| 1. |
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| 2. |
- Bileviciute-Ljungar, Indre, et al.
(författare)
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Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome : A Pilot Study
- 2020
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Ingår i: Frontiers in Psychiatry. - : FRONTIERS MEDIA SA. - 1664-0640. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography. Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography.Methods: Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients.Result: There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations.Conclusion: This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted.
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| 3. |
- Björklund, Åsa K., et al.
(författare)
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The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing
- 2016
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:4, s. 451-460
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Tidskriftsartikel (refereegranskat)abstract
- Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system.
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| 4. |
- Borgström, Anna, et al.
(författare)
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Postoperative pain and bleeding after adenotonsillectomy versus adenotonsillotomy in pediatric obstructive sleep apnea an RCT
- 2019
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 276:11, s. 3231-3238
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Our previous randomized controlled trial (RCT) of children with obstructive sleep apnea (OSA) showed no significant differences between adenotonsillectomy (ATE) and adenotonsillomy (ATE) in improving nocturnal respiration and symptoms after one year. This is the continuous report with the evaluation of postoperative morbidity concerning bleeding and pain.METHODS: A double-blinded RCT including 79 children, aged 2-6 years, with moderate to severe OSA, randomized to either ATE (n = 40) or ATT (n = 39). From one to ten days postoperatively, parents filled in a logbook with six pain-related outcomes (parent and child grading pain at different levels, days of analgesic use and return to normal diet). Peri- and postoperative bleeding were also registered.RESULTS: 63 patients (80%) returned the logbook. There were significant differences between groups in only two of the six pain-related outcomes in favor of the ATT group; first day when the children graded themselves as pain free (p = 0.021, Log Rank Test), and first day the caregiver estimated pain VAS ≤ 5 (p = 0.007, Log Rank Test). Two (5%) cases of postoperative bleeding occurred in the ATE group, one of which needed a return to theatre. No case of postoperative bleeding was seen in the ATT group.CONCLUSIONS: The results from this RCT are in line with previous comparative studies between ATT and ATE. Children operated with ATT had significantly less postoperative pain in one-third of the outcomes, and less bleeding than ATE. However, as the differences in morbidity between the surgical methods were minor the clinical significance is uncertain.TRIAL REGISTRATION: This study was approved by the Swedish Regional Ethics Board in Stockholm, Sweden (Dnr 2011/925-32 and 2013/2274-32) and registered at ClinicalTrials.gov (Trial registration number NCT01676181).
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| 5. |
- Borgström, A., et al.
(författare)
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Trends and changes in paediatric tonsil surgery in Sweden 1987-2013: A population-based cohort study
- 2017
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The objective of this study was to longitudinally describe the history of tonsil surgery in Swedish children and adolescents regarding incidence, indications for surgery, surgical methods and the age and gender distributions. Setting A retrospective longitudinal population-based cohort study based on register data from the Swedish National Patient Register (NPR) and population data from Statistics Sweden. Participants All Swedish children 1-<18â €..years registered in the NPR with a tonsil surgery procedure 1987-2013. Results 167â €..894 tonsil surgeries were registered in the NPR 1987-2013. An increase in the total incidence rate was observed, from 22/10â €..000 person years in 1987 to 47/10â €..000 in 2013. The most marked increase was noted in children 1-3â €..years of age, increasing from 17 to 73/10â €..000 person years over the period. The proportion children with obstructive/sleep disordered breathing (SDB) indications increased from 42.4% in 1987 to 73.6% in 2013. Partial tonsillectomy, tonsillotomy (TT), increased since 1996 and in 2013 55.1% of all tonsil procedures were TTs. Conclusions There have been considerable changes in clinical practice for tonsil surgery in Swedish children over the past few decades. Overall, a doubling in the total incidence rate was observed. This increase consisted mainly of an increase in surgical procedures due to obstructive/SDB indications, particularly among the youngest age group (1-3â €..years old). TT has gradually replaced tonsillectomy as the predominant method for tonsil surgery.
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| 6. |
- Browaldh, Nanna, et al.
(författare)
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15-year efficacy of uvulopalatopharyngoplasty based on objective and subjective data
- 2011
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Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 131:12, s. 1303-1310
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Tidskriftsartikel (refereegranskat)abstract
- Conclusions: This follow-up showed a stable and significant decrease in median oxygen desaturation index 4% (ODI(4)) values over the years. Approximately two-thirds of the patients fulfilled the success criteria (ODI4 reduction of 50% and andlt;20) after 15 years. A majority had improved/cured excessive daytime sleepiness (EDS) and were satisfied. No increased mortality rate was seen. Objectives: To evaluate sleep apnoea recordings and symptoms in patients with obstructive sleep apnoea syndrome 15 years after uvulopalatopharyngoplasty (UPPP) compared to baseline and previous follow-ups. Methods: This was a non-randomized, prospective intervention study on 50 patients who underwent UPPP during 1985-88. Their initial median age was 49 years (range 38-71) and ODI4 was 26.5 (4-82). Results: In all, 13 patients had died; 26 patients underwent sleep apnoea recordings. Median ODI4 had decreased from 26.5 (range 4-82) to 8.5 (0-60), p andlt; 0.01, a mean reduction of 52%; 65% of patients achieved the success criteria. One-third was objectively categorized as non-snorers. Median body mass index was unchanged. The questionnaires were answered by 32 of 37 patients; 88% reported improved or cured EDS and 78% were satisfied. Pharyngeal disturbances ratings were low. The standardized mortality rate did not differ from the general Swedish population.
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| 7. |
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| 8. |
- Browaldh, N, et al.
(författare)
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SKUP(3) RCT; continuous study : Changes in sleepiness and quality of life after modified UPPP.
- 2016
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Ingår i: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 26:6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives/HypothesisOur previous study showed that modified uvulopalatopharyngoplasty (UPPP), including tonsillectomy, significantly improved nocturnal respiration in obstructive sleep apnea syndrome (OSAS) patients. This is a continuous study of changes in daytime sleepiness and quality of life.Study DesignProspective randomized controlled trial (RCT), two parallel arms.MethodsSixty‐five patients with apnea‐hypopnea index ≥ 15, body mass index < 36, Epworth Sleepiness Scale (ESS) ≥ 8, Friedman stage I or II, failing nonsurgical treatment. The intervention group (n = 32) underwent surgery, and the controls (n = 33) had no treatment. At baseline and the 7‐month follow‐up, polysomnography, questionnaires, and vigilance tests were implemented.ResultsAll patients answered the questionnaires, and 48 took the vigilance test. Epworth Sleepiness Scale decreased significantly in the intervention group, from a mean (standard deviation) of 12.5(3.2) to 6.8(3.9), but nonsignificantly in the control group, from 12.9(3.1) to 12.5(3.9), a significant group difference (P < 0.001). The physical and mental component score on the Short Form‐36 questionnaire increased significantly in the intervention group, from a mean 47.8(8.3) to 51.2(8.8) and from 42.1(10.6) to 48.1(9.7), respectively, but with nonsignificant changes in the controls: 49.0(9.0) to 48.3(9.1) and 41.0(10.2) to 42.7(11.5), significant group differences (P = 0.007, P = 0.031), respectively. The sleep latency/vigilance test showed a significant mean increase in the intervention group of 7(12.4) minutes and a decrease in the controls of 2.2(10.6), a significant group difference (P = 0.011). There were significant correlations between changes in subjective outcomes and nocturnal respiration.ConclusionThis RCT shows that modified UPPP was effective in improving daytime sleepiness and quality of life in OSAS patients. It strengthens the body of evidence on the potential effect of surgery offered to selected patients.
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| 9. |
- Browaldh, N, et al.
