The piercing-stretching suture technique for the treatment of simple oral floor ranula.

BACKGROUND: Oral floor ranulas are pseudocysts located in the floor of the mouth that result from the extravasation of mucus from a sublingual gland. Historically, there has been little consensus on the ideal first-line treatment. Currently, definitive treatment involves sublingual gland excision, which can injure the lingual nerve and submandibular duct. Minimally invasive surgical techniques have been proposed, but so far have been associated with a high rate of recurrence. METHODS: The so-called piercing-stretching suture technique was performed in 14 naïve adult and paediatric patients (6 females, with a mean age of 20.3 years (range, 7-55 years)). Clinical and ultrasonographic evaluations were performed in all patients; post-operative sialendoscopy was conducted in two paediatric patients. RESULTS: The surgical procedure was successful in all patients, and complete recovery of the ranula was seen in all but one of the patients who underwent suture replacement. No major or minor complications were encountered. CONCLUSION: This minimally invasive procedure may be considered a reliable and first-line treatment for management of simple oral floor ranulas.

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia.

BACKGROUND: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. METHODS: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs ≥ 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). RESULTS: Chest CT scores showed a significant correlation with FEV1 (p = 0.0002), age (p <  0.0001), BMI (p = 0.0002) and number of lung lobes involved (p <  0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation (≥ 2/year) were older (p = 0.01), had lower FEV1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED). CONCLUSIONS: In our PCD population the number of exacerbations (≥ 2/year) and PA colonization were the two most relevant factors associated with severity of disease.

A goitrous model for Bartolomeo Vivarini (1432-1499).

INTRODUCTION: Bartolomeo Vivarini (Venezia 1432c.-Venezia 1499c.) was an Italian painter during the Renaissance. The artist was widely influenced by Andrea Mantegna, whose opera was characterized by personages with anatomical details meticulously described. MATERIALS AND METHODS: Some of the most valued paintings of Bartolomeo Vivarini were analyzed. Purpose of the present article is to describe these artworks focusing on female personages represented with thyroid swelling. RESULTS: A recurring female model in Vivarini's artworks is portrayed with a goitrous neck. This might display a real prevalence of thyroid diseases among young women in the Renaissance age (e.g. postpartum thyroiditis). CONCLUSIONS: Representation of goiter in the artworks of Vivarini and Mantegna reflects the increased anatomic accuracy and knowledge developed in art since Renaissance and Baroque.

Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus.

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

In reply to "Commentary to: Endoscopic and clinical benefits of hyaluronic acid in children with chronic adenoiditis and middle ear disease", by Zhengcai Lou.

Some considerations will be expressed in consideration of the commentary previously published. In particular, we underline that no other medications were administered to the patients during the study period and any clinical evaluation was postponed in case of acute upper respiratory tract infection in the previous 14 days. We strongly advocate antibiotic treatment during any acute otitis media episode, and we agree that topically administered hyaluronic acid should be considered as a supporting treatment, "complementary to traditional therapies" in children with recurrent disease.

Combined interventional sialendoscopy and intraductal steroid therapy for recurrent sialadenitis in Sjögren's syndrome: Results of a pilot monocentric trial.

OBJECTIVES: To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialadenitis due to Sjögren's syndrome (SS). DESIGN: A pilot therapeutic study. SETTING: ENT Clinics, Universities of Milan and Pavia. STUDY POPULATION: We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B). OUTCOMES MEASURES: The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain, the EULAR SS Disease Activity Index (ESSDAI), (iii) severity of pain by means of a 0-10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire. RESULTS: The postoperative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77-93) and 75% (95% CI: 47%-88%) in the groups A and B, respectively. The percentage of patients with glandular swelling decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the postoperative mean pain VAS (group A P<.001; group B P=.004), Xerostomia Inventory (P<.001 and P=.003) and ESSPRI scores (P<.001 and P=.008). Interventional sialendoscopy followed by outpatient intraductal steroid irrigations was more effective than interventional sialendoscopy alone, when pain VAS, Xerostomia Inventory and ESSPRI scores before and after treatment were analysed together using the multivariate Hotelling T2 test (P=.0173). CONCLUSIONS: This pilot study confirms that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis and improves the subjective sensation of oral dryness and other disease symptoms in patients with SS. The study results also suggest that the improvement is greater when interventional sialendoscopy is combined with a cycle of outpatient steroid ductal irrigations. Larger controlled randomised studies are certainly needed to confirm these preliminary data.

Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells.

Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.

Salivary lithotripsy in the era of sialendoscopy.

The traditional management of obstructive salivary disorders has been replaced by minimally-invasive gland-preserving techniques including shock-wave lithotripsy, sialendoscopy, interventional radiology and endoscopically video-assisted trans-oral and cervical stone retrieval, of which sialendoscopy is considered to be the method of first choice. Primary endoscopically controlled stone extraction without prior fragmentation is only possible in 15-20% of cases; in more than 80%, fragmentation is necessary because of the size, impactation and location of the stone, or an alternative treatment such as transoral duct surgery or combined approaches are required. Moreover, about 10-20% of all stones cannot be adequately accessed by means of a sialendoscope or any alternative surgical method and, in such cases, extra-corporeal shock wave lithotripsy (ESWL) is the treatment of choice. However, in endoscopically accessible stones, ESWL is being gradually replaced by endoscopically assisted intra-corporeal techniques, including endoscopically guided laser and pneumatic intracorporeal lithotripsy. We describe the currently most widely used techniques for salivary lithotripsy, including ESWL, and endoscopically guided laser, electrohydraulic, electrokinetic and pneumatic intra-corporeal lithotripsy, and discuss their indications given the widespread use of advanced rehabilitative sialendoscopy and combined therapeutic approaches.

Nasal cytology in children: scraping or swabbing?

Nasal cytology has become a valuable tool in the assessment of a multitude of nasal pathologies in children. Collection methods differ significantly and even though the use of the nasal curette is regarded as the most reliable in adults, most practitioners use the nasal swab in children. However, no studies have validated the reliability and supposed better tolerability of the latter. We have compared these two sampling methods regarding their tolerability and analysed the diagnostic accuracy of the cotton nasal swab (NSW) to identify nasal cytotypes and rhinitis phenotypes, using nasal scraping (NSC) for comparison. In a multicentric prospective study we recruited 208 children and performed nasal cytology by means of NSW and NSC. Microscopic evaluating of the nasal cytotypes was performed and tolerability of NSW and NSC was tested. Our data revealed a significantly inferior diagnostic accuracy of NSW compared to NSC regarding reliability and cell counts. Our study is the first to shed light on the role of the sampling tools for pediatric nasal cytology. We documented a poor diagnostic accuracy of NSW, thus suggesting using only the nasal curette in clinical practice. Furthermore, tolerability did not differ between the two, refuting the common thesis that swabs are to be preferred when doing nasal cytology in children.

The role of interventional sialendoscopy and intraductal steroid therapy in patients with recurrent sine causa sialadenitis: a prospective cross-sectional study.

OBJECTIVES: To verify the role of interventional sialendoscopy and steroidal ductal irrigation in patients with recurrent sialadenitis. DESIGN: A prospective, cross-sectional pilot study. SETTING: University of Milan. PARTICIPANTS: Fifty-four patients with sine causa recurrent sialadenitis who underwent interventional sialendoscopy (group A, 36 patients) or interventional sialendoscopy followed by a intraductal steroidal irrigations (group B, 18 patients). MAIN OUTCOMES MEASURES: The number of episodes of sialadenitis three and 6 months before and after sialendoscopy, and their severity assessed by means of a 0-10 pain visual analogue scale. RESULTS: In the population as a whole, a significant post-treatment reduction in the number of episodes of 30.7 ± 5.5 after 3 months and 34.6 ± 10.2 after 6 months (P < 0.001) and a significant reduction in pain visual analogue scale values of 4.7 ± 0.4 after 6 months (P < 0.001) occurred. There was a statistically significant reduction in both parameters at the same time points in both treatment groups (P ≥ 0.001), with no significant between-group difference in pain visual analogue scale values, an albeit non-significant trend in favour of group B in terms of the number of episodes 3 months after therapy that became significant after 6 months (11.0 ± 9.9 versus 20.5 ± 9.5; P = 0.05). CONCLUSIONS: Interventional sialendoscopy is effective for the treatment of recurrent sialadenitis; the addition of intraductal steroidal irrigations seems to increase its value in the medium term. Further studies of larger case series with longer follow-up are needed to establish the possibly primary role of steroid therapy in blocking inflammation.

