Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study.

OBJECTIVE: To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma. STUDY DESIGN: Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk profile assessed at baseline. RESULTS: Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P =.004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14. 8%), a decrease of 4.19% (CI, -8.75 to 0.36, P =.071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor. CONCLUSIONS: We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city.

Successful techniques for retention of study participants in an inner-city population.

The purpose of this work was to describe methods of retaining participants in studies of inner-city populations, including the timing and intensity of contacts; and to describe the characteristics of participants who did not complete all follow-up interviews and/or return all peak flow diaries in the National Cooperative Inner-City Asthma Study. A cohort study design was used involving hospital emergency rooms and community clinics in seven major urban areas. Participants included 1337 4- to 9-year-old asthmatic children and their caretakers. Nearly 89% of participants completed 3-, 6-, and 9-month follow-up interviews. The 15% of participants who completed a baseline interview on the weekends were significantly more likely to complete follow-up interviews on a weekend. The percent of follow-up interviews conducted in person increased over time from 5% to 8%. The percent of participants with complete follow-up increased as the number of contact names increased (86% with zero contacts, 91% with two contracts; p = 0.03, test for trend). Participants who required at least four phone calls to complete the 3- and 6-month assessment were significantly more likely to be black, have higher participant stress, and have a smoker in the household (p < 0.05). Multiple logistic regression suggests that higher social support and lower parental stress were both predictors of completed interviews. Within our study sample of inner-city minority participants with asthmatic children, only a small proportion of participants missed any follow-up interviews. Increased caretaker stress, decreased social support, and inability to provide several alternate contacts were all predictive of retention problems. Having a flexible staff, computer tracking, and face-to-face recruitment appear essential to achieving nearly complete follow-up within a population historically difficult to follow.

Design and methods of the National Cooperative Inner-City Asthma Study.

The National Cooperative Inner-City Asthma Study (NCICAS) was established to identify and then intervene on those factors which are related to asthma morbidity among children in the inner-city. This paper describes the design and methods of the broad-based initial Phase I epidemiologic investigation. Eight research centers enrolled 1,528 children, 4 to 9 years of age, from English- or Spanish-speaking families, all of whom resided in major metropolitan inner-city areas. The protocol included an eligibility assessment and an extensive baseline visit, during which symptom data, such as wheezing, lost sleep, changes in activities of daily living, inpatient admissions, and emergency department and clinic visits were collected. A comprehensive medical history for each child was taken and adherence to the medical regimen was assessed. Access, as well as barriers, to the medical system were addressed by a series of questions including the location, availability, and consistency of treatment for asthma attacks, follow-up care, and primary care. The psychological health of the caretaker and of the child was also measured. Asthma knowledge of the child and caretaker was determined. Sensitization to allergens was assessed by skin-prick allergen testing and exposure to cigarette smoke and the home environment were assessed by questionnaire. For more than a third of the families, in-home visits were conducted with dust sample allergen collection and documentation of the home environment, such as the presence of pets and evidence of smoking, mildew, and roaches. Urine specimens were collected to measure passive smoke exposure by cotinine assays, blood samples were drawn for banking, and children age 6 to 9 years were given spirometric lung function assessment. At 3, 6 and 9 months following the baseline assessment, telephone interviews were conducted to ask about the child's symptoms, unscheduled emergency department or clinic visits, and hospitalizations. At this time, peak flow measurements with 2-week diary symptom records were collected.

Characteristics of inner-city children with asthma: the National Cooperative Inner-City Asthma Study.

