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Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Sinusitis With or Without the Presence of Nasal Polyps

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ClinicalTrials.gov Identifier: NCT03781804
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : July 1, 2019
Sponsor:
Information provided by (Responsible Party):
Optinose US Inc.

Brief Summary:
This is a 24-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of intranasal administration of 186 and 372 μg twice daily (BID) of OPN-375 in subjects with chronic sinusitis (CS) with or without nasal polyps.

Condition or disease Intervention/treatment Phase
Chronic Sinusitis Drug: OPN-375 Phase 3

Detailed Description:

The primary objective of this study is to compare the efficacy of intranasal administration of twice-daily doses of 186 and 372 µg of OPN-375 (fluticasone propionate) with placebo in subjects with chronic sinusitis using the following co-primary endpoints:

  1. A change from baseline in symptoms as measured by a composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4.
  2. A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 378 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A 24-Week Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 186 and 372 μg of OPN-375 Twice a Day (BID) in Subjects With Chronic Sinusitis With or Without the Presence of Nasal Polyps
Actual Study Start Date : November 27, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sinusitis

Arm Intervention/treatment
Active Comparator: OPN-375 186 μg BID
OPN-375 186 μg BID x 24 Weeks
Drug: OPN-375
OPN-375, BID

Active Comparator: OPN-375 372 μg BID
OPN-375 372 μg BID x 24 Weeks
Drug: OPN-375
OPN-375, BID

Placebo Comparator: Placebo
Matching Placebo BID x 24 Weeks
Drug: OPN-375
OPN-375, BID




Primary Outcome Measures :
  1. Change from baseline in symptoms as measured by a composite score for each symptom of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4 [ Time Frame: 4 Weeks ]
    Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.

  2. Change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses [ Time Frame: Baseline, Week 24 ]
    Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent ranges from -100% to 100%.


Secondary Outcome Measures :
  1. Change in Sinonasal Outcome Test 22 (SNOT-22) Total Score [ Time Frame: 24 Weeks ]
    Change from baseline to Week 24 in subject symptoms and functioning, as measured by Sinonasal Outcome Test - 22 (SNOT-22) total score. SNOT-22 is a subject-completed questionnaire that consists of 22 questions. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be. The total score can range from 0-110, 0 being the best and 110 being the worst.

  2. Change in the 36-Item Short Form Health Survey version 2 (SF-36v2) mental composite score (MCS) [ Time Frame: 24 Weeks ]
    Change from baseline to Week 24/ET on the MCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.

  3. Change in the SF-36v2 physical composite score (PCS) [ Time Frame: 24 Weeks ]
    Change from baseline to Week 24/ET on the PCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.

  4. Change in frequency of acute exacerbations of chronic sinusitis [ Time Frame: 24 Weeks ]
    Change in frequency of acute exacerbations of chronic sinusitis, defined as a worsening of symptoms that requires escalation of treatment.

  5. Change in facial pain or pressure sensation measured by AM and PM diary symptom scores [ Time Frame: 12 Weeks ]
    Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.

  6. Change from baseline in nasal discharge (anterior and/or posterior) measured by AM and PM diary symptom scores [ Time Frame: 12 Weeks ]
    Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.

  7. Change from baseline in nasal congestion measured by AM and PM diary symptom scores [ Time Frame: 12 Weeks ]
    Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours), The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.

  8. Change in sense of smell scores measured by AM and PM diary symptom scores [ Time Frame: 12 Weeks ]
    Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours) The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent.

  9. Change from baseline to Week 24/ET in the Lund-Mackay Staging System total score [ Time Frame: Baseline, Week 24 ]
    Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC). The total LM score for a CT scan ranges from 0-24.

  10. Change from baseline to Week24/ET in the Lund-Mackay Staging System total scores for sinus pairs [ Time Frame: Baseline, Week 24 ]
    Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC).

  11. Change from baseline to Week 24/ET in average percent of sinus volume occupied by disease for the maxillary sinus as measured by CT scan assessment [ Time Frame: Baseline, Week 24 ]
  12. Change from baseline to Week 24/ET in average percent of sinus volume occupied by disease for the ethmoid sinus as measured by CT scan assessment [ Time Frame: Baseline, Week 24 ]
  13. Change from baseline to week 24/ET in the Zinreich modification of Lund-Mackay Staging System total score [ Time Frame: Baseline, Week 24 ]

    Zeinrich Modification of the Lund-Mackay Staging System:

    Zinreich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% for each sinus. Total score ranges from 0 to 40.


  14. Change from baseline to week 24/ET in the Zinreich modification of Lund-Mackay Staging System for the sinus pairs [ Time Frame: Baseline, Week 24 ]

    Zeinrich Modification of the Lund-Mackay Staging System:

    Zinreich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100%


  15. Time comparison to first acute exacerbation of chronic sinusitis [ Time Frame: 24 Weeks ]
    Comparing the distribution of time to first acute exacerbation of chronic sinusitis, defined as a worsening of symptoms that requires escalation of treatment

  16. Percentage of subjects requiring rescue medication after Week 4 [ Time Frame: 8 Weeks ]
    Recording of each dose of approved rescue medication after the Week 4 visit through Week 12

  17. Change from baseline to defined timepoints - subject symptoms and functioning as measured by the Sinonasal Outcome Test - 22-item (SNOT-22) total score and sub domains [ Time Frame: 24 Weeks ]
    The SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional consequences of their nasal disorder across several domains including: rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be.

  18. Change in baseline to Week 24/ET as measured by the Euroqol 5-dimension (EQ-5D) instrument [ Time Frame: 24 Weeks ]
    The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The subject is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the subject's health state. Scores for health state range from 0 to 1. The EQ VAS records the subject's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the subject's own judgement. VAS scores range from 0 to 100.

  19. Change in baseline to Week 24/ET as measured by the Short-Form 36 health survey, version 2 (SF-36v2) [ Time Frame: 24 Weeks ]
    The SF-36v2 is a multipurpose, 36-item subject-completed validated questionnaire that measures 8 domains of health: physical functioning, role limitations due to physical health (RP), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The SF-36v2 survey with a 4-week recall will be used. It yields scale scores for each of these 8 health domains , each of which is scored from 0 to 100.

  20. Change in baseline to Week 24/ET as measured by the Short-Form 6-Dimension (SF-6D) Instrument [ Time Frame: 24 Weeks ]
    The SF-6D is a single health state index derived from the 11 items from the SF-36v2. SF-6D scores range from 0.291 to 1

  21. Change in sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 24 Weeks ]
    The PSQI is a validated, self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate 7 "component" scores (each ranging between 0 and 3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging between 0 and 21.

  22. Change in depressive symptoms from baseline to Week 24/ET as measured by change in the severity of depression as measured by the Quick Inventory of Depression Symptomatology (QIDS) [ Time Frame: 24 Weeks ]
    The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27.

  23. Change in olfactory impairment from baseline to Week 24/ET as measured by the Smell Identification Test (SIT)™ [ Time Frame: 24 Weeks ]
    The SIT is a test comprised of 4 booklets each containing 10 microencapsulated (scratch and sniff) odors. Forced choice response alternatives accompany each test item. The test provides an absolute indication of smell loss (anosmia; mild, moderate or severe hyposomia) as well as an index to detect malingering.

  24. Change in overall health from baseline to Week 24/ET as measured by the percent of subjects improved as indicated by the Patient Global Impression of Change (PGIC) at Week 24/ET [ Time Frame: Week 4, Week 24 ]
    Global impression of change will be assessed using a subject-completed PGIC scale range: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse

  25. Change in work productivity from baseline to Week 24/ET as measured by the Health and Work Performance Questionnaire (HPQ). [ Time Frame: 24 Weeks ]
    The Health and Work Performance Questionnaire measures work productivity (absenteeism and presenteeism). - Absenteeism is measured in missed work days over the past four weeks (range 0-20); absenteeism is measured in % productivity at work (0-100%), with higher values indicating improved productivity. - Presenteeism can be converted to number of days of productive time lost per month, and when added to the number of lost days due to absenteeism provides an estimate of total productive work days lost.


Other Outcome Measures:
  1. Evaluation of Safety by recording the severity of adverse events (AEs) [ Time Frame: 24 Weeks ]
    Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe

  2. Evaluation of Safety-Nasal Examination [ Time Frame: 24 Weeks ]
    Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum.

  3. Evaluation of Safety by ocular examination - Intraocular Pressure [ Time Frame: 24 Weeks ]
    Assessment of safety by averaging intraocular pressure measurement of 2 or 3 measurements to determine.

  4. Evaluation of Safety by ocular examination - Cataract Evaluation [ Time Frame: 24 Weeks ]
    Cataracts should be again assessed present or absent, If cataract is diagnosed, cataract type per localization should be specified and cataract should be graded 1=mild, 2=moderate, 3=pronounced, 4=severe

  5. Evaluation of Safety measuring vital signs- blood pressure [ Time Frame: 24 Weeks ]
    Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)

  6. Evaluation of Safety measuring vital signs- Pulse [ Time Frame: 24 Weeks ]
    Measure pulse in beats per minute (bpm)

  7. Evaluation of Safety measuring vital signs- Weight [ Time Frame: 24 Weeks ]
    Assessment of safety from physical examination-weight measured in kg or lb

  8. Evaluation of Safety - Monitoring Concomitant Medication Usage [ Time Frame: 24 Weeks ]
    Assessment for safety from the collection of information for concomitant medications usage



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. men or women aged 18 years and older at baseline visit
  2. women of child bearing potential must be abstinent, or if sexually active,

    1. be practicing an effective method of birth control before entry and throughout the study, or
    2. be surgically sterile, or
    3. be postmenopausal (amenorrhea for at least 1 year).
  3. women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening)
  4. must have a history of chronic sinusitis and be currently experiencing 2 or more of the following symptoms, 1 of which has to be either nasal congestion or nasal discharge (anterior and/or posterior nasal discharge) for equal to or greater than 12 weeks:

    • nasal congestion
    • nasal discharge (anterior and/or posterior nasal discharge)
    • facial pain or pressure
    • reduction or loss of smell
  5. endoscopic evidence of nasal mucosal disease, with edema, purulent discharge, or polyps in middle meatus, bilaterally
  6. must have confirmatory evidence via a computed tomography(CT) scan of bilateral sinus disease (have at least 1 sinus on each side of nose with a Lund-Mackay score of ≥1)
  7. baseline CT scan must show a combined ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus
  8. must have at least moderate symptoms (as defined in protocol), of nasal congestion as reported by the subject, on average, for the 7-day period preceding Visit 1 (Screening) run-in
  9. must have an average morning score of at least 1.5 for congestion (as defined in protocol) recorded on the subject diary for a 7 days period of the single-blind run-in
  10. must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization
  11. subjects with comorbid asthma or chronic obstructive pulmonary disorder (COPD) must be stable with no exacerbations (eg, no emergency room visits, hospitalizations, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Inhaled corticosteroid use must be limited to stable doses of no more than 1,000 μg/day of beclomethasone (or equivalent) for at least 3 months before Visit 1 (Screening) with plans to continue use throughout the study.
  12. must be able to cease treatment with oral steroids, intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at the baseline visit
  13. must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening)
  14. must be able to use the exhalation delivery system correctly; all subjects will be required to demonstrate correct use of the practice exhalation delivery system (EDS) at Visit 1 (Screening).
  15. must be capable, in the opinion of the investigator, of providing informed consent to participate in the study. Subjects must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

  1. women who are pregnant or lactating
  2. inability to have each nasal cavity examined for any reason, including nasal septum deviation
  3. inability to achieve bilateral nasal airflow
  4. is currently taking XHANCE®
  5. have previously used XHANCE® for more than 1 month and did not achieve an adequate symptomatic response
  6. the nasal/sinus anatomy prevents the accurate assessment of sinus volume via CT scan
  7. history of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery
  8. have current evidence of sinus mucocele or evidence of allergic fungal sinusitis
  9. have a polyp extending outside the ostiomeatal complex/middle turbinate (anterior or inferior) that is below the inferior turbinate attachment as determined by the nasoendoscopy at screening
  10. have a nasal septum perforation
  11. have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening)
  12. have evidence of significant mucosal injury, ulceration (eg exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy
  13. have current, ongoing rhinitis medicamentosa (rebound rhinitis)
  14. have significant oral structural abnormalities (eg, a cleft palate)
  15. have a diagnosis of cystic fibrosis
  16. history of Churg-Strauss syndrome or dyskinetic ciliary syndromes
  17. symptom resolution or last dose of antibiotics for purulent nasal infection, acute sinusitis, or upper respiratory tract infection was less than 4 weeks prior to Visit 1 (Screening). Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution.
  18. planned sinonasal surgery during the period of the study
  19. allergy, hypersensitivity, or contraindication to corticosteroids or steroids
  20. has used oral steroids in the past for treatment of chronic sinusitis and did not experience any relief of symptoms
  21. has a steroid eluting sinus stent still in place within 30 days of Visit 1
  22. allergy or hypersensitivity to any excipients in study drug
  23. exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral, intra-articular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD
  24. have nasal candidiasis
  25. history or current diagnosis of any form of glaucoma or ocular hypertension (intraocular pressure at screening of >21)
  26. history of intraocular pressure elevation on any form of steroid therapy
  27. history or current diagnosis of the presence (in either eye) of a sub-capsular cataract
  28. history of immunodeficiency
  29. any serious or unstable concurrent disease, psychiatric disorder, or any significant condition that, in the opinion of the investigator could confound the results of the study or could interfere with the subject's participation or compliance in the study
  30. have a positive drug screen or a recent (within 1 year of Visit 1 (Screening) history of drug or alcohol abuse, or dependence that, in the opinion of the investigator could interfere with the subject's participation or compliance in the study
  31. have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
  32. have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1 (Screening)
  33. is using strong cytochrome P450 3A4 (CYP3A4) inhibitor (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole)
  34. is an employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or is a family member of the employee or the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03781804


Contacts
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Contact: Amy Berman 267-521-0524 amy.berman@optinose.com
Contact: Jennifer Ballestas 267-521-0529 jennifer.ballestas@optinose.com

  Show 34 Study Locations
Sponsors and Collaborators
Optinose US Inc.
Investigators
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Study Director: Jennifer Carothers Optinose US Inc.
Study Chair: John Messina Optinose US Inc.

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Responsible Party: Optinose US Inc.
ClinicalTrials.gov Identifier: NCT03781804     History of Changes
Other Study ID Numbers: OPN-FLU-CS-3205
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: July 1, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Sinusitis
Nasal Polyps
Chronic Disease
Paranasal Sinus Diseases
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Polyps
Pathological Conditions, Anatomical
Disease Attributes
Pathologic Processes