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| Name | Class |
|---|---|
| Spanish Clinical Research Network - SCReN | NETWORK |
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Define and characterize the neutrophilic phenotype of severe asthma.
Neutrophilic asthma (NA) is the asthma phenotype less known, causes a severe disease and does not have a specific treatment. Research on the neutrophilia mechanisms, new neutrophil (NEU) types and bronchial microbiome, can provide an opportunity to better understand the NA pathogenesis.
OBJECTIVES: 1. To describe the clinical characteristics of NA and its sub-phenotypes (SUBSTUDY 1); 2. To determine the NEU types associated with the NA and its sub-phenotypes (SUBSTUDY 2); and 3. To identify the bronchial microbiological flora of the NA, specifically related to lung microbiome and the immune response against Chlamydia Pneumoniae (SUBSTUDY 3).
METHODS: Multicenter prospective study including 100 patients with severe asthma (GINA/GEMA criteria): 50 with non-neutrophilic asthma (<65% NEU in induced sputum [IS]); and 50 with NA (> 64% NEU in IS). SUBSTUDY 1: clinical variables (years of evolution, exacerbations, asthma control test, mini asthma quality of life questionnary), comorbidities (GERD, nasal polyposis, obesity, ASS), pulmonary function (FEV1, exhaled fraction of nitric oxide, total lung capacity, Aspergillus), prick-test and CT scan chest; SUBSTUDY 2 (in IS and plasma): apoptotic index by means NE culture and flux cytometer (Annexin-V-FITC), NEU phenotype by surface markers (CD16, CD66b, CD62L, HLADR, CD177, CD11b, CD63, CXCR2, CXCR4) with density gradient study and determination of cytokines (IL-6, IL-8, IL-17, IL-1, IL-22) by ELISA; SUBSTUDY 3 (in IS): bronchial microbiome for 16 subunit rRNA by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and anti-Chlamydia Pneumoniae Immunoglobuling A by ELISA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neutrophilic asthma | Patients 18 to 80 years old diagnosed of severe asthma, requiring treatment at least with long acting beta agonists (LABA) + high doses inhaled corticosteroids (ICS) with eosinophil count in blood<300/mm3. They must be ex-smokers with less than 10 packs-year and no other relevant pulmonary disease. |
| |
| Non neutrophilic asthma | Patients 18 to 80 years old diagnosed of severe asthma, requiring treatment at least with LABA+ high doses ICS, with eosinophil count in blood<300/mm3. They must be ex-smokers with less than 10 packs-year and no other relevant pulmonary disease. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Induced sputum | Diagnostic Test | Characterization with flow cytometry of the phenotype of the neutrophils isolated in the sputum, microbiome |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phenotype of neutrophils | To determine the types of neutrophils (in induced sputum and blood) associated with neutrophilic asthma and its subphenotypes according to flow cytometry | 24 hours |
| Microbiome analysis | To analyse the bronchial microbiological flora of neutrophilic asthma | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical demographic characteristics | To describe the clinical characteristics and natural history of the neutrophilic asthma and its subphenotypes | 1 year |
| Demographic characteristics | To describe demographic characteristics |
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Inclusion Criteria:
Exclusion Criteria:
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Patients bewteen 18-80 years with severe asthma.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90. | Barcelona | 08041 | Spain | |||
| Hospital de la Santa Creu i Sant Pau |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25415406 | Background | Nair P, Aziz-Ur-Rehman A, Radford K. Therapeutic implications of 'neutrophilic asthma'. Curr Opin Pulm Med. 2015 Jan;21(1):33-8. doi: 10.1097/MCP.0000000000000120. | |
| 9309987 | Background | Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):737-43. doi: 10.1164/ajrccm.156.3.9610046. |
| Label | URL |
|---|---|
| Website of the spanish guideline of asthma | View source |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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Induced Sputum
| 1 year |
| Barcelona |
| 08041 |
| Spain |
| 24641293 | Background | Simpson JL, Baines KJ, Ryan N, Gibson PG. Neutrophilic asthma is characterised by increased rhinosinusitis with sleep disturbance and GERD. Asian Pac J Allergy Immunol. 2014 Mar;32(1):66-74. doi: 10.12932/AP0322.32.1.2014. |
| 17925424 | Background | Shaw DE, Berry MA, Hargadon B, McKenna S, Shelley MJ, Green RH, Brightling CE, Wardlaw AJ, Pavord ID. Association between neutrophilic airway inflammation and airflow limitation in adults with asthma. Chest. 2007 Dec;132(6):1871-5. doi: 10.1378/chest.07-1047. Epub 2007 Oct 9. |
