Publications by authors named "Geertjan Wesseling"

42 Publications

Exhaled volatile organic compounds detect pulmonary exacerbations early in children with cystic fibrosis: results of a 1 year observational pilot study.

J Breath Res 2021 Feb 25;15(2):026012. Epub 2021 Feb 25.

Department of Paediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

In patients with cystic fibrosis (CF), pulmonary exacerbations (PEx) have an important influence on well-being, quality of life, and lung function decline. Early detection combined with early treatment may prevent severe PEx. To determine whether early detection of PEx is possible by non-invasive markers (volatile organic compounds) in exhaled breath. In a 1 year prospective observational pilot study, 49 children with CF were studied. At clinical visits with an interval of 2 months, lung function, volatile organic compounds (VOCs) in exhaled breath by means of gas chromatography-time-of-flight-mass spectrometry, and medication use were assessed. PEx were recorded. Random forest (RF) classification modelling was used to select discriminatory VOCs, followed by building of receiver operating characteristic curves. An inverse relation between the predictive power of a set of VOCs and time between exhaled breath sampling and the onset of PEx was found. When this time period was within 7 d, the RF model with the nine most discriminatory VOCs was able to correctly predict 79% of the children with an upcoming PEx or remaining stable (sensitivity 79% and specificity 78%). This result was validated by means of bootstrapping within the RF classification model. PEx in children with CF can be detected at an early stage by means of exhaled VOCs. The highest predictive value was reached if time between sampling and the onset of an exacerbation was no longer than 7 d.
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http://dx.doi.org/10.1088/1752-7163/abda55DOI Listing
February 2021

Exhaled volatile organic compounds detect pulmonary exacerbations early in children with Cystic Fibrosis: results of a one-year observational pilot study.

J Breath Res 2021 Jan 11. Epub 2021 Jan 11.

Department of Toxicology, Maastricht University, Maastricht, Limburg, NETHERLANDS.

Background: In patients with Cystic fibrosis (CF), pulmonary exacerbations (PEx) have an important influence on well-being, quality of life, and lung function decline. Early detection combined with early treatment may prevent severe PEx.

Aim: To determine whether early detection of PEx is possible by non-invasive markers (volatile organic compounds) in exhaled breath.

Methods: In a one-year prospective observational pilot study, 49 children with CF were studied. At clinical visits with an interval of 2 months, lung function, volatile organic compounds (VOCs) in exhaled breath by means of gas chromatography-time-of-flight-mass spectrometry, and medication use were assessed. PEx were recorded. Random Forest (RF) classification modelling was used to select discriminatory VOCs, followed by building of Receiver Operating Characteristic curves.

Results: An inverse relation between the predictive power of a set of VOCs and time between exhaled breath sampling and the onset of PEx was found. When this time period was within 7 days, the RF model with the 9 most discriminatory VOCs was able to correctly predict 79% of the children with an upcoming PEx or remaining stable (sensitivity 79% and specificity 78%). This result was validated by means of bootstrapping within the RF classification model.

Conclusion: PEx in children with CF can be detected at an early stage by means of exhaled VOCs. The highest predictive value was reached if time between sampling and the onset of an exacerbation was no longer than 7 days.
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http://dx.doi.org/10.1088/1752-7163/abda55DOI Listing
January 2021

Nutritional Interventions to Improve Asthma-Related Outcomes through Immunomodulation: A Systematic Review.

Nutrients 2020 Dec 16;12(12). Epub 2020 Dec 16.

Department of Nutrition and Movement Sciences, NUTRIM (School of Translational Research in Metabolism), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.

Asthma is a chronic inflammatory disease of the airways, characterized by T-helper (Th) 2 inflammation. Current lifestyle recommendations for asthma patients are to consume a diet high in fruits and vegetables and to maintain a healthy weight. This raises the question of whether other nutritional interventions may also improve asthma-related outcomes and whether these changes occur via immunomodulation. Therefore, we systematically reviewed studies that reported both asthma-related outcomes as well as immunological parameters and searched for relations between these two domains. A systematic search identified 808 studies, of which 28 studies met the inclusion criteria. These studies were divided over six nutritional clusters: herbs, herbal mixtures and extracts ( = 6); supplements ( = 4); weight loss ( = 3); vitamin D3 ( = 5); omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) ( = 5); and whole-food approaches ( = 5). Fifteen studies reported improvements in either asthma-related outcomes or immunological parameters, of which eight studies reported simultaneous improvements in both domains. Two studies reported worsening in either asthma-related outcomes or immunological parameters, of which one study reported a worsening in both domains. Promising interventions used herbs, herbal mixtures or extracts, and omega-3 LCPUFAs, although limited interventions resulted in clinically relevant results. Future studies should focus on further optimizing the beneficial effects of nutritional interventions in asthma patients, e.g., by considering the phenotypes and endotypes of asthma.
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http://dx.doi.org/10.3390/nu12123839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765612PMC
December 2020

Applying the electronic nose for pre-operative SARS-CoV-2 screening.

