Experiences of Patients with Unilateral Vocal Fold Paralysis: A Mixed-Methods Study of the Insider's Perspective.

OBJECTIVE: Unilateral vocal fold paralysis (UVFP) is often characterized by severe dysphonia and has a significant impact on a patient's communication in daily and vocational situations. Having a better understanding of how UVFP influences quality of life and patient experiences can help improve patient-centered care in this population. Therefore, the purpose of this study was to explore the lived experiences of patients with UVFP. METHODS: Twenty-five adults with UVFP (age range: 39-84years) participated in the study. Quantitative data were collected from 22 participants, using the Voice Handicap Index (VHI), Dysphonia Severity Index (DSI), and Acoustic Voice Quality Index (AVQI). Qualitative data were collected from 25 individual semistructured interviews, which were recorded, transcribed, and analyzed with the software program NVivo. The interviews were coded using an inductive thematic approach. RESULTS: Quantitative results showed a mean DSI of - 1.6, mean AVQI of 3.80, and mean VHI of 45.8 in the participant group. A statistically significant, moderate (positive) correlation was found between VHI and time after onset (in years). From the qualitative analysis of the interviews, four main themes were identified: emotional impact, psychosocial impact, physical complaints, and coping strategies. Voice problems caused by UVFP generally had a negative impact on patients' emotional and psychological well-being, with considerable effects on participation, self-identity, and professional activity. Participants demonstrated a combination of problem-focused and emotion-focused coping strategies to accommodate to these issues. Half of the participant group also showed avoidance as a coping style. VHI scores were significantly higher in participants who reported experiencing current emotional and participation problems due to UVFP, and who had not yet accepted their new voice. CONCLUSION: The themes from this study emphasize the importance of focused anamnesis and emotive counseling in practice, with specific attention to the psychosocial and emotional impact of UVFP.

Immediate effects of straw phonation in air or water on the laryngeal function and configuration of female speech-language pathology students visualised with strobovideolaryngoscopy: A randomised controlled trial.

