Rhinosinusitis: A Prospective Study

االله الرحمن الرحيم بسم

Pathological l & Radiological i l Evidences in the Pathogenesis es s of Chronic Rhinosinusitis: A Prospective Study Prof. Dr. H. ABDEL FATAH, MD A. Prof. Dr. K. NOWEAM, MD Dr. Z. MANDOUR, MD Chronic Rhinosinusitis (CRS) It is a term that has been used to describe a number of entities characterized by chronic symptoms of nasal and sinus inflammation or infection. There has been a lack of consensus regarding definitions and treatment of CRS. The absence of widely accepted definitions for CRS has resulted in a paucity of research directed at understanding its pathophysiology and has hampered efforts to improve treatment.

Task Force- Definition Chronic Rhinosinusitis is a group of disorders characterized by inflammation of the mucosa of the nose and Paranasal sinuses of at least 12 weeks duration. Chronic Bacterial Rhinosinusitis ()- Definition* It is an infective bacterial inflammatory process affecting the mucosa of the nasal cavities and paranasal sinuses. * Armed force institute of pathology.

Fungal Rhinosinusitis (FS)- Definition* It is an inflammatory reaction due to fungal infection, most commonly Aspergillus. It is classified in four clinico-pathological categories: 1. Noninvasive mycotic colonization with formation of a mycetoma or fungus ball. 2. Chronic invasive (moderately immuno- compromised hosts). 3. Fulminating (immuno-compromised hosts). 4. Allergic Fungal Sinusitis () [hypersensitivity reaction to antigens]. * Armed force institute of pathology. Diffuse Sinonasal Polyposis ()- Definition* It is a chronic inflammatory condition characterized by multiple l giant polyps filling the sinuses and nasal cavity. * Armed force institute of pathology.

Aim of the work To study the etiologic factors implicated in the pathogenesis of Chronic Rhinosinusitis. Patients and Methodology 121 patients suffering from, and (ORL Department in Mont-Godinne, UCL, Belgium). 80 individuals presented to radiology department for non-ent purposes considered as control group (Mont-Godinne, UCL, Belgium).

Patients and Methodology All patients subjected to following pre-operative scheme: Full history taking. General medical examination. Routine E.N.T. examination. Routine laboratory tests. Ig-E level (normal less than 200 IU/ml) Patients and Methodology- cont. Endoscopic assessment of nasal cavity. Acoustic Rhinomanometry (anatomy) Intra-operative biopsy from the ethmoid air cells for Histopathological examination and fungal staining [periodic acid Schiff stain]. Radiological assessment with C.T. scan for both patients & control was used & score was calculated according to Modified Lund-MacKay system (1995) for sinus pathology.

Modified Lund & Mackay system Radiological grading of sinus systems proposed by Lund & Mackay Sinus system Maxillary sinus Anterior ethmoid sinus Posterior ethmoid sinus Sphenoid sinus Frontal sinus Ostiomeatal complex points for each side left right Scoring for all sinus systems, except the ostiomeatal complex: 0 = no opacification, 1 = partial opacification, 2 = total opacification. For the ostiomeatal complex: 0 = not occluded, 2 = occluded.

Patients and Methodology Investigations for allergy component (Skin-Prick test). Preoperative objective evaluation of smell University of Pennsylvania Smell Identification Test (UPSIT). Four booklets of 40-odorants, each page contains microencapsulated odorant released by a pencil tip (UPSIT). Patients and Methodology- Exclusion Criteria Neoplastic lesions of nose & paranasal sinuses. Granulomatous lesions of nose & paranasal sinuses. Individuals with previous nasal surgery.

