to a decrease in FEV1 of -11.9 ml, 95% CI -19.9 to -3.9. Age was a significant predictor of both FEV1 and FVC. CONCLUSION: Exposure to particulates in aluminium potrooms seems to increase the decline in FEV15 thereby increasing the risk of development of chronic obstructive lung disease in pot operators.

Allergen sensitization and exposure to irritants in infancy.

We investigated the relationship between residence in the neighbourhood of an aluminium smelter and the prevalence of atopy in schoolchildren (7-13 years of age). Atopy was assessed in 556 of the 620 participants by a skin prick test with eight common aeroallergens. The median exposures to sulphur dioxide and fluoride during the pollen season in the age interval 19-36 months were 24 and 3.1 micrograms/m3 in the spring and 20 and 3.3 micrograms/m3 in the summer, respectively. The odds ratio (OR) of having atopy was 2.0 (95% CI: 1.2-3.3) in those children who had lived in the index area for 7 years or more compared with those who had lived there less than 7 years (cumulative effect). The OR of atopy was 2.5 (1.4-4.4) in those who had lived in the index area during the age interval of 19-36 months compared with rural residence during this age-interval (age-specific effect). When the age-specific effect and the cumulative effect were compared in the same logistic model, the former decreased to 1.1 (0.4-3.0), whereas the latter was 2.2 (0.7-6.6). The results indicate that exposure to these low levels of irritants during early childhood increases allergen sensitization in children.

Increased variability in bronchial responsiveness in aluminum potroom workers with work-related asthma-like symptoms.

In a longitudinal study, we studied the variability in bronchial responsiveness (BR) to methacholine in aluminum potroom workers suffering from work-related asthma-like symptoms (WASTH) and in symptom-free workers. In the index group, 26 men suffering from WASTH were selected from a cross-sectional survey. The reference group comprised 45 symptom-free men recruited from the enrollment of new employees. Bronchial responsiveness was expressed as the dose-response slope (DRS) of the line through origin and the last data point. The standard deviation of the log-transformed DRS was positively associated with symptom score (P = .012) and the mean BR (P < .001). Our results indicate that the severity of respiratory symptoms in aluminum potroom workers with WASTH reflects the variability in BR.

Bronchial responsiveness, eosinophilia, and short term exposure to air pollution.

The number of capillary blood eosinophils and the prevalence of bronchial hyperresponsiveness (BHR) were compared between schoolchildren living in a polluted area (Ardal) and unpolluted area (Laerdal). In Ardal there is an aluminium smelter emitting sulphur dioxide and fluoride to the environment. Daily measurements of these pollutants in ambient air were available. The mean number of eosinophils in Ardal was 220 x 10(6)/l compared with 106 x 10(6)/l in Laerdal. The prevalence of BHR was 15.9% in Ardal and 11.8% in Laerdal. The odds ratio of having BHR in relation to these pollutants during the last 24 hours were: 1.12 (95% confidence interval (CI) 1.01 to 1.24) by increasing sulphur dioxide with 10 micrograms/m3, and 1.31 (95% CI 1.07 to 1.60) when fluoride exposure increased with 1 micrograms/m3. Similarly, these exposures were associated with a decrease in eosinophils of -21 x 10(6)/l (95% CI -36 to -6) and -52 x 10(6)/l (95% CI -98 to -8), respectively, in atopics. It is hypothesised that recent exposure to irritants induces changes in the airways leading to BHR in addition to recruitment of eosinophils to the airways in atopic subjects.

Postnatal maternal smoking increases the prevalence of asthma but not of bronchial hyperresponsiveness or atopy in their children.

We have compared the prevalence of asthma, bronchial hyperresponsiveness (BHR), and atopy in relation to parental smoking in children aged 7 to 13 years. Information on the presence of asthma was obtained from a questionnaire, BHR was assessed by a methacholine challenge test, and atopy was defined as a positive response to a skin prick test. A complete history of the parents' smoking habits during their children's life, including prenatal smoking habits, was recorded. The prevalence of maternal smoking increased from 37.9% during pregnancy to 45.3% at the cross-sectional survey. None of the outcomes was significantly related to paternal smoking, whereas postnatal maternal smoking was positively associated with asthma (odds ratio [OR] = 2.8; 95% confidence interval [CI], 1.3 to 6.1). A negative association between prenatal maternal smoking and atopy was found (OR = 0.6; 95% CI, 0.3 to 0.9). We found no significant association between BHR and parental smoking. Our results indicate that postnatal maternal smoking increases the prevalence of asthma in the offspring without inducing BHR.

Bronchial responsiveness decreases in relocated aluminum potroom workers compared with workers who continue their potroom exposure.

We have compared the bronchial responsiveness (BR) of 12 aluminum potroom workers (index group) who were relocated due to work-related asthmatic symptoms (WASTH) and 26 subjects (reference group) with WASTH who continued to work in potrooms. The subjects were examined at regular intervals during a 2-year follow-up period. BR was expressed as the log-transformed dose-response slope [Ln(DRS 5)]. The monthly change in BR (delta BR) in the index group was -4.87 x 10(-2) compared with -1.58 x 10(-2) in the reference group. After adjustment for potential confounders, the difference between the index group and the reference group was -2.39 x 10(-2) (95% CI: -4.07 x 10(-2) to -0.71 x 10(-2)), i.e. 49% of the decrease in BR in the index group could be explained by the removal from exposure. No improvement in lung function was found in the index group compared with the reference group. The results indicate that the removal of potroom workers from exposure causes a decrease in BR.

Relation of exposure to airway irritants in infancy to prevalence of bronchial hyper-responsiveness in schoolchildren.

To find out whether exposure to sulphur dioxide during infancy is related to the prevalence of bronchial hyper-responsiveness (BHR), we studied schoolchildren (aged 7-13 years) from two areas of Norway--a valley containing a sulphur-dioxide-emitting aluminium smelter and a similar but non-industrialised valley. Bronchial responsiveness was assessed in 529 of the 620 participants. The median exposures to sulphur dioxide and fluoride were 37.1 micrograms/m3 and 4.4 micrograms/m3 at ages 0-12 months and 37.9 micrograms/m3 and 4.4 micrograms/m3 at 13-36 months. The risk of BHR increased with exposure to sulphur dioxide and fluoride at these ages; the odds ratio for a 10 micrograms/m3 increase in sulphur dioxide exposure at 0-12 months was 1.62 (95% CI 1.11-2.35) and that for a 1 microgram/m3 increase in fluoride exposure was 1.35 (1.07-1.70) at 0-12 months and 1.38 (1.05-1.82) at 13-36 months. Exposure to these low concentrations of airway irritants during early childhood is associated with an increased prevalence of BHR in schoolchildren.