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  • 1. A, Borgström
    et al.
    P, Nerfeldt
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Questionnaire OSA-18 has poor validity compared to polysomnography in pediatric obstructive sleep apnea.2013Ingår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464Artikel i tidskrift (Refereegranskat)
  • 2. Borgström, A.
    et al.
    Nerfeldt, P.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Adenotonsillotomy Versus Adenotonsillectomy in Pediatric Obstructive Sleep Apnea: An RCT.2017Ingår i: Pediatrics, Vol. 139, nr 7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Adenotonsillectomy (ATE) is a well-established and effective treatment of pediatric obstructive sleep apnea (OSA). In recent years, a more conservative method, adenotonsillotomy (ATT), has gained popularity because it is associated with less postoperative morbidity. Yet no previous randomized study has compared these 2 methods regarding their effectiveness in treating pediatric OSA in terms of polysomnographic data, which was the primary aim of this study. The hypothesis was that ATT is noninferior to ATE after 1 year.

    METHODS: Seventy-nine children, aged 2 to 6 years, with OSA (Apnea-Hypopnea Index [AHI] 5–30) were randomized to ATT (n = 40) or ATE (n = 39). Polysomnography (PSG) and questionnaire OSA-18 were assessed at baseline and 1 year postsurgery.

    RESULTS: Mean difference between groups in the primary outcome, change in AHI, was 0.83, 95% confidence interval –3.2 to 4.9, not exceeding the noninferiority margin of 5. After ATE, AHI decreased from median 12.7 (interquartile range 8.3–19.1) to 2.0 (1.2–3.1) and after ATT from 15.8 (8.5–21.2) to 4.0 (1.2–5.1). For both groups, significant improvements of PSG and OSA-18 questionnaire outcomes were observed, with no significant differences between groups. Five children (13%) in the ATT group needed repeated surgery for tonsil regrowth and recurrence of OSA.

    CONCLUSIONS: The results suggest that ATT is noninferior to ATE in treating pediatric OSA regarding PSG outcomes after 1 year. ATT could be considered an alternative to ATE for treatment of pediatric OSA. However, after ATT, there is a nonnegligible risk of recurrence of OSA, and this should be taken into account when selecting surgical method.

  • 3.
    Borgström, Anna
    et al.
    Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institute, Stockholm Sweden.
    Nerfeldt, Pia
    Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institute, Stockholm Sweden.
    Friberg, Danielle
    Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institute, Stockholm Sweden.
    Sunnergren, Ola
    Department of Otorhinolaryngology, Ryhov County Hospital, Jönköping, Sweden.
    Stalfors, Joacim
    Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Trends and changes in paediatric tonsil surgery in Sweden 1987-2013: a population-based cohort study.2017Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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–<18 years registered in the NPR with a tonsil surgery procedure 1987–2013.

    Results 167 894 tonsil surgeries were registered in the NPR 1987–2013. An increase in the total incidence rate was observed, from 22/10 000 person years in 1987 to 47/10 000 in 2013. The most marked increase was noted in children 1–3 years of age, increasing from 17 to 73/10 000 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 (1–3 years old). TT has gradually replaced tonsillectomy as the predominant method for tonsil surgery.

  • 4. Browaldh, N
    et al.
    Bring, J
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    SKUP(3) RCT; continuous study: Changes in sleepiness and quality of life after modified UPPP.2016Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 26, nr 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives/Hypothesis

    Our 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 Design

    Prospective randomized controlled trial (RCT), two parallel arms.

    Methods

    Sixty‐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.

    Results

    All 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.

    Conclusion

    This 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.

  • 5. E, Pajediene
    et al.
    I, Bileviciute-Ljungar
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Sleep patterns among patients with chronic fatigue: A polysomnography-based study.2018Ingår i: The clinical respiratory journal, Vol. 12, nr 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    The purpose of this study was to detect treatable sleep disorders among patients complaining of chronic fatigue by using sleep questionnaires and polysomnography.

    Methods

    Patients were referred to hospital for investigations and rehabilitation because of a suspected diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The criteria for further referral to full‐night polysomnography (PSG) were symptoms of excessive daytime sleepiness and/or tiredness in the questionnaires.

