Detection of multiple druggable mutations of lung cancer from cytology specimens by MINtS: An advanced medicine A trial.

Most multigene mutation tests require tissue specimens. However, cytological specimens are easily obtained in the clinical practice and provide high-quality DNA and RNA. We aimed to establish a test that utilizes cytological specimens and performed a multi-institutional study to investigate the performance of MINtS, a test based on next-generation sequencing. A standard procedure for specimen isolation was defined. The specimens were considered suitable for the test if >100 ng DNA and >50 ng RNA could be extracted from them. In total, 500 specimens from 19 institutions were investigated. MINtS detected druggable mutations in 63% (136 of 222) of adenocarcinomas. Discordant results between MINtS and the companion diagnostics were observed in 14 of 310 specimens for the EGFR gene, and 6 of 339 specimens for the ALK fusion genes. Confirmation by other companion diagnostics for the EGFR mutations or the clinical response to an ALK inhibitor all supported the results obtained by MINtS. MINtS along with the isolation procedure presented in the current study will be a platform to establish multigene mutation tests that utilize cytological specimens. UMIN000040415.

Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®.

BACKGROUND: Bird antigens are some of the most relevant antigens in hypersensitivity pneumonitis (HP). Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings. For the screening and diagnosis of HP, the measurement of bird-specific antibodies should be standardized. The aim of this study was to clarify the utility of serum IgG (sIgG) and IgA (sIgA) antibodies to bird antigens in screening and diagnosing acute/chronic bird-related HP with ImmunoCAP® in multi-centre clinical research. METHODS: We executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients. RESULTS: The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects. For sIgG, the optimal cutoff values by receiver operating characteristic (ROC) analysis were 24.6 mgA/L for pigeon, 14.0 mgA/L for parrot, and 8.7 mgA/L for budgerigar. By measuring multiple bird antigens and combining sIgG values of two species, the sensitivity and specificity for acute and recurrent-type chronic bird-related HP patients were 85-91% and 73-80%, respectively. For recurrent and insidious types of chronic bird-related HP, the sensitivity and specificity were 48-61% and 73-80%, respectively. CONCLUSIONS: Measurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP.

Scanning electoronmicroscopical analysis of the loose bodies of synovial chondoromatosis in temporomandibular joint.

The aim of this study is to reveal the morphological property about the loose bodies (LBs) of temporomandibular joint (TMJ) by scanning electron microscope (SEM). We obtained specimens from two female cases of released loose body by surgical operation. These specimens were fixed by soaking in a mixture of 5% glutaraldehyde or 4% formaldehyde for one week. They were cut into half pieces. These specimens were observed at an accelerating voltage of 3 kV under a SEM (JSM-5500, JEOL, Tokyo). In the electron microscopic findings, it seems to be separated into two different parts as inside part and outside part. On the inside part, collagen fibers were running very densely in the same direction in an orderly neatly manner. Whereas, we observed waved collagen fibers running irregularly with many spaces on the outside part. Outside part seems to be porous pattern compared with inside part. It might be that the surface and outside part included many active fibroblasts. As results, it seems that the LBs might develop in a multi-layer style, in which fibrous tissues were piled up loosely around the inside part. The proliferating activity of LBs grows from the inside to outside of SC in TMJ.

Pulmonary Mycobacterium heckeshornense infection in a healthy woman.

Pulmonary infection due to Mycobacterium heckeshornense (M. heckeshornense) in healthy adults without underlying diseases is very rare and optimal treatments have not yet been established. A 39-year-old woman was admitted to our hospital for further examinations following the identification of a pulmonary cavitary nodule. Acid-fast bacilli were cultured from specimens obtained by bronchofiberscopy, and identified with M. heckeshornense using nucleotide sequencing. Antimycobacterial chemotherapy was effective temporarily, while the nodular lesion subsequently worsened. The patient underwent lobectomy and has not relapsed thus far. A lung specimen showed marked granulomatous inflammation with extensive caseous necrosis and the preservation of some parts of alveolar septa within caseous necrosis, indicating an exudative process and resistance to chemotherapy. M. heckeshornense is strongly pathogenic and switching to surgical intervention needs to be considered when chemotherapy is insufficient.