Surg Endosc 2020 Dec 2. Epub 2020 Dec 2.

Department of Surgery, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.

Background: Infection with SARS-CoV-2 causes corona virus disease (COVID-19). The most standard diagnostic method is reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal and/or an oropharyngeal swab. The high occurrence of false-negative results due to the non-presence of SARS-CoV-2 in the oropharyngeal environment renders this sampling method not ideal. Therefore, a new sampling device is desirable. This proof-of-principle study investigated the possibility to train machine-learning classifiers with an electronic nose (Aeonose) to differentiate between COVID-19-positive and negative persons based on volatile organic compounds (VOCs) analysis.

Methods: Between April and June 2020, participants were invited for breath analysis when a swab for RT-PCR was collected. If the RT-PCR resulted negative, the presence of SARS-CoV-2-specific antibodies was checked to confirm the negative result. All participants breathed through the Aeonose for five minutes. This device contains metal-oxide sensors that change in conductivity upon reaction with VOCs in exhaled breath. These conductivity changes are input data for machine learning and used for pattern recognition. The result is a value between - 1 and + 1, indicating the infection probability.

Results: 219 participants were included, 57 of which COVID-19 positive. A sensitivity of 0.86 and a negative predictive value (NPV) of 0.92 were found. Adding clinical variables to machine-learning classifier via multivariate logistic regression analysis, the NPV improved to 0.96.

Conclusions: The Aeonose can distinguish COVID-19 positive from negative participants based on VOC patterns in exhaled breath with a high NPV. The Aeonose might be a promising, non-invasive, and low-cost triage tool for excluding SARS-CoV-2 infection in patients elected for surgery.
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http://dx.doi.org/10.1007/s00464-020-08169-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709806PMC
December 2020

Chronic obstructive pulmonary disease and atrial fibrillation: an interdisciplinary perspective.

Eur Heart J 2021 Feb;42(5):532-540

Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, 1 Port Road, SA 5000 Adelaide, Australia.

Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ∼25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening.
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http://dx.doi.org/10.1093/eurheartj/ehaa822DOI Listing
February 2021

Cluster-randomised trial of a nurse-led advance care planning session in patients with COPD and their loved ones.

Thorax 2019 04 19;74(4):328-336. Epub 2019 Jan 19.

Department of Research and Education, CIRO, Horn, Limburg, The Netherlands.

Rationale: Advance care planning (ACP) is uncommon in patients with chronic obstructive pulmonary disease (COPD).

Objectives: To assess whether a nurse-led ACP-intervention can improve quality of patient-physician end-of-life care communication in patients with COPD. Furthermore, the influence of an ACP-intervention on symptoms of anxiety and depression in patients and loved ones was studied. Finally, quality of death and dying was assessed in patients who died during 2-year follow-up.

Methods: A multicentre cluster randomised-controlled trial in patients with advanced COPD was performed. The intervention group received an 1.5 hours structured nurse-led ACP-session. Outcomes were: quality of patient-physician end-of-life care communication, prevalence of ACP-discussions 6 months after baseline, symptoms of anxiety and depression in patients and loved ones and quality of death and dying.

Results: 165 patients were enrolled (89 intervention; 76 control). The improvement of quality of patient-physician end-of-life care communication was significantly higher in the intervention group compared with the control group (p<0.001). The ACP-intervention was significantly associated with the occurrence of an ACP-discussion with physicians within 6 months (p=0.003). At follow-up, symptoms of anxiety were significantly lower in loved ones in the intervention group compared with the control group (p=0.02). Symptoms of anxiety in patients and symptoms of depression in both patients and loved ones were comparable at follow-up (p>0.05). The quality of death and dying was comparable between both groups (p=0.17).

Conclusion: One nurse-led ACP-intervention session improves patient-physician end-of-life care communication without causing psychosocial distress in both patients and loved ones.
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http://dx.doi.org/10.1136/thoraxjnl-2018-211943DOI Listing
April 2019

Publisher Correction: Early detection of pulmonary exacerbations in children with Cystic Fibrosis by electronic home monitoring of symptoms and lung function.

Sci Rep 2018 Dec 13;8(1):17946. Epub 2018 Dec 13.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-36407-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292896PMC
December 2018

Risk factors for lung disease progression in children with cystic fibrosis.

Eur Respir J 2018 06 7;51(6). Epub 2018 Jun 7.

Dept of Paediatric Respiratory Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

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) % pred) and pulmonary exacerbation rate. Potential risk factors at baseline included sex, age, best FEV % 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 The data of 545 children were analysed. PPI use was associated with both annual decline of FEV % pred (p=0.017) and future pulmonary exacerbation rate (p=0.006). Moreover, lower FEV % 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.
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http://dx.doi.org/10.1183/13993003.02509-2017DOI Listing
June 2018

Early detection of pulmonary exacerbations in children with Cystic Fibrosis by electronic home monitoring of symptoms and lung function.

Sci Rep 2017 09 27;7(1):12350. Epub 2017 Sep 27.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

Pulmonary exacerbations (PEx) in Cystic Fibrosis (CF) are associated with an increased morbidity and even mortality. We investigated whether early detection of PEx in children with CF is possible by electronic home monitoring of symptoms and lung function. During this one-year prospective multi-centre study, 49 children with CF were asked to use a home monitor three times a week. Measurements consisted of a respiratory symptom questionnaire and assessment of Forced Expiratory Volume in one second (FEV1). Linear mixed-effects and multiple logistic regression analyses were used. In the 2 weeks before a PEx, the Respiratory Symptom Score (RSS) of the home monitor increased (p = 0.051). The FEV1 as percentage of predicted (FEV1%pred) did not deteriorate in the 4 weeks before a PEx. Nevertheless, the FEV1%pred at the start of exacerbation was significantly lower than the FEV1%pred in the non-exacerbation group (mean difference 16.3%, p = 0.012). The combination of FEV1%pred and RSS had a sensitivity to predict an exacerbation of 92.9% (CI 75.0-98.8%) and a specificity of 88.9% (CI 50.7-99.4%). The combination of home monitor FEV1%pred and RSS can be helpful to predict a PEx in children with CF at an early stage.
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http://dx.doi.org/10.1038/s41598-017-10945-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617859PMC
September 2017

Predictors of long-term smoking cessation in patients with COPD: results from a randomised controlled trial.

Eur Respir J 2017 06 22;49(6). Epub 2017 Jun 22.

Dept of Family Medicine, Maastricht University Medical Centre, CAPHRI Care and Public Health Research Institute, Maastricht, The Netherlands.

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http://dx.doi.org/10.1183/13993003.00561-2017DOI Listing
June 2017

Factors associated with changes in health-related quality of life in children with cystic fibrosis during 1-year follow-up.

Eur J Pediatr 2017 Aug 9;176(8):1047-1054. Epub 2017 Jun 9.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre + (MUMC+), Maastricht, The Netherlands.

There are limited data on health-related quality of life (HRQoL) changes over time in children with cystic fibrosis (CF). We investigated associations between clinical and treatment variables with changes in HRQoL during 1 year. Forty-nine children with CF aged 6-18 years were followed in this multicentre, observational cohort study during 1 year. HRQoL was measured by the validated disease specific cystic fibrosis questionnaire-revised (CFQ-R). The CFQ-R total score as well as most domain scores improved significantly (8.0 points and [3.3-31.7] points respectively) during the one-year follow-up. Age at baseline demonstrated a strong longitudinal association with the change of CFQ-R total score (2.853 points decrease of CFQ-R total score per year increase in age) and several domain scores. Below 12 years of age, CFQ-R total score improved in most children, whereas a deterioration was observed in most children above 12 years. The number of PEx was associated with an increase of treatment burden score (4.466 points decrease per extra PEx).

Conclusion: In the group as a whole, HRQoL improved significantly over time. However, changes over time were significantly influenced by age: below 12 years of age, HRQoL improved in most patients whereas a deterioration was observed in most children >12 years. Strategies how to preserve or ideally to improve HRQoL in adolescence should be developed. What is known: • Quality of life in patient with CF is diminished • Although CF is a chronic disease, longitudinal data on QoL in children with CF are scarce. What is new: • Below 12 years of age, quality of life improved in most children during the 1-year follow-up whereas a deterioration in quality of life was observed in most children above 12 years. • the treatment burden score of QoL correlated with the exacerbation rate.
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http://dx.doi.org/10.1007/s00431-017-2928-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511302PMC
August 2017

Not So New.

Am J Respir Crit Care Med 2017 03;195(6):839

1 Maastricht University Maastricht, the Netherlands.

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http://dx.doi.org/10.1164/rccm.201612-2430LEDOI Listing
March 2017

Effectiveness of Teamwork in an Integrated Care Setting for Patients with COPD: Development and Testing of a Self-Evaluation Instrument for Interprofessional Teams.

Int J Integr Care 2016 Apr 8;16(1). Epub 2016 Apr 8.

Saw Swee Hock School of Public Health, National University Singapore, National University Health System, Singapore, Singapore; Department Patient & Care, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Family Medicine and Chronic Care, Vrije Universiteit Brussels, Brussels, Belgium.

Introduction: Teamwork between healthcare providers is conditional for the delivery of integrated care. This study aimed to assess the usefulness of the conceptual framework Integrated Team Effectiveness Model for developing and testing of the Integrated Team Effectiveness Instrument.

Theory And Methods: Focus groups with healthcare providers in an integrated care setting for people with chronic obstructive pulmonary disease (COPD) were conducted to examine the recognisability of the conceptual framework and to explore critical success factors for collaborative COPD practice out of this framework. The resulting items were transposed into a pilot instrument. This was reviewed by expert opinion and completed 153 times by healthcare providers. The underlying structure and internal consistency of the instrument were verified by factor analysis and Cronbach's alpha.

Results: The conceptual framework turned out to be comprehensible for discussing teamwork effectiveness. The pilot instrument measures 25 relevant aspects of teamwork in integrated COPD care. Factor analysis suggested three reliable components: teamwork effectiveness, team processes and team psychosocial traits (Cronbach's alpha between 0.76 and 0.81).

Conclusions And Discussion: The conceptual framework Integrated Team Effectiveness Model is relevant in developing a practical full-spectrum instrument to facilitate discussing teamwork effectiveness. The Integrated Team Effectiveness Instrument provides a well-founded basis to self-evaluate teamwork effectiveness in integrated COPD care by healthcare providers. Recommendations are provided for the improvement of the instrument.
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http://dx.doi.org/10.5334/ijic.2454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015529PMC
April 2016

Biomarkers in Exhaled Breath Condensate Are Not Predictive for Pulmonary Exacerbations in Children with Cystic Fibrosis: Results of a One-Year Observational Study.

PLoS One 2016 6;11(4):e0152156. Epub 2016 Apr 6.

Department of Pediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

Background: Cystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis.

Aim: To investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF.

Methods: In this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured using high sensitivity bead based flow immunoassays. Pulmonary exacerbations were recorded during the study and were defined in two ways. The predictive power of inflammatory markers and the other covariates was assessed using conditionally specified models and a receiver operating characteristic curve (SAS version 9.2). In addition, k-nearest neighbors (KNN) algorithm was applied (SAS version 9.2).

Results: Sixty-five percent of the children had one or more exacerbations during the study. The conditionally specified models showed an overall correct prediction rate of 55%. The area under the curve (AUC) was equal to 0.62. The results obtained with the KNN algorithm were very similar.

Conclusion: Although there is some evidence indicating that the predictors outperform random guessing, the general diagnostic accuracy of EBC acidity and the EBC inflammatory markers IL-6, IL-8, TNF-α and MIF is low. At present it is not possible to predict pulmonary exacerbations in children with CF with the chosen biomarkers and the method of EBC analysis. The biochemical measurements of EBC markers should be improved and other techniques should be considered.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152156PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822839PMC
August 2016

Dietary plant stanol ester consumption improves immune function in asthma patients: results of a randomized, double-blind clinical trial.

Am J Clin Nutr 2016 Feb 13;103(2):444-53. Epub 2016 Jan 13.

Department of Human Biology, School for Nutrition, Toxicology and Metabolism, and

Background: In vitro and ex vivo studies have suggested that plant sterols and stanols can shift the T helper (Th) 1/Th2 balance toward a Th1-type immune response, which may be beneficial in Th2-dominant conditions such as asthma and allergies.

Objective: We evaluated in vivo whether plant stanol esters affect the immune response in asthma patients.

Design: Fifty-eight asthma patients participated in a randomized, double-blind, placebo-controlled intervention study. All subjects started with a 2-wk run-in period in which they consumed 150 mL control soy-based yogurt without added plant stanol esters/d. Next, an 8-wk experimental period was started in which one-half of the participants received plant stanol enriched soy-based yogurts (4.0 g plant stanols/d), whereas the other one-half of subjects continued the consumption of control yogurts. After 4 wk of daily plant stanol consumption, all participants were vaccinated against hepatitis A virus (HAV), and the increase of antibody titres was monitored weekly until 4 wk after vaccination.

Results: Asthma patients in the plant stanol ester group showed higher antibody titres against HAV 3 and 4 wk after vaccination [19% (P = 0.037) and 22% (P = 0.030), respectively]. Also, substantial reductions in plasma total immunoglobulin E, interleukin (IL)-1β, and tumor necrosis factor-α were shown in the plant stanol ester group. The increase in serum plant stanol concentrations was correlated significantly with the decrease in IL-13 concentrations and the Th1 switch in the Th1/Th2 balance. However, no absolute differences in cytokine production between the plant stanol ester group and the control group were shown.

Conclusion: To the best of our knowledge, we are among the first authors to show that plant stanol ester consumption improves the immune function in vivo in asthma patients. This trial was registered at clinicaltrials.gov as NCT01715675.
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http://dx.doi.org/10.3945/ajcn.115.117531DOI Listing
February 2016

Do we need tailored smoking cessation interventions for smokers with COPD? A comparative study of smokers with and without COPD regarding factors associated with tobacco smoking.

Respiration 2015 28;90(3):211-9. Epub 2015 May 28.

Department of Family Medicine, Maastricht University Medical Centre, CAPHRI School for Public Health and Primary Care, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1159/000398816DOI Listing
July 2016

Medically unexplained dyspnoea and panic.

Respirology 2015 Jul 30;20(5):828-30. Epub 2015 Mar 30.

Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.

Medically unexplained dyspnoea in the pulmonary setting is often accompanied by considerable levels of anxiety, suggestive of psychopathology, in particular panic disorder (PD). This pilot study investigates the value of the Multidimensional Dyspnea Profile as a tool to facilitate identification of a specific dyspnoea profile suggestive of comorbid PD. The verbal descriptors, feeling depressed, air hunger and concentrating on breathing, significantly differentiated between the two groups of patients with pulmonary disease with and without PD.
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http://dx.doi.org/10.1111/resp.12516DOI Listing
July 2015

Exacerbations in patients with chronic obstructive pulmonary disease receiving physical therapy: a cohort-nested randomised controlled trial.

BMC Pulm Med 2014 Apr 26;14:71. Epub 2014 Apr 26.

Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University, PO Box 616, Maastricht, MD 6200, The Netherlands.

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.
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http://dx.doi.org/10.1186/1471-2466-14-71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108017PMC
April 2014

The prevalence of chronic obstructive pulmonary disease in Maastricht, the Netherlands.

Respir Med 2012 Jun 19;106(6):871-4. Epub 2012 Feb 19.

Program Development Centre, CIRO+, Centre of Expertise for Chronic Organ Failure, Horn, The Netherlands.

Background: Chronic obstructive pulmonary disease (COPD) is an increasing public health problem worldwide. Although epidemiologic data on COPD are important to raise awareness of the burden of disease, there are no actual spirometry-based data on the prevalence of COPD in the Netherlands.

Methods: Using the Burden of Obstructive Lung Disease (BOLD) protocol and study design, a population-based sample of adults, aged ≥ 40 years, in the area of Maastricht, the Netherlands was surveyed. Post-bronchodilator spirometry and questionnaires with information on smoking history and reported respiratory disease were collected. COPD was defined as post-bronchodilator FEV(1)/FVC ratio < 0,7 (GOLD) or < the lower limit of normal (LLN) (95th percentile) of the population distribution for FEV(1)/FVC. Data were statistically weighted for the total number of people in the Maastricht population.

Results: Overall prevalence of COPD was 24%, and was higher for men (28.5%) than for women (195%). (unweighted p = 0.002) The prevalence of GOLD stage 2 or higher COPD was 10%. The prevalence of LLN-defined COPD was 19% and 10% for stage 2 or higher. Overall prevalence of current smoking was 23%. The prevalence of COPD increased with age and amount of pack-years, although 14% of never smokers fulfilled spirometric criteria for COPD. The prevalence of doctor-diagnosed COPD was only 8.8%.

Conclusion: Almost one quarter of the Maastricht population aged ≥ 40 years had COPD. Considering the ageing population and still an important smoking prevalence, this burden is bound to increase and imposes great demands to public health care and society in the Netherlands.
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http://dx.doi.org/10.1016/j.rmed.2012.01.008DOI Listing
June 2012

Low-grade adipose tissue inflammation in patients with mild-to-moderate chronic obstructive pulmonary disease.

Am J Clin Nutr 2011 Dec 9;94(6):1504-12. Epub 2011 Nov 9.

NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Center+, Netherlands.

Background: Low-grade systemic inflammation is common in chronic obstructive pulmonary disease (COPD), but its source remains unclear. Adipose tissue is a potent producer of inflammatory mediators and may contribute to systemic inflammation in COPD, possibly via hypoxia.

Objective: We studied the influence of COPD and exercise-induced oxygen desaturation on adipose tissue inflammation (ATI) and its contribution to systemic inflammation.

Design: Subcutaneous adipose tissue biopsies were investigated in 28 clinically stable COPD patients [forced expiratory volume in 1 s: 58 ± 16% predicted; BMI (in kg/m(2)): 24.9 ± 2.9] and 15 age-, sex-, and body composition-matched healthy control subjects. Fat mass was measured with dual-energy X-ray absorptiometry. Patients were prestratified by oxygen desaturation assessed by incremental cycle ergometry. The adipocyte size and adipose tissue expression of 19 inflammatory and hypoxia-related genes were measured, and adipose tissue macrophages (ATMs) were histologically quantified. Systemic inflammatory markers included C-reactive protein (CRP) and a panel of 20 adipokines.

Results: COPD patients had comparable fat mass but higher CRP and HOMA-IR than did control subjects. COPD patients and control subjects had comparable adipose tissue gene expression, adipocyte size, ATM infiltration, and systemic adipokine concentrations. Desaturating COPD patients had no different ATI status than did nondesaturating COPD patients. COPD patients with high CRP had significantly greater ATM infiltration than did patients with low CRP, which was independent of BMI and fat mass.

Conclusions: In COPD patients, mild-to-moderate COPD, per se, does not enhance ATI or its contribution to systemic inflammation compared with in well-matched healthy control subjects. However, to our knowledge, our study provides a first indication for a possible role of ATMs in the systemic inflammatory response in COPD that requires additional investigation. This trial was registered at www.trialregister.nl as NTR1402.
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http://dx.doi.org/10.3945/ajcn.111.023911DOI Listing
December 2011

Prevention of asthma in genetically susceptible children: a multifaceted intervention trial focussed on feasibility in general practice.

Pediatr Allergy Immunol 2011 Dec 13;22(8):794-802. Epub 2011 Jul 13.

Department of General Practice, Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.

Background: Although the effectiveness of the multifaceted allergen-reducing interventions for the prevention of asthma in susceptible children was showed to be proven, the feasibility was not clear.

Methods: The research question of the PREVention of asthma in susceptible children (PREVASC) trial was focused on the assessment of the effectiveness and feasibility of a multifaceted intervention on the prevention of allergic asthma in general practice. The effectiveness and feasibility of an intervention aimed at the simultaneous reduction in the environmental exposures to inhalant- and food allergens in susceptible children was investigated. A total of 476 children susceptible for developing asthma were initially included during pregnancy and were randomly divided over an intervention group of n = 222 children whose parents were offered a multifaceted environmental exposure-reducing intervention. Controls (n = 221) received usual care. The main outcome was 'diagnosis of allergic asthma at age 6'.

Results: A significant reduction in inhalant allergen exposure levels of house dust mite [(Der p1), p = 0.043], cat [(Fel d1), p = 0.037], and dog [(Can f1), p = 0.012] was reached. Significantly more intervention group children started using cow's milk and solids after the age of 6 months (p ≤ 0.001). No statistical difference, however, was reached between groups on the duration of breast-feeding (p = 0.635) and the reduction in smoke exposure (p = 0829). At age 6, the intervention had no influence on the development of main outcome allergic asthma (OR = 1.010 (CI 0.580-1.758).

Conclusion: Other primary preventive asthma-reducing interventions were shown to be effective in reducing the occurrence of asthma for at least the first 7-8 yr of life. The multifaceted PREVASC allergic asthma primary preventive intervention was effective in reducing the exposure to inhalant and food allergens, but was not feasible for the parents. A lack of sufficient room for improvement focus on stimulating adherence seemed to be involved. It is suggested that a multifaceted environmental exposure-reducing intervention may have to be adapted to the personal circumstances of patients at baseline.
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http://dx.doi.org/10.1111/j.1399-3038.2011.01192.xDOI Listing
December 2011

Smoking cessation and development of respiratory health in smokers screened with normal spirometry.

Respir Med 2011 Feb 17;105(2):243-9. Epub 2010 Sep 17.

Department of General Practice, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

Background: Case-finding of chronic obstructive pulmonary disease (COPD) using spirometry may deter people with normal lung function from stopping smoking. The objective of this study was to observe the percentage of smokers screened with normal lung function that quit smoking.

Methods: As part of a study on early detection of COPD, 518 smokers were screened with normal lung function (post-bronchodilator FEV(1)/FVC ≥ 70%). They were invited for a follow-up measurement after an average of 2.4 years. Non-smoking was validated by carbon monoxide (<10 ppm), and respiratory health related quality of life was measured with the Clinical COPD Questionnaire (CCQ).

Results: A total of 255 participants were followed up (49%). The point prevalence rate of non-smoking at follow-up was 18% (N = 47), and 9% assuming that all non-respondents were smokers. This rate was not lower than the expected rate of quitting in the Dutch population (8-9%) and primary "care as usual" in smokers screened with abnormal lung function (10%; p > 0.05 for all comparisons). The average decline in post-bronchodilator FEV(1) was 26 mL/year, which was unrelated to smoking status at follow-up. Non-smokers showed a clinically meaningful and statistically significant (p < 0.001) improvement in CCQ respiratory symptoms (-0.96) and total score (-0.51).

Conclusions: Our results do not suggest that early detection of airflow limitation to motivate smoking cessation reduces the rate of quitting in smokers shown to have normal lung function. Such smokers should be advised to quit smoking on the grounds that they are likely to improve their respiratory health in the short term and reduce their risk for smoking related diseases in the long term.
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http://dx.doi.org/10.1016/j.rmed.2010.07.010DOI Listing
February 2011

Reliability and validity of the clinical COPD questionniare and chronic respiratory questionnaire.

