Philip Fireman

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.

Asthma and bacterial sinusitis in children

Signs, symptoms, and radiographic abnormalities of sinusitis are frequent in children with asthma; it is not known whether sinus inflammation is associated with bacterial infection or other mechanisms. Eight asthmatic patients with exacerbation of asthma despite bronchodilator therapy were studied after maxillary sinusitis was confirmed by radiographs. All had cough, wheezing, nasal stuffiness, rhinorrhea and were afebrile. Four patients had headaches, and two had facial pain. Maxillary sinus aspirates were obtained, and bacterial cultures were positive in five: Branhamella catarrhalis (2), nontypeable Hemophilus influenzae (2), Streptococcus pneumoniae (1). Nose and throat cultures did not correlate with sinus cultures. All patients received bronchodilators, and four of eight patients received steroids. All were treated for 14 to 28 days with antibiotics during which seven of the eight patients improved clinically including all with positive sinus cultures. Asthma-symptoms diary scores were kept by five; all demonstrated improvement. Pulmonary-function tests improved in five of seven patients after the antibiotic and asthma therapy including the four patients with positive cultures. Sinus radiographs cleared in three, improved in three, and were unchanged in two patients after antibiotic therapy.

Otitis media and eustachian tube dysfunction: Connection to allergic rhinitis

Otitis media and otitis media with effusion are among the most common childhood illnesses and contribute a great deal to health care costs. The cause of otitis media is multifactorial. Eustachian tube dysfunction, bacterial or viral infection of the middle ear, and nasal inflammation resulting from allergic rhinitis or upper respiratory infection are acknowledged contributing factors. Data from epidemiology studies indicate that 25% to 40% of upper respiratory infections in children younger than 3 years are accompanied by an episode of otitis media, 40% to 50% of children older than 3 years with chronic otitis media have confirmed allergic rhinitis. Studies of the pathogenesis of otitis media have identified interactions among infection, allergic reactions, and eustachian tube dysfunction. Nasal inflammation due to allergen challenge results in classic signs and symptoms of allergic rhinitis and eustachian tube dysfunction. Eustachian tube dysfunction leads to increased negative pressure in the middle ear and improper ventilation. Both viral upper respiratory infection and nasal allergic reaction provoke nasal inflammation, eustachian tube dysfunction, and enhanced nasal protein transudation and secretion, which is likely to be sustained and modulated by inflammatory mediators and cytokines. In a study of experimental infection with influenza A virus, histamine release increased from peripheral blood basophils of patients with allergic rhinitis. These data support an interaction between viral infection and nasal allergy in enhancing certain pathophysiologic responses. Viral upper respiratory infections may promote secondary bacterial infections by altering bacterial adherence, modulating host immune and inflammatory responses, and impairing eustachian tube function. In acute otitis media, bacteria are cultured front approximately 70% of middle ear effusions with Streptococcus pneumoniae being the most common organism. Initial management of otitis media consists of appropriate antimicrobial therapy. In the presence of allergic rhinitis, antiallergic therapies may be used to augment symptom resolution and therapeutic response. Surgical insertion of tympanostomy or ventilation tubes to promote drainage of unresolved effusions has become common. Further delineation of the pathogenesis of otitis media and otitis media with effusion will guide appropriate medical management and may decrease the need and frequency of surgical procedures.

Analysis of nasal secretions during experimental rhinovirus upper respiratory infections

BACKGROUND To determine the underlying mechanisms for rhinovirus-induced nasal secretions, nasal lavage fluids were analyzed during experimental rhinovirus infections. METHODS Twenty patients with allergic rhinitis and 18 nonallergic control subjects were inoculated with rhinovirus type 39. Nasal lavage was performed before and on days 2 through 7 after viral inoculation, and the lavage fluids were assayed for proteins and mast cell mediators. RESULTS The secretion of total protein and both plasma proteins (albumin and IgG) and glandular proteins (lactoferrin, lysozyme, and secretory IgA) increased after rhinovirus inoculation. Analysis of the specific protein constituents revealed that nasal secretions during the initial response to the rhinovirus infection were predominantly due to increased vascular permeability. Allergic subjects tended to have fewer symptoms and more vascular permeability than control subjects, and increased histamine secretion after rhinovirus inoculation was more frequently seen in the allergy group. CONCLUSION Nasal secretions found early in the course of a viral upper respiratory infection are due to increased vascular permeability, whereas glandular secretions predominate later in the infection.

Nasal and otologic effects of experimental influenza A virus infection.

Past studies showed that experimental rhinovirus colds in adults resulted in eustachian tube dysfunction and abnormal middle ear pressures. In the present study, the symptoms and pathophysiologic findings accompanying experimental influenza viral infection were documented. A total of 33 healthy adult volunteers were intranasally challenged with an influenza A/Kawasaki/86 (H1N1) virus and cloistered over a 9-day postchallenge period to monitor for evidence of infection, signs and symptoms of illness, and the extent and frequency of pathophysiologic responses of the nose, eustachian tube, and middle ear. Results showed a protective effect of high (≥16) prechallenge specific hemagglutination-inhibition antibody titer on the rate of infection and the magnitude and extent of provoked symptoms and pathophysiologic findings. Infected subjects with low (<16) prechallenge serum antibody titers (n = 21) developed significant respiratory illness. These subjects also had objectively measurable increases in nasal secretion production, and decreased nasal patency and mucociliary clearance rates. More than 80% of the infected subjects developed eustachian tube dysfunction, and approximately 80% had middle ear underpressures of less than −100 mm H2O on study days 4 and 5. Five of 21 infected subjects with low prechallenge antibody titers had otoscopic evidence of otitis media with effusion. These results support a causal role for viral upper respiratory tract infection in the pathogenesis of otitis media, possibly mediated by the early development of eustachian tube dysfunction and abnormal middle ear pressure.

