Research examining transmissibility of bat coronaviruses to humans at the Wuhan Institute of Virology
First cases not linked to workers at the Wuhan Institute of Virology
Severe economic impact on China
Preponderance of early cases linked to workers at Huanan Market in Wuhan, China
Evidence of SARSr-CoVs found in raccoon dogs sold in the Huanan Market
Geneotype of SARSr-CoV-2 not optimized for human transmission
Chinese government denial that Huanan Market sold live animals.
Earliest case reported 30 km from Huanan Market
We are prone to confirmation bias when intrinsic or extrinsic factors prompt us to focus on or test a particular hypothesis. Confirmation bias can be induced by our own values and motives (e.g., values, fears, politics, economic incentives), and by the way in which a problem or a question is framed .
Confirmation bias in the laboratory
Empirical evidence for confirmation bias in information search dates back to Peter Wason’s research from the 1960s on the psychology of how people test rules. The most famous example is his Card Selection task (sometimes called the four-card task). Research participants are shown four cards and are asked which two cards they should turn to test a rule. You can try it out right here.
Which two cards would you turn to test the rule, “ All cards with an even number on one side have a vowel on the other side ”?
Most of us choose cards 2 and A , and both cards have the potential to confirm the hypothesis. If you turned over the 2 and found a vowel, that would confirm your hypothesis. If you turned over the A and found an even number, that would confirm your hypothesis. However, we would need to turn over the 2 and B cards to test whether this set of cards disconfirm the rule. Only if an even number is paired with a consonant is the rule violated. If you turned over the 2 and found a Z, for instance, or turned over the B and found a 4, then you would know the rule was wrong.
Another way we exhibit confirmation bias is in the kinds of questions we choose to ask, research shows. Many questions can only provide evidence that supports the hypothesis they test (e.g., “What makes you the right person for this job?”). We tend to be unbalanced in the number of questions we ask that would confirm or disconfirm our hypotheses.
In a classic 1978 paper , psychologists Mark Snyder and William Swann asked 58 undergraduate women at the University of Minnesota to test whether another participant fit a personality profile. Half tested whether their partner was an extravert. The other half tested whether their partner was an introvert.
To perform this test, each participant was shown a list of 26 questions and told to pick the 12 questions that would help them best test the hypothesis about their partner’s personality. The full list of questions fell into three categories. Eleven questions were the kind people usually ask of people they know are extraverts (“What kind of situations do you seek out if you want to meet new people?”). Ten questions were the kind people usually ask of people they know are introverts (“In what situations do you wish you could be more outgoing?”). The last five questions were irrelevant to extraversion and introversion (e.g., “What kind of charities do you like to contribute to?”).
Participants testing for evidence of extraversion were 52% more likely than participants testing for evidence of introversion to ask questions that would confirm extraversion. By contrast, participants testing for evidence of introversion were 115% more likely than participants testing for evidence of extraversion to ask questions that would confirm introversion.
Evidence that confirmation bias influences how we interpret and weigh information comes from research on framing effects in decision making. Framing effects occur when the way you consider a decision (e.g., by choosing versus rejecting one of two options), changes which option you choose. Imagine you are a judge deciding a child custody case between two parents getting a divorce, Parents A and B. Parent A gets along well with the child and is average in terms of income, health, working hours, and other characteristics typical of adults in the United States, whereas the characteristics of Parent B are more extreme. Parent B earns and travels for work more, has an active social life, minor health problems, and is very close with the child. How you decide between these two parents might depend on the frame through which you ask the question.
Average income Average health Average working hours Reasonable rapport with the child Relatively stable social life
Above-average income Very close relationship with the child Extremely active social life Lots of work-related travel Minor health problems
In 1993, psychologist Eldar Shafir showed 170 Princeton University undergraduates the information above and asked them to make a decision . He asked half to whom they would award custody. A majority (64%) awarded custody to Parent B. He asked the other half of participants to whom they would deny custody. A majority (55%) also denied custody to Parent B! How did the frame lead more participants to both award and deny custody to Parent B? The way the question was framed (award versus deny) led participants to change the way they interpreted and weighed the evidence. Participants who chose a parent in the “award frame” focused on positive features of the parents, which favored parent B. Participants who rejected a parent in the “deny frame” focused on negative features of the parents, which favored Parent A.
Confirmation bias in the newsroom
Investigative journalism can be influenced by confirmation bias at many stages. Confirmation bias can influence which stories editors and journalists decide are likely to be worth reporting. It can influence which journalists are assigned to stories (those who share the cognitive biases of their editor and, therefore, also believe the stories to be important and newsworthy). Most important, it can influence how they collect evidence and transform that evidence into information for the public. Confirmation bias can influence what data is gathered and featured, which sources are interviewed and deemed credible, how evidence and quotes are interpreted and analyzed, which aspects of the story are featured prominently, which are downplayed and which are removed.
Whether a news organization decided to report on the SARS-CoV-2 lab leak hypothesis , for instance, was a decision made by its editors who greenlight the stories and the journalist(s) who reported it . Journalists made decisions about what evidence they deemed credible and worth reporting to the public, which sources to interview, trust and quote , and how to contrast evidence for a lab leak against evidence for zoonotic or other origins (if those alternatives were present at all).
Tips to reduce confirmation bias
Confirmation bias can be reduced with interventions that range from simple decision strategies to more intensive training interventions. A simple strategy one can apply immediately is when testing a hypothesis, make sure to test if alternatives or its negative are true (a “ consider-the-opposite ” strategy). Our justice system assumes that a person is innocent until proven guilty, but many jurors, investigators, judges and the public do not. Most presume guilt . Asking ourselves to explicitly consider whether an accused person is innocent can increase our propensity to consider evidence that challenges their criminal case.
When reporting on a story, remember that people’s default is to adopt a positive test strategy. Remember to examine the neglected diagonal — evidence disconfirming the main hypothesis and confirming its alternatives.
New research by my collaborators and me finds that even one-shot debiasing training interventions can help people recognize confirmation bias and reduce its influence on their own judgments and decisions, in the short and long term.
In a 2015 study, we brought 278 Pittsburghers into the laboratory. Each participant completed a pretest consisting of three tests of their susceptibility to confirmation bias and two other biases (i.e., bias blind spot and correspondence bias ). One-third of the participants then watched a 30-minute training video developed by IARPA (the Intelligence Advanced Research Projects Activity). In the video, a narrator defines biases, actors demonstrate in skits how a bias might influence a judgment or decision, and then strategies are reviewed to reduce the bias. You can watch it here:
The other two-thirds of participants played a 90-minute “ serious” detective game . The game elicited each of the three biases during game play. At the end of each level, experts described the three biases and gave examples of how they influence professional judgments and decisions. Participants then received personalized feedback on the biases they exhibited during game play and strategies to mitigate the biases. They also practiced implementing those strategies.
After completing one of these two interventions, all participants completed a post-test that included scales measuring how the interventions influenced their susceptibility to each of the three biases. Two months later, participants completed a third round of bias scales online, which tested whether the intervention produced a lasting change.
This project was a long shot. Most decision scientists think that cognitive biases are like visual illusions — that we can learn that they exist, but we can’t do much to prevent or reduce them . What we found was striking. Whether participants watched the video or played the game, participants exhibited large reductions in their susceptibility to all three cognitive biases both immediately and even two months later.
In a 2019 paper with Anne-Laure Sellier and Irene Scopelliti — the Cartier-chaired professor of creativity and marketing at HEC Paris and a professor of marketing and behavioral science in the Bayes Business School at City, University of London, respectively — I found that debiasing training can improve decision making outside the laboratory, when people are not reminded of cognitive biases and do not know that their decisions are being observed. We conducted a naturalistic experiment in which 318 students enrolled in Masters degree programs at HEC Paris played our serious game once across a 20-day period.
We surreptitiously measured the extent to which the game influenced their susceptibility to confirmation bias by inserting a business case based on a real-world event, with which we measured their susceptibility to confirmation bias, into their courses. Students did not know that the course and game were connected.
Business cases are essentially a role playing game or simulation of a problem that business leaders might face. Students are presented with the problem and evidence (e.g., data, opinions of different employees and managers). They then conduct an analysis and decide their best course of action under those circumstances.
