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International Journal of Chronic... 2023To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm).
PURPOSE
To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm).
PATIENTS AND METHODS
We used data from the Korean National Health and Nutrition Examination Survey between 2007 and 2012, linked to the Health Insurance Review and Assessment Service. Clinical characteristics and medical utilization, including inpatient admission, emergency department visit, prescribed medication, and medical cost, were retrospectively compared among three groups: normal spirometry, PRISm, and chronic obstructive pulmonary disease (COPD).
RESULTS
A total of 7115 smokers were included (4743 normal spirometry, 689 PRISm, and 1683 COPD subjects). The mean age was the highest in the COPD group, followed by the PRISm and normal groups, and the proportion of women was the highest in the PRISm group. The tobacco exposure, socioeconomic status (SES), and schooling level of the PRISm group were at levels between those of the normal and COPD groups. However, the PRISm group had the highest proportion of current smokers, highest body mass index (BMI), and lowest mean FEV and FVC % predicted. During the study period, the medical utilization of 92 smokers (13.4%) in the PRISm group and 436 smokers (25.9%) in the COPD group was related to respiratory diseases. Emergency department visit or hospitalization and overall medical cost of the PRISm group were comparable to those of the COPD group, except for outpatient clinic visit. Old age, women, low BMI, low SES, low schooling level, high amount of tobacco exposure, wheezing, and decreased FEV and FVC % predicted were factors associated with medical utilization in PRISm.
CONCLUSION
Medical utilization was comparable between the PRISm and COPD groups. Smokers with PRISm who were older, women, or heavy smokers with low BMI, low SES and schooling level, wheezing, or low FEV and FVC might need close observation and early treatment.
Topics: Female; Humans; Forced Expiratory Volume; Lung; Nutrition Surveys; Pulmonary Disease, Chronic Obstructive; Respiratory Sounds; Retrospective Studies; Smokers; Spirometry; Vital Capacity
PubMed: 37822330
DOI: 10.2147/COPD.S425934 -
EMBO Molecular Medicine Sep 2023SARS-CoV-2 may directly and indirectly damage lung tissue and other host organs, but there are few system-wide, untargeted studies of these effects on the human body....
SARS-CoV-2 may directly and indirectly damage lung tissue and other host organs, but there are few system-wide, untargeted studies of these effects on the human body. Here, we developed a parallelized mass spectrometry (MS) proteomics workflow enabling the rapid, quantitative analysis of hundreds of virus-infected FFPE tissues. The first layer of response to SARS-CoV-2 in all tissues was dominated by circulating inflammatory molecules. Beyond systemic inflammation, we differentiated between systemic and true tissue-specific effects to reflect distinct COVID-19-associated damage patterns. Proteomic changes in the lungs resembled those of diffuse alveolar damage (DAD) in non-COVID-19 patients. Extensive organ-specific changes were also evident in the kidneys, liver, and lymphatic and vascular systems. Secondary inflammatory effects in the brain were related to rearrangements in neurotransmitter receptors and myelin degradation. These MS-proteomics-derived results contribute substantially to our understanding of COVID-19 pathomechanisms and suggest strategies for organ-specific therapeutic interventions.
Topics: Humans; COVID-19; SARS-CoV-2; Proteomics; Inflammation; Lung
PubMed: 37519267
DOI: 10.15252/emmm.202317459 -
Medicine and Science in Sports and... Oct 2023We assessed the cardiorespiratory optimal point (COP)-the minimal V̇E /V̇O 2 in a given minute of an incremental cardiopulmonary exercise test-in patients with heart...
INTRODUCTION
We assessed the cardiorespiratory optimal point (COP)-the minimal V̇E /V̇O 2 in a given minute of an incremental cardiopulmonary exercise test-in patients with heart failure (HF) and aimed to determine 1) its association with patient and disease characteristics, 2) changes after an exercise-based cardiac rehabilitation program (CR), and 3) the association with clinical outcomes.
METHODS
We studied 277 HF patients (67 (58-74) yr, 30% female, 72% HF with restricted ejection fraction) between 2009 and 2018. Patients participated in a 12- to 24-wk CR program, and COP was assessed pre- and post-CR. Patient and disease characteristics and clinical outcomes (mortality and cardiovascular-related hospitalization) were extracted from patient files. The incidence of clinical outcomes was compared across COP tertiles (low, <26.0; moderate, 26.0-30.7; high, >30.7).
RESULTS
Median COP was 28.2 (24.9-32.1) and was reached at 51% ± 15% of V̇O 2peak . Lower age, female sex, higher body mass index, the absence of a pacemaker or the absence of chronic obstructive pulmonary disease, and lower N-terminal prohormone brain natriuretic peptide concentrations were associated with a lower COP. Participation in CR reduced COP (-0.8; 95% confidence interval, -1.3 to -0.3). Low COP had a reduced risk (adjusted hazard ratio, 0.53; 95% confidence interval, 0.33-0.84) for adverse clinical outcomes as compared with high COP.
CONCLUSIONS
Classic cardiovascular risk factors are associated with a higher, more unfavorable, COP. CR-based exercise training reduces COP, whereas a lower COP is associated with a better clinical prognosis. As COP can be established during a submaximal exercise test, this may offer novel risk stratification possibilities for HF care programs.
Topics: Humans; Female; Male; Heart Failure; Cardiac Rehabilitation; Prognosis; Exercise Test; Lung; Stroke Volume
PubMed: 37192340
DOI: 10.1249/MSS.0000000000003206 -
Immunological Reviews Aug 2023The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the... (Review)
Review
The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar compartments. We have reported that one of the most dominant molecular species of PG, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and PI inhibit inflammatory responses induced by multiple toll-like receptors (TLR2/1, TLR3, TLR4, and TLR2/6) by interacting with subsets of multiprotein receptor components. These lipids also exert potent antiviral effects against RSV and influenza A, in vitro, by inhibiting virus binding to host cells. POPG and PI inhibit these viral infections in vivo, in multiple animal models. Especially noteworthy, these lipids markedly attenuate SARS-CoV-2 infection including its variants. These lipids are natural compounds that already exist in the lung and, thus, are less likely to cause adverse immune responses by hosts. Collectively, these data demonstrate that POPG and PI have strong potential as novel therapeutics for applications as anti-inflammatory compounds and preventatives, as treatments for broad ranges of RNA respiratory viruses.
Topics: Animals; Humans; Phospholipids; Pulmonary Surfactants; Antiviral Agents; Toll-Like Receptor 2; COVID-19; SARS-CoV-2; Lung; Anti-Inflammatory Agents; Phosphatidylglycerols
PubMed: 37144896
DOI: 10.1111/imr.13207 -
Radiology Jul 2023Background An artificial intelligence (AI) algorithm has been developed for fully automated body composition assessment of lung cancer screening noncontrast low-dose CT...
Background An artificial intelligence (AI) algorithm has been developed for fully automated body composition assessment of lung cancer screening noncontrast low-dose CT of the chest (LDCT) scans, but the utility of these measurements in disease risk prediction models has not been assessed. Purpose To evaluate the added value of CT-based AI-derived body composition measurements in risk prediction of lung cancer incidence, lung cancer death, cardiovascular disease (CVD) death, and all-cause mortality in the National Lung Screening Trial (NLST). Materials and Methods In this secondary analysis of the NLST, body composition measurements, including area and attenuation attributes of skeletal muscle and subcutaneous adipose tissue, were derived from baseline LDCT examinations by using a previously developed AI algorithm. The added value of these measurements was assessed with sex- and cause-specific Cox proportional hazards models with and without the AI-derived body composition measurements for predicting lung cancer incidence, lung cancer death, CVD death, and all-cause mortality. Models were adjusted for confounding variables including age; body mass index; quantitative emphysema; coronary artery calcification; history of diabetes, heart disease, hypertension, and stroke; and other PLCO lung cancer risk factors. Goodness-of-fit improvements were assessed with the likelihood ratio test. Results Among 20 768 included participants (median age, 61 years [IQR, 57-65 years]; 12 317 men), 865 were diagnosed with lung cancer and 4180 died during follow-up. Including the AI-derived body composition measurements improved risk prediction for lung cancer death (male participants: χ = 23.09, < .001; female participants: χ = 15.04, = .002), CVD death (males: χ = 69.94, < .001; females: χ = 16.60, < .001), and all-cause mortality (males: χ = 248.13, < .001; females: χ = 94.54, < .001), but not for lung cancer incidence (male participants: χ = 2.53, = .11; female participants: χ = 1.73, = .19). Conclusion The body composition measurements automatically derived from baseline low-dose CT examinations added predictive value for lung cancer death, CVD death, and all-cause death, but not for lung cancer incidence in the NLST. Clinical trial registration no. NCT00047385 © RSNA, 2023 See also the editorial by Fintelmann in this issue.
Topics: Female; Male; Humans; Middle Aged; Early Detection of Cancer; Lung Neoplasms; Artificial Intelligence; Cardiovascular Diseases; Body Composition; Lung
PubMed: 37489991
DOI: 10.1148/radiol.222937 -
International Journal of Molecular... Aug 2023Lung fibrosis is a progressive fatal disease in which deregulated wound healing of lung epithelial cells drives progressive fibrotic changes. Persistent lung injury due... (Review)
Review
Lung fibrosis is a progressive fatal disease in which deregulated wound healing of lung epithelial cells drives progressive fibrotic changes. Persistent lung injury due to oxidative stress and chronic inflammation are central features of lung fibrosis. Chronic cigarette smoking causes oxidative stress and is a major risk factor for lung fibrosis. The objective of this manuscript is to develop an adverse outcome pathway (AOP) that serves as a framework for investigation of the mechanisms of lung fibrosis due to lung injury caused by inhaled toxicants, including cigarette smoke. Based on the weight of evidence, oxidative stress is proposed as a molecular initiating event (MIE) which leads to increased secretion of proinflammatory and profibrotic mediators (key event 1 (KE1)). At the cellular level, these proinflammatory signals induce the recruitment of inflammatory cells (KE2), which in turn, increase fibroblast proliferation and myofibroblast differentiation (KE3). At the tissue level, an increase in extracellular matrix deposition (KE4) subsequently culminates in lung fibrosis, the adverse outcome. We have also defined a new KE relationship between the MIE and KE3. This AOP provides a mechanistic platform to understand and evaluate how persistent oxidative stress from lung injury may develop into lung fibrosis.
Topics: Humans; Pulmonary Fibrosis; Adverse Outcome Pathways; Lung Injury; Lung; Oxidative Stress; Fibrosis
PubMed: 37569865
DOI: 10.3390/ijms241512490 -
Thoracic Surgery Clinics Aug 2023Screening with low-dose computed tomography has been shown to decrease lung cancer mortality. However, the issues of low detection rates and false positive results... (Review)
Review
Screening with low-dose computed tomography has been shown to decrease lung cancer mortality. However, the issues of low detection rates and false positive results remain, highlighting the need for adjunctive tools in lung cancer screening. To this end, researchers have investigated easily applicable, minimally invasive tests with high validity. We herein review some of the more promising novel markers utilizing plasma, sputum, and airway samples.
Topics: Humans; Lung Neoplasms; Early Detection of Cancer; Lung; Sputum; Tomography, X-Ray Computed; Mass Screening
PubMed: 37414477
DOI: 10.1016/j.thorsurg.2023.04.011 -
Respiratory Research Nov 2023Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function,...
BACKGROUND
Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.
METHODS
In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography-mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini-Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst.
RESULTS
We found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways.
CONCLUSIONS
Metabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers.
Topics: Humans; Smokers; Niacin; Lung; Pulmonary Emphysema; Emphysema; Niacinamide; Pulmonary Disease, Chronic Obstructive
PubMed: 37925418
DOI: 10.1186/s12931-023-02576-2 -
Respiratory Research Nov 2023Interstitial lung disease (ILD) and pulmonary hypertension (PH) represent the major causes of mortality in systemic sclerosis (SSc). Patients with systemic sclerosis and...
BACKGROUND
Interstitial lung disease (ILD) and pulmonary hypertension (PH) represent the major causes of mortality in systemic sclerosis (SSc). Patients with systemic sclerosis and combined PH and ILD (SSc-PH-ILD) generally have a poor prognosis. Predictors of survival and of potential benefit of treatment are lacking in patients with SSc-PH-ILD.
OBJECTIVE
To identify specific plasma protein expression patterns associated with survival in patients with SSc-PH-ILD.
MATERIALS AND METHODS
Post-hoc analysis of a prospective multicenter French study in patients with PH-ILD. An untargeted proteomic analysis using mass spectrometry was performed to identify plasma protein changes associated with long-term overall survival in patients with SSc-PH-ILD.
RESULTS
Thirty two patients were included in the analysis, of whom 13 died during follow-up (median survival: 76.5 months). At baseline, survivors had less severe hemodynamic impairment [pulmonary vascular resistance of 4.4 Wood Units (IQR 3-5.2) vs. 6.2 Wood Units (IQR 4.2-10.7)] and higher carbon monoxide diffusing capacity [median 39% (IQR 35-44%) vs. 25% (IQR 22-30.5%)], than the 13 patients who died. Seven proteins, associated with haemostasis and fibrosis, were differentially expressed according to patients' survival. In the survivor group, two proteins were increased (ADAMTS13, SERPIND1) and five were decreased (PTGDS, OLFM1, C7, IGFBP7, FBN1) compared to the non-survivor groups.
CONCLUSION
The prognosis of SSc-PH-ILD patients is poor. This proteomic approach found 7 plasma proteins (involved in haemostasis and fibrosis pathways) associated with survival. These potential biomarkers may be good candidates to prognostic enrichment.
Topics: Humans; Hypertension, Pulmonary; Prospective Studies; Proteomics; Scleroderma, Systemic; Lung Diseases, Interstitial; Biomarkers; Pulmonary Arterial Hypertension; Fibrosis; Blood Proteins; Lung
PubMed: 37936223
DOI: 10.1186/s12931-023-02578-0 -
Chest Jul 2023Frailty, measured as a single construct, is associated variably with poor outcomes before and after lung transplantation. The usefulness of a comprehensive frailty...
BACKGROUND
Frailty, measured as a single construct, is associated variably with poor outcomes before and after lung transplantation. The usefulness of a comprehensive frailty assessment before transplantation is unknown.
RESEARCH QUESTION
How are multiple frailty constructs, including phenotypic and cumulative deficit models, muscle mass, exercise tolerance, and social vulnerabilities, measured before transplantation, associated with short-term outcomes after lung transplantation?
STUDY DESIGN AND METHODS
We conducted a retrospective cohort study of 515 lung recipients who underwent frailty assessments before transplantation, including the short physical performance battery (SPPB), transplant-specific frailty index (FI), 6-min walk distance (6MWD), thoracic sarcopenia, and social vulnerability indexes. We tested the association between frailty measures before transplantation and outcomes after transplantation using logistic regression to model 1-year survival and zero-inflated negative binomial regression to model hospital-free days (HFDs) in the first 90 days after transplantation. Adjustment covariates included age, sex, native lung disease, transplantation type, lung allocation score, BMI, and primary graft dysfunction.
RESULTS
Before transplantation, 51.3% of patients were frail by FI (FI ≥ 0.25) and no patients were frail by SPPB. In multivariate adjusted models that also included FI, SPPB, and 6MWD, greater frailty by FI, but not SPPB, was associated with fewer HFDs (-0.006 per 0.01 unit worsening; 95% CI, -0.01 to -0.002 per 0.01 unit worsening) among discharged patients. Greater SPPB deficits were associated with decreased odds of 1-year survival (OR, 0.51 per 1 unit worsening; 95% CI, 0.28-0.93 per 1 unit worsening). Correlation among frailty measurements overall was poor. No association was found between thoracic sarcopenia, 6MWD, or social vulnerability assessments and short-term outcomes after lung transplantation.
INTERPRETATION
Both phenotypic and cumulative deficit models measured before transplantation are associated with short-term outcomes after lung transplantation. Cumulative deficit measures of frailty may be more relevant in the first 90 days after transplantation, whereas phenotypic frailty may have a stronger association with 1-year survival.
Topics: Humans; Frailty; Retrospective Studies; Sarcopenia; Lung Transplantation; Lung
PubMed: 36681147
DOI: 10.1016/j.chest.2023.01.017