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Objectives: In many countries, workers who developed asbestosis due to their occupation are eligible for government support. Based on the results of clinical examination, a team of pulmonologists determine the eligibility of patients to these programs. In this Dutch cohort study, we aim to demonstrate the potential role of an artificial intelligence (AI)-based system for automated, standardized, and cost-effective evaluation of applications for asbestosis patients. Methods: A dataset of n = 523 suspected asbestosis cases/applications from across the Netherlands was retrospectively collected. Each case/application was reviewed, and based on the criteria, a panel of three pulmonologists would determine eligibility for government support. An AI system is proposed, which uses thoracic CT images as input, and predicts the assessment of the clinical panel. Alongside imaging, we evaluated the added value of lung function parameters. Results: The proposed AI algorithm reached an AUC of 0.87 (p < 0.001) in the prediction of accepted versus rejected applications. Diffusion capacity (DLCO) also showed comparable predictive value (AUC = 0.85, p < 0.001), with little correlation between the two parameters (r-squared = 0.22, p < 0.001). The combination of the imaging AI score and DLCO achieved superior performance (AUC = 0.95, p < 0.001). Interobserver variability between pulmonologists on the panel was estimated at alpha = 0.65 (Krippendorff's alpha). Conclusion: We developed an AI system to support the clinical decision-making process for the application to the government support for asbestosis. A multicenter prospective validation study is currently ongoing to examine the added value and reliability of this system alongside the clinic panel. Key Points: • Artificial intelligence can detect imaging patterns of asbestosis in CT scans in a cohort of patients applying for state aid. • Combining the AI prediction with the diffusing lung function parameter reaches the highest diagnostic performance. • Specific cases with fibrosis but no asbestosis were correctly classified, suggesting robustness of the AI system, which is currently under prospective validation. [ABSTRACT FROM AUTHOR]

A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients (p = 0.003), but not in PRD patients (p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients., (© 2024. The Author(s).)

Background and Objective: Bronchiectasis is a frequent incidental finding on chest computed tomography (CT), but its relevance in lung cancer screening is not fully understood. We investigated the association between bronchiectasis and respiratory symptoms, pulmonary function, and emphysema in lung cancer screening participants with and without chronic obstructive pulmonary disease (COPD)., Methods: We included 3260 (ex-)smokers from the Dutch-Belgian lung cancer screening trial (NELSON). Bronchiectasis was scored by chest radiologists. The relationship with pulmonary function (FEV1%predicted, FEV1/FVC), respiratory complaints (cough, dyspnea, wheezing, mucus hypersecretion), and CT-quantified emphysema (15th percentile) was examined with independent t-tests and multivariate regression., Results: Bronchiectasis was present in 5.4% (n = 175/3260). There was no difference in prevalence between subjects with and without COPD (68/1121 [5.9%] vs. 109/2139 [5.1%]; p = .368). COPD subjects with bronchiectasis had a lower FEV1%predicted (76.2% vs. 85.0%; p < .001), lower FEV1/FVC (0.58 vs. 0.62; p < .001), and more emphysema (- 938 HU vs. - 930 HU; p = .001) than COPD subjects without bronchiectasis. In COPD subjects, bronchiectasis was independently associated with a lower FEV1%predicted (B =  - 7.7; CI [- 12.3, - 3.3]), lower FEV1/FVC (B =  - 2.5; CI [- 4.3, - 0.8]), more cough (OR 2.4; CI [1.3, 4.3]), more mucus hypersecretion (OR 1.8; CI [1.0, 3.1]) and more dyspnea (OR 2.3; CI [1.3, 3.9]). In those without COPD (n = 2139), bronchiectasis was associated with more cough, mucus hypersecretion, and wheezing, but not with deteriorating lung function., Conclusion: Bronchiectasis was present in 5.4% of our lung cancer screening participants and was associated with more respiratory symptoms and, in those with COPD, with lower lung function and more emphysema., Clinical Relevance Statement: In a lung cancer screening population, bronchiectasis has a prevalence of 5.4% with a mainly mild severity. This finding is of little clinical relevance unless mild COPD is also present. In those subjects, bronchiectasis was associated with a lower lung function, more respiratory symptoms, and more emphysema., Key Points: • Bronchiectasis was found in 5.4% of lung cancer screening participants, consisting of (ex-)smokers with and without mild COPD. • In those with mild COPD, bronchiectasis was associated with a lower lung function, more respiratory symptoms, and more emphysema. • Incidental findings of mild bronchiectasis are not very relevant in a lung cancer screening population, unless COPD is also present., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: We aimed to assess which sociodemographic factors are associated with current asthma and indicators of lung function in 10‐year‐old children. Methods: We analysed data of 5237 children (Mean age: 9.7, SD: 0.3) from the Generation R Study (2012‐2016), a population‐based cohort study in the Netherlands. Indicators of sociodemographic factors included parental educational level, net household income, financial difficulties, parental employment status and child ethnic background. Current asthma (yes/no) was defined as ever doctor‐diagnosed‐asthma combined with wheezing symptoms or asthma‐medication use in the past 12 months. Lung function was measured by spirometry and included forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow after exhaling 75% of FVC (FEF75). Within‐study sex‐, height‐ and age‐adjusted lung function measurements' z‐scores were converted. Results: After adjustment for all sociodemographic factors, an independent association was observed between ethnic background with current asthma and lung function. Compared with children with a Dutch background, children with a nonwestern ethnic background had a higher odds of having current asthma (OR: 1.61, 95% CI: 1.02, 2.53), lower FVC z‐score (−0.25, 95% CI: −0.35, −0.14), higher FEV1/FVC z‐score (0.26, 95% CI: 0.14, 0.37) and higher FEF75% z‐score (0.15, 95% CI: 0.04, 0.25). Conclusions: Among 10‐year‐old children, ethnic background was associated with current asthma and lung function after adjusting for a wide range of sociodemographic factors. No associations were found between socioeconomic status indicators and current asthma. Explanations for these associations such as language barriers, suboptimal care or pathophysiological differences require further investigation. [ABSTRACT FROM AUTHOR]

Background: Asthma is one of the most common chronic diseases in childhood. According to guidelines, a diagnosis of asthma should be confirmed using lung function testing in children aged >6 years. Previous studies indicate that asthma in children is probably overdiagnosed. However, the extent has not previously been assessed.Aim: To assess the extent and characteristics of confirmed and unconfirmed diagnoses of asthma in children who were diagnosed by their GP as having asthma or who were treated as having asthma.Design and Setting: Retrospective analysis in four academic primary healthcare centres in Utrecht, the Netherlands.Method: Routine care registration data of children aged 6-18 years who received a diagnosis of asthma or were treated as having asthma were analysed.Results: In only 16.1% (n = 105) of the children diagnosed with asthma was the diagnosis confirmed with spirometry, whereas in 23.2% (n = 151) the signs and symptoms did give rise to suspected asthma but the children should have undergone further lung function tests. In more one-half (53.5%, n = 349) of the children the signs and symptoms made asthma unlikely and thus they were most likely overdiagnosed. The remaining 7.2% (n = 47) were probably correctly classified as not having asthma. The main reasons for classifying asthma without children undergoing further lung function tests were dyspnoea (31.9%, n = 174), cough (26.0%, n = 142), and wheezing (10.4%, n = 57).Conclusion: Overdiagnosis of childhood asthma is common in primary care, leading to unnecessary treatment, disease burden, and impact on quality of life. However, only in a small percentage of children is a diagnosis of asthma confirmed by lung function tests. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to the impact of electronic-learning (e-learning) and repeated performance feedback on spirometry test quality in family practice. It informs that the study was undertaken as a cluster trial with 19 family practices in the Netherlands. It states that the Medical Ethics Committee of the Elkerliek approved the study. Several tables and charts related to the study are also presented.

