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- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 2. |
- Elidottir, Helga, et al.
(författare)
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Cystic fibrosis in Iceland and the high prevalence of the N1303K variant
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Ingår i: Pediatric Pulmonology. - 8755-6863.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cystic fibrosis (CF) is most common in populations of Northern European ancestry where the F508del variant predominates. In 2020, Iceland became a member of the European Cystic Fibrosis Society Patient Registry, and we launched an epidemiological study of CF in Iceland. The study aimed to determine the prevalence and the genetic variants present in the country. Furthermore, we aimed to describe the previous and the current situation regarding lung function, infections, complications, treatment, and follow-up to understand the strengths and weaknesses of CF care in Iceland. Methods: This retrospective study included all individuals in Iceland with a confirmed CF diagnosis between 1955 and 2021. We conducted a medical records search for CF diagnosis codes and found 30 people with CF who were included in the study. Two hundred sixteen clinical variables were registered. A descriptive analysis of these was performed. Results: The prevalence of CF in Iceland is 0.372:10,000 inhabitants. The F508del is the most common CF transmembrane conductance regulator (CFTR) variant (46.4%), closely followed by N1303K (44.6%). Staphylococcus aureus was the most common airway pathogen, followed by Pseudomonas aeruginosa. Nasal polyps and CF-related diabetes were the most common complications. Modern CF medications, including the recent CFTR modulators, are available. Conclusion: Even though Iceland has a relatively low prevalence of CF, it holds the highest known prevalence of the N1303K variant in Europe. Access to necessary treatment is satisfactory, but improvements are advisable for some aspects of the routine assessments by best practice guidelines.
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| 3. |
- Jónsdóttir, Brynja, et al.
(författare)
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IL-8 predicts early mortality in patients with acute hypercapnic respiratory failure treated with noninvasive positive pressure ventilation
- 2017
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Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with Acute Hypercapnic Respiratory Failure (AHRF) who are unresponsive to appropriate medical treatment, are often treated with Noninvasive Positive Pressure Ventilation (NPPV). Clinical predictors of the outcome of this treatment are scarce. Therefore, we evaluated the role of the biomarkers IL-8 and GDF-15 in predicting 28-day mortality in patients with AHRF who receive treatment with NPPV. Methods: The study population were 46 patients treated with NPPV for AHRF. Clinical and background data was registered and blood samples taken for analysis of inflammatory biomarkers. IL-8 and GDF-15 were selected for analysis, and related to risk of 28-day mortality (primary endpoint) using Cox proportional hazard models adjusted for gender, age and various clinical parameters. Results: Of the 46 patients, there were 3 subgroup in regards to primary diagnosis: Acute Exacerbation of COPD (AECOPD, n = 34), Acute Heart Failure (AHF, n = 8) and Acute Exacerbation in Obesity Hypoventilation Syndrome (AEOHS, n = 4). There was significant difference in the basic characteristic of the subgroups, but not in the clinical parameters that were used in treatment decisions. 13 patients died within 28 days of admission (28%). The Hazard Ratio for 28-days mortality per 1-SD increment of IL-8 was 3.88 (95% CI 1.86-8.06, p < 0.001). When IL-8 values were divided into tertiles, the highest tertile had a significant association with 28 days mortality, HR 10.02 (95% CI 1.24-80.77, p for trend 0.03), compared with the lowest tertile. This correlation was maintained when the largest subgroup with AECOPD was analyzed. GDF-15 was correlated in the same way, but when put into the same model as IL-8, the significance disappeared. Conclusion: IL-8 is a target to explore further as a predictor of 28 days mortality, in patients with AHRF treated with NPPV.
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| 4. |
- Jónsdóttir, Brynja
(författare)
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Novel Biomarkes in Acute Respiratory Failure and Chronic Obstructive Pulmonary Disease.
