Clinical characteristics for distinguishing between acute cardiogenic pulmonary edema and community-acquired pneumonia in elderly patients: a prospective observational study.

Heart failure and pneumonia are highly prevalent in elderly patients. We conducted a study to evaluate the differences in the patterns of symptoms, laboratory findings, and computed tomography (CT) results in elderly patients with acute cardiogenic pulmonary edema (ACPE) and community-acquired pneumonia (CAP). From January 1, 2015 to December 31, 2017, we studied 140 patients aged >75 years who were diagnosed with ACPE and CAP. Symptoms, laboratory findings, mean ostial pulmonary vein (PV) diameter and patterns on CT images were assessed. The primary measures of diagnostic accuracy were assessed using the positive likelihood ratio (LR+). The cutoff value of ostial PVs for differentiating patients with ACPE from CAP was evaluated using the receiver operating characteristic (ROC) analysis. Ninety-three patients with ACPE, 36 with CAP, and 11 with complicated ACPE/CAP were included. In patients with ACPE, edema (LR+ 5.4) was a moderate factor for rule-in, and a high brain natriuretic peptide level (LR+ 4.2) was weak. In patients with CAP, cough (LR+ 5.7) and leukocytosis (LR+ 5.2) were moderate factors for rule-in, while fever (LR+ 3.8) and a high C-reactive protein level (LR+ 4.8) were weak factors. The mean diameter of ostial PVs in patients with ACPE was significantly larger than that of patients with CAP (15.8±â€Š1.8 mm vs 9.6±1.5 mm, p< 0.01). ROC analysis revealed that an ostial PV diameter cutoff of 12.5 mm was strong evidence for distinguishing ACPE from CAP with an area under the ROC curve of 0.99 and LR+ 36.0. In conclusion, as ACPE and CAP have similar symptoms and laboratory findings, dilated ostial PVs were useful in characterizing CT images to distinguish ACPE from CAP.

Association between chronic kidney disease and synergistic, potentially nephrotoxic medication use in elderly hospitalized patients: A single-center cross-sectional study
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OBJECTIVE: In elderly patients, age-related, disease-related, and drug-related factors are associated with chronic kidney disease (CKD). Little is known about which factors are the best predictors for CKD in elderly patients. MATERIALS AND METHODS: The study was based on 784 patients aged 75 years or older for whom the clinical and serum creatinine on admission to our hospital were available. Impaired renal function, including CKD and transient renal insufficiency, was defined as a non-indexed glomerular filtration rate (GFR) below 60 mL/min. A logistic regression model was developed for predictors of CKD and was internally validated using bootstrapping. RESULTS: Approximately 61% of the patients, who had CKD (46%) and transient renal insufficiency (15%), had a non-indexed GFR < 60 mL/min. Synergistic use of 3 drugs potentially impairing renal function, diuretics, ACE-I/ARB, and NSAIDs (odds ratio (OR), 4.66; 95% confidence interval (CI), 1.48 - 17.7, p = 0.012) was a significantly associated factor for CKD in a multivariate logistic regression analysis. Age (OR 1.56, 95% CI 1.04 - 2.33, p = 0.03), female gender (OR 1.58, 95% CI 1.04 - 2.39, p = 0.03), any prescription ACE-I/ARB either alone or in combinations with diuretics or NSAIDs (OR 2.74, 95% CI 1.83 - 4.13, p = 0.0001), and proteinuria (OR 1.98, 95% CI 1.27 - 3.10, p = 0.003), were included as the best model for CKD. The area under the curve (AUC) of the best model and the bootstrapping validation were 0.68 and 0.71, respectively. CONCLUSION: Given the widespread use of ACE-I/ARB for elderly patients, our findings suggest that caution is needed when they are prescribed because of the possibility of the patient developing CKD.

Deep learning facilitates the diagnosis of adult asthma.

