ORIGINAL ARTICLE
Impact of intranasal sodium hyaluronate on the short-term quality of life of patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis Elena Cantone, MD1,2 , Giovanni Castagna, MD1 , Stefania Sicignano, MD1 , Immacolata Ferranti, MD1 , Felice Rega, MD1 , Vittoria Di Rubbo, MD1 and Maurizio Iengo, MD1
Background: Functional endoscopic sinus surgery (FESS) has become the treatment of choice for patients with medically resistant chronic rhinosinusitis (CRS) and nasal polyps. Despite the consolidated use of different treatments, the postoperative period is oen very painful and uncomfortable, especially during the first month. Although evidence on the effectiveness of sodium hyaluronate (SH) on postoperative care following FESS is available, data on the quality of life (QoL) from the patients’ perspective are still lacking. This study aimed to evaluate for the first time the effectiveness of nasal douche with SH in reducing patients’ discomfort during the first month following FESS. Methods: A double-blind randomized controlled study was carried out on 124 subjects undergoing FESS for CRS with nasal polyposis. They were divided into 2 groups: group I was treated with nasal douche containing 9 mg of high molecular weight SH plus saline solution and group II was treated with saline solution alone. To assess QoL in CRS patients, the Short Form-36 (SF-36) test, the Sino-Nasal Outcome Test-22 (SNOT-22), and the visual analogue scale (VAS) questionnaires were administered.
C
hronic rhinosinusitis (CRS) is a multifactorial disease with a prevalence of 10%. Its predisposing factors include allergy, immune-associated disorders, defects in the mucociliary clearance system, and biofilms-associated chronic bacterial infections.1 CRS significantly affects the quality of life (QoL) of patients. The currently available treatments aim to attain what is called disease clinical control, that is the elimination or 1 Department
of Neuroscience, Reproductive and Odontostomatologic Science, ENT Unit, “Federico II” University, Naples, Italy; 2 Department of Molecular Medicine and Medical Biotechnology, “Federico II” University, Naples, Italy
Correspondence to: Elena Cantone, MD, Viale della Liberta, ` 75, 81030 Lusciano (Caserta) Italy; e-mail: [email protected] Received: 21 September 2013; Revised: 21 December 2013; Accepted: 28 January 2014 DOI: 10.1002/alr.21310 View this article online at wileyonlinelibrary.com.
Results: At baseline, there were no statistically significant differences between the 2 groups. However, aer 30 days of long postoperative treatments, we found clinically significant improvements in QoL of subjects treated with SH, as evidenced by all QoL scales. Conclusion: Our data indicate that SH significantly improves patients’ short-term QoL following FESS in terms of C 2014 both general health and specific sinonasal status. ARS-AAOA, LLC.
Key Words: chronic rhinosinusitis; disease severity; endoscopic sinus surgery; FESS; quality of life; postoperative How to Cite this Article: Cantone E, Castagna G, Sicignano S, et al Impact of intranasal sodium hyaluronate on the short-term quality of life of patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014;4:484–487.
mitigation of symptoms to the point where subjects no longer feel the discomfort of the disease, possibly in combination with a healthy mucosa. The available CRS medical treatments comprise antibiotics, corticosteroids, and topical therapy; however, their efficacy is still debated.2 Oral antibiotics are considered therapeutic options in CRS treatment, whereas oral steroids are strongly recommended for short-time management of CRS with nasal polyps and in the perioperative period.3, 4 Existing evidence suggests that topical therapies, such as sinonasal saline irrigations and topical nasal steroids, have become an integral component in the management of CRS.5 However, for patients with medically resistant CRS and nasal polyps, the surgical approach, particularly functional endoscopic sinus surgery (FESS), represents the best treatment of choice.2, 6 Although FESS is considered the gold standard treatment for CRS, surgical outcome depends not only on the performance of the procedure itself, but also
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
484
Postoperative discomfort after FESS
on the postoperative care of nasal cavities. Furthermore, despite the consolidated use of different treatments, the postoperative period is often very painful and uncomfortable. For instance, during the first month, patients’ shortterm QoL is compromised by edema, extensive crust formation, mucosal alterations, excessive secretion, and impaired sinonasal ventilation. For these reasons, clinicians nowadays are constantly searching for agents able to promote cleansing of the nasal cavities and postoperative regeneration of the nasal mucosa. In recent years, mounting evidence suggests that sodium hyaluronate (SH)—the major component of many extracellular matrices, including those in respiratory epithelial cells and serous gland cells of the nasal and trachea-bronchial mucosa—serves important biological roles beyond its generally accepted function as a structural component of interstitial and connective