Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.

Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161.

Innate lymphoid cells (ILCs) are emerging as a family of effectors and regulators of innate immunity and tissue remodeling. Interleukin 22 (IL-22)- and IL-17-producing ILCs, which depend on the transcription factor RORγt, express CD127 (IL-7 receptor α-chain) and the natural killer cell marker CD161. Here we describe another lineage-negative CD127(+)CD161(+) ILC population found in humans that expressed the chemoattractant receptor CRTH2. These cells responded in vitro to IL-2 plus IL-25 and IL-33 by producing IL-13. CRTH2(+) ILCs were present in fetal and adult lung and gut. In fetal gut, these cells expressed IL-13 but not IL-17 or IL-22. There was enrichment for CRTH2(+) ILCs in nasal polyps of chronic rhinosinusitis, a typical type 2 inflammatory disease. Our data identify a unique type of human ILC that provides an innate source of T helper type 2 (T(H)2) cytokines.

Trajectories of early-onset rhinitis in the Singapore GUSTO mother-offspring cohort.

BACKGROUND: The natural history of childhood rhinitis is not well described. OBJECTIVE: This study aimed to identify different rhinitis trajectories in early childhood and their predictors and allergic associations. METHODS: Rhinitis symptoms were ascertained prospectively from birth until 6 years using standardized questionnaires in 772 participants. Rhinitis was defined as one or more episodes of sneezing, runny and/or blocked nose >2 weeks duration. Latent trajectories were identified using group-based modelling, and their predictive risk factors and allergic associations were examined. RESULTS: Three rhinitis trajectory groups were identified: 7.6% (n = 59) were termed early transient rhinitis, 8.6% (n = 66) late transient rhinitis, and 6.6% (n = 51) persistent rhinitis. The remaining 77.2% (n = 596) were classified as non-rhinitis/reference group. Early transient rhinitis subjects were more likely of Indian ethnicity, had siblings, reported childcare attendance, early wheezing and eczema in the first 3 years of life. Late transient rhinitis was associated with antenatal exposure to smoking, higher maternal education levels, and wheezing at age 36-72 months. Persistent rhinitis was associated with male gender, paternal and maternal history of atopy, eczema, and house dust mite sensitization. CONCLUSIONS & CLINICAL RELEVANCE: Risk factors for early transient rhinitis involve a combination of genetic and early environmental exposures, whereas late transient rhinitis may relate to maternal factors and early respiratory infections independent of atopy. In contrast, persistent rhinitis is strongly associated with atopic risk and likely represents the typical trajectory associated with allergic disorders. Allergic rhinitis symptoms may commence as early as the first year of life and may inform development of early interventive strategies.

Data Science-Based Analysis of Patient Subgroup Structures Suggest Effects of Rhinitis on All Chemosensory Perceptions in the Upper Airways.

Viral rhinitis contributes significantly to olfactory dysfunction, but it is unclear how many patients have other chemosensory symptoms in addition to olfactory loss. This was addressed in the present reanalysis of data previously published in Pellegrino R, Walliczek-Dworschak U, Winter G, Hull D, Hummel T. 2017. Investigation of chemosensitivity during and after an acute cold. Int Forum Allergy Rhinol. 7(2):185-191, using unsupervised and supervised machine-learning methods. Fifty-eight patients with acute rhinitis and 59 healthy controls were assessed for orthonasal and retronasal olfactory function, taste, and intranasal trigeminal sensitivity. Unsupervised analysis showed that during rhinitis, clinical scores of olfactory function, expressed as threshold, discrimination, identification (TDI) values, were trimodally distributed. Two minor modes were separated from the main mode at TDI = 30.5, which corresponds to the established limit of hyposmia. This trimodal distribution was not observed after the rhinitis subsided. Olfactory function was not significantly impaired in 40% of all rhinitis patients, whereas it was transiently impaired in 59%. For this group, supervised machine-learning algorithms could be trained with information on retronasal olfactory function, gustatory function, and trigeminal sensitivity to assign patients to subgroups based on orthonasal olfactory function with a balanced classification accuracy of 64-65%. The ability to recognize patients with olfactory loss based on retronasal olfactory function as well as gustatory function and trigeminal sensitivity suggests in turn that these modalities are affected by rhinitis. However, the only modest accuracy at which this information allowed to reproduce the olfactory diagnosis indicated they are involved in the symptomatology of rhinitis to a lesser extent compared with the orthonasal olfactory function.