BACKGROUND: A promising way to obtain vocal economy and efficiency is by semi-occluding the vocal tract while phonating. Current knowledge about the immediate effects of semi-occluded vocal tract (SOVT) phonation on the laryngeal function and configuration is based mainly on computer modelling or excised larynges studies. In in vivo SOVT studies, electroglottography (EGG) has been the most commonly used laryngeal outcome, showing contradictory results between studies. Therefore, exploring these aspects by direct visualisation of the human larynx during SOVT phonation using strobovideolaryngoscopy (SVL) is needed. AIMS: The aim of this study was to investigate and compare the immediate effects of straw phonation (SP) in air, SP in 2 cm water, and SP in 5 cm water (with stirring straws), on the laryngeal function and configuration of a homogeneous group of vocally healthy female speech-language pathology students, visualised with flexible SVL. METHODS & PROCEDURE: A randomised controlled trial was used. Fifty-two female speech-language pathology students (mean age: 18.7 years, SD: 0.6) were assigned randomly to one of three experimental groups or a control group: (1) SP in air, (2) SP in 2 cm water, (3) SP in 5 cm water or (4) [u] phonation with similar soft onset and slightly pursed lips as in SP but without a straw (control group). The participants underwent flexible SVL during habitual [u] phonation, followed by the specific SOVT exercise of their group assignment. All video samples were evaluated randomly and blindly by two experienced investigators using the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) rating form, first independently and then by consensus. OUTCOME & RESULTS: Compared to habitual phonation, the vibrational amplitude decreased during SP in 5 cm water and SP in 2 cm water, being more prominent in the first, more flow-resistant exercise. The mucosal wave also decreased during SP in 5 cm water. The anteroposterior (AP) supraglottic compression similarly increased during SP in air, SP in 2 cm water, and SP in 5 cm water. Further, a rise in mediolateral (ML) compression and a decrease in phase symmetry and regularity were found during SP in 2 cm water. A similar decrease in regularity was observed during SP in 5 cm water. CONCLUSIONS & IMPLICATIONS: Both SP in air and SP in water cause positive immediate laryngeal effects for voice training opportunities. More AP supraglottic activity found during each SP exercise might indicate epilarynx narrowing, an economic phenomenon associated with SOVT. Immersing the straw in water additionally diminished the vibrational amplitude, lowering vocal fold impact stress and risk for phonotrauma during the exercise. The decreased regularity of the vibrational cycles during SP in water might be due to the varying back pressure created by the water bubbling. The impact of SP in water on ML supraglottic compression needs further investigation. WHAT THIS PAPER ADDS: What is already known on the subject A promising way to obtain vocal economy and efficiency is by semi-occluding the vocal tract while phonating. Current knowledge about the immediate effects of semi-occluded vocal tract (SOVT) phonation on the laryngeal function and configuration is based mainly on computer modelling or excised larynges studies. In in vivo SOVT studies, electroglottography (EGG) has been the most commonly used laryngeal outcome, showing contradictory results between studies. Therefore, exploring these aspects by direct visualisation of the human larynx during SOVT phonation using strobovideolaryngoscopy (SVL) is needed. What this paper adds to existing knowledge Group results of the current study generally support earlier computer modelling and in vivo studies, strengthening the current SOVT knowledge. Both SP in air and SP in water cause positive immediate laryngeal effects for voice training opportunities. More anteroposterior (AP) supraglottic activity found during each SP exercise might indicate epilarynx narrowing, an economic phenomenon associated with SOVT. Immersing the straw in water additionally diminished the vibrational amplitude, lowering vocal fold impact stress and risk for phonotrauma during the exercise. The decreased regularity of the vibrational cycles during SP in water might be due to the varying back pressure created by the water bubbling. The impact of SP in water on ML supraglottic compression needs further investigation. What are the potential or actual clinical implications of this work? Current results support that both SP in air and SP in water can be useful exercises in voice training. SP in water has shown the additional gain of lowering the vibrational amplitude during the exercise, hence supporting its appropriateness for vocal warm-ups by minimising vocal fold impact stress and the risk of phonotrauma. In the future, large-scale randomised controlled trials in other subgroups of voice users, including dysphonic patients, are needed to support evidence-based practice. SVL can facilitate the search for individualised training and therapy approaches.

Voice Outcome of Glottoplasty in Trans Women.

PURPOSE: This study investigates the short- and longer-term effects of glottoplasty up to six months after surgery on acoustic voice parameters, listener perceptions, and client's satisfaction in trans women. Secondly, the impact of chondrolaryngoplasty and voice therapy on the glottopasty outcomes was investigated. METHOD: A prospective longitudinal non-controlled trial was used. Thirty-five trans women undergoing glottoplasty or a combination of glottopasty and chondrolaryngoplasty were included in this study. A voice assessment was conducted before surgery and 1 week, 1 month and 6 months after surgery. The following outcome parameters were measured: fundamental frequency (fo), intensity, frequency and intensity range, Dysphonia Severity Index (DSI), Acoustic Voice Quality Index (AVQI), Voice Handicap Index (VHI), Trans Woman Voice Questionnaire (TWVQ), and visual analogue scales (VAS) measuring client's satisfaction. Listener perceptions of masculinity-femininity were collected using a listening experiment. RESULTS: Significant differences over time were found for all fo and intensity parameters, DSI, AVQI, VHI and TWVQ scores. Listener perception and self-perception of femininity was higher after surgery. Significant differences in evolution of listener perceptions were found between the groups with and without voice therapy. CONCLUSION: Glottoplasty improves voice related quality of life and is an effective method to increase the fo and associated perceptual femininity. After glottoplasty an immediate and short-term decrease in voice quality, vocal capacity and frequency range was measured with a progressive recovery on the longer term. Long term side effects of glottoplasty are a reduction in speaking intensity and intensity range. Voice therapy seems to improve the outcomes of glottoplasty, but should be further investigated in future studies.

Intonation Parameters in Gender Diverse People.