    Results

    Of a total of 381 patients, 78 (20.5%) patients underwent PSG: 66 women and 12 men, mean age 48.6 years, standard deviation ±9.9 years. On the basis of the PSG, 31 (40.3%) patients were diagnosed with obstructive sleep apnoea, 7 (8.9%) patients with periodic limb movement disorder, 32 (41.0%) patients with restless legs syndrome and 54 (69.3%) patients had one or more other sleep disorder. All patients were grouped into those who fulfilled the diagnostic criteria for ME/CFS (n = 55, 70.5%) and those who did not (n = 23, 29.5%). The latter group had significantly higher respiratory (P = .01) and total arousal (P = .009) indexes and a higher oxygen desaturation index (P = .009).

    Conclusions

    More than half of these chronic fatigue patients, who also have excessive daytime sleepiness and/or tiredness, were diagnosed with sleep disorders such as obstructive sleep apnoea, periodic limb movement disorder and/or restless legs syndrome. Patients with such complaints should undergo polysomnography, fill in questionnaires and be offered treatment for sleep disorders before the diagnose ME/CFS is set.

  • 6. Fehrm, Johan
    et al.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bring, Johan
    Browaldh, Nanna
    Blood pressure after modified uvulopalatopharyngoplasty: results from the SKUP3 randomized controlled trial.2017Ingår i: Sleep medicine, Vol. 34, s. 156-161Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    Obstructive 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.

    Methods

    We 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.

    Results

    A 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).

    Conclusions

    Blood 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.

  • 7.
    Fehrm, Johan
    et al.
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Nerfeldt, Pia
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Sundman, Joar
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Kirurgiska Vetenskaper, Uppsala Universitet.
    Adenopharyngoplasty vs Adenotonsillectomy in Children With Severe Obstructive Sleep Apnea A Randomized Clinical Trial2018Ingår i: JAMA Otolaryngology - Head and Neck Surgery, ISSN 2168-6181, E-ISSN 2168-619X, Vol. 144, nr 7, s. 580-586Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 8. Forkel, Marianne
    et al.
    Berglin, L
    Kekäläinen, E
    Carlsson, A
    Svedin, E
    Michaëlsson, J
    Nagasawa, M
    Erjefält, JS
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Mori, M
    Flodström-Tullberg, M
    Bergquist, A
    Mjösberg, J
    Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers.2017Ingår i: European journal of immunology, Vol. 47, nr 8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 9.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Heavy snorer’s disease: a progressive local neuropathy.1999Ingår i: Acta oto-laryngologicaArtikel i tidskrift (Refereegranskat)
  • 10.
    Friberg, Danielle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    B, Carlsson-Nordlander
    H, Larsson
    E, Svanborg
    UPPP for habitual snoring: a 5-year follow-up with respiratory sleep recordings.1995Ingår i: The LaryngoscopeArtikel i tidskrift (Refereegranskat)
  • 11.
    Friberg, Danielle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    B, Gazelius
    Evaluation of the vascular reaction in pharyngeal mucosa.1998Ingår i: Acta oto-laryngologicaArtikel i tidskrift (Refereegranskat)
  • 12.
    Friberg, Danielle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    B, Gazelius
    LE, Lindblad
    B, Nordlander
    Habitual snorers and sleep apnoics have abnormal vascular reactions of the soft palatal mucosa on afferent nerve stimulation.1998Ingår i: The LaryngoscopeArtikel i tidskrift (Refereegranskat)
  • 13.
    Friberg, Danielle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    B, Gazelius
    T, Hökfelt
    B, Nordlander
    Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers.1997Ingår i: Regulatory peptidesArtikel i tidskrift (Refereegranskat)
  • 14.
    Friberg, Danielle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    C, Lundberg
    Antibiotic prophylaxis in major head and neck surgery when clean-contaminated wounds are established.1990Ingår i: Scandinavian journal of infectious diseases. SupplementumArtikel i tidskrift (Refereegranskat)
  • 15.
    Friberg, Danielle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    J, Sundquist
    X, Li
    K, Hemminki
    K, Sundquist
    Sibling risk of pediatric obstructive sleep apnea syndrome and adenotonsillar hypertrophy.2009Ingår i: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 32, nr 8, s. 1077-1083Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 16.
    Friberg, Danielle
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    K, Lundkvist
    X, Li
    K, Sundquist
    Parental poverty and occupation as risk factors for pediatric sleep-disordered breathing2015Ingår i: Sleep medicine, Vol. 16, nr 9, s. 1169-1175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives/Background

    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.

    Methods

    A nationwide dataset was constructed by linking Swedish census data to hospital discharge register data on all first hospitalizations of children and adolescents aged 0–18 years during the study period 1997–2007. The outcome was SDB, defined as diagnostic codes for obstructive sleep apnea (OSA), adenotonsillar hypertrophy, or tonsillar hypertrophy. Familial SES was defined as family income and maternal education. The odds ratio (OR) was calculated with a 95% confidence interval (CI).

