- Email: [email protected]
157 Simultaneous sulfite and sulfur dioxide (SO2) sensitivity
157
SIMULTANEOUS SULFITE AND SULFUR DIOXIDE (SO?)
SENSITIVITY.
J.D. Sprenger,
159
THE PREVALENCE AND DEGREE OF SENSITIVITY TO INGESTED SULFITES . Durham’ v’ . . -’ 110 Quantitative inkormation about the prevalence sulfite sensitivity and degree of‘ idiosyncratic is not available. We orally challenged 134 selected patients from among 1073 patients seen during a 1.4 year interval for asthma and related unusual allergic symptoms with doses of 0.01, 0.1, 1 .O sequential encapsulated & 2.0 r&i potassium metabisulfite (FW 178.05). Baseline FVC, FEVl and FEF25,75 were measured using standard methods and repeated 30-40 minutes after each challenge with an electronic spirometer. The test was stopped with the onset of symptoms and arbitrarily considered positive when a 215% (1 SD) decrease fran baseline FEVl was detected. A positive PD15 was detected in 10 patients with 0.01, 15 with 0.1, 17 with 1.0 ana 8 with 2.0 mM sulfite; 37% (50/134) of the patients. Evaluation of the cumulative log dose distribution of PD1 positive patients yielaed this compares an ED50 of 0.08 mM ? p&0.0037); with an estimated average tolerance for 30 mM in a 60 Kg normal adult (0.5 mM/Kg BW, pet-s. comm. K. V. Rajagopalan). Interestingly, 3 patients with exquisite sensitivity were drawn fran the hydrogen sulfide same community , where containing artesian well water is aerated and the resulting potable product contains 0.016 mM/L of sulfite. Conservatively, these findings suggest a minimum 4.6% (50/1073) prevalence and more than 300-fold idiosyncratic increase in sulfite sensitivity exists among asthmatic patients.
188
SULFITE CHALLENGES IN PATIENTS WITH SYSTEMIC MASTOCYTOSIS (SM) OR UMEXPLAIMED ANAPHYLAXIS QJEA). W.J. Meggs, M.D., Ph.D., F.M. Atkins, M.D., R.H. Wright, R.N., M. Fishman, M.A. Kaliner, M.D., and D.D. Metcalfe, M.D., Bethesda, Maryland. Single-blind challenges with oral sodium bisulfite capsules (1, 5, 10, 25, 50, 100, and 200 mg given every 30 min) were performed in 8 patients with SM and 25 patients with UEA in order to determine whether sulfite sensitivity was a factor in the paroxysmal exacerbations of their illnesses. Positive challenges were followed on subsequent days by a series of placebo challenges. Vital signs and pulmonary function tests were obtained sequentially. Plasma histamine levels were measured in 7 patients with SM and 23 patients with UEA before and after sulfite administration. There were neither clinical reactions nor changes in vital signs and pulmonary functions in patients with SM and in 23 of 25 patients with UEA. Two patients with frequent UEA experienced anaphylaxis in temporal association with both placebo and sulfite administration. Plasma histamine levels were elevated after sulfite challenge in 6 of 7 patients with SM and 15 of 23 patients with UEA. The geometric mean plasma histamine levels before and after challenge in patients with SM rose from 1064 to 1966 pg/ml, and in patients with UEA rose from 66 to 140 pg/ml (overall level of significance was px.02). These results indicate that the patients with 5111and UEA entered into this protocol were not clinically responsive to sulfites, although the approximate twofold rise in histamine suggests that oral sulfites can alter plasma histamine levels.
M.D., L.C. Altman,
Ph.D. and W.E. Pierson, M.D., M.D., J. Koenig, Seattle, Washington To examine the relationship between sulfite and SO;! sensitivity, we carried out oral sulfite and inhaled SO2 challenges in a patient with documented sulfite sensitivity. The challenges 1) resting exposure to 1 ppm SO2, 2) involved: SOP exposure with exercise, 3) clean air exposure with exercise, and 4) oral ingestion of aqueous potassium metabisulfite from 1 to 100 mg. Vital signs, pulmonary function tests and serum samples for neutrophil chemotactic activity (NCA) were obtained prior to and for 4 hr following the NCA assays were performed challenge testing. using microchemotaxis techniques and 51Cr labelThe clean air-exercise challed neutrophils. lenge evoked no changes in pulmonary function tests and no release of NCA. In contrast the SOe-exercise challenge produced a fall in FEVl of 20% at 20 min and an increase in NCA which peaked at 31% above baseline 2 hr after the maxExposure to SO2 without imal FEVl change. exercise produced no significant changes in pulmonary function tests. Oral metabisulfite at 100 mg produced a dramatic reaction with sensorium changes, a fall in FEVl of 48% at 20 min and a maximal increase in NCA of 35% above baseline 2 hr after the maximal change in pulmonary These studies show that sulfite function tests. and SO2 sensitivity coexist in one patient, and that the mechanism of sulfite sensitivity may be via the release of SO2 from sulfite radicals Furthermore, these data suggest that (HSOs-). sulfites and SO2 can stimulate mediator release from tissue mast cells.
