Hearing outcome after myringoplasty in Sweden: A nationwide registry-based cohort study.

OBJECTIVES: To present hearing results after successful primary myringoplasty surgeries registered in the Swedish Quality Registry for Myringoplasty and to evaluate the chance of hearing improvement and the risk of hearing loss. DESIGN: A retrospective nationwide cohort study based on prospectively collected registry data between 2002 and 2012. SETTINGS: Registry data from secondary and tertiary hospitals performing myringoplasty. PARTICIPANTS: Patients with healed tympanic membrane after primary myringoplasty surgery performed from 2002 to 2012 in Sweden. MAIN OUTCOME MEASURES: Postoperative hearing results, hearing gain and air-bone gap (ABG). RESULTS: In 2226 myringoplasties, air conduction audiograms were recorded, and the average preoperative pure tone average (PTA4 ) of the group was 28.5 dB, which improved postoperatively to 19.6 dB with an average of 8.8 dB improvement. Bone conduction was measured for 1476 procedures. Closure of the ABG to 10 dB or less was achieved in 51% of the ears and to less than 20 dB in 89% of the ears. Sixty-one percent of patients with preoperatively deteriorated hearing experienced improved hearing, but 3% of all patients experienced deteriorated hearing. After the surgery, 93% of the patients were satisfied. CONCLUSIONS: Hearing results after successful myringoplasty surgery are often favourable, but although the tympanic membrane is healed, hearing improvement is not guaranteed, and hearing deterioration can also occur.

TLR3 in human eosinophils: functional effects and decreased expression during allergic rhinitis.

BACKGROUND/AIM: Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils. METHODS: BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved. RESULTS: TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-kappaB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release. CONCLUSIONS: Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.

Nasal challenge with LPS stimulates the release of macrophage inflammatory protein 1alpha.

BACKGROUND: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1alpha in LPS-induced nasal inflammation. METHODS: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1alpha levels analyzed and expression of MIP-1alpha mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP-1alpha release, cell survival, and the involved signal pathways, were investigated. RESULTS: LPS challenge caused an increase of MIP-1alpha in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time- and concentration-dependent release of MIP-1alpha, which was reduced by inhibitors of transcription and of nuclear factor (NF)-kappaB, protein kinase C (PKC) and p38 MAPK pathways. CONCLUSIONS: Nasal LPS challenge results in release of MIP-1alpha. The release most likely originates from recruited neutrophils, via NF-kappaB-, PKC- and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apoptosis. MIP-1alpha may constitute an important mediator in neutrophilic airway disease.

Tinnitus and taste disturbances reported after myringoplasty: Data from a national quality registry.

OBJECTIVES/HYPOTHESIS: Postoperative tinnitus and taste disturbances after myringoplasty are more common than previously reported. STUDY DESIGN: This study was a retrospective analysis of prospectively collected data from the Swedish National Quality Registry for Myringoplasty. METHODS: The analysis was performed on extracted data from all counties in Sweden collected from database A from 2002 to 2012 and database B from 2013 to 2016. Tinnitus and taste disturbance complications 1 year after myringoplasty were analyzed in relation to gender, age, procedure, and success rate. In database A, physicians reported tinnitus and taste disturbances. In database B, patients reported the complications. RESULTS: A major difference was found when the complications were reported by physicians compared to when the complications were reported by patients. In database A, tinnitus was reported in 1.2% of the patients and taste disturbances in 0.5%. In database B, the frequencies were 12.3% and 11.2%, respectively. Tinnitus and taste disturbances were more frequent after conventional myringoplasty compared to those after fat grafting and were more frequent after primary compared to those after revision surgery when reported by physicians. Patients, however, reported the same frequency of tinnitus after fat graft myringoplasty compared to that after conventional myringoplasty (12.0% vs. 12.6%) and fewer taste disturbances after revision surgery. In follow-up assessments, complications persisted after surgery over a long time period. CONCLUSION: Tinnitus and taste disturbances are more common after myringoplasty when patients report their symptoms than when physicians report the symptoms. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:209-215, 2019.

Expression of Toll-like receptor 9 in nose, peripheral blood and bone marrow during symptomatic allergic rhinitis.

BACKGROUND: Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocytes in bone marrow and peripheral blood. Toll-like receptor 9 (TLR9) is a receptor for unmethylated CpG dinucleotides found in bacterial and viral DNA. The present study was designed to examine the expression of TLR9 in the nasal mucosa and in leukocytes derived from different cellular compartments during symptomatic allergic rhinitis. METHODS: The study was based on 32 patients with seasonal allergic rhinitis and 18 healthy subjects, serving as controls. Nasal biopsies were obtained before and after allergen challenge. Bone marrow, peripheral blood and nasal lavage fluid were sampled outside and during pollen season. The expression of TLR9 in tissues and cells was analyzed using immunohistochemistry and flow cytometry, respectively. RESULTS: TLR9 was found in several cell types in the nasal mucosa and in different leukocyte subpopulations derived from bone marrow, peripheral blood and nasal lavage fluid. The leukocyte expression was generally higher in bone marrow than in peripheral blood, and not affected by symptomatic allergic rhinitis. CONCLUSION: The widespread expression of TLR9 in the nasal mucosa along with its rich representation in leukocytes in different compartments, demonstrate the possibility for cells involved in allergic airway inflammation to directly interact with bacterial and viral DNA.

Lipopolysaccharide-induced down-regulation of uteroglobin in the human nose.

