Adult genitourinary sarcoma: analysis using hospital-based cancer registry data in Japan.

BACKGROUND: Genitourinary sarcomas are rare in adults and few large-scale studies on adult genitourinary sarcoma are reported. We aimed to elucidate the clinical characteristics, survival outcomes, and prognostic factors for overall survival of adult genitourinary sarcoma in Japan. METHODS: A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with genitourinary sarcoma in 2013. The datasets were registered from 121 institutions. RESULTS: A total of 116 men and 39 women were included, with a median age of 66 years. The most common primary site was the kidney in 47 patients, followed by the paratestis in 36 patients. The most common histological type was liposarcoma in 54 patients, followed by leiomyosarcoma in 25 patients. The 5-year overall survival rates were 57.6%. On univariate analysis, male gender, paratestis as primary organ, and histological subtype of liposarcoma were predictive of favorable survival while primary kidney, bladder, or prostate gland location were predictive of unfavorable survival. On multivariate analysis, primary paratestis was an independent predictor of favorable survival while primary kidney, bladder, or prostate gland were independent predictors of unfavorable survival. CONCLUSIONS: This is the first report showing the clinical characteristics and survival outcomes of adult genitourinary sarcoma in Japan using a real-world large cohort database.

Impact of an online nutrition management application service on glycaemic management in individuals with diabetes: A propensity-score-matched retrospective cohort study.

AIMS: To assess the impact of 'Oishi Kenko', a nutrition management application (app), on glycaemic control in patients with diabetes. MATERIALS AND METHODS: A propensity-score-matched retrospective cohort study was performed using data from the KAMOGAWA-DM cohort study conducted between January and June 2022 in Japan. We analysed data from patients with type 1 and type 2 diabetes, comparing users who used the Oishi Kenko app (app group) with non-users (control group) over 3 months. RESULTS: Among the 50 participants who actively used it, 47 participants in both the app and control cohorts were selected from the KAMOGAWA-DM cohort according to propensity-score matching. Within the app group, the median glycated haemoglobin (HbA1c) level was 51 mmol/mol (6.9%) at baseline, which slightly decreased to 50 mmol/mol (6.8%) at the 3-month mark (median change 0.0%). Conversely, in the control group, the baseline HbA1c level of 51 mmol/mol (6.9%) exhibited a marginal increase of 52 mmol/mol (7.0%) after 3 months (median change 0.20%). The median HbA1c level change between the groups was statistically significant, with the app group showing a significant positive change compared with the control group (p = 0.012). CONCLUSION: The Oishi Kenko app effectively improved glycaemic control in patients with diabetes; hence, it may be a promising tool for patient-driven dietary management.

Retroperitoneal sarcoma: a 10-year follow-up analysis using hospital-based cancer registry data in Japan.

OBJECTIVES: We sought clinical characteristics, survival outcomes, and prognostic factors for overall survival of retroperitoneal sarcoma in Japan. METHODS: A Japanese hospital-based cancer registry database with a pivotal 10-year follow-up was used to identify and enroll patients, registered from 106 institutions, diagnosed with retroperitoneal sarcoma in 2008-2009. Treating hospitals were divided by hospital care volume; high-volume hospitals and low-volume hospitals were defined as ≥ 4 and < 4 cases/year, respectively. RESULTS: A total of 91 men and 97 women were included, with a median age of 64 years. The most common histological type was liposarcoma in 101 patients, followed by leiomyosarcoma in 38 patients. The 5-year and 10-year overall survival rates were 44.1 and 28.3%. The majority of patients (n = 152, 80.9%) were treated at low-volume hospitals. High-volume hospital patients had higher 10-year overall survival rates than low-volume hospital patients (51.2% vs 23.2%, P = 0.026). Multivariate analysis revealed age over 60 years, treatment in low-volume hospitals and chemotherapy were independent predictors of unfavorable survival while treatment with surgery was an independent predictor of favorable survival. CONCLUSIONS: The possibility of surgical removal was suggested to be the most important prognostic factor for retroperitoneal sarcoma. Better survival was shown in patients treated at high-volume hospitals in our series.

Maediastinal germ cell tumors: analysis using hospital-based cancer registry data in Japan.

