The causes of acute cough: a tertiary-care hospital study in Japan.

OBJECTIVES: Cough is the most frequent presenting complaint in general practice and has an adverse effect on an individual's well-being. Understanding the causes of cough is critical for appropriate patient management. According to its duration, cough is classified as acute, subacute, and chronic. While acute respiratory infection is considered to be the major cause of acute cough, there is little evidence. METHODS: We retrospectively assessed the prevalence of acute cough in all patients presenting with cough to the respiratory clinic of Japanese Red Cross Wakayama Medical Center from May 2018 to April 2019. We subsequently assessed the causes of acute cough, after stratifying patients with acute cough into two subgroups based on the chest X-ray findings. RESULTS: Among 685 patients (329 males; mean age, 61.8 ± 18.6 years) who presented with cough as a chief complaint, 274 (125 males; mean age, 57.6 ± 20.9 years) reported to have acute cough; chest X-ray abnormalities were detected in 113 of these patients. The most frequent cause of acute cough among 113 patients with chest X-ray abnormalities was pneumonia (55.8%), followed by lung cancer (9.7%) and pneumonia exacerbating asthma (7.1%). Among the 161 patients with acute cough without chest X-ray abnormalities, the most frequent cause was upper respiratory tract infection (57.1%), followed by asthma (23.6%) and cough variant asthma (6.2%). CONCLUSIONS: Cough is the most frequent presenting complaint in general practice. Infections are the most frequent causes of acute cough regardless of the chest X-ray findings.

[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.

Intrapleural urokinase directly under medical thoracoscopy for the diagnosis of tuberculous pleurisy.

Medical thoracoscopy, also called "local anesthetic thoracoscopy" and "pleuroscopy," is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surfaces and channels to conduct diagnostic and therapeutic procedures. However, this technique is not helpful when substantial fibrous adhesions exist. We reported the first case of intrapleural urokinase directly under medical thoracoscopy for the diagnosis of malignant pleural mesothelioma with severe multiloculated pleural effusions in 2019. This is the second report regarding the efficacy of intrapleural urokinase directly under medical thoracoscopy for the diagnosis of multiloculated pleural effusions. Urokinase-induced intrapleural fibrinolysis, which removed the fibrous septa, consequently improved the field of view under endoscopy within only 10 min. Fibrinolytic effect appeared very rapidly. This technique is available for tuberculous pleurisy with severe multiloculated pleural effusion.

Visceral pleural biopsy under medical thoracoscopy for the diagnosis of lung adenocarcinoma.

Medical thoracoscopy is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surface and allows for diagnostic procedures. The diagnostic yield of medical thoracoscopy is high and is generally based on parietal pleural biopsy findings. Pleural biopsies are valuable for a diagnosis. However, visceral pleural biopsies are uncommon because of the risk of prolonged air leak. In this study, we report a rare case of the successful diagnosis of lung adenocarcinoma, based on the findings of visceral pleural biopsy under medical thoracoscopy. To avoid lung injury and pneumothorax, we focused on maintaining the thoracoscope and biopsy forceps in a straight angle as much as possible. While looking straight ahead at the visceral pleural nodule as closely as possible, biopsy samples were carefully obtained while confirming that the normal lung was not held. With careful consideration, visceral pleural biopsies may expand the diagnostic capability of medical thoracoscopy.

Correlation of Immune-Related Adverse Events and Effects of Pembrolizumab Monotherapy in Patients with Non-Small Cell Lung Cancer.

PURPOSE: The effects of immune checkpoint inhibitors have been reported to be linked with immune-related adverse events (irAEs). In patients with advanced non-small-cell lung cancer, who tested positive for programmed death-ligand 1 (PD-L1), pembrolizumab, an immune checkpoint inhibitor can be used as a treatment, and it was found to improve overall survival. However, there are only a few reports on the relationship between the therapeutic effects of pembrolizumab in patients with lung cancer and the irAEs of pembrolizumab. The purpose of this study was to determine the correlation between immune-related adverse events and the effects of pembrolizumab monotherapy in patients with non-small-cell lung cancer. PATIENTS AND METHODS: From February 2017 to August 2019, we conducted a retrospective analysis of the effects of pembrolizumab treatment and immune-related adverse events in 94 patients with non-small-cell lung cancer treated with pembrolizumab only. RESULTS: In 63 cases, irAEs were observed. The most common irAE was rash. PD-L1 positivity ≥ 50% tended to cause irAEs. The median progression-free survival (PFS) rates with and without irAEs were 371 days (95% CI, 184-NR) and 67 days (95% CI, 51-87 days), respectively. In a multivariate analysis, irAEs and Eastern Cooperative Oncology Group performance status (PS) were the factors related to PFS. CONCLUSION: In patients with lung cancer, who were treated with pembrolizumab monotherapy, the development of irAEs was likely indicative of the positive effects of pembrolizumab. This novel finding appears to be useful for clinicians who work with pembrolizumab for lung cancer treatment.

[Successful treatment of small cell lung cancer with secondary immune thrombocytopenic purpura].

Chest CT on admission of a 58-year-old woman with bloody sputum showed a mass shadow at the hilum of the right lung suggesting invasion to the mediastinum, and contralateral mediastinal lymph node (#6) metastasis. Bronchial brush cytology yielded a diagnosis of small cell lung cancer (SCLC). The clinical stage was T4N3M0, stage IIIB, limited disease (LD). On admission, her platelet count was only 40 x 10(3)/microl. Blood biochemistry and bone marrow puncture revealed immune thrombocytopenic purpura (ITP). We speculated that she had secondary ITP (ITP-like syndrome) associated with cancer. Only 11 cases of lung cancer with secondary ITP have ever been reported, 4 cases of which attained complete response of cancer and complete remission of ITP by anti-cancer therapy. Therapeutic procedures employed were surgery in 3 cases of adenocarcinoma and a high dose chemotherapy (HDC) with autologous peripheral blood stem cell transplantation (APBSCT) in 1 case of SCLC. In the present case, concurrent chemoradiotherapy (four cycles of cisplatin/etoposide (PE) combined with 45Gy of thoracic radiotherapy) was performed, which resulted in a complete response of SCLC and a complete remission of the secondary ITP. This is apparently the first report of successful treatment of SCLC with secondary ITP by standard chemoradiotherapy. In a SCLC patient with ITP-like symptoms, treatment for SCLC may simultaneously resolve the ITP-like symptoms.

[A case of malignant pleural mesothelioma with gastrointestinal metastases which were diagnosed by endoscopic biopsy].

A 63-year-old man who had general malaise and dyspnea on effort, was admitted to our hospital. Chest X-ray film on admission showed left pleural effusion. Chest and abdominal CT after left chest drainage revealed left pleural thickening, mediastinal lymph node swelling, multiple lung nodules, osteolytic change of the left 4th rib, and multiple liver tumors. Right pleural effusion and ascites was also recognized. Cytology of the left pleural effusion suggested malignant mesothelioma. He had a skin tumor on his anterior chest. Biopsy revealed metastasis of malignant epithelioid mesothelioma. Upper gastrointestinal endoscopy showed a duodenal tumor and colonoscopy showed a cecal erosion. Endoscopic biopsy revealed metastases of malignant mesothelioma identical to the skin tumor. Because of the left pleural thickening, the primary site was considered to be in the left pleura. Here we report a case of malignant pleural mesothelioma (MPM) with multiple distant metastases to the duodenum, cecum, skin, lung, liver, and rib. Gastrointestinal metastases of MPM detected by endoscopic biopsy are very rare. Only one case of cecal metastasis has ever been reported.

Osimertinib Administration as the Primary Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy for Brain Metastasis of De Novo T790M-positive Lung Cancer.

A 69-year-old woman underwent left upper lobectomy for left upper lobe lung adenocarcinoma. She later perceived a left visual field defect, and a brain metastasis was detected on head magnetic resonance imaging (MRI). Epidermal growth factor receptor (EGFR) testing identified two separate EGFR mutations: an L858R mutation in exon 21 and a de novo T790M mutation in exon 20. Treatment with osimertinib was started. After one month, head MRI showed that the brain metastasis had shrunk, and the visual field defect had also improved. In this case, first-line osimertinib was effective for treating brain metastasis of de novo T790M-positive lung cancer.

Endobronchial Manifestation of Methotrexate-induced Lymphoproliferative Disorder.

Lymphoproliferative disorders can occur in patients with autoimmune disorders who undergo long-term methotrexate therapy (MTX-LPD). Although the manifestations of MTX-LPD are diverse, little attention is paid to endobronchial involvement. We herein describe two patients with MTX-LPD who presented with parenchymal pulmonary tumors and endobronchial involvement of LPD; one had lymphomatoid gramulomatosis and the other LPD. The patients had no tumors adjacent to the endobronchial lesions. The endobronchial findings included multiple protruded mucosal lesions covered with white material, which was pathologically consistent with LPD. Recognition of the findings may help in making an earlier diagnosis of MTX-LPD in appropriate settings.

Sarcoid-Like Granulomatosis Induced by Nivolumab Treatment in a Lung Cancer Patient.

Nivolumab, an anti-PD-1 antibody, inhibits binding between PD-1 and PD-1 ligand and activates antigen-specific T cells that have become unresponsive to cancer cells. Although it is recommended as a second-line therapy in gene mutation-negative non-small-cell lung cancer, interstitial pneumonia is a well-known side effect of the drug; however, granulomatous lesions have rarely been reported. We describe the case of an 81-year-old male with cT1aN2M1b stage IV pleomorphic carcinoma of the left upper lobe of the lung. After primary treatment with carboplatin and paclitaxel, recurrence was observed in the left supraclavicular lymph node and left adrenal gland. We initiated the administration of nivolumab as a secondary treatment. Reduction was observed in the swelling of the left supraclavicular lymph node and left adrenal gland, but the tumor shadow in the right upper lobe appeared to increase. Bronchoscopy was performed, and the biopsy result showed granulomas; the findings resembled a sarcoid-like granulomatous reaction. The shadows eventually disappeared with nivolumab discontinuation; thus, we concluded that the sarcoid-like granulomatous reaction had resulted from nivolumab administration. Based on our observations, we suggest that when invasive shadows are observed after nivolumab administration, it is necessary to differentiate between disease progression and interstitial pneumonia. Moreover, the decision to reinitiate nivolumab treatment requires careful judgment in future instances of cancer recurrence.

Pleuritis Caused by Mycobacterium kyorinense without Pulmonary Involvement.

We herein describe the first known case of pleuritis caused by Mycobacterium kyorinense without pulmonary involvement. A 48-year-old man undergoing immunosuppressant therapy presented with cough and dyspnea. An accumulation of pleural fluid was noted; however, computed tomography revealed no pulmonary lesions. Cultures of the fluid yielded non-tuberculous mycobacteria, which was identified as Mycobacterium kyorinense. The patient recovered after 6 months of therapy with clarithromycin and moxifloxacin. Clinicians should be aware that Mycobacterium kyorinense can cause pleuritis without pulmonary involvement. When mycobacterial species are isolated from the pleural fluid, precise identification and drug susceptibility testing are warranted.

Desmoplastic Small Round Cell Tumor of the Pleura Successfully Treated with a Lower Dose of Pazopanib.

Desmoplastic small round cell tumor (DSRCT) is an aggressive mesenchymal tumor which primarily affects the abdomen. Even a multimodal approach rarely achieves durable remission and the optimal therapy for extended disease is unknown. We herein describe a rare case of DSRCT arising from the pleura in a 32-year-old man. Initial therapy, which included chemotherapy, surgery and radiotherapy, achieved a partial response for only two months. Although salvage chemotherapies had no effect, pazopanib treatment shrank the tumors and was well-tolerated on an outpatient basis. From the viewpoint of quality of life, pazopanib may therefore be a good therapeutic option for this aggressive disease.