Risk factors for SARS-CoV-2 infection: a test-negative case-control study with additional population controls in Norway.

OBJECTIVES: This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group. DESIGN AND SETTING: Test-negative design (TND), multicentre case-control study with additional population controls in South-Eastern Norway. PARTICIPANTS: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls. PRIMARY OUTCOME MEASURES: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group. RESULTS: In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8). CONCLUSIONS: Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case-control study designs during the pandemic.

Loss to 5-year follow-up in the population-based Telemark Study: risk factors and potential for bias.

OBJECTIVES: This study aimed to characterise participants lost to follow-up and identify possible factors associated with non-participation in a prospective population-based study of respiratory health in Norway. We also aimed to analyse the impact of potentially biased risk estimates associated with a high proportion of non-responders. DESIGN: Prospective 5-year follow-up study. SETTING: Randomly selected inhabitants from the general population of Telemark County in south-eastern Norway were invited to fill in a postal questionnaire in 2013. Responders in 2013 were followed-up in 2018. PARTICIPANTS: 16 099 participants aged 16-50 years completed the baseline study. 7958 responded at the 5-year follow-up, while 7723 did not. MAIN OUTCOME MEASURES: χ2 test was performed to compare demographic and respiratory health-related characteristics between those who participated in 2018 and those who were lost to follow-up. Adjusted multivariable logistic regression models were used to assess the relationship between loss to follow-up, background variables, respiratory symptoms, occupational exposure and interactions, and to analyse whether loss to follow-up leads to biased risk estimates. RESULTS: 7723 (49%) participants were lost to follow-up. Loss to follow-up was significantly higher for male participants, those in the youngest age group (16-30 years), those in lowest education level category and among current smokers (all p<0.001). In multivariable logistic regression analysis, loss to follow-up was significantly associated with unemployment (OR 1.34, 95% CI 1.22 to 1.46), reduced work ability (1.48, 1.35 to 1.60), asthma (1.22, 1.10 to 1.35), being woken by chest tightness (1.22, 1.11 to 1.34) and chronic obstructive pulmonary disease (1.81, 1.30 to 2.52). Participants with more respiratory symptoms and exposure to vapour, gas, dust and fumes (VGDF) (1.07 to 1.00-1.15), low-molecular weight (LMW) agents (1.19, 1.00 to 1.41) and irritating agents (1.15, 1.05 to 1.26) were more likely to be lost to follow-up. We found no statistically significant association of wheezing and exposure to LMW agents for all participants at baseline (1.11, 0.90 to 1.36), responders in 2018 (1.12, 0.83 to 1.53) and those lost to follow-up (1.07, 0.81 to 1.42). CONCLUSION: The risk factors for loss to 5-year follow-up were comparable to those reported in other population-based studies and included younger age, male gender, current smoking, lower educational level and higher symptom prevalence and morbidity. We found that exposure to VGDF, irritating and LMW agents can be risk factors associated with loss to follow-up. Results suggest that loss to follow-up did not affect estimates of occupational exposure as a risk factor for respiratory symptoms.

Association of respiratory symptoms with body mass index and occupational exposure comparing sexes and subjects with and without asthma: follow-up of a Norwegian population study (the Telemark study).