We found that students who played the debiasing training game before doing the case were 19% less likely to make an inferior hypothesis-confirming decision in the case (than participants who played the debiasing training game after doing the case.
These experiments give us hope that debiasing training can work. There is still much exciting work to be done to see when and how debiasing training interventions reduce cognitive biases and which features of these and other interventions are most effective.
Cognitive biases like confirmation bias can help us save time and energy when our initial hypotheses are correct, but they can also create catastrophic mistakes . Learning to understand, spot and correct them — especially when the stakes are high — is a valuable skill for all journalists.
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Carey Morewedge
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How did life begin on earth a lightning strike of an idea..
Yahya Chaudhry
Harvard Correspondent
Researchers mimic early conditions on barren planet to test hypothesis of ancient electrochemistry
About four billion years ago, Earth resembled the set of a summer sci-fi blockbuster. The planet’s surface was a harsh and barren landscape, recovering from hellish asteroid strikes, teeming with volcanic eruptions, and lacking enough nutrients to sustain even the simplest forms of life.
The atmosphere was composed predominantly of inert gases like nitrogen and carbon dioxide, meaning they did not easily engage in chemical reactions necessary to form the complex organic molecules that are the building blocks of life. Scientists have long sought to discover the key factors that enabled the planet’s chemistry to change enough to form and sustain life.
Now, new research zeroes in on how lightning strikes may have served as a vital spark, transforming the atmosphere of early Earth into a hotbed of chemical activity. In the study, published in Proceedings of the National Academy of Sciences , a team of Harvard scientists identified lightning-induced plasma electrochemistry as a potential source of reactive carbon and nitrogen compounds necessary for the emergence and survival of early life.
“The origin of life is one of the great unanswered questions facing chemistry,” said George M. Whitesides, senior author and the Woodford L. and Ann A. Flowers University Research Professor in the Department of Chemistry and Chemical Biology. How the fundamental building blocks of “nucleic acids, proteins, and metabolites emerged spontaneously remains unanswered.”
One of the most popular answers to this question is summarized in the so-called RNA World hypothesis, Whitesides said. That is the idea that available forms of the elements, such as water, soluble electrolytes, and common gases, formed the first biomolecules. In their study, the researchers found that lightning could provide accessible forms of nitrogen and carbon that led to the emergence and survival of biomolecules.
A plasma vessel used to mimic cloud-to-ground lightning and its resulting electrochemical reactions. The setup uses two electrodes, with one in the gas phase and the other submerged in water enriched with inorganic salts.
Credit: Haihui Joy Jiang
Researchers designed a plasma electrochemical setup that allowed them to mimic conditions of the early Earth and study the role lightning strikes might have had on its chemistry. They were able to generate high-energy sparks between gas and liquid phases — akin to the cloud-to-ground lightning strikes that would have been common billions of years ago.
The scientists discovered that their simulated lightning strikes could transform stable gases like carbon dioxide and nitrogen into highly reactive compounds. They found that carbon dioxide could be reduced to carbon monoxide and formic acid, while nitrogen could be converted into nitrate, nitrite, and ammonium ions.
These reactions occurred most efficiently at the interfaces between gas, liquid, and solid phases — regions where lightning strikes would naturally concentrate these products. This suggests that lightning strikes could have locally generated high concentrations of these vital molecules, providing diverse raw materials for the earliest forms of life to develop and thrive.
“Given what we’ve shown about interfacial lightning strikes, we are introducing different subsets of molecules, different concentrations, and different plausible pathways to life in the origin of life community,” said Thomas C. Underwood, co-lead author and Whitesides Lab postdoctoral fellow. “As opposed to saying that there’s one mechanism to create chemically reactive molecules and one key intermediate, we suggest that there is likely more than one reactive molecule that might have contributed to the pathway to life.”
The findings align with previous research suggesting that other energy sources, such as ultraviolet radiation, deep-sea vents, volcanoes, and asteroid impacts, could have also contributed to the formation of biologically relevant molecules. However, the unique advantage of cloud-to-ground lightning is its ability to drive high-voltage electrochemistry across different interfaces, connecting the atmosphere, oceans, and land.
The research adds a significant piece to the puzzle of life’s origins. By demonstrating how lightning could have contributed to the availability of essential nutrients, the study opens new avenues for understanding the chemical pathways that led to the emergence of life on Earth. As the research team continues to explore these reactions, they hope to uncover more about the early conditions that made life possible and to improve modern applications.
“Building on our work, we are now experimentally looking at how plasma electrochemical reactions may influence nitrogen isotopes in products, which has a potential geological relevance,” said co-lead author Haihui Joy Jiang, a former Whitesides lab postdoctoral fellow. “We are also interested in this research from an energy-efficiency and environmentally friendly perspective on chemical production. We are studying plasma as a tool to develop new methods of making chemicals and to drive green chemical processes, such as producing fertilizer used today.”
Harvard co-authors included Professor Dimitar D. Sasselov in the Department of Astronomy and Professor James G. Anderson in the Department of Chemistry and Chemical Biology, Department of Earth and Planetary Sciences, and the Harvard John A. Paulson School of Engineering and Applied Sciences.
The study not only sheds light on the past but also has implications for the search for life on other planets. Processes the researchers described could potentially contribute to the emergence of life beyond Earth.
“Lightning has been observed on Jupiter and Saturn; plasmas and plasma-induced chemistry can exist beyond our solar system,” Jiang said. “Moving forward, our setup is useful for mimicking environmental conditions of different planets, as well as exploring reaction pathways triggered by lightning and its analogs.”
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A pilot study on proteomic predictors of mortality in stable copd.
1. Introduction
2. materials and methods, 2.1. study design and ethics, 2.2. study population, 2.3. biological sample obtention, 2.4. liquid chromatography–tandem mass spectrometry (lc–ms/ms), 2.5. immune-based multiplexing, 2.6. data analysis, 2.6.1. calculation of the sample size, 2.6.2. descriptive statistics and comparisons between groups, 2.7. functional classification of proteins and network analysis, 2.8. generation of predictive models, 3.1. general characteristics of the patients, 3.2. proteomic profile, 3.3. prediction of death and days of survival ( table 4 and table 5 ), 3.3.1. conventional approach.
Fitting
Prediction (Internal Validation)
Model Name
Prot
Se/Sp/Acc/MCC
Cov
Se
Sp
MCC
Cov
PPV (Rep|Our)
NPV (Rep|Our)
Acc (Rep|Our)
31
1.00
1.00
0.78
1.00
0.79
0.77
1.00|1.00
0.84|0.91
0.90|0.93
10
1.00
1.00
0.89
1.00
0.89
0.82
1.00|1.00
0.91|0.95
0.95|0.96
10
1.00
1.00
1.00
0.90
0.88
0.73
0.90|0.82
1.00|1.00
0.95|0.93
10
1.00
0.68
0.80
1.00
0.80
0.53
0.82|0.70
1.00|1.00
0.89|0.86
Fitting
Prediction
Model Name
Proteins
R
Conformal Accuracy
Q
Conformal Accuracy
31
0.64
1.00
0.18
0.95
10
0.81
1.00
0.52
0.95
10
0.64
1.00
0.25
0.91
10
0.71
1.00
0.36
0.95
3.3.2. AI Free Choice of Proteins
4. discussion, 4.1. previous studies, 4.2. interpretation of novel findings, 4.2.1. differentially abundant proteins, 4.2.2. prediction of death and days of survival, 4.3. strengths and potential limitations, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.
WHO. COPD Factsheet. 2023. Available online: https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd) (accessed on 19 July 2024).
Global Initiative for Chronic Obstructive Lung Disease Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2023 Report). 2023. Available online: www.goldcopd.org (accessed on 19 July 2024).
