The authors have no funding, financial relationships, or conflicts of interest to disclose.
Long-term results of endoscopic sinus surgery–oriented treatment for chronic rhinosinusitis with asthma
Article first published online: 5 AUG 2013
© 2013 The American Laryngological, Rhinological and Otological Society, Inc.
Volume 124, Issue 1, pages 24–28, January 2014
How to Cite
Chen, F.-H., Zuo, K.-J., Guo, Y.-B., Li, Z.-P., Xu, G., Xu, R. and Shi, J.-B. (2014), Long-term results of endoscopic sinus surgery–oriented treatment for chronic rhinosinusitis with asthma. The Laryngoscope, 124: 24–28. doi: 10.1002/lary.24196
- Issue published online: 20 DEC 2013
- Article first published online: 5 AUG 2013
- Accepted manuscript online: 20 MAY 2013 03:08AM EST
- Manuscript Accepted: 19 APR 2013
- Manuscript Revised: 17 MAR 2013
- Manuscript Received: 23 FEB 2013
- This study was supported by grants from the National Natural Science Grant of China (81071030, 81170896, 31270967, 81272062, 81273272, and 81271055) and Guangdong Province Technology Projects (No. 2010B031600088).
- Chronic rhinosinusitis;
- nasal polyps;
- aspirin intolerance;
- sinus surgery
The aims of this study were to evaluate the efficacy of functional endoscopic sinus surgery (FESS)–oriented multimodality treatment in chronic rhinosinusitis (CRS) patients with asthma and its impact on asthma.
Prospective, nonrandomized cohort.
Twenty-seven CRS patients with asthma who underwent FESS with postoperative topical corticosteroid spray were evaluated preoperatively; 25 of them were evaluated 1 year and 3 years postoperatively. CRS was evaluated by visual analogue scale, clinical control of CRS, and objective measurement endoscopy Lund-Kennedy scores. Asthma was assessed by subjective asthma control test and asthma control level, also by objective antiasthma medication use and pulmonary function tests.
VAS scores of general symptoms (8.09 ± 0.87 preoperatively) were significantly improved at 1 year (2.94 ± 2.21) and 3 years (3.77 ± 2.16) postoperation (P = .000). No difference in these items was found between 1 year and 3 years (P = .463). Endoscopy Lund-Kennedy scores at 1 year (4.34 ± 3.09) and 3 years (5.80 ± 3.38) postoperatively were significantly better (9.33 ± 2.03 preoperatively, P = .000), and there was no difference between 1 year and 3 years of follow-up (P > .05). Significantly, asthma control level improved postoperatively (P = .025). However, antiasthma drug and pulmonary function showed no significant change postoperatively (P > .05).
FESS-oriented multimodality treatment improves CRS with asthma significantly and persistently. Asthma control level improved. Antiasthma medication use and pulmonary function remained stable.
Level of Evidence
4. Laryngoscope, 124:24–28, 2014
Chronic rhinosinusitis (CRS) is a common disease and a significant health problem. Although the medical and functional endoscopic sinus surgery (FESS) treatments for CRS have improved markedly, a subgroup of CRS patients remains quite resistant to all kinds of therapy, which is called difficult-to-treat rhinosinusitis (DTRC) or refractory CRS (RCRS). Asthma is considered one of the important factors for RCRS.
Coexistence of asthma and rhinosinusitis has been noted in the medical literature for centuries. Forty percent of CRS patients have been shown to have asthma, and sinus x-ray or computed tomography (CT) showed that 93% of those with asthma also had sinusitis.[2, 3] Although several studies of CRS with asthma exhibited a significant improvement during short-term follow-up, the outcomes were worse than in patients without asthma.[4, 5] Hzowever, the long-term effect of FESS-oriented multimodality treatment has not been sufficiently studied.
On the other hand, the impact of endoscopic sinus surgery (ESS) on asthma is controversial. Asthma has been reported as improved, unchanged, and deteriorated in various studies.[6-8] Previously, we reported the outcome of 25 patients with CRS and asthma 1 year postoperatively and of 12 of the 25 patients 3 years postoperatively in 2011. The results showed that FESS-based comprehensive treatment had a persistent and significant effect on CRS without significant improvement in asthma (asthma control test [ACT], asthma drug use, and pulmonary function). Nevertheless, the group at 3 years was small and could not fully demonstrate the long-term effect and its impact on asthma.
Thus, this prospective study was carried out to evaluate the 3-year long-term effect of FESS-oriented multimodality treatment for CRS asthma. Also we investigated the impact of this comprehensive treatment on asthma. We wanted to see whether FESS-oriented multimodality treatment improved both CRS and asthma.
MATERIALS AND METHODS
We prospectively recruited consecutive patients with CRS (≥18 years) undergoing FESS in Otorhinolaryngology Hospital, First Affiliated Hospital at Sun Yat-san University, from September 2006.
Inclusion criteria were as follows: CRS with asthma; adequate medical treatment for at least 3 months without a satisfactory result; ≥18 years old; no present smoking. Exclusion criteria were as follows: immunodeficiencies, cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, diabetes mellitus, neoplasia, or fungal rhinosinusitis, pregnant or lactating, upper airway infection in 1 month, and asthma in acute exacerbation. Diagnostic criteria were as follows: CRS was defined according to a European position paper on rhinosinusitis and nasal polyps. Asthma was diagnosed by Global Initiative For Asthma (GINA) guidelines. Allergy rhinitis diagnosis was based on allergy rhinitis and its impact on asthma. The local medical ethics committee approved the study, and all patients provided informed consent before enrollment.
All patients were treated and followed up with the same protocol. The multimodality treatment included FESS and at least 12 months of drug therapy, which consisted of preoperative prednisone, postoperative nasal lavage, and nasal steroid spray. All subjects received a 1-week course of oral prednisone (30 mg per day) before surgery. Then, FESS was performed by Messerklinger technique with middle turbinate preservation using general anesthesia by two rhinologic professors. The surgery extent was decided according to CT scan. Expandable sponges (Merocel; Medtronic-XOMED, Jacksonville, FL) were packed for 24 to 48 hours and then extracted. Normal saline lavage was applied for 2 to 3 months. All patients were treated with topical steroid spray for 12 months. Patients with allergy rhinitis were given antihistamine if allergy rhinitis was uncontrolled by topical spray. One year postoperatively, if CRS reached a well-controlled level, medical therapy was stopped. If CRS was partly controlled or uncontrolled, local steroid spray continued until CRS reached a well-controlled level.
Visit 1 (baseline recording) was at 7 days before FESS, and patients were evaluated by an ENT physician and a pulmonologist. Visit 2 and visit 3 (end of study) were at 1 year and 3 years postoperatively, to determine short-term outcome and long-term outcome, respectively. For subject measurements, symptoms were scored on a visual analogue scale (VAS) of 0 to 10 cm, with 0 cm being “not troublesome” and 10 cm being “worst thinkable troublesome.” Five VAS scores concerning the following symptoms were noted: general symptom, nasal congestion, nasal discharge, olfactory reduction/loss, and facial pain/headache. For objective assessment, endoscopy results were scored with the system proposed by Lund-Kennedy endoscopy. A CT scan of paranasal sinuses was performed before the study in all patients. Assessment of current clinical control of CRS was evaluated. Asthma was evaluated by ACT, asthma medication use, and pulmonary function. ACT ranged from 0 to 25 and was graded into “well controlled,” “partially controlled,” and “lack of control.” Pre-FESS, antiasthma medication was recorded in visit 1, and the changes in antiasthma medication use in visit 2 and 3 were evaluated and graded into “stop medicine,” “reduction,” “unchanged,” or “increased” compared with medication use pre-ESS. Pulmonary function tests, including forced vital capacity (FVC), FVC of predicted (FVC%), forced expiratory volume in 1 second (FEV1), FEV1 of predicted (FEV1%), peak expiratory flow (PEF), PEF of predicted (PEF%) and FEV1/FVC ratio were measured at three visits using a spirometer that met American Thoracic Society standards (Sensor Medics Inc. 2100, Yorba Linda, CA)
Statistical analysis was performed with SPSS 16.0 for windows (SPSS Inc., Chicago, IL). Values were expressed as means and standard deviation or medians and ranges for continuous variables and numbers and percentages for categorical variables. Two-way analysis of variance for repeated measures was used to estimate the effect of treatment. Ordinal levels were compared by using a χ2 trend test. The level of significance was .05.
Twenty-seven patients were enrolled from September 2006 to May 2009. These included 11 men and 16 women with a median age of 42 years (range, 25–66 years) at presentation. Patient characteristics are summarized in Table 1.
|Age, yr||42 (25–66)|
|Course, yr||7.36 ± 6.41|
|Polyps, no. (%)||23 (85)|
|AR, no. (%)||19 (70)|
|Aspirin intolerance, no. (%)||5 (18)|
|Nasal surgery history, no. (%)||7 (26)|
|Normal lung function, no. (%)||20 (74.1)|
Twenty-five (92%) patients were followed for 3 years, with two patients lost. Five patients (20%) required revision surgery because symptoms and nasal polyps recurred and resisted medicine therapy. Three experienced aspirin intolerance. The median time to last surgery was 36 months (range, 24–62 months).
Table 2 shows that VAS scores of general symptoms, nasal obstruction, and nasal discharge were significantly improved in 1 year and 3 years postoperatively. No difference in these items was found between 1 year and 3 years. In addition, olfaction improved remarkably in the first year, whereas it reduced significantly in the third year. There is no difference between the baseline and the third year, nor between the baseline and the first year. Finally, facial pain/headache was no different for those three evaluation times.
|No.||General||Obstruction||Discharge||Olfactory Loss||Facial Pain/Headache|
|Baseline||27||8.09 ± 0.87||7.25 ± 1.80||7.13 ± 1.68||8.44 ± 2.13||2.11 ± 3.24|
|1 yr||25||2.94 ± 2.21||1.86 ± 2.36||2.25 ± 2.14||5.38 ± 3.52||0.61 ± 1.74|
|3 yr||25||3.77 ± 2.16||2.77 ± 2.65||3.62 ± 2.78||6.79 ± 3.50||0.75 ± 1.54|
There were no differences in grades of clinical control between 1 year and 3 years postoperatively (likelihood χ2 = 6.148, P > .05) (Table 3).
|No.||Well Controlled||Partly Controlled||Uncontrolled|
|1 yr||25||10 (40.0)||11 (44.0)||4 (16.0)|
|3 yr||25||6 (24.0)||14 (56.0)||5 (20.0)|
Nasal endoscopy Lund-Kennedy score was 9.33 ± 2.03 preoperatively. As might be expected, it reduced remarkably to 4.34 ± 3.09 in the first year and 5.80 ± 3.38 in the third year. There was a significant difference between them (F = 21.467, P = .000) but not in the postoperative evaluations.
Patients in the well-controlled group increased from two patients preoperatively to nine patients and eight patients in the first year and the third years postoperatively, respectively. Patients in the lack-of-control group were reduced from three patients preoperatively to zero and two patients in 1 year and 3 years postoperatively, respectively. There was a significant difference in ACT grades (likelihood χ2 = 1.177, P = .025). Both differences between baseline and 1 year postoperatively (likelihood χ2 = 6.051, P = .049) and between baseline and 3 years postoperatively (likelihood χ2 = 7.023P = .030) were significant. There were no differences in ACT grades between 1 year and 3 years postoperatively (likelihood χ2 = 3.405, P = .182) (Table 4).