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Background: Dyspnea is a common manifestation of a range of conditions and diseases, sometimes with multiple contributing factors. A subgroup of these patients present with acute hypecapnic respiratory failure (AHRF) and are treated with non-invasive positive pressure ventilation (NPPV). Despite the biomarkers and clinical signs available to predict outcome in patients with respiratory failure of differing etiologies, further knowledge is needed to stratify patients according to risk of treatment failure or mortality at early stages of disease before the source of the deterioration may be apparent. Chronic obstructive pulmonary disease (COPD) is a common cause of dyspnea and, in its advanced stages, of respiratory failure. COPD is to some extent preventable, e.g. with smoking avoidance or cessation. Identification of predictors of COPD development in the general population is essential to recognise individuals at high risk of developing COPD and initiating preventive measures and early treatment. Aims: The aim of Study I was to evaluate whether the biomarkers interleukin-8 (IL-8) and growth differentiation factor 15 (GDF-15) are predictive of 28-day mortality in patients with AHRF of different underlying causes receiving NPPV treatment. In Study II, suppression of tumorigenicity 2 (ST2) was evaluated as predictive of 28-day and 18-month mortality, in the same cohort as in Study I. A secondary goal was to test the hypothesis that a decrease in ST2 concentration during the first 12 hours of NPPV treatment could indicate treatment efficacy. Study III evaluated the prognostic value of ST2 with respect to all-cause mortality in patients suffering from acute dyspnea, with stratification of the study cohort according to the suggested ST2 cut-off points for risk stratification in cardiac disease, 35 ng/mL and 70 ng/mL. Study IV assessed the value of IL-8, ST2, and GDF-15 in predicting diagnosis of COPD in secondary care and of all-cause mortality in a large population-based prospective cohort study. Subjects: Studies I and II were based on a small cohort (n=46) of patients with AHRF treated with NPPV in the Intermediate Emergency Care Department of Skåne University Hospital, Malmö, Sweden. Study III comprised a population presenting to the emergency department (ED) at Skåne University Hospital, Malmö, Sweden with acute dyspnea of differing etiologies (n=1251). Study IV was based on the cardiovascular cohort of the population-based Malmö Diet and Cancer Study (n=4292). Methods: Biomarker analysis was conducted with the Proseek biomarker panel (Proximity extension assay) and with the Presage ST2 assay for ST2. Statistical analysis was conducted with SPSS. In Studies I and II, patients were analysed in subgroups according to primary discharge diagnosis. The Study III subgroup analysis was based on hospital admission status, and Study IV according to COPD diagnosis in secondary care over a mean follow-up period 21 years. Cox proportional hazard models were used to determine the prognostic value of the biomarker concentrations for mortality and COPD diagnosis. Data regarding mortality was confirmed by the Swedish National Cause of Death Registry. Results: In Study I and II, the small cohort of 46 patients with AHRF treated with NPPV included three subgroups categorized by primary diagnosis: acute exacerbation of COPD (AECOPD, n=34), acute heart failure (AHF, n=8), and acute exacerbation in obesity hypoventilation syndrome (AEOHS, n=4). Plasma concentrations of IL-8 and ST2 were predictive of 28-day mortality independent of CRP concentration. This association was maintained when the subgroup with AECOPD was analyzed. In Study II, plasma ST2 was an independent predictor of 18-month mortality, although these findings may have been driven by deaths within the first 28 days. Decrease in ST2 values during the first 12 hours was not indicative of concurrent clinical improvement. In Study III, ST2 concentrations in patients seeking the ED with acute onset dyspnea (n=1251) were predictive of 3-month and 12-month mortality independent of NT-proBNP levels. Stratification of the Study III cohort according to the ST2 cut-off levels of 35 and 70 ng/mL was shown practicable in identifying high risk patients. In Study IV, comprising a large general population cohort (n=4292), GDF-15 was found positively associated with COPD diagnosis in secondary care during a mean follow-up period of 21 years, adjusted for smoking and other confounding factors. GDF-15, ST2, and IL-8 demonstrated a significant association with all-cause mortality during a mean follow-up period of 21.5 years, with GDF-15 showing the strongest association. Conclusions: IL-8 and ST2 concentrations show association with acute clinical deterioration in respiratory failure and present targets for further exploration of prognostic value. The ST2 cut-off points of 35 ng/mL and 70 ng/mL used for risk stratification in acute cardiac disease can adequately identify high risk patients with acute dyspnea. Plasma GDF-15 concentration shows an association with long-term prognosis and mortality in respiratory failure, and, in the general population, can identify which individuals might develop COPD.
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