Celli, B.R.; Fabbri, L.M.; Aaron, S.D.; Agusti, A.; Brook, R.; Criner, G.J.; Franssen, F.M.E.; Humbert, M.; Hurst, J.R.; O’donnell, D.; et al. An Updated Definition and Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbations: The Rome Proposal. Am. J. Respir. Crit. Care Med. 2021 , 204 , 1251–1258. [ Google Scholar ] [ CrossRef ]
Esteban, C.; Quintana, J.M.; Aburto, M.; Moraza, J.; Egurrola, M.; España, P.P.; Pérez-Izquierdo, J.; Capelastegui, A. Predictors of mortality in patients with stable COPD. J. Gen. Intern. Med. 2008 , 23 , 1829–1834. [ Google Scholar ] [ CrossRef ]
Nishimura, K.; Izumi, T.; Tsukino, M.; Oga, T. Dyspnea Is a Better Predictor of 5-Year Survival Than Airway Obstruction in Patients with COPD. Chest 2002 , 121 , 1434–1440. [ Google Scholar ] [ CrossRef ]
Oga, T.; Nishimura, K.; Tsukino, M.; Sato, S.; Hajiro, T. Analysis of the factors related to mortality in chronic obstructive pulmonary disease: Role of exercise capacity and health status. Am. J. Respir. Crit. Care Med. 2003 , 167 , 544–549. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Domingo-Salvany, A.; Lamarca, R.; Ferrer, M.; Garcia-Aymerich, J.; Alonso, J.; Félez, M.; Khalaf, A.; Marrades, R.M.; Monsó, E.; Serra-Batlles, J.; et al. Health-related Quality of Life and Mortality in Male Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2002 , 166 , 680–685. [ Google Scholar ] [ CrossRef ]
Almagro, P.; Calbo, E.; de Echaguïen, A.O.; Barreiro, B.; Quintana, S.; Heredia, J.L.; Garau, J. Mortality After Hospitalization for COPD. Chest 2002 , 121 , 1441–1448. [ Google Scholar ] [ CrossRef ]
Connors, A.F., Jr.; Dawson, N.V.; Thomas, C.; Harrell, F.E., Jr.; Desbiens, N.; Fulkerson, W.J.; Kussin, P.; Bellamy, P.; Goldman, L.; Knaus, W.A. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am. J. Respir. Crit. Care Med. 1996 , 154 , 959–967. [ Google Scholar ] [ CrossRef ]
Solanes-Garcia, I.; Casan, P. Causes of death and prediction of mortality in COPD. Arch Bronconeumol. 2010 , 46 , 343–346. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Lüthi-Corridori, G.; Boesing, M.; Roth, A.; Giezendanner, S.; Leuppi-Taegtmeyer, A.B.; Schuetz, P.; Leuppi, J.D. Predictors of Length of Stay, Rehospitalization and Mortality in Community-Acquired Pneumonia Patients: A Retrospective Cohort Study. J. Clin. Med. 2023 , 12 , 5601. [ Google Scholar ] [ CrossRef ]
Hartl, S.; Lopez-Campos, J.L.; Pozo-Rodriguez, F.; Castro-Acosta, A.; Studnicka, M.; Kaiser, B.; Roberts, C.M. Risk of death and re-admission of hospital-admitted COPD exacerbations: European COPD Audit. Eur. Respir. J. 2016 , 47 , 113–121. [ Google Scholar ] [ CrossRef ]
Han, M.-Z.; Hsiue, T.-R.; Tsai, S.-H.; Huang, T.-H.; Liao, X.-M.; Chen, C.-Z. Validation of the GOLD 2017 and new 16 subgroups (1A–4D) classifications in predicting exacerbation and mortality in COPD patients. Int. J. Chronic Obstr. Pulm. Dis. 2018 , 13 , 3425–3433. [ Google Scholar ] [ CrossRef ] [ PubMed ]
de Torres, J.P.; Casanova, C.; Marín, J.M.; Pinto-Plata, V.; Divo, M.; Zulueta, J.J.; Berto, J.; Zagaceta, J.; Sanchez-Salcedo, P.; Cabrera, C.; et al. Prognostic evaluation of COPD patients: GOLD 2011 versus BODE and the COPD comorbidity index COTE. Thorax 2014 , 69 , 799–804. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Flynn, R.W.V.; MacDonald, T.M.; Chalmers, J.D.; Schembri, S. The effect of changes to GOLD severity stage on long term morbidity and mortality in COPD. Respir. Res. 2018 , 19 , 249. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Smith, M.C.; Wrobel, J.P. Epidemiology and clinical impact of major comorbidities in patients with COPD. Int. J. Chronic Obstr. Pulm. Dis. 2014 , 9 , 871–888. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Divo, M.; Cote, C.; de Torres, J.P.; Casanova, C.; Marin, J.M.; Pinto-Plata, V.; Zulueta, J.; Cabrera, C.; Zagaceta, J.; Hunninghake, G.; et al. Comorbidities and Risk of Mortality in Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2012 , 186 , 155–161. [ Google Scholar ] [ CrossRef ]
Negewo, N.A.; Gibson, P.G.; McDonald, V.M. COPD and its comorbidities: Impact, measurement and mechanisms. Respirology 2015 , 20 , 1160–1171. [ Google Scholar ] [ CrossRef ]
Sato, S.; Oga, T.; Muro, S.; Tanimura, K.; Tanabe, N.; Nishimura, K.; Hirai, T. Changes in mortality among patients with chronic obstructive pulmonary disease from the 1990s to the 2000s: A pooled analysis of two prospective cohort studies. BMJ Open 2023 , 13 , e065896. [ Google Scholar ] [ CrossRef ]
Fähndrich, S.; Herr, C.; Teuteberg, S.; Söhler, S.; Soriano, D.; Classen, J.; Adams, J.; Weinhold, V.; Waschki, B.; Zeller, T.; et al. Midregional proatrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all-cause mortality in recently diagnosed mild to moderate COPD—Results from COSYCONET. Respir. Res. 2024 , 25 , 56. [ Google Scholar ] [ CrossRef ]
Hu, H.S.; Wang, Z.; Jian, L.Y.; Zhao, L.M.; Liu, X.D. Optimizing inhaled corticosteroid use in patients with chronic obstructive pul-monary disease: Assessing blood eosinophils, neutrophil-to-lymphocyte ratio, and mortality outcomes in US adults. Front Immunol. 2023 , 14 , 1230766. [ Google Scholar ] [ CrossRef ]
Echevarria, C.; Steer, J.; Prasad, A.; Quint, J.K.; Bourke, S.C. Admission blood eosinophil count, inpatient death and death at 1 year in exacerbating patients with COPD. Thorax 2023 , 78 , 1090–1096. [ Google Scholar ] [ CrossRef ]
Husebø, G.R.; Gabazza, E.C.; D’Alessandro Gabazza, C.; Yasuma, T.; Toda, M.; Aanerud, M.; Nielsen, R.; Bakke, P.S.; Eagan, T.M.L. Coag-ulation markers as predictors for clinical events in COPD. Respirology 2021 , 26 , 342–351. [ Google Scholar ] [ CrossRef ]
Rønnow, S.R.; Langholm, L.L.; Karsdal, M.A.; Manon-Jensen, T.; Tal-Singer, R.; Miller, B.E.; Vestbo, J.; Leeming, D.J.; Sand, J.M.B. Endo-trophin, an extracellular hormone, in combination with neoepitope markers of von Willebrand factor improves prediction of mortality in the ECLIPSE COPD cohort. Respir. Res. 2020 , 21 , 202. [ Google Scholar ] [ CrossRef ]
Rabe, K.F.; Martinez, F.J.; Ferguson, G.T.; Wang, C.; Singh, D.; Wedzicha, J.A.; Trivedi, R.; Rose, E.S.; Ballal, S.; McLaren, J.; et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N. Engl. J. Med. 2020 , 383 , 35–48. [ Google Scholar ] [ CrossRef ]
