Usefulness of serum transthyretin for prediction of the 1-year outcome in idiopathic pulmonary fibrosis: An evaluation of sarcopenic and nutritional indicators.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) often experience sarcopenia and malnutrition. However, this has not been fully examined through longitudinal surveys. This study investigated whether sarcopenia and malnutrition were associated with 1-year outcomes in IPF. METHODS: We evaluated sarcopenia and nutritional status in 64 outpatients with IPF. We assessed the time-to-event for respiratory-related hospitalizations or deaths 12 months after enrollment. Sarcopenia was diagnosed by the criteria of the Asian Working Group for Sarcopenia, 2019. Nutritional status was assessed by serum transthyretin and the Geriatric Nutritional Risk Index (GNRI). RESULTS: The average age was 73.6 ± 7.9 years, and the percent predicted forced vital capacity (FVC) was 81.9 ± 15.7%. Of the 64 patients, 24 (37.5%) had sarcopenia. The median serum transthyretin level and mean GNRI were 23.8 mg/dL and 102, respectively. Eleven patients (17.2%) experienced respiratory-related hospitalization or death within the first year. Cox regression analysis showed that the % predicted diffusion capacity for carbon monoxide, lowest oxygen saturation in the 6-min walk test, serum transthyretin level, and GNRI were significant predictors of 1-year outcomes. The Kaplan-Meier method, which divided the patients into two groups based on a transthyretin level of 22.6 mg/dL, showed a significant difference (P < 0.001, log-rank test). Sarcopenia and the percent predicted FVC did not predict the 1-year outcomes. CONCLUSIONS: This pilot study represents the first longitudinal survey assessing patients with IPF for sarcopenia and malnutrition. Serum transthyretin levels may predict respiratory-related hospitalization or death within 1 year in patients with IPF.

Efficacy of dupilumab for severe chronic rhinosinusitis with nasal polyps and asthma: A prospective study.

BACKGROUND: Dupilumab exerts clinical effects, including improved sinus opacification, olfactory function, and quality of life, in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNPs). Meanwhile, only a few studies have reported its effects on nasal airway resistance and olfactory function, particularly in the Japanese population. Predictors of response remain unclear. OBJECTIVE: To assess the comprehensive efficacy and therapeutic response to dupilumab in patients with severe CRSwNP with comorbid asthma. METHODS: In 16 adult patients with severe CRSwNP with comorbid asthma, the efficacy of 48-week dupilumab treatment, including olfactory function measured by a T&T olfactometer, nasal airway resistance measured by rhinomanometry, nasal polyp score, Lund-Mackay computed tomography score, and 22-item Sinonasal Outcome Test (SNOT-22), was assessed. Regarding asthma, the annualized rate of exacerbations, 7-item Asthma Control Questionnaire (ACQ-7), and spirometry were assessed. Treatment responsiveness was analyzed. RESULTS: With 48-week dupilumab treatment, olfactory function, nasal airway resistance, nasal polyp score, Lund-Mackay computed tomography score, and SNOT-22 scores improved significantly. Regarding comorbid asthma, the annualized rate of exacerbations decreased, and ACQ-7 scores and lung function improved significantly. According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020/European Forum for Research and Education in Allergy and Airway Diseases criteria, 15 patients (94%) were moderate-to-excellent responders at 48 weeks of treatment. Patients with higher SNOT-22 scores, ACQ-7 scores, the rate of asthma exacerbations in the previous year, and blood eosinophil counts benefited more from the treatment. CONCLUSION: Dupilumab improved upper and lower airway outcomes especially in patients with severe CRSwNP with comorbid, poorly controlled asthma. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000038669.

Prevalence and clinical relevance of comorbid pertussis infection in adult patients with asthma: A prospective, cross-sectional study.

