Prevalence of Bronchiectasis in Patients with Chronic Rhinosinusitis in a Tertiary Care Center.

BACKGROUND: Whereas chronic rhinosinusitis (CRS) is associated with asthma, and vice versa, the association between CRS and other lower respiratory conditions is not well-established. Bronchiectasis is characterized by permanent damage of the airways, and as many as 45% of bronchiectasis patients have CRS, but the prevalence of bronchiectasis among CRS patients is not known. OBJECTIVE: To determine the prevalence of bronchiectasis among CRS patients and to characterize demographic and clinical features of patients with bronchiectasis and CRS. METHODS: Electronic medical records of patients with rhinosinusitis were searched by computer algorithm supplemented with manual chart review to identify patients with CRS, asthma, and/or bronchiectasis. Demographic and clinical features and antibiotic courses for sinopulmonary infections 2 years before and after sinus surgery were obtained by manual chart review. RESULTS: The prevalence of bronchiectasis as determined by International Classification of Diseases, Ninth Revision code was significantly higher in CRS patients than in asthmatic patients (2.3% vs 1.7%; P < .003). Similarly, based on a text word search of "bronchiectasis" in the chest computed tomography (CT) scan reports, patients with CRS who had chest CT scans had a higher prevalence of bronchiectasis than did asthmatic patients with chest CT scans (24.3% vs 19.5%; P = .005). Patients with CRS and concurrent bronchiectasis did not have a reduction in the frequency of sinopulmonary infections after sinus surgery compared with patients with CRS without bronchiectasis (P < .05). CONCLUSIONS: Bronchiectasis is an important comorbidity in patients with CRS and may identify a severe phenotype of chronic sinonasal disease.

Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting.

BACKGROUND: Although patients with chronic rhinosinusitis without nasal polyps (CRSsNP) represent a majority of the chronic rhinosinusitis (CRS) population, they have not been completely characterized phenotypically. OBJECTIVE: To perform a comprehensive phenotypic characterization of subjects with CRSsNP, using CRS with nasal polyps (CRSwNP) as a comparator. METHODS: Patients with a history of CRS with positive sinus computed tomography (>18 years old) evaluated in the allergy/immunology or otolaryngology clinics of an academic center between 2002 and 2012 were identified via International Classification of Diseases, Ninth Revision codes. A retrospective chart review was performed on a subset of 507 patients with CRSsNP and 874 with CRSwNP. Characteristics analyzed included demographics, comorbid conditions, and radiologic sinus severity. RESULTS: Of the total CRS population, approximately 82% had CRSsNP and 18% had CRSwNP. Of the 507 patients in the CRSsNP group, 319 (63%) were female compared with 393 of 847 (45%) in the CRSwNP group. The prevalence of atopy was 52% in CRSsNP versus 76% in CRSwNP (P < .0001). In CRSsNP, atopic patients had more severe radiographic disease compared with nonatopic patients (P < .005). The prevalence of asthma was 36% in CRSsNP versus 56% in CRSwNP (P < .0001). Comorbid asthma was not associated with radiographic sinus disease severity in CRSsNP but was associated with severity in CRSwNP (P < .0001). CONCLUSIONS: The relative prevalence of CRS phenotypes in the western population is approximately 80% CRSsNP and 20% CRSwNP. Patients with CRSsNP were predominantly female, whereas patients with CRSwNP were predominantly male. The prevalence of asthma was higher in our cohort of patients with CRSsNP than previously described. Atopy was associated with more severe radiographic sinonasal disease in CRSsNP, whereas asthma was not associated with radiographic sinonasal disease severity.

Chronic rhinosinusitis management beyond intranasal steroids and saline solution irrigations.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease with clinical manifestations that are influenced by the presence or absence of nasal polyposis. Understanding of the current and future treatment modalities for CRS is essential in preventing exacerbation and morbidity associated with this chronic condition. OBJECTIVE: The aim of this article is to review the evidence behind current medical therapies and potential new treatments for CRS. METHODS: Scientific literature regarding intranasal and systemic antibiotics, intranasal systemic corticosteroids, and monoclonal antibodies as interventions for CRS with and without nasal polyps was reviewed. RESULTS: The literature supports the use of topical or systemic glucocorticoids in patients with nasal polyps, and there appears to be a role for systemic antibiotics in the treatment of acute exacerbations of CRS with nasal polyps. The response to corticosteroids or antibiotics in the treatment of exacerbations of CRS without nasal polyps is variable. Due to the lack of appropriately designed trials, there is weak evidence for the adjunctive use of immunotherapy at this time. Monoclonal antibodies that target Immunoglobulin E and T helper cell 2 cytokines have been clinically effective in symptom reduction for some patients with CRS with nasal polyps although further studies are needed. CONCLUSION: Current therapies used in the treatment of CRS are discussed.

