Comparison of User Satisfaction and Preference with Inhalant Devices Between a Pressurized Metered-Dose Inhaler and Ellipta in Stable Asthma Patients: A Randomized, Crossover Study.

INTRODUCTION: Inhalation therapy involves two types of adherence: adherence to the drug and adherence to the procedures for the inhalation device. User satisfaction and preference are key factors for maintaining good adherence of both types, and they should be evaluated based on three conditions being well maintained: asthma control level (ACL), adherence, and adequate device operability during usage duration. We compared user satisfaction and preference between a pressurized metered-dose inhaler (pMDI) and a dry powder inhaler (Ellipta), while maintaining the three conditions during usage in stable asthma patients. METHODS: In this open-label, randomized, two-way crossover study, patients with stable asthma [Asthma Control Questionnaire (ACQ) scores < 0.75] were classified into a 20-64-year age group (G1) and a ≥ 65-year age group (G2) and randomly assigned to either a formoterol/fluticasone combination (FFC) as the pMDI group or a vilanterol/fluticasone combination (VFC) as the Ellipta group. Satisfaction and preference levels were evaluated at week 4. ACL was measured using the ACQ and Japan Asthma Control Survey questionnaires at weeks 0 and 4. Device operability and respiratory resistance were also examined. RESULTS: Forty-four patients (23 G1, age 45.8 ± 1.9 years; 21 G2, 74.1 ± 1.3 years) were enrolled and maintained good ACL during the study. Adherence to FFC pMDI and VFC Ellipta was > 97% in all groups. Device operability did not differ significantly between FFC pMDI and VFC Ellipta in the G1 (p = 0.189) or G2 (p = 0.506) group. Overall satisfaction was marginally higher with the FFC pMDI than with the VFC Ellipta in G2 (p = 0.012) but non-significantly different in G1 (p = 0.733). Factors affecting overall satisfaction in G2 were difference of inhalation device and body mass index. Respiratory resistance did not change significantly over the study in G2. CONCLUSION: Based on maintaining good ACL, adherence, and device operability, FFC pMDI showed significantly higher satisfaction and preference levels than VFC Ellipta in elderly persons. TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier, jRCTs041180001 (registered 21 August 2018).

Open-label study to evaluate the treatment continuation rate after a dose reduction of lubiprostone due to onset of adverse events.

OBJECTIVE: To investigate the continuation rate with a reduced lubiprostone dose (12 mcg twice daily, BD) after the onset of adverse events (AEs) in patients with chronic constipation (CC). METHODS: In this exploratory, open-label, multicenter study, patients with CC received lubiprostone 24 mcg BD and the dose was reduced to 12 mcg BD in subjects experiencing AEs. The primary objective was the continuation rate after dose reduction due to nausea/vomiting. Secondary objectives included the continuation rate after dose reduction due to diarrhea/any AE and efficacy, including changes in number of weekly bowel movements and Bristol Stool Form Scale. RESULTS: Of the 146 patients included in the study, 42 (28.8%) received lubiprostone 12 mcg BD (dose-reduced group) due to any AE. Thirty-six (85.7%) subjects in the dose-reduced group continued treatment and completed the study. 22/27 (81.5%) and 17/19 (89.5%) patients in whom the dose was reduced due to nausea/vomiting or diarrhea, respectively, continued treatment. There was no clinically relevant difference in efficacy after dose reduction. CONCLUSION: These results suggest that treatment withdrawal due to AEs associated with lubiprostone 24 mcg BD could be minimized in patients with CC after dose reduction to 12 mcg BD, thus resulting in improved long-term outcomes. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (https://jrct.niph.go.jp/latest-detail/jRCTs031180069).

Serum periostin reflects dynamic hyperinflation in patients with asthma.

