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BACKGROUND: Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis. METHODS: Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50-64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile. RESULTS: Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormal R5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted. CONCLUSIONS: Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.

BACKGROUND: Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis. METHODS: Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50-64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile. RESULTS: Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormal R5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted. CONCLUSIONS: Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.

BACKGROUND: Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis. METHODS: Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50-64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile. RESULTS: Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormal R5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted. CONCLUSIONS: Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.

This study presents a separable nonlinear least squares (SNLLS) implementation of the minimum distance (MD) estimator employing a fixed-weight matrix for estimating structural equation models (SEMs). In contrast to the standard implementation of the MD estimator, in which the complete set of parameters is estimated using nonlinear optimization, the SNLLS implementation allows a subset of parameters to be estimated using (linear) least squares (LS). The SNLLS implementation possesses a number of benefits, such as faster convergence, better performance in ill-conditioned estimation problems, and fewer required starting values. The present work demonstrates that SNLLS, when applied to SEM estimation problems, significantly reduces the estimation time. Reduced estimation time makes SNLLS particularly useful in applications involving some form of resampling, such as simulation and bootstrapping.

This study presents a separable nonlinear least squares (SNLLS) implementation of the minimum distance (MD) estimator employing a fixed-weight matrix for estimating structural equation models (SEMs). In contrast to the standard implementation of the MD estimator, in which the complete set of parameters is estimated using nonlinear optimization, the SNLLS implementation allows a subset of parameters to be estimated using (linear) least squares (LS). The SNLLS implementation possesses a number of benefits, such as faster convergence, better performance in ill-conditioned estimation problems, and fewer required starting values. The present work demonstrates that SNLLS, when applied to SEM estimation problems, significantly reduces the estimation time. Reduced estimation time makes SNLLS particularly useful in applications involving some form of resampling, such as simulation and bootstrapping.

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively). Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

This study presents a separable nonlinear least squares (SNLLS) implementation of the minimum distance (MD) estimator employing a fixed-weight matrix for estimating structural equation models (SEMs). In contrast to the standard implementation of the MD estimator, in which the complete set of parameters is estimated using nonlinear optimization, the SNLLS implementation allows a subset of parameters to be estimated using (linear) least squares (LS). The SNLLS implementation possesses a number of benefits, such as faster convergence, better performance in ill-conditioned estimation problems, and fewer required starting values. The present work demonstrates that SNLLS, when applied to SEM estimation problems, significantly reduces the estimation time. Reduced estimation time makes SNLLS particularly useful in applications involving some form of resampling, such as simulation and bootstrapping.

RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation. OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population. METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation). CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.

Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID. Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes. Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype. Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively). Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID. Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes. Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype. Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.

Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID. Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes. Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype. Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively). Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively). Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID. Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes. Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype. Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.

BACKGROUND: Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis. METHODS: Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50-64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile. RESULTS: Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormal R5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted. CONCLUSIONS: Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.

BACKGROUND: Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis. METHODS: Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50-64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile. RESULTS: Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormal R5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted. CONCLUSIONS: Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.

Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID. Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes. Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype. Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.

BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively). Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

This study presents a separable nonlinear least squares (SNLLS) implementation of the minimum distance (MD) estimator employing a fixed-weight matrix for estimating structural equation models (SEMs). In contrast to the standard implementation of the MD estimator, in which the complete set of parameters is estimated using nonlinear optimization, the SNLLS implementation allows a subset of parameters to be estimated using (linear) least squares (LS). The SNLLS implementation possesses a number of benefits, such as faster convergence, better performance in ill-conditioned estimation problems, and fewer required starting values. The present work demonstrates that SNLLS, when applied to SEM estimation problems, significantly reduces the estimation time. Reduced estimation time makes SNLLS particularly useful in applications involving some form of resampling, such as simulation and bootstrapping.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.

This study presents a separable nonlinear least squares (SNLLS) implementation of the minimum distance (MD) estimator employing a fixed-weight matrix for estimating structural equation models (SEMs). In contrast to the standard implementation of the MD estimator, in which the complete set of parameters is estimated using nonlinear optimization, the SNLLS implementation allows a subset of parameters to be estimated using (linear) least squares (LS). The SNLLS implementation possesses a number of benefits, such as faster convergence, better performance in ill-conditioned estimation problems, and fewer required starting values. The present work demonstrates that SNLLS, when applied to SEM estimation problems, significantly reduces the estimation time. Reduced estimation time makes SNLLS particularly useful in applications involving some form of resampling, such as simulation and bootstrapping.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.