    Results

    34,933 of three million children had a first hospital diagnosis of SDB. The OR was significantly increased in offspring in families with a low income (1.79) and maternal education (1.21). Significantly increased ORs were found in 14 of 38 maternal (37%) and 13 of 48 paternal (27%) occupations, and six of them involved both parents: drivers, welders, and workers in mechanics and iron metalware, chemical processing, and manufacture of food and glass. A significantly decreased OR was found in 12 (25%) of the paternal occupations, e.g., scientists, physicians, teachers, artists, administrators, and farmers, as well as in maternal occupations, such as artists and farmers, with offspring aged 0–6 years.

    Conclusion

    This study indicates that low familial SES and parental occupations associated with a low educational level increased, whereas academic parental occupations and farmers decreased the risk of SDB in offspring.

  • 17.
    Friberg, Danielle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    T, Ansved
    K, Borg
    B, Carlsson-Nordlander
    H, Larsson
    E, Svanborg
    Histological indications of a progressive snorers disease in an upper airway muscle.1998Ingår i: American journal of respiratory and critical care medicineArtikel i tidskrift (Refereegranskat)
  • 18. J, Sundman
    et al.
    J, Bring
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Poor interexaminer agreement on Friedman tongue position.2017Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, nr 5, s. 554-556Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 19. J, Sundquist
    et al.
    X, Li
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    K, Hemminki
    K, Sundquist
    Obstructive sleep apnea syndrome in siblings: an 8-year Swedish follow-up study.2008Ingår i: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 31, nr 6, s. 817-823Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 20. K, Lundkvist
    et al.
    A, Januszkiewicz
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Uvulopalatopharyngoplasty in 158 OSAS patients failing non-surgical treatment2009Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 21. K, Lundkvist
    et al.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Pharyngeal disturbances in OSAS patients before and 1 year after UPPP2010Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, s. 1399-1405Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 22. K, Lundkvist
    et al.
    K, Sundquist
    X, Li
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Familial risk of sleep-disordered breathing2012Ingår i: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 13, nr 6, s. 668-673Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 23.
    Maric, Jovana
    et al.
    Med Univ Graz, Inst Expt & Clin Pharmacol, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Ravindran, Avinash
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Stockholm, Sweden.
    Mazzurana, Luca
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Björklund, Åsa K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Van Acker, Aline
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Rao, Anna
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Friberg, Danielle
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden;Karolinska Inst, CLINTEC, Stockholm, Sweden.
    Dahlen, Sven-Erik
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res, Stockholm, Sweden.
    Heinemann, Akos
    Med Univ Graz, Inst Expt & Clin Pharmacol, Graz, Austria.
    Konya, Viktoria
    Med Univ Graz, Inst Expt & Clin Pharmacol, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Mjösberg, Jenny
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Prostaglandin E-2 suppresses human group 2 innate lymphoid cell function2018Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 141, nr 5, s. 1761-1773.e6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 24.
    Maric, Jovana
    et al.
    Med Univ Graz, Otto Loewi Res Ctr, Pharmacol Sect, Graz, Austria;BioTechMed, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Ravindran, Avinash
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Solna, Sweden;Karolinska Univ Hosp, Clin Immunol & Transfus Med, Stockholm, Sweden.
    Mazzurana, Luca
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Van Acker, Aline
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Rao, Anna
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Kokkinou, Efthymia
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Ekoff, Maria
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Solna, Sweden;Karolinska Univ Hosp, Clin Immunol & Transfus Med, Stockholm, Sweden.
    Thomas, Dominique
    Goethe Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany.
    Fauland, Alexander
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden.
    Nilsson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Karolinska Inst, Dept Med, Immunol & Allergy Unit, Solna, Sweden;Karolinska Univ Hosp, Clin Immunol & Transfus Med, Stockholm, Sweden.
    Wheelock, Craig E.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden.
    Dahlen, Sven-Erik
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res, Stockholm, Sweden.
    Ferreiros, Nerea
    Goethe Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany.
    Geisslinger, Gerd
    Goethe Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany;Fraunhofer Inst Mol Biol & Appl Ecol IME, Project Grp Translat Med & Pharmacol TMP, Frankfurt, Germany.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Karolinska Inst, Dept Clin Sci Intervent & Technol, CLINTEC, Stockholm, Sweden.
    Heinemann, Akos
    Med Univ Graz, Otto Loewi Res Ctr, Pharmacol Sect, Graz, Austria;BioTechMed, Graz, Austria.
    Konya, Viktoria
    Med Univ Graz, Otto Loewi Res Ctr, Pharmacol Sect, Graz, Austria;BioTechMed, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Mjosberg, Jenny
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Cytokine-induced endogenous production of prostaglandin D-2 is essential for human group 2 innate lymphoid cell activation2019Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, nr 6, s. 2202-2214.e5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 25. Marquardt, Nicole
    et al.
    Ivarsson, MA
    Sundström, E
    Åkesson, E
    Martini, E
    Eidsmo, L
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Mjösberg, J
    Kublickas, M
    Ek, S
    Tegerstedt, G
    Seiger, Å
    Westgren, M
    Michaëlsson, J
    Fetal CD103+ IL-17-Producing Group 3 Innate Lymphoid Cells Represent the Dominant Lymphocyte Subset in Human Amniotic Fluid.2016Ingår i: Journal of immunology (Baltimore, Md. : 1950), Vol. 197, nr 8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45+ cells in AF is represented by a subset of fetal CD103+ group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF. Fetal CD103+ ILC3s could also be detected at high frequency in second-trimester mucosal tissues (e.g., the intestine and lung). Taken together, our data indicate that CD103+ ILC3s accumulate with gestation in the fetal intestine and subsequently egress to the AF. The dominance of ILC3s producing IL-17 and TNF in AF suggests that they could be involved in controlling intra-amniotic infections and inflammation and as such could be important players in regulating subsequent premature birth.

