Successful application of lorlatinib in a 23-year-old patient with anaplastic lymphoma kinase (ALK)-positive lung cancer and multiple brain metastases.

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive lung cancer has a better long-term prognosis with ALK-inhibitor than other lung cancers. However, resistance to ALK-inhibitors and the control of metastases in the central nervous system (CNS) remain to be a challenge in the management of ALK-positive lung cancer. CASE: We present the case of a 23-year-old man who developed multiple brain metastases while receiving alectinib treatment for ALK-positive lung cancer. After 3 months of lorlatinib initiation, brain metastases disappeared, and complete response (CR) was maintained. CONCLUSION: While lorlatinib can be used as first line therapy, this drug may be considered as second line or later option for patients with multiple brain metastases if the patient has already been treated with other ALK-inhibitors since lorlatinib is thought to have good CNS penetration. This treatment option should be verified by further research.

Efficacy of paclitaxel-carboplatin with bevacizumab as a late-line therapy for patients with advanced nonsquamous non-small cell lung cancer: A platinum rechallenge.

BACKGROUND: There is no well-established late-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel-carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late-line therapy in a clinical setting. METHODS: Thirty patients with nonsquamous NSCLC who received paclitaxel-carboplatin with bevacizumab therapy as a late-line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated. RESULTS: The median progression-free survival (PFS) was 6.3 (range, 4.9-6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2-17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported. CONCLUSIONS: With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel-carboplatin and bevacizumab, a late-line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option.

Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers.

Although anti-PD-1/PD-L1 monotherapy has achieved clinical success in non-small cell lung cancer (NSCLC), definitive predictive biomarkers remain to be elucidated. In this study, we performed whole-transcriptome sequencing of pretreatment tumor tissue samples and pretreatment and on-treatment whole blood samples (WB) samples obtained from a clinically annotated cohort of NSCLC patients (n = 40) treated with nivolumab (anti-PD-1) monotherapy. Using a single-sample gene set enrichment scoring method, we found that the tumors of responders with lung adenocarcinoma (LUAD, n = 20) are inherently immunogenic to promote antitumor immunity, whereas those with lung squamous cell carcinoma (LUSC, n = 18) have a less immunosuppressive tumor microenvironment. These findings suggested that nivolumab may function as a molecular targeted agent in LUAD and as an immunomodulating agent in LUSC. In addition, our study explains why the reliability of PD-L1 expression on tumor cells as a predictive biomarker for the response to nivolumab monotherapy is quite different between LUAD and LUSC.

Association of immune-related pneumonitis with clinical benefit of anti-programmed cell death-1 monotherapy in advanced non-small cell lung cancer.

BACKGROUND: The association between the development of checkpoint inhibitor pneumonitis (CIP) with tumor response and survival has remained unclear so far. The aim of the present study was to evaluate the association between CIP and the clinical efficacy of anti-programmed cell death-1 antibody in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Between January 2016 and August 2019, 203 advanced NSCLC patients were administered with nivolumab or pembrolizumab. Comparisons were made between patients with and without CIP. We evaluated the time-to-treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). RESULTS: CIP was observed in 28 (14%) patients. CIP was associated with a longer PFS (18.9 months [95% confidence interval, CI: 8.7 months-not reached] vs. 3.9 months [95% CI: 3.4-5.1 months, p < 0.01]) and longer OS (27.4 [95% CI: 20.7 months-not reached] vs. 14.8 months [95% CI: 11.2-17.9 months, p = 0.003]). Most patients discontinued the immune checkpoint inhibitor (ICI) treatment when they developed CIP. Seven patients (25%) lived for more than 300 days from treatment discontinuation and did not show any long-term tumor growth after treatment discontinuation. CONCLUSION: CIP was associated with prolonged PFS and OS. Additionally, 25% of CIP patients did not show any tumor growth for long periods after treatment discontinuation. Careful management of CIP can help in obtaining the best clinical efficacy from anti-PD-1 antibody.

Relationship between Programmed Cell Death Protein Ligand 1 Expression and Immune-related Adverse Events in Non-small-cell Lung Cancer Patients Treated with Pembrolizumab.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs). A correlation between the development of irAEs and efficacy has been suggested; however, it is unclear whether there is a relationship between programmed death ligand 1 (PD-L1) expression and the development of these events. METHODS: We performed a retrospective study of advanced or metastatic non-small cell lung cancer (NSCLC) patients who were treated with pembrolizumab monotherapy at our institution between May 2015 and April 2018 (n = 44). Patients were categorized into two groups, specifically those with irAEs (irAE group) or without (non-irAE group), and we evaluated the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Predictors of irAEs were examined by multivariate analysis. RESULTS: irAEs of any grade occurred in 31 (70.5%) patients. The median PFS was 10.9 months in the irAE group versus 3.7 months in the non-irAE group (P < 0.001). ORR and DCR were also higher in the irAE group than in the non-irAE group. Furthermore, high PD-L1 expression (≥50%) was a predictive factor of irAE based on logistic regression (P = 0.004). CONCLUSIONS: In patients with advanced NSCLC treated with pembrolizumab monotherapy, ORR, DCR, and PFS were significantly better in the irAE group than in the non-irAE group. High PD-L1 expression, at the time of pretreatment, was identified as an independent predictor of irAE development. We believe that more careful management of irAEs for individuals with high PD-L1 expression is needed to improve clinical benefits. Further, PD-L1 expression might be useful for ICI risk management.

A Remarkable Clinical Response to Pembrolizumab in a Rare Spindle Cell Carcinoma of the Lung.

Spindle cell carcinoma of the lung consists of only spindle-shaped tumor cells, and accounts for approximately 13.3% of all sarcomatoid carcinomas (SCs), which are a rare subtype of poorly differentiated non-small cell lung cancer (NSCLC). Spindle cell carcinoma of the lung has very poor prognosis owing to resistance to chemotherapy and radiotherapy. This case report describes a 76-year-old man who presented with complaints of dry cough and right-sided neck pain and was later diagnosed with spindle cell carcinoma of the lung. He had a medical history of type 2 diabetes, angina pectoris, atrial fibrillation, hypertension, hyperlipidemia, and hepatitis B and a 20 pack-year history of smoking. A computed tomography (CT) scan revealed a mass with a thick-walled cavity in the right upper lobe of the lung. His neck pain was consistent with PET-CT images, indicating metastases due to invasion of lung cancer cells. The expression of PD-L1 in more than 90% of the tumor cells of the lung biopsy tissue led to the administration of pembrolizumab. The lung and metastatic tumors dramatically decreased in size after 9 weeks, and no tumor regrowth was observed over 11 courses of pembrolizumab administration. To the best of our knowledge, there are no previous reports describing the use of pembrolizumab for spindle cell carcinoma of the lung. This case report suggests that immunotherapy could be a promising treatment option for rare types of lung cancers, including spindle cell carcinoma.

Clinical Characteristics and Outcomes of Patients with Asthma-COPD Overlap in Japanese Patients with COPD.

Purpose: Asthma-COPD overlap (ACO) has been reported as an association with a lower quality of life, frequent exacerbations, and higher mortality than those with COPD alone. However, clinical characteristics and outcomes of ACO remain controversial. Patients and Methods: We conducted a prospective observational study analyzing data of patients with stable COPD enrolled from the Ishinomaki COPD Network Registry. Patients with features of asthma who had a history of respiratory symptoms that vary over time and intensity, together with documented variable expiratory airflow limitation, were identified, and then defined as having ACO. The characteristics, frequency of exacerbations, and mortality during the 3-year follow-up were compared between patients with ACO and patients with COPD alone. Results: Among 387 patients with COPD, 41 (10.6%) were identified as having ACO. Patients with ACO tended to be younger, have higher BMI, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids. Inflammatory biomarkers including fractional exhaled nitric oxide, blood eosinophil count, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were significantly higher in patients with ACO than in those with COPD alone. Lung function, mMRC score, CAT score, and comorbidity index were not different between the groups. The annual rate of all exacerbations and severe exacerbations required hospital admission were not different between ACO and COPD alone (0.20 vs 0.14, 0.12 vs 0.10, events per person, respectively). Mortality was significantly higher in patients with COPD alone compared with those with ACO during the study period (P=0.037). Conclusion: The results of our study indicate that ACO is not associated with poor clinical features nor outcomes in an outpatient COPD cohort receiving appropriate treatment.

Prognostic factors for patients with metastatic or recurrent thymic carcinoma receiving palliative-intent chemotherapy.

BACKGROUND: Thymic malignancies are a model of rare cancer. However, little clinical data is available based on the large database. We aimed to clarify the prognostic factors, particularly the metastatic sites, for thymic malignancies using one of the largest, representative, multi-institutional databases, the NEJ023 database. PATIENTS AND METHODS: Patients with Stage IVA/IVB or recurrent thymic carcinoma were enrolled between 1995 and 2014. Clinicopathologic information was evaluated, and the patients were subdivided according to the metastatic organs of involvement (serosal dissemination, liver, lymph node, pulmonary, and bone metastasis). A Kaplan-Meier analysis and multivariate Cox regression were used to evaluate survival. RESULTS: Two hundred and seventy-nine patients with metastases and a predominantly squamous histology (66.7%) were included. Most patients (53.0%) had serosal dissemination, whereas 26.5%, 21.9%, 19.7%, and 15.8% had pulmonary, lymph node, bone and liver metastases, respectively. Over a median follow-up time of 21.5 months, the median overall survival (mOS) was 30.7 months. When the subjects were grouped according to involved metastatic sites, patients with more than 3 involved metastatic organs had the worst survival outcome. Among patients with isolated involvement, those with bone metastasis had the poorest survival, followed by patients with liver metastasis. Subjects with hypoalbuminemia also had poor survival outcomes. When patients treated with platinum and anthracycline-containing pharmacotherapy were compared with those treated with platinum and non-anthracycline-containing pharmacotherapy, no significant difference was observed. Bone metastasis (P = 0.0005), liver metastasis (P =  0.047), and hypoalbuminemia (P =  0.0021) were identified as prognostic factors in a multivariate analysis. CONCLUSION: The site of metastatic involvement affects the survival outcomes of patients with thymic carcinoma, and this result may reflect the sensitivity of metastatic sites to pharmacotherapy. As a next step, controlling liver metastasis with pharmacotherapy could help to improve the prognosis of patients with thymic carcinoma.

Radiation eye dose to medical staff during respiratory endoscopy under X-ray fluoroscopy.

Although the clinical value of fluoroscopically guided respiratory endoscopy (bronchoscopy) is clear, there have been very few studies on the radiation dose received by staff during fluoroscopically guided bronchoscopy. The International Commission on Radiological Protection (ICRP) is suggesting reducing the occupational lens dose limit markedly from 150 to 20 mSv/year, averaged over defined periods of five years. The purpose of this study was to clarify the current occupational eye dose of bronchoscopy staff conducting fluoroscopically guided procedures. We measured the occupational eye doses (3-mm-dose equivalent, Hp(3)) of bronchoscopy staff (physicians and nurses) over a 6-month period. The eye doses of eight physicians and three nurses were recorded using a direct eye dosimeter, the DOSIRIS. We also estimated eye doses using personal dosimeters worn at the neck. The mean ± SD radiation eye doses (DOSIRIS) to physicians and nurses were 7.68 ± 5.27 and 2.41 ± 1.94 mSv/6 months, respectively. The new lens dose limit, 20 mSv/year, may be exceeded among bronchoscopy staff, especially physicians. The eye dose of bronchoscopy staff (both physicians and nurses) was underestimated when measured using a neck dosimeter. Hence, the occupational eye dose of bronchoscopy staff should be monitored. To reduce the occupational eye dose, we recommend that staff performing fluoroscopically guided bronchoscopy wear Pb glasses. correct evaluation of the lens dose [Hp(3)] using an eye dosimeter such as the DOSIRIS is necessary for bronchoscopy staff.

Association Between Skin Reaction and Clinical Benefit in Patients Treated with Anti-Programmed Cell Death 1 Monotherapy for Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Anti-programmed cell death 1 antibody is a standard therapy for advanced non-small cell lung cancer (NSCLC). However, immune-related adverse events (irAEs), such as skin reactions, are frequently observed. Although skin reactions are associated with clinical efficacy in melanoma, this association in advanced NSCLC and predictors of irAEs remain unclear. Accordingly, this study identified potential correlations of skin reactions with clinical efficacy and clinical predictors of development of skin reactions. SUBJECTS, MATERIALS, AND METHODS: We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 155) during January 2016 to April 2018. Treatment efficacy was evaluated in patients with and without skin reactions, and associated predictive markers were determined. A 6-week landmark analysis was conducted to assess the clinical benefit of early skin reactions. RESULTS: Skin reactions were observed in 51 patients with a median time to onset of 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions (57% vs. 19%, p < .001). Median progression-free survival (PFS) durations of 12.9 and 3.5 months and overall survival durations of not reached and 11.4 months were observed in patients with and without skin reactions, respectively. In the 6-week landmark analysis, the ORR was significantly higher in patients with skin reactions, and skin reactions were significantly associated with increased PFS. A multivariate analysis identified pre-existing rheumatoid factor (RF) as an independent predictor of skin reactions. CONCLUSION: Skin reactions appeared beneficial in patients treated with nivolumab/pembrolizumab for advanced NSCLC and could be predicted by pre-existing RF. Further large-scale validations studies are warranted. IMPLICATIONS FOR PRACTICE: This single-institutional medical record review that included 155 patients with advanced non-small cell lung cancer who were treated with nivolumab or pembrolizumab monotherapy revealed that overall response rate and progression-free survival were significantly better in patients with skin reactions. Pre-existing rheumatoid factor was an independent predictor of skin reactions.

Association of low body surface area with dose reduction and/or discontinuation of nintedanib in patients with idiopathic pulmonary fibrosis: a pilot study.

BACKGROUND: We have often encountered adverse events requiring dose reduction and/or discontinuation of nintedanib in patients with idiopathic pulmonary fibrosis. OBJECTIVES: The objectives of this study were to clarify the incidence of dose reduction and/or discontinuation following the commercialization of nintedanib and to investigate predictors of dose reduction and/or discontinuation of nintedanib at our hospital. METHODS: We retrospectively identified 25 patients who had received nintedanib 150 mg twice daily at Sendai Kousei Hospital and categorized them into two groups according to whether they had or had not required dose reduction and/or discontinuation and sought to identify predictors of dose reduction and/or discontinuation. RESULTS: Seventeen patients developed adverse events, which included diarrhea (n=10, 44%), hepatotoxicity (n=7, 28%), and anorexia (n=2, 16%). No adverse event-related deaths occurred during the study period. Patients who required dose reduction and/or discontinuation were significantly older than those who did not (72 years vs 67 years; P=0.047). Body surface area (BSA) was significantly lower in the group that needed dose reduction and/or discontinuation than in the group that did not (1.63 m2 vs. 1.78 m2; P=0.028). Multivariate logistic regression revealed that the association of low BSA with dose reduction and/or discontinuation was statistically significant. CONCLUSIONS: A low BSA was associated with dose reduction and/or discontinuation of nintedanib in patients with idiopathic pulmonary fibrosis. Further studies in larger patient samples are needed to validate these findings.

Profiling Preexisting Antibodies in Patients Treated With Anti-PD-1 Therapy for Advanced Non-Small Cell Lung Cancer.

Importance: Administration of anti-programmed cell death protein 1 (anti-PD-1) is now standard therapy in advanced non-small cell lung cancer (NSCLC). However, immune checkpoint inhibitors, including anti-PD-1, have not been assessed in patients with subclinical disease with advanced NSCLC, and no useful clinical biomarkers have been associated with immune-related adverse events (irAEs) among these patients treated with anti-PD-1. Objective: To assess the safety and efficacy of anti-PD-1 treatment in patients with subclinical disease with advanced NSCLC and with or without preexisting autoimmune markers, including rheumatoid factor, antinuclear antibody, antithyroglobulin, and antithyroid peroxidase; and to assess potential clinical biomarkers that may be meaningfully and conveniently associated with clinical benefit or with irAEs following anti-PD-1 treatment. Design, Setting, and Participants: This medical records analysis retrospectively evaluated 137 patients who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital in Japan between January 2016 and January 2018. Treatment efficacy and irAEs were evaluated along with candidate factors that may be associated with irAEs. Exposures: Absence or presence of specific autoimmune markers and antibodies before treatment. Main Outcomes and Measures: Preexisting antibodies and autoimmune markers, progression-free survival (PFS), and irAEs. Results: Of 137 patients with advanced NSCLC, 105 were men, the median age was 68 (range, 36-88) years, 99 underwent nivolumab monotherapy, 38 underwent pembrolizumab monotherapy, and 134 had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median PFS was 6.5 (95% CI, 4.4-12.9) months among patients with examined preexisting antibodies and 3.5 (95% CI, 2.4-4.1) months among patients without, suggesting significantly better prognosis in the former. The hazard ratio for disease progression or death in the presence of the examined preexisting antibodies was 0.53 (95% CI, 0.36-0.79; P = .002). The PFS was significantly longer among patients with any preexisting antibodies than among those without. The examined preexisting antibodies (48 patients [73%]) and rheumatoid factor (26 patients [39%]) were more common among patients who developed irAEs. Multivariate analysis indicated that the presence of the examined preexisting antibodies was independently associated with irAEs (odds ratio, 3.25; 95% CI, 1.59-6.65; P = .001). Skin reactions were more frequent among patients with preexisting rheumatoid factor (47% vs 24%, P = .02), whereas thyroid dysfunction was more frequent among patients with preexisting antithyroid antibodies (20% vs 1%, P < .001). Conclusions and Relevance: The presence of the examined preexisting antibodies was associated with clinical benefit and with the development of irAEs in patients with NSCLC treated with nivolumab or pembrolizumab. Thus, the presence of these autoimmune markers may help determine the risk-benefit ratio for individual patients with NSCLC, maximizing therapeutic benefits while minimizing irAEs.

Clinical characteristics and outcomes in Japanese patients with COPD according to the 2017 GOLD classification: the Ishinomaki COPD Network Registry.

PURPOSE: The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations. The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations. However, the clinical characteristics and outcomes in these patients are not well documented. PATIENTS AND METHODS: In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. All patients with stable COPD were classified into the four groups defined by GOLD 2017. The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups. RESULTS: Four hundred and one patients with stable COPD were identified. There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D. Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A. Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period. Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B). Mortality was not different between the high-risk and low-risk groups. CONCLUSION: The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality.

Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab.