tissues. In this regard, SH has been shown to promote wound healing, repairing of mucosal surfaces, and cell motility.7, 8 Particularly, studies show that topical application of SH significantly improves the healing process of the nasal mucosa, preventing extensive crust formation, and eventually leading to the recovery of smell parameters and cooling sensation.9 A prospective randomized controlled trial suggests that a new absorbable SH hydrogel, similar to a nasal dressing/packing following FESS, promotes the postoperative re-epithelization process and reduces the presence of synechia, edema, crust, and mild mucopurulent drainage.10 Furthermore, SH, in association with intranasal corticosteroid and systemic antihistamine, reduces the neutrophil count shown on nasal cytology in patients with allergic and nonallergic rhinitis and improves several clinical and endoscopic parameters.11 Although evidence of the effectiveness of SH on postoperative care following FESS is currently available, there still remains a dearth of evidence evaluating its actual impact on QoL from the patient’s perspective. In particular, given that the therapeutic effects of a drug as experienced by the patients can reflect the effectiveness of a treatment much more closely than clinician-rated outcomes, the medical need for an effective therapy after FESS provides a novel area of research. Currently, the severity of symptoms following FESS and their impact upon QoL is assessed through a wide array of questionnaires, among which is the 22-item Sino-Nasal Outcome Test (SNOT-22).12 The goal of the present study was to evaluate the effect of intranasal administration of 9 mg of high molecular weight SH on the improvement of postoperative discomfort and short-term QoL following FESS. A double-blind randomized control trial was carried out on 124 patients undergoing FESS for CRS with nasal polyposis. For the assessment of QoL in CRS patients, the Short Form-36 (SF-36) test, the Sino-Nasal Outcome Test-22 (SNOT-22), and the Visual Analogue Scale (VAS) questionnaires were administered.
485
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
Patients and methods A double-blind randomized controlled study was carried out at the University of Naples, Federico II, from January 2011 to April 2013, on 124 patients (70 males, 54 females, mean age 41.2 years) undergoing FESS for CRS with grade II nasal polyposis.13 Two subjects dropped out of the study. Patients suffering from systemic diseases, acetylsalicylic acid (ASA) sensitivity, cystic fibrosis, primitive ciliary dyskinesia, grade I nasal polyposis, choanal atresia, and with a history of previous interventions were excluded from the study. All participants gave their informed consent to participate in the study, which was fully approved by the local Board of Medical Ethics. The diagnosis of CRS was based on the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) diagnostic criteria and confirmed by nasal endoscopy and computed tomography (CT) scans with axial, coronal, and sagittal images.6 Nasal endoscopy with a 2.7-mm 30-degree rigid endoscope (Storz, Tuttlingen, Germany) was performed before surgery and after postoperative treatment, without decongestant or local anesthesia and scored as previously described by Lund and Kennedy.14 All surgical procedures were performed by the same surgeon, according to the nomenclature of Stammberger and Posawetz.15 After surgery, the nose was not packed and the day after surgery all subjects were randomized into 2 groups (group I and group II) and given the treatment. The investigational arm (group I), comprising 62 subjects, was treated with intranasal administration of 9 mg of high molecular weight SH (3 mL) plus saline solution (2 mL sodium chloride 0.9%). The control arm (group II), comprising 60 subjects, was treated with 5 mL sodium chloride (0.9%) alone. In both groups, treatments were administered twice a day for 30 consecutive days using a nebulizer ampoule for nasal douche. This device produces particles greater than 10 μm and acts only on the upper airways over a time of 60 to 90 seconds for each application.9 This method of delivery was chosen because it is better tolerated, more useful for the nebulization of high molecular weight SH, and faster to administer than classic aerosol devices. To assess QoL, groups were asked to answer 3 questionnaires. The first was the Italian Short Form-36 (SF-36) questionnaire. This questionnaire, which measures patients’ general health status, contains 36 questions that refer to 8 health concepts grouped into subgroups (physical functioning, physical role functioning, bodily pain, general health, vitality, social role functioning, emotional role functioning, and mental health). Each question was asked independently. The second was the 22-item Sino-Nasal Outcome Test (SNOT-22)12 which is a validated patient self-report measure encompassing all major symptoms included in the diagnostic criteria set in the EPOS 2012 for CRS.6 The third was the Visual Analogue Scale (VAS) questionnaire, which includes questions about headache, nose congestion, runny nose, secretion from the nose into the throat, feeling of fullness in the face, face pain, toothache,
Cantone et al.
