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Tomoko Tajiri,1 Motohiko Suzuki,2,3 Takeo Kutsuna,4 Hirono Nishiyama,1 Keima Ito,1 Norihisa Takeda,1 Kensuke Fukumitsu,1 Yoshihiro Kanemitsu,1 Satoshi Fukuda,1 Takehiro Umemura,1 Hirotsugu Ohkubo,1 Ken Maeno,1 Yutaka Ito,1 Tetsuya Oguri,1 Masaya Takemura,1 Kosho Yoshikawa,4 Akio Niimi1 1Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 2Department of Otorhinolaryngology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 3Department of Otorhinolaryngology, Nagoya City East Medical Center, Nagoya, Aichi, Japan; 4Department of Respiratory Medicine, Daido Hospital, Nagoya, Aichi, JapanCorrespondence: Tomoko Tajiri, Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan, Tel +81-52-853-8216, Email tomokot@med.nagoya-cu.ac.jpObjective: 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.Keywords: omalizumab, antigen-specific IgE, pollen, allergic rhinitis, allergic asthma

Keima Ito,1 Tomoko Tajiri,1 Hirono Nishiyama,1 Ryota Kurokawa,1 Jenifer Maries Go Yap,1 Norihisa Takeda,1 Kensuke Fukumitsu,1 Yoshihiro Kanemitsu,1 Satoshi Fukuda,1 Takehiro Uemura,1 Hirotsugu Ohkubo,1 Ken Maeno,1 Yutaka Ito,1 Tetsuya Oguri,1,2 Masaya Takemura,1,2 Akio Niimi1 1Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanCorrespondence: Tomoko Tajiri, Email tomokot@med.nagoya-cu.ac.jpPurpose: Recently, single-inhaler triple therapy (SITT) has demonstrated efficacy in patients with uncontrolled asthma who were symptomatic despite treatment with inhaled corticosteroids/long-acting β 2 agonists. However, the characteristics of patients who benefit from SITT remain unclear in the real-world. The aim of this study was to examine the predictors of responsiveness to SITT in patients with asthma.Patients and Methods: A total of 45 patients with asthma who had regularly visited our respiratory clinic and were started on SITT from March 2019 to March 2021 were retrospectively analyzed. Patients’ demographic characteristics, residual respiratory symptoms, type 2 biomarkers, and lung function before SITT were assessed from the patients’ medical records. Predictors of responsiveness to four-week SITT were evaluated in these patients. The definition of responders was based on the physician-assessed global evaluation of treatment effectiveness.Results: Thirty-four (75%) of 45 patients were identified as responders to SITT. Non-responders showed significantly lower forced vital capacity (FVC) (%predicted) values, and complained of dyspnea more frequently than responders before SITT (p = 0.01 and p = 0.02, respectively). There were no significant differences in demographic characteristics and type 2 biomarkers between responders and non-responders. Clinical predictors of poor response to SITT were residual dyspnea (OR = 0.14, p = 0.02), low FVC (%predicted) values (OR = 1.05, p = 0.01), and FVC (%predicted) < 80% (OR = 0.11, p = 0.02). Multivariate analysis showed that poor response to SITT was associated with residual dyspnea before SITT (OR = 0.14, p = 0.02). On the other hand, patients with residual dyspnea had significantly lower FEF25– 75 (%predicted) values than patients without residual dyspnea before SITT (p = 0.04).Conclusion: Residual dyspnea, reflecting small airways dysfunction, may predict poor responsiveness to short-term SITT in patients with asthma.Keywords: single-inhaler triple therapy, long-acting muscarinic antagonists, asthma, small airways dysfunction, dyspnea

S-1, an oral fluoropyrimidine derivative, is widely used for the treatment of several solid tumors. However, there are no predictive markers for its effectiveness.We retrospectively screened 108 patients with advanced non-small cell lung cancer (NSCLC) treated via S-1 monotherapy and investigated its relationship with cytokeratin 19 fragment (CYFRA 21-1) and CEA pretreatment levels.Sixty-one patients with high CYFRA 21-1 levels had a statistically significant shorter progression-free survival (PFS) and overall survival (OS) than 46 patients with normal levels (median PFS = 42 days vs. 70 days, respectively; p = 0.0014; median OS = 197 days vs. 316 days, respectively, p = 0.0239).Serum CYFRA 21-1 levels have predictive and prognostic roles in the management of patients with advanced NSCLC on S-1 monotherapy.