  • 26. N, Browaldh
    et al.
    A, Markström
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Elective tracheostomy is an alternative treatment in patients with severe obstructive sleep apnoea syndrome and CPAP failure.2009Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, s. 1121-1126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 27. N, Browaldh
    et al.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    E, Svanborg
    P, Nerfeldt
    15-year efficacy of uvulopalatopharyngoplasty based on objective and subjective data2011Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251Artikel i tidskrift (Refereegranskat)
  • 28. N, Browaldh
    et al.
    J, Bring
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    SKUP3: 6 and 24 months follow-up of changes in respiration and sleepiness after modified UPPP.2018Ingår i: The LaryngoscopeArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    Our 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 Design

    Single‐center prospective cohort study.

    Methods

    Sixty‐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.

    Results

    Eight 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.

    Conclusion

    Modified 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.

  • 29. N, Browaldh
    et al.
    P, Nerfeldt
    M, Lysdahl
    J, Bring
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    SKUP3 randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea.2013Ingår i: ThoraxArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    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/m2, 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.

  • 30. P, Nerfeldt
    et al.
    BY, Nilsson
    J, Uddén
    S, Rössner
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Weight reduction improves nocturnal respiration in obese sleep apnoea patients-: A randomized controlled pilot study2008Ingår i: Obesity Research and Clinical Practice, ISSN 1871-403X, E-ISSN 1878-0318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    Randomized controlled pilot study of the effect of weight reduction on nocturnal respiratory parameters in obese patients with obstructive sleep apnoea syndrome (OSAS).

    Methods

    Twenty 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.

    Results

    Eleven 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).

    Conclusions

    This pilot study indicates that weight reduction improves nocturnal respiration in obese OSAS patients after 3 months’ dietary treatment compared to expectancy.

  • 31. P, Nerfeldt
    et al.
    BY, Nilsson
    L, Mayor
    J, Uddén
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    A two-year weight reduction program in obese sleep apnea patients2010Ingår i: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 6, nr 5, s. 479-486Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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

  • 32. P, Nerfeldt
    et al.
    BY, Nilsson
    L, Mayor
    J, Uddén
    S, Rössner
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Weight reduction improves sleep, sleepiness and metabolic status in obese sleep apnoea patients.2008Ingår i: Obesity Research and Clinical Practice, ISSN 1871-403X, E-ISSN 1878-0318, Vol. 2, nr 4, s. 251-262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Method

    In this prospective intervention study, 33 obese patients with obstructive sleep apnoea syndrome (OSAS) (24 men, 9 women) were consecutively enrolled for a weight reduction program at the Obesity Unit, Karolinska University Hospital. 23 of 33 patients used OSAS-device, 19 with Continuous Positive Airway Pressure and 4 with Mandibular Retaining Device. The patients were investigated with questionnaires, blood tests and ambulant nocturnal polysomnography before and after a 6-month program. Patients with OSAS-device slept without it during the sleep studies. The intervention consisted of 8 weeks low calorie diet and group meetings, followed by a day-care program of behaviour change support.