The real-world "ControL'Asma" study: a nationwide taskforce on asthma control in children and adolescents.

BACKGROUND: Asthma control is the goal of asthma management. A nationwide study on this aspect was launched by the Italian Society of Paediatric Allergy and Immunology (ControL'Asma study). OBJECTIVE: To define variables associated with different asthma control grades in a nationwide population of asthmatic children and adolescents. METHODS: This cross-sectional real-world study included 480 asthmatic children and adolescents (333 males, median age 11.2 years) consecutively enrolled in 10 third level pediatric allergy clinics. According to the Global Initiative for Asthma (GINA) document, history, medication use, perception of asthma symptoms assessed by visual analog scale (VAS), clinical examination, lung function, childhood asthma control test (cACT)/asthma control test (ACT), and asthma control level were evaluated. RESULTS: Considering GINA criteria, asthma was well controlled in 55% of patients, partly controlled in 32.4%, and uncontrolled in 12.6%. Regarding cACT/ACT, asthma was uncontrolled in 23.2%. Patients with uncontrolled asthma had the lowest lung function parameters and VAS scores, more frequent bronchial obstruction and reversibility, and used more oral and inhaled corticosteroids (CS). CONCLUSIONS: The ControL'Asma study, performed in a real-world setting, showed that asthma in Italian children and adolescents was usually more frequent in males. Asthmatic patients had an early onset and allergic phenotype with very frequent rhinitis comorbidity. Uncontrolled and partly controlled asthma affected about half of the subjects, and the assessment of asthma symptom perception by VAS could be a reliable tool in asthma management.

Effects of Wnt signaling on epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood. OBJECTIVE: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues. METHODS: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients. RESULTS: ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear ß-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear ß-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP. CONCLUSION: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.

Impaired small airway function in non-asthmatic chronic rhinosinusitis with nasal polyps.

BACKGROUND: There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non-asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non-asthmatic patients with CRSwNPs remains unclear. OBJECTIVE: This study analysed the lung function of non-asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs. METHODS: The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non-asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients. RESULTS: Non-asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF75 ) and FEF50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non-asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF50 was associated with the recurrence of non-asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type-2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non-asthmatic CRSwNP patients was related to serum IgE levels. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence that non-asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type-2 inflammation.

Chronic invasive fungal rhinosinusitis vs sinonasal squamous cell carcinoma: the differentiating value of MRI.

OBJECTIVES: To investigate MRI features in discriminating chronic invasive fungal rhinosinusitis (CIFRS) from sinonasal squamous cell carcinomas (SNSCC). METHODS: MRI findings of 33 patients with CIFRS and 47 patients with SNSCC were retrospectively reviewed and compared. Multivariate logistic regression analysis was performed to identify significant imaging features in distinguishing between CIFRS and SNSCC. The ROC curves and the AUC were used to evaluate diagnostic performance. RESULTS: There were significant differences in cavernous sinus involvement (p < 0.001), sphenoid sinus involvement (p < 0.001), meningeal involvement (p = 0.024), T2 signal intensity (p = 0.006), and enhancement pattern (p < 0.001) between CIFRS and SNSCC. Multivariate logistic regression analysis identified cavernous sinus involvement (odds ratio [OR] = 0.06, 95% confidence interval [95% CI] = 0.02-0.20) and sphenoid sinus involvement (OR = 0.14, 95% CI = 0.05-0.45) as significant indicators for CIFRS and T2 isointensity to gray matter (OR = 4.44, 95% CI = 1.22-16.22) was a significant indicator for SNSCC. ROC curve analysis showed the AUC from a combination of three imaging features was 0.95 in differentiating CIFRS and SNSCC. CONCLUSIONS: MRI showed significant differences between CIFRS and SNSCC features. In immunocompromised patients, a sinonasal hypointense mass on T2WI with septal enhancement or loss of contrast enhancement, and involvement of cavernous sinus, sphenoid sinus, and meninges strongly suggest CIFRS. KEY POINTS: • Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from sinonasal squamous cell carcinomas (SNSCC) in clinical practice. • Cavernous sinus and sphenoid sinus involvement appear to be significant indicators for CIFRS. T2 isointensity to gray matter appears to be a significant indicator for SNSCC. • Loss of contrast enhancement and septal enhancement can be used to distinguish CIFRS from SNSCC with a high degree of specificity.

Janus looks both ways: How do the upper and lower airways interact?

Our understanding of the relationship between the upper and lower airways has greatly increased as a consequence of epidemiologic and pharmacologic studies. A consistent body of scientific evidence supports the concept that rhinitis, rhinosinusitis and asthma may be the expression of a common inflammatory process, which manifests at different sites of the respiratory tract, at different times. This paradigm states that allergic reactions may begin at the local mucosa, but tend to propagate along the airway. Central to the allergic diathesis is the eosinophil and its interaction with the airway epithelium. The implications of the interplay between upper and lower airway are not only academic, but also important for diagnostic and therapeutic reasons. Furthermore, there is significant overlap in symptomatology and pathophysiology for childhood sleep disordered breathing (SDB) and asthma. Recent evidence supports an association between these two conditions, but causality has not been demonstrated. Regardless, it is important to recognize the overlap and evaluate for the other condition when one is present. In children with poorly controlled asthma, the presence of SDB may significantly contribute to asthma morbidity and, as such, should be actively excluded. On the other hand, clinical evaluation for asthma should be considered in children with SDB. Future robust longitudinal research is needed to explore the association between upper and lower airway diseases using objective measures in children.

Differences in self-reported symptoms in patients with chronic odontogenic and non-odontogenic rhinosinusitis.

PURPOSE: To evaluate the possible differences in self-reported symptoms between patients with chronic odontogenic rhinosinusitis (CORS) and patients with chronic non-odontogenic rhinosinusitis (CnORS). MATERIALS AND METHODS: The study included 64 patients diagnosed with chronic rhinosinusitis according to EPOS guidelines. 32 patients had CORS, and the control group were 32 patients with CnORS. Patients were matched according to gender and age. All the patients underwent a CT scan evaluated by a radiologist, and were evaluated by an oral surgeon and otorhinolaryngologist before being assigned to one of the groups. The severity of the symptoms was assessed through questioners SNOT-22 (sino-nasal outcome test) and VAS (visual analogue scale) symptom score. Kolmogorov-Smirnov's, Fisher's and Mann-Whitney U test were used in the statistical analysis of the data. RESULTS: People with CORS show similar symptomatology on SNOT-22 score to patients with CnORS, with no significant statistical difference between any of the SNOT-22 symptoms. VAS symptom score showed that odontogenic group had a significantly higher score for fever (p = .004) and halitosis (p = .003). CONCLUSION: Halitosis and fever might be the most important symptoms in differentiating between CORS and CnORS symptomatology. Better diagnostic tools, such as VAS symptom score might help medical professionals to be quicker at recognizing CORS specific symptomatology, and help them treat the disease as early and adequately as possible.

Type 1/type 2 inflammatory cytokines correlate with olfactory function in patients with chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction secondary to chronic rhinosinusitis (CRS) has been highly associated with impaired quality of life. Asian CRS patients showed a distinct inflammatory profile, with less type 2 endotype compared with European and North American. This study aimed to explore the pattern of the inflammatory cytokines in CRS patients from China and their association with olfactory function. METHODS: Institutional review board-approved prospective study in which the olfactory function of 71 CRS patients was assessed with Sniffin' Sticks before the nasal endoscopic surgery. A set of cytokines and inflammatory mediators including type 1 and type 2 inflammatory cytokines were measured in nasal mucus by using a multiplex flow cytometric bead assay (CBA). Baseline characteristics in CRS patients were collected and the Spearman r statistic was performed to assess the association of olfactory function with cytokines and inflammatory mediators. RESULTS: A total of 71 nasal mucus samples of CRS patients, including 25 chronic rhinosinusitis without nasal polyposis (CRSsNP) patients and 46 chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, were evaluated in this study. The nasal mucus levels of type 1 inflammatory cytokine IFN-γ (interferon-γ), type 2 inflammatory cytokines including IL-4, IL-5 and GM-CSF (granulocyte-macrophage colony-stimulating factor) and anti-inflammatory cytokine IL-10 were significantly and inversely correlated with olfactory function in total patients with CRS (r = -0.308, p = 0.009; r = -0.250, p = 0.036; r = -0.399, p = 0.001; r = -0.269, p = 0.023; r = -0.273, p = 0.021, respectively). In CRSsNP, the olfactory function was inversely correlated with levels of type 1 inflammatory cytokine TNF-α (tumor necrosis factor-α) (r = -0.637, p = 0.001) and IL-10 (r = -0.468, p = 0.018). Nevertheless, the olfactory function in CRSwNP was inversely correlated with type 2 inflammatory cytokines including IL-4 (r = -0.303, p = 0.041) and IL-5 (r = -0.383, p = 0.009). CONCLUSION: Both type 1 and type 2 inflammatory cytokines may contribute to the pathogenesis of CRS-associated olfactory dysfunction in the Chinese population.

Is there "hidden hearing loss" in patients with chronic rhinosinusitis?

Objective: This study was to investigate whether there is impairment of auditory function in chronic rhinosinusitis (CRS).Study sample: A total of 85 patients were allocated into either the CRS group (n = 65) or a simple deviated nasal septum group (n = 20). Both groups without other risk factors for sensorineural hearing loss exhibited normal thresholds at standard audiometric frequencies. Another group (n = 30) of healthy subjects without CRS or a deviated nasal septum were gender and age matched.Design: Analyse the results of audiology test including pure tone audiometry, an acoustic impedance test, distortion product otoacoustic emissions (DPOAE) and the auditory brainstem response (ABR) for each subject analyse the test results of for each object.Results: The group differences were statistically significant for each high-frequency pure tone (p < 0.05). The ABR showed a difference between groups in amplitude. The DPOAE pass rate of the CRS group was lower than that of the control group.Conclusions: This study showed a significant correlation between CRS and auditory impairment. CRS might impair cochlear functions by damaging inner ear hair cells and/or, outer hair cells (OHCs), consequently altering the activity of the entire auditory pathway originating in the ventral cochlear nucleus (VCN) to the inferior colliculus.

NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis.

BACKGROUND: Chronic rhinosinusitis is common and sometimes complicated by nasal polyps (NPs). Corticosteroid nasal sprays are often unsatisfactory because they are ineffective at delivering medication to high/deep sites of inflammation. OBJECTIVE: We sought to assess whether an exhalation delivery system with fluticasone (EDS-FLU) capable of high/deep drug deposition improves outcomes. METHODS: Patients (n = 323) 18 years and older with moderate-to-severe congestion and NPs were randomized to twice-daily EDS-FLU (93, 186, or 372 µg) or exhalation delivery system (EDS)-placebo for 24 weeks (16 double-blind plus 8 open-label when all received 372 µg). Coprimary end points were change in nasal congestion/obstruction at 4 weeks and summed bilateral polyp grade at 16 weeks. Secondary end points included symptoms, polyp elimination, and functioning. RESULTS: EDS-FLU was superior on both coprimary end points (P < .001 vs EDS-placebo, all doses). Mean polyp grade improved continuously through week 24 (P < .009, all comparisons), with polyps eliminated on at least 1 side in approximately 25% of patients at week 24 versus 8.7% with EDS-placebo (P ≤ .014, all comparisons). Sino-Nasal Outcomes Test scores also improved significantly versus those in patients receiving EDS-placebo (-21.1 to -21.4 vs -11.7 at week 16, P < .05 all doses). At the end of the double-blind period, EDS-FLU (all doses) significantly improved all 4 defining disease symptoms. In most patients (68%), those receiving EDS-FLU reported "much" or "very much" improvement. The number of patients eligible for surgery decreased by 62%-67%. The safety profile was similar to that reported in prior trials evaluating conventional corticosteroid nasal sprays in comparable populations. CONCLUSION: EDS-FLU produces clinically and statistically significant improvement in all 4 diagnostically defining disease symptoms, polyp grade, and quality of life in patients with chronic rhinosinusitis with NPs.

