| 1. |
- Powell, Nelson, et al.
(författare)
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Patterns in pharyngeal airflow associated with sleep-disordered breathing
- 2011
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Ingår i: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 12:10, s. 966-974
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Kjellström, Barbro, et al.
(författare)
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Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension
- 2020
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Ingår i: European Respiratory Journal Open Research. - Sheffield : European Respiratory Society (ERS). ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong treatment. The aim of the present study was to investigate adherence to disease-specific treatment in patients with PAH or CTEPH. Methods: The study comprised an adult population diagnosed with PAH (n=384) or CTEPH (n=187) alive in 2016-2017. The study utilised three registries: the Swedish PAH registry, the National Board of Health and Welfare, and Statistics Sweden. Withdrawals from pharmacies of disease-specific oral treatments were studied. Adherence was assessed as: 1) Number of days covered defined as the difference between the total number of daily dosages dispensed and the total number of days covered; and 2) Manual assessment by two persons that independently reviewed each patient's prescription fill history to detect anomalies or patterns of deteriorating or improving adherence over time. Results: The mean age was 61±16 years, 61% were female and mean time since diagnosis was 4.6 years. Adherence was 62% using the Number of days covered method and 66% by the Manual assessment method. Drug-specific adherence varied from 91% for riociguat to 60% for sildenafil. Good adherence was associated with shorter time since diagnosis in patients with PAH and with lower number of concomitant other chronic treatments in patients with CTEPH. Age, sex, socioeconomic status or number of pulmonary hypertension (PH) treatments were not associated with adherence. Conclusion: Adherence to oral disease-specific treatment was 60-66% and associated with time since diagnosis and number of concomitant chronic treatments. Sex, age or socioeconomic factors did not affect adherence.
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| 3. |
- Mihaescu, Mihai, 1976-, et al.
(författare)
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Computational Modeling of Upper Airway Before and After Adenotonsillectomy for Obstructive Sleep Apnea
- 2008
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Ingår i: The Laryngoscope. - 0023-852X .- 1531-4995. ; 118:2, s. 360-362
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Tidskriftsartikel (refereegranskat)abstract
- Adenotonsillectomy, the first-line surgical treatment for obstructive sleep apnea (OSA) in children, is successful in only 50% of obese children. Computational fluid dynamics tools, which have been applied to differentiate OSA patients from those without OSA based on the airway flow characteristics, can be potentially used to identify patients likely to benefit from surgical intervention. We present computational modeling of the upper airway before and after adenotonsillectomy in an obese female adolescent with OSA. The subject underwent upper airway imaging on a 1.5 Tesla magnetic resonance imaging (MRI) scanner, and three-dimensional airway models were constructed using airway boundary coordinates from cross-sectional MRI scans. Our results using computational simulations indicate that, in an obese child, the resolution of OSA after adenotonsillectomy is associated with changes in flow characteristics that result in decreased pressure differentials across the airway walls and thus lower compressive forces that predispose to airway collapse. Application of such findings to an obese child seeking surgical treatment for OSA can potentially lead to selection of the surgical procedure most likely to result in OSA resolution. Effective intervention for OSA in this high-risk group will result in reduction in morbidity and the public health concerns associated with OSA.
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| 4. |
- Mihaescu, Mihai, 1976-, et al.
(författare)
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Modeling Flow in a Compromised Pediatric Airway Breathing Air and Heliox
- 2008
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Ingår i: The Laryngoscope. - : Wiley, The Triological Society. - 0023-852X .- 1531-4995. ; 118:12, s. 2205-2211
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Tidskriftsartikel (refereegranskat)abstract
- Objectives/Hypothesis: The aim of this study was to perform computer simulations of flow within an accurate model of a pediatric airway with subglottic stenosis. It is believed that the airflow characteristics in a stenotic airway are strongly related to the sensation of dyspnea. Methodology: Computed tomography images through the respiratory tract of an infant with subglottic stenosis, were used to construct the three-dimensional geometry of the airway. By using computational fluid dynamics (CFD) modeling to capture airway flow patterns during inspiration and expiration, we obtained information pertaining to flow velocity, static airway wall pressure, pressure drop across the stenosis, and wall shear stress. These simulations were performed with both air and heliox. Results: Unlike air, heliox maintained laminar flow through the stenosis. The calculated pressure drop over stenosis was lower for the heliox flow, in contrast to the airflow case. This lead to an approximately 40% decrease in airway resistance when using heliox, and presumably causes a decrease in the level of effort required for breathing. Conclusions: CFD simulations offer a quantitative method of evaluating airway flow dynamics in patients with airway abnormalities. CFD modeling illustrated the flow features and quantified flow parameters within a pediatric airway with subglottic stenosis. Simulations with air and heliox conditions mirrored the known clinical benefits of heliox as compared with air. We anticipate that computer simulation models will ultimately allow a better understanding of changes in flow caused by specific medical and surgical interventions in patients with conditions associated with dyspnea.
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| 5. |
- Mylavarapu, Goutham, et al.
(författare)
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Importance of paranasal sinuses in computational modeling of nasal airflow
- 2009
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Ingår i: 47th AIAA Aerospace Sciences Meeting including the New Horizons Forum and Aerospace Exposition. - : AIAA. - 9781563479694 ; , s. 2009-0772-
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Konferensbidrag (refereegranskat)abstract
- This paper investigates the importance of including paranasal sinuses in the computational modeling of the nasal airflow. Three dimensional models of human nasal airway with and without including paranasal sinuses were reconstructed from Computed Tomography (CT) axial images of a subject with healthy nasal airway. The reconstruction process was performed using MIMICS® software program. The airway volume was discretized using TGRID® mesh generator. Steady Reynolds-Averaged Navier-Stokes (RANS) simulations were carried in both inspiratory and expiratory phases of respiratory cycle at a peak flow rate of 15 L/min in FLUENT®. The results show that the left and right nasal resistances change with less than 11% when paranasal sinuses are included in the computational model of the nasal airway. The flow into the sinuses is characterized by very low velocities during both inspiration and expiration conditions. The velocity distributions in the main nasal passage show small change predominantly in regions closer to the paranasal sinuses when compared to the model where sinuses were not included.