    Results

    27 of 33 patients (82%, 21 men and 6 women) completed the study. After the intervention there were highly significant decreases (p < 0.001) in Body Mass Index from mean(S.D.) 40(5) to 34(3), apnoea–hypopnoea index from 43(24) to 26(20) and Epworth Sleepiness Scale (ESS)-score from 9(4) to 6(4). Sleep quality (arousal index, sleep efficiency, percentage deep sleep) and metabolic status (blood pressure, blood glucose levels, lipidemia) were also significantly improved. There was a significant correlation between increased percentage deep sleep and reduced ESS-score. There were no differences due to gender or use/no use of OSAS-device.

    Conclusion

    The results suggest that weight loss, induced by low calorie diet and behaviour change support, significantly improves nocturnal respiratory parameters, sleep quality, daytime sleepiness and metabolic status in obese OSAS patients after 6 months.

  • 33. P, Nerfeldt
    et al.
    F, Aoki
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Polygraphy vs. polysomnography: missing osas in symptomatic snorers–a reminder for clinicians2014Ingår i: Sleep and Breathing, ISSN 1520-9512, E-ISSN 1522-1709Artikel i tidskrift (Refereegranskat)
  • 34. P, Nerfeldt
    et al.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Effectiveness of Oral Appliances in Obstructive Sleep Apnea with Respiratory Arousals2016Ingår i: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 15, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study Objectives

    To 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).

    Methods

    A 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.

    Results

    Sixty-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).

    Conclusions

    OSA 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.

  • 35. P, Nerfeldt
    et al.
    P, Graf
    S, Borg
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Prevalence of high alcohol and benzodiazepine consumption in sleep apnea patients studied with blood and urine tests.2004Ingår i: Acta oto-laryngologicaArtikel i tidskrift (Refereegranskat)
  • 36. Renoux, VM
    et al.
    Zriwil, A
    Peitzsch, C
    Michaëlsson, J
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Soneji, S
    Sitnicka, J
    Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in Fetal and Adult Tissues2015Ingår i: ImmunityArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Natural killer (NK) cells are cytotoxic lymphocytes and play a vital role in controlling viral infections and cancer. In contrast to B and T lymphopoiesis where cellular and regulatory pathways have been extensively characterized, the cellular stages of early human NK cell commitment remain poorly understood. Here we demonstrate that a LinCD34+CD38+CD123CD45RA+CD7+CD10+CD127 population represents a NK lineage-restricted progenitor (NKP) in fetal development, umbilical cord blood, and adult tissues. The newly identified NKP has robust NK cell potential both in vitro and in vivo, generates functionally cytotoxic NK cells, and lacks the ability to produce T cells, B cells, myeloid cells, and innate lymphoid-like cells (ILCs). Our findings identify an early step to human NK cell commitment and provide new insights into the human hematopoietic hierarchy.

  • 37.
    Sundman, Joar
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Dept Otorhinolaryngol, S-14186 Stockholm, Sweden.
    Fehrm, Johan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Dept Otorhinolaryngol, S-14186 Stockholm, Sweden.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Low inter-examiner agreement of the Friedman staging system indicating limited value in patient selection2018Ingår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 275, nr 6, s. 1541-1545Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Friedman staging system is a clinical method for selecting patients with obstructive sleep apnoea who are likely to benefit from uvulopalatopharyngoplasty. The objective of this study was to evaluate the system by determining its inter-examiner agreement. Twelve patients with obstructive sleep apnoea were examined by 14 doctors. The Friedman stage was derived from tonsil size and tongue position, and a Cohen's kappa analysis was performed to assess inter-examiner agreement. One hundred and sixty-eight ratings were performed. The median kappa for tongue position was 0.32 (first and third quartiles: 0.21 and 0.44) and was 0.62 (0.50 and 0.63) for tonsil size. The median kappa for the Friedman stage was 0.38 (0.24 and 0.55), which corresponds to only a slight or fair agreement. The Friedman staging system demonstrated a low inter-examiner agreement, indicating that the system is an uncertain method for selecting patients for uvulopalatopharyngoplasty. Level of evidence: 2B.