Calverley, P.M.; Anzueto, A.R.; Carter, K.; Grönke, L.; Hallmann, C.; Jenkins, C.; Wedzicha, J.; Rabe, K.F. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): A double-blind, randomised, parallel-group, active-controlled trial. Lancet Respir. Med. 2018 , 6 , 337–344. [ Google Scholar ] [ CrossRef ]
Lipson, D.A.; Crim, C.; Criner, G.J.; Day, N.C.; Dransfield, M.T.; Halpin, D.M.G.; Han, M.K.; Jones, C.E.; Kilbride, S.; Lange, P.; et al. Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2020 , 201 , 1508–1516. [ Google Scholar ] [ CrossRef ]
Enríquez-Rodríguez, C.J.; Casadevall, C.; Faner, R.; Castro-Costa, A.; Pascual-Guàrdia, S.; Seijó, L.; López-Campos, J.L.; Peces-Barba, G.; Monsó, E.; Barreiro, E.; et al. COPD: Systemic proteomic profiles in frequent and infrequent exacerbators. ERJ Open Res. 2024 , 10 . [ Google Scholar ] [ CrossRef ]
Enríquez-Rodríguez, C.J.; Pascual-Guardia, S.; Casadevall, C.; Caguana-Vélez, O.A.; Rodríguez-Chiaradia, D.; Barreiro, E.; Gea, J. Proteomic Blood Profiles Obtained by Totally Blind Biological Clustering in Stable and Exacerbated COPD Patients. Cells 2024 , 13 , 866. [ Google Scholar ] [ CrossRef ]
Arostegui, I.; Legarreta, M.J.; Barrio, I.; Esteban, C.; Garcia-Gutierrez, S.; Aguirre, U.; Quintana, J.M. IRYSS-COPD Group A Computer Application to Predict Adverse Events in the Short-Term Evolution of Patients with Exacerbation of Chronic Obstructive Pulmonary Disease. JMIR Med. Inform. 2019 , 7 , e10773. [ Google Scholar ] [ CrossRef ]
Austin, P.C.; White, I.R.; Lee, D.S.; van Buuren, S. Missing Data in Clinical Research: A Tutorial on Multiple Imputation. Can. J. Cardiol. 2021 , 37 , 1322–1331. [ Google Scholar ] [ CrossRef ]
Pastor, M.; Gomez-Tamayo, J.C.; Sanz, F. Flame: An open-source framework for model development, hosting, and usage in production envoiironments. J. Cheminform. 2021 , 13 , 31. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Castillo, E.G.; Pérez, T.A.; Ancochea, J.; Sanz, M.T.P.; Almagro, P.; Martínez-Camblor, P.; Miravitlles, M.; Rodríguez-Carballeira, M.; Navarro, A.; Lamprecht, B.; et al. Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: A pooled analysis of individual patient data. ERJ Open Res. 2020 , 6 . [ Google Scholar ] [ CrossRef ]
Chicco, D.; Warrens, M.J.; Jurman, G. The coefficient of determination R-squared is more informative than SMAPE, MAE, MAPE, MSE and RMSE in regression analysis evaluation. PeerJ Comput. Sci. 2021 , 7 , e623. [ Google Scholar ] [ CrossRef ]
Kiddle, S.J.; Whittaker, H.R.; Seaman, S.R.; Quint, J.K. Prediction of five-year mortality after COPD diagnosis using primary care records. PLoS ONE 2020 , 15 , e0236011. [ Google Scholar ] [ CrossRef ]
Gedebjerg, A.; Szépligeti, S.K.; Wackerhausen, L.-M.H.; Horváth-Puhó, E.; Dahl, R.; Hansen, J.G.; Sørensen, H.T.; Nørgaard, M.; Lange, P.; Thomsen, R.W. Prediction of mortality in patients with chronic obstructive pulmonary disease with the new Global Initiative for Chronic Obstructive Lung Disease 2017 classification: A cohort study. Lancet Respir. Med. 2018 , 6 , 204–212. [ Google Scholar ] [ CrossRef ]
van Hirtum, P.V.; Sprooten, R.T.M.; van Noord, J.A.; van Vliet, M.; de Kruif, M.D. Long term survival after admission for COPD exacerbation: A comparison with the general population. Respir. Med. 2018 , 137 , 77–82. [ Google Scholar ] [ CrossRef ]
Lorenzana, I.; Galera, R.; Casitas, R.; Martínez-Cerón, E.; Castillo, M.A.; Alfaro, E.; Cubillos-Zapata, C.; García-Río, F. Dynamic hy-perinflation is a risk factor for mortality and severe exacerbations in COPD patients. Respir. Med. 2024 , 225 , 107597. [ Google Scholar ] [ CrossRef ]
Nishimura, K.; Kusunose, M.; Shibayama, A.; Nakayasu, K. Is Frailty a Mortality Predictor in Subjects with Chronic Obstructive Pulmonary Disease? Int. J. Chronic Obstr. Pulm. Dis. 2023 , 18 , 2955–2960. [ Google Scholar ] [ CrossRef ]
Nishimura, K.; Kusunose, M.; Sanda, R.; Mori, M.; Shibayama, A.; Nakayasu, K. Comparison of Predictive Properties between Tools of Patient-Reported Outcomes: Risk Prediction for Three Future Events in Subjects with COPD. Diagnostics 2023 , 13 , 2269. [ Google Scholar ] [ CrossRef ]
Medina-Mirapeix, F.; Valera-Novella, E.; Morera-Balaguer, J.; Bernabeu-Mora, R. Prognostic value of the five-repetition sit-to-stand test for mortality in people with chronic obstructive pulmonary disease. Ann. Phys. Rehabil. Med. 2022 , 65 , 101598. [ Google Scholar ] [ CrossRef ]
Liu, S.-F.; Chin, C.-H.; Tseng, C.-W.; Chen, Y.-C.; Kuo, H.-C. Exertional Desaturation Has Higher Mortality Than Non-Desaturation in COPD. Medicina 2021 , 57 , 1110. [ Google Scholar ] [ CrossRef ]
Waschki, B.; Kirsten, A.; Holz, O.; Müller, K.C.; Meyer, T.; Watz, H.; Magnussen, H. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: A prospective cohort study. Chest 2011 , 140 , 331–342. [ Google Scholar ] [ CrossRef ]
Deng, M.; Lu, Y.; Zhang, Q.; Bian, Y.; Zhou, X.; Hou, G. Global prevalence of malnutrition in patients with chronic obstructive pulmonary disease: Systemic review and meta-analysis. Clin. Nutr. 2023 , 42 , 848–858. [ Google Scholar ] [ CrossRef ]
van Gestel, Y.R.; Hoeks, S.E.; Sin, D.D.; Hüzeir, V.; Stam, H.; Mertens, F.W.; van Domburg, R.T.; Bax, J.J.; Poldermans, D. COPD and cancer mortality: The influence of statins. Thorax 2009 , 64 , 963–967. [ Google Scholar ] [ CrossRef ]
Wasswa-Kintu, S.; Gan, W.Q.; Man, S.F.P.; Pare, P.D.; Sin, D.D. Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: A systematic review and meta-analysis. Thorax 2005 , 60 , 570–575. [ Google Scholar ] [ CrossRef ]
Zheng, Y.; Huang, Y.; Zheng, X.; Peng, J.; Chen, Y.; Yu, K.; Yang, Y.; Wang, X.; Yang, X.; Qian, J.; et al. Deaths from COPD in patients with cancer: A population-based study. Aging 2021 , 13 , 12641–12659. [ Google Scholar ] [ CrossRef ]
Lüthi-Corridori, G.; Boesing, M.; Ottensarendt, N.; Leuppi-Taegtmeyer, A.B.; Schuetz, P.; Leuppi, J.D. Predictors of Length of Stay, Mortality and Rehospitalization in COPD Patients: A Retrospective Cohort Study. J. Clin. Med. 2023 , 12 , 5322. [ Google Scholar ] [ CrossRef ]
Abdullah, A.S.; Eigbire, G.; Ali, M.; Awadalla, M.; Wahab, A.; Ibrahim, H.; Salama, A.; Alweis, R. Relationship of Atrial Fibrillation to Outcomes in Patients Hospitalized for Chronic Obstructive Pulmonary Disease Exacerbation. J. Atr. Fibrillation 2019 , 12 , 2117. [ Google Scholar ] [ CrossRef ]
Liao, K.-M.; Chen, C.-Y. Incidence and risk factors of atrial fibrillation in Asian COPD patients. Int. J. Chronic Obstr. Pulm. Dis. 2017 , 12 , 2523–2530. [ Google Scholar ] [ CrossRef ]
