Search

Recurrence of oestrogen receptor (ER)-positive breast cancer rarely occurs postoperatively after a long period. Breast cancer cells survive and settle in distant organs in a dormant state, a phenomenon known as “tumour dormancy.” Here, we present a 66-year-old woman with recurrence of ER-positive breast cancer in the left lung 23 years after surgery accompanied with non-tuberculous mycobacterium infection (NTM). At the age of 43 years, the patient underwent a right mastectomy and adjuvant hormonotherapy to completely cure breast cancer. Twenty-three years after the operation, when the patient was 66 years old, computed tomography presented nodular shadows in the lower lobes bilaterally with bronchiectasis and ill-defined satellite tree-in-bud nodules. Mycobacterium intracellulare was detected in cultured bronchoalveolar lavage fluid obtained from the left lower lobe by bronchoscopy. Rifampicin, ethambutol, and clarithromycin were started, which resulted in shrinkage of the nodule in the right lower lobe and satellite nodules; however, the nodule in the left lower lobe increased in size gradually. Wedge resection of the left lower lobe containing the nodule by video-assisted thoracoscopic surgery was performed, which demonstrated that the nodule was adenocarcinoma in intraoperative pathological diagnosis; therefore, a left lower lobectomy and mediastinal lymph node dissection were performed. The tumour was revealed to be consistent with recurrence of previous breast cancer according to its morphology and immunohistochemical staining. Furthermore, caseous epithelioid cell granulomas existed in the periphery of the tumour. It is reported that inflammatory cytokines induce reawakening of dormant oestrogen-dependent breast cancer and, in our case, NTM infection might have stimulated the dormant tumour cells in the lower lobe.

Background Pleuroparenchymal fibroelastosis (PPFE) is a rare fibrosing lung disease with a predilection for the upper lobe and its progression causes hypoventilation, resulting in hypercapnia. Even though the association between sleep-related hypoventilation (SRH) and chronic obstructive pulmonary disease was well documented, its impact in patients with PPFE was not evaluated. The aim of this study is to clarify the impact of SRH on prognosis in PPFE. Methods A retrospective review of the medical records of 52 patients with PPFE who underwent transcutaneous carbon dioxide monitoring during sleep was done. Patients were stratified into SRH (n = 28) and non-SRH (n = 24) groups based on American Academy of Sleep Medicine criteria. The impact of SRH on the prognosis of PPFE, as well as the clinical factors and comorbidities of PPFE associated with SRH, were evaluated. Results Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLco) in the SRH group were significantly lower than the non-SRH group (P Conclusions SRH may be a poor prognostic factor for PPFE. Additionally, SRH may modify susceptibility to Aspergillosis in patients with PPFE. HOT plus NPPV may improve the disease outcomes in patients with SRH.

Background and objectives Chronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), are complex syndromes with diverse clinical symptoms due to multiple pathophysiological conditions. In this study, using common and shared risk factors for the exacerbation of asthma and COPD, we sought to clarify the exacerbation-prone phenotypes beyond disease labels, and to specifically investigate the role of the IL4RA gene polymorphism, which is related to type 2 inflammation, in these exacerbation-prone phenotypes. Methods The study population comprised patients with asthma (n = 117), asthma-COPD overlap (ACO; n = 37) or COPD (n = 48) and a history of exacerbation within the previous year. Cluster analyses were performed using factors associated with both asthma and COPD exacerbation. The association of the IL4RA gene polymorphism rs8832 with each exacerbation-prone phenotype was evaluated by multinomial logistic analyses using non-asthma non-COPD healthy adults as controls (n = 1,529). In addition, the genetic influence of rs8832 was also examined in asthma patients with allergic rhinitis and no history of exacerbation (n = 130). Results Two-step cluster analyses identified five clusters that did not necessarily correspond to the diagnostic disease labels. Cluster 1 was characterized by high eosinophil counts, cluster 2 was characterized by smokers with impaired lung function, cluster 3 was characterized by the presence of gastroesophageal reflux, cluster 4 was characterized by non-allergic females, and cluster 5 was characterized by allergic rhinitis and elevated total immunoglobulin E levels. A significant association with rs8832 was observed for cluster 5 (odds ratio, 3.88 (1.34–11.26), p = 0.013) and also for the type 2 exacerbation-prone phenotypes (clusters 1 and 5: odds ratio, 2.73 (1.45–5.15), p = 1.9 × 10−3). Discussion Our results indicated that the clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD, and may support the use of the treatable traits approach for the prevention of exacerbations in patients with chronic inflammatory airway diseases.

