Anaphylaxis to sublingual immunotherapy.
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Administration, Sublingual↗
Biomedical subjects
E H Dunsky
Publications and source records attributed to E H Dunsky.
A comparative, volumetric survey of airborne pollen in Philadelphia, Pennsylvania (1991-1997) and Cherry Hill, New Jersey (1995-1997).
BACKGROUND: Aeroallergen sampling provides information regarding the onset, duration, and severity of the pollen season that clinicians use to guide allergen selection for skin testing and treatment. OBJECTIVE: This atmospheric survey reports: 1) airborne pollen contributors in Philadelphia, Pennsylvania (1991 to 1997) and suburban Cherry Hill, New Jersey (1995 to 1997); 2) pollen onset, duration, and peak level; and 3) the relationship between airborne pollen and selected meteorologic variables. METHODS: At both locations, separated by 11 km. sampling was performed with a volumetric Rotorod Sampler (Sampling Technologies, Minnetonka, MN). RESULTS: In Philadelphia and Cherry Hill, respectively, 3-year average measurements included 75.0 and 74.2% tree pollen, 10.2 and 8.3% grass pollen, and 14.8 and 17.5% weed pollen. Prominent airborne pollen taxa were Acer, Quercus, Betula, Pinus, Cupressaceae, Poaceae, Ambrosia, and Rumex. The tree, grass, and weed pollen seasons extended from mid-March to mid-June, late April to mid-June, and mid-August to late September, respectively. A secondary Poaceae pollen peak occurred in September. There was a statistically significant correlation between simultaneous weekly average pollen levels in Philadelphia and in Cherry Hill (Acer, r(p) = 0.987, Quercus, r(p) = 0.645, Betula, r(p) = 0.896, Pinus, r(p) = 0.732, Cupressaceae, r(p) = 0.695, Poaceae, r(p) = 0.950, Ambrosia, r(p) = 0.903, and Rumex, r(p) = 0.572, P <0.001). Daily Poaceae pollen levels were positively influenced by same-day high temperature (r(s) = 0.333 in Philadelphia and r(s) = 0.426 in Cherry Hill, P < 0.05). Daily Ambrosia pollen levels were inversely influenced by same-day total precipitation (r(s) = -0.174 in Philadelphia and r(s) = -0.257 in Cherry Hill, P < 0.05). CONCLUSIONS: This is the first volumetric survey performed in either Philadelphia or Cherry Hill. Copious amounts of airborne pollen were seen from late April to early May and in early September. Pollen onset, duration, and year-to-year variability were similar at both sites. An awareness of local aeroallergen patterns is critical in the effective testing and treatment of atopic individuals.
Air Pollution↗
Comparisons of peak diurnal expiratory flow variation, postbronchodilator FEV(1) responses, and methacholine inhalation challenges in the evaluation of suspected asthma.
STUDY OBJECTIVES: The validity of peak expiratory flow variation (PEFvar) as defined by National Heart, Lung, and Blood Institute (NHLBI) guidelines as a diagnostic tool for suspected asthma or its comparative value to methacholine inhalation challenge (MIC) or postbronchodilator (BD) FEV(1) responses has not been formally assessed. We prospectively analyzed the correlation of 28 different PEFvar indexes (including 4 NHLBI-compatible indexes) with MIC and pre-BD and post-BD FEV(1) responses in suspected asthmatic subjects with normal findings on lung examination, chest radiography, and baseline spirometry. DESIGN: Participants were asked to record peak expiratory flow four times daily for 2 to 3 weeks, followed by an MIC. During a minimum 6-month follow-up period, a clinical diagnosis of asthma was made or ruled out based on testing results and response to antiasthma therapy. SETTING: Medical school-affiliated subspecialty private practice of allergy, asthma, and immunology. PARTICIPANTS: One hundred twenty-one suspected asthmatic patients with normal findings on lung examination, chest radiography, and baseline spirometry. MEASUREMENTS AND RESULTS: Fifty-seven subjects completed both the peak flow diary and the MIC and were accepted for statistical analysis. There were no statistically significant correlations between any peak expiratory flow index and MIC. Among the three diagnostic tools evaluated, MIC had the highest sensitivity (85.71%). All the PEFvar indexes and post-BD responses had low sensitivity and high false-negative rates. CONCLUSIONS: PEFvar and post-BD FEV(1) responses are poor substitutes for MIC in the assessment of patients with suspected asthma with normal findings on lung examination, chest radiography, and spirometry. Our findings warrant a reconsideration of the NHLBI guidelines recommendation of the utility of PEFvar as a diagnostic tool for asthma in clinical practice.