|No.||Well Controlled||Partial Controlled||Lack of Control|
|Baseline||27||2 (7.4)||22 (81.5)||3 (11.1)|
|1 yr||25||9 (36.0)||16 (64.0)||0|
|3 yr||25||8 (32.0)||15 (60.0)||2 (8.0)|
ACT scores were 22.12 ± 2.18, 23.65 ± 1.85, and 22.50 ± 3.50 preoperatively and 1 year and 3 years postoperatively, respectively (F = 2.481, P = .091). There was no difference in ACT scores between the three times of evaluation.
In visit 1, all patients needed daily inhaled glucocorticosteroids and β2-agonist, five of them needed fast dilation inhalator weekly, and none of them needed daily systemic glucocorticosteroids. Postoperative changes are shown in Table 5. No patients increased antiasthma medication, and no significant differences were found in visits 2 and 3 (likelihood χ2 = 1.572, P = .456).
|1 yr||25||3 (12.0)||5 (20.0)||17 (68.0)||0 (0.0)|
|3 yr||25||3 (12.0)||2 (8.0)||20 (80.0)||0 (0.0)|
Pulmonary function was not improved in FEV1, FEV1%, FEV1/FVC, PEF, and PEF% (Table 6).
|Baseline||2.32 ± 0.14||85.54 ± 19.82||73.56 ± 9.83||5.94 ± 0.50||86.31 ± 4.92|
|1 yr||2.39 ± 0.20||83.10 ± 14.15||73.14 ± 11.38||6.93 ± 0.61||95.87 ± 6.09|
|3 yr||2.04 ± 0.18||83.48 ± 18.69||71.52 ± 10.32||5.56 ± 0.560||84.06 ± 5.90|
This study was to evaluate the short-term and long-term results of FESS-based comprehensive treatment in asthmatic CRS patients and its impact on asthma, including ACT scores, antiasthma medication, and pulmonary function.
Subjective and objective improvement of CRS was observed in short-term and long-term outcome. Forty percent of patients had CRS well controlled, and 44% had CRS partially controlled in the first year postoperatively. Except facial pain/pressure and headache, the other symptoms were remarkably improved. In the third year, well-controlled CRS was reduced to 24% and partially controlled was 56%. Endoscopy scores were improved in both evaluations. Currently, several studies suggest improvement in both short-term and long-term results. For short-term follow-up, Smith et al. reported FESS outcomes of 51 patients with a mean follow-up of 1.4 years. Quality-of-life and nasal endoscopic scores improved significantly. Ragab et al. reported improvement in 22 asthmatic CRS patients, evaluated by VAS scores and nasal endoscopic scores, with a 12-month follow-up. For long-term outcome, Dejima et al. report CRS was significantly improved with a mean observation period of 37.4 months. However, these follow-up time points differed from 6 months to 5 years, which cannot concisely demonstrate long-term efficacy.
Our study has the advantage that it was prospectively designed and evaluated patients in two time points, 1 year and 3 years postoperatively, which could be more accurate and concise for demonstrating the change after ESS. We used subjective symptoms determined by VAS scores, objective Lund-Kennedy endoscopic scores, and comprehensive CRS controlled levels; all of these evaluation methods are widely accepted with excellent comparability.
In our investigation, obstruction and discharge kept persistent and there was significant improvement in 3 years' follow-up. However, olfactory function rose in 1 year and then became worse; no significant change was found at 3 years compared to baseline. We found the symptom most improved is congestion, followed by rhinorrhea. Olfaction loss is most common to recur postoperatively.
Of note, the long-term outcome of CRS with asthma is far from satisfactory. In our study there were still 16% and 20% uncontrolled in the first and third year postoperatively, respectively. Nasal endoscopy showed most patients had different degrees of nasal polyp recurrence, edema, or discharge. Five percent of patients needed revision surgery. Furthermore, studies indicated asthma was at risk of recurrence and had worse endoscopy scores after FESS.