BACKGROUND: We explored whether the use of deep learning to model combinations of symptom-physical signs and objective tests, such as lung function tests and the bronchial challenge test, would improve model performance in predicting the initial diagnosis of adult asthma when compared to the conventional machine learning diagnostic method. METHODS: The data were obtained from the clinical records on prospective study of 566 adult out-patients who visited Kindai University Hospital for the first time with complaints of non-specific respiratory symptoms. Asthma was comprehensively diagnosed by specialists based on symptom-physical signs and objective tests. Model performance metrics were compared to logistic analysis, support vector machine (SVM) learning, and the deep neural network (DNN) model. RESULTS: For the diagnosis of adult asthma based on symptom-physical signs alone, the accuracy of the DNN model was 0.68, whereas that for the SVM was 0.60 and for the logistic analysis was 0.65. When adult asthma was diagnosed based on symptom-physical signs, biochemical findings, lung function tests, and the bronchial challenge test, the accuracy of the DNN model increased to 0.98 and was significantly higher than the 0.82 accuracy of the SVM and the 0.94 accuracy of the logistic analysis. CONCLUSIONS: DNN is able to better facilitate diagnosing adult asthma, compared with classical machine learnings, such as logistic analysis and SVM. The deep learning models based on symptom-physical signs and objective tests appear to improve the performance for diagnosing adult asthma.

Accuracy of objective tests for diagnosing adult asthma in symptomatic patients: A systematic literature review and hierarchical Bayesian latent-class meta-analysis.

BACKGROUND: We obtain summary estimates of the accuracy of additional objective tests for the diagnosis of adult asthma using systematic review and meta-analysis of diagnostic test accuracy studies. METHODS: Medline, Embase, and other relevant electronic databases were searched for papers published between January 1989 and December 2016. Studies were included if they evaluated the diagnostic accuracy of objective tests, including airway reversibility (AR), airway hyperresponsiveness (AHR), and fractionated exhaled nitric oxide (FeNO) for the diagnosis of adult asthma in patients with symptoms suggestive of asthma. If papers were assessed appropriate using the adapted QUADAS-2 tool, meta-analysis was conducted using the hierarchical bivariate model. This hierarchical model accounts for both within and between study variability. RESULTS: Sixteen studies reported the performance of the evaluated objective tests at presentation. For diagnosis of adult asthma, overall sensitivity and specificity for AR were 0.39 (95% confidence interval [CI] 0.18 to 0.66) and 0.95 (95% CI 0.86 to 1.00); for AHR, 0.86 (95% CI 0.61 to 1.00) and 0.95 (95% CI 0.77 to 1.00); for FeNO, 0.65 (95% CI 0.53 to 0.77) and 0.83 (95% CI 0.75 to 0.90). Comprehensive comparison of three diagnostic tools for adult asthma using the back-calculated likelihood rate (LR) showed that AR and AHR corresponded to a higher LR+, and AHR gave a lower LR-. CONCLUSIONS: In the current situation of no gold standard for diagnosis of adult asthma, AR and AHR are appropriate for ruling-in the true diagnosis, and AHR is superior for ruling-out a diagnosis. Since each objective test had a specific characteristic, it should be chosen depending on the situation, such as the capacity of the institution and the conditions of patients.

Staphylococcus aureus enterotoxin sensitization involvement and its association with the CysLTR1 variant in different asthma phenotypes.

BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. OBJECTIVE: To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. METHODS: We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. RESULTS: A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. CONCLUSION: SE sensitization contributes to TH2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.

Characteristics of phenotypes of elderly patients with asthma.