BACKGROUND: Occupational exposure and increased body mass index (BMI) are associated with respiratory symptoms. This study investigated whether the association of a respiratory burden score with changes in BMI as well as changes in occupational exposure to vapours, gas, dust and fumes (VGDF) varied in subjects with and without asthma and in both sexes over a 5-year period. METHODS: In a 5-year follow-up of a population-based study, 6350 subjects completed a postal questionnaire in 2013 and 2018. A respiratory burden score based on self-reported respiratory symptoms, BMI and frequency of occupational exposure to VGDF were calculated at both times. The association between change in respiratory burden score and change in BMI or VGDF exposure was assessed using stratified regression models. RESULTS: Changes in respiratory burden score and BMI were associated with a ß-coefficient of 0.05 (95% CI 0.04 to 0.07). This association did not vary significantly by sex, with 0.05 (0.03 to 0.07) for women and 0.06 (0.04 to 0.09) for men. The association was stronger among those with asthma (0.12; 0.06 to 0.18) compared with those without asthma (0.05; 0.03 to 0.06) (p=0.011). The association of change in respiratory burden score with change in VGDF exposure gave a ß-coefficient of 0.15 (0.05 to 0.19). This association was somewhat greater for men versus women, with coefficients of 0.18 (0.12 to 0.24) and 0.13 (0.07 to 0.19), respectively (p=0.064). The estimate was similar among subjects with asthma (0.18; -0.02 to 0.38) and those without asthma (0.15; 0.11 to 0.19). CONCLUSIONS: Increased BMI and exposure to VGDF were associated with increased respiratory burden scores. The change due to increased BMI was not affected by sex, but subjects with asthma had a significantly larger change than those without. Increased frequency of VGDF exposure was associated with increased respiratory burden score but without statistically significant differences with respect to sex or asthma status.

Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors.

BACKGROUND: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete. OBJECTIVES: This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics. METHOD: In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17-58] years, 53% females) were examined 17 (6-32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT. RESULTS: Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05. CONCLUSIONS: Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.

Influence of asthma and obesity on respiratory symptoms, work ability and lung function: findings from a cross-sectional Norwegian population study.

BACKGROUND: Although asthma and obesity are each associated with adverse respiratory outcomes, a possible interaction between them is less studied. This study assessed the extent to which asthma and overweight/obese status were independently associated with respiratory symptoms, lung function, Work Ability Score (WAS) and sick leave; and whether there was an interaction between asthma and body mass index (BMI) ≥25 kg/m2 regarding these outcomes. METHODS: In a cross-sectional study, 626 participants with physician-diagnosed asthma and 691 without asthma were examined. All participants completed a questionnaire and performed spirometry. The association of outcome variables with asthma and BMI category were assessed using regression models adjusted for age, sex, smoking status and education. RESULTS: Asthma was associated with reduced WAS (OR=1.9 (95% CI 1.4 to 2.5)), increased sick leave in the last 12 months (OR=1.4 (95% CI 1.1 to 1.8)) and increased symptom score (OR=7.3 (95% CI 5.5 to 9.7)). Obesity was associated with an increased symptom score (OR=1.7 (95% CI 1.2 to 2.4)). Asthma was associated with reduced prebronchodilator and postbronchodilator forced expiratory volume in 1 s (FEV1) (ß=-6.6 (95% CI -8.2 to -5.1) and -5.2 (95% CI -6.7 to -3.4), respectively) and prebronchodilator forced vital capacity (FVC) (ß=-2.3 (95% CI -3.6 to -0.96)). Obesity was associated with reduced prebronchodilator and postbronchodilator FEV1 (ß=-2.9 (95% CI -5.1 to -0.7) and -2.8 (95% CI -4.9 to -0.7), respectively) and FVC (-5.2 (95% CI -7.0 to -3.4) and -4.2 (95% CI -6.1 to -2.3), respectively). The only significant interaction was between asthma and overweight status for prebronchodilator FVC (ß=-3.6 (95% CI -6.6 to -0.6)). CONCLUSIONS: Asthma and obesity had independent associations with increased symptom scores, reduced prebronchodilator and postbronchodilator FEV1 and reduced prebronchodilator FVC. Reduced WAS and higher odds of sick leave in the last 12 months were associated with asthma, but not with increased BMI. Besides a possible association with reduced FVC, we found no interactions between asthma and increased BMI.

Effect of high-intensity training on bone health and body composition in lung transplant recipients: A secondary analysis of a randomized controlled trial.

