Impact of sinus surgery on type 2 airway and systemic inflammation in asthma.

Objective: Asthma is frequently associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Although endoscopic sinus surgery (ESS) improves asthma control in CRSwNP patients with asthma, the mechanism that underlies the response to surgical treatment is still unclear. We evaluated the relevance of changes in asthma control and changes in airway/systemic inflammation in eosinophilic CRSwNP patients with not well controlled asthma who underwent ESS.Methods: We prospectively assessed changes in the asthma control questionnaire (ACQ) score, blood eosinophil counts (B-Eos), forced expiratory volume in 1 s (FEV1), and fraction of exhaled nitric oxide (FeNO) levels at 1-week before and 8 and 52 weeks after ESS.Results: Twenty-five subjects were analyzed. The ACQ score, B-Eos, and FeNO decreased, and FEV1 increased significantly after ESS. In the period from baseline to 52 weeks after ESS, changes in ACQ were significantly correlated with the changes in blood eosinophil counts (r = 0.58, p<.01) and FeNO (r = 0.45, p<.05). Ten subjects (40%) showed consistently improved asthma control at 52-weeks after ESS. In the remaining subjects, although the ACQ score temporarily improved at 8-weeks after ESS, but eventually deteriorated at 52-weeks. Higher levels of total immunoglobulin E were associated with long-term improved asthma control after ESS.Conclusions: In eosinophilic CRSwNP patients with asthma, sinus surgery impacts asthma control through the suppression of airway/systemic type 2 inflammation. The present study reinforced the common pathophysiology of type 2 inflammation between the upper and lower airways.

Factors associated with non-intervention of antifibrotic agents in IPF patients.

BACKGROUND: The efficacy of antifibrotic agents in idiopathic pulmonary fibrosis (IPF) has been demonstrated and early introduction is recommended, especially in patients with preserved performance status (PS). We aimed to determine the proportion of untreated IPF cases using real-world data and to assess the factors associated with non-intervention. METHODS: A prospective observational study using questionnaires was performed on 518 patients with interstitial lung disease (ILD) and their attending physicians who visited a clinic, general hospital, or tertiary respiratory center between December 2019 and October 2020. Patients responded with subjective symptoms and PS, whereas physicians responded with diagnosis, treatment, and reasons for their treatment choices. Principal component analysis (PCA) was performed using age, sex, BMI, medical facility, specialized tests, and symptom severity. RESULTS: We included 207 patients with IPF. Among them, 168 has a good PS (≤2), which could be indicative of treatment; 130 (77.4%) were not treated with antifibrotic agents. The PCA revealed a trend consistent with that of antifibrotic agent therapy and the distribution of medical facilities, with a treatment intervention rate of 16% in general hospitals and 62% in tertiary respiratory centers. In general hospitals, low symptom severity (PS, mMRC, and no use of long-term oxygen therapy) was a relevant factor for non-intervention with antifibrotic agents (p < 0.001). CONCLUSION: Antifibrotic treatment interventions varied by facility in cases with good PS. Patients with milder symptoms are not being treated early in general hospitals and more collaboration between general hospitals and specialized facilities is necessary.

Relief of Airflow Limitation and Airway Inflammation by Endoscopic Sinus Surgery in a Patient with Severe Asthma with Eosinophilic Chronic Rhinosinusitis.

Although endoscopic sinus surgery (ESS) is beneficial in improving asthma symptoms, its impact on the lung function in patients with asthma and chronic rhinosinusitis remains unclear. We herein report a case of severe asthma with eosinophilic chronic rhinosinusitis, in which ESS substantially improved airflow limitation and concomitantly reduced fractional exhaled nitric oxide and blood eosinophil counts. ESS likely relieved airflow limitation by suppressing type 2 inflammatory pathways. This case highlights ESS as a promising strategy for achieving clinical remission in patients with severe asthma and chronic rhinosinusitis.

