Outcome of Preoperative Oral Steroids on Patients With Sinonasal Polyposis
Article information
Abstract
Background and Objectives
This study aimed to evaluate whether preoperative oral prednisolone improves the intraoperative parameters and postoperative outcomes over a 3-month period in patients of sinonasal polyposis who undergo functional endoscopic sinus surgery.
Methods
In a triple-blind, randomized controlled study, 43 patients diagnosed with sinonasal polyposis in the Department of ENT, AIIMS, Jodhpur, were enrolled. After obtaining institutional ethics clearance and registering the clinical trial, randomization was conducted to assign participants into experimental and control groups. Preoperatively, patients were assessed using the clinical severity score (Sino-nasal Outcome Test; SNOT-22), radiological severity score (Lund-Mackay score), and endoscopic severity scores (discharge-inflammation-polyp [DIP] score and Lund-Kennedy score). Intraoperative assessment was done using the Perioperative Sinus Endoscopy (POSE) score, the duration of surgery, intraoperative blood loss, and visual analog scale for visual field during surgery and for the ease of disease removal. Postoperatively, at 3 months all the preoperative parameters were reassessed, and, using independent t-test, comparison was made between the two groups.
Results
Twenty-one patients were included in the experimental group (48%), and 22 in the control group (51%). Although the mean duration of surgery in the experimental group was shorter than in the control group, the difference was not statistically significant. Similarly, although the postoperative SNOT-22 score was lower in the experimental group compared to the control group, there was no statistically significant difference in outcomes between the two groups across any of the parameters assessed.
Conclusion
Although the role of oral steroids has been established in the treatment of sinonasal polyposis, our study did not find any significant difference between the group that received oral steroids prior to surgery and the group that received placebo.
INTRODUCTION
Chronic rhinosinusitis (CRS) with nasal polyps is a disease that is characterized by the presence of symptoms such as anterior or posterior nasal discharge, nasal congestion, and reduced sense of smell with or without facial pain or pressure, for more than 12 weeks. Presence of nasal polyps and computed tomography (CT) scan findings are also essential for diagnosis [1].
According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020), the prevalence of chronic rhinosinusitis is between 5%–12% in the general population [2]. Patients with CRS absent themselves from work because of sinusitis 6.5% of the time, have a 36% reduction in on-the-job effectiveness, and suffer a 38% loss of productivity [3,4].
CRS has been classically divided as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), based on clinical and endoscopic findings. This classification does not take into account the heterogenicity or the pathophysiological basis of the disease. The need for a change in the classification has been recognized due to changing treatment modalities [5,6].
Treatment is aimed at reduction of these symptoms. Topical nasal corticosteroids in combination with antihistaminics, nasal saline irrigation, oral corticosteroids, and, in rare cases, antibiotics are part of the armamentarium [7].
Studies have explored the efficacy of local steroid sprays such as mometasone furoate and fluticasone proprionate. The mode of action comprises of a myriad of anti-inflammatory effects. This includes decreasing the production of pro-inflammatory mediators and increasing the transcription of anti-inflammatory genes. This, in turn, reduces airway inflammatory cell infiltration secondary to suppression of the production of pro-inflammatory mediators, cell chemotactic factors, and adhesion molecules [8].
Methylprednisolone treatment causes significant decrease in number of eosinophils, serum eosinophilic cationic protein, and soluble IL-5Ra. Oral corticosteroids also cause stabilization of IgE levels [9].
Short courses of oral steroids have been indicated for a rapid reduction in polyp size, thereby enhancing the ability of intranasal steroids to gain access to the polypoid tissue, improving olfaction and reducing nasal air-flow resistance [10].
The current level of evidence for the use of systemic corticosteroids according to the EPOS 2020 has been reported as Ia [2].
Various scoring systems have been studied to answer the question of whether or not a course of preoperative oral corticosteroids could lead to a considerable difference in the intraoperative and postoperative outcome of patients with sinonasal polyposis. There is evidence to suggest that it could lead to less bleeding, better visualization, and less trauma to the tissues; however, no solid support to this is what has not popularized this practice and prevented it from becoming a standard treatment protocol [11].
Sino-nasal Outcome Test (SNOT-22) is a self-assessment questionnaire that measures the severity of symptoms and disease burden in patients with CRS, with each question being scored between 0 to 5, in increasing order of symptom severity, the total sum of the score being 110 [4].