Physical activity in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Physical activity is an important parameter in patients with chronic obstructive pulmonary disease, but has not been studied in detail in patients with interstitial lung disease. This study aimed to evaluate physical activity in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Physical activity was monitored in 31 stable IPF patients using an accelerometer for 1 month. The following factors reflecting physical activity were measured: the number of steps, walking distance, the time spent at magnitude of movement (MM) 1-6, physical activity-related energy expenditure (PAEE) and total energy expenditure. We also measured the following clinical parameters: the modified Medical Research Council (MRC) scale, Krebs von den Lungen-6 (KL-6), pulmonary function parameters, 6-min walk test (6MWT) results and high-resolution computed tomography (HRCT) findings of the chest. We determined the relationship between these parameters and physical activity. RESULTS: We recorded 24 days of physical activity data. The time spent at MM < 1 was more than 10 h per day, whereas that at MM > 1 was approximately 1 h per day. The modified MRC scale, serum KL-6 levels, 6MWT distance, and the extent of honeycomb and reticular abnormality on HRCT were associated with several facets of physical activity. In particular, lower KL-6 levels were correlated with higher physical activity based on the number of steps, walking distance, the time spent at MM 1-4 and PAEE. CONCLUSIONS: The modified MRC scale, 6MWT distance, extent of fibrosis on HRCT and serum KL-6 levels are strongly associated with physical activity.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): revolutionizing the landscape of lung disease diagnostics.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a revolutionary diagnostic tool for lung diseases, including lung cancer, sarcoidosis, and lymphoproliferative diseases. This minimally invasive procedure offers a superior diagnostic yield while ensuring maximum patient safety when compared to traditional invasive techniques such as mediastinoscopy and thoracoscopy. By enabling real-time imaging and sampling of mediastinal and hilar lymph nodes and masses directly from the bronchoscope, EBUS-TBNA has redefined the precision of diagnostic bronchoscopy. This comprehensive review explores the origins, development, and current status of EBUS-TBNA, highlighting its successes and identifying potential areas for improvement. Technological advancements have continuously enhanced the reliability and efficacy of EBUS-TBNA over time. The mechanisms underlying the superior diagnostic yield of EBUS-TBNA are thoroughly discussed, further solidifying its position as the gold standard for lung cancer staging and diagnosis. Furthermore, this review delves into the crucial role of EBUS-TBNA in lung cancer diagnosis, supported by studies comparing its accuracy, safety, and cost-effectiveness to other diagnostic tools. Looking ahead, ongoing research aims to expand the applications of EBUS-TBNA and improve its diagnostic performance. Notable advancements in needle design and sampling techniques hold promise for further enhancing its efficacy. Maximizing its potential through comprehensive training and continuous technological developments will enable broader clinical applications, ultimately leading to improved patient outcomes. As EBUS-TBNA continues to evolve, its diagnostic impact is expected to increase, solidifying its position as an indispensable tool in the diagnosis and management of lung diseases.

Clinical significance of interleukin 33 (IL-33) in patients with eosinophilic pneumonia.

BACKGROUND: Interleukin 33 (IL-33) works as a functional mediator in allergic disease by enhancing the activity of eosinophils and inducing expression of T helper 2 (Th2)-associated cytokines. However, the role of IL-33 in pulmonary eosinophilia has not been elucidated. We investigated the levels of IL-33 in eosinophilic pneumonia (EP) together with associated cytokines, and discussed the clinical significance of IL-33 in EP. METHODS: Sera and bronchoalveolar lavage fluid (BALF) were obtained from 16 patients with EP, including acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP). Twelve patients with acute respiratory distress syndrome (ARDS) were also included for comparison. The concentration of IL-33 and Th2 cytokines (IL-4, IL-5, IL-13) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of serum IL-33 was significantly higher in patients with AEP than in CEP. In CEP, only patients with atopic factors showed mild increase of serum IL-33. The concentration of BALF IL-33 was also significantly elevated in AEP, however, it remained quite low in CEP. Among Th2 cytokines, IL-5 was significantly increased in both serum and BALF in AEP, and the level of IL-5 was positively correlated with that of IL-33. ARDS showed no increase of serum and BALF IL-33. CONCLUSIONS: The remarkable increase of BALF IL-33 in AEP indicated the local production of IL-33 in lungs. IL-33 is considered to be a local key molecule for triggering pulmonary eosinophilia, together with IL-5. BALF IL-33 appears to be a useful marker for discriminating AEP from CEP and ARDS.

[Clinical evaluation of inpatients with tuberculosis diagnosed after admission--comparison of characteristics of patients diagnosed with and without the acid-fast bacillus test].

PURPOSE: To evaluate the clinical characteristics of patients in whom tuberculosis was not suspected before admission but was diagnosed after admission. METHODS: We enrolled 39 inpatients who were diagnosed with tuberculosis between April 2007 and March 2011 at Jichi Medical University Hospital. The patients were divided into 2 groups as follows: those who underwent a preadmission acid-fast bacillus (AFB) test (AFB group) and those who did not (non-AFB group). We retrospectively evaluated the clinical characteristics of these 2 groups of patients. RESULTS: A total of 22 patients and 17 patients comprised the non-AFB and AFB groups, respectively. The prevalence rates of malignancy (9 vs. 2 patients, p = 0.04), extrapulmonary tuberculosis without pulmonary tuberculosis (9 vs. 2 patients, p = 0.04), and smear-negative tuberculosis (16 vs. 7 patients, p = 0.04) were higher in the non-AFB group than in the AFB group. In contrast, the computed tomographic findings of the patients with pulmonary tuberculosis revealed that compared with the AFB group, the non-AFB group had less consolidation (2 vs. 11 patients, p < 0.01) and fewer cavitary lesions (0 vs. 6 patients, p < 0.01) and more nodular lesions (8 vs. 2 patients, p < 0.01). We then divided the inpatients into groups with and without malignancy and compared their clinical characteristics. The mean interval from admission to diagnosis of tuberculosis was significantly longer in the patients with malignancy as an underlying disease than in those without malignancy (23.5 vs. 10.5 days; p < 0.01). CONCLUSION: Malignancy was the most frequent underlying disease in the tuberculosis inpatients in the non-AFB group and could be the reason for the delayed diagnosis of tuberculosis.

Prevalence of systemic and local risk factors for pulmonary non-tuberculous mycobacterial disease in Japan: a single-institution study.

Objective: To identify the prevalence of risk factors for pulmonary non-tuberculous mycobacterial (NTM) disease in a Japanese population. Patients and Methods: We reviewed 337 consecutive Japanese patients (210 women) with pulmonary NTM disease, including 225 patients with Mycobacterium avium complex (MAC) disease (95.8%) at our hospital during 2006-2017. We calculated the prevalence of risk factors reported in Western countries among mycobacterial species. Results: Pulmonary MAC disease cases comprised 78.2% of pulmonary NTM patients in their 40s, increasing to 100% at age ≥80 years. Body mass index (BMI) was <18.5 in approximately 40% of patients, which was significantly higher than the prevalence of underweight in the Japanese population. The percentage of male heavy smokers (Brinkman index ≥600) was 58.2% of pulmonary NTM disease and was high for all mycobacterial species. In pulmonary MAC disease, systemic factors were observed in the order of malignant tumors (other than lung cancer), diabetes, rheumatoid arthritis, and tuberculosis. Local factors were observed in the order of bronchiectasis, chronic obstructive pulmonary disease, lung cancer, and bronchial asthma. Conclusion: The risk factors reported in Western countries were relatively highly prevalent among Japanese pulmonary NTM disease patients. This observation may help elucidate disease onset mechanisms.