| 21. |
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| 22. |
- 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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| 23. |
- Donoso, Felipe, et al.
(author)
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Predictors of histopathological esophagitis in infants and adolescents with esophageal atresia within a national follow-up programme.
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:4
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Journal article (peer-reviewed)abstract
- PURPOSE: Esophageal atresia (EA) is a congenital anomaly of the foregut. Although the survival has improved over the years there is a significant gastrointestinal morbidity affecting physical function and health-related quality of life. The aims of the study were to identify and evaluate predictors of histopathological esophagitis in infants and adolescents with EA.METHODS: Single centre, cross-sectional study including one and 15-year-old patients operated for EA that participated in the national follow-up programme between 2012 and 2020 according to a pre-established protocol including upper endoscopy with oesophageal biopsies and 24h-pH-test. Data was collected from patients' medical records and pH-analysis software. Regression models were used to identify predictors of histopathological oesophagitis. Possible predictors were abnormal reflux index, endoscopic esophagitis, hiatal hernia, symptoms of gastroesophageal reflux (GER) and age.RESULTS: 65 patients were included, 47 children and 18 adolescents. All children were treated with PPI during their first year of life. Symptoms of GER were reported by 13 (31.7%) of the infant's caregivers, 34 of the children (72.3%) had abnormal reflux index and 32 (68.1%) had histopathological esophagitis. The corresponding numbers for adolescents were 8 (50%), 15 (83.3%) and 10 (55.6%). We found no significant associations between histopathological esophagitis and endoscopic esophagitis, symptoms of GER, hiatus hernia or age group. Abnormal reflux index was an independent predictor of histopathological esophagitis. Seven patients with normal reflux index had histopathological esophagitis, all grade I.CONCLUSIONS: We found a high prevalence of histopathological esophagitis despite PPI treatment in accordance with recommendations. No significant difference between the two age groups was seen. Abnormal reflux index was an independent predictor of histopathological esophagitis. However, we cannot recommend the use of pH-metry as a substitute for esophageal biopsies; future studies are needed to elucidate if esophageal biopsies might be postponed in infants with normal reflux index.
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| 24. |
- Donoso, Felipe, et al.
(author)
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Pulmonary function in children and adolescents after esophageal atresia repair
- 2020
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In: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 55:1, s. 206-213
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Journal article (peer-reviewed)abstract
- IntroductionRespiratory morbidity after esophageal atresia (EA) is common. The aims of this study were to assess pulmonary function, to identify risk factors for pulmonary function impairment (PFI), and to investigate the relations between respiratory morbidity, defined as medical treatment for respiratory symptoms or recent pneumonia and PFI after EA repair.Material and MethodsSingle center retrospective observational study including patients with EA who participated in the follow‐up program for 8‐ or 15‐year old patients from 2014 to 2018 and performed pulmonary function testing by body plethysmography, dynamic spirometry, impulse oscillometry, and diffusing capacity of the lungs. Univariate and multiple stepwise logistic regression with PFI as outcome were performed. Anastomotic leak, episodes of general anesthesia, extubation day, birth weight, age at follow up, gross classification, and abnormal reflux index were independent variables.ResultsIn total, 47 patients were included. PFI was found in 19 patients (41%) and 16 out of 19 patients (84%) had an obstructive pattern. Respiratory morbidity was found in 23 (52%, NA = 3) of the patients with no correlation to PFI. Birth weight, age at follow‐up, and episodes of general anesthesia were identified as risk factors for PFI.ConclusionRespiratory morbidity and PFI were common in children and adolescents after EA repair. The major component of PFI was obstruction of the airways. The risk for PFI increased with lower birth weight and older age at follow up. The poor correlation between respiratory morbidity and PFI motivates the need of clinical follow up including pulmonary function tests.
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| 25. |
- Ek, A., et al.
(author)
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Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey
- 2013
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In: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 68:10, s. 1314-1321
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Journal article (peer-reviewed)abstract
- BackgroundAsthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality-of-life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects. MethodsThis Swedish cohort (age 17-76years) consists of 605 well-characterized asthmatics with and without CRS, 110 individuals with CRS only, and 226 controls and is part of the Global Allergy and Asthma European Network (GA(2)LEN) survey. The Mini Asthma Quality of Life Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire, spirometry, skin prick test (SPT), exhaled nitric oxide (FeNO), smell test, and peak nasal inspiratory flow were used. ResultsSubjects having both asthma and CRS have lower mAQLQ scores in all domains (P<0.001) and a lower EQ-5D index value and EQ-5D VAS value (P<0.001) compared to those with asthma only. Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1-91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3-93.4] and 104.0 [102.5-105.5], respectively P<0.05). Multiple regression analysis shows that low asthma quality of life is associated with having CRS (P<0.0001), lower lung function (P=0.008), current smoking (P=0.01), BMI>30kg/m(2) (P=0.04), high age (P=0.03), and a negative SPT (P=0.04). ConclusionsComorbid CRS was a significant and independent negative predictor of quality of life in asthmatics. Other negative factors were lower lung function, current smoking, obesity, advanced age, and having nonatopic asthma.
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| 26. |
- Ekbom, Emil, et al.
(author)
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Asthma and treatment with inhaled corticosteroids: associations with hospitalisations with pneumonia
- 2019
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In: Bmc Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: Pneumonia is an important cause of morbidity and mortality. COPD patients using inhaled corticosteroids (ICS) have an increased risk of pneumonia, but less is known about whether ICS treatment in asthma also increases the risk of pneumonia. The aim of this analysis was to examine risk factors for hospitalisations with pneumonia in a general population sample with special emphasis on asthma and the use of ICS in asthmatics. Methods: In 1999 to 2000, 7340 subjects aged 28 to 54 years from three Swedish centres completed a brief health questionnaire. This was linked to information on hospitalisations with pneumonia from 2000 to 2010 and treatment with ICS from 2005 to 2010 held within the Swedish National Patient Register and the Swedish Prescribed Drug Register. Results: Participants with asthma (n = 587) were more likely to be hospitalised with pneumonia than participants without asthma (Hazard Ratio (HR 3.35 (1.97-5.02)). Other risk factors for pneumonia were smoking (HR 1.93 (1.22-3.06)), BMI < 20 kg/m(2) (HR 2.74 (1.41-5.36)) or BMI > 30 kg/m(2) (HR 2.54 (1.39-4.67)). Asthmatics (n = 586) taking continuous treatment with fluticasone propionate were at an increased risk of being hospitalized with pneumonia (incidence risk ratio (IRR) 7.92 (2.32-27.0) compared to asthmatics that had not used fluticasone propionate, whereas no significant association was found with the use of budesonide (IRR 1.23 (0.36-4.20)). Conclusion: Having asthma is associated with a three times higher risk of being hospitalised for pneumonia. This analysis also indicates that there are intraclass differences between ICS compounds with respect to pneumonia risk, with an increased risk of pneumonia related to fluticasone propionate.
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| 27. |
- Ekbom, Emil, et al.
(author)
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Impaired diffusing capacity for carbon monoxide is common in critically ill Covid-19 patients at four months post-discharge
- 2021
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In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 182
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Journal article (peer-reviewed)abstract
- There is limited knowledge about the long-term effects on pulmonary function of COVID-19 in patients that required intensive care treatment. Spirometry and diffusing capacity for carbon monoxide (DLCO) were measured in 60 subjects at 3-6 months post discharge. Impaired lung function was found in 52% of the subjects, with reduced DLCO as the main finding. The risk increased with age above 60 years, need for mechanical ventilation and longer ICU stay as well as lower levels of C-reactive protein at admission. This suggests the need of follow-up with pulmonary function testing in intensive-care treated patients.
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| 28. |
- Ekström, Magnus, et al.