In 1995, Lund-Kennedy scoring system was developed which is an endoscopic scoring system based on degree of scarring, crusting, oedema, polyps, and discharge. However, since this system is used primarily for patients who have already undergone surgery, in an attempt to improve upon this, Wright and Agrawal [11] developed the Perioperative Sinus Endoscopic (POSE) scoring system in 2007 to assess the impact of perioperative systemic steroids on postsurgical outcomes in CRS patients.
Another scoring system was introduced by Durr et al. [12] known as discharge-inflammation-polyp (DIP) score. Each of the three criteria were then given a score from 0–10, based on the severity of each, for both right and left side separately [12].
The Lund-Mackay scoring is a system of grading changes in CT scans of patients with chronic rhinosinusitis [13].
Poetker et al. [14], in an evidence-based review, attempted to ascertain the role of oral corticosteroids in the management of CRSsNP and CRSwNP. The study concluded that for patients of CRSsNP the use of oral corticosteroids was merely optional whereas for CRSwNP the use of oral corticosteroids as a short-term option was strongly recommended.
Rudmik et al. [15] identified the role of topical therapy in the field of rhinology. It has many advantages, such as direct delivery of high dosage to target site, with reduced systemic absorption and thereby minimal adverse effects. The challenges posed, though, are the implementation of correct application techniques, epistaxis and local discomfort.
In a Cochrane review by Chong et al. [16], published in 2016 looking at the primary medical management options for patients with chronic rhinosinusitis, the efficacy of intranasal steroids versus placebo or no intervention was analyzed. It was noted that in terms of disease severity, there seemed to be improvement in all symptoms, a moderate degree of benefit for nasal blockage, and a small degree of benefit in rhinorrhoea in intervention group.
In a double-blinded randomized control trial done by Aukema et al. [17], 54 patients were included who had either CRSwNP or CRSsNP. It showed that treatment with a brief period of high-dose prednisolone led to a noticeable improvement in subjective symptoms and objective measures most notably regression in nasal polyp size.
In a Cochrane review assessing efficacy of oral corticosteroids versus placebo or no intervention, the authors found that patients experienced enhanced health-related quality of life and reduced severity of symptoms when treated with oral corticosteroids [18].
In another Cochrane review, the authors found that there was a reduction in the size of nasal polyps in the patients who were administered combination therapy in the form of both intranasal and oral corticosteroids as compared to those receiving intranasal corticosteroids alon; however, this study lacked a longer follow-up period and the quality of evidence was found to be very low [19].
METHODS
The study was a triple-blinded, randomized, placebo-controlled, parallel-group investigation conducted by the Department of Otorhinolaryngology and Diagnostic and Interventional Radiology at AIIMS, Jodhpur, India. The study spanned 20 months from November 2021 to June 2023, following approval from the Institutional Ethics Committee (IEC number AIIMS/IEC/2021/3644) and registration with the Clinical Trials Registry of India (CTRI/2021/11/037934). Informed consent was obtained after explaining the study protocol using a patient information sheet.
Originally, the study intended to include 50 participants based on previous hospital records; however, the sample size was adjusted to 43 due to the surge in mucormycosis cases during the COVID-19 pandemic, which affected elective procedures. Eligible participants were adults over 15 years old undergoing functional endoscopic sinus surgery for CRSwNP.
Patients with recent oral steroid use or autoimmune disorders requiring immunomodulatory drugs were excluded from the study. Randomization was ensured through opaque sealed envelopes containing slips marked “A” or “B,” determining whether participants received prednisolone or a placebo, known only to the principal investigator until result analysis.
Before surgery, patients underwent thorough preoperative assessments, including anterior rhinoscopy and diagnostic nasal endoscopy, where DIP score and Lund-Kennedy score were assessed. Patient’s subjective symptom severity was noted using SNOT-22 score. Treatment began with a 21-day medical management regimen, including corticosteroid sprays, antihistamines, nasal irrigations, and steam inhalations.
Patients who did not respond to medical treatment underwent non-contrast computed tomography (NCCT) of the nose and paranasal sinuses and Lund-Mackay score was noted, followed by enrolment for surgery.
During surgery, the operating surgeon was blinded to the treatment arm. Intraoperative assessments were noted down by the surgeon using the POSE score and a proforma detailing surgery duration, blood loss, visual field clarity, and ease of disease removal.