INTRODUCTION: Dynamic hyperinflation (DH) is sometimes observed and is associated with impaired daily life activities of asthma. We assessed the relationship between DH and asthma biomarkers (blood eosinophil, fractional exhaled nitric oxide (F eNO) and serum periostin) in patients with asthma. METHODS: Fifty patients with stable asthma were prospectively recruited and underwent blood test, F eNO measurement, spirometry and metronome-paced tachypnoea (MPT) test to assess DH. In MPT tests, inspiratory capacity (IC) was measured at baseline and after 30 s of MPT with breathing frequencies of 20, 30 and 40 breaths·min-1. DH was assessed by the decline of IC from baseline, and maximal IC reduction ≥10% was considered as positive DH. RESULTS: Thirty patients (60%) showed positive DH. Patients with positive DH showed higher serum periostin levels (107.0±30.7 ng·mL-1) than patients with negative DH (89.7±23.7) (p=0.04). Patients in Global Initiative for Asthma treatment steps 4-5 (n=19) showed higher serum periostin levels (p=0.01) and more severe IC reduction after MPT (p<0.0001) than patients in steps 1-3 (n=31). Maximal IC reduction after MPT was significantly correlated with asthma control test score (r=-0.28, p=0.05), forced expiratory volume in 1 s (r=-0.56, p<0.0001), and serum periostin levels (r=0.41, p=0.003). CONCLUSION: Serum periostin may have the possibility to reflect DH in patients with stable asthma.

A novel pathophysiologic link between upper and lower airways in patients with chronic rhinosinusitis: Association of sputum periostin levels with upper airway inflammation and olfactory function.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma are collectively called unified airway diseases. Periostin has been implicated in the pathophysiologic link of these conditions but only by serum measurements. We sought to investigate sputum levels of periostin and their association with upper airway inflammation and olfactory function in CRS patients. METHODS: We prospectively recruited 56 CRS patients who underwent endoscopic sinus surgery (20 with and 36 without comorbid asthma), and 28 healthy controls between October 2015 and December 2017. Lower and upper airway indices such as sputum periostin levels and eosinophil and neutrophil counts, exhaled fractional nitric oxide (FeNO) levels, and olfactory function were evaluated in the three groups. Radiological severity of CT images and tissue eosinophilia of surgical specimens were also assessed in the CRS patients. RESULTS: Sputum periostin levels were highest, and olfactory function was most impaired, in the CRS patients with comorbid asthma, followed by those without asthma and controls in this order. CRS with asthma group showed higher sputum eosinophils and FeNO levels than the other two groups, while CRS patients without asthma showed significantly higher neutrophils in sputum than the other two groups. When confined to CRS patients, olfactory dysfunction was correlated with sputum eosinophil counts. Eosinophil counts of nasal polyps showed a significant positive correlation with sputum periostin and FeNO levels. Radiological severity of CRS was correlated with sputum eosinophil counts and FeNO levels. CONCLUSIONS: Periostin levels and inflammatory cells such as eosinophils and neutrophils in the lower airways are increased in patients with CRS, suggesting the presence of mutual interactions between upper and lower airways even if asthma does not coexist. Olfactory dysfunction and eosinophilic nasal polyps may be potential indicators of Th2-driven inflammation in the lower airways. TRIAL REGISTRATION: This study was registered on the UMIN Clinical Trials Registry (Registry ID UMIN000018672).

Small airway inflammation is associated with residual airway hyperresponsiveness in Th2-high asthma.

Background: Asthma is characterized by airway inflammation, variable airflow obstruction, and airway hyperresponsiveness (AHR). Generally, AHR takes longer to resolve than does airflow obstruction or clinical symptoms. AHR occasionally persists despite adequate asthma treatment.Objective: To evaluate factors which associates with residual AHR in patients with seemingly remitted airway inflammation.Methods: Patients who exhibited high fractional exhaled nitric oxide (FeNO) levels (>25 ppb) at the first visit (Visit 1) and normalized FeNO levels (<25 ppb) after adequate asthma treatment, including inhaled corticosteroid administration (Visit 2), were analyzed. Patients underwent a blood test, FeNO and small airway/alveolar nitric oxide concentration (CANO) measurements and a methacholine challenge test (continuous inhalation method) at both visits. Clinical indices were compared between patients with and without residual AHR.Results: Fifty patients were analyzed. All exhibited high FeNO levels at Visit 1 [mean, 54.0 ppb (95% confidence interval, 42.4-65.5)] and improvement of FeNO levels at Visit 2 [20.4 (19.2-21.6)] (p < 0.0001). Thirty-three patients (66%) had remission of AHR at Visit 2. No significant differences were observed between patients with and without residual AHR in terms of FeNO levels, lung function parameters and blood eosinophil counts at both visits. CANO level at Visit 2 was the only factor that significantly differed between patients with residual AHR [2.7 (1.9-3.6)] and those who achieved AHR remission [0.8 (0.5-1.0)] (p < 0.0001).Conclusion: Small airway inflammation, as assessed by CANO, was associated with residual AHR in patients with Th2-high asthma.