OBJECTIVES/HYPOTHESIS: Although intonation is often addressed in speech training for gender diverse individuals, the relationship between intonation and femininity/masculinity ratings remains unclear. The aim of this study was to examine differences in intonation parameters in gender diverse individuals. Moreover, the relationship between acoustic intonation parameters and femininity/masculinity ratings was investigated. METHODS: Speech samples of semistructured speech were elicited from cisgender (cis) (107 ciswomen, 104 cis men), transgender (trans) (19 trans women, 10 trans men), and non-binary (n = 11) individuals using a prosody protocol. An objective acoustic analysis was performed to compare intonation parameters (upward/downward/flat intonation shift, general and final intonation shift, general fundamental frequency range, fundamental frequency variation index) between groups. In addition, a listening experiment was conducted, consisting of a cis and gender diverse listening panel (n = 41). The listeners were asked to rate the femininity/masculinity of speech samples (n = 57) using a visual analogue scale. Correlational analyses were used to examine the relationship between intonation parameters and femininity/masculinity ratings. RESULTS: Similarity was found in the intonation parameters of participants with a similar gender identity. In non-binary speakers, no significant differences in acoustic intonation parameters were found between these speakers and the cisgender speakers. In addition, no significant correlations were found between the acoustic intonation parameters and the femininity/masculinity ratings in the groups with cis men, cis women, and non-binary participants. However, moderate to strong significant correlations were found between acoustic intonation parameters and femininity/masculinity ratings in the trans participants. CONCLUSIONS: Intonation is a "speech marker" that distinguishes between groups with a different gender identity. No relationship was observed between intonation and femininity/masculinity ratings for cisgender and non-binary speakers. However, the significant relationship between these parameters for transgender participants (trans men and trans women) provides evidence for intonation exercises in gender affirming voice, speech, and communication training, and therefore contribute to evidence-based intonation training in transgender persons.

Longitudinal Vocal Outcomes and Voice-Related Quality of Life After Selective Bilateral Laryngeal Reinnervation: A Case Study.

PURPOSE: Bilateral vocal fold paralysis (BVFP) is a severe disorder that can result in respiratory, swallowing, and voice-related problems. Most surgical treatments do not restore laryngeal function and often need to compromise voice quality to preserve respiratory function. Laryngeal reinnervation (LR) may offer a solution to this problem, but literature on longitudinal outcomes of this procedure is scarce. This study aims to report the longitudinal vocal outcomes of BVFP after LR and subsequent voice therapy. METHOD: The case of a 23-year-old man with BVFP after a traumatic dissection of both recurrent laryngeal nerves is described. Selective bilateral LR of both adductors and abductors was performed 5 months after the onset of BVFP. Voice therapy was provided after the LR procedure. Multidimensional voice assessments, including acoustic, perceptual, and patient-reported outcome measures (PROMs), were conducted 2, 5, 6.5, 8, and 31 months after LR. RESULTS: An improvement of vocal capabilities and voice quality was noticed 6.5 months after LR, after 4.5 months of voice therapy, with normative values after 2.5 years. PROMs showed an improvement of voice-related quality of life, but some limitations to activities of daily living were still present. Inspiratory arytenoid abduction was not observed on laryngeal videostroboscopic findings in this patient, but tracheostomy was not required. CONCLUSIONS: Voice therapy after LR helps establish healthy and efficient voice use without increasing compensatory hyperfunctional behavior. More research is needed to examine potential merits of voice therapy in the rehabilitation of vocal and respiratory functions after LR.

Short-Term Acoustic Effects of Speech Therapy in Transgender Women: A Randomized Controlled Trial.