Immunologic-mediated eustachian tube obstruction: a double-blind crossover study

Eight subjects with seasonal allergic rhinitis confirmed by positive skin tests and serum radioallergosorbent test to ragweed or timothy grass pollen were identified. A double-blind provocative antigen challenge was performed with intranasal insufflation of 50 mg of dry pollen to which the subject was either sensitive (ragweed or timothy) or not sensitive (pine). Before and after pollen insufflation, measurements of nasal function by nasal rhinomanometry and eustachian tube (ET) function by the nine-step tympanometry test were performed for up to 14 days. The ability to dilate the ET was documented in 14 of the 16 ears of the eight subjects before challenge. Within 30 min after antigen challenge transient obstruction of the ET associated with inability to dilate upon swallowing was observed in all 14 ears. Clinical symptoms of allergic rhinitis, including rhinorrhea and nasal obstruction, were produced in all subjects. ET function changes were reversible in three of 14 ears within 2 hr but persisted for more than 3 days in six of the ears. As a control, insufflation of pine pollen did not alter ET function or rhinomanometric values or produce clinical symptoms in the eight subjects. These findings suggest an allergic basis for ET obstruction and possibly for the development of otitis media with effusion.

Otologic manifestations of experimental rhinovirus infection

Episodes of acute otitis media are commonly associated with viral upper respiratory tract infections. Rhinoviruses account for approximately 40% of these infections, and were previously shown to alter eustachian tube function and middle ear pressures. However, progression to otitis media has not been prospectively documented. In the present study, changes in tympanometric pressures and otoscopic findings resulting from experimental intranasal rhinovirus type‐39 inoculation were documented in 60 adult volunteers. Fifty‐seven (95%) subjects became infected and 34 (60%) of these had a clinical cold. Prior to viral inoculation, 3 (5%) subjects had middle ear pressures of less than −100 mm H2O and two of these subjects developed middle ear effusions following infection. In all, 22 (39%) subjects developed middle ear pressures of less than −100 mm H2O. No subject with normal middle ear pressures prior to infection developed evidence of effusion. This study extends the otologic manifestations of rhinovirus infection to include otitis media. Furthermore, these results support the hypothesized relationship between upper respiratory tract infections, eustachian tube dysfunction, and otitis media.

Hypersensitivity to tetanus toxoid

Abstract A high incidence of cutaneous hypersensitivity reactions to tetanus toxoid, 63 per cent immediate, 32 per cent Arthus type, and 74 per cent delayed reactions, were found in 70 tetanus-immunized individuals who had no history of clinical hypersensitivity to tetanus toxoid. No statistically significant differences in tetanus antibody levels or cutaneous hypersensitivity reactions were noted between age groups from 6 months to 49 years. The mean natural logarithm of the antibody titers (± S. E. M.) decreased significantly (p

Effect of rhinovirus 39 infection on cellular immune parameters in allergic and nonallergic subjects

Patients with allergic rhinitis (AR), compared with nonallergic persons, have been reported to respond differently to a variety of stimuli, some of which are immunologic in nature. This study compared the systemic cellular immune responses to experimental rhinovirus (RV) 39 challenge in RV-39-seronegative AR (n = 20) and nonallergic (n = 18) subjects. Peripheral blood was obtained before, 4 or 7 days after, and 23 days after RV-39 intranasal challenge and assayed for the number and function of various white blood cells. All subjects were infected, as manifested by viral shedding in nasal secretions or seroconversion. RV-39 induced marked changes from baseline values in both immune cell number and functions. Compared with nonallergic subjects, AR subjects manifested different responses for the following parameters: (1) numbers of total white blood cells and lymphocytes (smaller increases on day 4), (2) helper/suppressor T cell ratio (absence of an increase on day 7 and presence of an increase on day 23), (3) number of IL-2 receptor-positive suppressor T cells (presence of a decrease on day 7), (4) natural killer (NK) cell numbers (absence of an increase on day 4 and presence of increases on days 7 and 23), (5) NK/T cell ratio (absence of an increase on day 4 and a decrease on day 7), (6) NK cell activity (a blunted decrease on day 7 and absence of a decrease on day 23), and (7) RV-39-induced lymphocyte proliferation (exaggerated increase on day 4). The results show that intranasal challenge with RV-39 induced RV-39-specific and nonspecific systemic cellular immune responses and a unique immunologic response pattern in AR subjects.

Diagnosis of sinusitis in children: emphasis on the history and physical examination.

Sinusitis can occur as an acute, subacute, recurrent acute, or chronic clinical disease process in children. Sinusitis most often manifests as a prolongation or complication of a viral upper respiratory tract infection. Because children average six to eight upper respiratory tract infections per year, sinusitis is probably a more frequent diagnosis in the pediatric age group compared with adults who average two to three upper respiratory infections per year. Upward of 5 to 13% of children may experience sinusitis, but precise incidence data are not available because many imaging techniques currently available are inappropriate procedures for a prospective pediatric survey. Symptoms of acute sinusitis in children can vary from the more common persistent, purulent rhinorrhea and cough to the less common symptoms of fever, headache, facial pain, and swelling. Recurrent acute and chronic sinusitis may be associated with another condition such as a host-defense defect, cystic fibrosis, asthma, or a local condition that predisposes to obstruction of the sinus ostia such as nasal polyps, deviated septum, foreign body, or allergic inflammation. Diagnosis of sinusitis can be made on the basis of a careful history and physical examination with radiography reserved for confirmation of clinical impression or documentation of disease. Although fiberoptic rhinoscopy is used more frequently as an adjunct in adults for the evaluation and management of sinusitis, more studies need to be performed to document its clinical usefulness in children.