Early-onset Chronic Obstructive Pulmonary Disease Research Articles

Role of Myeloperoxidase, Oxidative Stress, and Inflammation in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a lung complication of premature births. The leading causes of BPD are oxidative stress (OS) from oxygen treatment, infection or inflammation, and mechanical ventilation. OS activates alveolar myeloid cells with subsequent myeloperoxidase (MPO)-mediated OS. Premature human neonates lack sufficient antioxidative capacity and are susceptible to OS. Unopposed OS elicits inflammation, endoplasmic reticulum (ER) stress, and cellular senescence, culminating in a BPD phenotype. Poor nutrition, patent ductus arteriosus, and infection further aggravate OS. BPD survivors frequently suffer from reactive airway disease, neurodevelopmental deficits, and inadequate exercise performance and are prone to developing early-onset chronic obstructive pulmonary disease. Rats and mice are commonly used to study BPD, as they are born at the saccular stage, comparable to human neonates at 22-36 weeks of gestation. The alveolar stage in rats and mice starts at the postnatal age of 5 days. Because of their well-established antioxidative capacities, a higher oxygen concentration (hyperoxia, HOX) is required to elicit OS lung damage in rats and mice. Neutrophil infiltration and ER stress occur shortly after HOX, while cellular senescence is seen later. Studies have shown that MPO plays a critical role in the process. A novel tripeptide, N-acetyl-lysyltyrosylcysteine amide (KYC), a reversible MPO inhibitor, attenuates BPD effectively. In contrast, the irreversible MPO inhibitor-AZD4831-failed to provide similar efficacy. Interestingly, KYC cannot offer its effectiveness without the existence of MPO. We review the mechanisms by which this anti-MPO agent attenuates BPD.

Assessing the causal role of physical activity and leisure sedentary behaviours with chronic obstructive pulmonary disease: a Mendelian randomisation study

BackgroundObservational studies show that patients with chronic obstructive pulmonary disease (COPD) tend to be sedentary during leisure time. Physical activity (PA) may reduce the risk of COPD, but the causal...

Predicting early-onset COPD risk in adults aged 20-50 using electronic health records and machine learning.

Chronic obstructive pulmonary disease (COPD) is a major public health concern, affecting estimated 164 million people worldwide. Early detection and intervention strategies are essential to reduce the burden of COPD, but current screening approaches are limited in their ability to accurately predict risk. Machine learning (ML) models offer promise for improved accuracy of COPD risk prediction by combining genetic and electronic medical record data. In this study, we developed and evaluated eight ML models for primary screening of COPD utilizing routine screening data, polygenic risk scores (PRS), additional clinical data, or a combination of all three. To assess our models, we conducted a retrospective analysis of approximately 329,396 patients in the UK Biobank database. Incorporating personal information and blood biochemical test results significantly improved the model's accuracy for predicting COPD risk, achieving a best performance of 0.8505 AUC, a specificity of 0.8539 and a sensitivity of 0.7584. These results indicate that ML models can be effectively utilized for accurate prediction of COPD risk in individuals aged 20 to 50 years, providing a valuable tool for early detection and intervention.

Causal association of rheumatoid arthritis with obstructive lung disease: Evidence from Mendelian randomization study

BackgroundObservational studies have found an association between rheumatoid arthritis (RA) and risk of obstructive lung disease (ORDs). However, whether RA plays a role in ORDs development remains unclear. ObjectivesThis study aimed to explore the causal association of RA with ORDs. MethodsBoth univariable and multivariable Mendelian randomization (MR) analyses were employed. Summary statistics for RA were obtained from the genome-wide association study (GWAS) meta-analysis, and the GWAS data source of ORDs, including the chronic obstructive pulmonary disease (COPD) and asthma, was accessed from the FinnGen Biobank. Causal Analysis Using Summary Effect Estimates (CAUSE) method was used to improve statistical power. multivariable and two-step mediation MR was applied to calculate the independent and mediated effects. ResultsThe causal estimates by univariable and CAUSE results indicated genetic predisposition to RA had an effect on the increased risk of asthma/COPD (A/C) (ORCAUSE = 1.03; 95% CI: 1.02–1.04), COPD/asthma related infections (ACI) (ORCAUSE = 1.02; 95% CI: 1.01–1.03) and COPD/asthma related pneumonia or pneumonia derived septicemia (ACP) (ORCAUSE = 1.02; 95% CI: 1.01–1.03). Genetic predisposition to RA was significantly associated with early onset COPD (ORCAUSE = 1.02; 95% CI: 1.01–1.03) and asthma (ORCAUSE = 1.02; 95% CI: 1.01–1.03) risk and suggestively associated with non-allergic asthma (nAA) risk. After adjustment for confounders, independent causal effects remained for the associations of RA with risk of A/C, ACI, and ACP, as well as COPD, early-onset COPD, and asthma [total, nAA and allergic asthma (AA)] risk. Mediation analyses revealed no potential mediator. ConclusionThis study indicates a causal effect of increased genetic predisposition to RA on an increased risk of ORDs, including COPD and asthma, especially early-onset COPD and nAA, and on asthma/COPD related infections, pneumonia or pneumonia derived septicemia.

But I Still Can’t Breathe!: A Case Challenge

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that can cause life-threatening lung and liver damage and occasionally affects the skin. When it affects the lungs, it leads to early-onset chronic obstructive pulmonary disease. Alpha-1 antitrypsin, a protease inhibitor, is a defensive protein produced in the liver that protects the lungs from a powerful enzyme called neutrophil elastase. The inequality of alpha-1 antitrypsin to neutrophil elastase causes progressive degenerative damage to the lung. AATD often goes undiagnosed or misdiagnosed because of a lack of awareness of the disorder and because it has similar clinical features as asthma. Early identification and treatment of AATD are essential to preventing irreversible lung damage, respiratory failure, and even death.

Classification of COPD: fostering prevention and precision medicine in the Lancet Commission on COPD

Chronic obstructive pulmonary disease (COPD) is a highly prevalent and heterogeneous chronic disease of the lower airways and lungs that is associated with huge morbidity, disability, and mortality worldwide and disproportionately affects poor and vulnerable people. 1 Safiri S Carson-Chahhoud K Noori M et al. Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990–2019: results from the global burden of disease study 2019. BMJ. 2022; 378: e069679 PubMed Google Scholar Pathologically, COPD is characterised by variable degrees of chronic inflammation and remodelling of small airways (bronchiolitis) and destruction of alveolar walls (emphysema). 2 Brusselle GG Joos GF Bracke KR New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2011; 378: 1015-1026 Summary Full Text Full Text PDF PubMed Scopus (529) Google Scholar Diagnosis of COPD relies on respiratory symptoms and the presence of spirometric airflow limitation. 3 Global Initiative for Chronic Obstructive Lung DiseaseGlobal strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. https://goldcopd.org/2022-gold-reports-2/Date: 2022 Date accessed: July 30, 2022 Google Scholar COPD has long been considered a self-inflicted disease that occurs in adult cigarette smokers as a result of accelerated decline in lung function. 4 Fletcher C Peto R The natural history of chronic airflow obstruction. BMJ. 1977; 1: 1645-1648 Crossref PubMed Scopus (1799) Google Scholar However, epidemiological evidence has shown that many other factors, including indoor and outdoor air pollution, occupational exposures, and use of e-cigarettes and cannabis, also cause COPD. Furthermore, in addition to accelerated lung function decline in adulthood, several other lung function trajectories—characterised by impaired lung development in utero or impaired lung growth in early life—have been linked to COPD. 5 Lange P Celli B Agustí A et al. Lung-function trajectories leading to chronic obstructive pulmonary disease. N Engl J Med. 2015; 373: 111-122 Crossref PubMed Scopus (343) Google Scholar Indeed, COPD can be elicited by early-life events such as prematurity, childhood asthma, and childhood respiratory infections. Importantly, tuberculosis and HIV—common chronic infections, especially in low-income and middle-income countries—can lead to airway obstruction and COPD. Finally, although COPD is a complex disease caused by multiple gene–environment interactions throughout the life course, it is mainly genetically determined in specific subgroups of patients with early-onset COPD or a positive family history (eg, people with α1 antitrypsin deficiency). Towards the elimination of chronic obstructive pulmonary disease: a Lancet CommissionDespite substantial progress in reducing the global impact of many non-communicable diseases, including heart disease and cancer, morbidity and mortality due to chronic respiratory disease continues to increase. This increase is driven primarily by the growing burden of chronic obstructive pulmonary disease (COPD), and has occurred despite the identification of cigarette smoking as the major risk factor for the disease more than 50 years ago. Many factors have contributed to what must now be considered a public health emergency: failure to limit the sale and consumption of tobacco products, unchecked exposure to environmental pollutants across the life course, and the ageing of the global population (partly as a result of improved outcomes for other conditions). Full-Text PDF