PURPOSE: This study measured and compared the acoustic short-term effects of pitch elevation training (PET) and articulation-resonance training (ART) and the combination of both programs, in transgender women. METHOD: A randomized controlled study with cross-over design was used. Thirty transgender women were included and received 14 weeks of speech training. All participants started with 4 weeks of sham training; after which they were randomly assigned to one of two groups: One group continued with PET (5 weeks), followed by ART (5 weeks); the second group received both trainings in opposite order. Participants were recorded 4 times, in between the training blocks: pre, post 1 (after sham), post 2 (after training 1), and post 3 (after training 2). Speech samples included a sustained vowel, continuous speech during reading, and spontaneous speech and were analyzed using Praat software. Fundamental frequency (f o), intensity, voice range profile, vowel formant frequencies (F 1-2-3-4-5 of /a/-/i/-/u/), formant contrasts, vowel space, and vocal quality (Acoustic Voice Quality Index) were determined. RESULTS AND CONCLUSIONS: Fundamental frequencies increased after both the PET and ART program, with a higher increase after PET. The combination of both interventions showed a mean increase of the f o of 49 Hz during a sustained vowel, 49 Hz during reading, and 29 Hz during spontaneous speech. However, the lower limit (percentile 5) of the f o during spontaneous speech did not change. Higher values were detected for F 1-2 of /a/, F 3 of /u/, and vowel space after PET and ART separately. F 1-2-3 of /a/, F 1-3-4 of /u/, vowel space, and formant contrasts increased after the combination of PET and ART; hence, the combination induced more increases in formant frequencies. Intensity and voice quality measurements did not change. No order effect was detected; that is, starting with PET or ART did not change the outcome.

Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors.

BACKGROUND: Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated. OBJECTIVE: We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors. METHODS: Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining. RESULTS: Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5. CONCLUSION: Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions.

Home-based intensive treatment of chronic radiation-associated dysphagia in head and neck cancer survivors (HIT-CRAD trial).

BACKGROUND: Chronic radiation-associated dysphagia (C-RAD) is considered to be one of the most severe functional impairments in head and neck cancer survivors treated with radiation (RT) or chemoradiation (CRT). Given the major impact of these late toxicities on patients' health and quality of life, there is a strong need for evidence-based dysphagia management. Although studies report the benefit of strengthening exercises, transference of changes in muscle strength to changes in swallowing function often remains limited. Therefore, combining isolated strengthening exercises with functional training in patients with C-RAD may lead to greater functional gains. METHODS: This 3-arm multicenter randomized trial aims to compare the efficacy and possible detraining effects of mere strengthening exercises (group 1) with a combination of strengthening exercises and functional swallowing therapy (group 2) and non-invasive brain stimulation added to that combination (group 3) in 105 patients with C-RAD. Patients will be evaluated before and during therapy and 4 weeks after the last therapy session by means of swallowing-related and strength measures and quality of life questionnaires. DISCUSSION: Overall, this innovative RCT is expected to provide new insights into the rehabilitation of C-RAD to optimize post-treatment swallowing function. TRIAL REGISTRATION: International Standard Randomized Controlled Trials Number (ISRCTN) registry ID ISRCTN57028065. Registration was accepted on 15 July 2021.

Effects of speech therapy for transgender women: A systematic review.

Background: For transgender women, communication and speech characteristics might not be congruent with their gender expressions. This can have a major influence on their psychosocial functioning. Higher quality of life scores were observed the more their voice was perceived as feminine. Speech language pathologists may play an important role in this, as the gender affirming hormone treatment for transgender women does not affect the voice. Aim: This systematic review aimed to provide speech and language pathologists with the current literature concerning the effects of speech therapy in transgender women in terms of acoustic and perceptual outcomes. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for reporting this systematic review. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (using the PubMed interface) and Embase (using the embase.com interface) were used as electronic databases. All individual studies which measured the effects of speech therapy in transgender women were evaluated with a risk of bias assessment tool and levels of evidence. Relevant data were extracted from these studies and a narrative synthesis was performed. Results: 14 studies were identified through the databases and other sources. These studies show positive outcome results concerning pitch elevation, oral resonance, self-perception and listener perception. However, methodological issues contribute to problems with generalization and reproducibility of the studies. Conclusion: There is an urgent need for effectiveness studies using RCT designs, larger sample sizes, multidimensional voice assessments, well-described therapy programs, investigators blinded to study process, and longer-term follow-up data. Speech and language pathologists who work with transgender women may find these results essential for defining therapy goals.

Effect of tongue-strengthening exercises on tongue strength and swallowing-related parameters in chronic radiation-associated dysphagia.

