The pathophysiology of chronic asthma is complex, in that it involves smooth-muscle dysfunction, acute and chronic inflammation, and structural changes within the airway, collectively termed airway remodeling. It has generally been assumed that airway inflammation is responsible for the various manifestations of asthma including shortness of breath, wheezing, bronchial hyperresponsiveness, smooth-muscle dysfunction and, ultimately, structural changes. However, inflammation is not the sole mediator of this disease. As effective as inhaled glucocorticoid therapy is, it alone is often insufficient to adequately control asthma in patients with moderate-to-severe persistent asthma. 4

In addition, multiple studies have shown that doubling the dose of inhaled glucocorticoid in patients inadequately controlled on inhaled glucocorticoid therapy Generic Viagra pharmacy alone fails to provide significant improvement in efficacy, while increasing the potential for systemic and adverse effects. This unresponsiveness calls into question the paradigm that airway inflammation is solely responsible for the manifestations of asthma and that glucocorticoid-independent mechanisms need to be considered. Whether this reflects our limited understanding of the pathogenesis of airway remodeling and/or a lack of effective therapies to target glucocorticoid-insensitive mechanisms remain an open issue.

The literature describing the pathology of severe, steroid-dependent childhood asthma is virtually nonexistent. This case series is among the first to combine historical and clinical features, pulmonary physiology, and endobronchial biopsy results in a group of children with severe steroid-dependent asthma. All of the subjects studied had a long, if not lifelong Cialis in Canada history of severe, persistent, high-risk asthma refractory to aggressive management that included long-term oral and high-dose inhaled glucocorticoid therapy.

A majority of these patients had been intubated at least once due to severe asthma exacerbations. In every case, the endobronchial biopsies revealed significant changes to the structure of the airways, with little to no airway inflammation present. These findings suggest that noninflam-matory-mediated mechanisms may contribute to severe asthma in children.