Asthma morbidity has increased dramatically in the past decade, especially among poor and minority children in the inner cities. The National Cooperative Inner-City Asthma Study (NCICAS) is a multicenter study designed to determine factors that contribute to asthma morbidity in children in the inner cities. A total of 1,528 children with asthma, ages 4 to 9 years old, were enrolled in a broad-based epidemiologic investigation of factors which were thought to be related to asthma morbidity. Baseline assessment included morbidity, allergy evaluation, adherence and access to care, home visits, and pulmonary function. Interval assessments were conducted at 3, 6, and 9 months after the baseline evaluations. Over the one-year period, 83% of the children had no hospitalizations and 3.6% had two or more. The children averaged 3 to 3.5 days of wheeze for each of the four two-week recall periods. The pattern of skin test sensitivity differed from other populations in that positive reactions to cockroach were higher (35%) and positive reactions to house dust mite were lower (31%). Caretakers reported smoking in 39% of households of children with asthma, and cotinine/creatinine ratios exceeded 30 ng/mg in 48% of the sample. High exposure (> 40 ppb) to nitrogen dioxide was found in 24% of homes. Although the majority of children had insurance coverage, 53% of study participants found it difficult to get follow-up asthma care. The data demonstrate that symptoms are frequent but do not result in hospitalization in the majority of children. These data indicate a number of areas which are potential contributors to the asthma morbidity in this population, such as environmental factors, lack of access to care, and adherence to treatment. Interventions to reduce asthma morbidity are more likely to be successful if they address the many different asthma risks found in the inner cities.

Psychosocial characteristics of inner-city children with asthma: a description of the NCICAS psychosocial protocol. National Cooperative Inner-City Asthma Study.

Previous research has demonstrated a significant reciprocal relationship between psychosocial factors and asthma morbidity in children. The National Cooperative Inner-City Asthma Study investigated both asthma-specific and non-specific psychosocial variables, including asthma knowledge beliefs and management behavior, caregiver and child adjustment, life stress, and social support. This article presents these psychosocial characteristics in 1,528 4-9-year-old asthmatic urban children and their caretakers. Caretakers demonstrated considerable asthma knowledge, averaging 84% correct responses on the Asthma Information Quiz. However, respondents provided less than one helpful response for each hypothetical problem situation involving asthma care, and most respondents had more than one undesirable response, indicating a potentially dangerous or maladaptive action. Both adults and children reported multiple caretakers responsible for asthma management (adult report: average 3.4, including the child); in addition, children rated their responsibility for self-care significantly higher than did adults. Scores on the Child Behavior Checklist indicated increased problems compared to normative samples (57.3 vs. 50, respectively), and 35% of children met the criteria for problems of clinical severity. On the Brief Symptom Inventory, adults reported elevated levels of psychological distress (56.02 vs norm of 50); 50% of caretakers had symptoms of clinical severity. Caretakers also experienced an average of 8.13 undesirable life events in the 12 months preceding the baseline interview. These findings suggest that limited asthma problem-solving skills, multiple asthma managers, child and adult adjustment problems, and high levels of life stress are significant concerns for this group and may place the inner-city children in this study population at increased risk for problems related to adherence to asthma management regimens and for asthma morbidity.

Articulation of asthma and its care among low-income emergency care recipients.

Low-income minority patients from East St. Louis, Illinois, a depressed midwestern urban city, who had visited acute care settings with asthma symptoms, participated in a focus group. Questions were constructed around the Health Belief Model to characterize participants' experiences in receiving asthma care, their confidence in long-term asthma self-management, barriers they perceived to managing their asthma, and recommendations they would make for improving asthma care in their community. Analysis of comments suggests an appreciable understanding of asthma triggers, limited coping behaviors for asthma symptoms, very limited practice of active asthma management, perception of the health care system as frequently insensitive to their needs or their knowledge of their own care, exchange of well-articulated information regarding how to deal with the system, and an apparent lack of awareness of any potential contribution of patient education or support system.

Chronic fatigue syndrome: point and counterpoint.

Two clinical investigators with divergent views on chronic fatigue syndrome (CFS) were invited to debate their positions at the 1993 annual meeting of The Infectious Disease Society of America. Major points of the discourse focused on the value of the US Centers for Disease Control and Prevention case definition of CFS, the potential roles of infectious and allergic problems in the syndrome, the confounding problem of concurrent psychiatric problems, and the utility of diagnostic tests.

