Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study.

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

Effects of indoor environments and outdoor air pollutants in residential areas on acute exacerbation in patients with severe asthma.

This study aimed to determine the effects of indoor environment (IE) and outdoor air pollutants (OAPs) in residential areas on acute exacerbation (AE) in patients with severe asthma. A total of 115 participants were recruited. To characterize IE, we used structured questionnaires and estimated OAP concentrations using a land-use regression model. Participants who were exposed to passive smoking and lived in houses where the kitchen and living room were not separated showed a significantly higher rate of AE (p = 0.014 and 0.0016, respectively). The mean concentration of PM2.5 in residential areas during the last 3 years was significantly higher in participants with AE than that in those without AE (19.8 ± 3.1 vs. 21.0 ± 2.5 µg/m3, p = 0.033). Moreover, the serum level of 8-hydroxy-2'-deoxyguanosine significantly increased in participants with AE compared to those without AE (56.9 ± 30.0 vs. 94.7 ± 44.5 ng/mL, p = 0.0047) suggesting enhanced oxidative stress in those with AE.

WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study.

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Multicenter Prospective Observational Study to Evaluate the Therapeutic Effect and Safety of a Combination of Montelukast and Levocetirizine for Allergic Rhinitis when Administered to Patients with Allergic Rhinitis and Asthma.

INTRODUCTION: Allergic rhinitis and asthma share a common inflammatory mechanism and are closely related, recognized as "one airway disease." Thus, the guidelines recommend allergic rhinitis and asthma be treated together, and leukotriene antagonists and antihistamines have been administered simultaneously; however, there are few reports of the use of combination drugs so far. METHODS: The aim of the study was to evaluate the treatment effects and adverse events of Monterizine® (a combination of montelukast and levocetirizine); a total of 2,254 patients with perennial allergic rhinitis and asthma were prospectively enrolled from 60 hospitals nationwide in Korea. They were followed up for 3 (Period 1) or 6 months (Period 2). Total nasal symptom score (TNSS), satisfaction, and safety data were collected and compared to baseline. RESULTS: TNSS scores were analyzed for 2,254 subjects. At Period 1 (n = 2,024) and 2 (n = 1,861), the scores decreased significantly from baseline (-1.20 ± 2.49 and -1.63 ± 2.78, p < 0.001). The mean quality of life (QoL) was significantly improved at Period 1 and 2 relative to baseline (-3.75 ± 6.58, -4.83 ± 7.11, both p < 0.0001). There were no serious adverse drug reactions, but there were some minor reactions including nasopharyngitis (2.92%), rhinitis (0.37%), and somnolence (0.34%). CONCLUSIONS: TNSS score and QoL were significantly improved by 3-6 months' treatment with Monterizine without significant adverse reactions. These results indicate that Monterizine, as a combination drug, is effective and safe for improving nasal symptoms and quality of life in patients with allergic rhinitis who also have asthma.

Patient characteristics, pain treatment patterns, and incidence of total joint replacement in a US population with osteoarthritis.

BACKGROUND: Currently available medications for chronic osteoarthritis pain are only moderately effective, and their use is limited in many patients because of serious adverse effects and contraindications. The primary surgical option for osteoarthritis is total joint replacement (TJR). The objectives of this study were to describe the treatment history of patients with osteoarthritis receiving prescription pain medications and/or intra-articular corticosteroid injections, and to estimate the incidence of TJR in these patients. METHODS: This retrospective, multicenter, cohort study utilized health plan administrative claims data (January 1, 2013, through December 31, 2019) of adult patients with osteoarthritis in the Innovation in Medical Evidence Development and Surveillance Distributed Database, a subset of the US FDA Sentinel Distributed Database. Patients were analyzed in two cohorts: those with prevalent use of "any pain medication" (prescription non-steroidal anti-inflammatory drugs [NSAIDs], opioids, and/or intra-articular corticosteroid injections) using only the first qualifying dispensing (index date); and those with prevalent use of "each specific pain medication class" with all qualifying treatment episodes identified. RESULTS: Among 1 992 670 prevalent users of "any pain medication", pain medications prescribed on the index date were NSAIDs (596 624 [29.9%] patients), opioids (1 161 806 [58.3%]), and intra-articular corticosteroids (323 459 [16.2%]). Further, 92 026 patients received multiple pain medications on the index date, including 71 632 (3.6%) receiving both NSAIDs and opioids. Altogether, 20.6% of patients used an NSAID at any time following an opioid index dispensing and 17.2% used an opioid following an NSAID index dispensing. The TJR incidence rates per 100 person-years (95% confidence interval [CI]) were 3.21 (95% CI: 3.20-3.23) in the "any pain medication" user cohort, and among those receiving "each specific pain medication class" were NSAIDs, 4.63 (95% CI: 4.58-4.67); opioids, 7.45 (95% CI: 7.40-7.49); and intra-articular corticosteroids, 8.05 (95% CI: 7.97-8.13). CONCLUSIONS: In patients treated with prescription medications for osteoarthritis pain, opioids were more commonly prescribed at index than NSAIDs and intra-articular corticosteroid injections. Of the pain medication classes examined, the incidence of TJR was highest in patients receiving intra-articular corticosteroids and lowest in patients receiving NSAIDs.

Association between cognitive function and asthma in adults.

BACKGROUND: Cognitive deficits are associated with asthma globally; however, the association between cognitive function and asthma has not been fully elucidated. OBJECTIVE: To assess the relationship between asthma and cognitive function. METHODS: A total of 202 patients with asthma aged older than 18 years were analyzed retrospectively from August 2019 to February 2020. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) test. We compared the associations of clinical parameters with cognitive function (MoCA, ≥23 vs <23) and lung function (forced expiratory volume in 1 second [FEV1], ≥70% vs <70%). RESULTS: Of the total participants, 89 (44.1%) indicated cognitive impairment, of whom 23.1% were aged less than 65 years and 72.9% were aged 65 years or older. MoCA scores were significantly different according to age (24.91 ± 3.89 for ages <65 years vs 19.11 ± 5.11 for ages ≥65 years, P < .001) and lung function (23.29 ± 5.17 for FEV1 ≥70% vs 21.23 ± 5.21 for FEV1 <70%, P = .006), but not according to asthma control (22.35 ± 5.38 for nonsevere asthma vs 22.88 ± 4.91 for severe asthma, P = .55). Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.014-1.13; P = .01), educational status (OR, 6.068; CI, 2.175-16.927; P = .001), and asthma duration (OR, 1.007; CI, 1.001-1.013; P = .02) were significantly associated with cognitive impairment. CONCLUSION: Cognitive impairment was largely observed in adults (44.1%) with asthma and was more prevalent in older adults than in younger adults. Longer asthma duration and lower lung function were more associated with cognitive dysfunction.

Health outcomes coding trends in the US Food and Drug Administration's Sentinel System during transition to International Classification of Diseases-10 coding system: A brief review.

BACKGROUND AND PURPOSE: The transition from International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM) to ICD-10-CM poses a challenge to epidemiologic studies that use diagnostic codes to identify health outcomes and covariates. We evaluated coding trends in health outcomes in the US Food and Drug Administration's Sentinel System during the transition. METHODS: We reviewed all health outcomes coding trends reports on the Sentinel website through November 30, 2019 and analyzed trends in incidence and prevalence across the ICD-9-CM and ICD-10-CM eras by visual inspection. RESULTS: We identified 78 unique health outcomes (22 acute, 32 chronic, and 24 acute or chronic) and 140 time-series graphs of incidence and prevalence. The reports also included code lists and code mapping methods used. Of the 140 graphs reviewed, 81 (57.9%) showed consistent trends across the ICD-9-CM and ICD-10-CM eras, while 51 (36.4%) and 8 (5.7%) graphs showed inconsistent and uncertain trends, respectively. Chronic HOIs and acute/chronic HOIs had higher proportions of consistent trends in prevalence definitions (83.9% and 78.3%, respectively) than acute HOIs (28.6%). For incidence, 55.6% of acute HOIs showed consistent trends, while 41.2% of chronic HOIs and 39.3% of acute/chronic HOIs showed consistency. CONCLUSIONS: Researchers using ICD-10-CM algorithms obtained by standardized mappings from ICD-9-CM algorithms should assess the mapping performance before use. The Sentinel reports provide a valuable resource for researchers who need to develop and assess mapping strategies. The reports could benefit from additional information about the algorithm selection process and additional details on monthly incidence and prevalence rates. KEY POINTS: We reviewed health outcomes coding trends reports on the US FDA Sentinel website through November 30, 2019 and analyzed trends in incidence and prevalence across the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) and ICD-10-CM eras by code mapping method and the type of health outcomes of interest (acute, chronic, acute or chronic). More than a third of the 140 time-series graphs of incidence and prevalence of health outcomes showed inconsistent or uncertain trends. Consistency in trends varied by code mapping method, type of health outcomes of interest, and whether the measurement was incidence or prevalence. Studies using ICD-9-CM-based algorithms mapped to ICD-10-CM codes need to assess the performance of the mappings and conduct manual refinement of the algorithms as needed before using them.

Trichomonas vaginalis-secreted cysteinyl leukotrienes promote migration, degranulation and MCP-1 production in mast cells.

Trichomonas vaginalis, a flagellated extracellular protozoan parasite that infects the human genitourinary tract, is usually transmitted by sexual contact. Our previous study showed that the leukotriene B4 (LTB4 ), a T vaginalis-secreted lipid mediator, induces interleukin (IL)-8 production and promotes mast cell degranulation and migration via BLT1 in human. In this study, we investigated whether T vaginalis produces another leukotrienes and whether it causes increased MCP-1 production, mast cell migration and degranulation by activating mast cells. We found that cysteinyl leukotrienes (CysLTs) were contained in T vaginalis-derived secretory product (TvSP) by ELISA. The TvSP-stimulated human mast cell line (HMC-1) exhibited significantly increased monocyte chemoattractant protein-1 (MCP-1) secretion compared to the unstimulated cells. Inhibition of NOX2 activation of cells by treatment of NOX inhibitor or NOX2 siRNA reduced TvSP-stimulated MCP-1 production in HMC-1 cells. It was also confirmed that the receptor for CysLTs is expressed in mast cells. The CysLT receptor (CysLTR) antagonist inhibited TvSP-stimulated MCP-1 production of mast cells, as well as ROS production, migration and degranulation of mast cells, and reduced phospho-NF-kB expression. These results suggest that T vaginalis-secreted CysLTs promote migration, degranulation and MCP-1 production in human mast cells through CysLT receptor-mediated NOX2 activation.

Predictive factors of response to inhaled corticosteroids in newly diagnosed asthma: A real-world observational study.

BACKGROUND: Asthma is characterized by chronic airway inflammation, and inhaled corticosteroids (ICSs) have been recommended as first-line treatment. However, response to ICS treatment is various, and the prediction of response to ICSs is still difficult, especially in individuals with newly diagnosed asthma. OBJECTIVE: To assess the clinical factors and biomarkers associated with response to ICSs in newly diagnosed asthma. METHODS: A total of 150 ICS-naive patients with newly diagnosed asthma in the allergy clinic of a single tertiary hospital in Korea from January 2014 to January 2019 were included in this study. All patients initially received moderate-dose ICSs and were treated for more than 1 year. We compared the clinical characteristics and parameters between patients with and without acute exacerbation (AE) during the study period. RESULTS: In this study, 99 patients had no AE (stable asthma group), and 51 patients presented with more than 1 AE (unstable asthma group). The mean (SD) blood eosinophil count (635.7 [780.3] × 103/µL vs 373.4 [266.8] × 103/µL, P = .003) and sputum eosinophil count (15.2% [23.9%] vs 8.3% [15.4%], P = .051) were higher and the sputum neutrophil count (42.9% [35.1%] vs 61.3% [35.1%], P = .057) was lower in the stable asthma group than in the unstable asthma group. CONCLUSION: High blood and sputum eosinophil counts can predict a good response to ICS treatment in terms of prevention of AE in individuals with newly diagnosed asthma. The sputum neutrophil count may be an effective predictor of response to ICSs, even though additional studies must be conducted.

Incidence rates of and risk factors for opioid overdose in new users of prescription opioids among US Medicaid enrollees: A cohort study.