BACKGROUND: Loss of bone mineral and skeletal muscle mass is common after lung transplantation (LTx), and physical activity (PA) may prevent further deterioration. We aimed to assess the effects of 20-week high-intensity training (HIT) on body composition, bone health, and PA in LTx recipients, 6-60 months after surgery. METHODS: In a randomized controlled trial, 51 LTx recipients underwent Dual-energy X-ray absorptiometry (DXA), and PA level and sedentary time were objectively recorded by accelerometers for seven consecutive days. Of these, 39 participants completed the study, including 19 participants in the HIT group and 20 participants in the standard care group. RESULTS: Following the intervention, ANCOVA models revealed a nonsignificant between-group difference for change in lean body mass (LBM) and bone mineral density (BMD) of the lumbar spine of 0.4% (95% CI = -3.2, 1.5) (p = .464) and 1.0% (95% CI=-1.3, 3.4) (p = .373), respectively. Trabecular bone score (TBS) of the lumbar spine (L1-L4), however, increased by 2.2 ± 5.0% in the exercise group and decreased by -1.6 ± 5.9% in the control group, giving a between-group difference of 3.8% (95% CI=0.1, 7.5) (p = .043). There were no between-group differences in PA or sedentary time. CONCLUSION: High-intensity training after LTx improved TBS significantly, but not PA, LBM or BMD.

Determinants of cardiorespiratory fitness in very long-term survivors of allogeneic hematopoietic stem cell transplantation: a national cohort study.

PURPOSE: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O2peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function. METHODS: In a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17-54) years, 56% females] were examined, 17 (6-26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test. RESULTS: Chronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DLCO) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O2peak was 36.4 (34.7-38.0) mL/min/kg [89 (85-93)% of predicted]. V̇O2peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O2peak was associated with low DLCO, low LVEF, BOS, overweight, and inactivity. CONCLUSION: Half of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.

Possible risk factors for poor asthma control assessed in a cross-sectional population-based study from Telemark, Norway.

This cross-sectional study of the general population of Telemark County, Norway, aimed to identify risk factors associated with poor asthma control as defined by the Asthma Control Test (ACT), and to determine the proportions of patients with poorly controlled asthma who had undergone spirometry, used asthma medication, or been examined by a pulmonary physician. In 2014-2015, the study recruited 326 subjects aged 16-50 years who had self-reported physician-diagnosed asthma and presence of respiratory symptoms during the previous 12 months. The clinical outcome measures were body mass index (BMI), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) in serum and serum C-reactive protein (CRP). An ACT score ≤ 19 was defined as poorly controlled asthma. Overall, 113 subjects (35%) reported poor asthma control. The odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with poorly controlled asthma were: self-reported occupational exposure to vapor, gas, dust, or fumes during the previous 12 months (OR 2.0; 95% CI 1.1-3.6), body mass index ≥ 30 kg/m2 (OR 2.2; 95% CI 1.2-4.1), female sex (OR 2.6; 95% CI 1.5-4.7), current smoking (OR 2.8; 95% CI 1.5-5.3), and past smoking (OR 2.3; 95% CI 1.3-4.0). Poor asthma control was also associated with reduced FEV1 after bronchodilation (ß -3.6; 95% CI -7.0 to -0.2). Moreover, 13% of the participants with poor asthma control reported no use of asthma medication, 51% had not been assessed by a pulmonary physician, and 20% had never undergone spirometry. Because these data are cross-sectional, further studies assessing possible risk factors in general and objectively measured occupational exposure in particular are needed. However, our results suggest that there is room for improvement with regards to use of spirometry and pulmonary physician referrals when a patient's asthma is inadequately controlled.

Lifestyle, sick leave and work ability among Norwegian employees with asthma-A population-based cross-sectional survey conducted in Telemark County, Norway.

