Long acting beta 2 agonists and theophylline in stable chronic obstructive pulmonary disease

Cazzola, Mario; Donner, Claudio F.; Matera, Maria Gabriella

doi:10.1136/thx.54.8.730

Cited by 29 publications

(24 citation statements)

References 71 publications

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“…It is marketed as Theolan in Ireland by Elan, and in Southeast Asia by Elan Pharma. Theophylline is the most frequently prescribed oral bronchodilator for the chronic maintenance treatment of chronic obstructive airway disorders [224]. However, there is no evidence that theophylline has any selectivity for a particular isoenzyme, such as PDE4 [225].…”

Section: Pde4 Inhibitorsmentioning

confidence: 99%

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Jeon

Heo

Kim

et al. 2005

CMLS, Cell. Mol. Life Sci.

225

174

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Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.

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Section: Pde4 Inhibitorsmentioning

confidence: 99%

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Jeon

Heo

Kim

et al. 2005

CMLS, Cell. Mol. Life Sci.

225

174

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“…This difference placed our study group at a higher prevalence of both systemic inflammation and cardiac stress. Furthermore, we did not adjust for current medications which may elicit anti-inflammatory or adverse cardiovascular effects [33,34,35]. Paradoxically, these limitations do not weaken the strength of our data, because our inclusion criteria and the lack of adjustment for potentially cardiotoxic medications tend to dilute the impact of an impaired lung function on CRP and the effect of systemic inflammation on NT-proBNP, respectively.…”

Section: Discussionmentioning

confidence: 99%

A Link between Impaired Lung Function and Increased Cardiac Stress

Wieshammer

Dreyhaupt²,

Basler³

2009

Respiration

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Background: Patients with impaired lung function often have systemic inflammation. C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are markers for inflammation and cardiac stress, respectively. Objectives: To evaluate the association between both markers and the potential impacts of lung disease on this relationship. Methods: CRP and NT-proBNP were prospectively measured in 697 consecutive outpatients (57.5 ± 16.4 years) with chronic dyspnea. The patients were stratified into quartiles according to CRP levels (quartile 1: median CRP 0.35 mg/l; quartile 2: 1.50 mg/l; quartile 3: 3.62 mg/l; quartile 4: 10.90 mg/l) and classified into 2 categories based on the presence (n = 176) or absence (n = 521) of heart disease. Results: Patients with at least moderately severe airway obstruction and those with interstitial lung disease had higher CRP values than patients without lung disease (median 3.50 vs. 4.34 vs. 1.80 mg/l, respectively; p < 0.01). In patients without heart disease, NT-proBNP values increased from CRP quartiles 1–3 to quartile 4 (median 47.4 vs. 82.1 pg/ml; p < 0.01) after adjusting for important covariates such as age, sex, body mass index, renal function and arterial hypertension. Likewise, the values for NT-proBNP were lower in CRP quartiles 1–3 than in quartile 4 (median 212.0 vs. 647.7 pg/ml; p < 0.01) in patients with heart disease after additional adjustment for the type of cardiac disorder. Lung disease had no direct effect on the relationship between CRP and NT-proBNP. Conclusion: Systemic inflammation that originates in the lung places an excess burden on the heart, which may contribute to the functional impairment of patients with advanced pulmonary disease.

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“…Apparently, the withdrawal of theophylline can worsen lung function, clinical status, exercise performance, and ratings of dyspnea (Kirsten et al, 1993). Studies comparing theophylline with ␤ 2 -AR agonists found similar improvements in spirometry and in various measures of patients' functional state and well-being (Cazzola et al, 1999b). However, very few studies have compared theophylline with inhaled mAChR antagonists.…”

Section: B Theophyllinementioning

confidence: 99%