BACKGROUND: Viral or atypical bacterial respiratory infections are involved in the new development and the pathogenesis of asthma. Though an association between pertussis and asthma has been expected, few studies have reported it consistently. We assessed the prevalence and clinical relevance of pertussis infection in adult patients with asthma. METHODS: In this prospective, cross-sectional study, newly referred, adult patients with asthma (n = 107) and with non-asthmatic subacute/chronic cough (n = 31) were enrolled. The prevalence of pertussis in patients with asthma and in those with non-asthmatic subacute/chronic cough was assessed. Next, the prevalence of newly diagnosed asthma was compared between asthmatic patients with and without pertussis. Finally, demographic characteristics of patients, blood test results, pulmonary function test results, and questionnaire scores were compared between the two patient groups. RESULTS: The prevalence of pertussis infection was significantly higher in patients with asthma than in those with non-asthmatic subacute/chronic cough (36% vs 10%; P = 0.004). The prevalence of newly diagnosed asthma was significantly higher in asthmatic patients with pertussis than in those without (74.4% vs 50.0%; P = 0.014). The physical, psychological, and total scores of the Leicester Cough Questionnaire were significantly lower in asthmatic patients with pertussis than in those without (all P < 0.05). The acid-reflux, dyspeptic, and total scores of the Frequency Scale for Symptoms of Gastroesophageal Reflux Disease (GERD) (FSSG) were significantly higher in asthmatic patients with pertussis than in those without (all P ≤ 0.05). The FSSG acid-reflux score was negatively correlated with the cough-specific quality of life (QOL) score only in asthmatic patients with pertussis (rho = -0.68, P = 0.01). CONCLUSIONS: The prevalence of pertussis infection was significantly higher in adult patients with asthma than in those with non-asthmatic subacute/chronic cough. In patients with asthma, comorbid pertussis infection may play a role in newly diagnosed asthma and may contribute to impaired cough-specific QOL partly due to worsening acid-reflux symptoms of GERD.

A rare case of a huge malignant pleural mesothelioma presenting in the posterior mediastinum.

We report a case of a 69-year-old woman with pleural mesothelioma presenting in the posterior mediastinum with a maximum diameter of 25 cm. She had a chronic cough and a pleural effusion was noted on chest X-ray. The examination of the effusion showed high hyaluronic acid levels, and mesothelioma was suspected. A chest computed tomography scan showed a huge mediastinal mass, which caused rapid progression of respiratory failure and compression of the heart. Sufficient tissue samples could not be obtained before death. The patient died approximately 1 month after the initial visit, and a pathological autopsy was performed. The diagnosis of malignant pleural mesothelioma was made. Malignant pleural mesothelioma with a huge posterior mediastinal mass such as in this case is considerably rare; however, it is a rapidly progressing form of the disease and is reported here as an important differential diagnosis for mediastinal tumours.

Benefit-Risk Profile of P2X3 Receptor Antagonists for Treatment of Chronic Cough: Dose-Response Model-Based Network Meta-Analysis.

BACKGROUND: Refractory or unexplained chronic cough disrupts quality of life and burdens health care systems around the world. The P2X3 receptor antagonist gefapixant is approved in many countries for its antitussive effects, but taste disturbances are a common adverse effect. Four newer, more selective P2X3 receptor antagonists have been developed to address this problem. RESEARCH QUESTION: How does the benefit-risk profile vary across the five available P2X3 receptor antagonists? STUDY DESIGN AND METHODS: A systematic review and network meta-analysis was conducted to evaluate the efficacy of P2X3 receptor antagonists, including gefapixant, sivopixant, eliapixant, camlipixant, and filapixant. Primary outcomes were a reduction rate in 24-h cough frequency and incidence of taste disturbance. Dose-response curves and median effective dose (ED50) were calculated. Effect size at ED50 was ranked according to the surface under the cumulative ranking curve. The confidence was evaluated by Confidence In Network Meta-Analysis. RESULTS: Sixteen randomized controlled trials involving 4,904 participants were analyzed. The gefapixant regimen demonstrated an ED50 of 90.7 mg/d for cough frequency reduction. Gefapixant showed the highest antitussive effectiveness at ED50 (reduction rate in 24-h cough frequency: median, 28.1%; 95% credible interval [CrI], 21.0%-35.6%; ranked 1 of 5; moderate certainty) but the highest prevalence of taste disturbance (absolute risk difference per 100 patients: median, 38; 95% CrI, 27-51; ranked 5 of 5; high certainty) and the highest prevalence of discontinuation. Camlipixant had a well-balanced profile (reduction rate in 24-h cough frequency: median, 14.7%; 95% CrI, 5.4%-26.0%; ranked 3 of 5; low certainty; and taste disturbance; absolute risk difference per 100 patients; median, 2; 95% CrI, 1-6; ranked 2 of 5; low certainty). Placebo had a mean of 33.1% reduction in 24-h cough frequency. INTERPRETATION: When used at safe doses, gefapixant had a favorable risk-benefit profile compared with the other four agents. Camlipixant showed initial promise, which may be further investigated by phase III trials currently underway. CLINICAL TRIAL REGISTRATION: UMIN000050622; URL.