Effect of anti-reflux treatment on gastroesophageal reflux-associated chronic cough: Implications of neurogenic and neutrophilic inflammation.

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 prokinetic agents are the current treatment for GER-associated cough. The aim was to evaluate the effects of anti-reflux treatment and its associations with cellular and neurogenic inflammation.Methods: Thirty-seven patients with GER-associated cough suspected based on characteristic symptoms such as heartburn and worsening of cough by phonation and rising were recruited. A PPI, rabeprazole 20 mg daily, and a prokinetic agent, itopride 50 mg t.i.d., were administered for 4 weeks in a prospective, observational manner. Before and after treatment, subjective cough measures [visual analog scale (VAS) and the Japanese version of the Leicester Cough Questionnaire (J-LCQ)], the modified frequency scale for the symptoms of GERD [FSSG, consisting of 2 domains: acid-reflux (AR) and functional dyspepsia symptoms], sputum and plasma SP levels, and sputum cell differentials were examined. Patients with good response to treatment [Δ (decrease of) VAS >15 mm; n = 21) were compared with poor responders (ΔVAS ≤15 mm).Results: Anti-reflux treatment significantly improved the cough VAS, J-LCQ, and AR symptoms, and ΔVAS and ΔAR were significantly correlated. Decreases of plasma and sputum SP levels and sputum neutrophil counts were significantly greater in responders than in poor responders. Both baseline values and post-treatment changes of plasma SP and sputum neutrophils were significantly correlated for all patients.Conclusions: Successful treatment of GER-associated cough may be associated with the attenuation of neurogenic and neutrophilic inflammation.

Clinical impact of gastroesophageal reflux disease in patients with subacute/chronic cough.

BACKGROUND: While gastroesophageal reflux disease (GERD) is one of the commonest causes of subacute/chronic cough along with cough-variant asthma (CVA) and rhinosinusitis, its clinical impact remains unknown. Therefore, we sought to investigate the impact of GERD in patients with subacute/chronic cough. METHODS: Between April 2012 and March 2018, a total of 312 patients presenting subacute or chronic cough lasting for ≥3 weeks [median cough duration, 4.9 (0.7-434) months] underwent diagnostic tests. GERD symptoms and cough-specific QoL were evaluated through the Frequency Scale for Symptoms of Gastroesophageal reflux (FSSG) and the Japanese version of the Leicester Cough Questionnaire (J-LCQ). According to the FSSG domains, patients with GERD were arbitrarily categorized into 3 groups; acid-reflux predominant, dysmotility predominant, and pauci-symptoms groups, respectively. RESULTS: The average scores of J-LCQ was 12.5 (SD3.7). One hundred-forty three were diagnosed as having GERD-related cough based on classical reflux symptoms including heartburn and characteristic triggers of cough such as phonation, rinsing, lying, and eating. Most of them (89.8%) had other causative diseases including CVA. Cough lasted longer (p = 0.019) and required a longer time until alleviation (p = 0.003) in patients with GERD than in those without GERD. They also scored lower J-LCQ than counterpart group (p < 0.0001). In terms of symptom stratification, dysmotility predominant group showed significant more response to specific GERD treatments than the remnants (p = 0.002). CONCLUSIONS: These results indicate that GERD is associated with the aggravation of other causes including CVA. Particularly, dysmotility symptoms may be potential therapeutic target for GERD-related cough.

Prevention of hypoxemia during endobronchial ultrasound-guided transbronchial needle aspiration: Usefulness of high-flow nasal cannula.

BACKGROUND: Hypoxemia during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often encountered even in patients without respiratory impairment before the procedure. The aim of this study was to evaluate the efficacy of a high-flow nasal cannula (HFNC) in preventing hypoxemia during EBUS-TBNA. METHODS: The present investigation was designed as a prospective pilot study. Eligible subjects were adults who could undergo EBUS-TBNA under intravenous midazolam sedation. The main exclusion criteria were as follows: age > 80 years with impaired oxygenation and peripheral oxygen saturation (SpO2) < 95% at room air. The primary outcome was the oxygenation level during the procedure. Cutaneous carbon dioxide tension (PcCO2) and complications were evaluated as secondary outcomes. HFNC use was started at an inspired O2 fraction of 30% and was titrated to maintain SpO2 over 90%. The lowest SpO2 values during EBUS-TBNA were retrospectively compared between patients who underwent HFNC and those were given a conventional nasal cannula as a historical control group. RESULTS: Twelve patients received HFNCs. The mean lowest SpO2 during the procedure was 93%. Although the mean SpO2 tended to decrease in the early stages, it remained over 90% throughout the procedure. The mean highest PcCO2 was 39 mmHg (range, 30-46 mmHg). There were no major complications. In patients who underwent EBUS-TBNA using a conventional nasal cannula, the mean lowest SpO2 was 88%, which was significantly lower than that in the HFNC cases (p = 0.005). CONCLUSION: HFNC could be an effective and safe device for prevention of hypoxemia during EBUS-TBNA.

A Rare Case of Isolated Chronic Cough Caused by Pulmonary Lymphangitic Carcinomatosis as a Primary Manifestation of Rectum Carcinoma.

A 36-year old man was referred to our hospital due to isolated chronic cough that was refractory to anti-asthma medications, including inhaled corticosteroids/long-acting ß2 agonists. Chest X-ray showed diffuse nodular and enhanced vascular shadows with Kerley lines in both lungs. A blood analysis showed elevated serum carcinoembryonic antigen (CEA) and CA19-9 levels. A transbronchial biopsy revealed well to moderately differentiated adenocarcinoma, the origin of which was immunohistochemically suspected to be the gastrointestinal tract. Colonoscopy confirmed the diagnosis of primary rectum carcinoma. Pulmonary lymphangitic carcinomatosis was therefore regarded as the origin of the cough. Lymphangitic carcinomatosis is an uncommon diagnosis but important to consider in patients with persistent cough.

Tiotropium Attenuates Refractory Cough and Capsaicin Cough Reflex Sensitivity in Patients with Asthma.

BACKGROUND: Asthmatic cough is often refractory to standard treatments such as inhaled corticosteroids (ICS) and long-acting ß2 agonists (LABA). Tiotropium may modulate cough reflex sensitivity of acute viral cough, but its efficacy in asthmatic cough remains unknown. OBJECTIVE: To evaluate whether tiotropium improves cough and cough reflex sensitivity in patients with asthma refractory to ICS/LABA. METHODS: Seventeen consecutive patients with asthma with chronic cough despite the use of ICS/LABA (13 women; 43.4 ± 19.0 years; average ICS dose, 651 ± 189 µg/d; fluticasone equivalent) were additionally treated with tiotropium (5 µg/d) for 4 to 8 weeks to examine its effects on pulmonary function and capsaicin cough reflex sensitivity (cough thresholds C2 and C5). Cough severity, cough-specific quality of life, and asthma control were also evaluated using cough visual analog scales (VASs), the Japanese version of Leicester Cough Questionnaire (J-LCQ), and Asthma Control Test (ACT), respectively. Patients with an improved cough VAS score of 15 mm or more were considered responders to tiotropium. RESULTS: Tiotropium significantly improved cough VAS, J-LCQ, and ACT scores, but not FEV1. Changes in cough VAS score correlated with those in C2 (r = -0.58; P = .03), C5 (r = -0.58; P = .03), and ACT scores (r = -0.62; P = .02), but not in FEV1 in the overall patients. When analyses were confined to the 11 responders, tiotropium significantly improved capsaicin cough reflex sensitivity within the subgroup (C2: P = .01 and C5: P = .02) and versus the nonresponders (C2: P = .004 and C5: P = .02). CONCLUSION: Tiotropium may alleviate asthmatic cough refractory to ICS/LABA by modulating cough reflex sensitivity but not through bronchodilation.

