{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T03:34:29Z","timestamp":1794022469705,"version":"4.8.0"},"reference-count":228,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Drug Discov"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1038\/s41573-025-01290-6","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T09:50:32Z","timestamp":1758534632000},"page":"98-115","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities\u00a0\u00a0"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3271-3788","authenticated-orcid":false,"given":"Alvar","family":"Agusti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Faner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"1290_CR1","doi-asserted-by":"publisher","first-page":"2300239","DOI":"10.1183\/13993003.00239-2023","volume":"61","author":"A Agusti","year":"2023","unstructured":"Agusti, A. et al. Global initiative for chronic obstructive lung disease 2023 report: GOLD executive summary. Eur. Respir. J. 61, 2300239 (2023).","journal-title":"Eur. Respir. J."},{"key":"1290_CR2","unstructured":"Fletcher, C., Peto, R., Tinker, C. & Speizer, F. The Natural History of Chronic Bronchitis and Emphysema. (Oxford University Press, 1976)."},{"key":"1290_CR3","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1136\/bmj.1.6077.1645","volume":"1","author":"C Fletcher","year":"1977","unstructured":"Fletcher, C. & Peto, R. The natural history of chronic airflow obstruction. Br. Med. J. 1, 1645\u20131648 (1977).","journal-title":"Br. Med. J."},{"key":"1290_CR4","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1411532","volume":"373","author":"P Lange","year":"2015","unstructured":"Lange, P. et al. Lung-function trajectories leading to chronic obstructive pulmonary disease. N. Engl. J. Med. 373, 111\u2013122 (2015).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR5","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/S2213-2600(18)30529-0","volume":"7","author":"A Agusti","year":"2019","unstructured":"Agusti, A. & Faner, R. Lung function trajectories in health and disease. Lancet Respir. Med. 7, 358\u2013364 (2019).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR6","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/S2213-2600(17)30434-4","volume":"5","author":"A Agust\u00ed","year":"2017","unstructured":"Agust\u00ed, A., Noell, G., Brugada, J. & Faner, R. Lung function in early adulthood and health in later life: a transgenerational cohort analysis. Lancet Respir. Med. 5, 935\u2013945 (2017).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR7","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1056\/NEJMra1900475","volume":"381","author":"A Agusti","year":"2019","unstructured":"Agusti, A. & Hogg, J. C. Update on the pathogenesis of chronic obstructive pulmonary disease. N. Engl. J. Med. 381, 1248\u20131256 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR8","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/S2213-2600(21)00555-5","volume":"10","author":"A Agust\u00ed","year":"2022","unstructured":"Agust\u00ed, A., Mel\u00e9n, E., DeMeo, D. L., Breyer-Kohansal, R. & Faner, R. Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene\u2013environment interactions across the lifespan. Lancet Respir. Med. 10, 512\u2013524 (2022).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR9","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/S0140-6736(24)00016-3","volume":"403","author":"E Melen","year":"2024","unstructured":"Melen, E. et al. Lung function trajectories: relevance and implementation in clinical practice. Lancet 403, 1494\u20131503 (2024).","journal-title":"Lancet"},{"key":"1290_CR10","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1136\/thoraxjnl-2014-205507","volume":"69","author":"A Agusti","year":"2014","unstructured":"Agusti, A. The path to personalized medicine in COPD. Thorax 69, 857\u2013864 (2014).","journal-title":"Thorax"},{"key":"1290_CR11","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/S2213-2600(23)00261-8","volume":"11","author":"LM Fabbri","year":"2023","unstructured":"Fabbri, L. M. et al. COPD and multimorbidity: recognising and addressing a syndemic occurrence. Lancet Respir. Med. 11, 1020\u20131034 (2023).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR12","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00132-2017","volume":"4","author":"BR Celli","year":"2018","unstructured":"Celli, B. R. & Agust\u00ed, A. COPD: time to improve its taxonomy? ERJ Open Res. 4, 00132-2017 (2018).","journal-title":"ERJ Open Res."},{"key":"1290_CR13","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/S0140-6736(22)01273-9","volume":"400","author":"D Stolz","year":"2022","unstructured":"Stolz, D. et al. Towards the elimination of chronic obstructive pulmonary disease: a lancet commission. Lancet 400, 921\u2013972 (2022).","journal-title":"Lancet"},{"key":"1290_CR14","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1183\/13993003.01359-2015","volume":"47","author":"A Agusti","year":"2016","unstructured":"Agusti, A. et al. Treatable traits: toward precision medicine of airway diseases. Eur. Respir. J. 47, 410\u2013419 (2016).","journal-title":"Eur. Respir. J."},{"key":"1290_CR15","doi-asserted-by":"publisher","first-page":"1801269","DOI":"10.1183\/13993003.01269-2018","volume":"52","author":"R Boaventura","year":"2018","unstructured":"Boaventura, R., Sibila, O., Agusti, A. & Chalmers, J. D. Treatable traits in bronchiectasis. Eur. Respir. J. 52, 1801269 (2018).","journal-title":"Eur. Respir. J."},{"key":"1290_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106572","volume":"187","author":"A Agusti","year":"2021","unstructured":"Agusti, A. et al. Moving towards a treatable traits model of care for the management of obstructive airways diseases. Respir. Med. 187, 106572 (2021).","journal-title":"Respir. Med."},{"key":"1290_CR17","doi-asserted-by":"publisher","first-page":"230143","DOI":"10.1183\/16000617.0143-2023","volume":"33","author":"A Papi","year":"2024","unstructured":"Papi, A. et al. From treatable traits to GETomics in airway disease: moving towards clinical practice. Eur. Respir. Rev. 33, 230143 (2024).","journal-title":"Eur. Respir. Rev."},{"key":"1290_CR18","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1056\/NEJMoa1713901","volume":"378","author":"DA Lipson","year":"2018","unstructured":"Lipson, D. A. et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N. Engl. J. Med. 378, 1671\u20131680 (2018).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1056\/NEJMoa1916046","volume":"383","author":"KF Rabe","year":"2020","unstructured":"Rabe, K. F. et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N. Engl. J. Med. 383, 35\u201348 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1164\/rccm.202201-0209PP","volume":"206","author":"D Singh","year":"2022","unstructured":"Singh, D. et al. Blood eosinophils and chronic obstructive pulmonary disease: a global initiative for chronic obstructive lung disease science committee 2022 review. Am. J. Respir. Crit. Care Med. 206, 17\u201324 (2022).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR21","doi-asserted-by":"publisher","first-page":"230084","DOI":"10.1183\/16000617.0084-2023","volume":"32","author":"S Lea","year":"2023","unstructured":"Lea, S., Higham, A., Beech, A. & Singh, D. How inhaled corticosteroids target inflammation in COPD. Eur. Respir. Rev. 32, 230084 (2023).","journal-title":"Eur. Respir. Rev."},{"key":"1290_CR22","doi-asserted-by":"publisher","first-page":"2401875","DOI":"10.1183\/13993003.01875-2024","volume":"65","author":"C Leung","year":"2025","unstructured":"Leung, C. et al. Transcriptomic profiling of the airway epithelium in COPD links airway eosinophilia to type 2 inflammation and corticosteroid response. Eur. Respir. J. 65, 2401875 (2025).","journal-title":"Eur. Respir. J."},{"key":"1290_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037483","volume":"7","author":"A Agusti","year":"2012","unstructured":"Agusti, A. et al. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS ONE 7, e37483 (2012).","journal-title":"PLoS ONE"},{"key":"1290_CR24","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/S0140-6736(04)16900-6","volume":"364","author":"JC Hogg","year":"2004","unstructured":"Hogg, J. C. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 364, 709\u2013721 (2004).","journal-title":"Lancet"},{"key":"1290_CR25","first-page":"833","volume":"128","author":"GW Hunninghake","year":"1983","unstructured":"Hunninghake, G. W. & Crystal, R. G. Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers. Am. Rev. Respir. Dis. 128, 833\u2013838 (1983).","journal-title":"Am. Rev. Respir. Dis."},{"key":"1290_CR26","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1164\/ajrccm.165.1.145a","volume":"165","author":"TF Murphy","year":"2002","unstructured":"Murphy, T. F., Sethi, S., Hill, S. L. & Stockley, R. A. Inflammatory markers in bacterial exacerbations of COPD. Am. J. Respir. Crit. Care Med. 165, 132 (2002).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR27","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1136\/thoraxjnl-2020-216037","volume":"76","author":"VV Polosukhin","year":"2021","unstructured":"Polosukhin, V. V. et al. Small airway determinants of airflow limitation in chronic obstructive pulmonary disease. Thorax 76, 1079\u20131088 (2021).","journal-title":"Thorax"},{"key":"1290_CR28","doi-asserted-by":"publisher","first-page":"190073","DOI":"10.1183\/16000617.0073-2019","volume":"29","author":"M Cazzola","year":"2020","unstructured":"Cazzola, M., Stolz, D., Rogliani, P. & Matera, M. G. \u03b11-antitrypsin deficiency and chronic respiratory disorders. Eur. Respir. Rev. 29, 190073 (2020).","journal-title":"Eur. Respir. Rev."},{"key":"1290_CR29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S2213-2600(16)30430-1","volume":"5","author":"NG McElvaney","year":"2017","unstructured":"McElvaney, N. G. et al. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir. Med. 5, 51\u201360 (2017).