Respir Med 2010 Nov 11;104(11):1675-82. Epub 2010 Jun 11.

Department of General Practice, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands.

Background: Questionnaires are often used in assessing health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). It is important that these questionnaires have good reliability, validity, and responsiveness. The aim of this study was to investigate and compare these properties in the disease specific Clinical COPD Questionnaire (CCQ) and the Chronic Respiratory Questionnaire self-reported (CRQ-SR).

Methods: Two hundred ninety six participants with spirometry confirmed mild to moderate COPD were included in a smoking cessation trial. It was assumed that health-related quality of life would improve in participants who stopped smoking. The questionnaires were administered at baseline and at weeks 5, 26, and 52 after the target quit date.

Results: At baseline, 292 (97%) participants returned the CCQ and 296 (100%) the CRQ-SR questionnaire. For both instruments, the internal consistency was good (Cronbach's alpha >70%) as was the convergent validity with each other but not with spirometry. The CCQ was responsive to improvements in respiratory symptoms at both week 26 (-1.02, SD = 0.81) and 52 (-1.04, SD = 0.91) and in the total score at week 26 (-0.54, SD = 0.50) and 52 (-0.43, SD = 0.44). The mastery domain and the total score of the CRQ-SR were responsive at week 26 (1.14, SD = 0.82; 0.67, SD = 0.97 respectively) but not at week 52 (0.04, SD = 0.93; 0.38, SD = 0.57 respectively).

Conclusion: Both the CCQ and CRQ-SR are equally reliable and valid. The long-term responsiveness of the CCQ is better. Both questionnaires can be used in future studies involving patients with mild to moderate COPD. However, when the follow-up exceeds 26 weeks, the CCQ is the recommended alternative. Netherlands Trial Register: ISRCTN 64481813.
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http://dx.doi.org/10.1016/j.rmed.2010.04.023DOI Listing
November 2010

Mono and multifaceted inhalant and/or food allergen reduction interventions for preventing asthma in children at high risk of developing asthma.

Cochrane Database Syst Rev 2009 Jul 8(3):CD006480. Epub 2009 Jul 8.

Department of General Practice, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center, P Debyeplein 1, PO box 616, Maastricht, Netherlands, 6200 MD.

Background: Allergen exposure is one of the environmental factors seemingly associated with the development of asthma. If asthma is a multi-factorial disease, it is hypothesised that prevention might only prove effective if most or all relevant environmental factors are simultaneously avoided.

Objectives: To assess effect(s) of monofaceted and multifaceted interventions compared with control interventions in preventing asthma and asthma symptoms in high risk children.

Search Strategy: We searched the Cochrane Airways Trials Register (December 2008).

Selection Criteria: Randomised controlled trials of allergen exposure reduction for the primary prevention of asthma in children. Interventions were multifaceted (reducing exposure to both inhalant and food allergens) or monofaceted (reducing exposure to either inhalant or food allergens) Follow up had to be from birth (or during pregnancy) up to a minimum of two years of age.

Data Collection And Analysis: We included in the analysis studies assessing the primary outcome (current diagnosis: asthma) and/or one of the secondary outcomes (current respiratory symptoms: wheezing, nocturnal coughing and dyspnoea). We pooled multifaceted and monofaceted intervention trials separately. We made an indirect comparison of their effects using tests for interaction to calculate relative odds ratios.

Main Results: We included three multifaceted and six monofaceted intervention studies (3271 children). Physician diagnosed asthma in children less than five years, and asthma as defined by respiratory symptoms and lung function criteria in children aged five years and older, both favoured treatment with a multifaceted intervention compared to usual care (< 5 years: odds ratio (OR) 0.72, 95% confidence interval (CI) 0.54 to 0.96, and > 5 years: OR 0.52, 95% CI 0.32 to 0.85). However, there was no significant difference in outcome between monofaceted intervention and control interventions (< 5 years: OR 1.12, 95% CI 0.76 to 1.64, and > 5 years: OR 0.83, 95% CI 0.59 to 1.16). Indirect comparison between these treatments did not demonstrate a significant difference between multiple interventions and mono-interventions in reducing the frequency of asthma diagnosis in children under five years (relative OR 0.64 (95% CI 0.40 to 1.04, P = 0.07) or five years and older (relative OR 0.63, 95% CI 0.35 to 1.13, P = 0.12). There was also no significant difference between either mono- and multifaceted intervention and control in reducing the likelihood of symptoms of nocturnal coughing at follow up. Wheezing, however, showed a significant difference between multifaceted and mono-interventions (relative OR 0.59, 95% CI 0.35 to 0.99, P = 0.04), but the significance was lost when data on treatment only was analysed.

