Computational fluid dynamic analysis of aggressive turbinate reductions: is it a culprit of empty nose syndrome?

BACKGROUND: Empty nose syndrome (ENS) remains highly controversial, with aggressive inferior turbinate reduction (ITR) or mucociliary dysfunction frequently implicated. However, the appropriate degree of ITR is highly debatable. METHODS: We applied individual computed tomography (CT)-based computational fluid dynamics (CFD) to 5 patients receiving relatively aggressive ITR but with no ENS symptoms, and compared them to 27 symptomatic ENS patients who all had histories of aggressive ITRs, and 42 healthy controls. Patients' surgical outcomes were confirmed with 22-item Sino-Nasal Outcome Test (SNOT-22) (ITR: 6.40 ± 4.56; ENS: 58.2 ± 15.9; healthy: 13.2 ± 14.9), Nasal Obstruction Symptom Evaluation (NOSE) scores (ITR: 4.00 ± 2.24; ENS: 69.4 ± 17.1; healthy: 11.9 ± 12.9), and Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) (≥11 for ENS). RESULTS: Both aggressive ITR without ENS symptoms and symptomatic ENS patients had significantly lower nasal resistance (ITR: 0.059 ± 0.020 Pa·s/mL; ENS: 0.052 ± 0.015 Pa·s/mL; healthy: 0.070 ± 0.021 Pa·s/mL) and higher cross-sectional areas surrounding the inferior turbinate (ITR: 0.94 ± 0.21 cm2 ; ENS: 1.19 ± 1.05 cm2 ; healthy: 0.42 ± 0.22 cm2 ) than healthy controls. The lack of significant differences among patient groups indicated similar degrees of surgeries between ITR with and without ENS symptom cohorts. However, symptomatic ENS patients have paradoxical significantly less airflow in the inferior meatus (ITR: 47.7% ± 23.6%; ENS: 25.8% ± 17.6%; healthy: 36.5 ± 15.9%; both p < 0.01), but higher airflow around the middle meatus (ITR: 49.7% ± 22.6%; ENS: 66.5% ± 18.3%; healthy: 49.9% ± 15.1%, p < 0.0001) than aggressive ITR without symptoms and controls. Aggressive ITR patients have increased inferior meatus airflow as expected (p < 0.05). This imbalanced airflow produced less inferior wall-shear-stress distribution among symptomatic ENS patients only (ITR: 42.45% ± 11.4%; ENS: 32.2% ± 12.6%; healthy: 49.7% ± 9.9%). ENS patients (n = 12) also had impaired nasal trigeminal function, as measured by menthol lateralization detection thresholds (ITR: 15.2 ± 1.2; ENS: 10.3 ± 3.9; healthy: 13.8 ± 3.09, both p < 0.0001). Surprisingly, aggressive ITR patients without ENS symptoms have better menthol lateralization detection thresholds (LDTs) than healthy controls. CONCLUSION: Although turbinate tissue loss is linked with ENS, the degree of ITR that might distinguish postoperative patient satisfaction in their nasal breathing vs development of ENS symptoms is unclear. Our results suggest that a combination of distorted nasal aerodynamics and loss of mucosal sensory function may potentially lead to ENS symptomology.

Asymptomatic vs symptomatic septal perforations: a computational fluid dynamics examination.

BACKGROUND: A nasal septal perforation (NSP) can lead to frustrating symptoms for some patients while remaining completely asymptomatic for others, without a clear mechanism differentiating them. METHODS: We applied individual computed tomography (CT)-based computational fluid dynamics (CFD) to examine the nasal aerodynamics differences between 5 asymptomatic and 15 symptomatic NSP patients. Patients' symptoms were confirmed through interviews, 22-item Sino-Nasal Outcome Test score (asymptomatic, 25 ± 18.8; symptomatic, 53.7 ± 18.2), nasal obstruction symptom evaluation score (asymptomatic, 28.0 ± 32.1; symptomatic, 62.2 ± 32.2), and review of medical history. RESULTS: No statistical differences were found in perforation location, size (asymptomatic, 1.94 ± 1.88 cm2 ; symptomatic, 1.36 ± 1.44 cm2 ), nasal resistance (asymptomatic, 0.059 ± 0.012 Pa·s/mL; symptomatic, 0.063 ± 0.022 Pa·s/mL), and computed flow rate shunting across the perforation (asymptomatic, 52.9 ± 30.9 mL/s; symptomatic, 27.4 ± 23.6 mL/s; p > 0.05). However, symptomatic patients had significantly higher wall shear stress (WSS) and heat flux, especially along the posterior perforation margin (WSS, 0.54 ± 0.12 vs 1.15 ± 0.49 Pa, p < 0.001; heat flux, 0.21 ± 0.05 vs 0.37 ± 0.14 W/cm2 , p < 0.01). A WSS cutoff at 0.72 Pa can separate asymptomatic vs symptomatic NSP with 87% sensitivity and 100% specificity. Flow visualization showed flow peaks toward the posterior margin that may be responsible for the high WSS and heat flux among symptomatic NSPs. CONCLUSION: This study is the first CFD examination of asymptomatic and symptomatic NSP with regional aerodynamics and stress abnormalities, beyond size or location, being implicated as the mechanism behind the symptomology of NSP. This finding could serve as an objective basis for future personalized treatment decisions and optimization.

Investigation of the abnormal nasal aerodynamics and trigeminal functions among empty nose syndrome patients.

BACKGROUND: Abnormal nasal aerodynamics or trigeminal functions have been frequently implicated in the symptomology of empty nose syndrome (ENS), yet with limited evidence. METHODS: Individual computed tomography (CT)-based computational fluid dynamics (CFD) was applied to 27 ENS patients to simulate their nasal aerodynamics and compared with 42 healthy controls. Patients' symptoms were confirmed with Empty Nose Syndrome 6-item Questionnaire (ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22), and Nasal Obstruction Symptom Evaluation (NOSE) scores. Nasal trigeminal sensitivity was measured with menthol lateralization detection thresholds (LDTs). RESULTS: ENS patients had significantly lower (∼25.7%) nasal resistance and higher (∼2.8 times) cross-sectional areas compared to healthy controls (both p < 0.001). Despite inferior turbinate reductions, CFD analysis demonstrated that ENS patients had increased airflow concentrated in the middle meatus region (66.5% ± 18.3%) compared to healthy controls (49.9% ± 15.1%, p < 0.0001). Significantly less airflow (25.8% ± 17.6%) and lower peak wall shear stress (WSS) (0.58 ± 0.24 Pa) were found in the inferior meatus (vs healthy: 36.5% ± 15.9%; 1.18 ± 0.81 Pa, both p < 0.05), with the latter significantly correlated with the symptom scores of ENS6Q (r = -0.398, p = 0.003). Item-wise, complaints of "suffocation" and "nose feels too open" were also found to be significantly correlated with peak WSS around the inferior turbinate (r = -0.295, p = 0.031; and r = -0.388, p = 0.004, respectively). These correlations were all negative, indicating that less air-mucosal stimulations resulted in worse symptom scores. ENS patients (n = 12) also had impaired menthol LDT when compared to healthy controls (p < 0.0001). CONCLUSION: This is the first CFD examination of nasal aerodynamics in a large cohort of ENS patients. The results indicated that a combination of loss of neural sensitivity and poorer inferior air-mucosal stimulation may potentially lead to ENS symptomology.

Computational fluid dynamics evaluation of posterior septectomy as a viable treatment option for large septal perforations.

BACKGROUND: Numerous surgical techniques exist to treat nasal septal perforation (NSP). The surgical closure of large NSPs (>2 cm) is still challenging. Posterior septectomy has been reported as a simple alternative to treat large NSP, yet its mechanisms for symptom relief are not clear, and if failed, its consequence cannot be easily reversed. METHODS: Ten NSP patients were recruited: 5 underwent posterior septectomy and 5 underwent conventional flap or button repair. Computational fluid dynamics (CFD) simulated the nasal aerodynamics based on computed tomography (CT) scans. All patients had preoperative CT; however, only 4 had postoperative CT: 2 underwent posterior septectomy and the other 2 underwent flap repair. We examined surgical outcomes and the nasal airflow features among the 2 treatment options. RESULTS: Both groups of patients had good outcomes based on chart review. Patients undergoing septectomy had significantly larger perforation size (2.32 ± 0.87 vs 1.21 ± 0.60 cm), higher flow rate across the perforation (47.8 ± 28.6 vs 18.3 ± 12.2 mL/second), and higher wall shear stress (WSS) along the posterior perforation margin (1.39 ± 0.52 vs 1.15 ± 0.58 Pa). The posterior WSS significantly correlated with crossover flow velocity (r = 0.77, p = 0.009) and was reduced by almost 67% postseptectomy, and by 29% postrepair. CONCLUSION: This is the first CFD analysis on an NSP patient cohort. NSP resulted in flow disturbance and increased WSS that potentially led to symptomatology. The removal of high stress points along the posterior margin may explain why posterior septectomy can be an effective treatment option. Aerodynamic abnormalities, in addition to perforation size and location, could serve as basis for future treatment decisions.

Computational fluid dynamics and trigeminal sensory examinations of empty nose syndrome patients.

OBJECTIVE: The precise pathogenesis of empty nose syndrome (ENS) remains unclear. Various factors such as nasal aerodynamics and sensorineural dysfunction have been suspected, although evidence is limited. This study reported the first examination of both nasal aerodynamics and trigeminal sensory factors in actual ENS patients. STUDY DESIGN: Prospective case control. METHODS: We enrolled six patients diagnosed with ENS. Three patients had pre- and post-inferior turbinate (IT) reduction computed tomography scans, which allowed comparison of their nasal aerodynamics changes through computational fluid dynamic (CFD) simulation. Their symptoms were confirmed through Sino-nasal Outcome Test-22, ENS 6-item Questionnaire, acoustic rhinometry, and rhinomanometry findings. Nasal trigeminal sensitivity that potentially mediates their perception of airflow was assessed via menthol lateralization detection thresholds (LDT) and compared with 14 healthy controls. RESULTS: Post-surgical reductions in nasal resistance were observed and significantly lower than normal (P < 0.05). Computational fluid dynamic analysis showed that, paradoxically for all ENS patients, IT reduction did not draw more airflow to the airway surrounding the ITs, but rather resulted in nasal airflow forming into a narrow jet toward the middle meatus region, leaving the airway surrounding the IT with significantly reduced airflow intensity and air-mucosal interactions (inferior region flow percentage reduced from 35.7% ± 15.9% to post-surgery 17.7% ± 15.7%, P < 0.05; inferior wall-shear-stress reduced from 7.5 ± 4.2 × 10-2 Pa to 3.4 ± 3.1 × 10-2 Pa, P < 0.01). Empty nose syndrome patients also had significantly impaired menthol LDT compared to healthy controls (P < 0.005). CONCLUSION: The results indicated that a combinatory of factors, including paradoxically distorted nasal aerodynamic, impaired sensorineural sensitivity, and potential predisposing conditions, may contribute to the development of ENS. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:E176-E184, 2017.

Correction of aberrant NADPH oxidase activity in blood-derived mononuclear cells from type II diabetes mellitus patients by a naturally fermented papaya preparation.

UNLABELLED: Supplementation of standardized fermented papaya preparation (FPP) to adult diabetic mice improves dermal wound healing outcomes. Peripheral blood mononuclear cells (PBMC) from type II diabetes mellitus (T2DM) patients elicit a compromised respiratory burst activity resulting in increased risk of infections for the diabetic patients. AIMS: The objectives of the current study were to determine the effect of FPP supplementation on human diabetic PBMC respiratory burst activity and to understand underlying mechanisms of such action of FPP. RESULTS: When stimulated with phorbol 12-myristate 13-acetate, the production of reactive oxygen species by T2DM PBMC was markedly compromised compared to that of the PBMC from non-DM donors. FPP treated ex vivo improved respiratory burst outcomes in T2DM PBMC. FPP treatment significantly increased phosphorylation of the p47phox subunit of NADPH oxidase. In addition, the protein and mRNA expression of Rac2 was potently upregulated after FPP supplemention. The proximal human Rac2 gene promoter is G-C rich and contains consensus binding sites for Sp1 and AP-1. While FPP had no significant effect on the AP-1 DNA binding activity, the Sp1 DNA binding activity was significantly upregulated in PBMC after treatment of the cells with FPP. INNOVATION: This work provided first evidence that compromised respiratory burst performance of T2DM PBMC may be corrected by a nutritional supplement. CONCLUSION: FPP can correct respiratory burst performance of T2DM PBMC via an Sp-1-dependant pathway. Studies testing the outcome of FPP supplementation in diabetic patients are warranted.