OBJECTIVES: Mediastinal germ cell tumors are rare and few large-scale studies on mediastinal germ cell tumors are reported. We aimed to investigate the clinical characteristics and survival outcomes of patients with mediastinum germ cell tumors in Japan. METHODS: A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with mediastinal germ cell tumors in 2012-2013. The datasets were registered from 80 institutions. RESULTS: The selection criteria were met by 123 patients, the majority of whom were male. The median age at diagnosis was 39 years (range 25-89 years) and the most common age groups at diagnosis was 30-39 years, followed by 40-49 years and ≥ 50 years. The histology of non-seminoma (55.3%) was slightly more frequent than that of seminoma (44.7%). The most common histological subtype in non-seminoma was yolk sac tumor, followed by mixed germ cell tumor. The 5-year survival of seminoma and non-seminoma were 96.4% and 57.3%, respectively (p < 0.001). Non-seminomatous mediastinal germ cell tumors, malignant teratomas, mixed germ cell tumors, and yolk sac tumors had comparable survival rates, while those with choriocarcinoma showed the worst prognosis. CONCLUSIONS: This is the first report showing the clinical characteristics and survival outcomes of mediastinal germ cell tumors in Japan using a real-world large cohort database.

Clinicopathological features of adrenal malignancies: Analysis of hospital-based cancer registry data in Japan.

OBJECTIVE: To identify the clinicopathological features of adrenal malignancies and analyze the prognoses of patients with adrenal cortical carcinoma (ACC) and malignant pheochromocytoma (MPCC). PATIENTS AND METHODS: We used a hospital-based cancer registry data in Japan to extract cases of adrenal malignancies that were histologically confirmed, diagnosed, and initially treated from 2012-2015. For survival analysis, we used data from the 2008-2009 cohort to estimate 5-year overall survival (OS) by the Kaplan-Meier method. RESULTS: A total of 989 adrenal malignancies were identified in the 2012-2015 cohort. The most common histologies were ACC (26.4%), diffuse large B-cell lymphoma (DLBCL; 25.4%), neuroblastoma (22.2%), and MPCC (11.9%). While most ACC and MPCC patients were in their 60s, DLBCL patients accounted for 61.5% of adrenal malignancies in the over-70 cohort. Among ACC patients with clinical staging data, 46.3% of patients were stage IV. Although surgery was a chief strategy for all stages, younger patients tended to receive combination therapy, including surgery and chemotherapy or hormone therapy. In the 2008-2009 cohort, the 5-year OS rates of ACC (n = 49) and MPCC (n = 23) patients were 56.2% and 86.4% while ACC patients without surgery had 1- and 2-year OS rates of 25.0% and 12.5%. CONCLUSION: In Japan, DLBCL accounted for the majority of adrenal malignancies in older patients. Despite advanced staging, ACC patients were mainly treated with surgery and their prognosis was not satisfactory. Such epidemiological data may be useful in considering initial management strategies.

Gastric epithelial attachment of Helicobacter pylori induces EphA2 and NMHC-IIA receptors for Epstein-Barr virus.

Epstein-Barr virus (EBV)-associated gastric cancer belongs to 1 of the 4 subtypes of gastric cancer and accounts for 10% of total gastric cancers. However, most cases of gastric cancer have a history of Helicobacter pylori infection. Therefore, we investigated the possibility that H. pylori infection promotes the development of EBV-associated gastric cancer. H. pylori was exposed to principal EBV receptor, CD21, negative gastric epithelial cells, and then infected with EBV recombinant expressing enhanced green fluorescent protein. Changes in EBV infectivity due to prior H. pylori exposure were analyzed using flow cytometry. The treatment of gastric epithelial cells with H. pylori increased the efficiency of EBV infection. An increase was also observed when CagA-deficient, VacA-deficient, and FlaA-deficient H. pylori strains were used, but not when cag pathogenicity island-deficient H. pylori was used. The treatment of epithelial cells with H. pylori induced the expression of accessory EBV receptors, EphA2 and NMHC-IIA, and increased the efficiency of EBV infection depending on their expression levels. When gastric epithelial cells were treated with EPHA2 or NMHC-IIA siRNA, EBV infection via H. pylori attachment was decreased. The adhesion of H. pylori induced the expression of accessory EBV receptors in gastric epithelial cells and increased the efficiency of EBV infection.

Impact of sinus surgery on type 2 airway and systemic inflammation in asthma.

Objective: Asthma is frequently associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Although endoscopic sinus surgery (ESS) improves asthma control in CRSwNP patients with asthma, the mechanism that underlies the response to surgical treatment is still unclear. We evaluated the relevance of changes in asthma control and changes in airway/systemic inflammation in eosinophilic CRSwNP patients with not well controlled asthma who underwent ESS.Methods: We prospectively assessed changes in the asthma control questionnaire (ACQ) score, blood eosinophil counts (B-Eos), forced expiratory volume in 1 s (FEV1), and fraction of exhaled nitric oxide (FeNO) levels at 1-week before and 8 and 52 weeks after ESS.Results: Twenty-five subjects were analyzed. The ACQ score, B-Eos, and FeNO decreased, and FEV1 increased significantly after ESS. In the period from baseline to 52 weeks after ESS, changes in ACQ were significantly correlated with the changes in blood eosinophil counts (r = 0.58, p<.01) and FeNO (r = 0.45, p<.05). Ten subjects (40%) showed consistently improved asthma control at 52-weeks after ESS. In the remaining subjects, although the ACQ score temporarily improved at 8-weeks after ESS, but eventually deteriorated at 52-weeks. Higher levels of total immunoglobulin E were associated with long-term improved asthma control after ESS.Conclusions: In eosinophilic CRSwNP patients with asthma, sinus surgery impacts asthma control through the suppression of airway/systemic type 2 inflammation. The present study reinforced the common pathophysiology of type 2 inflammation between the upper and lower airways.

[Renal Mucinous Tubular and Spindle Cell Carcinoma : A Case Report].

Renal mucinous tubular and spindle cell carcinoma (MTSCC) is a rare kidney cancer subtype with limited cases reported in the literature. Renal MTSCC has many similarities with papillary renal cell carcinoma (pRCC), and it is therefore often difficult to make a differential diagnosis between them. Herein, we report a case of renal MTSCC. The patient was a 76-year-old woman. Computed tomography revealed a left renal tumor. Magnetic resonance imaging (MRI) demonstrated an iso-intensity or high signal intensity mass on T2-weighted images, high signal intensity on diffusion-weighted images, and weak and gradual enhancement. We diagnosed the patient with left renal cell carcinoma (cT1bN0M0) and performed laparoscopic left nephrectomy in May 2019. The histopathological diagnosis was renal MTSCC. Six months after surgery, the patient remains free of recurrence and of metastasis. MRI is effective for the preoperative differentiation of renal MTSCC from pRCC since renal MTSCC presents an iso-intensity or high signal intensity on MRI T2-weighted images reflecting the mucin component in the intervening stroma within the tumor.

[A Case of Upper Urinary Tract MALT Lymphoma with Remarkable Thickness of Renal Pelvis and Ureter Wall].

A 78-year-old man was referred to Tsukuba University Hospital for right hydronephrosis. He had undergone ureteroscopy and ureteral stenting in another hospital, but no tumor was revealed in renal pelvis and ureter. The urinary cytology was negative. Computed tomography (CT) revealed remarkable thickening of right renal pelvis and ureter wall. CT also showed para-aortic, iliac, supraclavicular and mediastinal lymph node (LN) swelling. 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) revealed high uptake at thickened right renal pelvis and ureter wall and enlarged LNs. The soluble interleukin-2 receptor was elevated to 1,110 U/ml (normal range: 613 U/ml). Those findings suggested that the malignant lymphoma originated from the renal pelvis and ureter rather than urothelial cancer. Therefore we performed open biopsy of iliac LN and periureteral tissue. The pathological diagnosis was mucosa associated lymphoid tissue (MALT) lymphoma. The patient was trasferred to the department of hematology, and treated with rituximab and bendamustine. After 6 courses of chemotherapy, swelling of renal pelvis, ureter and LN was markedly reduced. The ureteral sent could be removed. MALT lymphoma of the upper urinary tract is extremely rare and pretreatment diagnosis is difficult. In 8 of 11 reported cases, the diagnosis was made by nephroureterectomy. In our cases, open biopsy could avoid nephroureterectomy.

Development of a Machine Learning Model for Classifying Cooking Recipes According to Dietary Styles.

To complement classical methods for identifying Japanese, Chinese, and Western dietary styles, this study aimed to develop a machine learning model. This study utilized 604 features from 8183 cooking recipes based on a Japanese recipe site. The data were randomly divided into training, validation, and test sets for each dietary style at a 60:20:20 ratio. Six machine learning models were developed in this study to effectively classify cooking recipes according to dietary styles. The evaluation indicators were above 0.8 for all models in each dietary style. The top ten features were extracted from each model, and the features common to three or more models were employed as the best predictive features. Five well-predicted features were indicated for the following seasonings: soy sauce, miso (fermented soy beans), and mirin (sweet cooking rice wine) in the Japanese diet; oyster sauce and doubanjiang (chili bean sauce) in the Chinese diet; and olive oil in the Western diet. Predictions by broth were indicated in each diet, such as dashi in the Japanese diet, chicken soup in the Chinese diet, and consommé in the Western diet. The prediction model suggested that seasonings and broths could be used to predict dietary styles.

Current advances in pulmonary functional imaging.

Recent advances in imaging analysis have enabled evaluation of ventilation and perfusion in specific regions by chest computed tomography (CT) and magnetic resonance imaging (MRI), in addition to modalities including dynamic chest radiography, scintigraphy, positron emission tomography (PET), ultrasound, and electrical impedance tomography (EIT). In this review, an overview of current functional imaging techniques is provided for each modality. Advances in chest CT have allowed for the analysis of local volume changes and small airway disease in addition to emphysema, using the Jacobian determinant and parametric response mapping with inspiratory and expiratory images. Airway analysis can reveal characteristics of airway lesions in chronic obstructive pulmonary disease (COPD) and bronchial asthma, and the contribution of dysanapsis to obstructive diseases. Chest CT is also employed to measure pulmonary blood vessels, interstitial lung abnormalities, and mediastinal and chest wall components including skeletal muscle and bone. Dynamic CT can visualize lung deformation in respective portions. Pulmonary MRI has been developed for the estimation of lung ventilation and perfusion, mainly using hyperpolarized 129Xe. Oxygen-enhanced and proton-based MRI, without a polarizer, has potential clinical applications. Dynamic chest radiography is gaining traction in Japan for ventilation and perfusion analysis. Single photon emission CT can be used to assess ventilation-perfusion (V˙/Q˙) mismatch in pulmonary vascular diseases and COPD. PET/CT V˙/Q˙ imaging has also been demonstrated using "Galligas". Both ultrasound and EIT can detect pulmonary edema caused by acute respiratory distress syndrome. Familiarity with these functional imaging techniques will enable clinicians to utilize these systems in clinical practice.

Gender Difference in the Relationship between Extrapulmonary Factors and Reduced Lung Function in Early Adulthood.

(1) Background: Reduced lung function in early adulthood is associated with future risks to health outcomes that have not been fully explored by gender. We investigated gender-specific relationships between lung function and extrapulmonary variables, assessing their potential as screening markers for respiratory dysfunction in young adults. (2) Methods: The participants were 151 medical students. Clinical data, handgrip strength (HS); body composition parameters such as skeletal muscle mass index (SMI), whole-body phase angle (WBPhA), and bone mineral content (BMC); and pulmonary function variables, vital capacity (VC), forced VC (FVC), and forced expiratory volume in one second (FEV1), were measured. (3) Results: FEV1 was significantly correlated with BMI, SMI, WBPhA, BMC, and both left and right HS (p < 0.0001, respectively) across all participants. According to gender, FEV1 had the strongest positive association with left HS in males (p < 0.0001) and BMC in females (p < 0.0001). The area under the curve for detecting the bottom quartile of FEV1 was 0.705 (cut-off 41.0 kg, sensitivity 91%) for left HS in males and 0.742 (cut-off 2.11 kg, sensitivity 81%) for BMC in females. (4) Conclusions: Gender-specific relationships between intrapulmonary and extrapulmonary factors such as left HS and BMC could be useful for screening suspected respiratory dysfunction in early adulthood.

Factors associated with non-intervention of antifibrotic agents in IPF patients.

