Israel Medical Association Journal

The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA[1] and COPD[2], which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1β secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1β[3] targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.

Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment