Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients

Asai, Kuniya; Kanazawa, Hiroshi; Kamoi, Hiroshi; Shiraishi, Satoshi; Hirata, Kazuto; Yoshikawa, Junichi

doi:10.1046/j.1365-2222.2003.01576.x

Cited by 156 publications

(144 citation statements)

References 23 publications

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“…Elevated VEGF levels have also been reported in sepsis, and this has been thought to lead to the capillary leak syndrome seen in sepsis (31). The increased expression of VEGF has been associated with several respiratory diseases, including bronchitis, airflow limitation, and asthma (32,33). Thus, in the present study, the statistical significance of the decrease in oxygen dependency increased as the severity of the BPD worsened.…”

Section: Discussionsupporting

confidence: 55%

Effects of Intravitreal Anti-VEGF Therapy on the Clinical Course of Bronchopulmonary Dysplasia

et al. 2016

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Objectives: To demonstrate the effects of the injection of intravitreal bevacizumab (IVB) on the clinical course of established bronchopulmonary dysplasia (BPD). Methods: This is a multicenter retrospective case-control study performed without any randomization or masking procedure. A total of 70 patients with BPD, including 35 cases (the IVB group) and 35 controls (the control group) were studied. Patients in the IVB group received intravitreal anti-VEGF (bevacizumab) treatment for type 1 prethreshold retinopathy of prematurity (ROP). The control group consisted of infants with BPD whose gestational age, birthweight, and gender were matched with those of the IVB group. None of the infants in the control group needed to be treated for ROP using either anti-VEGF or laser photocoagulation. Results: There was no statistically significant difference (P = 0.11) between the groups in terms of the total duration of oxygen prior to the IVB injection (65.9 ± 23.5 and 79.1 ± 33.1 days in the IVB group and control group, respectively). However, after the injection of IVB, the total duration of oxygen was significantly lower in the IVB group (mean 7 (1 -70) days vs. 16 (1 -98) days, P = 0.01). In 14 cases with mild BPD and their matched controls, the median time (25% -75%) for the discontinuation of oxygen therapy was 3 (2 -7) days and 10 (5 -15) days, respectively (P = 0.36). In 21 cases with moderate and severe BPD and their matched controls, the median time (25 -75%) for the discontinuation of oxygen therapy was 14 (7 -21) days and 22 (16 -43) days, respectively (P = 0.024). Conclusions: Intravitreal bevacizumab injection treatment for ROP cases with BPD was found to be associated with a shorter duration of oxygen use. The results of the study not only demonstrate a pathogenic correlation between ROP and BPD through an abnormal vasculogenesis, but also raise a question regarding whether or not the systemic side effects of IVB are actually adverse.

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Section: Discussionsupporting

confidence: 55%

Effects of Intravitreal Anti-VEGF Therapy on the Clinical Course of Bronchopulmonary Dysplasia

et al. 2016

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“…3 Changes in inflammatory cells and cytokines in induced sputa during MDI-specific inhalation challenge testing in positive and negative groups mast cells and eosinophils, and has been shown to enhance inflammatory processes. In addition, levels of VEGF are usually increased in the sputum of allergic asthma [37] and TDI-OA patients [38]. In this study, increased VEGF levels were noted in patients with MDI-OA and correlated with IL-8 levels.…”

Section: Discussionsupporting

confidence: 56%

Histamine Release and Inflammatory Cell Infiltration in Airway Mucosa in Methylene Diphenyl Diisocyanate (MDI)-Induced Occupational Asthma

et al. 2008

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Introduction Although methylene diphenyl diisocyanate (MDI) is widely used in industries, there have been few studies of the pathogenic mechanisms of MDI-induced occupational asthma (MDI-OA). Methods We performed immunohistochemical analyses, measured inflammatory mediators and cytokines, and quantified histamine release (HR) from peripheral basophils in MDI-OA patients. Thirteen MDI-exposed workers (five MDI-OA, two MDI-induced esoinophilic bronchitis, and six asymptomatic exposed controls, AEC) were enrolled. Results and Discussion Immunochemical analyses indicated significantly increased anti-eosinophilic cationic proteinstained cells in MDI-OA patients as compared with controls (P<0.05). Sputum eosinophil cationic protein levels were increased after MDI-specific inhalation challenge test in MDI-OA/EB patients (P<0.02). Sputum eosinophil counts were highly correlated with IL-8 and MMP-9 levels (P<0.05 and P<0.01, respectively). Basophil HR was significantly increased in MDI-OA patients after stimulations with anti-IgG4 and MDI-human serum albumin conjugates (both P<0.05). Eosinophil activation is a major feature of airway inflammation in MDI-OA patients. Increased HR by MDI may contribute to the pathogenic mechanisms of MDI-OA.

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“…These findings are in accordance with recent literature (20)(21)(22)(23)(24), although, to the best of our know ledge, this is the first study to report mRNA expression levels of both VEGF and its receptor FLT-1 in human nasal polyp tissue. Mounting evidence suggests that, besides its influence on blood vessel formation, VEGF may even be directly involved in the pathogenesis of bronchial asthma (30,31). Similarly, we hypothesized that VEGF may mediate upper airway remodeling observed in the development of sinonasal polyposis.…”

Section: Discussionmentioning

confidence: 93%

“…Th2 cells, a key element in bronchial asthma pathophysiology, have been shown to express receptors for VEGF. Moreover, evidence exists showing that high VEGF levels may be directly associated with asthma severity, as they correlate directly with disease activity and inversely with airway caliber and airway responsiveness (30,31). VEGF has been shown not only to promote cell growth, but also to inhibit apoptosis in epithelial cells and to auto-regulate its own production in a positive manner in non-neoplastic primary human airway epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Investigation of angiogenetic pathways in nasal polyposis

et al. 2012

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Abstract. Tissue angiogenesis is a complex phenomenon that results in the growth of new blood vessels from the microcirculation. This process has been known to play a crucial role in tumor growth as well as several benign diseases. The aim of this study was to assess mRNA expression of various angiogenic factors and chemokines in nasal polyps and compare the results to normal nasal mucosa. mRNA expression was measured using real-time RT-PCR for the following angiogenic factors and chemokines: VEGF, VEGFR-1, Ang-1, Ang-2, Tie-2A, Tie-2B, SDF-1α, SDF-1β, CXCR4 and YY1. Biopsy specimens from nasal polyps in the polyposis group and middle turbinates in the control group were studied. A total of 18 nasal polyposis patients were studied and compared to 10 control subjects. Results showed VEGF, VEGFR-1, Ang-1, Ang-2, Tie-2A, Tie-2B, SDF-1α and SDF-1β mRNA expression to be significantly higher in nasal polyposis patients compared to the control group (p<0.05). The findings of this study support the role of angiogenic growth factors in the pathogenenesis of nasal polyposis. Further studies are required to confirm these results and evaluate potential clinical implications. IntroductionNasal polyposis (NP) constitutes a chronic inflammatory disease of the nose and sinuses characterized by the appearance of protruding tissue swellings of the nasal mucosa. These swellings most commonly originate from the middle meatus and anterior ethmoids. On histologic examination, they are typically characterized by proliferation of the epithelial layer, glandular hyperplasia, thickening of the basal membrane, focal fibrosis, edema and cellular infiltration of the stromal layer. Nasal polyps are relatively common in the general population and significantly affect patient quality of life. Despite these facts, etiology of the disease remains largely unknown (1-4).Tissue angiogenesis is a complex phenomenon that results in the growth of new blood vessels from the microcirculation (5-7). This process has been known to play a crucial role in tumor growth, where it is regarded as a prerequisite allowing for the expansion of tumor populations beyond the size restricted by oxygen and nutrient diffusion (6). It also facilitates tumor progression and metastasis by causing degradation of the epithelial basement membrane and providing cancer cells with new capillaries for entering the circulation (7,8).Increasing evidence shows that angiogenesis may also play a critical role in benign disorders (9,10). The phenomenon, appearing in the form of growth of new blood vessels or the enlargement of existing ones, has been strongly associated with airway remode ling in chronic asthma and chronic obstructive pulmonary disease (11,12). In addition, using immunohistochemistry it has been shown that vascular endothelial growth factor (VEGF), possibly the most important driver of angiogenesis, along with its receptors, are strongly expressed in nasal polyp tissues, thus supporting a role in the development of chronic inflammation and edema in this disease (13).Re...

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Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients

Abstract: The VEGF levels in induced sputum were increased in asthmatics and its levels were associated with degree of airway narrowing and airway vascular permeability. These findings provide strong evidence that VEGF may play an important role in the pathogenesis of bronchial asthma.

Cited by 156 publications

References 23 publications

Effects of Intravitreal Anti-VEGF Therapy on the Clinical Course of Bronchopulmonary Dysplasia

Effects of Intravitreal Anti-VEGF Therapy on the Clinical Course of Bronchopulmonary Dysplasia

Histamine Release and Inflammatory Cell Infiltration in Airway Mucosa in Methylene Diphenyl Diisocyanate (MDI)-Induced Occupational Asthma

Investigation of angiogenetic pathways in nasal polyposis

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