Influenza Associated Aspergillosis In-depth Investigation

Study Overview
=================
Brief Summary
-----------------
This trial is aimed to study the immunological and pathological characteristics of influenza versus non-influenza severe community-acquired pneumonia patients in ICU.

Detailed Description
-----------------
This trial is aimed to study the immunological and pathological characteristics of influenza versus non-influenza severe community-acquired pneumonia patients in ICU, and correlate findings with occurrence of secondary invasive pulmonary aspergillosis infection. All consecutive patients aged 18 or older admitted to ICU during the inclusion period with respiratory distress due to influenza positive/negative community acquired pneumonia (CAP) will be included.

Official Title
-----------------
Unraveling the Pathogenesis of Influenza-associated Aspergillosis: a Single-center, Prospective Cohort Pilot Study

Conditions
-----------------
Influenza With Pneumonia, Invasive Pulmonary Aspergillosis

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients older than 18 years, admitted to ICU with respiratory distress with microbiologically confirmed diagnosis of influenza (for inclusion in the influenza group) All patients older than 18 years, admitted to ICU for respiratory distress due to community- acquired pneumonia , with a microbiologically confirmed absence of influenza (for inclusion in the control group) Exclusion Criteria: Age < 18 years old Pregnant women No informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Influenza positive CAPIV<br>All consecutive patients older than 18 years, admitted to the ICU with respiratory distress with microbiologically confirmed diagnosis of influenza | |
| Influenza negative CAPIV<br>All consecutive patients older than 18 years, admitted to the ICU for respiratory distress due to community-acquired pneumonia (CAP) and with a microbiologically confirmed absence of influenza | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in immune cell profile in blood between influenza and non-influenza CAPIV patients at ICU. | Immunophenotyping of blood will be performed to determine number of neutrophils, T- and B-cell subsets, NK cell and myeloid cell subsets. Difference in influenza positive and influenza negative patients is expected. | through study completion, after 3 influenza seasons (3 years) | 
| Difference in cytokine production of mononuclear cells to fungal stimulation in blood between influenza and non-influenza CAPIV patients at ICU. | Key cytokine reaction of mononuclear cells (PBMC) after fungal stimulation will be performed. Difference in influenza positive and influenza negative patients is expected. | through study completion, after 3 influenza seasons (3 years) | 
| Difference in function of blood neutrophils between influenza and non-influenza CAPIV patients at ICU. | Functional analysis by killing assay will be performed. | through study completion, after 3 influenza seasons (3 years) | 
| Difference in in immune cell profile in BAL fluid between influenza and non-influenza CAPIV patients at ICU. | Immunophenotyping of BAL fluid will be performed to determine number of neutrophils, T- and B-cell subsets, NK cell and myeloid cell subsets. Difference in influenza positive and influenza negative patients is expected. | through study completion, after 3 influenza seasons (3 years) | 
| Difference in cytokine production of mononuclear cells to fungal stimulation in BAL fluid between influenza and non-influenza CAPIV patients at ICU. | Key cytokine reaction of mononuclear BAL fluid cells after fungal stimulation will be performed. Difference in influenza positive and influenza negative patients is expected. | through study completion, after 3 influenza seasons (3 years) | 
| Difference in function of BAL fluid neutrophils between influenza and non-influenza CAPIV patients at ICU. | Functional analysis by killing assay will be performed. | through study completion, after 3 influenza seasons (3 years) | 
| Difference in pathological hallmarks between influenza and non-influenza CAPIV patients at ICU. | Biopsies of respiratory tract tissue will be compared between two groups. | through study completion, after 3 influenza seasons (3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in longitudinal alterations in phagocytic cell and mononuclear inflammatory cell subsets in blood and BAL fluid and their response to fungal stimulation between the main study arms. | Longitudinal alterations in advanced immunophenotyping results and (fungal) cell stimulation will be analysed and compared between groups. | through study completion, after 3 influenza seasons (3 years) | 
| Longitudinal differences in anatomopathological characteristics of the respiratory tract in CAPIV +/- influenza | Respiratory tract biopsies will be compared longitudinally throughout the disease course. | through study completion, after 3 influenza seasons (3 years) | 
| Correlation of findings with invasive pulmonary aspergillosis incidence | All data will be compared within each group between patients that develop IPA vs no development of IPA. | through study completion, after 3 influenza seasons (3 years) | 
| Correlation of findings with outcome | All data will be compared to outcome measures (length of ICU stay, mortality, etc) to find hallmarks of severe disease. | through study completion, after 3 influenza seasons (3 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza, IPA, ICU, Immunology