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.

Effect of experimental rhinovirus 39 infection on the nasal response to histamine and cold air challenges in allergic and nonallergic subjects.

To determine whether a viral upper respiratory tract infection can alter the responsiveness of the nasal mucosa, paired intranasal histamine and cold air challenge sessions were performed before and after (8 to 13 days) experimental rhinovirus infection in 18 nonallergic subjects and 20 subjects with seasonal allergic rhinitis. The nasal response to the challenges was measured as symptom scores for rhinorrhea and congestion, counts for sneezing, weight for expelled secretions, and inspiratory conductance for nasal patency. For both sessions, a greater response was observed in allergic subjects for sneezing, symptoms of rhinorrhea and congestion, secretion weights provoked by histamine challenge, and secretion weights provoked by cold air challenge when compared with the nonallergic subjects. A comparison of the responses to the paired challenge sessions showed greater responses for sneezing, secretion weight and rhinorrhea to histamine and for secretion weight to cold air challenges performed after rhinovirus infection. No differences were observed between allergic and nonallergic subjects with respect to the degree of enhanced responsiveness secondary to viral infection. These results document an increased responsiveness of the nose to these stimuli during the postsymptomatic period of a rhinovirus infection in both allergic and nonallergic subjects.

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.

Rhinovirus 39 infection in allergic and nonallergic subjects.

To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.

Asthma. A role for IVIG therapy?

Asthma is a multifactorial, reversible, obstructive lung disease that manifests airway inflammation as well as airway hyperreactivity. In addition to IgE-mediated respiratory reactions, the pathophysiology of asthma can be triggered by both viral respiratory and bacterial sinopulmonary infections. Even though most asthma patients do not manifest undue susceptibility to infection, a subset of asthma patients with recurrent sinopulmonary as well as upper-respiratory infections may have an associated immune deficiency syndrome. In a subset of these patients, deficiencies of serum IgG subclasses have also been described in the presence of low-normal or normal serum IgG and also deficient serum IgA. In addition to the usual asthma therapy with beta 2 agonist and theophylline bronchodilators as well as cromolyn and steroids, many of these immunodeficiency patients will benefit from iv gamma-globulin therapy. However, we suggest that an inability to synthesize specific serum antibody to injected vaccines or immunogens be a prerequisite before initiating iv gamma-globulin therapy. The clinician should not rely on serum IgG subclass levels alone as a criterion for initiation of passive immune globulin therapy. There may be another cohort of asthma patients who could benefit from iv gamma-globulin therapy. In a small open-label pilot study severe steroid-dependent asthma patients who were not immunodeficient and did not have undue susceptibility to infection were treated with iv gamma-globulin with a very large dosage protocol of 2000 mg/kg monthly.(ABSTRACT TRUNCATED AT 250 WORDS)

Otitis media and nasal disease: a role for allergy.

Otitis media with effusion (OME) is common in children, although it can occur at any age. Allergies probably contribute to the development of OME, with other major risk factors being bacterial infection and eustachian tube obstruction (ETO). We have demonstrated that patients with allergic rhinitis often develop ETO when challenged with allergens; therefore, ETO could be a link between OME and allergies. Nasal obstruction and ETO in allergic rhinitis can be alleviated or attenuated by pretreatment with intranasal corticosteroids. Therapy for allergic rhinitis complicated by OME includes treatment of the ear infection with antibiotics and the relief of allergic symptoms with antiallergy medications, including antihistamines, intranasal cromolyn, and intranasal corticosteroids, as well as environmental control and appropriate immunotherapy.

Hyper-M-immunoglobulinemia in children with bronchial asthma.

Radial immunodiffusion was used to measure the concentrations of IgG, IgA, and IgM in the sera of 224 asthmatic children, ages 6 months to 14 years. IgM was greater than two standard deviations above age-matched normal values in 51% of these asthmatic subjects. Immunoglobulin profiles were repeated up to four years later in 29 individuals with elevated IgM and increased IgM synthesis was sustained in 14 of these asthmatic subjects. Serum IgE concentrations were elevated in 23 of 35 asthmatic patients. There was no statistical difference in mean IgE between asthmatic children with normal or increased IgM. The distribution of IgE in each group was similar. Only 10 of 224 subjects had an IgA concentration less than 2 SD below age-matched control subjects. The significance and possible mechanisms of hyper-M-immunoglobulinemia are discussed.