Comorbid functional dyspepsia reflects IL-33-mediated airway neuronal dysfunction in asthma.

BACKGROUND: Neuronal dysfunction is implicated in the pathophysiology of asthma and functional dyspepsia (FD). However, the relationship between these diseases remains unclear. OBJECTIVE: This study aimed to clarify the clinical implications of comorbid FD in asthma and to explore the unified pathway between asthma and FD by focusing on airway neuronal dysfunction. METHODS: Clinical indices and biomarkers, including capsaicin cough sensitivity (C-CS), were compared between patients with asthma with and without FD. C-CS was determined on the basis of capsaicin concentration that induced at least 2 coughs (C2) or 5 coughs (C5). Additionally, the associations of airway inflammation with airway innervation and gastrointestinal motility were evaluated in mouse models of type 2 airway inflammation. RESULTS: Patients with asthma with FD had worse asthma control and cough severity and lower C2 and C5 thresholds than those without FD. The severity of FD symptoms was negatively correlated with C2 and C5 thresholds. FD and poor asthma control were predictors of heightened C-CS (defined as C5 ≤ 2.44 µmol) in asthma. A mouse model of papain-induced airway inflammation developed airway hyperinnervation and gastrointestinal dysmotility, and both pathologies were ameliorated by an anti-IL-33 antibody. Moreover, papain-induced gastrointestinal dysmotility was mitigated by silencing the airway sensory neurons using QX-314, a sodium channel blocker. Furthermore, sputum IL-33 levels were significantly elevated in patients with asthma with FD or heightened C-CS compared to their counterparts. CONCLUSION: FD is significantly associated with airway neuronal dysfunction in asthma. IL-33-mediated airway neuronal dysfunction may contribute to the interaction between asthma and FD.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Efficacy of dupilumab for airway hypersecretion and airway wall thickening in patients with moderate-to-severe asthma: A prospective, observational study.

BACKGROUND: Dupilumab has clinical effects in patients with moderate-to-severe asthma. When considering interleukin (IL)-4 and IL-13 signaling, effects of dupilumab on airway mucus hypersecretion and airway remodeling are expected, but they have been reported in only a few short-term studies. Its efficacy for airway hyperresponsiveness (AHR) remains unknown. We comprehensively assessed the efficacy of dupilumab, especially for subjective and objective measures of airway mucus hypersecretion and airway dimensions in moderate-to-severe asthmatic patients. METHODS: In 28 adult patients with moderate-to-severe uncontrolled asthma, the comprehensive efficacy of 48-week dupilumab treatment, including the Cough and Sputum Assessment Questionnaire (CASA-Q), radiological mucus scores and airway dimensions on computed tomography (CT), was assessed prospectively. Treatment responsiveness to dupilumab was analyzed. RESULTS: With 48-week dupilumab treatment, all four cough and sputum domain scores of CASA-Q improved significantly. Radiological mucus scores and airway wall thickening on CT were significantly decreased. The decreases in mucus scores were significantly associated with improvements in Asthma Control Questionnaire scores, Asthma Quality of Life Questionnaire (AQLQ) overall scores, airway obstruction, and airway type 2 inflammation. When defined by > 0.5 improvement in AQLQ overall scores, 18 patients (64%) were identified as responders. CONCLUSIONS: Dupilumab reversed subjective and objective measures of airway mucus hypersecretion and some aspects of airway remodeling in patients with moderate-to-severe uncontrolled asthma.

Prevalence and causes of chronic cough in Japan.

BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.

Efficacy and safety of macrolide therapy for adult asthma: A systematic review and meta-analysis.

BACKGROUND: The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine the efficacy and safety of macrolide therapy for adult asthma. METHODS: We searched randomized controlled trials from MEDLINE via the PubMed, CENTRAL, and Ichushi Web databases. The primary outcome was asthma exacerbation. The secondary outcomes were serious adverse events (including mortality), asthma-related quality of life (symptom scales, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire), rescue medication (puffs/day), respiratory function (morning peak expiratory flow, evening peak flow, and forced expiratory volume in 1 s), bronchial hyperresponsiveness, and minimum oral corticosteroid dose. Of the 805 studies, we selected seven studies for the meta-analysis, which was conducted using a random-effects model. SYSTEMATIC REVIEW REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000050824). RESULTS: No significant difference between macrolide and placebo for asthma exacerbations was observed (risk ratio 0.71, 95 % confidence interval [CI] 0.46-1.09; p = 0.12). Macrolide therapy for adult asthma showed a significant improvement in rescue medication with short-acting beta-agonists (mean difference -0.41, 95 % CI -0.78 to -0.04; p = 0.03). Macrolide therapy did not show more serious adverse events (odd ratio 0.61, 95 % CI 0.34-1.10; p = 0.10) than those with placebo. The other secondary outcomes were not significantly different between the macrolide and placebo groups. CONCLUSIONS: Macrolide therapy for adult asthma may be more effective than placebo and could be a treatment option.