PURPOSE: To measure incidence rates of and risk factors for opioid overdose among new users of prescription opioids in the Medicaid population. METHODS: A cohort study using Medicaid claims from four states (1999-2012) among adults continuously enrolled in Medicaid for ≥3 years free of opioid prescriptions and opioid overdose before cohort entry. Exposure and outcome of interest were prescription opioid use and apparent incident opioid overdose identified in inpatient and outpatient claims (sensitivity ≈ 97%; positive predictive value ≈ 87%), respectively. RESULTS: Among new prescription opioid users (1 336 140 persons; 246 466 person-years), the overall opioid overdose incidence rate per 100 000 person-years was 247.1 (95% confidence interval [CI], 227.5-266.7), with 251.0 (CI, 188.6-313.5) in 2002 and 225.5 (CI, 142.0-309.0) in 2012. A lower hazard for opioid overdose was seen for age 65-80 years (adjusted hazard ratio [HR], 0.50; CI, 0.37-0.66) and 80-100 years (0.35; 0.23-0.52) vs 18-35 years; females (0.79; 0.67-0.93) vs males; and other/unknown race/ethnicity (0.71; 0.54-0.93) vs whites. A higher hazard was seen for initial opioid dose in morphine milligram equivalents (MMEs), 50-100 MME/day (1.52; 1.24-1.86) and >100 MME/day (1.98; 1.55-2.53), vs <50 MME/day; prior diagnosis of substance use disorders (2.30; 1.91-2.79) or mental health conditions (1.75; 1.47-2.08); and prior prescriptions for benzodiazepines (1.43; 1.13-1.81). CONCLUSION: In Medicaid enrollees in four study states during 2002 to 2012, opioid overdose incidence rate per 100 000 person-years among apparent new users of prescription opioids was 247.1, with 251.0 in 2002 and 225.5 in 2012. Younger ages, white race/ethnicity, higher MME opioid daily doses, prior substance use disorders, mental health conditions, and benzodiazepine prescriptions were associated with a higher risk of opioid overdose incidence.

Re-exposure to low osmolar iodinated contrast media in patients with prior moderate-to-severe hypersensitivity reactions: A multicentre retrospective cohort study.

OBJECTIVES: To evaluate the outcomes of re-exposure to low-osmolar iodinated contrast medium (LOCM) in patients with a history of moderate-to-severe hypersensitivity reaction (HSR). METHODS: We retrospectively evaluated a cohort comprising all subjects satisfying the following conditions at 11 centres: (1) experienced a moderate-to-severe HSR to LOCM by December 2014, and (2) underwent contrast-enhanced computed tomography after the initial HSR between January 2014 and December 2014. RESULTS: A total of 150 patients with 328 instances of re-exposure were included; the recurrence rate of HSR was 19.5%. Patients with severe initial HSR exhibited a higher recurrence rate of severe HSR compared to patients with moderate initial HSR, despite more intensive premedication. In the multivariate analysis, the independent risk factors for recurrence of HSR were diabetes, chronic urticaria, drug allergy other than to iodinated contrast media (ICM) and severe initial HSR. The risk of recurrent HSR was 67.1% lower in cases where the implicated ICM was changed to another one (odds ratio: 0.329; P = 0.001). However, steroid premedication did not show protective effects against recurrent HSR. CONCLUSION: In high-risk patients who have previously experienced a moderate-to-severe initial HSR to LOCM, we should consider changing the implicated ICM to reduce recurrence risk. KEY POINTS: • In patients with moderate-to-severe HSR, steroid premedication only shows limited effectiveness. • Changing the implicated ICM can reduce the recurrence of HSR to ICM. • Diabetes, chronic urticaria and drug allergies increase the risk of ICM HSR.

Comparison between skin prick test and serum immunoglobulin E by CAP system to inhalant allergens.

BACKGROUND: Skin prick tests (SPTs) and measurements of serum specific immunoglobulin E (sIgE) antibodies are the most commonly used diagnostic tools for confirming sensitization. However, disagreement between the tests has been observed. OBJECTIVE: To compare SPT and the CAP system for diagnosis of sensitization to common inhalant allergens. METHODS: Subjects included 2,635 patients 10 to 90 years old who underwent analyses by SPT and CAP at the Dong-A University Hospital (Busan, Korea) from June 2011 through May 2016. The 2 test results were compared for 17 inhalant allergens. RESULTS: Agreement between the SPT and sIgE level was 75.3%. Overall agreement was moderate (κ = 0.59), with strong agreement for house dust mites and birch (κ > 0.7) and weak agreement for Tyrophagus putrescentiae and dog (κ < 0.3). When CAP was compared with SPT as the reference, the sensitivity was 75.8% and the specificity was 75.2%. Mean wheal size by SPT showed a positive correlation with sIgE levels (r = 0.59), which decreased with age. CONCLUSION: There was a discrepancy between SPT and CAP for diagnosing allergic sensitization among inhalant allergens. The allergic sensitization and correlation between the tests decreased with age. Cautious interpretation of the clinical relevance of allergen sensitization based on SPT and CAP results is required, especially in older patients.

The quality of Medicaid and Medicare data obtained from CMS and its contractors: implications for pharmacoepidemiology.

BACKGROUND: Administrative claims of United States Centers for Medicare and Medicaid Services (CMS) beneficiaries have long been used in non-experimental research. While CMS performs in-house checks of these claims, little is known of their quality for conducting pharmacoepidemiologic research. We performed exploratory analyses of the quality of Medicaid and Medicare data obtained from CMS and its contractors. METHODS: Our study population consisted of Medicaid beneficiaries (with and without dual coverage by Medicare) from California, Florida, New York, Ohio, and Pennsylvania. We obtained and compiled 1999-2011 data from these state Medicaid programs (constituting about 38% of nationwide Medicaid enrollment), together with corresponding national Medicare data for dually-enrolled beneficiaries. This descriptive study examined longitudinal patterns in: dispensed prescriptions by state, by quarter; and inpatient hospitalizations by federal benefit, state, and age group. We further examined discrepancies between demographic characteristics and disease states, in particular frequencies of pregnancy complications among men and women beyond childbearing age, and prostate cancers among women. RESULTS: Dispensed prescriptions generally increased steadily and consistently over time, suggesting that these claims may be complete. A commercially-available National Drug Code lookup database was able to identify the dispensed drug for 95.2-99.4% of these claims. Because of co-coverage by Medicare, Medicaid data appeared to miss a substantial number of hospitalizations among beneficiaries ≥ 45 years of age. Pregnancy complication diagnoses were rare in males and in females ≥ 60 years of age, and prostate cancer diagnoses were rare in females. CONCLUSIONS: CMS claims from five large states obtained directly from CMS and its contractors appeared to be of high quality. Researchers using Medicaid data to study hospital outcomes should obtain supplemental Medicare data on dual enrollees, even for non-elders. TRIAL REGISTRATION: Not applicable.

Predictors of Asthma Control by Stepwise Treatment in Elderly Asthmatic Patients.

The geriatric population is increasing, and asthma severity increases with age. We determined the predictors of asthma control, exacerbation, and the factors that affect asthma-specific quality of life (A-QOL) in elderly asthmatic patients. This was a prospective, multicenter, real-life study for 6 months with stepwise pharmacologic treatment based on the Global Initiative for Asthma (GINA) guideline. A total of 296 asthmatic patients aged ≥ 60 yr were recruited from 5 university centers in Korea. The improved-asthma control group was defined as the group of patients who maintained well-controlled or improved disease and the not-improved asthma control group was defined as the remaining patients. Fewer number of medications for comorbidities (2.8 ± 3.3 in the improved vs. 4.5 ± 4.4 in the control) and higher physical functioning (PF) scale (89.8 ± 14.2 in the improved vs. 82.0 ± 16.4 in the control) were significant predictors in the improved-asthma control group (OR = 0.863, P = 0.004 and OR = 1.028, P = 0.018, respectively). An asthma control test (ACT) score of ≤ 19 at baseline was a significant predictor of asthma exacerbation (OR = 3.938, P = 0.048). Asthma duration (F = 5.656, P = 0.018), ACT score (F = 12.237, P = 0.001) at baseline, and the presence of asthma exacerbation (F = 5.565, P = 0.019) were significant determinants of changes in A-QOL. The number of medications for comorbidities and performance status determined by the PF scale may be important parameters for assessing asthma control in elderly asthmatic patients.

Activation of MAPK Is Required for ROS Generation and Exocytosis in HMC-1 Cells Induced by Trichomonas vaginalis-Derived Secretory Products.

Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men. Mast cells have been reported to be predominant in vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen-activated protein kinase (MAPK), activated by various stimuli, have been shown to regulate the transcriptional activity of various cytokine genes in mast cells. In this study, we investigated whether MAPK is involved in ROS generation and exocytotic degranulation in HMC-1 cells induced by T. vaginalis-derived secretory products (TvSP). We found that TvSP induces the activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47(phox) in HMC-1 cells. Stimulation with TvSP also induced up-regulation of CD63, a marker for exocytosis, along the surfaces of human mast cells. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP induces intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling.