Abstract
Purpose
Despite advances in the diagnosis and treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), their recurrence rate remains significant. There is a need for promptly-obtainable, inexpensive, minimally-invasive prognostic parameters to enable rhinologists to identify patients at higher risk of recurrent CRSwNP. The prognostic role of the neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR), previously discussed as potential markers of inflammation, has already been investigated in CRSwNP.
The aim of the present study was to test the prognostic value of the NLR and ELR, and also of the basophil-to-lymphocyte ratio (BLR) (given the emerging role of basophils in CRSwNP) in a large series of CRSwNP.
Materials and methods
The study concerned 240 patients who underwent FESS for CRSwNP from 2009 to 2014 and had a postoperative follow-up longer than 12 months. We considered patients with recurrences as those with endoscopic evidence of at least grade I polyposis.
Results
In our series, the mean NLR, ELR and BLR were significantly higher in patients whose disease recurred than in those remaining recurrence-free (p = 0.03, p = 0.0001, and p = 0.0002, respectively), but the discriminatory power of the NLR, ELR, or BLR in terms of disease recurrence was unacceptable (AUCs = 0.600, 0.678, and 0.662, respectively).
Conclusions
The heterogeneous prognostic role of NLR, ELR and BLR identified in the clinically and pathologically different sub-cohorts of CRSwNP considered supports the hypothesis that CRSwNPs with a similar clinical picture may differ considerably in terms of the biological and pathogenic mechanisms of polyp formation and growth.
1
Introduction
Despite advances in the diagnostic methods used (videorhinoscopy, imaging and laboratory investigations) and in the treatment options (including functional endoscopic sinus surgery [FESS]) for cases of chronic rhinosinusitis with nasal polyps (CRSwNP), the rate of recurrence remains significant. There is an undeniable need for novel, more effective prognostic parameters or multi-parameter panels that would enable rhinologists to pinpoint patients at higher risk of recurrent CRSwNP after sinonasal surgery . Such parameters could help us to tailor each patient’s information, rational follow-up, and postoperative medical treatment to their real risk of recurrence.
Several variables, including asthma, allergy, acetylsalicylic acid (ASA) intolerance, percentages of eosinophils and basophils in the nasal tissue and blood, and IgE levels, have been considered putatively related to CRSwNP recurrence . Occasionally, some new biomarker involved in angiogenesis or proliferation, or related to adhesion molecules or tissue remodeling have been tested using immunohistochemistry and/or polymerase chain reaction to see if they can help us predict the course of CRSwNP . Boztepe et al. very recently investigated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in terms of CRSwNP recurring after FESS, given that the NLR had already been proposed as a potential marker of inflammation . In their very interesting but also very preliminary paper, Boztepe et al. included 112 patients with CRSwNP who underwent FESS. They considered as recurrences any cases in which a patient’s symptoms recurred. When the NLRs of 88 recurrence-free patients were compared with those of 24 patients whose disease recurred, the ratio was significantly higher in the latter. The authors rightly concluded that further studies were mandatory to confirm their results. Yenigün reported in a Turkish ENT journal that, in a sample of 158 patients with CRSwNP, patients who had recurrent polyposis had significantly higher preoperative NLR and ELR values than patients remaining recurrence-free. A very recent preliminary investigation conducted by our research group also showed a significant direct association between CRSwNP recurrences and serum basophil counts .
Given the importance of identifying promptly-available, minimally-invasive and inexpensive predictors of disease recurrence, the aim of the present study was to analyze the prognostic value of the NLR, ELR, and basophil-to-lymphocyte ratio (BLR) in a large series of CRSwNP (240 cases). Appropriate statistical methods were used to assess the relationship between three ratios and patients’ demographic details, crucial comorbidities (i.e. asthma, allergy, ASA intolerance) and histopathological features.
2
Materials and methods
2.1
Patients
Adult patients with evidence of polyposis involving at least two recesses but not extending to the nasal cavity (multiple polyps occupying the middle meatus, grade 2), or polyps extending beyond the middle meatus (grade 3) were first treated medically for 3 months with: local mometasone furoate 200 μg daily (100 μg/nostril), the dosage recommended by Stjarne et al. ; or fluticasone furoate 110 μg daily (55 μg/nostril), and oral therapy with methylprednisolone (32 mg daily on days 1–5, then 16 mg daily on days 6–10, then 8 mg daily on days 11–20), as suggested by Van Zele et al. . If this medical therapy failed, patients underwent FESS with or without septoplasty/turbinoplasty under general anesthesia. Patients with polyps confined to one recess (grade 1) were not treated surgically.
The present study concerns 240 patients (149 males and 91 females, mean age 48.9 ± 15.2 years) who underwent FESS for CRSwNP from January 2009 to June 2014. Exclusion criteria were a postoperative follow-up shorter than 12 months or a diagnosis of eosinophilic granulomatosis with polyangitis (EGPA) (formerly Churg–Strauss syndrome). We also excluded patients with inflammatory, autoimmune, acute or chronic infectious diseases other than sinusitis, malignancies, hematological disorders, a history of systemic corticosteroid therapy, or chronic renal insufficiency.
The preoperative diagnostic work-up for all patients included nasal endoscopy (with rigid 0° and 30° [Ø 4 mm] optical instruments), nasal cytology, serum neutrophil, eosinophil, basophil, and lymphocyte counts, assays of total and specific serum IgE for common airborne allergens, and paranasal high-resolution computerized tomography (CT). Asthmatic patients underwent spirometry with methacholine challenge.
After surgery, patients performed nasal irrigations with isotonic saline solution twice a day (using 20 ml per irrigation) and local nasal therapy with mometasone furoate 200 μg daily (100 μg/nostril), using the dosage recommended by Stjarne et al. , or fluticasone furoate 110 μg daily (55 μg/nostril). All laboratory tests were performed approximately 1 month before surgery, at least 3 months after withdrawing oral steroids, and at least 1 month after stopping nasal steroid treatment.
During periods of pollination, patients with a known pollen allergy were treated with antihistamines. Patients with asthma received appropriate therapy.
2.2
Clinical history and features
We identified patients with a history of aspirin intolerance. The American Rheumatism Association criteria, revised in 2012 by the International Chapel Hill Consensus Conference Nomenclature of Vasculitides , were considered for the diagnosis of EGPA.
2.3
Laboratory features: serum neutrophil, eosinophil, basophil, and lymphocyte counts
All patients had a blood sample taken approximately 1 month before surgery to obtain their neutrophil, eosinophil, basophil, and lymphocyte counts, and their NLR, ELR and BLR were calculated. We also measured serum total IgE, and specific IgE for dermatophagoides pteronyssinus and farinae, birch pollen, pellitory, grass mix, cat and dog dander, alternaria alternata, aspergillus fumigatus, and common ragweed. All assays were performed at the same laboratory (the EIA Unit, Laboratory Medicine Service, Padova General Hospital).
2.4
Histopathological features: eosinophil component in polyps
Three high-power fields (400 × magnification) from each surgical specimen were examined to quantify the eosinophil component, and two patterns of polyposis were recognized: (i) polyposis rich in eosinophils (≥ 10 eosinophils per field); and (ii) polyposis poor in eosinophils (< 10 eosinophils per field).
2.5
Follow-up
Patients underwent postoperative nasal endoscopy under topical anesthesia (lidocaine 20 mg/ml plus xylometazoline 1 mg/ml; volume ratio 1:1). Endoscopic follow-ups were performed using rigid 0° and 30° (Ø 4 mm) instruments and scheduled 3, 6, 12 months and then yearly after surgery. We considered patients with recurrences as those with endoscopic evidence of at least grade I polyposis.
2.6
Statistical analysis
The statistical methods applied were the Mann–Whitney U test and Fisher’s exact test, as appropriate.
The receiver operating curve (ROC) approach (failure versus parameter) was used to set the analytically best-fitting cut-off for binarizing the continuous variables, NLR, ELR and BLR, according to the highest level of the positive likelihood ratio. The best performance coincides with an area under the ROC curve (AUC) of 1.0. Additional statistics derived from the model (sensitivity, specificity, positive predictive accuracy, negative predictive accuracy, and accuracy) were also calculated.
A p-value < 0.05 was considered significant, while values in the range of 0.10 > p ≥ 0.05 were assumed to indicate a statistical trend. The STATA™ 8.1 statistical package was used for all analyses.
2
Materials and methods
2.1
Patients
Adult patients with evidence of polyposis involving at least two recesses but not extending to the nasal cavity (multiple polyps occupying the middle meatus, grade 2), or polyps extending beyond the middle meatus (grade 3) were first treated medically for 3 months with: local mometasone furoate 200 μg daily (100 μg/nostril), the dosage recommended by Stjarne et al. ; or fluticasone furoate 110 μg daily (55 μg/nostril), and oral therapy with methylprednisolone (32 mg daily on days 1–5, then 16 mg daily on days 6–10, then 8 mg daily on days 11–20), as suggested by Van Zele et al. . If this medical therapy failed, patients underwent FESS with or without septoplasty/turbinoplasty under general anesthesia. Patients with polyps confined to one recess (grade 1) were not treated surgically.
The present study concerns 240 patients (149 males and 91 females, mean age 48.9 ± 15.2 years) who underwent FESS for CRSwNP from January 2009 to June 2014. Exclusion criteria were a postoperative follow-up shorter than 12 months or a diagnosis of eosinophilic granulomatosis with polyangitis (EGPA) (formerly Churg–Strauss syndrome). We also excluded patients with inflammatory, autoimmune, acute or chronic infectious diseases other than sinusitis, malignancies, hematological disorders, a history of systemic corticosteroid therapy, or chronic renal insufficiency.
The preoperative diagnostic work-up for all patients included nasal endoscopy (with rigid 0° and 30° [Ø 4 mm] optical instruments), nasal cytology, serum neutrophil, eosinophil, basophil, and lymphocyte counts, assays of total and specific serum IgE for common airborne allergens, and paranasal high-resolution computerized tomography (CT). Asthmatic patients underwent spirometry with methacholine challenge.
After surgery, patients performed nasal irrigations with isotonic saline solution twice a day (using 20 ml per irrigation) and local nasal therapy with mometasone furoate 200 μg daily (100 μg/nostril), using the dosage recommended by Stjarne et al. , or fluticasone furoate 110 μg daily (55 μg/nostril). All laboratory tests were performed approximately 1 month before surgery, at least 3 months after withdrawing oral steroids, and at least 1 month after stopping nasal steroid treatment.
During periods of pollination, patients with a known pollen allergy were treated with antihistamines. Patients with asthma received appropriate therapy.
2.2
Clinical history and features
We identified patients with a history of aspirin intolerance. The American Rheumatism Association criteria, revised in 2012 by the International Chapel Hill Consensus Conference Nomenclature of Vasculitides , were considered for the diagnosis of EGPA.
2.3
Laboratory features: serum neutrophil, eosinophil, basophil, and lymphocyte counts
All patients had a blood sample taken approximately 1 month before surgery to obtain their neutrophil, eosinophil, basophil, and lymphocyte counts, and their NLR, ELR and BLR were calculated. We also measured serum total IgE, and specific IgE for dermatophagoides pteronyssinus and farinae, birch pollen, pellitory, grass mix, cat and dog dander, alternaria alternata, aspergillus fumigatus, and common ragweed. All assays were performed at the same laboratory (the EIA Unit, Laboratory Medicine Service, Padova General Hospital).
2.4
Histopathological features: eosinophil component in polyps
Three high-power fields (400 × magnification) from each surgical specimen were examined to quantify the eosinophil component, and two patterns of polyposis were recognized: (i) polyposis rich in eosinophils (≥ 10 eosinophils per field); and (ii) polyposis poor in eosinophils (< 10 eosinophils per field).
2.5
Follow-up
Patients underwent postoperative nasal endoscopy under topical anesthesia (lidocaine 20 mg/ml plus xylometazoline 1 mg/ml; volume ratio 1:1). Endoscopic follow-ups were performed using rigid 0° and 30° (Ø 4 mm) instruments and scheduled 3, 6, 12 months and then yearly after surgery. We considered patients with recurrences as those with endoscopic evidence of at least grade I polyposis.
2.6
Statistical analysis
The statistical methods applied were the Mann–Whitney U test and Fisher’s exact test, as appropriate.
The receiver operating curve (ROC) approach (failure versus parameter) was used to set the analytically best-fitting cut-off for binarizing the continuous variables, NLR, ELR and BLR, according to the highest level of the positive likelihood ratio. The best performance coincides with an area under the ROC curve (AUC) of 1.0. Additional statistics derived from the model (sensitivity, specificity, positive predictive accuracy, negative predictive accuracy, and accuracy) were also calculated.
A p-value < 0.05 was considered significant, while values in the range of 0.10 > p ≥ 0.05 were assumed to indicate a statistical trend. The STATA™ 8.1 statistical package was used for all analyses.
3
Results
The mean follow-up after surgery was 30.25 ± 12.24 months (median 36 months). Forty-eight patients developed recurrent CRSwNP after a mean 22.75 ± 9.56 months (median 24 months). The Mann–Whitney U test ruled out any difference in mean follow-up periods between patients with and without recurrent disease (p = 0.45).
3.1
Analysis of potentially prognostic variables (see also Table 1 )
The recurrence rate was significantly higher for patients with eosinophilic-type than for non-eosinophilic type CRSwNP (Fisher’s exact test, p = 0.000). Fisher’s exact test disclosed significant associations between recurrent CRSwNP and allergy (p = 0.000), asthma (p = 0.000), and ASA intolerance (p = 0.018).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