Follow-up evaluations at 3 months post-surgery included objective assessments, such as repeat diagnostic nasal endoscopy and NCCT scoring, along with subjective evaluations based on patient-reported outcomes using the SNOT-22 questionnaire.
Statistical analysis was performed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). Paired and unpaired t-tests were used for comparative analysis between the two groups.
RESULTS
The experimental group comprised 21 patients, with a mean age of 30.81 (range 16–66) years. The control group comprised 22 patients, with a mean age of 37.9 (range 19–65) years. In the experimental group, there were 4 females, and, in the control group, there were 5 females. Based on the age and sex distribution of the two groups, the groups were comparable (Fig. 1).
Gender distribution between study groups.
Unpaired t-test was applied to do a comparative analysis between the two groups based on their preoperative radiological score (Lund-Mackay), clinical symptom severity (SNOT-22), and endoscopy scores (DIP score and Lund Kennedy). For all the aforementioned scores, the p-values were found to be >0.05 implying the groups were comparable.
Comparison of intraoperative scores between the study groups
The mean intraoperative duration in the experimental group was 2.25 hours (SD 0.86), compared to 2.34 hours (SD 0.70) in the control group, with a p-value of 0.705, indicating no statistical significance. The mean intraoperative blood loss was 244.7 mL (SD 161.0) in the experimental group and 241.8 mL (SD 121.2) in the control group, resulting in a nonsignificant p-value of 0.964. The mean POSE score was 19.29 (SD 5.78) in the experimental group and 19.23 (SD 6.54) in the control group, with a p-value of 0.975, showing no statistical significance. The blinded surgeons graded the ease of surgery on a visual analog scale (VAS) from 1 to 10, with 10 indicating extreme ease and 1 being extremely tough. The mean VAS score for the experimental group was 7.19 (SD 1.60) compared to 6.95 (SD 1.96) for the control group, yielding a p-value of 0.669, which was not statistically significant. Similarly, the intraoperative visual field was graded on a VAS from 1 to 10, with 10 indicating an excellent field and 1 being a poor field. The mean VAS score for the experimental group was 7.60 (SD 1.56) versus 7.61 (SD 1.43) for the control group, with a p-value of 0.968, indicating no significant difference (Table 1).
Comparison of intraoperative scores between the study groups
Comparison of postoperative scores between the study groups
The mean Lund-Mackay score in the experimental group was 6.05 (SD 4.33), identical to the control group at 6.05 (SD 5.00). The p-value of 0.968 indicated no statistically significant difference in postoperative radiological scores between the groups. The mean postoperative SNOT-22 score was 6.62 (SD 7.57) in the experimental group and 10.59 (SD 10.83) in the control group. However, the p-value of 0.173 indicated no significant difference in symptom severity between the groups at 3 months postoperatively. For the DIP score, the mean value was 10.24 (SD 10.74) in the experimental group and 11.18 (SD 10.30) in the control group, with a p-value of 0.770, showing no statistical significance. Similarly, the mean Lund-Kennedy score was 3.67 (SD 2.63) in the experimental group and 3.41 (SD 2.52) in the control group. The p-value of 0.745 confirmed no statistically significant difference between the groups (Table 2).
Comparison of postoperative scores between the study groups
DISCUSSION
In a study by Stevens et al. [1], they noticed a 62% male preponderance as compared to 38% females in their study, thus we can say that our findings have been consistent with the universal sex distribution of the disease.
As per the systematic review published in Current Medical Research and Opinion in 2020, CRSwNP has been found to be prevalent in the middle ages with an average age being around 42 years which is consistent with our study population [20].
Berkiten et al. [21] in their study, administered oral methylprednisolone at a dose of 1 mg/kg/day for 5 days, which was tapered and stopped at day 20. The patients were assessed based on Total Nasal Symptom Score (TNSS) and CT scans after treatment, and the results were compared. They concluded that oral steroid treatment resulted in clinical and radiological improvement, also contributing to a decrease in duration of surgery and hence.
However, our study did not observe a statistically significant difference in intraoperative POSE scores between the experimental and control groups (19.29 vs. 19.23; p<0.975).
In our study, no statistically significant differences were observed in intraoperative blood loss or surgery duration between the two groups. Similarly, the surgeons’ assessments of the intraoperative visual field and the ease of surgery showed no significant differences between the groups.
