Exploratory Analysis of Pulmonary Microbiome in Intubated Patients

Intubation Complication Clinical Trial

Official title:

Exploratory Analysis of Pulmonary Microbiome in Patients Intubated for Non-pulmonary Conditions- A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03720093
• Other study ID #: Microbiota Polmonare in ICU
• Status: Completed
• Start date: October 8, 2017
• Est. completion date: January 24, 2020

Study information

• Verified date: July 2020
• Source: University of Milano Bicocca
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This prospective, multicentric study investigates the modifications of pulmonary microbiome that occur in patients who need mechanical ventilation for non-pulmonary conditions. Genomic analysis will be performed by 16S RNA amplification on biological samples (bronchial aspirate) collected from patients.

Description:

The microbiome is defined as a community of microorganisms (such as bacteria, fungi, and viruses) that inhabit a particular organ. This prospective, multicentric, observational study investigates the bacterial changes that occur in the pulmonary microbiome during the first 72 hours of mechanical ventilation in patients who have been intubated for non-pulmonary conditions in intensive care units (ICU).

To this aim, genetic analyses will be performed on bronchial aspirate samples that will be collected from patients during their staying in ICU. Demographic and clinical information will be retrieved from patients' clinical reports and recorded in an apposite clinical report forms (CRF) in anonymized way. In particular, the reason for the admission to ICU, absence fo concomitant pulmonary diseases, comorbidities, body mass index, hematological examination results, concomitant therapies, antibiotic therapy performed in the 30 days prior to the admission, ventilation associated pneumonia (VAP)-preventing procedures, complications during mechanical ventilation, length of mechanical ventilation will be recorded in the CRF.

The study will last 24 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: January 24, 2020
• Est. primary completion date: November 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• patients undergo mechanical ventilation for non-pulmonary conditions (i.e. neurological condition)

• patients who are expected to need mechanical ventilation for >48 hours

Exclusion Criteria:

• diagnosis at the ICU admission of pneumonia

• need of mechanical ventilation for pulmonary conditions.

Related Conditions & MeSH terms

• Intubation Complication

Locations

Country	Name	City	State
Italy	Ospedale Niguarda	Milano
Italy	ASST-Monza	Monza	MB
Italy	Ospedale di Parma	Parma

Sponsors (4)

Lead Sponsor	Collaborator
University of Milano Bicocca	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Niguarda Hospital, University Hospitals Parma Medical Center

Country where clinical trial is conducted

Italy, 

References & Publications (8)

Berdal JE, Bjørnholt J, Blomfeldt A, Smith-Erichsen N, Bukholm G. Patterns and dynamics of airway colonisation in mechanically-ventilated patients. Clin Microbiol Infect. 2007 May;13(5):476-80. — View Citation

Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I, Yadav A, Bushman FD, Collman RG. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med. 2011 Oct 15;184(8):957-63. doi: 10.1164/rccm.201104-0655OC. Epub 2011 Jun 16. — View Citation

McDonald D, Ackermann G, Khailova L, Baird C, Heyland D, Kozar R, Lemieux M, Derenski K, King J, Vis-Kampen C, Knight R, Wischmeyer PE. Extreme Dysbiosis of the Microbiome in Critical Illness. mSphere. 2016 Aug 31;1(4). pii: e00199-16. doi: 10.1128/mSphere.00199-16. eCollection 2016 Jul-Aug. — View Citation

Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, Flores SC, Fontenot AP, Ghedin E, Huang L, Jablonski K, Kleerup E, Lynch SV, Sodergren E, Twigg H, Young VB, Bassis CM, Venkataraman A, Schmidt TM, Weinstock GM; Lung HIV Microbiome Project. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013 May 15;187(10):1067-75. doi: 10.1164/rccm.201210-1913OC. — View Citation

Ojima M, Motooka D, Shimizu K, Gotoh K, Shintani A, Yoshiya K, Nakamura S, Ogura H, Iida T, Shimazu T. Metagenomic Analysis Reveals Dynamic Changes of Whole Gut Microbiota in the Acute Phase of Intensive Care Unit Patients. Dig Dis Sci. 2016 Jun;61(6):1628-34. doi: 10.1007/s10620-015-4011-3. Epub 2015 Dec 29. — View Citation

Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, Chen H, Berger KI, Goldring RM, Rom WN, Blaser MJ, Weiden MD. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2013 Jul 1;1(1):19. doi: 10.1186/2049-2618-1-19. Erratum in: Microbiome. 2014;2:21. Gao, Zhan [added]. — View Citation

Segal LN, Rom WN, Weiden MD. Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs. Ann Am Thorac Soc. 2014 Jan;11(1):108-16. doi: 10.1513/AnnalsATS.201310-339FR. Review. — View Citation

Zaborin A, Smith D, Garfield K, Quensen J, Shakhsheer B, Kade M, Tirrell M, Tiedje J, Gilbert JA, Zaborina O, Alverdy JC. Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness. mBio. 2014 Sep 23;5(5):e01361-14. doi: 10.1128/mBio.01361-14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of pulmonary microbiome between the time of intubation and 72 hours post-intubation, through genetic analysis of bacterial 16 Svedberg (16S) ribosomal RNA in bronchial aspirate.	Two samples of bronchial aspirate were collected (one at the time of incubation and one 72 hours post-intubation) and analyzed by Polymerase Chain Reaction (PCR) by amplifying 16 Svedberg (16S) ribosomal RNA. Primers that specifically recognize hypervariable regions of 16S sub-unit will be used. At 5' end an adaptor will be inserted to prepare the MiSeqsequencing library. The classification of microbiome taxa will be expressed as diversity measure (diversity index alpha or beta); the frequency of the most represented taxa and the confidence interval will be calculated. Differences in microbiome composition will be represented with the analysis of principal coordinates (PCoA) based on phylogenetic distance (matrix UNIFRAC).	At the time of intubation and after 72 hours from intubation