CONCLUSION: Lipopolysaccharide (LPS) challenge of the human nose has the capacity to reduce the amount of natural anti-inflammatory proteins, such as uteroglobin. OBJECTIVES: Nasal challenge with LPS, an activator of innate immunity, has been shown to increase the amount of pro-inflammatory mediators in nasal lavage fluid. Uteroglobin is a newly described anti-inflammatory mediator that is secreted in the nose. This study examined the effect of nasal LPS application on the level of uteroglobin in nasal lavage fluid as well as on the expression of uteroglobin in nasal mucosa. MATERIALS AND METHODS: Thirty-eight volunteers were challenged nasally with either 50 microg LPS or vehicle; 6 h later, nasal lavage fluid was collected and a nasal biopsy was obtained. Levels of uteroglobin, albumin and the pro-inflammatory mediators interleukin (IL)-6 and IL-8 were analysed in the lavage fluids using enzyme-linked immunosorbent assays (ELISAs). Biopsies were used for either quantification of uteroglobin mRNA by real-time PCR or for localization of the corresponding protein with immunohistochemistry. RESULTS: The uteroglobin level decreased in nasal lavage fluid following LPS challenge, whereas the levels of IL-6 and albumin increased. Uteroglobin was mainly seen in the respiratory epithelium and its mRNA expression decreased as a consequence of the LPS challenge.

Myringoplasty Outcomes From the Swedish National Quality Registry.

OBJECTIVES/HYPOTHESIS: Data from patients registered for myringoplasty during 2002 to 2012 in the Swedish National Quality Registry for Myringoplasty. STUDY DESIGN: Both conventional myringoplasty and fat-graft techniques were used aimed at healing the tympanic membrane in noninfected ears. METHODS: Analysis was performed on data in a national database collected from 32 ear, nose, and throat clinics. Surgical procedures and outcomes, and patient satisfaction from a questionnaire were studied. RESULTS: The database was comprised of 3,775 surgical procedures, with follow-up available for analysis. One-third were children under the age of 15 years. The most common indication for surgery was infection prophylaxis. The overall healing rate of the tympanic membrane after surgery was 88.5%, with a high mean patient satisfaction. Complications registered were postoperative infection, tinnitus, or taste disturbance that occurred in 5.8% of patients. CONCLUSIONS: Swedish results for a large number of patients who completed myringoplasty are presented. The success rate in this study is comparable to other studies, and good patient-reported outcome measures of myringoplasty are presented. Databases for surgical procedures and clinical audits are systematic processes for continuous learning in healthcare. This study shows that clinical databases can be utilized to analyze national results of surgical procedures. LEVEL OF EVIDENCE: 2b Laryngoscope, 127:2389-2395, 2017.

Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis.

BACKGROUND: Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. METHODS: 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins. RESULTS: mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season. CONCLUSION: The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation.

A role for neutrophils in intermittent allergic rhinitis.

OBJECTIVE: In patients with intermittent allergic rhinitis, allergen challenge may induce both early- and late-phase responses. The aim of this study was to examine the correlation between inflammatory cells in the nasal lavage fluid and clinical parameters following pollen challenge. MATERIAL AND METHODS: Nasal lavage fluids were obtained from 29 patients with intermittent allergic rhinitis before and 1 and 6 h after allergen provocation, representing the control, early and late phases, respectively. Symptom and rhinoscopic scores were registered on the same occasions. Inflammatory cells were determined in the nasal fluid. RESULTS: The early phase was characterized by increased symptom scores, rhinoscopic signs of oedema and secretion and neutrophilia. In the late phase, symptom scores had diminished, but the signs of ongoing secretion remained. Both the total nasal symptom score and the secretion score correlated with the number of neutrophils in lavage fluids at 1 h. The eosinophil count did not increase during the early or late phases. CONCLUSION: A single allergen provocation induces an early-phase response dominated by neutrophils, with secretion being the only clinical sign remaining during the late phase. The increase in neutrophil numbers correlated with the registration of secretory symptoms. The presented data indicate a role for neutrophils in intermittent allergic rhinitis and their relation with secretory parameters makes it intriguing to speculate that neutrophils may function as promoters of nasal secretion.

Altered levels of the soluble IL-1, IL-4 and TNF receptors, as well as the IL-1 receptor antagonist, in intermittent allergic rhinitis.

BACKGROUND: The effects of cytokines are modulated by soluble cytokine receptors (SCR) and receptor antagonists. Therefore, allergic disease may depend on altered proportions between cytokines, their SCR and receptor antagonists, rather than absolute changes in cytokine levels. Little is known about SCR in intermittent allergic rhinitis (IAR). OBJECTIVE: To examine the concentrations of SCR, i.e. sIL-1R2, sIL-4R, sIL-6R and sTNFR1, as well as the interleukin-1 receptor antagonist (IL-1Ra) in nasal fluids from allergen-challenged patients with IAR and healthy controls. METHODS: 30 patients with birch- or grass-pollen-induced IAR and 30 healthy controls were studied. In the patients nasal fluids were obtained before as well as 1 and 6 h after allergen provocation. RESULTS: Both symptom scores and rhinoscopic signs of rhinitis increased in the patients after allergen challenge. Comparisons between patients and controls showed that sIL-4R was lower in patients before and 1 and 6 h after provocation. IL-1Ra was lower before and 1 h after provocation. In addition, lower concentrations of sTNFR1 were found in patients after 1 h, while sIL-1R2 concentrations were higher after 1 h. Comparisons of patients before and after challenge showed that IL-1Ra and sTNFR1 decreased after 1 h, while sIL-1R2 increased. No significant differences were found compared to 6 h. sIL-6R did not significantly differ between the study groups. CONCLUSIONS: After allergen challenge, significant changes in the nasal fluid levels of IL-1Ra, sIL-1R2 and sTNFR1 were found. By contrast, sIL-4R remained at lower levels than in controls both before and after challenge. Since sIL-4R modulates IgE synthesis, this may play a role in the pathogenesis of IAR.