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.

Utility of budgerigar/pigeon/parrot-specific IgG antibody with ImmunoCAP® in bird-related hypersensitivity pneumonitis caused by other bird species and duvet.

BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is an extrinsic allergic alveolitis caused by inhalation of bird antigens. Although the measurement of serum-specific IgG antibodies against budgerigar, pigeon, and parrot with ImmunoCAP® is available in Japan, the utility of the test for patients with causes by bird breeding other than these three species, including contact with wild birds/poultry/bird manure, and use of a duvet is unknown. METHODS: Of the 75 BRHP patients who participated in our previous study, 30 were included. Six cases were caused by bird breeding of species other than pigeon, budgerigar, and parrot, seven were in contact with wild birds/poultry/bird manure, and 17 were using a duvet. Bird-specific IgG antibodies were compared among the patients, 64 controls, and 147 healthy participants. RESULTS: In patients with BRHP caused by bird breeding, budgerigar and parrot-specific IgG levels were significantly higher than in disease controls. Only parrot-specific IgG was significantly higher than in disease controls in patients caused by duvet use. However, among patients with acute episodes (acute and recurrent type of chronic BRHP), IgG antibodies against all three species were significantly higher than those of disease controls caused by bird breeding and the use of a duvet. CONCLUSIONS: Bird-specific IgG antibody with ImmunoCAP® was useful for screening and diagnosing BRHP caused by other bird species and duvets.

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy.

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.

Impaired inflammatory responses to multiple toll-like receptor ligands in alveolar macrophages of streptozotocin-induced diabetic mice.

OBJECTIVE: To investigate the effect of hyperglycemic state on the activation of alveolar macrophages (AMs) mediated via Toll-like receptors (TLRs) typically associated with bacterial infection. METHODS: AMs obtained from normoglycemic control mice and streptozotocin-induced diabetic mice were stimulated ex vivo with the following: a TLR2 ligand, peptidoglycan (PGN); a TLR4 ligand, lipopolysaccharide (LPS); or a TLR5 ligand, flagellin (FLG). Cytokine production and mRNA expression were measured by ELISA and real-time PCR, respectively. TLR expression was assessed by real-time PCR and flow cytometry. RESULTS: AMs from diabetic mice produced significantly less TNF-α after PGN or FLG stimulation, and less IL-6 after FLG stimulation, compared with AMs from control mice. The decrease in the production of these cytokines was associated with reduced mRNA expression of the corresponding cytokines. In contrast, production of TNF-α and IL-6 after LPS stimulation did not differ between groups. Furthermore, there was no substantial difference in the expression of TLR2, TLR4, and TLR5 in AMs between the groups. The increased JNK phosphorylation induced by PGN or FLG stimulation was downregulated in AMs from diabetic mice. CONCLUSIONS: Hyperglycemic state impairs the reactivity of AMs to multiple TLR ligands. This effect might result from hyperglycemia-induced alteration of intracellular signaling and is unlikely due to the modulation of TLR expression.

A case of pulmonary tuberculosis with false negative QuantiFERON TB-2G Test.

A 57-year-old man was admitted to our hospital with a high fever and productive cough. He had a previous history of total gastrectomy and splenectomy at the age of 45 years due to gastric cancer. He also showed severe macrocytic anemia with low vitamin B12, and an infiltrative shadow was found in the right lung on an X-ray. Sputum examination on admission revealed no significant pathogenic bacteria, and an acid-fast stain and a M. tuberculosis PCR test were negative. QuantiFERON TB-2G Test (QFT) was negative on admission. Because pneumococcal antigen in the urine was positive, we initially diagnosed pneumococcal pneumonia and treatment with antibiotics was started. However, symptoms were not resolved with several antibiotics, finally, a thoracoscopic lung biopsy under general anesthesia was performed for a definitive diagnosis. The biopsy showed epithelioid cell granuloma in the alveolar spaces, and the 8 weeks culture of sputum taken on admission revealed M. tuberculosis. Finally, a pulmonary tuberculosis was diagnosed and treatment with four drugs of HERZ was begun. We have encountered a case of pulmonary tuberculosis combined with a lobar pneumococcal pneumonia, and negative for QFT. In general, splenectomy is known as a risk factor of pneumococcal infection. And vitamin B12 deficiency due to gastrectomy is one of the risk factors for cellular immunity impairment and was possibly to the false negative QFT and development of TB.