(författare)
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SKUP3 : 6 and 24 months follow-up of changes in respiration and sleepiness after modified UPPP.
- 2018
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Ingår i: The Laryngoscope. - : John Wiley & Sons. - 0023-852X .- 1531-4995. ; 128:5, s. 1238-1244
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveOur previous randomized controlled trial of patients with obstructive sleep apnea syndrome (OSAS) showed that modified uvulopalatopharyngoplasty (UPPP), including tonsillectomy, significantly improved nocturnal respiration, daytime sleepiness, and quality of life in the intervention group compared to controls who had delayed surgery after 6 months. This is the continuous report with the 6‐ and 24‐month postoperative results.Study DesignSingle‐center prospective cohort study.MethodsSixty‐five patients with apnea–hypopnea index (AHI) ≥ 15, body mass index (BMI) < 36, Epworth Sleepiness Scale (ESS) ≥ 8, and Friedman stage I or II underwent UPPP after failing nonsurgical treatment. The results from polysomnography and ESS at 6 and 24 months were compared to baseline.ResultsEight percent and 20% dropped out from the 6‐ and 24‐month follow‐ups, respectively. The AHI value decreased significantly from mean (standard deviation) 52.9 (20.5) at baseline to 23.6 (20.2) after 6 months, and to 24.1 (20.9) after 24 months (P < 0.001). Patients with tonsil size 2, and 3 to 4, had significant reductions in the AHI after both follow‐ups. The median ESS score decreased significantly from 13 (range 8–21) to 6.5 (1–18) after 6 months, and to 5 (2–17) after 24 months (P < 0.001). The BMI remained unchanged. There were significant modest correlations for the reductions in AHI and ESS after 24 months.ConclusionModified UPPP was effective in improving nocturnal respiration and daytime sleepiness in OSAS patients at both 6‐ and 24‐month follow‐up. Patients with tonsil size 2, and 3 to 4, benefitted similarly from surgery with improved respiration.
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| 10. |
- Browaldh, Nanna, et al.
(författare)
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SKUP3 randomised controlled trial : polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea
- 2013
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 68:9, s. 846-853
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the 6-month efficacy of uvulopalatopharyngoplasty (UPPP) compared with expectancy in selected patients with obstructive sleep apnoea syndrome (OSAS).DESIGN: A prospective single-centre randomised controlled trial with two parallel arms stratified by Friedman stage and body mass index (BMI).PARTICIPANTS: 65 consecutive patients with moderate to severe OSAS (apnoea-hypopnoea index (AHI) ≥15 events/h sleep), BMI <36 kg/m(2), Epworth sleepiness scale ≥8, Friedman stage I or II.INTERVENTION: Surgical treatment with UPPP. The control group underwent UPPP after a delay of 6 months.OUTCOMES: Changes in AHI and other polysomnography parameters at baseline compared with the 6-month follow-up.RESULTS: All patients (32 in the intervention group and 33 in the control group) completed the trial. The mean (SD) AHI in the intervention group decreased significantly (p<0.001) by 60% from 53.3 (19.7) events/h to 21.1 (16.7) events/h . In the control group the mean AHI decreased by 11% from 52.6 (21.7) events/h to 46.8 (22.8) events/h, with a significant difference between the groups (p<0.001). The mean time in the supine position and the BMI were unchanged in both groups. Subgroup analyses for Friedman stage, BMI group and tonsil size all showed significant reductions in AHI in the intervention group compared with controls. There were no severe complications after surgery.CONCLUSIONS: This trial demonstrates the efficacy of UPPP in treating selected patients with OSAS with a mean reduction in AHI of 60% compared with 11% in controls, a highly significant and clinically relevant difference between the groups.TRIAL REGISTRATION NUMBER: NCT01659671.
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| 11. |
- Carrasco, Anna, et al.
(författare)
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The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naive CD27(-)CD21(hi) B cells and a relative reduction of ILCs. The enrichment of naive B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.
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| 12. |
- Crump, Casey, et al.
(författare)
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Preterm birth and risk of sleep-disordered breathing from childhood into mid-adulthood
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 48:6, s. 2039-2049
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Preterm birth (gestational age <37 weeks) has previously been associated with cardiometabolic and neuropsychiatric disorders into adulthood, but has seldom been examined in relation to sleep disorders. We conducted the first population-based study of preterm birth in relation to sleep-disordered breathing (SDB) from childhood into mid-adulthood.METHODS: A national cohort study was conducted of all 4 186 615 singleton live births in Sweden during 1973-2014, who were followed for SDB ascertained from nationwide inpatient and outpatient diagnoses through 2015 (maximum age 43 years). Cox regression was used to examine gestational age at birth in relation to SDB while adjusting for other perinatal and maternal factors, and co-sibling analyses assessed for potential confounding by unmeasured shared familial factors.RESULTS: There were 171 100 (4.1%) persons diagnosed with SDB in 86.0 million person-years of follow-up. Preterm birth was associated with increased risk of SDB from childhood into mid-adulthood, relative to full-term birth (39-41 weeks) [adjusted hazard ratio (aHR), ages 0-43 years: 1.43; 95% confidence interval (CI), 1.40, 1.46; P <0.001; ages 30-43 years: 1.40; 95% CI, 1.34, 1.47; P <0.001]. Persons born extremely preterm (<28 weeks) had more than 2-fold risks (aHR, ages 0-43 years: 2.63; 95% CI, 2.41, 2.87; P <0.001; ages 30-43 years: 2.22; 95% CI, 1.64, 3.01; P <0.001). These associations affected both males and females, but accounted for more SDB cases among males (additive interaction, P = 0.003). Co-sibling analyses suggested that these findings were only partly due to shared genetic or environmental factors in families.CONCLUSIONS: Preterm-born children and adults need long-term follow-up for anticipatory screening and potential treatment of SDB.
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| 13. |
- Enqvist, Monika, et al.
(författare)
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Systemic and Intra-Nodal Activation of NK Cells After Rituximab Monotherapy for Follicular Lymphoma.
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Monotherapy with the anti-CD20 monoclonal antibody rituximab can induce complete responses (CR) in patients with follicular lymphoma (FL). Resting FcRγIII+ (CD16+) natural killer (NK) cells respond strongly to rituximab-coated target cells in vitro. Yet, the contribution of NK cells in the therapeutic effect in vivo remains unknown. Here, we followed the NK cell repertoire dynamics in the lymph node and systemically during rituximab monotherapy in patients with FL. At baseline, NK cells in the tumor lymph node had a naïve phenotype albeit they were more differentiated than NK cells derived from control tonsils as determined by the frequency of CD56dim NK cells and the expression of killer cell immunoglobulin-like receptors (KIR), CD57 and CD16. Rituximab therapy induced a rapid drop in NK cell numbers coinciding with a relative increase in the frequency of Ki67+ NK cells both in the lymph node and peripheral blood. The Ki67+ NK cells had slightly increased expression of CD16, CD57 and higher levels of granzyme A and perforin. The in vivo activation of NK cells was paralleled by a temporary loss of in vitro functionality, primarily manifested as decreased IFNγ production in response to rituximab-coated targets. However, patients with pre-existing NKG2C+ adaptive NK cell subsets showed less Ki67 upregulation and were refractory to the loss of functionality. These data reveal variable imprints of rituximab monotherapy on the NK cell repertoire, which may depend on pre-existing repertoire diversity.
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| 14. |
- Ericsson, Elisabeth, 1959-, et al.
