Long-term Breastfeeding in the Prevention of Allergic Rhinitis: Allergic Rhinitis Cohort Study for Kids (ARCO-Kids Study).

OBJECTIVES: There is a great deal of interest in the possibility that environmental factors may influence the risk of developing allergic rhinitis (AR) in early life. We investigated the simultaneous effects of mode of delivery and duration of breastfeeding on the development of AR in children. METHODS: Data from 1,374 children participating in the Allergic Rhinitis Cohort Study for kids (ARCO-kids study) was analyzed. All subjects were divided into AR or non-allergic rhinitis (NAR) groups. Data on environmental factors, mode of delivery and duration of breastfeeding were collected using a questionnaire. RESULTS: Compared with short-term breastfeeding (<6 months), long-term breastfeeding (≥12 months) was significantly associated with a lower prevalence of AR (adjusted odds ratio [aOR], 0.54; 95% confidence interval [CI], 0.34 to 0.88). Children in the AR group also had a higher cesarean delivery rate than those in the NAR group (39.1% vs. 32.8%, P=0.05). Regarding the combined effects of mode of delivery and duration of breastfeeding, long-term breastfeeding with a vaginal delivery strongly suppressed the development of AR, compared to short-term breastfeeding with a cesarean delivery (aOR, 0.47; 95% CI, 0.30 to 0.73). CONCLUSION: Long-term breastfeeding (≥12 months) and a vaginal delivery are associated with a lower risk of developing childhood AR.

Comparison of level and degree of upper airway obstruction by Müller's maneuver and drug-induced sleep endoscopy in obstructive sleep apnea patients.

OBJECTIVE: This study aimed to compare and analyze the level and degree of observed upper airway obstruction in patients with obstructive sleep apnea (OSA) using Müller's maneuver (MM) and drug-induced sleep endoscopy (DISE). We sought to find a method for evaluating the upper airway that could be used to determine surgical sites. METHODS: This study included 80 OSA patients who visited Kyung Hee Medical Center and underwent polysomnography (PSG) from March 2013 to March 2014. Obstructive levels observed by MM were classified into retropalatal level, or the lateral wall and retroglossal level. These levels were compared with those determined by DISE through the VOTE classification. RESULTS: Based on the results of MM and DISE, lateral wall and retropalatal level obstructions showed relatively high conformity, while retroglossal level obstruction exhibited considerable differences. When evaluated at each level, patients with obstruction on MM also showed partial or complete obstruction on DISE at same level, and patients with no obstruction on DISE also showed no obstruction on MM at same level. CONCLUSION: Both examination methods revealed the same obstruction levels in all cases except epiglottic level, but there were some differences in obstructive degree. MM is capable of detecting obstruction levels in the upper airway and can be used to determine surgical sites in cases when DISE cannot be used due to a patient's condition or a clinic's circumstances.

Long-term Effects of Specific Allergen Immunotherapy Against House Dust Mites in Polysensitized Patients With Allergic Rhinitis.

PURPOSE: Allergen-specific immunotherapy is the only currently available treatment to modify the natural history of allergic rhinitis (AR). If patients are polysensitized, it is difficult to identify the allergen causing the allergic symptoms. We evaluated the effectiveness of immunotherapy against house dust mites (HDMs) in AR patients polysensitized to both HDMs and seasonal allergens. METHODS: Thirty AR patients polysensitized to both HDMs and seasonal allergens (group A) and 30 patients sensitized to HDMs only (group B) were enrolled in this study. All subjects who received immunotherapy against HDMs for more than 2 years were evaluated by the multiple allergen simultaneous test (MAST) to determine the specific IgE level in luminescence units, total eosinophil counts in peripheral blood, serum total IgE, total nasal symptom scores, and the rhinoconjunctivitis quality of life questionnaire (RQLQ) before and after immunotherapy. RESULTS: There were no statistical differences in levels of total and specific IgE, or total eosinophil count between the two groups. The total nasal symptom scores, RQLQ and medication scores significantly decreased after immunotherapy in both groups, however no significant differences were noted between the two groups. CONCLUSIONS: We determined that the primary causative allergen of AR in Seoul, Korea is perennial allergens, such as HDMs, rather than seasonal allergens. This study provides a reference for the selection of allergens to use in immunotherapy for polysensitized AR patients living in an urban environment.

