Clinical corticosteroid therapy: Impact on oral mucosal wound healing

描述(申请人提供)：皮质类固醇是一种有效的抗炎激素，自20世纪50年代初以来一直被有效地用于减少牙科手术后的肿胀和疼痛。患者报告说，当他们经历了使用和不使用这种疗法的手术时，他们强烈倾向于使用皮质类固醇。然而，由于这些激素是有效的免疫抑制剂，临床医生强烈担心皮质类固醇可能会延迟愈合，从而增加术后感染的风险。出于这个原因，尽管已知有好处，许多口腔外科医生并不给他们的患者使用皮质类固醇。令人惊讶的是，皮质类固醇对口腔(粘膜)组织愈合的影响从未被系统研究过，因此仍不清楚。最近来自我们实验室的证据，使用了一个在人类中建立的口腔创伤模型，发现口腔炎症的减少与更快的愈合时间有关。这有力地表明，皮质类固醇的抗炎特性不会阻碍口腔组织的愈合，而且可能会增强口腔组织的愈合。这项研究将澄清这一重要观点。60名成年志愿者(30名男性，30名女性)将接受口腔手术中常见的单次静脉注射皮质类固醇(125毫克甲基强的松龙)或安慰剂。然后，受试者将由牙周科医生在口腔硬腭上放置三个小伤口。伤后6小时取1个创面，伤后24小时取1个创面取材，以确定两个时间点的组织炎症程度。第三个伤口将每天拍摄，直到愈合，以确定治愈率。最后，将在第14天对愈合的组织进行活检，以评估疤痕的形成。大约一个月后，受试者将在口腔的另一侧接受相同的程序，并将接受替代药物治疗(受试者之间的药物顺序将相互平衡)。这项研究设计将使我们能够直接评估皮质类固醇对愈合率、炎症和疤痕形成的影响，并将受试者作为自己的对照。这项研究的结果将对临床牙科产生直接影响，通过提供关于皮质类固醇治疗如何影响口腔组织愈合的洞察力。如果治愈率不受影响，或者，正如我们预测的那样，在服用皮质类固醇后愈合速度缩短，这强烈主张在牙科手术中使用皮质类固醇。相反，如果皮质类固醇损害组织愈合，那么它们的使用就会受到质疑，特别是对于牙科小手术和术后感染风险较高的个人。通过更好地确定何时适合皮质类固醇治疗，这些结果将减少与口腔手术相关的直接成本(随访)、间接成本(收入损失)和无形成本(疼痛和痛苦)，从而对医疗保健产生财务影响。这项研究还将更好地了解口腔组织愈合的机制。公共卫生意义：这些结果将通过提供皮质类固醇给药如何影响组织愈合的洞察力，立即对牙科临床产生影响，并可能对整容外科产生影响。如果使用皮质类固醇后治愈率未受影响或缩短，则强烈主张在牙科手术中使用皮质类固醇；相反，如果皮质类固醇损害组织愈合，则其使用受到质疑，特别是对于牙科小程序和术后感染风险较高的个人。通过更好地确定何时以及对谁来说，皮质类固醇治疗是合适的，这些结果将通过减少与口腔手术相关的直接成本(随访)、间接成本(收入损失)和无形成本(疼痛和痛苦)来影响医疗费用。

DESCRIPTION (provided by applicant): Corticosteroids are potent anti-inflammatory hormones that have been used effectively since the early 1950s to reduce swelling and pain following Dental surgery. Patients report a strong preference for corticosteroids when they have experienced surgery with and without this therapy. Nevertheless, because these hormones are potently immunosuppressant, there is a strong concern by clinicians that corticosteroids may delay healing, thereby increasing the risk of post-operative infection. For this reason, despite the known benefits, many oral surgeons do not administer corticosteroids to their patients. Surprisingly, the effects of corticosteroids on the healing of oral (mucosal) tissues have never been systematically examined and, hence, remain unclear. Recent evidence from our laboratory, using a well established oral wound model in humans, has found that reduced inflammation in the mouth relates to faster healing times. This strongly suggests that the anti- inflammatory properties of corticosteroids will not hinder, and may augment, the healing of oral tissues. This study will clarify this important point. Sixty adult volunteers (30 men, 30 women) will receive either corticosteroid, in a single intravenous dose common in oral surgery (125 mg methylprednisolone), or placebo. Subjects will then have three small wounds placed on the oral hard palate by a periodontist. A tissue biopsy will be obtained from one wound at 6h and one wound at 24h post-wounding to determine the degree of tissue inflammation at two time points. The third wound will be photographed daily until healed to determine healing rates. Finally, a biopsy of healed tissue will be obtained on Day 14 to assess scar formation. Approximately one month later, subjects will undergo the same procedure on the opposite side of the mouth and will receive the alternate drug treatment (drug order will be counter-balanced between subjects). This study design will enable us to directly assess the effects of corticosteroids on healing rates, inflammation and scar formation, using subjects as their own controls. The results of this study will have an immediate impact upon clinical Dentistry, by providing insight of how corticosteroid administration impacts upon oral tissue healing. If the rate of healing is unaffected or, as we predict, shortened following corticosteroid administration this strongly advocates corticosteroid administration in Dental surgeries. Conversely, if corticosteroids impair tissue healing then their use is put to question, especially for minor Dental procedures and in individuals at a higher risk of post-surgical infection. By better identifying when corticosteroid therapy is appropriate, these results will have a financial impact on health care by reducing direct costs (follow-up visits), indirect costs (loss of income) and intangible costs (pain and suffering) related to oral surgeries. This study will also provide a better understanding of the mechanisms which underlie oral tissue healing. Public Health Significance: These results will have an immediate impact upon clinical Dentistry, and possibly on cosmetic surgery, by providing insights of how corticosteroid administration impacts upon tissue healing. If the rate of healing is unaffected or shortened following corticosteroid administration, this strongly advocates corticosteroid administration in Dental surgeries; conversely, if corticosteroids impair tissue healing then their use is put to question, especially for minor Dental procedures and in individuals at a higher risk of post-surgical infection. By better identifying when, and for whom, corticosteroid therapy is appropriate, these results will impact health care expenses by reducing direct costs (follow-up visits), indirect costs (loss of income) and intangible costs (pain and suffering) related to oral surgeries.