Warming, P.E.; Garcia, R.; Hansen, C.J.; Simons, S.O.; Torp-Pedersen, C.; Linz, D.; Tfelt-Hansen, J. Atrial fibrillation and chronic ob-structive pulmonary disease: Diagnostic sequence and mortality risk. Eur. Heart J. Qual. Care Clin. Outcomes 2023 , 9 , 128–134. [ Google Scholar ] [ CrossRef ]
Trudzinski, F.C.; Jörres, R.A.; Alter, P.; Kahnert, K.; Waschki, B.; Herr, C.; Kellerer, C.; Omlor, A.; Vogelmeier, C.F.; Fähndrich, S.; et al. Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET. Sci. Rep. 2020 , 10 , 10544. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Seyhan, E.C.; Özgül, M.A.; Tutar, N.; Ömür, I.; Uysal, A.; Altın, S. Red Blood Cell Distribution and Survival in Patients with Chronic Obstructive Pulmonary Disease. COPD J. Chronic Obstr. Pulm. Dis. 2013 , 10 , 416–424. [ Google Scholar ] [ CrossRef ]
Valvi, D.; Mannino, D.M.; Müllerova, H.; Tal-Singer, R. Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two United States cohorts. Int. J. Chronic Obstr. Pulm. Dis. 2012 , 7 , 173–182. [ Google Scholar ] [ PubMed ]
Oh, Y.-M.; Park, J.H.; Kim, E.-K.; Hwang, S.C.; Kim, H.J.; Kang, D.R.; Yoo, K.H.; Lee, J.-H.; Kim, T.-H.; Lim, S.Y.; et al. Anemia as a clinical marker of stable chronic obstructive pulmonary disease in the Korean obstructive lung disease cohort. J. Thorac. Dis. 2017 , 9 , 5008–5016. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Kim, Y.J.; Lim, B.; Kyung, S.Y.; Park, J.-W.; Jeong, S.H. Comorbidity and Inflammatory Markers May Contribute to Predict Mortality of High-Risk Patients with Chronic Obstructive Pulmonary Disease Exacerbation. J. Clin. Med. Res. 2016 , 8 , 531–536. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Chen, Z.; Zha, L.; Feng, G.; An, Q.; Shi, F.; Xu, J.; Xu, Q.; Xia, H.; Zhang, M.; Li, L. Prognostic Value of Serum Cholinesterase Levels for In-Hospital Mortality among Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. COPD J. Chronic Obstr. Pulm. Dis. 2023 , 20 , 178–185. [ Google Scholar ] [ CrossRef ]
Urban, M.H.; Stojkovic, S.; Demyanets, S.; Hengstenberg, C.; Valipour, A.; Wojta, J.; Burghuber, O.C. Soluble ST2 and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease—A 10-Year Cohort Study. J. Clin. Med. 2021 , 11 , 56. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Holmgaard, D.B.; Mygind, L.H.; Titlestad, I.; Madsen, H.; Pedersen, S.S.; Mortensen, O.H.; Pedersen, C. Calprotectin—A Marker of Mortality in COPD? Results from a Prospective Cohort Study. COPD J. Chronic Obstr. Pulm. Dis. 2013 , 10 , 581–587. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Ferrari, R.; Tanni, S.E.; Caram, L.M.; Corrêa, C.; Corrêa, C.R.; Godoy, I. Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease. Respir. Res. 2013 , 14 , 24. [ Google Scholar ] [ CrossRef ]
Agustí, A.; Edwards, L.D.; Rennard, S.I.; MacNee, W.; Tal-Singer, R.; Miller, B.E.; Vestbo, J.; Lomas, D.A.; Calverley, P.M.A.; Wouters, E.; et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Persistent Systemic Inflammation is Associated with Poor Clinical Outcomes in COPD: A Novel Phenotype. PLoS ONE 2012 , 7 , e37483. [ Google Scholar ] [ CrossRef ]
Wu, S.; Huang, K.; Chang, C.; Chu, X.; Zhang, K.; Li, B.; Yang, T. Serum Proteomic Profiling in Patients with Chronic Obstructive Pulmonary Disease. Int. J. Chronic Obstr. Pulm. Dis. 2023 , 18 , 1623–1635. [ Google Scholar ] [ CrossRef ]
Ubhi, B.K.; Cheng, K.K.; Dong, J.; Janowitz, T.; Jodrell, D.; Tal-Singer, R.; MacNee, W.; Lomas, D.A.; Riley, J.H.; Griffin, J.L.; et al. Targeted metabolomics identifies perturbations in amino acid metabolism that sub-classify patients with COPD. Mol. Biosyst. 2012 , 8 , 3125–3133. [ Google Scholar ] [ CrossRef ]
Zhang, Z.; Wang, J.; Li, Y.; Liu, F.; Chen, L.; He, S.; Lin, F.; Wei, X.; Fang, Y.; Li, Q.; et al. Proteomics and metabolomics profiling reveal panels of circulating diagnostic biomarkers and molecular subtypes in stable COPD. Respir. Res. 2023 , 24 , 73. [ Google Scholar ] [ CrossRef ]
Gregory, A.; Xu, Z.; Pratte, K.; Lee, S.; Liu, C.; Chase, R.; Yun, J.; Saferali, A.; Hersh, C.P.; Bowler, R.; et al. Clustering-based COPD subtypes have distinct longitudinal outcomes and multi-omics biomarkers. BMJ Open Respir. Res. 2022 , 9 , e001182. [ Google Scholar ] [ CrossRef ]
Gandhi, R.; Kalsariya, V.; Katara, R.; Murugan, Y. Sarcopenia, Eosinophil-to-Platelet Ratio, and C-reactive Protein as Predictors of Adverse Events in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Prospective Observational Study. Cureus 2024 , 16 , e56651. [ Google Scholar ] [ CrossRef ]
Zhou, R.; Pan, D. Association between admission heart rate and in-hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease and respiratory failure: A retrospective cohort study. BMC Pulm. Med. 2024 , 24 , 111. [ Google Scholar ] [ CrossRef ]
Bhat, R.; Kamath, S.; Jain, A.; Acharya, V.; Antony, T.; Holla, R.; Jha, A. RV in COPD—The complicated matters of the heart—Correlation of ECHO and biomarker with COPD severity and outcome. Lung India 2024 , 41 , 192–199. [ Google Scholar ] [ CrossRef ]
Zhou, W.-Q.; Song, X.; Dong, W.-H.; Chen, Z. Independent effect of the triglyceride-glucose index on all-cause mortality in critically ill patients with chronic obstructive pulmonary disease and asthma: A retrospective cohort study. Chronic Respir. Dis. 2024 , 21 . [ Google Scholar ] [ CrossRef ]
Holm, A.M.; Andreassen, S.L.; Christensen, V.L.; Kongerud, J.; Almås, Ø.; Auråen, H.; Henriksen, A.H.; Aaberge, I.S.; Klingenberg, O.; Rustøen, T. Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD. Int. J. Chronic Obstr. Pulm. Dis. 2020 , 15 , 799–807. [ Google Scholar ] [ CrossRef ]
Fortis, S.; Wan, E.S.; Kunisaki, K.; Eyck, P.T.; Ballas, Z.K.; Bowler, R.P.; Crapo, J.D.; Hokanson, J.E.; Wendt, C.; Silverman, E.K.; et al. Increased mortality associated with frequent exacerbations in COPD patients with mild-to-moderate lung function impairment, and smokers with normal spirometry. Respir. Med. X 2021 , 3 , 100025. [ Google Scholar ] [ CrossRef ]
Song, W.; Li, D.; Tao, L.; Luo, Q.; Chen, L. Solute carrier transporters: The metabolic gatekeepers of immune cells. Acta Pharm. Sin. B 2020 , 10 , 61–78. [ Google Scholar ] [ CrossRef ]
Merle, N.S.; Church, S.E.; Fremeaux-Bacchi, V.; Roumenina, L.T. Complement System Part I—Molecular Mechanisms of Activation and Regulation. Front. Immunol. 2015 , 6 , 262. [ Google Scholar ] [ CrossRef ]