Utility of the Shortness of Breath in Daily Activities Questionnaire (SOBDA-Q) to Detect Sedentary Behavior in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Sedentary behavior has been shown to be an independent predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). However, physicians have difficulty ascertaining patients' activity levels because they tend to avoid shortness of breath. The reformed shortness of breath (SOB) in the daily activities questionnaire (SOBDA-Q) specifies the degree of SOB by measuring low-intensity activity behavior in everyday living. Therefore, we aimed to explore the utility of the SOBDA-Q in detecting sedentary COPD. We compared the modified Medical Research Council dyspnea scale (mMRC), COPD assessment test (CAT), and SOBDA-Q with physical activity levels (PAL) in 17 healthy patients, 32 non-sedentary COPD patients (PAL ≥ 1.5 METs·h), and 15 sedentary COPD patients (PAL < 1.5 METs·h) in this cross-sectional study. CAT and all domains of the SOBDA-Q in all patients are significantly correlated with PAL, even after adjusting for age. The dietary domain has the highest specificity, and the outdoor activity domain has the highest sensitivity for detecting sedentary COPD. Combining these domains helped determine patients with sedentary COPD (AUC = 0.829, sensitivity = 1.00, specificity = 0.55). The SOBDA-Q is associated with PAL and could be a useful tool for determining patients with sedentary COPD. Moreover, eating and outing inactivity claims reflect sedentary behavior in patients with COPD.

Detection of impaired gas exchange using the 1-minute sit-to-stand test in patients with interstitial lung disease.

BACKGROUND: Although pulmonary function tests (PFTs) are important in patients with interstitial lung disease (ILD), they cannot be easily performed in a primary healthcare setting. This study aimed to examine the usefulness of the difference between pulse oxygen saturation (SpO2) at rest and the lowest SpO2 during the 1-min sit-to-stand test (delta SpO2-1STST) for predicting pulmonary function impairment. METHODS: We retrospectively reviewed 116 patients with ILD who underwent 1STST and PFTs. RESULTS: The delta SpO2-1STST and diffusing capacity for carbon monoxide (DLco) strongly correlated (ρ = 0.70). The delta SpO2-1STST was effective in predicting impaired gas exchange (cut-off value, -4%; AUC, 0.86; sensitivity, 74%; specificity, 87%). CONCLUSIONS: The Delta SpO2-1STST may be a reasonable tool for predicting abnormalities in PFTs.

Invasive thymoma extending to the right atrium with superior vena cava syndrome presenting massive intracardiac thrombosis immediately after the start of chemotherapy: an autopsy case report.

Invasive thymomas with intraluminal tumor thrombi are rare. Removal of the thymoma and infiltration of the superior vena cava (SVC) is a curative alternative. We report an autopsy case of invasive thymoma with intraluminal growth into the intracardiac right atrium extension. Furthermore, the patient died of massive intracardiac thrombosis 5 days after the start of chemotherapy. A 66-year-old man with SVC syndrome was referred to our hospital. He had been aware of swelling of the face for 6 months. The patient was diagnosed with invasive thymoma by a CT-guided needle biopsy of the anterior mediastinal mass. Contrast-enhanced chest computed tomography showed a mass in the anterior mediastinum extending to the SVC and right atrium. As a result of discussion with surgeons and radiotherapists, we planned a multidisciplinary treatment in which neoadjuvant chemotherapy would reduce the tumor size, and surgery and postoperative radiotherapy were followed by chemotherapy. He was administered neo-adjuvant chemotherapy with CBDCA + PTX (carboplatin, area under the curve = 6, and paclitaxel, 200 mg/m2). On the 4th day of chemotherapy, he suddenly developed obstructive shock due to intracardiac thrombosis in the right ventricle. We believe that chemotherapy may trigger rapid thrombus formation. If an invasive thymoma spreads into a large vessel or the right atrium, surgical treatment should be considered if possible. However, if surgery is impossible, administration of anticoagulants should be considered to prevent thrombus formation before chemotherapy.

The 1-minute sit-to-stand test to detect desaturation during 6-minute walk test in interstitial lung disease.

Although the 6 min walk test (6MWT) is well-established for assessing desaturation in patients with interstitial lung disease (ILD), it cannot be easily performed in primary healthcare settings. This retrospective observational study aimed to evaluate the usefulness of the 1 min sit-to-stand test (1STST) for assessing desaturation during 6MWT in ILD patients with normal resting blood oxygen levels. We included 116 patients, and the pulse oxygen saturation (SpO2) for both methods was analyzed. The SpO2 nadir during the 1STST and 6MWT correlated strongly (ρ = 0.82). The frequency of patients with nadir SpO2 < 90% was consistent for both tests (κ = 0.82). 1STST was superior to diffusing capacity for carbon monoxide in detecting desaturation during the 6MWT. These findings were similarly stratified according to performance status or dyspnea scale. The 1STST can easily measure exertional desaturation in ILD patients with normal resting blood oxygen levels and is an alternative to the 6MWT.