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR30","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1056\/NEJMoa032158","volume":"350","author":"JC Hogg","year":"2004","unstructured":"Hogg, J. C. et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 350, 2645\u20132653 (2004).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR31","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1164\/rccm.201705-0903OC","volume":"198","author":"MA Bewley","year":"2018","unstructured":"Bewley, M. A. et al. Opsonic phagocytosis in chronic obstructive pulmonary disease is enhanced by Nrf2 agonists. Am. J. Respir. Crit. Care Med. 198, 739\u2013750 (2018).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR32","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1378\/chest.11-2348","volume":"141","author":"LE Donnelly","year":"2012","unstructured":"Donnelly, L. E. & Barnes, P. J. Defective phagocytosis in airways disease. Chest 141, 1055\u20131062 (2012).","journal-title":"Chest"},{"key":"1290_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-13-101","volume":"13","author":"A Noguera","year":"2012","unstructured":"Noguera, A. et al. An investigation of the resolution of inflammation (catabasis) in COPD. Respir. Res. 13, 101 (2012).","journal-title":"Respir. Res."},{"key":"1290_CR34","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1172\/JCI121087","volume":"129","author":"SA Christenson","year":"2019","unstructured":"Christenson, S. A. et al. An airway epithelial IL-17A response signature identifies a steroid-unresponsive COPD patient subgroup. J. Clin. Invest. 129, 169\u2013181 (2019).","journal-title":"J. Clin. Invest."},{"key":"1290_CR35","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1111\/j.1399-0039.2005.00354.x","volume":"65","author":"AW Ryan","year":"2005","unstructured":"Ryan, A. W. et al. Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1. Tissue Antigens 65, 150\u2013155 (2005).","journal-title":"Tissue Antigens"},{"key":"1290_CR36","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nri705","volume":"2","author":"FY Liew","year":"2002","unstructured":"Liew, F. Y. TH1 and TH2 cells: a historical perspective. Nat. Rev. Immunol. 2, 55\u201360 (2002).","journal-title":"Nat. Rev. Immunol."},{"key":"1290_CR37","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1417","volume":"11","author":"A Higham","year":"2022","unstructured":"Higham, A., Dungwa, J., Pham, T. H., McCrae, C. & Singh, D. Increased mast cell activation in eosinophilic chronic obstructive pulmonary disease. Clin. Transl. Immunol. 11, e1417 (2022).","journal-title":"Clin. Transl. Immunol."},{"key":"1290_CR38","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1007\/s10787-022-00967-3","volume":"30","author":"J Li","year":"2022","unstructured":"Li, J. et al. COPD lung studies of Nrf2 expression and the effects of Nrf2 activators. Inflammopharmacology 30, 1431\u20131443 (2022).","journal-title":"Inflammopharmacology"},{"key":"1290_CR39","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1111\/all.14661","volume":"76","author":"A Higham","year":"2021","unstructured":"Higham, A. et al. Type 2 inflammation in eosinophilic chronic obstructive pulmonary disease. Allergy 76, 1861\u20131864 (2021).","journal-title":"Allergy"},{"key":"1290_CR40","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1111\/all.14016","volume":"75","author":"L George","year":"2020","unstructured":"George, L. et al. Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma. Allergy 75, 370\u2013380 (2020).","journal-title":"Allergy"},{"key":"1290_CR41","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1164\/rccm.201408-1458OC","volume":"191","author":"SA Christenson","year":"2015","unstructured":"Christenson, S. A. et al. Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 191, 758\u2013766 (2015).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR42","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1164\/rccm.202009-3448OC","volume":"203","author":"Z Wang","year":"2021","unstructured":"Wang, Z. et al. Inflammatory endotype\u2013associated airway microbiome in chronic obstructive pulmonary disease clinical stability and exacerbations: a multicohort longitudinal analysis. Am. J. Respir. Crit. Care Med. 203, 1488\u20131502 (2021).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR43","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1186\/s12931-020-01552-4","volume":"21","author":"AS Beech","year":"2020","unstructured":"Beech, A. S. et al. Bacteria and sputum inflammatory cell counts; a COPD cohort analysis. Respir. Res. 21, 289 (2020).","journal-title":"Respir. Res."},{"key":"1290_CR44","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1164\/rccm.202105-1162LE","volume":"205","author":"I Van Rossem","year":"2022","unstructured":"Van Rossem, I., Hanon, S., Verbanck, S. & Vanderhelst, E. Blood eosinophil counts in chronic obstructive pulmonary disease: adding within-day variability to the equation. Am. J. Respir. Crit. Care Med. 205, 727\u2013729 (2022).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR45","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12931-020-1279-4","volume":"21","author":"GH Long","year":"2020","unstructured":"Long, G. H. et al. The stability of blood eosinophils in chronic obstructive pulmonary disease. Respir. Res. 21, 15 (2020).","journal-title":"Respir. Res."},{"key":"1290_CR46","doi-asserted-by":"publisher","first-page":"2003802","DOI":"10.1183\/13993003.04167-2020","volume":"56","author":"A Higham","year":"2020","unstructured":"Higham, A. & Singh, D. Stability of eosinophilic inflammation in COPD bronchial biopsies. Eur. Respir. J. 56, 2003802 (2020).","journal-title":"Eur. Respir. J."},{"key":"1290_CR47","doi-asserted-by":"publisher","first-page":"1700853","DOI":"10.1183\/13993003.00853-2017","volume":"50","author":"VL Kim","year":"2017","unstructured":"Kim, V. L. et al. Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort. Eur. Respir. J. 50, 1700853 (2017).","journal-title":"Eur. Respir. J."},{"key":"1290_CR48","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1136\/thoraxjnl-2017-210408","volume":"73","author":"D Mayhew","year":"2018","unstructured":"Mayhew, D. et al. Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations. Thorax 73, 422\u2013430 (2018).","journal-title":"Thorax"},{"key":"1290_CR49","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1111\/jcmm.16206","volume":"25","author":"T Southworth","year":"2021","unstructured":"Southworth, T. et al. The relationship between airway immunoglobulin activity and eosinophils in COPD. J. Cell Mol. Med. 25, 2203\u20132212 (2021).","journal-title":"J. Cell Mol. Med."},{"key":"1290_CR50","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1164\/rccm.201908-1550OC","volume":"201","author":"MA Martinez-Garcia","year":"2020","unstructured":"Martinez-Garcia, M. A. et al. Inhaled steroids, circulating eosinophils, chronic airway infection, and pneumonia risk in chronic obstructive pulmonary disease. a network analysis. Am. J. Respir. Crit. Care Med. 201, 1078\u20131085 (2020).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR51","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nri2735","volume":"10","author":"W Paul","year":"2010","unstructured":"Paul, W. & Zhu, J. How are TH2-type immune responses initiated and amplified? Nat. Rev. Immunol. 10, 225\u2013235 (2010).","journal-title":"Nat. Rev. Immunol."},{"key":"1290_CR52","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202302584RR","volume":"38","author":"EJ Goetzl","year":"2024","unstructured":"Goetzl, E. J. Th2 cells in rapid immune responses and protective avoidance reactions. FASEB J. 38, e23485 (2024).","journal-title":"FASEB J."},{"key":"1290_CR53","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-016-0650-5","volume":"16","author":"HT Tan","year":"2016","unstructured":"Tan, H. T., Sugita, K. & Akdis, C. A. Novel biologicals for the treatment of allergic diseases and asthma. Curr. Allergy Asthma Rep. 16, 70 (2016).","journal-title":"Curr. Allergy Asthma Rep."},{"key":"1290_CR54","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nri.2017.118","volume":"18","author":"JA Walker","year":"2018","unstructured":"Walker, J. A. & McKenzie, A. N. J. T(H)2 cell development and function. Nat. Rev. Immunol. 18, 121\u2013133 (2018).","journal-title":"Nat. Rev. Immunol."},{"key":"1290_CR55","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1091\/mbc.e08-10-1014","volume":"20","author":"EA Severson","year":"2009","unstructured":"Severson, E. A., Lee, W. Y., Capaldo, C. T., Nusrat, A. & Parkos, C. A. Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol. Biol. Cell 20, 1916\u20131925 (2009).","journal-title":"Mol. Biol. Cell"},{"key":"1290_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2021.153477","volume":"223","author":"G Karpathiou","year":"2021","unstructured":"Karpathiou, G., Papoudou-Bai, A., Ferrand, E., Dumollard, J. M. & Peoc\u2019h, M. STAT6: A review of a signaling pathway implicated in various diseases with a special emphasis in its usefulness in pathology. Pathol. Res. Pract. 223, 153477 (2021).","journal-title":"Pathol. Res. Pract."},{"key":"1290_CR57","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/imr.12577","volume":"280","author":"D Yang","year":"2017","unstructured":"Yang, D., Han, Z. & Oppenheim, J. J. Alarmins and immunity. Immunol. Rev. 280, 41\u201356 (2017).","journal-title":"Immunol. Rev."},{"key":"1290_CR58","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.coi.2014.09.004","volume":"31","author":"C Cayrol","year":"2014","unstructured":"Cayrol, C. & Girard, J.-P. IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy. Curr. Opin. Immunol. 31, 31\u201337 (2014).","journal-title":"Curr. Opin. Immunol."},{"key":"1290_CR59","doi-asserted-by":"publisher","first-page":"8702","DOI":"10.3390\/ijms24108702","volume":"24","author":"L Riera-Martinez","year":"2023","unstructured":"Riera-Martinez, L., Canaves-Gomez, L., Iglesias, A., Martin-Medina, A. & Cosio, B. G. The role of IL-33\/ST2 in COPD and its future as an antibody therapy. Int. J. Mol. Sci. 24, 8702 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"1290_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9327","volume":"6","author":"ES Cohen","year":"2015","unstructured":"Cohen, E. S. et al. Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation. Nat. Commun. 6, 8327 (2015).","journal-title":"Nat. Commun."},{"key":"1290_CR61","doi-asserted-by":"publisher","first-page":"2202210","DOI":"10.1183\/13993003.02210-2022","volume":"62","author":"S Strickson","year":"2023","unstructured":"Strickson, S. et al. Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE\/EGFR signalling complex. Eur. Respir. J. 62, 2202210 (2023).","journal-title":"Eur. Respir. J."},{"key":"1290_CR62","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1016\/j.bbadis.2014.06.009","volume":"1842","author":"E Pace","year":"2014","unstructured":"Pace, E. et al. Cigarette smoke alters IL-33 expression and release in airway epithelial cells. Biochim. Biophys. Acta 1842, 1630\u20131637 (2014).","journal-title":"Biochim. Biophys. Acta"},{"key":"1290_CR63","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.immuni.2015.02.011","volume":"42","author":"J Kearley","year":"2015","unstructured":"Kearley, J. et al. Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection. Immunity 42, 566\u2013579 (2015).","journal-title":"Immunity"},{"key":"1290_CR64","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00347-2024","volume":"64","author":"M Abdo","year":"2024","unstructured":"Abdo, M. et al. Association of airway inflammation and smoking status with IL-33 level in sputum of patients with asthma or COPD. Eur. Respir. J. 64, 2400347 (2024).","journal-title":"Eur. Respir. J."},{"key":"1290_CR65","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1164\/rccm.202210-1881OC","volume":"208","author":"A Faiz","year":"2023","unstructured":"Faiz, A. et al. IL-33 expression is lower in current smokers at both transcriptomic and protein levels. Am. J. Respir. Crit. Care Med. 208, 1075\u20131087 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR66","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.4049\/jimmunol.178.6.3373","volume":"178","author":"SI Bogiatzi","year":"2007","unstructured":"Bogiatzi, S. I. et al. Cutting edge: proinflammatory and Th2 cytokines synergize to induce thymic stromal lymphopoietin production by human skin keratinocytes. J. Immunol. 178, 3373\u20133377 (2007).","journal-title":"J. Immunol."},{"key":"1290_CR67","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.4049\/jimmunol.181.4.2790","volume":"181","author":"S Ying","year":"2008","unstructured":"Ying, S. et al. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J. Immunol. 181, 2790\u20132798 (2008).","journal-title":"J. Immunol."},{"key":"1290_CR68","doi-asserted-by":"publisher","first-page":"L375","DOI":"10.1152\/ajplung.00045.2007","volume":"293","author":"K Zhang","year":"2007","unstructured":"Zhang, K. et al. Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease. Am. J. Physiol. Lung Cell Mol. Physiol. 293, L375\u2013L382 (2007).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"1290_CR69","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1159\/000329131","volume":"4","author":"J Calven","year":"2012","unstructured":"Calven, J. et al. Viral stimuli trigger exaggerated thymic stromal lymphopoietin expression by chronic obstructive pulmonary disease epithelium: role of endosomal TLR3 and cytosolic RIG-I-like helicases. J. Innate Immun. 4, 86\u201399 (2012).","journal-title":"J. Innate Immun."},{"key":"1290_CR70","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41577-022-00735-y","volume":"23","author":"R Ebina-Shibuya","year":"2023","unstructured":"Ebina-Shibuya, R. & Leonard, W. J. Role of thymic stromal lymphopoietin in allergy and beyond. Nat. Rev. Immunol. 23, 24\u201337 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"1290_CR71","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1007\/s40265-021-01616-9","volume":"81","author":"D Singh","year":"2021","unstructured":"Singh, D., Lea, S. & Mathioudakis, A. G. Inhaled phosphodiesterase inhibitors for the treatment of chronic obstructive pulmonary disease. Drugs 81, 1821\u20131830 (2021).","journal-title":"Drugs"},{"key":"1290_CR72","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3390\/cells14090659","volume":"14","author":"RT Sherpa","year":"2025","unstructured":"Sherpa, R. T., Koziol-White, C. J. & Panettieri, R. A. Jr Advancing obstructive airway disease treatment: dual PDE3\/4 inhibition as a therapeutic strategy. Cells 14, 659 (2025).","journal-title":"Cells"},{"key":"1290_CR73","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1111\/j.1476-5381.2009.00170.x","volume":"157","author":"KH Banner","year":"2009","unstructured":"Banner, K. H. & Press, N. J. Dual PDE3\/4 inhibitors as therapeutic agents for chronic obstructive pulmonary disease. Br. J. Pharmacol. 157, 892\u2013906 (2009).","journal-title":"Br. J. Pharmacol."},{"key":"1290_CR74","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94888","volume":"3","author":"J Beute","year":"2018","unstructured":"Beute, J. et al. A pathophysiological role of PDE3 in allergic airway inflammation. JCI Insight 3, e94888 (2018).","journal-title":"JCI Insight"},{"key":"1290_CR75","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1124\/pr.116.012518","volume":"68","author":"PJ Barnes","year":"2016","unstructured":"Barnes, P. J. Kinases as novel therapeutic targets in asthma and chronic obstructive pulmonary disease. Pharmacol. Rev. 68, 788\u2013815 (2016).","journal-title":"Pharmacol. Rev."},{"key":"1290_CR76","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1080\/17476348.2020.1732821","volume":"14","author":"C Pelaia","year":"2020","unstructured":"Pelaia, C., Vatrella, A., Sciacqua, A., Terracciano, R. & Pelaia, G. Role of p38-mitogen-activated protein kinase in COPD: pathobiological implications and therapeutic perspectives. Expert Rev. Respir. Med. 14, 485\u2013491 (2020).","journal-title":"Expert Rev. Respir. Med."},{"key":"1290_CR77","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1183\/09031936.00170711","volume":"42","author":"K Gaffey","year":"2013","unstructured":"Gaffey, K., Reynolds, S., Plumb, J., Kaur, M. & Singh, D. Increased phosphorylated p38 mitogen-activated protein kinase in COPD lungs. Eur. Respir. J. 42, 28\u201341 (2013).","journal-title":"Eur. Respir. J."},{"key":"1290_CR78","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1183\/09031936.00036707","volume":"31","author":"T Renda","year":"2008","unstructured":"Renda, T. et al. Increased activation of p38 MAPK in COPD. Eur. Respir. J. 31, 62\u201369 (2008).","journal-title":"Eur. Respir. J."},{"key":"1290_CR79","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115606","volume":"258","author":"YR Bai","year":"2023","unstructured":"Bai, Y. R. et al. The recent advance of Interleukin-1 receptor associated kinase 4 inhibitors for the treatment of inflammation and related diseases. Eur. J. Med. Chem. 258, 115606 (2023).","journal-title":"Eur. J. Med. Chem."},{"key":"1290_CR80","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj3289","volume":"15","author":"S Lavazais","year":"2023","unstructured":"Lavazais, S. et al. IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases. Sci. Transl. Med. 15, eabj3289 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1290_CR81","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/S2213-2600(23)00324-7","volume":"11","author":"KB Hisert","year":"2023","unstructured":"Hisert, K. B. et al. Understanding and addressing the needs of people with cystic fibrosis in the era of CFTR modulator therapy. Lancet Respir. Med. 11, 916\u2013931 (2023).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR82","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1164\/rccm.202109-2064TR","volume":"205","author":"M Dransfield","year":"2022","unstructured":"Dransfield, M. et al. Cystic fibrosis transmembrane conductance regulator: roles in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 205, 631\u2013640 (2022).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR83","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1164\/rccm.201304-0733OC","volume":"188","author":"SV Raju","year":"2013","unstructured":"Raju, S. V. et al. Cigarette smoke induces systemic defects in cystic fibrosis transmembrane conductance regulator function. Am. J. Respir. Crit. Care Med. 188, 1321\u20131330 (2013).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR84","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1465-9921-15-69","volume":"15","author":"F Hassan","year":"2014","unstructured":"Hassan, F. et al. Accumulation of metals in GOLD4 COPD lungs is associated with decreased CFTR levels. Respir. Res. 15, 69 (2014).","journal-title":"Respir. Res."},{"key":"1290_CR85","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1164\/rccm.201205-0875OC","volume":"187","author":"M Le Gars","year":"2013","unstructured":"Le Gars, M. et al. Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo. Am. J. Respir. Crit. Care Med. 187, 170\u2013179 (2013).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR86","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1165\/rcmb.2016-0226OC","volume":"56","author":"SV Raju","year":"2017","unstructured":"Raju, S. V. et al. The cystic fibrosis transmembrane conductance regulator potentiator ivacaftor augments mucociliary clearance abrogating cystic fibrosis transmembrane conductance regulator inhibition by cigarette smoke. Am. J. Respir. Cell Mol. Biol. 56, 99\u2013108 (2017).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"1290_CR87","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1513\/AnnalsATS.201805-325RL","volume":"16","author":"K Teerapuncharoen","year":"2019","unstructured":"Teerapuncharoen, K. et al. Acquired cystic fibrosis transmembrane conductance regulator dysfunction and radiographic bronchiectasis in current and former smokers: a cross-sectional study. Ann. Am. Thorac. Soc. 16, 150\u2013153 (2019).