Patients and Methodology- Grouping I. Control group. II. Patients group: according to endoscopic examination, biopsy and CT were sub-divided into three main sub-groups: Chronic bacterial Rhinosinusitis () group (73 patients). Allergic Fungal sinusitis () group (25 patients) according to DeShazo (1997), criteria. Diffuse Sinonasal Polyposis () group (23 patients). Diagnostic criteria DeShazo (1997) described five common characteristics: 1. Radiographic evidence of. 2. Presence of allergic mucin (identified Grossly or Histopathological) 3. Positive fungal stain or culture from the sinus at the time of surgery. 4. Absence of contributory factors (as diabetes mellitus, immuno-deficiencies) 5. Absence of fungal invasion.

Results Sex distribution Indication Male Female Control Count 37 43 80 % within indication 46.2% 53.8% 100.0% Count 33 40 73 % within indication 45.2% 54.8% 100.0% Count 5 20 25 % within indication 20.0% 80.0% 100.0% Count 16 7 23 % within indication code 69.6% 30.4% 100.0% Count 91 110 201 % within indication 45.3% 54.7% 100.0% Person Chi-square = 0.008 Significant female predilection in significant male predominate in No sex predilection in

, and - sex distribution - Female predilection Estrogens lower immune status thus rendering female more prone to fungal infection*. M/F ratio may be age dependent**. * The immune system as a potential target for environmental Cited By in Scopus (69) estrogens (endocrine disrupters): a new emerging field, Sattar Ansar Ahmed Toxicology Volume 150, Issues 1-3, 7 September 2000, Pages 191-206 206. ** Itzhak Brook, Himal Bajracharya, Daniel Hinthorn. chronic Sinusitis. emedicine Infectious Diseases. 2008

- Age distribution Age categories Indication 30 30-40- 50-60- 70+ Count 5 0 5 0 10 5 25 % within indication 20.0% 0 % 20.0%.0% 40.0% 20.0% 100% Person Chi-square = 0.000 Statistically significant increase with the patient age in (60-70 years) Otherwise no significant correlation with patient age in and., and - Age distribution

- Age distribution Several authors have postulated that the increase in incidence of with age is due to decrease in the activity of cellular and humoral immunity as well as ciliary function (*,**,***). * Miller AE: Selective decline in cellular immune response to varicella zoster in the elderly. Neurology 1980;30:582. * Ruckdeschel JC, Schimpff SC, Smyth AC, et al. Herpes zoster and impaired cell- mediated immunity to the varicella zoster virus in patients with Hodgkin's disease. Am J Med 1977;62:77. * Sorenson OS, Haahr S, Moller-Larsen A, et al. Cell-mediated and humoral immunity to herpes virus during and after herpes zoster infections. Infect Immun 1980;29:369., and - Acoustic Rhinomanometry Indication Non-obstructive obstructive Rhinomanometry Acoustic Rhinomanometry Obstructive Rhinomanometry Count 51 22 73 % within indication 69.9% 30.1% 100.0% Count 20 5 25 % within indication 80.0% 20.0% 100.0% Count 9 14 23 % within indication 39.1% 60.9% 100.0% Count 80 41 121 % within indication 66.1% 33.9% 100.0% Person Chi-square = 0.006 Statistically significant decreased airway diameter in and to a lesser extent in, being lowest in. Evidently is not related to obstruction.

, and - Acoustic Rhinomanometry CRS, and - Allergy test t (skin prick test) t) Skin Prick Test non allergic allergic Count 35 38 73 % within indication 47.9% 52.1% 100.0% Count 10 15 25 % within indication 40.0% 0% 60.0% 0% 100.0% 0% Count 12 11 23 % within indication 52.2% 47.8% 100.0% Count 57 64 121 % within indication 47.1% 52.9% 100.0% Person Chi-square = 0.682 No statistically significant association of positive skin prick test within all groups, apart from a trend of increased positivity in.

CRS, and - Allergy test (skin prick test) CRS, and - Allergy test (skin prick test) Atopy is characteristic of ; 2/3 of patients report a history of allergic rhinitis, and 90% of patients demonstrate elevated specific IgE to one or more fungal antigens*. Patients with nasal polyps have the same prevalence of positive skin prick tests t to a series of allergens as the normal population. ** John E McClay and Bradley Marple Allergic Fungal Sinusitis. Otolaryngology and Facial Plastic Surgery 2008. **** Pepys J, Duveen GE. Negative skin tests in allergic rhinitis and nasal Polyposis. Int Arch Allergy 1951;2:147-60.

