The relationship between airway responsiveness measured before and after the allergen-induced late asthmatic response.

Single blind allergen (Ag) and saline solution bronchial challenges were performed on two successive study days in ten asthmatic subjects. Histamine challenges were performed before, at approximately 2 h (or after resolution of the immediate bronchial response [IR]), and 24 h after saline solution or Ag inhalation. Specific airway conductance (SGaw) was measured after delivery of challenge agents until a 50 percent fall in SGaw was observed. The SGaw was monitored over 8 h for immediate and late asthmatic responses (LAR). Results were expressed as provocative concentrations eliciting a 50 percent decrease in SGaw (SGawPC50HIS). No significant changes from baseline SGaw or SGawPC50HIS were demonstrated after saline solution. Eight subjects (dual reactors) exhibited both an IR and LAR after Ag and two had isolated IRs. Of the eight dual reactors, five had greater than 50 percent decreases in SGawPC50HIS immediately after resolution of the IR and six exhibited such decrements 24 h after Ag provocation. Mean baseline SGawPC50HIS (N = 10) on the Ag challenge day was 3.2 +/- 4.59 mg/ml and decreased to 0.92 +/- 4.56 mg/ml at 102 to 187 minutes after Ag (p = 0.0009) and was significantly decreased from baseline at 1.47 +/- 3.8 mg/ml 24 h after Ag (p = 0.0004). One of the two patients with isolated IR also showed an early onset increase in airway responsiveness (EOR). There was a significant correlation between the percentage of fall from baseline in SGawPC50HIS immediately after the IR and that at 24 h after Ag (r = 0.811, p = 0.005). There was no significant correlation between the decrease in SGawPC50HIS after the IR and the magnitude of the LAR. These data suggest that (1) the early events occurring prior to the LAR may determine changes in airway responsiveness observed at 24 h after Ag challenge, and (2) the EAR to histamine is not exclusively associated with the LAR.

Evaluation of cutaneous responses and lung function from exposure to opiate compounds among ethical narcotics-manufacturing workers.

We recently demonstrated morphine-6-hemisuccinate-human serum albumin conjugate (M-6-HS-HSA)-specific IgG in serum from ethic narcotics-manufacturing workers. In this article, we present results of epicutaneous tests to opiate compounds and lung-function studies in these same workers. Thirty-nine workers, exposed to opiates, were evaluated for possible work-related changes in lung function and were administered a questionnaire concerning opiate exposure and health history in February 1988. In December 1988, 33 employees with occupational exposure to opiates, six other workers (New Jersey referent) employed at the same factory with minimal exposure to opiate compounds, and 17 nonexposed individuals from Cincinnati, Ohio, were subjected to epicutaneous threshold testing with a panel of six opiate compounds and nine common aeroallergens. In opiate-exposed workers, significantly lower epicutaneous threshold concentrations were detected (compared to New Jersey referent and Cincinnati control subjects) for dihydrocodeine (p less than 0.01), hydrocodone (p less than 0.05), codeine (p less than 0.01), and morphine (p less than 0.05). Significant associates existed among epicutaneous threshold concentrations between the agents tested; that is, individuals with a positive morphine skin test would generally have a positive codeine skin test, etc. Atopic status (positive cutaneous test results to two or more of nine common aeroallergens) was not significantly associated (p greater than 0.05) with positive opiate skin sensitivity. Although the mean cross-shift decrements in FEV1 for all workers were nonsignificant, five opiate-exposed individuals demonstrated cross-shift decrements in FEV1 of greater than 10%. Daily maximum-minus-minimum changes in workweek PEFR (PEFRmax-min) were significantly reduced for Monday through Thursday (p less than 0.05) compared to PEFRmax-min changes during a nonwork, nonexposure 3-day weekend. Ten exposed workers demonstrated daily PEFRmax-min changes of greater than 20%, suggesting acute airway obstruction. Increased cutaneous reactivity to opiate compounds among opiate-exposed workers may reflect development of pharmacologic hyperresponsiveness to opiate compounds.

Selective desensitization to seminal plasma protein fractions after immunotherapy for postcoital anaphylaxis.

A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and immunologic studies of rapid venom immunotherapy in Hymenoptera-sensitive patients.

A 2- to 5-hour regimen of rapid venom immunotherapy (RVIT) was administered to 33 patients with anaphylactic sensitivity to Hymenoptera venom in a hospital setting in which full emergency resuscitation equipment was available. The RVIT was administered as 10 increasing doses of each treatment venom every 10 to 15 minutes to achieve a final dose on day 1 of 58.55 micrograms per venom. Patients returned for booster venom injections of 60 micrograms on day 3, 70 micrograms on day 7, 80 micrograms on day 21, and 100 micrograms on day 35 after RVIT. Serial antigen-induced leukocyte histamine release studies were performed on day 1 in 10 patients before and after RVIT, as well as 3 1/2 months after initiation of RVIT. Of 33 patients, 32 achieved a cumulative venom dose on day 1 of at least 50 micrograms, and the entire group received a mean dose of 95.46 micrograms. Local reactions during RVIT occurred in 18 (55%) patients. Four patients (12%) experienced mild systemic reactions during or after completion of RVIT. Subsequent booster venom doses administered to 29 patients were well tolerated. A decrease in venom-induced leukocyte-histamine release from baseline was detected in three (30%) patients immediately after RVIT and in seven (70%) patients months after achieving maintenance doses. Cutaneous sensitivity decreased by at least one log10 concentration in eight (32%) of 25 patients. Twenty-two natural re-sting events occurred in 12 (50%) of 24 patients surveyed after successful completion of RVIT, of whom seven identified the insect as one for which they had been treated. No systemic reactions were reported. Results of this study indicate that RVIT is a safe, alternative method of venom administration for patients who are at immediate risk for re-sting anaphylactic episodes.

Progesterone-responsive urticaria and eosinophilia.

A 30-year-old black albino woman was first observed with a 4-year history of monthly urticarial episodes associated with hypereosinophilia. Hives consistently began at the end of menses and lasted for 1 to 2 weeks. A comprehensive evaluation excluded underlying malignancy and infection. There was no evidence of extracutaneous visceral involvement consistent with the primary hypereosinophilic syndrome. A 6-month prospective evaluation was performed, during which daily hive symptoms were recorded and weekly determinations of eosinophils, serum total IgE, progesterone, estradiol, and 24-hour urine histamine were obtained. Eosinophil counts (range, 4002 to 37,350 cells per cubic millimeter) increased in association with the onset of hives and decreased to baseline levels after their resolution. The 24-hour urine histamine peaked at the onset of each urticarial episode. When serum progesterone levels increased, the hives were quiescent and peripheral eosinophils decreased to baseline levels. Progesterone caused in vitro dose-related inhibition of antihuman IgE-induced histamine release from peripheral basophils of this patient. Treatment with oral medroxyprogesterone resulted in remission of urticaria and a decrease in eosinophil counts. This patient represents a unique case of chronic cyclic urticaria and hypereosinophilia that appears to be modulated by the effects of progesterone.