Abstract
Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. ...However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30–74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of
MDC1
, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of
MDC1
rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Data on characteristics, outcomes, and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who develop pneumonitis during systemic anti-cancer therapy (pneumonitis) are currently ...lacking.
We conducted a retrospective cohort study of 910 consecutive patients diagnosed with advanced NSCLC between January 2004 and January 2014. Of these, 140 patients were excluded because they did not receive systemic anti-cancer therapy at this hospital.
A total of 770 patients were included in the study, of whom 44 (6%) were diagnosed with pneumonitis. The mortality rate of pneumonitis was 36%. The incidence of pneumonitis was independently associated with pre-existing ILD (adjusted odds ratio, 2.99, P = 0.008), and survivors were significantly associated with younger age (P = 0.003) and radiographic non-acute interstitial pneumonia pattern (P = 0.004). In all patients, pneumonitis was identified as an independent predictor of overall survival (OS) (adjusted hazard ratio 1.53, 95% CI, 1.09-2.09, P = 0.015). Performance status was poor in 82% of survivors of pneumonitis; in 62% of survivors, the PS worsened after the pneumonitis improved. Additionally, 54% of survivors received no further systemic anti-cancer therapy after pneumonitis. The median survival time of survivors after pneumonitis was 3.5 months (95% CI, 2.3-7.2 months).
Our study indicated that 6% of patients with advanced NSCLC developed pneumonitis during systemic anti-cancer therapy. The early mortality rate of pneumonitis is high, and the survival and PS after pneumonitis is extremely poor. Additionally, pneumonitis has an adverse impact on the survival of patients with advanced NSCLC. These data should be considered for the management of pneumonitis, and we recommend that future work focuses on pneumonitis particularly to improve the survival of patients with advanced NSCLC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset ...asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population.
This community-based prospective cohort study enrolled 9804 generally healthy participants (30–74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment.
Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV1/FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to severe sleep disordered breathing than those non-elderly.
Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Early enteral nutrition is recommended for mechanically ventilated patients in several studies and guidelines. In contrast, the effects of early enteral nutrition on noninvasive ventilation (NIV) ...have not been investigated extensively. The lack of an established method of airway protection suggests that enteral nutrition administration to these patients could increase airway complications and worsen outcomes.
Between January 2007 and January 2015, 150 patients were admitted to our respiratory department for acute respiratory failure and received NIV for >48 h. Of these, 107 subjects incapable of oral intake were retrospectively analyzed. Clinical background and complications were compared in subjects who did and did not receive enteral nutrition.
Sixty of the 107 subjects (56%) incapable of oral intake who received NIV also received enteral nutrition. Serum albumin concentration was significantly lower in subjects who received enteral nutrition than in those who did not (mean 2.7 ± 0.68 mg/dL vs 3.0 ± 0.75 mg/dL,
= .048). The rate of airway complications was significantly higher (53% 32/60 vs 32% 15/47,
= .03), and median NIV duration was significantly longer (16 interquartile range 7-43 d vs 8 5-20 d,
= .02) in subjects who received enteral nutrition than in those who did not. Multivariate analysis showed that enteral nutrition was unrelated to in-hospital mortality.
Among subjects receiving NIV, enteral nutrition was associated with increased risk of airway complications but did not affect mortality. Enteral nutrition should be carefully considered in these patients.
Abstract
Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, ...a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as “new-onset prolonged cough”. Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary
Background
It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment ...outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated associations between early depth of response and survival outcomes among patients receiving nivolumab for NSCLC.
Methods
Using records from prospective observational cohorts, we identified 83 previously treated advanced patients with NSCLC who received nivolumab during 2016–2017. Thirty-one patients who achieved disease control were analyzed. Tumor assessments followed the Response Evaluation Criteria in Solid Tumors (RECIST). Using Kaplan-Meier and receiver operating characteristic (ROC) curve analyses, treatment outcomes were compared with percent tumor reductions from baseline to the first evaluation (8–12 weeks after starting nivolumab).
Results
Early depth of response was predictive of 6-month progression-free survival (area under the ROC curve, 0.848). Based on ROC results, early tumor shrinkage was defined as a > 10% reduction by the first evaluation. Early tumor shrinkage was associated with significantly longer median progression-free survival (early tumor shrinkage: 16.6 months, 95% confidence interval CI 8.5 months–not reached; no early shrinkage: 5.1 months, 95% CI 3.9–6.8 months;
P
< 0.001) and significantly longer median overall survival (
P
= 0.046).
Conclusions
Early depth of tumor shrinkage was associated with outcomes after ICI treatment. Because of its simplicity and predictive ability, early tumor shrinkage may be a promising factor for use in clinical settings. However, confirmation of our results is needed.
Purpose
Recently, based on results of the PACIFIC trial, durvalumab after chemoradiotherapy (CRT) became the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC). However, ...in the PACIFIC trial, patients were recruited and randomized after CRT, and certain patients were considered ineligible after CRT in the real world. No study has been conducted on the patients who were ineligible for the PACIFIC trial, and hence, we conducted a retrospective study on them.
Methods
We identified 82 patients with stage III NSCLC who received definitive platinum-based concurrent CRT and had World Health Organization performance status of 0–1. We investigated the proportion, clinical characteristics, and prognoses of patients who became ineligible for the PACIFIC trial after CRT.
Results
After CRT, 19 of 82 patients (23%) became ineligible for the PACIFIC trial. Comparison between eligible and ineligible patients revealed that old age (
p
= 0.042), male gender (
p
= 0.031), and radiation therapy with V20 ≥ 35% (
p
= 0.032) were associated with ineligibility after CRT. Moreover, ineligible patients showed shorter PFS (6.6 vs. 15.7 months, hazard ratio HR 2.61, 95% confidence interval CI 1.16–5.89,
p
= 0.016) and shorter OS (18.6 vs. 44.3 months, HR 3.03, 95% CI 1.29–7.10,
p
= 0.007) than eligible patients.
Conclusions
Our study revealed the clinical characteristics and prognoses of patients who became ineligible for the PACIFIC trial after CRT. Physicians should be careful while prescribing CRT for patients with characteristics such as old age, male gender, and radiation therapy with V20 ≥ 35%.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Subjects with subclinical respiratory dysfunction who do not meet the chronic obstructive pulmonary disease (COPD) criteria have attracted attention with regard to early COPD intervention. Our aim ...was to longitudinally investigate the risks for the development of airflow limitation (AFL) and dyspnoea, the main characteristics of COPD, in a large-scale community-based general population study. The Nagahama study included 9789 inhabitants, and a follow-up evaluation was conducted after 5 years. AFL was diagnosed using a fixed ratio (forced expiratory volume in one second (FEV
)/forced vital capacity (FVC) < 0.7). We enrolled normal subjects aged 40-75 years with no AFL, dyspnoea or prior diagnosis of asthma or COPD at baseline. In total, 5865 subjects were analysed, 310 subjects had subclinical respiratory dysfunction (FEV
/FVC < the lower limit of normal; n = 57, and FEV
< 80% of the predicted value (preserved ratio impaired spirometry); n = 256). A total of 5086 subjects attended the follow-up assessment, and 449 and 1021 subjects developed AFL and dyspnoea, respectively. Of these, 100 subjects developed AFL with dyspnoea. Baseline subclinical respiratory dysfunction was independently and significantly associated with AFL with dyspnoea development within 5 years. Subjects with subclinical respiratory dysfunction are at risk of developing COPD-like features and require careful monitoring.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Recent studies indicate the benefit of treatment with osimertinib over that with conventional epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for untreated EGFR-mutated ...non-small cell lung cancer (NSCLC). Cobas ver2 is the only companion diagnostic method for detecting EGFR mutations with osimertinib treatment. We clinically experience false negative cases with this test, but its actual sensitivity is unknown. Moreover, no study has suggested the importance of tumour dissection, and most facilities do not routinely perform them on small biopsies. The purpose of this study was to evaluate the sensitivity of cobas in clinical practice and clarify the role of dissection as a component of the cobas testing.
We examined 132 patients with EGFR-mutated NSCLC diagnosed by bronchoscopy and confirmed with PCR clamp. Patients were tested with cobas and the EGFR-positive rate was calculated. Samples with undetected EGFR mutations were retested after tumour dissection and the rate of samples whose EGFR mutation was corrected to positive was assessed. To evaluate tumour cellularity, the tumour content ratio was assessed by calculating tumour cell count over the total cell count on the slide.
The positive rate of EGFR mutation identification was 76% with cobas, although EGFR mutation-negative patients retained responses to TKI therapy equivalent to positive patients did; however, the tumour content ratio of negative samples was significantly lower than that of positive samples. Twenty-nine negative samples underwent dissection and 24% were corrected to positive. Moreover, 53% of the samples with a tumour content ratio below 10% was negative for cobas, but 33% of these turned positive after dissection.
Cobas had a high false negative rate in clinical practice, and tumour content ratio might be associated with this rate. Dissection could improve the sensitivity of cobas, especially in samples with low tumour cellularity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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