Discussion
TABLE 1. Patient demographics at baseline Group I
Group II
Participants, n (%)
62 (51)
60 (49)
Male, n (%)
36 (52)
33 (48)
Female, n (%)
26 (49)
27 (51)
41.4 ± 2.4
42.4 ± 1.4
Age (years), mean ± SD
CRS is 1 of the most common health care challenges for which the increasing demand for medical care significantly contributes to rising healthcare costs. CRS not only causes significant physical suffering but also results in substantial functional and emotional impairment. Generally, CRS patients not responding to medical therapies resort to FESS surgery. Indeed, many studies have shown that FESS is highly effective on CRS-related QoL.16 However, because the postoperative period, the first month after surgery, is often very painful and uncomfortable for the patient, early care following FESS is crucial to reducing complications and improving long-term outcomes. Although many studies have investigated the use of topical agents to improve postoperative intranasal symptoms and to aid healing following FESS, there is still an unmet medical need for an effective therapy.17–19 Recently, SH treatment following FESS has been shown to stimulate the mucociliary clearance, thereby improving wound healing and reducing exacerbations in patients with chronic bronchitis.8, 9 Furthermore, additional evidence has reported the effectiveness of 9 mg nebulized high molecular weight SH in the treatment of sinonasal clinical, endoscopic, and psychological parameters in patients undergoing FESS for sinonasal remodeling.8, 9 There is now mounting evidence that the patient’s perspective on treatment outcomes is a crucial element for improving high-quality care. Indeed, patient-rated therapeutic outcomes in terms of symptoms can provide a much more realistic picture of the effectiveness of a treatment than those of clinician-rated outcomes.2 For these studies, the impact of chronic diseases, including CRS, and the impact of medical and surgical care are determined and recorded either with the VAS or with validated symptombased questionnaires. However, so far, these studies have primarily focused on assessing long-term but not short-term QoL following FESS.20, 21 To the best of our knowledge, this study is the first to investigate the therapeutic effect of 9 mg nebulized high molecular weight SH on the short-term QoL from the perspective of the patients undergoing FESS for CRS with nasal polyposis. In the present study the subjects enrolled were divided into 2 groups: group I was treated with 9 mg of high molecular weight SH plus saline solution, and group II was treated with saline solution alone.
SD = standard deviation.
tearing, coughing, nose bleeds, and nasal crusting. The disease was divided into mild, moderate, and severe based on total severity VAS scores (mild, VAS = 0-3; moderate, VAS = 4−7; and severe, VAS = 8−10). A VAS > 5 affected patient QoL.6 QoL tools, as well as nasal endoscopy, was administered at baseline before surgery (T0) and 30 days after postoperative treatment (T30).
Statistical analysis Continuous baseline characteristics were described as either median, mean, or standard deviation where appropriate. Difference between groups were tested with the Mann-Whitney U test; p < 0.05 was considered statistically significant. Data were tabulated in a Microsoft Excel (Microsoft Corporation, Redmond, WA) spreadsheet and imported into the Statistical Package for the Social Sciences (SPSS-PC, version 16; SPSS Inc., Chicago, IL).
Results A total of 122 patients were enrolled in the study. The 2 groups of patients were well matched. At baseline, no statistically significant differences were observed in the clinical, endoscopic, and QoL tools, nor in any of the examined parameters (Table 1). After postoperative treatment, the endoscopic score (p = 0.0001), the total VAS score (p < 0.05), the mean SNOT-22 sum score (p < 0.05), and SF-36 (p < 0.05) results were better in group I than in group II (Table 2). In addition, after treatment, the results of the 8 SF-36 test subgroups, ie, physical functioning, physical role functioning, bodily pain, general health, vitality, social role functioning, emotional role functioning, and mental health, were gener-ally better in group I than in group II.
TABLE 2. Baseline data (T0) and posttreatment data (T30) in group I and group II Endoscopic score (mean ± SD)
Total VAS score (mean)
SNOT-22 (sum score-mean)
SF-36 (mean)
T0
T30
T0
T30
T0
T30
T0
T30
Group I
6.9 ± 3.8
1.43 ± 1.85
7.2 points
3.8 points
68.0 ± 27.8
47.80 ± 25.4
40.16%
83.70%
Group II
7.1 ± 3.6
4.16 ± 3.35
6.7 points
5.6 points
67.0 ± 28.0
59.33 ± 23.2
38.61%
73.00%
SD = standard deviation; SF-36 = Short Form-36; SNOT-22 = 22-item SinoNasal Outcomes Test; T0 = before surgery; T30 = 30 days posttreatment; VAS = visual analogue scale.
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
486
Postoperative discomfort after FESS
Whereas at baseline there were no statistically significant differences between the 2 groups, clinically significant improvements in the QoL of subjects treated with SH were observed after treatment, as evidenced by the clinical and instrumental analyses performed in this study. Our data thus suggest that SH plays and important role in improving the severity of intranasal symptoms and the accompanying discomfort following FESS. In addition, SH may significantly enhance the QoL both in terms of the general health status (SF-36) and in terms of the specific sinonasal status (SNOT-22). Furthermore, as also suggested by other authors,8 our study indicated that SH is significantly better tolerated than saline in patients undergoing FESS. Together, these findings demonstrate that treatment with intranasal administration of 9 mg of high molecular weight SH can prevent FESS-postoperative patients from having to
undergo additional pharmacological treatments, especially for pain, which often requires drugs associated with relevant adverse reactions and considerable health care costs. Moreover, because of the high incidence of these conditions, a substantial economic burden is imposed on society not only in terms of direct costs (medical and nonmedical), but also in terms of indirect costs (disability, reduced working capacity, and absence from work).
Conclusion This study evaluated for the first time the general and disease-specific short-term QoL in patients undergoing FESS for CRS with nasal polyposis. Our encouraging findings indeed demonstrate the effectiveness of intranasal SH not only in the postoperative care of patients undergoing FESS but also in FESS-related discomfort.
References 1.
2.
3.
4.
5.
6.
7.
487
Hastan D, Fokkens WJ, Bachert C, et al. Chronic rhinosinusitis in Europe—an underestimated disease. A GA2 LEN study. Allergy. 2011;66: 1216–1223. Cazzavillan A, Castelnuovo P, Berlucchi M, et al. Management of chronic rhinosinusitis. Pediatr Allergy Immunol. 2012;23(Suppl 22):32–44. Poetker DM, Jakubowski LA, Lal D, et al. Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidencebased review with recommendations. Int Forum Allergy Rhinol. 2013;3:104–120. Soler ZM, Oyer SL, Kern RC, et al. Antimicrobials and chronic rhinosinusitis with or without polyposis in adults: an evidenced-based review with recommendations. Int Forum Allergy Rhinol. 2013;3: 31–47. Rudmik L, Hoy M, Schlosser RJ, et al. Topical therapies in the management of chronic rhinosinusitis: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3:281–298. Fokkens WJ, Lund VJ, Mullol J, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012;(23):3 p preceding table of contents, 1–298. Forteza R, Lieb T, Aoki T, et al. Hyaluronan serves a novel role in airway mucosal host defense. FASEB J. 2001;15:2179–2186.
8.
9.
10.
11.
12.
13.
14.
Gelardi M, Guglielmi AVN, De Candia N, et al. Effect of sodium hyaluronate on mucociliary clearance after functional endoscopic sinus surgery. Eur Ann Allergy Clin Immunol. 2013;45:103–108. Macchi A, Terranova P, Digilio E, et al. Hyaluronan plus saline nasal washes in the treatment of rhinosinusal symptoms in patients undergoing functional endoscopic sinus surgery for rhino-sinusal remodeling. Int J Immunopathol Pharmacol. 2013;26:137–145. Shi R, Zhou J, Wang B, et al. The clinical outcomes of new hyaluronan nasal dressing: a prospective, randomized, controlled study. Am J Rhinol Allergy. 2013;27:71–76. Gelardi M, Iannuzzi L, Quaranta N. Intranasal sodium hyaluronate on the nasal cytology of patients with allergic and nonallergic rhinitis. Int Forum Allergy Rhinol. 2013;3:807–813. Hopkins C, Gillett S, Slack R, et al. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009;34:447–454. Gwaltney JM Jr, Jones JG, Kennedy DW. Medical management of sinusitis: educational goals and management guidelines. The International Conference on Sinus Disease. Ann Otol Rhinol Laryngol Suppl. 1995;167:22–30. Lund VJ, Kennedy DW. Quantification for staging sinusitis. The Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995;167:17–21.
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
15. Stammberger H, Posawetz W. Functional endoscopic sinus surgery. Concept, indications and results of the Messerklinger technique. Eur Arch Otorhinolaryngol. 1990;247:63–76. 16. Bhattacharyya N. Symptom outcomes after endoscopic sinus surgery for chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2004;130: 329–333. 17. Desrosiers MY, Kilty SJ. Treatment alternatives for chronic rhinosinusitis persisting after ESS: what to do when antibiotics, steroids and surgery fail. Rhinology. 2008;46:3–14. 18. Portela RA, Hootnick J, McGinn J. Perioperative care in functional endoscopic sinus surgery: a survey study. Int Forum Allergy Rhinol. 2012;2:27–33. 19. Rudmik L, Soler ZM, Orlandi RR, et al. Early postoperative care following endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2011;1:417–430. 20. Bezerra TF, Piccirillo JF, Fornazieri MA, et al. Assessment of quality of life after endoscopic sinus surgery for chronic rhinosinusitis. Braz J Otorhinolaryngol. 2012;78:96–102. 21. Cornet ME, Georgalas C, Reinartz SM, et al. Longterm results of functional endoscopic sinus surgery in children with chronic rhinosinusitis with nasal polyps. Rhinology. 2013;51:328–334.
