Effects of a single-dose pretreatment with captopril on the immediate response to nasal challenge with allergen

We performed a double-blind, placebo-controlled, crossover study using 12 subjects to determine the effects of a single 50-mg dose of captopril on the response to nasal challenge with increasing doses of allergen. Levels of kinins, histamine and N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity were measured in nasal lavages, and symptom scores and the number of sneezes were recorded. Captopril had no significant effects on histamine, TAME-esterase, sneezing or symptom scores. Peak postchallenge kinin levels, however, were significantly elevated (p less than 0.05) compared to placebo, while an increase in the magnitude of the dose-response curve was of marginal significance (p = 0.058). Thus, captopril causes increases in the kinin levels in nasal secretions during the allergic response. If increased kinin levels persist or worsen with chronic therapy, it is possible that they could exacerbate allergic symptoms during repeated seasonal exposure.     

Inflammatory mediators in late antigen-induced rhinitis

To investigate the mechanisms responsible for the late-phase response in patients with allergies, we measured four biochemical mediators (histamine, tosyl-L-arginine methyl ester [TAME]-esterase, kinin, and prostaglandin D2) in nasal secretions after nasal challenge with pollen antigen in 12 patients with allergy. Nine patients had an immediate response and a recurrence of symptoms 3 to 11 hours after challenge. The clinical symptoms during recurrence were accompanied by a second increase in levels of histamine, TAME--esterase, and kinin over base-line values, although kinin levels were lower than during the immediate response. In contrast, although the levels of prostaglandin D2 were significantly increased during the immediate response, they did not increase above base line during the late response. Rechallenge with allergen 11 hours after the initial provocation, however, was associated with reappearance of all four biochemical mediators, including prostaglandin D2. We conclude that the late response to nasal challenge with allergen is accompanied by a second increase in the concentrations of histamine and TAME--esterase but differs from the immediate response in the lack of prostaglandin D2 production and in the amount of kinin generated. Since histamine is released only by mast cells and basophils and prostaglandin D2 is not produced by basophils, we suggest that these cells are partly responsible for the late-phase response.     

Radiographic staging of juvenile angiofibroma

A staging system for juvenile angiofibroma based on computerized tomographic findings is suggested. The need for such an endeavor has come about because of a lack of standardization of tumor data in both individual series and interinstitutional reports. The various stages reflect the number of anatomic sites occupied by a lesion rather than the actual tumor size. The "simpler" tumors are confined to the medial part of the skull base and are entirely extracranial. As a tumor extends laterally and/or intracranially, the staging designation, and therefore the treatment plan, changes accordingly. Presumably, with the application of consistent diagnostic tools and standardized stage designations, the analysis of both morbidity and treatment data will become more meaningful.     

Nasal challenge with cold, dry air induces a late-phase reaction

Nasal challenge of susceptible persons with cold, dry air (CDA) (breathing air at a temperature of -7 to -10 degrees C and a relative humidity of 0 to 10% at a flow rate of 12.5 ml/min for 15 min) stimulates nasal symptoms and release of histamine and other mediators associated with mast-cell activation. To investigate whether such a nonantigenic stimulus induces a late-phase reaction (LPR) in the nose, we challenged 12 preselected volunteers who had previously shown an immediate response to CDA. We monitored the subjects' responses for 10 h by means of symptom diaries and the levels of histamine and TAME-esterase activity in nasal lavage fluids. All 12 subjects showed an immediate response, whereas 8 had a LPR, as indicated by a recurrence of symptoms (rhinorrhea and congestion) hours later, accompanied by an increase in the levels of histamine and TAME-esterase activity. Rhinorrhea and congestion were concomitant with the late reelevation of mediators. Control challenges of these subjects with warm, moist air (WMA), as well as serial nasal lavages without any stimulation of the nose, failed to induce an early- or a late-phase response. The amount of both mediators and symptoms generated during the 10 h after the initial reaction to CDA challenge was significantly greater (p less than 0.02) than after WMA challenge or after performance of nasal lavages without a challenge. The ability of CDA to induce a LPR strengthens the connection between initial mast-cell activation and the occurrence of a LPR.     

Mediator release after nasal airway challenge with allergen

An in vivo model of human allergic disease has been developed in which nasal challenge with antigen leads to physiologic changes, together with a release of increased amounts of inflammatory mediators into nasal secretions obtained by washing the nose with saline. In 105 experiments involving 35 subjects, only allergic subjects consistently demonstrated an increase in the concentrations of the mast cell mediator, histamine, and the putative mast cell mediators, TAME-esterase and PGD2. The release of each mediator was significantly (p less than 0.001) related to the physiologic change (sneezing). The release of each mediator also correlated significantly with the release of the other 2 mediators (p less than 0.001). This system, for the first time, clearly relates an in vivo symptom and mediator release and thus should provide an excellent tool for the further study of the allergic response and nasal pathophysiology.     

From the Cover: Advertisements impact the physiological efficacy of a branded drug

We conducted randomized clinical trials to examine the impact of direct-to-consumer advertisements on the efficacy of a branded drug. We compared the objectively measured, physiological effect of Claritin (Merck & Co.), a leading antihistamine medication, across subjects randomized to watch a movie spliced with advertisements for Claritin or advertisements for Zyrtec (McNeil), a competitor antihistamine. Among subjects who test negative for common allergies, exposure to Claritin advertisements rather than Zyrtec advertisements increases the efficacy of Claritin. We conclude that branded drugs can interact with exposure to television advertisements.     

Acute bacterial rhinosinusitis causes hyperresponsiveness to histamine challenge in mice

OBJECTIVES: To develop a physiologic test of nasal responsiveness in mice and to evaluate whether mice with acute bacterial sinusitis develop nasal hyperresponsiveness. DESIGN: Several experimental studies will be described. The first was a titration pilot study. The second was a randomized, placebo-controlled study. The remainder were before-and-after trials. SPECIES: BALB/c or C57BL/6 mice. INTERVENTIONS: For these experiments, we exposed mice to histamine intranasally, then counted the number of sneezes and nose rubs as the primary outcome measure of nasal responsiveness. First, we constructed a dose-response curve. Second, we treated the mice with desloratadine, a histamine 1 receptor antagonist, prior to histamine exposure. Third, we challenged, with intranasal histamine, mice made allergic using 2 techniques. Fourth, we infected mice with Streptococcus pneumoniae to determine whether acute sinusitis causes nasal hyperresponsiveness to histamine exposure. RESULTS: Nasal histamine challenge led to a reproducible, dose-dependent increase in sneezing and nose rubs. The response to histamine exposure was blocked by desloratadine (P < or = .05). Allergic mice had a significant increase in responsiveness (P < or = .05) over baseline after exposure to antigen. Mice with acute sinusitis had a sustained increase in responsiveness, although less severe than after allergy, compared with baseline values that lasted 12 days after infection (P < or = .05). CONCLUSIONS: Nasal challenge with histamine is a physiologic test of nasal responsiveness. The hyperresponsiveness of allergic mice to histamine exposure parallels the response to nonspecific stimuli during the human allergic reaction. In addition, we showed that acute bacterial sinusitis causes nasal hyperresponsiveness in mice.     

Antigen stimulation of TH2 cells augments acute bacterial sinusitis in mice

BACKGROUND: Previously, we showed that an ongoing nasal allergic response augmented bacterial sinusitis in mice. In those experiments mice were sensitized to ovalbumin (OVA) by means of intraperitoneal injections of OVA-alum and then exposed to OVA intranasally before being infected with Streptococcus pneumoniae. OBJECTIVE: We sought to study the importance of TH2 cells and to eliminate potential alum effects. METHODS: In this study we sensitized mice by adoptively transferring OVA-specific TH2- or TH1-skewed cells. RESULTS: TH2 passive sensitization followed by intranasal OVA showed a robust local eosinophilic response (5-fold increase) compared with that seen in mice with only TH2 passive sensitization alone (P <.001). Mice with TH2 passive sensitization and intranasal OVA exposure followed by infection showed an increase in the number of recovered S pneumoniae (P <.05) and an increase in sinus inflammation compared with that seen in those with infection alone (P <.01). In contrast, mice passively sensitized with TH1 followed by intranasal OVA exposure and infection showed no significant increase in the recovery of S pneumoniae and sinus inflammation compared with those with infection alone. CONCLUSIONS: These data support the importance of antigen-stimulated TH2 cells in the augmented response to infection in allergic mice. Whether the increased infection is related to the direct effect of TH2 cells and their cytokines or subsequent recruitment of other cells, such as eosinophils, will be determined in further studies.