Mandal, J.; Malla, B.; Steffensen, R.; Costa, L.; Egli, A.; Trendelenburg, M.; Blasi, F.; Kostikas, K.; Welte, T.; Torres, A.; et al. Man-nose-binding lectin protein and its association to clinical outcomes in COPD: A longitudinal study. Respir. Res. 2015 , 16 , 150. [ Google Scholar ] [ CrossRef ]
Santos, N.C.D.; Miravitlles, M.; Camelier, A.A.; Almeida, V.D.C.; Maciel, R.R.B.T.; Camelier, F.W.R. Prevalence and Impact of Comor-bidities in Individuals with Chronic Obstructive Pulmonary Disease: A Systematic Review. Tuberc. Respir. Dis. 2022 , 85 , 205–220. [ Google Scholar ] [ CrossRef ]
Kyriakopoulos, C.; Chronis, C.; Papapetrou, E.; Tatsioni, A.; Gartzonika, K.; Tsaousi, C.; Gogali, A.; Katsanos, C.; Vaggeli, A.; Tselepi, C.; et al. Prothrombotic state in patients with stable COPD: An observational study. ERJ Open Res. 2021 , 7 . [ Google Scholar ] [ CrossRef ]
Manon-Jensen, T.; Langholm, L.L.; Rønnow, S.R.; Karsdal, M.A.; Tal-Singer, R.; Vestbo, J.; Leeming, D.J.; Miller, B.E.; Bülow Sand, J.M. End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort. Respir. Med. 2019 , 160 , 105814. [ Google Scholar ] [ CrossRef ]
Liu, Y.; Liu, H.; Li, C.; Ma, C.; Ge, W. Proteome Profiling of Lung Tissues in Chronic Obstructive Pulmonary Disease (COPD): Platelet and Macrophage Dysfunction Contribute to the Pathogenesis of COPD. Int. J. Chronic Obstr. Pulm. Dis. 2020 , 15 , 973–980. [ Google Scholar ] [ CrossRef ]
Jankowski, M.; Undas, A.; Kaczmarek, P.; Butenas, S. Activated factor XI and tissue factor in chronic obstructive pulmonary disease: Links with inflammation and thrombin generation. Thromb. Res. 2011 , 127 , 242–246. [ Google Scholar ] [ CrossRef ]
Mannino, D.M.; Tal-Singer, R.; Lomas, D.A.; Vestbo, J.; Barr, G.; Tetzlaff, K.; Lowings, M.; Rennard, S.I.; Snyder, J.; Goldman, M.; et al. Plasma Fibrinogen as a Biomarker for Mortality and Hospitalized Exacerbations in People with COPD. Chronic Obstr. Pulm. Dis. 2015 , 2 , 23–34. [ Google Scholar ] [ CrossRef ]
Sand, J.M.B.; Rønnow, S.R.; Langholm, L.L.; Karsdal, M.A.; Manon-Jensen, T.; Tal-Singer, R.; Miller, B.E.; Vestbo, J.; Leeming, D.J. Combining biomarkers of clot resolution and alveolar basement membrane destruction predicts mortality in the ECLIPSE COPD cohort. Respir. Med. 2020 , 173 , 106185. [ Google Scholar ] [ CrossRef ]
Langholm, L.L.; Rønnow, S.R.; Sand, J.M.B.; Leeming, D.J.; Tal-Singer, R.; Miller, B.E.; Vestbo, J.; Karsdal, M.A.; Manon-Jensen, T. Increased von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated with Emphysema, Exacer-bations and Elevated Mortality Risk. Int. J. Chronic Obstr. Pulm. Dis. 2020 , 15 , 543–552. [ Google Scholar ] [ CrossRef ]
Foti, M.; Locati, M. (Eds.) Cytokine Effector Functions in Tissues ; Academic Press: Cambridge, MA, USA, 2017; ISBN 978-0-12-804214-4. [ Google Scholar ]
Kaneko, N.; Kurata, M.; Yamamoto, T.; Morikawa, S.; Masumoto, J. The role of interleukin-1 in general pathology. Inflamm. Regen. 2019 , 39 , 12. [ Google Scholar ] [ CrossRef ]
Costa, C.; Rufino, R.; Traves, S.L.; e Silva, J.R.L.; Barnes, P.J.; Donnelly, L.E. CXCR3 and CCR5 Chemokines in Induced Sputum from Patients with COPD. Chest 2008 , 133 , 26–33. [ Google Scholar ] [ CrossRef ]
Peng, J.; Yu, Q.; Fan, S.; Chen, X.; Tang, R.; Wang, D.; Qi, D. High Blood Eosinophil and YKL-40 Levels, as Well as Low CXCL9 Levels, are Associated with Increased Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Int. J. Chronic Obstr. Pulm. Dis. 2021 , 16 , 795–806. [ Google Scholar ] [ CrossRef ]
Kubysheva, N.I.; Postnikova, L.B.; Soodaeva, S.K.; Novikov, D.V.; Eliseeva, T.I.; Novikov, V.V.; Karaulov, A.V. Comparative Study of the Levels of IL-1β, IL-4, IL-8, TNFα, and IFNγ in Stable Course and Exacerbation of Chronic Obstructive Pulmonary Disease of Varying Severity. Bull. Exp. Biol. Med. 2022 , 173 , 745–748. [ Google Scholar ] [ CrossRef ]
Di Francia, M.; Barbier, D.; Mege, J.L.; Orehek, J. Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pul-monary disease. Am. J. Respir. Crit. Care Med. 1994 , 150 , 1453–1455. [ Google Scholar ] [ CrossRef ]
Schols, A.M.; Buurman, W.A.; Van den Brekel, A.S.; Dentener, M.A.; Wouters, E.F. Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. Thorax 1996 , 51 , 819–824. [ Google Scholar ] [ CrossRef ]
Nguyen, H.Q.; Herting, J.R.; Pike, K.C.; Gharib, S.A.; Matute-Bello, G.; Borson, S.; Kohen, R.; Adams, S.G.; Fan, V.S. Symptom profiles and inflammatory markers in moderate to severe COPD. BMC Pulm. Med. 2016 , 16 , 173. [ Google Scholar ] [ CrossRef ]
Mendy, A.; Forno, E.; Niyonsenga, T.; Gasana, J. Blood biomarkers as predictors of long-term mortality in COPD. Clin. Respir. J. 2018 , 12 , 1891–1899. [ Google Scholar ] [ CrossRef ]
Dahl, M.; Vestbo, J.; Lange, P.; Bojesen, S.E.; Tybjærg-Hansen, A.; Nordestgaard, B.G. C-reactive Protein as a Predictor of Prognosis in Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2007 , 175 , 250–255. [ Google Scholar ] [ CrossRef ]
Kelly, E.; Owen, C.A.; Pinto-Plata, V.; Celli, B.R. The role of systemic inflammatory biomarkers to predict mortality in chronic obstructive pulmonary disease. Expert. Rev. Respir. Med. 2013 , 7 , 57–64. [ Google Scholar ] [ CrossRef ]
Gea, J.; Sancho-Muñoz, A.; Chalela, R. Nutritional status and muscle dysfunction in chronic respiratory diseases: Stable phase versus acute exacerbations. J. Thorac. Dis. 2018 , 10 , S1332–S1354. [ Google Scholar ] [ CrossRef ]
Marquis, K.; Debigaré, R.; Lacasse, Y.; LeBlanc, P.; Jobin, J.; Carrier, G.; Maltais, F. Midthigh Muscle Cross-Sectional Area Is a Better Predictor of Mortality than Body Mass Index in Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2002 , 166 , 809–813. [ Google Scholar ] [ CrossRef ]
Plante, E.; Vance, R. Selection of preschool language tests: A data-based approach. Language, Speech, and Hearing Services in Schools 1994 , 25 , 15–24. [ Google Scholar ] [ CrossRef ]
Owusuaa, C.; Dijkland, S.A.; Nieboer, D.; van der Rijt, C.C.D.; van der Heide, A. Predictors of mortality in chronic obstructive pulmonary disease: A systematic review and meta-analysis. BMC Pulm. Med. 2022 , 22 , 125. [ Google Scholar ] [ CrossRef ]
White, N.; Kupeli, N.; Vickerstaff, V.; Stone, P. How accurate is the ‘Surprise Question’ at identifying patients at the end of life? A systematic review and meta-analysis. BMC Med. 2017 , 15 , 139. [ Google Scholar ] [ CrossRef ]
Aryal, S.; Diaz-Guzman, E.; Mannino, D.M. Influence of sex on chronic obstructive pulmonary disease risk and treatment out-comes. Int. J. Chronic Obstr. Pulm. Dis. 2014 , 9 , 1145–1154. [ Google Scholar ]
Ntritsos, G.; Franek, J.; Belbasis, L.; Christou, M.A.; Markozannes, G.; Altman, P.; Fogel, R.; Sayre, T.; Ntzani, E.E.; Evangelou, E. Gen-der-specific estimates of COPD prevalence: A systematic review and meta-analysis. Int. J. Chronic Obstr. Pulm. Dis. 2018 , 13 , 1507–1514. [ Google Scholar ] [ CrossRef ]
Drummond, M.B.; Wise, R.A.; Hansel, N.N.; Putcha, N. Comorbidities and Chronic Obstructive Pulmonary Disease: Prevalence, Influence on Outcomes, and Management. Semin. Respir. Crit. Care Med. 2015 , 36 , 575–591. [ Google Scholar ] [ CrossRef ]
Bai, S.; Ye, R.; Wang, C.; Sun, P.; Wang, D.; Yue, Y.; Wang, H.; Wu, S.; Yu, M.; Xi, S.; et al. Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype. Front. Mol. Biosci. 2021 , 8 , 650604. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Gea, J.; Enríquez-Rodríguez, C.J.; Pascual-Guardia, S. Metabolomics in COPD. Arch. Bronconeumol. 2023 , 59 , 311–321. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Gea, J.; Casadevall, C.; Nebot, P.; Enríquez-Rodríguez, C.J.; Faner, R.; Cosio, B.G.; Haro, N.; Pascual-Guardia, S.; Peces-Barba, G.; Monsó, E.; et al. Aging and metabolic changes in COPD patients. Am. J. Respir. Crit. Care Med. 2004 , 209 , A4314. [ Google Scholar ]
Click here to enlarge figure
COPD 4-Year Survivors (n = 23)
COPD 4-Year Non-Survivors (n = 11)
Age, year
67 ± 9
72 ± 7
Males, n (% in the group)
15 (65%)
9 (82%)
BMI, kg/m
25.4 ± 6.6
25.0 ± 6.5
FE, n (% in the group)
7 (30%)
7 (64%)
AE last year, n
1.7 ± 1.8
2.4 ± 3.8
Current, n (%)
6 (26%)
4 (36%)
Ex-smoker, n (%)
17 (74%)
7 (64%)
Pack/year smoking
52.2 ± 24.2
54.0 ± 20.6
Post-BD FEV , % pred
42 ± 15
42 ± 15
Post-BD FEV /FVC, % pred
49 ± 12
44 ± 9
DLco, %pred
48 ± 20
44 ± 13
I-II, n (% in the group)
5 (22%)
4 (36%)
III-IV, n (% in the group)
18 (78%)
7 (64%)
A-B, n (% in the group)
7 (30%)
2 (18%)
E, n (% in the group)
16 (70%)
9 (82%)
Leucocytes, /µL
8763 ± 2673
8313 ± 2673
Neutrophils, /µL
5627 ± 2333
5795 ± 2302
Eosinophils, /µL
259 ± 240
170 ± 123
CRP, mg/dL
0.8 ± 1.4
1.0 ± 1.1
Fibrinogen, mg/dL
211 ± 57
203 ± 37
Protein/ Ig Fraction
Protein Name
Functional Classification
%Δ
p-Value
A2M
Alpha-2-macroglobulin
Hemostasis
26.105
0.024
F12
Coagulation factor XII
Hemostasis
−27.265
0.038
F2
Prothrombin
Hemostasis
−14.521
0.046
PDGFB
Platelet-derived growth factor subunit B
Hemostasis
−69.182
0.015
PLG
Plasminogen
Hemostasis
−20.748
0.017
C1QA
Complement C1q subcomponent subunit A
Complement cascade
18.952
0.045
C1QC
Complement C1q subcomponent subunit C
Complement cascade
21.426
0.032
CFH
Complement factor H
Complement cascade
−17.151
0.022
CCL17
C-C motif chemokine 17
Cytokine
−63.547
0.035
CXCL9
C-X-C motif chemokine 9
Cytokine
85.719
0.029
IL1B
Interleukin-1 beta
Cytokine
−73.025
0.003
IGLV3-10
Immunoglobulin lambda variable 3-10
Adaptive immunity
53.784
0.046
PGLYRP2
N-acetylmuramoyl-L-alanine amidase
Other immune-related pathways
−25.314
0.018
GARIN1B
Golgi-associated RAB2 interactor protein 1B
Orphan
54.938
0.021
GPX3
Glutathione peroxidase 3
Orphan
−28.710
0.050
Protein/ Ig Fraction
Protein Name
Functional Classification
MCC
p-Value
F10
Coagulation factor X
Hemostasis
−0.403
0.022
PROZ
Vitamin K-dependent protein Z
Hemostasis
0.357
0.041
PTPN11
Tyrosine-protein phosphatase non-receptor type 11
Hemostasis
0.506
0.004
TLN1
Talin-1
Hemostasis
0.346
0.048
CFP
Properdin
Complement cascade
−0.403
0.022
CSF2
Granulocyte–macrophage colony-stimulating factor
Cytokine
−0.381
0.033
CXCL5
C-X-C motif chemokine 5
Cytokine
−0.403
0.022
IGHV2-5
Immunoglobulin heavy variable 2-5
Adaptive immunity
0.346
0.048
IGKV6-21
Immunoglobulin kappa variable 6-21
Adaptive immunity
−0.358
0.034
IGLV3-25
Immunoglobulin lambda variable 3-25
Adaptive immunity
−0.346
0.048
ATRN
Attractin
Other immune-related pathways
−0.451
0.016
GULP1
PTB domain-containing engulfment adapter protein 1
Other immune-related pathways
0.357
0.041
SLC2A(3,14)
Solute carrier family 2, facilitated glucose transporter member 13 and/or 14
Other immune-related pathways
0.471
0.007
IGFALS
Insulin-like growth factor-binding protein complex acid labile subunit
Orphan
−0.403
0.022
MYL6(B)
Myosin light polypeptide 6 or chain 6b
Orphan
−0.384
0.027
OR5M11
Olfactory receptor 5M11
Orphan
0.403
0.022
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Enríquez-Rodríguez, C.J.; Casadevall, C.; Faner, R.; Pascual-Guardia, S.; Castro-Acosta, A.; López-Campos, J.L.; Peces-Barba, G.; Seijo, L.; Caguana-Vélez, O.A.; Monsó, E.; et al. A Pilot Study on Proteomic Predictors of Mortality in Stable COPD. Cells 2024 , 13 , 1351. https://doi.org/10.3390/cells13161351
Enríquez-Rodríguez CJ, Casadevall C, Faner R, Pascual-Guardia S, Castro-Acosta A, López-Campos JL, Peces-Barba G, Seijo L, Caguana-Vélez OA, Monsó E, et al. A Pilot Study on Proteomic Predictors of Mortality in Stable COPD. Cells . 2024; 13(16):1351. https://doi.org/10.3390/cells13161351
Enríquez-Rodríguez, Cesar Jessé, Carme Casadevall, Rosa Faner, Sergi Pascual-Guardia, Ady Castro-Acosta, José Luis López-Campos, Germán Peces-Barba, Luis Seijo, Oswaldo Antonio Caguana-Vélez, Eduard Monsó, and et al. 2024. "A Pilot Study on Proteomic Predictors of Mortality in Stable COPD" Cells 13, no. 16: 1351. https://doi.org/10.3390/cells13161351
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Hypothesis confirmation and non-confirmation table.
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COMMENTS
Don't talk about hypotheses as being "either confirmed, partially
2. Conflation of rejection in a null hypothesis significance test with rejection of a substantive hypothesis. 3. Rejection of null hypothesis A taken as support for, or confirmation of, favored alternative hypothesis B. 4.
Confirmation
confirmation into a three-place relation concerning the evidence, the target hypothesis, and (a conjunction of) auxiliaries. Originally, Glymour presented his sophisticated neo-Hempelian approach
Confirmation and Induction
Confirmation and Induction. The term "confirmation" is used in epistemology and the philosophy of science whenever observational data and evidence "speak in favor of" or support scientific theories and everyday hypotheses. Historically, confirmation has been closely related to the problem of induction, the question of what to believe ...