OBJECTIVE: To investigate whether physician-diagnosed asthma modifies the associations between multiple lifestyle factors, sick leave and work ability in a general working population. METHODS: A cross-sectional study was conducted in Telemark County, Norway, in 2013. A sample of 16 099 respondents completed a self-administered questionnaire. We obtained complete data on lifestyle, work ability and sick leave for 10 355 employed persons aged 18-50 years. We modelled sick leave and work ability using multiple logistic regression, and introduced interaction terms to investigate whether associations with lifestyle factors were modified by asthma status. RESULTS: Several lifestyle risk factors and a multiple lifestyle risk index were associated with sick leave and reduced work ability score among persons both with and without physician-diagnosed asthma. A stronger association between lifestyle and sick leave among persons with asthma was confirmed by including interaction terms in the analysis: moderate lifestyle risk score * asthma OR = 1.4 (95% CI 1.02-2.1); high lifestyle risk score * asthma OR = 1.6 (95% CI 1.1-2.3); very high lifestyle risk score * asthma OR = 1.6 (95% CI 0.97-2.7); obesity * asthma OR = 1.5 (95% CI 1.02-2.1); past smoking * asthma OR = 1.4 (95% CI 1.01-1.9); and current smoking * asthma OR = 1.4 (95% CI 1.03-2.0). There was no significant difference in the association between lifestyle and work ability score among respondents with and without asthma. CONCLUSIONS: In the present study, we found that physician-diagnosed asthma modified the association between lifestyle risk factors and sick leave. Asthma status did not significantly modify these associations with reduced work ability score. The results indicate that lifestyle changes could be of particular importance for employees with asthma.

Cardiorespiratory Fitness and Physical Activity following Lung Transplantation: A National Cohort Study.

BACKGROUND: Low cardiorespiratory fitness and inactivity are common after lung transplantation (LTx). The causes of exercise intolerance are incompletely understood. OBJECTIVES: The aim of this study was to objectively assess cardiorespiratory fitness and physical activity, evaluate causes of exercise intolerance, and explore clinical factors associated with cardiorespiratory fitness after bilateral LTx (BLTx). MATERIALS AND METHODS: Peak oxygen uptake (V∙O2peak) and exercise-limiting factors were evaluated by a treadmill cardiopulmonary exercise test (CPET) 6-60 months after BLTx. Physical activity was measured with accelerometers, and results were compared with Norwegian normative data and the World Health Organization's (WHO) recommendations for physical activity. RESULTS: In 54 included BLTx recipients (mean age 50 ± 15 years, 50% females), V∙O2peak (mL × kg-1 × min-1) was 21.8 ± 7.7 for men and 22.4 ± 6.2 for women, corresponding to 57 ± 17 and 70 ± 12% of predicted, respectively. Three patients (6%) met criteria for normal V∙O2peak. Deconditioning limited V∙O2peak in 22 patients (41%), while ventilatory limitation and abnormal gas exchange were observed in 14 (26%) and 20 (37%) patients, respectively (some had more than 1 finding). Forty-three patients (86%) did not meet the WHO physical activity recommendations. There was a moderate correlation between V∙O2peak and physical activity (r = 0.642, p < 0.01). Body mass index, physical activity, forced expiratory volume after 1 second, sex, and hemoglobin together accounted for 73% of the variability in V∙O2peak. CONCLUSIONS: Low cardiorespiratory fitness was observed in the majority of BLTx recipients. Both deconditioning and cardiopulmonary limitations were common findings. Nearly 90% were classified as being inactive according to physical activity recommendations. CPET appears to identify a deconditioned subgroup of BLTx recipients for whom exercise training may be especially beneficial.

Chronic Rhinosinusitis Related to Occupational Exposure: The Telemark Population Study.