Impact of intranasal sodium hyaluronate on the short-term quality of life of patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis Elena Cantone, MD1,2 , Giovanni Castagna, MD1 , Stefania Sicignano, MD1 , Immacolata Ferranti, MD1 , Felice Rega, MD1 , Vittoria Di Rubbo, MD1 and Maurizio Iengo, MD1
Background: Functional endoscopic sinus surgery (FESS) has become the treatment of choice for patients with medically resistant chronic rhinosinusitis (CRS) and nasal polyps. Despite the consolidated use of different treatments, the postoperative period is oen very painful and uncomfortable, especially during the first month. Although evidence on the effectiveness of sodium hyaluronate (SH) on postoperative care following FESS is available, data on the quality of life (QoL) from the patients’ perspective are still lacking. This study aimed to evaluate for the first time the effectiveness of nasal douche with SH in reducing patients’ discomfort during the first month following FESS. Methods: A double-blind randomized controlled study was carried out on 124 subjects undergoing FESS for CRS with nasal polyposis. They were divided into 2 groups: group I was treated with nasal douche containing 9 mg of high molecular weight SH plus saline solution and group II was treated with saline solution alone. To assess QoL in CRS patients, the Short Form-36 (SF-36) test, the Sino-Nasal Outcome Test-22 (SNOT-22), and the visual analogue scale (VAS) questionnaires were administered.
C
hronic rhinosinusitis (CRS) is a multifactorial disease with a prevalence of 10%. Its predisposing factors include allergy, immune-associated disorders, defects in the mucociliary clearance system, and biofilms-associated chronic bacterial infections.1 CRS significantly affects the quality of life (QoL) of patients. The currently available treatments aim to attain what is called disease clinical control, that is the elimination or 1 Department
of Neuroscience, Reproductive and Odontostomatologic Science, ENT Unit, “Federico II” University, Naples, Italy; 2 Department of Molecular Medicine and Medical Biotechnology, “Federico II” University, Naples, Italy
Correspondence to: Elena Cantone, MD, Viale della Liberta, ` 75, 81030 Lusciano (Caserta) Italy; e-mail: [email protected] Received: 21 September 2013; Revised: 21 December 2013; Accepted: 28 January 2014 DOI: 10.1002/alr.21310 View this article online at wileyonlinelibrary.com.
Results: At baseline, there were no statistically significant differences between the 2 groups. However, aer 30 days of long postoperative treatments, we found clinically significant improvements in QoL of subjects treated with SH, as evidenced by all QoL scales. Conclusion: Our data indicate that SH significantly improves patients’ short-term QoL following FESS in terms of C 2014 both general health and specific sinonasal status. ARS-AAOA, LLC.
Key Words: chronic rhinosinusitis; disease severity; endoscopic sinus surgery; FESS; quality of life; postoperative How to Cite this Article: Cantone E, Castagna G, Sicignano S, et al Impact of intranasal sodium hyaluronate on the short-term quality of life of patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014;4:484–487.
mitigation of symptoms to the point where subjects no longer feel the discomfort of the disease, possibly in combination with a healthy mucosa. The available CRS medical treatments comprise antibiotics, corticosteroids, and topical therapy; however, their efficacy is still debated.2 Oral antibiotics are considered therapeutic options in CRS treatment, whereas oral steroids are strongly recommended for short-time management of CRS with nasal polyps and in the perioperative period.3, 4 Existing evidence suggests that topical therapies, such as sinonasal saline irrigations and topical nasal steroids, have become an integral component in the management of CRS.5 However, for patients with medically resistant CRS and nasal polyps, the surgical approach, particularly functional endoscopic sinus surgery (FESS), represents the best treatment of choice.2, 6 Although FESS is considered the gold standard treatment for CRS, surgical outcome depends not only on the performance of the procedure itself, but also
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
484
Postoperative discomfort after FESS
on the postoperative care of nasal cavities. Furthermore, despite the consolidated use of different treatments, the postoperative period is often very painful and uncomfortable. For instance, during the first month, patients’ shortterm QoL is compromised by edema, extensive crust formation, mucosal alterations, excessive secretion, and impaired sinonasal ventilation. For these reasons, clinicians nowadays are constantly searching for agents able to promote cleansing of the nasal cavities and postoperative regeneration of the nasal mucosa. In recent years, mounting evidence suggests that sodium hyaluronate (SH)—the major component of many extracellular matrices, including those in respiratory epithelial cells and serous gland cells of the nasal and trachea-bronchial mucosa—serves important biological roles beyond its generally accepted function as a structural component of interstitial and connective tissues. In