CRS, and - Eosinophilia Indication normal Eosinophilia Eosinophilia high Eosinophilia Count 66 7 73 % within indication 90.4% 9.6% 100.0% Count 20 5 25 % within indication 80.0% 20.0% 100.0% Count 16 7 23 % within indication 69.6% 30.4% 100.0% Count 102 19 121 % within indication 84.3% 15.7% 100.0% Person Chi-square = 0.045 Statistically significant Eosinophilia in with less significant correlation with fungal sinusitis. CRS, and - Eosinophilia

CRS, and - Eosinophilia The increase of polyps infiltrated with Eosinophils supports the theory of Ig-E mediated hyper-sensitivity being an important etiologic factor of Eosinophilic Polyposis *. Manning et al and Feger et al offer strong immunologic and histologic data to support the argument that represents an immunologically i ll mediated d disorder d rather than a point on the spectrum of infectious fungal 7. disease.* * Ogawa H. Atopic aspect of eosinophilic nasal polyposis and a possible mechanism of eosinophil accumulation. Acta Otolaryngol Suppl (Stockh) 1986;430:12-7. ** John E McClay and Bradley Marple Allergic Fungal Sinusitis. Otolaryngology and Facial Plastic Surgery 2008 CRS, and - Eosinophilia Eosinophilic activation associated with was further emphasized by Feger et al, who studied Eosinophilic cationic protein levels in the serum and mucin of patients with *. No differences in serum eosinophilic cationic protein were detected between patients with and controls, but eosinophilic cationic protein levels were significantly higher in the mucin of patients with *. ** John E McClay and Bradley Marple Allergic Fungal Sinusitis. Otolaryngology and Facial Plastic Surgery 2008

CRS, and - Ig-E Indication normal Ig E IGE CODE High Ig E Count 70 3 73 % within indication 95.9% 4.1% 100.0% Count 15 10 25 % within indication 60.0% 0% 40.0% 0% 100.0% 0% Count 21 2 23 % within indication 92% 8% 100.0% Count 108 13 121 % within indication 89.3% 10.7% 100.0% Person Chi-square = 0.000000 Statistically significant increase in fungal sinusitis. CRS, and - Ig-E And this was agreed by the following researchers

- Ig-E * Blumstein GI, Tuft L. Allergy treatment in recurrent nasal Polyposis. Its importance and value. Am J Med Sci 1957;234:269 80. ** Moloney JR. Nasal polyps, nasal polypectomy, asthma and aspirin i sensitivity. Their association in 445 cases of nasal polyps. J Laryngol Otol 1977; 91: 837-46. *** English GM. Nasal polyposis. In: English GM, editor. Otolaryngology, Vol. 2. Philadelphia: Harper and Row;1985;p.1-30. CRS, and - UPSIT test Indication Normal olfaction Olfaction Hyposmia Anosmia Ttl Count 48 23 2 73 %within indication 65.8% 31.5% 2.7% 100.0% Count 20 5 0 25 % within indication 80.0% 20.0%.0% 100.0% Count 5 12 6 23 % within indication 21.7% 52.2% 26.1% 100.0% Count 73 40 8 121 % within indication 60.3% 33.1% 6.6% 100.0% Statistically significant olfaction impairment in Person Chi-square = 0.000 rather than in and likely attributed to the extensive obstruction documented in Acoustic Rhinomanometry analysis.

CRS, and - UPSIT test CRS, and - UPSIT test This emphasis the fact that is not related to obstruction and does spare olfaction.

CRS, and - Tobacco Indication Tobacco code non smoker smoker Ttl Count 24 49 73 % within indication 32.9% 67.1% 100.0% Count 20 5 25 % within indication 80.0% 20.0% 100.0% Count 10 13 23 % within indication 43.5% 56.5% 100.0% Count 54 67 121 % within indication 44.6% 55.4% 100.0% Statistically significant correlation between smoking and (co-factor) with no correlation in or. Person Chi-square = 0.000000 CRS, and - Tobacco

CRS, and - Tobacco Smokers were found to have significantly higher concentrations of benzene and toluene in their blood than non- smokers*. These aromatic hydrocarbons are noted to have various pathophysiologic effects that may aggravate or induce nasal and sinus diseases*. * International Agency for Research on Cancer. Tobacco smoking. IARC monographs on the evaluation of carcinogenic risk of chemicals to humans. Lyon, France: IARC; 1986. CRS, and - Septal deviation Control Indication non deviated septum deviation deviated Count 47 33 80 % within indication 58.8% 41.2% 100.0% Count 41 32 73 % within indication 56.2% 43.8% 100.0% Count 25 0 25 % within indication 100.0%.0% 100.0% Count 12 11 23 % within indication 52.2% 47.8% 100.0% Count 125 76 201 % within indication code Septal deviation was encountered in and with no significant correlation, (co-factor). 62.2% 37.8% 100.0% Person Chi-square = 0.001

CRS, and - Septal deviation - Septal deviation No association of Septal deviation with could be explained by the already high-lighted h ht fact that is not related to obstruction per se.

CRS, and - Right frontal sinus involvement- CT Control Indication Non Right frontal sinus opacification Partial Count 78 1 1 80 % within indication 97.5% 1.2% 1.2% 100% Count 64 4 5 73 % within indication 87.7% 5.5% 6.8% 100% Count 20 0 5 25 % within indication 80.0% 0% 0% 20.0% 0% 100% Count 7 5 11 23 % within indication 30.4% 21.7% 47.8% 100% Count 169 10 22 201 % within indication code 84.1% 5.0% 10.9% 100% Preferential involvement of the frontal region in Person Chi-square = 0.000 and rather than in likely reflecting the local obstructive element. CRS, and - Right frontal sinus involvement- CT

CRS, and - Left frontal sinus involvement- CT Indication code non Left frontal sinus opacification partial total Control Count 78 1 1 80 % within indication 97.5% 1.2% 1.2% 100% Count 64 6 3 73 % within indication 87.7% 8.2% 4.1% 100% Count 20 0 5 25 % within indication 80.0%.0% 20.0% 100% Count 7 8 8 23 % within indication 30.4% 34.8% 34.8% 100% Count 169 15 17 201 % within indication 84.1% 7.5% 8.5% 100% The same applies for the left side Person Chi-square = 0.000 CRS, and - Left frontal sinus involvement- CT

CRS, and - Right frontal recess involvement- CT Control Indication Right frontal recess opacification non Count 78 2 80 % within indication 97.5% 2.5% 100% Count 50 23 73 % within indication 68.5% 31.5% 100% Count 20 5 25 % within indication 80.0% 20.0% 100% Count 4 19 23 % within indication 17.4% 82.6% 100% Count 152 49 201 % within indication 75.6% 24.4% 100% The same applies for the right frontal recess Person Chi-square = 0.000 CRS, and - Right frontal recess involvement- CT

CRS, and - Left frontal recess involvement- CT Control Indication Left frontal recess opacification non Count 75 5 80 % within indication 93.8% 6.2% 100% Count 44 29 73 % within indication 60.2% 39.8% 100% Count 17 8 25 % within indication 68% 32% 100% Count 5 18 23 % within indication 21.7% 78.3% 100% Count 141 60 201 % within indication 70.1% 29.9% 100% The same applies for the left frontal recess Person Chi-square = 0.000 CRS, and - Left frontal recess involvement- CT

CRS, and - Right OMC involvement- CT Indication non Right OMC opacification Control Count 73 7 80 % within indication 91.2% 8.8% 100% Count 23 50 73 % within indication 31.5% 68.5% 100% Count 0 25 25 % within indication 0% 100% 100% Count 0 23 23 % within indication 0% 100% 100% Count 96 105 201 % within indication 47.8% 52.2% 100% Statistically significant opacification of the OMC in & Person Chi-square = 0.000000 CRS, and - Right OMC involvement- CT

CRS, and - Left OMC involvement- CT Indication non Left OMC opacification Control Count 71 9 80 % within indication 88.8% 11.2% 100% Count 24 49 73 % within indication 32.9% 67.1% 100% Count 15 10 25 % within indication 60.0% 40.0% 100% Count 0 23 23 % within indication 0% 100% 100% Count 110 91 201 % within indication 54.7% 45.3% 100% The same applies for the left side Person Chi-square = 0.000 CRS, and - Left OMC involvement- CT

CRS, Fungal sinusitis and - OMC involvement- CT The statistically significant opacification of the OMC in and correlated in the former with established obstruction ti and in the latter with the fact that the fungus tends to settle primarily at the OMC region, (air-borne deposition). CRS, and - Right Anterior ethmoid air cells - CT Control Indication non Right anterior ethmoid opacification partial Count 74 5 1 80 % within indication 92.5% 6.2% 1.2% 100% Count 24 36 13 73 % within indication 32.9% 49.3% 17.8% 100% Count 5 15 5 25 % within indication 20.0% 60.0% 20.0% 100% Count 0 7 16 23 % within indication.0% 30.4% 69.6% 6% 100% Count 103 63 35 201 % within indication 51.2% 31.3% 17.4% 100% Significant correlation between anterior ethmoidal cells opacification with and Person Chi-square = 0.000

CRS, and - Right Anterior ethmoid air cells - CT CRS, and - Left Anterior ethmoid air cells - CT Control Indication non Left anterior ethmoid opacification partial total Count 70 9 1 80 % within indication 87.5% 11.2% 1.2% 100% Count 24 37 12 73 % within indication 32.9% 50.7% 16.4% 100% Count 10 10 5 25 % within indication 40.0% 40.0% 20.0% 100% Count 0 8 15 23 % within indication.0% 34.8% 65.2% 100% Count 104 64 33 201 % within indication 51.7% 31.8% 16.4% 100% The same applies for the left side Person Chi-square = 0.000

CRS, and - Left Anterior ethmoid air cells - CT CRS, and - Anterior ethmoid air cells involvement- CT The significant correlation between anterior ethmoidal cells opacification in and can be explained by the secondary effect to primary OMC obstruction, (Messerklinger 1967, 69 Stummberger 85).

CRS, and - Right Posterior ethmoid air cells - CT Control Indication Right posterior ethmoid opacification non partial total Count 74 6 0 80 % within indication 92.5% 7.5%.0% 100% Count 45 23 5 73 % within indication 61.6% 31.5% 6.8% 100% Count 10 5 10 25 % within indication 40.0% 20.0% 40.0% 100% Count 3 11 9 23 % within indication 13.0% 47.8% 39.1% 100% Count 132 45 24 201 % within indication 65.7% 22.4% 11.9% 100% Posterior ethmoid air cells preferentially involved in Person Chi-square = 0.000 rather than in and less involvement in CRS, and - Right Posterior ethmoid air cells - CT

CRS, and - Left Posterior ethmoid air cells - CT Control indication non Left posterior ethmoid opacification partial total Count 72 8 0 80 % within indication 90.0% 10.0%.0% 100.0% Count 48 21 4 73 % within indication 65.8% 28.8% 5.5% 100.0% Count 10 15 0 25 % within indication 40.0% 60.0%.0% 100.0% Count 3 11 9 23 % within indication 13.0% 47.8% 39.1% 100.0% Count 133 55 13 201 % within indication code The same applies for the left side 66.2% 27.4% 6.5% 100.0% Person Chi-square = 0.000 CRS, and - Left Posterior ethmoid air cells - CT