Background: Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM) is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by in vitro spectral analysis of elastin powder. We hypothesized that FCFM images capture in vivo elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated.Methods: In a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls) spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κw.Results: The patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κw 0.744). The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV1 %predicted between the different patterns by histology (p = 0.001) and FCFM (p = 0.048), regardless of asthma or atopy.Conclusion: FCFM captures the elastic fibre pattern within the airway wall in humans in vivo. The association between post-bronchodilator FEV1 %predicted and both histological and FCFM elastic fibre patterns points towards a structure-function relationship between extracellular matrix in the airway wall and lung function.Trial Registration: Netherlands Trial Register NTR1306. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines for asthma care emphasize the use of objective measures of asthma severity, and yet little data exist on the relationship between FEV1 and asthma outcomes over long-term follow-up. Methods: We explored the association between measures of FEV1 percentage of predicted (FEV1% predicted) and subsequent asthma attacks over 3-year intervals. Subjects were identified from two longitudinal cohort studies conducted in the United States and the Netherlands. Persons were included in the analysis if they reported ever having an attack of wheezing with associated shortness of breath prior to or during the follow-up period Results: Over the course of longitudinal follow-up at 3-year intervals, 195 subjects in the Netherlands cohort contributed 510 observations, and 698 subjects in the US cohort contributed 1,268 observations (for each observation, the report of an attack since their last visit was paired with the subject's FEV1 recorded 3 years prior). Overall, subjects in the Netherlands cohort experienced 114 attacks (22% of the observations) and subjects in the US cohort had 517 attacks (40.6% of the observations). FEV1% predicted was significantly associated with risk of an asthma attack over the 3 years following its measurement. After adjusting for current smoking and gender, FEV1% predicted remained an independent predictor of subsequent asthma attacks. Conclusions: These findings support the use of spirometry as an objective measure of asthma severity and risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Donation after circulatory death (DCD) is a procedure in which after planned withdrawal of life-sustaining treatment (WLST), the dying process is monitored. A DCD procedure can only be continued if the potential organ donor dies shortly after WLST. This study performed an external validation of 2 existing prediction models to identify potentially DCD candidates, using one of the largest cohorts., Methods: This multicenter retrospective study analyzed all patients eligible for DCD donation from 2010 to 2015. The first model (DCD-N score) assigned points for absence of neurological reflexes and oxygenation index. The second model, a linear prediction model (LPDCD), yielded the probability of death within 60 min. This study determined discrimination (c-statistic) and calibration (Hosmer and Lemeshow test) for both models., Results: This study included 394 patients, 283 (72%) died within 60 min after WLST. The DCD-N score had a c-statistic of 0.77 (95% confidence intervals, 0.71-0.83) and the LPDCD model 0.75 (95% confidence intervals, 0.68-0.81). Calibration of the LPDCD 60-min model proved to be poor (Hosmer and Lemeshow test, P < 0.001)., Conclusions: The DCD-N score and the LPDCD model showed good discrimination but poor calibration for predicting the probability of death within 60 min. Construction of a new prediction model on a large data set is needed to obtain better calibration., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background/objective: Limited research exists regarding the association between grandmaternal smoking during pregnancy and the risk for asthma and altered lung function in grandchildren. This study aimed to investigate this association in a three-generation design., Methods: 37 291 participants (25 747 adults and 11 544 children) were included from the Lifelines study, a prospective longitudinal three generation cohort study in The Netherlands. Spirometry was available in 69.5% and 61.1% of the included adults and children. Logistic and linear regression were used to analyse the association between grandmaternal smoking during pregnancy and (1) asthma, (2) early childhood asthma (ie, onset before 6 years) and (3) lung function level. Maternal and paternal grandmaternal smoking were studied separately and the analyses were stratified by adult/child and by gender. The analyses were adjusted for gender, current smoking, birth variables and socioeconomic status., Results: In the adult population, maternal grandmaternal smoking during pregnancy was associated with a higher risk for asthma (OR (95% CI): 1.38 (1.06 to 1.79)), early childhood asthma (1.49 (95% CI 1.06 to 2.11)) and a lower FEV1/FVC% predicted (B (95% CI): -1.04 (-1.91 to -0.16) in men. These findings were not observed in a separate analysis of children that participated in this study. There was also no significant association between paternal grandmaternal smoking and asthma/lung function., Conclusion: Maternal grandmaternal smoking during pregnancy is associated with higher asthma risk and lower lung function in male grandchildren and a reverse effect in male grandchildren of subsequent generations. Our study highlights the deep-rooted effects of tobacco smoking across generations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The COVID-19 pandemic has led to many cases of pneumonia with extensive lung abnormalities on CT-scans. The consequences of COVID-19 pneumonia on survivors' pulmonary function and quality of life are unknown. The purpose of this study is to examine the impact of COVID-19 pneumonia on pulmonary function, health-related quality of life (HRQoL) and perceived dyspnoea., Methods: A prospective longitudinal cohort study regarding patients discharged from our hospital after PCR-proven, non-critical COVID-19 pneumonia was conducted. Cases were classified as moderate or severe pneumonia according to WHO definitions. Six weeks post-discharge subjects underwent interviews and pulmonary function tests, and completed questionnaires to assess their HRQoL, perceived dyspnoea (Borgscale and mMRC), and symptoms of depression and anxiety (HADS)., Results: 101 patients were included. Twenty-eight (27.7%) pneumonias were classified as moderate cases of COVID-19 pneumonia and 73 (72.3%) were classified as severe cases. Diffusion limitation (DLCOc < 80% of predicted value) was found in 66 (71.7%) of 92 cases, obstruction in 26 (25.7%) of 101, and restriction in 21 (21.2%) of 99. Diffusion capacity was significantly lower in cases after severe pneumonia. In the entire group, HADS scores ≥8 for depression were found in 16.6% and in 12.5% for anxiety. Across all SF-36 domains, except for bodily pain, significant impairment was found. FEV1 and DLCOc showed significant positive correlations with mMRC scores and multiple SF-36 domains, especially physical functioning., Conclusion: COVID-19 non-critical pneumonia survivors have significant impairment in diffusion capacity and HRQOL six weeks after being discharged from hospital., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The relevance of timing of exposure in the associations of secondhand tobacco smoke (SHS), pets, and dampness or mould exposure with lung function is unclear. We investigated the relevance of timing of these exposures for lung function in adolescence., Methods: We used data from participants of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort with spirometric measurements at ages 12 and 16 years (n=552). Data on residential exposure to SHS, pets, and dampness or mould were obtained by repeated parental questionnaires. We characterised timing of exposure through longitudinal patterns using latent class growth modelling and assessed associations of these patterns with FEV 1 and FVC at ages 12 and 16 and FEV 1 and FVC growth between ages 12 and 16 using linear regression models., Results: Childhood SHS exposure was associated with reduced FEV 1 growth/year (95% CI) (-0.34% (-0.64% to -0.04%)). Late childhood and early life pet exposure was associated with increased FEV 1 growth (0.41% (0.14% to 0.67%)) and reduced FVC growth (-0.28% (-0.53% to -0.03%)), respectively, compared with very low exposure. Early life dampness or mould exposure was associated with reduced lung function growth. All time windows of SHS exposure tended to be associated with lower attained lung function and pet exposure tended to be associated with higher FEV 1 ., Conclusion: SHS exposure during childhood could lead to reduced lung function growth and lower attained lung function in adolescence. While pet exposure in late childhood may not adversely affect lung function, early childhood pet exposure may slow down FVC growth in adolescence., Competing Interests: Competing interests: GHK received grants from the Dutch Lung Foundation, grants from Ubbo Emmius Foundation, grants from Teva The Netherlands and grants from Stichting Astma Bestrijding, outside the submitted work. UG reports receiving grants from the Dutch Lung Foundation during the conduct of this study., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The prevalence of asthma and obesity have increased over the last decades. A possible association between these two chronic illnesses has been suggested, since the prevalence of asthmatic symptoms rises with increasing Body Mass Index (BMI). However, asthma is only one of several possible causes of shortness of breath in obese children. The aim of this study is to evaluate the prevalence of overtreatment with asthma medication in a cohort overweight/obese children with respiratory symptoms visiting a pediatric outpatient clinic., Methods: Children referred to a pediatric outpatient clinic aged ≥4- ≤ 18 years with overweight/obesity (defined as BMI-sds > 1.1) and asthmatic symptoms were included. The diagnosis asthma was evaluated and classified in no, unlikely, probable and confirmed asthma, based on clinical parameters and/or spirometry results. Overtreatment was defined as asthma medication prescribed in participants classified as no or unlikely asthma. And undertreatment as probable or confirmed asthma without asthma medication prescribed ., Results: Three hundred thirty-eight participants were included, of which 92.6% (313/338) had a prescription for asthma medication. Overtreatment was observed in 27.2% (92/338) participants. Nine participants were undertreated., Conclusion: More than 25% overtreatment with asthma medication was observed in a cohort overweight/obese children with asthmatic symptoms. This finding emphasizes that the diagnosis of asthma must be confirmed before commencement of medication. The diagnosis of asthma should be based on standard questionnaires evaluating asthmatic symptoms, lung functions test and regular reassessments. Further studies concerning overtreatment with asthma medication in normal weight pediatric populations are warranted, to evaluate whether overtreatment is specific for overweight/obese children.

Background: Up to 10% of patients with Cystic Fibrosis develop cirrhotic CF-related liver disease with portal hypertension: CF cirrhosis (CFC). In a nationwide study, we aimed to determine the role of CFC on survival in the Netherlands between 1 and 1-2009 and1-1-2015., Methods: We identified all CFC patients in the Netherlands, based on ultrasonographic liver nodularity and portal hypertension. A non-cirrhotic control group was obtained from the national Dutch CF patient registry. We compared groups with regards to baseline lung function and nutritional status and survival and age at death over a 6-year period. In case of death of CFC patients, the clinical reported cause was recorded., Results: At baseline, we found no significant difference in lung function and nutritional status between the CFC patients (N = 95) and controls (N = 980). Both the 6-year survival rate (77 vs. 93%; P < .01) and the median age at death (27 vs. 37 years; P = .02) was significantly lower in CFC compared to controls. In the deceased CFC patients, the reported primary cause of death was pulmonary in 68% of cases, and liver failure related in 18% of cases., Conclusions: In the Netherlands, the presence of CFC is associated with a higher risk for early mortality and an approximately 10-year lower median age at death. This substantial poorer outcome of CFC patients was not reflected in a lower baseline lung function or a diminished nutritional status. However, in the case of mortality, the reported primary cause of death in CFC patients is predominantly pulmonary failure and not end-stage liver disease., (Copyright © 2018. Published by Elsevier B.V.)

Evidence for the effects of air pollution exposure on lung function growth into adolescence is scarce. We investigated associations of air pollution exposure with lung function and lung function growth until age 16.We conducted both longitudinal (n=915) and cross-sectional (n=721) analyses of associations of air pollution exposure with forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) growth from ages eight to 16 and FEV 1 and FVC at age 16. We estimated residential concentrations of nitrogen dioxide (NO 2 ), "soot" and particulate matter (PM x , where x is the 50% cut-off aerodynamic diameter in µm) with diameters of <2.5 µm (PM 2.5 ), <10 µm (PM 10 ) and 2.5-10 µm (PM coarse ) during the preschool, primary school and secondary school time windows by land use regression models. Associations with (growth in) FEV 1 and FVC were analysed by linear (mixed effects) regression.Higher air pollution exposure was associated with reduced FEV 1 growth ( e.g. adjusted difference -0.26% (95% CI -0.49 to -0.03%) per interquartile range increase in secondary school PM 2.5 ) and lower FEV 1 (adjusted difference -2.36% (95% CI -3.76 to -0.94%)), but was not adversely associated with FVC. Associations with FEV 1 were stronger in boys than girls and were not modified by asthma status.Higher air pollution exposure may lead to increased airway obstruction, but not reduced lung volume in adolescence., Competing Interests: Conflict of interest: G.H. Koppelman reports grants from the Lung Foundation of the Netherlands, during the conduct of the study; grants from the Lung Foundation of the Netherlands, the Ubbo Emmius Foundation, the TETRI Foundation and TEVA Netherlands, outside the submitted work. All funds were paid to G.H. Koppelman's institution., (Copyright ©ERS 2018.)

To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch CF Registry (2009-2014).Lung disease progression was expressed as a decline in lung function (forced expiratory volume in 1 s (FEV 1 ) % pred) and pulmonary exacerbation rate. Potential risk factors at baseline included sex, age, best FEV 1 % pred, best forced vital capacity % pred, genotype, body mass index z-score, pancreatic insufficiency, medication use (proton pump inhibitors (PPIs), prophylactic antibiotics and inhaled corticosteroids), CF-related diabetes, allergic bronchopulmonary aspergillosis and colonisation with Pseudomonas aeruginosa The data of 545 children were analysed. PPI use was associated with both annual decline of FEV 1 % pred (p=0.017) and future pulmonary exacerbation rate (p=0.006). Moreover, lower FEV 1 % pred at baseline (p=0.007), prophylactic inhaled antibiotic use (p=0.006) and pulmonary exacerbations in the baseline year (p=0.002) were related to pulmonary exacerbations in subsequent years.In a cohort of Dutch children with CF followed for 5 years, we were able to identify several risk factors for future exacerbations. In particular, the association between PPI use and lung disease progression definitely requires further investigation., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

Background: Little is known on the prevalence and characteristics of asthma in middle-aged and older adults, since previous studies mainly focused on children and young adults. Therefore, the aim was to investigate the prevalence of physician-diagnosed asthma and its comorbidities, in a population-based cohort of adults 45 years of age and over., Methods: We identified participants with physician-diagnosed asthma in the Rotterdam Study; a prospective population-based cohort in the Netherlands. Pulmonary function measurements and comorbidities of the asthma cases were assessed at baseline and compared to those of the general population., Results: Out of 14,621 participants (mean age 65.5 years; 59% women), 524 subjects (31.5%males) had physician-diagnosed asthma at study entry, implicating an asthma prevalence of 3.6% [95% Confidence Interval (CI) 3.3%-3.9%] (2.8% in males and 4.2% in females). Asthmatic subjects had a significantly higher prevalence of obesity and depressive symptoms (Odds Ratio [OR]: 2,02 [95% CI 1,66-2,47] and [OR]: 2,01 [95% CI 1,52-2,66] respectively). Longer duration of asthma and current smoking were associated with lower lung function in asthmatic subjects., Conclusion: Four percent of middle-aged and older adults have physician-diagnosed asthma. These adult asthmatics suffer more frequently from obesity and depression than subjects without obstructive lung disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Exacerbations of COPD are a major burden to patients, and yet little is understood about heterogeneity. It contributes to the current persistent one-size-fits-all treatment. To replace this treatment by more personalized, precision medicine, new insights are required. We assessed the heterogeneity of exacerbations by functional respiratory imaging (FRI) in 3-dimensional models of airways and lungs., Methods: The trial was designed as a multicenter trial of patients with an acute exacerbation of COPD who were assessed by FRI, pulmonary function tests, and patient-reported outcomes, both in the acute stage and during resolution., Results: Forty seven patients were assessed. FRI analyses showed significant improvements in hyperinflation (a decrease in total volume at functional residual capacity of -0.25±0.61 L, p ≤0.01), airway volume at total lung capacity (+1.70±4.65 L, p =0.02), and airway resistance. As expected, these improvements correlated partially with changes in the quality of life and in conventional lung function test parameters. Patients with the same changes in pulmonary function differ in regional disease activity measured by FRI., Conclusion: FRI is a useful tool to get a better insight into exacerbations of COPD, and significant improvements in its indices can be demonstrated from the acute phase to resolution even in relatively small groups. It clearly visualizes the marked variability within and between individuals in ventilation and resistance during exacerbations and is a tool for the assessment of the heterogeneity of COPD exacerbations., Competing Interests: Disclosure WHVG received an ERS Fellowship STRTF 2016 and reports a grant from Novartis to the institution for an investigator-initiated trial outside of the submitted work. WV reports grants from GSK, during the conduct of the study, and personal fees from FLUIDDA nv, outside of the submitted work. JDB is the founder and shareholder of FLUIDDA nv, a company that develops and markets part of the technology described in this paper. AC reports a grant from GSK, outside of the submitted work. OSU reports grants from AstraZeneca, GSK, Prosonix, and Edmond Pharma; personal fees from Boehringer Ingelheim, Aerocrine, Napp, Mundipharma, Sandoz, Takeda, Zentiva, and Cipla; and grants and personal fees from Chiesi, outside of the submitted work. CVH reports a grant from FLUIDDA nv, during the conduct of the study and also outside of the submitted work. HAMK reports that his institution has received a per patient fee for participation in the trial reported from FLUIDDA nv. BH, MP, and WDB report no conflicts of interest in this work.

COPD exacerbations are commonly quantified as rate per year. However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes. In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life. A total of 166 COPD patients reported symptom changes during 12 months. Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year. Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman's rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ). The correlation between exacerbation frequency and exacerbation-free weeks was -0.71 (p < 0.001). However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak (r = -0.25; p < 0.01). Smokers had less exacerbation-free weeks than non-smokers (β = -5.709, p < 0.05). More exacerbation-free weeks were related to better CRQ Total (r = 0.22, p < 0.05), Mastery (r = 0.22, p < 0.05), and Fatigue (r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores. In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time. Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does.

Background and Objective: Non-invasive ventilation (NIV) is an established treatment for respiratory failure in patients with amyotrophic lateral sclerosis (ALS). Several studies have shown room for improvement with regard to respiratory care for ALS patients, including latency of referral. These studies focused on the time period starting at the moment of referral to a home ventilation service (HVS) onwards. In the current study we performed a nationwide survey to gain insight in the trajectory before referral. We questioned the assessment of respiratory impairment by ALS physicians/care teams, including criteria for referral to an HVS., Methods: We requested 40 ALS care teams in the Netherlands to fill in an online questionnaire on respiratory management in ALS patients., Results: Thirty-two ALS care teams (80%) responded. Forced vital capacity was the most frequently used test at each outpatient visit (72%) and often served as a criterion (78%) for referral to an HVS. Other respiratory function measurements that were performed less often included peak cough flow (50%), maximum inspiratory/expiratory pressure (31% /28%) and sniff nasal inspiratory pressure (13%). Morning headache was the most frequently questioned complaint (94%), followed by daytime sleepiness (91%). Dyspnoea and orthopnoea were reported by 38% and 59% as important complaints. Out of all patients under the care of the ALS care teams, the mean estimated proportion of patients that was referred to an HVS was 69% (range 20-100%). When physicians refrained from referral, the most often cited reasons were patient's decision to withhold NIV (94%) and cognitive impairment (50%). Sixteen percent of the respondents stated bulbar impairment as a reason to refrain from referral., Conclusion: Despite findings in previous studies on the superiority of SNIP and PCF as compared to FVC, our study shows that a majority of ALS care teams still prefers to use FVC for the assessment of respiratory dysfunction and for the timing of referral to an HVS. Another finding is that bulbar impairment is not an obstacle for referral for NIV.

eHealth is an appealing medium to improve healthcare and its value (in addition to standard care) has been assessed in previous studies. We aimed to assess whether an eHealth intervention could improve asthma control while reducing 50% of routine outpatient visits.In a multicentre, randomised controlled trial with a 16-month follow-up, asthmatic children (6-16 years) treated in eight Dutch hospitals were randomised to usual care (4-monthly outpatient visits) and online care using a virtual asthma clinic (VAC) (8-monthly outpatient visits with monthly web-based monitoring). Outcome measures were the number of symptom-free days in the last 4 weeks of the study, asthma control, forced expiratory volume in 1 s, exhaled nitric oxide fraction, asthma exacerbations, unscheduled outpatient visits, hospital admissions, daily dose of inhaled corticosteroids and courses of systemic corticosteroids.We included 210 children. After follow-up, symptom-free days differed statistically between the usual care and VAC groups (difference of 1.23 days, 95% CI 0.42-2.04; p=0.003) in favour of the VAC. In terms of asthma control, the Childhood Asthma Control Test improved more in the VAC group (difference of 1.17 points, 95% CI 0.09-2.25; p=0.03). No differences were found for other outcome measures.Routine outpatient visits can partly be replaced by monitoring asthmatic children via eHealth., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

This study assesses the validity, reliability, and responsiveness of the Dutch version of the London Chest Activity of Daily Living scale (LCADL).The English LCADL version was translated into Dutch and then back-translated to English to check if the translation was conceptually equivalent to the original LCADL.Measurement properties were evaluated in191 patients with chronic obstructive pulmonary disease (COPD) (70 males; age 62 ± 9 years; FEV1 33 ± 10% pred). Construct validity was assessed using disease-specific health status, generic functional status, and functional and peak exercise capacity (Wmax). LCADL was completed twice to assess test-retest reliability. Responsiveness was assessed after 8 to 12 weeks inpatient pulmonary rehabilitation.LCADL correlated significantly with the St. George Respiratory Questionnaire (r = 0.24 to 0.64), functional status (r = 0.45 to 0.82), walking distance (r = -0.3 to -0.58), and Wmax (-0.27 to -0.38) and Wmax % pred (-0.26 to -0.43). Test-retest reliability was high (ICC 0.87 to 0.98). The smallest detectable change for the LCADL total and domain score self-care, domestic, physical, and leisure was 4.5, 2.9, 3.3, 4.9, and 2.2, respectively. Improvement in LCADL after PR correlated significantly with improvement in Chronic Respiratory Questionnaire (-0.43; P < 0.001).The Dutch LCADL is a reliable, valid, and responsive instrument to assess limitations in performing activities of daily living in patients with severe COPD., Competing Interests: The authors have no conflicts of interest to disclose.

Recent studies have shown that maternal obesity is associated with increased risk of wheezing in the offspring. We assessed whether impaired neonatal lung function could explain this association. We measured neonatal lung function in 2606 children of our prospective birth cohort. Information about daily symptoms of wheezing was obtained using questionnaires. Consultations and prescriptions for wheezing illnesses were derived from general practitioner patient files. Higher maternal body mass index (BMI) was associated with increased risk of wheezing in the first year of life and more consultations and prescriptions for wheezing illnesses until the age of 5 years. Lung function could partially explain the association with wheezing in the first year of life. Adding respiratory resistance to the model decreased the incidence rate ratio from 1.023 (95% CI 1.008-1.039) to 1.015 (95% CI 0.998-1.032). Anthropometrics of the 5-year-olds largely explained the association with consultations. Intermediates or confounders could not explain the association with prescriptions. There is an association between higher maternal BMI and increased risk of wheezing illnesses. In the first year of life, it is largely explained by an impaired lung function in early life, especially in children of nonatopic mothers. At the age of 5 years, infant lung function is of minor influence in this association., (Copyright ©ERS 2015.)

Background: There is limited knowledge about the extent to which estimates of air pollution effects on health are affected by the choice for a specific exposure model., Objectives: We aimed to evaluate the correlation between long-term air pollution exposure estimates using two commonly used exposure modeling techniques [dispersion and land use regression (LUR) models] and, in addition, to compare the estimates of the association between long-term exposure to air pollution and lung function in children using these exposure modeling techniques., Methods: We used data of 1,058 participants of a Dutch birth cohort study with measured forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) measurements at 8 years of age. For each child, annual average outdoor air pollution exposure [nitrogen dioxide (NO2), mass concentration of particulate matter with diameters ≤ 2.5 and ≤ 10 μm (PM2.5, PM10), and PM2.5 soot] was estimated for the current addresses of the participants by a dispersion and a LUR model. Associations between exposures to air pollution and lung function parameters were estimated using linear regression analysis with confounder adjustment., Results: Correlations between LUR- and dispersion-modeled pollution concentrations were high for NO2, PM2.5, and PM2.5 soot (R = 0.86-0.90) but low for PM10 (R = 0.57). Associations with lung function were similar for air pollutant exposures estimated using LUR and dispersion modeling, except for associations of PM2.5 with FEV1 and FVC, which were stronger but less precise for exposures based on LUR compared with dispersion model., Conclusions: Predictions from LUR and dispersion models correlated very well for PM2.5, NO2, and PM2.5 soot but not for PM10. Health effect estimates did not depend on the type of model used to estimate exposure in a population of Dutch children.

Decreased physical performance due to loss of muscle mass (i.e. sarcopenia) is prevalent in ageing and appears more pronounced in chronic disease. A comprehensive profile of the sarcopenic phenotype in chronic obstructive pulmonary disease (COPD) is not yet available. The aim of the present study was to characterise prevalence, functional implications and predictive value of sarcopenia with or without abdominal obesity in Dutch COPD patients eligible for pulmonary rehabilitation.505 COPD patients (aged 37-87 years; 57% male) underwent assessment of lung function, body composition and physical functioning, before entering pulmonary rehabilitation. Sarcopenia was assessed by appendicular skeletal muscle index (ASMI) and abdominal obesity by android/gynoid percentage fat mass (A/G%FM) using dual energy X-ray absorptiometry.86.5% of patients were sarcopenic and showed lower physical functioning, while coexistent abdominal obesity (78.0%) resulted in higher physical functioning. Implications on endurance were less pronounced in women. The predictive value for physical functioning was higher for the "three-compartment" model (ASMI, bone mineral content and A/G%FM) than the "two-compartment" model (fat-free mass index and fat mass index) or "one-compartment" model (body mass index).In patients eligible for pulmonary rehabilitation, sarcopenia is highly prevalent in all body mass index categories and associated with impaired strength, and in men also with decreased endurance. Abdominal obesity seems to have protective effects on physical functioning. ASMI is a better predictor for physical functioning than fat-free mass index., (Copyright ©ERS 2015.)

Background: Sarcoidosis patients frequently experience fatigue, exercise intolerance and muscle weakness, resulting in reduced quality of life (QOL). Scientific studies on the benefits of physical training in sarcoidosis have been scarce, so the aim of this pilot study was to examine the impact of a 13-week physical training program on fatigue, physical functions and QOL in fatigued sarcoidosis patients and/or patients with exercise intolerance., Methods: 18 sarcoidosis patients participated in a 13-week physical training program. The Fatigue Assessment Scale (FAS), World Health Organization Quality of Life-BREF assessment instrument (WHOQOL-BREF),Medical Research Council (MRC) dyspnea scale, Visual Analogue Scale (VAS), six-minute walk test (6MWT), submaximal bicycle test and muscle strength of the quadriceps and elbow flexors were assessed at baseline and after the program., Results: FAS scores had decreased (mean difference -2.7 points, 95% CI -4.4 to -1.1) after completion of the training program, along with improvements in WHOQOLBREF psychological health domain (mean difference 0.9 points, 95% CI 0.2 to 1.7) and MRC dyspnea score (mean difference -0.4 points, 95% CI -0.8 to -0.1). 6MWD improved by 34.6 m (95% CI 20.3 to 49.0) and mean heart rate on the bicycle test improved (mean difference 8.4 beats/minute, 95% CI -13.8 to -3.0), as did quadriceps strength (mean difference 10.7 kg, 95% CI 5.5 to 15.9)., Conclusion: Fatigue reduced after a period of physical training in sarcoidosis patients. Moreover, psychological health and physical functions improved. Future studies are warranted to assess the benefits of physical training in sarcoidosis.

Background: In 2007, an Asthma/chronic obstructive pulmonary disease (COPD) (AC) service was implemented in the North of the Netherlands to support General Practitioners (GPs) by providing advice from pulmonologists on a systematic basis., Aims: To evaluate the feasibility and effectiveness of this service on patient-related outcomes., Methods: We report baseline data on 11,401 patients and follow-up data from 2,556 patients. GPs can refer all patients with possible obstructive airway disease (OAD) to the service, which is conducted by the local laboratory. Patients are assessed in the laboratory using questionnaires and spirometry. Pulmonologists inspect the data through the internet and send the GP diagnosis and management advice., Results: A total of 11,401 patients were assessed by the service, covering almost 60% of all adult patients with projected asthma or COPD in the area. In all, 46% (n = 5,268) of the patients were diagnosed with asthma, 18% (n = 2,019) with COPD and 7% (n = 788) with the overlap syndrome. A total of 740 (7%) patients were followed up after 3 months because the GP advised them to change medication. In this group, the proportion of unstable COPD patients (Clinical COPD Questionnaire (CCQ) ⩾ 1) decreased from 63% (n = 92) at baseline to 49% (n = 72). The proportion of patients with uncontrolled asthma (Asthma Control Questionnaire (ACQ) ⩾ 1.5) decreased from 41% (n = 204) to 23% (n = 115). In all, 938 (8%) patients were followed up after 12 months. From these patients, the proportion of unstable COPD patients (CCQ ⩾ 1) decreased from 47% (n = 115) to 44% (n = 107). The proportion of patients with uncontrolled asthma (ACQ⩾1.5) decreased from 16% (n = 95) to 14% (n = 85)., Conclusion: The AC service assessed a considerable proportion of patients with OAD in the area, improved patients' outcomes, and is considered to be feasible and effective.

Background: The prevalence of tobacco smoking in patients with chronic obstructive pulmonary disease (COPD) is high. It is assumed that this group of smokers has more difficulties quitting than smokers without COPD. In order to increase the effectiveness of smoking cessation treatments in smokers with COPD it is important to identify any smoking-related factors which are specific to this group of smokers., Objective: To compare smokers with COPD with smokers without COPD regarding factors associated with tobacco smoking and quitting., Methods: We conducted a questionnaire survey in all smoking patients with a recorded diagnosis of COPD from a large Dutch primary health care network. We compared this group with twice as many age-, sex- and health care centre-matched smokers without COPD., Results: Respondents were 107 smokers with COPD and 86 smokers without COPD. The number of attempts to quit was similar in both groups but more smokers with COPD had ever used pharmacological, behavioural and alternative smoking cessation treatments. Furthermore, smokers with COPD more often received triggers to quit from their environment and from their general practitioner, and they were more concerned about, and aware of, the health risks of smoking. Importantly, smokers with COPD reported higher levels of depression and cigarette dependence and a lower self-efficacy to refrain from smoking than smokers without COPD., Conclusion: Smokers with COPD differ from smokers without COPD on several factors which are associated with tobacco smoking and quitting. Taking into account these differences may help to increase the effectiveness of smoking cessation treatments for the specific group of smokers with COPD., (© 2015 S. Karger AG, Basel.)

Background: Respiratory health effects of damp housing are well recognised, but less is known about the effect of dampness and water damage in schools. The HITEA study previously reported a higher prevalence of respiratory symptoms in pupils from moisture damaged schools, but the role of specific microbial exposures remained unclear., Objectives: To study associations between school dampness, levels of fungal and bacterial markers, respiratory symptoms and lung function in children., Methods: Primary schools in Spain, the Netherlands and Finland were selected on the basis of the observed presence (n=15) or absence (n=10) of moisture, dampness and/or mould. Settled dust was repeatedly sampled in 232 classrooms and levels of 14 different microbial markers and groups of microbes were determined. Parental reports of respiratory symptoms were available from 3843 children aged 6-12 years, of whom 2736 provided acceptable forced spirometry testing. Country-specific associations between exposure and respiratory health were evaluated by multilevel mixed-effects logistic and linear regression models and combined using random-effects meta-analysis., Results: The prevalence of respiratory symptoms was higher in moisture damaged schools, being more pronounced in Finnish pupils. Effects on lung function were not apparent. Levels of microbial markers were generally higher in moisture damaged schools, varied by season and were lower in Finnish schools. Wheeze tended to be inversely associated with microbial levels. All other respiratory symptoms were not consistently associated with microbial marker levels., Conclusions: Health effects of moisture and microbial exposures may vary between countries, but this requires further study., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Unlabelled: Both disposable and non-disposable T-piece resuscitator (TPR) devices are used. Accuracy of the disposable and non-disposable infant TPR was compared. Peak inspiratory pressures (PIP) and positive end-expiratory pressures (PEEP) were measured during ventilation of a test lung. Measured PIP ±1 cmH2O and PEEP ±0.5 cmH2O of the desired pressures were considered acceptable. We tested the following: (A) Accuracy of setting pressures using built-in manometers of three disposable TPRs, (B) Minimal and maximal PIP and PEEP levels for the non-disposable and disposable TPR were measured using different gas flow rates, and (C) Accuracy of 25 caregivers setting pressures (PIP 25 cmH2O and PEEP 5 cmH2O). The results of the tests performed were as follows: (A) With pressures set: PIP 20, 25, 30, and 40 cmH2O and PEEP 5-8 cmH2O with 1 cmH2O stepwise increment, measured PIPs and PEEPs were in acceptable range. (B) At gas flow rates 5, 8, 10, and 15 L/min (disposable vs. non-disposable), min-max PIP were 4.0-43.2 vs. 2.9-77.1 cmH2O and min-max PEEP were 0.3-22.3 and 0.6-59.7 cmH2O. (C) Set PIP (cmH2O) by participants using disposable vs. non-disposable TPR was 25.8 (0.8) vs. 25.9 (1.3) (ns). PEEP was 5.4(0.5) vs. 4.7(0.5); p < 0.001., Conclusion: The accuracy of the disposable TPR is comparable to that of the non-disposable TPR.

Background: Physical exercise training aims at reducing disease-specific impairments and improving quality of life in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations in particular negatively impact COPD progression. Physical therapy intervention seems indicated to influence exacerbations and their consequences. However, information on the effect of physical therapy on exacerbation occurrence is scarce. This study aims to investigate the potential of a protocol-directed physical therapy programme as a means to prevent or postpone exacerbations, to shorten the duration or to decrease the severity of exacerbations in patients with COPD who have recently experienced an exacerbation. Besides, this study focuses on the effect of protocol-directed physical therapy on health status and quality of life and on cost-effectiveness and cost-utility in patients with COPD who have recently experienced an exacerbation., Methods/design: A prospective cohort of 300 COPD patients in all GOLD stages will be constructed. Patients will receive usual multidisciplinary COPD care including guideline-directed physical therapy. Patients in this cohort who have GOLD stage 2 to 4 (post-bronchodilator FEV1/FVC < 0.7 and FEV1 < 80% of predicted), who receive reimbursement by health insurance companies for physical therapy (post-bronchodilator Tiffeneau-index < 0.6) and who experience a COPD exacerbation will be asked within 56 days to participate in a cohort-nested prospective randomised controlled trial (RCT). In this RCT, the intervention group will receive a strict physical therapy programme for patients with COPD. This protocol-directed physical therapy (pdPT) will be compared to a control group that will receive sham-treatment, meaning no or very low-intensity exercise training (ST). An economic evaluation will be embedded in the RCT. Anthropometric measurements, comorbidities, smoking, functional exercise capacity, peripheral muscle strength, physical activity level, health related quality of life, patients' perceived benefit, physical therapy compliance, motivation level, level of effective mucus clearance, exacerbation symptoms and health care contacts due to COPD will be recorded. Follow-up measurements are scheduled at 3 and 6 weeks, 3, 6, 12 and 24 months after inclusion., Discussion: Ways to minimise potential problems regarding the execution of this study will be discussed., Trial Registration: The Netherlands National Trial Register NTR1972.

Purpose: To assess psychometric properties of the Pelican instrument, an online Dutch self-administered Quality of Life instrument for childhood asthma for scientific and clinical use., Methods: A cohort study was done in two asthma populations and healthy children. One asthma population had assessment at start, 4 and 8 weeks. The other asthma population and healthy children had one assessment. All children were aged 6-12 years. Children completed the Pelican instrument, Paediatric Asthma Quality of Life Questionnaire, feeling thermometer and Childhood Asthma Control Test. Lung function and fraction exhaled nitric oxide were measured. Parents completed Functional Status II, Asthma Control Questionnaire, Childhood Asthma Control Test questionnaires and symptom diaries. We assessed interpretability, structural validity, internal consistency, reliability, construct and discriminative validity of the Pelican instrument., Results: Eighty-five asthmatic (mean age 8.5 years) and 49 healthy children (mean age 8.4 years) participated. The Pelican instrument has 5 domains with 21 items after factor analysis. Internal consistency was 0.89 (CI 0.85-0.92), domain reliability showed Cronbach's α's from 0.64 to 0.76 and item-to-scale correlations from 0.61 to 0.81. Test-retest reliability was confirmed ICC = 0.88 (CI 0.79-0.93). Construct validity was demonstrated by significant moderate correlations with other relevant asthma outcomes like PAQLQ (r = -0.59, p < 0.01). Discriminative capacity between controlled or uncontrolled asthma (t = 3.20, p < 0.01, Δ = 0.64) and asthma versus healthy subjects (t = 6.31, p < 0.01, Δ = 0.94) was found., Conclusions: The psychometric properties of the Pelican instrument were acceptable in Dutch paediatric asthma patients between 6 and 12 years old.

Background/objectives: A poor dietary quality may accelerate disturbances in body composition in chronic obstructive pulmonary disease (COPD), but only limited studies have investigated dietary intake from this perspective. The objective of the current study was to investigate dietary intake in relation to low fat-free mass and abdominal obesity in COPD., Subjects/methods: Dietary intake was assessed by means of a cross-check dietary history method in 564 COPD patients referred for pulmonary rehabilitation. The Dutch Food Composition Database was used to calculate nutrient intake, which was compared with the 2006 recommendations from the Dutch Health Council. Body composition was assessed by DEXA scan., Results: In general, the reported intake of macronutrients represented a typical western diet. With regard to micronutrients, vitamin D and calcium intakes were below the recommended levels in the majority of patients (>75%), whereas vitamin A, C and E intakes were below the recommended levels in over one-third of patients. Patients with inadequate vitamin D intake more frequently reported a low intake of protein (P=0.02) and micronutrients (P<0.001). Patients with a low fat-free mass index (FFMI) more often had low intake of protein, while abdominally obese patients more often had low intake of protein and most micronutrients (P<0.05). Patients with both low FFMI and abdominal obesity appeared most often to be consuming a poor-quality diet., Conclusions: Our data indicate that dietary quality is low in COPD patients referred for pulmonary rehabilitation and differs between patients with different body composition profiles.

Background: It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood., Objective: We investigated whether replicated genes for COPD associate with transient early wheeze (TEW) and lung function levels in 6- to 8-year-old children and whether cigarette smoke exposure in utero and after birth (environmental tobacco smoke [ETS]) modifies these effects., Methods: The association of COPD-related genotypes of 20 single nucleotide polymorphisms in 15 genes with TEW, FEV1, forced vital capacity (FVC), and FEV1/FVC ratio was studied in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort (n = 1996) and replicated in the Child, parents and health: lifestyle and genetic constitution (KOALA) and Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts., Results: AGER showed replicated association with FEV1/FVC ratio. TNS1 associated with more TEW in PIAMA and lower FEV1 in ALSPAC. TNS1 interacted with ETS in PIAMA, showing lower FEV1 in exposed children. HHIP rs1828591 interacted with cigarette smoke exposure in utero in PIAMA and with ETS in ALSPAC, with lower lung function in nonexposed children. SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMA only, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD., Conclusion: Our findings indicate relevant involvement of at least 3 COPD genes in lung development and lung growth by demonstrating associations pointing toward reduced airway caliber in early childhood. Furthermore, our results suggest that COPD genes are involved in the infant's lung response to smoke exposure in utero and in early life., (Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.)

Background: During their career, professional football players undergo periodic medical examinations intended to screen and monitor their fitness and health. In the Netherlands, information about the content of these examinations is lacking and it is not known whether they comply with current Dutch occupational medicine guidelines., Aims: To explore the content of medical examinations undertaken in Dutch professional football clubs, and assess whether they comply with current Dutch occupational medicine guidelines., Methods: An observational study conducted among physicians working for all clubs in the Dutch first- and second-tier professional football leagues, using an electronic questionnaire., Results: Cardiovascular assessment based on different instruments was used in all clubs and respiratory assessment based on different instruments was used in most (87%). Other assessments such as mental health (7%), neurological (27%) or urinary (22%) assessments were only undertaken in some clubs. Seven out of the 26 clubs met some of the relevant aspects of current Dutch occupational medicine guidelines., Conclusions: The medical examinations currently undertaken in Dutch professional football clubs are diverse in nature and not consistent from one club to another. Only a limited number of clubs meet Dutch guidelines for periodic medical examinations of workers.

Background: Air pollution has been associated with respiratory health effects. There is little direct evidence that reductions in air pollution related to abatement policies lead to actual improvement in respiratory health. We assessed whether a reduction in (traffic policy-related) air pollution concentrations was associated with changes in respiratory health., Methods: Air pollution concentrations and respiratory health were measured in 2008 and 2010 at eight busy urban streets and at four suburban background control locations. Respiratory function was assessed twice in 661 residents by spirometry and measurements of airway resistance. Nitric oxide (NO) in exhaled air was measured as a marker for airway inflammation., Results: Air pollution concentrations were lower in 2010 than in 2008. The declines in pollutants varied among locations, with the largest decline observed in a street with a large reduction in traffic intensity. In regression analyses adjusted for important covariates, reductions in concentrations of soot, NO2, NOx, Cu, and Fe were associated with increases in forced vital capacity (FVC) (∼1% increase per interquartile range [IQR] decline). Airway resistance decreased with a decline in particulate matter (PM10) and PM2.5 (9% per IQR), although these associations were somewhat less consistent. No associations were found with exhaled NO. Results were driven largely by one street where traffic-related air pollution showed the largest reduction. Forced expiratory volume and FVC improved by 3% to 6% in residents of this street compared with suburban background residents. This was accompanied by a suggestive reduction in airway resistance., Conclusions: Reductions in air pollution may lead to small improvements in respiratory function.

Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12 months for pulmonary function tests, 6 minute walk test (6 MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59 years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60 years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11 years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6 years, with some decline in pulmonary function and 6 MWT. Bone marrow fat fractions were decreased, indicating the presence of storage macrophages. Lung involvement was not related to the extent of visceromegaly, cytopenia or bone marrow involvement. In conclusion, in NPD-B patients pulmonary disease is the most debilitating feature. Disease manifestations are mostly stable in attenuated patients. Bone marrow infiltration is a less prominent feature of the disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Respiratory tract exacerbation rate (RTE-R) is a key clinical efficacy end point in cystic fibrosis (CF) trials. Chest CT scanning holds great potential as a surrogate end point. Evidence supporting the ability of CT scan scores to predict RTE-R is an important step in validating CT scanning as a surrogate end point. The objective of this study was to investigate the association between CT scan scores and RTE-R in a cohort of pediatric patients with CF., Methods: A retrospective review of data from pediatric patients with CF included chest CT scans, spirometry, and 2 years follow-up. RTE-R was defined as the number of IV antibiotics courses per year. CT scans were scored with the Brody-II system, assessing bronchiectasis, airway wall thickening, mucus, and opacities., Results: One hundred fifteen patients contributed 170 CT scans. Median age and FEV(1) at first CT scan were 12 years (range, 5-20 years) and 90% predicted (range, 23% predicted-132% predicted), respectively. Analyzing exacerbation counts using Poisson regression models, bronchiectasis score and FEV(1) both were found to be strong independent predictors of RTE-R in the subsequent 2 years. For the bronchiectasis score categorized in quartiles, RTE-R increased by factors of 1.8 (95% CI, 0.6-6.1; P = .31), 5.5 (95% CI, 1.9-15.4; P = .001), and 10.6 (95% CI, 3.8-29.4; P < .001), respectively, for each quartile compared with the quartile with the best (ie, lowest) scores. Similarly, time to first respiratory tract exacerbation was significantly associated with quartiles of both bronchiectasis score and FEV(1)., Conclusions: The CT scan bronchiectasis score is strongly associated with RTE-R in pediatric patients with CF, providing an important piece of evidence in the validation of CT scans as an end point for CF clinical trials.

Aims: For children with stable asthma, to test non-inferiority of care provided by a hospital-based specialised asthma nurse versus a general practitioner (GP) or paediatrician., Methods: Randomised controlled trial evaluating standard care by a GP, paediatrician or an asthma nurse, with two-year follow-up., Results: 107 children were recruited, 45 from general practice and 62 from hospital. After two years, no significant differences between groups were found for airway responsiveness, FEV1, asthma control, medication, school absence or parental work absence. In the general practice group there was a significantly lower frequency of regular review visits ('regular' = at least one review per six months) compared to the paediatrician and specialised asthma nurse group, both after one year [45.7% versus 87.9% and 94.3%, respectively, (p<0.0005)] and after two years [26.5% versus 87.9% and 75.8%, respectively, (p<0.0005)]. We found no significant differences in unplanned visits. In most cases the asthma nurse was able to provide care without consultation with the paediatrician., Conclusion: The degree of disease control in stable childhood asthma managed by an asthma nurse is not inferior to traditional management by primary or secondary care physicians. The results also suggest that a lower review frequency does not detract from good disease control.

Objective: To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation are lacking., Design: Prospective longitudinal cohort study., Setting: Outpatient clinic of a tertiary level pediatric hospital., Patients: The cohort consisted of 64 infants; 33 received extracorporeal membrane oxygenation for meconium aspiration syndrome, 14 for congenital diaphragmatic hernia, four for sepsis, six for persistent pulmonary hypertension of the neonate, and seven for respiratory distress syndrome of infancy. Evaluation was at 6 mos and 12 mos; 39 infants were evaluated at both time points ., Interventions: None., Measurements and Main Results: Functional residual capacity and forced expiratory flow at functional residual capacity were measured and expressed as z score. Mean (sem) functional residual capacities in z score were 0.0 (0.2) and 0.2 (0.2) at 6 mos and 12 mos, respectively. Mean (sem) forced expiratory flow was significantly below average (z score = 0) (p < .001) at 6 mos and 12 mos: -1.1 (0.1) and -1.2 (0.1), respectively. At 12 mos, infants with diaphragmatic hernia had a functional residual capacity significantly above normal: mean (sem) z score = 1.2 (0.5)., Conclusions: Infants treated with extracorporeal membrane oxygenation have normal lung volumes and stable forced expiratory flows within normal range, although below average, within the first year of life. There is reason to believe, therefore, that extracorporeal membrane oxygenation either ameliorates the harmful effects of mechanical ventilation or somehow preserves lung function in the very ill neonate.