(author)
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Breathlessness across generations : results from the RHINESSA generation study
- 2022
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In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 77:2, s. 172-177
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Journal article (peer-reviewed)abstract
- Background: Breathlessness is a major cause of suffering and disability globally. The symptom relates to multiple factors including asthma and lung function, which are influenced by hereditary factors. No study has evaluated potential inheritance of breathlessness itself across generations.Methods: We analysed the association between breathlessness in parents and their offspring in the Respiratory Health in Northern Europe, Spain and Australia generation study. Data on parents and offspring aged ≥18 years across 10 study centres in seven countries included demographics, self-reported breathlessness, asthma, depression, smoking, physical activity level, measured Body Mass Index and spirometry. Data were analysed using multivariable logistic regression accounting for clustering within centres and between siblings.Results: A total of 1720 parents (mean age at assessment 36 years, 55% mothers) and 2476 offspring (mean 30 years, 55% daughters) were included. Breathlessness was reported by 809 (32.7%) parents and 363 (14.7%) offspring. Factors independently associated with breathlessness in parents and offspring included obesity, current smoking, asthma, depression, lower lung function and female sex. After adjusting for potential confounders, parents with breathlessness were more likely to have offspring with breathlessness, adjusted OR 1.8 (95% CI 1.1 to 2.9). The association was not modified by sex of the parent or offspring.Conclusion: Parents with breathlessness were more likely to have children who developed breathlessness, after adjusting for asthma, lung function, obesity, smoking, depression and female sex in both generations. The hereditary components of breathlessness need to be further explored.
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| 29. |
- Ekström, Magnus, et al.
(author)
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Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.
- 2024
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In: Respiratory research. - : BioMed Central (BMC). - 1465-993X .- 1465-9921. ; 25:1
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Journal article (peer-reviewed)abstract
- Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64years. Breathlessness (modified Medical Research Council [mMRC]≥2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.We included 25,948 people aged 57.5±[SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI≥30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers.Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.
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| 30. |
- Ellingsen, Jens, 1979-
(author)
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Chronic obstructive pulmonary disease: exacerbations and mortality : Prognostic value of biomarkers and comorbidities
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. COPD is associated with systemic inflammation, and comorbidities are common. A characteristic feature is acute exacerbations (AECOPDs), i.e., episodes of worsening symptoms. AECOPDs are associated with increased mortality.Aim: To find prognostic risk factors for COPD mortality and AECOPDs, focusing on comorbidities and inflammatory biomarkers.Methods: In Paper I, associations between comorbidities, pharmacological treatment, and mortality were analysed in a real-world cohort of almost 18,000 primary care COPD patients. Data from medical records and national registers were analysed in Cox proportional hazards regressions.Papers II–IV were based on the Tools Identifying Exacerbations (TIE) cohort study of 572 COPD patients recruited from primary and secondary care in three Swedish regions. Participants were invited to three yearly visits, including phlebotomy, spirometry, and health questionnaires.In Paper II, the ability of blood neutrophil-to-lymphocyte ratio (NLR) and eosinophils (B-Eos) to predict AECOPDs was analysed with mixed-effects logistic regressions.In Paper III, the ability of C-reactive protein (CRP), fibrinogen, blood leukocytes (B-Leu), and four blood cell indices to predict AECOPDs was analysed with ordinal logistic regressions.In Paper IV, an algorithm for clinical phenotyping previously developed to predict mortality was studied. The algorithm’s ability to predict AECOPDs and mortality was analysed with Cox proportional hazards regressions; additionally, the identified phenotypes were analysed concerning differences in blood-based inflammatory biomarkers.Results: Several comorbidities, including heart diseases, were associated with increased mortality risk. Some pharmacological treatments were associated with increased or decreased mortality risk (Paper I). NLR, B-Eos, CRP, fibrinogen, and B-Leu (Papers II–III) predicted AECOPDs after adjustment for confounders, whereas other blood cell indices were of limited value (Paper III). The clinical phenotyping algorithm predicted AECOPDs and mortality, and the phenotypes had different patterns of inflammatory biomarkers (Paper IV).Conclusions: Comorbidities, particularly heart diseases, are substantial risk factors for mortality in COPD and should be an integral part of management of COPD patients. NLR, B-Eos, CRP, fibrinogen, and B-Leu are independent predictors of AECOPDs and should be further investigated as parts of, e.g., risk prediction tools. A previously developed algorithm for clinical phenotyping predicts mortality and AECOPDs.
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