  • 38.
    Sundman, Joar
    et al.
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bring, Johan
    Statisticon AB, Uppsala, Sweden..
    Lowden, Arne
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    Nagai, Roberta
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    Browaldh, Nanna
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Sleep Quality After Modified Uvulopalatopharyngoplasty: Results From the SKUP3 Randomized Controlled Trial2018Ingår i: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, nr 1, artikel-id zsx180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study Objectives: To investigate whether uvulopalatopharyngoplasty (UPPP) improves sleep quality in patients with obstructive sleep apnea (OSA) using the Functional Outcomes of Sleep Questionnaire (FOSQ) and the Karolinska Sleep Questionnaire (KSQ).

    Methods: Randomized controlled trial used to compare modified UPPP with controls at baseline and after 6 months. The controls received delayed surgery and a 6-month postoperative follow-up. All operated patients were offered a 24-month follow-up. At each follow-up, patients underwent polysomnography and vigilance testing and completed questionnaires. Nine scales were evaluated: five subscales and the total score in the FOSQ and three subscales in the KSQ.

    Results: Sixty-five patients, mean 42.3 years (SD 11.5), Friedman stage I and II, body mass index < 36 kg/m(2), and moderate-to-severe OSA, were randomized to intervention (n = 32) or control (n = 33). In the FOSQ and in the KSQ, the mean rate of missing values was 6.2% (range 0%-19%) and 20.5% (3%-38%), respectively. In 8 of 9 scales, significant differences were observed between the groups in favor of UPPP. There were significant correlations between results from the questionnaires and objective measures from polysomnography and the vigilance test. At the 6- and 24-month postoperative follow-ups, eight of nine scales were significantly improved compared with baseline.

    Conclusions: In selected patients with OSA, subjective sleep quality was significantly improved 6 months after UPPP compared with controls, with stable improvements 24 months postoperatively. The correlations between subjective and objective outcomes and the long-term stability suggest a beneficial effect from surgery, although a placebo effect cannot be excluded.

  • 39. V, Konya
    et al.
    P, Czarnewski
    M, Forkel
    A, Rao
    E, Kokkinou
    EJ, Villablanca
    S, Almer
    U, Lindforss
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    C, Höög
    P, Bergman
    J, Mjösberg
    Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells.2018Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 141, nr 1, s. 279-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 1α,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3s to IL-23 plus IL-1β 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-1β 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-1β signaling pathway, as well as the IL-1β–inducible cytokines IL-6, IL-8, and macrophage inflammatory protein 1α/β. 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.

  • 40.
    Vangeti, Sindhu
    et al.
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden.
    Gertow, Jens
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden.
    Yu, Meng
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden.
    Liu, Sang
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden.
    Baharom, Faezzah
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden.
    Scholz, Saskia
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Starkhammar, Magnus
    Capio Ear Nose & Throat Clin Globen, S-12177 Johanneshov, Sweden.
    Ahlberg, Alexander
    Karolinska Univ Hosp Huddinge, Dept Clin Sci Intervent & Technol, Div Ear Nose & Throat Dis, S-14186 Stockholm, Sweden.
    Smed-Sörensen, Anna
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden.
    Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection2019Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 202, nr 7, s. 2069-2081Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Influenza A virus (IAV) infection constitutes an annual health burden across the globe. Plasmacytoid dendritic cells (PDCs) are central in antiviral defense because of their superior capacity to produce type I IFNs in response to viruses. Dendritic cells (DCs) differ depending on their anatomical location. However, only limited host-pathogen data are available from the initial site of infection in humans. In this study, we investigated how human tonsil PDCs, likely exposed to virus because of their location, responded to IAV infection compared with peripheral blood PDCs. In tonsils, unlike in blood, PDCs are the most frequent DC subset. Both tonsil and blood PDCs expressed several genes necessary for pathogen recognition and immune response, generally in a similar pattern. MxA, a protein that renders cells resistant to IAV infection, was detected in both tonsil and blood PDCs. However, despite steady-state MxA expression and contrary to previous reports, at high IAV concentrations (typically cytopathic to other immune cells), both tonsil and blood PDCs supported IAV infection. IAV exposure resulted in PDC maturation by upregulation of CD86 expression and IFN-alpha secretion. Interestingly, blood PDCs secreted 10-fold more IFN-alpha in response to IAV compared with tonsil PDCs. Tonsil PDCs also had a dampened cytokine response to purified TLR ligands compared with blood PDCs. Our findings suggest that tonsil PDCs may be less responsive to IAV than blood PDCs, highlighting the importance of studying immune cells at their proposed site of function.

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