Relevant factors associated with the development of chronic cough after recovery from COVID-19.

BACKGROUND: Cough is one of the symptoms of the post-COVID-19 condition. However, the factors associated with its development remain unclear. We evaluated the factors associated with chronic cough in the post-COVID-19 condition. METHODS: In this survey, 170 individuals who previously had COVID-19 and were admitted to Aichi Hospital between October 2020 and October 2021 were included. Using self-developed questionnaires and visual analog scales, 19 symptoms, including cough, were assessed. Cough-specific quality of life (QoL), reflux-related symptoms, and abnormal laryngeal sensations were also evaluated. The patients' clinical characteristics and indices, including cough-specific QoL, at admission were extracted from their medical records. Multivariate regression analyses were conducted to determine the factors associated with cough-related outcomes, such as prevalence, QoL, and severity, in the post-COVID-19 condition. RESULTS: The median length (range) of the survey after recovery from COVID-19 was 158 (95-467) days. Cough was prevalent (n = 41, 24 %) and often accompanied by other symptoms, including gastrointestinal symptoms. Cough-specific QoL after recovery was correlated with reflux-related symptoms and abnormal laryngeal sensations. Multivariate analyses revealed that gastrointestinal symptoms, sputum, and chronic cough before contracting COVID-19 are significant predictors of cough-related outcomes in the post-COVID-19 condition. Meanwhile, other indices including cough-specific QoL on the acute phase were not reliable predictors in the post-COVID-19 condition. CONCLUSIONS: Cough during the post-COVID-19 condition had a negative impact on daily life activities. Gastrointestinal symptoms could play a significant role in the pathophysiology of cough in such a condition.

Effectiveness of remdesivir-based therapy for moderate COVID-19: comparison of Omicron and other variant phases.

Remdesivir is an antiviral drug for the treatment of coronavirus disease 2019 (COVID-19), and the sustained antiviral activity against Omicron variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been reported. In this single-center retrospective study, we first compared the clinical effectiveness of remdesivir-based therapy between Omicron and other variant phases of moderate COVID-19 in a real-world setting. Between Dec 2020 and July 2022, a total of 406 patients with COVID-19 pneumonia were treated with remdesivir-based therapy on admission. The oxygen deterioration rate after initiation of treatment significantly decreased in the Omicron variant phase compared to the alpha and delta variant phases. In an adjusted multivariate Cox proportional hazards model, Omicron variant phase was significantly associated with delayed oxygen deterioration and early recovery from hypoxia. These favorable outcomes during the Omicron variant phase, compared to previous variant phases, might be due to the attenuation and the popularization of vaccination.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study.

Background: Current guidelines on the management of chronic cough do not provide recommendations for the operation of specialist cough clinics. The objective of the present study was to develop expert consensus on goals and standard procedures for specialist cough clinics. Methods: We undertook a modified Delphi process, whereby initial statements proposed by experts were categorised and presented back to panellists over two ranking rounds using an 11-point Likert scale to identify consensus. Results: An international panel of 57 experts from 19 countries participated, with consensus reached on 15 out of 16 statements, covering the aims, roles and standard procedures of specialist cough clinics. Panellists agreed that specialist cough clinics offer optimal care for patients with chronic cough. They also agreed that history taking should enquire as to cough triggers, cough severity rating scales should be routinely used, and a minimum of chest radiography, spirometry and measurements of type 2 inflammatory markers should be undertaken in newly referred patients. The importance of specialist cough clinics in promoting clinical research and cough specialty training was acknowledged. Variability in healthcare resources and clinical needs between geographical regions was noted. Conclusions: The Delphi exercise provides a platform and guidance for both established cough clinics and those in planning stages.

