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- Heikkilä, Katriina, et al.
(author)
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Job strain and COPD exacerbations: an individual-participant meta-analysis
- 2014
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 44:1, s. 247-251
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Journal article (peer-reviewed)abstract
- To the Editor:Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and disability worldwide (1). The clinical course of COPD is characterised by exacerbations, which can be minor and manageable at home or in primary care, or severe, leading to hospitalisation or even death. Known causes of exacerbations include tobacco smoke, air pollution, dusts and fumes, and respiratory infections (1, 2). One less well understood risk factor is stress, which could plausibly lead to COPD exacerbations as it can trigger inflammation (3, 4) and is associated with increased smoking (5), which are both implicated in COPD pathology (2). Work is an important source of stress in the age groups in which COPD is typically diagnosed (1, 6). However, we are not aware of previous investigations of work-related stress and the risk of COPD exacerbations.In this study, we examined the associations between job strain (the most widely studied conceptualisation of work-related stress) and severe COPD exacerbations using individual-level data from 10 prospective cohort studies from the Individual Participant Data Meta-analysis in Working Populations (IPD-Work) Consortium (7). Job strain is defined as a combination of high demands (excessive amounts of work) and low control (having little influence on what tasks to.
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2. |
- Sörenson, Sverre, et al.
(author)
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Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy
- 2013
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49:1, s. 115-120
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Journal article (peer-reviewed)abstract
- Aim of the study: The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo. less thanbrgreater than less thanbrgreater thanMethods: In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks. less thanbrgreater than less thanbrgreater thanResults: VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028). less thanbrgreater than less thanbrgreater thanConclusion: Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.
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3. |
- Lowe, Adrian J, et al.
(author)
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Impact of Maternal Obesity on Inhaled Corticosteroid Use in Childhood : A Registry Based Analysis of First Born Children and a Sibling Pair Analysis
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Journal article (peer-reviewed)abstract
- BackgroundIt has been proposed that maternal obesity during pregnancy may increase the risk that the child develops allergic disease and asthma, although the mechanisms underpinning this relationship are currently unclear. We sought to assess if this association may be due to confounding by genetic or environmental risk factors that are common to maternal obesity and childhood asthma, using a sibling pair analysis.MethodsThe study population comprised a Swedish national cohort of term children born between 1992 and 2008 to native Swedish parents. Maternal body mass index (BMI) was measured at 8-10 weeks gestation. Unconditional logistic regression models were used to determine if maternal obesity was associated with increased risk of inhaled corticosteroid (ICS) in 431,718 first-born children, while adjusting for potential confounders. An age-matched discordant sib-pair analysis was performed, taking into account shared genetic and environmental risk factors.ResultsMaternal over-weight and obesity were associated with increased risk that the child would require ICS (for BMI >= 35 kg/m(2), aOR = 1.30, 95% CI = 1.10-1.52 compared with normal weight mothers) in children aged 6-12 years. Similar effects were seen in younger children, but in children aged 13-16 years, maternal obesity (BMI >= 30) was related to increased risk of ICS use in girls (aOR = 1.28, 95% CI = 1.07-1.53) but not boys (OR = 1.05, 95% CI = 0.87-1.26). The sib-pair analysis, which included 2,034 sib-pairs older than six years who were discordant for both ICS use and maternal BMI category, failed to find any evidence that increasing maternal weight was related to increased risk of ICS use.ConclusionMaternal obesity is associated with increased risk of childhood ICS use up to approximately 12 years of age, but only in girls after this age. These effects could not be confirmed in a sib pair analysis, suggesting either limited statistical power, or the effects of maternal BMI may be due to shared genetic or environmental risk factors.
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4. |
- Bråbäck, Lennart, et al.
