The product of trunk muscle area and density on the CT image is a good indicator of energy expenditure in patients with or at risk for COPD.

BACKGROUND: Physical inactivity due to cachexia and muscle wasting is well recognized as a sign of poor prognosis in chronic obstructive pulmonary disease (COPD). However, there have been no reports on the relationship between trunk muscle measurements and energy expenditure parameters, such as the total energy expenditure (TEE) and physical activity level (PAL), in COPD. In this study, we investigated the associations of computed tomography (CT)-derived muscle area and density measurements with clinical parameters, including TEE and PAL, in patients with or at risk for COPD, and examined whether these muscle measurements serve as an indicator of TEE and PAL. METHODS: The study population consisted of 36 male patients with (n = 28, stage 1-4) and at risk for (n = 8) COPD aged over 50 years. TEE was measured by the doubly labeled water method, and PAL was calculated as the TEE/basal metabolic rate estimated by the indirect method. The cross-sectional areas and densities of the pectoralis muscles, rectus abdominis muscles, and erector spinae muscles were measured. We evaluated the relationship between these muscle measurements and clinical outcomes, including body composition, lung function, muscle strength, TEE, and PAL. RESULTS: All the muscle areas were significantly associated with TEE, severity of emphysema, and body composition indices such as body mass index, fat-free mass, and trunk muscle mass. All trunk muscle densities were correlated with PAL. The product of the rectus abdominis muscle area and density showed the highest association with TEE (r = 0.732) and PAL (r = 0.578). Several trunk muscle measurements showed significant correlations with maximal inspiratory and expiratory pressures, indicating their roles in respiration. CONCLUSIONS: CT-derived measurements for trunk muscles are helpful in evaluating physical status and function in patients with or at risk for COPD. Particularly, trunk muscle evaluation may be a useful marker reflecting TEE and PAL.

Efficacy and Safety of Anti-Programed Death-1 Blockade in Previously Treated Large-Cell Neuroendocrine Carcinoma.

BACKGROUND: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare tumor with an aggressive clinical course. However, there is limited knowledge of its treatment strategy. This retrospective study aimed to assess the efficacy and safety of anti-programed death-1 (PD-1) blockade monotherapy in previously treated advanced LCNEC. METHODS: Eleven patients with previously treated advanced LCNEC who received immune checkpoint inhibitor monotherapy between January 2015 and November 2020 were retrospectively analyzed for efficacy and safety. RESULTS: Of a total of 11 patients (median [range] age, 66 [37-79] years; 8 men [73%] and 3 women [27%]), 8 patients had performance status (PS) 0-1 [73%] and 3 patients had PS 2 [27%]; 9 patients received 1 prior chemotherapy [82%] and 2 patients received 2 prior chemotherapies [18%]. The median follow-up duration was 4.6 months. Although PD-1 blockade was administered at median cycles of 3 (range, 1-12), overall response rate, median progression-free survival, and median overall survival were 9.1%, 2.7 months, and 4.6 months, respectively. Any adverse events were observed in 9 patients (82%), including 1 patient with grade 3 pneumonitis as a serious adverse event. CONCLUSION: Anti-PD-1 blockade monotherapy as a subsequent line for previously treated advanced LCNEC exhibited usefulness and tolerability and was identified as a valid treatment option.

Non-exercise Activity Thermogenesis Correlated With Clinical Parameters in Patients With or At-Risk for Chronic Obstructive Pulmonary Disease (COPD): A Pilot Study.

BACKGROUND: Attention to physical activity has grown in patients with chronic obstructive pulmonary disease (COPD), as it serves as a robust indicator for mortality associated with COPD. Non-exercise activity thermogenesis (NEAT) is the energy expenditure due to physical activities besides active sports-like exercises and resistance training in daily life, and decreased NEAT may be related to physical inactivity in patients with COPD. We examined whether NEAT assessed using a questionnaire reflects clinical parameters in patients with or at risk for COPD. METHODS: The study participants consisted of 36 male patients (COPD=28; stage1=6, stage2=14, stage3/4=8, and at-risk for COPD=8) older than 50 years of age. The participants underwent anthropometric measurements, lung function testing, a six-minute walk test, muscle strength testing, and questionnaires, e.g., the COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and Hospital Anxiety and Depression Scale. Image analysis with chest computed tomography (CT) included the number of trunk muscles, bronchial wall thickening, and emphysema (percentage of the lung field occupied by low attenuation area <-950 HU). We evaluated the relationship between these clinical parameters and NEAT questionnaire scores using Pearson correlation analysis and the Tukey-Kramer test. RESULTS: The NEAT score was correlated with the severity of airflow limitation and airway wall thickness measured by chest CT, symptoms evaluated by the mMRC dyspnea scale and CAT, and inspiratory muscle strength and pectoralis muscle area assessed by CT. CONCLUSION: Our study revealed the significance of NEAT as a valuable indicator in assessing the health status of patients with or at risk for COPD. The NEAT score was correlated with various clinical traits, suggesting that incorporating NEAT assessments using a questionnaire can contribute to a comprehensive understanding of the clinical condition in these patients. Further large-scale studies are warranted to validate and generalize these findings across diverse COPD populations.

A case of bunashimeji mushroom-induced hypersensitivity pneumonitis diagnosed by inhalational provocation test in a hospital room.

A 66-year-old woman was admitted to our hospital with a 2-month history of dry cough and exertional dyspnea. She had worked as a mushroom farmer and had been exposed to mushroom for more than 40 years. The patient showed elevated levels of KL-6 (2966 U/mL) and surfactant protein D (410 ng/mL), and computed tomography of the chest revealed ground-glass opacities and fine nodular shadows in both lungs, suggesting mushroom-induced hypersensitivity pneumonitis. Pulmonary function testing revealed decreases in forced vital capacity (78% of predicted) and carbon monoxide diffusing capacity (67% of predicted). The inhalational provocation test was positive for bunashimeji mushrooms. Precipitating antibody was only identified for spores or bodies of bunashimeji mushrooms, and lymphocyte stimulation testing with spores or bodies of bunashimeji mushrooms also yielded positive results. Bunashimeji mushroom-induced hypersensitivity pneumonitis was therefore diagnosed. Radiological findings and pulmonary function were improved by corticosteroid therapy and the patient has since remained healthy with allergen avoidance.

Improvement of sleep parameters by titration polysomnography could predict adherence to positive airway pressure therapy in obstructive sleep apnea.

STUDY OBJECTIVES: Poor adherence to continuous positive airway pressure (CPAP) has been a critical issue in treating obstructive sleep apnea. Because long-term CPAP adherence may be established shortly after treatment begins, early intervention is essential. This study aimed to identify the potential factors affecting CPAP therapy adherence during diagnostic polysomnography and auto CPAP titration polysomnography. METHODS: This retrospective observational study included 463 patients with obstructive sleep apnea who underwent consecutive diagnostic polysomnography and titration polysomnography. We recorded their demographic, anthropometric, and lifestyle factors and obtained self-reported comments regarding their sleep status following both polysomnography evaluations. CPAP adherence was evaluated following 3 months of treatment. RESULTS: A total of 312 patients (67.4%) fulfilled the criteria for good adherence. Each patient's CPAP adherence was categorized as "poor" (< 4 hours/night or <70% of nights), "good" (≥ 4 hours/night and ≥ 70% of nights), or "excellent" (≥ 6 hours/night and ≥ 80% of nights). There were no significant differences in arterial oxyhemoglobin saturation measured by pulse oximetry and apnea-hypopnea index during diagnostic polysomnography among 3 groups. The polysomnographic evaluations indicated that patients with better adherence displayed more significant improvements in sleep parameters, including apnea-hypopnea index, sleep efficacy, sleep latency, and sleep architecture, which were correlated with an improvement in self-reported sleep quality. CONCLUSIONS: Polysomnographic evaluations enabled CPAP adherence prediction and a comparison of self-reported sleep quality with and without CPAP; CPAP adherence led to improvements in polysomnographic parameters. Our findings suggest that titration polysomnography and self-reported sleep improvement with CPAP could be used for adherence prediction in clinical practice. CITATION: Shirahata T, Uchida Y, Uchida T, et al. Improvement of sleep parameters by titration polysomnography could predict adherence to positive airway pressure therapy in obstructive sleep apnea. J Clin Sleep Med. 2023;19(8):1465-1473.

Impact of non-exercise activity thermogenesis on physical activity in patients with COPD.

Physical inactivity is associated with comorbidities and mortality in chronic obstructive pulmonary disease (COPD) patients. Although non-exercise activity thermogenesis (NEAT) is important for evaluating the physical activity level (PAL) of patients with chronic diseases, it has not yet been assessed in COPD patients. This study included male patients with COPD (n = 28) and high risk for COPD (n = 8). Total energy expenditure (TEE) and basal metabolic rate (BMR) were measured using the doubly labeled water (DLW) method and indirect calorimetry, respectively. PAL was calculated as TEE/BMR, while the NEAT was obtained from a questionnaire. Physical activity was also assessed using an accelerometer. The total NEAT score was correlated with PAL (r = 0.534, P < 0.001), while PAL was correlated more strongly with the non-locomotive NEAT score (r = 0.548, P < 0.001) than the locomotive NEAT score (r = 0.278, P = 0.10). Regarding accelerometer-obtained data, this questionnaire mainly reflected steps/day and the duration of light locomotive and non-locomotive daily activities. The NEAT score is a possible option for evaluating PAL in daily clinical practice. The present results indicated that non-locomotive activity may have a greater impact on PAL than locomotive activity in COPD patients.

Possible association of high-density lipoprotein cholesterol levels with trunk muscle deficits and decrease in energy expenditure in patients with or at risk for COPD: A pilot study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with low muscle mass and function caused by malnutrition and physical inactivity. We aimed to investigate possible associations between serum biomarkers and clinical traits including computed tomography-derived muscle measurements and energy expenditure indices in COPD. METHODS: Total energy expenditure (TEE) was measured by the doubly labeled water method, while physical activity level (PAL) was calculated as TEE/basal metabolic rate. Cross-sections and densities of pectoralis, rectus abdominis, and erector spinae muscles were measured. Serum biomarkers included adiponectin, insulin-like growth factor-1, and high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol (C). RESULTS: HDL-C levels were significantly correlated with all muscle areas, densities, and TEE. Only LDL-C levels were correlated with PAL. CONCLUSIONS: HDL-C level was a potential biomarker for trunk muscle volumes and functions, as well as total energy expenditure in COPD.

Real-world outcomes of chemotherapy for lung cancer patients undergoing hemodialysis: A multicenter retrospective cohort study (NEJ-042).

INTRODUCTION: Malignant tumors are the major cause of death in hemodialysis patients. Management of these patients remains challenging as there is no evidence that chemotherapy is beneficial, and a lack of information about actual clinical practice. METHODS: This multicenter retrospective study included hemodialysis patients who were diagnosed with lung cancer from January 2002 to June 2018. We reviewed their clinical information including patient characteristics associated with lung cancer and end-stage renal disease, regimen, efficacy and safety of chemotherapy, and outcomes. RESULTS: A total of 162 patients from 22 institutions in Japan were registered. Of 158 eligible patients, 91 received chemotherapy (80 as palliative chemotherapy and 11 as chemoradiotherapy) and 67 received best supportive care only regardless of cancer stage. In small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients who received cytotoxic chemotherapy, the objective response rates (ORR) and median overall survival (OS) were 68.1 %, 12.3 months and 37.0 %, 8.5 months, respectively. The ORR and median OS in patients with EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKI) were 44.4 % and 38.6 months. The treatment-related adverse events (Grade 3 or higher) induced by cytotoxic chemotherapy were myelosuppression and febrile neutropenia; treatment-related death (TRD) was observed in one patient. TRD occurred in 3 of 18 patients who received EGFR-TKI. CONCLUSION: Chemotherapy should be considered for hemodialysis patients with EGFR-mutant NSCLC and SCLC. However, the survival benefits of chemotherapy for NSCLC patients with EGFR-wild type are unclear; physicians should carefully consider whether to offer chemotherapy to this patient subset.