BACKGROUND: The efficacy of antifibrotic agents in idiopathic pulmonary fibrosis (IPF) has been demonstrated and early introduction is recommended, especially in patients with preserved performance status (PS). We aimed to determine the proportion of untreated IPF cases using real-world data and to assess the factors associated with non-intervention. METHODS: A prospective observational study using questionnaires was performed on 518 patients with interstitial lung disease (ILD) and their attending physicians who visited a clinic, general hospital, or tertiary respiratory center between December 2019 and October 2020. Patients responded with subjective symptoms and PS, whereas physicians responded with diagnosis, treatment, and reasons for their treatment choices. Principal component analysis (PCA) was performed using age, sex, BMI, medical facility, specialized tests, and symptom severity. RESULTS: We included 207 patients with IPF. Among them, 168 has a good PS (≤2), which could be indicative of treatment; 130 (77.4%) were not treated with antifibrotic agents. The PCA revealed a trend consistent with that of antifibrotic agent therapy and the distribution of medical facilities, with a treatment intervention rate of 16% in general hospitals and 62% in tertiary respiratory centers. In general hospitals, low symptom severity (PS, mMRC, and no use of long-term oxygen therapy) was a relevant factor for non-intervention with antifibrotic agents (p < 0.001). CONCLUSION: Antifibrotic treatment interventions varied by facility in cases with good PS. Patients with milder symptoms are not being treated early in general hospitals and more collaboration between general hospitals and specialized facilities is necessary.

Relief of Airflow Limitation and Airway Inflammation by Endoscopic Sinus Surgery in a Patient with Severe Asthma with Eosinophilic Chronic Rhinosinusitis.

Although endoscopic sinus surgery (ESS) is beneficial in improving asthma symptoms, its impact on the lung function in patients with asthma and chronic rhinosinusitis remains unclear. We herein report a case of severe asthma with eosinophilic chronic rhinosinusitis, in which ESS substantially improved airflow limitation and concomitantly reduced fractional exhaled nitric oxide and blood eosinophil counts. ESS likely relieved airflow limitation by suppressing type 2 inflammatory pathways. This case highlights ESS as a promising strategy for achieving clinical remission in patients with severe asthma and chronic rhinosinusitis.

KaPPA-View4: a metabolic pathway database for representation and analysis of correlation networks of gene co-expression and metabolite co-accumulation and omics data.

Correlations of gene-to-gene co-expression and metabolite-to-metabolite co-accumulation calculated from large amounts of transcriptome and metabolome data are useful for uncovering unknown functions of genes, functional diversities of gene family members and regulatory mechanisms of metabolic pathway flows. Many databases and tools are available to interpret quantitative transcriptome and metabolome data, but there are only limited ones that connect correlation data to biological knowledge and can be utilized to find biological significance of it. We report here a new metabolic pathway database, KaPPA-View4 (http://kpv.kazusa.or.jp/kpv4/), which is able to overlay gene-to-gene and/or metabolite-to-metabolite relationships as curves on a metabolic pathway map, or on a combination of up to four maps. This representation would help to discover, for example, novel functions of a transcription factor that regulates genes on a metabolic pathway. Pathway maps of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and maps generated from their gene classifications are available at KaPPA-View4 KEGG version (http://kpv.kazusa.or.jp/kpv4-kegg/). At present, gene co-expression data from the databases ATTED-II, COXPRESdb, CoP and MiBASE for human, mouse, rat, Arabidopsis, rice, tomato and other plants are available.

Breakfast Skipping is associated with More Deleterious Lifestyle Behaviors among Japanese Men: The TRF-Japan Study Using the Original "Taberhythm" Smartphone Application.

Background: Time-restricted eating has been increasingly recognized as a promising option to reduce food intake and combat obesity. Especially in Asian countries such as Japan, because of the wide variety of food choices available, a dietary approach that emphasizes meal timing can be more practical and easier to implement and adhere to, compared with approaches that focus on specific dietary content, such as low-fat or low-carbohydrate diets. Objectives: We aimed to identify eating patterns among Japanese men and women using a smartphone application (app) called "Taberhythm." In addition, we sought to evaluate the relationship of breakfast eating habits with lifestyle behaviors and body mass index, and determine whether sex differences were present. Methods: A total of 3369 smartphone users were eligible to participate in this observational study. Users recorded 1 mo of lifestyle logs using the app; 254 participants (178 women, 38 ± 12 y old, body mass index 23.3 ± 4.9 kg/m2) had sufficient records to calculate daily fasting duration and sleep duration, and were eligible for the analyses. Results: Fasting duration was ∼12.6 h and was longer in women than men, among participants who never skipped breakfast. Breakfast skipping was associated with longer screen time, and more frequent snacking, only in men. Men with irregular breakfast eating patterns had a longer duration of fasting after awakening that was associated with obesity. Conclusions: We investigated eating patterns among Japanese people using a smartphone app and revealed that skipping breakfast was more deleterious in men than in women.