The ongoing battle to address respiratory health in people experiencing homelessness

The ongoing battle to address respiratory health in people experiencing homelessness

Generation of four severe early-onset chronic obstructive pulmonary disease (COPD) patient-derived induced pluripotent stem cell lines from peripheral blood mononuclear cells

Evidence highlights the concept of multiple trajectories leading to COPD. Early-life events (i.e., in utero lung development) may influence the maximally attained lung function and increase the risk to develop COPD. Human pluripotent stem cells (hiPSC) represent a unique opportunity to model lung development. We generated hiPSC lines from four highly characterized COPD patients with early onset and severe phenotype. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using integration-free Sendai Virus. The cell lines had normal karyotype, expressed pluripotency hallmarks, and differentiated into the three primary germ layers.These lines offer a tool to study early-life origins of COPD.

Respiratory outcomes of "new" bronchopulmonary dysplasia in adolescents: A multicenter study.

ObjectiveLong‐term respiratory consequences of bronchopulmonary dysplasia (BPD) in preterm infants born in the post‐surfactant era (“new” BPD) remain partially unknown. The present study aimed to evaluate the respiratory outcomes of “new” BPD in adolescents who were born preterm.MethodsThis multicenter, cross‐sectional study included 286 adolescents born between 2003 and 2005 (mean age: 14.2 years); among them, 184 and 102 were born extremely preterm (EP; <28 weeks' gestation) and moderate–late preterm (32 to <37 weeks' gestation), respectively. Among EP adolescents, 92 had BPD, and 92 did not. All participants underwent lung function tests, skin prick testing, and questionnaires on asthma symptoms and quality of life.ResultsEP adolescents with BPD had significantly lower forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC than other included adolescents. FEV1/FVC ratios were below the lower limit of normal (z‐score <−1.645) in 30.4% of EP adolescents with BPD, 13.0% of EP adolescents without BPD, and 11.8% of adolescents who were born moderate–late preterm. Bronchodilator response and air‐trapping were significantly higher in BPD adolescents than in other adolescents. Diffusion capacity was significantly lower in EP adolescents than in moderate–late preterm adolescents. Asthma symptoms and quality‐of‐life scores were similar among groups.ConclusionEP adolescents with “new” BPD had poorer pulmonary function than EP adolescents without BPD or moderate–late preterm adolescents. Further studies are needed to determine whether “new” BPD is associated with early‐onset chronic obstructive pulmonary disease in adulthood.

Lifelong pulmonary sequelae of bronchopulmonary dysplasia.

To summarize the current literature evaluating long-term pulmonary morbidity among surviving very preterm infants with bronchopulmonary dysplasia (BPD). BPD predisposes very preterm infants to adverse respiratory signs and symptoms, greater respiratory medication use, and more frequent need for rehospitalization throughout early childhood. Reassuringly, studies also indicate that older children and adolescents with BPD experience, on average, similar functional status and quality of life when compared to former very preterm infants without BPD. However, measured deficits in pulmonary function may persist in those with BPD and indicate an increased susceptibility to early-onset chronic obstructive pulmonary disease during adulthood. Moreover, subtle differences in exercise tolerance and activity may put survivors with BPD at further risk of future morbidity in later life. Despite advances in neonatal respiratory care, a diagnosis of BPD continues to be associated with significant pulmonary morbidity over the first two decades of life. Long-term longitudinal studies are needed to determine if recent survivors of BPD will also be at increased risk of debilitating pulmonary disease in adulthood.

Lung MRI as a Potential Complementary Diagnostic Tool for Early COPD

IntroductionMany knowledge gaps in the nature of early chronic obstructive pulmonary disease (COPD) still exist, mainly because COPD has always been considered a disease of the elderly. Little attention has been paid to the pathologic changes in the lungs of young adults with risk factors for COPD, such as bronchopulmonary dysplasia. One major limitation is the current lack of noninvasive ways to sensitively measure or image functional declines from subjects who are at risk for COPD but haven't yet developed more significant clinical symptoms of the disease. MethodsWe report the use of lung magnetic resonance imaging with hyperpolarized gas in the diagnostic workup for bronchopulmonary dysplasia with underlying chronic airflow limitation in presence of spirometry criteria that meet the diagnosis of early-onset COPD. ConclusionsIn the postsurfactant era, where more young adults will be spirometrically diagnosed with COPD, patients should be classified not only on the basis of their airflow limitation, but also on lung abnormalities identified with safe, comprehensive imaging technologies that allow regular, longitudinal follow-up.

Determinants of the Appearance and Progression of Early-Onset Chronic Obstructive Pulmonary Disease in Young Adults. A Case–Control Study With Follow-Up

Introduction and ObjectivesDeterminants of chronic obstructive pulmonary disease (COPD) in the early stages of its natural history are not well known. Improving our knowledge of these factors will help to design interventions that can modify prognosis.Study objectives are: (a) to characterize a COPD population of young adults aged 35–50 years from a multidimensional point of view; (b) to compare these patients with smokers with normal lung function; and (c) to create a cohort of young adults aged 35–50 years (smokers or former smokers), with and without COPD, who will be followed in the future to improve understanding of the natural history of the disease. Participants and MethodThis is a case–control multicenter study aimed at establishing a well-characterized cohort of young adults, smokers or former-smokers, with and without COPD, for subsequent follow-up.A total of 311 participants (101 cases and 210 controls) were selected from approximately 30 primary care settings and 12 hospitals in 8 Spanish regions. Subjects were smokers or former smokers (>10 pack-years) aged 35–50 years. Diagnosis of COPD was based on a post-bronchodilator result of FEV1/FVC<70%.The main study variables were: questionnaires on health, symptoms, exacerbations and daily physical activity, lung function tests, blood and sputum samples, and low-dose computed tomography. In the statistical analysis, COPD patient characteristics will be described and compared with control subjects using a logistic regression analysis.

Whole-Genome Sequencing in Severe Chronic Obstructive Pulmonary Disease.

Genome-wide association studies have identified common variants associated with chronic obstructive pulmonary disease (COPD). Whole-genome sequencing (WGS) offers comprehensive coverage of the entire genome, as compared with genotyping arrays or exome sequencing. We hypothesized that WGS in subjects with severe COPD and smoking control subjects with normal pulmonary function would allow us to identify novel genetic determinants of COPD. We sequenced 821 patients with severe COPD and 973 control subjects from the COPDGene and Boston Early-Onset COPD studies, including both non-Hispanic white and African American individuals. We performed single-variant and grouped-variant analyses, and in addition, we assessed the overlap of variants between sequencing- and array-based imputation. Our most significantly associated variant was in a known region near HHIP (combined P = 1.6 × 10-9); additional variants approaching genome-wide significance included previously described regions in CHRNA5, TNS1, and SERPINA6/SERPINA1 (the latter in African American individuals). None of our associations were clearly driven by rare variants, and we found minimal evidence of replication of genes identified by previously reported smaller sequencing studies. With WGS, we identified more than 20 million new variants, not seen with imputation, including more than 10,000 of potential importance in previously identified COPD genome-wide association study regions. WGS in severe COPD identifies a large number of potentially important functional variants, with the strongest associations being in known COPD risk loci, including HHIP and SERPINA1. Larger sample sizes will be needed to identify associated variants in novel regions of the genome.

Cognitive Impairment in Chronic Obstructive Pulmonary Disease (COPD): Possible Utility of Marine Bioactive Compounds.

Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow limitation. Early-onset COPD in non-smoker subjects is ≥60 years and in the elderly is often associated with different comorbidities. Cognitive impairment is one of the most common feature in patients with COPD, and is associated with COPD severity and comorbidities. Cognitive impairment in COPD enhances the assistance requirement in different aspects of daily living, treatment adherence, and effectual self-management.This review describes various bioactive compounds of natural marine sources that modulate different targets shared by both COPD and cognitive impairment and hypothesizes a possible link between these two syndromes.

Whole exome sequencing analysis in severe chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is substantially influenced by genetic factors. Alpha-1 antitrypsin deficiency demonstrates that rare coding variants of large effect can influence COPD susceptibility. To identify additional rare coding variants in patients with severe COPD, we conducted whole exome sequencing analysis in 2543 subjects from two family-based studies (Boston Early-Onset COPD Study and International COPD Genetics Network) and one case-control study (COPDGene). Applying a gene-based segregation test in the family-based data, we identified significant segregation of rare loss of function variants in TBC1D10A and RFPL1 (P-value<2x10-6), but were unable to find similar variants in the case-control study. In single-variant, gene-based and pathway association analyses, we were unable to find significant findings that replicated or were significant in meta-analysis. However, we found that the top results in the two datasets were in proximity to each other in the protein-protein interaction network (P-value=0.014), suggesting enrichment of these results for similar biological processes. A network of these association results and their neighbors was significantly enriched in the transforming growth factor beta-receptor binding and cilia-related pathways. Finally, in a more detailed examination of candidate genes, we identified individuals with putative high-risk variants, including patients harboring homozygous mutations in genes associated with cutis laxa and Niemann-Pick Disease Type C. Our results likely reflect heterogeneity of genetic risk for COPD along with limitations of statistical power and functional annotation, and highlight the potential of network analysis to gain insight into genetic association studies.

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, with increasing prevalence, in particular in the elderly. COPD is characterised by abnormal tissue repair resulting in (small) airways disease and emphysema. There is accumulating evidence that ageing hallmarks are prominent features of COPD. These ageing hallmarks have been described in different subsets of COPD patients, in different lung compartments and also in a variety of cell types, and thus might contribute to different COPD phenotypes. A better understanding of the main differences and similarities between normal lung ageing and the pathology of COPD may improve our understanding of the mechanisms driving COPD pathology, in particular in those patients that develop the most severe form of COPD at a relatively young age, i.e. severe early-onset COPD patients.In this review, after introducing the main concepts of lung ageing and COPD pathology, we focus on the role of (abnormal) ageing in lung remodelling and repair in COPD. We discuss the current evidence for the involvement of ageing hallmarks in these pathological features of COPD. We also highlight potential novel treatment strategies and opportunities for future research based on our current knowledge of abnormal lung ageing in COPD.

Gene-based segregation method for identifying rare variants in family-based sequencing studies.

Whole-exome sequencing using family data has identified rare coding variants in Mendelian diseases or complex diseases with Mendelian subtypes, using filters based on variant novelty, functionality, and segregation with the phenotype within families. However, formal statistical approaches are limited. We propose a gene-based segregation test (GESE) that quantifies the uncertainty of the filtering approach. It is constructed using the probability of segregation events under the null hypothesis of Mendelian transmission. This test takes into account different degrees of relatedness in families, the number of functional rare variants in the gene, and their minor allele frequencies in the corresponding population. In addition, a weighted version of this test allows incorporating additional subject phenotypes to improve statistical power. We show via simulations that the GESE and weighted GESE tests maintain appropriate type I error rate, and have greater power than several commonly used region-based methods. We apply our method to whole-exome sequencing data from 49 extended pedigrees with severe, early-onset chronic obstructive pulmonary disease (COPD) in the Boston Early-Onset COPD study (BEOCOPD) and identify several promising candidate genes. Our proposed methods show great potential for identifying rare coding variants of large effect and high penetrance for family-based sequencing data. The proposed tests are implemented in an R package that is available on CRAN (https://cran.r-project.org/web/packages/GESE/).

Exome Sequencing Analysis in Severe, Early-Onset Chronic Obstructive Pulmonary Disease.

Genomic regions identified by genome-wide association studies explain only a small fraction of heritability for chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin deficiency shows that rare coding variants of large effect also influence COPD susceptibility. We hypothesized that exome sequencing in families identified through a proband with severe, early-onset COPD would identify additional rare genetic determinants of large effect. To identify rare genetic determinants of severe COPD. We applied filtering approaches to identify potential causal variants for COPD in whole exomes from 347 subjects in 49 extended pedigrees from the Boston Early-Onset COPD Study. We assessed the power of this approach under different levels of genetic heterogeneity using simulations. We tested genes identified in these families using gene-based association tests in exomes of 204 cases with severe COPD and 195 resistant smokers from the COPDGene study. In addition, we examined previously described loci associated with COPD using these datasets. We identified 69 genes with predicted deleterious nonsynonymous, stop, or splice variants that segregated with severe COPD in at least two pedigrees. Four genes (DNAH8, ALCAM, RARS, and GBF1) also demonstrated an increase in rare nonsynonymous, stop, and/or splice mutations in cases compared with resistant smokers from the COPDGene study; however, these results were not statistically significant. We demonstrate the limitations of the power of this approach under genetic heterogeneity through simulation. Rare deleterious coding variants may increase risk for COPD, but multiple genes likely contribute to COPD susceptibility.

An efficient method to genotype the polymorphisms of cholinergic nicotinic receptor subunit genes and their associations with COPD onset risk

ABSTRACTBackground: Single-nucleotide polymorphisms (SNPs) in the cholinergic nicotinic receptor subunit genes on chromosome 15q25.1, including CHRNA3, CHRNB4 and CHRNA5, are well-established biomarkers of chronic obstructive pulmonary disease (COPD) and lung cancer. Thus, there is great demand for a rapid, easy and inexpensive method to detect these variations for purpose of risk prediction in large populations. Aim of the Study: The aim of this study was to establish an accurate and efficient method for genotyping CHRN SNPs and testing their association with age at onset of COPD in Chinese population as well as the clinical stage in COPD patients. Materials and Methods: We designed a method to specifically genotype 5 SNPs of CHRN genes based on a modified high-resolution melt (HRM) method and then validated the genotyping results by direct sequencing of 120 samples. We further used the HRM method to genotype these 5 SNPs in 1,013 COPD patients. Results: Requiring little time, few material costs and only a simplified protocol, the modified HRM method could accurately distinguish the genotypes of CHRN SNPs, demonstrating kappa coefficients >0.96 based on the results from direct sequencing. Furthermore, the data showed that the GG genotype of SNP rs56218866 was associated with a significantly earlier age of COPD onset than A (AA+AG) genotypes (61.0 ± 8.93 vs. 67.8 ± 9.88; P = 0.031), which was not found for the other SNPs. No significant association was observed between the COPD stages and any of the above SNPs. Conclusion: A simple, rapid and efficient HRM method was introduced for CHRN SNP genotyping and a suggestion that the SNP rs56218866A>G is associated with early-onset COPD in a Chinese population was found.

Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers.

COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD.