About

Nithin Adappa, M.D., is a Professor of Otorhinolaryngology: Head and Neck Surgery at the Hospital of the University of Pennsylvania. He has been on faculty at the University of Pennsylvania since 2010, specializing in rhinology and skull base surgery. Dr. Adappa serves as the co-fellowship director of the Rhinology and Skull Base Surgery Fellowship and is the Surgical Director of the AERD center. His clinical expertise includes revision sinus surgery, treatment of sinus cancers, endoscopic CSF leak repairs, and collaboration with neurosurgery on endoscopic anterior cranial base tumor resection, including pituitary tumors, craniopharyngiomas, Rathke's cleft cysts, and meningiomas. He is also involved in academic publishing as an associate editor of the 'Atlas of Endoscopic Sinus and Skull Base Surgery' and has authored over 70 peer-reviewed papers. His research focuses on the management of chronic rhinosinusitis, sinonasal tumors, and the genetic and immunological factors influencing upper respiratory health, including the role of taste receptor polymorphisms in disease susceptibility.

Research topics

• Medicine
• Surgery
• Internal medicine
• Biology
• Radiology

Selected publications

• Post‐Operative Surveillance After Resection of Uncommon Benign Sinonasal Tumors: A Multi‐Institutional Review

  International Forum of Allergy & Rhinology · 2025-11-10

  reviewOpen access

  Beyond the most common types of benign sinonasal tumors, such as osteoma or papilloma, there is a range of rarer benign neoplasms that are less well-understood in terms of behavior and optimal management [1]. These tumors may arise from mesenchymal, vascular, or neural, among other tissues, and are heterogeneous in pathology within categories [2]. The literature currently lacks comprehensive guidance on management and post-operative surveillance for these rare tumors. In this multi-institutional study, we report our outcomes following endoscopic gross total resection (GTR) of rare benign sinonasal tumors and offer guidance on optimal surveillance strategies. A retrospective chart review was conducted of patients with benign sinonasal tumors undergoing GTR at the University of Pennsylvania, Massachusetts Eye and Ear, University of California-Irvine, and Henry Ford Health System from January 2010 to January 2025. Patients with malignancy, inverted papilloma, osteoma, or juvenile angiofibroma were excluded. Only patients undergoing GTR via the endoscopic approach with at least 6 months of postoperative follow-up were included. Basic demographic information and relevant clinical features were collected, including pathology, recurrence rate, frequency of surveillance visits, and modality of post-operative surveillance—endoscopy, magnetic resonance imaging (MRI), or computed tomography (CT). Surveillance visits were defined as post-operative visits, excluding debridements or “sick visits.” Tumors were categorized according to the 2024 International Consensus Statement on Sinonasal Tumors [1] recommendations and WHO classification [2]. A total of 47 patients were included in the analysis, with tumors categorized as mesenchymal (n = 20, 42.5%), vascular (n = 17, 36.2%), or neural (n = 10, 21.3%). Mesenchymal tumors included solitary fibrous tumor (SFT; n = 8), angioleiomyoma (n = 3), pleomorphic adenoma (n = 3), fibrous dysplasia (n = 2), inflammatory myofibroblastic tumor (n = 1), ossifying fibroma (n = 1), chondroma (n = 1), and lipoma (n = 1). Vascular tumors comprised lobular capillary hemangioma (LCH; n = 8), hemangioma unspecified (n = 3), cavernous hemangioma (n = 3), intraosseous hemangioma (n = 2), and arteriovenous malformation (AVM; n = 1). Neural tumors consisted exclusively of schwannomas. Mean follow-up duration was 24.1 months with a median of 17.8 months (Table 1). By category, the mean follow-up was 26.3 months for mesenchymal, 18.0 months for vascular, and 30.2 months for neural tumors. The average number of postoperative visits in the first year was 2.7, with similar means across categories: mesenchymal (2.6), vascular (2.9), and neural (2.6). In the second year, the average number of visits was 1.1 overall, with little variation across tumor types: mesenchymal (1.1), vascular (1.2), and neural (1.1). Surveillance modalities varied by tumor category (Table 2). For mesenchymal tumors, the most common surveillance approach was endoscopy alone (n = 15, 75.0%), followed by MRI with endoscopy (n = 3, 15.0%) and CT with endoscopy (n = 2, 10.0%). Among vascular tumors, endoscopy alone was also most frequently used (n = 10, 58.8%), followed by CT with endoscopy (n = 4, 23.5%), MRI with endoscopy (n = 1, 5.9%), and CT with MRI and endoscopy (n = 2, 11.8%). In neural tumors, the predominant modality was MRI with endoscopy (n = 6, 60.0%), followed by endoscopy alone (n = 3, 30.0%) and CT with MRI and endoscopy (n = 1, 10.0%). Mean follow-up (SD), months MRI+ endoscopy Inflammatory myofibroblastic tumor The existing literature currently lacks data supporting optimal post-operative surveillance strategies after GTR of uncommon benign sinonasal tumors. In this multi-institutional study, we analyzed outcomes and post-operative surveillance strategies for 47 uncommon benign tumors of mesenchymal, vascular, or neural origin. We observed only one recurrence (a cavernous hemangioma), with a mean follow-up of over 2 years, suggesting favorable outcomes following complete resection and underscoring the importance of tumor-specific surveillance algorithms. Mesenchymal tumors were the most common tumor type and included solitary fibrous tumors most frequently among others. Prior studies have reported recurrence rates as high as 25% for SFTs within 5 years of resection [1, 3-6]. In our series, we observed no recurrences among all 20 mesenchymal tumors, including 8 SFTs with a mean follow-up time of over 3 years. Vascular tumors were the second most common group in our cohort, including AVMs, cavernous hemangiomas, and LCH. With a mean follow-up time of 18 months, one patient experienced recurrence of a cavernous hemangioma. There were no recurrences among patients with other vascular tumors, a finding consistent with previous studies showing far higher rates of recurrence for cavernous hemangioma compared to LCH. Lastly, all 10 neural tumors were schwannomas with no post-operative recurrences and an average post-operative follow-up of over 30 months. Our analysis is limited by both a relatively small sample size and the heterogeneity within each tumor type category. Another potential limitation is the absence of a defined follow-up interval, which makes expressing recurrence in terms of a rate difficult, or a standardized surveillance regimen. Overall, our multi-institutional study represents the largest review of outcomes and post-operative surveillance strategy for uncommon benign sinonasal tumors after endoscopic GTR. Across 47 tumors—20 mesenchymal, 17 vascular, and 10 neural—we observed one recurrence during an average follow-up of over 2 years. The existing literature on post-operative surveillance after endoscopic GTR for uncommon benign sinonasal tumors is sparse, and we believe that our results provide a useful reference point for clinicians who encounter these tumors and achieve a complete resection. We hope that this study can provide a basis for future, larger multi-institutional studies designed to provide surveillance recommendations tailored by pathology. The authors declare no conflicts of interest.

  PublisherOA PDFDOI

• Craniofacial Pain Locations and Outcomes After Endoscopic Sinus Surgery for Unilateral Sphenoid Sinusitis: A Multi‐Institutional Study

  The Laryngoscope · 2025-01-03 · 1 citations

  article

  INTRODUCTION: Unilateral sphenoid sinus opacification on computed tomography is caused by a variety of pathologies including inflammatory and infectious sinusitis, benign and malignant tumors, and encephaloceles. The purpose of this study was to report craniofacial pain locations and outcomes in inflammatory unilateral sphenoid sinusitis (USS) patients who underwent endoscopic sinus surgery (ESS). METHODS: A multi-institutional retrospective cohort study was conducted on all adult patients who had ESS for USS from 2015 to 2022. Patient demographics, presenting symptoms and nasal endoscopy findings, extent of surgical dissection, and craniofacial pain locations and outcomes were recorded. Exclusion criteria included age <18 years, non-inflammatory etiology, immunodeficiency, invasive fungal sinusitis, lack of follow-up, lack of preoperative pain location, and neoplasia. Descriptive statistics were calculated. RESULTS: Of 57 patients with USS, 44 (77.2%) reported craniofacial pain at one or more locations. Retrobulbar (n = 19, 43.2%) was the most common pain location followed by frontal (n = 17, 38.6%) and occipital (n = 10, 22.7%). Surgical intervention resulted in pain resolution in 33/44 patients (75%), with a mean follow-up of 83.7 (±97.8) days. There were no significant associations between presenting symptoms, imaging findings, endoscopy, surgical extent, or final pathology and the presence or resolution of facial pain (p > 0.05). CONCLUSION: In USS patients, the most common craniofacial pain locations were retrobulbar, occipital, and frontal, with a minority being vertex. Based on short-term follow-up, ESS resolved the craniofacial pain in 75% of cases. There were no clinical variables that predicted the presence or resolution of craniofacial pain. LEVEL OF EVIDENCE: 4 Laryngoscope, 135:1915-1919, 2025.

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• Isolated Sphenoid Sinusitis: Frequency of Skull Base Erosion and Associated Complications

  Journal of Neurological Surgery Part B Skull Base · 2025-02-01

  article
  PublisherDOI

• Mechanisms of Mitochondrial Toxicity and Cytotoxicity Caused by <i>Pseudomonas aeruginosa</i> Pyocyanin in Human Nasal Epithelial Cells

  International Forum of Allergy & Rhinology · 2025-12-19

  articleOpen access

  ABSTRACT Background Pseudomonas aeruginosa is an opportunistic pathogen in cystic fibrosis‐related chronic rhinosinusitis (CF‐CRS) that produces phenazine metabolites pyocyanin and 1‐hydroxyphenazine (1‐HP), which may have detrimental effects on mitochondria, reactive oxygen species (ROS), Ca 2+ signaling, and apoptosis. However, prior studies utilized lung cancer cells or dissociated animal cells. We sought to better define human nasal epithelial responses to phenazines, including the role of Ca 2+ . Methods Live cell imaging was used to measure Ca 2+ and mitochondrial function in RPMI2650 nasal carcinoma cells and primary human nasal epithelial cells (HNECs) cultured in submersion and at air–liquid interface (ALI). Gene expression was measured by quantitative PCR. Ciliary beat frequency (CBF) was quantified by high‐speed imaging. Results Pyocyanin, but not 1‐HP, increased mitochondrial Ca 2+ dependent on phospholipase C and endoplasmic reticulum (ER) Ca 2+ release, correlating with protein kinase C activation. Mitochondrial membrane potential decreased and mitochondrial ROS increased with both pyocyanin and 1‐HP in a Ca 2+ ‐independent manner. Both pyocyanin and 1‐HP decreased viability of RPMI2650s and other squamous carcinoma cell lines over 24 h, whereas HNECs survived, possibly due to differential regulation of protein homeostasis genes, including activating transcription factor 6 ( ATF6 ). Mitochondrial ROS was enhanced in CF‐CRS ALIs, which may explain why pyocyanin reduced CBF in CF but not non‐CF ALIs. Conclusions Ca 2+ signaling is not required for phenazine mitochondrial toxicity. The greater sensitivity of cancer cells to phenazine cytotoxicity necessitates use of primary cells when studying host responses to bacterial phenazines. Enhanced ROS production and ciliotoxicity in CF‐CRS may contribute to susceptibility to P. aeruginosa infection.

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• Utility of Endoscopic Endonasal Cyst Fenestration and Marsupialization in the Treatment of Pediatric Craniopharyngioma

  Journal of Neurological Surgery Part B Skull Base · 2025-02-01

  article
  PublisherDOI

• Area Deprivation Index Is Associated With Extent of Disease at Presentation in Inverted Papilloma

  International Forum of Allergy & Rhinology · 2025-01-19 · 1 citations

  articleOpen access

  Sinonasal inverted papilloma (IP) is the most common benign tumor found in the nasal cavity and has the potential for locally destructive effects and malignant transformation [1-3]. Birkenbeuel et al. demonstrate that in 565 patients with squamous cell carcinoma transformation of their IP, the 5-year overall survival rate was 62% and a mean recurrence time of 24.3 months [4]. Therefore, follow-up is crucial in detection of recurrence and preemptive revision resection prior to malignant transformation. While postulated, it has not yet been examined how socioeconomic factors may affect the disease presentation in IP patients. In the present study, we hypothesize that the area deprivation index (ADI), a geographic-level metric of socioeconomic disadvantage at the “neighborhood level,” may be higher in patients with more advanced diseases. Approval was obtained from the University of Pennsylvania and Zucker School of Medicine at Hofstra/Northwell Institutional Review Boards. This is a multi-institutional retrospective analysis of all patients who underwent resection of IP at two tertiary care centers over a 10-year period from 2008 to 2018. Chart review was conducted to gather data on demographics, disease presentation, and operative management. All factors were analyzed based on the ADI, which was provided by the University of Wisconsin Neighborhood Atlas and assigns discrete ordinal rankings of a census block group's deprivation relative to national data. ADI scores were assigned to patients based on their most recent documented residential address at the time of their rhinology care, and patients with higher ADI scores reside in a relatively more disadvantaged community. The difference in mean ADI was compared using the Student's t-test. The significance level was set at an alpha (p-value) < 0.05 and was two-tailed. All statistical analysis was done using STATA version 13 (StataCorp, College Station, TX). Two hundred forty-seven patients with IP undergoing surgical resection were identified in the medical record and met the inclusion criteria for this study. The average age was 57.3 years, with a majority (65.9%) male, privately insured (68.3%), and white race (74.0%). The mean ADI score in the population was 37.8 ± 25.2. ADIs were calculated based on the home address of each patient and compared based on several surgical and pathological factors (Table 1). Patients necessitating a completely open approach, as opposed to an endoscopic or combined endoscopic/open approach to their tumor (see Table 2), had a significantly higher mean ADI (54.7 vs. 37.3, p = 0.02). Patients with dysplastic lesions displayed significantly higher mean ADI (44.7 vs. 35.3, p = 0.007) as did patients with extra-sinus extension (48.8 vs. 36.5, p = 0.01). Patients with postoperative chemotherapy or chemoradiation also demonstrated a significantly higher ADI than those without these adjuvant therapies (49.5 vs. 37.1, p = 0.04). Finally, patients with multiple sinus involvement at presentation had on average higher ADI than those with single-sinus involvement of tumor (43.6 vs. 36.3, p = 0.05). Meanwhile, no associations were found when stratifying by insurance status. The correlation between ADI and disease presentation in IP patients raises concerns about disparities in disease burden and multiple sinus involvement that may lead to more extensive surgery and complications such as recurrence. Tong et al. previously demonstrated that multiple sinus attachment is significantly associated with increased odds of recurrence; moreover, multiple sinus attachment was also associated with increased rates of primary open surgical approach as opposed to endoscopic or combined approaches [5]. More broadly, this study's findings also align with a growing body of research indicating that patients residing in socially disadvantaged communities composed of lower income, educational attainment, and employment opportunities face significant challenges in accessing timely and quality surgical services [6]. The use of geographic indices to operationalize community and socioeconomic disadvantage continues to accumulate, with higher ADI previously being associated with increased likelihood of baseline severity of disease and revision surgery rates in the setting of chronic rhinosinusitis with nasal polyps (CRSwNP) [7, 8]. In the context of IP, delayed diagnoses can result in disease progression, rendering management more complex and increasing the risk of complications [4, 5]. More extensive surgical resections and adjuvant therapy necessitate more specialized support and follow-up care, which might not be readily available or accessible for patients from socioeconomically disadvantaged communities. Indeed, Samuelson et al. and Poetker et al. both established that rhinology care utilization at their institutions amongst patients with chronic rhinosinusitis with nasal polyps was dominated by white, female, and privately insured patients [9, 10]. This study is limited to a two-institution retrospective preliminary investigation; therefore, multi-institutional longitudinal studies tracking the long-term impact of socioeconomic status on treatment adherence, disease recurrence, and overall survival rates can provide valuable insights into the effectiveness of interventions over time and across populations in IP. Additionally, this study did not evaluate for other potentially confounding environmental factors intimately tied to health care disparities such as air quality, heat stress, and particulate matter. Future studies should aim to better incorporate these factors by operationalizing a metric which capture cumulative exposure to these environmental risk factors. This study demonstrates that patients from socioeconomically disadvantaged communities exhibited higher rates of multiple sinus involvement and extra-sinus extension which required correspondingly higher rates of open surgical approaches. These findings align with existing research on disparities in accessing surgical services and highlight potential barriers to timely and quality care for IP patients from resource-deprived areas. This study emphasizes the need for further investigation into the intricate relationship between socioenvironmental factors and timely diagnosis, management, and outcomes of IP. The authors have nothing to report. The authors declare no conflicts of interest.

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• Factors influencing aspirin therapy after desensitization (ATAD) tolerance in aspirin-exacerbated respiratory disease (AERD) patients

  Annals of Allergy Asthma & Immunology · 2025-09-27 · 2 citations

  articleOpen access

  BACKGROUND: For more than 40 years, aspirin desensitization with aspirin therapy after desensitization (ATAD) has been a recognized treatment for aspirin-exacerbated respiratory disease (AERD). This study aimed to characterize the rate of ATAD-associated complications leading to discontinuation and identify associated risk factors. OBJECTIVE: To evaluate the rate and causes of ATAD intolerance and identify demographic factors that may predict intolerance in patients with AERD. METHODS: A total of 360 patients with AERD who underwent aspirin desensitization and ATAD at a tertiary center from August 2016 to April 2024 were reviewed. A joint model combining linear mixed and Cox proportional hazards models was used to assess associations between demographic factors, aspirin dosage, and ATAD intolerance. RESULTS: Of 278 patients included, 4 (1.4%) failed desensitization and 44 (15.8%) discontinued ATAD. Furthermore, 10 patients (3.6%) experienced major complications requiring emergency department visit or hospitalization. Common discontinuation causes included gastrointestinal symptoms, anaphylaxis, cutaneous reactions, and airway symptom exacerbation. On average, aspirin dosage decreased overtime (-10 mg daily per month; P < .0001) and was lower in older patients (-7.78 mg daily; P < .0001), reflecting current dosage practices. Peri-/post-menopausal female status was associated with reduced ATAD intolerance risk (hazard ratio [HR] = 0.4; P = .041), whereas pre-menopausal status with a nonsignificant increase (HR = 2.28; P = .087). ATAD intolerance was more likely in Hispanic/Latino (HR = 8.2; P = .0013) and African American patients (HR = 4.03; P = .0015) and increased modestly with age (HR = 1.08; P < .0001). Longitudinal aspirin dosage was not associated with overall intolerance or intolerance due to gastrointestinal complications specifically after adjustment. CONCLUSION: ATAD tolerance was lower in Hispanic/Latino, African American, and older patients, higher in peri-/post-menopausal females, and not associated with longitudinal aspirin dosage.

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• Expert Strategies: Skull Base Reconstruction—Global Perspectives, Insights, and Algorithms through a Mixed Methods Approach

  International Forum of Allergy & Rhinology · 2025-05-15 · 3 citations

  articleOpen access

  OBJECTIVE: There is limited consensus on endoscopic skull base surgery (ESBS) reconstruction principles. This study aims to generate comprehensive themes regarding ESBS reconstruction by pooling the experiences of ESBS experts, with comparison to a literature review of current published evidence. METHODS: Structured qualitative interviews of ESBS experts regarding postoperative management and reconstruction of various defect locations were conducted. RESULTS: A total of 68 experts comprising 40 academic teams across 13 countries with an average of 18 years of ESBS experience were included. We propose 10 stepwise algorithms for common skull base reconstruction scenarios based on these expert interviews. When available, the nasoseptal flap is used for all high_flow cerebrospinal leak defects. Multilayered reconstruction is favored at all anatomical subsites with increasing number of layers for increasing defect size and complexity. Heterogeneity exists in terms of inlay technique and materials, free grafting versus various pedicled flap options for low-flow defects or in the absence of a nasal septum, nasal packing, tissue sealant, lumbar drain use, and postoperative management. Commonalities and discrepancies between experts were summarized. CONCLUSION: Skull base reconstruction and post-ESBS management is highly complex with a wide variety of practice patterns and expert strategies. Further research of higher quality evidence is warranted to identify optimal management patterns, though the current work aims to inform surgeons on these controversial areas by drawing from numerous experiences.

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• <scp>MMP11</scp> as a Prognostic Indicator for Inverted Papilloma Histologic Grade and Recurrence

  The Laryngoscope · 2025-08-22

  articleOpen access

  OBJECTIVES: Inverted papilloma (IP) is a benign, but locally aggressive sinonasal tumor with a high recurrence rate and potential for malignant transformation into squamous cell carcinoma ex-IP (SCC). Currently, no reliable biomarkers exist to predict recurrence or severity. Matrix metalloproteinase-11 (MMP11) has been implicated in tumor progression and extracellular matrix remodeling in various malignancies and has been shown to be progressively upregulated in IP transformation. This study investigates the relationship between MMP11 expression and IP histologic severity and recurrence risk. METHODS: Patient demographics and tumor characteristics were collected retrospectively at a tertiary care center from 2008 to 2023. Patient specimens were categorized into normal sinus tissue (NST), IP without dysplasia (IPND), IP with severe dysplasia (IPSD), and SCC. Immunohistochemical staining for MMP11 was performed, and quantitative analysis was conducted using DAB-Quant software. RESULTS: A total of 52 patients were included, with a mean follow-up of 68.8 months. MMP11 expression was significantly elevated in IPSD and SCC compared to IPND (36.7% and 36.5% vs. 21.1%, p = 0.02 and p = 0.01). Patients with recurrence exhibited higher MMP11 expression in their initial resection specimens compared to non-recurrent cases (31.1% vs. 18.1%, p < 0.01). High MMP11 expression (> 50%) was associated with a shorter time to recurrence (17.5 vs. 32 months, p = 0.03), independent of histologic grade. CONCLUSION: MMP11 expression correlates with increased IP histologic grade, risk of recurrence, and shorter time to recurrence. Elevated MMP11 expression may identify patients at higher risk for recurrence, allowing for targeted surveillance strategies and treatment options.

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• Correlation of the Sinonasal Outcome Test‐22 With the University of Washington Quality of Life in Assessing Quality of Life in Sinonasal Malignancy Utilizing a Multicenter Prospective Observational Cohort Registry

  International Forum of Allergy & Rhinology · 2025-01-06 · 2 citations

  article

  Key points In this multi-center sinonasal malignancies (SNM) cohort, the Sino-nasal Outcome Test has a correlation with the University of Washington Quality of Life (UWQOL) for assessing QOL. The use of both instruments remains recommended to provide complete and complementary information. Future design of an easy-to-use tool specific to SNM is needed to encompass all aspects of QOL.

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Frequent coauthors

• James N. Palmer

  165 shared

• Noam A. Cohen

  Philadelphia VA Medical Center

  73 shared

• Michael A. Kohanski

  University of Pennsylvania

  67 shared

• Edward C. Kuan

  University of California, Irvine

  44 shared

• Jordan T. Glicksman

  Massachusetts Eye and Ear Infirmary

  38 shared

• Alan D. Workman

  Lemuel Shattuck Hospital

  37 shared

• Arjun K. Parasher

  University of South Florida

  30 shared

• Jennifer E. Douglas

  University of Pennsylvania

  30 shared

Education

• B.A., Economics

  University of Michigan

  2001

• M.D.

  Case Western Reserve University School of Medicine

  2005

Awards & honors

• Fellowship Director for the Rhinology and Skull Base Fellows…
• Unit Based Clinical Leader Physician, Hospital of the Univer…