Effects of Low-Dose Theophylline During Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

Condition(s) targeted: COPD

Intervention: Theophylline (Drug)

Phase: N/A

Status: Completed

Sponsored by: Hospital Universitari Son Dureta

Official(s) and/or principal investigator(s):
Borja G Cosio, MD, Principal Investigator, Affiliation: Hospital Universitario Son Dureta

Molecular mechanisms of COPD exacerbations and the modulating effect of low dose theophylline on that inflammation are elucidated in this project. NF-kappa B-dependent pathway and acetylation status of nuclear histones are to be studied. Design: controlled, prospective and randomized study with or without theophylline, a potent HDAC activator. Objectives: 1) To determine NF-kB activation, histone deacetylase (HDAC) and histone acetyl-transferase (HAT) activity in sputum macrophages and blood monocytes during an episode of exacerbation and 3 months later, once stability is achieved. To correlate these measurements with inflammatory and oxidative stress markers and with pulmonary function and clinical variables. 2) To assess the effect of theophylline on previous molecular, functional and clinical data. Method: 25 patients with COPD will be recruited during an episode of exacerbation requiring hospitalization. NF-kB activation, HDAC and HAT activity, markers of inflammation and oxidative stress will be determined with specific assays. These determinations will be repeated once the patient is stable and compared with smokers and non smoker controls with normal lung function

Official title: Molecular Mechanisms of COPD Exacerbations. Effect of Low-Dose Theophylline

Study design: Basic Science, Randomized, Single Blind (Outcomes Assessor), Active Control, Single Group Assignment

Primary outcome: HDAC activity in alveolar macrophages

Secondary outcome:

Lung function

Inflammatory cytokine release in sputum and serum

Minimum age: 40 Years. Maximum age: 75 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Severe COPD according to GOLD guidelines

- Age between 40 and 75

- Admission to hospital due to COPD exacerbation

Exclusion Criteria:

- History of asthma

- Pulmonary embolism

- Pneumonia

- Other chronic inflammatory disease

- Patient on theophylline at the time of admission

- Patient on oral steroids at the time of admission

Hospital Universitario Son Dureta, Palma de Mallorca, Baleares 07014, Spain

Related publications:

Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ. Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med. 2004 Sep 6;200(5):689-95. Epub 2004 Aug 30.

Starting date: June 2005
Ending date: December 2007
Last updated: May 2, 2008