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- Donoso, Felipe, 1984-
(author)
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Function and morbidity of the esophagus and respiratory system in the growing child with esophageal atresia
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Background: Esophageal atresia (EA) is a congenital malformation that consists of various degrees of discontinuity of the esophagus and affects about 1:3000 live births. EA is usually corrected at birth with survival rates over 90%, which has shifted the focus towards improvement of associated morbidity and health-related quality of life.The aims of this thesis were to investigate how morbidity in the esophagus and respiratory system in children with EA relates with diagnostic and function tests included in the follow-up programme after EA repair and evaluate the efficacy of the recommended proton pump inhibitor (PPI) prophylaxis.Methods: The study population consists of 169 children treated for EA in the Department of Pediatric Surgery at University Children’s Hospital, Uppsala between 1994 and 2018. The patients participated in the multidisciplinary follow-up programme that was established in 2011 for patients with EA. The thesis is based on four observational studies that investigated the outcome of the patients and generalisability of the results; risk factors for anastomotic strictures and the efficacy of PPI-treatment regimen in reducing its incidence; pulmonary function and risk factors for pulmonary function impairment; and association between ambulatory 24h pH test, endoscopic findings of esophagitis and hiatal hernia, symptoms of gastroesophageal reflux (GER), and histopathological esophagitis. The studies were approved by the Regional Committee for Medical Research Ethics.Results: The demographics and outcome of our study population are comparable with centres of higher caseload, showing low mortality rate but significant morbidity, especially considering anastomotic strictures and patients with long gap EA. Long gap EA, higher birth weight, and anastomotic tension were independent risk factors of anastomotic stricture formation. Prophylactic PPI-treatment did not reduce anastomotic strictures compared with symptomatic PPI-treatment. Respiratory morbidity and obstruction of the airways were common in children and adolescents after EA repair. The risk for pulmonary function impairment increased with lower birth weight and older age at follow-up. Neither ambulatory 24h pH-metry, clinical symptoms of GER nor endoscopic esophagitis were reliable tools to identify histopathological esophagitis in children and adolescents after EA repair and cannot replace esophageal biopsies.Conclusion: The poor correlation between clinical symptoms and morbidity of the esophagus and respiratory system justifies the need of clinical follow-up programmes in patients with EA. A general recommendation to stop prophylactic PPI-treatment after EA repair cannot be supported, however, sufficient evidence is available to support randomised controlled studies.
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- Gagatek, Sebastian Grzegorz, et al.
(author)
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Validation of clinical clusters for long-term mortality in two European COPD cohorts
- 2020
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In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 56:Suppl. 64
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Journal article (other academic/artistic)abstract
- Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with a variable mortality risk. A simple clinical algorithm has been validated for short-term mortality by Burgel et al. (ERJ 2017).Aim: To study if Burgel’s clinical algorithm is valid to predict long-term mortality.Methods: Data from two COPD cohorts, the Swedish PRAXIS Study (PS) (n=784, mean age (SD) 64.0 years (7.5), 42% males) and the Rotterdam Study (RS) (n=735, mean age (SD) 72 years (9.2), 57% males), with 9-years of follow-up data including mortality was used. The five clinical clusters were derived from baseline data on age, body mass index, dyspnea grade (mMRC), FEV 1 (%pred) and comorbidity (cardiovascular disease or diabetes). Mortality risk was estimated by unadjusted Cox models.Results: The distribution of clinical clusters (1-5) was: 29%/45%/8%/6%/12% in PS and 23%/26%/36%/0/15% in RS. The cumulative proportion of deaths after 9-years of follow-up was highest among COPD clusters 1 (65%) and 4 (72%), and lowest among cluster 5 (10%) in the PS cohort. In RS, Cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared to cluster 5, the meta-analysed hazard ratio (HR) (95%CI) for cluster 1 was 9.95 (6.52–15.19) and for cluster 4, 13.49 (6.41–28.38). The meta-analysed HR for clusters 2 and 3, compared with cluster 5, were: 2.80 (1.77 – 4.36) and 4.73 (3.02 – 7.42), respectively.Conclusions: Burgel’s clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with best prognosis and clusters 2 and 3 with intermediate prognosis in two independent COPD cohorts from Sweden and Netherlands.
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- Kirkeleit, Jorunn, et al.
(author)
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Early life origins of lung ageing : A study of lung function decline the ECRHS and NFBC1966 cohorts
- 2020
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In: European Respiratory Journal. - : ERS Publications. - 0903-1936 .- 1399-3003. ; 56
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Journal article (other academic/artistic)abstract
- Objective: To determine whether early life factors associated with poor lung growth and submaximal attained lung function contribute to accelerated lung function decline later in life.Methods: Participants in the European Community Respiratory Health Survey (ECRHS) and the Northern Finland Birth Cohort 1966 (NFBC1966) with lung function measured in a first (n=10,971), second (n=7,981) and third wave (n=4,849), aged 20 – 68 years, were included. Mean annual decline in maximum forced expired volume in 1 second (FEV1) and forced vital capacity (FVC) were main outcomes. Information on early life factors was provided by standardized interviews and questionnaires. We estimated the effect of early life factors including maternal age, parental smoking, season of birth, parental asthma and respiratory infections using mixed effects models, adjusted for age, FEV1 and FVC at baseline, height, and smoking habits.Results: Decline in FEV1 was accelerated in women born of a mother with asthma (β = 2.4 ml; 95% CI 0.6-4.3) or who smoked during pregnancy (1.9; 0.2-3.6), and in men having a father with asthma (3.5; 0.2-6.9) or born by Cesarean section (7.9; 1.6-14.2). Accelerated decline in FVC was associated with paternal asthma in men (4.3; 0.1-8.5) and early menarche (<12 years) in women (2.4; 0.4-4.4). No statistically significant effect on lung function decline was found for other investigated early life factors.Conclusion: Early life risk factors contribute to an accelerated lung function decline with ageing, following sex-specific patterns. Decline in FEV1 versus FVC showed slightly different patterns.
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- Timm, Signe, et al.
(author)
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Does parental or grandparental farm upbringing influence risk of asthma in offspring?
- 2020
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In: European Respiratory Journal. - : ERS Publications. - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Journal article (other academic/artistic)abstract
- Background: Farm upbringing has been associated with lower risk of asthma, and also with methylation of asthma-related genes. As such, farm upbringing has the potential to transfer less asthma risk across generations. We aimed to study generational effects from parental farm upbringing on offspring asthma.Methods: Our study involved three generations: 5,759 participants from the ECRHS study (born 1945-71, denoted G1), their 9,991 parents (G0) and their 8,260 offspring (G2) participating in RHINESSA. Questionnaire data on upbringing and asthma were available for all generations; direct information for G1 and G2, and via G2 for G0. Parental and grandparental place of upbringing was categorised as (1) both parents from farm (2) mother from farm, father from village/city (3) father from farm, mother from village/city (4) both parents from village or one parent from village and one from city (5) both parents from city (ref.). Data was analysed in Cox regression with G2 age as time scale.Results: Parental farm upbringing was not related to offspring asthma when compared to city upbringing (HR 1.12, 95 % CI 0.74-1.69) Findings remained similar when stratified by offspring upbringing and asthma phenotypes. Quantitative bias analyses showed similar estimates for alternative data sources. Grandparental farm upbringing was not associated with offspring asthma in either the maternal (HR 1.05, 95% CI 0.67-1.65) or paternal line (HR 1.02, 95% CI 0.62-1.68).Conclusion: This multi-generation analysis suggests no evidence of an association between parental or grandparental farm upbringing and offspring asthma.
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