MERANO, ITALY— While efforts to understand and treat asthma typically have focused on airways themselves, observations of enhanced growth of airway vasculature in asthma now bring blood vessels under the microscope.[1] Because expansion of airway vasculature could contribute to bronchial wall thickening and, thus, hyperreactivity, vessels may represent a new target for asthma therapies.

Gastone Salvato, MD, Head Physician Emeritus of the Division of Medicine, General Hospital in Merano, Italy, examined lung tissue from 40 asthmatic and non-asthmatic subjects. He found more blood vessels covering a higher percentage of area of the tunica propria in the asthmatic than in the non-asthmatic specimen sections. Among asthma patients, vessel density was also correlated with disease severity. “This suggests that the inflammatory process underlying severe asthma induces growth of new vessels,” Dr. Salvato hypothesized in his recent paper.

In contrast with some previous studies of vascularization in samples obtained from asthma patients postmortem, Dr. Salvato’s investigation is unlikely to have been confounded by patients’ drug regimens or other artifacts, such as edema, he noted. And in the 10 days before biopsy, “my patients were not [receiving] corticosteroid treatment,” therapy that probably contributed to variability of others’ results, Dr. Salvato told RESPIRATORY REVIEWS.

Dr. Salvato took bronchoscopic biopsy samples from 20 patients with allergic asthma and 20 non-asthmatic control patients. Eight of the asthma patients had mild cases (symptoms less than once a day and peak expiratory flow [PEF] greater than 80% of expected), six had moderate cases (symptoms every day and PEF between 60% and 80% of expected), and six had severe cases (repeated attacks during the day and night and PEF less than 30% of expected). Each biopsy sample was sectioned and stained for microscopy; vessels within the lamina propria were then counted and the proportion of vascular to nonvascular area calculated.

Both mean vessel density and the percentage of vascular area significantly differed between asthmatic and non-asthmatic specimens (226.70 vs 172.05 per mm2 and 8.61% vs 6.81%, respectively). Furthermore, the mean number of vessels per square millimeter was greater in samples from patients with severe asthma (303.7) than in samples from those with moderate (205.0) or mild (185.3) asthma. Microscopy revealed eosinophils and free extracellular eosinophil granules (apparent products of allergen-induced eosinophil cytolysis) in blood vessel lumens of asthma patients but not in those from controls.

VASCULAR GROWTH, TONE AS THERAPY TARGETS?

“The intravascular eosinophil activation could have influenced the vascular morphological changes by releasing toxic proteins, such as eosinophil cationic protein,” Dr. Salvato explained. If changes in airway vessels indeed contribute to asthma symptoms, then vascular growth and tone may represent therapeutic targets. “I envision drugs with anti-angiogenic activity” as potential asthma-fighting agents, said Dr. Salvato. “If the number of vessels is reduced, ... the area for recruitment of inflammatory cells and leakage of plasma and mediators is smaller.” He added, “Reducing vasodilatation could also [provide] good results, because fewer inflammatory mediators and eosinophils, which seem to play a key role in ... damage, would reach the tissue.”

—Mimi Zucker, PhD