The optimal chemotherapy for concurrent chemoradiotherapy (cCRT) of lung cancer is still unclear.We investigated the therapeutic effect of different chemotherapy regimens for cCRT of lung cancer in 65 patients at our hospital.Of the 65 patients, 53 were male and 12 female. The median age was 64 years and 58 participants had a smoking history. The histological type was adenocarcinoma in 34 cases, squamous cell carcinoma in 22 cases, and others in 9 cases. Induction therapy consisted of cisplatin plus vinorelbine (CDDP+VNR) in 50 cases, and weekly carboplatin plus paclitaxel (CBDCA+PTX) in 15 cases. In all patients, the overall response rate, disease control rate, median progression survival, and median overall survival were 78.5%, 95.4%, 337 days, and 1,037 days, respectively. The median progression-free survival was 337 days in total; it was significantly longer for CDDP+VNR than CBDCA+PTX. The median overall survival was 1,037 days in total; it tended to be slightly longer for CDDP+VNR than CBDCA+PTX.Different chemotherapy regimens for cCRT possibly have different therapeutic effects.

Introduction: Inhaled corticosteroids (ICS) are fundamental agents to subside airway inflammation and improve forced expiratory volume in 1 s (FEV1) among asthmatics. Alveolar concentrations of nitric oxide (CANO), as well as the classical fraction of exhaled nitric oxide (FeNO50), are associated with the pathophysiology of asthma. However, the association between pretreatment CANO levels and response to anti-asthma treatments, including ICS, remains unknown. Methods: We retrospectively analyzed 107 patients newly diagnosed with asthma. ICS in combination with long-acting β2-agonists (ICS/LABA) was initiated. FEV1 and FeNO levels were evaluated at diagnosis and were followed up at 6 and 12 months after the treatment intervention. CANO levels were estimated using various expiratory flows of FeNO measurements. Factors associated with annual changes in FEV1 (ΔFEV1) were analyzed. Patients with a ΔFEV1 Results: FEV1, FeNO50, and CANO levels significantly improved by anti-asthma treatments. The average ΔFEV1 was 85 (176) mL. Eighty-two patients continuously took ICS/LABA treatment. Higher pretreatment CANO levels and continuous use of LABA were independent predictive factors for the improvement of FEV1 on multivariate analysis. The decline in FeNO50 and CANO levels by the anti-asthma treatments was significantly greater in 81 responders than in 26 poor-responders. CANO, but not FeNO50, levels at 12 months were significantly higher in poor-responders than in responders (p = 0.009). Conclusion: Levels of CANO, but not FeNO50, predict changes in pulmonary function in ICS-naïve asthmatics. Meanwhile, persistently high levels of CANO may be related to poor responsiveness to treatments assessed by ΔFEV1.

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.

Acute eosinophilic pneumonia (AEP) is an acute respiratory illness with diffuse pulmonary infiltrates and pulmonary eosinophilia. While the etiology of AEP remains unclear, a relationship between cigarette smoking and AEP onset has been suggested. The use of heated tobacco products (HTPs) has been growing, but the impact of these products on our health is not fully understood. We herein report a case of AEP that developed after switching from conventional cigarette to HTP smoking. The patient's condition improved after the cessation of HTP smoking and corticosteroid treatment initiation. In cases of AEP, physicians should consider HTPs use as a possible cause.

Background Organic cation transporter 6 (OCT6) encoded by solute carrier family 22 member 16 (SLC22A16) is involved in regulating cellular sensitivity and resistance to platinum derivatives. SLC22A16 has functional genetic variants but the association between these variants and the effectiveness of antitumor drugs remains unexplored. Patients and methods This study retrospectively analyzed data from 160 patients with advanced non-small cell lung cancer treated with platinum-based combination chemotherapy for first-line chemotherapy between October 2010 and May 2018. We investigated the association between the genetic variant of SLC22A16 and clinical outcomes. Results Patients with the rs714368 GG genotype had a shorter progression-free survival than those with AA or AG. Gene polymorphism was not associated with adverse effects. The predictive effect of rs714368 was confirmed in multivariate analysis using a Cox proportional hazards model. Conclusion A genetic variant of SLC22A16 is a potential predictive biomarker for response to platinum-based chemotherapy for non-small cell lung cancer.

