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Biomedical subjects

P Fireman

Publications and source records attributed to P Fireman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Lower airway responses to influenza A virus in healthy allergic and nonallergic subjects.

Acute asthma is considered a complication of respiratory viral infections. This investigation assessed the effects of influenza A virus infection on both the patency and responsiveness of the lower airways. Subjects with allergic rhinitis (AR; n = 21) and without AR (non-AR; n = 25) were intranasally inoculated with influenza A virus and monitored for 8 d in a cloistered environment for changes in symptoms, signs, and airway physiology (pulmonary function, bronchial methacholine provocation). All subjects were infected after inoculation. Significant increases in nasal symptoms and secretion weights were observed, with peak effects on Days 3 and 4. Cough was a relatively minor symptom, and none of the subjects developed wheezing. Likewise, there were no significant changes in the measured functions of the lower airways. No effects on allergy status were observed. Under these experimental conditions, influenza A virus infection did not produce detectable alterations in lower airway function in health AR and non-AR subjects.

Adult↗
PubMed1996

Lower airway responses to rhinovirus 39 in healthy allergic and nonallergic subjects.

Acute asthma is considered to be a complication of respiratory viral infections. This investigation assessed the effects of rhinovirus 39 (RV-39) infection both on the patency and responsiveness of the lower airways. Subjects with allergic rhinitis (AR; n = 50) and without AR (non-AR; n = 46) were intranasally inoculated with RV-39, and monitored for 8 days in an enclosed environment for changes in symptoms, signs, and airway physiology (pulmonary function, bronchial methacholine provocation). All subjects were infected postinoculation. Significant increases in nasal symptoms and secretion weights were observed, with peak effects on days 2-3. Cough was a relatively minor symptom and none of the subjects developed wheezing. Likewise, there were no significant changes in the measured functions of the lower airways. No allergy status effects were observed. Under these experimental conditions, rhinovirus 39 infection did not produce detectable alterations in lower airway function in healthy subjects with and without allergic rhinitis.

Adult↗
PubMed1996

Anaphylaxis.

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Anaphylaxis↗
PubMed1996

Pattern of nasal secretions during experimental influenza virus infection.

To define the pattern of secretion production during influenza virus infection, 28 adult subjects were inoculated with influenza-A virus (H1N1) and cloistered for a period of 8 days. On each day, symptoms associated with virus infection were scored, nasal secretions were collected and nasal lavages were performed. Recovered lavage fluids were submitted for virus culture and assayed for proteins, histamine, and bradykinin. Twenty-one subjects were infected with influenza-A virus and had significant increases in daily secretion weights and symptom scores extending from day 2 to 7, post-inoculation. Plasma-derived proteins in the nasal lavage fluids showed an early increase to peak at day 4 and then decreased. Glandular proteins showed a later increase to peak at day 5. Bradykinin but not histamine was significantly elevated and tracked the changes in the glandular proteins. In contrast, a shallow increase in symptoms confined to day 2 post-inoculation, but no increase in daily secretion weights was documented in the seven uninfected subjects. There, an increase in plasma proteins was observed on days 1 and 2, but no change in glandular proteins was obvious. These results support a biphasic secretory response during influenza-virus infection with transudation dominating the early period and glandular secretions contributing later.

Adult↗
PubMed1995

Cytokines, immunoglobulins, and bacterial pathogens in middle ear effusions.

OBJECTIVE: To elucidate the role of cytokines, immunoglobulins, and bacterial pathogens in the middle ear effusions (MEEs) of children with otitis media (OM). DESIGN: Paired MEEs and serum samples collected from consecutive patients were assayed for immunoglobulins. Middle ear effusions were cultured for bacterial pathogens and assayed for interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and interferon gamma. The medical charts of the patients were retrospectively reviewed to define the history of OM. SUBJECTS: Seventy-five patients with a history of recurrent acute OM, persistent OM with effusion, or both. Exclusion criteria included the presence of a major coexisting condition, or an unclear or atypical history of OM. SETTING: A private practice at a tertiary care children's hospital. INTERVENTIONS: At the time of tympanostomy tube placement, with the patient under general anesthesia, one MEE and a serum sample were collected. RESULTS: Interleukin-1 beta was detected in 58% (44/75) MEEs; interleukin-6, 83% (60/72); tumor necrosis factor alpha, 37% (28/75) [corrected]; and interferon gamma, 61% (45/74). Concentrations of interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha in MEEs were highly correlated with each other (P < .01 for each association) suggesting increased local production and the expected effects of cytokines stimulating their own production during OM. High concentrations of tumor necrosis factor alpha in MEEs were also associated with a history of multiple placements of tympanostomy tubes (r = .63). CONCLUSIONS: These data suggest a regulatory role for cytokines in inflammation during OM, and suggest that high concentrations of tumor necrosis factor alpha in MEEs may be a marker for OM chronicity.