Efficacy and Feasibility of Programmed Death-1/Programmed Death Ligand-1 Blockade Therapy in Non-Small Cell Lung Cancer Patients With High Antinuclear Antibody Titers.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has been described to markedly improve patient survival. However, reports describing the antitumor therapeutic efficacy and safety of ICIs in patients with autoantibodies are scarce. METHODS: This study examined the efficacy and feasibility of ICIs in antinuclear antibody (ANA)-positive patients with non-small cell lung cancer (NSCLC). An ANA titer greater than 1:40 and 1:80 was defined as positive and high, respectively. Patients who were treated with ICIs at Saitama Medical University, International Medical Center between January 2016 and December 2018 were retrospectively reviewed. RESULTS: One hundred and nineteen of the 266 patients (44.7%) who received nivolumab, pembrolizumab, and atezolizumab had positive ANA titers. Their median age was 69 (range, 39-84) years. The overall response rate of the ANA-positive patients was 35.9% (37/103), which was not less than that of the ANA-negative group. The median progression-free survival in the ANA-positive group was 6.3 months versus 4.3 months in the ANA-negative group (p = 0.08). Twenty-seven ANA-positive patients (10.2%) had high ANA titers. However, ICI efficacy was not decreased in these patients. Regardless of the cutoff of ANA titers (1:40 or 1:80), the rate of patients who experienced adverse events were not significantly different between the two groups. CONCLUSION: The administration of ICIs to ANA-positive patients has clinical benefits. The prevalence of adverse events in the ANA-positive group was not higher than that in the ANA-negative group.

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab.

BACKGROUND: The safety of pembrolizumab monotherapy in treatment-naïve non-small cell lung cancer (NSCLC) patients with high programed death-ligand 1 (PD-L1) expression and pre-existing interstitial lung disease (ILD) has not yet been determined. Here, we aimed to evaluate the prognosis, efficacy and safety associated with pembrolizumab in such settings. METHODS: In this single-institution retrospective study conducted from May 2017 to October 2019, pembrolizumab was administered to 72 Japanese patients with treatment-naïve advanced NSCLC with PD-L1 tumor proportion score (TPS) ≥50%. Patients with ILD were assigned to the ILD group, and those without to the non-ILD group. Between-group comparisons were then performed. RESULTS: Of the 72 patients, 61 (84.7%) were male. The median age was 70 years. A total of 64 patients (88.9%) had a smoking history, median PD-L1 TPS status was 77.5%, and 10 of the 72 patients (13.9%) had ILD on pretreatment computed tomography. The objective response rate (ORR) was 45.8% and disease control rate (DCR) was 75.0%. The ORR was 70.0% and DCR was 90.0% in the ILD group, while the ORR was 41.9% and DCR was 72.6% in the non-ILD group. The median overall survival was 568 days; the value in the non-ILD group was 521 days, while in the ILD group was not reached. There was no significant difference between the two groups (log-lank, P = 0.73). CONCLUSIONS: Pembrolizumab was administered to patients with pre-existing ILD with no difference in prognosis compared to patients without ILD. In patients with ILD, physicians should consider the expected long-term prognosis and risk of adverse events.

Energy expenditure and physical activity in COPD by doubly labelled water method and an accelerometer.

