Association between Inhalation Instruction Method in Community Pharmacies and Inhaler Device Handling Error in Patients with Obstructive Lung Disease: An Evaluation of the Impact of Practical Demonstration by Pharmacists.

Inhaler devices play an important role in the management of obstructive lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Some of these patients show suboptimal inhaler techniques; however, time for inhaler instruction by pharmacists is limited in daily clinical practice. Therefore, sufficient education regarding inhaler device handling should be provided within a limited time frame. The current study aimed to investigate the instruction methods provided by community pharmacists and their influence on inhaler device handling techniques in outpatient clinical care settings. We retrospectively collected the data of outpatients with obstructive lung diseases who were referred to our hospital and who underwent inhalation technique assessments conducted by community pharmacists. The prevalence of handling errors, clinical characteristics of patients, and instruction methods were analyzed. In total, 138 patients (170 devices) were included in this study. Approximately 70.0% of patients received verbal explanations combined with leaflets about inhaler instructions. In a device-based analysis, 63 (37.1%) of 170 devices had at least one technical error and 18 (10.6%) of the devices had critical errors. Patients without critical errors received practical demonstration instructions from pharmacists combined with leaflets and verbal explanations more frequently than those with critical errors (22.8 vs. 0%, p < 0.01). This study revealed that patients with obstructive lung diseases commonly present with inhaler device handling errors and critical errors were observed with non-negligible frequency in daily practice in Japan. Combined instruction with leaflet, verbal explanation, and pharmacist demonstration may be effective in improving proper inhaler treatment.

Factors affecting in-hospital mortality of non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: The incidence and prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) are reportedly increasing in many parts of the world. However, there are few published data on NTM-PD-related death. Using data from a national inpatient database in Japan, we aimed in this study to identify the characteristics of patients with NTM-PD and clinical deterioration and to identify risk factors for in-hospital mortality. METHODS: We examined data from the Diagnosis Procedure Combination (DPC) database in Japan from July 2010 to March 2014. We extracted data for HIV-negative NTM-PD patients who required unscheduled hospitalization. We evaluated these patients' characteristics and performed multivariable logistic regression analysis to identify risk factors for all-cause in-hospital mortality. RESULTS: A total of 16,192 patients (median age: 78 years; women: 61.2%) were identified. The median body mass index (BMI) was 17.5 kg/m2 (IQR 15.4-20.0). All cause In-hospital death occurred in 3166 patients (19.6%). The median BMI of the patients who had died was 16.0 kg/m2 (IQR 14.2-18.4). Multivariable analysis revealed that increased mortality was associated with male sex, lower BMI, lower activities of daily living scores on the Barthel index, hemoptysis, and comorbidities, including pulmonary infection other than NTM, interstitial lung disease, pneumothorax, and malignant disease. CONCLUSIONS: We found associations between being underweight and having several comorbidities and increased in-hospital mortality in patients with NTM-PD. Preventing weight loss and management of comorbidities may have a crucial role in improving this disease's prognosis.

Early Arterial Embolization and Mortality in Mechanically Ventilated Patients With Hemoptysis: A Nationwide Retrospective Cohort Study.