(författare)
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Kirurgisk behandling av barn med sömnrelaterade andningsstörningar
- 2009
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Ingår i: Kirurgisk behandling av barn med sömnrelaterade andningsstörningar.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Kirurgisk behandling av barn med sömnrelaterade andningsstörningar Moderator: Danielle Friberg, överläkare, Karolinska Huddinge I panelen: Elisabet Ericsson, disputerad sjuksköterska, Hälsohögskolan, Jönköping, Claes Hemlin, överläkare, Sophiahemmet, Anne-Charlotte Hessén Söderman, överläkare, Karolinska Danderyd, Elisabeth Hultcrantz, professor, Universitetssjukhuset, Linköping, Pia Nerfeldt, disputerad specialistläkare, Karolinska Huddinge, Joacim Stalfors, överläkare, Sahlgrenska, Göteborg. Bakgrund: Barn med sömnrelaterade andningsstörningar (SRBD) o/e obstruktivt sömnapnésyndrom (OSAS) behandlas primärt med kirurgi (adenotonsillektomi), varav cirka 80 % blir botade. Det finns flera riskfaktorer till SRBD/OSAS: kraniofaciala missbildningar, neuromuskulära sjukdomar samt övervikt/fetma, som ökar även bland barn. Cirka 1-3 % av barnen har OSAS och 12 % har SRBD och dessa barn löper ökad risk för inlärningssvårigheter, dålig viktsutveckling, hjärtkärlsjukdomar och dödlighet. Fram till nu har dessa barn blivit styvmoderligt behandlade i rutinsjukvården. Detta symposium vill belysa hur vi kan förbättra oss. Material och metod: Med mentometerknappar inbjuds auditoriet att delta i kliniska frågeställningar. Typfall demonstreras. Nya kirurgiska metoder presenteras; tonsillotomi, tonsillektomi med coblation eller radiofrekvens, vilka har utvärderats gentemot sedvanlig ”kall” tonsillektomi. Resultat från Kvalitetsregister för tonsilloperation kommer att redovisas. Likaså den nyvaliderade OSA-18, som är ett sjukdomsspecifikt hälsorelaterat livskvalitetsformulär för barn med misstänkt SRBD/OSAS. Ett polysomnografilab för barn har nyligen startats på Karolinska Huddinge, där flera studier planeras. Resultat: Panelmedlemmarna presenterar sina resultat för auditoriet, vilka sen får delta i diskussionen med eller utan mentometer. Diskussion: Hur kan vi förbättra omhändertagandet av barn med SRBD/OSAS? Hur ska vi välja ut de som ska opereras? Hur fungerar OSA-18 och hur kan vi använda formuläret i vår vardag? Vilken operationsmetod är att föredra på vilket barn? Vilka frågor kan det förnyade tonsilloperationsregistret besvara? Vilka barn ska följas upp efter kirurgi? Barn med riskfaktorer, hur ska vi hantera dem? Kan vi erbjuda de barn som inte blir bra på kirurgi alternativ behandling? Vilken ytterligare forskning behövs?
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| 15. |
- Fehrm, Johan, et al.
(författare)
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Adenopharyngoplasty vs Adenotonsillectomy in Children With Severe Obstructive Sleep Apnea A Randomized Clinical Trial
- 2018
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Ingår i: JAMA Otolaryngology - Head and Neck Surgery. - : American Medical Association (AMA). - 2168-6181 .- 2168-619X. ; 144:7, s. 580-586
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Adenotonsillectomy (ATE) is the primary surgical method for treating obstructive sleep apnea (OSA) in children. However, children with severe OSA have an increased risk for residual OSA after ATE. Previous studies indicate that adenopharyngoplasty (APP), a modified ATE with closure of the tonsillar pillars, might improve the surgical outcome, but the overall evidence is weak. OBJECTIVE To determine whether APP is more effective than ATE for treating severe OSA in otherwise healthy children. DESIGN, SETTING. AND PARTICIPANTS A blinded randomized clinical trial was conducted at the otorhinolaryngology department at Karolinska University Hospital, Stockholm, Sweden. Eighty-three children, aged 2 to 4 years, with an obstructive apnea-hypopnea index (OAHI) score of 10 or higher, were randomized to APP (n = 36) or ATE (n = 47). Participants were recruited from December 1, 2014, through November 31, 2016. INTERVENTIONS Adenotonsillectomy was performed in all 83 patients in both groups by the cold steel technique. The APP group also underwent closure of the tonsillar pillars with 2 inverted sutures on each side. MAIN OUTCOMES AND MEASURES The primary outcome was the difference between the groups in OAHI score change before and after surgery. A higher score indicates worse problems and a score of 10 or higher is defined as severe OSA. The outcome was evaluated per protocol and with intention-to-treat analysis. Secondary outcomes were other polysomnography variables and the Obstructive Sleep Apnea-18 (OSA-18) questionnaire (possible total symptom score range, 18-126; higher scores indicate worse quality of life). Polysomnography was performed and the OSA-18 questionnaire was completed preoperatively and 6 months postoperatively. RESULTS A total of 83 children (49 [59%] boys; mean [SD] age, 36.6 [9.2] months) were included in the study. Of these, 74(89%) (APP, n = 30; ATE, n = 44) completed the study. The mean (SD) preoperative OAHI score was 23.8 (11.8) for APP and 23.8 (11.5) for ATE. Both the APP and ATE groups had a significant decrease in mean OAHI score after surgery (-21.7; 95% CI, -26.3 to -17.2; and -21.1; 95% CI, -24.5 to -17.7, respectively), but there was no significant difference between the groups (0.7; 95% CI, -4.8 to 6.1). Furthermore, no significant differences between the groups were seen regarding other polysomnography variables (eg, respiratory distress index: mean, 0.6; 95% CI, -5.0 to 6.3) or the OSA-18 questionnaire (eg, total symptom score: -0.5; 95% CI, -13 to12). One patient from each group was readmitted owing to postoperative bleeding, but no other complications were seen. CONCLUSIONS AND RELEVANCE This trial did not show that APP was more effective than ATE alone to treat otherwise healthy children with severe OSA. This finding suggests that ATE should continue to be the primary treatment for OSA in children.
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| 16. |
- Fehrm, Johan, et al.
(författare)
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Blood pressure after modified uvulopalatopharyngoplasty : results from the SKUP3 randomized controlled trial.
- 2017
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Ingår i: Sleep medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 34, s. 156-161
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveObstructive sleep apnea (OSA) is a risk factor for hypertension. The SKUP3 study showed that modified uvulopalatopharyngoplasty (UPPP) significantly improved nocturnal respiration, sleepiness, and quality of life. The aim of this study was to evaluate the impact of surgery on blood pressure in patients with OSA.MethodsWe used a single-center randomized controlled trial to compare modified UPPP with controls at baseline and after six months. The controls received delayed surgery with an additional six-month follow-up. All operated patients also had a follow-up after 24 months. Polysomnography was performed at each follow-up, with systolic and diastolic blood pressure (SBP, DBP) measured the morning after.ResultsA total of 65 patients were randomized to intervention (n = 32) or control (n = 33). At follow-up (n = 61/65, 94%), there were significant differences between the groups in both mean SBP (−9.4 mmHg [95% CI: −17.9, −0.83], p < 0.05) and mean DBP (−6.4 mmHg [95% CI: −12.8, −0.04], p < 0.05), in favor of UPPP. Blood pressure and respiratory parameters at follow-up correlated. The analyses of all operated patients showed a significant decrease in mean (SD) blood pressure after six months (n = 49/65, 75%; SBP: −4.5 [9.0], p = 0.001; DBP: −2.2 [6.6], p = 0.030) as well as after 24 months (n = 35/65, 54%; SBP: −8.9 [11.5], p < 0.0001; DBP: −4.2 [9.4], p = 0.012).ConclusionsBlood pressure was significantly decreased after surgery, indicating that modified UPPP decreases the blood pressure, in a selected group of patients with moderate to severe OSA. The long-term effect was also significant, but these results are uncertain due to a high proportion of missing values.
