The Prognostic Nutritional Index before durvalumab after chemoradiation predict the overall survival in patients with stage III non-small cell lung cancer.

BACKGROUND: Adjuvant durvalumab after chemoradiation has become the standard of care for patients with stage III NSCLC, according to the PACIFIC trial. Whether biomarkers before durvalumab for patients with stage III NSCLC showed predictive and prognostic effects remains unknown. METHODS: This is a retrospective study in the Fujieda Municipal General Hospital between October 2018 and March 2022. We assessed the predictive value of the Prognostic Nutritional Index (PNI) in stage III non-small cell lung cancer (NSCLC) patients treated with durvalumab after chemoradiation. RESULTS: After applying the inclusion and exclusion criteria, the study included 56 patients for further analysis. The median follow-up period was 17.6 months (range, 3.0-45.4 months). According to receiver operating characteristic curve results, the PNI cutoff value to predict overall survival (OS) was 37.9, with sensitivity and specificity at 67.9% and 67.9%. Accordingly, the patients were divided into low- and high-PNI groups. Patients with the low-PNI group had a significantly shorter progression-free survival compared to the high-PNI group (median, 9.1 vs. 21.3 months, p = 0.032). OS was also shorter in the low-PNI group (median, 19.0 months vs. not reached, p < 0.001). In the multivariate Cox hazards regression analyses, the high-PNI was an independent prognostic factor for OS (hazard ratio, 0.187; 95% confidence interval, 0.046-0.760; p = 0.019).It seems that PNI could be used as a predictor for OS in patients with stage III NSCLC treated with durvalumab after chemoradiation.KEY MESSAGESInadequate immunocompetence and nutritional status after chemoradiation therapy may result in poor antitumor efficacy of ICIs.Pretreatment immune and nutritional assessment using PNI could be considered an independent predictor for the survival of stage III NSCLC patients treated with durvalumab after chemoradiation therapy.

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.

Involvement of autophagy in exacerbation of eosinophilic airway inflammation in a murine model of obese asthma.

Obesity is a common comorbidity in patients with asthma, and obese asthma patients present the most refractory phenotype among patients with severe asthma. Similar to the observations in non-obese asthma patients, clinical studies have revealed heterogeneity in obese asthma patients, including the occurrences of T helper (Th)2-high and Th2-low phenotypes. However, the mechanisms underlying obesity-related asthma are not completely understood. Though macroautophagy/autophagy is involved in asthma and obesity, its role in obesity-associated asthma is unknown. We hypothesized that autophagy is involved in the pathogenesis of obese asthma. For our investigations, we used high-fat diet-induced Atg5 (autophagy related 5)-deficient mice and epithelial cell-specific atg5-/- (Scgb1a1/CCSP-atg5-/-) obesity-induced mice. House dust mite (HDM)-sensitized atg5-/- obese mice exhibited marked eosinophilic inflammation and airway hyper-reactivity (AHR), compared to wild-type (WT) obese mice. Analyses of atg5-/- obese mice showed increased levels of Th2 cells but not ILC2s together with elevated expression of Th2 cytokines in the lung. In response to the HDM challenge, activated epithelial autophagy was observed in lean but not obese WT mice. Epithelium-specific deletion of Atg5 induced eosinophilic inflammation in Scgb1a1/CCSP-atg5-/- obese mice, and genetic analyses of epithelial cells from HDM-immunized atg5-/- obesity-induced mice showed an elevated expression of thymic stromal lymphopoietin (TSLP) and IL33. Notably, HDM-sensitized atg5-/- mice developed TSLP- and IL33-dependent eosinophilic inflammation and AHR. Our results suggest that autophagy contributes to the exacerbation of eosinophilic inflammation in obese asthma. Modulations of autophagy may be a therapeutic target in obesity-associated asthma.Abbreviations: AHR: airway hyper-reactivity; BAL: bronchoalveolar lavage; Cdyn: dynamic compliance; BM: bone marrow; HDM: house dust mite; HFD: high-fat diet; ILC2s: type 2 innate lymphocyte cells; ROS: reactive oxygen species; RL: lung resistance; TSLP: thymic stromal lymphopoietin; TCC: total cell count; WT: wild type.

The Geriatric Nutritional Risk Index and Prognostic Nutritional Index Predict the Overall Survival of Advanced Non-Small Cell Lung Cancer Patients.

We aimed to assess the prognostic and predictive significance of pretreatment Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) measurements on advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Patients with advanced NSCLC treated between February 2014 and August 2020 were retrospectively analyzed. The optimal cutoff points for GNRI and PNI were measured with receiver operating characteristic (ROC) curve analysis according to overall survival (OS). The predictive factors for progression-free survival (PFS) and OS were evaluated with univariate and multivariate analyses via the Cox hazards regression. A total of 160 patients were included in the study. Significant differences between the low and high-GNRI or PNI groups were found regarding ECOG-PS. The low-GNRI and low-PNI groups had significantly shorter PFS and OS than the high-GNRI and high-PNI groups. A multivariate analysis using a Cox regression model revealed that the high-GNRI group was an independent prognostic factor of OS and PFS, and the PNI group was an independent prognostic factor of OS. Pretreatment GNRI and PNI may therefore be a potential effective predictor of the survival of advanced NSCLC patients undergoing first-line treatment.

Palliative Care for Idiopathic Pulmonary Fibrosis Patients: Pulmonary Physicians' View.

CONTEXT: Although idiopathic pulmonary fibrosis (IPF) has worse outcomes compared with most malignancies, patients with IPF receive poor access to optimal palliative care. OBJECTIVES: This study aimed to characterize the practice of pulmonologists regarding palliative care and end-of-life communication for patients with IPF and identify perceived difficulties and barriers thereto. METHODS: Self-administered questionnaires were sent by mail to representative pulmonologists from Shizuoka prefecture, Japan. Physician-reported practice, difficulties, timing of end-of-life communication, and barriers related to palliative care were investigated. RESULTS: Among the 135 participants, 130 (96%) completed the questionnaire. Most of the participants reported that patients with IPF complained of dyspnea and cough. However, less morphine was prescribed for IPF than for lung cancer. The participants experienced greater difficulty in providing palliative care for IPF than for lung cancer. Moreover, actual end-of-life discussions in patients with IPF were conducted later than the physician-perceived ideal timing. Among the barriers identified, few established treatment and difficulty in predicting prognosis (odds ratio [OR] 2.0; P = 0.04), discrepancies in understanding and care goals among patients, family, and medical staff (OR 2.2; P = 0.03), and inadequate communication about goal of care (OR 2.3; P = 0.003) were significantly associated with the physician-perceived difficulties in providing palliative care for patients with IPF. CONCLUSION: Pulmonologists experienced greater difficulty in providing palliative care to patients with IPF than to those with lung cancer. Clinical studies on the optimal palliative care for patients with IPF are urgently required.

Clinical significance of serum S100 calcium-binding protein A4 in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. There are no established serum biomarkers for predicting the outcomes of IPF. S100 calcium-binding protein A4 (S100A4) is considered as a marker of fibroblasts; however, its clinical application remains to be investigated. We evaluated the clinical relevance of S100A4 in IPF patients. METHODS: Serum S100A4 levels in 95 consecutive IPF patients and 50 healthy controls (HC) were measured using enzyme-linked immunosorbent assay. S100A4 expression in lung tissues was determined using immunohistochemistry/immunofluorescence and its association with disease progression (defined as deterioration in lung function or death) and mortality was assessed using Kaplan-Meier method and Cox hazards analysis. RESULTS: Serum S100A4 levels were undetectable in all HC but were detectable in 26 (27.3%) of the 95 IPF patients (P < 0.01). Immunostaining of lung tissues from IPF patients showed aggregation of numerous S100A4-expressing cells around the fibroblastic foci and mature fibrotic regions. IPF patients with higher serum S100A4 levels had a significantly worse prognosis than those with low serum levels (2-year cumulative survival rate: 41.7% vs 77.0%, respectively, P < 0.01). On multivariate analyses, baseline serum S100A4 levels (per 10 ng/mL increase) were independently associated with higher disease progression rate (odds ratio: 1.06, P = 0.01) and higher mortality (hazard ratio: 1.18, P = 0.03). CONCLUSION: S100A4 is a promising serum biomarker that may help predict disease progression/mortality. Our findings may help establish treatment strategies for IPF.

Effect of rifampicin and clarithromycin on the CYP3A activity in patients with Mycobacterium avium complex.

