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Cross-Talk Between Human Mast Cells and Epithelial Cells By IgE-Mediated Periostin Production in Eosinophilic Nasal Polyps
AB186 Abstracts
607
High Burden of Obstructive Sleep Apnea in Subgroups of Chronic Rhinosinusitis: Importance of Phenotyping Chronic Rhinosinusitis Patients for Stratifying Risk Factors for This Major Comorbidity
SUNDAY
Jessica W. Hui, MD1, Mohamed Benhammuda2, Vahid Kalantari3, Arpita Mehta3, Raj Kota3, Pete Batra, MD4, Phillip LoSavio, MD4, Mary C. Tobin, MD3, Mahboobeh Mahdavinia, MD, PhD3; 1Internal Medicine/ Pediatrics Division, Department of Pediatrics, Rush University Medical Center, Chicago, IL, 2Department of Immunology and Microbiology, Allergy/Immunology Section, Rush University Medical Center, Chicago, IL, 3Allergy/Immunology section, Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL, 4Department of Otorhinolaryngology-Head and Neck Surgery, Rush University Medical Center, Chicago, IL. RATIONALE: It is widely known that patients with chronic rhinosinusitis (CRS) commonly suffer from sleep disruption. Many of these patients have the associated diagnosis of obstructive sleep apnea (OSA). However, little is known about the risk factors for developing OSA in the CRS population. This study aims to identify these risk factors. METHODS: We performed a cohort study of 1004 patients with confirmed diagnostic criteria for CRS. Patient charts were reviewed to identify those with sleep study confirmed OSA. Patient charts were further reviewed for demographic information (age, ethnicity, race, sex, BMI) and medical history including: duration of CRS, presence of nasal polyps, number of endoscopic sinus surgeries, asthma, asthma hospitalizations, asthma ED visits, AERD, allergic rhinitis, eczema, food allergy, GERD, GERD treatment, anosmia and Lund-Mackay score (LMS). RESULTS: 970 patients were included. Logistic or linear regression analyses were performed to correct for BMI. Blacks were at higher risk for OSA (20.7% vs. 10.5% in Latinos and 8% in whites). Higher age was associated with higher risk for OSA. Male gender was a risk factor for OSA (14.2% in Male vs 9.4% Female). OSA was more common in CRSsNP patients. In CRSsNP cases, OSA was associated with GERD and duration of CRS. 25% of male CRSsNP patients above 40 had OSA; this prevalence increased to 40% in male black CRSsNP patients above 40yrs. CONCLUSIONS: Patients with CRS should be screened for OSA. Especially male, black CRSsNP cases who are older than 40 years old.
608
3D Quantitation of Sinonasal Inflammation Correlates with Symptoms and Disease-Specific Quality of Life in Patients with Rhinosinusitis
Sooyoung Lim, BS1, Michael Ramirez, BS1, Katherine McKeough, BS2, Adam Starkey, BS3, Fawwaz Qayyum, BS4, Jonathan Garneau, MD5, Megan K. Ford, MD6, William F. Sensakovic, PhD7, Daniel T. Ginat, MD8, Samuell G. Armato, III, PhD8, Fuad M. Baroody, MD, FAAAAI9, Jayant M. Pinto, MD9; 1Pritzker School of Medicine, 2Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago, 3Department of Radiology, The University of Chicago, 4Department of Radiology, The University of Chicago, 5Mount Sinai Health System. New York, NY, 6Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 7Department of Radiology, Florida Hospital, Orlando, FL, 8Department of Radiology, The University of Chicago, Chicago, IL, 9The University of Chicago, Chicago, IL. RATIONALE: Traditional methods of staging Chronic Rhinosinusitis (CRS) do not differentiate between degrees of partial mucosal sinus inflammation limiting their utility as biomarkers. We hypothesized that software-aided quantitative measurement of sinus inflammation would generate a metric of disease burden that would correlate with clinical parameters in symptomatic patients. METHODS: Adults with rhinologic complaints undergoing CT imaging were recruited at an urban, academic, tertiary care center (n547 with Lund MacKay [LM] scores>4). 3D volumetric image analysis was performed using a validated, semi-automated method yielding a Modified Lund MacKay (MLM) score (which allowed for a continuous scale to quantitate
