10.2217/14750708.2.2.255 © 2005 Future Medicine Ltd ISSN 1475-0708 Therapy (2005) 2(2), 255–259 255 R ESEARCH A RTICLE For reprint orders, please contact: reprints@futuremedicine.com Relationship between duration, fatality rate and severity of disease and serum epidermal growth factor in human acute lung injury Afsaneh Vazin, Mojtaba Mojtahedzadeh, Atabak Najafi, Azita Khalilzadeh & Mohammad Abdollahi † † Author for correspondence Tehran University of Medical Sciences, Faculty of Pharmacy, Tehran 14155–6451, Iran Tel.: + 98 21 695 9104 mohammad@tums.ac.ir Keywords: acute lung injury, epidermal growth factor Aim: The present study was undertaken to clarify whether serum concentrations of epidermal growth factor (EGF) are changed during the first week after the onset of acute lung injury (ALI) and to determine whether the change of EGF concentration was specific for ALI by including a control subject. Methods: We enrolled 30 consecutive patients with ALI, prospectively identified on admission to the intensive care unit, and ten patients in the same unit with chronic interstitial disease. The serum EGF concentration was measured on days 1 to 7 after the onset of ALI. Results: At each day tested, the mean EGF level of the patients with ALI was not significantly higher than that of the non-ALI controls and normal volunteers. In a univariate analysis, the mean EGF level in nonsurvivors was not higher at different days (p > 0.05). The overall fatality was not associated with increased serum EGF levels. Conclusion: It is concluded that the concentration of EGF in the serum of ALI patients does not change significantly. The present study was undertaken to clarify whether serum concentrations of epidermal growth factor (EGF) are changed during the first week after the onset of acute lung injury (ALI) and to determine whether the change of EGF concentration was specific for ALI by including a control subject. Whether it is caused by direct assault from pneumonia or indirectly through sepsis or trauma, ALI represents a sig- nificant healthcare burden [1,2]. Fatality and morbidity associated with ALI are considerable, with a significant impact on public health [3]. The clinical course of patients with ALI is varia- ble and influenced by different factors. One of the most important mechanisms that deter- mines the severity of lung injury is the magni- tude of injury to the alveolar epithelial barrier. The possibility of repairing epithelial injury at an early stage is a major determinant of recovery. Specific treatments to accelerate alveolar epithe- lial repair do not exist, although progress in studies with experimental models of ALI suggest that specific treatments may be possible in the future. The majority of treatment modalities tested recently were based on diminution of the inflammatory response in the lung in order to minimize the initial injury. However, an alterna- tive therapeutic approach is to accelerate the repair process in the alveolar epithelium in the early stages of ALI in order to enhance resolu- tion of pulmonary edema and improve out- comes in these patients. Little is known at present about the cellular and molecular mecha- nisms of alveolar epithelial repair in ALI. In particular, soluble mediators, which play a key role in alveolar epithelial repair in these patients must be identified and characterized if novel therapeutic strategies are to be developed [4]. Although the extracellular matrix, in particular fibronectin, more than likely plays an important role in the alveolar repair process [5], growth fac- tors such as EGF have also been shown to aug- ment alveolar epithelial repair in vivo and in vitro [4,6]. For example, it has been demon- strated that in a monolayer of mammary epithe- lial cells, the addition of EGF or transforming growth factor (TGF)-α result in accelerated wound closure that was associated with an upregulation of several integrin molecules [6]. Moreover, elevated levels of EGF were reported in the fluid of skin wounds in humans [7]. EGF can upregulate sodium transport and markedly increase net alveolar fluid clearance in rats [8]. Furthermore, studies in bleomycin-injured rats and transgenic mice strongly suggest that EGF plays a role in alveolar repair and remodeling after lung injury [9]. Given the mounting evi- dence implicating growth factors in lung home- ostasis and disease, there are experimental data that support the role of growth factors in pre- venting damage or facilitate recovery by restor- ing or inducing an optimal balance of signals in the lung. A number of studies have shown that administration of a growth factor prior to ALI may be protective [10]. However, EGF concen- trations in the serum of patients with established ALI and its association with clinical outcomes of the disease has not been yet evaluated. part of