A comparison of patient attitudes toward asthma self-management among acute and preventive care settings.

This study characterizes the attitudes regarding asthma and asthma care of low-income, African-American adults who receive care from acute care settings. As a point of reference, their attitudes and knowledge were compared with those of a group of patients receiving asthma care from a private setting that stresses preventive asthma self-management. Patients were assessed regarding attitudes toward (1) routine asthma self-care and decisions as to when to self-treat versus seek asthma care, (2) administration of asthma medications, (3) satisfaction with acute-care services, and (4) the desire for asthma education. Asthma morbidity, sociodemographic characteristics, awareness of environmental triggers, and daily stressors were also assessed. Responses of adults receiving most of their asthma care from acute care settings suggest the same pattern of failure to treat asthma regularly and delay in seeking care as implicated in asthma deaths among children. Emphasis on self-treatment of asthma symptoms, not preventive self-management, was apparent among the attitudes of the acute care patients. Lack of regular care, delay of treatment, and reliance on self-treatment via over-the-counter medications was noted. Implications of these findings for the development of asthma education programs are addressed.

The allergens of Epicoccum nigrum Link. I. Identification of the allergens by immunoblotting.

Two atmospheric isolates of Epicoccum nigrum (EN) were grown under sporulation conditions. Dialyzed extracts of spores, (greater than 95% pure) and pure mycelia were used for skin testing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting. By skin testing, 49 of the 126 atopic patients were found to be sensitive to EN in St. Louis, Mo., and Corpus Christi, Texas, combined. On immunoblotting, which was performed on 17 sera, 44 bands (12.3 to 119.0 kd) were detected; six were unique to spore, four were unique to mycelium, and 34 were common to both. No single band bound IgE from all sera. The most frequent band corresponding to 42 kd occurred in 11 sera. Five other bands were recognized by more than one half, whereas the remainder bound fewer sera. All skin test-positive patients had positive immunoblots; the number of bands recognized varied from three to 25. Spore or mycelium-specific, as well as common bands were recognized by 13 of 17 sera. Two sera recognized only spore and mycelium-specific bands. Only spore-specific bands were bound by two sera. No strain differences were detected. The binding patterns were comparable in the sera from both St. Louis, Mo., and Corpus Christi, Texas. These data suggest that EN is a significant allergen in urban communities. Allergenic proteins occur in both spore and mycelium, suggesting that both must be included in the reagents for skin testing and immunotherapy.

Grass aeropollen of the western United States Gulf Coast.

Volumetric air sampling was performed at Corpus Christi, Tex., September 1987 to August 1989. Grass aeropollen during all of 1988 accounted for 15.3% of total pollen captured during two major peaks, one in May and another during September and October. The remaining grass pollen, about one-quarter of the total, was found throughout the year with low levels in the winter and mid-summer. This bimodal pollen release corresponds to the flowering of two major types of grasses occurring in the western Gulf Coast region, the cool temperate species which are predominantly spring flowering in response to long-day photoperiodicity, and the more common warm temperate and subtropical species flowering by and large in the fall as short-day plants. Supplementing the already rich grass flora and adding to the high proportion of total aeropollen was the long distance dispersal of grass pollen found perhaps in sufficiently high quantities to trigger allergic symptoms and to cause grass pollinosis out of season, at least in acutely sensitive individuals. This occurred in late March, well before the spring peak in May. Correlations existed between near-drought conditions and reduced pollen shed in 1988, and normal precipitation and much higher pollen shed during parts of 1987 and 1989, illustrating the importance of environmental factors such as moisture on annual pollen frequency and level of pollinosis which can be variable and annually unpredictable. What is predictable is the genetically controlled timing of pollen maturation and release which will be generally the same year by year.(ABSTRACT TRUNCATED AT 250 WORDS)

Asteraceae aeropollen of the western United States Gulf Coast.

