Non-tuberculosis Mycobacterial Pulmonary Disease Caused by Mycobacterium kiyosense, a New Species.

Non-tuberculosis mycobacterial (NTM) pulmonary disease (NTM-PD) is quite common, and newly identified species are being reported increasingly frequently thanks to advances in identification technologies. A 56-year-old woman had mild sputum production showed bronchiectasis with multiple small nodules, consistent with NTM-PD, on chest computed tomography. Mycobacterial species were isolated from the specimens; however, conventional methods could not identify the species. We conducted whole-genome sequencing and identified the NTM isolates as Mycobacterium kiyosense, a species newly registered in 2023 from Japan. She was diagnosed with NTM-PD caused by M. kiyosense and received watchful waiting.

Palliative care for interstitial lung disease: A nationwide survey of pulmonary specialists.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) is progressive with high symptom burdens and poor prognosis. Patients with ILD need optimal palliative care to maintain their quality of life, however, few nationwide surveys have addressed palliative care for ILD. METHODS: A nationwide, self-administered questionnaire was conducted. Questionnaires were sent by mail to pulmonary specialists certified by the Japanese Respiratory Society (n = 3423). The current practices of PC for ILD, end-of-life communication, referral to a PC team, barriers to PC for ILD, and comparison of PC between ILD and lung cancer (LC). RESULTS: 1332 (38.9%) participants completed the questionnaire, and the data of 1023 participants who had cared for ILD patients in the last year were analysed. Most participants reported that ILD patients often or always complained of dyspnoea and cough, but only 25% had referred them to a PC team. The timing of end-of-life communication tended to be later than the physician-perceived ideal timing. The participants experienced significantly greater difficulty in symptomatic relief and decision-making in PC for ILD compared to LC. Prescription of opioids for dyspnoea was less frequent for ILD than for LC. ILD-specific barriers in PC included an 'inability to predict prognosis', 'lack of established treatments for dyspnoea', 'shortage of psychological and social support', and 'difficulty for patients/families to accept the disease's poor prognosis'. CONCLUSION: Pulmonary specialists experienced more difficulty in providing PC for ILD compared to LC and reported considerable ILD-specific barriers in PC. Multifaceted clinical studies are needed to develop optimal PC for ILD.

End-of-life care for idiopathic pulmonary fibrosis patients with acute exacerbation.

BACKGROUND: Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). AE-IPF patients require optimal palliative care; however, the real-world clinical situations are poorly understood. We aimed to survey the palliative care received by AE-IPF patients, especially with respect to opioid use for dyspnea and the end-of-life discussions (EOLd). METHODS: Self-administered questionnaires were dispatched to 3423 of the certified pulmonary physicians in Japan. They were asked to report a care report form of one patient each with AE-IPF who died very recently about opioid use for dyspnea and EOLd. We further explored the factors associated with the early use of opioids for dyspnea. RESULTS: Among the 3423 physicians, 1226 (35.8%) returned the questionnaire with the report forms of 539 AE-IPF patients. Of 539 AE-IPF patients, 361 (67.0%) received opioids for dyspnea. Of the 361 patients, 72 (20.0%) received opioids during the initial treatment with an intention of recovery (early use), while 289 (80.0%) did when the recovery was deemed impossible. EOLd was held before the onset of AE in 124 patients (23.0%); however, the majority of patients had EOLd after the admission for AE-IPF. EOLd before the onset of AE was significantly associated with the early use of opioids. CONCLUSION: In terminally ill AE-IPF patients, opioids are usually administered when the recovery is deemed impossible, and EOLd are rarely held before the onset of AE. Further studies are warranted on the efficacy of opioids for dyspnea and the appropriate timing of EOLd.

Clinical practice of high-flow nasal cannula therapy in COVID-19 pandemic era: a cross-sectional survey of respiratory physicians.

BACKGROUND: Despite the rapid widespread use of a high-flow nasal cannula (HFNC) during the COVID-19 pandemic, its indications and appropriate use as perceived by physicians remain poorly known. METHODS: In September 2021, we sent a questionnaire to each respiratory physician from 15 institutions in Shizuoka prefecture, Japan. In this survey, we compared the perceptions of HFNC indications and interventions during implementation to those of non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV). Furthermore, this study examined concerns about SARS-CoV-2 infection spread and psychological distress experienced among respondents. RESULTS: Of the 140 respiratory physicians contacted, 87 (62.1%) completed the survey. The results indicate that 96.5% of the respondents agreed with the indication of HFNC for COVID-19, whereas only 13.7% agreed with NIV. The physicians reported that patients with HFNC had a lower frequency of sustained sedation, physical restraint, and implementation in the ICU than that of patients with NIV and IMV. The HFNC was introduced as a respiratory modality following conventional oxygen therapy (COT) in patients with COVID-19, regardless of full or do-not-intubate codes. Additionally, they reported that patients with COVID-19 switched from COT to HFNC significantly earlier than those without COVID-19. Simultaneously, this survey revealed persistent concerns of SARS-CoV-2 infection spread and psychological distress (47.1% and 53.3%, respectively) among respiratory physicians during HFNC use. CONCLUSION: Clinically, HFNC is considered useful for COVID-19 patients by most respiratory physicians. However, HFNC remains a concern for COVID-19 spread and psychological distress among several respiratory physicians, indicating the need for urgent action.

Chromatin-remodeling factor BAZ1A/ACF1 targets UV damage sites in an MLL1-dependent manner to facilitate nucleotide excision repair.

Ultraviolet (UV) light irradiation generates pyrimidine dimers on DNA, such as cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts. Such dimers distort the high-order DNA structure and prevent transcription and replication. The nucleotide excision repair (NER) system contributes to resolving this type of DNA lesion. There are two pathways that recognize pyrimidine dimers. One acts on transcribed strands of DNA (transcription-coupled NER), and the other acts on the whole genome (global genome-NER; GG-NER). In the latter case, DNA damage-binding protein 2 (DDB2) senses pyrimidine dimers with several histone modification enzymes. We previously reported that histone acetyltransferase binding to ORC1 (HBO1) interacts with DDB2 and facilitates recruitment of the imitation switch chromatin remodeler at UV-irradiated sites via an unknown methyltransferase. Here, we found that the phosphorylated histone methyltransferase mixed lineage leukemia 1 (MLL1) was maintained at UV-irradiated sites in an HBO1-dependent manner. Furthermore, MLL1 catalyzed histone H3K4 methylation and recruited the chromatin remodeler bromodomain adjacent to zinc finger domain 1A (BAZ1A)/ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1). Depletion of MLL1 suppressed BAZ1A accumulation at UV-irradiated sites and inhibited the removal of CPDs. These data indicate that the DDB2-HBO1-MLL1 axis is essential for the recruitment of BAZ1A to facilitate GG-NER.

Impact of end-of-life respiratory modalities on quality of dying and death and symptom relief in patients with interstitial lung disease: a multicenter descriptive cross-sectional study.

BACKGROUND: Respiratory modalities applied at the end of life may affect the burden of distressing symptoms and quality of dying and death (QODD) among patients with end-stage interstitial lung disease (ILD); however, there have been few studies into respiratory modalities applied to these patients near death. We hypothesized that high-flow nasal cannula (HFNC) might contribute to improved QODD and symptom relief in patients with end-stage ILD. OBJECTIVES: This multicenter study examined the proportion of end-of-life respiratory modalities in a hospital setting and explored its impact on QODD and symptom relief among patients dying with ILD. METHODS: Consecutive patients with ILD who died in four participating hospitals in Japan from 2015 to 2019 were identified and divided into four groups according to end-of-life respiratory modality: conventional oxygen therapy (COT), HFNC, non-invasive ventilation (NIV), and invasive mechanical ventilation (IMV). In addition, a mail survey was performed to quantify the QODD and symptom relief at their end of life from a bereaved family's perspective. QODD and symptom relief were quantified using the Good Death Inventory (GDI) for patients with a completed bereavement survey. The impact of end-of-life respiratory modalities on QODD and symptom relief was measured by multivariable linear regression using COT as a reference. RESULTS: Among 177 patients analyzed for end-of-life respiratory modalities, 80 had a completed bereavement survey. The most common end-of-life respiratory modality was HFNC (n = 76, 42.9%), followed by COT (n = 62, 35.0%), NIV (n = 27, 15.3%), and IMV (n = 12, 6.8%). Regarding the place of death, 98.7% of patients treated with HFNC died outside the intensive care unit. Multivariable regression analyses revealed patients treated with HFNC had a higher GDI score for QODD [partial regression coefficient (B) = 0.46, 95% CI 0.07-0.86] and domain score related to symptom relief (B = 1.37, 95% CI 0.54-2.20) than those treated with COT. CONCLUSION: HFNC was commonly used in patients with end-stage ILD who died in the hospital and was associated with higher bereaved family ratings of QODD and symptom relief. HFNC might contribute to improved QODD and symptom relief in these patients who die in a hospital setting.

