Tateaki Naito

Cumulative incidence of and predictive factors for lung cancer in IPF.

Background and objective:  Previous studies have indicated a high incidence of lung cancer in IPF, and some have identified its risk factors. However, those studies were retrospective and the clinical characteristics of IPF patients developing lung cancer were evaluated only when those patients had developed the cancer. The true cumulative incidence of lung cancer after the diagnosis of IPF and its predictive factors at the initial diagnosis of IPF remain unknown. The present study was conducted to elucidate the cumulative incidence and risk factors for lung cancer in IPF patients by retrospective longitudinal cohort analysis.

Higher Sensitivity and Specificity for Diffusion-weighted Imaging of Malignant Lung Lesions without Apparent Diffusion Coefficient Quantification

PURPOSE To compare the performance of apparent diffusion coefficient (ADC) with that of signal intensity of the lesion-to-spinal cord ratio (LSR) in differentiating lung cancer from benign lesions on high-b value diffusion-weighted (DW) magnetic resonance (MR) images. MATERIALS AND METHODS This study received institutional review board approval; written informed consent was provided by all patients. Twenty-eight patients (six women, 22 men; mean age, 64.2 years) with pulmonary nodules seen at chest computed tomography were prospectively reviewed. Two DW images with different motion-probing gradient strengths (b(h) = 1000 sec/mm(2) and b(l) = 0 sec/mm(2)) were analyzed semiquantitatively by measuring the signal intensities of the lesions and the spinal cord. ADC was calculated by using linear regression analysis of the natural logarithm of mean signal intensity versus the gradient factor. For reference, LSR was also measured on the same image with a diffusion gradient of b(h) = 1000 sec/mm(2). RESULTS The LSR of cancer nodules was significantly higher than that of benign lesions, while there were no significant differences between them in relation to ADC. In the receiver operating characteristic curve analysis, LSR had a higher area under the curve than did ADC (0.911 vs 0.600). By using a cutoff value of 1.135, LSR had a positive predictive value of 86.7% a negative predictive value of 90%, and an accuracy of 85.7% for the detection of lung cancer with LSR. CONCLUSION LSR measurement on high-b value DW imaging may be useful for differentiating between benign and malignant lung nodules.

Interstitial lung diseases associated with amyopathic dermatomyositis

The aim of the present study was to clarify the clinical characteristics and prognosis of patients with interstitial lung disease (ILD) associated with amyopathic dermatomyositis (ILD-ADM). The study consisted of 14 consecutive patients with ILD-ADM. Patients were classified into two categories, acute/subacute and chronic forms, according to the clinical presentation of ILD. The clinical features, responsiveness to therapy, and prognosis between the two forms were compared. Nine ILD-ADM patients were categorised as the acute/subacute form, and five as the chronic form. Arterial oxygen tension was significantly lower in the acute/subacute ILD than chronic ILD patients. On high-resolution computed tomography, ground-glass opacities were frequently found in the two forms, but consolidation was more common in acute/subacute ILD than chronic ILD. Bronchoalveolar lavage analysis showed higher numbers of total cells and lymphocytes in acute/subacute ILD than chronic ILD. Histologically, the most common finding was nonspecific interstitial pneumonia in the two forms, while diffuse alveolar damage was only found in acute/subacute ILD. Acute/subacute ILD was generally resistant to therapy, while chronic ILD responded well. Notably, the mortality of acute/subacute ILD was much higher than that of chronic ILD (67 versus 0%, respectively). In conclusion, interstitial lung disease associated with amyopathic dermatomyositis includes two different forms, the acute/subacute and chronic forms, with distinct prognoses.

Possible therapeutic effect of direct haemoperfusion with a polymyxin B immobilized fibre column (PMX-DHP) on pulmonary oxygenation in acute exacerbations of interstitial pneumonia.

Background and objective:  Acute exacerbations of interstitial pneumonias (IP) can occasionally occur, and have an extremely poor prognosis. Recently, direct haemoperfusion with a polymyxin B immobilized fibre column (PMX‐DHP) was shown to have a beneficial effect in acute exacerbations of IPF. However, little is known about the efficacy of PMX‐DHP in acute exacerbations of other IP. This study investigated the effectiveness and safety of PMX‐DHP in acute exacerbations of IP.

A Validation and Potential Modification of the Pneumonia Severity Index in Elderly Patients with Community-Acquired Pneumonia

OBJECTIVES: To evaluate the discriminatory power of the Pneumonia Severity Index (PSI) in elderly patients with community‐acquired pneumonia (CAP) and to improve its performance.

Anamorelin (ONO-7643) for the treatment of patients with non–small cell lung cancer and cachexia: Results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04)

Cachexia, described as weight loss (mainly in lean body mass [LBM]) and anorexia, is common in patients with advanced cancer. This study examined the efficacy and safety of anamorelin (ONO‐7643), a novel selective ghrelin receptor agonist, in Japanese cancer patients with cachexia.

