Diagnostic utility of FeNO for CTVA

A 50-year-old woman was referred to our hospital for further examination of severe constricting pain at the right-side dominant anterior chest. She had medical history of outgrown childhood asthma and allergies to several animals. Chest auscultation revealed no wheezes, rhonchi and other crackles. Laboratory findings showed an eosinophilia and an elevation of total immunoglobulin E. The results of an electrocardiogram, a chest X-ray and a chest CT were unremarkable. A fractional exhaled nitric oxide value remarkably elevated, but the abnormalities in pulmonary function test were modest. Her chest pain was ameliorated after inhaling procaterol. Based on these findings, a diagnosis of chest tightness variant asthma was formulated, and we started treatment with inhaled corticosteroid / long acting β2 agonist. At two-weeks after treatment, her symptom markedly improved and a fractional exhaled nitric oxide value decreased, which led to a definitive diagnosis of chest tightness variant asthma. A fractional exhaled nitric oxide value further decreased to the normal range in consistent with symptom disappearance at 10-months after treatment, indicating the usefulness of fractional exhaled nitric oxide as a promising marker for the diagnosis and clinical improvement of chest tightness variant asthma

A thymoma dramatically responded to PSL

A 76-year-old woman with a history of angina pectoris, hypertension and dyslipidemia was pointed out an abnormal opacity in the right hilar region on routine chest X-ray. Chest computed tomography showed masses in the anterior mediastinum with the invasion of the adjacent ascending aorta, right brachiocephalic vein and right pleura. Histologic examination led to a diagnosis of Masaoka stage IVa thymoma. Three courses of chemotherapy were given, but further tumor progression was seen. Thereafter, the patient was followed without aggressive treatments. One year after the initial diagnosis, she presented with dyspnea and right chest pain. Chest CT revealed right massive pleural effusion with pleural dissemination and much further progression of existing tumors. For the purpose of symptom palliation, a low dose (5 mg / day) of prednisolone was commenced, which unexpectedly led to marked alleviation of patient’s symptoms and dramatic decrease of pleural effusion. To the best of our knowledge, this is the first report of an invasive thymoma responded to low-dose corticosteroid. The present case suggests that corticosteroids, even at low doses, might be potentially effective for invasive thymoma after failure of surgery, chemotherapy and radiotherapy

Utility of FeNO for diagnosing cough

Cough is one of the most common symptoms seen in clinical practice, however the differential diagnosis is often difficult. The utility of fractional exhaled nitric oxide (FeNO) measurement in the differential diagnosis of the etiology of cough has been reported. NIOX VERO® (NOV) is a new hand-held device that will replace NIOX MINO®, but its diagnostic utility has not been fully elucidated in clinical practice. In this study, the performance of NOV for FeNO measurements was determined. We retrospectively analyzed 243 consecutive patients complaining cough. Among 243 patients, final diagnosis was cough variant asthma (CVA) in 74 (30.5%), bronchial asthma (BA) in 48 (19.8%), post-infectious cough (PIC) in 52 (21.4%), atopic chough (AC) in 24 (9.9%), gastroesophageal reflux disease (GERD) in 10 (4.1%), and Others in 35 (14.4%). FeNO values were significantly higher in CVA and BA as compared to PIC, AC, GERD, and Others. In the multivariate analysis, only FeNO value was identified as independent factors to discriminate CVA and non-CVA other than BA. These findings indicated that FeNO measured by using NOV could be used as a diagnostic marker of intractable cough, especially for the differential diagnosis of CVA from non-CVA

Emergence of quantum critical behavior in metallic quantum-well states of strongly correlated oxides