BACKGROUND: The characteristics of phenotypes of elderly patients with asthma are unknown. The aim of this study was to classify these phenotypes using lung function tests and images from high-resolution computed tomography (HRCT), and to identify associations between clinical characteristics and phenotypes. METHODS: A cross-sectional study was conducted in 165 elderly patients (>65 years of age) who underwent a multidimensional assessment of clinical and functional status and comorbidity. The patients were divided into three phenotypes: (1) asthma-predominant, (2) asthma-obstructive airway disease (OAD) overlap without emphysema, and (3) asthma-OAD overlap with emphysema (asthma-emphysema overlap) based on chest HRCT. A receiver operating characteristic (ROC) curve was constructed to evaluate the cutoff for differentiating between the two OAD phenotypes. Multivariate analysis was also used to distinguish between these two phenotypes. RESULTS: The phenotypes were asthma-predominant in 48 patients (29%), asthma-OAD without emphysema in 36 (22%), and asthma-emphysema in 81 (49%). Patients with asthma-emphysema were more frequent smokers. In multivariate analysis, smoking status (odds ratio 2.92: 95% CI 1.21-7.00, P = 0.03) and % predicted FEV1 ≤70% (odds ratio 3.18: 95% CI 1.13-8.92, P = 0.03) differed significantly between the asthma-emphysema and asthma-OAD without emphysema phenotypes. CONCLUSIONS: Half of elderly patients with asthma are characterized by asthma-emphysema overlap. Our results showed that elderly patients with asthma who are smokers and have moderate or severe OAD are also likely to have emphysema.

Effects on asthma and induction of interleukin-8 caused by Asian dust particles collected in western Japan.

OBJECTIVE: Asian dust storms (ADS) contain various airborne particles that may augment airway inflammation by increasing the level of interleukin-8. The objective of the study was to investigate the association of exposure to an ADS with worsening of symptoms of adult asthma and the effect of ADS particles on interleukin-8 transcriptional activity. METHODS: The subjects were 112 patients with mild to moderate asthma who recorded scores for their daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF) from March to May 2011. Interleukin-8 transcriptional activity was assessed in THP-G8 cells that were exposed to airborne particles collected during days of ADS exposure. RESULTS: Of the 112 patients, 31 had comorbid allergic rhinitis (AR) and/or chronic sinusitis (CS), and had worsened scores for upper respiratory tract symptoms on ADS days compared to non-ADS days. Scores for lower respiratory tract symptoms during ADS days were higher than non-ADS days in all patients. Three patients also had unscheduled hospital visits for exacerbation of asthma on ADS days. However, there was no significant difference in daily morning PEF between ADS and non-ADS days. Airborne particles collected on ADS days induced interleukin-8 transcriptional activity in THP-G8 cells compared to the original soil of the ADS. CONCLUSION: Exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma. ADS airborne particles may increase airway inflammation through enhancement of interleukin-8 transcriptional activity.

Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids.

BACKGROUND: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. OBJECTIVE: We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. METHODS: Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. RESULTS: High serum periostin levels (≥ 95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). CONCLUSIONS: Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.

The effect of body position on pulmonary function, chest wall motion, and discomfort in young healthy participants.

OBJECTIVE: The purpose of this study was to investigate the effect of different recumbent positions on pulmonary function, chest wall motion, and feelings of discomfort in young nonobese healthy volunteers. METHODS: Twenty healthy volunteers (age, 28.0±1.4 years; height, 167.5±10.1 cm; weight, 62.3±10.2 kg) were studied in the sitting position and in the following 6 recumbent positions: supine, left retroversion at a 45° tilt, left anteversion at a 45° tilt, right retroversion at a 45° tilt, right anteversion at a 45° tilt, and prone. After 5 minutes of a selected position, pulmonary functions, including vital capacity (VC), forced expiratory volume in 1 second, maximal inspiratory and expiratory mouth pressures (MIP and MEP, respectively), and breathing pattern components at the chest wall were assessed. Discomfort was assessed using a modified Borg scale. RESULTS: When participants changed position from sitting to each of the 6 recumbent positions, forced expiratory volume in 1 second values decreased significantly (P < .05). None of the participants showed changes in the MIP or MEP in any of the 6 recumbent positions. Rib cage motion was restricted in all recumbent positions except supine, left anteversion at a 45° tilt, and prone. In all 6 recumbent positions, discomfort was experienced during the pulmonary tests. However, in the left retroversion at a 45° tilt position, no discomfort was experienced during the MIP and MEP assessments. CONCLUSION: In young, nonobese, healthy volunteers, recumbent positions caused diminished pulmonary functions and induced feelings of discomfort.