ABCC10/MRP7, an ATP-binding cassette (ABC) transporter, has been implicated in the extracellular transport of taxanes. Our group reported that the ABCC10 single nucleotide polymorphism (SNPs), rs2125739, influences docetaxel cytotoxicity in lung cancer cell lines as well as its side effects in clinical practice. In this study, we investigated whether the rs2125739 variant could affect paclitaxel (PTX) cytotoxicity in lung cancer cell lines. We also investigated the effect of rs2125739 on the efficacy and safety of nanoparticle albumin-bound PTX (nab-PTX) in clinical practice. The association between rs2125739 genotypes and the 50% inhibitory concentration (IC

A 63-year-old man had received chemoradiotherapy 7 years ago for stage IIIA pulmonary adenocarcinoma of the left lower lobe and stereotactic irradiation 3 years ago for stage IA pulmonary squamous cell carcinoma of the left upper lobe. An esophageal stent was placed because of esophageal narrowing caused by tumor invasion. Five months later, he was diagnosed with an aortoesophageal fistula. Because invasive surgery posed challenges, thoracic endovascular aortic repair (TEVAR) was performed. We report this rare case of aortoesophageal fistula treated using TEVAR. However, the therapeutic effect was temporary. Further studies investigating the indications for TEVAR are warranted.

Purpose ABCC11/MRP8 (ABCC11) is an ATP-binding cassette transporter that is involved in regulating cellular sensitivity and resistance for many anti-cancer drugs. Since 5-fluorouracil (5-FU) is one of the substrates for ABCC11, we examined whether ABCC11 is a predictive marker for an oral 5-FU derivative drug S-1 treatment in non-small cell lung cancer (NSCLC). Methods Real-time PCR and MTS assay were carried on 21 human NSCLC cell lines. The drug resistance capabilities of ABCC11 are evaluated by analyzing the resistance profiles of a clone of HeLa cell in which the pump was ectopically expressed. Blood samples of 106 NSCLC patients were collected. Results There was a significant correlation between dihydropyrimidine dehydrogenase (DPD) gene expression and the IC50 for 5-FU. We then classified NSCLC cell lines into two groups based on the phenotype of the SNP538 (G > A) in ABCC11: a combined G/G and G/A group, and an A/A group. The distribution of the IC50 for 5-FU in combination with a potent inhibitor of DPD 5-chloro-2, 4-dihydropyrimidine (CDHP), which is contained in S-1, showed a significant reduction in the A/A group compared with the combined G/G and G/A group. Next, the clinical usefulness of the ABCC11 SNP in treatment containing S-1 was examined in 106 NSCLC patients, and the disease control rate was found to be significantly better in the A/A group than in the combined G/G and G/A group. Conclusions These results indicate that the SNP538(G > A) in the ABCC11 gene is a potential determinant for S-1 treatment.

Objective: Gastroesophageal reflux disease (GERD) is an important cause of chronic cough. Substance P (SP) has been implicated in the pathophysiology of cough. Proton pump inhibitors (PPIs) and pro...

Nintedanib has been shown to significantly reduce the annual rate of decline in the forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF) in previous randomized trials. A 71-year-old man developed exertional dyspnea and was diagnosed with IPF. Four months after treatment with nintedanib, high-resolution computed tomography findings revealed reduced areas of ground-glass opacity and consolidation; 13 months after treatment, the FVC showed improvement from 3.07 to 3.43 L, and the serum Krebs von den Lungen (KL)-6 concentration showed a decline to normal levels. We herein report a patient with IPF who was considered a super responder to nintedanib.

Asthma is a significant comorbidity of eosinophilic chronic rhinosinusitis (CRS). Type2-driven biomarkers such as sinus tissue eosinophilia and fractional nitric oxide (FeNO) may be utilized to detect high risk patients who develop asthma symptoms after endoscopic sinus surgery (ESS) in CRS patients.Thirty-six CRS patients without asthma who agreed to undergo ESS between October 2015 and December 2017 were prospectively observed for 12 months following ESS. They were monitored for the development of typical asthma symptoms including dyspnea, wheezes, and cough which responded to anti-asthma medication. Biomarkers were compared between patients who developed asthma symptoms after ESS (asthma symptoms group) and those who did not (non-asthma group). Biomarker changes following ESS intervention were also evaluated.Six patients were lost to follow after ESS. Thus, 30 CRS patients [16 with nasal polyps (NPs) proved by surgery] were followed. Seven (23%) newly complained of asthma symptoms during follow-up. Levels of FeNO and the prevalence of eosinophilic NPs (eosinophils ≥ 70/high power fields) were significantly higher in the asthma symptom group than in non-asthma group [50.7 ppbEosinophils in NPs (≥70/high power fields) and preoperative FeNO may be significant biomarkers for predicting the development of asthma symptoms after ESS.

The frequency scale for the symptoms of GERD (FSSG) questionnaire, which originally consists of acid-reflux and dysmotility symptom domains, is a succinct questionnaire to evaluate gastroesophageal reflux disease (GERD) symptoms. To evaluate the utility of subjective questionnaire of GERD for the diagnosis of GERD-related cough by using FSSG questionnaire. We recruited 256 patients with subacute/chronic cough between April 2012 and March 2018, who were analyzed using FSSG questionnaire and blood eosinophil counts. GERD-related cough was inferred through the presence of classic reflux symptoms including heartburn and/or typical coughing trigger (e.g. phonation, rising, lying, eating, and intake of certain food). The diagnosis was confirmed by response to specific treatments for GERD. Receiver operating characteristic curve analysis was performed to determine the cutoff score for the diagnosis. One-hundred ten patients (43%) were diagnosed as having GERD-related cough. FSSG questionnaire was relevant for diagnosing GERD-related cough, with the area under the curve (AUC) of 0.70 (p p The subjective questionnaire of GERD (FSSG) would be helpful in diagnosing GERD-related cough, particularly in patients with low blood or sputum eosinophil counts.

Background Sensitisation to moulds and Staphylococcus aureus enterotoxins (SEs) is associated with the pathophysiology of both asthma and chronic rhinosinusitis (CRS). The purpose of this study was to clarify the contribution of sensitisation to these allergens to Type 2 inflammation in the blood, nose and the lower airways, and clinical outcomes in CRS patients. Methods We prospectively enrolled 56 CRS patients who underwent endoscopic sinus surgery (ESS) (20 with comorbid asthma) and 28 healthy controls between October 2015 and December 2017. CRS patients were followed up for 12 months after surgery. Type 2 inflammation-related biomarkers were analysed using blood, resected tissue samples and sputum. 10 allergens including Alternaria, Aspergillus and SEs were measured. Type 2 inflammation-related biomarkers and clinical outcomes were compared in the stratification with the presence or absence of allergen sensitisation. Results Sensitisation rate to moulds and SEs in asthmatic patients was increased when changing the cut-off value of specific IgE titre from 0.35 UA·mL−1 to 0.10 UA·mL−1 (1.7- and 4.5-fold, respectively). Moulds and SEs affected the prevalence of asthma and eosinophilic CRS by interacting with each other. All Type 2 inflammation-related biomarkers except for eosinophils in sinus tissue were significantly higher in patients with mould or SE (mould/SE) sensitisation (≥0.10 UA·mL−1) (n=19) than in those without (n=37) and healthy subjects (all p, Alternaria, Aspergillus and S. aureus enterotoxins are important allergens affecting Type 2 inflammation and clinical outcomes in CRS patients. Sensitisation to moulds/SEs (≥0.10 UA·mL−1) would be meaningful in the pathophysiology of CRS. https://bit.ly/3bUG8ZT

