Variation in Viscoelastic Properties of Pulmonary Mucus in Patients Undergoing Mechanical Ventilation

Official title

Study of the Variation in Viscoelastic Properties of Pulmonary Mucus in Patients Undergoing Mechanical Ventilation With or Without NIV

Overview

Ventilator-associated pneumonia (VAP) is defined as an infection of the lung parenchyma in patients undergoing invasive mechanical ventilation for at least 48 hours. It is one of the types of pneumonia acquired in intensive care units (ICUs) and is one of the most common infections in this population, representing a major complication. The diagnosis of VAP is based on three main criteria: clinical suspicion, adiological imaging, and microbiological cultures of the lower respiratory tract. However, these elements have significant limitations. New rapid diagnostic techniques, such as multiplex polymerase chain reaction (PCR), can quickly identify pathogens and resistance mechanisms in just a few hours. These promising tools could reduce the time to initiate targeted treatment while limiting the excessive use of antibiotics. However, no single tool is currently accurate enough to diagnose VAP, and diagnosis is based on a combination of factors. Today, scores exist that can be used to assess the probability of PAVM, such as the CIPS. These are useful tools but lack specificity. The clinical, biological and radiological criteria used to calculate the score can also be observed in other pathologies. Thus, although they are sensitive to the detection of PAVM, they are often insufficient to establish a definitive diagnosis. They must be supplemented by other diagnostic approaches, such as microbiological cultures and more detailed imaging examinations, to obtain a more accurate assessment. It is also essential to mention the importance of gaining a better understanding of the lung microbiome. Indeed, it appears to play a central role not only in the pathophysiology of MVAP, but also in its diagnosis and management. The work of Fromentin et al. shows that it is possible to observe dysbiosis associated with a loss of microbial diversity and the onset of certain pulmonary infections. Thus, structural variations in mucus could reflect changes in the pulmonary microbiome. It is therefore essential to remember that mucus plays an essential protective role in the respiratory tract by trapping particles, bacteria and pathogens, while facilitating their transport thanks to its viscoelastic properties. However, in mechanically ventilated patients, these mucociliary clearance mechanisms are often impaired, promoting the accumulation of secretions, bacterial proliferation and, ultimately, the onset of MVAP. The work of Patarin and Giovanna and al. suggests that biochemical and microbiological changes in mucus could be a criterion for initiating treatment in recurrent pulmonary infections in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis. These observations suggest the potential value of early characterisation of mucus in ventilated patients in order to detect additional diagnostic clues that would enable rapid and appropriate treatment.

Detailed description

Nowadays, micro-rheological analyses make it possible to accurately measure the viscoelastic properties of mucus directly at the patient's bedside. These tools offer a unique opportunity to explore bronchial secretions as an element for early diagnosis, monitoring and personalisation of FMAP treatments.

These analyses are based on mucus sampling, which is performed by bronchial aspiration. This is a simple, quick procedure that is commonly performed on demand in intensive care units to prevent complications, particularly airway obstruction.

There are no prospective studies on specific rheological markers in the prediction of FMAP, making it necessary to explore their role in the pathophysiology, diagnosis and management of this condition in greater depth.

Primary outcome measures

• Describe changes in the viscoelastic properties of mucus over time in patients on mechanical ventilation [Time frame: From date of initiation of mechanical ventilation up to the date of extubation or tracheostomy decannulation, assessed up to 30 days]

Secondary outcome measures (4)

• Highlight a correlation between changes in viscoelastic characteristics and the secondary onset of PAVM [Time frame: From date of initiation of mechanical ventilation up to the date of extubation or tracheostomy decannulationn assessed up to 30 days]
• Highlight that changes in the viscoelastic properties of mucus precede the onset and therefore the diagnosis of PAVM [Time frame: From date of initiation of mechanical ventilation up to the date of extubation or tracheostomy decannulationn assessed up to 30 days]
• Propose a threshold for variation in viscoelastic parameters that allows patients with PAVM to be distinguished from those who do not develop it [Time frame: one year]
• Enable early bacterial identification by rheological signature [Time frame: one year]

Eligibility criteria

Inclusion criteria

• Adult patients (> 18 years old)
• Hospitalised in the intensive care unit of the CHIAP
• Placed on mechanical ventilation, regardless of the length of hospitalisation before and after
• French-speaking patients, able to understand the study information leaflet
• No objection from the patient

Exclusion criteria

• Pregnant or breastfeeding women
• Patients deprived of their liberty, under guardianship or curatorship

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• CHI Aix-Pertuis — Aix-en-Provence

Publications

• Patarin J, Ghiringhelli E, Cracowski C, Camara B. Change of mucus rheology in patients with Cystic Fibrosis, COPD and Asthma. Conf paper. 2018 Sep. doi: 10.1183/13993003.congress-2018.PA5051
• Tomaiuolo G, Rusciano G, Caserta S, Carciati A, Carnovale V, Abete P, Sasso A, Guido S. A new method to improve the clinical evaluation of cystic fibrosis patients by mucus viscoelastic properties. PLoS One. 2014 Jan 3;9(1):e82297. doi: 10.1371/journal.pone.0082297. eCollection 2014. PMID 24404129
• Patarin J, Ghiringhelli E, Darsy G, Obamba M, Bochu P, Camara B, Quetant S, Cracowski JL, Cracowski C, Robert de Saint Vincent M. Rheological analysis of sputum from patients with chronic bronchial diseases. Sci Rep. 2020 Sep 24;10(1):15685. doi: 10.1038/s41598-020-72672-6. PMID 32973305
• Fromentin M, Ricard JD, Roux D. Respiratory microbiome in mechanically ventilated patients: a narrative review. Intensive Care Med. 2021 Mar;47(3):292-306. doi: 10.1007/s00134-020-06338-2. Epub 2021 Feb 9. PMID 33559707

Identifiers

NCT: NCT07490028 · 20241213-16 · 2024-A02744-43

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