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| 17. |
- Fehrm, Johan, et al.
(författare)
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Effectiveness of Adenotonsillectomy vs Watchful Waiting in Young Children With Mild to Moderate Obstructive Sleep Apnea : A Randomized Clinical Trial
- 2020
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Ingår i: JAMA Otolaryngology - Head and Neck Surgery. - : American Medical Association (AMA). - 2168-6181 .- 2168-619X. ; 146:7, s. 647-654
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Adenotonsillectomy (ATE) is one of the most common surgical procedures to treat children with obstructive sleep apnea (OSA), but to our knowledge there are no randomized clinical trials confirming the benefit of surgery compared with watchful waiting in children between 2 and 4 years of age.Objective: To determine whether ATE is more effective than watchful waiting for treating otherwise healthy children with mild to moderate OSA.Design, Setting, and Participants: This randomized clinical trial was conducted from December 2014 to December 2017 at the Otorhinolaryngology Department of the Karolinska University Hospital, Stockholm, Sweden. A total of 60 children, 2 to 4 years of age, with an obstructive apnea-hypopnea index (OAHI) score of 2 or greater and less than 10, were randomized to ATE (n = 29) or watchful waiting (n = 31). A total of 53 participants (88%; ATE, n = 25; watchful waiting, n = 28) completed the study. Data were analyzed from August 2018 to December 2018.Interventions: Adenotonsillectomy.Main Outcomes and Measures: The primary outcome was the difference between the groups in mean OAHI score change. Secondary outcomes were other polysomnography parameters, score on the Obstructive Sleep Apnea-18 (OSA-18) questionnaire, and subgroup analyses. Polysomnography and the OSA-18 questionnaire were completed at baseline and after 6 months.Results: Of the 60 included children, 34 (57%) were boys and the mean (SD) age at first polysomnography was 38 (9) months. Both groups had a decrease in mean OAHI score, and the difference in mean OAHI score change between the groups was small (-1.0; 95% CI, -2.4 to 0.5), in favor of ATE. However, there were large differences between the groups in favor of ATE regarding the OSA-18 questionnaire (eg, total OSA-18 score: -17; 95% CI, -24 to -10). Also, a subgroup analysis of 24 children with moderate OSA (OAHI ≥5 and <10) showed a meaningful difference in mean OAHI score change between the groups in favor of ATE (-3.1; 95% CI, -5.7 to -0.5). Of 28 children, 10 (36%) in the watchful waiting group received ATE after the follow-up, and 7 of these had moderate OSA at baseline.Conclusions and Relevance: This randomized clinical trial found only small differences between the groups regarding changes in OAHI, but further studies are needed. However, there were large improvements in quality of life after ATE. These results suggest that otherwise healthy children with mild OSA and mild effect on quality of life may benefit from watchful waiting, while children with moderate OSA should be considered for ATE.Trial Registration: ClinicalTrials.gov Identifier: NCT02315911.
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| 18. |
- Fehrm, Johan, et al.
(författare)
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Postoperative morbidity after adenotonsillectomy versus adenopharyngoplasty in young children with obstructive sleep apnea : an RCT
- 2020
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Nature. - 0937-4477 .- 1434-4726. ; 277:10, s. 2821-2827
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: In our previous randomized controlled trial (RCT), comparing adenotonsillectomy (ATE) with adenopharyngoplasty (APP) in children with severe obstructive sleep apnea (OSA), there were no differences in respiratory sleep parameters or quality of life. The purpose of the present report was to evaluate postoperative morbidity from this RCT.METHODS: The study was a blinded RCT in 83 children (ATE = 47; APP = 36), 2-4 years of age, with an obstructive apnea-hypopnea index of ≥ 10. Pain was assessed from the first until the tenth day after surgery with a logbook that reported pain by child (FPS-R, Faces Pain Scale-Revised) and caregiver (visual analogue scale), analgesic use, return to normal diet, and weight change. Bleeding, infection, satisfaction with treatment, speech, and swallowing were assessed with a questionnaire and medical records 6 months after surgery.RESULTS: Sixty-four children (77%) returned the logbook and 65 (78%) answered the questionnaire. The median (interquartile range) day the children graded themselves as pain free (FPS-R = 0) was 7 (6-10) after ATE, compared with 9 (7 to > 10) after APP (p = 0.018). There were no other significant differences between the groups regarding any other pain-related outcomes, bleeding, infection, satisfaction, swallowing, or speech, but three children (11%) reported impaired speech after APP compared to none after ATE (p = 0.067).CONCLUSION: The results regarding postoperative morbidity were in favor of ATE and the results from our previous report showed no advantages of APP. Therefore, APP should not be recommended in young, otherwise healthy children with OSA.
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| 19. |
- Filipovic, Iva, et al.
(författare)
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29-Color Flow Cytometry : Unraveling Human Liver NK Cell Repertoire Diversity
- 2019
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have demonstrated extraordinary diversity in peripheral blood human natural killer (NK) cells and have suggested environmental control of receptor expression patterns on distinct subsets of NK cells. However, tissue localization may influence NK cell differentiation to an even higher extent and less is known about the receptor repertoire of human tissue-resident NK cells. Advances in single-cell technologies have allowed higher resolution studies of these cells. Here, the power of high-dimensional flow cytometry was harnessed to unravel the complexity of NK cell repertoire diversity in liver since recent studies had indicated high heterogeneity within liver NK cells. A 29-color flow cytometry panel allowing simultaneous measurement of surface tissue-residency markers, activating and inhibitory receptors, differentiation markers, chemokine receptors, and transcription factors was established. This panel was applied to lymphocytes across three tissues (liver, peripheral blood, and tonsil) with different distribution of distinct NK cell subsets. Dimensionality reduction of this data ordered events according to their lineage, rather than tissue of origin. Notably, narrowing the scope of the analysis to the NK cell lineage in liver and peripheral blood separated subsets according to tissue, enabling phenotypic characterization of NK cell subpopulations in individual tissues. Such dimensionality reduction, coupled with a clustering algorithm, identified CD49e as the preferred marker for future studies of liver-resident NK cell subsets. We present a robust approach for diversity profiling of tissue-resident NK cells that can be applied in various homeostatic and pathological conditions such as reproduction, infection, and cancer.
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| 20. |
- Forkel, Marianne, et al.
(författare)
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Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers
- 2017
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 47:8, s. 1280-1294
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Tidskriftsartikel (refereegranskat)abstract
- Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties, and functionality of ILC1s, ILC2s, and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in nonfibrotic livers as compared with that in mucosal tissues, with NKp44− ILC3s accounting for the majority of total intrahepatic ILCs. The frequency of ILC2s, representing a small fraction of ILCs in nonfibrotic livers, increased in liver fibrosis and correlated directly with the severity of the disease. Notably, intrahepatic ILC2s secreted the profibrotic cytokine IL-13 when exposed to IL-33 and thymic stromal lymphopoetin (TSLP); these cytokines were produced by hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells in response to TLR-3 stimulation. In summary, the present results provide the first detailed characterization of intrahepatic ILCs in human adult and fetal liver. The results indicate a role for ILC2s in human liver fibrosis, implying that targeting ILC2s might be a novel therapeutic strategy for its treatment.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Friberg, Danielle, et al.