Changes in histological features of nasal polyps in a Korean population over a 17-year period.

OBJECTIVE: Nasal polyps can be categorized as eosinophilic or non-eosinophilic, depending on inflammatory cell infiltration. There are geographical differences in the prevalence of types of pathologic polyps. The aim of this study was to evaluate the change in the prevalence of histological subtypes of polyps over time in a Korean population. STUDY DESIGN: A retrospective cross-sectional study with histologic analysis. SETTING: A single academic medical center. SUBJECTS AND METHODS: A total of 230 patients with nasal polyps were enrolled between 1993-1994 (group A) and 2010-2011 (group B). Specimens were fixed in formalin and embedded into paraffin blocks. Slides were stained with hematoxylin-eosin (H&E) and were subsequently reviewed by 2 of the authors. The numbers of eosinophils per high power field (HPF), as well as other cellular, epithelial, and stromal markers, were recorded. RESULTS: We compared nasal polyp eosinophil counts according to time period. The average eosinophil count/HPF increased from 6.8 in group A to 19.3 in group B (P = .006). The prevalence of eosinophilic polyps also increased from 24.0% in group A to 50.9% in group B (P < .001). Among other histologic markers, lymphocytes, basement membrane thickening, and gland hyperplasia showed significant differences between groups. CONCLUSION: After comparison of histopathologic findings of nasal polyps from 1993 and 2011 at 1 academic medical center in Korea, the prevalence of eosinophilic nasal polyps, which are known to be rare among Asians, has significantly increased.

Changes of histamine receptors and CC chemokines in nasal epithelial cells and fibroblasts after respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) is reported as the most influential factor that triggers hyperreactivity of the airway and causes asthma in infants and children. However, the mechanisms remain to be elucidated. The study evaluated the changes in the levels of four types of histamine receptor (HR) and CC chemokines, such as eotaxin and regulated on activation, normal T cell expressed and presumably secreted (RANTES), in nasal epithelial cells and fibroblasts after RSV infection. METHODS: Nasal cavity mucosa attained from 20 patients who had undergone inferior turbinoplasty were cleaned by normal saline mixed with gentamicin. Each sample was divided in half. One-half was used for incubation of epithelial cells, and the other half was used for culturing fibroblasts. The levels of HR 1 (H1R), 2 (H2R), 3 (H3R), 4 (H4R), eotaxin, and RANTES were measured by real-time polymerase chain reaction 0, 12, and 36 hours after infection with RSV. RESULTS: H1R was significantly increased at 12 and 36 hours compared with 0 hours in both cell types. The level of H2R was significantly increased in epithelial cells from 0 to 36 and 12 to 36 hours and in fibroblasts from 0 to 12 and 0 to 36 hours. There were significant increases of H3R level in fibroblasts from 0 to 12 and 0 to 36 hours, and of H4R in epithelial cells and fibroblasts from 0 to 12 and 0 to 36 hours. Eotaxin and RANTES were also significantly increased in both epithelial cells and fibroblasts from 0 to 12 and 0 to 36 hours. CONCLUSION: RSV infection increases the levels of all four HRs, especially H1R and H2R, as well as the levels of eotaxin and RANTES in nasal epithelial cells and fibroblasts. These findings suggest that RSV infection might cause respiratory tract hyperreactivity by increasing the content of HRs and CC chemokines.

Change of prevalence and clinical aspects of fungal ball according to temporal difference.