OBJECTIVES: Hemoptysis, a symptom common across various respiratory diseases, can cause airway obstruction leading to a life-threatening condition. Arterial embolization has been used to control bleeding from the lower airways. However, limited studies have evaluated its effects on in-hospital mortality in patients with hemoptysis requiring mechanical ventilation. The objective of this study was to clarify whether early intervention by arterial embolization reduced mortality in mechanically ventilated patients with hemoptysis. DESIGN: Retrospective cohort study from July 2010 to March 2017. SETTING: More than 1,200 acute-care hospitals, comprising approximately 90% of all tertiary-care emergency hospitals in Japan. PATIENTS: The study cohort was patients with pulmonary diseases hospitalized for hemoptysis and mechanically ventilated within 2 days of admission. INTERVENTIONS: We compared patients who had undergone arterial embolization within 3 days of endotracheal intubation (early embolization group) with patients who did not (control group). MEASUREMENTS AND MAIN RESULTS: A total of 12,287 patients with hemoptysis requiring mechanical ventilation were analyzed. After 1:4 propensity score matching, there were 226 and 904 patients in the early embolization and control groups, respectively. The early embolization group was associated with lower 7-day and 30-day mortalities (7-d mortality: 1.3% vs 4.0%; odds ratio, 0.39; 95% CI, 0.16-0.97; p = 0.044 and 30-d mortality: 7.5% vs 16.8%; odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001) and shorter duration of mechanical ventilation (median 6 d, interquartile range 4-13 d vs 8 d, interquartile range 4-19 d; p = 0.003) compared with the control group. CONCLUSIONS: Our results show that early intervention by arterial embolization may be effective in reducing 7-day and 30-day mortalities in patients with life-threatening hemoptysis requiring mechanical ventilation.

Old age and underlying interstitial abnormalities are risk factors for development of ARDS after pleurodesis using limited amount of large particle size talc.

BACKGROUND AND OBJECTIVE: Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. METHODS: We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. RESULTS: Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. CONCLUSION: Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis.

A case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion.

BACKGROUND: Meigs' syndrome is defined as the presence of a benign ovarian tumor with pleural effusion and ascites that resolve after removal of the tumor. The pathogenesis of the production of ascites and pleural effusion in this syndrome remains unknown. Aside from pleural effusion and ascites, pericardial effusion is rarely observed in Meigs' syndrome. Here, we report the first case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion. CASE PRESENTATION: An 84-year-old Japanese non-smoking woman with a history of lung cancer, treated by surgery, was admitted due to gradual worsening of dyspnea that had occurred over the previous month. She had asymptomatic and unchanging pericardial effusion and a pelvic mass, which had been detected 3 and 11 years previously, respectively. The patient was radiologically followed-up without the need for treatment. Two months before admission, the patient underwent a right upper lobectomy for localized lung adenocarcinoma and intraoperative pericardial fenestration confirmed that the pericardial effusion was not malignant. However, she began to experience dyspnea on exertion leading to admission. A chest, abdomen, and pelvis computed tomography scan confirmed the presence of right-sided pleural and pericardial effusion and ascites with a left ovarian mass. Repeated thoracentesis produced cultures that were negative for any microorganism and no malignant cells were detected in the pleural effusions. Pleural fluid accumulation persisted despite a tube thoracostomy for pleural effusion drainage. With a suspicion of Meigs' syndrome, the patient underwent surgical resection of the ovarian mass and histopathological examination of the resected mass showed ovarian fibroma. Pleural and pericardial effusion as well as ascites resolved after tumor resection, confirming a diagnosis of Meigs' syndrome. This clinical course suggests a strong association between pericardial effusion and ovarian fibroma, as well as pleural and peritoneal fluid. CONCLUSIONS: In female patients with unexplained pericardial effusion and an ovarian tumor, clinicians should consider the possibility of Meigs' syndrome. Although a malignant disease should be suspected in all patients with undiagnosed pleural and/or pericardial effusion, Meigs' syndrome is curable by tumor resection and should be differentiated from malignancy.

Reduction in the need for surgery and mortality after early administration of fibrinolytics following empyema drainage.