(författare)
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Long-term evaluation of satisfaction and side effects after modified uvulopalatopharyngoplasty
- 2020
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Ingår i: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 130:1, s. 263-268
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES/HYPOTHESIS: We have previously shown that modified uvulopalatopharyngoplasty (UPPP) is effective to treat obstructive sleep apnea (OSA) and that the effect is stable after 24 months. This continuous report includes questionnaires and phone interviews.STUDY DESIGN: Prospective intervention study.METHODS: Sixty-five patients with apnea-hypopnea index (AHI) score ≥ 15, body mass index <36 kg/m2 , and Epworth Sleepiness Scale (ESS) score ≥ 8 underwent modified UPPP after failing nonsurgical treatment. The results from a patient questionnaire at 6 and 24 months after surgery were correlated with age, body mass index, and ESS and AHI scores. Patients reporting side effects and/or regretting the surgery after 24 months were selected for phone interviews 9 years after surgery.RESULTS: The response rate was 80% and 74% at the 6- and 24-month follow-ups, respectively. Of those who responded to the questionnaire, 96% and 83% were satisfied after 6 and 24 months, respectively; 98% and 92% recommended the surgery. Side effects (globus, mucus, and voice and swallowing disorders) occurred in 38% and 31%, respectively. Dissatisfaction correlated significantly with high postoperative AHI and ESS scores, but not with occurrence of side effects. Younger subjects had a higher rate of recommendation and lower rate of side effects than did older subjects. Phone interviews after 9 years were responded to by 14 of 16 selected patients, and the responders reported minor or no side effects.CONCLUSIONS: The vast majority of the OSA patients were satisfied 24 months after surgery, even though a third of them were experiencing side effects. Younger patients had fewer side effects than did older patients. Patients with better OSA outcomes were also more satisfied. After 9 years the side effects were no longer problematic.LEVEL OF EVIDENCE: 2b Laryngoscope, 2019.
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| 28. |
- Friberg, Danielle
(författare)
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Nerve lesions in pharynx : an aetiology of obstructive sleep apnoea
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- "Heavy snorers disease" is defined as the progression from habitual snoring to obstructive sleep apnoea (OSA). Apart from a significant weight gain, the aetiology underlying progression to a collapse of the upper airways during inspiration and sleep remains unclear. Previous studies have shown that nocturnal respiratory disturbances became worse even in some OSA patients who did not gain weight. Chronic vibration of a tissue may cause neuronal damage. Therefore, our hypothesis is that the snoring vibration, may cause a progressive pharyngeal nerve lesion. To study whether uvulopalatopharyngoplasty (UPPP) prevents progression in habitual snorers without OSA, we performed a five-year follow-up in 56 such patients. In the patients' estimation, the postoperative results were good. However, sleep recordings before and five years after surgery in 53 of them showed a slight but significant increase in respiratory disturbances, significantly correlated to weight gain. Six patients developed OSA postoperatively, one of them despite a weight loss of 10 kg. The patency of the upper airways depends on the balance between the negative intrapharyngeal pressure developed during inspiration and its counteraction by dilating muscles. The reflexogenic dilation is probably mediated by afferent nerve endings in the pharyngeal mucosa. To investigate whether there are signs of a local nerve lesion, three methods were used in patients with habitual snoring and various degrees of respiratory disturbances and in non-snoring controls: 1) Biopsies of m. palatopharyngeus from 21 patients (10 with OSA) and 10 controls were investigated. The severity of the morphological abnormalities, including signs of efferent nerve lesions (e.g., type-grouping), was significantly greater in patients than in controls. The individual abnormality score correlated significantly to the amount of obstructive breathing, but not to the oxygen desaturation index. 2) The vascular reaction in the soft palatal mucosa after afferent nerve stimulation was recorded by a laser Doppler perfusion monitoring method in 35 patients (24 with OSA) and in 13 controls. Electrical stimulation activates nerve endings of C-fibre type, which release vasoactive agents- e.g., substance P (SP) and calcitonin gene-related peptide (CGRP)- resulting in vasodilation. The snorers and some mild OSA patients showed significantly more vasodilation after stimulation, than did controls, indicating sensitized nerves, e.g., due to sprouting. Patients with moderate-to-severe OSA demonstrated significantly less vasodilation than in controls, indicating degenerated nerves. 3) Biopsies of the soft palatal mucosa from 21 patients (10 with OSA) and 11 controls were immunohistochemically stained with PGP 9.5 (specific nerve-protein), SP and CGRP. All three substances showed an increase in the number of varicose nerve endings, in and below the epithelium in nine of 10 patients with rnild-to-moderate OSA and in four of 11 habitual snorers, compared to controls. This indicates a nerve lesion, e.g., nervous sprouting. CONCLUSIONS: UPPP does not completely prevent the development of OSA, especially if the patients gain weight postoperatively. The histological and physiological methods used indicate a progressive local nerve lesion. This lesion may be an aetiology to the collapse of upper airways in OSA.
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| 29. |
- Friberg, Danielle, et al.
(författare)
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Nytt vårdförlopp för barn med OSDB är godkänt att tas i bruk. Obstruktiv sömnrelaterad andningsstörning – ett vanligt och potentiellt allvarligt tillstånd : [New Swedish National care process for pediatric obstructive sleep disordered breathing]
- 2023
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Ingår i: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- Obstructive sleep disordered breathing (OSDB) is a spectrum from habitual snoring and labored breathing to obstructive sleep apnea (OSA), which is common and potentially serious in children. The process contains a new question at child care centers, directed at caretakers with children at age 18 months and 3 years, concerning habitual snoring (3 times a week or more). A primary care doctor verifies the suspicion of OSDB in case of a positive answer to one of 7 additional questions or 4 status findings (e.g. tonsil hypertrophy). The process starts with the suspicion of OSDB, from the age of 18 months to 18 years, and ends when symptoms are improved after watchful waiting or upper airway surgery. National equality is a goal, with increased access to nocturnal respiratory recordings of children with comorbidities or doubtful cases. Also, with short waiting time to first visit at ORL department, and to surgery. Children with comorbidities or severe symptoms get postoperative follow-ups with a nurse after 6 months. The new ICD code for OSDB is R06.8A.
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| 30. |
- Friberg, Danielle, et al.
(författare)
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Parental poverty and occupation as risk factors for pediatric sleep-disordered breathing.
- 2015
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Ingår i: Sleep Medicine. - : Elsevier BV. - 1878-5506 .- 1389-9457. ; 16:9, s. 1169-1175
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have found associations between pediatric sleep-disordered breathing (SDB) and socioeconomic status (SES), as well as a neighborhood-related disadvantage. This study analyzes the association among familial SES, parental occupation, and SDB in Swedish offspring.
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| 31. |
- Friberg, Danielle, et al.
(författare)
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Sibling risk of pediatric obstructive sleep apnea syndrome and adenotonsillar hypertrophy.
- 2009
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 32:8, s. 1077-1083
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:To estimate sibling risk of hospitalization for children with sleep disordered breathing (SDB), diagnosed with (1) obstructive sleep apnea syndrome (OSAS), or (2) adenotonsillar hypertrophy in the total Swedish population.Design, Setting, and Participants:Using the MigMed database at the Karolinska Institute, we divided the population of Sweden aged 0–18 years into sibling groups based on a shared mother and father and presence of a primary hospital diagnosis of OSAS or adenotonsillar hypertrophy for each individual born between 1978 and 1986, during the follow-up period 1997–2004. Individuals with at least one affected sibling were identified and the incidence rates were computed, using standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Reference groups were boys and girls with unaffected siblings of 2 or more.Results:After accounting for socioeconomic status, age, and geographic region, boys with at least one sibling with OSAS had an increased risk of having OSAS (SIR, 33.2; 95% CI, 16.5–64.8), and in girls the SIR was 40.5 (19.4–81.4). For hypertrophy of the tonsils or hypertrophy of the adenoids and tonsils the corresponding SIRs were 4.53 (3.0–6.8) for boys and 4.94 (3.3–7.4) for girls.Conclusions:The study indicate an increased sibling risk of sleep disordered breathing in children, which may be due to heritable genes and/or shared environment such as increased awareness among family members or referring doctors. Caregivers should ask parents if siblings have similar symptoms, and thus offer them early treatment.
