•Smoking and chronic obstructive pulmonary disease are known risk factors of severe COVID-19.•Cumulative smoking exposure was positively associated with COVID-19 outcomes.•In patients aged <65 years, ...chronic obstructive pulmonary disease affected disease severity in those with >30 pack-years.
Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan.
The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV).
The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio OR: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years.
Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Statistical fine-mapping prioritizes putative causal variants from a large number of candidate variants, and is widely used in expression quantitative loci (eQTLs) studies. In eQTL ...fine-mapping, the existence of causal variants for gene expression is not guaranteed, since the genetic heritability of gene expression explained by nearby (cis-) variants is limited. Here we introduce a refined fine-mapping algorithm, named Knockoff–Finemap combination (KFc). KFc estimates the probability that the causal variant(s) exist in the cis-window of a gene through construction of knockoff genotypes (i.e. a set of synthetic genotypes that resembles the original genotypes), and uses it to adjust the posterior inclusion probabilities (PIPs). Utilizing simulated gene expression data, we show that KFc results in calibrated PIP distribution with improved precision. When applied to gene expression data of 465 genotyped samples from the Japan COVID-19 Task Force (JCTF), KFc resulted in significant enrichment of a functional score as well as reporter assay hits in the top PIP bins. When combined with functional priors derived from an external fine-mapping study (GTEx), KFc resulted in a significantly higher proportion of hematopoietic trait putative causal variants in the top PIP bins. Our work presents improvements in the precision of a major fine-mapping algorithm.
We investigated the association between complete blood count, including neutrophil-to-lymphocyte ratio (NLR) in combination with patient characteristics, and coronavirus disease (COVID-19) outcomes ...to identify the best prognostic indicator. We analyzed data of patients with confirmed COVID-19 from the nationwide database of the Japan COVID-19 Task Force between February 2020 and November 2021. A composite outcome was defined as the most severe condition, including noninvasive positive-pressure ventilation, high-flow nasal cannula, invasive mechanical ventilation, extracorporeal membrane oxygenation, or death. Of 2425 patients in the analysis, 472 (19.5%) experienced a composite outcome. NLR was the best predictor of composite outcomes, with an area under the curve (AUC) of 0.81, and a sensitivity and specificity of 72.3% and 75.7%, respectively, using a cut-off value of 5.04. The combination of NLR and an oxygen requirement on admission had the highest AUC (0.88). This simple combination may help identify patients at risk of progression to severe disease.
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IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rationale. Little is known about the applicability of respiratory muscle training based on exertional pathophysiological conditions in patients with chronic obstructive pulmonary disease (COPD). The ...aim of this study was to investigate the relationship between breathing timing and exertional responses, as well as whether exertional changes in the inspiratory duty cycle (Ti/Ttot) affect pathophysiological conditions, including respiratory muscles. Methods. Forty-five stable COPD patients (mean age: 71.2 years, severe and very severe COPD: 80%) were evaluated based on exertional cardiopulmonary function and respiratory muscle strength. To compare exertional responses and the balance of inspiratory-to-expiratory muscle strength, the patients were divided into two groups according to whether the Ti/Ttot increased (Ti/Ttot-increased group: resting Ti/Ttot ≤ peak Ti/Ttot, n = 21) or decreased during exercise (Ti/Ttot-decreased group: resting Ti/Ttot > peak Ti/Ttot, n = 24). Results. At peak exercise, the Ti/Ttot was positively correlated with minute ventilation ( V ̇ E), and oxygen uptake ( V ̇ O 2 ) in all patients. No significant differences were seen in breathing frequency, tidal volume, or V ̇ E at peak exercise between the two groups. Compared with the Ti/Ttot-increased group, the Ti/Ttot-decreased group had significantly lower mean values of V ̇ O 2 and ΔFO2 (the inspired minus expired oxygen concentration) at peak exercise, and significantly higher mean values of the absolute ratio of maximal inspiratory pressure/maximal expiratory pressure. Conclusions. The exertional change of breathing timing affected exercise tolerance and the balance of inspiratory-to-expiratory muscle strength; this finding might be helpful in making the contradictory choice of managing COPD patients with inspiratory or expiratory muscle training.
Diffuse pulmonary ossification (DPO) is an uncommon diffuse lung disease characterized by metaplastic bone formation in the lung parenchyma and is rarely diagnosed in life. While DPO usually occurs ...as a secondary disease, idiopathic cases are extremely rare. We describe three cases of idiopathic DPO, two of which were definitively diagnosed by surgical lung biopsy. One case was observed in a 43-year-old man with a history of recurrent pneumothorax who developed pneumothorax after the surgical biopsy. Few reports have described cases of DPO with recurrent pneumothorax; however, pneumothorax should be considered as a potential complication when such patients are encountered.
Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of ...patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.
Recently, the immune checkpoint inhibitor (ICI) pembrolizumab was demonstrated to be superior to platinum doublet chemotherapy in the first-line setting in patients with tumor programmed death-ligand ...1 (PD-L1) expression of at least 50%. However, because patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements were not included in that study, the efficacy of pembrolizumab in lung cancers carrying EGFR mutations could not be determined. Here we describe two cases of response to pembrolizumab in EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression. These cases indicate that ICI is an effective treatment for EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression.
IntroductionThe rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients ...have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale.Methods and analysisIn this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives.Ethics and disseminationThis trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.
Abstract only Variations in the incidence of acute myocardial infarction (AMI) during the day and week may differ among the subpopulations within the communities. It is well known that AMI onset ...shows characteristic circadian variations involving a definite morning peak and a vague nighttime peak: the former is often explained by biologic rhythms, while the latter by socioeconomic factors. Interestingly, we previously found that female patients aged 65 years or more showed a morning peak alone, whereas and male patients aged less than 65 years with an occupation and the habits of cigarette smoking and alcohol intake showed a nighttime peak alone. On the other hand, it is also reported that working population shows a weekly variation with an increased incidence for the AMI onset on Mondays. Accordingly, circadian variation for the onset of AMI could be influenced by each or combination of working status, gender, and the day of the week. However, there are few reports investigating circadian variation of AMI onset in relation with working status, gender and/or weekly variation. Therefore, we sought to investigate circadian variation patterns of AMI onset in relation with week variation according to gender and/or working status, especially in the working populations. From the registry database of the Osaka Acute Coronary Insufficiency Study (OACIS), a prospective observational study of AMI in Osaka area, Japan, a total of 7755 consecutive patients whose time of AMI onset was definitely identified between 1998 and 2009 were enrolled. The mean age of study population was 66+12 years old, 5872 (76%) were male, and 3364 (48%) had occupation. As previously reported, an increased incidence of AMI onset was observed in the morning and at the nighttime in overall populations. Interestingly, however, subgroup analysis revealed that the nighttime peak was completely attributable to the increase of nighttime onset on the weekend in the working subjects, especially working men, whereas the morning peak was common throughout the week with a peak on Monday in all other subgroups. As the weekend nighttime peak for AMI onset was not evident in other subgroups, this phenomenon may account for the social and/or economic reasons on the weekend in the working population. Although confirmation in other cohorts is required, this finding may help identify triggers of AMI and guide subjects to prevent an onset of AMI.
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