OBJECTIVES: Although intrapleural administration of fibrinolytics is an important treatment option for the management of empyema, the addition of fibrinolytics failed to reduce the need for surgery and mortality in previous randomized controlled trials. This study aimed to investigate the effects of administrating fibrinolytics in the early phase (within 3 days of chest tube insertion) of empyema compared with late administration or no administration. METHODS: We used the Japanese Diagnosis Procedure Combination Inpatient Database to identify patients aged ≥16 years who were hospitalized and underwent chest tube drainage for empyema. A 1:2 propensity score matching and stabilized inverse probability of treatment weighting were conducted. RESULTS: Among the 16 265 eligible patients, 3082 and 13 183 patients were categorized into the early and control group, respectively. The proportion of patients who underwent surgery was significantly lower in the early fibrinolytics group than in the control group; the odds ratio (95% confidence interval) was 0.69 (0.54-0.88) in the propensity score matching (P = 0.003) and 0.64 (0.50-0.80) in the stabilized inverse probability of treatment weighting analysis (P < 0.001). All-cause 30-day in-hospital mortality, length of hospital stay, duration of chest tube drainage, and total hospitalization costs were also more favourable in the early fibrinolytics group. CONCLUSIONS: The early administration of fibrinolytics may reduce the need for surgery and death in adult patients with empyema.

Epidemiology of chronic pulmonary aspergillosis: A nationwide descriptive study.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) has recently gained attention owing to its substantial health burden. However, the precise epidemiology and prognosis of the disease are still unclear due to the lack of a nationwide descriptive analysis. This study aimed to elucidate the epidemiology of patients with CPA and to investigate their prognosis. METHODS: Using a national administrative database covering >99% of the population in Japan, we calculated the nationwide incidence and prevalence of CPA from 2016 to 2022. Additionally, we clarified the survival rate of patients diagnosed with CPA and identified independent prognostic factors using multivariate Cox proportional hazard analysis. RESULTS: During the study period, while the prevalence of CPA remained stable at 9.0-9.5 per 100,000 persons, its incidence declined to 2.1 from 3.5 per 100,000 person-years. The 1-, 3-, and 5-year survival rates were 65%, 48%, and 41%, respectively. During the year of CPA onset, approximately 50% of patients received oral corticosteroids (OCS) at least once, while about 30% underwent frequent OCS treatment (≥4 times per year) within the same timeframe. Increased mortality was independently associated with older age (>65 years) (hazard ratio [HR], 2.65; 95% confidence interval (CI), 2.54-2.77), males (1.24; 1.20-1.29), a history of chronic obstructive pulmonary disease (1.05; 1.02-1.09), lung cancer (1.12; 1.06-1.18); and ILD (1.19; 1.14-1.24); and frequent OCS use (1.13; 1.09-1.17). Conversely, decreased mortality was associated with a history of tuberculosis (HR, 0.81; 95% CI, 0.76-0.86), non-tuberculous mycobacteria (0.91; 0.86-0.96), and other chronic pulmonary diseases (0.89; 0.85-0.92). CONCLUSIONS: The incidence of CPA decreased over the past decade, although the prevalence was stable and much higher than that in European countries. Moreover, the patients' prognosis was poor. Physicians should be vigilant about CPA onset in patients with specific high-risk underlying pulmonary conditions.

Association of Novel Antihyperglycemic Drugs Versus Metformin With a Decrease in Asthma Exacerbations.

BACKGROUND: Similar to metformin, dipeptidyl peptidase-4 inhibitors (DPP-4 Is), glucagon-like peptidase 1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2 Is) may improve control of asthma owing to their multiple potential mechanisms, including differential improvements in glycemic control, direct anti-inflammatory effects, and systemic changes in metabolism. OBJECTIVE: To investigate whether these novel antihyperglycemic drugs were associated with fewer asthma exacerbations compared with metformin in patients with asthma comorbid with type 2 diabetes. METHODS: Using a Japanese national administrative database, we constructed 3 active comparators-new user cohorts of 137,173 patients with a history of asthma starting the novel antihyperglycemic drugs and metformin between 2014 and 2022. Patient characteristics were balanced using overlap propensity score weighting. The primary outcome was the first exacerbation requiring systemic corticosteroids, and the secondary outcomes included the number of exacerbations requiring systemic corticosteroids. RESULTS: DPP-4 Is and GLP-1 RAs were associated with a higher incidence of exacerbations requiring systemic corticosteroids compared with metformin (DPP-4 Is: 18.2 vs 17.4 per 100 person-years, hazard ratio: 1.09, 95% confidence interval [CI]: 1.05-1.14; GLP-1 RAs: 24.9 vs 19.0 per 100 person-years, hazard ratio: 1.14, 95% CI: 1.01-1.28). In contrast, the incidence of exacerbations requiring systemic corticosteroids was similar between the SGLT-2 Is and metformin groups (17.3 vs 18.1 per 100 person-years, hazard ratio: 1.00, 95% CI: 0.97-1.03). While DPP-4 Is and GLP-1 RAs were associated with more exacerbations requiring systemic corticosteroids, SGLT-2 Is were associated with slightly fewer exacerbations requiring systemic corticosteroids (53.7 vs 56.6 per 100 person-years, rate ratio: 0.95, 95% CI: 0.91-0.99). CONCLUSIONS: While DPP-4 Is and GLP-1 RAs were associated with poorer control of asthma compared with metformin, SGLT-2 Is offered asthma control comparable to that of metformin.

