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.

Comparison of different reference values for lung function: implications of inconsistent use among centers.

BACKGROUND: For interpretation of pulmonary function tests (PFTs), reference values based on sex, age, height and ethnicity are needed. In Norway, the European Coal and Steel Community (ECSC) reference values remain widely used, in spite of recommendations to implement the more recent Global Lung Function Initiative (GLI) reference values. OBJECTIVE: To assess the effects of changing from ECSC to GLI reference values for spirometry, DLCO and static lung volumes, using a clinical cohort of adults with a broad range in age and lung function. METHODS: PFTs from 577 adults (18-85 years, 45% females) included in recent clinical studies were used to compare ECSC and GLI reference values for FVC, FEV1, DLCO, TLC and RV. Percent predicted and lower limit of normal (LLN) were calculated. Bland-Altman plots were used to assess agreement between GLI and ECSC % predicted values. RESULTS: In both sexes, GLI % predicted values were lower for FVC and FEV1, and higher for DLCO and RV, compared to ECSC. The disagreement was most pronounced in females, with mean (SD) difference 15 (5) percent points (pp) for DLCO and 17 (9) pp for RV (p < 0.001). With GLI, DLCO was below LLN in 23% of the females, with ECSC in 49% of the females. CONCLUSIONS: The observed differences between GLI and ECSC reference values are likely to entail significant consequences with respect to criteria for diagnostics and treatment, health care benefits and inclusion in clinical trials. To ensure equity of care, the same reference values should be consistently implemented across centers nationwide.

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.

Relation of sputum neutrophilia to the development of chronic lung allograft dysfunction after lung transplantation.

Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation (LuTx) and is associated with elevated proportions of neutrophils in bronchoalveolar lavage (BAL). Induced sputum is a less-invasive sampling method than BAL and assesses markers of inflammation on the surfaces of large central airways. We wanted to examine whether % neutrophil levels in induced sputum were elevated prior to CLAD diagnosis among LuTx recipients, and whether sputum markers of inflammation can be used as a tool for predicting the development of CLAD. Induced sputum samples were collected at 1, 3, 6, 12, and 24 months post-LuTx in 36 patients with a history of COPD or pulmonary fibrosis, and of these, 16 developed CLAD either during or after the sputum surveillance period. At 2 years, median (IQR) % neutrophils in induced sputum were significantly higher among patients with CLAD compared with those without CLAD [73 (52-80) % vs 59 (41-76) %, p = .01]. Interestingly, we found a significant increase in the rate of change in % neutrophils beginning at 90 days preceding the diagnosis of CLAD. This suggests using sputum neutrophil percentage as a surveillance modality for monitoring lung allograft function after LuTx.

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.

Effect of high-intensity training on peak oxygen uptake and muscular strength after lung transplantation: A randomized controlled trial.

BACKGROUND: Peak oxygen uptake (VO2peak) remains low after lung transplantation (LTx). We evaluated the effect of high-intensity interval training (HIIT) on VO2peak, muscular strength, health-related quality of life (HRQOL), pulmonary function, and physical function after LTx. METHODS: In this randomized controlled trial, 54 participants were enrolled from 6 to 60 months after LTx. The HIIT group (n = 25) followed a supervised HIIT program, consisting of endurance and strength trainings 3 times a week for 20 weeks. The control group (n = 29) received usual care. The primary outcome was a change in VO2peak measured by cardiopulmonary exercise testing. The secondary outcomes were changes in 1-repetition maximum (1RM) for arm press and leg press, HRQOL (36-Item Short-Form Health Survey [SF-36]), pulmonary function (forced expiratory volume in 1 sec, diffusing capacity of the lungs for carbon monoxide), and physical function (1RM in handgrip, 15-sec stair run, and 30-sec chair stand). RESULTS: A total of 46 participants completed the study, including 23 of 25 in the intervention group. For the primary outcome, the intention-to-treat analysis revealed a non-significant between-group difference for change in VO2peak of 0.7 ml/(kg.min) (95% CI = ‒0.3, 1.8) (p = 0.17). The between-group differences for 1RM arm press and leg press and mental aspect of SF-36 were 4.9 kg (95% CI = ‒0.1, 9.9) (p = 0.05), 11.6 kg (95% CI = 0.1, 23.0) (p < 0.05), and 5.7 kg (95% CI = 0.9, 10.4) (p = 0.02), respectively. There were no between-group differences in pulmonary function or physical function. When excluding participants with an attendance of <70% (n = 16), the between-group difference for VO2peak was 1.2 ml/(kg.min) (95% CI = 0.1, 2.4) (p = 0.032). CONCLUSIONS: HIIT improved muscular strength and HRQOL but did not improve VO2peak more than usual care after LTx. However, with acceptable adherence, HIIT appears to have beneficial effects on VO2peak.

Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD.

