John W. Georgitis

Sinusitis: Bench to bedside: Current findings, future directions

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days--an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Chronic sinusitis : characterization of cellular influx and inflammatory mediators in sinus lavage fluid

Chronic sinusitis is a recurrent disorder commonly found in atopic individuals, yet few studies have explored the role of inflammatory mediators in sinusitis. Sinus lavage fluid from ten patients with chronic sinusitis obtained during endoscopic surgery was analyzed for total cell counts and then assayed for histamine, immunoreactive leukotriene C4/D4/E4 (LTC4/D4/E4), and prostaglandin D2 (PGD2). All ten patients had been unresponsive to medical treatment, including oral corticosteroids in most cases. High concentrations of histamine, LTC4/D4/E4 and PGD2 were found in sinus fluid and were comparable to levels seen in nasal secretions of allergic rhinitis patients following allergen challenge. In the sinus fluid, inflammatory cells were predominantly neutrophils with only low percentages of mast cells, basophils or eosinophils. On the basis of the histamine and PGD2 concentrations in sinus fluid, we conclude that mast cell/basophil activation does occur in chronic sinusitis and may contribute to the persistent inflammation present in sinusitis.

Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children.

OBJECTIVE To compare the safety and efficacy of ipratropium bromide 0.03% (IB) with beclomethasone dipropionate 0.042% (BDP) in the treatment of perennial rhinitis in children. METHODS Thirty-three children with nonallergic perennial rhinitis (NAPR) and 113 with allergic perennial rhinitis (APR) were randomly assigned to either IB or BDP for 6 months in a single-blind, multicenter protocol in which the physician was blinded to treatment. At each visit, patients and physicians rated symptom control of rhinorrhea, nasal congestion, and sneezing. Patients also completed quality of life questionnaires at baseline and after 6 months of therapy. RESULTS Both treatments showed a significant improvement in control of rhinorrhea, congestion, and sneezing compared with baseline over the 6 months of treatment (P < .05). Only for the control of sneezing was BDP consistently better than IB (P < .05). Among the patients given IB, 61% to 73% assessed the control of rhinorrhea as good or excellent on different study visit days, 43% to 60% similarly rated the control of nasal congestion, and 39% to 43% the control of sneezing. The results for BDP were 68% to 78% for the control of rhinorrhea, 55% to 72% for the control of nasal congestion, and 54% to 68% for the control of sneezing. Quality of life assessment documented that both drugs significantly reduced interference with daily activities and disturbance of mood due to rhinorrhea compared with baseline (P < .05). Both treatments were well tolerated with IB causing less nasal bleeding and irritation than BDP. CONCLUSIONS Ipratropium bromide was safe and effective in controlling rhinorrhea and diminishing the interference by rhinorrhea in school attendance, concentration on school work, and sleep. Ipratropium bromide was as effective as BDP in the control of rhinorrhea and showed a relatively good effect on congestion. Patient and physician assessment favored BDP in the control of sneezing.

Ipratropium Nasal Spray in Children with Perennial Rhinitis

OBJECTIVE To compare the efficacy and safety of ipratropium nasal spray and placebo administered twice each day for 4 weeks in pediatric patients with perennial rhinitis who had rhinorrhea as a major complaint. METHODS This was a multicenter, double-blind, parallel group study. Patients aged 6 to 18 years with symptoms of perennial nonallergic (PNAR) or perennial allergic rhinitis (PAR) were randomized to receive ipratropium (42 micrograms per nostril) or placebo nasal spray, double-blind, twice each day for 4 weeks. Efficacy was evaluated by nasal symptoms, especially anterior rhinorrhea, and quality of life. Previous caregivers for rhinitis and medications used in the past were also evaluated. RESULTS A total of 202 patients were empanelled, 162 with PAR, 40 with PNAR; of these 151 with mild-severe rhinorrhea were evaluated for efficacy. Treatment with ipratropium reduced symptoms of rhinorrhea primarily in patients with PNAR. In patients with PAR this response was less pronounced, and was seen as a modest decrease in the severity of rhinorrhea noted in the first 2 weeks of treatment. Quality of life assessments confirmed that rhinorrhea was bothersome to these pediatric patients, and suggested that treatment with ipratropium nasal spray was associated with an improvement, especially in the patients with PNAR. There were few adverse events; these were similar in the two treatment groups. CONCLUSIONS Ipratropium nasal spray 0.03% administered at a dose of 42 micrograms/nostril bid is a safe and effective new therapy for control of anterior rhinorrhea in pediatric patients with PNAR. Twice daily administration is adequate for patients with PNAR, but patients with PAR might benefit from more frequent administration (e.g., tid).

Nasal Inflammatory Mediator Release in Ragweed Allergic Rhinitis: Correlation with Cellular Influx into Nasal Secretions

Lipid-derived mediators are found in nasal secretions during the early and late phase of allergic responses. To explore this early response further, concentrations of inflammatory mediators were measured along with characterization of specific cell influx during dose-dependent ragweed challenges. Ten allergic rhinitis subjects underwent two unilateral nasal lavages using 3-fold concentrations of short ragweed antigen. Low doses of ragweed (0.016-0.114 units Amb a I) did not provoke cell influx (1 of 18 challenges), whereas moderate doses (0.432-1.3 units Amb a I) induced cell influxes in 7 of 18 and at high doses in 8 of 17 challenges (3.39-11.7 units Amb a I). The differential of the cellular influx was greater than 50% neutrophils in 7 challenges; greater than 50% eosinophils in 3, and a mixed pattern in 6. There was a significant association between the dose of antigen and the level of prostaglandin D2 (PGD2), leukotrienes (LTs) C4, D4 and E4. Challenges with an eosinophilic influx tended to be associated with higher concentrations of mediators than neutrophilic influxes. Similar to the immediate skin response, the early allergic response in the nose demonstrated a cell influx with release of PGD2, LTsC4, D4 and E4. Nasal cellular inflammation therefore can occur within minutes of allergen exposure.

Sinusitis: Bench to bedsideCurrent findings, future directions

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days-an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Onset-of-action for antihistamine and decongestant combinations during an outdoor challenge

BACKGROUND Medications containing a combination antihistamine-decongestant are commonly used for allergic rhinitis yet onset-of-action comparisons for symptom relief after a single dose have not been performed. OBJECTIVE To determine the onset of symptom relief and efficacy of antihistamine-decongestant medications (acrivastine-pseudoephedrine and loratadine-pseudoephedrine) compared with placebo in an outdoor park. METHODS This study was conducted during the spring of 1997 using a double-blind, placebo-controlled design. Patients completed baseline rhinitis symptom diaries from 7:30 to 9:30 AM. Subjects with qualifying symptom scores received one dose of either acrivastine-pseudoephedrine, loratadine-pseudoephedrine, or placebo at 10:00 AM. Symptom diaries were recorded for the next 4 hours. RESULTS Of 593 patients randomized to treatment, 592 were included in efficacy analysis. Acrivastine-pseudoephedrine and loratadine-pseudoephedrine demonstrated a mean onset-of-action by 45 and 30 minutes respectively for total symptom and rhinitis symptom scores for the five sites. Onset-of-action for nasal congestion scores was 45 minutes for both medications. Sites having higher pollen exposure (>100 pollen grains over 6 hours) demonstrated a difference between the antihistamine combinations: acrivastine-pseudoephedrine had an onset of action at 45 minutes for total symptom and rhinitis symptom scores, and 15 minutes for nasal congestion scores whereas loratadine-pseudoephedrine had onset-of-action for nasal congestion score of 105 minutes but failed to reach significance at any timepoint for total symptom and rhinitis symptom scores. CONCLUSIONS Both antihistamine-decongestant combinations demonstrate an onset-of-action within 60 minutes of administration but under conditions of higher pollen exposure, the acrivastine combination was more effective for total symptoms, rhinitis symptoms, and nasal congestion with an onset-of-action within 45 minutes for rhinitis symptoms and 15 minutes for congestion.

The anticholinergic treatment of allergic perennial rhinitis

Anticholinergic agents have been used for nonallergic rhinitis expressly to control rhinorrhea. In allergic rhinitis, rhinorrhea can be extremely troublesome and unresponsive to traditional pharmacotherapeutic rhinitis treatments. Anticholinergic agents, through their specific ability to decrease nasal secretory response, should have beneficial effects for allergic rhinitis. In a recent trial ipratropium bromide at concentrations of 0.03% and 0.06% reduced rhinorrhea in allergic subjects without any demonstrable rebound effect. Therefore anticholinergic therapies may be a useful adjunct in controlling the rhinorrhea associated with allergic rhinitis.

The applicability of rhinomanometry in nonatopic children: comparison of three techniques

Three techniques for rhinomanometry were evaluated in 10 nonatopic children. Each child performed anterior, posterior, and forced oscillation rhinomanometry during 2 to 5 hr. Nasal airflow and transnasal driving pressure were measured continuously over several breaths. From the nasal airflow-pressure tracings, nasal airway resistance (Rn) was determined at a linear and a turbulent airflow. Individual average Rn values at linear airflow ranged from 1.0 to 5.4 cm H2O sec/L and at turbulent airflow from 1.5 to 7.6 cm H2O sec/L. There was no significant difference between the means on the log, scale of the individual average Rn measurements obtained by the conventional rhinomanometric techniques. Posterior and forced oscillation rhinomanometry exhibited a higher intrasubject variation in Rn than anterior rhinomanometry. In assessing performance, anterior rhinomanometry was the easiest method for the children to do. Two children despite multiple training sessions were unable to perform posterior or forced oscillation rhinomanometry. These findings indicate that anterior rhinomanometry is the easiest method for use in children.

Acute Asthma Management in Children: Factors Identifying Patients at Risk for Intensive Care Unit Treatment

The hospitalization and mortality rates incurred from childhood asthma continue to rise despite recent progress into the pathophysiology and treatment of reactive airway disease. We believe that there are specific factors that identify children at risk for death from asthma. The objective of the study was to determine those risk factors that identify children at increased risk for nonfatal, but life-threatening asthma exacerbations resulting in pediatric intensive care unit (PICU) admission. Patients aged 10 months-16 years admitted to Brenner Childrens Hospital for status asthmaticus between April 1991 and December 1992 were evaluated with regard to the prevalence of eight different factors using two categories for asthma: (1) life-threatening asthma requiring PICU admission and (2) non-life-threatening asthma requiring routine hospitalization. Risk factors associated with an increased prevalence of non-fatal, but life-threatening asthma requiring PICU sensitivity state. The classification employed here seemed to provide some merits in delineating the features of adulthood asthma.