Epidemiology of patients with severe asthma in Japan: a nationwide descriptive study.

Background: The 2014 European Respiratory Society/American Thoracic Society guidelines defined severe asthma based on treatment intensity and estimated the proportion of severe asthma among all asthma cases to be 5-10%. However, data supporting the estimate and comprehensive and sequential data on asthma cases are scarce. We aimed to estimate the national prevalence and proportion of severe asthma during the last decade. Methods: Using a Japanese national administrative database, which covers ≥99% of the population, we evaluated the prevalence and proportion of severe asthma in 2013, 2015, 2017 and 2019. Additionally, we elucidated the demographic characteristics, treatments and outcomes of patients with asthma. Results: The national prevalence of mild-moderate and severe asthma in 2019 was 800 and 36 per 100 000 persons, respectively. While the prevalence of mild-moderate asthma remained almost constant in the study years, the prevalence of severe asthma decreased, resulting in a reduction in the proportion of severe asthma from 5.6% to 4.3%. Although treatment modalities have evolved, such as the increased use of combination inhalers and asthma biologics, approximately 15% of mild-moderate and 45% of severe asthma cases were still considered "uncontrolled". The number of deaths from asthma decreased in patients with both mild-moderate and severe asthma. Conclusions: This study revealed that the prevalence of severe asthma in Japan decreased during the study period and fell below 5% in the most recent data. Despite treatment evolution, a substantial proportion of patients with both mild-moderate and severe asthma still have poor asthma control.

Epidemiology of patients with lymphangioleiomyomatosis: A descriptive study using the national database of health insurance claims and specific health checkups of Japan.

BACKGROUND: Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the national administrative database to estimate the incidence and prevalence of lymphangioleiomyomatosis over six years (2014-2019) and describe changes in clinical practice and mortality. METHODS: We extracted data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between January 2013 and December 2020. This database covers ≥99% of the population. We used the diagnostic code for lymphangioleiomyomatosis to estimate the incidence and prevalence from 2014 to 2019. Additionally, we examined the demographic characteristics, treatments, comorbidities, and mortality of the patients. RESULTS: In women, the incidence and prevalence of lymphangioleiomyomatosis in 2019 were approximately 3 per 1,000,000 person-years and 28.7 per 1,000,000 persons, respectively. While, in men, the incidence and prevalence of lymphangioleiomyomatosis were <0.2 per 1,000,000 person-years and 0.8 per 1,000,000 persons, respectively. From 2014 to 2019, the proportion of prescriptions of sirolimus and everolimus increased, while the use of home oxygen therapy, chest drainage, comorbid pneumothorax, and bloody phlegm decreased. The mortality rate remained stable at approximately 1%. CONCLUSIONS: The incidence and prevalence of lymphangioleiomyomatosis were higher in women than those reported previously. Although the incidence did not change during the 6-year period, the prevalence gradually increased. Moreover, lymphangioleiomyomatosis was observed to be rare in men. The practice of treating patients with lymphangioleiomyomatosis changed across the six years while mortality remained low, at approximately 1%.

Lung Adenocarcinoma Size Decrease after SARS-CoV-2 Vaccination during Long-Term Pembrolizumab Treatment: A Case Report.

A man in his late 40s was diagnosed with clinical stage 4B lung adenocarcinoma with a PD-L1 tumor proportion score of 100% and high tumor mutational burden. A partial response was achieved after administration of pembrolizumab. The patient received two doses of a SARS-CoV-2 vaccine (BNT162b2) after 59 courses, and a chest computed tomography revealed consolidation in the peri-tumoral area, which subsequently disappeared, and the tumor continued to shrink in the next 4 months. This case provides indirect evidence for the persistence of cancer immunity during long-term treatment with immune checkpoint inhibitors and the potential for further activation.

Effectiveness and safety of the co-administration of Yokukan-San (Japanese herbal medicine) with antipsychotics in hospitalized older patients with pneumonia.

AIM: Behavioral and psychological symptoms and delirium frequently occur in hospitalized older patients with pneumonia and are associated with longer hospital stays. Yokukan-San (YKS, traditional Japanese [Kampo] medicine) and antipsychotics are often used to treat delirium and behavioral and psychological symptoms in Japan. Hence, this study aimed to assess the effectiveness and safety of the co-administration of YKS with atypical antipsychotics in older patients with pneumonia. METHODS: We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify older patients (≥65 years) hospitalized for pneumonia who received antipsychotics within 3 days of hospitalization. The patients were divided into two groups: those who received atypical antipsychotics alone (control group) and those who received both atypical antipsychotics and YKS (YKS group). We compared length of hospital stay, in-hospital mortality, bone fractures, and administration of potassium products between the two groups using propensity score overlap weighting. RESULT: We identified 4789 patients in the YKS group and 61 641 in the control group. After propensity score overlap weighting, length of hospital stay was statistically significantly shorter in the YKS group (percentage difference -3.0%; 95% confidence interval -5.8% to -0.3%). The proportion of patients who received potassium products was higher in the YKS group (odds ratio 1.34; 95% confidence interval 1.15-1.55). In-hospital death and bone fractures were not significantly different. CONCLUSION: Co-administration of YKS with atypical antipsychotics could be a reasonable treatment option for hospitalized older patients with pneumonia and aggressive psychiatric symptoms. Geriatr Gerontol Int 2023; 23: 849-854.

Association Between Systemic Corticosteroid Use and Mortality in Patients with Epiglottitis.

OBJECTIVES: To clarify whether treatment with systemic corticosteroids at a certain dose was associated with better outcomes in patients with epiglottitis requiring airway management (tracheotomy or airway intubation). METHODS: This was a retrospective cohort study on patients hospitalized for epiglottitis requiring airway management from a nationwide inpatient database (between July 2010 and March 2019). Patients treated with systemic corticosteroids equivalent to methylprednisolone ≥40 mg/d within 2 days of admission and patients who were not treated with corticosteroids within 2 days of admission were compared after inverse probability of treatment weighting using covariate balancing propensity score. The primary outcome was all-cause 30-day in-hospital mortality, and secondary outcomes included all-cause 7-day in-hospital mortality, length of hospital stay, and total medical cost. RESULTS: There were 1986 and 1771 patients in the corticosteroid and control groups, respectively. A total of 72 of 3757 (1.9%) patients died within 30 days of admission, including 17 of 1986 (0.9%) patients in the corticosteroid group and 55 of 1771 (3.1%) in the control group (weighted odds ratio, 0.28 [95% confidence interval, 0.11-0.70]; weighted risk difference, -2.2% [-3.2% to -1.3%]). Treatment with corticosteroids was associated with lower total medical costs (weighted median, $6,187 vs. $6,587; weighted difference, $-1,123 [-2,238 to -8]) but not all-cause 7-day in-hospital mortality (weighted odds ratio, 0.63 [0.22-1.82]; weighted risk difference, -0.3% [-0.9 to 0.2]) and length of hospital stay (weighted median, 13 vs. 13 days; weighted difference, -0.2 days [-2.1 to 1.8]). CONCLUSIONS: Systemic corticosteroids may be beneficial to patients with epiglottitis requiring airway management. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:344-349, 2023.

Pulmonary carcinoid tumour with remarkably high levels of pro-gastrin-releasing peptide: A case report.

An 86-year-old woman presented with chronic cough and chest pain. Computed tomography revealed two masses in the right lower lobe of the lung accompanied by multiple lymphadenopathies and metastasis to the rib. The pro-gastrin-releasing peptide (ProGRP) levels were notably elevated (888 pg/mL). Based on these findings, our initial clinical diagnosis was small-cell lung cancer. However, the pathological diagnosis turned out to be an atypical carcinoid. The patient was finally treated with everolimus. Clinicians should be aware that carcinoid tumours are sometimes difficult to distinguish from small-cell lung cancer with respect to high ProGRP levels and multiple metastases.

Multiple Brain Metastases in a Patient with ROS1 Fusion-Positive Lung Adenocarcinoma as a Disease Flare due to Crizotinib Cessation Caused by Disseminated Aseptic Inflammation from Crizotinib-Associated Renal Cysts: A Case Report.

Rapid tumor growth after cessation of molecularly targeted drugs, called "disease flare," may occur and affect the prognosis of lung cancer. However, this phenomenon has never been reported in ROS proto-oncogene 1 (ROS1) fusion-positive lung adenocarcinoma. Herein, we report a disease flare in a patient with ROS1 fusion-positive lung adenocarcinoma. A 60-year-old female was diagnosed with stage IVA ROS1 fusion-positive lung adenocarcinoma via bronchoscopy. Although crizotinib, an ROS1 tyrosine kinase inhibitor, achieved a partial response, a mass lesion appeared in the patient's right kidney 12 months after starting crizotinib, which was diagnosed pathologically as crizotinib-associated renal cysts (CARCs). Given that readministration of crizotinib repeatedly induced CARC-like aseptic inflammation that appeared to be disseminated around surgical site, crizotinib treatment had to be abandoned. Around 25 days after crizotinib cessation, she was referred to the emergency department with a convulsive seizure and hemiparesis due to new, rapidly growing brain metastases. Whole-brain irradiation and administration of another ROS1 tyrosine kinase inhibitor, entrectinib, markedly ameliorated the metastases and improved hemiparesis. This has been the first report of a disease flare after crizotinib cessation due to CARCs in a patient with ROS1 fusion-positive lung adenocarcinoma. Attention should be paid to disease flare, especially in the brain, when molecularly targeted medication is stopped due to adverse events in ROS1 fusion-positive lung adenocarcinoma. Switching to drugs that penetrate the blood-brain barrier could overcome disease flare in the brain.

Molecular cloning of two novel mucin-like genes in the disease-susceptibility locus for diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a rare complex genetic disease affecting East Asians and is strongly associated with the class I human leukocyte antigens (HLA)-B54 in Japanese and HLA-A11 in Koreans. We recently showed that an HLA-associated major susceptibility gene for DPB is probably located within the 200 kb in the class I region 300 kb telomeric of the HLA-B locus on the chromosome 6p21.3. We cloned two novel mucin-like genes designated panbronchiolitis related mucin-like 1 and 2 (PBMUCL1 and PBMUCL2) in the candidate region, which form a mucin-like gene cluster together with two adjacent genes, MUC21 and DPCR1. PBMUCL1 gene expression was remarkably upregulated by polyinosine-polycytidylic acid [poly(I:C)] stimulation in normal human bronchial epithelial cells redifferentiated at the air-liquid interface. We found genetic polymorphisms in PBMUCL1 gene which were associated with DPB: the A-allele of the PBMUCL1 intron 2 single nucleotide polymorphism (SNP) was positively associated and variable numbers of tandem repeats (VNTR) polymorphism in exon 3 (1,890-base pair deletion) was negatively associated. Despite a strong association with HLA-B in the Japanese, the mucin-like gene PBMUCL1 is also one of the candidate genes of DPB susceptibility.

Effect of heme oxygenase-1 polymorphisms on lung function and gene expression.

BACKGROUND: Oxidative stress induced by smoking is considered to be important in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Heme oxygenase-1 (HMOX1) is an essential enzyme in heme catabolism that is induced by oxidative stress and may play a protective role as an antioxidant in the lung. We determined whether HMOX1 polymorphisms were associated with lung function in COPD patients and whether the variants had functional effects. METHODS: We genotyped five single nucleotide polymorphisms (SNPs) in the HMOX1 gene in Caucasians who had the fastest (n = 278) and the slowest (n = 304) decline of FEV1 % predicted, selected from smokers in the NHLBI Lung Health Study. These SNPs were also studied in Caucasians with the lowest (n = 535) or the highest (n = 533) baseline lung function. Reporter genes were constructed containing three HMOX1 promoter polymorphisms and the effect of these polymorphisms on H2O2 and hemin-stimulated gene expression was determined. The effect of the HMOX1 rs2071749 SNP on gene expression in alveolar macrophages was investigated. RESULTS: We found a nominal association (p = 0.015) between one intronic HMOX1 SNP (rs2071749) and lung function decline but this did not survive correction for multiple comparisons. This SNP was in perfect linkage disequilibrium with rs3761439, located in the promoter of HMOX1. We tested rs3761439 and two other putatively functional polymorphisms (rs2071746 and the (GT)n polymorphism) in reporter gene assays but no significant effects on gene expression were found. There was also no effect of rs2071749 on HMOX1 gene expression in alveolar macrophages. CONCLUSIONS: We found no association of the five HMOX1 tag SNPs with lung function decline and no evidence that the three promoter polymorphisms affected the regulation of the HMOX1 gene.

Multiple cerebral infarctions in ROS1-rearranged lung adenocarcinoma.

Rearrangements of specific tyrosine kinases are associated with an elevated risk of venous thrombosis in lung adenocarcinoma, although their effects on arterial thrombosis have not been fully elucidated. Here, we report two cases of ROS proto-oncogene 1 (ROS1)-rearranged lung adenocarcinoma with cerebral infarction during the peri-diagnostic period. Two cases took contrasting clinical courses: one patient could not receive targeted therapy because of a significant decline in performance status, whereas in the other patient, the performance status was maintained and targeted therapy drastically reduced the tumour size. Our cases suggest close monitoring could be considered in the selected cohort.

Pulmonary disease as a risk factor for transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is a severe condition characterised by noncardiogenic pulmonary oedema that develops within 6 h of blood transfusion. Patient factors and blood products have both been implicated in the development of TRALI; however, the role of pulmonary disease has not been investigated. We aimed to determine whether pulmonary disease is a risk factor for TRALI. We conducted a nested case-control study using data from the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan, between July 2010 and March 2015. Case patients who developed TRALI were 1:4-matched with control patients for sex, age and same hospital for receipt of blood transfusion. We conducted a multivariable conditional logistic regression analysis to evaluate the associations of TRALI with various factors including comorbidities, body mass index (BMI) and plasma-containing blood products. We identified 2 019 501 hospitalised patients who received a blood transfusion. Among these patients, 72 developed TRALI. The 72 case patients had higher proportions of haematological malignancy, trauma and interstitial lung disease (ILD) than the 288 matched control patients. The multivariable conditional logistic regression analysis showed that occurrence of TRALI was associated with ILD (odds ratio, 3.88; 95% confidence interval, 1.11-13.6), BMI ≥25.0 kg·m-2 (2.10; 1.05-4.24) and plasma-containing blood products (1.94; 1.10-3.42), but not with infectious lung disease or obstructive airway disease. In conclusion, ILD was an independent risk factor for the development of TRALI. Physicians should be aware of the increased risk of TRALI in patients with ILD.