Background: Excessive activation of afferent nerves in the esophagus is assumedly a major mechanisms of cough associated with GER, which may lead to sensitization of cough reflex. Transient receptor potential (TRP) channels have an important role for converting external stimuli into biological response. We reported an increased gene expression of TRPV1 and TRPV4 in the esophagus of GER patients with cough ERS 2019. However, association between protein expression of these channels in the esophagus and GER-associated cough is still unknown. Method: We prospectively recruited untreated GER patients with (n=32, C+) and without (n=5, C-) cough. Esophageal endoscopy was performed to determine the presence and severity of reflux esophagitis (RE), and to obtain biopsy specimens, which were examined for TRPV1 and TRPV4 protein expression by western blot analysis. Result: Age, sex distribution, smoking history, prevalence/severity of RE, and GER symptom scores did not differ between the C+ and C- groups. TRPV4 expression was significantly increased in the C+ group than in the C- group (p Conclusions: Cough in GER patients is associated with the increased expression of TRPV4 in the esophagus but not with RE or reflux symptoms. Further studies are needed to elucidate the pathogenesis and precise roles of the increased TRPV4.

Background: Asthmatic cough is often refractory to inhaled corticosteroids and long-acting β2 agonists (ICS/LABA). We preliminary reported tiotropium (Tio) alleviates asthmatic cough refractory to ICS/LABA by modulating cough reflex sensitivity (CRS) but not thorough bronchodilation (JACIP 2018). Rationale: We aimed to evaluate antitussive effects of Tio vs theophylline (Theo) in patients with refractory asthmatic cough in a randomized parallel fashion. Methods: 52 consecutive asthmatics [11 males; aged 51 (16) yrs; ICS dose 702 (251) μg] with chronic cough refractory to ICS/LABA were randomized by 2:1 ratio to additionally receive Tio 5 μg or Theo 400 mg for 4 wks. Spirometry, capsaicin CRS (C2 and C5), and FeNO levels were measured before and after treatments. Cough visual analog scales (VAS), Leicester Cough Questionnaire (LCQ), and Asthma Control Test (ACT) were also repeated. Patients with an improved cough VAS of ≥15 mm were considered responders to treatments. Results: 34 in Tio group and 12 in Theo group were finally analyzed. Both Tio and Theo improved cough VAS (p=0.0001, p=0.04, respectively) and LCQ (p=0.0007, p=0.03, respectively). Only Tio improved ACT scores (p=0.0005). C2 improved in both groups (p=0.003, p=0.02, respectively), but C5 improved only in Tio group (p=0.02). FEV1 and FeNO levels did not change in either group. Changes in each index did not differ between the groups. Changes in cough VAS but not other indices correlated with those in C5 (r=-0.36, p=0.03) in Tio group. 21 responders to Tio were solely predicted by elevated CRS by multivariate analysis. Conclusion: We could replicate our previous study, and newly found that elevated CRS might predict response to Tio.

Organic cation transporter 6 (OCT6) encoded by solute carrier family 22 member 16 (SLC22A16) is involved in regulating cellular sensitivity and resistance to platinum derivatives. SLC22A16 has functional genetic variants but the association between these variants and the effectiveness of antitumor drugs remains unexplored.This study retrospectively analyzed data from 160 patients with advanced non-small cell lung cancer treated with platinum-based combination chemotherapy for first-line chemotherapy between October 2010 and May 2018. We investigated the association between the genetic variant of SLC22A16 and clinical outcomes.Patients with the rs714368 GG genotype had a shorter progression-free survival than those with AA or AG. Gene polymorphism was not associated with adverse effects. The predictive effect of rs714368 was confirmed in multivariate analysis using a Cox proportional hazards model.A genetic variant of SLC22A16 is a potential predictive biomarker for response to platinum-based chemotherapy for non-small cell lung cancer.