Authors' Conclusions: The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children.
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http://dx.doi.org/10.1002/14651858.CD006480.pub2DOI Listing
July 2009

What mediates the effect of confrontational counselling on smoking cessation in smokers with COPD?

Patient Educ Couns 2009 Jul 16;76(1):16-24. Epub 2009 Jan 16.

Department of General Practice, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre, Maastricht, The Netherlands.

Objective: Within the framework of a randomized, active treatment controlled trial, we used a mediation analysis to understand the mechanisms by which an intervention that uses confrontation with spirometry for smoking cessation achieves its effects.

Methods: Participants were 228 smokers from the general population with previously undetected chronic obstructive pulmonary disease (COPD), who were detected with airflow limitation by means of spirometry. They received two equally intensive behavioural treatments by a respiratory nurse combined with nortriptyline for smoking cessation: confrontational counselling with spirometry versus conventional health education and promotion (excluding confrontation with spirometry and COPD).

Results: Cotinine validated abstinence rates from smoking at 5 weeks after the target quit date were 43.1% in the confrontational counselling group versus 31.3% in the control group (OR=1.67, 95%CI=0.97-2.87). The effect of confrontational counselling on abstinence was independently mediated by the expectation of getting a serious smoking related disease in the future (OR=1.76, 95%CI=1.03-3.00), self-exempting beliefs (OR=0.42, 95%CI=0.21-0.84), and self-efficacy (OR=1.38, 95%CI=1.11-1.73).

Conclusion: We conclude that confrontational counselling increases risk perceptions and self-efficacy, and decreases self-exempting beliefs (risk denial) in smokers with previously undetected COPD. These changes in mediators are associated with a higher likelihood of smoking cessation.

Practice Implications: Apart from the intensity, the content of smoking cessation counselling may be an important factor of success. A confrontational counselling approach as we applied may have the potential to alter smoking-related cognitions in such a way that smokers are more successful in quitting. Nurses can be trained to deliver this treatment.
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http://dx.doi.org/10.1016/j.pec.2008.11.017DOI Listing
July 2009

Acute exacerbations of COPD: recommendations for integrated care.

Expert Rev Respir Med 2008 Aug;2(4):489-94

Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are significant events that come with high costs for patients and for society. Initial management of exacerbations consists of pharmacotherapy and a reassessment of pre-existing management and self-management strategies. Currently, care for AECOPDs is often suboptimal. Integrated care consisting of self-management support, delivery system design, decision support and clinical information systems will probably improve the quality of healthcare delivery for patients with AECOPDs. In this review, we summarize current knowledge related to the epidemiology and management of AECOPDs, identify shortcomings in current clinical practice and give recommendations for innovative, integrated and optimized care for these patients.
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http://dx.doi.org/10.1586/17476348.2.4.489DOI Listing
August 2008

Influence of house dust mite impermeable covers on health-related quality of life of adult patients with asthma: results of a randomized clinical trial.

J Asthma 2007 Dec;44(10):843-8

Department of General Practice, Radboud University Nijmegen Medical Centre, The Netherlands.

The aim of this study was to evaluate the effect of house dust mite impermeable covers on asthma-specific health-related quality of life in adult asthmatic patients that were trained in guided self-management. In a 2-year randomized placebo-controlled clinical trial, information on the quality of life was collected. The improvement of Mini Asthma Quality of Life Questionnaire (AQLQ) score in the allergens-avoidance group (0.26) was comparable to the improvement in the placebo group (0.30) and not significant. HDM-impermeable covers for pillows, duvets, and mattresses did not result in improved health-related quality of life.
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http://dx.doi.org/10.1080/02770900701752318DOI Listing
December 2007

Occasional review: influenza in COPD: pathogenesis, prevention, and treatment.

Int J Chron Obstruct Pulmon Dis 2007 ;2(1):5-10

Dept of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

Influenza viruses cause respiratory tract infections that in patients with underlying lung diseases such as chronic obstructive pulmonary disease (COPD) are associated with exacerbations and excess morbidity and mortality. Typically, influenza B is associated with relatively mild, local outbreaks, whereas influenza A is the cause of world-wide pandemics. Upon infection, two antigens present on the viral surface, hemagglutinin and neuraminidase result in human immunity, but since many subtypes of these antigens exist that vary over time, immunity in the population is blunted. Vaccination is advocated in high-risk groups including patients with underlying (lung) diseases and in the elderly, and needs to be repeated annually with vaccines expected to cover the expected change in viral antigenicity. When started early, antiviral drugs, especially neuraminidase-inhibitors can be prescribed in adjunct to nonspecific interventions in an attempt to shorten disease duration and to prevent complications in case of an influenza infection. Currently, the effectiveness of antiviral drugs specifically in patients with COPD has not been proven.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692115PMC
http://dx.doi.org/10.2147/copd.2007.2.1.5DOI Listing
June 2008