188
NEUTROPHIL CHEMOTACTIC ACTIVITY IN SULFITE SENSIL.C. Altman, M.D., J.D. Sprenqer, TIVE PATIENTS. M.D., S. Marshall, M.D., L.E. Johnson, M.D., J. Koenig, Ph.D. and W.E. Pierson, M.D., and G. H. Ayers, M.D. Seattle, Washington. To determine whether mast cell degranulation is involved in sulfite sensitivity, we performed oral challenges with increasing doses of aqueous potassium metabisulfite (l-200 mg) in 6 patients with histories strongly suggestive of sulfite These included bronchospasm in all sensitivity. 6, headache in 4 of 6, and flushing with hypotension in 1. Vital signs, pulmonary function tests and serum samples for neutrophil chemotactic activity were obtained prior to and for 6 hours post challenge. Neutrophil chemotactic activit was measured in microchemotaxis chambers using 5r Cr labeled neutrophils. Three of the 6 subjects had positive challenges with a fall in FEVl 5 20%. The positive responses occurred at 10, 50 and 100 mgs respectively. Reductions in FEVl were maximal at 20 min following the provocative dose and returned to normal by 2 hr. The mean maximal increase in neutrophil chemotactic activity in the challenge positive group was 23% above baseline versus 14% in the challenge negative group (not significant). Maximal neutrophil chemotactic activity release occurred between 30-120 min after the maximal fall in FEV1. These studies show that neutrophil chemotactic activity ,is released following sulfite challenge, however, release of neutrophil chemotactic activity-does not coincide with pulmonary function changes.
144
SIMULTANEOUS SULFITE AND SULFUR DIOXIDE (SO?)
SENSITIVITY.
J.D. Sprenger,
159
THE PREVALENCE AND DEGREE OF SENSITIVITY TO INGESTED SULFITES . Durham’ v’ . . -’ 110 Quantitative inkormation about the prevalence sulfite sensitivity and degree of‘ idiosyncratic is not available. We orally challenged 134 selected patients from among 1073 patients seen during a 1.4 year interval for asthma and related unusual allergic symptoms with doses of 0.01, 0.1, 1 .O sequential encapsulated & 2.0 r&i potassium metabisulfite (FW 178.05). Baseline FVC, FEVl and FEF25,75 were measured using standard methods and repeated 30-40 minutes after each challenge with an electronic spirometer. The test was stopped with the onset of symptoms and arbitrarily considered positive when a 215% (1 SD) decrease fran baseline FEVl was detected. A positive PD15 was detected in 10 patients with 0.01, 15 with 0.1, 17 with 1.0 ana 8 with 2.0 mM sulfite; 37% (50/134) of the patients. Evaluation of the cumulative log dose distribution of PD1 positive patients yielaed this compares an ED50 of 0.08 mM ? p&0.0037); with an estimated average tolerance for 30 mM in a 60 Kg normal adult (0.5 mM/Kg BW, pet-s. comm. K. V. Rajagopalan). Interestingly, 3 patients with exquisite sensitivity were drawn fran the hydrogen sulfide same community , where containing artesian well water is aerated and the resulting potable product contains 0.016 mM/L of sulfite. Conservatively, these findings suggest a minimum 4.6% (50/1073) prevalence and more than 300-fold idiosyncratic increase in sulfite sensitivity exists among asthmatic patients.