Intraoperative bronchial blood flow evaluation using indocyanine green fluorescence for bronchoplasty: A case report.

INTRODUCTION AND IMPORTANCE: Blood flow evaluation of bronchial arteries using indocyanine green fluorescence (ICG-FL) is rarely reported during pulmonary resection. We present the case of a patient with bronchiectasis and a history of bronchial artery embolization (BAE) for hemoptysis. Bronchial artery blood flow was evaluated using ICG-FL during lobectomy with bronchoplasty. CASE PRESENTATION: A 63-year-old woman presented with right middle lobe bronchiectasis (due to nontuberculous mycobacteriosis) and repeated hemoptysis, which had previously been corrected each time with hemostasis by BAE. Bronchoscopy revealed a swollen blood vessel proximal to the right middle lobe bronchus that was suspected of being the origin of bleeding. Right middle lobectomy with bronchoplasty was performed to prevent hemoptysis. ICG-FL was used to detect the patency of the right bronchial arteries, and the arteries surrounding the right middle lobe bronchus were ligated. The proximal side of the right middle lobe bronchus was cut in a deep wedge shape, and the bronchus was anastomosed. ICG-FL revealed that the blood supply was maintained at the bronchial anastomosis. No bronchial anastomotic leakage was observed after the surgery. CLINICAL DISCUSSION: The key to successful bronchoplasty is the maintenance of blood flow. Bronchial artery blood flow theoretically decreases after BAE. In this case, ICG-FL was able to detect bronchial artery patency before cutting the bronchus as well as the maintenance of blood flow at the bronchial anastomosis after bronchoplasty. CONCLUSION: Intraoperative blood flow evaluation of the bronchus using ICG-FL may reduce the risk of bronchial anastomotic leakage caused by ischemia after bronchoplasty.

Detection of type2 biomarkers for response in COPD.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease. It is important to identify patients who would respond to anti-inflammatory treatment. This prospective study aims to determine how inflammatory biomarkers could be used to predict the potential effect of inhaled corticosteroids (ICS) in terms of symptoms and lung function. We evaluated the levels of blood eosinophils, exhaled nitric oxide fraction at a flow rate of 50 ml s-1 (FeNO), alveolar nitric oxide concentration (Calv), immunoglobulin E and atopy in 43 patients with symptomatic COPD and correlated these expression levels with the changes in the COPD Assessment Test (CAT) and lung function by 12 weeks of add-on therapy with ciclesonide 400 µg d-1 on bronchodilators. The mean changes in the CAT score and FEV1 were -1.4 points and +90 ml, respectively, with significant variation in the levels of change. The area under the receiver's operating characteristic curve (AUC) for FeNO in predicting improvements in both the CAT score and FEV1 was 0.92. The AUC for Calv and blood eosinophils was 0.82 and 0.65. Two cutoffs were chosen, one corresponding to a high value of FeNO associated with certainty for response inclusion (FeNO = 35 ppb; sensitivity = 0.67, specificity = 0.94; positive predictive value = 0.80) and the other with certainty for response exclusion (FeNO = 20 ppb; sensitivity = 1.00, specificity = 0.58, negative predictive value = 1.00). Baseline FeNO values were significantly correlated with changes in FEV1 and CAT (all p < 0.0001). FeNO could be a valuable biomarker for identifying individuals who respond to steroid therapy among patients with symptomatic COPD in terms of symptoms and airflow limitation. The study was prospectively registered with the University Hospital Medical Information Network (UMIN) in Japan (protocol ID 000010711).

Cryptococcosis as a cause of organizing pneumonia.

In cases showing organizing pneumonia (OP) with radiologic findings and pathological images, it is necessary to differentiate between idiopathic and secondary diseases as the cause of OP. Cryptococcus infection as a cause of OP is not well known. We herein report two cases of secondary pulmonary cryptococcosis in immunocompromised patients who showed OP, and the usefulness of bronchoscopy and serum cryptococcal antigen test for an early diagnosis. Common to both cases was that antibiotic therapy and corticosteroid therapy were ineffective, while antifungal agents were effective. In cases of immunocompromised patients who present OP with radiologic findings or pathological images, prompt administration of antifungal treatment at an early stage is important when pulmonary cryptococcosis is identified by bronchoscopy and serum cryptococcal antigen test.

Combination of assist use of short-acting beta-2 agonists inhalation and guidance based on patient-specific restrictions in daily behavior: Impact on physical activity of Japanese patients with chronic obstructive pulmonary disease.

BACKGROUND: Assist use of inhaled short-acting beta 2 agonists (SABAs) is reportedly effective for preventing shortness of breath on exertion in chronic obstructive pulmonary disease (COPD) patients. However, it is unclear what strategy would be useful for improving physical activity in such patients. The aim is to investigate the effects of assisted use of SABA (procaterol) on physical activity in Japanese COPD patients targeting patient-specific restrictions in daily behavior. METHODS: Fourteen patients with stable COPD (age: 72.1±1.5, %FEV1: 55.6±4.5%) were asked to inhale 20 µg of procaterol 15 minutes before patient-specific daily physical activity that had been identified as limited by a questionnaire and document their usage in a diary. Physical activity was measured using a triaxial accelerometer and the results were collected every month for 2 months. In the first month, a clinician assessed whether inhalation of SABA was appropriate based on a usage diary and coached patients to conduct adequate assist use of SABA for limited physical activity. RESULTS: The strategy significantly improved the physical activity level, assessed using the values of the metabolic equivalents (METs) multiplied by physical activity endurance, at ≥3.0 METs (p<0.05), and physical activity endurance at ≥2.5 and ≥3.0 METs, (p<0.05, p<0.05, respectively). The degree of improvement of physical activity level was significantly positively correlated with the baseline %FVC and %FEV1 (p<0.05, p<0.05, respectively). CONCLUSIONS: Assist use of SABA targeting patient-specific restrictions, particularly when better lung function is still preserved, could be a useful approach for improving physical activity in patients with COPD.

Medication persistence rates and predictive factors for discontinuation of antifibrotic agents in patients with idiopathic pulmonary fibrosis: a real-world observational study.

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF), continuing treatment with antifibrotic agents is crucial to decrease the reduction of forced vital capacity and mortality rate. However, predictive factors for the discontinuation of antifibrotic agents are unknown. This study aims to investigate the clinical characteristics and predictive factors for the discontinuation of antifibrotic agents in patients with IPF. METHODS: This was a double-center retrospective study that enrolled patients with IPF treated with pirfenidone or nintedanib between 2009 and 2017. We compared clinical parameters between the medication-continuing group and the discontinued group. The predictive factors were determined using Cox proportional hazards analyses. RESULTS: A total of 66 subjects were included: 43 received pirfenidone and 23 received nintedanib. At 1 year, 23 of 66 patients had discontinued due to adverse events (n = 12), disease progression (n = 9), or death (n = 2). The characteristics of the discontinuation group were poor performance status (PS) and delay from diagnosis to treatment. In the receiver operating characteristic (ROC) analysis associated with the discontinuation of antifibrotic agents, PS was the highest area under the ROC curve (AUC) value (cut-off value, 2; AUC, 0.83; specificity, 63%; sensitivity, 87%). This finding was consistent even when analyzing, except for examples of death and adjusting for the type of antifibrotic agent. The treatment persistence rate by PS was PS 0-1 = 90%, PS 2 = 65%, and PS 3 = 19%. Analysis of the relationship between PS and administration period of antifibrotic agents revealed that delays from diagnosis to treatment led to worsening of dyspnea, a decline in lung function, and deterioration of PS. CONCLUSIONS: PS may be informative for predicting discontinuation of medication. Our data reinforced the importance of early initiation of antifibrotic treatment, and we suggest PS should be used as a guide for starting antifibrotic agents in everyday practice. The reviews of this paper are available via the supplementary material section.

Characteristics of 2017 GOLD COPD group A: a multicenter cross-sectional CAP study in Japan.

PURPOSE: The 2017 GOLD ABCD classification shifts patients from groups C-D to A-B. Group A was the most widely distributed group in several studies. It would be useful to understand the characteristics for group A patients, but little has been reported concerning these issues. PATIENTS AND METHODS: This was a multicenter cross-sectional study using the COPD Assessment in Practice study database from 15 primary or secondary care facilities in Japan. We investigated the clinical characteristics of group A by stratification according to a mMRC grade 0 or 1. RESULTS: In 1,168 COPD patients, group A patients accounted for approximately half of the patients. Compared with the groups B-D, group A was younger and had a higher proportion of males, higher pulmonary function, and higher proportion of monotherapy with long-acting muscarinic antagonist or long-acting ß-agonist. The prevalence of mMRC grade 1 patients was about two-thirds of group A. Compared with the mMRC 0 patients, mMRC 1 patients showed a tendency to have a higher proportion of exacerbations (P=0.054) and had a significantly lower pulmonary function. Regardless of the mMRC grade, 60% of group A patients were treated with monotherapy of long-acting muscarinic antagonist or long-acting ß-agonist. CONCLUSION: Group A patients accounted for approximately half of the patients, and they were younger, had higher pulmonary function, and had lower pharmacotherapy intensity compared with groups B-D. By stratifying according to the mMRC grade 0 or 1 in group A patients, there were differences in the exacerbation risk and airflow limitation.

Deep Sternal Wound Tuberculosis with Hypo-gamma-globulinemia.

A 44-year-old man was referred to our hospital for the treatment of a pulmonary and deep sternal wound tuberculosis infection, which is an extremely rare type of extrapulmonary tuberculosis. Laboratory testing revealed a serum immunoglobulin (Ig) G level of 286 mg/dL, IgA of 22 mg/dL and IgM of 13 mg/dL. We therefore diagnosed him with hypo-gamma-globulinemia. He was treated with anti-tuberculosis medications and intravenous immunoglobulin. At present, the tuberculosis has not relapsed in the past six years. It may be useful to assess the humoral immunity status in tuberculosis patients with a normal T cell function, and immunoglobulin therapy may be beneficial for protecting such patients from reactivation of tuberculosis.

Exhaled nitric oxide measurements in patients with acute-onset interstitial lung disease.

It is important to identify the underlying cause of acute-onset interstitial lung disease (ILD). This study aims to assess whether there are differences in the exhaled nitric oxide (eNO) level between different subtypes of acute-onset ILD. Forty patients with a combination of illness ≤4 weeks in duration and diffuse radiographic infiltrates were classified into groups based on the etiology. The eNO at a flow rate of 50 ml s-1 (FeNO), the alveolar nitric oxide concentration (Calv), and the systemic inflammatory markers of the groups were compared. The median FeNO value of patients with acute eosinophilic pneumonia (AEP) (48.1 ppb) was significantly higher than that of the other groups (17.4 ppb in cryptogenic organizing pneumonia, 20.5 ppb in hypersensitivity pneumonia, and 12.0 ppb for sarcoidosis) (p < 0.0005) as well as blood eosinophils (p < 0.005) and Calv levels (p < 0.005). The area under the receiver's operating characteristic curve (AUC) for FeNO to identify AEP was 0.90 with a cut-off of 23.4 ppb. The AUC for Calv and blood eosinophils was 0.85 and 0.82, respectively. Even in patients with blood eosinophil numbers <5 × 105 cells µl-1, FeNO maintained a good diagnostic value for AEP (AUC = 0.85). eNO can be useful for differentiating AEP from other types of acute-onset ILD, regardless of the blood eosinophil levels.

A trial of oral corticosteroids for persistent systemic and airway inflammation in severe asthma.

INTRODUCTION: The fraction of exhaled nitric oxide (FeNO) and blood eosinophils, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic patients. Little is known concerning the relationship between the FeNO levels and blood eosinophils in asthmatics. METHODS: Twenty severe asthmatics with persistent FeNO elevation (≥40 ppb) and blood eosinophilia (≥3%) despite maintenance therapy including high-daily-dose inhaled corticosteroids were analyzed. We investigated the response of FeNO and blood eosinophils to systemic corticosteroids treatment and the change in Asthma Control Questionnaire (ACQ) according to differences in the response of FeNO and blood eosinophils to steroid. RESULTS: The changes in blood eosinophils were not correlated with the changes in FeNO levels by systemic steroid treatment (r = 0.37, P = 0.11). 50% of the subjects showed both ≥20% reductions in FeNO levels and blood eosinophils. There were significant differences in the ACQ score between the steroid response group and poor response group (P < 0.005). The group in which both FeNO and blood eosinophils were suppressed fulfilled the change in score of ≥0.5 on the ACQ. CONCLUSIONS: In the patients with severe asthma, responses to systemic corticosteroids were variable in terms of FeNO and blood eosinophils. It was necessary to suppress both persistent eosinophilia and high FeNO for the improvement of asthma control.