The primary ciliary dyskinesia-related genetic risk score is associated with susceptibility to adult-onset asthma.

Background: Disturbance of mucociliary clearance is an important factor in the pathogenesis of asthma. We hypothesized that common variants in genes responsible for ciliary function may contribute to the development of asthma with certain phenotypes.

Methods: Three independent adult Japanese populations (including a total of 1,158 patients with asthma and 2,203 non-asthmatic healthy participants) were studied.

Expression quantitative trait loci for ETV4 and MEOX1 are associated with adult asthma in Japanese populations.

ETS variant transcription factor 4 (ETV4) is a recently identified transcription factor that regulates gene expression-based biomarkers of asthma and IL6 production in an airway epithelial cell line. Given that ETV4 has not yet been implicated in asthma genetics, we performed genetic association studies of adult asthma in the ETV4 region using two independent Japanese cohorts (a total of 1532 controls and 783 cases). SNPs located between ETV4 and mesenchyme homeobox 1 (MEOX1) were significantly associated with adult asthma, including rs4792901 and rs2880540 (P = 5.

Identification of distinct phenotypes related to benralizumab responsiveness in patients with severe eosinophilic asthma.

Purpose: To characterize the clinical phenotypes of severe eosinophilic asthma based on early responsiveness to benralizumab in terms of forced expiratory volume in 1 second (FEV1) improvement.

Patients And Methods: Sixty-four participants diagnosed with severe eosinophilic asthma and who had completed 4 months of benralizumab treatment were included in this analysis. Pre-treatment clinical factors were compared between responders and non-responders according to improvements in ACT or FEV1.

Genetic impact of CDHR3 on the adult onset of asthma and COPD.

Background: Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases caused by complex gene-environment interactions. A functional single nucleotide polymorphism of cadherin-related family member 3 (CDHR3), known as a receptor of rhinovirus-C, is associated with childhood-onset asthma especially in atopic individuals.

Objective: Here, we identified risk factors for adult-onset asthma and COPD, focusing on the impact of the CDHR3 variant in atopic individuals.

ORMDL3/GSDMB genotype as a risk factor for early-onset adult asthma is linked to total serum IgE levels but not to allergic sensitization.

Background: An orosomucoid-like 3 (ORMDL3)/gasdermin B (GSDMB) gene locus on chromosome 17q is consistently associated with childhood-onset asthma, which is highly atopic. As some evidence suggests the relationship between asthma and allergic sensitization reflects asthma patient susceptibility to augmented IgE responses driven by common environmental allergens rather than an increased asthma risk after allergen exposure, we aimed to determine any relationships between this locus region and childhood-onset adult asthma with regard to serum total IgE levels or allergic sensitization.

Methods: We conducted a case-control association study using three independent Japanese populations (3869 total adults) and analyzed the ORs for association of rs7216389, an expression quantitative trait locus for ORMDL3/GSDMB, with adult asthma according to onset age.

The Concavity of the Maximal Expiratory Flow-Volume Curve Reflects the Extent of Emphysema in Obstructive Lung Diseases.

A concave-shaped maximal expiratory flow-volume (MEFV) curve is a spirometric feature in chronic obstructive pulmonary disease (COPD). The MEFV curve is characterized by an increase in the Obstructive Index, which is defined as a ratio of forced vital capacity to the volume-difference between two points of half of the peak expiratory flow on the MEFV curve. We hypothesized that the Obstructive Index would reflect the severity of emphysema in patients with COPD and asthma-COPD overlap (ACO).

A cis-eQTL allele regulating reduced expression of CHI3L1 is associated with late-onset adult asthma in Japanese cohorts.

Background: The chitinase-like protein YKL-40 plays a major role in inhibiting the inflammasome. Deregulation of inflammasome activation is emerging as a key modulator of pathologic airway inflammation in patients with asthma. We determined whether cis-expression quantitative trait loci (eQTLs) of the gene that encodes YKL-40, chitinase 3-like 1 (CHI3L1), are involved in the onset of asthma or in specific asthma phenotypes.

Association analyses of eQTLs of the TYRO3 gene and allergic diseases in Japanese populations.

Background: TYRO3 is a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family and functions to limit type 2 immune responses implicated in allergic sensitization. Recent studies have shown that multiple intronic variants of TYRO3 were associated with asthma, implying that genetic variation could contribute to errant immune activation. We therefore hypothesized that expression quantitative trait loci (eQTLs) of the TYRO3 gene influence the development of allergic diseases (including asthma and allergic rhinitis) in Japanese populations.

Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone.

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with a worse prognosis than some types of cancer. In patients with IPF, lung cancer is critical because of the associated high mortality rate from its progression and fatal complications from anticancer treatments. Therefore, preventing lung cancer in patients with IPF is primordial.

Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations.

Background: Recent studies have demonstrated that a coding SNP (rs6967330, Cys529→Tyr) in cadherin-related family member 3 (CDHR3), which was previously associated with wheezing illness and hospitalizations in infancy, could support efficient human rhinovirus C (RV-C) entry and replication. Here, we sought to examine the genetic contribution of this variant to the development of adult asthma.

Methods: We performed a candidate gene case-control association study of 2 independent Japanese populations (a total of 3366 adults).

[GENETIC INTERACTIONS BETWEEN ADRB2 AND PTGER4 ON RESPONSES TO SALMETEROL OR MONTELUKAST IN JAPANESE PATIENTS WITH MILD PERSISTENT ASTHMA].

Background: Long-acting β-agonists (LABA) and leukotriene receptor antagonists (LTRA) are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. In our previous study, the Gly16Arg genotype of the β-adrenergic receptor (ADRB2) gene did not influence the differential bronchodilator effect of salmeterol versus montelukast as an add-on therapy to ICS within 16 weeks of follow-up (the J-Blossom study).

Methods: We examined if genes encoding CYSLTR1, CYSLTR2, PTGER2 or PTGER4 could explain differential responses to salmeterol versus montelukast using the participants of the J-Blossom study.

Limited value of transbronchial lung biopsy for diagnosing Mycobacterium avium complex lung disease.

Background And Aims: It remains unclear whether transbronchial lung biopsy (TBLB) is useful for diagnosing Mycobacterium avium complex (MAC) lung disease.

Methods: Thirty-eight consecutive patients with MAC lung disease, who were evaluated with TBLB tissue culture between June 2006 and May 2010, were included. Bronchial washing (BW) and histopathological evaluation were performed in all patients.

Role of Lung Function Genes in the Development of Asthma.

Although our previous GWAS failed to identify SNPs associated with pulmonary function at the level of genomewide significance, it did show that the heritability for FEV1/FVC was 41.6% in a Japanese population, suggesting that the heritability of pulmonary function traits can be explained by the additive effects of multiple common SNPs. In addition, our previous study indicated that pulmonary function genes identified in previous GWASs in non-Japanese populations accounted for 4.

[FACTORS ASSOCIATED WITH THE PRESENCE OF ALLERGEN-SPECIFIC IgE RESPONSES IN ASTHMA PATIENTS WHO HAD NO IgE RESPONSES DETECTABLE BY MAST-26].

Aim: To elucidate the characteristics of patients with asthma who have specific IgE responses to inhaled allergens detected by ImmunoCAP, which is not detectable by MAST-26.

Methods: A total of 168 patients with adult asthma who reside in the Kanto region were recruited. Levels of total serum IgE and allergen specific IgE antibodies towards 14 common inhaled allergens (MAST-26) were measured.

Central nervous system manifestations of tuberculosis-associated immune reconstitution inflammatory syndrome during adalimumab therapy: a case report and review of the literature.

A 64-year-old neurologically asymptomatic woman with rheumatoid arthritis who was treated with the tumor necrosis factor (TNF)-α antagonist adalimumab developed disseminated tuberculosis (TB). After receiving anti-TB therapy and discontinuing adalimumab, she exhibited paradoxical worsening due to immune reconstitution inflammatory syndrome (IRIS) with the appearance of meningitis and brain tuberculomas. This case indicates that continuing anti-TNF therapy may be necessary to prevent IRIS in patients who develop TB, particularly disseminated TB, during the course of anti-TNF therapy.

Heritability of pulmonary function estimated from genome-wide SNPs in healthy Japanese adults.

Background: Pulmonary function is a heritable trait, and recent genome-wide association studies (GWASs) have identified a number of loci influencing the trait. Genome-wide Complex Trait Analysis (GCTA) is a novel method provided by a software package that estimates the total additive genetic influence caused by common single nucleotide polymorphisms (SNPs) on whole-genome arrays. We conducted a GWAS and assessed the heritability of pulmonary function in an adult Japanese population using this approach.

Clinical experience with pirfenidone in five patients with scleroderma-related interstitial lung disease.

Interstitial lung disease is the most common complication and cause of death among patients with scleroderma. Scleroderma-related interstitial lung disease has usually been treated with cyclophosphamide; however, its effect was evaluated to be modest and long-term administration of this drug is associated with adverse effects. Herein, we report our clinical experience of administering pirfenidone, which is an antifibrotic agent, in five patients with scleroderma-related interstitial lung disease.

Benign myoepithelioma in the intrathoracic trachea.

A 67-year-old woman who was followed as a patient with bronchial asthma for 1.5 years visited our hospital with progressive dyspnea. Although the chest radiography findings were normal, a chest computed tomography scan revealed a mass obliterating the intrathoracic tracheal lumen.

[Effects of thymic stromal lymphopoietin (TSLP) genotypes on asthma phenotypes defined by the atopy cluster -influence of smoking habits-].

Introduction: We have previously reported that a distinct sensitization pattern was associated with thymic stromal lymphopoietin (TSLP) genotype. The aim of this study is to identify the characteristics of asthma phenotypes determined by a cluster analysis of IgE responsiveness and the relationship between these phenotypes and TSLP genotypes.

Patients And Methods: We studied 297 patients of adult asthma and 1571 non-asthmatic healthy adults from Ibaraki, a prefecture in central Japan and Kamishihoro, a cedar-free, birch-dominant town in northern Japan.

Genome-wide association study for levels of total serum IgE identifies HLA-C in a Japanese population.

Most of the previously reported loci for total immunoglobulin E (IgE) levels are related to Th2 cell-dependent pathways. We undertook a genome-wide association study (GWAS) to identify genetic loci responsible for IgE regulation. A total of 479,940 single nucleotide polymorphisms (SNPs) were tested for association with total serum IgE levels in 1180 Japanese adults.

Prevalence of underlying lung disease in smokers with epidermal growth factor receptor-mutant lung cancer.

The prevalence of underlying lung diseases, such as emphysema and interstitial lung disease in smokers with epidermal growth factor receptor (EGFR)-mutant lung cancer remains unclear. This study aimed to clarify the correlation between the EGFR mutation status and the prevalence of underlying lung disease in smokers with lung cancer. A total of 88 consecutive smokers with non-small cell or non-squamous cell lung cancer who underwent surgical resection at our hospital from January 2007 through December 2010 were included in this study.

The search for common pathways underlying asthma and COPD.

Recently, several genes and genetic loci associated with both asthma and chronic obstructive pulmonary disease (COPD) have been described as common susceptibility factors for the two diseases. In complex diseases such as asthma and COPD, a large number of molecular and cellular components may interact through complex networks involving gene-gene and gene-environment interactions. We sought to understand the functional and regulatory pathways that play central roles in the pathobiology of asthma and COPD and to understand the overlap between these pathways.