Herpes zoster in patients with lung cancer treated with PD-1/PD-L1 antibodies.

Background: There are no available clinical data on immunotherapy and the risk of herpes zoster. Materials & methods: This retrospective study included patients with recurrent or advanced lung cancer who were inoperable and ineligible for radiotherapy and were treated with either a PD-1/PD-L1 antibody (136 patients) or an EGFR tyrosine kinase inhibitor (149 patients) at Jichi Medical University Hospital between January 2016 and December 2018. Results: Herpes zoster-free survival was significantly shorter in the PD-1/PD-L1 antibody-treated group compared with the EGFR tyrosine kinase inhibitor-treated group (hazard ratio: 0.20; 95% CI: 0.048-0.84; p = 0.016). PD-1/PD-L1 antibody administration was independently and significantly associated with herpes zoster occurrence. Conclusion: Clinicians should anticipate herpes zoster in patients with lung cancer during treatment with PD-1/PD-L1 antibodies.

There are no available clinical data on immunotherapy and the risk of herpes zoster. This retrospective study included patients with recurrent or advanced lung cancer who were inoperable and ineligible for radiotherapy and were treated with either an immune checkpoint inhibitor (136 patients) or an EGFR tyrosine kinase inhibitor (149 patients) through the authors' university between January 2016 and December 2018. The herpes zoster-free period was significantly shorter in the immune checkpoint inhibitor-treated group compared with the EGFR tyrosine kinase inhibitor-treated group (hazard ratio: 0.20; 95% CI: 0.048­0.84; p = 0.016). Immune checkpoint inhibitor antibody administration was independently and significantly associated with herpes zoster occurrence. Clinicians should be cautious of herpes zoster in patients with lung cancer during treatment with immune checkpoint inhibitors.

[A case of chronic lower respiratory tract infection in which the traditional herbal medicine Hochuekkito was effective to prevent exacerbation].

A thin, 63-year-old man was receiving low-dose macrolide therapy for a diagnosis of chronic lower respiratory tract infection, but frequent exacerbations due to Streptococcus pneumoniae were observed. High-resolution computed tomography (CT) of the chest showed bronchiectasis and small centrilobular nodules in the right lower lobe. He had previously had several episodes of exacerbation of chronic lower respiratory tract infection, for which he had received antibiotic treatments (oral fluoroquinolones or intravenous cephems). However, he continued to experience recurrent exacerbations, and Pseudomonas aeruginosa was also isolated from his sputum. To improve his general condition, Hochuekkito, a herbal medicine, was initiated. His body weight and serum albumin level gradually increased, and after 6 months of administration, neither S. pneumoniae nor P. aeruginosa were isolated from his

[Interstitial pneumonia with anti-PL-7 antibody difficult to distinguish from rheumatoid lung].

A 63-year-old woman had abnormal shadows on a chest radiograph taken on a medical examination during treatment for rheumatoid arthritis. The chest radiograph showed linear and reticular shadows and ground glass opacities in the bibasilar lung fields. Though we considered rheumatoid arthritis due to joint disorder and a positive reaction for serum anti-CCP antibody, there were no bone lesions or articular narrowing on radiographs of the fingers. We diagnosed antisynthetase syndrome after we obtained a positive reaction for serum anti-PL-7 antibody. Antisynthetase syndrome demonstrates findings similar to those of rheumatoid arthritis, and this disease should be taken into consideration if chest computed tomography demonstrates consolidation with predominant patchy and irregular bronchovascular bundle thickening with a subpleural distribution.