Adolescent↗
PubMed1995

Product characteristics and pharmacokinetics of intranasal ipratropium bromide.

The in vivo absorption potential of ipratropium bromide nasal spray was evaluated in studies involving healthy volunteers (0.03%, 0.06%, and 0.12% dosage strengths) and patients with perennial rhinitis (0.03% and 0.06%) and the common cold (0.06%). The dose used was two sprays per nostril, corresponding to a total dose of 84 micrograms, 168 micrograms, and 336 micrograms for the three dosage strengths. These studies indicate that 10% or less of active drug is absorbed systemically after nasal administration based on the amount of unchanged drug excreted in urine in a 24-hour interval. In most instances, the plasma drug concentrations were undetectable. In none of these studies did plasma ipratropium concentrations reach a level where systemic anticholinergic effects are known to occur.

Absorption↗
PubMed1995

State and trait negative affect as predictors of objective and subjective symptoms of respiratory viral infections.

State and trait negative affect (NA) were measured in healthy people immediately before an illness was induced through exposure to a respiratory virus. State NA, disease-specific health complaints (e.g., runny nose, congestion, and sneezing), and an associated objective marker of disease severity (mucus secretion weights) were assessed daily during the illness. Baseline trait and state NA were both associated with increased numbers of subsequent complaints. Although greater numbers of complaints among people high in state NA were explicable in terms of greater disease severity, the association of trait NA and symptoms was independent of objective disease. The trait NA complaint association was also independent of state NA and hence not attributable to trait-elicited state affect. Greater trait NA was associated with biases in complaining during but not before illness. This suggested failure to discriminate between symptoms rather than increased sensitivity or hypochondriacal response.

Adolescent↗
PubMed1995

Influenza A virus--induced acute otitis media.

To better understand the significance of viral upper respiratory tract infections in the pathogenesis of acute otitis media (OM), 27 adults underwent intranasal inoculation with influenza A virus. Monitoring consisted of antibody titer determination, tympanometry, and otoscopy. Microbiologic analysis consisted of cultures and polymerase chain reaction (PCR)-based detection for influenza A virus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. All subjects became infected with the challenge virus. By day 4, 16 (59%) developed middle ear pressures of -100 mm H2O or below and 4 (25%) of them developed OM. One subject (4%) developed purulent OM requiring myringotomy for pain relief. Middle ear effusion cultures were negative. PCR analysis of that subject's middle ear effusion and nasal washes were positive for influenza A virus and S. pneumoniae. These findings support a causal role for viral upper respiratory tract infections in the pathogenesis of OM, possibly mediated by middle ear underpressures and viral and bacterial middle ear infection.

Acute Disease↗
PubMed1995

Effect of rhinovirus 39 (RV-39) infection on immune and inflammatory parameters in allergic and non-allergic subjects.

The economic impact and medical complication rate of the common cold are well documented, but many of the physiological, inflammatory, and immune responses to common cold viruses have only recently been investigated. The purpose of this study was to compare selected systemic immune and inflammatory responses to experimental rhinovirus (RV)-39 challenge in seronegative allergic rhinitis and non-allergic rhinitis subjects. Peripheral blood was obtained before (baseline), during (acute), and 23 days after (convalescent) RV-39 intranasal challenge and assayed for leucocyte histamine release, serum immunoglobulins, allergen-specific IgE antibodies, plasma histamine, and platelet aggregation. All subjects were infected, as manifested by viral shedding in nasal secretions or seroconversion. RV-39 infection induced significant acute increases in serum IgE, leucocyte histamine release, and platelet aggregation, but caused no changes in serum IgG, serum IgA, serum IgM, and plasma histamine. The first change was confined to the allergic rhinitis subjects. There was no evidence that the acute rise in total serum IgE was due to an elevation of a pre-existing, pollen-specific serum IgE antibody. The results show that intranasal challenge with RV-39 induced changes in systemic immune and inflammatory parameters with a unique response pattern in allergic rhinitis subjects.