Fungal ball in paranasal sinus was reported to be rare, but these days we have encountered numerous cases. We retrospectively analyzed the data of 4,485 patients with chronic rhinosinusitis (CRS) who underwent sinus surgery from 1999 to 2010. Patients were categorized into group A (patients from 1999 to 2004) and group B (patients from 2005 to 2010). We compared the prevalence and clinical aspects of fungal ball between the two groups by analyzing the medical records, PNS CT findings, surgical findings, and pathologic reports. One hundred and twelve patients were diagnosed with fungal ball during the study periods. The prevalence of fungal ball was 0.9 % (23/2,333) in group A and 4.1 % (89/2,152) in group B, showing that it increased 4.6 times over 6 years. The prevalence of underlying diseases was 21.7 % (5/23) for hypertension and 8.7 % (2/23) for diabetes in group A, and 23.6 % (21/89) for hypertension and 14.6 % (13/89) for diabetes in group B. On PNS CT examination, calcification was identified in 78.2 % (18/23) of cases in group A and 44.9 % (40/89) in group B. The most involved paranasal sinus in group A was the co-involved maxillary and ethmoid sinuses at 26.1 % (6/23), whereas, the most prevalent involved sinus in group B was the maxillary sinus at 33.7 % (30/89). We found that the prevalence of fungal ball has increased steadily each year since 2005, accompanied by changes in the clinical aspects. These facts should be kept in mind when diagnosing and treating patients with medically intractable CRS.

Local IgE-mediated hypersensitivity to Alternaria in pediatric adenoid tissue.

OBJECTIVE: Fungus may contribute to the development and exacerbation of allergic airway diseases. Several studies have demonstrated the presence of humoral immune responses to fungi, including Alternaria and Aspergillus, in patients with nasal polyposis, asthma, or rhinitis. The purpose of this study was to evaluate the role of Alternaria- and Aspergillus-specific IgE antibodies in allergic inflammation of adenoid tissue. METHODS: Thirty-nine atopic subjects who were sensitized to more than one common aeroallergen and 39 non-atopic subjects undergoing adenotonsillectomy were recruited. The Phadia ImmunoCAP was used to quantify total IgE, Alternaria- and Aspergillus-specific IgE, eosinophil cationic protein (ECP), and mast cell tryptase in adenoid tissue homogenates. Alternaria- and Aspergillus-specific IgE were detected in the adenoid tissues from some of the subjects (37.2% and 24.4%, respectively) without systemic sensitization to common airborne fungi. RESULTS: Both Alternaria- and Aspergillus-specific IgE were more prevalent in adenoid tissues from atopic children (48.7% and 38.5%, respectively) than in tissues from non-atopic children (25.6% and 10.3%, respectively). Subjects with high Alternaria-specific IgE level showed significantly higher serum and adenoid total IgE and adenoid ECP and tryptase than those without specific IgE. Alternaria-specific IgE levels were significantly correlated with serum and adenoid total IgE and with tryptase and ECP levels in adenoid tissue. CONCLUSIONS: Adenoid tissues from atopic and non-atopic children displayed local IgE-mediated hypersensitivity to fungi in the absence of systemic fungal hypersensitivity. Locally-produced Alternaria-specific IgE may contribute to mast cell and eosinophil activation, especially in the presence of tissue eosinophilia.

Comparison of pre- and post-operative stress levels in patients with allergic rhinitis and non-allergic rhinitis.