Quality of dying and death in patients with interstitial lung disease compared with lung cancer: an observational study.

BACKGROUND: There is limited knowledge regarding the quality of dying and death (QODD) and end-of-life interventions in patients with interstitial lung disease (ILD). Hence, differences in QODD and end-of-life interventions between patients with ILD and those with lung cancer (LC) remain poorly understood. METHODS: The primary aim of this study was to explore the differences in QODD and end-of-life interventions among patients dying with ILD versus those dying with LC. We performed a mail survey to quantify the QODD of a bereaved family's perspective using the Good Death Inventory (GDI) score. Moreover, we examined the end-of-life interventions by medical chart review. RESULTS: Of 361 consecutive patients analysed for end-of-life interventions, 167 patients whose bereaved families completed questionnaires were analysed for QODD. Patients with ILD had lower GDI scores for QODD than those with LC (p=0.04), particularly in domains related to 'physical and psychological distress relief' and 'prognosis awareness and participation in decision making' (p=0.02, respectively). In end-of-life interventions, patients with ILD were less likely to receive specialised palliative care services (8.5% vs 54.3%; p<0.001) and opioids (58.2% vs 73.4%; p=0.003). Additionally, lower frequencies of participation of patients with ILD in end-of-life discussion were also observed (40.8% vs 62.4%; p=0.007). CONCLUSION: Patients with ILD had lower QODD and poorer access to palliative care and decision making than those with LC. Additional efforts to improve QODD in patients with ILD, particularly in symptom relief and decision-making processes, are urgently warranted.

Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study.

INTRODUCTION: Programmed cell death protein 1 immune checkpoint inhibitors (ICIs) have been reported to improve the survival of patients with NSCLC. On the expansion of clinical administration for a variety of cancers, immune-related adverse events have been typically recognized to be associated with ICIs, therefore, necessitating the monitoring and management of these patients. Among immune-related adverse events, immune-related interstitial lung disease (ir-ILD) is a serious complication that interrupts treatment and can occasionally be fatal. However, no prospective studies have investigated the incidence of ir-ILD and associated risk factors for its development in the clinical setting. METHODS: This is a prospective cohort study consisting of patients with NSCLC treated with ICIs. Baseline characteristics, including laboratory data, pulmonary function tests, daily symptoms of dyspnea defined by the modified Medical Research Council, and antitumor response were assessed. RESULTS: Among the 138 patients with NSCLC who received anti-programmed cell death protein 1 monotherapy, 20 patients (14.5%) had ir-ILD within median 51.5 days (interquartile range: 29-147). This was approximately three times higher than those in clinical trials. A total of 11 patients (55.0%), including all eight patients with high-grade ir-ILD (≥grade 3), developed ir-ILD within 60 days. Impaired spirometry, decreased forced vital capacity and forced expiratory volume in 1 second, and daily symptoms of dyspnea measured using the modified Medical Research Council scale were identified as risk factors for ir-ILD development. In addition, combination assessment of forced vital capacity and forced expiratory volume in 1 second successfully classified patients at risk for ir-ILD development. CONCLUSIONS: The incidence of ir-ILD was substantially higher in the clinical setting. Assessment of spirometry and daily dyspneic symptoms before ICI treatment may be useful in monitoring and managing patients with NSCLC.

Pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 hours after high-flow nasal cannula (HFNC) initiation is a good predictor of HFNC therapy in patients with acute exacerbation of interstitial lung disease.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy provides effective respiratory management in patients with hypoxemic respiratory failure. However, the efficacy and tolerability of HFNC for patients with acute exacerbation of interstitial lung disease (AE-ILD) have not been established. This study was performed to assess the efficacy and tolerability of HFNC for patients with AE-ILD and identify the early predictors of the outcome of HFNC treatment. METHODS: We retrospectively reviewed the records of patients with AE-ILD who underwent HFNC. Overall survival, the success rate of HFNC treatment, adverse events, temporary interruption of treatment, discontinuation of treatment at the patient's request, and predictors of the outcome of HFNC treatment were evaluated. RESULTS: A total of 66 patients were analyzed. Of these, 26 patients (39.4%) showed improved oxygenation and were successfully withdrawn from HFNC. The 30-day survival rate was 48.5%. No discontinuations at the patient's request were observed, and no serious adverse events occurred. The pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 h after initiating HFNC showed high prediction accuracy (area under the receiver operating characteristic curve, 0.802) for successful HFNC treatment. In the multivariate logistic regression analysis, an SpO2/FIO2 ratio of at least 170.9 at 24 h after initiation was significantly associated with successful HFNC treatment (odds ratio, 51.3; 95% confidence interval, 6.13-430; p < 0.001). CONCLUSIONS: HFNC was well tolerated in patients with AE-ILD, suggesting that HFNC is a reasonable respiratory management for these patients. The SpO2/FIO2 ratio 24 h after initiating HFNC was a good predictor of successful HFNC treatment. The reviews of this paper are available via the supplemental material section.

Impact of early inflammatory cytokine elevation after commencement of PD-1 inhibitors to predict efficacy in patients with non-small cell lung cancer.

Early elevation of inflammatory cytokines, such as IL-6 or TNF-α, or CRP, which is a surrogate marker for IL-6, following commencement of PD-1/L1 inhibitors (PD1-I) may represent early activation of immune-cells. Serum IL-6 and TNF-α were measured in 10 non-small cell lung cancer patients who were evaluable within the 7 days before and after commencement of PD1-I. For CRP, medical records were reviewed and 34 patients with measured CRP within the 7 days before and after the treatment were evaluated. In the 10 patients analyzed for IL-6/TNF-α, the serum levels of IL-6/TNF-α were not significantly different between pre- and post-initial PD1-I [IL-6 20.3 (2.6-49.9) and 22.9 (3.6-96.1) pg/mL, p = 0.453; TNF-α 1.6 (0.7-6.3) and 3.3 (0.7-9.6) pg/mL, p = 0.329]; however, all four responses were observed among the 7 IL-6-elevated cases, resulting in a response rate of 57%. In the 34 patients analyzed for CRP, CRP was significantly increased after initial PD1-I [1.8 (0.1-17.8) mg/dL, 2.4 (0.0-27.8), p = 0.001]. Notably, in the 31 evaluable cases, all responses were again observed in either the IL-6 or CRP elevated groups and the response rate was 46% (11 of 24). The median overall survival time was not reached in the elevated group and was 112 days in the non-elevated group (p = 0.069). The early increase in inflammatory cytokines with PD1-I was indicated to be predictive for the efficacy in patients with non-small cell lung cancer.

Efficacy and Tolerability of High-Flow Nasal Cannula Oxygen Therapy for Hypoxemic Respiratory Failure in Patients with Interstitial Lung Disease with Do-Not-Intubate Orders: A Retrospective Single-Center Study.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy may provide effective respiratory management of hypoxemic respiratory failure in patients with interstitial lung disease (ILD) with a do-not-intubate (DNI) order. OBJECTIVES: The aim was to assess the efficacy and tolerability of HFNC for these patients. METHODS: We retrospectively reviewed the records of patients requesting a DNI order for hypoxemic respiratory failure associated with ILD, comparing treatment with HFNC and noninvasive positive pressure ventilation (NPPV). Outcomes measured were 30-day survival, in-hospital mortality, temporary interruption and discontinuation of the treatment at the patient's request, adverse events, oral intake, and communication ability at the end of life. RESULTS: A total of 84 patients (HFNC, n = 54; NPPV, n = 30) were analyzed. Neither 30-day survival (HFNC 31.5% vs. NPPV 30.0%; p = 0.86) nor in-hospital mortality (HFNC 79.6% vs. NPPV 83.3%; p = 0.78) differed significantly. The temporary interruption and discontinuation rates were significantly lower in the HFNC group than in the NPPV group (3.7 vs. 23.3%; p = 0.009 and 0 vs. 10%; p = 0.043, respectively), and that group had significantly fewer adverse events. Among patients who died in the hospital, those treated with HFNC had significantly better oral intake and ability to converse until just before death. CONCLUSION: HFNC had a survival rate equivalent to that of NPPV and was better tolerated by patients with hypoxemic respiratory failure associated with ILD who had a DNI order. HFNC allowed patients to eat and converse until just before death, suggesting that HFNC in these patients is a reasonable palliative treatment.