Adolescent↗
PubMed1995

Effect of experimental influenza A virus infection on isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynges of allergic and nonallergic adult subjects.

Intranasal challenge with both influenza A virus and Streptococcus pneumoniae promotes otitis media with S. pneumoniae in chinchillas. We investigated whether influenza A virus infection promotes oropharyngeal colonization with S. pneumoniae and other middle ear pathogens by selectively inhibiting commensal bacteria. On study day 0, 12 allergic and 15 nonallergic adult subjects were intranasally inoculated with influenza A/Kawasaki (H1N1) virus. Every subject was infected with the virus as demonstrated by nasal shedding or seroconversion. Average upper respiratory symptom scores and nasal secretion weights from the entire subject group were elevated between days 2 and 6 (acute phase) and were not significantly different between allergic and nonallergic subjects. S. pneumoniae was not isolated from any subject prior to the virus challenge but was isolated in heavy density from 4 (15%) subjects on day 6 (P = 0.055). Staphylococcus aureus was isolated more frequently from the nonallergic subjects than from the allergic subjects on days 2 (80 versus 25%, respectively) 4, (67 versus 17%, respectively), and 6 (73 versus 25%, respectively) (P < 0.05). The isolation rates of other middle ear pathogens were not significantly different before virus challenge and during the acute and resolution phases (days 27 to 30) of the experimental infection for the entire subject group or either the allergic or nonallergic subgroup. Densities and isolation rates of commensal bacteria from the entire subject group were similar throughout the observational period. These results suggest that the virus infection promoted S. pneumoniae colonization of the oropharynx and that nonallergic persons may be more vulnerable to colonization with S. aureus than allergic persons. The altered colonization rates were not attributed to inhibition of commensal bacteria.

Acute Disease↗
PubMed1995

Reproducibility of the effects of intranasal ragweed challenges in allergic subjects.

BACKGROUND: Intranasal allergen challenges have been used to study the pathogenesis of disease expression, to evaluate the efficacy of therapies and to make diagnosis of allergic status. Few data, however, are available regarding the reproducibility of the responses to such provocative challenges. OBJECTIVE: The purpose of this study was to evaluate the reproducibility of selected responses of allergic subjects to intranasal pollen challenge. METHODS: Eighteen adults with ragweed allergy completed three dose-response challenge sessions at a minimum interval of 1 week. Sessions were single blinded and randomized to include two intranasal ragweed challenges (doses 10, 100, and 1000 PNU) and one placebo challenge conducted out of the ragweed season. Additionally, 12 of these subjects completed a third ragweed challenge session conducted during the ragweed season. Following administration of each dose, symptoms were scored, sneezes counted, and nasal patency measured by active posterior rhinomanometry. Total nasal secretion weight for each session was measured. RESULTS: For all measures, average dose response curves were identical for the two extra-seasonal ragweed challenges and these were significantly different from those of the placebo challenge session. Intra-individual responses to the two ragweed challenges were highly correlated between sneeze count and secretion weight, and were moderately correlated for objective and subjective measures of rhinorrhea and congestion. No significant increases in these responses were observed for the intra-seasonal ragweed challenge session. CONCLUSIONS: These results document a reproducible symptomatic and physiologic response to intranasal ragweed challenge.

Adult↗
PubMed1994

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.

Adolescent↗
PubMed1994

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 (> or = 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.

Adult↗
PubMed1994

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.

Acoustic Impedance Tests↗
PubMed1993

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.

Adolescent↗
PubMed1993

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.

Adult↗
PubMed1992

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.

Acute Disease↗