The effects of stressful events, such as surgery, on patients with allergic diseases are unclear. The aim of this study was to evaluate whether patients with allergic rhinitis (AR) are more susceptible to stress and oxidative stress than non-allergic individuals. 20 AR patients and 20 non-allergic rhinitis (NAR) patients were recruited to this study and underwent nasal septoplasty. To evaluate the degrees of stress and oxidative stress, we collected urine and blood samples 1 day before and 1 day after surgery. Stress was assessed by measuring urine cortisol levels. Oxidative stress was assessed by calculating the balance of reactive oxygen metabolites (ROM) measured by the diacron reactive oxygen metabolites test, and antioxidant capacity (AC) was measured by the biological antioxidant potential test. In both groups, the level of post-operative urine cortisol was significantly higher than the pre-operative level, with no significant difference between the two groups. ROM levels were significantly higher in both groups after surgery than before surgery. The antioxidant capacity of the AR group was lower after surgery than before surgery, while it was greater in the NAR group after surgery. There were no significant differences in pre- or post-operative ROM or AC levels between the two groups. The ROM/AC ratio was significantly higher after surgery in the AR group than it was in the NAR group. The post-operative ROM/AC imbalance of AR patients suggests that these patients might be vulnerable to stress, especially oxidative stress.

The effect of allergic rhinitis on the degree of stress, fatigue and quality of life in OSA patients.

Both allergic rhinitis (AR) and obstructive sleep apnea (OSA) are known to increase stress and fatigue, but the result of their coexistence has not been studied. The objective of this study was to evaluate the amount of stress and fatigue when AR is combined with OSA. One hundred and twelve patients diagnosed with OSA by polysomnography were enrolled. Among them, 37 patients were diagnosed with AR by a skin prick test and symptoms (OSA-AR group) and 75 patients were classified into the OSA group since they tested negative for allergies. We evaluated the Epworth sleepiness scale (ESS), stress score, fatigue score, ability to cope with stress, and rhinosinusitis quality of life questionnaire (RQLQ) with questionnaires and statistically compared the scores of both groups. There were no significant differences in BMI and sleep parameters such as LSAT, AHI, and RERA between the two groups. However, the OSA-AR group showed a significantly higher ESS score compared to the OSA group (13.7 ± 4.7 vs. 9.3 ± 4.8). Fatigue scores were also significantly higher in the OSA-AR group than in the OSA group (39.8 ± 11.0 vs. 30.6 ± 5.4). The OSA-AR group had a significantly higher stress score (60.4 ± 18.6 vs. 51.2 ± 10.4). The ability to cope with stress was higher in the OSA group, although this difference was not statistically significant. RQLQ scores were higher in the OSA-AR group (60.2 ± 16.7 compared to 25.1 ± 13.9). In conclusion, management of allergic rhinitis is very important in treating OSA patients in order to eliminate stress and fatigue and to minimize daytime sleepiness and quality of life.

IL-32 up-regulation is associated with inflammatory cytokine production in allergic rhinitis.

IL-32 is a described pro-inflammatory cytokine produced by T lymphocytes, natural killer cells, monocytes, and epithelial cells. However, the specific mechanism of IL-32 on allergic rhinitis (AR) has not been elucidated. Here, we report a significant increase of IL-32 protein and mRNA in the nasal mucosa of AR patients. In addition, in nasal mucosa tissue from AR patients, the level of IL-32 production correlated with inflammation, IL-1ß, IL-18, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In an AR animal model, IL-32 significantly increased IgE and inflammatory cytokine levels. IL-32 expression was induced by recombinant human GM-CSF via activation of caspase-1 in eosinophils. In addition, depletion of IL-32 prevents the production of inflammatory cytokines in eosinophils. In conclusion, IL-32 is an important cytokine involved in the inflammation of AR. The regulation of IL-32 expression may form the basis of a new strategy for the treatment of AR.

Changes of Alpha1-Antitrypsin Levels in Allergen-induced Nasal Inflammation.