Background: Eosinophilic nasal polyps (NPs) are associated with the presence of asthma in chronic rhinosinusitis (CRS) patients. Serum periostin has been considered a relevant biomarker for unified airway diseases. Objective: To determine the utility of biomarkers including serum periostin that reflects reduction of exacerbations of comorbid asthma in CRS patients. Methods: We prospectively recruited 56 CRS patients who were subjected to undergo endoscopic sinus surgery (ESS) (20 with asthma) between October 2015 and December 2017 and followed them for 1 year after ESS. Blood eosinophil count, serum periostin, and fractional nitric oxide (FeNO) were measured at enrollment. How these type 2-driven biomarkers reflect comorbid asthma was determined using receiver operating characteristic (ROC) analysis. The frequency of asthma exacerbations during 1 year was counted both before and after ESS. Associations between preoperative biomarkers including eosinophils in NPs and asthma exacerbations were evaluated. Results: Blood eosinophil count, FeNO, and serum periostin levels were significantly higher in CRS patients with asthma than in those without (p < 0.01 for all) and discriminated comorbid asthma among CRS patients (p < 0.05; AUC > 0.80 for all). The increased preoperative serum periostin correlated with lower absolute number of postoperative exacerbations (ρ = −0.49, p = 0.03) and its relative reduction after ESS (ρ = 0.53, p = 0.03) in asthmatic patients. Increased eosinophils in NPs were also associated with reduced asthma exacerbations. Conclusion: Preoperative increased serum periostin and eosinophils in NPs are associated with the preventive effect of ESS for asthma exacerbations in CRS patients comorbid with asthma.

International guidelines define severe uncontrolled asthma. Biologics or bronchial thermoplasty (Bio/BT) are recommended for such patients.To determine which definitions of severe uncontrolled asthma are associated with an additional Bio/BT treatment in patients with severe uncontrolled asthma.Consecutive 107 asthmatics (including 15 patients for whom Bio/BT was introduced within 3 months after examination), classified as treatment step 4 according to the Global Initiative for Asthma 2015 guideline, were eligible for this analysis. Patients were assessed using the European Thoracic Society/American Thoracic Society (ERS/ATS) severe uncontrolled asthma guideline as defined by these 4 characteristics: poor control (ACT20), frequent exacerbations (≥2/yr), admissions (≥1/yr), and airflow limitation (forced expiratory volume in 1 second80% of predicted), along with comorbidities, and biomarkers, including blood granulocytes, fractional nitric oxide, and capsaicin cough reflex sensitivity (C-CS). These indices were compared between patients with and without Bio/BT introduction, and multivariate logistic regression analysis was performed to determine the association of the 4 definitions with treatment needs for Bio/BT.Patients who were introduced to Bio/BT had heightened C-CS, heavier smoking history, and a greater prevalence of diabetes mellitus than those without (Although multiple factors such as treatment cost and asthma phenotypes affect treatment decision-making, the definition of poor asthma control, frequent exacerbations and admission by the ERS/ATS guidelines were important factors for an additional intensive treatment for severe uncontrolled asthma.UMIN Clinical Trials Registry: UMIN000024734.

Bronchial thermoplasty (BT) is a novel treatment for patients with severe asthma (1). Although respiratory adverse events such as asthma attack, atelectasis, and pneumonia are widely known as complications following BT (1), endobronchial organic lesions such as inflammatory bronchial polyps are not generally recognized as such by clinicians. We experienced a suspected case of an inflammatory bronchial polyp induced by BT that showed a spontaneous resolution. Written patient consent was obtained for this case report.

Periostin is a matricellular protein that is involved in the pathophysiology of allergic rhinitis, chronic rhinosinusitis, and asthma. Associations of serum periostin with systemic and airway eosinophilic inflammation and comorbid chronic rhinosinusitis in patients with asthma have been demonstrated. Although serum periostin is positioned as a marker of helper T cell 2 immune responses, its implication regarding the presence of comorbid upper airway diseases in patients with asthma remains unclear.To investigate the utility of serum periostin as a diagnostic biomarker for upper airway disease in patients with asthma.We prospectively enrolled 65 patients with stable asthma, 20 without upper airway disease, 22 with rhinitis, and 23 with chronic rhinosinusitis (13 with nasal polyps, 10 without). Serum periostin, eotaxin, total IgE, fractional exhaled nitric oxide, and blood and sputum eosinophil levels were measured and compared between upper airway disease subtypes. We evaluated the utility of each biomarker in detecting upper airway disease, associations among the biomarkers, and severity of upper airway disease as measured by the Lund-Mackay score for sinus computed tomography.Serum periostin levels were higher in patients with asthma who had chronic rhinosinusitis (109.6 ± 47.4 ng/ml) than in those without upper airway disease (83.2 ± 22.9 ng/ml) (P = 0.04). Serum periostin levels in patients with asthma who had chronic rhinosinusitis and nasal polyps were significantly higher (130.0 ± 46.6 ng/ml) than in those without nasal polyps (87.9 ± 37.7 ng/ml) (P = 0.001). Serum periostin levels were not associated with the presence or the severity of rhinitis. In contrast, receiver operating characteristic curve analyses showed moderate diagnostic accuracy for detecting chronic rhinosinusitis (area under the curve, 0.71; P = 0.01) and high accuracy for chronic rhinosinusitis with nasal polyps (area under the curve, 0.86; P = 0.0002). When we compared patients with asthma who had comorbid chronic rhinosinusitis and nasal polyps with patients with asthma without these comorbidities, we found serum periostin to be the sole biomarker among those tested for detecting the presence of nasal polyps. Serum periostin was also the sole biomarker that significantly correlated with Lund-Mackay score in patients with chronic rhinosinusitis (r = 0.44; P = 0.04).Serum periostin is useful for detecting chronic rhinosinusitis with nasal polyps and predicting radiological chronic rhinosinusitis severity in patients with asthma. Clinical trial registered with the UMIN Clinical Trials Registry (UMIN000017533).

Background: Cough-variant asthma (CVA) and cough-predominant asthma (CPA) are the major causes of persistent cough in Japan. The utility of fractional exhaled nitric oxide (FeNO) measurement in the differential diagnosis of persistent cough has been reported, but the influence of atopic status, which is associated with higher FeNO levels, on the diagnostic utility of FeNO has been unknown. Methods: We retrospectively analyzed 105 non-smoking patients with prolonged and chronic cough that were not treated with corticosteroids and anti-leukotrienes. Results: CPA was diagnosed in 37 patients, CVA in 40, and non-asthmatic cough (NAC) in 28. FeNO levels were significantly higher in the CPA [35.8 (7.0–317.9) ppb] and CVA [24.9 (3.1–156.0) ppb] groups than in the NAC group [18.2 (6.9–49.0) ppb] (p

Rationale: Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, although its association with severe asthma remains unknown.Objectives: To determine the clinical i...

Background Hospitalization is a major cause of medical expenditure for asthma. Budesonide inhalation suspension (BIS) may assist in reducing asthma-related symptoms in severe asthma exacerbation. However, its effectiveness for hospitalized patients remains poorly known. The objective of this study is to determine associations of BIS with asthma hospitalization. Methods We retrospectively analyzed 98 patients who were admitted to our hospital due to severe asthma exacerbation (24 treated with BIS in combination with procaterol) from April 2014 to January 2019. Length of stay, recovery time from symptoms (wheezes), and hospitalization costs were compared between the 2 groups according to clinical factors including the use of BIS and sings of respiratory infections (i.e. C-reactive protein, the presence of phlegm, and the use of antibiotics). Multivariate logistic regression analysis was performed to determine factors contributing to hospitalization outcomes. Results The use of BIS was associated with shorter length of stay, faster recovery time from symptoms, and more reduced hospitalization costs (6.0 vs 8.5 days, 2.5 vs 5.0 days, and 258,260 vs 343,350 JPY). Signs of respiratory infection were also associated with hospitalization outcomes. On a multivariate regression analysis, the use of BIS was a determinant of shortened length of stay and reduced symptoms and medical costs for asthma hospitalization along with signs of respiratory infection. Conclusions BIS may contribute to shorten length of hospital stay and to reduce symptoms and medical expenditure irrespective of the presence or absence of respiratory infection.

A 76-year-old man was admitted to our hospital with cough and dyspnea. He was diagnosed with advanced lung cancer. Nivolumab was given as second-line treatment, cytotoxic chemotherapy was given as third-line treatment, and nivolumab re-challenge was given as fourth-line treatment. Thereafter, 41 chemotherapy courses were administered over 2 years. Currently, he is being followed with no recurrence at least 10 months after treatment. Thus, the case of a patient with advanced lung cancer who was previously unsuccessfully treated with nivolumab and then demonstrated a long-term clinical response to a re-challenge with nivolumab after cytotoxic chemotherapy and radiation therapy is presented. Keywords: Lung cancer, Nivolumab, Immune checkpoint inhibitors, PD-L1