Combined measurements of fractional exhaled nitric oxide and nasal nitric oxide levels for assessing upper airway diseases in asthmatic patients.

BACKGROUND: Despite the close linkage between rhinitis, chronic rhinosinusitis (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation are rare. METHODS: Patients with asthma (without upper airway disease [UAD; n = 24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s (FeNO50), nasal NO levels, Lund-Macay-scores of sinus computed tomography and an asthma control questionnaire (ACQ) were evaluated. RESULTS: Asthma was associated with higher FeNO50 levels irrespective of the UAD category. FeNO50 levels were higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2 ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were higher in rhinitis patients than other UAD categories, irrespective of the asthma concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb) than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p < 0.0001). A receiver-operating-characteristic curve analysis for detecting comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve (0.87). Nasal NO levels were positively correlated with FeNO50 levels (ρ = 0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively correlated with the Lund-Macay (ρ = -0.46, p = 0.03) and ACQ scores (ρ = -0.52, p = 0.009) in asthmatics with CRS. CONCLUSIONS: Higher nasal NO levels reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO50 levels reflect the presence of CRS and asthma. These NO measurements are useful for assessing comorbid UAD in asthmatics.

Predictive and Prognostic Value of CYFRA 21-1 for Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) directed against epidermal growth factor receptor (EGFR) are important in the treatment of non-small cell lung cancer (NSCLC), especially those harboring EGFR mutations. But little is known regarding the clinical value of serum tumor marker levels measured prior to treatment. PATIENTS AND METHODS: We retrospectively reviewed 95 patients with advanced NSCLC treated with EGFR-TKIs, and inspected the relationship between serum tumor marker levels and clinical outcome. RESULTS: Forty-three patients with an elevated serum level of cytokeratin 19 fragment (CYFRA 21-1) had shorter progression-free (PFS) and overall (OS) survival than 52 patients with normal serum CYFRA 21-1 levels (99 vs. 123.5 days p=0.011; and 385 vs. 607 days, respectively, p=0.001). Regardless of EGFR mutation status, patients had shorter progression-free survival when serum CYFRA 21-1 was elevated. CONCLUSION: Serum CYFRA 21-1 level may be a predictive factor for patients with NSCLC treated with EGFR-TKIs, regardless of EGFR mutation status.

Optimal cut-off value and clinical usefulness of the Adherence Starts with Knowledge-12 in patients with asthma taking inhaled corticosteroids.

BACKGROUND: Non-adherence to inhalation regimens is common in asthmatic patients. The Adherence Starts with Knowledge-12 (ASK-12) survey was developed to detect and address patient-specific barriers to medication adherence. Our objective is to investigate the clinical usefulness of the ASK-12 for assessing and addressing adherence to inhalation therapy in asthma. METHODS: The ASK-12 was administered to 138 asthmatic patients. Using pharmacy-refill data, we examined the cut-off value of the ASK-12 to identify patients who were non-adherent to inhalation regimens and identify factors associated with non-adherence. To verify the usefulness of the ASK-12, inhalation regimens were prospectively switched to less-expensive and simpler (once-daily) dosing regimens in eight non-adherent asthmatic patients who reported specific-barriers in "inconvenience of twice-daily inhaler use" and "cost". RESULTS: Valid responses were received from 114 (82.6%) patients. A significant correlation was found between pharmacy-refill rates and the ASK-12 total score (r=-0.55, P<0.0001). The optimal cut-off value of the ASK-12 total score to discriminate non-adherent patients (defined by pharmacy-refill rate <80%) was 23, with 71.4% specificity and 93.3% sensitivity. Using this value, 52 (45.6%) patients were classified as non-adherent. Univariate followed by multivariate analysis identified younger age as a predictor of non-adherence to inhalation regimens (odds ratio, 2.67; 95% CI, -0.95 to -0.06; P=0.027). Switching inhaled medicines in eight patients resulted in significant improvements in both ASK-12 scores and asthma control. CONCLUSIONS: The ASK-12 is a brief, practical, and clinically useful measure for assessing and addressing adherence to inhalation regimens in asthma.

Predictive Role of CYFRA21-1 and CEA for Subsequent Docetaxel in Non-small Cell Lung Cancer Patients.

BACKGROUND/AIM: The aim of the present study was to determine the clinical value of tumor marker levels for previously treated NSCLC patients. PATIENTS AND METHODS: We retrospectively screened 113 previously treated patients with advanced NSCLC who were treated with docetaxel monotherapy regarding the pretreatment serum level of cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA). RESULTS: The thirty-two patients with normal CYFRA21-1 levels and high CEA levels had a significantly higher response rate than the other 81 patients (25% vs. 8.6%, p=0.031). The former group showed statistically longer progression-free survival (PFS) and overall survival (OS) than the latter group (median PFS, 180 vs. 59 days, p<0.001; median OS, 579 vs. 255 days, p=0.002). In multivariate analysis, tumor marker levels had a significant impact on PFS and OS. CONCLUSION: Combination of the two tumor markers is a predictive and prognostic marker of docetaxel monotherapy for previously treated NSCLC patients.

Serum Periostin as a Biomarker for Comorbid Chronic Rhinosinusitis in Patients with Asthma.

RATIONALE: 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. OBJECTIVES: To investigate the utility of serum periostin as a diagnostic biomarker for upper airway disease in patients with asthma. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).

Diagnostic utility of fractional exhaled nitric oxide in prolonged and chronic cough according to atopic status.

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 < 0.01 by Kruskal-Wallis test). The optimal cut-off for distinguishing asthmatic cough (AC; CPA and CVA) from NAC was 29.2 ppb [area under the curve (AUC) 0.74, p < 0.01]. Ninety-one percent of subjects with FeNO levels ≥29.2 ppb had AC. Meanwhile, 40% of AC patients had FeNO levels <29.2 ppb. Stratified cut-off levels were 31.1 ppb (AUC 0.83) in atopic subjects vs. 19.9 ppb (AUC 0.65) in non-atopic subjects (p = 0.03 for AUC). CONCLUSIONS: Although high FeNO levels suggested the existence of AC, lower FeNO levels had limited diagnostic significance. Atopic status affects the utility of FeNO levels in the differential diagnosis of prolonged and chronic cough.

The effect of bevacizumab for bone scintigraphy imaging: A case report.

A 65-year-old man presented with pulmonary nodules and a right humeral fracture. The 99mTc-hydroxy-methylene-diphosphonate (HMDP) bone scintigraphy showed high-intensity radioisotope (RI) uptake by a tumor of the right arm. Adenocarcinoma of the lung with an epidermal growth factor receptor (EGFR) mutation was diagnosed on pathological examination of the computed tomography (CT)-guided needle biopsy of the right humerus. Although, gefitinib therapy was initiated, the tumor progressed. The patient was then treated with second-line chemotherapy including bevacizumab. The CT scan showed a new bone metastasis in the ilium and right sacroiliac articulation. However, this new bone metastasis was not detected by HMDP-bone scintigraphy. Physicians should be wary of the interpretations of the findings of the 99mTc HMDP bone scintigraphy after the bevacizumab treatment.

Long-term use of a once-a-day fentanyl citrate transdermal patch in lung cancer patients.

Transdermal fentanyl is widely administered as an analgesic therapy for cancer patients. Recently, a novel fentanyl citrate transdermal patch was developed in Japan, which is the first such patch that requires changing only once a day. The patch releases more stable serum fentanyl concentrations and results in less frequent adverse skin symptoms compared with the conventional 72-h transdermal fentanyl patch. A previous study has reported the short-term analgesic effects and safety of this transdermal patch. However, the long-term efficacy has yet to be determined. Therefore, the present study retrospectively investigated the adverse effects and outcomes of treatment with this product in 46 lung cancer patients. In total, 35 (76%) patients were able to continue the treatment until the end of the observation period, including 32 (69%) who succumbed to the disease and three (7%) who were transferred from Nagoya City University Hospital to a hospice. Of the 11 (24%) discontinued cases, six were changed to a course of injectable opioids for the palliation of terminal symptoms, including dyspnea. Adverse effects were observed in 11 (24%) cases, but discontinuation due to adverse effects occurred in only four cases. Therefore, the present study indicates that palliative treatment with the once-a-day fentanyl citrate transdermal patch is well-tolerated by lung cancer patients.