Differences in the effectiveness of single, dual, and triple inhaled corticosteroid therapy for reducing future risk of severe asthma exacerbation: A systematic review and network meta-analysis.

Importance: The effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear. Objective: This network meta-analysis (NMA) extensively evaluated the treatment effects of single ICS; dual ICS i.e., ICS/long-acting ß2-adrenergic agonists (LABA); ICS/LABA as single maintenance and reliever therapy (SMART); and triple ICS, i.e., ICS/LABA/long-acting muscarinic antagonists (LAMA) in preventing severe asthma exacerbations. Data sources: A systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA. Study selection: Using the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified. Data extraction and synthesis: A pairwise meta-analysis was used to select trials based on the criteria for minimizing heterogeneity (I2). Subsequently, the "BUGSnet" package of R software was used to perform a Bayesian network meta-analysis. Main outcome measures: The main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations. Results: This review included 56 randomized control trials (RCTs; n = 78,171 patients). As the pairwise meta-analysis demonstrated that the annualized rate ratio of severe asthma exacerbation had moderate heterogeneity, we analyzed the risk rate of severe asthma exacerbation using a network meta-analysis. In terms of direct/indirect comparisons with non-ICS, single ICS, dual ICS, SMART, and triple ICS reduced severe asthma exacerbations by 34 %, 47 %, 58 %, and 57 %, respectively. SMART and triple ICS showed high effectiveness in reducing severe exacerbations. Conclusion: AND RELEVANCE: SMART and triple ICS were ranked higher in effectiveness in reducing severe asthma exacerbations in comparison with other therapies, indicating that these are the most effective treatments for reducing the future risk of severe asthma exacerbations.

Difference in TMPRSS2 usage by Delta and Omicron variants of SARS-CoV-2: Implication for a sudden increase among children.

It has been postulated from a combination of evidence that a sudden increase in COVID-19 cases among pediatric patients after onset of the Omicron wave was attributed to a reduced requirement for TMPRSS2-mediated entry in pediatric airways with lower expression levels of TMPRSS2. Epidemic strains were isolated from the indigenous population in an area, and the levels of TMPRSS2 required for Delta and Omicron variants were assessed. As a result, Delta variants proliferated fully in cultures of TMPRSS2-positive Vero cells but not in TMPRSS2-negative Vero cell culture (350-fold, Delta vs 9.6-fold, Omicron). There was no obvious age-dependent selection of Omicron strains affected by the TMPRSS2 (9.6-fold, Adults vs. 12-fold, Children). A phylogenetic tree was generated and Blast searches (up to 100 references) for the spread of strains in the study area showed that each strain had almost identical homology (>99.5%) with foreign isolates, although indigenous strains had obvious differences from each other. This suggested that the differences had been present abroad for a long period. Therefore, the lower requirement for TMPRSS2 by Omicron strains might be applicable to epidemic strains globally. In conclusion, the property of TMPRSS2-independent cleavage makes Omicron proliferate with ease and allows epidemics among children with fewer TMPRSS2 on epithelial surfaces of the respiratory organs.

A scoring algorithm for predicting the presence of adult asthma: a prospective derivation study.

