Clinical trial NCT04849039: Lung Microbiota and VAP Development (PULMIVAP)
Official title: "Pulmonary Microbiota and Related Immunity Role in Predicting Ventilator Associated- Pneumonia (VAP) Development in Mechanical Ventilated Patients"
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Mechanical Ventilation
Keywords: Observational
Cohort Study
Ventilator-associated pneumonia
Mechanical Ventilation
Lung microbiota
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: San Gerardo Hospital
name: University of Parma
First posted: 2021-04-19
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All adult patients mechanicaly ventilated for non pulmonary conditions

Brief summary: Ventilator-associated pneumonia (VAP) refers to a lower respiratory tract nosocomial infection acquired \>48h after being intubated in Intensive Care Units. Pathogenesis of VAP is mechanical and associated with microaspiration and leakage of oropharyngeal secretions around the endotracheal tube. A novel approach to VAP will attempt to explore how the abrupt ecological order of acute infection (high bacterial biomass, low community diversity) emerges from the dynamic homeostasis of a pre-existing ecosystem in which lung microbiota and local immunity interaction play their essential role.

Therefore, the investigators aim to explore if oral and lung microbiota modifications with local immunity changes, contribute in the pathogenesis of VAP in patients intubated for non-pulmonary reasons. Early changes in the host microbiota with the innate immunity system impairs tissue homeostasis and may represent a new distinct condition and a potential tool for early diagnosis and prevention of VAP.

Detailed description: Several factors are involved in the pathogenesis of VAP: the presence of endotracheal tube, the creation of bacterial biofilms around the device, host characteristics (comorbidities, surgery, antibiotic exposure) and, finally, immunological factors (including modulation of cytokine expression). In this study, patients mechanically ventilated for non-pulmonary reasons, will be followed up to 15 days of ventilation, estubation or death (whichever comes first). For microbiota analysis, all patients who develop VAP in the first 15 days of MV will be selected and matched (1:1; by center, gender, age (+/- 10 years), reason for intubation, duration of intubation), with a patient who do not developed VAP during MV. The optimal matching algorithm will be used to identify the control group that minimizes the total intra-pair dissimilarity.

The investigators plan to enroll about 700 MV patients for non-pulmonary conditions in order to describe VAP and non-VAP patients' characteristics identify. The investigators estimate that at least 70 patients will develop VAP in the first 15 days of MV. Microbiota and immunological analysis will be longitudinally performed on tracheal aspirate samples and oro-pharyngeal swab. The investigators will performe microbiota analyses on tracheal aspirate and oropharyngeal swab according to the following time schedule:

* VAP patient, 3 times: intubation (T0), the 24h before VAP development (T pre-VAP) and at VAP development (T-VAP).
* non-VAP patient, 2 times: intubation (T0) and a second sample, selected at the time point (day), corresponding to T-VAP of his/her matched VAP-patient (T no-VAP).

The investigators will perform immunological analysis on tracheal aspirate for all patients at intubation and at T-VAP or T no-VAP time.

Eligibility criteria: Inclusion Criteria:

* Older than 18 years
* Patients ventilated for reasons other than pulmonary failure with an expected need for MV longer than 48 hours

Exclusion Criteria:

* Admission in ICU with a pneumonia
* Clinical Pulmonary Infectious Score (CPIS) \> 6
* Antibiotic therapy \> 3 days prior to the start of MV

Primary outcomes:
measure: Lung/oral microbiota and VAP development
timeFrame: (Time frame for VAP patients: intubation (T0), 24h before VAP development (T pre- VAP) and at VAP development (T-VAP). Time frame for non-VAP patients: intubation (T0), samples corresponding to T-VAP of matched VAP patients (T no VAP))
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico
state: MI
Study officials:
References:
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