{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:52:20Z","timestamp":1789645940620,"version":"4.0.0"},"reference-count":161,"publisher":"European Respiratory Society (ERS)","issue":"165","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir Rev"],"accepted":{"date-parts":[[2022,7,4]]},"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:p>\n                    Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium\n                    <jats:italic>Haemophilus influenzae.<\/jats:italic>\n                    Here we review knowledge of non-typeable\n                    <jats:italic>H. influenzae<\/jats:italic>\n                    (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1\u03b2, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically\n                    <jats:italic>via<\/jats:italic>\n                    upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research.\n                  <\/jats:p>","DOI":"10.1183\/16000617.0008-2022","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T03:35:33Z","timestamp":1663731333000},"page":"220008","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Non-typeable\n                    <i>Haemophilus influenzae<\/i>\n                    airways infection: the next treatable trait in asthma?"],"prefix":"10.1183","volume":"31","author":[{"given":"Mary Ashley","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maisha","family":"Jabeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7594-4725","authenticated-orcid":false,"given":"Gurpreet","family":"Bharj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-2373","authenticated-orcid":false,"given":"Timothy S.C.","family":"Hinks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"2024102404044773000_31.165.220008.1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00105513"},{"key":"2024102404044773000_31.165.220008.2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S2213-2600(17)30293-X","article-title":"Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"5","author":"Soriano","year":"2017","journal-title":"Lancet Respir Med"},{"key":"2024102404044773000_31.165.220008.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30879-6"},{"key":"2024102404044773000_31.165.220008.4","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0054-2019"},{"key":"2024102404044773000_31.165.220008.5","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.immuni.2019.03.018","article-title":"The cytokines of asthma","volume":"50","author":"Lambrecht","year":"2019","journal-title":"Immunity"},{"key":"2024102404044773000_31.165.220008.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2006.00784.x"},{"key":"2024102404044773000_31.165.220008.7","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00528-2020"},{"key":"2024102404044773000_31.165.220008.8","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02295-2016"},{"key":"2024102404044773000_31.165.220008.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100645"},{"key":"2024102404044773000_31.165.220008.10","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00405-2015"},{"key":"2024102404044773000_31.165.220008.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.03.044"},{"key":"2024102404044773000_31.165.220008.12","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.jaci.2020.03.028","article-title":"Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma","volume":"146","author":"Durack","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"2024102404044773000_31.165.220008.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.08.055"},{"key":"2024102404044773000_31.165.220008.14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jaci.2020.04.018","article-title":"Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months","volume":"147","author":"Abdel-Aziz","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"2024102404044773000_31.165.220008.15","doi-asserted-by":"crossref","first-page":"B3","DOI":"10.1016\/j.vaccine.2008.04.013","article-title":"The impact of vaccines on penumonia: key lessons from Haemophilus influenzae type b conjugate vaccines","volume":"16","author":"Gassner","year":"2008","journal-title":"Vaccine"},{"key":"2024102404044773000_31.165.220008.16","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70734-0"},{"key":"2024102404044773000_31.165.220008.17","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.126722"},{"key":"2024102404044773000_31.165.220008.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.06.004"},{"key":"2024102404044773000_31.165.220008.19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jaci.2015.11.020","article-title":"Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1","volume":"138","author":"Hinks","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"2024102404044773000_31.165.220008.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)01813-9"},{"key":"2024102404044773000_31.165.220008.21","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201109-1640OC"},{"key":"2024102404044773000_31.165.220008.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.06.029"},{"key":"2024102404044773000_31.165.220008.23","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.120741"},{"key":"2024102404044773000_31.165.220008.24","doi-asserted-by":"publisher","DOI":"10.1080\/15412550802092969"},{"key":"2024102404044773000_31.165.220008.25","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.jaip.2018.11.013","article-title":"What are those neutrophils doing in severe asthma anyway?","volume":"7","author":"Busse","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2024102404044773000_31.165.220008.26","doi-asserted-by":"crossref","first-page":"00364\u20132019","DOI":"10.1183\/23120541.00364-2019","article-title":"The role of interleukin-17 in asthma: a protective response?","volume":"6","author":"Hynes","year":"2020","journal-title":"ERJ Open Res"},{"key":"2024102404044773000_31.165.220008.27","doi-asserted-by":"crossref","unstructured":"Bullone M , Carriero V , Bertolini F , et al. Elevated serum IgE, oral corticosteroid dependence and IL-17\/22 expression in highly neutrophilic asthma. Eur Respir J 2019; 54: 1900068.","DOI":"10.1183\/13993003.00068-2019"},{"key":"2024102404044773000_31.165.220008.28","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00117013"},{"key":"2024102404044773000_31.165.220008.29","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jaip.2018.08.024","article-title":"Children with neutrophil-predominant severe asthma have pro-inflammatory neutrophils with enhanced survival and impaired clearance","volume":"7","author":"Grunwell","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2024102404044773000_31.165.220008.30","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2004.024463"},{"key":"2024102404044773000_31.165.220008.31","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.9.2105083"},{"key":"2024102404044773000_31.165.220008.32","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.jaci.2019.03.027","article-title":"IL-17-high asthma with features of a psoriasis immunophenotype","volume":"144","author":"\u00d6stling","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"2024102404044773000_31.165.220008.33","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017-0162OC"},{"key":"2024102404044773000_31.165.220008.34","doi-asserted-by":"crossref","first-page":"9230234","DOI":"10.1155\/2018\/9230234","article-title":"Neutrophilic asthma is associated with increased airway bacterial burden and disordered community composition","volume":"2018","author":"Yang","year":"2018","journal-title":"Biomed Res Int"},{"key":"2024102404044773000_31.165.220008.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008578"},{"key":"2024102404044773000_31.165.220008.36","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201501-029OC"},{"key":"2024102404044773000_31.165.220008.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.03.008"},{"key":"2024102404044773000_31.165.220008.38","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052632"},{"key":"2024102404044773000_31.165.220008.39","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/all.14058","article-title":"Sputum microbiomic clustering in asthma and chronic obstructive pulmonary disease reveals a Haemophilus-predominant subgroup","volume":"75","author":"Diver","year":"2020","journal-title":"Allergy"},{"key":"2024102404044773000_31.165.220008.40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705508114"},{"key":"2024102404044773000_31.165.220008.41","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.1.132"},{"key":"2024102404044773000_31.165.220008.42","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000106981.89572.d1"},{"key":"2024102404044773000_31.165.220008.43","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31823aaeb3"},{"key":"2024102404044773000_31.165.220008.44","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-10-304"},{"key":"2024102404044773000_31.165.220008.45","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.3201\/eid2303.161552","article-title":"Epidemiology of invasive Haemophilus influenzae disease, Europe, 2007\u20132014","volume":"23","author":"Whittaker","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"2024102404044773000_31.165.220008.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2010.11.009"},{"key":"2024102404044773000_31.165.220008.47","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1128\/JCM.00141-18","article-title":"Clinical and bacteriologic analysis of nontypeable Haemophilus influenzae strains isolated from children with invasive diseases in Japan from 2008 to 2015","volume":"56","author":"Naito","year":"2018","journal-title":"J Clin Microbiol"},{"key":"2024102404044773000_31.165.220008.48","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00492-07"},{"key":"2024102404044773000_31.165.220008.49","doi-asserted-by":"crossref","first-page":"14734","DOI":"10.1038\/s41598-018-32973-3","article-title":"Patients with chronic obstructive pulmonary disease harbour a variation of Haemophilus species","volume":"8","author":"Osman","year":"2018","journal-title":"Sci Rep"},{"key":"2024102404044773000_31.165.220008.50","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01832-07"},{"key":"2024102404044773000_31.165.220008.51","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1128\/CDLI.7.1.25-30.2000","article-title":"Immune response to Haemophilus parainfluenzae in patients with chronic obstructive lung disease","volume":"7","author":"Mitchell","year":"2000","journal-title":"Clin Diagn Lab Immunol"},{"key":"2024102404044773000_31.165.220008.52","unstructured":"Zhang Y . Haemophilus parainfluenzae in Bronchiectasis . Dissertation. Edinburgh, University of Edinburgh, 2019. doi:10.7488\/era\/224"},{"key":"2024102404044773000_31.165.220008.53","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304-0775OC"},{"key":"2024102404044773000_31.165.220008.54","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012561"},{"key":"2024102404044773000_31.165.220008.55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066818"},{"key":"2024102404044773000_31.165.220008.56","doi-asserted-by":"crossref","first-page":"00130\u20132017","DOI":"10.1183\/23120541.00130-2017","article-title":"Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis","volume":"4","author":"Chen","year":"2018","journal-title":"ERJ Open Res"},{"key":"2024102404044773000_31.165.220008.57","doi-asserted-by":"crossref","first-page":"947072","DOI":"10.1155\/2013\/947072","article-title":"Regulation of tight junctions in upper airway epithelium","volume":"2013","author":"Kojima","year":"2013","journal-title":"Biomed Res Int"},{"key":"2024102404044773000_31.165.220008.58","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0101-2015"},{"key":"2024102404044773000_31.165.220008.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.04.010"},{"key":"2024102404044773000_31.165.220008.60","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.micinf.2017.07.002","article-title":"Nontypeable Haemophilus influenzae (NTHi) directly interfere with the regulation of E-cadherin in lung epithelial cells","volume":"19","author":"Kaufhold","year":"2017","journal-title":"Microbes Infect"},{"key":"2024102404044773000_31.165.220008.61","doi-asserted-by":"crossref","first-page":"e982424","DOI":"10.4161\/21688370.2014.982424","article-title":"NF-\u043aB inhibitors impair lung epithelial tight junctions in the absence of inflammation","volume":"3","author":"Ward","year":"2015","journal-title":"Tissue Barriers"},{"key":"2024102404044773000_31.165.220008.62","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402169"},{"key":"2024102404044773000_31.165.220008.63","doi-asserted-by":"publisher","DOI":"10.1378\/chest.101.4.916"},{"key":"2024102404044773000_31.165.220008.64","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e32831da8d3"},{"key":"2024102404044773000_31.165.220008.65","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1111\/cea.13359","article-title":"Goblet cell hyperplasia as a feature of neutrophilic asthma","volume":"49","author":"Alagha","year":"2019","journal-title":"Clin Exp Allergy"},{"key":"2024102404044773000_31.165.220008.66","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.chest.2016.07.003","article-title":"Plugs of the air passages: a clinicopathologic review","volume":"150","author":"Panchabhai","year":"2016","journal-title":"Chest"},{"key":"2024102404044773000_31.165.220008.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2019.02.403"},{"key":"2024102404044773000_31.165.220008.68","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107484200"},{"key":"2024102404044773000_31.165.220008.69","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1964fje"},{"key":"2024102404044773000_31.165.220008.70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206883200"},{"key":"2024102404044773000_31.165.220008.71","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.jaci.2019.12.907","article-title":"Long-term impact of inhaled corticosteroid use in asthma and chronic obstructive pulmonary disease (COPD): review of mechanisms that underlie risks","volume":"146","author":"Singanayagam","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"2024102404044773000_31.165.220008.72","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008033430504"},{"key":"2024102404044773000_31.165.220008.73","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063070"},{"key":"2024102404044773000_31.165.220008.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2011.07.020"},{"key":"2024102404044773000_31.165.220008.75","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201409-1654PP"},{"key":"2024102404044773000_31.165.220008.76","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-2992"},{"key":"2024102404044773000_31.165.220008.77","doi-asserted-by":"publisher","DOI":"10.1080\/15412550903140881"},{"key":"2024102404044773000_31.165.220008.78","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201601-0002OC"},{"key":"2024102404044773000_31.165.220008.79","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12582"},{"key":"2024102404044773000_31.165.220008.80","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1890"},{"key":"2024102404044773000_31.165.220008.81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.01.014"},{"key":"2024102404044773000_31.165.220008.82","doi-asserted-by":"publisher","DOI":"10.3390\/cells5040040"},{"key":"2024102404044773000_31.165.220008.83","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/infdis\/129.2.93","article-title":"Effect of a toxin produced by Haemophilus influenzae on ciliated respiratory epithelium","volume":"129","author":"Denny","year":"2017","journal-title":"J Infect Dis"},{"key":"2024102404044773000_31.165.220008.84","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-22-3-265"},{"key":"2024102404044773000_31.165.220008.85","doi-asserted-by":"crossref","unstructured":"Short B , Carson S , Devlin AC , et al. Non-typeable Haemophilus influenzae chronic colonization in chronic obstructive pulmonary disease (COPD). Crit Rev Microbiol; 47: 192\u2013205. doi:10.1080\/1040841X.2020.1863330","DOI":"10.1080\/1040841X.2020.1863330"},{"key":"2024102404044773000_31.165.220008.86","doi-asserted-by":"crossref","unstructured":"Nardini S . The influence of tobacco smoking on lung disease. In: Donner C, Goldstein R, Ambrosino N, eds. Pulmonary Rehabilitation. London, CRC Press, 2005; 27\u201333. doi:10.1201\/b13288-6","DOI":"10.1201\/b13288-6"},{"key":"2024102404044773000_31.165.220008.87","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-016-0483-8"},{"key":"2024102404044773000_31.165.220008.88","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-254359"},{"key":"2024102404044773000_31.165.220008.89","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-5806fje"},{"key":"2024102404044773000_31.165.220008.90","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.310.6989.1225"},{"key":"2024102404044773000_31.165.220008.91","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.08.013"},{"key":"2024102404044773000_31.165.220008.92","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.00226302"},{"key":"2024102404044773000_31.165.220008.93","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00362.2016"},{"key":"2024102404044773000_31.165.220008.94","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx042"},{"key":"2024102404044773000_31.165.220008.95","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200801-136OC"},{"key":"2024102404044773000_31.165.220008.96","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.virol.2016.08.020","article-title":"Non-typeable Haemophilus influenzae protects human airway epithelial cells from a subsequent respiratory syncytial virus challenge","volume":"498","author":"Hartwig","year":"2016","journal-title":"Virology"},{"key":"2024102404044773000_31.165.220008.97","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(21)00077-7"},{"key":"2024102404044773000_31.165.220008.98","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1080\/23744235.2021.1985732","article-title":"High rate of bacterial respiratory tract co-infections upon admission amongst moderate to severe COVID-19 patients","volume":"54","author":"Cohen","year":"2022","journal-title":"Infect Dis (Lond)"},{"key":"2024102404044773000_31.165.220008.99","doi-asserted-by":"crossref","first-page":"e354","DOI":"10.1016\/S2666-5247(21)00090-2","article-title":"Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study","volume":"2","author":"Russell","year":"2021","journal-title":"Lancet Microbe"},{"key":"2024102404044773000_31.165.220008.100","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1998.0269"},{"key":"2024102404044773000_31.165.220008.101","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.040451-0"},{"key":"2024102404044773000_31.165.220008.102","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00286-18"},{"key":"2024102404044773000_31.165.220008.103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2011.00001","article-title":"Non-typeable Haemophilus influenzae invasion and persistence in the human respiratory tract","volume":"1","author":"Clementi","year":"2011","journal-title":"Front Cell Infect Microbiol"},{"key":"2024102404044773000_31.165.220008.104","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1128\/iai.62.2.673-679.1994","article-title":"Haemophilus influenzae resides and multiplies intracellularly in human adenoid tissue as demonstrated by in situ hybridization and bacterial viability assay","volume":"62","author":"Forsgren","year":"1994","journal-title":"Infect Immun"},{"key":"2024102404044773000_31.165.220008.105","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2009.03.012"},{"key":"2024102404044773000_31.165.220008.106","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200403-354OC"},{"key":"2024102404044773000_31.165.220008.107","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719654115"},{"key":"2024102404044773000_31.165.220008.108","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.congress-2019.PA5440"},{"key":"2024102404044773000_31.165.220008.109","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.congress-2020.2323"},{"key":"2024102404044773000_31.165.220008.110","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb10820.x"},{"key":"2024102404044773000_31.165.220008.111","doi-asserted-by":"publisher","DOI":"10.1086\/508428"},{"key":"2024102404044773000_31.165.220008.112","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00305-09"},{"key":"2024102404044773000_31.165.220008.113","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12931-017-0539-4","article-title":"Mechanisms of corticosteroid insensitivity in COPD alveolar macrophages exposed to NTHi","volume":"18","author":"Khalaf","year":"2017","journal-title":"Respir Res"},{"key":"2024102404044773000_31.165.220008.114","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/S0140-6736(85)92559-0","article-title":"Oral immunisation with killed Haemophilus influenzae for protection against acute bronchitis in chronic obstructive lung disease","volume":"326","author":"Clancy","year":"1985","journal-title":"Lancet"},{"key":"2024102404044773000_31.165.220008.115","doi-asserted-by":"crossref","first-page":"6102","DOI":"10.1016\/j.vaccine.2019.07.100","article-title":"Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: a phase 2 clinical trial","volume":"37","author":"Wilkinson","year":"2019","journal-title":"Vaccine"},{"key":"2024102404044773000_31.165.220008.116","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1016\/j.vaccine.2019.04.041","article-title":"Safety and immunogenicity of non-typeable Haemophilus influenzae\u2013Moraxella catarrhalis vaccine","volume":"37","author":"Van Damme","year":"2019","journal-title":"Vaccine"},{"key":"2024102404044773000_31.165.220008.117","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00864-13"},{"key":"2024102404044773000_31.165.220008.118","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2007.12.005"},{"key":"2024102404044773000_31.165.220008.119","doi-asserted-by":"publisher","DOI":"10.1111\/1574-6968.12203"},{"key":"2024102404044773000_31.165.220008.120","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00660-10"},{"key":"2024102404044773000_31.165.220008.121","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S2213-2600(20)30504-X","article-title":"Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: an international, observational, multicohort study","volume":"9","author":"Keir","year":"2021","journal-title":"Lancet Respir Med"},{"key":"2024102404044773000_31.165.220008.122","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12073"},{"key":"2024102404044773000_31.165.220008.123","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1007\/s00405-017-4586-8","article-title":"Recurrent otorrhea in chronic suppurative otitis media: is biofilm the missing link?","volume":"274","author":"Jensen","year":"2017","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"2024102404044773000_31.165.220008.124","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028523"},{"key":"2024102404044773000_31.165.220008.125","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90011-1"},{"key":"2024102404044773000_31.165.220008.126","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2009.00246.x"},{"key":"2024102404044773000_31.165.220008.127","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.4.631"},{"key":"2024102404044773000_31.165.220008.128","doi-asserted-by":"crossref","first-page":"943","DOI":"10.3389\/fimmu.2019.00943","article-title":"Evolution of C-reactive protein","volume":"10","author":"Pathak","year":"2019","journal-title":"Front Immunol"},{"key":"2024102404044773000_31.165.220008.129","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S108698"},{"key":"2024102404044773000_31.165.220008.130","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw222"},{"key":"2024102404044773000_31.165.220008.131","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.03.003"},{"key":"2024102404044773000_31.165.220008.132","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1164\/ajrccm\/147.2.398","article-title":"A Double-blind study of troleandomycin and methylprednisolone in asthmatic subjects who require daily corticosteroids","volume":"147","author":"Nelson","year":"1993","journal-title":"Am Rev Respir Deisease"},{"key":"2024102404044773000_31.165.220008.133","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)62409-X"},{"key":"2024102404044773000_31.165.220008.134","doi-asserted-by":"publisher","DOI":"10.1159\/000236773"},{"key":"2024102404044773000_31.165.220008.135","first-page":"131","article-title":"[Effects of various drugs on IL8 production by eosinophils collected from patients with allergic inflammation]","volume":"51 Suppl. A","author":"Koyama","year":"1998","journal-title":"Jpn J Antibiot"},{"key":"2024102404044773000_31.165.220008.136","doi-asserted-by":"publisher","DOI":"10.1378\/chest.122.1.213"},{"key":"2024102404044773000_31.165.220008.137","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(96)70068-4"},{"key":"2024102404044773000_31.165.220008.138","doi-asserted-by":"publisher","DOI":"10.1159\/000320319"},{"key":"2024102404044773000_31.165.220008.139","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1056\/NEJMoa1104623","article-title":"Azithromycin for prevention of exacerbations of COPD","volume":"365","author":"Albert","year":"2012","journal-title":"N Engl J Med"},{"key":"2024102404044773000_31.165.220008.140","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.prrv.2012.08.001","article-title":"Macrolide antibiotics for cystic fibrosis","volume":"13","author":"Southern","year":"2012","journal-title":"Paediatr Respir Rev"},{"key":"2024102404044773000_31.165.220008.141","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60953-2"},{"key":"2024102404044773000_31.165.220008.142","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2290"},{"key":"2024102404044773000_31.165.220008.143","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2012-202698"},{"key":"2024102404044773000_31.165.220008.144","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31281-3"},{"key":"2024102404044773000_31.165.220008.145","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201809-1739OC"},{"key":"2024102404044773000_31.165.220008.146","doi-asserted-by":"crossref","first-page":"2000194","DOI":"10.1183\/13993003.00194-2020","article-title":"Airway abundance of Haemophilus influenzae predicts response to azithromycin in adults with persistent uncontrolled asthma","volume":"55","author":"Taylor","year":"2020","journal-title":"Eur Respir J"},{"key":"2024102404044773000_31.165.220008.147","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-216331"},{"key":"2024102404044773000_31.165.220008.148","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2019-000489"},{"key":"2024102404044773000_31.165.220008.149","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2012-202003"},{"key":"2024102404044773000_31.165.220008.150","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00588-2019"},{"key":"2024102404044773000_31.165.220008.151","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01563-08"},{"key":"2024102404044773000_31.165.220008.152","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2011.07.001"},{"key":"2024102404044773000_31.165.220008.153","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S2213-2600(13)70038-9","article-title":"Risks of population antimicrobial resistance associated with chronic macrolide use for inflammatory airway diseases","volume":"1","author":"Serisier","year":"2013","journal-title":"Lancet Respir Med"},{"key":"2024102404044773000_31.165.220008.154","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/all.13629","article-title":"Treatable traits in the European U-BIOPRED adult asthma cohorts","volume":"74","author":"Simpson","year":"2019","journal-title":"Allergy Eur J Allergy Clin Immunol"},{"key":"2024102404044773000_31.165.220008.155","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1164\/rccm.201806-1182OC","article-title":"Remotely monitored therapy and nitric oxide suppression identifies nonadherence in severe asthma","volume":"199","author":"Heaney","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2024102404044773000_31.165.220008.156","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/S2213-2600(21)00004-7","article-title":"The inflammatory profile of exacerbations in patients with severe refractory eosinophilic asthma receiving mepolizumab (the MEX study): a prospective observational study","volume":"9","author":"McDowell","year":"2021","journal-title":"Lancet Respir Med"},{"key":"2024102404044773000_31.165.220008.157","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00528-2020"},{"key":"2024102404044773000_31.165.220008.158","doi-asserted-by":"crossref","first-page":"e0227921","DOI":"10.1128\/spectrum.02279-21","article-title":"Identifying bacterial airways infection in stable severe asthma using Oxford nanopore sequencing technologies","volume":"10","author":"Jabeen","year":"2022","journal-title":"Microbiol Spectr"},{"key":"2024102404044773000_31.165.220008.159","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.5.1973-1980.1998"},{"key":"2024102404044773000_31.165.220008.160","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.021659"},{"key":"2024102404044773000_31.165.220008.161","doi-asserted-by":"crossref","first-page":"00614\u20132020","DOI":"10.1183\/23120541.00614-2020","article-title":"Chronic infection by nontypeable Haemophilus influenzae fuels airway inflammation","volume":"7","author":"Saliu","year":"2021","journal-title":"ERJ Open Res"}],"container-title":["European Respiratory Review"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/16000617.0008-2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:05:16Z","timestamp":1740355516000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/16000617.0008-2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":161,"journal-issue":{"issue":"165","published-online":{"date-parts":[[2022,9,20]]},"published-print":{"date-parts":[[2022,9,30]]}},"alternative-id":["10.1183\/16000617.0008-2022"],"URL":"https:\/\/doi.org\/10.1183\/16000617.0008-2022","relation":{},"ISSN":["0905-9180","1600-0617"],"issn-type":[{"value":"0905-9180","type":"print"},{"value":"1600-0617","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,20]]}}}