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"1290_CR88","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1378\/chest.13-0274","volume":"144","author":"MT Dransfield","year":"2013","unstructured":"Dransfield, M. T. et al. Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD. Chest 144, 498\u2013506 (2013).","journal-title":"Chest"},{"key":"1290_CR89","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1001\/jama.2023.2065","volume":"329","author":"AA Diaz","year":"2023","unstructured":"Diaz, A. A. et al. Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease. JAMA 329, 1832\u20131839 (2023).","journal-title":"JAMA"},{"key":"1290_CR90","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.727806","volume":"12","author":"C Audousset","year":"2021","unstructured":"Audousset, C., McGovern, T. & Martin, J. G. Role of Nrf2 in disease: novel molecular mechanisms and therapeutic approaches - pulmonary disease\/asthma. Front. Physiol. 12, 727806 (2021).","journal-title":"Front. Physiol."},{"key":"1290_CR91","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11050965","volume":"11","author":"PJ Barnes","year":"2022","unstructured":"Barnes, P. J. Oxidative stress in chronic obstructive pulmonary disease. Antioxidants 11, 965 (2022).","journal-title":"Antioxidants"},{"key":"1290_CR92","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","volume":"1865","author":"I Bellezza","year":"2018","unstructured":"Bellezza, I., Giambanco, I., Minelli, A. & Donato, R. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim. Biophys. Acta Mol. Cell Res. 1865, 721\u2013733 (2018).","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"1290_CR93","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1164\/rccm.202203-0482OC","volume":"207","author":"EM Ryan","year":"2023","unstructured":"Ryan, E. M. et al. NRF2 activation reprograms defects in oxidative metabolism to restore macrophage function in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 207, 998\u20131011 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR94","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nri3452","volume":"13","author":"E Latz","year":"2013","unstructured":"Latz, E., Xiao, T. S. & Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13, 397\u2013411 (2013).","journal-title":"Nat. Rev. Immunol."},{"key":"1290_CR95","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.cell.2010.01.040","volume":"140","author":"K Schroder","year":"2010","unstructured":"Schroder, K. & Tschopp, J. The inflammasomes. Cell 140, 821\u2013832 (2010).","journal-title":"Cell"},{"key":"1290_CR96","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00002-2016","volume":"2","author":"R Faner","year":"2016","unstructured":"Faner, R. et al. The inflammasome pathway in stable COPD and acute exacerbations. ERJ Open Res. 2, 00002-02016 (2016).","journal-title":"ERJ Open Res."},{"key":"1290_CR97","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1183\/09031936.00128008","volume":"33","author":"PJ Barnes","year":"2009","unstructured":"Barnes, P. J. & Celli, B. R. Systemic manifestations and comorbidities of COPD. Eur. Respir. J. 33, 1165\u20131185 (2009).","journal-title":"Eur. Respir. J."},{"key":"1290_CR98","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1056\/NEJMra2032506","volume":"386","author":"GG Brusselle","year":"2022","unstructured":"Brusselle, G. G. & Koppelman, G. H. Biologic therapies for severe asthma. N. Engl. J. Med. 386, 157\u2013171 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR99","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1056\/NEJMoa1708208","volume":"377","author":"ID Pavord","year":"2017","unstructured":"Pavord, I. D. et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N. Engl. J. Med. 377, 1613\u20131629 (2017).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR100","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/j.jaip.2019.01.036","volume":"7","author":"A Yousuf","year":"2019","unstructured":"Yousuf, A., Ibrahim, W., Greening, N. J. & Brightling, C. E. T2 biologics for chronic obstructive pulmonary disease. J. Allergy Clin. Immunology: Pract. 7, 1405\u20131416 (2019).","journal-title":"J. Allergy Clin. Immunology: Pract."},{"key":"1290_CR101","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.2147\/COPD.S418944","volume":"18","author":"D Singh","year":"2023","unstructured":"Singh, D. et al. Benralizumab prevents recurrent exacerbations in patients with chronic obstructive pulmonary disease: a post hoc analysis. Int. J. Chron. Obstruct. Pulmon. Dis. 18, 1595\u20131599 (2023).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"1290_CR102","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1164\/rccm.201405-0992OC","volume":"191","author":"SI Rennard","year":"2015","unstructured":"Rennard, S. I. et al. CXCR2 antagonist MK-7123. A phase 2 proof-of-concept trial for chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 191, 1001\u20131011 (2015).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR103","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s12931-017-0633-7","volume":"18","author":"PMA Calverley","year":"2017","unstructured":"Calverley, P. M. A. et al. A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease. Respir. Res. 18, 153 (2017).","journal-title":"Respir. Res."},{"key":"1290_CR104","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1080\/15412555.2017.1335697","volume":"14","author":"A Eich","year":"2017","unstructured":"Eich, A. et al. A randomized, placebo-controlled phase 2 trial of CNTO 6785 in chronic obstructive pulmonary disease. COPD 14, 476\u2013483 (2017).","journal-title":"COPD"},{"key":"1290_CR105","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1378\/chest.126.3.926","volume":"126","author":"DA Mahler","year":"2004","unstructured":"Mahler, D. A., Huang, S., Tabrizi, M. & Bell, G. M. Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: a pilot study. Chest 126, 926\u2013934 (2004).","journal-title":"Chest"},{"key":"1290_CR106","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.rmed.2011.10.020","volume":"106","author":"P Kuna","year":"2012","unstructured":"Kuna, P., Jenkins, M., O\u2019Brien, C. D. & Fahy, W. A. AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide\/formoterol in patients with COPD. Respir. Med. 106, 531\u2013539 (2012).","journal-title":"Respir. Med."},{"key":"1290_CR107","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.coph.2020.11.003","volume":"56","author":"MG Matera","year":"2021","unstructured":"Matera, M. G., Cazzola, M. & Page, C. Prospects for COPD treatment. Curr. Opin. Pharmacol. 56, 74\u201384 (2021).","journal-title":"Curr. Opin. Pharmacol."},{"key":"1290_CR108","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1056\/NEJMoa2021713","volume":"383","author":"JD Chalmers","year":"2020","unstructured":"Chalmers, J. D. et al. Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N. Engl. J. Med. 383, 2127\u20132137 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR109","doi-asserted-by":"publisher","first-page":"240055","DOI":"10.1183\/16000617.0055-2024","volume":"33","author":"L Perea","year":"2024","unstructured":"Perea, L., Faner, R., Chalmers, J. D. & Sibila, O. Pathophysiology and genomics of bronchiectasis. Eur. Respir. Rev. 33, 240055 (2024).","journal-title":"Eur. Respir. Rev."},{"key":"1290_CR110","doi-asserted-by":"publisher","first-page":"11485","DOI":"10.1021\/acs.jmedchem.1c02141","volume":"65","author":"T Inghardt","year":"2022","unstructured":"Inghardt, T. et al. Discovery of AZD4831, a mechanism-based irreversible inhibitor of myeloperoxidase, as a potential treatment for heart failure with preserved ejection fraction. J. Med. Chem. 65, 11485\u201311496 (2022).","journal-title":"J. Med. Chem."},{"key":"1290_CR111","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1056\/NEJMoa2413181","volume":"392","author":"FC Sciurba","year":"2025","unstructured":"Sciurba, F. C. et al. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. N. Engl. J. Med. 392, 1710\u20131720 (2025).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR112","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1056\/NEJMoa1905248","volume":"381","author":"GJ Criner","year":"2019","unstructured":"Criner, G. J. et al. Benralizumab for the prevention of COPD exacerbations. N. Engl. J. Med. 381, 1023\u20131034 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR113","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/S2213-2600(19)30338-8","volume":"8","author":"GJ Criner","year":"2020","unstructured":"Criner, G. J. et al. Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies. Lancet Respir. Med. 8, 158\u2013170 (2020).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR114","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1056\/NEJMoa2406673","volume":"391","author":"DJ Jackson","year":"2024","unstructured":"Jackson, D. J. et al. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. N. Engl. J. Med. 391, 2337\u20132349 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR115","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1513\/AnnalsATS.201306-188MG","volume":"11","author":"JM Beck","year":"2014","unstructured":"Beck, J. M. ABCs of the lung microbiome. Ann. Am. Thorac. Soc. 11, S3\u2013S6 (2014).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"1290_CR116","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","volume":"378","author":"M Castro","year":"2018","unstructured":"Castro, M. et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N. Engl. J. Med. 378, 2486\u20132496 (2018).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR117","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2332\/allergolint.55.329","volume":"55","author":"M Kondo","year":"2006","unstructured":"Kondo, M. et al. Elimination of IL-13 reverses established goblet cell metaplasia into ciliated epithelia in airway epithelial cell culture. Allergol. Int. 55, 329\u2013336 (2006).","journal-title":"Allergol. Int."},{"key":"1290_CR118","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1056\/NEJMoa2303951","volume":"389","author":"SP Bhatt","year":"2023","unstructured":"Bhatt, S. P. et al. Dupilumab for COPD with type 2 inflammation indicated by elevated eosinophils. N. Engl. J. Med. 389, 205\u2013214 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR119","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1056\/NEJMoa2401304","volume":"390","author":"SP Bhatt","year":"2024","unstructured":"Bhatt, S. P. et al. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. N. Engl. J. Med. 390, 2274\u20132283 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR120","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1007\/s11626-018-0233-y","volume":"54","author":"JL Carson","year":"2018","unstructured":"Carson, J. L. et al. Interleukin-13 stimulates production of nitric oxide in cultured human nasal epithelium. In Vitro Cell. Dev. Biol. Anim. 54, 200\u2013204 (2018).","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"1290_CR121","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/j.jaip.2022.11.043","volume":"11","author":"ID Pavord","year":"2023","unstructured":"Pavord, I. D. et al. Baseline FeNO independently predicts the dupilumab response in patients with moderate-to-severe asthma. J. Allergy Clin. Immunol. Pract. 11, 1213\u20131220.e1212 (2023).","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"1290_CR122","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00686-2023","volume":"9","author":"A Higham","year":"2023","unstructured":"Higham, A., Beech, A., Dean, J. & Singh, D. Exhaled nitric oxide, eosinophils and current smoking in COPD patients. ERJ Open Res. 9, 00686-2023 (2023).","journal-title":"ERJ Open Res."},{"key":"1290_CR123","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1056\/NEJMe2305752","volume":"389","author":"A Agusti","year":"2023","unstructured":"Agusti, A. Biologics for COPD \u2014 finally here. N. Engl. J. Med. 389, 274\u2013275 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR124","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1016\/S2213-2600(21)00167-3","volume":"9","author":"KF Rabe","year":"2021","unstructured":"Rabe, K. F. et al. Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial. Lancet Respir. Med. 9, 1288\u20131298 (2021).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR125","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1016\/j.jaci.2008.04.005","volume":"121","author":"WB Cherry","year":"2008","unstructured":"Cherry, W. B., Yoon, J., Bartemes, K. R., Iijima, K. & Kita, H. A novel IL-1 family cytokine, IL-33, potently activates human eosinophils. J. Allergy Clin. Immunol. 121, 1484\u20131490 (2008).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1290_CR126","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12931-018-0807-y","volume":"19","author":"D Tworek","year":"2018","unstructured":"Tworek, D. et al. The association between airway eosinophilic inflammation and IL-33 in stable non-atopic COPD. Respir. Res. 19, 108 (2018).","journal-title":"Respir. Res."},{"key":"1290_CR127","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36642-y","volume":"13","author":"E England","year":"2023","unstructured":"England, E. et al. Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE\/EGFR to reduce inflammation and epithelial dysfunction. Sci. Rep. 13, 9825 (2023).","journal-title":"Sci. Rep."},{"key":"1290_CR128","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/cpt.3147","volume":"115","author":"F Reid","year":"2024","unstructured":"Reid, F. et al. A randomized phase 1 study of the anti-interleukin-33 antibody tozorakimab in healthy adults and patients with chronic obstructive pulmonary disease. Clin. Pharmacol. Ther. 115, 565\u2013575 (2024).","journal-title":"Clin. Pharmacol. Ther."},{"key":"1290_CR129","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02231-2024","volume":"66","author":"D Singh","year":"2025","unstructured":"Singh, D. et al. A phase 2a trial of the IL-33 mAb tozorakimab in patients with COPD: FRONTIER-4. Eur. Respir. J. 66, 2402231 (2025).","journal-title":"Eur. Respir. J."},{"key":"1290_CR130","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2020.106175","volume":"173","author":"CF Vogelmeier","year":"2020","unstructured":"Vogelmeier, C. F. et al. COPDCompEx: a novel composite endpoint for COPD exacerbations to enable faster clinical development. Respir. Med. 173, 106175 (2020).","journal-title":"Respir. Med."},{"key":"1290_CR131","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00249-2023","volume":"9","author":"T Wilkinson","year":"2023","unstructured":"Wilkinson, T. et al. A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2. ERJ Open Res. 9, 00249-2023 (2023).","journal-title":"ERJ Open Res."},{"key":"1290_CR132","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/S2213-2600(21)00556-7","volume":"10","author":"AJ Yousuf","year":"2022","unstructured":"Yousuf, A. J. et al. Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease - COPD-ST2OP : a phase IIa, placebo-controlled trial. Lancet Respir. Med. 10, 469\u2013477 (2022).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR133","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.jaci.2021.03.044","volume":"148","author":"SG Kelsen","year":"2021","unstructured":"Kelsen, S. G. et al. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: a randomized clinical trial. J. Allergy Clin. Immunol. 148, 790\u2013798 (2021).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1290_CR134","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1164\/rccm.202210-2005OC","volume":"208","author":"J Corren","year":"2023","unstructured":"Corren, J. et al. Efficacy of tezepelumab in severe, uncontrolled asthma: pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am. J. Respir. Crit. Care Med. 208, 13\u201324 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR135","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S2213-2600(24)00324-2","volume":"13","author":"D Singh","year":"2025","unstructured":"Singh, D. et al. Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe chronic obstructive pulmonary disease (COURSE): a randomised, placebo-controlled, phase 2a trial. Lancet Respir. Med. 13, 47\u201358 (2025).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR136","doi-asserted-by":"publisher","first-page":"4964","DOI":"10.3390\/molecules27154964","volume":"27","author":"L Crocetti","year":"2022","unstructured":"Crocetti, L., Floresta, G., Cilibrizzi, A. & Giovannoni, M. P. An overview of PDE4 inhibitors in clinical trials: 2010 to early 2022. Molecules 27, 4964 (2022).","journal-title":"Molecules"},{"key":"1290_CR137","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s12931-019-1142-7","volume":"20","author":"D Singh","year":"2019","unstructured":"Singh, D. et al. Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Respir. Res. 20, 180 (2019).","journal-title":"Respir. Res."},{"key":"1290_CR138","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1186\/s12931-020-01512-y","volume":"21","author":"D Singh","year":"2020","unstructured":"Singh, D. et al. Efficacy and safety of CHF6001, a novel inhaled PDE4 inhibitor in COPD: the PIONEER study. Respir. Res. 21, 246 (2020).","journal-title":"Respir. Res."},{"key":"1290_CR139","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12931-020-1329-y","volume":"21","author":"M Govoni","year":"2020","unstructured":"Govoni, M. et al. Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis. Respir. Res. 21, 72 (2020).","journal-title":"Respir. Res."},{"key":"1290_CR140","doi-asserted-by":"publisher","first-page":"1801074","DOI":"10.1183\/13993003.01074-2018","volume":"52","author":"D Singh","year":"2018","unstructured":"Singh, D., Abbott-Banner, K., Bengtsson, T. & Newman, K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur. Respir. J. 52, 1801074 (2018).","journal-title":"Eur. Respir. J."},{"key":"1290_CR141","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.2147\/COPD.S307160","volume":"16","author":"GT Ferguson","year":"2021","unstructured":"Ferguson, G. T., Kerwin, E. M., Rheault, T., Bengtsson, T. & Rickard, K. A dose-ranging study of the novel inhaled dual PDE 3 and 4 inhibitor ensifentrine in patients with COPD receiving maintenance tiotropium therapy. Int. J. Chron. Obstruct. Pulmon. Dis. 16, 1137\u20131148 (2021).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"1290_CR142","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1164\/rccm.202306-0944OC","volume":"208","author":"A Anzueto","year":"2023","unstructured":"Anzueto, A. et al. Ensifentrine, a novel phosphodiesterase 3 and 4 inhibitor for the treatment of chronic obstructive pulmonary disease: randomized, double-blind, placebo-controlled, multicenter phase iii trials (the ENHANCE Trials). Am. J. Respir. Crit. Care Med. 208, 406\u2013416 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR143","doi-asserted-by":"publisher","first-page":"1700188","DOI":"10.1183\/13993003.00188-2017","volume":"50","author":"CE Charron","year":"2017","unstructured":"Charron, C. E. et al. RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-alpha and -gamma selectivity, suppresses COPD inflammation. Eur. Respir. J. 50, 1700188 (2017).","journal-title":"Eur. Respir. J."},{"key":"1290_CR144","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1056\/NEJMoa2109927","volume":"386","author":"SR Ytterberg","year":"2022","unstructured":"Ytterberg, S. R. et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N. Engl. J. Med. 386, 316\u2013326 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR145","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.jaci.2021.02.042","volume":"148","author":"IE Braithwaite","year":"2021","unstructured":"Braithwaite, I. E. et al. Inhaled JAK inhibitor GDC-0214 reduces exhaled nitric oxide in patients with mild asthma: a randomized, controlled, proof-of-activity trial. J. Allergy Clin. Immunol. 148, 783\u2013789 (2021).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1290_CR146","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2022.102133","volume":"75","author":"H Chen","year":"2022","unstructured":"Chen, H. et al. Effects of inhaled JAK inhibitor GDC-4379 on exhaled nitric oxide and peripheral biomarkers of inflammation. Pulm. Pharmacol. Ther. 75, 102133 (2022).","journal-title":"Pulm. Pharmacol. Ther."},{"key":"1290_CR147","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.2147\/COPD.S257474","volume":"15","author":"SM Rowe","year":"2020","unstructured":"Rowe, S. M. et al. Efficacy and safety of the CFTR potentiator icenticaftor (QBW251) in COPD: results from a phase 2 randomized trial. Int. J. Chron. Obstruct. Pulmon. Dis. 15, 2399\u20132409 (2020).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"1290_CR148","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1164\/rccm.202303-0458OC","volume":"208","author":"FJ Martinez","year":"2023","unstructured":"Martinez, F. J. et al. Icenticaftor, a CFTR potentiator, in COPD: a multicenter, parallel-group, double-blind clinical trial. Am. J. Respir. Crit. Care Med. 208, 417\u2013427 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR149","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102206","volume":"64","author":"LJV Galietta","year":"2022","unstructured":"Galietta, L. J. V. TMEM16A (ANO1) as a therapeutic target in cystic fibrosis. Curr. Opin. Pharmacol. 64, 102206 (2022).","journal-title":"Curr. Opin. Pharmacol."},{"key":"1290_CR150","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1164\/rccm.201908-1641OC","volume":"201","author":"HL Danahay","year":"2020","unstructured":"Danahay, H. L. et al. TMEM16A potentiation: a novel therapeutic approach for the treatment of cystic fibrosis. Am. J. Respir. Crit. Care Med. 201, 946\u2013954 (2020).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR151","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00793-2024","volume":"11","author":"A Agust\u00ed","year":"2025","unstructured":"Agust\u00ed, A., Aliberti, S., Blasi, F., Miravitlles, M. & Papi, A. Occluding mucous airway plugs in patients with obstructive lung diseases: a new treatable trait? ERJ Open Res. 11, 00793-2024 (2025).","journal-title":"ERJ Open Res."},{"key":"1290_CR152","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1471","volume":"13","author":"B Klughammer","year":"2023","unstructured":"Klughammer, B. et al. A randomized, double-blind phase 1b study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of the NLRP3 inhibitor selnoflast in patients with moderate to severe active ulcerative colitis. Clin. Transl. Med. 13, e1471 (2023).","journal-title":"Clin. Transl. Med."},{"key":"1290_CR153","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/S2213-2600(21)00506-3","volume":"10","author":"IA Yang","year":"2022","unstructured":"Yang, I. A., Jenkins, C. R. & Salvi, S. S. Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment. Lancet Respir. Med. 10, 491\u2013511 (2022).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR154","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1164\/rccm.202001-0172LE","volume":"202","author":"R Breyer-Kohansal","year":"2020","unstructured":"Breyer-Kohansal, R. et al. Factors associated with low lung function in different age bins in the general population. Am. J. Respir. Crit. Care Med. 202, 292\u2013296 (2020).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR155","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102731","volume":"75","author":"N Hernandez-Pacheco","year":"2024","unstructured":"Hernandez-Pacheco, N. et al. Exploring the genetics of airflow limitation in lung function across the lifespan \u2013 a polygenic risk score study. eClinicalMedicine 75, 102731 (2024).","journal-title":"eClinicalMedicine"},{"key":"1290_CR156","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1164\/rccm.202107-1663SO","volume":"205","author":"FJ Martinez","year":"2022","unstructured":"Martinez, F. J. et al. Treatment trials in young patients with COPD and pre-COPD patients: time to move forward. Am. J. Respir. Crit. Care Med. 205, 275\u2013287 (2022).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR157","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1164\/rccm.200901-0047OC","volume":"180","author":"R Kohansal","year":"2009","unstructured":"Kohansal, R. et al. The natural history of chronic airflow obstruction revisited: an analysis of the framingham offspring cohort. Am. J. Respir. Crit. Care Med. 180, 3\u201310 (2009).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR158","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1164\/rccm.202203-0444OC","volume":"207","author":"G Wang","year":"2023","unstructured":"Wang, G. et al. Plasticity of individual lung function states from childhood to adulthood. Am. J. Respir. Crit. Care Med. 207, 406\u2013415 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR159","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1056\/NEJMoa0907441","volume":"362","author":"W Checkley","year":"2010","unstructured":"Checkley, W. et al. Maternal vitamin a supplementation and lung function in offspring. N. Engl. J. Med. 362, 1784\u20131794 (2010).","journal-title":"N. Engl. J. Med."},{"key":"1290_CR160","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1378\/chest.10-1758","volume":"140","author":"MA Martinez-Garcia","year":"2011","unstructured":"Martinez-Garcia, M. A. et al. Factors associated with bronchiectasis in patients with COPD. Chest 140, 1130\u20131137 (2011).","journal-title":"Chest"},{"key":"1290_CR161","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1183\/09031936.00170014","volume":"45","author":"JR Hurst","year":"2015","unstructured":"Hurst, J. R., Elborn, J. S. & Soyza, A. D. COPD-bronchiectasis overlap syndrome. Eur. Respir. J. 45, 310\u2013313 (2015).","journal-title":"Eur. Respir. J."},{"key":"1290_CR162","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.2147\/COPD.S163243","volume":"13","author":"S Dou","year":"2018","unstructured":"Dou, S. et al. High prevalence of bronchiectasis in emphysema-predominant COPD patients. Int. J. Chron. Obstruct. Pulmon. Dis. 13, 2041\u20132047 (2018).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"1290_CR163","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00399-2021","volume":"7","author":"L Traversi","year":"2021","unstructured":"Traversi, L. et al. ROSE: radiology, obstruction, symptoms and exposure - a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group. ERJ Open Res. 7, 00399-2021 (2021).","journal-title":"ERJ Open Res."},{"key":"1290_CR164","doi-asserted-by":"publisher","first-page":"621","DOI":"10.2147\/COPD.S357491","volume":"17","author":"MA Martinez-Garcia","year":"2022","unstructured":"Martinez-Garcia, M. A. & Miravitlles, M. The impact of chronic bronchial infection in COPD: a proposal for management. Int. J. Chron. Obstruct. Pulmon. Dis. 17, 621\u2013630 (2022).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"1290_CR165","doi-asserted-by":"publisher","first-page":"1602086","DOI":"10.1183\/13993003.02086-2016","volume":"49","author":"R Faner","year":"2017","unstructured":"Faner, R. et al. The microbiome in respiratory medicine: current challenges and future perspectives. Eur. Respir. J. 49, 1602086 (2017).","journal-title":"Eur. Respir. J."},{"key":"1290_CR166","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/j.chom.2023.04.018","volume":"31","author":"W Liang","year":"2023","unstructured":"Liang, W. et al. Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease. Cell Host Microbe 31, 1054\u20131070.e1059 (2023).","journal-title":"Cell Host Microbe"},{"key":"1290_CR167","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1600-0773.1970.tb00558.x","volume":"28","author":"H Rosenberg","year":"1970","unstructured":"Rosenberg, H., Airaksinen, M. M. & Tammisto, T. Inhibition of energy production by halothane metabolites. Acta Pharmacol. Toxicol. 28, 327\u2013333 (1970).","journal-title":"Acta Pharmacol. Toxicol."},{"key":"1290_CR168","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s12931-020-01436-7","volume":"21","author":"M Lonergan","year":"2020","unstructured":"Lonergan, M. et al. Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD. Respir. Res. 21, 166 (2020).","journal-title":"Respir. Res."},{"key":"1290_CR169","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12890-019-0867-x","volume":"19","author":"L Millares","year":"2019","unstructured":"Millares, L. et al. Relationship between the respiratory microbiome and the severity of airflow limitation, history of exacerbations and circulating eosinophils in COPD patients. BMC Pulm. Med. 19, 112 (2019).","journal-title":"BMC Pulm. Med."},{"key":"1290_CR170","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00778-7","volume":"12","author":"CA Castellani","year":"2020","unstructured":"Castellani, C. A. et al. Mitochondrial DNA copy number can influence mortality and cardiovascular disease via methylation of nuclear DNA CpGs. Genome Med. 12, 84 (2020).","journal-title":"Genome Med."},{"key":"1290_CR171","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.jaci.2020.02.040","volume":"147","author":"AJ Dicker","year":"2021","unstructured":"Dicker, A. J. et al. The sputum microbiome, airway inflammation, and mortality in chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 147, 158\u2013167 (2021).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1290_CR172","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1513\/AnnalsATS.202108-974OC","volume":"19","author":"M Mart\u00ednez-Garc\u00eda","year":"2022","unstructured":"Mart\u00ednez-Garc\u00eda, M. et al. Chronic bronchial infection is associated with more rapid lung function decline in chronic obstructive pulmonary disease. Ann. Am. Thorac. Soc. 19, 1842\u20131847 (2022).