Relationship between upper airway diseases, exhaled nitric oxide, and bronchial hyperresponsiveness to methacholine.

OBJECTIVE: The "united airway disease" concept is based on the bidirectional interaction between asthma and rhinitis. The aim of this study was to determine the relationship between upper airway diseases and bronchial hyperresponsiveness (BHR), as well as their association with the fractional concentration of exhaled nitric oxide (FeNO) and atopy in patients with persistent symptoms suggestive of asthma requiring methacholine challenge testing (MCT) to confirm asthma diagnosis. METHODS: A cross-sectional prospective study was carried out in adult patients with persistent asthma-like symptoms and negative bronchodilator testing. FeNO and MCT were performed in all patients. Asthma was confirmed based on the presence of suggestive symptoms and MCT results. Associated upper airway diseases included allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). RESULTS: The study included 575 patients; asthma was confirmed in 32.3%, and FeNO values ≥ 50 ppb were found in 27% of the patients. Elevated FeNO was significantly associated to AERD. The prevalence of atopy in asthma patients was 86.6%. Atopy was present in 90.4% of patients with asthma and FeNO levels ≥ 50 ppb. A significant association was found between AERD, asthma, and FeNO ≥ 50 ppb. CONCLUSIONS: Patients with symptoms suggestive of asthma but negative bronchodilator testing are commonly seen in usual practice. In this population, the association of high FeNO levels and BHR to atopy, as well as to AERD, suggests the presence eosinophilic inflammation in both the upper and lower airways and supports the "one airway" hypothesis.

In Search of an Association Between Genotype and Phenotype in Hereditary Angioedema due to C1-INH Deficiency.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is caused by mutations affecting the SERPING1 gene. Adult patients (≥ 18 years old) diagnosed with C1-INH-HAE were clustered according to a modified SERPING1 gene mutation classification [5]. Demographic, clinical, and laboratory data were studied. Published manuscripts on the genotype/phenotype relationship were reviewed. Eighty-eight patients participated in the study, with 78 having a classifiable mutation. We compared the data in the 3 largest groups: class 0 only (n = 32), class II only (n = 18), class III only (n = 22). Antigenic C4 and C1 inhibitors were higher in class II (p = 0.008 and p = 0.02, respectively), and facial attacks in the last 6 months were more frequent in class III (p = 0.04)). All the other differences were non-significant. Twelve manuscripts on phenotype/genotype correlation were found: missense mutations in SERPING1 gene were associated with delay in disease onset and lower severity score in some studies, whereas the CC F12-C46T/C polymorphism produced earlier disease onset. Our study shows minimal differences regarding clinical phenotype in patients with class 0, II, and III SERPING1 gene mutations, with a tendency to class III having a more severe phenotype. The study should be performed in a larger sample to confirm if they are significant.We propose that larger multicenter, international studies are performed, comparing different SERPING1 gene mutation classifications, combining polymorphisms in other involved genes (kallikrein-kinin system, regulation of vasculature, plasminogen activation) and using different variables and clinical scores to assess C1-INH-HAE disease activity and/or severity in order to study possible genotype/phenotype relationships.

Ocular manifestations associated with brucellosis: a 26-year experience in Peru.

BACKGROUND: Brucellosis has unusual clinical manifestations. Ocular involvement caused by brucellosis remains poorly recognized in areas in which brucellosis is endemic. METHODS: A prospective study was performed to evaluate patients attending the Instituto de Medicina Tropical "Alexander von Humboldt" and the Hospital Nacional Cayetano Heredia (Lima, Peru) from January 1980 through December 2005 who received a diagnosis of brucellosis with ocular involvement. Diagnosis was made on the basis of clinical findings as well as agglutinations and/or culture positive for Brucella melitensis. RESULTS: During a period of 26 years, 1551 patients with brucellosis were seen, including 52 patients with ocular brucellosis. We found that 7 (0.7%) of 965 patients with acute brucellosis and 45 (7.9%) of 570 patients with chronic brucellosis had ocular brucellosis (P<.001). In 16 patients with brucellosis, the disease stage was unclassified. The most frequent ocular presentation was uveitis, which was found in 43 (82.7%) of the 52 patients with ocular brucellosis. Posterior uveitis was the most frequent uveal syndrome (21 cases; 45.7%). Patients with panuveitis had the worst visual prognosis: 8 of 9 patients with panuveitis were legally blind, including 5 patients with no light perception. CONCLUSIONS: Brucellosis may involve the eye and can lead to serious complications. In patients with brucellosis, early ophthalmologic evaluation can lead to prompt treatment and might prevent blindness from severe ocular damage.

Brucellar uveitis: intraocular fluids and biopsy studies.

BACKGROUND: Ocular brucellosis is usually diagnosed by clinical criteria and serological tests. Little is known with regard to the ocular immunology of brucellosis and the use of intraocular diagnostic tests. We report retrospectively the laboratory findings of patients with ocular involvement associated with brucellosis. MATERIALS AND METHODS: Patients with uveitis with no evident etiologic diagnosis were evaluated at the Instituto de Medicina Tropical "Alexander von Humboldt" of the Universidad Peruana Cayetano Heredia and the Hospital Nacional Cayetano Heredia. Patients were tested for brucellosis, tuberculosis, syphilis, toxoplasmosis, toxocariasis, and human T-cell lymphotropic virus-1. Blood and intraocular fluid samples were examined. Patients with a diagnosis of brucellar uveitis were selected as cases and patients with a diagnosis of uveitis of other etiology were included as controls. The Goldmann-Witmer coefficient was determined. RESULTS: Twelve patients with clinical and laboratory findings suggestive of brucellar uveitis were considered as cases. Seven patients with uveitis of other etiology were selected as controls. Four (33.3%) patients with ocular brucellosis had negative ocular agglutinations and eight (66.7%) had positive agglutinations. No control cases had positive agglutinations for Brucella melitensis. The sensitivity of the test was 66.7% and the specificity 100%. Only one patient had a positive culture for B. melitensis in subretinal fluid. The Goldmann-Witmer coefficient was calculated in six cases of brucellosis uveitis and five uveitis controls. It was highly positive in three patients with ocular brucellosis. Tissue samples showed lymphoplasmacytic infiltrates. CONCLUSIONS: Intraocular serological tests could be used to support the diagnosis of ocular brucellosis.