Although weight loss suggests poor prognosis of COPD, only a few studies have examined total energy expenditure (TEE) or physical activity level (PAL) using the doubly labelled water (DLW) method. We evaluated TEE and PAL using the DLW method together with a triaxial accelerometer to elucidate the relationships between TEE, PAL and clinical parameters leading to a practical means of monitoring COPD physical status. This study evaluated 50- to 79-year-old male patients with mild to very severe COPD (n=28) or at risk for COPD (n=8). TEE, activity energy expenditure for 2 weeks and basal metabolic rate were measured by DLW, an accelerometer and indirect calorimetry, respectively. All patients underwent pulmonary function, chest-computed tomography, 6-min walk test, body composition and grip strength tests. Relationships between indices of energy expenditure and clinical parameters were analysed. Bland-Altman analysis was used to examine the agreement of TEE and PAL between the DLW method and the accelerometer. TEE and PAL using DLW in the total population were 2273±445 kcal·day-1 and 1.80±0.20, respectively. TEE by DLW correlated well with that from the accelerometer and grip strength (p<0.0001), and PAL by DLW correlated well with that from the accelerometer (p<0.0001), grip strength and 6-min walk distance (p<0.001) among various clinical parameters. However, the accelerometer underestimated TEE (215±241 kcal·day-1) and PAL (0.18±0.16), with proportional biases in both indices. TEE and PAL can be estimated by accelerometer in patients with COPD if systematic errors and relevant clinical factors such as muscle strength and exercise capacity are accounted for.

Clinical impact of post-progression survival on overall survival in patients receiving nivolumab monotherapy as a second-line treatment for advanced non-small cell lung cancer.

BACKGROUND: The effect of second-line treatment on overall survival (OS) may be affected by subsequent treatment in patients with non-small cell lung cancer (NSCLC); however, in such patients, the correlation between post-progression survival (PPS) and OS is unclear. Our study assessed the correlation of progression-free survival (PFS) and PPS with OS, using individual patient data, in advanced NSCLC patients who were treated with second-line nivolumab monotherapy, METHODS: Between January 2016 and March 2019, we evaluated 92 NSCLC patients who received second-line nivolumab treatment after first-line platinum-based combination chemotherapy. Using individual patient data, the correlations of PFS and PPS with OS were examined. RESULTS: Linear regression and Spearman rank correlation analysis demonstrated that PPS was strongly correlated with OS (r = 0.85, p < 0.05, R2 = 0.75), while PFS was moderately correlated with OS (r = 0.65, p < 0.05, R2 = 0.42). Performance status at the beginning of second-line treatment, immune checkpoint inhibitor rechallenge, and the number of treatment regimens used post-progression, after the second-line treatment significantly correlated with PPS (p < 0.05). In advanced NSCLC patients who underwent second-line treatment with nivolumab, in comparison to PFS, there was a stronger correlation between PPS and OS. CONCLUSIONS: Our findings suggest that subsequent treatment for disease progression after a second-line nivolumab treatment had a significant impact on OS.

Chemoradiotherapy followed by durvalumab in patients with unresectable advanced non-small cell lung cancer: Management of adverse events.

BACKGROUND: Chemoradiotherapy followed by durvalumab is the standard treatment for the patients with local advanced non-small cell lung cancer (NSCLC). There is a real-world data about the management of adverse events, such as pneumonitis, according to the different institutions. Here, we present the experience regarding the management of adverse events after the initiation of durvalumab as daily practice. METHODS: From July 2018 to August 2019, 41 patients with locally advanced NSCLC, who underwent chemoradiotherapy followed by durvalumab, were retrospectively analyzed in the study using our medical records. RESULTS: The median age of patients was 72 years (range: 51-80 years). A total of 33 patients were male and eight were female, and 40 patients (98%) received a total radiation dose of 60 Gy as concomitant chemoradiotherapy. The median V20 for the entire cohort was 18.9% (range: 3.5-29.9). Any adverse events during chemoradiotherapy and durvalumab were observed in 32 patients (78.0%), while three patients (7.3%) experienced grade 3 toxicities. In total, 25 (61.0%) patients experienced pneumonitis, four (9.8%) thyroid dysfunction, three (7.3%) myopathy, two (4.9%) rash or eruption, one (2.4%) bowel disease and one (2.4%) malaise. Grade 3 pneumonitis, thyroid dysfunction and myopathy were observed in one (2.4%), one (2.4%) and one (2.4%), respectively. A total of 22 (53.7%) patients were unable to continue durvalumab due to pneumonitis. However, durvalumab was finally readministered to six patients. CONCLUSIONS: The adherence to lung dose constraints such as V20 as well as close treatment monitoring are a prerequisite for the management of pneumonitis during maintenance therapy with durvalumab.