A novel protective barrier enclosure for performing bronchoscopy.

Healthcare workers performing bronchoscopy, especially in urgent cases, may be at risk of aerosol-transmitted infection with severe acute respiratory syndrome coronavirus 2. Therefore, such healthcare workers require thorough protection from aerosol droplets. To this end, we developed a novel handmade protective barrier enclosure for performing flexible bronchoscopy. The use of this enclosure did not entail any special technique for handling the bronchoscope during bronchoscopy. The enclosure may be helpful in protecting bronchoscopists from the risk of aerosol-transmitted infections, including coronavirus disease 2019.

A comparative study of the Parker Flex-Tip tube versus standard portex tube for oral fiberoptic intubation in bronchoscopy performed by pulmonologists with limited experience.

BACKGROUND: Fiberoptic tracheal intubation (FTI) in bronchoscopy is widely performed with a conventional Portex tracheal tube (PTT). Occasionally, it is difficult for pulmonologists with limited experience to insert a tube beyond the vocal cords and advance it into the trachea. A new endotracheal tube, the Parker Flex-Tip tube (PFT), was recently designed. We compared the usefulness and safety of PFT versus PTT for FTI in bronchoscopy performed by pulmonologists with limited experience. METHODS: Forty consecutive patients were enrolled and randomly assigned to either the PFT group (n = 20) or PTT group (n = 20). The time required for the tip of the endotracheal tube to pass from the mouth to the carina, the number of vomiting reflexes, the number of attempts to pass the tube through the vocal cords during intubation, complications, and technical difficulty of intubation were evaluated. RESULTS: Both the PFT and PTT groups exhibited high intubation success rates (100% vs. 90%, respectively). The PFT group was intubated faster than the PTT group (11.5 [5-45] s vs. 22.5 [8-270] s, respectively, p < 0.01). The PFT group showed fewer vomiting reflexes and tube impingements than the PTT group (p < 0.05). Operators felt it was easier to intubate with PFT versus PTT (p < 0.01). Complications were not significantly different between the two groups. CONCLUSION: For pulmonologists with limited experience who perform FTI in bronchoscopy, intubation using PFT versus PTT is faster and easier, without an increase in complications.

Highly sensitive detection of driver mutations from cytological samples and cfDNA in lung cancer.

BACKGROUND: Bronchoscopy is a minimally invasive procedure for establishing the diagnosis of lung cancer. It sometimes fails to obtain tissue samples but readily collects cytological samples. METHODS: We developed PNA-LNA dual-PCR (PLDP), which amplified mutant sequences by a high-fidelity DNA polymerase in the presence of a peptide nucleic acid (PNA) oligomer having a wild-type sequence. Mutations are detected either by locked nucleic acid (LNA) probes for quick detection of a limited number of mutations, which are EGFR, KRAS, and BRAF mutations in the current study, or by direct sequencing for a comprehensive screening. In a total of 233 lung cancer samples, the results for cytological samples by PLDP were compared with those for tissue samples by cobas® EGFR mutation test (cobas) or by the PNA-LNA PCR clamp method (P-LPC). Moreover, the performance of PLDP using cell-free DNA (cfDNA) was investigated. RESULTS: Peptide nucleic acid-LNA dual-PCR was able to detect each synthesized mutant sequence with high sensitivity. PLDP detected EGFR mutations in 80 out of 149 clinical samples, while the cobas or the P-LPC detected in 66 matched. The correctness of PLDP was confirmed both by clinical response and by the results of sequencing using a next-generation sequencer. PLDP detected mutations from cfDNA in approximately 70% of patients who harbors mutations in the tumor. CONCLUSIONS: Peptide nucleic acid-LNA dual-PCR exhibited an excellent performance, even using cytological samples. PLDP is applicable for the investigation of cfDNA. The combination of bronchoscopy and PLDP is attractive and will expand the utility of bronchoscopy in clinical practice.