CRS, and - Posterior ethmoid air cells involvement- CT Preferential posterior ethmoid air cells involvement in rather than in and less involvement in still related to the widespread nature of. CRS, and - Right Maxillary sinus involvement - CT Control Indication non Right maxillary sinus opacification partial total Count 61 19 0 80 % within indication 76.2% 23.8%.0% 100.0% Count 20 46 7 73 % within indication 27.4% 63.0% 9.6% 100.0% Count 5 10 10 25 % within indication 60.0% 22% 18% 100.0% Count 1 10 12 23 % within indication 4.3% 43% 43.5% 52.2% 2% 100.0% 0% Count 87 85 29 201 % within indication 43.3% 42.3% 14.4% 100.0% Person Chi-square = 0.000 Significant involvement of the maxillary sinus in as well as CRS

CRS, and - Right Maxillary sinus involvement - CT CRS, and - Left Maxillary sinus involvement - CT Control Indication non Left maxillary sinus opacification partial total Count 64 16 0 80 % within indication 80.0% 20.0%.0% 100.0% Count 19 44 10 73 % within indication 26.0% 60.3% 13.7% 100.0% Count 15 5 5 25 % within indication 60.0% 20.0% 20.0% 100.0% Count 2 10 11 23 % within indication 8.7% 87% 43.5% 47.8% 100.0% 0% Count 100 75 26 201 % within indication code 49.8% 37.3% 3% 12.9% 100.0% 0% The same applies for the left side Person Chi-square = 0.000

CRS, and - Left Maxillary sinus involvement - CT CRS, and - Maxillary sinus involvement - CT The significant involvement of the maxillary sinus in as well as CRS could be secondary to the preferential involvement of the OMC. Less significant involvement still appreciated in could be explained on immunologic basis rather than OMC obstruction.

CRS, and - Right sphenoid sinus involvement - CT Control Indication non Right sphenoid sinus opacification partial total Count 78 1 1 80 % within indication 97.5% 1.2% 1.2% 100.0% Count 63 9 1 73 % within indication 86.3% 12.3% 1.4% 100.0% Count 15 5 5 25 % within indication 78.0% 10% 12.0% 100.0% Count 6 11 6 23 % within indication 26.1% 47.8% 26.1% 100.0% 0% Count 162 26 13 201 % within indication 80.6% 12.9% 6.5% 100.0% Significant correlation between sphenoid sinus opacification with and Person Chi-square = 0.000 CRS, and - Right sphenoid sinus involvement - CT

CRS, and - Left Sphenoid sinus involvement - CT Control Indication non Left sphenoid sinus opacification partial total Count 76 4 0 80 % within indication 95.0% 5.0%.0% 100.0% Count 62 9 2 73 % within indication 85% 12.3% 2.7% 100.0% Count 20 3 2 25 % within indication 80% 12 % 8% 100.0% Count 8 9 6 23 % within indication i 34.8% 39.1% 26.1% 100.0% 0% Count 166 25 10 201 % within indication code 82,7% 12.4% 4.9% 49% 100.0% 0% The same applies for the left side Person Chi-square = 0.000 CRS, and - Left Sphenoid sinus involvement - CT

CRS, and - Sphenoid sinus involvement - CT This correlation between sphenoid sinus opacification in and could be explained by the same latter mentioned hypothesis, as well as, organism infestation is more in proximal anterior sinus group due to increased liability of particle deposition. Conclusion Old age and female predilection for indicates an immunological i l response deficiency. i Smoking is an important co-factor in development of. Skin prick test and Ig-E increase in indicating an immunological response dependent reaction supporting the literature provided the evidence of its allergic origin.

Conclusion tends to affect primarily ethmoidal paranasal region and to a lesser extend the frontal as well as the maxillary and sphenoid sinuses. BCRS exhibits tendency for regional affection of paranasal sinuses rather than diffusion encountered in or. Presence of obstructive areas and anatomical variations is an important predisposing and perpetuating element in the pathogenesis of. Thank you