Reactive Legionella pneumophila arthritis diagnosed by polymerase chain reaction

Legionellosis is a systemic infectious disease which involves primarily the lower respiratory tract with various extrapulmonary manifestations such as sinusitis, cellulitis, pancreatitis, peritonitis, and pyelonephritis [1]. However, there is limited information about joint complication with Legionella pneumophila. Recently, Andereya et al. [2] described the reactive arthritis as an atypical extrapulmonary manifestation of L. pneumophila infection in this journal. Several microbiologically proven septic arthritis with L. pneumophila have also been reported [3, 4]. We describe a case of Legionella arthritis (LA) diagnosed by the polymerase chain reaction (PCR) method. An 80-year-old woman with chronic renal failure presented with cough, fever, and fatigue. She had no joint symptoms at the initial presentation. Chest radiograph showed a consolidation on the left lower lung Weld. Blood and sputum cultures were sterile, but the urinary antigen for L. pneumophila serogroup 1 was detected (Binax NOW Legionella). She was diagnosed as having L. pneumophila pneumonia. After administering intravenous ciproXoxacin for 2 weeks, symptoms and radiographic Wnding had almost improved. However, 2 days after switching antimicrobials to oral levoXoxacin, the left ankle began to swell. The swelling subsequently spread to the right ankle and high fever relapsed. White blood cell (WBC) count and serum C-reactive protein level increased. Chest radiograph showed no evidence of the recurrence of pneumonia. Magnetic resonance imaging of the joints revealed increasing of articular Xuid. Aspiration of the joints yielded a white purulent Xuid with a WBC count of 50,000 per mm3, but Gram stains revealed no organisms. Aerobic and anaerobic cultures of the specimens including buVered charcoal yeast extract plate culture were negative. Polarization microscopy revealed no crystalline structures in the specimens. Serum rheumatoid factor and antinuclear antibodies were negative. Finally, articular Xuid was found to be positive for L. pneumophila by PCR amplifying 245 base-pair fragment of 16S ribosomal DNA gene [5]. Fever and joint symptoms relieved within a few days after re-starting intravenous ciproXoxacin and she had recovered from arthritis without any restriction of movement in her joints. Extrapulmonary legionellosis in joints is an extremely rare condition. Previously reported cases and our case shared several characteristics (Table 1). First, small joints such as wrists and ankles were multiply aVected. Second, all cases showed slow progression with more than 2 weeks of the duration of symptoms. These presentations were rather similar with noninfectious arthritis such as rheumatoid arthritis or pseudogout, because septic arthritis was usually monoarticular, aVecting larger joint such as knee or hip, and aggressively destroys the joint within a few days. Third, the onset of the articular symptoms was not always coincident with pneumonia. Cases 1 and 4 developed arthritis after treatment of pneumonia and case 3 had no obvious evidence of pneumonia. In addition to these atypical presentations, the poor sensitivity T. Naito · T. Suda (&) · K. Saga · K. Chida Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan e-mail: suda@hama-med.ac.jp

Modified GAP index for prediction of acute exacerbation of idiopathic pulmonary fibrosis in non-small cell lung cancer

Predicting the incidence rate of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) and its prognosis in patients with non‐small cell lung cancer (NSCLC) and IPF is difficult. The aim was to study the incidence of IPF‐AE during the clinical course of the disease and its prognosis in patients with both NSCLC and IPF.

Efficacy of a consensus protocol therapy in adults with acute, severe asthma.

BACKGROUND International guidelines recommend multiple doses of inhaled beta2-agonists and anticholinergics plus early administration of systemic corticosteroids for acute, severe asthma. This study examined the efficacy of this protocol in adults and analyzed those factors associated with unresponsiveness to the protocol therapy. OBJECTIVE Ninety-three consecutive patients 18 to 55 years old presenting for treatment of acute asthma with a peak expiratory flow rate (PEFR) < or = 50% of the predicted value were analyzed. METHODS All subjects received 400 microg of salbutamol every 20 minutes for three doses and 400 microg of oxitropium bromide with each of the three salbutamol doses by means of a metered-dose inhaler with a spacer device, plus intravenously 8 mg betamethasone. PEFR was measured at baseline and at 20, 40, 60, and 120 minutes. RESULTS Sixty-nine percent of subjects improved sufficiently to be discharged. In 31% of subjects, the protocol therapy failed. There were no significant differences in age, sex, smoking status, or beta-agonist use within 6 hours between the two groups. Logistic regression analysis demonstrated that a PEFR < 35% of the predicted value at presentation (odds ratio [OR]; 16.3, 95% confidence interval [CI] 4.5 to 59.9), viral respiratory tract infection symptoms > or = 2 days (OR, 4.8, 95% CI 1.3 to 17.1), and asthma hospitalization in the past year (OR, 4.6, 95% CI 1.1 to 19.9) were significantly associated with unresponsiveness to the protocol. CONCLUSIONS Unresponsiveness to protocol therapy occurs in nearly one-third of individuals presenting with acute, severe asthma. Our findings underscore the need to explore more effective strategies for improving lung function and reducing hospital admission rates.

Plasma epidermal growth factor receptor mutation testing with a chip-based digital PCR system in patients with advanced non-small cell lung cancer

OBJECTIVES Epidermal growth factor receptor (EGFR) mutation testing is a companion diagnostic to determine eligibility for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-based EGFR testing by digital polymerase chain reaction (dPCR), which enables accurate quantification of target DNA, has shown promise as a minimally invasive diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation test developed using chip-based dPCR-based detection of 3 EGFR mutations (exon 19 deletions, L858R in exon 21, and T790M in exon 20). MATERIALS AND METHODS Forty-nine patients with NSCLC harboring EGFR-activating mutations were enrolled, and circulating free DNAs (cfDNAs) were extracted from the plasma of 21 and 28 patients before treatment and after progression following EGFR-TKI treatment, respectively. RESULTS Using reference genomic DNA containing each mutation, the detection limit of each assay was determined to be 0.1%. The sensitivity and specificity of detecting exon 19 deletions and L858R mutations, calculated by comparing the mutation status in the corresponding tumors, were 70.6% and 93.3%, and 66.7% and 100%, respectively, showing similar results compared with previous studies. T790M was detected in 43% of 28 cfDNAs after progression with EGFR-TKI treatment, but in no cfDNAs before the start of the treatment. CONCLUSION This chip-based dPCR assay can facilitate detection of EGFR mutations in cfDNA as a minimally invasive method in clinical settings.