BACKGROUND: Radiation-associated dysphagia (RAD) is highly prevalent in head and neck cancer (HNC) patients, with insufficient tongue strength (TS) as a characteristic of this disabling complication. The effects of tongue-strengthening exercises (TSE) on TS, swallowing, and quality of life (QoL) have not been studied in this population. METHODS: A prospective phase 2 study using an 8 weeks during TSE protocol was carried out in 15 patients with chronic RAD. Outcome parameters were maximal isometric pressure (MIP), TS during swallowing (Pswal), swallowing function, and QoL. All parameters were evaluated at baseline, after 4 and 8 weeks of training, and 4 weeks after the last training session. RESULTS: MIP increased significantly, without detraining effects. Pswal did not increase significantly, but relevant effect sizes were measured. Swallowing function ameliorated, but did not result in increased functional oral intake, self-reported outcome or QoL. CONCLUSION: TSE in patients with RAD results in increased strength and swallowing function.

Very late xerostomia, dysphagia, and neck fibrosis after head and neck radiotherapy.

BACKGROUND: Acute and late toxicity after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC) impacts on patient quality of life; yet, very late toxicity data remain scarce. This study assessed dysphagia, xerostomia, and neck fibrosis 3-8 years after IMRT. METHODS: A retrospective analysis using generalized estimated equations was performed on 60 patients with HNC treated with fractionated IMRT between 2000 and 2015 who had a follow-up ≥8 years. Toxicity was scored using LENT-SOMA scales. RESULTS: A trend towards a nonlinear global time effect (P = .05) was noted for dysphagia with a decrease during the 5 years post-treatment and an increase thereafter. A significant decrease in xerostomia (P = .001) and an increase in neck fibrosis (P = .04) was observed until 8 years. CONCLUSIONS: Dysphagia, xerostomia, and neck fibrosis do not appear stable over time and remain highly prevalent in the very late follow-up. Our findings support the need for prospective trials investigating very late toxicity in patients with HNC.

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

BACKGROUND: Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. OBJECTIVE: We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. METHODS: In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1ß, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-ß1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering. RESULTS: Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE. CONCLUSION: Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

Prevalence of allergic sensitization versus allergic rhinitis symptoms in an unselected population.

BACKGROUND: Allergic rhinitis (AR) is the most common allergic disorder and its prevalence has significantly increased worldwide, nowadays affecting up to 40% of the population in young adults. The objective of the present survey was to evaluate the prevalence of allergic sensitization and the prevalence of clinically diagnosed AR in a sample of the Belgian population, and to estimate the effect of age and gender. METHODS: We performed a cross-sectional population-based study at an annual public fair in Ghent. Participants underwent a skin prick test (SPT) to 3 aeroallergens: a mix of trees (hazel, alder, and birch), grass pollen, and house dust mite (HDM). The clinical relevance of sensitization was assessed by relating relevant symptoms of AR to the corresponding SPT. RESULTS: A total of 2,320 participants (1,475 females, median age 44.7 years, range 3-86) were included in this study. The standardized prevalence rates of sensitization were 13.2% for tree mix, 25.9% for grass pollen, and 25.9% for HDM. Sensitization to at least one of the allergens was present in 40.3% of the subjects. Symptomatic sensitization related to trees was reported in 9.7% of cases, grass-related AR was 17.6%, and HDM-related AR was 17.1%. The overall prevalence of AR was 30.9%. CONCLUSION: In this study we demonstrated a 40.3% prevalence of a positive SPT to one or more common aeroallergens. A clinical diagnosis of AR was present in 30.9% of cases, peaking in the third and fourth decades of life. It is to be expected that in the next decades, when this generation grows older, the general AR prevalence will further increase.

Local inflammation in chronic upper airway disease.

Chronic Rhinosinusitis (CRS), a chronic upper airway inflammation, is an inflammation of the nose and the paranasal cavities and is highly prevalent. Chronic rhinosinusitis is currently classified as CRS with nasal polyps or CRS without nasal polyps. This review highlights the pathophysiological differences in CRS on remodeling and on T-cell patterns. Nasal polyps have a high co-morbidity with the lower airway inflammatory disease, asthma. Evidence is accumulating for the role of superantigens, Staphylococcus aureus enterotoxins, in CRS with nasal polyps and asthma, both T helper 2 -biased diseases. Until today there are no biomarkers involved in the diagnosis of CRS or the treatment follow-up. Further differentiation of the phenotype of the disease is needed, which will reflect in the development of new biomarkers and in new innovative treatment options. Defining and predicting response to therapy in individual CRS patients is a challenge for future research.

RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP.

BACKGROUND: The receptor for advanced glycation end products (RAGE) is a multiligand receptor that exists as a membrane-bound (mRAGE) form and a soluble (sRAGE) form. RAGE is reported to play a role in diverse pathologies including lower airway conditions, but the exact mechanism of action remains poorly understood. In the upper airways, the involvement of RAGE remains completely unexplored. OBJECTIVE: To investigate the involvement of RAGE in the human upper airway conditions chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Protein levels of sRAGE, mRAGE, IL-5, and eosinophil cationic protein (ECP) were quantitatively assessed in inflamed tissue of CRSsNP and CRSwNP patients. Nasal tissue of subjects without disease served as control. Ex vivo human sinonasal tissue stimulation assays were used to assess the effect of Staphylococcus aureus and ECP on sRAGE processing. RESULTS: sRAGE protein levels were higher in CRSsNP tissue, whereas mRAGE protein levels were lower than in controls. In CRSwNP patients, both tissue sRAGE and mRAGE protein levels were reduced. Low tissue sRAGE protein concentrations were associated with high IL-5 and ECP protein levels. In vitro, S aureus induced the release of sRAGE from the tissue, while ECP was shown to be implicated in the breakdown of free sRAGE. CONCLUSIONS: We demonstrate for the first time that RAGE protein is highly expressed in human upper airways under normal physiology and that it is subject to differential processing in CRSsNP and CRSwNP, identifying S aureus and ECP as novel and crucial players in this process.

Pathogenesis of chronic rhinosinusitis: inflammation.

Chronic rhinosinusitis (CRS) is a heterogeneous group of inflammatory diseases of the nasal and paranasal cavities either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP). CRSsNP and CRSwNP are prevalent medical conditions associated with substantial impaired quality of life, reduced workplace productivity, and serious medical treatment costs. Despite recent research evidence that contributes to further unveiling the pathophysiology of these chronic airway conditions, the cause remains poorly understood and appears to be multifactorial. A diverse spectrum of alterations involving histopathology, inflammatory cell and T-cell patterns, remodeling parameters (eg, TGF-ß), eicosanoid and IgE production, microorganisms, and epithelial barrier malfunctions is reported in the search to describe the pathogenesis of this heterogeneous group of upper airway diseases. Furthermore, novel evidence indicates considerable heterogeneity within the CRSwNP subgroup determining the risk of comorbid asthma. The characterization of specific disease subgroups is a challenging scientific and clinical task of utmost importance in the development of diagnostic tools and application of individualized treatments. This review focuses on recent evidence that sheds new light on our current knowledge regarding the inflammatory process of CRS to further unravel its pathogenesis.

Pathophysiology of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS), a disease presenting with chronic symptoms such as nasal obstruction, rhinorrhea, hyposmia and facial pain, is highly prevalent and has a considerable impact on quality of life and health care expenditures. The disease is characterized by chronic inflammation of the sinonasal mucosa and can present with nasal polyps. Current consensus classifies CRS into CRS with nasal polyps and CRS without nasal polyps. This review illustrates the diversity of pathophysiological observations in CRS and highlights selected etiological hypotheses. A wide spectrum of alterations is described regarding histopathology, pattern of T cells and inflammatory effector cells, remodeling, immunoglobulin production, chemokine and eicosanoid production, and the role of microorganisms. The pathophysiological diversity observed in CRS seems to stand in contrast to its nonspecific clinical presentation, but is of the utmost importance in the development and application of highly individualized treatments. Identification of specific disease subgroups and their etiologies is an important and challenging task for future research.