OBJECTIVE: The aim of this study was to investigate the association between occupational exposure and chronic rhinosinusitis. METHODS: A random population from the region of Telemark, aged 16 to 50 years, answered a respiratory questionnaire including questions on chronic rhinosinusitis and exposure in the occupational environment. RESULTS: A total of 16,099/48,142 subjects responded. The prevalence of chronic rhinosinusitis was 9%. Exposure associated with chronic rhinosinusitis comprised paper dust [odds ratio (OR) 1.3, 95% confidence interval (95% CI) 1.1 to 1.5], cleaning agents (OR 1.2, 95% CI 1.0 to 1.3), metal dust (OR 1.3, 95% CI 1.1 to 1.6), animals (OR 1.2, 95% CI 1.0 to 1.5), moisture/mould/mildew (OR 1.3, 95% CI 1.1 to 1.5), and physically strenuous work (OR 1.4, 95% CI 1.2 to 1.7). CONCLUSION: Occupational exposure to paper dust, cleaning agents, metal dust, animals, moisture/mould/mildew, and physically strenuous work was independently related to having chronic rhinosinusitis. An occupational history should be reviewed when assessing patients with chronic rhinosinusitis.

Risk factors for impaired pulmonary function and cardiorespiratory fitness in very long-term adult survivors of childhood acute lymphoblastic leukemia after treatment with chemotherapy only.

BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk of late treatment-related side-effects. Data regarding prevalence and risk factors for impairments in pulmonary function and cardiorespiratory fitness are limited, and reported findings are inconsistent and inconclusive. MATERIAL AND METHODS: In a cross-sectional study, 116 ALL survivors (median 5 years at diagnosis, 29 years at follow-up, 53% females) were examined, median 23 years after treatment with chemotherapy only. Individual cumulative doses of cytostatic agents were calculated. Methods included blood tests, echocardiography, pulmonary function tests and cardiorespiratory exercise test. RESULTS: Females had lower % predicted gas diffusing capacity (DLCO) than males (mean [SD] 84 [13] versus 97 [14], p < .001). Impairment in DLCO was found in 34% females versus 7% males, p < .001. In a multiple linear regression model, female gender, body mass index (BMI) and smoking were risk factors for reduced % predicted DLCO, with a borderline significant effect of left ventricular ejection fraction (LVEF). Impaired cardiorespiratory fitness was found in 42% of the survivors, with a borderline increased risk in females, p = .06. Smoking and BMI were risk factors for reduced % predicted VO2peak. Subjects exposed to anthracyclines had lower LVEF% and % predicted VO2peak than those not exposed, (mean [SD] 56.2 [4.3] versus 59.2 [5.2], p = .01 and 86.9 [18.4] versus 92.8 [18.4], p = .03, respectively). CONCLUSIONS: Impairments in pulmonary function and cardiorespiratory fitness are common in very long-term survivors of childhood ALL. Risk factors are female gender, BMI and smoking. In order to preserve pulmonary function and cardiorespiratory fitness, we suggest increased attention and targeted advice on modifiable lifestyle factors such as smoking, inactivity and overweight.

Cause-specific death after surgical resection for early-stage non-small-cell lung cancer.

OBJECTIVES: Surgical resection is the recommended treatment for patients with early-stage non-small-cell lung cancer. However, it is believed that causes other than lung cancer can lead to death following surgical resection. Investigating the risk factors for overall mortality and analysing the specific causes of death may indicate the degree of influence of other causes of death. METHODS: We assessed individual risk factors affecting overall and cause-specific mortality in a Cox proportional hazards model in a cohort of patients with resected Stage I/II non-small-cell lung cancer (n = 756) from 2007 to 2015 in a tertiary university centre. The follow-up period ranged from 3 days to 9.3 years. Median survival time was 7.3 years (95% confidence interval 6.0-7.9). A few patients died of cardiovascular disease (n = 19) and were included in the group 'other cause'. In a competing risk model, we evaluated the risk factors for specific causes of death in patients dying of lung cancer and dying of non-lung cancer specific conditions. RESULTS: The overall survival was 94%, 62% and 50% at 1, 5 and 7 years, respectively. At the end of the follow-up period, the risk of having died of, respectively, lung cancer or other causes was 36% and 24%. The cumulative incidence of death of lung cancer increased continuously during the study. Risk factors predicting death of all causes and death of non-small-cell lung cancer were increasing age, severely reduced lung function, Eastern Cooperative Oncology Group Performance Status ≥2, preoperative examination without positron emission tomography/computed tomography, histological tumour diagnosis other than adenocarcinoma and squamous cell carcinoma and increasing disease stage. In patients dying of other causes, age, gender, body mass index, smoking and Eastern Cooperative Oncology Group Performance Status ≥2 affected the mortality rate. CONCLUSIONS: The probability of having died of lung cancer continued to increase beyond 5 years after the operation. Surveillance of risk factors associated with an increased mortality rate should be considered in the postoperative follow-up examination after lung cancer resection.

Military small arms fire in association with acute decrements in lung function.

OBJECTIVE: After introduction of unleaded ammunition, Norwegian Armed Forces received reports of acute respiratory symptoms in soldiers after exposure to fumes from firing the standard weapon, HK416. The aim of the present study was to examine lung function before and after exposure to fumes from HK416 in a double-blinded standardised study design using three different types of ammunition. METHODS: Fifty-four healthy, non-smoking male volunteers (19-62 years) fired the weapons for 60 min with either leaded, unleaded or 'modified' unleaded ammunition. Gaseous and particulate emissions were monitored. Spirometry and exhaled nitric oxide (eNO) were performed within 14 days before (T0), shortly after (T1) and 24 hours after (T2) shooting. Methacholine provocation and diffusing capacity of carbon monoxide (DLCO) were carried out at T0 and T2. RESULTS: The mean forced expiratory volume in 1 s on a group level was significantly reduced both at T1 and T2 compared with T0, with means and 95% CI of 226 mL (158 to 294 mL) and 285 mL (218 to 351 mL), respectively. The same significant pattern was seen for DLCO, forced vital capacity and eNO. The methacholine test indicated a slight increase in bronchial hyper-reactivity. However, there were no significant differences between types of ammunition used. CONCLUSION: Exposure to fumes from military weapons might be a respiratory hazard for soldiers who do live-fire training regularly or are in a closed combat environment.

Gender-specific survival after surgical resection for early stage non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. The incidence and mortality rate of lung cancer in women has increased. Studies have indicated that females with non-small cell lung cancer (NSCLC) have better survival than males. We aimed to examine the impact of gender on 1-, 5- and 10-year survival after surgery for stage I and II NSCLC. MATERIALS AND METHODS: During the period 2003-2013, 692 patients operated for stage I and II NSCLC were prospectively registered. Patients were stratified into four groups according to gender and age over or less than 66 years. The relationship between gender and age on overall survival was investigated. Adjustment for multiple confounders was performed using the Cox proportional hazard regression model. RESULTS: Surgical resection was performed in 368 (53.2%) males and 324 (46.8%) females. During the study period, mortality was 35.2% in younger females, 34.9% in younger males, 42.8% in older females and 51.2% in older males. Stratified by age, there were no significant gender differences with regard to survival [hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.46, p = .23]. Comparing the younger and the older patients adjusted for confounders, the mortality risk was significantly increased in elderly patients [females, adjusted HR 1.60, 95% CI 1.12-2.28]. Compared with population data, standardized mortality ratio was increased to 4.1 (95% CI 3.5-4.7) in males and to 6.5 (95% CI 5.4-7.6) in females. CONCLUSION: Overall survival did not differ significantly between males and females. Adjusted for confounding factors, we found a significantly increased mortality risk in elder patients compared to their younger counterparts. However, five-year overall survival of more than 50% for older patients with NSCLC should encourage surgical treatment also in elderly lung cancer patients.

Sputum neutrophils are elevated in smelter workers, and systemic neutrophils are associated with rapid decline in FEV1.

