Case of familial interstitial lung disease attributed to ATP-binding cassette transporter 3 gene mutation in identical twins.

Mutations in ABCA3 can result in surfactant deficiency, leading to respiratory distress syndrome in term neonates, and interstitial lung disease (ILD) in children. Here, we report an extremely rare case of ILD in an identical twin with novel ABCA3 germline mutations. Interestingly, they showed mostly similar, but slightly different, clinical features.

Cryptotanshinone is a candidate therapeutic agent for interstitial lung disease associated with a BRICHOS-domain mutation of .

Interstitial lung disease (ILD) represents a large group of diseases characterized by chronic inflammation and fibrosis of the lungs, for which therapeutic options are limited. Among several causative genes of familial ILD with autosomal dominant inheritance, the mutations in the BRICHOS domain of cause protein accumulation and endoplasmic reticulum stress by misfolding its proprotein. Through a screening system using these two phenotypes in HEK293 cells and evaluation using alveolar epithelial type 2 (AT2) cells differentiated from patient-derived induced pluripotent stem cells (iPSCs), we identified Cryptotanshinone (CPT) as a potential therapeutic agent for ILD.

Alternative Gene Expression by TOLLIP Variant Is Associated With Lung Function in Chronic Hypersensitivity Pneumonitis.

Background: Chronic hypersensitivity pneumonitis (CHP) is a heterogeneous fibrotic interstitial pneumonia resulting from the immune response of susceptible individuals to inhaled antigens. Genetic predispositions have been suggested in CHP; however, the link between susceptibility genes and fibrotic progression has not been elucidated fully. Recent data suggest that variants in Toll-interacting protein gene (TOLLIP) are associated with lung diseases.

Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Is Elevated in Patients with Asthma and Airway Obstruction.

Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease.

A case of imatinib-related obstructive bronchiolitis followed long term.

Obstructive bronchiolitis (OB) is an intractable disease causing stenosis in the surrounding bronchiolar region and bronchiolar lumen obstruction. Causes of OB are lung and hematopoietic stem-cell transplantation, collagen diseases, infections, and foods, but there are very few reports of drug-induced OB [1]. Imatinib is a drug used for the treatment of leukemia, gastrointestinal stromal tumors, etc.

A homozygous SFTPA1 mutation drives necroptosis of type II alveolar epithelial cells in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by scattered fibrotic lesions in the lungs. The pathogenesis and genetic basis of IPF remain poorly understood. Here, we show that a homozygous missense mutation in caused IPF in a consanguineous Japanese family.

Development of an Exhaled Breath Monitoring System with Semiconductive Gas Sensors, a Gas Condenser Unit, and Gas Chromatograph Columns.

Various volatile organic compounds (VOCs) in breath exhaled by patients with lung cancer, healthy controls, and patients with lung cancer who underwent surgery for resection of cancer were analyzed by gas condenser-equipped gas chromatography-mass spectrometry (GC/MS) for development of an exhaled breath monitoring prototype system involving metal oxide gas sensors, a gas condenser, and gas chromatography columns. The gas condenser-GC/MS analysis identified concentrations of 56 VOCs in the breath exhaled by the test population of 136 volunteers (107 patients with lung cancer and 29 controls), and selected four target VOCs, nonanal, acetoin, acetic acid, and propanoic acid, for use with the condenser, GC, and sensor-type prototype system. The prototype system analyzed exhaled breath samples from 101 volunteers (74 patients with lung cancer and 27 controls).

Pharmacological effects of lysozyme on COPD and bronchial asthma with sputum: A randomized, placebo-controlled, small cohort, cross-over study.

Background: Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA); the treatment ameliorates dyspnea and improves quality of life (QOL).

Aim: Efficacy and safety of lysozyme hydrochloride (LYS), an oral mucolytic enzyme preparation, for patients with COPD or BA were investigated.

Patients And Methods: This study was a placebo-controlled, double-blind, randomized, cross-over design.

Comparison of clinical features and polysomnographic findings between men and women with sleep apnea.

Background: There is a scarcity of reports comparing gender differences in polysomnographic findings among Asian patients with sleep apnea (SA). In this study, we elucidated gender differences in the clinical features and polysomnographic findings of SA patients in Japan.

Methods: We conducted a case-matched control study to compare the gender differences.

Survey to determine the efficacy and safety of guideline-based pharmacological therapy for chronic obstructive pulmonary disease patients not previously receiving maintenance treatment.

Objective: To investigate the potential beneficial effects of guideline-based pharmacological therapy on pulmonary function and quality of life (QOL) in Japanese chronic obstructive pulmonary disease (COPD) patients without prior treatment.

Research Design And Methods: Multicenter survey, open-label study of 49 Japanese COPD patients aged ≥ 40 years; outpatients with >10 pack years of smoking history; ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 70%; predicted FEV1 < 80%; treated with bronchodilators and/or inhaled corticosteroids as maintenance therapy until week 48.

Main Outcome Measures: The primary endpoint was change in pulmonary function (trough FEV1, trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after initiation of therapy.

Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia.

The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has been identified in parent-child cases of familial interstitial pneumonia. It has been shown that this mutation induces endoplasmic reticulum (ER) stress. Synoviolin is an E3 ubiquitin ligase that is localized to the ER and is an important factor in the degradation of ER-related proteins.

Histological types and localizations of lung cancers in patients with combined pulmonary fibrosis and emphysema.

Background: Most patients with combined pulmonary fibrosis and emphysema (CPFE) are males, and heavy smokers. CPFE is more prevalent than fibrosis in patients with lung cancer, and patients with CPFE usually have a poor prognosis. This study reviewed the differences in the prevalence of lung cancer among patients with normal, fibrosis, emphysema and CPFE via chest computed tomography (CT), and the relationship between histopathology and the localizations of lung cancer.

The utility of galactomannan antigen in the bronchial washing and serum for diagnosing pulmonary aspergillosis.

Background: The diagnosis of pulmonary aspergillosis is difficult because the sensitivity of the conventional methods for the detection of Aspergillus such as culture and cytology, is poor. To improve the sensitivity for Aspergillus detection, the detection of galactomannan antigen has been investigated. The serum galactomannan (GM) antigen has been recognized to be a useful tool for the diagnosis of invasive pulmonary aspergillosis.

Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations.

Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations.

Clinical relevance of plasma miR-106b levels in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by both chronic inflammation in the airway and systemic inflammation; however, the molecular mechanism of COPD has not been fully elucidated. By measuring microRNA (miRNA) expression in the plasma of COPD subjects, we aimed to identify the clinical relevance of plasma miRNA levels in these patients. Blood samples were obtained from COPD patients and age-matched normal controls.

Extended survival observed in adoptive activated T lymphocyte immunotherapy for advanced lung cancer: results of a multicenter historical cohort study.

Purpose: To clarify the long-term effect of immunotherapy, the effect of adoptive activated T lymphocyte immunotherapy on advanced lung cancer was evaluated in terms of survival time. In addition, the performance status of cancer patients under immunotherapy was examined.

Experimental Design: Over 5 × 10(9) alpha-beta T lymphocytes cultured ex vivo with an immobilized anti-CD3 antibody and interleukin-2 were injected intravenously into patients, once every 2 weeks for 3 months or longer.

T/NK cell type chronic active Epstein-Barr virus disease in adults: an underlying condition for Epstein-Barr virus-associated T/NK-cell lymphoma.

A chronic infectious mononucleosis-like illness caused by Epstein-Barr virus (EBV) is called 'chronic active EBV disease', which is defined as an EBV-associated lymphoproliferative disease. This lymphoproliferative disease is rare and predominantly occurs in Japanese children. Between 1998 and 2010, seven adult-onset cases (aged 20-45 years, median 39 years) were identified, which initially presented with inflammatory diseases, including hepatitis, interstitial pneumonitis, uveitis, nephritis and hypersensitivity to mosquito bites.

The relationship between the clinical course and cytokine in a patient with cigarette smoking-induced acute eosinophilic pneumonia - A case report.

A 19-year-old female was admitted to our hospital because of a sudden onset fever and cough, and she was diagnosed to have acute eosinophilic pneumonia (AEP). The cause was thought to be cigarette smoking, because she had started smoking just before the development of AEP and her condition improved after cigarette smoking cessation, without corticosteroid treatment. The cytokines which are thought to be involved in eosinophilic accumulation in the lungs were analyzed using bronchoalveolar lavage fluid (BALF) and serum.

Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction.

Keloid is a clinically intractable disease that causes disfigurement, itching, and pain due to abnormal proliferation of fibroblasts and production of collagen. Pirfenidone is a novel anti-fibrotic agent that inhibits the progression of fibrosis occurring in the keloid lesions of the lung and kidney. In order to examine whether pirfenidone has a therapeutic effect on keloid lesions, we prepared an in vitro wound contraction model with keloid fibroblasts.

Effects of inhaled tiotropium plus transdermal tulobuterol versus tiotropium alone on impulse oscillation system (IOS)-assessed measures of peripheral airway resistance and reactance, lung function and quality of life in patients with COPD: a randomized crossover study.

Background: The addition of transdermal tulobuterol (Tulo) to inhaled tiotropium bromide (Tio) produced beneficial effects on spirometry-assessed parameters of respiratory function, disease-related symptoms and quality of life in patients with chronic obstructive pulmonary disease (COPD).

Aim: To compare the effects of Tio plus Tulo versus Tio alone on peripheral airway obstruction and quality of life in Japanese patients with COPD using impulse oscillation system (IOS)-assessed measures.

Patients And Methods: Patients aged 50-80 years with clinically stable COPD and a forced expiratory volume in 1 s (FEV(1)) that was 30-80% of the predicted value were randomized to receive Tio 18 μg once daily, or combination therapy with Tio 18 μg once daily plus Tulo 2 mg once daily for 4 weeks.

Two patients with bepridil-induced interstitial pneumonia.

Two patients developed bepridil-induced interstitial pneumonia during treatment of arrhythmia. The first patient was a 69-year-old man who received bepridil to maintain sinus rhythm in atrial fibrillation and who developed dyspnea on the 20th day after administration. The second patient was a 72-year-old man who received bepridil for paroxysmal atrial fibrillation and who developed dyspnea on the 60th day after administration.

[Identification of propionibacterium acnes in a case with stage III pulmonary sarcoidosis involving hepatosplenic disease].

A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X-ray on admission showed multiple small nodular shadows in both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover, abdominal CT showed some nodules in the liver and spleen, and serum ACE was slightly increased to 23.

Clinical features and genetic analysis of surfactant protein C in adult-onset familial interstitial pneumonia.

Familial cases of interstitial pneumonia (FIP) have been reported to be linked to mutations of the surfactant protein C (SP-C) gene. Based on this knowledge, we evaluated the characteristics of patients with adult-onset FIP in the Tokyo area using clinical and radiopathological findings, and further evaluated the genetic background of patients with FIP compared with sporadic IP patients using genetic sequencing of the SP-C gene. A total of 22 patients with FIP from 13 families were identified, and the mean age at first diagnosis of these patients was 50 +/- 2.