Exploring the impact of inflammatory endotypes on olfactory function and quality of life in chronic rhinosinusitis patients

Abstract Objectives The aim of this observational cross-sectional study was to determine the endotypic inflammatory pattern of a sample of patients with CRS in Brazil, correlate it with olfactory function, and evaluate the clinical severity of the disease. Methods In this cross-sectional study, 73 CRS patients were recruited. Patients were classified into type 2 and non-type 2 endotypic patterns based on IgE and eosinophilia levels. All subjects performed the University of Pennsylvania Smell Identification Test (UPSIT®) and responded to the Sino-Nasal Outcome Test (SNOT-22). Results The majority of patients had type 2 CRS (n = 57, 78.1%). Patients with type 2 CRS compared to non-type 2 CRS had a higher prevalence of nasal polyps (93% vs. 12.5%), asthma (40.3% vs. 12.5%), and non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD, 17.5% vs. 0%). Type 2 patients also had significantly lower UPSIT® and higher SNOT-22, Lund-Kennedy, and Lund-Mackay scores. Conclusion Our study provides evidence that type 2 CRS is associated with a higher prevalence of nasal polyps, asthma, and NERD, as well as decreased olfactory function and worse quality of life scores. These data will contribute to the body of knowledge on CRS and the development of treatments for this disease in Brazil. Level of evidence: 3.

Clinical treatment options oriented to the endotype of chronic rhinosinusitis / 临床耳鼻咽喉头颈外科杂志

Chronic rhinosinusitis（CRS） is an inflammatory disease involving the mucosa of the nasal and paranasal sinuses for more than 12 weeks and can be classified as CRS with nasal polyp（CRSwNP） and CRS without nasal polyp（CRSsNP） depending on the phenotype. Clinical treatments reveal significant differences in disease prognosis and improvement in quality of life in patients with the same clinical phenotype. Inflammatory cells infiltration and inflammatory mediators are important factors driving CRS endotypes. In particular, CRS with predominantly eosinophilic infiltration and type 2 CRS present severe clinical symptoms, comorbidities, and high recurrence rates. CRS endotype-oriented treatment methods may better contribute to improving patient prognosis and quality of life. This article summarizes the current progress of CRS endotype research and reviews the endotype-oriented treatment options.

Recent research on the relationship between pulmonary microbiome and asthma endotypes in children / 中国当代儿科杂志

Bronchial asthma is not considered a singular disease, but rather a collection of syndromes with multiple phenotypes and mechanisms that involve various signaling pathways. It typically emerges during the preschool years, and its etiology is intricate and diverse. In recent years, the advancement of high-throughput sequencing technology has revealed that early alterations in lung microbiota may be associated with asthma incidence and progression. Moreover, significant variations in lung microbiota have been observed among different airway inflammation profiles, known as asthma endotypes. Hence, a comprehensive understanding of the characteristics of lung microbiota in children with asthma can aid in managing disease progression and improving long-term prognosis. Additionally, such insights may spark novel approaches to diagnosing and treating childhood asthma.

Predominant endotype of nasal polyps in a sample of Filipinos following endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis

Objective@#To determine the prevalence of eosinophilic and non-eosinophilic nasal polyps in Filipino patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) who underwent endoscopic sinus surgery. @*Methods@#Design: Retrospective Chart Review. Setting: Tertiary Government Training Hospital. Participants: A consecutive sample of adult patients who underwent endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis at the Rizal Medical Center from 2015-2019.@*Results@#Out of 66 patients who underwent endoscopic sinus surgery during the study period, 36 (54.55%) had an eosinophilic endotype while 30 (45.45%) had a non-eosinophilic endotype. @*Conclusion@#The slight predominance of eosinophilic nasal polyps found in our sample may suggest a contrasting trend compared to our Asian neighbors, who have a predominantly non[1]eosinophilic endotype – Indonesia (90.47%), Thailand (81.9%), South Korea (66.7%) and China (53.6%). However, this predominance is still lower than the 78-88% eosinophilia reported among Caucasians. Larger series may confirm these preliminary findings

Valoración de la calidad de vida en pacientes con asma severa posterior al tratamiento con biológicos en el marco de la medicina personalizada

RESUMEN El asma severa incluye un pequeño porcentaje de pacientes que varía de acuerdo a los diferentes países, aun así, los pacientes con asma grave no controlada tienen una morbilidad desproporcionadamente alta junto a una utilización de la asistencia sanitaria. Objetivos: Evaluar la respuesta al tratamiento con biológicos en pacientes asmáticos severos y la importancia de realizar la clasificación de fenotipo y endotipo, en una muestra de pacientes asmáticos severos entre 18 y 60 años de ambos sexos que concurrieron al servicio de Alergia e Inmunología del Hospital Nuevo San Roque, Córdoba, Argentina en el periodo marzo 2016 y marzo 2019. Material y métodos: Se realizó análisis de historia clínica, determinación de IgE, eosinófilos, clasificación de asma según GINA, espirometría, pruebas cutáneas, Test de control de Asma (Asthma control Test) (ACT) y respuesta según Evaluación Global Efectividad Tratamiento por el médico (Global evaluation of treatment effectiveness) (GETE). Resultados: Un total de 12 pacientes asmáticos severos, con test cutáneos positivos (Prick test), valores de IgE y eosinófilos elevados. En los valores espirometricos de pos BD, se observaron diferencias en las tres etapas de seguimiento, los valores iniciales fueron de 50,1 ± 4,4, aumentando a 83,5 ± 4,4 a los 6 meses, y con resultados medios de 88,5 ± 4,15 a los 12 meses. Los valores de ACT fueron al inicio 10,17 ± 1,44, a los 6 meses 22,33 ± 0,68 y al año de 24,67 ± 0,14. Puntaje GETE a los 6 meses, la mayoría de los pacientes refirió tener GETE control completo del asma (42%) o mejor control del asma (33%), mientras que el profesional que los asistió no refirió haber observado ningún paciente con nivel excelente mientras que el 75% fueron clasificados como mejor control del asma. Conclusión: La evaluación inicial correcta del paciente asmático y el tratamiento de precisión adecuado son las herramientas que deben aplicarse para obtener no solamente la remisión de las manifestaciones clínicas si no también una amplia mejoría en su calidad de vida.

ABSTRACT BACKGROUND Severe asthma includes a small percentage of patients that varies across different countries, yet patients with uncontrolled severe asthma have disproportionately high morbidity and healthcare utilization. Objectives: To assess the response to treatment with biologics in severe asthmatic patients and the importance of performing the phenotype and endotype classification in a sample of severe asthmatic patients between 18 and 60 years of age of both sexes who attended the Allergy and Immunology service of the Nuevo Hospital San Roque, Córdoba, Argentina from March 2016 to March 2019. Material and methods :Analysis of: medical history, measurement of laboratory parameters: IgE, eosinophils, asthma classification according to GINA, spirometry, skin tests, Asthma control Test (ACT) and response according to Global evaluation of treatment effectiveness (Global Evaluation Effectiveness Treatment by the doctor). Results: A total of 12 severe asthmatic patients, with positive Prick tests, elevated IgE and eosinophil values. Regarding spirometry: in the post BD values, differences were observed in the three stages of follow-up: the initial spirometry values were 50.1 ± 4.4, increasing to 83.5 ± 4.4 at 6 months, and with mean results of 88.5 ± 4.15 at 12 months. The ACT values were at baseline 10.17 ± 1.44, at 6 months 22.33 ± 0.68 and at one year: 24.67 ± 0.14. GETE score At 6 months, most of the GETE patients reported having complete asthma control (42%) or better asthma control (33%), while the professional who assisted them did not report having observed any patient with an excellent level; and 75% were classified as better asthma control. Conclusion: The correct initial evaluation of the asthmatic patient and the appropriate precision treatment are the tools that must be applied to obtain not only the remission of the clinical manifestations but also a broad improvement in their quality of life.

Phenotypes and endotypes of atopic dermatitis: Clinical implications

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, characterized by a complex pathophysiology and a variety of clinical phenotypes. However, heterogeneous clinical phenotypes are generally not considered in treating AD. To date, phenotypes and endotypes have been proposed to classify AD mainly based on differences in age, IgE, severity, race, skin barrier dysfunction, immune (Th2/Th17/Th22) polarization, and skin microbiome. Various biologics to target polarized immune pathways, including dupilumab, have been newly developed for the personalized treatment of moderate-to-severe AD. Further understanding of AD pathophysiology and identification of novel biomarkers will not only allow clinically useful stratification of AD and but also achieve precision medicine for the prevention and treatment of AD.

Biomarkers in Chronic Rhinosinusitis with Nasal Polyp: Personalized Medicine Based on Endotype / 대한이비인후과학회지

Chronic rhinosinusitis (CRS) is divided into CRS with nasal polyp (CRSwNP) and CRS without nasal polyp (CRSsNP) according to the presence of a nasal polyp. Some of the CRSwNP patients are relatively well managed without recurrences while others are difficult due to recurrence and refractoriness after surgical or medical treatment. Thus CRSwNP is not a single disease but is rather considered as a disease that has a variety of disease spectrum. Various biomarkers have been proposed to distinguish endotypes of CRSwNP. CRSwNP with high tissue eosinophil infiltration with robust type 2 inflammation (e.g., IL-5) is usually associated with comorbid asthma and is likely to recur. This type of CRSwNP is relatively common in Western countries. However, in Asian countries, CRSwNP is often presented as a heterogeneous disease comprising a mixture of type 1 (e.g., IFN-γ), type 2 and type 3 (e.g., IL-17) inflammation. In Asians, up-regulation of IL-8, IFN-γ and associated neutrophilic inflammation is prone to have disease refractoriness. Different underlying inflammatory profile indicates different underlying pathogenesis. Therefore, in the era of precision medicine, treatment should be based upon according to endotype.

Towards the heterogeneity of sepsis / 医学研究生学报

Sepsis is a heterogeneous syndrome which varies in etiology, pathogenesis, clinical manifestation, treatment and prognosis. According to the difference in these respects, sepsis can be divided into different phenotypes and endotypes, which may serve as valuable guidance in the individualized clinical treatment and precise prognostic judgment of the disease.

Obesity-Associated Metabolic Signatures Correlate to Clinical and Inflammatory Profiles of Asthma: A Pilot Study

PURPOSE: Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. METHODS: Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin (IL)-1β, -4, -5, -6, -13, and tumor necrosis factor (TNF)-α, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. RESULTS: Body composition, asthma control, and the levels of IL-1β, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. CONCLUSIONS: GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.

Biomarkers of adult asthma and personalized medicine

The concept of personalized medicine for disease diagnosis, treatment, and management, considering individual variability, including susceptibility, clinical manifestations, and drug responsiveness, is a global emerging trend in medicine, which is also inevitable. However, clinical applications of personalized medicine in the real-world practice have been limited to certain cancers so far. Furthermore, this new concept to the diagnosis and treatment of adult asthma has not been applied to clinical use. Asthma is a multifactorial and heterogeneous disease. It seems to encompass a broad spectrum of clinical manifestations with different underlying pathophysiological mechanisms. Thus, it is not easy to categorize by their clinical features alone. Endotypical categorization that considering specific pathophysiological mechanisms will be more helpful in applying the concept of personalized medicine. The success of personalized medicine depends on patient selection for precise prescription of asthma medications. In the recent years, many investigators and physicians have devoted a lot of effort to the discovery of reliable biomarkers in asthmatic patients, which will be able to actualize the personalized medicine in near future. Despite such great efforts toward investigation of good biomarkers, few things have turned out to be practical in the clinic. Easily interpretable biomarkers of asthma are necessary to assess early detection, determination of treatment, prognosis prediction, and monitoring of exacerbation. Herein, we review recent studies regarding disease classifications and biomarkers of asthma.

Phenotype and endotype in pediatric asthma

Asthma is not a homogeneous disease presenting variable clinical features, but a complex disorder consisting of many different disease entities characterized by variable air-flow limitation. To date, there are little effective preventive-strategies for the development of asthma, and it has been emphasized that early identification and intervention are the best ways to reduce the associated morbidities, quality of life, and socioeconomic burden. Predicting the natural course of asthma is still difficult, although various phenotypic approaches and predictive scores are developed and widely used. The present phenotypes and predictive scores may be reliable in the population, but those appear to be unreliable in each individual in real practice. Either undertreatment or overtreatment in childhood asthma is an important issue, because they are associated with poor compliance, increments of socioeconomic burdens, and poor quality of life. There is no doubt about the clinical efficacy of inhaled corticosteroid (ICS) in childhood asthma, but the negative effect of long-term use of ICS on the height is emerging. Therefore general physicians should consider an individualized management using specific phenotypes and endotypes, and regularly re-evaluate the drug-response, level of control, and adherence/compliance to avoid inadequate treatment.

Phenotypes and endotypes of severe asthma in children / 소아과

Severe childhood asthma is a complicated and heterogeneous disorder with distinct phenotypes. Children with severe asthma have more persistent symptoms despite receiving treatment, more atopy, greater airway obstruction, and more air trapping than those with mild-to-moderate asthma. They also have higher morbidity and substantial airflow limitations that persist throughout adulthood. Identification of the phenotype clusters and endotypes of severe asthma can allow further modulation of the natural history of severe asthma and may provide the pathophysiologic rationale for appropriate management strategies.

Advances in the Investigation of Asthma Phenotypes / 소아알레르기및호흡기학회지

Asthma is a complex and heterogeneous disease, which is comprised of seperate phenotypes sharing common characteristics, such as airway inflammation, bronchial hyperresponsiveness and variable airflow limitation. Traditionally, asthma phenotypes have been described by combinations of clinical characteristics, according to the expert's recommendation, but they are now focusing on the pathobiologic mechanisms often using exploratory statistical methods. Several phenotypes and endotypes have been suggested by biased or unbiased phenotyping approaches. However, more detailed studies are still needed. In the future, more integrated large-scaled consortium of cohorts, including clinical information, genetics, molecular biology, and experiments will promote to understand the pathobiologic mechanisms of asthma phenotypes for the personalized therapy.