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Biomedical subjects

Philip Fireman

Publications and source records attributed to Philip Fireman.

8 recordsLinked to original sources
PubMed2003

Elevations of local leukotriene C4 levels during viral upper respiratory tract infections.

BACKGROUND: One potential mechanism by which respiratory viruses trigger illness and complications is via the local elaboration of inflammatory mediators. OBJECTIVE: To determine whether there is an increase in local leukotriene C4 (LTC4) levels during experimental infection with influenza A virus (FLU), rhinovirus (RV), or respiratory syncytial virus (RSV). METHODS: Healthy adults were intranasally inoculated with a safety-tested strain of FLU (n = 29), RV (n = 16), or RSV (n = 21). Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed before and then daily after challenge. Lavage samples were submitted for viral culture and assayed for LTC4 levels by radioimmunoassay. Serum antibody titers to the challenge viruses were assayed at baseline and 21 days after challenge. RESULTS: All subjects were infected as evidenced by viral shedding and/or seroconversion. Following infection, significant increases (P < 0.05 by analysis of variance) in LTC4 levels were measured for each virus. Furthermore, there was a temporal association between the local LTC4 levels and the development of illness. CONCLUSIONS: The results of this study, which used an adult experimental model, demonstrate elevations in locally produced LTC4 during respiratory infection with FLU, RV, and RSV. Future studies using antileukotriene agents may help elucidate the precise role of leukotrienes in mediating disease expression.

Adolescent↗
PubMed2002

Clinically important improvements in asthma-specific quality of life, but no difference in conventional clinical indexes in patients changed from conventional beclomethasone dipropionate to approximately half the dose of extrafine beclomethasone dipropionate.

STUDY OBJECTIVE: Clinical trials of asthma treatments usually use measures of asthma control to assess efficacy. However, it is also important to determine whether patients themselves benefit from interventions. The aim of this study was to evaluate health-related quality of life in patients with asthma switched from conventional chlorofluorocarbon (CFC) beclomethasone dipropionate (BDP) to hydrofluroalkane-134a (HFA) BDP extrafine aerosol at half the daily dose. DESIGN: Open-label, 12-month, parallel-group, randomized trial. SETTING: Fifty-seven centers in four countries (United States, Belgium, the Netherlands, and United Kingdom). PATIENTS: Four hundred seventy-three patients with a > or = 6-month history of asthma, stable symptoms, and maintained on CFC-BDP, 400 to 1,600 microg/d. INTERVENTIONS: HFA-BDP, 200 to 800 microg/d (n = 354), or CFC-BDP, 400 to 1,600 microg/d (n = 119). MEASUREMENTS AND RESULTS: The Asthma Quality of Life Questionnaire (AQLQ) and pulmonary function tests were completed at months 0, 2, 4, 8, and 12. For 1 month before each visit, patients made daily recordings of symptoms, peak expiratory flow, and beta(2)-agonist use. Two hundred ninety-six patients completed the study (HFA-BDP, 83.6%; CFC-BDP, 83.2%). At month 12, improvements in overall AQLQ scores were greater in the HFA-BDP group than in the CFC-BDP group (p = 0.0024). The number of patients who need to be treated with HFA-BDP for one to have a clinically important improvement in overall asthma-specific quality of life compared with CFC-BDP was 7.3. There was no evidence of differences (p > 0.05) between treatment groups for airway caliber, symptoms, or beta(2)-agonist use. CONCLUSION: Clinically important improvements in the AQLQ score were observed at month 12 for HFA-BDP vs CFC-BDP, while conventional clinical indexes of pulmonary function and asthma control were similar in the two groups.

Adult↗
PubMed2002

Systemic steroid for chronic otitis media with effusion in children.

OBJECTIVE: To determine the efficacy of a short course of an adrenocorticosteroid agent (prednisolone) given with amoxicillin as compared with that of amoxicillin alone for the treatment of chronic middle ear effusion (MEE). The efficacy of 2 weeks versus 4 weeks of amoxicillin with and without steroid was also assessed. METHODS: In a double-blind, randomized trial, children who were 1 to 9 years of age and had MEE of at least 2 months' duration were assigned to 1 of 4 treatment arms: 1) steroid + amoxicillin for 14 days, then amoxicillin for 14 more days; 2) steroid + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days; 3) placebo (for steroid) + amoxicillin for 14 days, then amoxicillin for 14 more days; or 4) placebo (for steroid) + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days. Children were examined by otoscopy, tympanometry, and audiometry at entry and 2 and 4 weeks after entry; those without MEE at the 4-week visit returned monthly for up to 3 more visits or until recurrence of effusion. Serum immunoglobulin (Ig) G, IgM, IgA, and varicella titers were obtained at entry, and allergy skin testing was performed at the 4-week visit. RESULTS: A total of 144 children was entered; 135 children (94%) returned for the 2-week visit, and 132 (92%) were seen for the 4-week visit. At the 2-week visit, 33.3% of children in the steroid + amoxicillin group had no MEE compared with 16.7% in the placebo + amoxicillin group (95% confidence interval for the difference in proportions: 2.4%-31.0%). At the 4-week visit, the percentage of children with no MEE in the steroid-treated group was 32.8%, whereas that in the placebo group was 20.0% (95% confidence interval for the difference in proportions in the 2 groups: -2.0%-27.7%). Comparing change in middle ear status from the 2- to the 4-week visit, there were no significant differences in recurrence of MEE or additional clearance of MEE between those who were treated with amoxicillin for 2 weeks and those who were treated for 4 weeks. By the 4-month visit, 68.4% of children who were in the steroid group and had no MEE at the 4-week visit had recurrence of MEE as did 69.2% of such children in the placebo group. A total of 126 (87.5%) children underwent allergy skin testing. Of the 122 children who had a positive reaction to histamine, 51 (41.8%) had 1 or more positive reactions to the test allergens. There was no difference in response to treatment between those with positive allergy tests and those without. CONCLUSIONS: There was a significant difference in the proportion of children who were effusion-free immediately after 14 days of treatment with steroid and amoxicillin compared with those who were treated only with amoxicillin for 14 days. Within 2 weeks of finishing treatment, there was no longer any significant difference between the 2 groups regardless of whether amoxicillin was continued or not. Therefore, we conclude that treatment with the dose and type of steroid used in this study should not be universally recommended for treatment of chronic otitis media with effusion, and treatment with amoxicillin, if used, should not continue beyond 14 days.

Acoustic Impedance Tests↗
PubMedDate not supplied

Virus-provoked rhinitis in patients who have allergies.

The most common illnesses in humans are the respiratory tract infections caused by viruses. When limited to the upper respiratory region, these infections often are designated as "a common cold." Viruses commonly associated with these upper respiratory infections (URI) include rhinoviruses (RVs), respiratory syncytial virus, influenza virus, parainfluenza virus, corona virus, and adenoviruses. Clinical observations have suggested that patients with allergic rhinitis and asthma experience more pronounced symptoms during a viral URI than patients who do not have allergies and who are infected with the same virus under similar circumstances. Using an experimental virus infection model in human volunteers with and without allergic rhinitis, several groups of clinical investigators have studied the effects of experimental RV infections. These observations indicate that the experimental virus infection may induce host responses that provoke enhanced immunoglobulin E (IgE) synthesis. Whether this translates into enhanced symptoms has been suggested in one study but not in another. This article will review these studies, which suggest that it is the host response to the virus and not the virus itself that plays the major role in symptom pathogenesis.

Humans↗
PubMedDate not supplied

Children's adherence to recommended asthma self-management.

PURPOSE: Adherence to peak expiratory flow rate monitoring by children with asthma was evaluated, and a behavioral strategy to enhance adherence to daily monitoring was tested. DESIGN AND METHODS: Forty-two 7- through 11-year-old children with persistent asthma were recruited into a 5-week randomized, controlled clinical trial. Adherence data were collected electronically by PeakLog and the self-report Asthma Diary. RESULTS: Adherence declined over time. At week 5, intervention group adherence (Median = 79%) was higher than the usual care group adherence (Median = 64%), but the difference was not statistically significant. The effect size did suggest that differences between groups were present. CONCLUSIONS: Even small improvements in adherence to asthma treatment may be clinically significant in light of the alarming increases in asthma morbidity and mortality. Contingency management shows promise for improving adherence outcomes. Future research should engage larger sample sizes and increase the number and intensity of sessions to teach behavioral strategies.

Asthma↗
PubMedDate not supplied

Understanding asthma pathophysiology.

Asthma is best described as a chronic disease that involves inflammation of the pulmonary airways and bronchial hyperresponsiveness that results in the clinical expression of a lower airway obstruction that usually is reversible. Physiologically, bronchial hyperresponsiveness is documented by decreased bronchial airflow after bronchoprovocation with methacholine or histamine. Other triggers that provoke airway obstruction include cold air, exercise, viral upper respiratory infection, cigarette smoke, and respiratory allergens. Bronchial provocation with allergen induces a prompt early phase immunoglobulin E (IgE)-mediated decrease in bronchial airflow (forced expiratory volume in 1 second) followed in many patients by a late-phase IgE-mediated reaction with a decrease in bronchial airflow for 4-8 hours. The gross pathology of asthmatic airways displays lung hyperinflation, smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial cell sloughing, cilia cell disruption, and mucus gland hypersecretion. Microscopically, asthma is characterized by the presence of increased numbers of eosinophils, neutrophils, lymphocytes, and plasma cells in the bronchial tissues, bronchial secretions, and mucus. Initially, there is recruitment of leukocytes from the bloodstream to the airway by activated CD4 T-lymphocytes. The activated T-lymphocytes also direct the release of inflammatory mediators from eosinophils, mast cells, and lymphocytes. In addition, the subclass 2 helper T-lymphocytes subset of activated T-lymphocytes produces interleukin (IL)-4, IL-5, and IL-13. IL-4 in conjunction with IL-13 signals the switch from IgM to IgE antibodies. The cross-linkage of two IgE molecules by allergen causes mast cells to degranulate, releasing histamine, leukotrienes, and other mediators that perpetuate the airway inflammation. IL-5 activates the recruitment and activation of eosinophils. The activated mast cells and eosinophils also generate their cytokines that help to perpetuate the inflammation. Regardless of the triggers of asthma, the repeated cycles of inflammation in the lungs with injury to the pulmonary tissues followed by repair may produce long-term structural changes ("remodeling") of the airways. This review will discuss in greater detail the relationships of inflammation and airway hyperresponsiveness to the pathophysiology of asthma.

Airway Obstruction↗