Adolescent↗
Effect of functional endoscopic sinus surgery on bronchial asthma outcomes.
BACKGROUND: For more than 70 years, the coexistence of asthma and paranasal rhinosinusitis has been noted in the medical literature. Causal relationships have been proposed but not proved. To date, limited evidence exists suggesting that asthma improves after surgical correction of rhinosinusitis. OBJECTIVE: To determine whether asthma control improved after first-time functional endoscopic sinus surgery (FESS). PATIENTS AND METHODS: A retrospective medical record analysis was performed on 13 patients with chronic bronchial asthma who underwent FESS for medically refractory chronic rhinosinusitis. Patients received comprehensive asthma care before and after FESS (mean, 19.3 and 33.1 months, respectively). Outcomes analyzed included pre- and post-FESS individual and group mean asthma symptom scores, medication use scores, pulmonary function test results, and emergency department visits or hospital admissions for asthma. Patient medical records were obtained from a private allergy-immunology practice affiliated with a medical school. The surgical procedure was performed at a tertiary care teaching hospital by a single ear, nose, and throat surgeon (R.L.). RESULTS: Following FESS, there was no statistically significant change in group mean asthma symptom scores, asthma medication use scores, pulmonary function test results, and the number of emergency department visits or hospital admissions. Only a few patients demonstrated statistically significant improvement after FESS in asthma symptom scores (1 patient), medication use scores (1 patient), or pulmonary function test results (2 patients). CONCLUSIONS: The data do not support the hypothesis that first-time FESS for medically refractory chronic rhinosinusitis in adult patients with chronic asthma leads to reduced postoperative asthma symptoms or asthma medication use or improved pulmonary function. Based on this limited study, a reexamination of the benefits of sinus surgery to coexisting asthma is in order.
Adolescent↗
Retrospective analyses of methacholine inhalation challenges.
We retrospectively analyzed 198 methacholine inhalation challenges (MICs) of symptomatic patients with normal results of lung examinations, spirometry, and chest radiographs. During MIC, five parameters (FEV1, FEF25-75%, FVC, sGaw, TGV) were measured. Using established changes in these parameters at < or = 8 mg/ml methacholine, there were 175 positive tests (no false positives) and 23 negative tests (15 true negatives, 5 false negatives, and 3 unavailable for follow-up). The MIC sensitivity determined by FEV1 responses was significantly lower than the sensitivity using responses in either three (FEV1, FEF25-75%, and FVC; p < 0.001) or five (FEV1, FEF25-75%, FVC, sGaw, and TGV; p < 0.001) parameter sets. Sensitivities were 60.6 percent, 91.1 percent, and 97.2 percent, respectively. All positive MICs (100 percent) were identified by examining changes in the five-parameter set vs 97.3 percent in the three-parameter set; it was a significant difference at p < 0.01. We conclude that the measurement and analysis of non-FEV1 parameters in addition to FEV1 significantly increases the sensitivity of the MIC.
Adolescent↗
In vivo clearance and tissue uptake of an anti-DNA monoclonal antibody and its complexes with DNA.
In vivo clearance and tissue localization of a purified mouse anti-DNA monoclonal antibody (MoAb) (A52 IgG2b) and its complexes with DNA were studied in normal BALB/c and autoimmune NZB/NZW mice. The plasma half-life of the autoantibody in both mouse strains was significantly shorter (T 1/2 = 10-15 min), compared with that of purified NZB myeloma proteins (T 1/2 greater than or equal to 180 min). DNA antigen and DNA-A52 IgG complexes in antibody excess were cleared very rapidly (T 1/2 = 4-8 min), while complexes formed in antigen excess persisted in the circulation much longer (T 1/2 = 60 min). Organ studies showed that the anti-DNA MoAb was transiently retained by the liver and the spleen but demonstrated a particular affinity for the kidney tissue. We suggest that tissue damage in SLE glomerulonephritis may be facilitated by direct interaction of anti-DNA antibodies with glomerular components.
Animals↗
Effect of cimetidine on exogenous histamine inhibition of histamine release in vivo.
