Pembrolizumab plus chemotherapy in Japanese patients with metastatic squamous non-small-cell lung cancer in KEYNOTE-407.

The global phase III KEYNOTE-407 (NCT02775435) trial showed that pembrolizumab plus chemotherapy prolonged overall and progression-free survival (OS/PFS) versus placebo plus chemotherapy in patients with metastatic squamous non-small-cell lung cancer (NSCLC). We present outcomes of patients from Japan enrolled in KEYNOTE-407. Patients were randomized 1:1 to receive pembrolizumab 200 mg or placebo with paclitaxel 200 mg/m2 every 3 weeks (Q3W) or nab-paclitaxel 100 mg/m2 (weekly) plus carboplatin area under the concentration-time curve of 6 mg/mL/min Q3W for four cycles, followed by pembrolizumab or placebo Q3W for a total of 35 cycles. Primary end-points were OS and PFS per RECIST version 1.1 by blinded independent central review. Fifty patients were randomized at Japanese sites (pembrolizumab plus chemotherapy, n = 22; placebo plus chemotherapy, n = 28). Median follow-up time at data cut-off (May 9, 2019) was 15.1 (range, 0.5-24.0) months. Median OS (95% confidence interval [CI]) was 17.3 (12.5-not reached) versus 11.0 (8.6-19.5) months in the pembrolizumab plus chemotherapy versus placebo plus chemotherapy group (hazard ratio [HR] 0.56; 95% CI, 0.27-1.15). Median PFS (95% CI) was 8.3 (6.1-13.0) versus 7.2 (3.9-8.8) months (HR 0.65; 95% CI, 0.35-1.23). Grade 3-5 adverse events (AEs) occurred in 86% and 75% of patients, respectively. There were three fatal AEs, two of which were treatment-related (one from each treatment group, pneumonitis and pulmonary hemorrhage). Efficacy and safety outcomes were consistent with the global study and support the use of pembrolizumab plus chemotherapy in Japanese patients with metastatic squamous NSCLC.

A single-center, person-month-based analysis of the risk of developing Pneumocystis pneumonia (PCP) in immunosuppressed non-HIV patients: Preventive effects of trimethoprim-sulfamethoxazole.

OBJECTIVE: We performed a retrospective study to evaluate the risk factors for acquiring Pneumocystis pneumonia (PCP) by pharmacologically immunosuppressed HIV-negative patients. METHODS: Patients who received corticosteroids, immunosuppressive agents, anticancer agents, and radiotherapy with or without trimethoprim-sulfamethoxazole (TMP-SMX) at Himeji Medical Center between 2010 and 2021 were evaluated. Drugs and doses of the treatments for each patient were divided by month into person-month units. Each person-month datum includes information on the administered drug (or radiotherapy), average doses, and whether the patient had PCP during the corresponding month. ROC curves with person-month data were generated for each treatment, and AUCs >0.7 were identified as possessing positive classification utility. The risks for PCP according to gender, age (grouped by median) and each treatment were examined by univariate analysis, followed by multivariate analysis to identify independent factors. RESULTS: Of a total of 17,733 patients (214,676 person-months), 32 developed PCP. The cut-off values by ROC analysis were 13.7 mg/day for corticosteroid (prednisolone equivalent), 0.92 mg/day (6.45 mg/week) for methotrexate (MTX), and 34.3 mg/day for TMP-SMX. The cut-off values for other treatments could not be estimated. The above three drugs and male sex were significant variables in univariate analysis and were all confirmed as independent factors by multivariate analysis. CONCLUSION: The results suggest that a monthly average dose of ≥13.7 mg/day of prednisolone, ≥0.92 mg/day of MTX and male sex are significant independent risk factors for PCP, and that prophylaxis with ≥34.3 mg/day of TMP-SMX is to be recommended.

First-line durvalumab plus platinum-etoposide in extensive-stage small-cell lung cancer: CASPIAN Japan subgroup analysis.

BACKGROUND: In the phase 3 CASPIAN study (NCT03043872), first-line durvalumab plus etoposide and cisplatin or carboplatin (EP) significantly improved OS versus EP alone in patients with extensive-stage (ES)-SCLC (HR 0.73 [95% CI 0.59-0.91; p = 0.0047]). Here we report results for a preplanned subgroup analysis of patients recruited in Japan. METHODS: Treatment-naïve patients with ES-SCLC received either 4 cycles of durvalumab 1500 mg plus EP q3w followed by maintenance durvalumab 1500 mg q4w until disease progression or up to 6 cycles of EP q3w. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and tolerability. RESULTS: In the Japan subgroup, 18 patients were randomized to durvalumab plus EP and 16 patients to EP. At the interim analysis with a median follow-up of 12.5 months in the subgroup, OS numerically favored durvalumab plus EP versus EP (HR 0.77 [95% CI 0.26‒2.26]; median not reached vs 15.2 months). PFS was similar for durvalumab plus EP versus EP (HR 0.90 [95% CI 0.43‒1.89]). Confirmed ORR was 89% with durvalumab plus EP versus 69% with EP. Adverse events (AEs) of CTCAE grade 3 or 4 were reported in 78% versus 94% of patients in the durvalumab plus EP versus EP arms. There were no AEs leading to treatment discontinuation or death in the Japan subgroup. CONCLUSION: First-line durvalumab plus EP was effective and well tolerated in Japanese patients with ES-SCLC. Despite the small size of the Japan subgroup, results were generally consistent with the global study population.

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy.

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy's effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25-8.8). Median survival time was 9.9 months (95% CI 9.2-10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889-9.328; 60 days, HR: 2.351, 95% CI 1.104-5.009; 90 days, HR: 2.416, 95% CI 1.232-4.739; and 120 days, HR: 2.521, 95% CI 1.357-4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.

Pneumocystis jirovecii pneumonia mortality risk associated with preceding long-term steroid use for the underlying disease: A multicenter, retrospective cohort study.

OBJECTIVE: Long-term steroid use increases the risk of developing Pneumocystis pneumonia (PcP), but there are limited reports on the relation of long-term steroid and PcP mortality. METHODS: Retrospective multicenter study to identify risk factors for PcP mortality, including average steroid dose before the first visit for PcP in non-human immunodeficiency virus (HIV)-PcP patients. We generated receiver operating characteristic (ROC) curves for 90-day all-cause mortality and the mean daily steroid dose per unit body weight in the preceding 10 to 90 days in 10-day increments. Patients were dichotomized by 90-day mortality and propensity score-based stabilized inverse probability of treatment weighting (IPTW) adjusted covariates of age, sex, and underlying disease. Multivariate analysis with logistic regression assessed whether long-term corticosteroid use affected outcome. RESULTS: Of 133 patients with non-HIV-PcP, 37 died within 90 days of initial diagnosis. The area under the ROC curve for 1-40 days was highest, and the optimal cutoff point of median adjunctive corticosteroid dosage was 0.34 mg/kg/day. Past steroid dose, underlying interstitial lung disease and emphysema, lower serum albumin and lower lymphocyte count, higher lactate dehydrogenase, use of therapeutic pentamidine and therapeutic high-dose steroids were all significantly associated with mortality. Underlying autoimmune disease, past immunosuppressant use, and a longer time from onset to start of treatment, were associated lower mortality. Logistic regression analysis after adjusting for age, sex, and underlying disease with IPTW revealed that steroid dose 1-40 days before the first visit for PcP (per 0.1 mg/kg/day increment, odds ratio 1.36 [95% confidence interval = 1.16-1.66], P<0.001), low lymphocyte counts, and high lactate dehydrogenase revel were independent mortality risk factor, while respiratory failure, early steroid, and sulfamethoxazole/trimethoprim for PcP treatment did not. CONCLUSION: A steroid dose before PcP onset was strongly associated with 90-day mortality in non-HIV-PcP patients, emphasizing the importance of appropriate prophylaxis especially in this population.

[Study on pulmonary lesions in which nontuberculous mycobacteria were detected by percutaneous aspiration--a proposal to add "culture positivity of percutaneous aspiration material" to the bacteriological diagnostic criteria of pulmonary nontuberculous mycobacterial diseases].