In a study by Hissaria et al. [22], the prednisolone-treated group demonstrated a 45% reduction in symptom severity based on mean MRI scores (p<0.001). Additionally, polyp size significantly decreased, with a mean reduction of 48%. This study does not look at the long-term outcome of these patients, nor does it look at the efficacy of short-term systemic steroids followed by intranasal steroids. Our study used a combination of these two modalities, that is, oral with intranasal steroids versus placebo with intranasal steroids, and the results obtained at 3 months post-surgery were analyzed for significance in terms of difference of the means of the symptom severity score (SNOT-22), nasal endoscopy scores (DIP and Lund-Kennedy score), and CT severity score (Lund-Mackay score). As we can see from our comparative analysis of preoperative and postoperative scores in each of the two groups for all of the four domains mentioned above, using paired t-test, a significant improvement in symptoms (SNOT-22) was noted in both the experimental group and control group (p<0.05). Improvement was also noted in the endoscopy scores (DIP and Lund-Kennedy endoscopy scores) between the preoperative and postoperative values in each of the groups (p<0.05). Similarly, Lund-Mackay scores (CT severity score) also showed statistically significant improvement in the postoperative scores as compared to preoperative scores in each of the two groups (p<0.05). However, whether this improvement was attributed to the use of oral steroid, intranasal steroids, or the surgical procedure itself could not be concluded.
Kowalski et al. [23] conducted a randomized study where outcomes were measured in terms of symptom scores, smell tests, and VAS at 2, 20, and 28 weeks. They observed that the patients receiving steroids had a significant decrease in their polyp score and TNSS at 2 weeks up to 10 weeks; however, at 28 weeks, there was no significant difference noted between the two groups. Thus, the authors concluded that a short burst of oral corticosteroid treatment was more effective than topical therapy alone and could be recommended as an initial treatment modality. In our study, however, although the outcomes measured by us were similar, the endpoint was 3 months postoperatively. The mean SNOT-22 score in the experimental group at 3 months postoperatively was 6.62, and that in the control group was 10.59. The p-value obtained, however, was >0.05 (0.173) and hence the difference was not found to be statistically significant. The mean value of the Lund-Mackay score in the experimental group was 6.05 (SD 4.33), and that in the control group was also 6.05 (SD 5.00). The p-value was >0.05 (0.968), hence implying no significant difference between the two groups. Endoscopically, the mean value of DIP score in the experimental group was 10.24 (SD 10.74), while that in the control group was 11.18 (SD 10.30) with a p-value >0.05. Even the difference between the mean values of the Lund-Kennedy score postoperatively between the two groups was statistically not significant.
Our study did not find any significant difference in results between the two groups, namely the control and case arms. Despite literature suggesting a role for corticosteroids, this discrepancy could be attributed to confounders such as the use of hypotensive anesthesia, the administration of intranasal corti-costeroids in both arms, and variations in surgical expertise. A key limitation of our study is the presence of these confounders, which prevented the formulation of a protocol for the use of corticosteroids in patients with CRSwNP.
Notes
Availability of Data and Material
The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.
Conflicts of Interest
The authors have no potential conflicts of interest to disclose.
Author Contributions
Conceptualization: all authors. Data curation: Sukriti Nehra, Bikram Choudhury, Amit Goyal, Kapil Soni. Formal analysis: Sukriti Nehra, Bikram Choudhury. Investigation: Sukriti Nehra, Bikram Choudhuryy, Kapil Soni, Vidhu Sharma, Sarbesh Tiwari. Methodology: Sukriti Nehra, Bikram Choudhuryy, Amit Goyal, Vidhu Sharma, Sarbesh Tiwari. Project administration: Bikram Choudhury. Resources: Bikram Choudhury, Amit Goyal, Kapil Soni. Software: Sukriti Nehra, Sarbesh Tiwari. Supervision: Bikram Choudhury, Amit Goyal, Kapil Soni, Vidhu Sharma. Validation: Sukriti Nehra, Bikram Choudhury, Amit Goyal, Kapil Soni, Vidhu Sharma. Visualization: Kapil Soni. Writing—original draft: Sukriti Nehra. Writing—review & editing: Bikram Choudhury, Amit Goyal, Vidhu Sharma.
Funding Statement
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Acknowledgements
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