Marcella deTineo

Olfactory cleft inflammation is present in seasonal allergic rhinitis and is reduced with intranasal steroids.

Background Allergic rhinitis (AR) is commonly associated with olfactory loss, although the mechanism is not well studied. This study was designed to determine the effect of mometasone furoate (MF) on olfactory loss in seasonal AR (SAR) and study its effect on inflammation in the olfactory region. Methods We performed a randomized, double-blind, placebo-controlled, parallel clinical trial in 17 patients with SAR who had symptoms of impaired olfaction. Subjects received MF or placebo for 2 weeks during their allergy season. Before and after treatment, we measured nasal peak inspiratory flow (NPIF), chemosensory quality of life, and objective olfactory function (the University of Pennsylvania Smell Identification Test). Additionally, nasal cytology samples were obtained from each visit, and a unilateral endoscopic biopsy specimen of the olfactory epithelium was obtained at the end of the study and scored for inflammation. Results Treatment with MF was associated with improved nasal symptoms (p < 0.015), NPIF (p < 0.04), reduced nasal inflammation (p < 0.05), and chemosensory-specific quality of life (p < 0.03). Histological analysis of the olfactory region reveals fewer eosinophils in the MF group when compared with placebo (p < 0.012). We found no improvement in objective olfactory function (p > 0.05). Conclusion The use of MF in SAR is associated with reduced eosinophilic inflammation in the olfactory region and improved symptoms of AR. The presence of eosinophils in the olfactory area in SAR may indicate a direct, deleterious effect of inflammation on olfactory epithelium in this disease. In this study we show that inflammation in SAR can affect the olfactory cleft, implicating a direct role for allergic inflammation in smell loss. Treatment with intranasal steroids is associated with decreased inflammation in the olfactory region in humans. This treatment is also associated with improved olfactory quality of life.

Seasonal Allergic Rhinitis Affects Sinonasal Microbiota

Background Microbes and allergens can stimulate the nasal mucosa, potentially leading to the development of acute bacterial rhinosinusitis (ABRS). This study was designed to determine if allergen exposure alters the sinonasal microbiome. Methods We performed a parallel observational study of healthy adults with seasonal allergic rhinitis (SAR; grass or tree, n = 20) or nonallergic subjects (n = 19). Microbiota specimens were obtained by endoscopy from the middle meatus and vestibule before and during the relevant season and were analyzed by terminal restriction fragment length polymorphism analysis. Differences in bacterial microbiota were assessed by standard ecological measures of bacterial diversity. Quality of life and symptom scores were recorded, and nasal lavages for eosinophils were performed. Results SAR subjects had increased nasal symptoms in season, impaired disease-specific quality of life, and increased nasal eosinophils, compared with no changes in nonallergic subjects. During the season, SAR subjects had a significantly greater variety of organisms in the middle meatus compared with nonallergic subjects (p < 0.036) and increased bacterial diversity (Shannon index, p < 0.013). We found a significant positive correlation between bacterial diversity in the middle meatus during the season and the nasal lavage eosinophil count of SAR subjects. There were no significant changes in the nasal vestibule (p > 0.05, all comparisons). Conclusion The interaction of allergy and microbiota may affect the sinonasal physiology, with broad implications for several airway diseases. Characterization of the specific organisms involved using next-generation sequencing may clarify the relationship between allergic inflammation and ABRS. This finding may help explain why allergic inflammation predisposes to ABRS.

Effect of Intranasal Fluticasone Furoate and Intraocular Olopatadine on Nasal and Ocular Allergen-Induced Symptoms:

Background Nasal allergen challenge (NAC) leads to a nasal ocular reflex, which is augmented by allergic inflammation. This study was designed to confirm our previous observation that an intranasal steroid inhibits the nasal ocular reflex and to show that histamine does not play an important role in the genesis of this reflex. Methods We performed a randomized, double-blind, double-dummy, placebo (PL)-controlled, four-way crossover trial in subjects with seasonal allergic rhinitis out of season. Subjects were randomized to receive 1 week pretreatment with intranasal PL and intraocular (PL/PL), intranasal PL and intraocular olopatadine (PL/OLO), intranasal fluticasone furoate (FF) and intraocular PL (FF/PL), and the combination (FF/OLO). Subjects then underwent NAC on 2 consecutive days. The number of sneezes and nasal and ocular symptoms were recorded, and levels of tryptase and histamine were measured in nasal lavages. Results NAC after PL/PL resulted in increase in symptoms, histamine, and tryptase after the challenge on the 2nd day. There was a reduction in eye symptoms on the 2nd day of challenge from 6.0 after PL/PL to 0 after FF/PL (p = 0.001), 2.5 after PL/OLO (p = 0.3), and 1.5 after FF/OLO (p = 0.003). Furthermore, there was no significant difference between the response after FF/PL versus FF/OLO and a significant difference between FF/PL and PL/OLO (p = 0.02). Levels of tryptase followed a similar trend. The number of eosinophils in nasal lavages on the 2nd day of challenge were also reduced by the treatment arms containing FF compared with PL. Conclusion Our data confirm the existence of a nasal ocular reflex after NAC. OLO alone or the addition of OLO to FF does not impact ocular symptoms caused by the naso-ocular reflex, suggesting that mast cells are not activated to release histamine in the conjunctiva during this process.

Unilateral nasal allergic reactions increase bilateral sinus eosinophil infiltration

We have previously shown that unilateral nasal challenge with antigen causes an increase in the number of eosinophils in the ipsilateral maxillary sinus. Here we aimed to determine whether there was an eosinophil response in the contralateral maxillary sinus after unilateral nasal challenge with antigen. Twenty subjects with a history of seasonal allergic rhinitis and a positive nasal challenge to ragweed or grass allergens were studied outside of their allergy season. Catheters were placed in both maxillary sinuses and the subjects were challenged with antigen via the left nostril. The subjects recorded nasal symptoms before and after each allergen challenge and hourly for 8 h afterward. We performed nasal lavages of the nose and sinuses at the same time as symptoms were recorded. The lavages were analyzed for the number of eosinophils and levels of albumin. Subjects showed a symptomatic response to challenge accompanied by an influx of eosinophils into the nose and increased vascular permeability. The number of eosinophils increased in both maxillary sinuses. The total change from diluent in eosinophils during the late phase response was higher in the ipsilateral maxillary sinus (median = 8,505; range = 0-100,360) compared with the contralateral sinus (median = 1,596; range = -13,527-93,373; P = 0.03). We conclude that eosinophils increase in both maxillary sinuses after unilateral nasal challenge. We speculate that a central neurologic reflex initiated in the nose by the nasal challenge contributes to the bilateral eosinophil response in the maxillary sinuses. We further speculate that, since there are more eosinophils in the ipsilateral compared with the contralateral maxillary sinus, there is also an axonal reflex into the ipsilateral maxillary sinus that contributed to the eosinophil response.