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.

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 (CRSwNP). 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: In this prospective, observational study, we assessed the comprehensive efficacy and therapeutic response to dupilumab in severe CRSwNP patients with comorbid asthma. METHODS: In 16 adult severe CRSwNP patients 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 (LMS), 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, LMS, and SNOT-22 scores improved significantly. Regarding comorbid asthma, the rate of exacerbations decreased, and ACQ-7 scores and lung function improved significantly. According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2022/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, rates of asthma exacerbation in the previous year, and blood eosinophil counts benefited more from treatment. CONCLUSION: Dupilumab improved upper and lower airway outcomes especially in severe CRSwNP patients with comorbid, poorly controlled asthma.

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.

Unrealistic expectations and disclosure of incurability in patients with non-small cell lung cancer.

PURPOSE: Determining whether patients' unrealistic expectations of chemotherapy as a cure were associated with their perception of the disclosure of incurability. METHODS: This prospective study included consecutive patients with pretreated non-small cell lung cancer from four study sites. Patients and their oncologists were asked whether they perceived the disclosure of cancer incurability. Patients were also asked if they thought that chemotherapy was curative. We followed up on whether the deceased patients received specialized palliative care 14 months after their last enrollment. Multiple regression analyses were conducted to examine the association between the expectation of chemotherapy as a cure and patient/oncologist-reported perceptions of the disclosure of incurability. RESULTS: We analyzed 200 patients, 77 (38.5%) of whom had unrealistic expectations of a cure. Based on patients' perceptions, incurability was disclosed to 138 (69.0%) patients, and based on their oncologists' perceptions, incurability was disclosed to 185 (92.5%) patients (patient/oncologist agreements, κ = 0.19). Patients without a perception of the oncologist's disclosure of incurability-regardless of their oncologist's perception-were more likely to have unrealistic expectations of a cure than patients for whom both patient and oncologist perceptions were present. Patients who had unrealistic expectations of chemotherapy as a cure were shown to be significantly less likely to have received specialized palliative care, after adjusting for covariates (adjusted OR, 0.45; 95% CI, 0.23-0.91; p = .027). CONCLUSION: Oncologists' disclosure of incurability was not fully recognized by patients, and expectations of chemotherapy as a cure were associated with patients' perception of the disclosure of incurability.

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.

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.

Elements of End-of-Life Discussions Associated With Patients' Reported Outcomes and Actual End-of-Life Care in Patients With Pretreated Lung Cancer.

BACKGROUND: End-of-life discussions for patients with advanced cancer are internationally recommended to ensure consistency of end-of-life care with patients' values. This study examined the elements of end-of-life discussions associated with end-of-life care. MATERIALS AND METHODS: We performed a prospective observational study among consecutive patients with pretreated non-small cell lung cancer after the failure of first-line chemotherapy. We asked oncologists whether they had ever discussed "prognosis," "do not attempt resuscitation," "hospice," and "preferred place of death" with a patient at baseline. The quality of life (QOL) and depressive symptoms of patients were assessed using validated questionnaires at baseline and 3 months later. The end-of-life care that patients received was investigated using medical records. Oncologists' compassion and caregivers' preferences for hospice care were also assessed using questionnaires. Multiple regression analyses were conducted to examine the association between elements of end-of-life discussions and patient-reported outcomes as well as actual end-of-life care. RESULTS: We obtained 200 valid responses at baseline, 147 valid responses 3 months later, and 145 data points for medical care at the end-of-life stage. No element of the end-of-life discussion between the patient and their oncologist was significantly associated with patients' reported outcomes or actual end-of-life care. In addition, oncologists' compassion was significantly associated with improvement in both comprehensive QOL and depressive symptoms, and caregivers' preferences for hospice care and high educational level were significantly associated with hospice death. CONCLUSION: Oncologist-patient alliances and caregivers' involvement in end-of-life discussions may be influential in achieving optimal end-of-life care.

Dose and gender dependence of chlorine inhalation in a conscious ovine model.

Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl2 concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl2 premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO2/FiO2 ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO2/FiO2 ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO2/FiO2 ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl2 significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl2 concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl2 concentrations. No significant sex-dependent differences were found in measured endpoint variables.

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.

Shrinkage of Enlarged Hepatic Nodules by an Embolizing Congenital Extrahepatic Portosystemic Shunt.