this regard, SH has been shown to promote wound healing, repairing of mucosal surfaces, and cell motility.7, 8 Particularly, studies show that topical application of SH significantly improves the healing process of the nasal mucosa, preventing extensive crust formation, and eventually leading to the recovery of smell parameters and cooling sensation.9 A prospective randomized controlled trial suggests that a new absorbable SH hydrogel, similar to a nasal dressing/packing following FESS, promotes the postoperative re-epithelization process and reduces the presence of synechia, edema, crust, and mild mucopurulent drainage.10 Furthermore, SH, in association with intranasal corticosteroid and systemic antihistamine, reduces the neutrophil count shown on nasal cytology in patients with allergic and nonallergic rhinitis and improves several clinical and endoscopic parameters.11 Although evidence of the effectiveness of SH on postoperative care following FESS is currently available, there still remains a dearth of evidence evaluating its actual impact on QoL from the patient’s perspective. In particular, given that the therapeutic effects of a drug as experienced by the patients can reflect the effectiveness of a treatment much more closely than clinician-rated outcomes, the medical need for an effective therapy after FESS provides a novel area of research. Currently, the severity of symptoms following FESS and their impact upon QoL is assessed through a wide array of questionnaires, among which is the 22-item Sino-Nasal Outcome Test (SNOT-22).12 The goal of the present study was to evaluate the effect of intranasal administration of 9 mg of high molecular weight SH on the improvement of postoperative discomfort and short-term QoL following FESS. A double-blind randomized control trial was carried out on 124 patients undergoing FESS for CRS with nasal polyposis. For the assessment of QoL in CRS patients, the Short Form-36 (SF-36) test, the Sino-Nasal Outcome Test-22 (SNOT-22), and the Visual Analogue Scale (VAS) questionnaires were administered.
485
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
Patients and methods A double-blind randomized controlled study was carried out at the University of Naples, Federico II, from January 2011 to April 2013, on 124 patients (70 males, 54 females, mean age 41.2 years) undergoing FESS for CRS with grade II nasal polyposis.13 Two subjects dropped out of the study. Patients suffering from systemic diseases, acetylsalicylic acid (ASA) sensitivity, cystic fibrosis, primitive ciliary dyskinesia, grade I nasal polyposis, choanal atresia, and with a history of previous interventions were excluded from the study. All participants gave their informed consent to participate in the study, which was fully approved by the local Board of Medical Ethics. The diagnosis of CRS was based on the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) diagnostic criteria and confirmed by nasal endoscopy and computed tomography (CT) scans with axial, coronal, and sagittal images.6 Nasal endoscopy with a 2.7-mm 30-degree rigid endoscope (Storz, Tuttlingen, Germany) was performed before surgery and after postoperative treatment, without decongestant or local anesthesia and scored as previously described by Lund and Kennedy.14 All surgical procedures were performed by the same surgeon, according to the nomenclature of Stammberger and Posawetz.15 After surgery, the nose was not packed and the day after surgery all subjects were randomized into 2 groups (group I and group II) and given the treatment. The investigational arm (group I), comprising 62 subjects, was treated with intranasal administration of 9 mg of high molecular weight SH (3 mL) plus saline solution (2 mL sodium chloride 0.9%). The control arm (group II), comprising 60 subjects, was treated with 5 mL sodium chloride (0.9%) alone. In both groups, treatments were administered twice a day for 30 consecutive days using a nebulizer ampoule for nasal douche. This device produces particles greater than 10 μm and acts only on the upper airways over a time of 60 to 90 seconds for each application.9 This method of delivery was chosen because it is better tolerated, more useful for the nebulization of high molecular weight SH, and faster to administer than classic aerosol devices. To assess QoL, groups were asked to answer 3 questionnaires. The first was the Italian Short Form-36 (SF-36) questionnaire. This questionnaire, which measures patients’ general health status, contains 36 questions that refer to 8 health concepts grouped into subgroups (physical functioning, physical role functioning, bodily pain, general health, vitality, social role functioning, emotional role functioning, and mental health). Each question was asked independently. The second was the 22-item Sino-Nasal Outcome Test (SNOT-22)12 which is a validated patient self-report measure encompassing all major symptoms included in the diagnostic criteria set in the EPOS 2012 for CRS.6 The third was the Visual Analogue Scale (VAS) questionnaire, which includes questions about headache, nose congestion, runny nose, secretion from the nose into the throat, feeling of fullness in the face, face pain, toothache,
Cantone et al.
