Hiroki Nunokawa

Novel aspects on the pathogenesis of Mycoplasma pneumoniae pneumonia and therapeutic implications

Mycoplasma pneumoniae (Mp) is a leading cause of community acquired pneumonia. Knowledge regarding Mp pneumonia obtained from animal models or human subjects has been discussed in many different reports. Accumulated expertise concerning this critical issue has been hard to apply clinically, and potential problems may remain undiscovered. Therefore, our multidisciplinary team extensively reviewed the literature regarding Mp pneumonia, and compared findings from animal models with those from human subjects. In human beings, the characteristic pathological features of Mp pneumonia have been reported as alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area. Herein, we demonstrated the novel aspects of Mp pneumonia that the severity of the Mp pneumonia seemed to depend on the host innate immunity to the Mp, which might be accelerated by antecedent Mp exposure (re-exposure or latent respiratory infection) through up-regulation of Toll-like receptor 2 expression on bronchial epithelial cells and alveolar macrophages. The macrolides therapy might be beneficial for the patients with macrolide-resistant Mp pneumonia via not bacteriological but immunomodulative effects. This exhaustive review focuses on pathogenesis and extends to some therapeutic implications such as clarithromycin, and discusses the various diverse aspects of Mp pneumonia. It is our hope that this might lead to new insights into this common respiratory disease.

Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth Factor-β, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine Deaminase in Pleural Effusion

PurposeWe studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid.MethodsProspective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted.ResultsWe enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-β was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001).ConclusionsVEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

A Novel Diagnostic Scoring System to Differentiate between Legionella pneumophila Pneumonia and Streptococcus pneumoniae Pneumonia

Objective We investigated a novel diagnostic scoring system to differentiate Legionella pneumophila pneumonia from Streptococcus pneumoniae pneumonia. Methods We retrospectively reviewed the clinical data of 62 patients with L. pneumophila pneumonia (L-group) and 70 patients with S. pneumoniae pneumonia (S-group). Results The serum sodium (Na) levels tended to be lower according to the severity [age, dehydration, respiratory failure, orientation disturbance, low blood pressure (A-DROP)] score in the L-group. On a multivariate analysis, we found that four factors were independent predictive markers for inclusion in the L-group: relative bradycardia [hazard ratio (HR) 5.177, 95% confidence interval (CI): 1.072-24.993, p=0.041], lactate dehydrogenase (LDH) levels ≥292 IU/L (HR 6.804, 95% CI: 1.629-28.416, p=0.009), C-reactive protein (CRP) levels ≥21 mg/dL (HR 28.073, 95% CI: 5.654-139.462, p<0.001), and Na levels ≤137 meq/L (HR 5.828, 95% CI: 1.411-24.065, p=0.015). Furthermore, a total score [ranging from 0 to 4, the sum of the points for each factor (0 or 1)] ≥3 points indicated a higher probability of inclusion in the L-group than in the S-group. The diagnostic accuracy of a total score of 3 had a sensitivity of 36.3%, specificity of 100%, and area under the curve of 0.682 (95% CI: 0.558-0.806, p=0.004), and that of a total score of 4 had a sensitivity 27.4%, specificity of 98.2%, and area under the curve (AUC) of 0.627 (95% CI: 0.501-0.754, p=0.045). The diagnostic accuracy had low sensitivity but high specificity. Conclusions We found four markers that might be useful for differentiating L-group from S-group and created a novel diagnostic scoring system.

Diaphragmatic Dysfunction without Paradoxical Breathing: A Case of Nemaline Myopathy

1Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan 2Department of Cardiology, Kyorin University School of Medicine, Tokyo, Japan 3Divisions of Pulmonary, Critical Care and Sleep Medicine, Memorial Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Pawtucket, RI, USA *Corresponding authors Takeshi Saraya, MD, PhD Assistant Professor Department of Respiratory Medicine Kyorin University School of Medicine 6-20-2 Shinkawa, Mitaka City Tokyo 181-8611, Japan Tel. +81 (0) 422 44 0671 Fax: +81 (0) 422 44 0671 E-mail: sara@yd5.so-net.ne.jp

Diaphragm Ultrasonography as a Tool To Assess the Respiratory Issues of a Patient With Amyotrophic Lateral Sclerosis (ALS)

1Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan 2Department of Cardiology, Kyorin University School of Medicine, Tokyo, Japan 3Divisions of Pulmonary, Critical Care and Sleep Medicine, Memorial Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Pawtucket, RI, USA *Corresponding authors Takeshi Saraya, MD, PhD Assistant Professor Department of Respiratory Medicine Kyorin University School of Medicine 6-20-2 Shinkawa, Mitaka City Tokyo 181-8611, Japan Tel. +81 (0) 422 44 0671 Fax: +81 (0) 422 44 0671 E-mail: sara@yd5.so-net.ne.jp