OBJECTIVES: Culture positivity of percutaneous aspiration material" is not included in the current bacteriological criteria for diagnosis of pulmonary nontuberculous mycobacterial (NTM) diseases, which were published by the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) in 2007 or those released by the Japanese Society for Tuberculosis in 2008. However, percutaneous aspiration is a reliable technique for the detection of causative microorganisms isolated from the focus of infection. We discuss the benefits of including positive culture of percutaneous aspiration material in the bacteriological diagnostic criteria of pulmonary NTM diseases. METHODS: We reviewed the radiological images and clinical courses of pulmonary diseases in which NTM cultures were obtained from percutaneously aspirated materials at our hospital from 1991 to 2011. Aspiration was carried out under local anesthesia, usually with fluoroscopic guidance. After percutaneous insertion of a 22-gauge needle attached to a 20-mL syringe containing about 3 mL of saline, the lesion specimen was withdrawn together with the saline. After the needle was pulled out, the aspirated material and saline were transferred to test tubes for cytological and microbiological examinations. In patients with thin-walled cavitary lesions, saline was injected into the cavity and then aspirated. RESULTS: Percutaneous aspiration was performed in 2,742 patients and NTM disease was detected in 51 patients. Of these 51 patients, 12 had solitary nodular lesions, and in many of these patients, no NTM bacilli could be detected in the sputa or bronchial washing specimens. Mycobacterium avium was identified in 10 of the 12 cases. Four of these 10 patients were followed up after their diagnosis without any treatment: 3 showed spontaneous reduction in lesion size, while 1 patient's condition remained unchanged. Four of the remaining 6 cases were treated with anti-NTM medications, and lesion size reduced in 2 cases, while no change or deterioration was seen in the other 2. Aspiration from solitary small cavitary lesions showed a relatively high number of NTM colonies. Pneumothorax was the only complication of the aspiration procedure. DISCUSSION: If the diagnostic criteria for pulmonary NTM diseases include positive culture in percutaneous aspiration material, the diagnosis of solitary nodular NTM lesions would become easier; at present, these lesions are often diagnosed only upon surgical resection. Further, clinical studies on the possibility of spontaneous shrinkage of the solitary lesion and the value of its medical treatment would be promoted. Aspiration can easily differentiate NTM disease from pulmonary abscess or fungal infection in patients with a solitary lesion or small cavity.

Comparison of the harvest volume between maneuvers of endobronchial ultrasound-guided transbronchial needle aspiration including the "cross-fanning technique".

Recently, a certain volume of biopsy specimens has been required for genetic testing of tumors using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). This study aimed to verify the superiority of our newly devised EBUS-TBNA biopsy technique, the "cross-fanning technique," which combines rotation and up-down maneuvers, by comparing its harvest volume with that of other maneuvers. Using a bronchoscope simulator, ultrasonic bronchoscope, and 21-gauge puncture needle, we compared the weight of silicone biopsy specimens obtained by the following 4 procedures: Conventional maneuver; Up-down maneuver; Rotation maneuver, and; Cross-fanning technique. Each procedure was repeated 24 times in total, rotating the sequences of the maneuvers, and the operator/assistant pair to align the conditions. The means ±â€…standard deviations of the sample volumes for each puncture technique were as follows: 2.8 ±â€…1.2 mg; 3.1 ±â€…1.6 mg; 3.7 ±â€…1.2 mg, and; 3.9 ±â€…1.2 mg. There was a significant difference between the 4 groups (P = .024). The post hoc test showed a statistically significant difference between techniques A and D (P = .019). This study showed that the cross-fanning technique might contribute to the increased volume of tissue samples obtained by EBUS-TBNA biopsy.

Chemotherapy versus best supportive care in advanced lung cancer and idiopathic interstitial pneumonias: A retrospective multi-centre cohort study.

BACKGROUND: The clinical questions of whether chemotherapy as initial treatment, compared with best supportive care (BSC), improves overall survival (OS) and whether it increases the occurrence risk of acute exacerbation of idiopathic interstitial pneumonia (IIP) in patients with advanced-stage lung cancer and IIP remain inconclusive. This study addresses these issues, given that chemotherapy-related acute exacerbation of IIP may be a direct cause of mortality in these patients. METHODS: We enrolled 1003 patients from 110 Japanese institutions and collected clinical profiles from 707 and 296 patients in the chemotherapy (men: women, 645:62; mean age, 70.4 ± 6.9 years) and BSC (men: women, 261:35; mean age, 75.2 ± 7.8) groups, respectively. We used propensity score matching to create 222 matched pairs from both groups using patient demographic data (age, sex, smoking status, performance status, history of acute exacerbation of IIP, desaturation on exertion, clinical diagnosis of IIP, high-resolution computed tomography findings, serum fibrotic markers, pulmonary function status, and lung cancer histopathology). Logistic or Cox regression analyses were performed using matched data to assess the effects of chemotherapy on the risk of acute exacerbation of IIP or OS, respectively. RESULTS: In the well-matched cohort, chemotherapy improved OS (hazard ratio: 0.629, 95% confidence interval [CI]: 0.506-0.783, p < 0.0001); however, it involved significant acute exacerbation of IIP (odds ratio: 1.787, 95% CI: 1.026-3.113) compared to BSC. CONCLUSIONS: Compared with BSC, chemotherapy can improve OS in patients with advanced-stage lung cancer and IIP; however, it increases the risk of acute exacerbation of IIP.