Discussion
TABLE 1. Patient demographics at baseline Group I
Group II
Participants, n (%)
62 (51)
60 (49)
Male, n (%)
36 (52)
33 (48)
Female, n (%)
26 (49)
27 (51)
41.4 ± 2.4
42.4 ± 1.4
Age (years), mean ± SD
CRS is 1 of the most common health care challenges for which the increasing demand for medical care significantly contributes to rising healthcare costs. CRS not only causes significant physical suffering but also results in substantial functional and emotional impairment. Generally, CRS patients not responding to medical therapies resort to FESS surgery. Indeed, many studies have shown that FESS is highly effective on CRS-related QoL.16 However, because the postoperative period, the first month after surgery, is often very painful and uncomfortable for the patient, early care following FESS is crucial to reducing complications and improving long-term outcomes. Although many studies have investigated the use of topical agents to improve postoperative intranasal symptoms and to aid healing following FESS, there is still an unmet medical need for an effective therapy.17–19 Recently, SH treatment following FESS has been shown to stimulate the mucociliary clearance, thereby improving wound healing and reducing exacerbations in patients with chronic bronchitis.8, 9 Furthermore, additional evidence has reported the effectiveness of 9 mg nebulized high molecular weight SH in the treatment of sinonasal clinical, endoscopic, and psychological parameters in patients undergoing FESS for sinonasal remodeling.8, 9 There is now mounting evidence that the patient’s perspective on treatment outcomes is a crucial element for improving high-quality care. Indeed, patient-rated therapeutic outcomes in terms of symptoms can provide a much more realistic picture of the effectiveness of a treatment than those of clinician-rated outcomes.2 For these studies, the impact of chronic diseases, including CRS, and the impact of medical and surgical care are determined and recorded either with the VAS or with validated symptombased questionnaires. However, so far, these studies have primarily focused on assessing long-term but not short-term QoL following FESS.20, 21 To the best of our knowledge, this study is the first to investigate the therapeutic effect of 9 mg nebulized high molecular weight SH on the short-term QoL from the perspective of the patients undergoing FESS for CRS with nasal polyposis. In the present study the subjects enrolled were divided into 2 groups: group I was treated with 9 mg of high molecular weight SH plus saline solution, and group II was treated with saline solution alone.
SD = standard deviation.
tearing, coughing, nose bleeds, and nasal crusting. The disease was divided into mild, moderate, and severe based on total severity VAS scores (mild, VAS = 0-3; moderate, VAS = 4−7; and severe, VAS = 8−10). A VAS > 5 affected patient QoL.6 QoL tools, as well as nasal endoscopy, was administered at baseline before surgery (T0) and 30 days after postoperative treatment (T30).
Statistical analysis Continuous baseline characteristics were described as either median, mean, or standard deviation where appropriate. Difference between groups were tested with the Mann-Whitney U test; p < 0.05 was considered statistically significant. Data were tabulated in a Microsoft Excel (Microsoft Corporation, Redmond, WA) spreadsheet and imported into the Statistical Package for the Social Sciences (SPSS-PC, version 16; SPSS Inc., Chicago, IL).
Results A total of 122 patients were enrolled in the study. The 2 groups of patients were well matched. At baseline, no statistically significant differences were observed in the clinical, endoscopic, and QoL tools, nor in any of the examined parameters (Table 1). After postoperative treatment, the endoscopic score (p = 0.0001), the total VAS score (p < 0.05), the mean SNOT-22 sum score (p < 0.05), and SF-36 (p < 0.05) results were better in group I than in group II (Table 2). In addition, after treatment, the results of the 8 SF-36 test subgroups, ie, physical functioning, physical role functioning, bodily pain, general health, vitality, social role functioning, emotional role functioning, and mental health, were gener-ally better in group I than in group II.
TABLE 2. Baseline data (T0) and posttreatment data (T30) in group I and group II Endoscopic score (mean ± SD)
Total VAS score (mean)
SNOT-22 (sum score-mean)
SF-36 (mean)
T0
T30
T0
T30
T0
T30
T0
T30
Group I
6.9 ± 3.8
1.43 ± 1.85
7.2 points
3.8 points
68.0 ± 27.8
47.80 ± 25.4
40.16%
83.70%
Group II
7.1 ± 3.6
4.16 ± 3.35
6.7 points
5.6 points
67.0 ± 28.0
59.33 ± 23.2
38.61%
73.00%
SD = standard deviation; SF-36 = Short Form-36; SNOT-22 = 22-item SinoNasal Outcomes Test; T0 = before surgery; T30 = 30 days posttreatment; VAS = visual analogue scale.
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
486
Postoperative discomfort after FESS
Whereas at baseline there were no statistically significant differences between the 2 groups, clinically significant improvements in the QoL of subjects treated with SH were observed after treatment, as evidenced by the clinical and instrumental analyses performed in this study. Our data thus suggest that SH plays and important role in improving the severity of intranasal symptoms and the accompanying discomfort following FESS. In addition, SH may significantly enhance the QoL both in terms of the general health status (SF-36) and in terms of the specific sinonasal status (SNOT-22). Furthermore, as also suggested by other authors,8 our study indicated that SH is significantly better tolerated than saline in patients undergoing FESS. Together, these findings demonstrate that treatment with intranasal administration of 9 mg of high molecular weight SH can prevent FESS-postoperative patients from having to
undergo additional pharmacological treatments, especially for pain, which often requires drugs associated with relevant adverse reactions and considerable health care costs. Moreover, because of the high incidence of these conditions, a substantial economic burden is imposed on society not only in terms of direct costs (medical and nonmedical), but also in terms of indirect costs (disability, reduced working capacity, and absence from work).