BACKGROUND: To predict the presence of asthma in adult patients with respiratory symptoms, we developed a scoring algorithm using clinical parameters. METHODS: We prospectively analysed 566 adult outpatients who visited Kinki University Hospital for the first time with complaints of nonspecific respiratory symptoms. Asthma was comprehensively diagnosed by specialists using symptoms, signs, and objective tools including bronchodilator reversibility and/or the assessment of bronchial hyperresponsiveness (BHR). Multiple logistic regression analysis was performed to categorise patients and determine the accuracy of diagnosing asthma. RESULTS: A scoring algorithm using the symptom-sign score was developed, based on diurnal variation of symptoms (1 point), recurrent episodes (2 points), medical history of allergic diseases (1 point), and wheeze sound (2 points). A score of >3 had 35% sensitivity and 97% specificity for discriminating between patients with and without asthma and assigned a high probability of having asthma (accuracy 90%). A score of 1 or 2 points assigned intermediate probability (accuracy 68%). After providing additional data of forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratio <0.7, the post-test probability of having asthma was increased to 93%. A score of 0 points assigned low probability (accuracy 31%). After providing additional data of positive reversibility, the post-test probability of having asthma was increased to 88%. CONCLUSIONS: This pragmatic diagnostic algorithm is useful for predicting the presence of adult asthma and for determining the appropriate time for consultation with a pulmonologist.

Impact of Hyper- and Hypo-Uricemia on Kidney Function.

Uric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic mutations or polymorphism. Hyperuricemia increases urinary UA concentration and is frequently associated with urolithiasis, which is augmented by low urinary pH. Renal hypouricemia (RHU) is associated with renal stones by increased level of urinary UA, which correlates with the impaired tubular reabsorption of UA. Hyperuricemia causes gout nephropathy, characterized by renal interstitium and tubular damage because MSU precipitates in the tubules. RHU is also frequently associated with tubular damage with elevated urinary beta2-microglobulin due to increased urinary UA concentration, which is related to impaired tubular UA reabsorption through URAT1. Hyperuricemia could induce renal arteriopathy and reduce renal blood flow, while increasing urinary albumin excretion, which is correlated with plasma xanthine oxidoreductase (XOR) activity. RHU is associated with exercise-induced kidney injury, since low levels of SUA could induce the vasoconstriction of the kidney and the enhanced urinary UA excretion could form intratubular precipitation. A U-shaped association of SUA with organ damage is observed in patients with kidney diseases related to impaired endothelial function. Under hyperuricemia, intracellular UA, MSU crystals, and XOR could reduce NO and activate several proinflammatory signals, impairing endothelial functions. Under hypouricemia, the genetic and pharmacological depletion of UA could impair the NO-dependent and independent endothelial functions, suggesting that RHU and secondary hypouricemia might be a risk factor for the loss of kidney functions. In order to protect kidney functions in hyperuricemic patients, the use of urate lowering agents could be recommended to target SUA below 6 mg/dL. In order to protect the kidney functions in RHU patients, hydration and urinary alkalization may be recommended, and in some cases an XOR inhibitor might be recommended in order to reduce oxidative stress.

Construction of a Diagnostic Algorithm for Diagnosis of Adult Asthma Using Machine Learning with Random Forest and XGBoost.

An evidence-based diagnostic algorithm for adult asthma is necessary for effective treatment and management. We present a diagnostic algorithm that utilizes a random forest (RF) and an optimized eXtreme Gradient Boosting (XGBoost) classifier to diagnose adult asthma as an auxiliary tool. Data were gathered from the medical records of 566 adult outpatients who visited Kindai University Hospital with complaints of nonspecific respiratory symptoms. Specialists made a thorough diagnosis of asthma based on symptoms, physical indicators, and objective testing, including airway hyperresponsiveness. We used two decision-tree classifiers to identify the diagnostic algorithms: RF and XGBoost. Bayesian optimization was used to optimize the hyperparameters of RF and XGBoost. Accuracy and area under the curve (AUC) were used as evaluation metrics. The XGBoost classifier outperformed the RF classifier with an accuracy of 81% and an AUC of 85%. A combination of symptom-physical signs and lung function tests was successfully used to construct a diagnostic algorithm on importance features for diagnosing adult asthma. These results indicate that the proposed model can be reliably used to construct diagnostic algorithms with selected features from objective tests in different settings.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dL, and the Uur/Ucr and Cur/Ccr were 0.56±0.14% and 45.7±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.

Association between episodes of upper respiratory infection and exacerbations in adult patients with asthma.

BACKGROUND: Asthma has several phenotypical features, including recurrent exacerbations and recurrent episodes of upper respiratory infection (URI). PURPOSE: A retrospective study was performed to identify the characteristics of adult patients with recurrent exacerbations of asthma, especially in association with recurrent episodes of URI. METHODS: Information was collected using a self-administered questionnaire given to 7070 patients in autumn-winter 2006, 4859 patients in spring-summer 2007, and 4452 patients in autumn-winter 2007. The patients reported the degree of symptoms and the frequency of febrile episodes of URI and exacerbations. Severe exacerbations were defined as a self-report of asthma-related hospitalization, an emergency department visit, or a requirement for systemic corticosteroids. Recurrent febrile URI and exacerbations were defined as two or more episodes within the previous 6 months. A Poisson regression model was used to identify the factors that were predictors of a risk for exacerbations. RESULTS: Of the 6266 patients who completed the questionnaire, the frequencies of febrile URI and episodes of severe exacerbations were 1.54 and 0.54 per subject per year, respectively. Logistic regression analysis showed that an older age [odds ratio (OR): 1.57; 95% confidence interval (CI): 1.15-2.13], female sex (OR: 1.58; 95% CI: 1.20-2.08), recurrent febrile episodes of URI (OR: 2.68; 95% CI: 1.47-4.91), a history of previous exacerbation within 1 year (OR: 1.74; 95% CI: 1.28-2.34), disuse of inhaled corticosteroids (ICSs) (OR: 2.63; 95% CI: 1.68-4.12), and disuse of add-on leukotriene receptor antagonists (LTRAs) (OR: 1.42; 95% CI: 1.06-1.74) were independently associated with moderate to severe symptom-severity. Poisson regression analysis showed that the independent factors that contributed to the frequency of recurrent severe exacerbations were female sex (regression coefficient ß = 0.62, p < .01), an episode of sputum with coughing (ß = 1.23, p < .01), nocturnal awakening (ß = 1.22, p < .01), and severe exacerbation (ß = 0.78, p < .01) within the previous 6 months. CONCLUSION: Symptom-severity of asthma and the frequency of severe exacerbations were associated with previous exacerbations and susceptibility to URI.

Granulocyte-colony-stimulating Factor-resistant Neutropenia and Polyneuropathy Presenting as Severe Complications of Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) has multi-dimensional manifestations, including neutropenia and polyneuropathy. We herein report a 76-year-old woman with pSS initially presenting as severe granulocyte-colony-stimulating factor (G-CSF)-refractory neutropenia and axonal sensorimotor polyneuropathies (SMP). Systemic glucocorticoid administration had reduced neutrophil-associated immunoglobulin G (NAIgG) on the neutrophil surface as detected using flow cytometry, resulting in the development of neutropenia. A patient with pSS concomitant with axonal SMP might show severe neutropenia as aggressive autoimmune disease. Neutropenia can be treated with systemic glucocorticoids based on the assessment of NAIgG on the neutrophil surface.

Predictive Model for Adverse Events and Immune Response Based on the Production of Antibodies After the Second-Dose of the BNT162b2 mRNA Vaccine.