| 22561835 | Background | Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012 May 4;18(5):716-25. doi: 10.1038/nm.2678. |
| 17947611 | Background | Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med. 2008 Jan 15;177(2):148-55. doi: 10.1164/rccm.200707-1134OC. Epub 2007 Oct 18. |
| 22903959 | Background | Polosa R, Thomson NC. Smoking and asthma: dangerous liaisons. Eur Respir J. 2013 Mar;41(3):716-26. doi: 10.1183/09031936.00073312. Epub 2012 Aug 16. |
| 18079229 | Background | Sutherland ER, Martin RJ. Asthma and atypical bacterial infection. Chest. 2007 Dec;132(6):1962-6. doi: 10.1378/chest.06-2415. |
| 20685741 | Background | Uddin M, Nong G, Ward J, Seumois G, Prince LR, Wilson SJ, Cornelius V, Dent G, Djukanovic R. Prosurvival activity for airway neutrophils in severe asthma. Thorax. 2010 Aug;65(8):684-9. doi: 10.1136/thx.2009.120741. |
| 24035139 | Background | Newcomb DC, Peebles RS Jr. Th17-mediated inflammation in asthma. Curr Opin Immunol. 2013 Dec;25(6):755-60. doi: 10.1016/j.coi.2013.08.002. Epub 2013 Sep 11. |
| 25162311 | Background | Chesne J, Braza F, Mahay G, Brouard S, Aronica M, Magnan A. IL-17 in severe asthma. Where do we stand? Am J Respir Crit Care Med. 2014 Nov 15;190(10):1094-101. doi: 10.1164/rccm.201405-0859PP. |
| 25977288 | Background | Bruijnzeel PL, Uddin M, Koenderman L. Targeting neutrophilic inflammation in severe neutrophilic asthma: can we target the disease-relevant neutrophil phenotype? J Leukoc Biol. 2015 Oct;98(4):549-56. doi: 10.1189/jlb.3VMR1214-600RR. Epub 2015 May 14. |
| 20400675 | Background | Pillay J, Ramakers BP, Kamp VM, Loi AL, Lam SW, Hietbrink F, Leenen LP, Tool AT, Pickkers P, Koenderman L. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010 Jul;88(1):211-20. doi: 10.1189/jlb.1209793. Epub 2010 Apr 16. |
| 23226600 | Background | Beyrau M, Bodkin JV, Nourshargh S. Neutrophil heterogeneity in health and disease: a revitalized avenue in inflammation and immunity. Open Biol. 2012 Nov;2(11):120134. doi: 10.1098/rsob.120134. |
| 24955983 | Background | Green BJ, Wiriyachaiporn S, Grainge C, Rogers GB, Kehagia V, Lau L, Carroll MP, Bruce KD, Howarth PH. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS One. 2014 Jun 23;9(6):e100645. doi: 10.1371/journal.pone.0100645. eCollection 2014. |
| 24437410 | Background | Kiley JP, Caler EV. The lung microbiome. A new frontier in pulmonary medicine. Ann Am Thorac Soc. 2014 Jan;11 Suppl 1(Suppl 1):S66-70. doi: 10.1513/AnnalsATS.201308-285MG. No abstract available. |
| 23265859 | Background | Marri PR, Stern DA, Wright AL, Billheimer D, Martinez FD. Asthma-associated differences in microbial composition of induced sputum. J Allergy Clin Immunol. 2013 Feb;131(2):346-52.e1-3. doi: 10.1016/j.jaci.2012.11.013. Epub 2012 Dec 23. |
| 26220531 | Background | Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, Boushey H. The airway microbiome in patients with severe asthma: Associations with disease features and severity. J Allergy Clin Immunol. 2015 Oct;136(4):874-84. doi: 10.1016/j.jaci.2015.05.044. Epub 2015 Jul 26. |
| 11295645 | Background | Martin RJ, Kraft M, Chu HW, Berns EA, Cassell GH. A link between chronic asthma and chronic infection. J Allergy Clin Immunol. 2001 Apr;107(4):595-601. doi: 10.1067/mai.2001.113563. |
| 23291349 | Background | Brusselle GG, Vanderstichele C, Jordens P, Deman R, Slabbynck H, Ringoet V, Verleden G, Demedts IK, Verhamme K, Delporte A, Demeyere B, Claeys G, Boelens J, Padalko E, Verschakelen J, Van Maele G, Deschepper E, Joos GF. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax. 2013 Apr;68(4):322-9. doi: 10.1136/thoraxjnl-2012-202698. Epub 2013 Jan 3. |
| 15293621 | Background | Blasi F. Atypical pathogens and respiratory tract infections. Eur Respir J. 2004 Jul;24(1):171-81. doi: 10.1183/09031936.04.00135703. |
| 25215528 | Background | Frehn L, Jansen A, Bennek E, Mandic AD, Temizel I, Tischendorf S, Verdier J, Tacke F, Streetz K, Trautwein C, Sellge G. Distinct patterns of IgG and IgA against food and microbial antigens in serum and feces of patients with inflammatory bowel diseases. PLoS One. 2014 Sep 12;9(9):e106750. doi: 10.1371/journal.pone.0106750. eCollection 2014. |
| 15059128 | Background | Tuuminen T, Edelstein I, Punin A, Kislova N, Stratchounski L. Use of quantitative and objective enzyme immunoassays to investigate the possible association between Chlamydia pneumoniae and Mycoplasma pneumoniae antibodies and asthma. Clin Microbiol Infect. 2004 Apr;10(4):345-8. doi: 10.1111/j.1198-743X.2004.00822.x. |
| Website of the european guideline of asthma | View source |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |