Gene expression of vascular endothelial

growth factor and its receptors and

angiogenesis in bronchial asthma
.

Abstract 

Background: Angiogenesis is a feature of airway remodeling in bronchial asthma. The

mechanism responsible for this angiogenesis is unknown. Vascular endothelial growth factor
(VEGF) is a potent inducer of endothelial cells, which may contribute to chronic inflammation
and angiogenesis. Objective: We sought to investigate the molecular mechanisms underlying
increased vascularity, and we examined the mRNA expression of VEGF and its receptors (flt-1
and flk-1) within bronchial biopsy specimens from asthmatic patients and normal control
subjects. Methods: Endobronchial biopsy specimens were examined immunocytochemically by
staining with anti-type IV collagen mAb to evaluate vessel density by using computer-assisted
image analysis. Specimens were also analyzed for the presence of the mRNAs of VEGF and its
receptors with in situ hybridization. Results: The extent of airway vascularity was increased in
asthmatic subjects compared with that in control subjects (P < .01). Asthmatic subjects exhibited
a greater expression of VEGF, flt-1, and flk-1 mRNA+ cells in the airway mucosa compared
with that in control subjects (P < .001 for each comparison). The degree of vascularity was
associated with the number of VEGF, flt-1, and flk-1 mRNA+ cells. Numbers of cells expressing
VEGF mRNA inversely correlated with airway caliber (r = –0.83, P < .01) and airway
hyperresponsiveness (r = –0.97, P < .001). Colocalization studies showed that macrophages,
eosinophils, and CD34+ cells were the major sources of VEGF; CD34+ cells, macrophages, and
T cells expressed both flt-1 and flk-1. Conclusion: These findings provide evidence that VEGF
may play an important role in angiogenesis and subsequent airway remodeling in bronchial
asthma. (J Allergy Clin Immunol 2001;107:1034-8.)
Chronic cough as the sole presenting manifestation of
bronchial asthma
WM Corrao, SS Braman, and RS Irwin

Abstract

Six patients with chronic cough, without history of dyspnea or wheezing, had normal
base-line spirometry but hyper-reactive airways, as demonstrated with methacholine.
Maintenance therapy with bronchodilators promptly eliminated the cough in all patients.
Three to 12 months later therapy was discontinued for three days, cough returned, and
detailed pulmonary-function studies were carried out. Again, base-line values were
normal, but after methacholine one-second forced expiratory volume decreased an
average of 40 per cent in the patients as compared to 30 per cent in normal controls (P
less than 0.001). The point of identical flow was increased by methacholine to 43.5 per
cent of vital capacity in the patients, as compared to 6 per cent in normal controls (P
less than 0.001), and the alveolar plateau was 4.8 deltaN2 per liter, as compared to 1.4
in normal controls (P less than 0.01). Specific airway conductance was lowered in
patients and controls, but the post-methacholine value was significantly lower in the
patients. On the basis of their persistently hyper-reactive airways, inducible diffuse
airway bronchoconstriction and excellent response to bronchodilator therapy, these
patients appear to have a variant form of asthma in which the only presenting symptom
is cough.