TRPA1 agonists evoke coughing in guinea pig and human volunteers.

Rationale: Cough is the most frequent reason for consultation with a family doctor, or with a general or respiratory physician. Treatment options are limited and one meta-analysis concluded that over-the-counter remedies are ineffective. There is also increasing concern about their use in children.

Peroxisome proliferator-activated receptors as novel targets in lung disease.

Inflammatory diseases of the lung such as asthma and COPD represent a major worldwide health problem. There are potent antiinflammatory drugs available to treat asthma, such as the glucocorticoids, but these produce unwanted side effects and exhibit limited efficacy in the treatment of COPD. The identification of the peroxisome proliferator-activated receptors (PPARs) PPARgamma, PPARalpha, and PPARdelta opened up a new avenue of research as it was discovered that they exhibited antiinflammatory and immunomodulatory properties.

Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPARgamma regulates several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Synthetic PPARgamma agonists have been developed, such as the thiazolidinediones rosiglitazone and pioglitazone.

Steroid-resistant inflammation in a rat model of chronic obstructive pulmonary disease is associated with a lack of nuclear factor-kappaB pathway activation.

Rationale: Emphysema is one component of chronic obstructive pulmonary disease (COPD), a respiratory disease currently increasing in prevalence worldwide. The mainstay therapy adopted to treat patients with COPD is glucocorticoids; unfortunately, this treatment has limited impact on disease symptoms or underlying airway inflammation.

Objective: There is an urgent need to develop therapies that modify both the underlying inflammation, thought to be involved in disease progression, and the structural changes in the emphysematous lung.

New anti-inflammatory therapies and targets for asthma and chronic obstructive pulmonary disease.

Asthma and chronic obstructive pulmonary disease (COPD) are diseases of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma and COPD is still rising and is predicted to continue to rise in the foreseeable future. Beta-agonists and corticosteroids form the basis of the therapies available to treat asthma.

New advances and potential therapies for the treatment of asthma.

Asthma is a disease of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma is still rising and is predicted to continue to rise in the current century. Inhaled beta(2)-adrenoceptor agonists and corticosteroids form the basis of the treatments available to alleviate the symptoms of asthma.

Soft steroids: a new approach to the treatment of inflammatory airways diseases.

Inhaled synthetic glucocorticosteroids are widely used in the treatment of bronchial asthma where they provide very effective first line treatment. However, a range of unwanted side effects and the often complex dosing schedules associated with these drugs frequently result in poor patient compliance. The soft drug approach has been utilised as a means of delivering these potent anti-inflammatory agents close to their site of action while reducing the degree of systemic exposure and thus limiting or eliminating the associated systemic and local side effects.

Inhibition of guinea-pig and human sensory nerve activity and the cough reflex in guinea-pigs by cannabinoid (CB2) receptor activation.

1. There is considerable interest in novel therapies for cough, since currently used agents such as codeine have limited beneficial value due to the associated side effects. Sensory nerves in the airways mediate the cough reflex via activation of C-fibres and RARs.

Novel therapies for the treatment of inflammatory airway disease.

Asthma and chronic obstructive pulmonary disease (COPD) are diseases of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma and COPD is still rising and is predicted to continue to rise in the current century. The beta-agonists and corticosteroids form the basis of the treatments available to alleviate the symptoms of asthma, whereas the treatments available for COPD have been shown to have a limited effect on slowing the progression of the disease.

Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD.

Sensory nerves regulate central and local reflexes such as airway plasma leakage, and cough and their function may be enhanced during inflammation. Evidence suggests that dopamine receptor agonists may inhibit sensory nerve-mediated responses. In this study dopamine inhibited vagal sensory nerve induced microvascular leakage in the rat.