Critical pitfall: another cause of wheezing

An 87-year-old woman was referred to our hospital with progressive dyspnoea on effort over the previous 2 weeks. She had been treated for rheumatoid arthritis with oral prednisolone (5 mg/day) and tacrolimus (2 mg/day). At her first visit, vital signs and physical examination were normal except for slight rhonchi in anterior lung fields. Chest radiograph showed slight cardiomegaly, but no abnormal lesions were noted in either lung (figure 1A). Echocardiography demonstrated no evidence of congestive heart failure. She …

Hidden Disease with Pulmonary Alveolar Hemorrhage

A 77-year-old woman with recurrent glioblastoma was admitted to the neurosurgery department (day 1) for a second course of chemotherapy and physical rehabilitation after a second episode of severe convulsions. Ten months earlier, she had been diagnosed with glioblastoma and underwent craniotomy followed by radiotherapy and received a first course of oral chemotherapy with temozolomide (75mg/m2) and prednisolone (10mg/day) for 8 months. The Eastern Cooperative Oncology Group Performance status was 3,1 and she had been treated with zonisamide (200mg/ day) for convulsions and single-strength trimethoprime/sulfatomexazole per day for prevention of Pneumocystis jirovecii pneumonia during the preceding 8 months together with apixaban at 10mg/day and pilsicainide hydrochloride hydrate at 75mg/day for atrial fibrillation. On day 15, she showed pyrexia (39°C) without organ-specific symptoms. High fever spontaneously disappeared within a few days, and she was treated with a second course of oral temozolomide (100mg/m2) from day 17 to 21. On day 25, high fever recurred, and chest X-ray (Figure 1A) showed bilateral tiny nodules in the middle to lower lung fields with right-side predominance. These findings were confirmed on thoracic computed tomography (CT) (Figure 1B), but vital signs and results of physical examinations remained normal. She received daily antipyretic medications, and fever pattern showed morning temperature spikes over 39°C. Both sets of blood and sputum cultures were negative for bacteria, and sputum Gram and ZiehlNeelsen staining identified no pathogens. However, on

Spontaneous Regression of Epstein-Barr Virus-negative Diffuse Large B-cell Lymphoma that Presented with Multiple Pulmonary Nodules

A 70‐year‐old woman was admitted to a respiratory department because of bilateral inguinal lymphadenopathy, mediastinal lymphadenopathy, and re‐growth of a nodule in the left lower lobe, which had been identified one year earlier but had regressed spontaneously over the next 6 months. After diagnostic procedures to obtain tissue from the lung and lymph nodes, she was diagnosed with Epstein‐Barr virus‐negative diffuse large B‐cell lymphoma (DLBCL). Spontaneous regression or remission of lung involvement in a patient with DLBCL has rarely been reported and the precise mechanism is unknown, but this case clearly demonstrated regression and re‐growth of the lung nodules during her clinical course.

Tracheobronchial Amyloidosis in a Patient with Sjögren's Syndrome

A 65-year-old woman was referred to our respiratory department because of incidentally detected endobronchial deposits. She had been diagnosed with Sjögrens syndrome 12 years earlier. Bronchoscopy showed protrusion of the reddened, shiny or edematous mucosa at the orifice of the lower lobe bronchus, suggesting a submucosal tumor. Based on the pathological findings of the transbronchial biopsied specimens, the patient was diagnosed with non-classified type tracheobronchial amyloidosis associated with Sjögrens syndrome, which was negative for both λ and κ chains, transthyretin and amyloid A. She has remained in good health without a relapse of the tumor.

Pulmonary Aspergillosis Mimicking Primary Lung Cancer

Pulmonary aspergillosis; Mimicking lung cancer; Thoracic CT A 68-year-old man was transferred to our hospital because of abnormal lung nodule. He was a social drinker and a current smoker with a history of 70 pack-years. He had no symp-toms and was a good nutritional status. Based on the pulmonary function tests, he was diag-nosed with chronic obstructive lung disease stage II by Global Initiative on Obstructive Lung Disease staging system. Thoracic Computed Tomography (CT) showed the irregular-shaped nodule measuring 15 mm in size with spiculation at right S1 (Figure A), which accompanied by emphysematous lung changes. On thoracic FDG PET/CT, the nodule demonstrated the intense standardized uptake values both in the early (max 3.4) and delayed (max 4.2) phases, suggest-ing malignancy (Figure B). However, video-assisted thoracic surgery biopsied specimens on Hematoxylin and eosin stains showed that the nodule was consisted of central necrotic compo-nent surrounded by microabscesses and fibrotic granulomatous tissues (Figure C) in which con-tained filamentous fungi on Grocott’s methenamine silver stain (Figure D) with calcium oxalate crystal deposition, indicating of pulmonary aspergillosis. Pulmonary aspergillosismimicking cancer was an extremely rare event,