Dissertation committee:
Εμμανουήλ Καναβάκης, Καθηγητής Απόστολος Αρμαγανίδης, Καθηγητής Σπυρίδων Ζακυνθινός, Καθηγητής Θεόδωρος Βασιλακόπουλος, Αναπληρωτής Καθηγητής (επιβλέπων) Στυλιανός Λουκίδης, Επίκουρος Καθηγητής Πέτρος Μπακάκος, Επίκουρος Καθηγητής Παρασκευή Κατσαούνου, Λέκτορας
Summary:
Aim
Resistive breathing, due to airflow limitation, is observed during the natural
course of Chronic Obstructive Pulmonary Disease (COPD), especially during acute
exacerbations of COPD (AECOPD) and induces an inflammatory response,
characterized by elevated cytokine plasma levels.
Τhe aim of this study is to test the hypothesis that elevated cytokine plasma
levels in patients with severe AECOPD most probably originate from respiratory
muscles (especially the contracting diaphragm) and/or the mechanically stressed
"inflammatory" lung.
We also hypothesized that plasma cytokine levels would be decreased after
respiratory muscles relaxing, due to mechanical ventilation.
Methods:Thirty patients with severe AECOPD, that led to endotracheal intubation
and mechanical ventilation were studied. Blood samples were collected during
three phases of observation: Just before intubation, 20 minutes and 6 hours
after intubation and application of mechanical ventilation.
Seven patients with COPD in steady state, which were intubated and mechanically
ventilated for elective surgery procedures were used as the control group.
Blood samples were collected during two phases of observation: Just before and
20 minutes after intubation.
Luminex 100 IS technique (Luminex Corporation, Austin, TX, USA) was used to
access the plasma levels of the cytokines: IL-1α, IL-1β, IL-5, IL-6, IL-8,
IL-10, Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α), Epidermic Growth
Factor (EGF), Eotaxin, Monocyte Chemotactic Protein-1 (MCP-1), and Regulated
And Normal T cell Expressed and Secreted (RANTES).
Measurements were done with the Human Cytokine/Chemokine Milliplex MAP Kit
(MPXHCYTO-60K, Millipore Corporation, Billerica, MA, USA).
Results
Patients
IL-6 plasma levels 6 hours after intubation were found statistically
significantly lower compared to IL-6 levels before and 20 minutes after
intubation (p=0.043 and p=0.048 respectively).
IL-10 plasma levels 6 hours after intubation were found statistically
significantly lower compared to IL-10 levels 20 minutes after intubation
(p=0.05).
Eotaxin plasma levels 20 minutes and 6 hours after intubation were found
statistically significantly lower compared to Eotaxin plasma levels before
intubation (p=0.012 and p=0.019 respectively).
EGF plasma levels 20 minutes and 6 hours after intubation were found
statistically significantly lower compared to EGF levels before intubation
(p=0.009 and p=0.012 respectively).
IL-5, IL-8, TNF-α, INF-γ, MCP-1 and RANTES plasma levels didn't change
statistically significantly over time.
Controls: Plasma levels of all measured cytokines did not change significantly
over time in the control group.IL-1α and IL-1β plasma levels were found below
the lower detectable limit in both groups (patients with AECOPD and controls).
Conclusions: Application of mechanical ventilation in patients with AECOPD that
results in endotracheal intubation, leads to decreased plasma levels for
circulating IL-6, IL-10, Eotaxin and EGF. These findings suggest that the
origin of these cytokines could be the respiratory muscles and especially the
contracting diaphragm and/or the mechanically stressed "inflammatory" lung.
Keywords:
Chronic Obstructive Pulmonary Disease, Severe exacerbation, Systemic inflammation, Application of mechanical ventilation, Respiratory muscles and diaphragm