OBJECTIVES: In a previous study on smelter workers we, found significant relationship between exposure to dust and accelerated annual decline in forced expiratory volume in 1 s (FEV1). In this cross-sectional study at the end of a follow-up, we aimed to investigate the possible association between annual decline in FEV1 and markers of airways, and systemic inflammation in smelter workers. METHODS: Employees (n=76 (27 current smokers)) who had been part of a longitudinal study (9-13 years) that included spirometry (>6 measurements) and respiratory questionnaires, performed induced sputum, exhaled NO and had blood drawn. Participants with annual decline in FEV1≥45 mL were compared with participants with annual decline <45 mL; also 26 non-exposed controls were included. RESULTS: Compared with non-exposed controls, smelter workers demonstrated a significantly increased percentage of neutrophils (mean (SD)) (57% (17) vs 31% (15)) and matrix metalloproteinases 8 (MMP-8) levels in sputum, and MMP-9, surfactant protein D (SpD) and transforming growth factor ß (TGFb) levels in blood. A significant association in FEV1≥45 mL was found for blood neutrophils when controlling for smoking habits (OR=1.7 (95% CI 1.0 to 2.8), p=0.045). Airway and blood protein markers were not associated with annual decline in FEV1. CONCLUSIONS: All workers displayed airway and systemic inflammation characterised by increased levels of neutrophils and MMP-8 in sputum, and MMP-9, SpD and TGFß in blood compared with non-exposed controls. Blood neutrophils in particular were significantly elevated in those workers with the most rapid decline in lung function. A similar observation was not seen with airway neutrophils. In the present study, we were able to identify systemic but not airway inflammatory markers that can predict increased decline in FEV1 in smelter workers.

Survival After Surgical Resection for Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: The best curable therapy for lung cancer is surgical resection. Chronic obstructive pulmonary disease (COPD) may influence survival, and lung function is crucial in the preoperative assessment. We hypothesized that COPD would influence survival after lung cancer resection. METHODS: During the period 2003 to 2013, 688 patients were operated on for stage I and II non-small cell lung cancer and prospectively registered. Spirometry was performed, and COPD categorized according to the definition by the Global Initiative for Chronic Obstructive Lung Disease. An explanatory strategy was used to investigate the relationship between severe COPD and survival. RESULTS: COPD was present in 455 patients (66.1%) and was severe in 51 (7.4%) and mild to moderate in 404 (58.7%), whereas 233 patients (33.9%) had normal lung function. Cumulative survival was similar in patients with normal lung function and patients with mild to moderate COPD. Patients with severe COPD had significantly reduced cumulative survival after 2 and 5 years of 63.5% (95% confidence interval [CI], 48.4% to 75.2%) and 41.8% (95% CI, 26.5% to 56.3%), respectively, compared with nonsevere COPD at 81.7% (95% CI, 77.4% to 85.2%) and 61.3% (95% CI, 55.3% to 66.6%), respectively. Severe COPD was associated with a 69% increased risk of mortality (adjusted hazard ratio, 1.69; 95% CI, 1.12 to 2.55). CONCLUSIONS: With careful preoperative selection, surgical resection may safely be offered to lung cancer patients with severe COPD. However, these patients have decreased long-term overall survival. Similar survival between patients with normal lung function and mild to moderate COPD suggests that similar indications for lung cancer operations may be applied.

Annual decline in forced expiratory volume is steeper in aluminum potroom workers than in workers without exposure to potroom fumes.

BACKGROUND: Aluminum potroom exposure is associated with increased mortality of COPD but the association between potroom exposure and annual decline in lung function is unknown. We have measured lung volumes annually using spirometry from 1986 to 1996. The objective was to compare annual decline in forced expiratory volume in 1 s (dFEV1) and forced vital capacity (dFVC). METHODS: The number of aluminum potroom workers was 4,546 (81% males) and the number of workers in the reference group was 651 (76% males). The number of spirometries in the index group and the references were 24,060 and 2,243, respectively. RESULTS: After adjustment for confounders, the difference in dFEV1 and dFVC between the index and reference groups were 13.5 (P < 0.001) and -8.0 (P = 0.060) ml/year. CONCLUSION: Aluminum potroom operators have increased annual decline in FEV1 relative to a comparable group with non-exposure to potroom fumes and gases.

