Nasal airway obstruction in patients with cleft lip nasal deformity: A systematic review.

BACKGROUND: Cleft lip nasal deformity (CLND)-associated nasal airway obstruction (CL-NAO) may be inadequately characterized, with its functional implications subsequently underappreciated and neglected. The purpose of this systematic review is to (1) summarize the available assessment results in CL-NAO, (2) evaluate the reliability of current assessment tools, and (3) identify ongoing gaps and inconsistencies for future study. METHODS: A systematic search of the MEDLINE, EMBASE, and Scopus databases was performed for articles studying CL-NAO. Articles focusing on noncleft populations or surgical techniques were excluded. Extracted data included information about study design, patient demographics, medical history, and assessment scores. RESULTS: Twenty-six articles met criteria for inclusion. Assessments included patient-reported outcome measures (PROMs), anatomic characterizations of CLND, and nasal airflow and resistance studies. Objective assessments were generally more reliable than subjective assessments in CLND. Unilateral CLND was better represented in the literature than bilateral CLND. For unilateral CLND, the cleft side was more obstructed than the noncleft side, with stereotyped patterns of anterior nasal deformity but varied middle and posterior deformity patterns. Overall, there was considerable heterogeneity in study design regarding stratification of CLND cohorts by age, cleft phenotype and laterality, and surgical history. CONCLUSIONS: A wide range of subjective and objective assessment tools were used to characterize CL-NAO, including PROMs, anatomic measurements, and airflow and resistance metrics. Overall, objective assessments of CL-NAO were more reliable than subjective surveys, which may have resulted from variable expectations regarding nasal patency in the CLND population combined with large heterogeneity in study design.

Characterizing Olfactory Dysfunction in Patients with Unilateral Cleft Lip Nasal Deformities.

Background: Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood. Objective: To investigate the etiology of uCLND-associated olfactory dysfunction using clinical, computational, and histologic assessments. Methods: Inclusion criteria: uCLND patients >16 years undergoing septorhinoplasty. Exclusion criteria: prior septoplasty or rhinoplasty, pregnancy, sinusitis. Measured outcomes: patient-reported scores, rhinomanometry, smell identification and threshold tests, computational fluid dynamics (CFD) airflow simulations, and histologic analysis of olfactory epithelium. Results: Five uCLND subjects were included: 18-23 years, three male and two female, four left-sided cleft and one right-sided cleft. All subjects reported moderate to severe nasal obstruction. Smell identification and threshold tests showed varying degrees of hyposmia. Nasal resistance was higher on the cleft side versus noncleft side measured by rhinomanometry (median 3.85 Pa-s/mL, interquartile range [IQR] = 21.96, versus 0.90 Pa-s/mL, IQR = 5.17) and CFD (median 1.04 Pa-s/mL, IQR = 0.94 vs. 0.11 Pa-s/mL, IQR = 0.12). Unilateral olfaction varied widely and was dependent on unilateral percentage olfactory airflow. Biopsies revealed intact olfactory neuroepithelium. Conclusions: uCLND-associated olfactory dysfunction appears to be primarily conductive in etiology and highly susceptible to variations in nasal anatomy. Clinical Trial Registration number: NCT04150783.

Intranasal Spray Characteristics for Best Drug Delivery in Patients With Chronic Rhinosinusitis.

OBJECTIVES: To determine parameter combinations for effective drug delivery of intranasal spray steroids to the ostiomeatal complex (OMC) and maxillary sinus (MS) in patients with chronic rhinosinusitis (CRS). METHODS: Each patient's sinonasal cavity was reconstructed from computed tomography scans. Intranasal airflow and drug particle transport were simulated using computational fluid dynamic modeling. Airflow simulations were performed at 15 Pascal inhalation pressure. Intranasal spray particles of 1-100 µm were simulated at release speeds of 1, 5, and 10 m/s from 6 release locations (Bottom, Center, Top, Lateral, Lateral-Bottom, and Lateral-Top) at a nozzle insertion depth of 15 mm. Drug delivery simulations were performed in the head tilted forward position. RESULTS: Maximal OMC deposition was 0.78%-12.44%, while maximal MS deposition was 0.02%-1.03% across all simulations. In general, particles between 6 and 10 µm had the best OMC (at 1 m/s particle velocity) and MS (at 10 m/s particle velocity) deposition. Particles ranging from 21 to 30 µm also had superior OMC deposition. The lateral and lateral-top spray release locations produced maximum OMC deposition, but no one release location demonstrated an increase in MS deposition. CONCLUSION: This preliminary study suggests that it is challenging to determine a common set of intranasal spray parameter combinations for effective drug delivery to the OMC and MSs. Although drug particle size and spray particle velocity seem to impact particle deposition patterns, spray release location appears to vary with anatomical differences between subjects, particularly when the MS is the target location for particle deposition. Laryngoscope, 133:1036-1043, 2023.

Analyses on the influence of normal nasal morphological variations on odorant transport to the olfactory cleft.

OBJECTIVE: Olfaction requires a combination of sensorineural components and conductive components, but conductive mechanisms have not typically received much attention. This study investigates the role of normal nasal vestibule morphological variations in ten healthy subjects on odorant flux in the olfactory cleft. MATERIALS AND METHODS: Computed tomography images were used to create subject-specific nasal models. Each subject's unilateral nasal cavity was classified according to its nasal vestibule shape as Standard or Notched. Inspiratory airflow simulations were performed at 15 L/min, simulating resting inspiration using computational fluid dynamics modeling. Odorant transport simulations for three odorants (limonene, 2,4-dinitrotoluene, and acetaldehyde) were then performed at concentrations of 200 ppm for limonene and acetaldehyde, and 0.2 ppm for dinitrotoluene. Olfactory cleft odorant flux was computed for each simulation. RESULTS AND DISCUSSION AND CONCLUSION: Simulated results showed airflow in the olfactory cleft was greater in the Standard phenotype compared to the Notched phenotype. For Standard, median airflow was greatest in the anterior region (0.5006 L/min) and lowest in the posterior region (0.1009 L/min). Median airflow in Notched was greatest in the medial region (0.3267 L/min) and lowest in the posterior region (0.0756 L/min). Median olfactory odorant flux for acetaldehyde and limonene was greater in Standard (Acetaldehyde: Standard = 140.45 pg/cm2-s; Notched = 122.20 pg/cm2-s. Limonene: Standard = 0.67 pg/cm2-s; Notched = 0.65 pg/cm2-s). Median dinitrotoluene flux was greater in Notched (Standard = 2.86 × 10-4pg/cm2-s; Notched = 4.29 × 10-4 pg/cm2-s). The impact of nasal vestibule morphological variations on odorant flux at the olfactory cleft may have implications on individual differences in olfaction, which should be investigated further.

A systematic analysis of surgical interventions for the airway in the mature unilateral cleft lip nasal deformity: a single case study.

PURPOSE: Individuals with unilateral cleft lip nasal deformity (uCLND) often require rhinoplasty in adolescence to correct nasal obstruction. The intent of this study is to identify sites of greatest nasal obstruction and evaluate the effects of isolated and combinations of simulated surgical procedures on these sites using computational fluid dynamics (CFD). METHODS: Computed tomography imaging of an adolescent subject with uCLND was converted to an anatomically accurate three-dimensional nasal airway model. Initial analysis was performed to identify anatomic sites of obstruction based on CFD computed resistance values. Virtual surgery procedures corresponding to common uCLND surgical interventions were simulated. Resulting airspace models were then analyzed after conducting airflow and heat transfer simulations. RESULTS: The preoperative model had 21 obstructed sites with a nasal resistance of 0.075 Pa s/mL. Following simulated surgical procedures with functional interventions alone and in combinations, the three virtual surgery models with most improved nasal airflow were inferior turbinate reduction (ITR) with posterior septoplasty (resistance = 0.054 Pa s/ml, reduction in 14 of 21 obstructed sites), ITR with anterior septoplasty (resistance = 0.058 Pa s/ml, reduction in 8 of 21 obstructed sites), and ITR with both anterior and posterior septoplasty (resistance = 0.052 Pa s/ml, reduction in 17 of 21 obstructed sites). CONCLUSION: This study introduces a new technique for analysis of the impact of different simulated surgical interventions on uCLND-induced nasal obstruction. In this subject, simulated septoplasty with ITR on the non-cleft side provided maximal relief of nasal obstruction. The proposed technique can be further studied for possible utility in analyzing potential surgical interventions for optimal relief of nasal obstruction in patients with uCLND.

The role of normal nasal morphological variations from race and gender differences on respiratory physiology.

This study identifies anatomical and airflow-induced relationships based on nasal morphological variations due to inter- and intra-racial differences and gender. Subject-specific nasal airway reconstruction was created from computed tomography images in 16 subjects: 4 subjects from each ethnic group (Black, East Asian, Caucasian, and Latino) comprising of 2 males and 2 females. Volume, surface area and nasal index were calculated, as well as airflow rate and nasal resistance after computational fluid dynamics simulations in the nasal airway. Results showed that nasal airspace surface area (p = 0.0499) and volume (p = 0.0281) were significantly greater in males than in females. Nasal volume was greatest in East Asians (Median = 20.38cm3, Interquartile Range [IQR] = 4.58 cm3), Latinos had the greatest surface area (Median = 219.70cm2, IQR = 29.56cm2). On average, East Asian and Black females had larger nasal index than their male counterparts. Caucasians had the highest median nasal resistance (0.050 Pa.s/mL, IQR = 0.025 Pa.s/mL). Results indicate that there exist anatomical variabilities based on race and gender. However, these variabilities may not significantly influence nasal function.

Computational Analysis of Olfactory Airspace in Patients With Unilateral Cleft Lip Nasal Deformity.

OBJECTIVES: To evaluate the magnitude of olfactory recess opacity in patients with unilateral cleft lip nasal deformity (uCLND). DESIGN: Subject-specific 3-dimensional reconstruction of the nasal airway anatomy was created from computed tomography images in 11 (4 males and 7 females) subjects with uCLND and 7 (3 males, and 4 females) normal subjects. The volume and surface area of each subject's unilateral and bilateral olfactory airspace was quantified to assess the impact of opacification. Qualitatively speaking, patients with 75% to 100% olfactory recess opacification were classified as extreme, 50% to 75% as severe, 25% to 50% as moderate, and 0% to 25% as mild. RESULTS: Of the 11 subjects with uCLND, 5 (45%) were classified as having extreme olfactory recess opacification, 3 (27%) subjects had severe opacification, and 3 (27%) subjects had moderate opacification. Mean (±SD) bilateral olfactory recess volume was significantly greater in normal subjects than in subjects with uCLND (0.9668 cm3 ± 0.4061 cm3 vs 0.3426 cm3 ± 0.1316 cm3; P < .001). Furthermore, unilateral olfactory airspace volumes for the cleft and non-cleft sides in subjects with uCLND were considerably less than unilateral olfactory volume in subjects with normal anatomy (uCLND cleft side = 0.1623 cm3 ± 0.0933 cm3; uCLND non-cleft side = 0.1803 cm3 ± 0.0938 cm3; normal = 0.4834 cm3 ± 0.2328 cm3; P < .001). CONCLUSIONS: Our findings indicate a high prevalence of olfactory recess opacification among subjects with uCLND when compared to subjects with normal anatomy. The majority of subjects with uCLND had extreme olfactory recess opacity, which will likely influence their sense of smell.

Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema.

INTRODUCTION: Non-exudative (dry) age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss worldwide. Besides age-related eye disease study (AREDS) vitamin supplements, there are no efficacious pharmaceutical interventions for dry AMD available. While numerous pharmacologics are available to treat diabetic macular edema (DME), many patients respond suboptimally to existing therapies. Risuteganib is a novel anti-integrin peptide that targets the multiple integrin heterodimers involved in the pathophysiology of dry AMD and DME. Inhibiting these selected integrin heterodimers may benefit patients with these conditions. AREAS COVERED: This article offers a brief overview of current pharmaceuticals available for dry AMD and DME. The proposed role of integrins in AMD and DME is reviewed and later, risuteganib, a novel anti-integrin peptide is introduced. The data from initial Phase 1 and Phase 2 risuteganib clinical trials are discussed in the latter part of the paper. EXPERT OPINION: While there are currently limited treatment options for dry AMD, more data are needed before we can truly evaluate the benefits of adopting risuteganib into the clinic. Conversely, several effective treatment options exist for DME; hence, risuteganib must show that it can add to these results, especially in those with refractory disease, before retina specialists adopt risuteganib into their treatment regimens.