BACKGROUND: Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study aimed to evaluate whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We conducted a retrospective study of patients who received nivolumab monotherapy at Sendai Kousei Hospital (n = 70). The patients were categorized into two groups based on the incidence of irAEs: those with irAEs (irAE group) or those without (non-irAE group). Treatment efficacy was evaluated in each group. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were determined. RESULTS: The objective response rate was 57% in the irAE group versus 12% in the non-irAE group. Median progression-free survival was 12.0 months in the irAE versus 3.6 months in the non-irAE group. The incidence of both irAEs and pre-existing antithyroid antibody was significantly higher in responders than in nonresponders. Multivariate analysis identified incidence of irAEs and pre-existing antithyroid antibody as an independent predictor of treatment response. CONCLUSION: Objective response rate and progression-free survival were significantly better in the irAE than in the non-irAE group in patients with advanced NSCLC treated with nivolumab monotherapy. The development of irAEs was associated with clinical efficacy, and the presence of pre-existing antithyroid antibody might be correlated with treatment response to nivolumab monotherapy. IMPLICATIONS FOR PRACTICE: Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study evaluted whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer. Results showed that the objective response rate and progression-free survival were significantly better in the patients who developed irAEs than in the patients who did not develop irAEs, and the incidence of irAEs and positivity for antithyroid antibody at pretreatment were independent predictors of treatment response of nivolumab monotherapy. Therefore, the development of irAEs predicts clinical benefit and suggests that cautious management of irAEs can lead to achieving maximum clinical benefit from nivolumab monotherapy.

Two Cases of Tsunami Dust Pneumonia: Organizing Pneumonia Caused by the Inhalation of Dried Tsunami Sludge after the 2011 Great East Japan Earthquake.

We report two cases of organizing pneumonia (OP) secondary to the inhalation of the dried tsunami sludge which formed during the 2011 Great East Japan Earthquake and the consequent tsunami. After the disaster, both of these patients had been engaged in the restoration work. About half a month later, they developed shortness of breath and pulmonary infiltrates. These patients were diagnosed with interstitial pneumonia. Their biopsy specimens revealed multifocal peribronchiolitis and OP. An electron probe microanalysis of these specimens demonstrated the presence of elements from the earth's crust in the inflammatory lesions. These two cases indicate that exposure to dried tsunami sludge can cause OP.

Inflammatory biomarkers in asthma-COPD overlap syndrome.

BACKGROUND: The clinical phenotypes and underlying mechanisms of asthma-COPD overlap syndrome (ACOS) remain elusive. This study aimed to investigate a comparison of COPD patients with and without ACOS, focusing on inflammatory biomarkers, in an outpatient COPD cohort. METHODS: We conducted a cross-sectional study analyzing prospectively collected data from the Ishinomaki COPD Network registry. All participants were diagnosed with COPD, confirmed by using spirometry, and were aged 40-90 years and former smokers. Patients with features of asthma including both variable respiratory symptoms and variable expiratory airflow limitation were identified and defined as having ACOS. Then, the inflammatory biomarkers such as fractional exhaled nitric oxide level, blood eosinophil count and percentage, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were evaluated. RESULTS: A total of 257 patients with COPD were identified, including 37 (14.4%) with ACOS. Patients with ACOS tended to be younger, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids and theophylline. Mean fractional exhaled nitric oxide level was significantly higher in those with ACOS than in those without ACOS (38.5 parts per billion [ppb] vs 20.3 ppb, P<0.001). Blood eosinophil count and percentage were significantly increased in those with ACOS (295/mm3 vs 212/mm3, P=0.032; 4.7% vs 3.2%, P=0.003, respectively). Total IgE level was also significantly higher, and presence of antigen-specific IgE was observed more frequently in patients with ACOS. Receiver operating characteristic curve analysis indicated that the sensitivity and specificity of these biomarkers were relatively low, but combinations of these biomarkers showed high specificity for ACOS diagnosis. CONCLUSION: These results provide evidence that these inflammatory biomarkers can be used to support the diagnosis of ACOS.