Endoscopic and clinical benefits of hyaluronic acid in children with chronic adenoiditis and middle ear disease.

Hyaluronic acid (HA) is involved in modulating inflammatory airway processes and mucociliary clearance. Some studies have tested the effectiveness of the topical administration of HA in patients with upper airway diseases with positive preliminary results. A prospective, single-blind, 1:1 randomised controlled study was performed to assess the efficacy and safety of the daily topical administration of 9 mg of sodium hyaluronate in 3 mL of a 0.9 % sodium saline solution on the basis of endoscopic and clinical parameters in children with chronic adenoiditis associated with recurrent acute otitis media and otitis media with effusion; age- and gender-matched children receiving normal 0.9 % sodium chloride saline solution were used as controls. Analysis was based on 103 (mean age 63.3 ± 18.2 months; 52 males, 50.5 %) children: 54 in the study group and 49 in the control group. A statistically significant reduction in the mean number of all acute otitis media episodes (AOME) (mean reduction 0.8 ± 0.4 per month; p value 0.05) and AOME without tympanic membrane perforation (mean reduction 0.6 ± 0.3 per month; p value 0.04) after recruitment was documented only in the study group. HA significantly improved all the endoscopic outcomes (p values ranging between 0.05 and <0.01) but one. Nasal washing with saline solution was effective on only three of them (p values ranging between 0.03 and <0.01). No untoward effects were documented. Our results confirm the safety and document the positive effect of topically administered HA solution on children with chronic adenoiditis associated with middle ear disease.

Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders.

Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders.

Paediatric nasopharyngeal cytology: a new diagnostic opportunity?

The purpose of this investigation was to describe the first application of nasopharyngeal cytology (NPC), a new cytological technique to collect cellular material from the nasopharyngeal surface non-invasively in children with chronic adenoiditis associated with recurrent acute otitis media and/or otitis media with effusion. Cellular material was collected transorally using an extra-thin flexible wire nasopharyngeal swab and then examined under a light microscope. The diagnostic accuracy of NPC in detecting the presence of allergy and pathogens (compared to microbiological evaluation of nasopharyngeal aspirates, NPAs) was assessed. NPC was performed on 121 children (mean age 69.4 ± 15.5 months). Inflammatory cells and pathogens were detected in 61.1 % and 44.2 % of patients, respectively. The specificity of nasopharyngeal eosinophils in detecting allergy was good (91.9 %), as was the specificity of mast cells, but the sensitivities were less. The NPAs revealed bacterial colonisation in 84.7 % of the patients, and Streptococcus pneumoniae was the most frequently isolated (60.0 %). NPC revealed the presence of bacteria in 94.9 % of patients, including bacillary species in 33.9 %. NPC was highly sensitive in detecting pathogens (96.0 %). Its specificity in detecting bacillary species was fairly good (75.0 %), but the corresponding values of the specificity of NPC in detecting pathogens and its sensitivity in detecting bacillary species were poor. Our findings suggest the need for more structured studies that can test the real effectiveness and usefulness of NPC in defining nasopharyngeal cytological patterns in children with chronic nasopharyngeal diseases by comparing it with established diagnostic techniques.

Nasal nitric oxide in children with recurrent acute otitis media.

Recently, reduced Nasal nitric oxide (nNO) nNO levels have been reported in children with adenoidal hypertrophy predisposing to chronic nasosinusal inflammation. Given the strict anatomic and physiopathologic link between the nasopharyngeal and middle ear compartments, and considering the high prevalence of otitis prone children among those affected with chronic adenoiditis, we designed a study aimed to test any possible difference in nNO levels between non-allergic children with and without recurrent acute otitis media (RAOM) associated with chronic adenoiditis. The study involved 54 children with RAOM (44.4% males; mean age= 7.5±3.5 years) and 51 children without RAOM (47.4% males; mean age= 7.0±3.8 years). nNO levels were significantly reduced in children with RAOM compared to children without RAOM (676.9±250.7 ppb vs 831.8±320.4 ppb, respectively; p= 0.02). Our results could be related to reduced NO production by the ciliated paranasal, nasopharyngeal and middle ear epithelium and the impaired sinusal ostial and Eustachian tube patency due to chronic inflammation, and seem to confirm the involvement of NO pathway in recurrent upper airway infections related to impaired ciliated respiratory mucosa.

Sialendoscopy-assisted transfacial surgery for the removal of an iatrogenic foreign body in Stensen's duct: a stone and broken wire basket.

BACKGROUND: A foreign body is a rare cause of parotid gland obstructive sialadenitis; intra-oral penetration via Stensen's duct is unusual. The relatively recent introduction of interventional sialendoscopy to treat obstructive sialadenitis has allowed surgeons to adopt a gland-sparing approach by means of miniaturised endoscopes and instruments. However, unusual anatomy or pathological conditions can give rise to a risk of intraductal rupture that may lead to a subsequent iatrogenic foreign body. CASE REPORT: This paper describes the case of a patient with a 4 mm stone engaged by a broken wire basket stuck in a secondary branch of Stensen's duct. RESULTS: The iatrogenic foreign body was successfully retrieved by means of sialendoscopy-assisted transfacial surgery. CONCLUSION: This is the first reported case of an intraductal rupture of a miniaturised device during interventional sialendoscopy successfully resolved by means of combined endoscopy and external surgery. This proved to be an effective method of rescuing a foreign body stuck in Stensen's duct.

Combined effect of genetic variants in the GluN2B coding gene (GRIN2B) on prefrontal function during working memory performance.

BACKGROUND: The GluN2B subunit of N-methyl-d-aspartate receptors is crucially involved in the physiology of the prefrontal cortex during working memory (WM). Consistently, genetic variants in the GluN2B coding gene (GRIN2B) have been associated with cognitive phenotypes. However, it is unclear how GRIN2B genetic variation affects gene expression and prefrontal cognitive processing. Using a composite score, we tested the combined effect of GRIN2B variants on prefrontal activity during WM performance in healthy subjects. METHOD: We computed a composite score to combine the effects of single nucleotide polymorphisms on post-mortem prefrontal GRIN2B mRNA expression. We then computed the composite score in independent samples of healthy participants in a peripheral blood expression study (n = 46), in a WM behavioural study (n = 116) and in a WM functional magnetic resonance imaging study (n = 122). RESULTS: Five polymorphisms were associated with GRIN2B expression: rs2160517, rs219931, rs11055792, rs17833967 and rs12814951 (all corrected p < 0.05). The score computed to account for their combined effect reliably indexed gene expression. GRIN2B composite score correlated negatively with intelligence quotient, WM behavioural efficiency and dorsolateral prefrontal cortex activity. Moreover, there was a non-linear association between GRIN2B genetic score and prefrontal activity, i.e. both high and low putative genetic score levels were associated with high blood oxygen level-dependent signals in the prefrontal cortex. CONCLUSIONS: Multiple genetic variants in GRIN2B are jointly associated with gene expression, prefrontal function and behaviour during WM. These results support the role of GRIN2B genetic variants in WM prefrontal activity in human adults.

The presence of biofilm-producing bacteria on tonsils is associated with increased exhaled nitric oxide levels: preliminary data in children who experience recurrent exacerbations of chronic tonsillitis.

BACKGROUND: It has been suggested that bacterial biofilms may be a causative factor in the aetiopathogenesis of chronic tonsillitis. Involvement of exhaled nitric oxide has been previously considered, with conflicting findings. OBJECTIVE: A pilot study was performed to investigate the relationship between exhaled nitric oxide levels and the presence of tonsillar biofilm-producing bacteria in children with chronic tonsillitis. METHOD: Tonsillar biofilm-producing bacteria on bioptic specimens taken during tonsillectomy were assessed by means of spectrophotometry. RESULTS: Analysis was based on 24 children aged 5-10 years (median, 7.5 years). Biofilm-producing bacteria were found in 40.9 per cent of specimens. The median exhaled nitric oxide level was 11.6 ppb (range, 3.2-22.3 ppb). There was a significant relationship between the presence of biofilm-producing bacteria and increased exhaled nitric oxide levels (p = 0.03). Children with exhaled nitric oxide levels of more than 8 ppb were at three times greater risk of developing tonsillar biofilm-producing bacteria than those with lower levels. CONCLUSION: Our findings suggest the possibility of discriminating children with chronic biofilm-sustained tonsillar infections on the basis of exhaled nitric oxide levels.

Serum 25-hydroxyvitamin D levels in children with recurrent tonsillitis living in Milan.

Involvement of 25-hydroxyvitamin D in the etiopathogenesis of tonsillar disease in children is still debated; this study assesses possible differences in serum 25-hydroxyvitamin D levels between 309 Caucasian children (58.1% males; mean age 55.7 ± 31.0 months) living in Milan with a history of recurrent tonsillitis (RT) and healthy controls. Mean serum 25(OH)D levels were significantly reduced in the children with a history of RT (22.0 ± 8.7 ng/mL vs 24.6 ± 7.8 ng/mL; p=0.03), and the proportion of children with insufficient or deficient serum 25(OH)D levels was higher in the RT group (81.5% and 6.5% respectively) than in the control group (75.1% and 3.5%) (not significant). The multivariable model created to test the independent association between serum 25(OH)D levels and a history of RT after adjusting for age and season showed that the association was not significant. Our study failed to find any significant reduction in serum 25(OH)D levels after adjustment for age and season in a case series of children with RT in comparison with healthy controls, which suggests that vitamin D does not play a relevant role in the etiology of pediatric tonsillar infections.

Airborne nitric oxide and nasal cytology in patients with chronic rhinosinusitis and nasal polyps.

Nitric oxide (NO) is involved in eosinophilic inflammation. The fraction of exhaled nitric oxide (FENO) is increased in chronic rhinosinutis with nasal polyps (CRSwNP), whereas nasal NO (nNO) is reduced in chronic rhinosinutis. Nasal cytology can detect eosinophilic inflammation in CRSwNP. We aimed to describe the baseline rhinocytological characteristics and NO (FENO and nNO) levels in patients with CRSwNP, and assess their possible correlations. This longitudinal study involved 37 consecutive adult outpatients with CRSwNP and 36 healthy controls. They underwent a complete clinical otolaryngological assessment, measurement of FENO and nNO levels, and nasal scraping in order to collect material for nasal cytology. Disease severity was evaluated by means of endoscopic and Lund-Mackay radiological scores. Median FENO level was higher (p less than 0.001) in CRSwNP (28.3 ppb, 95%CI 13.0-33.6 ppb) than in the controls (7.5 ppb, 95%CI 6.1-8.9 ppb). Median nNO levels were lower (255.7, 95%CI 199.7-311.6 vs 385.5, 95%CI 345.0-425.9 ppb; p less than 0.001), and were lower in the patients with severe endoscopic obstruction (p=0.05). Lund-Mackay scores positively correlated with median FENO levels (R=0.11; p=0.05), and inversely with median nNO levels (R=-0.31; p=0.04). Metachromatic nasal cytotypes were more prevalent among CRSwNP patients who had previously undergone surgery (p=0.05). The number of metachromatic elements in the patients with CRSwNP positively correlated with their median FENO levels (R=0.24; p=0.002). Our results confirm the dynamic interplay between the upper and lower airways in patients with CRSwNP. FENO/nNO and nasal cytology can be useful for detecting and monitoring nasal inflammation in CRSwNP.