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| 32. |
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| 33. |
- Grote, Ludger, 1964, et al.
(författare)
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National Knowledge-Driven Management of Obstructive Sleep Apnea-The Swedish Approach
- 2023
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Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. Methods: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. Results: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. Conclusions: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).
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| 34. |
- J, Sundquist, et al.
(författare)
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Obstructive sleep apnea syndrome in siblings : an 8-year Swedish follow-up study.
- 2008
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 31:6, s. 817-823
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Tidskriftsartikel (refereegranskat)abstract
- Background:Understanding the genetic transmission of obstructive sleep apnea syndrome (OSAS) will help clinicians identify patients at risk and offer opportunities for intervention and treatment at specialist clinics.Objective:To estimate familial risk of hospitalization for OSAS in the adult population of Sweden, and to determine if there are any differences by age and sex.Design, setting, and participants:Using the MigMed database at the Karolinska Institute, we divided the population of Sweden into sibling groups based on a shared mother and father and ascertained the presence or absence of a primary hospital diagnosis of OSAS in each individual during the follow-up period, 1997 to 2004. Individuals were categorized as having or not having a sibling with OSAS, based on the presence or absence of the disorder in at least 1 of their siblings. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated for men and women with a sibling with OSAS, compared with men and women in the reference group (SIR = 1).Results:After accounting for socioeconomic status, age, geographic region, and period of diagnosis, men with at least 1 sibling who had OSAS had a SIR of 3.42 (95% CI, 2.18–5.36); the corresponding SIR in women was 3.25 (95% CI, 1.84–5.65).Conclusions:Our results indicate that physicians should consider family history of OSAS when deciding whether to refer a patient for further sleep examinations.
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| 35. |
- J, Sundman, et al.
(författare)
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Poor interexaminer agreement on Friedman tongue position.
- 2017
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 137:5, s. 554-556
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: The Friedman tongue position demonstrated only a slight inter-examiner agreement among 15 medical doctors, indicating that the method is difficult to perform and could be an uncertain method to select patients for uvulopalatopharyngoplasty.Objective: The Friedman staging system is a clinical tool for selecting patients with obstructive sleep apnea who are appropriate for uvulopalatopharyngoplasty. The objective of this study was to evaluate the staging system by determining the inter-examiner agreement of one of its key components, the Friedman tongue position.Methods: Eleven residents and four specialists in Otorhinolaryngology were recruited from a course in surgical management of obstructive sleep apnea. They examined each other’s tongue positions, resulting in a total of 210 evaluations. Cohen’s kappa analysis was performed to assess the inter-examiner agreement. The range of kappa is usually between 0–1, where 0 is complete disagreement and 1 is complete agreement.Results: The median kappa was 0.36 (1st and 3rd quartile, 0.23 and 0.42), corresponding to only a slight agreement.
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| 36. |
- K, Lundkvist, et al.
(författare)
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Pharyngeal disturbances in OSAS patients before and 1 year after UPPP
- 2010
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; , s. 1399-1405
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Tidskriftsartikel (refereegranskat)abstract
- Conclusions: The results indicate that conservative uvulopalatopharyngoplasty with tonsillectomy (UPPP) did not change the degree of pharyngeal disturbances in patients with obstructive sleep apnea syndrome (OSAS). Objectives: To investigate if the symptom scores of pharyngeal disturbances in OSAS patients were changed 1 year after UPPP, by using a questionnaire pre- and postoperatively, and to compare with healthy non-snoring controls. Methods: Fifty men and eight women, median age 46 years (range 25–75), median body mass index (BMI) 28 kg/m2 (20–38), and median preoperative oxygen desaturation index 16 (7–100) were included as they had all failed non-surgical treatment and wanted pharyngeal surgery. The questionnaire consisted of 10 questions with 4 degrees of disturbances; the maximum score was 30 and was evaluated before and 1 year after surgery. Fifteen age-, gender- and BMI-matched controls responded to the same questionnaire. Results: Responses to the questionnaire were provided pre- and postoperatively by 47 of 58 patients (81%). Their median score was unchanged from 5 (range 0–17) to 5 (0–19), compared with controls 1 (0–3). Analyses of separate questions showed a significant decrease in the score for ‘globus sensation’ and ‘swelling’ postoperatively.
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| 37. |
- K, Lundkvist, et al.
(författare)
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Uvulopalatopharyngoplasty in 158 OSAS patients failing non-surgical treatment
- 2009
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251.
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Tidskriftsartikel (refereegranskat)abstract
- Conclusions: Uvulopalatopharyngoplasty (UPPP) in patients with obstructive sleep apnoea syndrome (OSAS) who had failed treatment with continuous positive airway pressure (CPAP) and mandibular retaining device (MRD) was effective and safe. The satisfaction rate was high. We recommend UPPP in selected OSAS patients, especially younger patients. Objectives: To evaluate the efficacy and complication rate of UPPP. Patients and methods: This was a non-randomized prospective study of 139 men and 19 women, median age 45 years (range 20–75), median body mass index (BMI) 29 (range 20–48), who underwent UPPP. One year follow-up comprised ambulant sleep apnoea recordings and questionnaires with the Epworth Sleepiness Scale (ESS). Results: In all, 76% of the patients underwent sleep recordings preoperatively and postoperatively. The oxygen desaturation index (ODI4) decreased from median 23 (range 6–100) to 8 (range 0–60), p<0.001. Criteria of success (>50% reduction and ODI<20), was 64%. The ESS value decreased from median 12 (range 0–21) to 6 (0–22), p<0.001. In all, 88% of the patients were satisfied. Four of 158 patients (2.5%) had serious postoperative complications. There was neither sequel of complications nor mortality.
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| 38. |
- Kokkinou, Efthymia, et al.
(författare)
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CD45RA(+)CD62L(-) ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs
- 2022
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Ingår i: Science immunology. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2470-9468. ; 7:70
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Tidskriftsartikel (refereegranskat)abstract
- Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The discovery of naive-like ILCs suggests an ILC differentiation process that is akin to naive T cell differentiation. Delineating the mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here, we showed that tonsillar ILCs expressing CD45RA lacked proliferative activity, indicative of cellular quiescence. CD62L distinguished two subsets of CD45RA(+) ILCs. CD45RA(+)CD62L(+) ILCs (CD62L(+) ILCs) resembled circulating naive ILCs because they lacked the transcriptional, metabolic, epigenetic, and cytokine production signatures of differentiated ILCs. CD45RA(+)CD62L(-) ILCs (CD62L(-) ILCs) were epigenetically similar to CD62L(+) ILCs but showed a transcriptional, metabolic, and cytokine production signature that was more akin to differentiated ILCs. CD62L(+) and CD62L(-) ILCs contained uni- and multipotent precursors of ILC1s/NK cells and ILC3s. Differentiation of CD62L(+) and CD62L(-) ILCs led to metabolic reprogramming including up-regulation of genes associated with glycolysis, which was needed for their effector functions after differentiation. CD62L(-) ILCs with preferential differentiation capacity toward IL-22-producing ILC3s accumulated in the inflamed mucosa of patients with inflammatory bowel disease. These data suggested distinct differentiation potential of CD62L(+) and CD62L(-) ILCs between tissue microenvironments and identified that manipulation of these cells is a possible approach to restore tissue-immune homeostasis.
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| 39. |
- Konya, Viktoria, et al.