Burden of chronic obstructive pulmonary disease in the elderly population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease and an important health care problem in older adults. The impact of age and specific geriatric issues on COPD in elderly patients has not been well established. METHODS: A cross-sectional study of elderly COPD patients was conducted in Japan by using a regional COPD registry database. We compared indices of disease severity (pulmonary function, exercise tolerance, quality of life, and frequency of exacerbations), presence of comorbidities, geriatric conditions (cognitive function, mental status, and activities of daily living [ADL]), and adherence to prescribed drug regimens between elderly and younger patients with COPD. RESULTS: In total, 279 patients with stable COPD (median age, 74 years) were identified; 86% of these patients were elderly (65 years of age or older). Elderly COPD patients, especially those who were 75 years of age or older, had significantly more cases of dyspnea, lower exercise tolerance, and poorer ADL and a higher incidence of severe exacerbations than younger patients (all P<0.05). In addition, the prevalence of comorbidities, including cardiovascular disease and cancer, was significantly higher in elderly COPD patients. Elderly COPD patients had specific geriatric conditions, including cognitive impairment. Adherence to inhaled drug regimens in elderly patients was as favorable as that in younger patients. CONCLUSIONS: Age and specific geriatric conditions have a great negative impact on COPD in elderly patients. Geriatric conditions should be addressed in the management of elderly COPD patients.

Impact of a large-scale natural disaster on patients with chronic obstructive pulmonary disease: the aftermath of the 2011 Great East Japan Earthquake.

BACKGROUND: A large-scale natural disaster may exacerbate chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). The aftermath of a natural disaster can include poor access to medication, medical equipment, and medical supplies. Little is known about the impact on patients with COPD. METHODS: A retrospective cohort study was conducted at a regional medical center in Ishinomaki, the area affected most severely by the Great East Japan Earthquake in 2011. The study was performed 6 months after the disaster. The characteristics, clinical courses, and outcomes of COPD patients hospitalized after emergency visits during the study period were investigated and compared. RESULTS: One hundred patients (112 episodes) were identified. Within a few days after the disaster, patients undergoing oxygen therapy at home came to the hospital to receive oxygen. In the subacute phase (from the third to the fifth week), the number of hospitalizations due to COPD exacerbations was significantly increased compared to the numbers observed before the earthquake (p<0.05). On admission, COPD patients reported significantly reduced participation in the activities of daily living (ADLs) after as compared to before the disaster. The incidence of cases of exacerbated COPD normalized 6 weeks after the earthquake. CONCLUSIONS: The large-scale natural disaster that hit Japan in 2011 had a serious negative impact on the clinical outcomes of COPD patients in the disaster-affected area.

The impact of the 2011 Great East Japan Earthquake on hospitalisation for respiratory disease in a rapidly aging society: a retrospective descriptive and cross-sectional study at the disaster base hospital in Ishinomaki.

OBJECTIVE: To investigate the impact in an aging society of the 2011 Great East Japan earthquake on hospitalisation for respiratory disease at the disaster base hospital. DESIGN: Descriptive and cross-sectional study. SETTING: Emergency care in Japanese Red Cross Ishinomaki Hospital, a regional disaster base hospital in Miyagi, Japan. PARTICIPANTS: 322 emergency patients who were hospitalised for respiratory disease from 11 March to 9 May 2011, and 99 and 105 emergency patients who were hospitalised in the corresponding periods in 2009 and 2010, respectively. MAIN OUTCOME MEASURES: Description and comparison of patient characteristics and disease distribution in terms of age, time after the disaster and activities of daily living (ADL). RESULTS: 1769 patients were admitted to our hospital during the study period (compared to 850 in 2009 and 1030 in 2010), among whom 322 were hospitalised for respiratory disease (compared to 99 in 2009 and 105 in 2010). Pneumonia (n=190, 59.0%) was the most frequent cause of admission for pulmonary disease, followed by acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) (n=53, 16.5%), asthma attacks (n=27, 8.4%) and progression of lung cancer (n=22, 6.8%). Compared with the corresponding periods in 2009 and 2010, the increase in the absolute numbers of admissions was highest for pneumonia, followed by AE-COPD and asthma attacks. At hospitalisation, 195 patients were 'dependent' and 54 patients were 'partially dependent'. Respiratory admissions accompanied by deterioration of ADL after the disaster were more frequent in elderly and female patients. CONCLUSIONS: After the Great East Japan Earthquake, admissions for pneumonia and exacerbation of chronic respiratory disease in the elderly increased at the disaster base hospital.