American Journal of Rhinology & Allergy

Many researchers have focused on the definition and pathophysiology of localized mucosal allergy. However, there are few studies on its clinical characteristics and therapeutic outcomes. The goal of this study was to analyze the prevalence, epidemiology, clinical characteristics, and response to antiallergic medication of localized mucosal allergy patients compared with those in patients with allergic rhinitis.

Among 836 patients suspected to have rhinitis, 29 patients with localized mucosal allergy (group A) and 29 patients with allergic rhinitis (group B) were selected. Medical history, family history, symptoms, and their severity were obtained using a questionnaire. The change in minimal cross-sectional area (MCA) after provocation was measured by acoustic rhinometry. After 2 weeks of antihistamine medication, the changes in symptoms were compared between groups.

The prevalence of localized mucosal allergy was ∼3.5%. There were no differences in patient history, symptoms, or symptom severity. The decrease in MCA after provocation was not significantly different. After two weeks of oral antihistamine (ebastine 10 mg once daily), group A reported significantly less symptom improvement than group B.

Because patient or family history and clinical picture are very similar in localized mucosal allergy and allergic rhinitis, clinicians should take more care in differentiating them. Based on the reduced effectiveness of an oral antihistamine alone, a combined regimen of oral and topical antihistamine or anti-inflammatory medication is recommended for patients with localized mucosal allergy.

Allergic rhinitis (AR), the most common chronic allergic condition in outpatient medicine, is associated with immense health care costs and socioeconomic consequences. AR's impact may be partly from interacting of respiratory conditions via allergic inflammation. This study was designed to review potential interactive mechanisms of AR and associated conditions and consider the relevance of a bidirectional “unified airway” respiratory inflammation model on diagnosis and treatment of inflammatory airway disease.

MEDLINE was searched for pathophysiology and pathophysiological and epidemiologic links between AR and diseases of the sinuses, lungs, middle ear, and nasopharynx.

Allergic-related inflammatory responses or neural and systemic processes fostering inflammatory changes distant from initial allergen provocation may link AR and comorbidities. Treating AR may benefit associated respiratory tract comorbidities. Besides improving AR outcomes, treatment inhibiting eosinophil recruitment and migration, normalizing cytokine profiles, and reducing asthma-associated health care use in atopic subjects would likely ameliorate other upper airway diseases such as acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis media with effusion.

Epidemiological concordance of AR with several airway diseases conforms to a bidirectional “unified airway” respiratory inflammation model based on anatomic and histological upper and lower airway connections. Epidemiology and current understanding of inflammatory, humoral, and neural processes make links between AR and disorders including asthma, otitis media, NP, and CRS plausible. Combining AR with associated conditions increases disease burden; worsened associated illness may accompany worsened AR. AR pharmacotherapies include antihistamines, leukotriene antagonists, intranasal corticosteroids, and immunotherapy; treatments attenuating proinflammatory responses may also benefit associated conditions.

This study was performed to explore whether or not a neural reflex linking the esophagus and the nasal airway exists, as a pathogenic mechanism accounting for the association between gastroesophageal reflux (GER) disease and chronic rhinosinusitis (CRS). A prospective trial of healthy human volunteers was performed.

Ten healthy volunteers without GER or sinonasal disease were investigated using an acid infusion challenge test. Normal saline and hydrochloric acid were infused into the lower esophagus through an esophageal manometry catheter. Nasal responses in symptom score, nasal inspiratory peak flow, and mucus production were analyzed after the esophageal challenge.

A tendency for an increase in nasal mucus production was observed after esophageal stimulation with both normal saline and HCl. This returned to baseline level 45 minutes after the acid infusion. A similar trend was also observed with the measurements of nasal symptom scores and, to a lesser extent, nasal inspiratory peak flow.

