Pathogenesis of community-acquired pneumonia, chronic obstructive pulmonary disease and cystic fibrosis: mechanism of inflammatory response and the role of Th17 differentiatio

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 135

Inclusion Criteria

All patients with COPD, CF or CAP who are admitted to the Erasmus MC will be asked to participate in this study. The treating lung physician will assess eligibility.;COPD
- Age >/= 18 years
- Diagnosis of COPD according to GOLD criteria (FEV1/FVC<70%), classification into
GOLD II (FEV1 50-70% predicted) or GOLD III (FEV1 30- 50% predicted). In case of lungtransplantation: GOLD IV (FEV1 < 30% predicted).
- Stable disease. Patients have to be free of COPD exacerbation or respiratory tract
infection within a month prior to involvement in the study and they should not have received glucocorticoids or antibiotics in this period.;When patients have to undergo lungtransplantation, they will be asked whether material from their lungs can be used for this study. ;Community-acquired pneumonia
- Age >/= 18 years
- Clinical presentation of an acute illness with symptoms indicating CAP: fever, dyspnoea,
cough, pleuritic chest pain and new consolidations on chest X-ray have to be present.
- Normoxemic
- In case of hypoxemia (O2 saturation < 92%), patients are only included when patients are intubated and mechanically ventilated, because of respiratory insufficiency.;Cystic fibrosis
- Age >/= 18 years
- Diagnosis of CF confirmed by sweat-test and/or DNA analysis and/or
electrophysiology testing
- Stable phase (no signs of exacerbation)
- Exacerbation phase: characterized by signs of increased coughing, increased sputum production, dyspnea, fatigue;In some circumstances children with CF have to undergo a bronchoscopy for diagnostic reasons. In these cases we will ask the patients and/or their parents whether some extra material can be obtained from bronchoscopy for this study. Importantly, the children will not be approached to undergo a bronchoscopy, only for scientific reasons!;When patients have to undergo lungtransplantation, they will be asked whether material from their lungs can be used for this study. ;Healthy individuals
- Age >/= 18 years
- No signs of any disease
- Normal Lungfunction
- Normal Chest X-ray;In case children with CF are included with age <18 years, then age matched non-CF patients, without signs of inflammation or infection will be included as controls.

Exclusion Criteria

CAP:
- Hypoxemia (O2 saturation < 92%), unless patients are intubated and mechanically ventilated

COPD
- Use of antibiotics or glucocorticoids within a month prior to involvement in the study.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective is to assess whether Th17 cell lineage is critically<br /><br>involved in COPD, CF and pneumonia pathogenesis. Therefore, we will<br /><br><br /><br>(a) Analyse cytokine production by activated T cells that are present in the<br /><br>lungs of COPD and CF patients, as compared with activated T cells involved in<br /><br>host defense in pneumonia.<br /><br><br /><br>(b) Analyse cytokine production by antigen-experienced/memory T cells that are<br /><br>present in the<br /><br>peripheral blood of COPD and CF patients, as compared with activated T cells<br /><br>involved in host defense in pneumonia.<br /><br><br /><br>(c) Analyse whether naive T cells from COPD and CF patients are predisposed to<br /><br>Th17 polarization, when compared with naive T cells from control groups.<br /><br></p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objective is to investigate whether Th17 activity correlates with<br /><br>the presence of autoreactive B cells in COPD. Therefore, we will<br /><br><br /><br>(a) Determine the presence of auto-antibodies in COPD patients.<br /><br><br /><br>(b) Determine the repertoire of B cells presents in the lungs of COPD patients,<br /><br>as compared with B cells involved host defense in pneumonia.<br /><br><br /><br>(c) Correlate the presence of Th17 differentiation with the presence of<br /><br>auto-immune B cells.<br /><br><br /><br>Another secondary objective is to investigate whether in patients with<br /><br>pneumonia pneumococcal infections provoke a different inflammatory response<br /><br>than atypical pathogens. Therefore, we will<br /><br>Correlate the presence of Th17 cells and cytokine production by activated T<br /><br>cells with different pathogens causing pneumonia </p><br>