Microbiome and Exacerbations in Neutrophilic Asthma

Asthma Clinical Trial

— AsmaEx  

Official title:

Exacerbations in Neutrophilic Asthma: Influence of Bronchial Microbiome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04260282
• Other study ID #: IIBSP-ANE-2020-04
• Status: Recruiting
• Start date: January 1, 2021
• Est. completion date: January 1, 2025

Study information

• Verified date: January 2023
• Source: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Contact: Astrid Crespo, PhD
• Phone: 932919000
• Email: acrespo[@]santpau.cat
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Neutrophilic asthma (NA) is the least known severe asthma phenotype. It is associated with more exacerbations, worse control and impaired lung function. One of its possible etiologies is bronchial infections. The study of bronchial microbiology and its relationship with exacerbations is a new line of research.

Objectives: 1) To analyze bronchial microbiome in patients with AN and non-neutrophilic (ANN), with frequent exacerbations and without exacerbations. 2) To relate the presence of bronchial infections with differences in the microbiome. 3) Correlate the characteristics of the microbiome with other evidence used in exacerbations.

Methods: Prospective study involving 40 non-smoking asthmatics without bronchiectasis (20 with AN and 20 with ANN). Of these, 10 in each group will have frequent exacerbations (>2 rounds of systemic steroids in the last year, of >3 days each) and 10 non- frequent exacerbations. AN will be defined as >65% neutrophils in stable phase sputum. All patients will have two stable visits in which clinical variables, asthma control, lung function and induced sputum samples will be collected (for analysis of bronchial inflammatory cell count and for the study of the microbiome by 16 subunit rRNA). Specific Immunoglobulin A (IgA) for Chlamydia Pneumoniae will be determined. In exacerbations, sputum samples will be collected for culture and nasopharyngeal smears for the study of major respiratory viruses and bacteria by multiple polymerase chain reaction.

Description:

See above

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age between 18 -80

• Confirmed diagnose of asthma

• Severe persistent asthma

Exclusion Criteria:

• Respiratory infection during the previous month

• Other significant lung disease

Related Conditions & MeSH terms

• Asthma
• Exacerbation
• Microbiome

Intervention

Diagnostic Test:
• Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab
PCR for viruses and bacteria in nasal swab
• Induced sputum microbiome
Microbiome in induced sputum

Locations

Country	Name	City	State
Spain	Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90.	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau	GlaxoSmithKline, Sociedad Española de Neumología y Cirugía Torácica

Country where clinical trial is conducted

Spain, 

References & Publications (15)

Blasi F. Atypical pathogens and respiratory tract infections. Eur Respir J. 2004 Jul;24(1):171-81. doi: 10.1183/09031936.04.00135703. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Plaza Moral V; Comite Ejecutivo de GEMA. [GEMA(4.0). Guidelines for Asthma Management]. Arch Bronconeumol. 2015 Jan;51 Suppl 1:2-54. doi: 10.1016/S0300-2896(15)32812-X. Epub 2015 Nov 30. No abstract available. Spanish. — View Citation

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. — View Citation

Reddel HK, FitzGerald JM, Bateman ED, Bacharier LB, Becker A, Brusselle G, Buhl R, Cruz AA, Fleming L, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Pedersen SE, Sheikh A, Yorgancioglu A, Boulet LP. GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J. 2019 Jun 27;53(6):1901046. doi: 10.1183/13993003.01046-2019. Print 2019 Jun. No abstract available. — View Citation

Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G, Bruce KD. characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16s ribosomal DNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol. 2004 Nov;42(11):5176-83. doi: 10.1128/JCM.42.11.5176-5183.2004. — View Citation

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. — View Citation

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. — View Citation

Sutherland ER, Martin RJ. Asthma and atypical bacterial infection. Chest. 2007 Dec;132(6):1962-6. doi: 10.1378/chest.06-2415. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences between neutrophilic and non-neutrophilic asthma, with and without frequent exacerbations in bronchial microbiome using 16S rDNA sequencing	Qualitative and quantitative analysis of bronchial microbiome in patients including bacterial communities and major bacterial phyla in neutrophilic and non-neutrophilic asthma, with frequent exacerbations and without exacerbations.	6 months
Secondary	Changes in absolute and relative abundance using 16S rDNA sequencing of bronchial microbiota due to asthma exacerbations, in patients with neutrophilic and eosinophilic asthma	Influence of bronchial infections in qualitative and quantitative characteristics of lung microbiome. (Bacterial communities and major bacterial phyla)	1 year
Secondary	Changes in absolute and relative abundance of bronchial microbiota over a year using 16S rDNA sequencing	Qualitative and quantitative changes of lung microbiome (Bacterial communities and major bacterial phyla)	1 year
Secondary	Relationship between lung microbiome andlevels of specific immunoglobulin A of C. pneumoniae, PCR, and immunoglobulin G of aspergillus	Relationship between qualitative and quantitative characteristics of lung microbiome with levels of specific IgA C. pneumoniae, PCR, IgG aspergillus	6 months