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
opacification). We then used linear regression (in R) to test the association of the MLM with concurrent symptoms (total nasal symptom scores [TNSS]) and disease specific quality of life (Sinonasal Outcome Test-22 [SNOT-22]). RESULTS: MLM scores were significantly associated with both symptoms (b50.482, P50.025) and disease specific quality of life (b50.077, P50.004). These relationships were not affected by age, sex, race, smoking, season, atopy status, or smoking. Inflammation in the ethmoid and sphenoid sinuses appeared to drive these associations. These findings were even more robust when we limited our analyses to patients with more severe disease (LM>6). CONCLUSIONS: We demonstrate that a more precise and quantitative measurement of sinus inflammation by computer-aided 3D analysis correlates modestly with both symptoms and, for the first time, disease specific quality of life. Posterior sinuses appear to drive these findings, providing an anatomic target for clinicians to base therapy. The MLM is a promising imaging biomarker for clinical and research use.
609
Cross-Talk Between Human Mast Cells and Epithelial Cells By IgE-Mediated Periostin Production in Eosinophilic Nasal Polyps
Dae Woo Kim, MD1,2, Marianna Kulka, PhD3,4, A Ra Jo5, Kyung Mi Eun6, Narcy Arizmendi7, Brian P. Tancowny8, Seung-No Hong9, Hong Ryul Jin, MD6, Dong-Kyu Kim, MD10, Richard F. Lockey, MD11,12, Seong Ho Cho, MD, FAAAAI13,14; 1Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 2Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea, 3University of Alberta, Edmonton, AB, Canada, 4National Research Council Canada, Edmonton, AB, Canada, 5Division of Allergy-Immunology, Department of Internal Medicine, University of South Florida Morsani College of Medicine, 6Seoul National University Hospital and Boramae Medical Center, South Korea, 7Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, 8Johns Hopkins University, Baltimore, MD, 9Department of OtorhinolaryngologyHead and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, 10Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, South Korea, 11University of South Florida Morsani College of Medicine, Tampa, FL, 12Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL, 13University of South Florida, College of Medicine, Tampa, FL, 14Kyung Hee University, Seoul, South Korea. RATIONALE: Periostin is important in Th2 inflammation and tissue remodeling. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study is to investigate the role of periostin in CRSwNP. METHODS: Expressions of periostin and its receptor, integrin a V, were investigated in NP by IHC, qRT-PCR, and ELISA. Immunohistochemistry and immunocytochemistry were used to determine cellular sources of periostin in NP and a human mast cell line, LAD2. RESULTS: Periostin was upregulated and was positively and negatively correlated with IL-5/CCL-11 and IL-17A/IFN-g, respectively, in eosinophilic NP (ENP), but not in non-ENP. A positive correlation existed between periostin and Lund-Mackay CT scores (r50.542, p50.0392). Tryptase+ cells were a main source of periostin in ENP. Periostin levels correlated positively with total IgE in ENP homogenate (r50.733, p50.0025). Furthermore, when LAD2 cells were stimulated with IgE, IL-4, IL-13 or TNF-a, only IgE enhanced the levels of periostin mRNA (20-fold) and protein (48fold). Confocal microscopy with immunocytochemical staining showed periostin localized to LAD2 granules. Overexpression of integrin aV was detected in epithelial layers of ENP and correlated with the level of periostin. Integrin aV expression was positively associated with thymic stromal lymphopoietin at mRNA and protein levels. CONCLUSIONS: Periostin and integrin aV are up-regulated in ENP and correlate with Th2 markers and disease severity. Mast cells may be a source of NP periostin which affects epithelial cells, and be a possible novel target to treat ENP.
607
High Burden of Obstructive Sleep Apnea in Subgroups of Chronic Rhinosinusitis: Importance of Phenotyping Chronic Rhinosinusitis Patients for Stratifying Risk Factors for This Major Comorbidity
SUNDAY
Jessica W. Hui, MD1, Mohamed Benhammuda2, Vahid Kalantari3, Arpita Mehta3, Raj Kota3, Pete Batra, MD4, Phillip LoSavio, MD4, Mary C. Tobin, MD3, Mahboobeh Mahdavinia, MD, PhD3; 1Internal Medicine/ Pediatrics Division, Department of Pediatrics, Rush University Medical Center, Chicago, IL, 2Department of Immunology and Microbiology, Allergy/Immunology Section, Rush University Medical Center, Chicago, IL, 3Allergy/Immunology section, Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL, 4Department of Otorhinolaryngology-Head and Neck Surgery, Rush University Medical Center, Chicago, IL. RATIONALE: It is widely known that patients with chronic rhinosinusitis (CRS) commonly suffer from sleep disruption. Many of these patients have the associated diagnosis of obstructive sleep apnea (OSA). However, little is known about the risk factors for developing OSA in the CRS population. This study aims to identify these risk factors. METHODS: We performed a cohort study of 1004 patients with confirmed diagnostic criteria for CRS. Patient charts were reviewed to identify those with sleep study confirmed OSA. Patient charts were further reviewed for demographic information (age, ethnicity, race, sex, BMI) and medical history including: duration of CRS, presence of nasal polyps, number of endoscopic sinus surgeries, asthma, asthma hospitalizations, asthma ED visits, AERD, allergic rhinitis, eczema, food allergy, GERD, GERD treatment, anosmia and Lund-Mackay score (LMS). RESULTS: 970 patients were included. Logistic or linear regression analyses were performed to correct for BMI. Blacks were at higher risk for OSA (20.7% vs. 10.5% in Latinos and 8% in whites). Higher age was associated with higher risk for OSA. Male gender was a risk factor for OSA (14.2% in Male vs 9.4% Female). OSA was more common in CRSsNP patients. In CRSsNP cases, OSA was associated with GERD and duration of CRS. 25% of male CRSsNP patients above 40 had OSA; this prevalence increased to 40% in male black CRSsNP patients above 40yrs. CONCLUSIONS: Patients with CRS should be screened for OSA. Especially male, black CRSsNP cases who are older than 40 years old.
608
3D Quantitation of Sinonasal Inflammation Correlates with Symptoms and Disease-Specific Quality of Life in Patients with Rhinosinusitis
Sooyoung Lim, BS1, Michael Ramirez, BS1, Katherine McKeough, BS2, Adam Starkey, BS3, Fawwaz Qayyum, BS4, Jonathan Garneau, MD5, Megan K. Ford, MD6, William F. Sensakovic, PhD7, Daniel T. Ginat, MD8, Samuell G. Armato, III, PhD8, Fuad M. Baroody, MD, FAAAAI9, Jayant M. Pinto, MD9; 1Pritzker School of Medicine, 2Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago, 3Department of Radiology, The University of Chicago, 4Department of Radiology, The University of Chicago, 5Mount Sinai Health System. New York, NY, 6Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 7Department of Radiology, Florida Hospital, Orlando, FL, 8Department of Radiology, The University of Chicago, Chicago, IL, 9The University of Chicago, Chicago, IL. RATIONALE: Traditional methods of staging Chronic Rhinosinusitis (CRS) do not differentiate between degrees of partial mucosal sinus inflammation limiting their utility as biomarkers. We hypothesized that software-aided quantitative measurement of sinus inflammation would generate a metric of disease burden that would correlate with clinical parameters in symptomatic patients. METHODS: Adults with rhinologic complaints undergoing CT imaging were recruited at an urban, academic, tertiary care center (n547 with Lund MacKay [LM] scores>4). 3D volumetric image analysis was performed using a validated, semi-automated method yielding a Modified Lund MacKay (MLM) score (which allowed for a continuous scale to quantitate
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
opacification). We then used linear regression (in R) to test the association of the MLM with concurrent symptoms (total nasal symptom scores [TNSS]) and disease specific quality of life (Sinonasal Outcome Test-22 [SNOT-22]). RESULTS: MLM scores were significantly associated with both symptoms (b50.482, P50.025) and disease specific quality of life (b50.077, P50.004). These relationships were not affected by age, sex, race, smoking, season, atopy status, or smoking. Inflammation in the ethmoid and sphenoid sinuses appeared to drive these associations. These findings were even more robust when we limited our analyses to patients with more severe disease (LM>6). CONCLUSIONS: We demonstrate that a more precise and quantitative measurement of sinus inflammation by computer-aided 3D analysis correlates modestly with both symptoms and, for the first time, disease specific quality of life. Posterior sinuses appear to drive these findings, providing an anatomic target for clinicians to base therapy. The MLM is a promising imaging biomarker for clinical and research use.
609
Cross-Talk Between Human Mast Cells and Epithelial Cells By IgE-Mediated Periostin Production in Eosinophilic Nasal Polyps
Dae Woo Kim, MD1,2, Marianna Kulka, PhD3,4, A Ra Jo5, Kyung Mi Eun6, Narcy Arizmendi7, Brian P. Tancowny8, Seung-No Hong9, Hong Ryul Jin, MD6, Dong-Kyu Kim, MD10, Richard F. Lockey, MD11,12, Seong Ho Cho, MD, FAAAAI13,14; 1Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 2Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea, 3University of Alberta, Edmonton, AB, Canada, 4National Research Council Canada, Edmonton, AB, Canada, 5Division of Allergy-Immunology, Department of Internal Medicine, University of South Florida Morsani College of Medicine, 6Seoul National University Hospital and Boramae Medical Center, South Korea, 7Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, 8Johns Hopkins University, Baltimore, MD, 9Department of OtorhinolaryngologyHead and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, 10Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, South Korea, 11University of South Florida Morsani College of Medicine, Tampa, FL, 12Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL, 13University of South Florida, College of Medicine, Tampa, FL, 14Kyung Hee University, Seoul, South Korea. RATIONALE: Periostin is important in Th2 inflammation and tissue remodeling. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study is to investigate the role of periostin in CRSwNP. METHODS: Expressions of periostin and its receptor, integrin a V, were investigated in NP by IHC, qRT-PCR, and ELISA. Immunohistochemistry and immunocytochemistry were used to determine cellular sources of periostin in NP and a human mast cell line, LAD2. RESULTS: Periostin was upregulated and was positively and negatively correlated with IL-5/CCL-11 and IL-17A/IFN-g, respectively, in eosinophilic NP (ENP), but not in non-ENP. A positive correlation existed between periostin and Lund-Mackay CT scores (r50.542, p50.0392). Tryptase+ cells were a main source of periostin in ENP. Periostin levels correlated positively with total IgE in ENP homogenate (r50.733, p50.0025). Furthermore, when LAD2 cells were stimulated with IgE, IL-4, IL-13 or TNF-a, only IgE enhanced the levels of periostin mRNA (20-fold) and protein (48fold). Confocal microscopy with immunocytochemical staining showed periostin localized to LAD2 granules. Overexpression of integrin aV was detected in epithelial layers of ENP and correlated with the level of periostin. Integrin aV expression was positively associated with thymic stromal lymphopoietin at mRNA and protein levels. CONCLUSIONS: Periostin and integrin aV are up-regulated in ENP and correlate with Th2 markers and disease severity. Mast cells may be a source of NP periostin which affects epithelial cells, and be a possible novel target to treat ENP.