Controlling quantum critical phenomena in strongly correlated electron systems, which emerge in the neighborhood of a quantum phase transition, is a major challenge in modern condensed matter physics. Quantum critical phenomena are generated from the delicate balance between long-range order and its quantum fluctuation. So far, the nature of quantum phase transitions has been investigated by changing a limited number of external parameters such as pressure and magnetic field. We propose a new approach for investigating quantum criticality by changing the strength of quantum fluctuation that is controlled by the dimensional crossover in metallic quantum well (QW) structures of strongly correlated oxides. With reducing layer thickness to the critical thickness of metal-insulator transition, crossover from a Fermi liquid to a non-Fermi liquid has clearly been observed in the metallic QW of SrVO$_3$ by \textit{in situ} angle-resolved photoemission spectroscopy. Non-Fermi liquid behavior with the critical exponent ${\alpha} = 1$ is found to emerge in the two-dimensional limit of the metallic QW states, indicating that a quantum critical point exists in the neighborhood of the thickness-dependent Mott transition. These results suggest that artificial QW structures provide a unique platform for investigating novel quantum phenomena in strongly correlated oxides in a controllable fashion.Comment: 6 pages, 3 figure

Role of surfactant protein A in non-infectious lung diseases

Surfactant protein A (SP-A) is a large multimeric protein found in the airways and alveoli of the lungs. SP-A is a member of the collectin family of proteins, characterized by NH2-terminal collagen-like regions and COOH-terminal lectin domains. Although other surfactant proteins such as SP-B function to reduce surface tension in the lungs, SP-A as well as SP-D regulates the pulmonary immune response. To date, a number of studies have shown the immunoregulatory function of SP-A, mainly in the field of infectious diseases. By binding to a wide variety of pathogens, SP-A opsonizes and enhances pathogen uptake by phagocytes. In addition to the effect on pathogens, recent studies have shown that SP-A also modulates lung immune system in the area of non-infectious lung diseases. In this review, the potential role of SP-A in the multiple aspects of pulmonary host defense will be discussed, focusing mainly on non-infectious lung diseases such as acute and chronic pulmonary fibrosis and lung cancer

A case of atopic cough with aphonia

A 33-year-old woman admitted to our hospital for further examination of severe non-productive cough lasting for about two months. Her symptom did not ameliorate by treatments including long acting β2 agonists. She had a medical history of drug allergy to non-steroidal anti-inflammatory drugs. At the initial visit, she could not speak at all and communicated with us in writing. Chest auscultation revealed no wheezes, rhonchi and other crackles. Laboratory findings showed a mild eosinophilia with normal total and specific serum immunoglobulin E. The results of an electrocardiogram, a chest X-ray and a chest CT were unremarkable. A fractional exhaled nitric oxide value was within normal limit. Based on these observations, a diagnosis of atopic cough (AC) was suspected, and we started treatment with a histamine H1 receptor antagonist (H1-RA). She had become able to speak again in association with complete disappearance of cough by eight-weeks after treatment initiation, and her symptoms did not recur even after cessation of treatment. By the confirmation of remarkable clinical improvement in response to a H1-RA, a diagnosis of AC was made. To the best of our knowledge, this is the first report of an AC patient who presented severe cough with aphonia

Efficacy and safety of second-line chemotherapy for patients with advanced non-small cell lung cancer complicated by interstitial lung disease

Background: Treatment of non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is limited because of the risk of its acute exacerbation (AE). Furthermore, the efficacy and safety of second-line chemotherapy for these patients is unclear. Methods: To investigate the efficacy and safety of second-line chemotherapy for NSCLC patients with ILD, we retrospectively reviewed patients who were treated at our institute between April 2010 and December 2018. Results: Thirty-five patients received two or more regimens. Thirty-four patients were male and the median age at the initiation of second-line chemotherapy was 70 years. Almost all patients had a smoking history. Fourteen patients had adenocarcinoma and 15 had squamous cell carcinoma histology. Stages III and IV were observed in 20 and 11 patients, respectively. With respect to the type of ILD, 12 patients had usual interstitial pneumonia (UIP). The overall response rate and disease control rate were 11.4 and 68.6%, respectively. The median progression-free and median overall survival were 4.1 and 6.4 months, respectively. The AE of ILD was observed in eight patients, five of whom died. UIP and low percentage vital capacity were detected as significant risk factors for the AE of ILD. Conclusion: Second-line chemotherapy among patients with NSCLC complicated by ILD showed a certain effectiveness, but some patients experienced the AE of ILD, which may lead to death. The risk of the AE of ILD must be considered especially for patients with UIP and low percentage VC

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma

Background: Nivolumab is used for the treatment of malignant pleural mesothelioma (MPM). However, immune-related adverse events (irAEs) occur in patients treated with nivolumab. Several studies have reported the correlation between irAEs and therapeutic effects of immune checkpoint inhibitor, but none have reported the correlation in MPM. Here we report a retrospective study which shows the correlation between irAEs and therapeutic effects of nivolumab in patients with MPM. Methods: This study included patients treated with nivolumab at Tokushima University Hospital from February 2009 to September 2021. We retrospectively reviewed the medical records to evaluate the several clinical factors, such as the presence or absence of irAEs, their severities, progression-free survival (PFS), overall survival (OS) or objective response to the treatment. Results: Eleven patients received treatment with nivolumab. Objective response rate was 18.2% and the disease control rate was 90.9%. Median PFS was 6.8 months (95% confidence interval, 1.3 to 11.9 months) and median OS was 15.2 months (95% confidence interval, 8.9 to 21.5 months). IrAEs occurred in eight patients (72.7%), and grade ≥ 2 irAEs occurred in six patients (54.5%). PFS and OS were significantly longer in the grade ≥ 2 irAEs group than in grade < 2 irAEs group (median PFS 13.6 vs. 3.8 months, p = 0.0093; median OS not reached vs. 8.6 months, p = 0.0108). Conclusions: This is the first study to report the correlation between irAEs and therapeutic effects in patients with MPM. Because the presence of irAEs may be associated with a favorable clinical outcome, early detection and appropriate management of irAEs will increase the therapeutic benefits to patients

Radiation therapy induces an abscopal effect and upregulates programmed death-ligand 1 expression in a patient with non-small cell lung cancer

Radiation therapy (RT) activates the antigen presentation of dendritic cells and priming of cancer-specific cytotoxic CD8+ T cells, occasionally resulting in a systemic immune response to the tumor outside of the treatment field. The phenomenon of tumor regression at the site distant from irradiated fields is known as the abscopal effect. Several case reports have indicated a potential role of RT in overcoming primary and acquired resistance against immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) and melanoma patients. We herein report an NSCLC patient who developed acquired resistance to an RT-induced abscopal effect and subsequently experienced reactivation of the systemic antitumor immune response by pembrolizumab, an antiprogrammed death 1 antibody. In this case, RT not only induced an abscopal effect but also upregulated the programmed death-ligand 1 expression outside of the irradiated field when the patient developed resistance to the abscopal effect. This case can facilitate our understanding of the mechanism underlying the RT-induced systemic immune response against cancer cells and adaptive resistance mechanism of cancer cells from immune surveillance. These findings highlight the promising results of current clinical trials combining RT and immune checkpoint inhibitors. Ongoing clinical trials will further establish evidence supporting combination therapy with RT and immune checkpoint inhibitors

Efficacy of osimertinib in epidermal growth factor receptor-mutated non-small-cell lung cancer patients with pleural effusion

Background: Osimertinib is a standard first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although malignant pleural effusion (PE) is a common clinical problem in NSCLC, information about the efficacy of osimertinib in patients with PE is limited, especially regarding its efficacy in EGFR T790M-negative patients with PE remains unclear. Methods: We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who were treated with osimertinib in our institution between May 2016 and December 2020. Results: A total of 63 patients with EGFR mutated NSCLC were treated with osimertinib; 33 (12 with PE) had no EGFR T790M mutation, while 30 (12 with PE) had EGFR T790M mutation. In EGFR T790M-negative NSCLC, the progression-free survival (PFS) of the patients with PE was comparable to that of the patients without PE (median PFS 19.8 vs. 19.8 months, p = 0.693). In EGFR T790M- positive NSCLC, the PFS and overall survival (OS) of the patients with PE were significantly shorter than those of the patients without PE (median PFS 16.8 vs. 8.3 months, p = 0.003; median OS 44.9 vs. 14.2 months, p = 0.007). In the multivariate analysis, the presence of PE was independently associated with shorter PFS and OS in EGFR T790M-positive NSCLC patients, but not EGFR T790M-negative patients. Conclusions: These data suggest the efficacy of osimertinib may differ between EGFR T790M-positive and -negative NSCLC patients with PE