(author)
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Confounding with familial determinants affects the association between mode of delivery and childhood asthma medication : a national cohort study
- 2013
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In: Allergy, Asthma & Clinical Immunology. - : BioMed Central. - 1710-1484 .- 1710-1492. ; 9:1, s. 14-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Mode of delivery may affect the risk of asthma but the findings have not been consistent and factors shared by siblings may confound the associations in previous studies. METHODS: The association between mode of delivery and dispensed inhaled corticosteroid (ICS) (a marker of asthma) was examined in a register based national cohort (n=199 837). A cohort analysis of all first born children aged 2-5 and 6-9 years was performed. An age-matched sibling-pair analysis was also performed to account for shared genetic and environmental risk factors. RESULTS: Analyses of first-borns demonstrated that elective caesarean section was associated with an increased risk of dispensed ICS in both 2-5 (adjusted odds ratio (aOR)=1.19, 95% confidence interval (CI) 1.09-1.29) and 6-9 (aOR=1.21, 1.09-1.34) age groups. In the sibling-pair analysis, the increased risk associated with elective caesarean section was confirmed in 2-5 year olds (aOR=1.22, 1.05-1.43) but not in 6-9 year olds (aOR=1.06, 0.78-1.44). Emergency caesarean section and vacuum extraction had some association with dispensed ICS in the analyses of first-borns but these associations were not confirmed in the sibling-pair analyses. CONCLUSIONS: Confounding by familial factors affects the association between mode of delivery and dispensed ICS. Despite this confounding, there was some evidence that elective caesarean section contributed to a modestly increased risk of dispensed ICS but only up to five years of age.
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5. |
- von Kobyletzki, Laura B., et al.
(author)
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Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort
- 2012
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In: BMC Dermatology. - London, United Kingdom : BioMed Central (BMC). - 1471-5945. ; 12:11, s. 1-9
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Journal article (peer-reviewed)abstract
- Background: This study aimed to estimate the association between eczema in early childhood and the onset of asthma and rhinitis later in life in children.Methods: A total of 3,124 children aged 1-2 years were included in the Dampness in Building and Health (DBH) study in the year 2000, and followed up 5 years later by a parental questionnaire based on an International Study of Asthma and Allergies in Childhood protocol. The association between eczema in early childhood and the incidence of asthma and rhinitis later in life was estimated by univariable and multivariable logistic regression modelling.Results: The prevalence of eczema in children aged 1-2 years was 17.6% at baseline. Children with eczema had a 3-fold increased odds of developing asthma (adjusted odds ratio [aOR], 3.07; 95% confidence interval (CI) 1.79-5.27), and a nearly 3-fold increased odds of developing rhinitis (aOR, 2.63; 1.85-3.73) at follow-up compared with children without eczema, adjusted for age, sex, parental allergic disease, parental smoking, length of breastfeeding, site of living, polyvinylchloride flooring material, and concomitant allergic disease. When eczema was divided into subgroups, moderate to severe eczema (aOR, 3.56; 1.62-7.83 and aOR, 3.87; 2.37-6.33, respectively), early onset of eczema (aOR, 3.44; 1.94-6.09 and aOR, 4.05; 2.82-5.81; respectively), and persistence of eczema (aOR, 5.16; 2.62-10.18 and aOR, 4.00; 2.53-6.22, respectively) further increased the odds of developing asthma and rhinitis. Further independent risk factors increasing the odds of developing asthma were a parental history of allergic disease (aOR, 1.83; 1.29-2.60) and a period of breast feeding shorter than 6 months (aOR, 1.57; 1.03-2.39). The incidence of rhinitis was increased for parental history of allergic disease (aOR, 2.00; 1.59-2.51) and polyvinylchloride flooring (aOR, 1.60; 1.02-2.51).Conclusion: Eczema in infancy is associated with development of asthma and rhinitis during the following 5-year period, and eczema is one of the strongest risk factors. Early identification is valuable for prediction of the atopic march.
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6. |
- von Kobyletzki, Laura, et al.
(author)
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Evaluation of a parental questionnaire to identify atopic dermatitis in infants and preschool children
- 2012
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In: Journal of Allergy. - New York, USA : Hindawi Publishing Corporation. - 1687-9783 .- 1687-9791. ; 2012
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Journal article (peer-reviewed)abstract
- Aim: To develop and validate a questionnaire for detecting atopic dermatitis in infants and small children from the age of 2 months.Methods: Parents to 60 children answered a written questionnaire prior to a physical examination and individual semistructured interview. Qualitative and quantitative analyses of validity, sensitivity, specificity, and predictive values of the questionnaire were performed.Results: A total of 27 girls and 33 boys, aged 2 to 71 months, 35 with and 25 without physician-diagnosed eczema, participated. Validation of the questionnaire by comparisons with physicians' diagnoses showed a sensitivity of 0.91 (95% CI 0.77-0.98) and a specificity of 1 (95% CI 0.86-1).Conclusions: Three questions in a parental questionnaire were sufficient for diagnosing eczema in infants and small children.