Volumetric air sampling was performed near Corpus Christi, Texas during 1988 and supplemented with data from 1987 and 1989. Frequencies of captured pollen grains of Parthenium hysterophorus, Ambrosia and allied genera, Helianthus, and other Asteracea were examined. Asteraceous aerospora in 1988 accounted for 22.1% of all pollen found, of which 83.4% were pollen of Ambrosia, 12.4% of Parthenium, and the remainder (4.1%) representative of other genera. Capture of native Ambrosia species and P. hysterophorus peaked in September and October in 1987 and 1988, but Parthenium pollen was also found year round with a smaller secondary peak during May, 1988 and 1989. In the winter a different Ambrosia pollen was captured which compared with A. hispida found in the Yucatan Peninsula and southern Florida at a time when no ragweed was flowering in the vicinity of Corpus Christi. Such a pollen capture probably represents long distance dispersal (ca. 600 miles, 965 km) on strong easterly to southerly prevailing winds. Pollen capture occurred most frequently during daylight hours when percent relative humidity was lower and near midnight when inversions occur. Comparison of pollen capture with meteorologic data demonstrated that photoperiodic responses probably account for the initiation and termination of Ambrosia flowering, and to some extent that of Parthenium, and not sharply lowered temperatures or frost for ending pollen release. Previous plant surveys have shown that P. hysterophorus is more common in the Corpus Christi area than species of Ambrosia, or any other Asteraceae, even though ragweed pollen capture proved 6.9 times greater. This disparity is most likely due to limited long distance dispersal of Parthenium pollen, less pollen produced per another, and a less developed mechanism of wind pollination (passive dispersal or amphiphilous). Since both Parthenium and Ambrosia are significant allergenic plants, correlations between airborne pollen of Parthenium and allergic potential suggest that a prolonged pollination season and perhaps increased allergenicity of unique Parthenium pollen proteins allow Parthenium to be a major allergen despite significantly less ambient pollen.

Aeropollen of weeds of the western United States Gulf Coast.

Volumetric air sampling was performed near Corpus Christi, Texas during all of 1988. The most significant weeds releasing airborne pollen, besides the Asteraceae, were the Amaranthaceae and Chenopodiaceae at 14.8% of total pollen captured, which peaked in September and October. Greater pollen capture (74%) occurred from a peak at 11 PM at a time when inversions are frequent to 9 AM than during the period from late morning to 9 PM. Frequency of amaranth-chenopod pollen capture in the western Gulf Coast region showed no relationship with frequencies along the northern and eastern Gulf Coast nor in eastern North America generally, but rather with western North America where these grains have also been sampled at high levels. As in the West, therefore, amaranth-chenopod aeropollen is sufficiently frequent to be a major source of allergens in the western Gulf Coast region. Other weedy plants, Cannabis/Humulus, Rumex, and the Urticaceae (Parieteria/Urtica) each account for only about 1% of the total annual pollen shed, and consequently they are not nearly as potentially relevant here in pollinosis as are the amaranth-chenopods and Asteraceae. Plantago pollen is very infrequently sampled (less than 0.1%) even though several species are common in the area. Acalypha is newly reported as releasing airborne pollen, a genus related to Mercurialis known to release allergenic pollen in Europe.

Ritualistic use of the holly Ilex guayusa by Amazonian Jívaro Indians.

In Amazonian Peru and Ecuador leaf decoctions of the rainforest holly Ilex guayusa with high caffeine concentrations are used as a morning stimulant. After daily ingestion, ritualistic vomiting by male Achuar Indians, better known as Jívaros, reduces excessive caffeine intake, so that blood levels of caffeine and biotransformed dimethylxanthines do not cause undesirable CNS and other effects. Emesis is learned and apparently not due to emetic compounds.

The role of glutathione in lymphocyte activation--II. Effects of buthionine sulfoximine and 2-cyclohexene-1-one on early and late activation events.