We previously reported that exogenous histamine inhibits in vivo histamine release and eosinophil accumulation in ragweed-challenged skin sites of sensitive human subjects. The mechanism(s) involved were unclear. In this study, we repeated similar approaches in four of the same subjects pretreated for 3 days with cimetidine, an H2 receptor antagonist. The pattern of exogenous histamine effects was now different in that local exogenous histamine (50 ng/ml) did not significantly alter ragweed-induced mast cell alteration, histamine release, or the degree of eosinophil accumulation in skin challenge sites. These findings suggest that the observed exogenous histamine inhibitory effects may be mediated through the H2 receptor.
Biopsy↗
Diphenylhydantoin-induced hepatitis.
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Adolescent↗
Histamine suppression of in vivo eosinophil accumulation and histamine release in human allergic reactions.
Although it has been shown that histamine inhibits antigen-induced in vitro histamine release from basophils, it is unclear whether histamine inhibits in vivo mediator release in human allergic reactions. We report effects of exogenous histamine on histamine release and inflammatory cell responses in antigen-challenged skin sites in eight ragweed-sensitive individuals. Four heat-suction blisters in each subject were unroofed, and a collection chamber was appended to each blister base. Chamber A contained 1000 PNU/ml ragweed extract; chamber B contained buffered saline (control fluid); chamber C contained 1000 PNU/ml ragweed and 50 ng (5 x 10(-7) M) of histamine; and chamber D contained histamine alone (50 ng). Comparative analyses of chamber histamine levels in individual subjects showed that (1) histamine levels in chamber A were significantly greater than those in chamber B (p less than 0.01) and that histamine levels in chamber C were not significantly different than those in chamber D (p less than 0.5). Likewise, comparison of eosinophils attaching to membrane filters appended to the chamber bases for 2 hr showed that there were significantly more eosinophils in chamber A than in chamber B (p less than 0.01) and that there was no significant difference in eosinophil numbers on filters appended to chamber C vs chamber D. In three of four subjects studied, addition of exogenous histamine (50 ng/ml) to ragweed before intradermal injection inhibited the ultrastructural mast cell alterations seen within 10 min after injection of ragweed alone. In the one subject in which mast cell alterations were not prevented, exogenous histamine also did not inhibit antigen-induced histamine release or subsequent eosinophil accumulation in the skin chambers.
Eosinophils↗
Pigeon breeder's disease in children. A family study.
The findings in a family of seven with pigeon breeder's disease are reported, and the wide range of clinical and laboratory involvement is documented. An inhalational challenge and lung biopsy were performed on the 15-year-old patient who was the index case, and the diagnostic results are discussed. We emphasize the importance of thoroughly evaluating the members of the family and the environment when a patient suspected of hypersensitivity pneumonitis is encountered. All treated members responded well to therapy with steroids and ceasing exposure to antigenic material from pigeons. Serum precipitin tests to pigeon-derived antigens that were initially strongly positive in all seven family members became negative by 15 months following treatment.
Adolescent↗
In vivo release of eosinophil chemoattractant activity in human allergic skin reactions.
A search was made for in vivo release of factor(s) that may be responsible for prominent eosinophil accumulations in human allergic skin reactions. Using a specially designed skin chamber appended to the base of unroofed skin blisters, we have found at ragweed-challenged sites in sensitive subjects the release of significantly greater histamine (15 +/- 3 ng/ml) than at control sites (3 +/- 0.5 ng/ml). Eosinophil accumulation after 2 hr was also significantly greater on membrane filters appended to ragweed-challenged sites than control sites (55 +/- 15 vs 4 +/- 0.5). Intradermal injection of ultrafiltrates of the chamber fluids from antigen-challenged sites, but not of fluids from control sites, induced prominent eosinophil accumulation (mean = 25/mm2) when injected intradermally in autologous uninvolved skin. Neither ultrafiltered antigen solution nor histamine (employed in concentrations similar to those released in the chambers) evoked such in vivo responses when injected intradermally in the same subjects (mean = less than 1/mm2). The eosinophil responses to injected ultrafiltered chamber fluid from antigen-challenged sites peaked at 30 min, whereas even greater eosinophil responses to unaltered antigen started after 60 min. These findings suggest that in vivo release of a low m.w. factor or factors other than histamine is very likely responsible for at least part of the in vivo eosinophil accumulation in human allergic reaction sites. Additional findings suggest that a significant portion of the time lag between intradermal antigen and dermal eosinophil accumulation is encompassed by local mediator release.
Asthma↗
Comparison of plasma histamine and cyclic nucleotides after antigen and methacholine inhalation in man.
Serial determinations of plasma histamine and cyclic nucleotides (adenosine monophosphate [AMP] and guanosine monophosphate [GMP]) were performed after inhalation of antigen and methacholine in four groups of subjects. In the first group, consisting of six antigen-sensitive subjects exhibiting bronchospasm after inhalation of ragweed or grass antigen, plasma histamine was elevated within 2 min and persisted for 30 min after inhalation of antigen. Peak histamine levels were between 18 to 80 ng/ml. In the second group, consisting of four nonatopic subjects, neither bronchospasm nor histamine was observed, despite inhalation of the same or 10-fold increased concentrations of antigen. In the third group, consisting of six subjects (three atopic and three nonatopic) exhibiting bronchospasm after inhalation of 2.5 to 10 mg of methacholine, sustained increases of histamine began at 1 min and persisted for 60 min after inhalation of methacholine. In the fourth group, seven subjects (two atopic, five nonatopic) without demonstrable bronchospasm despite inhalation of 2.5- to 10-fold increased doses of methacholine, no histamine was detected in the plasma at any time after inhalation of methacholine. Serial measurements of cyclic nucleotides showed no consistent changes in serum levels of cyclic AMP or cyclic GMP following inhalation challenge. We conclude that serum levels of histamine but not cyclic nucleotides change during bronchospasm induced by either antigen or methacholine.
Adult↗
Effects of theophylline, terbutaline, and prednisone on antigen-induced bronchospasm and mediator release.
Eleven subjects demonstrating clinical, skin, and inhalation sensitivity to grass or ragweed pollen underwnet serial inhalation challenges, with and without orally administered theophylline, terbutaline, and prednisone. Comparisons of antigen sensitivity and mediator release were made during these challenges. All three drugs significantly reduced antigen sensitivity (PD20 inhalation units increasing from 670 to greater than or equal to 3,280). Peak plasma histamine levels after antigen challenge decreased from 11.4 ng/ml to less than or equal to 3.4 ng/ml during all drug administrations. Similarly, the percent increase in serum neutrophil chemotactic activity (NCA) also decreased, from 96% to less than or equal to 36% during drug administrations. However, even at antigen doses resulting in bronchospasm during drug administration the systemic appearance of NCA and histamine were reduced. We conclude that prednisone, theophylline, and terbutaline significantly reduce antigen-induced bronchospasm and mediator release. The occurrence of bronchospasm despite the inhibition of histamine and NCA suggests either that the local concentration of these mediators are critical or that other mediators produce the bronchospasm observed.
Adult↗
Patterns of mast cell alterations and in vivo mediator release in human allergic skin reactions.
Patterns of in vivo histamine release in skin sites challenged with ragweed antigen were compared in five human subjects sensitive to this antigen and four nonallergic individuals, using a newly developed skin-chamber technique. These findings were compared with inflammatory cell responses in the reaction sites and patterns of ultramicroscopic mast cell alterations in biopsy specimens of skin tests in the same subjects. Definite mast cell alterations occurred within 15 sec and appeared maximal within 5 to 10 min after antigen injection. Histamine levels in appended chambers increased after a lag of 10 to 30 min and were elevated for at least 60 min after antigen challenge. Eosinophils accumulated only in antigen-induced reaction sites. However, there was no precise quantitative correlation among the degree of change in these three measurements. These appear to be promising approaches to further in vivo studies of human allergic reactions.
Antigens↗
Early effects of corticosteroids on basophils, leukocyte histamine, and tissue histamine.
The comparative effect in 11 atopic subjects of a single intravenous injection of methylprednisolone on sequential studies of blood eosinophils, basophils, leukocyte sensitivity to antigen for histamine release, leukocyte histamine content, and skin histamine was examined. No significant changes occurred in any parameter after placebo treatment. In contrast, 4 hr after intravenous treatment with steroid there were significant decreases in mean eosinophil counts (-95%), basophil counts (-72%), and histamine content of 1 X 10(7) leukocyte samples (-62%). Temporal changes in the latter paralleled alterations in circulating basophil levels. No significant changes occured in the antigen histamine release sensitivity, or the total skin histamine. Studies over a longer period after steroids in 4 subjects showed eosinophil and basophil levels at a nadir at 8 hr, remaining suppressed for 24 hr, and returned to pretreatment levels by 72 hr. Results suggest that corticosteroids induce a prominent decrease in leukocyte histamine due to a depletion of basophils without a decrease in histamine content per basophil, and that skin tissue histamine stores remain unchanged by such treatment.
Basophils↗