188
SULFITE CHALLENGES IN PATIENTS WITH SYSTEMIC MASTOCYTOSIS (SM) OR UMEXPLAIMED ANAPHYLAXIS QJEA). W.J. Meggs, M.D., Ph.D., F.M. Atkins, M.D., R.H. Wright, R.N., M. Fishman, M.A. Kaliner, M.D., and D.D. Metcalfe, M.D., Bethesda, Maryland. Single-blind challenges with oral sodium bisulfite capsules (1, 5, 10, 25, 50, 100, and 200 mg given every 30 min) were performed in 8 patients with SM and 25 patients with UEA in order to determine whether sulfite sensitivity was a factor in the paroxysmal exacerbations of their illnesses. Positive challenges were followed on subsequent days by a series of placebo challenges. Vital signs and pulmonary function tests were obtained sequentially. Plasma histamine levels were measured in 7 patients with SM and 23 patients with UEA before and after sulfite administration. There were neither clinical reactions nor changes in vital signs and pulmonary functions in patients with SM and in 23 of 25 patients with UEA. Two patients with frequent UEA experienced anaphylaxis in temporal association with both placebo and sulfite administration. Plasma histamine levels were elevated after sulfite challenge in 6 of 7 patients with SM and 15 of 23 patients with UEA. The geometric mean plasma histamine levels before and after challenge in patients with SM rose from 1064 to 1966 pg/ml, and in patients with UEA rose from 66 to 140 pg/ml (overall level of significance was px.02). These results indicate that the patients with 5111and UEA entered into this protocol were not clinically responsive to sulfites, although the approximate twofold rise in histamine suggests that oral sulfites can alter plasma histamine levels.
M.D., L.C. Altman,
Ph.D. and W.E. Pierson, M.D., M.D., J. Koenig, Seattle, Washington To examine the relationship between sulfite and SO;! sensitivity, we carried out oral sulfite and inhaled SO2 challenges in a patient with documented sulfite sensitivity. The challenges 1) resting exposure to 1 ppm SO2, 2) involved: SOP exposure with exercise, 3) clean air exposure with exercise, and 4) oral ingestion of aqueous potassium metabisulfite from 1 to 100 mg. Vital signs, pulmonary function tests and serum samples for neutrophil chemotactic activity (NCA) were obtained prior to and for 4 hr following the NCA assays were performed challenge testing. using microchemotaxis techniques and 51Cr labelThe clean air-exercise challed neutrophils. lenge evoked no changes in pulmonary function tests and no release of NCA. In contrast the SOe-exercise challenge produced a fall in FEVl of 20% at 20 min and an increase in NCA which peaked at 31% above baseline 2 hr after the maxExposure to SO2 without imal FEVl change. exercise produced no significant changes in pulmonary function tests. Oral metabisulfite at 100 mg produced a dramatic reaction with sensorium changes, a fall in FEVl of 48% at 20 min and a maximal increase in NCA of 35% above baseline 2 hr after the maximal change in pulmonary These studies show that sulfite function tests. and SO2 sensitivity coexist in one patient, and that the mechanism of sulfite sensitivity may be via the release of SO2 from sulfite radicals Furthermore, these data suggest that (HSOs-). sulfites and SO2 can stimulate mediator release from tissue mast cells.
188
NEUTROPHIL CHEMOTACTIC ACTIVITY IN SULFITE SENSIL.C. Altman, M.D., J.D. Sprenqer, TIVE PATIENTS. M.D., S. Marshall, M.D., L.E. Johnson, M.D., J. Koenig, Ph.D. and W.E. Pierson, M.D., and G. H. Ayers, M.D. Seattle, Washington. To determine whether mast cell degranulation is involved in sulfite sensitivity, we performed oral challenges with increasing doses of aqueous potassium metabisulfite (l-200 mg) in 6 patients with histories strongly suggestive of sulfite These included bronchospasm in all sensitivity. 6, headache in 4 of 6, and flushing with hypotension in 1. Vital signs, pulmonary function tests and serum samples for neutrophil chemotactic activity were obtained prior to and for 6 hours post challenge. Neutrophil chemotactic activit was measured in microchemotaxis chambers using 5r Cr labeled neutrophils. Three of the 6 subjects had positive challenges with a fall in FEVl 5 20%. The positive responses occurred at 10, 50 and 100 mgs respectively. Reductions in FEVl were maximal at 20 min following the provocative dose and returned to normal by 2 hr. The mean maximal increase in neutrophil chemotactic activity in the challenge positive group was 23% above baseline versus 14% in the challenge negative group (not significant). Maximal neutrophil chemotactic activity release occurred between 30-120 min after the maximal fall in FEV1. These studies show that neutrophil chemotactic activity ,is released following sulfite challenge, however, release of neutrophil chemotactic activity-does not coincide with pulmonary function changes.
144