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7. |
- Johansson, Inger, 1953, et al.
(author)
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Lower incidence of CMV infection and acute rejections with valganciclovir
- 2013
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In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 13
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Journal article (peer-reviewed)abstract
- Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS).Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.
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8. |
- Broström, Anders, et al.
(author)
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Factors associated with undiagnosed obstructive sleep apnoea in hypertensive primary care patients
- 2012
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In: Scandinavian Journal of Primary Health Care. - : Informa Healthcare. - 0281-3432 .- 1502-7724. ; 30:2, s. 107-113
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Journal article (peer-reviewed)abstract
- Objective. In hypertensive primary care patients below 65 years of age, (i) to describe the occurrence of undiagnosed obstructive sleep apnoea (OSA), and (ii) to identify the determinants of moderate/severe OSA. Design. Cross-sectional. Setting. Four primary care health centres in Sweden. Patients. 411 consecutive patients (52% women), mean age 57.9 years (SD 5.9 years), with diagnosed and treated hypertension (BP andgt; 140/90). Main outcome measures. Occurrence of OSA as measured by the apnoea hypopnoea index (AHI). Results. Mild (AHI 5-14.9/h) and moderate/severe (AHI andgt; 15/h) OSA were seen among 29% and 30% of the patients, respectively. Comparing those without OSA with those with mild or moderate/severe OSA, no differences were found in blood pressure, pharmacological treatment (anti-hypertensive, anti-depressive, and hypnotics), sleep, insomnia symptoms, daytime sleepiness, or depressive symptoms. Obesity (BMI andgt; 30 kg/m(2)) was seen in 30% and 68% of the patients with mild and moderate/severe OSA, respectively. Male gender, BMI andgt; 30 kg/m(2), snoring, witnessed apnoeas, and sleep duration andgt; 8 hours were determinants of obstructive sleep apnoea. Conclusion. Previously undiagnosed OSA is common among patients with hypertension in primary care. Obesity, snoring, witnessed apnoeas, long sleep duration, and male gender were the best predictors of OSA, even in the absence of daytime sleepiness and depressive symptoms.
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9. |
- Bjerg, Anders, 1982, et al.
(author)
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Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA(2)LEN Study
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Journal article (peer-reviewed)abstract
- Background Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders. Methods In 2008 the Global Allergy and Asthma European Network (GA2LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds. Results Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years. Discussion In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
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10. |
- Powell, Nelson, et al.
(author)
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Patterns in pharyngeal airflow associated with sleep-disordered breathing
- 2011
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In: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 12:10, s. 966-974
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Journal article (peer-reviewed)abstract
- Objective: To establish the feasibility of a noninvasive method to identify pharyngeal airflow characteristics in sleep-disordered breathing.Methods: Four patients with sleep-disordered breathing who underwent surgery or used positive airway pressure devices and four normal healthy controls were studied. Three-dimensional CT imaging and computational fluid dynamics modeling with standard steady-state numerical formulation were used to characterize pharyngeal airflow behavior in normals and pre-and post-treatment in patients. Dynamic flow simulations using an unsteady approach were performed in one patient.Results: The pre-treatment pharyngeal airway below the minimum cross-sectional area obstruction site showed airflow separation. This generated recirculation airflow regions and enhanced turbulence zones where vortices developed. This interaction induced large fluctuations in airflow variables and increased aerodynamic forces acting on the pharyngeal wall. At post-treatment, for the same volumetric flow rate, airflow field instabilities vanished and airflow characteristics improved. Mean maximum airflow velocity during inspiration reduced from 18.3 ± 5.7 m/s pre-treatment to 6.3 ± 4.5 m/s post-treatment (P = 0.002), leading to a reduction in maximum wall shear stress from 4.8 ± 1.7 Pa pre-treatment to 0.9 ± 1.0 Pa post-treatment (P = 0.01). The airway resistance improved from 4.3 ± 1.4 Pa/L/min at pre-treatment to 0.7 ± 0.7 Pa/L/min at post-treatment (P = 0.004). Post-treatment airflow characteristics were not different from normal controls (all P ⩾ 0.39).Conclusions: This study demonstrates that pharyngeal airflow variables may be derived from CT imaging and computational fluid dynamics modeling, resulting in high quality visualizations of airflow characteristics of axial velocity, static pressure, and wall shear stress in sleep-disordered breathing.
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