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| 6. |
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| 7. |
- Katayama, S., et al.
(författare)
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Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication
- 2020
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Ingår i: European Respiratory Journal. - : NLM (Medline). - 0903-1936 .- 1399-3003. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and are recognised as a risk factor for the development of chronic asthma. We aimed to analyse whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development. METHODS: We analysed leukocyte transcriptomes from preschool children (6 months-3 years) at acute wheeze (n=107), and at a revisit 2-3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were followed clinically until age 7 years. Differential expression tests, weighted correlation network analysis and logistic regression were applied and correlations to 76 clinical traits evaluated. FINDINGS: Significant enrichment of genes involved in the innate immune responses was observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, which was associated with vitamin D levels (p<0.005) in infancy, and asthma medication and FEV1%/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio several years later, at age 7 years (p<0.005). A model that predicts leukotriene receptor antagonist medication at 7 years of age with high accuracy was developed (area under the curve 0.815, 95% CI 0.668-0.962). INTERPRETATION: Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children who will outgrow their wheeze from those who will develop chronic asthma.
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| 8. |
- Arruda, Lucas C. M., et al.
(författare)
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A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells in vitro and in vivo
- 2022
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 107:8, s. 1786-1795
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Tidskriftsartikel (refereegranskat)abstract
- Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34(+) blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34(+)CD38(-) phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo. Our results show that this CD34-specific BTE induces CD34-dependent T-cell activation and subsequent leukemia cell killing in a dose-dependent manner, further corroborated by enhanced T-cell-mediated killing at the singlecell level. Additionally, the BTE triggered efficient T-cell-mediated depletion of CD34(+) hematopoietic stem cells from peripheral blood stem cell grafts and CD34(+) blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BTE had in vivo efficacy by depleting CD34(+) blasts and leukemic stem cells without side effects. Taken together, these data demonstrate that the CD34-specific BTE has robust antitumor effects, supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes.
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| 9. |
- Ringman Uggla, Andreas, et al.
(författare)
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Low pulmonary expression of epithelial Na(+) channel and Na(+), K(+)-ATPase in newborn infants with congenital diaphragmatic hernia
- 2011
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 99:1, s. 14-22
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been suggested from several animal studies and clinical observations that congenital diaphragmatic hernia (CDH) with pulmonary hypoplasia is accompanied by a disturbed perinatal ion transport. This could lead to respiratory distress due to slower clearance of fetal lung fluid at birth. OBJECTIVES: The purpose of this study was to determine whether CDH is related to changes in the expression of three rate-limiting transporter proteins in lung epithelium at birth. METHODS: Tracheal aspirate was collected from 12 newborn infants with CDH and from 8 newborn control patients. Sampling was performed at postnatal age 18 and at 43 h in the CDH group and at 18 h in the control group. The protein abundance of α-, β- and γ-epithelial Na(+) channel (ENaC), aquaporin 5 and Na(+), K(+)-ATPase α(1) was analyzed using semiquantitative immunoblotting. RESULTS: The levels of β-ENaC, γ-ENaC and Na(+), K(+)-ATPase α(1) collected at 18 h postnatally were significantly lower in CDH infants compared to control infants. In the CDH group, no significant difference in the expression of the ENaC subunits, Na(+), K(+)-ATPase α(1) or aquaporin 5 could be detected between the two sampling time points. CONCLUSIONS: This downregulation may result in an abnormal lung fluid absorption which could be an important mechanism behind the respiratory distress seen in newborn CDH patients.
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| 10. |
- Mylavarapu, Goutham, et al.
(författare)
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Planning human upper airway surgery using Computational Fluid Dynamics
- 2013
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Ingår i: Journal of Biomechanics. - : Elsevier. - 0021-9290 .- 1873-2380. ; 46:12, s. 1979-1986
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Tidskriftsartikel (refereegranskat)abstract
- The study advances the idea of using computational fluid dynamics in the process of planning surgical treatment modalities for patients with obstructive airway disorders. It is hypothesized that the a priori knowledge of the functional outcome of surgical intervention on the flow and airway resistance can guide the surgeon in choosing an effective surgical strategy. Computed tomography images spanning the respiratory tract of an adult patient with a combined glottic and subglottic stenosis are used to reconstruct three-dimensional geometrical models of the airway. Computational fluid dynamics is used to obtain airway flow patterns during inspiration and expiration in these models. Numerical predictions about flow velocity, pressure distribution on the airway lumen, wall shear stress, and airway resistance are obtained so that the relevance of each individual stenotic level is quantified. Four different virtual surgeries in different combinations are assessed in order to remedy the constricted airway. The virtual surgery based airway models are evaluated by comparisons with the pre-treatment flow modeling results. The predicted numerical data revealed that the removal of the constriction at the level of the vocal folds will have the most significant effect on the airway resistance. The flow simulations offer a quantitative method of evaluating the airway resistance in patients with combined glottic and subglottic stenoses. Predictions of airway resistances and other numerical calculations from different virtual surgeries give additional inputs for the surgeon, in deciding the most appropriate surgery on a case-by-case basis.
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