Depletion of intracellular glutathione (GSH) inhibits the lectin-induced activation response of human T lymphocytes. GSH-depleted lymphocytes undergo a partial activation response to lectins but fail to undergo blast transformation. Several lines of evidence indicate that the inhibition of lymphocyte activation in GSH-depleted lymphocytes involves relatively late activation events. Firstly, lectin stimulation induces significant 14C-AIB uptake, IL-2 production and expression of IL-2 receptor but a near complete inhibition of 3H-uridine and 3H-thymidine incorporation. Comparable levels of IL-2 production and IL-2 receptor expression are seen in GSH-depleted lymphocytes allowed to recover from GSH depletion during lectin stimulation. However, in the latter case, 3H-uridine and 3H-thymidine incorporation are normal, and activation is completely restored. Exogenous IL-2 cannot restore activation in GSH-depleted lymphocytes. Furthermore, lymphocytes remain highly susceptible to inhibition by GSH depletion even after 48 h of lectin stimulation which is sufficient to induce early activation events in the Go----G1 transition, such as IL-2 receptor expression and IL-2 production. Exogenous GSH partially restores intracellular GSH levels and completely restores lymphocyte activation in GSH-depleted lymphocytes. Despite comparable degrees of GSH depletion, DL-buthionine-SR-sulfoximine and 2-cyclohexene-1-one inhibit lymphocyte activation to different degrees. The inhibition by 2-cyclohexene-1-one is consistently greater than would be predicted based on glutathione depletion per se. We conclude that GSH-dependent processes are important in relatively late steps of the activation sequence characterized by nuclear events with relative sparing of essential early steps in activation, such as IL-2 receptor expression and IL-2 production. The approximate minimal intracellular GSH concentration necessary to sustain a normal activation response is 2 nmol per 10(7) lymphocytes.

Phytohemagglutinin rapidly lyses S49 T-lymphoma cells and the cytotoxicity is not mediated by generation of cAMP or increase in cytosolic calcium.

Thymic-like lymphomas are very sensitive to killing by phytohemagglutinin. To investigate the mechanism of cytotoxicity, we studied the effect of PHA on cytosolic calcium [( Ca2+]i) and cAMP in the S49 mouse lymphoma cell line. PHA produced a slow continuing rise in [Ca2+]i. Estimation of cell number by Coulter counting showed that PHA induced rapid lysis of S49 cells in a dose-dependent manner. Nicardipine (10(-5) M) did not prevent PHA induced cell lysis or [Ca2+]i increase. Also ionomycin (10(-7) M) did not induce cell lysis. The data suggest that PHA induced increase in [Ca2+]i is the result rather than the cause of cell lysis. Elevated intracellular cAMP has an antiproliferative effect on S49 cells. PHA had no effect on cAMP levels in S49 cells. Also S49 cyc- clone which is deficient in Gs was susceptible to killing by PHA. These results suggest that the cytotoxic effect of PHA on S49 cells is rapid, but is not mediated by cAMP generation or an increase in [Ca2+]i, and other mechanisms should be investigated.

Allergic reactivity to Parthenium hysterophorus pollen: an ELISA study of 582 sera from the United States Gulf Coast.

Parthenium hysterophorus (PH) is a ubiquitous weed found in the U.S. Gulf Coast. In this study, 582 sera, contributed by 22 physicians from 18 Gulf Coast cities, were examined by ELISA for IgE directed against determinants in an aqueous extract of PH pollen, and these were compared to an extract of western ragweed (Ambrosia psilostachya [AP]). Overall, 65.6% of the sera tested were positive for one or both of the pollen extracts examined. Thirty-five percent of the sera were sensitive to PH and 57.6% were sensitive to AP. Thirty percent of the sera were positive to AP only, 8.0% were positive to PH only, and 27.9% of the sera were positive to both extracts. ELISA-inhibition analysis demonstrated that PH and AP extracts contained unique allergenic epitopes. Clinical correlation of in vitro reactivity with skin testing and patients' symptoms confirmed that PH sensitivity by ELISA was related in many cases to fall seasonal symptoms. These data demonstrate by in vitro analysis the presence of IgE directed against an extract of PH pollen in a significant number of patients with fall seasonal pollinosis in the U.S. Gulf Coast. Thus, allergic reactivity to PH may be a significant contributor to fall allergic disease in the U.S. Gulf Coast.