Genetic Homology between Bacteria Isolated from Pulmonary Abscesses or Pyothorax and Bacteria from the Oral Cavity.

Pulmonary abscesses and pyothorax are bacterial infections believed to be caused primarily by oral microbes. However, past reports addressing such infections have not provided genetic evidence and lack accuracy, as they used samples that had passed through the oral cavity. The aim of this study was to determine whether genetically identical bacterial strains exist in both the oral microbiota and pus specimens that were obtained percutaneously from pulmonary abscesses and pyothorax, without oral contamination. First, bacteria isolated from pus were identified by 16S rRNA gene sequencing. It was then determined by quantitative PCR using bacterial-species-specific primers that DNA extracted from paired patient oral swab sample suspensions contained the same species. This demonstrated sufficient levels of bacterial DNA of the targeted species to use for further analysis in 8 of 31 strains. Therefore, the whole-genome sequences of these eight strains were subsequently determined and compared against an open database of the same species. Five strain-specific primers were synthesized for each of the eight strains. DNA extracted from the paired oral swab sample suspensions of the corresponding patients was PCR amplified using five strain-specific primers. The results provided strong evidence that certain pus-derived bacterial strains were of oral origin. Furthermore, this two-step identification process provides a novel method that will contribute to the study of certain pathogens of the microbiota. IMPORTANCE We present direct genetic evidence that some of the bacteria in pulmonary abscesses and pyothorax are derived from the oral flora. This is the first report describing the presence of genetically homologous strains both in pus from pulmonary abscesses and pyothorax and in swab samples from the mouth. We developed a new method incorporating quantitative PCR and next-generation sequencing and successfully prevented contamination of pus specimens with oral bacteria by percutaneous sample collection. The new genetic method would be useful for enabling investigations on other miscellaneous flora; for example, detection of pathogens from the intestinal flora at the strain level.

Precut technique using an injection needle: A retrospective study on a new ancillary procedure for pleural biopsy.

The effectiveness of thoracoscopic biopsy as a diagnostic method for pleural diseases has been reported; however, obtaining a sufficient specimen size is sometimes difficult. Therefore, an ancillary technique, the precut technique using an injection needle, was devised to address this problem. This study aimed to evaluate the effectiveness and safety of the novel precut technique in patients with undiagnosed pleural effusion. This retrospective study included 22 patients who underwent pleural biopsy using the precut technique to examine exudative pleural effusion of unknown etiology. Thoracoscopy was performed under local anesthesia. The biopsy procedure was performed as follows: a needle was inserted into the pleura around the lesion using a semiflexible thoracoscope; the needle was positioned to make an incision in the pleura while injecting 1% lidocaine with epinephrine and lifting the pleura from the fascia; 2 or 3 precut incision lines were arranged in a triangle; and the specimen was obtained from the parietal pleura using forceps or a cryoprobe. Patient data including age, number of biopsies, biopsy specimen size, pathological and final diagnosis, and postoperative complications were examined. All patients were male with an average age of 74 years. Pleural effusion was found on the right and left sides in 16 and 6 patients, respectively. The average major axis of the biopsy specimens was 18 mm (range, 10-30 mm), which was sufficient to establish a pathological diagnosis. Only 1 patient experienced minor temporal bleeding as a complication. The precut technique enabled the procurement of specimens sufficient in size for pleural biopsy.

[A case of pleural tuberculoma with intra-pulmonary invasion during anti-tuberculosis therapy].

A 27-year-old woman who had been treated for pulmonary tuberculosis with anti-tuberculosis drugs for three months was admitted to our hospital because of pain in the chest and back. Chest CT showed improvement in the pulmonary tuberculosis lesions in the right middle lobe and S8, but there was a large pleural mass in the right lower lung field. Histopathological findings of the percutaneous biopsy showed epithelioid cell granulomas that were negative for acid-fast bacilli. We diagnosed the mass as pleural tuberculoma with intrapulmonary invasion. The pleural tuberculoma improved without any additional therapy.

[A case of bronchocentric granulomatosis resembling lung cancer on diagnostic imaging].

A 51-year-old man visited a local physician because of a chest radiographic abnormality which had been pointed out in October 2009 and March 2010. His chest CT images revealed a nodular lesion in the right middle lobe. Since the nodular lesion showed abnormal FDG accumulation on FDG-PET, the physician suspected lung cancer, but was unable to make a definitive diagnosis by CT-guided lung biopsy. The patient was thus referred to our hospital for detailed investigations. A nodular lesion with spiculation and pleural indentation was recognized in the S4 region on chest CT scans which was strongly suspected to be lung cancer. Since various examinations did not provide a definitive diagnosis, we performed surgery. The histological findings of the extirpated tumor were considered to be bronchocentric granulomatosis (BCG), because necrotic granulomatous lesions with epithelioid cells centered on the bronchioles and there was no evidence of fungus or acid-fast bacterium infection.

[A case of primary lung cancer with swollen mediastinal lymph nodes due to pre-existing sarcoidosis].

A 69-year-old man, who had been followed up for sarcoidosis at another hospital from 10 years previously, was referred to our hospital because of a new lesion in the left upper lobe. A chest CT scan revealed a nodular lesion at the orifice of the left B3b and mediastinal lymphadenopathy. Bronchoscopic biopsy established a diagnosis of squamous cell carcinoma. Because there had been no distant metastasis and no change in size of the mediastinal lymph nodes over the previous 5 years, left upper lobectomy with lymph node dissection was performed. The histology of the resected tumor indicated a moderately-differentiated squamous cell carcinoma, and the dissected lymph nodes contained non-caseous epithelioid cell granuloma without metastasis. Thus, we made a final diagnosis of squamous cell carcinoma (pT1N0M0, stage IA) that complicated the sarcoidosis. Surgical resection can be the first option for lung cancer complicating sarcoidosis with mediastinal lymphadenopathy, because making a preoperative assessment of N status is difficult.

[Two cases of pulmonary amebiasis].

CASE 1: A 74-year-old man having a week's fever and diagnosed with a liver abscess was treated with several antibiotics and percutaneous liver drainage. His respiration gradually worsened and chest computed tomography (CT) showed right pleural effusion and a left-lung mass. Percutaneous fine needle aspiration of the pulmonary mass detected Entamoeba histolytica. CASE 2: A 44-year old, zoo office worker admitted for fever and right chest pain was found in CT to have right pleural effusion and a mass with a liver abscess necessitating abscess drainage. Injected contrast medium detected a fistula connected to the right. Following surgical drainage, E. histolytica was detected from the resected lung. Both cases responded well to metronidazole.

[A case of yellow nail syndrome with bilateral pleural effusion].

A 68-year-old woman, suffering from dyspnea on exertion, was admitted to our hospital. She had noticed her nails become yellow 8 years previously. She had mild bilateral effusion. Examination of the pleural fluid revealed exudates which were lymphocyte-rich, a high concentration of adenosine deaminase (ADA) and elevated serum levels of soluble interleukin-2 receptors. These confirmed the diagnosis of yellow nail syndrome.

[Case of idiopathic pulmonary upper lobe fibrosis].

A 49-year-old man was referred to our hospital because of progressive volume reduction in bilateral upper lobes over 10 years. He was slim, with a straight back. Chest high-resolution computed tomography (HRCT) showed consolidation with small radiolucent areas in both upper lobes. Surgical biopsy by video-assisted thoracoscopy was performed in the right upper and lower lobes. The pathological findings of the upper lobe showed intraluminal fibrosis with alveolar collapse and proliferation of elastic fibers on the subpleural surface, but the lower lobe was normal. We diagnosed his illness as typical idiopathic pulmonary upper lobe fibrosis (IPUF), previously described by Amitani in 1992.

[A case of respiratory bronchiolitis-associated interstitial lung disease].