Why a Confirmation Strategy Dominates Psychological Science
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Evidence and Confirmation
What sorts of information confirm what hypotheses is a question which has long been controversial; it was discussed as avidly three centuries ago as it is today, when, under the heading of "confirmation theory," it is one of the central topics in contemporary philosophy of science. Its profound interest to philosophers is due to its ...
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Hypothesis-generating and confirmatory studies, Bonferroni correction
Hypothesis-generating studies differ methodologically from confirmatory studies. A generated hypothesis must be confirmed in a new study. An experiment is usually required for confirmation as an observational study cannot provide unequivocal results.
Confirmation of Scientific Hypotheses as Relations
Logical approaches to confirmation, such as the hypothetico-deductive method and the positive instance ac count of confirmation, are problematic because of their neglect of the semantic dimension of hypothesis confirmation. Probabilistic accounts of confirmation are no better than log ical approaches in this regard.
Confirmation and Hypothesis
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Why a confirmation strategy dominates psychological science.
Our research explored the incidence and appropriateness of the much-maligned confirmatory approach to testing scientific hypotheses. Psychological scientists completed a survey about their research goals and strategies. The most frequently reported goal is to test the non-absolute hypothesis that a particular relation exists in some conditions. As expected, few scientists reported testing ...
The Confirmation of Hypotheses
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Confirmation bias
Confirmation bias is a person's tendency to process information by looking for, or interpreting, information that is consistent with their existing beliefs.
Hypothesis Testing
Hypothesis testing is a formal procedure for investigating our ideas about the world using statistics. It is most often used by scientists to test specific predictions, called hypotheses, that arise from theories.
Confirmation Bias In Psychology: Definition & Examples
Confirmation bias in psychology is the tendency to favor information that confirms existing beliefs or values. People exhibiting this bias are likely to seek out, interpret, remember, and give more weight to evidence that supports their views, while ignoring, dismissing, or undervaluing the relevance of evidence that contradicts them.
Confirmation bias
Confirmation bias (also confirmatory bias, myside bias, [a] or congeniality bias [2]) is the tendency to search for, interpret, favor, and recall information in a way that confirms or supports one's prior beliefs or values. [3] People display this bias when they select information that supports their views, ignoring contrary information, or ...
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Confirmation bias influences the questions we explore in both our professional and personal lives, whether our investigation is on behalf of an audience of millions or an audience of one. In journalism, confirmation bias can influence a reporter's assessment of whether a story is worth pitching and an editor's decision to greenlight a story ...
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Ancient Plant, Insect Bits Confirm Greenland Melted in Recent Geologic
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IMAGES
COMMENTS
2. Conflation of rejection in a null hypothesis significance test with rejection of a substantive hypothesis. 3. Rejection of null hypothesis A taken as support for, or confirmation of, favored alternative hypothesis B. 4.
confirmation into a three-place relation concerning the evidence, the target hypothesis, and (a conjunction of) auxiliaries. Originally, Glymour presented his sophisticated neo-Hempelian approach
Confirmation and Induction. The term "confirmation" is used in epistemology and the philosophy of science whenever observational data and evidence "speak in favor of" or support scientific theories and everyday hypotheses. Historically, confirmation has been closely related to the problem of induction, the question of what to believe ...
Our research explored the incidence and appropriateness of the much-maligned confirmatory approach to testing scientific hypotheses. Psychological scientists completed a survey about their research goals and strategies. The most frequently reported goal is to test the non-absolute hypothesis that a particular relation exists in some conditions. As expected, few scientists reported testing ...
What sorts of information confirm what hypotheses is a question which has long been controversial; it was discussed as avidly three centuries ago as it is today, when, under the heading of "confirmation theory," it is one of the central topics in contemporary philosophy of science. Its profound interest to philosophers is due to its ...
The numerous ways in which confirmation bias may influence attempts to accept or reject the null hypothesis are discussed, with implications for research, teaching, and public policy development.
Hypothesis-generating studies differ methodologically from confirmatory studies. A generated hypothesis must be confirmed in a new study. An experiment is usually required for confirmation as an observational study cannot provide unequivocal results.
Logical approaches to confirmation, such as the hypothetico-deductive method and the positive instance ac count of confirmation, are problematic because of their neglect of the semantic dimension of hypothesis confirmation. Probabilistic accounts of confirmation are no better than log ical approaches in this regard.
Confirmation and Hypothesis. CONFIRMATION AND HYPOTHESIS*. LAWRENCE RESNICK. Lafayette College, Easton, Pennsylvania. This article consists in a critical examination of an argument which purports to prove that many scientific hypotheses held to be probable are actually certain. The argument rests on the assumption that since the nonphilosopher ...
Our research explored the incidence and appropriateness of the much-maligned confirmatory approach to testing scientific hypotheses. Psychological scientists completed a survey about their research goals and strategies. The most frequently reported goal is to test the non-absolute hypothesis that a particular relation exists in some conditions. As expected, few scientists reported testing ...
THE CONFIRMATION OF HYPOTHESES. IT is commonly said in philosophical discussions of scientific method. that while a~ scientific hypothesis of some generality or abstractness can be disconfirmed or eliminated,' it can be confirmed only in the sense in which evidence may tend to confirm or partially confirm hypoth- eses;2 it can never be ...
The confirmation bias advocates seem to be ignoring the important and difficult process of hypothesis generation, particularly under ambiguous and changing conditions.
Confirmation If a well-designed study delivers the results predicted by the hypothesis, then that hypothesis is confirmed. Note, however, that there is a difference between a confirmed hypothesis and a "proven" hypothesis.
Confirmation bias is a person's tendency to process information by looking for, or interpreting, information that is consistent with their existing beliefs.
Hypothesis testing is a formal procedure for investigating our ideas about the world using statistics. It is most often used by scientists to test specific predictions, called hypotheses, that arise from theories.
Confirmation bias in psychology is the tendency to favor information that confirms existing beliefs or values. People exhibiting this bias are likely to seek out, interpret, remember, and give more weight to evidence that supports their views, while ignoring, dismissing, or undervaluing the relevance of evidence that contradicts them.
Confirmation bias (also confirmatory bias, myside bias, [a] or congeniality bias [2]) is the tendency to search for, interpret, favor, and recall information in a way that confirms or supports one's prior beliefs or values. [3] People display this bias when they select information that supports their views, ignoring contrary information, or ...
Confirmation bias, as the term is typically used in the psychological literature, connotes the seeking or interpreting of evidence in ways that are partial to existing beliefs, expectations, or a hypothesis in hand. The author reviews evidence of such a bias in a variety of guises and gives examples of its operation in several practical contexts.
Abstract What have been called 'Bayesian confirmation measures' or 'evidential support measures' offer a numerical expression for the impact of a piece of evidence on a judicial hypothesis of interest. The Bayes' factor, sometimes simply called the 'likelihood ratio', represents the best measure of the value of the evidence. It satisfies a number of necessary conditions on ...
Revised on March 10, 2023. Confirmation bias is the tendency to seek out and prefer information that supports our preexisting beliefs. As a result, we tend to ignore any information that contradicts those beliefs. Confirmation bias is often unintentional but can still lead to poor decision-making in (psychology) research and in legal or real ...
Confirmation bias can prevent us from considering other information when making decisions because we tend to only see factors that support our beliefs. Here's what to know about confirmation bias.
Confirmation bias influences the questions we explore in both our professional and personal lives, whether our investigation is on behalf of an audience of millions or an audience of one. In journalism, confirmation bias can influence a reporter's assessment of whether a story is worth pitching and an editor's decision to greenlight a story ...
Researchers mimic early conditions on barren planet to test hypothesis of ancient electrochemistry.
To our knowledge, this is the first study to analyze the predictive ability of blood proteomics on long-term mortality (4 years) in stable COPD patients through the combination of two complementary conceptual approaches (non-hypothesis-biased and hypothesis-driven analyses).
Ancient Plant, Insect Bits Confirm Greenland Melted in Recent Geologic Past; Climate. Ancient Plant, Insect Bits Confirm Greenland Melted in Recent Geologic Past ... The new study lends further credence to the "fragile Greenland" hypothesis: An entire tundra ecosystem established itself where today ice is two miles deep.