Identification of potential allergens in white oak (Quercus alba) pollen by immunoblotting.

Aqueous extracts of white oak pollen were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred onto nitrocellulose membranes. The nitrocellulose membranes were blocked with phosphate-buffered saline 15% nonfat dry milk, incubated with dilutions of sera from atopic or control subjects, and probed with a radiolabeled or peroxidase-labeled antihuman IgE. The IgE binding bands were detected by autoradiography or enzymatic reaction; 45 to 50 protein bands were observed in silver-stained gels. IgE from 30 of the 38 sera tested from oak-sensitive subjects bound to 23 bands with molecular weights (MWs) between 106 to 108 kd (band 1) and 13.2 to 15.2 kd (band 23). No band was recognized by sera of every patient. Band 5 (MW 74.0 to 77.9 kd) and band 21 (MW 16.2 to 17.7 kd) were recognized by 71% of the patients' sera. Multiple bands were recognized by 30% to 50% of the sera tested. All patients who were skin test positive to oak by prick testing had positive immunoblots. Of 12 patients positive by intradermal skin testing, only four patients had positive immunoblots. The average number of allergens recognized by a single patient was 6.6. The maximum number of allergens to which any individual reacted was 18; the minimum number was one. Extracts separated under nonreducing conditions resulted in aggregates that did not enter the polyacrylamide gel. Of the protein that did enter the gel, the higher MW species elicited banding patterns similar to patterns observed under reducing conditions, whereas lower MW IgE binding bands were lost. These data suggest that the extractable proteins of white oak pollen contain multiple proteins that are potentially allergenic.

Successful use of aztreonam in a patient who failed oral penicillin desensitization.

A 69-year-old woman with Pseudomonas aeruginosa sepsis developed wheezing during the course of an oral penicillin desensitization. Despite treatment of the bronchospasm and readministration of the same dose of phenoxymethyl penicillin, wheezing recurred requiring stopping the desensitization procedure. Aztreonam, a monobactam antibiotic with activity against aerobic gram-negative bacilli, was administered along with an aminoglycoside. The patient tolerated a full course of aztreonam with no adverse reactions. This case report supports previous in vitro and in vivo studies, suggesting that aztreonam does not cross-react with penicillin-specific antibodies and that it may be well tolerated in beta-lactam-allergic individuals.

Facial swelling secondary to inhaled bronchodilator abuse: catecholamine-induced sialadenosis.

A patient with asthma presented with a history of recurrent episodes of facial swelling. The swelling occurred in the preauricular area and extended to the angle of the jaw. The patient attributed these episodes to a "food allergy" as they occurred during or immediately following meals. The only medication the patient was using was inhaled epinephrine (Primatene MistR), two puffs, ten to twenty times a day. Subsequent evaluation revealed that the patient had sarcoidosis. Differential diagnosis of the facial swelling included food-related angioedema, sarcoid parotitis, or catecholamine-induced sialadenosis, which is a rare complication associated with excessive catecholamine administration. A gallium-67 citrate scan demonstrated abnormal pulmonary and hilar uptake of the radiotracer, but not lacrimal or parotid gland uptake, strongly arguing against sarcoidosis as the cause of the facial swelling. Episodes of swelling completely abated when the patient stopped using the epinephrine inhalers. At 5 months of follow-up she has had two recurrent episodes of facial swelling, each time associated with the use of inhaled epinephrine. Thus this patient's facial swelling most likely represents catecholamine-induced sialadenosis. This adverse drug reaction, associated with excessive use of inhaled catecholamines must be kept in mind in patients who abuse inhaled beta-adrenergic agonists and report parotid swelling.