Non-response in a cross-sectional study of respiratory health in Norway.

OBJECTIVES: Declining participation in epidemiological studies has been reported in recent decades and may lead to biased prevalence estimates and selection bias. The aim of the study was to identify possible causes and effects of non-response in a population-based study of respiratory health in Norway. DESIGN: The Telemark study is a longitudinal study that began with a cross-sectional survey in 2013. SETTING: In 2013, a random sample of 50,000 inhabitants aged 16-50 years, living in Telemark county, received a validated postal questionnaire. The response rate was 33%. In this study, a random sample of 700 non-responders was contacted first by telephone and then by mail. OUTCOME MEASURES: Response rates, prevalence and OR of asthma and respiratory symptoms based on exposure to vapours, gas, dust or fumes (VGDF) and smoking. Causes of non-response. RESULTS: A total of 260 non-responders (37%) participated. Non-response was associated with younger age, male sex, living in a rural area and past smoking. The prevalence was similar for responders and non-responders for physician-diagnosed asthma and several respiratory symptoms. The prevalence of chronic cough and use of asthma medication was overestimated in the Telemark study, and adjusted prevalence estimates were 17.4% and 5%, respectively. Current smoking was identified as a risk factor for respiratory symptoms among responders and non-responders, while occupational VGDF exposure was a risk factor only among responders. The Breslow-Day test detected heterogeneity between productive cough and occupational VGDF exposure among responders. CONCLUSIONS: The Telemark study provided valid estimates for physician-diagnosed asthma and several respiratory symptoms, while it was necessary to adjust prevalence estimates for chronic cough and use of asthma medication. Reminder letters had little effect on risk factor associations. Selection bias should be considered in future investigations of the relationship between respiratory outcomes and exposures.

Construction of a Job Exposure Matrix to Dust, Fluoride, and Polycyclic Aromatic Hydrocarbons in the Norwegian Aluminum Industry using Prediction Models.

BACKGROUND: The Norwegian aluminum industry developed and implemented a protocol for prospective monitoring of employees' exposure using personal samplers. We analyzed these data to develop prediction lines to construct a job exposure matrix (JEM) for the period 1986-1995. METHODS: The protocol for personal monitoring of exposure was implemented in all seven Norwegian aluminum plants in 1986 and continued until 1995. Personal samplers were used to collect total dust, fluorides, and total polycyclic aromatic hydrocarbons (PAH). In addition, exposure could be categorized according to process, i.e. prebake, Søderberg, and 'other'. We constructed four-dimensional JEMs characterized by: Plant, Job descriptor, Process, and Year. Totally 8074, 6734, and 3524 measurements were available for dust, fluorides, and PAH, respectively. The data were analyzed using linear mixed models with two-way interactions. The models were assessed using the Akaike criterion (AIC) and unadjusted R (2). The significance level was set to 10% (two-sided) for retaining variables in the model. RESULTS: In 1986, the geometric mean (95% confidence interval in parentheses) for total dust, total fluorides, and PAH were 3.18 (0.46-22.2) mg m(-3), 0.58 (0.085-4.00) mg m(-3), and 33.9 (2.3-504) µg m(-3), respectively. During 10 years of follow-up, the exposure to total dust, fluorides, and PAH decreased by 9.2, 11.7, and 14.9% per year, respectively. Each model encompassed from 49 to 72 significant components of the interaction terms. The interaction components were at least as important as the main effects, and 65 to 91% of the significant components of the interaction terms were time-dependent. CONCLUSION: Our prediction models indicated that exposures were highly time-dependent. We expect that the time-dependent changes in exposure are of major importance for longitudinal studies of health effects in the aluminum industry.