(författare)
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Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells
- 2018
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 141:1, s. 279-292
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL-23-driven tissue-resident group 3 innate lymphoid cells (ILC3s) play essential roles in intestinal immunity, and targeting IL-23/12 is a promising approach in IBD therapy. Objective: We set out to define the role of 1 alpha,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3s to IL-23 plus Il-1 beta stimulation. Methods: Transcriptomes of sorted tonsillar ILC3s were assessed by using microarray analysis. ILC3 cytokine production, proliferation, and differentiation were determined by means of flow cytometry, ELISA, and multiplex immunoassay. Intestinal cell suspensions and ILC3s sorted from gut biopsy specimens of patients with IBD were also analyzed along with plasma 25-hydroxy vitamin D3 (25D) detection. Results: ILC3s stimulated with IL-23 plus IL-1 beta upregulated the vitamin D receptor and responded to 1,25D with downregulation of the IL-23 receptor pathway. Consequently, 1,25D suppressed IL-22, IL-17F, and GM-CSF production from tonsillar and gut ILC3s. In parallel, 1,25D upregulated genes linked to the IL-1 beta signaling pathway, as well as the IL-1 beta-inducible cytokines IL-6, IL-8, and macrophage inflammatory protein IL/1 beta. The 1,25D-triggered skewing in ILC3 function was not accompanied or caused by changes in viability, proliferation, or phenotype. Finally, we confirmed low 25D plasma levels in patients with IBD with active inflammation. Conclusion: In light of the beneficial targeting of IL-23/12 in patients with IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23 receptor pathway, providing a novel mechanism for how ILC3s could be manipulated to regulate intestinal inflammation.
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| 40. |
- Lundkvist, Karin, et al.
(författare)
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Familial risk of sleep-disordered breathing
- 2012
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Ingår i: Sleep Medicine. - : Elsevier BV. - 1878-5506 .- 1389-9457. ; 13:6, s. 668-673
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the incidence of hospitalization for paediatric obstructive sleep apnoea syndrome (OSAS) or sleep-disordered breathing (SDB) caused by adenotonsillar or tonsillar hypertrophy without infection in children with a parent affected by OSAS. Patients and methods: Using the MigMed database at Lund University, hospital data on all children aged 0-18 years in Sweden between 1997 and 2007 (total of 3 million individuals) were used to identify all first hospital admissions for OSAS or either adenotonsillar or tonsillar hypertrophy. Next, individuals were categorized as either having or not having a parent affected by OSAS. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated for boys and girls with a parent affected by OSAS. Children with OSAS or adenotonsillar or tonsillar hypertrophy without a parent affected by OSAS acted as the reference group (SIR = 1). Results: After accounting for socio-economic status, age, and geographic region, the SIRs of OSAS in boys and girls with a parent affected by OSAS were 3.09 (95% CI 1.83-4.90) and 4.46 (95% CI 2.68-6.98), respectively. The SIRs of adenotonsillar or tonsillar hypertrophy in boys and girls with a parent affected by OSAS were 1.82 (95% CI 1.54-2.14) and 1.56 (95% CI 1.30-1.87), respectively. Conclusion: This study indicates familial clustering of sleep-disordered breathing, which is important information for clinicians. (C) 2012 Elsevier B.V. All rights reserved.
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| 41. |
- Maric, Jovana, et al.
(författare)
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Cytokine-induced endogenous production of prostaglandin D-2 is essential for human group 2 innate lymphoid cell activation
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 143:6, s. 2202-2214.e5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We set out to examine PG production in human ILC2s and the implications of such endogenous production on ILC2 function. Methods: The effects of the COX-1/2 inhibitor flurbiprofen, the hematopoietic prostaglandin D2 synthase (HPGDS) inhibitor KMN698, and the CRTH2 antagonist CAY10471 on human ILC2s were determined by assessing receptor and transcription factor expression, cytokine production, and gene expression with flow cytometry, ELISA, and quantitative RT-PCR, respectively. Concentrations of lipid mediators were measured by using liquid chromatography-tandem mass spectrometry and ELISA. Results: We show that ILC2s constitutively express HPGDS and upregulate COX-2 upon IL-2, IL-25, and IL-33 plus thymic stromal lymphopoietin stimulation. Consequently, PGD2 and its metabolites can be detected in ILC2 supernatants. We reveal that endogenously produced PGD2 is essential in cytokine-induced ILC2 activation because blocking of the COX-1/2 or HPGDS enzymes or the CRTH2 receptor abolishes ILC2 responses. Conclusion: PGD2 produced by ILC2s is, in a paracrine/autocrine manner, essential in cytokine-induced ILC2 activation. Hence we provide the detailed mechanism behind how CRTH2 antagonists represent promising therapeutic tools for allergic diseases by controlling ILC2 function.
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| 42. |
- Maric, Jovana, et al.
(författare)
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Prostaglandin E-2 suppresses human group 2 innate lymphoid cell function
- 2018
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 141:5, s. 1761-1773.e6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Group 2 innate lymphoid cells (ILC2s) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. Prostaglandin (PG) E-2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation.Objective: We set out to investigate how PGE(2) regulates human ILC2 function.Methods: The effects of PGE(2) on human ILC2 proliferation and intracellular cytokine and transcription factor expression were assessed by means of flow cytometry. Cytokine production was measured by using ELISA, and real-time quantitative PCR was performed to detect PGE(2) receptor expression.Results: PGE(2) inhibited GATA-3 expression, as well as production of the type 2 cytokines IL-5 and IL-13, from human tonsillar and blood ILC2s in response to stimulation with a combination of IL-25, IL-33, thymic stromal lymphopoietin, and IL-2. Furthermore, PGE(2) downregulated the expression of IL-2 receptor alpha (CD25). In line with this observation, PGE(2) decreased ILC2 proliferation. These effects were mediated by the combined action of E-type prostanoid receptor (EP) 2 and EP4 receptors, which were specifically expressed on ILC2s.Conclusion: Our findings reveal that PGE(2) limits ILC2 activation and propose that selective EP2 and EP4 receptor agonists might serve as a promising therapeutic approach in treating allergic diseases by suppressing ILC2 function.
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| 43. |
- Mazzurana, Luca, et al.
(författare)
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Suppression of Aiolos and Ikaros expression by lenalidomide reduces human ILC3−ILC1/NK cell transdifferentiation
- 2019
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 202:1
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Tidskriftsartikel (refereegranskat)abstract
- The Ikaros family of transcription factors (TFs) are important regulators of lymphocyte function. However, their roles in human innate lymphoid cell (ILC) function remain unclear. Here, we found that Ikaros (IKZF1) is expressed by all ILC subsets, including NK cells, in blood, tonsil, and gut, while Helios (IKZF2) is preferentially expressed by ILC3 in tonsil and gut. Aiolos (IKZF3) followed the expression pattern of T-bet and Eomes, being predominantly expressed by ILC1 and NK cells. Differentiation of IFN-γ-producing ILC1 and NK cells from ILC3 by IL-1β plus IL-12-stimulation was associated with upregulation of T-bet and Aiolos. Selective degradation of Aiolos and Ikaros by lenalidomide suppressed ILC1 and NK cell differentiation and expression of ILC1 and NK cell-related transcripts (LEF1, PRF1, GRZB, CD244, NCR3, and IRF8). In line with reduced ILC1/NK cell differentiation, we observed an increase in the expression of the ILC3-related TF Helios, as well as ILC3 transcripts (TNFSF13B, IL22, NRP1, and RORC) and in the frequency of IL-22 producing ILC3 in cultures with IL-1β and IL-23. These data suggest that suppression of Aiolos and Ikaros expression inhibits ILC1 and NK cell differentiation while ILC3 function is maintained. Hence, our results open up for new possibilities in targeting Ikaros family TFs for modulation of type 1/3 immunity in inflammation and cancer.