Conclusion This study evaluated for the first time the general and disease-specific short-term QoL in patients undergoing FESS for CRS with nasal polyposis. Our encouraging findings indeed demonstrate the effectiveness of intranasal SH not only in the postoperative care of patients undergoing FESS but also in FESS-related discomfort.
References 1.
2.
3.
4.
5.
6.
7.
487
Hastan D, Fokkens WJ, Bachert C, et al. Chronic rhinosinusitis in Europe—an underestimated disease. A GA2 LEN study. Allergy. 2011;66: 1216–1223. Cazzavillan A, Castelnuovo P, Berlucchi M, et al. Management of chronic rhinosinusitis. Pediatr Allergy Immunol. 2012;23(Suppl 22):32–44. Poetker DM, Jakubowski LA, Lal D, et al. Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidencebased review with recommendations. Int Forum Allergy Rhinol. 2013;3:104–120. Soler ZM, Oyer SL, Kern RC, et al. Antimicrobials and chronic rhinosinusitis with or without polyposis in adults: an evidenced-based review with recommendations. Int Forum Allergy Rhinol. 2013;3: 31–47. Rudmik L, Hoy M, Schlosser RJ, et al. Topical therapies in the management of chronic rhinosinusitis: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3:281–298. Fokkens WJ, Lund VJ, Mullol J, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012;(23):3 p preceding table of contents, 1–298. Forteza R, Lieb T, Aoki T, et al. Hyaluronan serves a novel role in airway mucosal host defense. FASEB J. 2001;15:2179–2186.
8.
9.
10.
11.
12.
13.
14.
Gelardi M, Guglielmi AVN, De Candia N, et al. Effect of sodium hyaluronate on mucociliary clearance after functional endoscopic sinus surgery. Eur Ann Allergy Clin Immunol. 2013;45:103–108. Macchi A, Terranova P, Digilio E, et al. Hyaluronan plus saline nasal washes in the treatment of rhinosinusal symptoms in patients undergoing functional endoscopic sinus surgery for rhino-sinusal remodeling. Int J Immunopathol Pharmacol. 2013;26:137–145. Shi R, Zhou J, Wang B, et al. The clinical outcomes of new hyaluronan nasal dressing: a prospective, randomized, controlled study. Am J Rhinol Allergy. 2013;27:71–76. Gelardi M, Iannuzzi L, Quaranta N. Intranasal sodium hyaluronate on the nasal cytology of patients with allergic and nonallergic rhinitis. Int Forum Allergy Rhinol. 2013;3:807–813. Hopkins C, Gillett S, Slack R, et al. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009;34:447–454. Gwaltney JM Jr, Jones JG, Kennedy DW. Medical management of sinusitis: educational goals and management guidelines. The International Conference on Sinus Disease. Ann Otol Rhinol Laryngol Suppl. 1995;167:22–30. Lund VJ, Kennedy DW. Quantification for staging sinusitis. The Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995;167:17–21.
International Forum of Allergy & Rhinology, Vol. 4, No. 6, June 2014
15. Stammberger H, Posawetz W. Functional endoscopic sinus surgery. Concept, indications and results of the Messerklinger technique. Eur Arch Otorhinolaryngol. 1990;247:63–76. 16. Bhattacharyya N. Symptom outcomes after endoscopic sinus surgery for chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2004;130: 329–333. 17. Desrosiers MY, Kilty SJ. Treatment alternatives for chronic rhinosinusitis persisting after ESS: what to do when antibiotics, steroids and surgery fail. Rhinology. 2008;46:3–14. 18. Portela RA, Hootnick J, McGinn J. Perioperative care in functional endoscopic sinus surgery: a survey study. Int Forum Allergy Rhinol. 2012;2:27–33. 19. Rudmik L, Soler ZM, Orlandi RR, et al. Early postoperative care following endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2011;1:417–430. 20. Bezerra TF, Piccirillo JF, Fornazieri MA, et al. Assessment of quality of life after endoscopic sinus surgery for chronic rhinosinusitis. Braz J Otorhinolaryngol. 2012;78:96–102. 21. Cornet ME, Georgalas C, Reinartz SM, et al. Longterm results of functional endoscopic sinus surgery in children with chronic rhinosinusitis with nasal polyps. Rhinology. 2013;51:328–334.