These results support the possibility that a neural reflex exists between the esophagus and the paranasal sinuses via the vagus nerve. If indeed present, the reflex-mediated rhinitis derived from this neuropathic inflammation may contribute to the development of CRS in patients with GER. Further study is required to define the relationship between GER and CRS.

Cold dry air provocation is useful for evaluating nonspecific nasal hyperreactivity. However, there is no research on nasal volume and dimensions after cold dry air provocation. In this respect, acoustic rhinometry is a useful tool in objectively assessing nasal cavity volume and dimension. The goal of this study was to evaluate nonspecific hyperreactivity using cold dry air provocation with acoustic rhinometry.

Cold dry air provocation with acoustic rhinometry was performed on 21 healthy volunteers (group A), 24 patients with allergic rhinitis (group B), and 32 patients with nonallergic rhinitis (group C). The change in symptoms using a visual analog scale (VAS), amount of rhinorrhea, and change of total nasal volume (TNV) and minimal cross-sectional area (MCA) were measured in all three groups.

The two patient groups showed greater change in nasal symptoms (VAS, 2.0 ± 2.3 in group C versus 0.9 ± 1.8 in group A), more rhinorrhea (0.4 ± 0.7 g in group B and 0.3 ± 0.3 g in group C versus 0.1 ± 0.1 g in group A), and greater change in total nasal volume (TNV) and MCA. The patient group with history of nonspecific hyperreactivity showed more rhinorrhea (0.5 ± 0.7 g versus 0.1 ± 0.2 g) and greater change in TNV and MCA (TNV, 56.8 ± 39.5% versus 18.0 ± 17.0%; MCA, 86.6 ± 81.0% versus 11.5 ± 9.7%).

Cold dry air provocation with acoustic rhinometry could be a useful adjunct tool for detecting nonspecific hyperreactivity.

Chronic rhinosinusitis (CRS) is a common disease with a complex pathophysiology involving a microbial component. Culture-independent molecular analysis represents a promising new approach to clarify the microbiology of CRS, but standardized, optimized sampling methods still have not been defined. This study was designed to compare nucleic acid extraction rates and recovery of bacteria for two methods of sampling the maxillary sinus, mucosal biopsy, and brushing.

Samples were obtained from 20 patients undergoing maxillary sinus surgery. Total extracted nucleic acid concentration and bacterial burden were compared between sample types.

Total nucleic acid concentration varied across patients. No statistically significant difference in mean total DNA concentration from mucosal biopsy specimens or brushings was observed. However, compared with biopsy specimens, brush samples possessed a significant (p < 0.035) increase in bacterial copy number.

Endoscopically directed mucosal brushings of the maxillary sinus provide equivalent concentrations of total DNA to mucosal biopsy specimens but possess greater concentrations of bacterial DNA, likely because of the greater surface area sampled by this method. Given the additional advantage of lower risk associated with obtaining brush samples, we suggest they represent the preferred sampling method for future genomic sinus studies.

Hepatocyte growth factor (HGF) is a growth factor thought to attenuate Th2-driven eosinophilic airway inflammatory responses. Increased expression of HGF and its receptor c-Met in nasal polyps suggests a role in disease pathogenesis. The effect of HGF on human sinonasal epithelial cell (SNEC) responses to Th2 inflammatory cytokines in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been explored.

SNECs isolated from patients with CRSwNP and control subjects were grown in cell culture at the air–liquid interface. The Th2 cytokine IL-13 was applied for 24 hours in the presence or absence of HGF. Eotaxin-3 and c-Met expression was assessed using real-time PCR, immunohistochemistry, and flow cytometry.

SNECs obtained from both CRSwNP and control subjects showed markedly increased expression of eotaxin-3 after exposure to IL-13. HGF significantly blocked IL-13–induced expression of eotaxin-3 in control SNECs, but not in SNECs derived from CRSwNP subjects.