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| 44. |
- N, Browaldh, et al.
(författare)
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Elective tracheostomy is an alternative treatment in patients with severe obstructive sleep apnoea syndrome and CPAP failure.
- 2009
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; , s. 1121-1126
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Tidskriftsartikel (refereegranskat)abstract
- Conclusions.Elective tracheostomy with custom-made tubes was tolerated in a majority of patients with severe obstructivesleep apnoea syndrome (OSAS), as it reduced daytime symptoms and served as a link to other treatments.Objectives.Toevaluate the tolerability of elective tracheostomy and changes in excessive daytime sleepiness and nocturnal oxygendesaturations (ODI) in patients with severe OSAS and obesity.Patients and methods.The medical records of 10 patients,median age 53.5 years (range 3177), BMI 36 kg/m2(3150), ODI 81 (55126) during a 5-year period were reviewed.Inclusion criteria were failure of continuous positive airway pressure (CPAP), acceptance of tracheostomy, excessivedaytime sleepiness and ODI50. All patients received a custom-made tube. Sleep apnoea recordings and questionnaireswith Epworth sleepiness scale (ESS) were performed before and after tracheostomy.Results.Eight of 10 patients toleratedthe tube for more than 6 months. The ESS score was reduced from median 18 (range 823) to 5 (07) and the ODI valuesfrom 81 (55126) to 13 (187). Two patients insisted on decannulation because they had nocturnal breathing problems,two underwent palatal surgery and were decannulated, and five still have their tubes. Severe cough, sputum infections andstoma granuloma were seen in all patients.
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| 45. |
- Niessl, Julia, et al.
(författare)
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Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue
- 2021
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 6:64
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Tidskriftsartikel (refereegranskat)abstract
- Cross-reactive CD4+ T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with SARS-CoV-2–reactive CD8+ T cells. However, large numbers of memory CD8+ T cells reside in tissues, feasibly harboring localized SARS-CoV-2–specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19 (coronavirus disease 2019). We found that SARS-CoV-2–specific memory CD4+ T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2–specific memory CD8+ T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2–specific memory CD8+ T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus–specific memory CD8+ T cells, but were functionally less potent than other virus-specific memory CD8+ T cell responses. The presence of preexisting tissue-resident memory CD8+ T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.
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| 46. |
- P, Nerfeldt, et al.
(författare)
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A two-year weight reduction program in obese sleep apnea patients
- 2010
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Ingår i: Journal of Clinical Sleep Medicine (JCSM). - 1550-9389 .- 1550-9397. ; 6:5, s. 479-486
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives:To evaluate the effects of a 2-year weight reduction program on respiratory disturbances, arousal index, daytime sleepiness, metabolic status, and quality of life in obese patients with obstructive sleep apnea syndrome (OSAS).Methods:Prospective intervention study of 33 consecutive obese OSAS patients (24 men, 9 women); 19 subjects used continuous positive airway pressure and 4 used mandibular retaining device, except during nights with sleep recording. The program consisted of 8 weeks of low calorie diet followed by group meetings with behavioral change support.Results:Seventy percent of the patients completed the program; 67% completed the sleep recordings. The success rate for the apnea-hypopnea index (AHI) (< 20 and reduction ≥ 50%) was 15% in the intention to treat (ITT) analysis. The AHI showed a nonsignificant decrease in mean values, from 43 to 28. The oxygen desaturation index (ODI) decreased from 42 to 23 (p = 0.010), arousal index from 24 to 11 (p = 0.019), body mass index from 40 to 35 (p = 0.003) and the Epworth Sleepiness Scale (ESS) from 9 to 5 (p = 0.026), all ITT. Metabolic status, physical functioning, and vitality evaluations improved only in the per protocol analysis. Reduction in weight correlated significantly to reductions in ESS (p = 0.038) and insulin levels (p = 0.002), respectively. There were no differences based on gender or use/non-use of OSAS treatment device.Conclusions:Our weight reduction program showed a limited success in reducing AHI. However, there were significant improvements in weight, ODI, arousal index, and subjective symptoms. We recommend the program as an adjunct treatment for well-motivated obese OSAS patients.Citation:Nerfeldt P; Nilsson BY; Mayor L; Uddén J; Friberg D. A two-year weight reduction program in obese sleep apnea patients. J Clin Sleep Med 2010;6(5):479-486.Keywords: Sleep apnea, obesity, weight reduction, diet, quality of life, sleepiness, behavioral therapy
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| 47. |
- P, Nerfeldt, et al.
(författare)
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Effectiveness of Oral Appliances in Obstructive Sleep Apnea with Respiratory Arousals
- 2016
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Ingår i: Journal of Clinical Sleep Medicine (JCSM). - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Study ObjectivesTo compare adherence and treatment effects with an oral appliance (OA) in patients with different types of obstructive sleep apnea (OSA): those with mainly respiratory arousals (“arousers”), and those with oxygen desaturations (“desaturaters”) at polysomnography (PSG).MethodsA prospective intervention study on 72 “tired snorers” with “normal” home sleep study (HSS), but later diagnosed as OSA with PSG, who accepted OA treatment. They were offered evaluation with a follow-up PSG and questionnaires, including the Epworth Sleepiness Scale (ESS), general health (GH), satisfaction, and side effects.ResultsSixty-six patients, 33 arousers and 33 desaturaters, were adapted to OA. The 1-year adherence rate was significantly higher among arousers (85%) than desaturaters (55%) (p = 0.034). Thirty-six of 66 patients underwent follow-up PSG; the apnea-hypopnea index was significantly reduced in 22 arousers from a median of 14 to 3 (p < 0.001), and in 14 desaturaters from 18 to 7 (p = 0.002; no significant group difference). ESS and GH showed no significant improvements in either group, although sleepy “arousers” (ESS ≥ 10) significantly improved their ESS. In total, 77% reported side effects, while 63% were still satisfied with the OA treatment. Gender analysis showed a significant dominance of females classified as “arousers” (p = 0.025).ConclusionsOSA patients with mainly arousals at PSG showed higher adherence to OA treatment, compared to patients with desaturations. Both groups responded similarly to treatment: improved nocturnal respiration, but only a small reduction of symptoms. We suggest that “tired snorers” with “normal HSS” should be offered PSG, and if OSA, also OA treatment.
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| 48. |
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| 49. |
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| 50. |
- P, Nerfeldt, et al.
(författare)
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Weight reduction improves nocturnal respiration in obese sleep apnoea patients- : A randomized controlled pilot study
- 2008
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Ingår i: Obesity Research and Clinical Practice. - : Elsevier BV. - 1871-403X .- 1878-0318.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesRandomized controlled pilot study of the effect of weight reduction on nocturnal respiratory parameters in obese patients with obstructive sleep apnoea syndrome (OSAS).MethodsTwenty consecutive obese male patients fulfilling OSAS criteria at Karolinska University Hospital were randomized into two groups. Intervention with an 8-week weight reduction programme consisting of a low-calorie diet, together with group meetings, was evaluated compared to expectancy alone for the control group, followed by a crossover. Follow-up at 3 months included anthropometrics and ambulant sleep apnoea recordings.ResultsEleven of twenty men completed the protocol. There were significant differences between the intervention group (n = 6) and the control group (n = 5) in changes of weight (p < 0.01) and oxygen desaturation index (ODI4) (p < 0.05). We also found a significant positive correlation in these 11 males after the crossover between their reduction in weight and their reduction in ODI4 (p < 0.05).ConclusionsThis pilot study indicates that weight reduction improves nocturnal respiration in obese OSAS patients after 3 months’ dietary treatment compared to expectancy.
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