Blockade of peanut allergy with a novel Ara h 2-Fcγ fusion protein in mice.

BACKGROUND: Conventional immunotherapy for peanut allergy using crude peanut extracts is not recommended because of the unacceptably high risk of anaphylaxis. Allergen-specific immunotherapy is not currently undertaken for peanut allergy. OBJECTIVES: The objective of this study was to develop a novel peanut-human fusion protein to block peanut-induced anaphylaxis. METHODS: We genetically designed and expressed a novel plant-human fusion protein composed of the major peanut allergen Ara h 2 and human IgG Fcγ1. We tested the Ara h 2-Fcγ fusion protein (AHG2)'s function in purified human basophils. Transgenic mice expressing human FcεRIα and a murine peanut allergy model were used. RESULTS: AHG2 inhibited histamine release induced by whole peanut extract (WPE) from basophils of patients with peanut allergy, whereas the fusion protein itself did not induce mediator release. AHG2 inhibited the WPE-induced, peanut-specific, IgE-mediated passive cutaneous anaphylaxis in hFcεRIα transgenic mice. AHG2 also significantly inhibited acute anaphylactic reactivity, including the prototypical decrease in body temperature in WPE-sensitized mice challenged with crude peanut extract. Histologic evaluation of the airways showed that AHG2 decreased peanut-induced inflammation, whereas the fusion protein itself did not induce airway inflammation in peanut-sensitized mice. AHG2 did not exert an inhibitory effect in mice lacking FcγRII. CONCLUSION: AHG2 inhibited peanut-specific IgE-mediated allergic reactions in vitro and in vivo. Linking specific peanut allergen to Fcγ can provide a new approach for the allergen immunotherapy of peanut allergy.

Prostaglandin E(2) induces breast cancer related aromatase promoters via activation of p38 and c-Jun NH(2)-terminal kinase in adipose fibroblasts.

Aromatase is the key enzyme for estrogen biosynthesis. A distal promoter, PI.4, maintains baseline levels of aromatase in normal breast adipose tissue. In contrast, malignant breast epithelial cells secrete prostaglandin E(2) (PGE(2)), which stimulates aromatase expression via proximal promoters PI.3/PII in a cyclic AMP (cAMP)- and protein kinase C (PKC)-dependent manner in adjacent breast adipose fibroblasts (BAF), leading to increased local concentrations of estrogen. Although an effective treatment for breast cancer, aromatase inhibitors indiscriminately abolish estrogen synthesis in all tissues, causing major side effects. To identify drug targets to selectively block aromatase and estrogen production in breast cancer, we investigated PGE(2)-stimulated signaling pathways essential for aromatase induction downstream of cAMP and PKC in human BAFs. Here, we show that PGE(2) or its surrogate hormonal mixture dibutyryl cAMP (Bt(2)cAMP) + phorbol diacetate (PDA) stimulated the p38, c-jun NH(2)-terminal kinase (JNK)-1, and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathways. Inhibition or small interfering RNA-mediated knockdown of p38 or JNK1, but not ERK, inhibited PGE(2)- or Bt(2)cAMP + PDA-induced aromatase activity and expression via PI.3/PII. Conversely, overexpression of wild-type p38alpha or JNK1 enhanced PGE(2)-stimulated aromatase expression via PII. PGE(2) or Bt(2)cAMP + PDA stimulated c-Jun and activating transcription factor-2 (ATF2) phosphorylation and binding to the PI.3/PII region. Specific activation of protein kinase A (PKA) or EPAC with cAMP analogues stimulated p38 and JNK1; however, only PKA-activating cAMP analogues induced aromatase expression. The PKC activator PDA effectively stimulated p38 and JNK1 phosphorylation but not aromatase expression. Taken together, PGE(2) activation of p38 and JNK1 via PKA and PKC is necessary for aromatase induction in BAFs, and p38 and JNK1 are potential new drug targets for tissue-specific ablation of aromatase expression in breast cancer.