SNECs are active participants in sinonasal mucosal immunity, expressing inflammatory mediators in response to potential pathogens and endogenous cytokines. Although Th2 cytokines can elicit expression of proeosinophilic mediators by SNECs, HGF appears to have a down-regulating effect on this response. In patients with CRSwNP, SNECs are resistant to this attenuation, showing continued IL-13–induced eotaxin-3 expression despite HGF treatment. Abnormalities in the regulation of epithelial cell responses to endogenous cytokines and growth factors may contribute to the persistent eosinophilic inflammatory state in CRSwNP.

There have been no data on sublingual immunotherapy (SLIT) in Asian patients with allergic rhinitis (AR) sensitized to house-dust mites (HDMs). This study aimed to investigate the efficacy and immunologic change after 12 months of SLIT in Korean patients.

Fifty-eight patients, who had AR caused by Dermatophagoides pteronyssinus and Dermatophagoides farinae and who completed 12 months of SLIT were included. Symptom scores were evaluated before and after 12 months of SLIT, and medication scores were assessed throughout the study. Peripheral blood eosinophil counts, eosinophil cationic protein (ECP), total IgE, and specific IgE were also evaluated.

All of the symptoms of AR were significantly improved with reduced medication scores. In addition, there were significant decrements in peripheral blood eosinophil counts and ECP (p = 0.025 and p = 0.048, respectively). Specific IgE for D. farinae slightly increased (p = 0.019), whereas specific IgE for D. pteronyssinus and total IgE did not change significantly. Thirty-six (62%) of 58 patients were in the effective response group. Although not statistically significant, findings in the study showed that the effective response group had a tendency to have higher ECP levels before SLIT than the ineffective response group (p = 0.056).

SLIT improved the symptoms and medication scores in Korean patients with AR from HDM. Laboratory parameters including eosinophil counts, ECP, and specific IgE for D. farinae seemed to be modified after 1-year SLIT. A high ECP level may be a useful parameter to predict the effectiveness of SLIT and select the patient for the treatment.

Determination of predictive factors and specific values of olfactory function after endoscopic sinus surgery (ESS) using objective diagnostic methods may support consultation of respective patients. This study was designed to assess the longitudinal olfactory functional outcome after ESS in patients with severe chronic rhinosinusitis (CRS) with nasal polyposis, to evaluate associated clinical factors and to provide statistical models for prediction of olfactory recovery.

One hundred sixteen patients with nasal polyposis refractory to medical treatment underwent ESS. Olfactory testing was performed preoperatively and 1, 3, and 6 months after surgery using “Sniffin’ Sticks” (Burghardt, Wedel, Germany). Using multivariate linear and logistic regression analysis, statistical models were generated to predict (i) the 6th-month composite threshold-discrimination-identification (TDI) score and (ii) the probability of attaining normal olfaction at 6 months.

A significant stepwise increment of all olfactory function indices was found over time. Factors influencing final olfactory recovery were patients’ age, duration of olfactory deficit, previous paranasal sinus surgery, and aspirin-exacerbated respiratory disease. The first model explained 70% of the observed variation in postoperative TDI scores. The second model correctly classified 76% of the patients.

A significant progressive improvement of olfaction for at least 6 months was observed after ESS. The statistical models developed may be useful for consultation of ESS candidates in clinical practice.

Histological inflammation correlates with the degree of baseline olfactory dysfunction in patients with chronic rhinosinusitis (CRS); however, factors associated with improvement in olfactory status after endoscopic sinus surgery (ESS) remain elusive. Our purpose was to compare histopathological findings in CRS patients with olfactory loss and evaluate whether inflammatory markers can predict long-term olfactory improvement after ESS.

Adult (≥18 years) patients with CRS were prospectively enrolled after electing ESS due to failed medical management. Mucosal tissue specimens were collected at the time of surgery and underwent pathological review in a blinded fashion. Subjects completed the 40-item Smell Identification Test (SIT) preoperatively and at least 6 months postoperatively. Multivariate logistic regression was used to identify histological factors associated with postoperative improvement in SIT score.