BACKGROUND: The BNT162b mRNA vaccine for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mimics the immune response to natural infection. Few studies have predicted the adverse effects (AEs) after the second-dose vaccination. We present a predictive model for AEs and immune response after the second-dose of the BNT162b mRNA vaccine. METHODS: To predict AEs, 282 healthcare workers (HCWs) were enrolled in this prospective observational study. The classification and regression tree (CART) model was established, and its predictive efficacy was assessed. To predict immune response, 282 HCWs were included in the analysis. Moreover, the factors affected by anti-SARS-CoV-2 spike protein RBD antibody (s-IgG) were evaluated using serum samples collected 2 months after the second-dose vaccination. The s-IgG level was assessed using Lumipulse G1200. Multiple regression analyses were conducted to evaluate variables associated with anti-s-IgG titer levels. RESULTS: The most common AEs after the second-dose vaccination were pain (87.6%), redness (17.0%) at the injection site, fatigue (68.8%), headache (53.5%), and fever (37.5%). Based on the CART model, headache after the first-dose vaccination and age < 30 years were identified as the first and second discriminators for predicting the headache after the second-dose vaccination, respectively. In the multiple linear regression model, anti-s-IgG titer levels were associated with age, female sex, and AEs including headache and induration at the injection site after the second-dose vaccination. CONCLUSION: Headache after the first-dose vaccination can be a predictor of headache after the second-dose vaccination, and AEs are indicators of immune response.

Activation of the prefrontal cortex is associated with exertional dyspnea in chronic obstructive pulmonary disease.

BACKGROUND: Exertional dyspnea is the primary symptom that limits exercise in patients with chronic obstructive pulmonary disease (COPD). It is unknown which activated brain area is associated with this symptom in COPD patients. OBJECTIVES: To investigate the activation of cortical areas associated with dyspnea during exercise in COPD patients. METHODS: COPD patients (n = 10) and age-matched controls (n = 10) performed mild-intensity constant work rate cycle exercise (40% of their symptom-limited peak work rates) for 10 min, while cerebral hemodynamics and oxygenation were measured by near-infrared spectroscopy (NIRS). Ventilatory responses (breathing pattern and pulmonary gas exchange) and Borg scale ratings of dyspnea and leg fatigue were measured during exercise. Three NIRS probes were placed over the prefrontal and temporoparietal cortical regions of the subjects' heads. Changes in cortical oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total Hb) concentrations from baseline recordings were measured. Increased oxy-Hb (oxygenation) was assumed to reflect cortical activation. RESULTS: Oxy-Hb concentration was significantly increased in the prefrontal region during exercise in both groups but not in the temporoparietal regions. The change in prefrontal oxy-Hb concentration of COPD patients was not different from that of controls. Dyspnea scores were positively correlated with changes in oxy-Hb concentrations of the prefrontal regions in both groups. Multivariate analysis showed that oxy-Hb concentration in the prefrontal region was the best predictor of dyspnea in both groups. CONCLUSIONS: Exertional dyspnea was related to activation (oxygenation) of the prefrontal cortex in COPD patients and control subjects.

A History of Recurrent Episodes of Prolonged Cough as a Predictive Value for Determining Cough Variant Asthma in a Primary Care Setting.

BACKGROUND: Many patients visit primary care clinics with a complaint of cough. General practitioners (GPs) developed a list of the causative diseases of cough that can produce a patient's symptoms and signs. Then, the patients' medical histories were evaluated to determine whether the diagnosis of cough variant asthma (CVA) or post-infectious cough (PIC) could have been predicted. METHODS: We retrospectively investigated 195 outpatients with a complaint of cough. Medical histories of "recurrent episodes of prolonged cough" and "upper respiratory infection" were obtained during the initial visit. The accuracy of medical histories in predicting CVA and PIC was calculated on the area under the curve (AUC). RESULTS: Among eligible patients with cough, PIC was diagnosed in 99 patients (50.8%), CVA in 40 patients (20.5%), upper airway cough syndrome in 28 patients (14.4%), and chronic obstructive pulmonary disease in 11 patients (5.6%). Among the patients with CVA and those with PIC, 93% and 12%, respectively, had a history of recurrent episodes of prolonged cough. For the diagnosis of CVA, having a history of recurrent episodes of prolonged cough showed a moderately accurate AUC (0.76, 95% CI: 0.71-0.82). On the other hand, for the diagnosis of PIC, having no history of recurrent episodes of prolonged cough also showed a moderately accurate AUC (0.87, 95% CI: 0.82-0.92). CONCLUSION: The medical history of recurrent episodes of prolonged cough is useful for the prediction of CVA as well as PIC.