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"1290_CR173","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1111\/resp.14086","volume":"26","author":"M\u00c1 Martinez-Garcia","year":"2021","unstructured":"Martinez-Garcia, M. \u00c1 et al. Chronic bronchial infection and incident cardiovascular events in chronic obstructive pulmonary disease patients: a long-term observational study. Respirology 26, 776\u2013785 (2021).","journal-title":"Respirology"},{"key":"1290_CR174","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1055\/s-0043-1760865","volume":"36","author":"YW Cheng","year":"2023","unstructured":"Cheng, Y. W. & Fischer, M. Fecal microbiota transplantation. Clin. Colon Rectal Surg. 36, 151\u2013156 (2023).","journal-title":"Clin. Colon Rectal Surg."},{"key":"1290_CR175","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41392-023-01451-2","volume":"8","author":"Z Liu","year":"2023","unstructured":"Liu, Z. et al. Immunosenescence: molecular mechanisms and diseases. Signal Transduct. Target. Ther. 8, 200 (2023).","journal-title":"Signal Transduct. Target. Ther."},{"key":"1290_CR176","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.3389\/fimmu.2018.02936","volume":"9","author":"S S\u00e1nchez-Ram\u00f3n","year":"2018","unstructured":"S\u00e1nchez-Ram\u00f3n, S. et al. Trained immunity-based vaccines: a new paradigm for the development of broad-spectrum anti-infectious formulations. Front. Immunol. 9, 2936 (2018).","journal-title":"Front. Immunol."},{"key":"1290_CR177","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00354-z","volume":"6","author":"B Laup\u00e8ze","year":"2021","unstructured":"Laup\u00e8ze, B., Del Giudice, G., Doherty, M. T. & Van der Most, R. Vaccination as a preventative measure contributing to immune fitness. NPJ Vaccines 6, 93 (2021).","journal-title":"NPJ Vaccines"},{"key":"1290_CR178","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-025-01194-w","volume":"25","author":"Y Penders","year":"2025","unstructured":"Penders, Y. et al. Burden of respiratory syncytial virus disease in adults with asthma and chronic obstructive pulmonary disease: a systematic literature review. Curr. Allergy Asthma Rep. 25, 14 (2025).","journal-title":"Curr. Allergy Asthma Rep."},{"key":"1290_CR179","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1183\/09031936.00180812","volume":"41","author":"B Beghe","year":"2013","unstructured":"Beghe, B., Verduri, A., Roca, M. & Fabbri, L. M. Exacerbation of respiratory symptoms in COPD patients may not be exacerbations of COPD. Eur. Respir. J. 41, 993\u2013995 (2013).","journal-title":"Eur. Respir. J."},{"key":"1290_CR180","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/S2213-2600(22)00533-1","volume":"11","author":"J Jos\u00e9 Soler-Catalu\u00f1a","year":"2023","unstructured":"Jos\u00e9 Soler-Catalu\u00f1a, J. et al. Exacerbations in COPD: a personalised approach to care. Lancet Respir. Med. 11, 224\u2013226 (2023).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR181","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1164\/rccm.201104-0597OC","volume":"184","author":"M Bafadhel","year":"2011","unstructured":"Bafadhel, M. et al. Acute exacerbations of COPD: identification of biological clusters and their biomarkers. Am. J. Respir. Crit. Care Med. 184, 662\u2013671 (2011).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR182","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S2213-2600(24)00299-6","volume":"13","author":"S Ramakrishnan","year":"2025","unstructured":"Ramakrishnan, S. et al. Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial. Lancet Respir. Med. 13, 59\u201368 (2025).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR183","doi-asserted-by":"publisher","first-page":"EVIDoa2500012","DOI":"10.1056\/EVIDoa2500012","volume":"4","author":"CA Flynn","year":"2025","unstructured":"Flynn, C. A. et al. Mepolizumab for COPD with eosinophilic phenotype following hospitalization. NEJM Evid. 4, EVIDoa2500012 (2025).","journal-title":"NEJM Evid."},{"key":"1290_CR184","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1164\/rccm.202012-4510OC","volume":"204","author":"F Polverino","year":"2021","unstructured":"Polverino, F. et al. Metformin: experimental and clinical evidence for a potential role in emphysema treatment. Am. J. Respir. Crit. Care Med. 204, 651\u2013666 (2021).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR185","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1007\/s12325-024-02855-4","volume":"41","author":"D Singh","year":"2024","unstructured":"Singh, D. et al. Implications of cardiopulmonary risk for the management of COPD: a narrative review. Adv. Ther. 41, 2151\u20132167 (2024).","journal-title":"Adv. Ther."},{"key":"1290_CR186","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1378\/chest.08-1419","volume":"135","author":"K Ito","year":"2009","unstructured":"Ito, K. & Barnes, P. J. COPD as a disease of accelerated lung aging. Chest 135, 173\u2013180 (2009).","journal-title":"Chest"},{"key":"1290_CR187","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1136\/thoraxjnl-2014-206084","volume":"70","author":"N Mercado","year":"2015","unstructured":"Mercado, N., Ito, K. & Barnes, P. J. Accelerated ageing of the lung in COPD: new concepts. Thorax 70, 482\u2013489 (2015).","journal-title":"Thorax"},{"key":"1290_CR188","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","unstructured":"L\u00f3pez-Ot\u00edn, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Hallmarks of aging: an expanding universe. Cell 186, 243\u2013278 (2023).","journal-title":"Cell"},{"key":"1290_CR189","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2023.107294","volume":"216","author":"D Pellegrino","year":"2023","unstructured":"Pellegrino, D., Casas-Recasens, S., Faner, R., Palange, P. & Agusti, A. When GETomics meets aging and exercise in COPD. Respir. Med. 216, 107294 (2023).","journal-title":"Respir. Med."},{"key":"1290_CR190","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1183\/09031936.06.00087005","volume":"27","author":"M Morla","year":"2006","unstructured":"Morla, M. et al. Telomere shortening in smokers with and without COPD. Eur. Respir. J. 27, 525\u2013528 (2006).","journal-title":"Eur. Respir. J."},{"key":"1290_CR191","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01616-z","volume":"22","author":"E C\u00f3rdoba-Lan\u00fas","year":"2021","unstructured":"C\u00f3rdoba-Lan\u00fas, E. et al. Telomere length dynamics over 10-years and related outcomes in patients with COPD. Respir. Res. 22, 56 (2021).","journal-title":"Respir. Res."},{"key":"1290_CR192","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1164\/rccm.202302-0231OC","volume":"210","author":"S Casas-Recasens","year":"2024","unstructured":"Casas-Recasens, S. et al. Epigenome-wide association studies of COPD and lung function: a systematic review. Am. J. Respir. Crit. Care Med. 210, 766\u2013778 (2024).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR193","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00109-011-0732-8","volume":"89","author":"T Min","year":"2011","unstructured":"Min, T., Bodas, M., Mazur, S. & Vij, N. Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema. J. Mol. Med. 89, 577\u2013593 (2011).","journal-title":"J. Mol. Med."},{"key":"1290_CR194","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.761767","volume":"8","author":"S Casas-Recasens","year":"2021","unstructured":"Casas-Recasens, S. et al. Telomere length but not mitochondrial DNA copy number is altered in both young and old COPD. Front. Med. 8, 761767 (2021).","journal-title":"Front. Med."},{"key":"1290_CR195","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1165\/rcmb.2008-0289OC","volume":"40","author":"L Puente-Maestu","year":"2009","unstructured":"Puente-Maestu, L. et al. Abnormal transition pore kinetics and cytochrome C release in muscle mitochondria of patients with chronic obstructive pulmonary disease. Am. J. Respir. Cell Mol. Biol. 40, 746\u2013750 (2009).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"1290_CR196","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1146\/annurev-physiol-022516-034314","volume":"79","author":"PJ Barnes","year":"2017","unstructured":"Barnes, P. J. Senescence in COPD and its comorbidities. Annu. Rev. Physiol. 79, 517\u2013539 (2017).","journal-title":"Annu. Rev. Physiol."},{"key":"1290_CR197","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1164\/rccm.201704-0667OC","volume":"197","author":"M Ghosh","year":"2018","unstructured":"Ghosh, M. et al. Exhaustion of airway basal progenitor cells in early and established chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 197, 885\u2013896 (2018).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR198","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1016\/j.cell.2021.03.005","volume":"184","author":"JL Schneider","year":"2021","unstructured":"Schneider, J. L. et al. The aging lung: physiology, disease, and immunity. Cell 184, 1990\u20132019 (2021).","journal-title":"Cell"},{"key":"1290_CR199","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.chest.2020.01.027","volume":"158","author":"JR Baker","year":"2020","unstructured":"Baker, J. R., Donnelly, L. E. & Barnes, P. J. Senotherapy: a new horizon for COPD therapy. Chest 158, 562\u2013570 (2020).","journal-title":"Chest"},{"key":"1290_CR200","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1183\/09031936.00161911","volume":"40","author":"J Stolk","year":"2012","unstructured":"Stolk, J. et al. Randomized controlled trial for emphysema with a selective agonist of the gamma type retinoic acid receptor. Eur. Respir. J. 40, 306\u2013312 (2012).","journal-title":"Eur. Respir. J."},{"key":"1290_CR201","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1136\/thoraxjnl-2018-212630","volume":"74","author":"JP Ng-Blichfeldt","year":"2019","unstructured":"Ng-Blichfeldt, J. P., Gosens, R., Dean, C., Griffiths, M. & Hind, M. Regenerative pharmacology for COPD: breathing new life into old lungs. Thorax 74, 890\u2013897 (2019).","journal-title":"Thorax"},{"key":"1290_CR202","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.chest.2021.04.020","volume":"160","author":"MK Glassberg","year":"2021","unstructured":"Glassberg, M. K., Csete, I., Simonet, E. & Elliot, S. J. Stem cell therapy for COPD: hope and exploitation. Chest 160, 1271\u20131281 (2021).","journal-title":"Chest"},{"key":"1290_CR203","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi3360","volume":"16","author":"Y Wang","year":"2024","unstructured":"Wang, Y. et al. Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy. Sci. Transl. Med. 16, eadi3360 (2024).","journal-title":"Sci. Transl. Med."},{"key":"1290_CR204","volume":"2022","author":"W Li","year":"2022","unstructured":"Li, W., Li, G., Zhou, W., Wang, H. & Zheng, Y. Effect of autoimmune cell therapy on immune cell content in patients with COPD: a randomized controlled trial. Comput. Math. Methods Med. 2022, 8361665 (2022). Retraction 2023, 9763428 (2023).","journal-title":"Comput. Math. Methods Med."},{"key":"1290_CR205","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.778020","volume":"9","author":"E Skurikhin","year":"2021","unstructured":"Skurikhin, E. et al. Potential of stem cells and CART as a potential polytherapy for small cell lung cancer. Front. Cell Dev. Biol. 9, 778020 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"1290_CR206","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00020-2021","volume":"7","author":"DS Bui","year":"2021","unstructured":"Bui, D. S. et al. Lung function trajectory and biomarkers in the tasmanian longitudinal health study. ERJ Open Res. 7, 00020-2021 (2021).","journal-title":"ERJ Open Res."},{"key":"1290_CR207","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1164\/rccm.202205-0855LE","volume":"207","author":"N Olvera","year":"2023","unstructured":"Olvera, N. et al. Circulating biomarkers in young individuals with low peak FEV1. Am. J. Respir. Crit. Care Med. 207, 354\u2013358 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR208","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1164\/rccm.202303-0400SO","volume":"208","author":"M Cazzola","year":"2023","unstructured":"Cazzola, M. et al. An update on outcomes for COPD pharmacological trials: a COPD investigators report - reassessment of the 2008 American thoracic society\/European respiratory society statement on outcomes for COPD pharmacological trials. Am. J. Respir. Crit. Care Med. 208, 374\u2013394 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR209","doi-asserted-by":"publisher","first-page":"3719","DOI":"10.2147\/COPD.S178149","volume":"13","author":"JJ Soler-Catalu\u00f1a","year":"2018","unstructured":"Soler-Catalu\u00f1a, J. J. et al. Validation of clinical control in COPD as a new tool for optimizing treatment. Int. J. Chron. Obstruct. Pulmon. Dis. 13, 3719\u20133731 (2018).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"1290_CR210","doi-asserted-by":"publisher","first-page":"137","DOI":"10.2147\/COPD.S285385","volume":"16","author":"JJ Soler-Catalu\u00f1a","year":"2021","unstructured":"Soler-Catalu\u00f1a, J. J. et al. Clinical control criteria to determine disease control in patients with severe COPD: the CLAVE study. Int. J. Chron. Obstruct. Pulmon. Dis. 16, 137\u2013146 (2021).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"1290_CR211","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.chest.2023.02.049","volume":"164","author":"S Raoof","year":"2023","unstructured":"Raoof, S. et al. Lung imaging in COPD part 2: emerging concepts. Chest 164, 339\u2013354 (2023).","journal-title":"Chest"},{"key":"1290_CR212","doi-asserted-by":"publisher","first-page":"100974","DOI":"10.1016\/j.eclinm.2021.100974","volume":"37","author":"Y \u00c7olak","year":"2021","unstructured":"\u00c7olak, Y., Nordestgaard, B. G., Lange, P., Vestbo, J. & Afzal, S. Supernormal lung function and risk of COPD: a contemporary population-based cohort study. eClinicalMedicine 37, 100974 (2021).","journal-title":"eClinicalMedicine"},{"key":"1290_CR213","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.04055-2020","volume":"57","author":"Y \u00c7olak","year":"2021","unstructured":"\u00c7olak, Y., Nordestgaard, B. G., Vestbo, J., Lange, P. & Afzal, S. Relationship between supernormal lung function and long-term risk of hospitalisations and mortality: a population-based cohort study. Eur. Respir. J. 57, 2004055 (2021).","journal-title":"Eur. Respir. J."},{"key":"1290_CR214","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1111\/resp.14553","volume":"28","author":"C Schiffers","year":"2023","unstructured":"Schiffers, C. et al. Supranormal lung function: prevalence, associated factors and clinical manifestations across the lifespan. Respirology 28, 942\u2013953 (2023).","journal-title":"Respirology"},{"key":"1290_CR215","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/S0140-6736(09)61303-9","volume":"374","author":"SS Salvi","year":"2009","unstructured":"Salvi, S. S. & Barnes, P. J. Chronic obstructive pulmonary disease in non-smokers. Lancet 374, 733\u2013743 (2009).","journal-title":"Lancet"},{"key":"1290_CR216","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2188\/jea.JE20180039","volume":"29","author":"R Breyer-Kohansal","year":"2019","unstructured":"Breyer-Kohansal, R. et al. The LEAD (Lung, Heart, Social, Body) study: objectives, methodology, and external validity of the population-based cohort study. J. Epidemiol. 29, 315\u2013324 (2019).","journal-title":"J. Epidemiol."},{"key":"1290_CR217","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02104-2020","volume":"56","author":"A Agusti","year":"2020","unstructured":"Agusti, A. et al. Time for a change: anticipating the diagnosis and treatment of chronic obstructive pulmonary disease. Eur. Respir. J. 56, 2002104 (2020).","journal-title":"Eur. Respir. J."},{"key":"1290_CR218","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S2213-2600(21)00510-5","volume":"10","author":"MH Cho","year":"2022","unstructured":"Cho, M. H., Hobbs, B. D. & Silverman, E. K. Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder. Lancet Respir. Med. 10, 485\u2013496 (2022).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR219","doi-asserted-by":"publisher","unstructured":"Ghosh, A. J. et al. Clinical features of genetic resilience in chronic obstructive pulmonary disease. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2023.03.06.23286843 (2023).","DOI":"10.1101\/2023.03.06.23286843"},{"key":"1290_CR220","doi-asserted-by":"publisher","first-page":"EVIDoa2200279","DOI":"10.1056\/EVIDoa2200279","volume":"2","author":"G Nissen","year":"2023","unstructured":"Nissen, G. et al. Lung function of preterm children parsed by a polygenic risk score for adult COPD. NEJM Evid. 2, EVIDoa2200279 (2023).","journal-title":"NEJM Evid."},{"key":"1290_CR221","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01720-2023","volume":"63","author":"T Wang","year":"2024","unstructured":"Wang, T. et al. Associations of combined phenotypic aging and genetic risk with incidence of chronic respiratory diseases in the UK biobank: a prospective cohort study. Eur. Respir. J. 63, 2301720 (2024).","journal-title":"Eur. Respir. J."},{"key":"1290_CR222","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01954-2021","volume":"60","author":"J Zhang","year":"2022","unstructured":"Zhang, J. et al. A polygenic risk score and age of diagnosis of chronic obstructive pulmonary disease. Eur. Respir. J. 60, 2101954 (2022).","journal-title":"Eur. Respir. J."},{"key":"1290_CR223","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1164\/rccm.201912-2420LE","volume":"231","author":"S Casas-Recasens","year":"2021","unstructured":"Casas-Recasens, S. et al. Lung DNA methylation in COPD: relationship with smoking status and airflow limitation severity. Am. J. Respir. Crit. Care Med. 231, 129\u2013134 (2021).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1290_CR224","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S2213-2600(18)30100-0","volume":"6","author":"DS Bui","year":"2018","unstructured":"Bui, D. S. et al. Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life. Lancet Respir. Med. 6, 535\u2013544 (2018).","journal-title":"Lancet Respir. Med."},{"key":"1290_CR225","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1111\/resp.14142","volume":"26","author":"DO Okyere","year":"2021","unstructured":"Okyere, D. O. et al. Predictors of lung function trajectories in population-based studies: a systematic review. Respirology 26, 938\u2013959 (2021).","journal-title":"Respirology"},{"key":"1290_CR226","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1093\/ije\/dyr236","volume":"41","author":"CP Wild","year":"2012","unstructured":"Wild, C. P. The exposome: from concept to utility. Int. J. Epidemiol. 41, 24\u201332 (2012).","journal-title":"Int. J. Epidemiol."},{"key":"1290_CR227","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2021.106683","volume":"155","author":"P de Prado-Bert","year":"2021","unstructured":"de Prado-Bert, P. et al. The early-life exposome and epigenetic age acceleration in children. Environ. Int. 155, 106683 (2021).","journal-title":"Environ. Int."},{"key":"1290_CR228","doi-asserted-by":"publisher","first-page":"2003406","DOI":"10.1183\/13993003.03406-2020","volume":"57","author":"G Benincasa","year":"2021","unstructured":"Benincasa, G., DeMeo, D. L., Glass, K., Silverman, E. K. & Napoli, C. Epigenetics and pulmonary diseases in the horizon of precision medicine: a review. Eur. Respir. J. 57, 2003406 (2021).","journal-title":"Eur. Respir. J."}],"container-title":["Nature Reviews Drug Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01290-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01290-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01290-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T13:02:59Z","timestamp":1770296579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41573-025-01290-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":228,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["1290"],"URL":"https:\/\/doi.org\/10.1038\/s41573-025-01290-6","relation":{},"ISSN":["1474-1776","1474-1784"],"issn-type":[{"value":"1474-1776","type":"print"},{"value":"1474-1784","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,22]]},"assertion":[{"value":"21 August 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}