OBJECTIVES: Alpha1-antitrypsin (AAT) is the main inhibitor of human neutrophil elastase, and plays a role in counteracting the tissue damage caused by elastase in local inflammatory conditions. The study evaluated the involvement of AAT in nasal allergic inflammation. METHODS: Forty subjects with mono-sensitization to Dermatophagoides pteronyssinus (Dpt) were enrolled. Twenty allergic rhinitis patients frequently complained of nasal symptoms such as rhinorrhea, stuffiness, sneezing, and showed positive responses to the nasal provocation test (NPT) with Dpt (Group I). The other 20 asymptomatic patients showed sensitization to Dpt but negative NPT (Group II). The levels of AAT, eosinophil cationic protein (ECP), and Dpt-specific IgA antibodies were measured in the nasal lavage fluids (NLFs), collected at baseline, 10 minutes, 30 minutes, 3 hours, and 6 hours after the NPT. Nasal mucosa AAT expression was evaluated with immunohistochemical staining from Group I and Group II. RESULTS: At baseline, only the Dpt-specific IgA level was significantly increased in the NLFs of Group I compared with Group II, while ECP and AAT levels were not significantly different between two groups. After Dpt provocation, AAT, ECP, and Dpt-specific IgA levels were significantly increased in the NLFs of Group I during the early and late responses. The protein expression level of AAT was mostly found in the infiltrating inflammatory cells of the nasal mucosa, which was significantly increased in Group I compared to Group II. CONCLUSION: The increment of AAT showed a close relationship with the activation of eosinophils induced by allergen-specific IgA in the NLFs of patients with allergic rhinitis after allergen stimulation. These findings implicate AAT in allergen-induced nasal inflammation.

Short-term effect of multilevel surgery on adipokines and pro-inflammatory cytokines in patients with obstructive sleep apnea.

CONCLUSION: This study shows the possibility that multilevel surgery for obstructive sleep apnea (OSA) is helpful to improve the levels of pro-inflammatory cytokines and adipokines, which are related to complications of OSA. OBJECTIVES: The effects of multilevel surgery on adipokines and pro-inflammatory cytokines in patients with OSA were assessed. METHODS: Fifty-one patients with OSA underwent uvulopalatopharyngoplasty and radiofrequency tongue base reduction. Body mass index (BMI), Epworth sleepiness scale (ESS) and subjective symptoms using visual analog scales were assessed at baseline and 4 weeks after treatment. Adiponectin, leptin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were measured with a LINCOplex Human Immunoassay at baseline and 4 weeks after surgical treatment. RESULTS: Significant improvements in subjective symptoms and ESS were found at 4 weeks after multilevel surgery. No significant change in BMI was observed. Adiponectin level was significantly increased after surgical treatment. Postoperative leptin, IL-6, and TNF-α levels were significantly decreased. The percent changes of adiponectin, leptin, IL-6, and TNF-α after multilevel surgery were not significantly different among patients with mild, moderate, and severe OSA.

Immunological investigation in the adenoid tissues from children with chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is characterized by persistent inflammation and tissue remodeling of the nasal mucosa. Adenoidectomy is an effective surgical treatment in pediatric CRS. To evaluate the effect of pediatric CRS on the severity and characteristics of adenoid inflammation, the authors evaluated the expressions of inflammatory cell activation markers and tissue remodeling in adenoid tissues associated with cytokines tissue-remodeling-associated cytokines in adenoid tissues. STUDY DESIGN AND SETTING: A prospective controlled study on 40 pediatric patients admitting for adenotonsillectomy. SUBJECTS AND METHODS: Immunoassays were performed on adenoid tissues homogenates from 16 children with CRS and from 24 children without CRS to quantify the levels of inflammatory cell activation markers, such as soluble interleukin (IL)-2 receptor (sIL-2R), soluble CD23 (sCD23), IL-6, eosinophilic cationic protein (ECP), and tryptase, and the levels of cytokines associated with tissue remodeling, such as transforming growth factor (TGF)-beta1, matrix metalloproteinase (MMP) 2 and 9, and tissue inhibitor of metalloproteinase (TIMP)-1. RESULTS: The mean levels (the ratio to albumin level) of sIL-2R, TGF-beta1, MMP-2, MMP-9, and TIMP-1 were significantly higher in adenoid tissues of patients with CRS (27.31+/-30.32, 4894.65+/-2388.77, 500.13+/-604.59, and 23.06+/-10.37, respectively) than those without it (16.27+/-10.93, 2635.51+/-1448.63, 120.87+/-321.50, 16.74+/-11.10, and 7.39+/-3.12, respectively; all P<0.05). Regarding the severity of CRS, ECP level was significantly higher in patients with severe CRS than in those with mild to moderate CRS (P=0.033). CONCLUSIONS: Adenoid tissues in pediatric CRS patients had higher levels of tissue-remodeling-associated cytokines, which may explain the relationship between pediatric CRS and adenoid inflammation.

IgE response to staphylococcal enterotoxins in adenoid tissues from atopic children.

OBJECTIVES/HYPOTHESIS: To evaluate local production of staphylococcal superantigen (SAg)-specific IgE in adenoid tissue and to compare its prevalence with that in the tonsil and serum, as well as its relationship with markers of allergic inflammation within adenoid tissue. STUDY DESIGN: Prospective randomized study. METHODS: We recruited 18 atopic children who had rhinitis symptoms and were sensitized to more than one common aeroallergen, and 22 nonatopic children undergoing adenotonsillectomy. Immunoassays were performed using adenoid tissue homogenate to quantify the levels of three staphylococcal SAg-specific IgE (SEA, SEB, and TSST-1), total IgE, eosinophil cationic protein (ECP), mast cell tryptase, and soluble CD23. RESULTS: Three kinds of SAg-specific IgE were detected in the adenoid and tonsil tissues of atopic patients, but not in those of nonatopic patients. In atopic children, the prevalence of SEA-, SEB-, and TSST-1-specific IgE in adenoid tissues (61.1%, 27.8%, 33.3%, respectively) were higher than those in tonsil tissues (38.9%, 5.6%, 11.1%, respectively) and in sera (11.1%, 27.8%, 16.7%, respectively). Subjects with high SEA levels showed significantly higher serum and adenoid total IgE, with higher eosinophilia. Significant correlations were noted between SAg-specific IgE levels and tryptase levels in adenoid tissue. CONCLUSIONS: Local specific IgE response to staphylococcal SAgs, especially SEA may contribute to ongoing allergic inflammation in adenoid tissue from atopic children.

Local production of total IgE and specific antibodies to the house dust mite in adenoid tissue.

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non-atopic children. We hypothesized that locally produced total IgE and allergen-specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)-specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non-atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP-specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL-2 receptors (sIL-2R), soluble CD23 (sCD23), and IL-6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non-atopic individuals. Median values of DP-specific IgE and IgA antibodies were significantly higher in atopics than in non-atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP-specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non-atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL-2R, and IL-6 levels. The levels of DP-specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL-2R, sCD23, and IL-6. The presence of total IgE and DP-specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally-produced total IgE and DP-specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children.

B cells in murine cervical lymph nodes are conventional B-2 cells.

We investigated the characteristic features of cervical lymph node B cells to determine whether their behavior differs from that of B cells located elsewhere, because cervical lymph nodes may be exposed to continual antigenic stimulation from the naso- and/or oropharynx. B cells were isolated from cervical lymph nodes, spleen and peritoneal fluid of mice, cultured in medium, and exposed to various stimuli. The expression of various surface molecules characteristic of lymphoid B cells was assayed by flow cytometry, and immunoglobulin secreted into the culture supernatants was evaluated by enzyme-linked immunosorbent assay. B220+ cells were cultured in medium alone or with lipopolysaccharide, and their entrance into S phase in response to stimuli was measured by proliferative assays. Phenotypic characteristics of cervical lymph node B cells included CD5 low, CD23high, CD43low, B7.1low, B7.2low, and Syndecan-1low. Unstimulated lymphoid B cells did not secrete immunoglobulin, but, upon stimulation, secretion of IgM was increased more than secretion of IgA and IgG. B cells actively entered S phase after 48 hr stimulation. These results show that B cells in cervical lymph nodes are conventional B2 cells, like splenic B cells.