A 38-year-old woman was admitted to our university hospital with loss of muscle strength. She was diagnosed with dermatomyositis and underwent contrast-enhanced computed tomography of the entire body to check for malignant tumors. Computed tomography revealed multiple enhanced hepatic nodules and an extrahepatic portosystemic shunt. Although a needle biopsy of the nodule could not diagnose definitive hepatocellular carcinoma, some nodules increased in size after three months. Because of the inconclusive results of the second biopsy, we performed shunt embolization using a vascular plug. After another three months, the hepatic nodules shrank markedly, as expected.

Gastric neuroendocrine carcinoma presenting complete durable response by nivolumab treatment for multiple metastases and radiotherapy to oligoprogressive metastasis.

Gastric neuroendocrine carcinomas (NEC) are highly aggressive cancer with dismal prognosis. Platinum-based chemotherapy is used as the first-line treatment for this entity. However, there are no established therapeutic guidelines for platinum-resistant gastric NEC. We herein report a patient with metastatic gastric NEC who achieved durable and complete response to nivolumab with radiotherapy for oligoprogressive metastasis. A 70-year-old male patient had recurrences of resected gastric NEC, involving the liver and lymph nodes. His disease became refractory to cisplatin and etoposide combination therapy, after which he was treated with nivolumab. All the tumors showed marked shrinkage. However, 1 year after starting nivolumab, one metastatic lesion of the liver began to enlarge, and radiotherapy was performed to the lesion. Thereafter, a complete response was obtained, which has been maintained without any treatment for the past 2 years.

Effects of nebulized adipose-derived mesenchymal stem cells on acute lung injury following smoke inhalation in sheep.

INTRODUCTION: Treatment of ARDS caused by smoke inhalation is challenging with no specific therapies available. The aim of this study was to test the efficacy of nebulized adipose-derived mesenchymal stem cells (ASCs) in a well-characterized, clinically relevant ovine model of smoke inhalation injury. MATERIAL AND METHODS: Fourteen female Merino sheep were surgically instrumented 5-7 days prior to study. After induction of acute lung injury (ALI) by cooled cotton smoke insufflation into the lungs (under anesthesia and analgesia), sheep were placed on a mechanical ventilator for 48 hrs and monitored for cardiopulmonary hemodynamics in a conscious state. ASCs were isolated from ovine adipose tissue. Sheep were randomly allocated to two groups after smoke injury: 1) ASCs group (n = 6): 10 million ASCs were nebulized into the airway at 1 hr post-injury; and 2) Control group (n = 8): Nebulized with saline into the airways at 1 hr post-injury. ASCs were labeled with green fluorescent protein (GFP) to trace cells within the lung. ASCs viability was determined in bronchoalveolar lavage fluid (BALF). RESULTS: PaO2/FiO2 in the ASCs group was significantly higher than in the control group (p = 0.001) at 24 hrs. Oxygenation index: (mean airway pressure × FiO2/PaO2) was significantly lower in the ASCs group at 36 hr (p = 0.003). Pulmonary shunt fraction tended to be lower in the ASCs group as compared to the control group. GFP-labelled ASCs were found on the surface of trachea epithelium 48 hrs after injury. The viability of ASCs in BALF was significantly lower than those exposed to the control vehicle solution. CONCLUSION: Nebulized ASCs moderately improved pulmonary function and delayed the onset of ARDS.

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).

Relationship Between Safety and Cumulative Bevacizumab Dose in Patients With Metastatic Colorectal Cancer Who Received Long-term Bevacizumab Treatment.

BACKGROUND/AIM: Bevacizumab-based chemotherapy is the standard treatment for metastatic colorectal cancer (mCRC) but has several specific adverse events. The cumulative bevacizumab dose (CBD) increases with long-term treatment as it is often used beyond the first disease progression, based on existing evidence. However, the association between CBD and the frequency and severity of adverse events in mCRC patients who received bevacizumab for long-term treatment remains unclear. PATIENTS AND METHODS: Among the mCRC patients who received bevacizumab-based chemotherapy between March 2007 and December 2017 at the University of Tsukuba Hospital, those who continued treatment for more than 2 years were eligible for the study. The onset and worsening of proteinuria, hypertension, bleeding, and thromboembolic events were assessed to determine their relationship with CBD. RESULTS: Of the 109 patients who received bevacizumab-based chemotherapy, 24 were included in the study. Grade 3 proteinuria was observed in 21 (88%) and 9 (38%) patients. The severity of proteinuria markedly increased after administering >100 mg/kg of CBD and progressed to grade 3 at concentrations exceeding 200 mg/kg. Thromboembolic events were observed in three (13%) patients, and two of them developed acute myocardial infarction after receiving a CBD of >300 mg/kg. Grade 2 or higher hypertension and grade 1 bleeding were observed in 9 (38%) patients and in 6 (25%) patients, respectively, regardless of the CBD. CONCLUSION: Proteinuria and thromboembolic events occurred and worsened in mCRC patients when the bevacizumab dose exceeded the threshold dose.