BACKGROUND: The prevalence of pulmonary infections caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Furthermore, the treatment of infections caused by the Mycobacterium avium-intracellulare complex (MAC) remains challenging. The cytochrome P450 (CYP) enzyme inducer, rifampicin, and the CYP inhibitor, clarithromycin, have clinical activity against MAC and key drugs in the treatment of MAC infection. The interaction of rifampicin and clarithromycin may influence the therapeutic process. METHODS: Thirty-one Japanese chemo-naïve patients with pulmonary MAC infection were included in the study. Before and after 7-day administration of rifampicin and clarithromycin, the pharmacokinetics of midazolam, a CYP3A-specific probe, were analyzed. The concentrations of midazolam were determined by liquid chromatography-tandem mass spectrometry. None of the patients were receiving any other medications that might affect CYP3A activity. RESULTS: Of the patients, 24 (77.4%) were infected with Mycobacterium avium (M. avium) and 7 (22.6%) were infected with Mycobacterium intracellulare (M. intracellulare). The concentrations of midazolam were significantly reduced with administration of rifampicin and clarithromycin [the median (range) was 1.75 (0.70-8.22) to 1.04 (0.30-2.63) ng/mL, P<0.0001]. The differences in midazolam levels were not correlated with clinical characteristics. CONCLUSIONS: Coadministration of rifampicin and clarithromycin may increase CYP3A enzymatic activity.

Switch maintenance therapy with S-1 after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel in advanced lung squamous cell carcinoma.

Background Optimal maintenance therapy for lung squamous cell carcinoma (SCC) has not been established. The aim of this study was to evaluate the efficacy and safety of switch maintenance therapy with S-1, an oral fluoropyrimidine, after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in chemotherapy-naïve patients with advanced SCC. Methods Chemotherapy-naïve patients with advanced SCC received induction therapy with four cycles of carboplatin (at an area under the curve of 6, day 1 of a 28-day cycle) and nab-paclitaxel (100 mg/kg, days 1, 8, and 15). Patients who achieved disease control after induction therapy received maintenance therapy with S-1 (80 mg/m2, days 1-14 of a 21-day cycle) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) from the start of maintenance therapy. Results Seventy-two patients with SCC were enrolled to the study. After four cycles of induction therapy, 35 (48.6%) patients achieved disease control, and 31 (43.1%) of these patients received maintenance therapy. Median PFS from the start of maintenance therapy was 3.0 months (95% confidence interval: 2.1-3.8 months). The most common toxicities of grade 3 or higher during maintenance therapy were nausea (13.3%), neutropenia (10.0%), and diarrhea (6.7%). Conclusions Switch maintenance therapy with S-1 after induction therapy with carboplatin and nab-paclitaxel was associated with moderate efficacy and acceptable safety and may represent a feasible treatment option for patients with advanced SCC.

Synchronous Duodenal Cancer and Lung Cancer Harboring an Epidermal Growth Factor Receptor Mutation Treated with Erlotinib and Oral Fluoropyrimidine.

Chemotherapy for multiple primary cancers is challenging. We describe a case of synchronous duodenal cancer with lung cancer harboring an epidermal growth factor receptor (EGFR) mutation treated with erlotinib and S-1, an oral fluoropyrimidine agent. A 78-year-old woman with advanced EGFR-mutated lung adenocarcinoma was simultaneously diagnosed with duodenal adenocarcinoma. After the treatment with erlotinib, the lung cancer responded well, but her duodenal cancer showed no response. S-1 was added to erlotinib, and the duodenal cancer demonstrated a good response with tolerable toxicities. The concurrent use of erlotinib and S-1 was safe and efficacious for synchronous lung cancer harboring an EGFR mutation and duodenal cancer.

Combined Pulmonary Fibrosis and Emphysema Preceding Lupus Pleuritis.

An 83-year-old man, who was a former smoker, with anti-ribonucleoprotein (RNP) antibody-positive combined pulmonary fibrosis and emphysema presented with a cough and dyspnea. A chest radiograph showed bilateral pleural effusions. His laboratory data showed proteinuria and elevated levels of anti-nuclear antibodies, anti-double strand DNA antibodies, and CA125, with decreased serum complement levels. Thoracentesis showed an exudative pleural effusion with an increased lymphocyte count and elevated CA125 levels. A thoracoscopic biopsy specimen showed proliferation of CA125-positive mesothelial cells. Systemic lupus erythematosus was diagnosed. His symptoms and pleural effusion resolved after the initiation of systemic corticosteroid therapy. The detection of anti-RNP antibody and CA125 levels are helpful in the diagnosis of lupus pleuritis.

[THREE CASES OF DRUG-INDUCED PNEUMONIA CAUSED BY MESALAZINE].

We report three cases of drug-induced pneumonia caused by mesalazine. They were all diagnosed as ulcerative colitis and treated with mesalazine orally. Our three cases and literature review revealed that mesalazine-induced pneumonia resemble like eosinophilic pneumonia or organizing pneumonia and that have good prognosis with drug cessation or administration of corticosteroid. The patient of ulcerative colitis is increasing every year and it is anticipated that the patient with mesalazine-induced pneumonia may also increase. In the treatment of ulcerative colitis with mesalazine, we should pay attention with patient's cough or fever for early detection of drug-induced pneumonia.