Structural Changes in Airway Diseases: Remaining Questions and Future Research

Structural Changes in Airway Diseases: Remaining Questions and Future ResearchPhosphodiesterase Inhibitors: Selective phosphodiesterase inhibitors have been designed and studied, mainly in COPD. The breakdown of intracellular cyclic adenosine monophosphate following phosphodiesterase inhibition has been suggested to explain bronchodilatory and antiinflammatory effects and could lead to potential antiremodeling properties. The phosphodiesterase-3 inhibitor siguazodan has been shown to reduce in vitro proliferation of human ASM. In addition, the phosphodiesterase-4 inhibitor roflumilast reduced inflammation, subepithelial collagen deposition, and thickening of airway epithelium in an asthma mouse model. More info

Rapamycin: Rapamycin, SAR 943, a macrolid analog, decreases epithelial growth factor-induced proliferation in cultured human ASM cells. It has no effect on epithelial cells. In an asthma mouse model, rapamycin decreased fibronectin, mucus-containing cells, IL-4 and IL-5, the number of airway eosinophils, neutrophils, and lymphocytes in BAL fluid, and decreased airway response to methacho-line.
Bronchothermoplasty is an original mode of intervention that consists of applying an electric current to segmental and subsegmental bronchi, with the goal of destroying the smooth muscle and therefore reducing its capacity to contract. Although studies should determine the usefulness of this treatment, it has been shown to alter airway structure in a possibly beneficial way. In fact, Cox and colleagues249 report a persistent improvement of 2.9 doubling dose of methacholine bronchoprovocation test after 1 year of treatment.
Airway remodeling is a complex phenomenon that includes a variety of changes whose specific contributions to the change in airway function need further analyses. The time course and mechanisms by which such changes translate into modifications of airway responsiveness and symptomatic airway obstruction are to be evaluated more extensively in term of effects of the different treatments used for these conditions.

This entry was posted in Pulmonary Function and tagged airway inflammation, airway remodeling, antiasthmatic therapy, asthma.