Tiotropium for refractory cough in asthma via cough reflex sensitivity: A randomized, parallel, open-label trial.

BACKGROUND: We previously reported in an uncontrolled study that tiotropium alleviated chronic cough in asthma refractory to inhaled corticosteroids and long-acting ß2 agonists (ICS/LABA) by modulating capsaicin cough reflex sensitivity (C-CRS). OBJECTIVE: We sought to determine the antitussive effects of tiotropium for refractory cough in asthma in a randomized, parallel, open-label trial. METHODS: A total of 58 patients with asthma having chronic cough refractory to ICS/LABA were randomized in a 2:1 ratio to add tiotropium 5 µg (39 patients) or theophylline 400 mg (19 patients) for 4 weeks. Patients underwent workups, including capsaicin cough challenge test and subjective measures such as cough severity visual analog scales (VAS). We adopted C5, the lowest capsaicin concentration to induce at least 5 coughs, as an index of C-CRS. We also performed a posthoc analysis to identify factors predicting tiotropium responders, who found an improvement of at least 15 mm in cough severity VAS. RESULTS: A total of 52 patients (tiotropium, 38; theophylline, 14) completed the study. Both tiotropium and theophylline significantly improved cough severity VAS and cough-specific quality of life. Tiotropium, but not theophylline, significantly increased C5, whereas pulmonary function did not change in either group. In addition, changes in cough severity VAS correlated with changes in C5 values in the tiotropium group. A posthoc analysis revealed that heightened C-CRS (C5 ≤1.22 µM) before the addition of tiotropium was an independent predictor for tiotropium responders. CONCLUSION: Tiotropium may alleviate chronic cough in asthma refractory to ICS/LABA by modulating C-CRS. Heightened C-CRS may predict responsiveness to tiotropium for refractory cough in asthma. TRIAL REGISTRATION: Clinical Trials Registry ID: UMIN000021064 (https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000024253).

Targeting the interleukin-5 pathway improves cough hypersensitivity in patients with severe uncontrolled asthma.

BACKGROUND: Capsaicin cough sensitivity (C-CS) reflects airway neuronal dysfunction and may be a significant biomarker of asthma. Although mepolizumab reduces cough in patients with severe uncontrolled asthma, it is unclear whether the cough reduction is associated with improved C-CS. OBJECTIVE: To clarify the effect of biologics on C-CS and cough-specific quality of life (QoL) in patients with severe uncontrolled asthma using our previous study cohort. METHODS: Overall, 52 consecutive patients who visited our hospital for severe uncontrolled asthma were included in the original study cohort, and 30 patients were eligible for this study. Changes in C-CS and cough-specific QoL were compared between patients treated with the anti-interleukin-5 (IL-5) pathway (n = 16) and those treated with other biologics (n = 14). The C-CS was measured as the concentration of capsaicin required to induce at least 5 coughs. RESULTS: Biologics significantly improved C-CS (P = .03). Anti-IL-5 pathway therapies significantly improved C-CS, whereas other biologics did not (P < .01 and P = .89, respectively). The C-CS improved significantly more in the anti-IL-5 pathway group than in the group treated with other biologics (P = .02). Changes in C-CS significantly correlated with improvements in cough-specific QoL in the anti-IL-5 pathway group (r = 0.58, P = .01) but not in the group treated with other biologics (r = 0.35, P = .22). CONCLUSION: Anti-IL-5 pathway therapies improve C-CS and cough-specific QoL, and targeting the IL-5 pathway may be a therapeutic strategy for cough hypersensitivity in patients with severe uncontrolled asthma.

GENDER-RELATED VARIATIONS IN PATHOPHYSIOLOGICAL RESPONSES TO METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS PNEUMONIA AND SEPSIS.

ABSTRACT: In preclinical studies, the protective effects of female sex hormones and the immunosuppressive effects of male sex hormones were demonstrated. However, gender-related differences in multiorgan failure and mortality in clinical trials have not been consistently explained. This study aims to investigate gender-related differences in the development and progression of sepsis using a clinically relevant ovine model of sepsis. Adult Merino male (n=7) and female (n=7) sheep were surgically prepared with multiple catheters before the study. To induce sepsis, bronchoscopy instilled methicillin-resistant Staphylococcus aureus into sheep's lungs. The time from the bacterial inoculation until the modified Quick Sequential Organ Failure Assessment (q-SOFA) score became positive was measured and analyzed primarily. We also compared the SOFA score between these male and female sheep over time. Survival, hemodynamic changes, the severity of pulmonary dysfunction, and microvascular hyperpermeability were also compared. The time from the onset of bacterial inoculation to the positive q-SOFA in male sheep was significantly shorter than in female sheep. Mortality was not different between these sheep (14% vs. 14%). There were no significant differences in hemodynamic changes and pulmonary function between the two groups at any time point. Similar changes in hematocrit, urine output, and fluid balance were observed between females and males. The present data indicate that the onset of multiple organ failure and progression of sepsis is faster in male sheep than in female sheep, even though the severity of cardiopulmonary function is comparable over time. Further studies are warranted to validate the above results.

Specific IgE Response and Omalizumab Responsiveness in Severe Allergic Asthma.

Objective: Omalizumab has demonstrated clinical efficacy in patients with severe allergic asthma sensitized to perennial allergens and/or severe pollinosis through inhibition of IgE-dependent allergic response. When considering the "one airway, one disease" concept, sensitization to pollen could predict responsiveness to omalizumab. This study aimed to assess whether the pretreatment specific IgE response could be a predictor of responsiveness to omalizumab in severe allergic asthma sensitized to perennial allergens. Methods: In this retrospective study, 41 adult patients with severe allergic asthma sensitized to perennial allergens (27 females; mean age 59 years) who had completed 52-week omalizumab treatment were enrolled. The Global Evaluation of Treatment Effectiveness was performed, and demographic characteristics and the positive ratios of specific IgE responses classified into five subgroups (pollen, dust mite, house dust, mold, and animal dander) were compared between responders and non-responders. Multivariate logistic regression analyses were performed to identify predictors of responsiveness to omalizumab. Results: Thirty-one patients (76%) were identified as responders. The number of sensitized aeroallergen subgroups and sensitization to pollens were significantly higher in responders than in non-responders (both p<0.05). Multivariate logistic regression analysis showed that sensitization to pollen (OR = 8.41, p = 0.02) was independently associated with the effectiveness of omalizumab. Conclusion: Pretreatment serum pollen-specific IgE could be a predictor of responsiveness to omalizumab.

Decreased capsaicin cough reflex sensitivity predicts hospitalisation due to COPD.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) are often hospitalised due to severe acute exacerbation (AE) or community-acquired pneumonia (CAP). Previous studies revealed the association of cough reflex sensitivity with the pathophysiology of COPD and pneumonia. We hypothesised that cough reflex sensitivity may be associated with severe AE or CAP requiring hospitalisation in patients with COPD. METHODS: We prospectively recruited 68 patients with COPD between June 2018 and January 2020. Patient characteristics, lung and cardiac functions, and biomarkers, including capsaicin cough reflex sensitivity and blood eosinophil count, were evaluated at enrolment. All participants were monitored for AE or CAP requiring hospitalisation for 12 months. We determined the risk factors and ORs for hospitalisation in patients with COPD using a multivariate analysis. RESULTS: Eight patients experienced AE (n=3) or CAP (n=5) and required hospitalisation during follow-up. Patients in the hospitalisation+ group had higher modified Medical Research Council scores and blood eosinophil counts (≥300 µL) than those in the hospitalisation- group. Capsaicin cough reflex sensitivity tended to decrease in the hospitalisation+ group compared with that in the hospitalisation- group. Multivariate analysis revealed that a decreased capsaicin cough reflex and high eosinophil count (≥300 µL) were predictive risk factors for future hospitalisation due to AE-COPD or CAP. CONCLUSION: In addition to eosinophils, decreased capsaicin cough reflex sensitivity was associated with hospitalisation due to AE-COPD or CAP. Capsaicin cough reflex sensitivity in patients with COPD may play a role in the prevention of severe AE or pneumonia requiring hospitalisation. TRIAL REGISTRATION NUMBER: UMIN000032497.

Tracheal Glomus Tumor Complicated with Asthma Exacerbation in a Pregnant Woman.

A 34-year-old pregnant woman in the 34th week of gestation with uncontrolled asthma was admitted because of asthma exacerbation. Although she received bronchodilators and systemic corticosteroids, respiratory failure rapidly progressed. Chest computed tomography revealed a mass occluding approximately 80% of the tracheal lumen. After urgent Caesarean section, endobronchial resection was performed. The pathological findings of the resected tumor were compatible with tracheal glomus tumor. Tracheal tumors are often misdiagnosed as asthma, but its complication with asthma is rare. Even if the diagnosis of asthma is definitive, clinicians should consider coexisting diseases, including tracheal tumors, when asthma control is poor.