Although the concise mechanism of refractory inflammation in CRS with asthma remains unclear, it has been reported that the inflammatory hallmark of eosinophil inflammation in the mucous of CRS and asthma. Several pathologic processes are supposed to promote the accumulation of eosinophils. These include infiltration of progenitor cells; increase in local IL-3, IL-5, IL-13, GM-CSF, and eotaxin production; and upregulation of adhesion molecules. Various pathogens including Toll-like receptors (TLRs) ligands may trigger an abnormal immune response at the mucosal surface. Sinusitis and asthma can amplify each other via the systemic route, involving interleukin-5 and the bone marrow. Recently, nasal application of Staphylococcus aureus enterotoxin B has been shown to aggravate the allergen-induced features of allergic asthma in a mouse model.
Thus, we suggest that patients with CRS and asthma should use local steroid for a sufficient time after FESS to suppress the intractable inflammation in the sinuses. Soler et al. performed endoscopic sinus surgery with and without middle turbinate resection in CRS patients. Their results showed that patients undergoing middle turbinate resection had greater improvements in endoscopy and smell disability index scores than middle turbinate preservation. For further study, we performed “aggressive” ESS in another group of asthmatic CRS patients with resection of middle turbinate to compare the effect with middle turbinate preservation.
Apparently, various confounders not yet sufficiently defined influence the effects of FESS on concomitant asthma. Most studies have shown that ESS improves bronchial symptoms and reduces systematic steroid and fast bronchial dilation medication. However lung function in asthma patients with CRS has been reported to benefit from ESS by some authors but not others. Uri et al. examined the effect of FESS in a subgroup of 34 patients with massive nasal polyposis and asthma by following up at 2.1 years. They reported that FESS did not improve asthma. However, there was a significant decrease in oral corticosteroid and bronchodilator inhaler usage. Of note, 17 patients needed bronchodilator inhaler 6 to 10 times per day, and 18 patients were treated with prednisolone in a dosage of 5 mg to 40 mg/day before ESS. Goldstein et al. evaluated 13 patients and reported that FESS did not reduce postoperative asthma symptoms or antiasthma medication use or pulmonary function. By contrast, Senior et al. reported ESS improved symptoms of 30 asthma patients after a long-term follow-up of 6.5 years. However their study was retrospective designed, and they used a questionnaire without objective evaluation. Palmer et al. retrospectively reviewed the charts of a subgroup of 14 CRS patients with steroid-dependent asthma who underwent ESS. Fourteen of the 15 patients decreased their postoperative prednisone requirement.
The ACT is a validated, five-item, patient-completed measure of asthma control with a recall period of 4 weeks. ACT is predictive of GINA guideline–defined classification levels of asthma control. In our group of patients, ACT level was improved postoperatively.
However, antiasthma medication and pulmonary function remained stable. The reasons for these changes included the fact that the sequence of asthma improvement is from symptom to lung function. Second, most of our patients have normal lung function before FESS; therefore it is hard for their pulmonary function to improve significantly. Third, few of our patients need to use systemic steroid and fast bronchial dilation inhalator before surgery. Most of them inhaled glucocorticosteroids and β2-agonist daily. In studies that mentioned a reduction in antiasthma drugs, most of the patients used systemic steroid and fast bronchial dilation inhalator preoperatively.[7, 19] Finally, asthma is a multifactor disease. The mechanisms that influence the development and expression of asthma are complex and interactive. And the influence from the upper airway is just one of the aspects.
This study demonstrated that FESS-oriented multimodality treatment improved both the subjective and objective outcome in CRS with asthma. However, the long-term results were not satisfying. In this group, most patients had normal lung function preoperatively. Their asthma control levels were significantly improved but not their pulmonary function. Further studies are needed to improve the long-term effect of CRS with asthma.
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