A 37-year-old man was referred to our hospital with a cough. His blood test result and chest radiography findings were normal. High resolution chest computed tomography (HRCT) showed diffuse ground glass attenuation (GGA) with centrilobular distribution in the bilateral upper lung fields. As diagnosis could not be made using transbronchial lung biopsy and bronchoalveolar lavage, video-assisted lung biopsy was performed. The histological findings were a thickening of the alveolar walls with infiltration of lymphocyte-dominant inflammatory cells, and exudation of pigmented macrophages in the air spaces of the respiratory bronchioles and alveolis. We diagnosed his illness as respiratory bronchiolitis-associated interstitial lung disease. Six months after stopping smoking, his symptoms, and the GGA on chest HRCT improved.

[Two cases of anomalous systemic arterial supply to the basal segments of bilateral lungs].

We encountered two cases of systemic arterial supply to the basal segments of bilateral lung with elevated serum CEA levels. The patients were a 36-year-old man and a 30-year-old man with the abnormal chest shadows, discovered during physical checkups. A chest computed tomogram (CT) of the 36-year-old patient showed reticulonodular shadows in the bilateral lower lobe with anomalous vessels arising from the descending aorta and running into the lower lobe on each side, and his abdominal CT revealed a duplicated vena cava inferior. His aortogram confirmed an anomalous systemic arterial supply to the basal segments of bilateral lungs. The chest CT of the 30-year-old patient revealed a cystic lesion in the right lower lobe and no abnormality in the left lung field. His aortograms showed aberrant systemic arterial supplies to the bilateral lower lobe. Because the cystic lesion had increased in size, it was resected and an anomalous systemic artery was seen. Intralobar sequestration in the right lung and anomalous systemic arterial supply in the left lung was diagnosed. Serum CEA was high at the initial visit in each patient but it decreased spontaneously in the first patient, and after the resection of the cystic lesion in the second patient. We report two cases of anomalous systemic arterial supply to the basal segments of bilateral lung, which is extremely rare. Our literature search revealed that only 13 cases have been reported to date.

[High-sensitivity C-reactive protein and changes over time in forced expiratory volume in 1 second in adult-onset asthma].

PURPOSE: To study the possibility that changes in high-sensitivity C-reactive protein (hs-CRP) may be a predictor of forced expiratory volume in 1 second (FEV1) decline over time in adult asthmatic subjects. METHODS: Subjects with adult-onset asthma with no smoking history underwent complete medical evaluation at Yoka Public Hospital in both 2005 and in 2008 (n = 26). We analyzed the correlation between hs-CRP levels and FEV1 changes over time, in relation to whether or not they received inhaled corticosteroid (ICS) therapy. We also measured the cardio-ankle vascular index (CAVI), intima-media-thickness (IMT), and fraction of exhaled nitric oxide (FeNO) of hospital staff members who acted as non ICS asthmatic subjects (n = 11), and also performed multiple regression analysis. RESULTS: In the non-ICS asthmatic subjects group (n = 19), there was a significant correlation between log (hs-CRP) levels and FEV1 changes (R = -0.734, P < 0.001). After controlling for age, body mass index, CAVI, IMT, and FeNO, hs-CRP was found to be an independent risk factor. CONCLUSION: Hs-CRP levels are a predictor of FEV1 decline over time in adult-onset asthmatic patients with no smoking history, who are not receiving ICS therapy.

[Seven cases of diffuse alveolar hemorrhage with acute respiratory failure treated by plasma exchange].

We conducted a retrospective analysis of 7 cases of diffuse alveolar hemorrhage at our hospital, diagnosis of which was made on the presence of bloody bronchoalveolar lavage fluid. There were 3 men and 4 women, with a mean age of 68 years. A rapidly progressiving diffuse infiltrative shadow on chest X-ray film and failing to respond to antibiotic therapy were the major signs of the condition in these cases. Respiratory failure was seen in all cases. In addition to high-dose steroid therapy and mechanical ventilation, we immediately performed plasma exchange. All of the 3 MPO-ANCA-positive patients survived, but 3 of the 4 MPO-ANCA-negative patients died. Diffuse alveolar hemorrhage secondary to ANCA-associated vasculitis usually advances rapidly and its prognosis tends to be poor. However, early initiation of plasma exchange can be expected to improve the survival rate of patients with this disease.