Type 2/Th2-driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic inflammatory disease often accompanied by impairment of sense of smell. This symptom has been somewhat overlooked, and its relationship to inflammatory cytokines, tissue compression, neuronal loss, and neurogenesis is still unclear. METHODS: In order to elucidate potential mechanisms leading to CRS in humans, we have established a type 2/T helper type 2 cell (Th2)-mediated allergic CRS mouse model, based on house dust mite (HDM) and Staphylococcus aureus enterotoxin B (SEB) sensitization. The inflammatory status of the olfactory epithelium (OE) was assessed using histology, biochemistry, and transcriptomics. The sense of smell was evaluated by studying olfactory behavior and recording electro-olfactograms (EOGs). RESULTS: After 22 weeks, a typical type 2/Th2-mediated inflammatory profile was obtained, as demonstrated by increased interleukin (IL)-4, IL-5, and IL-13 in the OE. The number of mast cells and eosinophils was increased, and infiltration of these cells into the olfactory mucosa was also observed. In parallel, transcriptomic and histology analyses indicated a decreased number of immature olfactory neurons, possibly due to decreased renewal. However, the number of mature sensory neurons was not affected and neither the EOG nor olfactory behavior was impaired. CONCLUSION: Our mouse model of CRS displayed an allergic response to HDM + SEB administration, including the type 2/Th2 inflammatory profile characteristic of human eosinophilic CRSwNP. Although the sense of smell did not appear to be altered in these conditions, the data reveal the influence of chronic inflammation on olfactory neurogenesis, suggesting that factors unique to humans may be involved in CRSwNP-associated anosmia.

Impact of IgE sensitization and rhinitis on inflammatory biomarkers and lung function in adolescents with and without asthma.

BACKGROUND: Both allergic and non-allergic rhinitis are associated with worse asthma control. However, it is unclear how IgE sensitization and/or rhinitis are associated with lung function. We therefore evaluated the effect of rhinitis and sensitization on lung function, including the periphery of the airway system, and inflammatory biomarkers in individuals with and without asthma. METHODS: Participants in the BAMSE longitudinal birth cohort study underwent measures of spirometry, impulse oscillometry, and FeNO at age 16 years. Questionnaires were used to obtain data on asthma and rhinitis. Blood samples were analyzed for eosinophils and allergen-specific IgE. RESULTS: Groups based on the combination of asthma, rhinitis, and sensitization were compared to a healthy reference group. Lower FEV1 /FVC levels were seen for groups with asthma only (adjusted mean difference -2.8% units (95% CI -4.7; -1.0), P < 0.01), asthma with sensitization (-2.0 (-3.9; -0.2), P < 0.05), and asthma with sensitization and rhinitis (-2.5 (-3.6; -1.4), P < 0.001). The index of peripheral airway resistance R5-20 was higher in groups with asthma and sensitization (adjusted median difference 94.9 Pa L-1  s-1 (95% CI 60.4; 129.3), P < 0.001), as well as asthma with sensitization and rhinitis (36.9(15.0; 58.8), P < 0.01). These groups also had increased FeNO and blood eosinophil levels. CONCLUSIONS: We found signs of peripheral airway obstruction and increased levels of inflammatory biomarkers in the presence of allergic asthma, irrespective of rhinitis status. Despite having a reduced FEV1 /FVC, peripheral airway engagement was not seen in non-sensitized adolescents with asthma. We suggest that small airway disease is a feature related to the eosinophilic inflammation in allergic asthma in adolescence.