Estimating Culprit Drugs for Adverse Drug Reactions Based on Bayesian Inference.

The utility of big data in spontaneous adverse drug reactions (ADRs) reporting systems has improved the pharmacovigilance process. However, identifying culprit drugs in ADRs remains challenging, although it is one of the foremost steps to managing ADRs. Aiming to estimate the likelihood of prescribed drugs being culprit drugs for given ADRs, we devised a Bayesian estimation model based on the Japanese Adverse Drug Events Reports database. After developing the model, a validation study was conducted with 67 ADR reports with a gross of 1,387 drugs (67 culprit drugs and 1,320 concomitant drugs) prescribed and recorded at Yamaguchi University Hospital. As a result, the model estimated a culprit drug of ADRs with acceptable accuracy (area under the receiver operating characteristic curve 0.93 (95% confidence interval 0.88-0.97)). The estimation results provided by the model to healthcare practitioners can be used as one clue to determine the culprit drugs for various ADRs, which will improve the management of ADRs by shortening the treatment turnaround time and increasing the precision of diagnosis, leading to minimizing the adverse effects on patients.

Variant allele frequency changes in TP53 predict pembrolizumab response in patients with metastatic urothelial carcinoma.

Prognoses for patients with metastatic urothelial carcinoma (mUC) have improved with pembrolizumab treatment, an immune checkpoint inhibitor, but clinical benefits are limited to a subset of patients. Therefore, a non-invasive biomarker to predict pembrolizumab response is required. The present study retrospectively examined genomic alterations in 25 plasma circulating tumor DNA (ctDNA) samples using targeted sequencing of 77 genes from 16 patients with mUC during pembrolizumab treatment. A total of 11 (68.8%) patients demonstrated ≥2 genomic alterations, including TP53 mutations (as defined by ctDNA-positive status). The proportion of responders to pembrolizumab in the ctDNA-positive group was higher compared with that in the ctDNA-negative group (72.7 vs. 20.0%). Furthermore, among all detected genomic alterations, variant allele frequency decreases in TP53 during pembrolizumab treatment were mainly associated with therapeutic response. Collectively, these data suggest that profiling of ctDNA in plasma, particularly TP53, may be useful for predicting and monitoring therapeutic responses to pembrolizumab in patients with mUC.

A Real-World Study of Achievement Rate and Predictive Factors of Clinical and Deep Remission to Biologics in Patients with Severe Asthma.

BACKGROUND: Recent advances in biologics have provided new insights into the clinical course of asthma, including disease modification, clinical remission (CR), and deep remission (DR). However, the extent to which biologics achieve CR and DR in severe asthma patients is poorly understood. METHODS: To assess the achievement rate and predictors of CR and DR using long-term biologics, we retrospectively evaluated 54 severe asthma patients recently started on biologics. "CR" denotes the achievement of all three criteria: (1) absence of asthma symptoms, (2) no asthma exacerbations, and (3) no use of oral corticosteroids. DR denoted CR plus (4) normalized pulmonary function and (5) suppressed type 2 inflammation. RESULTS: CR and DR achievement rates were 68.5% and 31.5%, respectively. Compared with the non-deep remission group, the DR group had higher adult-onset asthma rates (94.1% vs. 70.3%, p = 0.078), shorter asthma duration (5 vs. 19 years, p = 0.006), and higher FEV1 (91.5% vs. 71.5%, p < 0.001). There were no significant differences in the Asthma Control Questionnaire scores, exacerbation frequency, or type 2 inflammation at baseline between groups. Asthma duration combined with FEV1 can stratify the achievement rates of CR and DR. CONCLUSIONS: the early introduction of biologics in severe asthma patients may help achieve CR and DR.