Impulse oscillometry (IOS) can be used to assess the mechanical properties of the respiratory airways. The method is easy to perform as it requires only tidal breathing and may provide complimentary information beyond that from dynamic spirometry. For the method to be clinically useful, reference values appropriate with regard to methodology and population are needed. The IOS equipment producer recommended reference values are derived from a German population[1], while method specific reference values for healthy non-smoking adult Caucasian are available from smaller datasets from Europe[2] and Australia[3].

Impulse oscillometry (IOS) can be used to assess the mechanical properties of the respiratory airways. The method is easy to perform as it requires only tidal breathing and may provide complimentary information beyond that from dynamic spirometry. For the method to be clinically useful, reference values appropriate with regard to methodology and population are needed. The IOS equipment producer recommended reference values are derived from a German population[1], while method specific reference values for healthy non-smoking adult Caucasian are available from smaller datasets from Europe[2] and Australia[3].

Impulse oscillometry (IOS) can be used to assess the mechanical properties of the respiratory airways. The method is easy to perform as it requires only tidal breathing and may provide complimentary information beyond that from dynamic spirometry. For the method to be clinically useful, reference values appropriate with regard to methodology and population are needed. The IOS equipment producer recommended reference values are derived from a German population[1], while method specific reference values for healthy non-smoking adult Caucasian are available from smaller datasets from Europe[2] and Australia[3].

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.

Impulse oscillometry (IOS) can be used to assess the mechanical properties of the respiratory airways. The method is easy to perform as it requires only tidal breathing and may provide complimentary information beyond that from dynamic spirometry. For the method to be clinically useful, reference values appropriate with regard to methodology and population are needed. The IOS equipment producer recommended reference values are derived from a German population[1], while method specific reference values for healthy non-smoking adult Caucasian are available from smaller datasets from Europe[2] and Australia[3].

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.

Impulse oscillometry (IOS) can be used to assess the mechanical properties of the respiratory airways. The method is easy to perform as it requires only tidal breathing and may provide complimentary information beyond that from dynamic spirometry. For the method to be clinically useful, reference values appropriate with regard to methodology and population are needed. The IOS equipment producer recommended reference values are derived from a German population[1], while method specific reference values for healthy non-smoking adult Caucasian are available from smaller datasets from Europe[2] and Australia[3].

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method: This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25-54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53-3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18-4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method: This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25-54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53-3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18-4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.

Background Fractional exhaled nitric oxide (FENO) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FENO and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FENO levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation. Methods FENO was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16–3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens. Results Subjects IgE-sensitised to cat or mite had higher FENO compared to non-atopic subjects (FENO (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FENO compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001). Conclusions The type and degree of IgE sensitisation should be considered in generating FENO reference values.

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method: This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25-54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53-3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18-4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.

Background Fractional exhaled nitric oxide (FENO) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FENO and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FENO levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation. Methods FENO was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16–3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens. Results Subjects IgE-sensitised to cat or mite had higher FENO compared to non-atopic subjects (FENO (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FENO compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001). Conclusions The type and degree of IgE sensitisation should be considered in generating FENO reference values.

Background Fractional exhaled nitric oxide (FENO) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FENO and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FENO levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation. Methods FENO was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16–3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens. Results Subjects IgE-sensitised to cat or mite had higher FENO compared to non-atopic subjects (FENO (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FENO compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001). Conclusions The type and degree of IgE sensitisation should be considered in generating FENO reference values.

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method: This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25-54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53-3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18-4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.

Background Fractional exhaled nitric oxide (FENO) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FENO and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FENO levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation. Methods FENO was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16–3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens. Results Subjects IgE-sensitised to cat or mite had higher FENO compared to non-atopic subjects (FENO (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FENO compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001). Conclusions The type and degree of IgE sensitisation should be considered in generating FENO reference values.

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method: This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25-54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53-3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18-4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.

Background Fractional exhaled nitric oxide (FENO) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FENO and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FENO levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation. Methods FENO was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16–3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens. Results Subjects IgE-sensitised to cat or mite had higher FENO compared to non-atopic subjects (FENO (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FENO compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001). Conclusions The type and degree of IgE sensitisation should be considered in generating FENO reference values.