Accuracy of Signs and Symptoms for the Diagnosis of Acute Rhinosinusitis and Acute Bacterial Rhinosinusitis.

PURPOSE: To evaluate the accuracy of signs and symptoms for the diagnosis of acute rhinosinusitis (ARS). METHODS: We searched Medline to identify studies of outpatients with clinically suspected ARS and sufficient data reported to calculate the sensitivity and specificity. Of 1,649 studies initially identified, 17 met our inclusion criteria. Acute rhinosinusitis was diagnosed by any valid reference standard, whereas acute bacterial rhinosinusitis (ABRS) was diagnosed by purulence on antral puncture or positive bacterial culture. We used bivariate meta-analysis to calculate summary estimates of test accuracy. RESULTS: Among patients with clinically suspected ARS, the prevalence of imaging confirmed ARS is 51% and ABRS is 31%. Clinical findings that best rule in ARS are purulent secretions in the middle meatus (positive likelihood ratio [LR+] 3.2) and the overall clinical impression (LR+ 3.0). The findings that best rule out ARS are the overall clinical impression (negative likelihood ratio [LR-] 0.37), normal transillumination (LR- 0.55), the absence of preceding respiratory tract infection (LR- 0.48), any nasal discharge (LR- 0.49), and purulent nasal discharge (LR- 0.54). Based on limited data, the overall clinical impression (LR+ 3.8, LR- 0.34), cacosmia (fetid odor on the breath) (LR+ 4.3, LR- 0.86) and pain in the teeth (LR+ 2.0, LR- 0.77) are the best predictors of ABRS. While several clinical decision rules have been proposed, none have been prospectively validated. CONCLUSIONS: Among patients with clinically suspected ARS, only about one-third have ABRS. The overall clinical impression, cacosmia, and pain in the teeth are the best predictors of ABRS. Clinical decision rules, including those incorporating C-reactive protein, and use of urine dipsticks are promising, but require prospective validation.

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on transcription factor expression and cytokine production patterns in different innate lymphoid cell (ILC) types, in parallel with those of adaptive CD4+ T-helper (TH) cells and CD8+ cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging for the immune response deviation into type 1 (orchestrated by ILC1s and Tc1, and TH1 cells), type 2 (characterized by ILC2s and Tc2 and TH2 cells), and type 3 (mediated by ILC3s and Tc17 and TH17 cells). In addition, cluster analysis has been applied to endotyping of CRS in recent years, which has provided additional novel insights into CRS pathogenesis. This review assessed pathologic mechanisms of CRS based on type 1, 2, and 3 immune responses and how they inform us to begin to understand CRS endotypes. This review also assessed recent cluster analysis studies of CRS endotypes. The impact of endotype on therapeutic management of CRS also is summarized. DATA SOURCES: Review of published literature. STUDY SELECTIONS: Relevant literature concerning CRS endotypes and possible underlying mechanisms was obtained from a PubMed search and summarized. RESULTS AND CONCLUSION: CRS with and without nasal polyps are composed of distinct endotypes with distinct deviated immune responses, pathogenic mechanisms, and different responses to medical and surgical treatment. An endotype of CRS with prominent type 2 immune responses is the best-studied endotype and generally can benefit from treatment with steroids and specific type 2 disrupting biologics.

Chronic Rhinosinusitis with Nasal Polyps in Older Adults: Clinical Presentation, Pathophysiology, and Comorbidity.

PURPOSE OF REVIEW: Chronic rhinosinusitis and nasal polyps (CRSwNP) is a common condition that significantly affects patients' life. This work aims to provide an up-to-date overview of CRSwNP in older adults, focusing on its aging-related clinical presentations, pathophysiology, and comorbidity associations including asthma. RECENT FINDINGS: Recent large population-based studies using nasal endoscopy have shown that CRSwNP is a mostly late-onset disease. Age-related changes in physiologic functions, including nasal epithelial barrier dysfunction, may underlie the incidence and different clinical presentations of CRSwNP in older adults. However, there is still a paucity of evidence on the effect of aging on phenotypes and endotypes of CRSwNP. Meanwhile, late-onset asthma is a major comorbid condition in patients with CRSwNP; they frequently present with type 2 inflammatory signatures that are refractory to conventional treatments when they are comorbid. However, as they are more commonly non-atopic, causative factors other than classical atopic sensitization, such as Staphylococcus aureus specific IgE sensitization, are suggested to drive the type 2 inflammation. There are additional comorbidity associations in older patients with CRSwNP, including those with chronic otitis media and head and neck malignancy. Age is a major determinant for the incidence and clinical presentations of CRSwNP. Given the heterogeneity in phenotypes and endotypes, longitudinal investigations are warranted to elucidate the effects of aging on CRSwNP.

Otolaryngologists adhere to evidence-based guidelines for chronic rhinosinusitis.

PURPOSE: To assess awareness of, opinion about and adherence to evidence-based guidelines on chronic rhinosinusitis among Dutch Otolaryngologists. METHODS: We assessed implementation of two guidelines, one Dutch and one European, that are both intended for diagnosis and treatment of patients with chronic rhinosinusitis. We invited 485 Otolaryngologists to fill out a questionnaire and report on their opinion on and adherence to the guidelines. The adherence was further tested by 4 clinical case scenarios, derived from guideline recommendations. RESULTS: 166 (34%) completed the questionnaire. 99% of the respondents was aware of one or both guidelines. Most respondents (90%) consider the guidelines as directing or supportive for their clinical practice based on the clinical case scenarios, between 62 and 99% of the respondents act according to guidelines. Concerning diagnosis, CT-imaging is performed more and allergy testing less than recommended. Where multiple treatment options are recommended, the responses are more heterogeneous as a result of this. Nonetheless, high recommended treatment was chosen more often. Otolaryngologists were reluctant in surgical treatment as a first option, which is according to the guidelines. CONCLUSIONS: Overall, both the EPOS and CBO guideline are well known among Dutch Otolaryngologists and 90% indicates that the guideline is important in their daily practice. Adherence to the guidelines is sufficient to high. If multiple treatment or diagnostic options are recommended this leads to a more heterogeneous response pattern. Recommendations with a high grade of recommendation were followed up most often.

Longitudinal improvement in nasal obstruction symptoms of chronic rhinosinusitis directly associates with improvement in mood.

PURPOSE: The effects of nasal obstruction in patients with chronic rhinosinusitis (CRS) are associated with depressed mood. We sought to validate this finding by determining whether improvement in nasal obstruction would translate to improvement in depressed mood. METHODS: This was a prospective observational study of 150 patients undergoing medical management for CRS. Data were collected at two timepoints: enrollment and a subsequent follow-up visit 3-12 months later. Impact of nasal obstruction was measured using the Nasal Obstruction Symptom Evaluation (NOSE) instrument and depressed mood was measured using the 2-item Patient Health Questionnaire (PHQ-2). Sinonasal symptoms associated with CRS were also measured using the 22-item Sinonasal Outcome Test (SNOT-22). Clinical and demographic characteristics were collected. The relationship between changes in PHQ-2 and NOSE scores was determined with correlation and linear regression. RESULTS: Change in PHQ-2 score was significantly correlated with change in NOSE score (ρ = 0.30, p < 0.001). After controlling for covariates, change in PHQ-2 score was associated with change in NOSE score (adjusted linear regression coefficient [ß] = 0.014, 95% CI 0.006-0.022, p = 0.001). We confirmed these relationships, finding that change in PHQ-2 was associated (adjusted ß = 0.037, 95% CI 0.013-0.061, p = 0.003) with change in the nasal subdomain score of the SNOT-22. Improvement in NOSE score by greater than 22 points was predictive of improvement in PHQ-2 score with sensitivity 54.5% and 83.8% specificity (p < 0.001). CONCLUSION: These results provide evidence that improvements in nasal manifestations/symptoms of CRS translate to significant improvements in mood.