Background: Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention., Method: The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee., Discussion: Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R2 of 0.82 and 0.74 (p < 0.01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking., Trial Registration: ClinicalTrials.gov: NCT00981851.

Background: There is a growing interest to use health status or disease control questionnaires in routine clinical practice. However, the validity of most questionnaires is established using techniques developed for group level validation. This study examines a new method, using patient interviews, to validate a short health status questionnaire, the Clinical COPD Questionnaire (CCQ), at the individual patient level., Methods: Patients with COPD who visited an outpatient clinic completed the CCQ before the consultation, and the specialist physician completed it after the consultation. After the consultation all patients had a semi-structured in-depth interview. The patients' CCQ scores were compared with those of the treating clinician, and with mean scores from 5 clinicians from a pool of 20 who scored the CCQ after reading the transcript of the in-depth interviews only. Agreement was assessed using Lin's concordance correlation coefficient (CCC), and Blant and Altman plots. Interviews with patients with low agreement were reviewed for possible explanations., Results: A total of 44 COPD patients (32 male, mean age 66 years, FEV1 45% of predicted) participated. Agreement between the patients' CCQ scores and those of the treating clinicians (CCC = 0.87) and the mean score of the reviewing clinicians (CCC = 0.86) was very high. No systematic error was detected. No explanation for individuals with low agreement was found., Conclusion: The validity of the CCQ on the individual patient level, as assessed by these methods, is good. Individual health status assessment with the CCQ is therefore sufficiently accurate to be used in routine clinical practice.

Chronic obstructive pulmonary disease (COPD) is a growing health problem, and an underestimated and underdiagnosed disease in primary care. The aim of this survey was to study the feasibility of detecting undiagnosed COPD patients in the general practice population with the aid of a telephone questionnaire. The study was held in 2 general practices in the Netherlands. During 2 weeks, all patients registered with these 2 practices and aged between 40 and 75 years were contacted through a call center. Persons known with a previous history or diagnosis of COPD or asthma or comorbidity were excluded from the telephone list. The telephone interview used the Respiratory Health Screening Questionnaire (DB Price, 2006). Based on the score on this instrument, respondents were classified as having a low, moderate or high risk of having COPD. Smoking behaviour and BMI were also recorded. Patients with medium and high risk for COPD were invited for spirometry, performed by 2 experienced registered nurses. The results of the telephone interview and spirometric findings were assessed by the attending GP, who established the final diagnosis. The call center reached 1032 persons, 813 of whom answered the questions. The percentage of smokers was 49.2%, with an average number of pack-years of 17.9 (SD = 17); mean BMI was 26.1. Spirometry and analysis by the GP showed that 15.7% of the medium-risk group had previously undiagnosed COPD, versus 39.6% of the high-risk group. The number of undiagnosed COPD patients in the general practice population is considerable. Case finding can focus on moderate- and high-risk groups after telephone risk assessment.

Background: During puberty, a gender shift in asthma prevalence occurs, with a preponderance of boys before puberty. The mechanisms underlying this gender shift are unclear., Objectives: We assessed associations of pubertal stages and transition through puberty with (1) the prevalence, incidence, and remission of asthma in male and female subjects; (2) total IgE levels; and (3) peak expiratory flow (PEF) fall during a shuttle run test (SRT)., Methods: In the TRacking Adolescents' Individual Lives Survey study (n = 2,230; 51% female subjects), associations between pubertal stages and the prevalence, incidence, and remission of asthma were tested by using logistic regression and generalized estimating equations at a mean age of 11.1 (SD, 0.6), 13.6 (SD, 0.5), and 16.3 (SD, 0.7) years. Multiple linear regression analyses were used to study log-transformed total IgE levels and PEF fall during a SRT dependent on early versus late pubertal stages at a mean age of 16.3 years., Results: The prevalence of asthma was similar in boys (7.7%) and girls (7.4%) at a mean age of 11.1 years. The prevalence of asthma was significantly higher in female (6.2%) than male (4.3%) subjects at 16.3 years of age. There were no significant associations between transition of pubertal stages and the presence of asthma, either cross-sectionally or longitudinally. Pubertal stages and log-transformed total IgE levels or PEF fall during a SRT at age 16.3 years were not correlated., Conclusions: A shift in the prevalence of asthma occurs between 11.1 and 16.3 years, which is due to both an increased incidence and decreased remission of asthma in female compared with male subjects. Pubertal stages could not be proved to explain the gender shift in asthma prevalence., (Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Introduction: Patients with COPD are known to be limited in their performance of activities of daily life (ADL). This observational study aims to investigate the ventilatory and metabolic demand of ADL in home settings of patients and evaluate possible mechanisms involved in physiological limitation during ADL in COPD., Methods: In their home settings, 21 stable patients with COPD (GOLD II-IV, mean FEV(1) 43% predicted) were asked to perform their most dyspnea causing activities at their usual pace until symptoms discouraged further performance. Ten healthy control subjects, matched for age and gender, performed comparable activities. Ventilatory and metabolic demands of the ADL were studied using a portable breath-by-breath system., Results: Compared with healthy controls, ADL time was shorter in patients (530 +/- 38 s vs. 318 +/- 37 s respectively) and activities resulted in important complaints of dyspnea. Oxygen consumption (V O(2)) during the activities was higher in patients compared to healthy subjects (957 +/- 51 vs. 768 +/- 63 mL/min resp.). Ventilatory demand (V E) for comparable activity (at isoV O(2)) was higher in patients and went together with complaints of dyspnea in patients, but not in healthy subjects. Ventilatory constraints like low ventilatory reserve and inspiratory reserve volume and dynamic hyperinflation occurred in more than 80% of the patients, especially in (very) severe patients., Conclusion: Patients with COPD experience limitations in the performance of ADL, which lead to reductions in ADL time and dyspnea complaints. There appears to be an important role for ventilatory limitations, which become more prominent as disease progresses., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Siblings with cystic fibrosis (CF) share many genetic and environmental factors but may present different phenotypes. Younger sibs are mostly earlier diagnosed with CF than their older sibs, but might be at risk for an earlier colonization with Pseudomonas aeruginosa (PA) than their older counterparts due to cross-infection within families., Aims: To analyze the effects of birth order and age at diagnosis on lung function, PA colonization, nutritional status, and survival during the first two decades of life in siblings with CF., Methods: A retrospective cohort study of 52 sibling pairs was performed in two Dutch CF centers. Data were analyzed both cross-sectionally and longitudinally using Kaplan-Meier curves and modified log-rank tests., Results: Median age at diagnosis was significantly higher in the older sib compared with the younger sib (3.0 and 0.2 years, respectively, P < 0.0001). At the age of 5, 10, and 15 years no difference in lung function was found. However, at the age of 20 years, forced expiratory volume in 1 sec (FEV(1)) in older sibs was 19.4% (95% CI: 5.9-32.9%, P = 0.007) lower than in younger sibs. In the younger sibs group, FEV(1) at age 20 years was significantly better in those who had a diagnosis before the age of 6 months (difference 22.9%, 95% CI: 0.1-45.8%, P < 0.05). In the first 10 years of life the younger sibs tended to be earlier colonized with PA than their older counterparts. No differences in nutritional status and survival were observed., Conclusion: In this sibling cohort study, an early diagnosis of CF was associated with better lung function after two decades of life. Although younger siblings tended to be colonized with PA at an earlier age, they showed better lung function outcomes. This underscores the importance of early diagnosis with newborn screening and early referral to a specialized center in the prevention of long-term deleterious effects on lung function.