The final cohort was comprised of 101 patients with a mean follow-up of 16.7 ± 6.0 months. Mean mucosal eosinophil count was higher in patients with hyposmia and anosmia (p < 0.001). Patients with preoperative anosmia were more likely to have greater severity of basement membrane (BM) thickening compared with subjects with hyposmia or normosmia (p = 0.021). In patients with olfactory dysfunction, 54.7% reported olfactory improvement of at least 4 points on postoperative SIT scores. After controlling for nasal polyposis, histological variables were not associated with postoperative improvement in olfaction.

Patients with severe olfactory dysfunction were more likely to have mucosal eosinophilia and BM thickening on ethmoid histopathological examination compared with normosmic patients. The presence of specific histological inflammatory findings did not, however, predict olfactory improvement after surgery.

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.

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.

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).

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.

Little information exists on the impact of baseline polyp size and previous nasal surgery on the efficacy of intranasal steroids. This study was designed to investigate whether baseline polyp size and previous nasal surgery influence the efficacy of an intranasal steroid delivered with a novel device.

A post hoc analysis of recently published results with intranasal administration using a novel bidirectional delivery device containing fluticasone propionate (Opt-FP) was performed in 109 patients with mild-to-moderate bilateral polyposis. Patients were allocated to subgroups based on summed polyp score at baseline (2, 3, or 4) and on their history of previous sinus surgery.

A highly significant and progressive reduction in summed polyp size was observed for Opt-FP versus placebo in all three polyp size subgroups (p < 0.001). A greater relative reduction in polyp size (p < 0.05) and an increase in peak nasal inspiratory flow (p < 0.001) were observed for Opt-FP at 12 weeks in the 28 patients with a baseline summed score of 3 and 4 compared with the 27 with a summed score of 2. Nevertheless, in patients with small polyps at baseline, the polyps were completely resolved on both sides in 7 of 27 patients. Previous sinus surgery had no impact on efficacy.

The highly significant progressive treatment effect of Opt-FP was observed regardless of baseline polyps score. Coupled with the complete removal of polyps in many patients with small polyps, this suggests that improved deposition to target sites achieved with the bidirectional delivery device may translate into true clinical benefits and reduced need for surgery.

Endoscopic sinus surgery (ESS) is reported to improve symptoms in ∼85% of patients. Reasons for failure include misdiagnosis, technical inadequacies, underlying severe hyperplastic disease, biofilm, and immunodeficiency. Only one previous case of unrecognized odontogenic maxillary sinusitis has been cited in the literature as a reason for failure to improve with sinus surgery. This study was designed to characterize clinical and radiographic findings in patients who fail to improve with ESS because of an unrecognized dental etiology.

Five patients, with odontogenic maxillary sinusitis with prior unsuccessful ESS, were prospectively enrolled. Demographics and clinical aspects including duration of illness, prior sinus surgeries and therapies, and radiographic data were assessed.

Five adults underwent an average of 2.8 sinus surgeries with persistence of disease and symptoms until their dental infection was treated. Duration of symptoms ranged from 3 to 15 years. In four of five patients, the periapical abscess was not noted on the original CT report but could be seen in retrospect. Three of five patients had been seen by their dentists and told they had no dental pathology. All five patients underwent dental extractions and one patient underwent an additional ESS after dental extraction. These procedures led to a resolution of sinusitis symptoms in all five patients.

Unrecognized periapical abscess is a cause of ESS failure and the radiological report frequently will fail to note the periapical infection. Dentists are unable to recognize periapical abscesses reliably with dental x-rays and exam. In patients with maxillary sinus disease, the teeth should be specifically examined as part of the radiological workup.

The identification of anatomic landmarks in endoscopic skull base or revision sinus surgery can be challenging. Normal anatomy is significantly altered with many paranasal tumors. Traditional endoscopic surgical landmarks extrapolated from inflammatory disease, such as the superior turbinate, may have been previously removed or involved in pathology. A frequently used rule to enter the sphenoid, “stay below or at the level of the orbital floor as dissection proceeds posteriorly and one will avoid the skull base,” is assessed anatomically.

The maxillary sinus roof height, relative to the nasal floor, was assessed as an operative landmark. Computed tomography (CT) performed on paranasal sinuses was studied. The relative height, ratio, and proportions of the maxillary sinus, ethmoid roof, cribriform fossa, and sphenoid planum were measured using computerized assessments.

Three hundred paranasal sinus systems were evaluated. The roof of the maxillary sinus was below the level of the skull base in 100% relative to the cribriform and 100% relative to the sphenoid planum. The mean distance of the maxillary roof below the skull base was 10.1 ± 2.7 mm for the cribriform and 11.0 ± 2.9 mm for the sphenoid.

The maxillary sinus roof can be used as a robust landmark to allow safe dissection and debulking of pathology. Pathology removal can proceed posterior with this landmark to enable a safe entry to the sphenoid sinus, and thus the true skull base, when normal structures such as the superior turbinate and ostium are not available.

The study was designed to assess the usefulness of postoperative antibiotics in patients undergoing endoscopic sinus surgery (ESS).

The effects of antibiotics in the postoperative period of ESS patients were evaluated in a prospective, randomized, double-blind, placebo-controlled study. Fifty patients were treated with amoxicillin/clavulanate for 2 weeks after ESS, while the other half received placebo. Preoperatively, the symptom, endoscopic, and CT scores were recorded. In the postoperative period, symptom and endoscopic scores were recorded on the 5th, 12th, 21st, and 30th days. In estimating the length of the blood crust formation episode, a Kaplan-Meier plot was used.

Seventy-five patients completed the study: forty in the antibiotic-treated group and thirty-five in the placebo group. On the 5th day, nasal obstruction and drainage were significantly better in the antibiotic-treated group. In addition, a statistically significant difference in the endoscopic scores was noted between the treatment and placebo groups on days 5 and 12.

The use of an antibiotic (amoxicillin/clavulanate) in the postoperative period is able to improve the outcome in the early blood crust healing phase: nasal obstruction and drainage are reduced and the endoscopic score objectively showed a faster recovery.

Insult from surgical trauma leads to a degeneration of the nasal epithelium, resulting in morphological–volumetric changes involving the entire cell or a specific cell component. Alterations in normal nasal mucosa were assessed by nasal cytology and other functional tests after either endoscopic turbinoplasty or laser-assisted turbinoplasty for reducing inferior turbinate enlargement.

A total of 150 patients with chronic nasal obstruction due to inferior turbinate hypertrophy were randomly assigned to undergo laser-assisted turbinoplasty or endoscopic turbinoplasty. Preoperative and postoperative assessment at 1 and 3 months follow-up included active anterior rhinomanometry, measurement of mucociliary transport time (MCTt), and nasal cytology to determine whether improved nasal breathing was accompanied by a restoration of preoperative nasal cytology and MCTt. One year after the operation, nasal cytology was repeated to definitively evaluate the presence of surgery-related cytological damage.

At both postoperative visits, nasal resistance had decreased similarly in both treatment groups; mean MCTt was significantly shorter in the endoscopic turbinoplasty-treated group (p < 0.05); at both visits, the number of altered ciliated cells had increased in the laser-assisted turbinoplasty-treated group but decreased in the endoscopic turbinoplasty-treated group, which, unlike the laser-assisted turbinoplasty-treated group, was also noted to have progressed toward a significant improvement in the goblet-to-ciliated cell ratio (p < 0.01).

When compared with laser-assisted turbinoplasty, endoscopic turbinoplasty is a conservative technique for inferior turbinate reduction that allows better restoration of preoperative nasal cytology and shorter MCTt.