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 = 5.63E−5 and 2.77E−5, respectively). The CC haplotype of these two SNPs was also significantly associated with adult asthma (P = 8.43E−7). Even when both SNPs were included in a logistic regression model, the association of either rs4792901 or rs2880540 remained significant (P = 0.013 or 0.007, respectively), suggesting that the two SNPs may have independent effects on the development of asthma. Both SNPs were expression quantitative trait loci, and the asthma risk alleles at both SNPs were correlated with increased levels of ETV4 mRNA expression. In addition, the asthma risk allele at rs4792901 was associated with increased serum IL6 levels (P = 0.041) in 651 healthy adults. Our findings imply that ETV4 is involved in the pathogenesis of asthma, possibly through the heightened production of IL6.

Background: The prevalence of non-tuberculous mycobacterial (NTM) pulmonary disease is globally increasing. The most common pathogen isolated in Japan is the Mycobacterium avium complex (MAC), and the natural history of MAC pulmonary disease (MAC-PD) remains unclear, even in mild cases of MAC-PD. Our previous study showed that serum dROM (oxidative stress marker) as well as the increase of total cell counts and neutrophil percentages in bronchoalveolar lavage fluid (BALF) were related to the commencement of chemotherapy (CT). Aims: To elucidate whether the level of oxidative stress in BALF reflect the disease severity and can be a marker for initiating CT in mild cases of MAC-PD. Methods: Between June 2016 and March 2019, 34 subjects who were suspected of MAC-PD and underwent diagnostic bronchoscopy were included, and all of patients did not show systemic inflammation. According to the findings of bronchoscopy, subjects were divided into MAC group and Non-MAC group. MAC group were subdivided into Treatment group (MAC-T) and Observation group (MAC-O). We measured malondialdehyde (MDA) in BALF and serum d-ROM as a marker of oxidative stress. Results: Total cell counts as well as neutrophil percentages in BALF were the highest in MAC-T group among three groups (P Conclusions: The level of MDA in BALF seemed to reflect the oxidative tissue damage in mild cases of MAC-PD, and it might be an indicator for disease severity and the commencement of CT.

Hintergrund: Die exzessive Inhalation von Aluminiumstaub führt gelegentlich zu einer überwiegend die Oberlappen betreffenden Lungenfibrose, die einer idiopathischen pleuroparenchymalen Fibroelastose (IPPFE) ähnelt und bei der es sich den Annahmen zufolge um eine sekundäre PPFE handelt. Fallbericht: Ein 67-jähriger Mann, der 50 Jahre lang in einem aluminiumverarbeitenden Unternehmen gearbeitet hatte, stellte sich mit Belastungsdyspnoe in unserer Klinik vor. Die Computertomographie (CT) des Thorax zeigte eine bilaterale dichte subpleurale Konsolidierung in den oberen und mittleren Lungenfeldern entsprechend einer IPPFE; eine etwaige sekundäre PPFE im Zusammenhang mit einer Aluminose wurde jedoch nicht ausgeschlossen. Aufgrund des kritischen Zustands des Patienten erfolgten eine transbronchiale Lungenbiopsie (TBLB) anstatt einer chirurgischen Lungenbiopsie sowie eine Elementaranalyse der entnommenen Gewebeprobe. Da die mittels TBLB gewonnene Probe bedauerlicherweise kein Alveolargewebe enthielt, konnte die Diagnose PPFE nicht pathologisch gesichert werden. Die radiologischen Befunde sprachen jedoch stark für eine PPFE. In der Elementaranalyse wurden hohe Mengen an Aluminium in den Bronchiolarwänden nachgewiesen, so dass die Diagnose einer Aluminose der Atemwege mit wahrscheinlich sekundärer PPFE infolge Aluminiumexposition gestellt wurde. Schlussfolgerungen: Eine TBLB mit Elementaranalyse kann zur Abgrenzung der idiopathischen PPFE von sekundären Ursachen bei staubbedingten Erkrankungen wie Aluminose hilfreich sein. Der vorliegende Fall zeigt, dass die Inhalation von Aluminium eine sekundäre PPFE verursachen kann; ein besonderes Augenmerk sollte auf die Vermeidung einer weiteren Exposition gelegt werden.