Introduction: Chronic obstructive pulmonary disease (COPD) may, in some patients, be characterized by recurring acute exacerbations. Often these exacerbations are associated with airway infections. As immunoglobulins (Ig) are important parts of the immune defence against airway infections, the aim of this study was to relate the levels of circulating immunoglobulins to clinical features in unselected patients with COPD included in a Norwegian multicenter study. Methods: Clinical and biological data, including circulating levels of immunoglobulins, were assessed in 262 prospectively included patients with COPD GOLD stage II-IV at five hospitals in south-eastern Norway. A revisit was done after one year, and survival was assessed after five years. Clinical features and survival of those with immunoglobulin levels below reference values were compared to those with normal levels. Results: In total, 11.5% of all COPD patients and 18.5% of those with GOLD stage IV had IgG concentrations below reference values. These patients were more likely to use inhaled or oral steroids, had lower BMI, and lower FEV1%. Moreover, they had significantly more COPD-related hospital admissions (2.8 vs 0.6), number of prednisolone courses (3.9 vs 1.2), and antibiotic treatments (3.7 vs 1.5) in the preceding year. Importantly, hypogammaglobulinemia was significantly associated with reduced survival in a log-rank analysis. In multivariate regression analysis, we found that the higher risk for acute exacerbations in these patients was independent of other risk factors and was associated with impaired survival. Conclusion: In conclusion, our study suggests that hypogammaglobulinemia may be involved in poor outcome in COPD and may thus be a feasible therapeutic target for interventional studies in COPD.

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.

Influence of Obesity on Work Ability, Respiratory Symptoms, and Lung Function in Adults with Asthma.

BACKGROUND: Asthma is defined by variable respiratory symptoms and lung function, and may influence work ability. Similarly, obesity may contribute to respiratory symptoms, affect lung function, and reduce work ability. Thus, assessment of the influence of obesity on work ability, respiratory symptoms, and lung function in adults with asthma is needed. OBJECTIVES: We hypothesized that patients with obesity and asthma have more respiratory symptoms and reduced work ability and lung function compared with normal-weight patients with asthma. METHODS: We examined 626 participants with physician-diagnosed asthma, aged 18-52 years, recruited from a cross-sectional general population study using a comprehensive questionnaire including work ability score, the asthma control test (ACT), height and weight, and spirometry with reversibility testing. RESULTS: Participants with a body mass index (BMI) ≥30 kg/m2 (i.e., obese) had a higher symptom score (OR 1.78, 95% CI 1.14-2.80), current use of asthma medication (1.60, 1.05-2.46), and incidence of ACT scores ≤19 (poor asthma control) (1.81, 1.03-3.18) than participants with BMI ≤24.9 kg/m2 (i.e., normal weight). Post-bronchodilator forced vital capacity (FVC) as a percentage of predicted (ß coefficient -4.5) and pre-bronchodilator forced expiratory volume in 1 s as a percentage of predicted (FEV1) (ß coefficient -4.6) were negatively associated with BMI ≥30 kg/m2. We found no statistically significant association of BMI >30 kg/m2 (compared to BMI <24.9 kg/m2) with sick leave (1.21, 0.75-1.70) or reduced work ability (1.23, 0.74-2.04). CONCLUSIONS: There were indications that patients with obesity had a higher symptom burden, poorer asthma control, higher consumption of asthma medication, and reduced lung function, in particular for FVC, compared with normal-weight patients.

Annual decline in forced expiratory volume and airway inflammatory cells and mediators in a general population-based sample.

BACKGROUND: Few studies have examined the relationships between sputum inflammatory markers and subsequent annual decline in forced expiratory volume in 1 s (dFEV1). This study investigated whether indices of airway inflammation are predictors of dFEV1 in a general population-based sample. METHODS: The study, conducted from 2003 to 2005, included 120 healthy Norwegian subjects aged 40 to 70 years old. At baseline, the participants completed a self-administered respiratory questionnaire and underwent a clinical examination that included spirometry, venous blood sampling, and induced sputum examination. From 2015 to 2016, 62 (52%) participants agreed to a follow-up examination that did not include induced sputum examination. Those with a FEV1/forced vital capacity (FVC) ratio <  0.70 underwent a bronchial reversibility test. The levels of cytokines, pro-inflammatory M1 macrophage phenotypes were measured in induced sputum using bead-based multiplex analysis. The associations between cytokine levels and dFEV1 were then analysed. RESULTS: The mean dFEV1 was 32.9 ml/year (standard deviation 26.3). We found no associations between dFEV1 and the baseline indices of sputum inflammation. Seven participants had irreversible airflow limitation at follow-up. They had lower FEV1 and gas diffusion at baseline compared with the remaining subjects. Moreover, two of these individuals had a positive reversibility test and sputum eosinophilia at baseline. CONCLUSIONS: In this cohort of presumably healthy subjects, we found no associations between sputum inflammatory cells or mediators and dFEV1 during 10 years of follow-up.

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.