Symptomatic radiation-induced rib fractures after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

Background and purpose: The present study investigated the relationships between the risk of radiation-induced rib fractures (RIRF) and clinical and dosimetric factors in stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). We also examined dosimetric parameters associated with symptomatic or asymptomatic RIRF and the dosimetric threshold for symptomatic RIRF. Materials and methods: We reviewed 244 cases of early-stage NSCLC treated with SBRT. Gray's test and the Fine-Gray model were performed to examine the relationships between clinical and dosimetric factors and grade ≥ 2 (i.e., symptomatic) RIRF. The effects of each dose parameter on grade ≥ 1 and ≥ 2 RIRF were assessed with the Fine-Gray model. The t-test was used to compare each dose parameter between the grade 1 and grade ≥ 2 groups. Optimal thresholds were tested using receiver operating characteristic (ROC) curves. Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥ 1 and grade ≥ 2 RIRF were 26.4 % and 8.0 %, respectively. Regarding clinical factors, only age was associated with the development of grade ≥ 2 RIRF (p = 0.024). Among dosimetric parameters, only V40Gy significantly differed between the grade 1 and grade ≥ 2 groups (p = 0.015). The ROC curve analysis of grade ≥ 2 RIRF showed that the optimal diagnostic thresholds for D3cc, D4cc, D5cc, and V40Gy were 45.86 Gy (area under the curve [AUC], 0.706), 39.02 Gy (AUC, 0.705), 41.62 Gy (AUC, 0.702), and 3.83 cc (AUC, 0.730), respectively. These results showed that V40Gy ≤ 3.83 cc was the best indicator of grade ≥ 2 RIRF. The 4-year incidence of grade ≥ 2 RIRF in the V40Gy ≤ 3.83 cc vs. > 3.83 cc groups was 1.8 % vs. 14.2 % (p = 0.001). Conclusion: The present results recommend V40Gy ≤ 3.83 cc as the threshold for grade ≥ 2 RIRF in SBRT.

Low Daily Step Count Associated with Small Erector Spine Muscle Area and Sarcopenia in Idiopathic Pulmonary Fibrosis.

Objective The daily step count is associated with mortality in idiopathic pulmonary fibrosis (IPF). However, the factors associated with this phenomenon are not yet fully understood. We therefore clarified its association with clinical parameters. Methods Fifty-nine patients with IPF with available data for daily step counts; 6-minute walk distance (6MWD); chest, abdominal, and pelvic computed tomography (CT); pulmonary function; psychological evaluations; and sarcopenia assessments were prospectively enrolled. The daily step count was measured continuously for seven consecutive days. The cross-sectional areas of the erector spinae muscles at the level of the 12th vertebra (ESMCSA) and psoas major muscle volume (PMV) obtained by CT were assessed. Results The average age of the patients was 73.3±8.1 years old, and the percent predicted forced vital capacity was 81.6% ±15.8%. The average daily step count was 4,258 (2,155-6,991) steps. The average 6MWD, ESMCSA, and PMV were 413±97 m, 25.5±6.7 cm2, and 270±75.6 cm3, respectively. A linear regression analysis for daily step count showed that the ESMCSA and 6MWD were independent factors for the daily step count, whereas the PMV and skeletal muscle index were not. The daily step count, ESMCSA, and 6MWD were lower in patients with sarcopenia than in those without sarcopenia. Conclusions A lower daily step count was associated with a smaller erector spinae muscle area and sarcopenia in patients with IPF. Further studies are warranted to confirm the importance of physical therapy for muscle strengthening in patients with IPF.

High-dimensional analysis of T-cell profiling variations following belimumab treatment in systemic lupus erythematosus.

OBJECTIVE: This study sought to elucidate the molecular impacts of belimumab (BEL) treatment on T-cell immune profiling in SLE. METHODS: We used mass cytometry with 25 marker panels for T-cell immune profiling in peripheral blood T cells (CD3+) from 22 patients with BEL-treated SLE and 20 controls with non-BEL-treated SLE. An unsupervised machine-learning clustering, FlowSOM, was used to identify 39 T-cell clusters (TCLs; TCL01-TCL39). TCLs (% of CD3+) showing significant (p<0.05) associations with BEL treatment (BEL-TCL) were selected by a linear mixed-effects model for comparing groups of time-series data. Furthermore, we analysed the association between BEL treatment and variations in regulatory T-cell (Treg) phenotypes, and the ratio of other T-cell subsets to Treg as secondary analysis. RESULTS: Clinical outcomes: BEL treatment was associated with a decrease in daily prednisolone use (coef=-0.1769, p=0.00074), and an increase in serum CH50 (coef=0.4653, p=0.003), C3 (coef=1.1047, p=0.00001) and C4 (coef=0.2990, p=0.00157) levels. Molecular effects: five distinct BEL-TCLs (TCL 04, 07, 11, 12 and 27) were identified. Among these, BEL-treated patients exhibited increased proportions in the Treg-like cluster TCL11 (coef=0.404, p=0.037) and two naïve TCLs (TCL04 and TCL07). TCL27 showed increased levels (coef=0.222, p=0.037) inversely correlating with baseline C3 levels. Secondary analyses revealed associations between BEL treatment and an increase in Tregs (coef=1.749, p=0.0044), elevated proportions of the fraction of Tregs with inhibitory function (fTregs, coef=0.7294, p=0.0178) and changes in peripheral helper T cells/fTreg (coef=-4.475, p=0.0319) and T helper 17/fTreg ratios (coef=-6.7868, p=0.0327). Additionally, BEL was linked to variations in T-cell immunoglobulin and mucin domain-containing protein-3 expression (coef=0.2422, p=0.039). CONCLUSIONS: The study suggests an association between BEL treatment and variations in T cells, particularly Tregs, in SLE pathologies involving various immune cells.

Clinical and dosimetric factors for symptomatic radiation pneumonitis after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

Background and purpose: The present study attempted to identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) in patients with early-stage non-small cell lung cancer (NSCLC). Materials and methods: We reviewed 244 patients with early-stage NSCLC treated with SBRT. The primary endpoint was the incidence of grade ≥2 RP. Gray's test was performed to examine the relationship between clinical risk factors and grade ≥2 RP, and the Fine-Gray model was used for a multivariate analysis. The effects of each dose parameter on grade ≥2 RP were evaluated with the Fine-Gray model and optimal thresholds were tested using receiver operating characteristic (ROC) curves. Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥2 RP was 15.3%. Gray's test revealed that tumor size, a central tumor, interstitial pneumonia, and the biologically effective dose correlated with RP. In the multivariate analysis, a central tumor and interstitial pneumonia remained significant factors (p < 0.001, p = 0.002). Among dose parameters, the total lung volume (%) receiving at least 8 Gy (V8), V10, V20, and the mean lung dose correlated with RP (p = 0.012, 0.011, 0.022, and 0.014, respectively). The results of the Fine-Gray model and ROC curve analyses showed that V10 >16.7% was the best indicator of symptomatic RP among dose parameters. Conclusion: The present results suggest that a central tumor and interstitial pneumonia are independent risk factors for symptomatic RP and lung V10 ≤16.7% is recommended as the threshold in SBRT.

Bronchial thermoplasty improves cough hypersensitivity and cough in severe asthmatics.

BACKGROUND: Cough is a troublesome symptom of asthma because it is associated with disease severity and poor asthma control. Bronchial thermoplasty (BT) may be effective in improving cough severity and cough-related quality of life in severe uncontrolled asthma. OBJECTIVE: To evaluate the efficacy of BT for cough in severe uncontrolled asthma. METHODS: Twelve patients with severe uncontrolled asthma were enrolled in this study between 2018 May and March 2021 and arbitrarily divided into cough-predominant [cough severity Visual Analog Scale (VAS) ≥ 40 mm, n = 8] and typical asthma (cough VAS <40 mm, n = 4) groups. Clinical parameters, such as capsaicin cough sensitivity [C-CS: the concentrations to inhaled capsaicin required to induce at least two (C2) and five (C5) coughs], lung function, and type-2-related biomarkers (fractional nitric oxides and absolute eosinophil counts) and cough-related indices [cough severity VAS and the Leicester Cough Questionnaire (LCQ)] were evaluated before and 3 months after performing BT. RESULTS: BT significantly improved both cough-related indices and C-CS in the cough-predominant group. Changes in C-CS were significantly correlated with changes in the LCQ scores (C5: r = 0.65, p = 0.02 for all patients, and r = 0.81, p = 0.01 for the cough-predominant group). CONCLUSIONS: BT may be effective for cough in severe uncontrolled asthma by improving C-CS. However, further larger cohort studies are necessary to confirm the effect of BT for cough in asthma. CLINICAL TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (Registry ID UMIN: 000031982).