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. Methods We conducted a longitudinal, retrospective, observational cohort study of 1523 healthy adults with baseline examinations at Tsukuba Medical Center Hospital in 2008 and retrospectively identified new-onset, physician-diagnosed asthma or COPD from 2009 to 2018. We assessed risk factors by the Cox regression analysis. The impact of CDHR3 variant rs6967330 was also examined in individuals with pre-existing atopy. Results Over 10 study years, 103 people developed airway diseases (79 asthma and 24 COPD; 52 females, average onset-age 55 years old, range 38-80). Higher body mass index (BMI) and lower forced expiratory volume in one second/forced vital capacity (FEV1 /FVC) ratio were significant risk factors (BMI: HR 1.072 [95% CI 1.005-1.14], P = .034; FEV1 /FVC ratio: HR 1.091 [1.044-1.14], P = .00011). Restriction to atopic individuals saw the A allele at rs6967330 and lower FEV1 /FVC ratio to associate with adult-onset disease (A allele: HR 2.89 [1.57-5.20], P = .00062; FEV1 /FVC ratio: HR 1.10 [1.04-1.17], P = .0010). Conclusion and clinical relevance Genetic susceptibility to rhinovirus-C infection in atopic individuals is a risk factor for chronic airway diseases even in later life.

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. Additionally, associations between the rs7216389 genotype and total serum IgE levels or allergic sensitization was examined. Results: Rs7216389 was associated with both childhood-onset adult asthma (OR for asthmatic patients afflicted at the age of 10 years or younger = 1.61, p = 0.00021) and asthmatic patients with higher levels of total serum IgE (OR for asthmatic patients with IgE ≥1000IU/mL = 1.55, p = 0.0033). In both healthy controls and in the combined healthy and asthmatic individuals, rs7216389 was correlated with increased total serum IgE levels (p 0.1). Conclusions: ORMDL3/GSDMB is an important susceptibility gene for childhood-onset adult asthma in Japanese populations and this association is linked to elevated total serum IgE levels but not to allergic sensitization.

Background: The number of nontuberculous mycobacterial lung disease (NTM) is rapidly increasing. Its natural history seems to be complicated, and it is sometimes difficult to decide when chemotherapy (CT) should be started. Our previous study showed that the increase of total cell counts and neutrophil percentages in bronchoalveolar lavage fluid (BALF) were related to the commencement of CT. Neutrophils produce reactive oxygen species, leading to the increase of oxidative stress. Aims: To elucidate whether oxidative stress as well as neutrophils are useful indicators to initiate CT in NTM patients. Methods: Between June 2016 and January 2019, 69 subjects that underwent diagnostic bronchoscopy were included. According to the finding of bronchoscopy, subjects were divided into NTM group and No-NTM group. NTM group were subdivided into Treatment group (NTM-T) and Observation group (NTM-O). We measured serum d-ROM as a marker of oxidants and serum BAP as a marker of antioxidants through a spectrophotometric procedure (FRAS4). Results: Total cell counts as well as neutrophil percentages in BALF were the highest in NTM-T group (P Conclusions: The current study suggested that the predominance of neutrophil in BALF and/or serum oxidative stress markers seemed to be a potential indicator to initiate CT in NTM patients.

Background Marfan Syndrome (MFS) is a heritable connective tissue disorder with a high degree of clinical variability including respiratory diseases; a rare case of MFS with massive intrathoracic bleeding has been reported recently. Case presentation A 32-year-old man who had been diagnosed with MFS underwent a Bentall operation with artificial valve replacement for aortic dissection and regurgitation of an aortic valve in 2012. Warfarin was started postoperatively, and the dosage was gradually increased until 2017, when the patient was transported to our hospital due to sudden massive haemoptysis. Computed tomography (CT) with a maximum intensity projection (MIP) revealed several giant pulmonary cysts with fluid levels in the apex of the right lung with an abnormal vessel from the right subclavian artery. Transcatheter arterial embolization was performed with angiography and haemostasis was achieved, which suggested that the bleeding vessel was the lateral thoracic artery (LTA) branch. CT taken before the incident indicated thickening of the cystic wall adjacent to the thorax; therefore, it was postulated that the bleeding originated from fragile anastomoses between the LTA and pulmonary or bronchial arteries. It appears that the vessels exhibited inflammation that began postoperatively, which extended to the cysts. Conclusion We experienced a case of MFS with massive haemoptysis from the right LTA. We have to be aware of the possibility that massive haemoptysis could be induced in MFS with inflamed pulmonary cysts.

Pulmonary arterial hypertension (PAH) secondary to pulmonary Langerhans cell histiocytosis (PLCH) is known to be a relatively common complication and is associated with a poor prognosis. However, the optimal therapeutic approach for these cases remains to be established. A 57-year-old man visited our hospital because of a progressive dry cough. A thoracic computed tomography examination showed a combination of diffuse thick-walled cysts and reticulonodular shadows that were predominant in bilateral upper lobes of the lungs. He was diagnosed as having PLCH based on the results of video-assisted thoracoscopic lung biopsies. During a 3-year clinical course, his condition deteriorated despite smoking cessation. A systemic evaluation demonstrated precapillary PAH caused by PLCH (PAH-PLCH), and treatment with tadalafil, a phosphodiesterase-5 inhibitor, was started. During a 50-month period of treatment with tadalafil, improvements in his dyspnea, 6-min walking distance, and hemodynamics were maintained without either overt hypoxemia or pulmonary edema. We considered that tadalafil therapy may be a useful option in the treatment of patients with PAH-PLCH.

Background: Recent studies suggest that there are several potential interactions between TGF-β, one of a key regulators of idiopathic pulmonary fibrosis (IPF), and oxidant/antioxidants in the lung. Therefore, an oxidant/antioxidant imbalance is now considered to be one of the pathogenetic factors of IPF. However, there is no consensus whether the oxidative stress (OS) markers are useful indicator of disease severity or disease progression in IPF. Aims: To evaluate the OS markers in patients with IPF, and to explore the relationship between OS levels and clinical state of IPF. Methods: Fifteen untreated patients with IPF and six healthy age-matched control subjects were studied. A pulmonary function test (at baseline and 3-month later), 6-minute walking test, the St. George9s Respiratory Questionnaire, and bronchoalveolar lavage fluid analysis were administered. We measured serum d-ROMs as a marker of oxidants and serum BAP as a marker of antioxidants through a spectrophotometric procedure (FRAS4). Results: Serum levels of d-ROMs were significantly increased, and serum levels of BAP were significantly decreased in patients with IPF compared to controls (dROMs: 427.7±54.4 vs 361.0±61.9 U. CARR, p p Conclusions: The current study suggested that an oxidant/antioxidant imbalance is significantly worse in patients with IPF compared with healthy controls. However, at the moment, OS markers might not be a useful indicator of disease severity or disease progression in IPF.

T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB.To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB.A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups.Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result.In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.