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Biomedical subjects

Paul A Greenberger

Publications and source records attributed to Paul A Greenberger.

At least 19 recordsLinked to original sources
PubMed2007

Investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are known to cause angioedema. OBJECTIVE: To evaluate the time to onset of angioedema and the subsequent episodes of angioedema in patients initially experiencing ACE-I- or ARB-induced angioedema. METHODS: A manual medical record review was conducted on 64 patients with a diagnosis of urticaria, angioedema, or anaphylaxis as a result of taking an ACE-I or ARB. Data recorded included demographic characteristics; time to onset of symptoms; concomitant medication use; laboratory test results; recurrent episodes of angioedema, urticaria, or anaphylaxis; and morbidity and mortality. RESULTS: The mean age of patients with angioedema was 60.2 years (age range, 32-92 years). Women (60%) and African Americans (69%) were affected more commonly. The primary location for angioedema was the lips and tongue. Sixty-one of 64 patients developed at least one episode of angioedema as the result of taking an ACE-I, and 3 patients had angioedema associated with an ARB. The mean time to onset of angioedema after initiation of therapy in 51 patients was 1.8 years, with 13 patients (25%) presenting within the first month and 6 patients (12%) developing angioedema in the first week. No patients required a tracheostomy or died. Also, none of the 6 patients, whose angioedema was attributed to an ACE-I who then received an ARB, developed recurrent angioedema in more than 8.1 patient-years of follow-up. CONCLUSIONS: Angioedema attributable to an ACE-I or ARB resolves on discontinued use of the medication. It most commonly affects women and African Americans and did so in the first month of treatment in 25% of patients. Physicians should be aware but not deterred necessarily from recommending an ARB in patients with ACE-I-induced angioedema because of the benefits of control of hypertension or reducing albuminuria in selected patients.

Adult↗
PubMed2006

Anaphylactic and anaphylactoid causes of angioedema.

Anaphylactic and anaphylactoid (pseudoallergic) reactions can be expected to occur with greater frequency as the number of immunomodulators are employed. The immune system will become sensitized to these new therapeutic agents or there may be first-dose reactions depending on the pathogenetic mechanism involved. Physicians should review their office or procedure room emergency preparedness protocols and medications. The lack of penicillin major and minor determinants for penicillin testing has made management of penicillin and cephalosporin allergic patients more complicated. In the absence of skin-testing materials, test-challenges will be necessary and performed with less comfort because of not knowing the current level of immunologic sensitization to penicillin. The indication for readministration of any incriminated medication/therapeutic agent should be reviewed. Often, there are not suitable alternatives. Various approaches have been presented to permit safer readministration of essential medications or diagnostic agents to prevent episodes of anaphylaxis or upper airway angioedema.

Anaphylaxis↗
PubMed2006

8. Drug allergy.

Drug reactions can be considered as being either predictable or unpredictable. A predictable reaction would be the result of the pharmacologic action of the medication. An unpredictable reaction might be idiosyncratic, might be drug intolerance, or might have or imply an immunologic basis, such as being IgE mediated. Immediate reactions that are not IgE mediated can be considered as pseudoallergic (non-IgE-mediated mast cell activation). This review will discuss allergic and immunologic reactions to immunomodulators, penicillins and cephalosporins, sulfonamides, aspirin, and nonselective nonsteroidal anti-inflammatory drugs and consider the serious drug-related conditions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The field of drug "allergy" has expanded to include adverse reactions associated with immunosuppressive medications, anticytokine therapies, and mAbs. The cytokine release reaction that occurs with anti-CD20 antibody infusions in patients with leukemia and white blood cell counts of greater than 50 x 10(9)/L is associated with high concentrations of TNF, IL-6, and IL-8. Because of the findings of fever, dyspnea, rigors, and hypotension, this reaction resembles the Jarisch-Herxheimer reaction that occurs 60 to 90 minutes after penicillin administration in patients with secondary syphilis. Furthermore, the care of the patient with penicillin allergy has been made more difficult in the absence of the major determinant, penicilloyl-polylysine, in that from 34% to 84% of patients who have positive skin test reactions to penicillin have exclusively positive reactions to the major determinant. SJS and TEN typically are caused by medications within 1 to 8 weeks of initiation of therapy. Evidence for death of the keratinocytes through (1) drug-specific cytotoxicity with the perforin-granzyme B-mediated killing and (2) activation of Fas on keratinocytes have provided explanations for the sloughing of skin. Unfortunately, intravenous immunoglobulin therapy for SJS and TEN has been disappointing.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Role of C-terminal cysteine residues of Aspergillus fumigatus allergen Asp f 4 in immunoglobulin E binding.

Among the several allergens cloned and expressed from Aspergillus fumigatus, Asp f 4 is a major one associated with allergic bronchopulmonary aspergillosis (ABPA). The structure-function relationship of allergens is important in understanding the immunopathogenesis, diagnosis, and treatment of allergic diseases. These include the epitopes, conformational or linear, deletion of the N or C terminus or both N and C termini, and glycosylation or nonglycosylation, all of which affect immune responses. Similarly, the role of cysteine residues present in allergens may yield useful information regarding the conformational structure of allergens and the immunoglobulin E (IgE) epitope interaction. Such information may help in developing new strategies towards immunotherapy. In order to define the role of cysteine in the interaction of the antibody with Asp f 4, we have constructed mutants by selectively deleting cysteine residues from the C-terminal region of the Asp f 4. Immunological evaluation of these engineered recombinant constructs was conducted by using sera from patients with ABPA, Aspergillus skin test-positive asthmatics, and healthy controls. The results demonstrate strong IgE binding with Asp f 4 and two truncated mutants, Asp f 4(1-234) (amino acids [aa] 1 to 234) and Asp f 4(1-241) (aa 1 to 241), while another mutant, Asp f 4(1-196) (aa 1 to 196), showed reactivity with fewer patients. The result suggests that deletion of cysteines and the alteration of IgE epitopes at the C-terminal end resulted in conformational changes, which may have a potential role in the immunomodulation of the disease.

Allergens↗
PubMed2003

Clinical aspects of allergic bronchopulmonary aspergillosis.

Allergic Bronchopulmonary Aspergillosis (ABPA) is characterized by recurrent pulmonary infiltrates that can result in central bronchiectasis and bronchiolitis obliterans especially if there is a lack of recognition and treatment. The incidence of ABPA is 1-2% in patients with persistent asthma and approximately 7% (range 2-15) in patients with cystic fibrosis. The diagnostic criteria are useful in that there is no single test (with the exception of central bronchiectasis in patients with asthma) that identifies ABPA. The differential diagnosis of ABPA includes many conditions including chronic eosinophilic pneumonia, Churg Strauss Syndrome, Hyper-IgE Syndrome, persistent asthma with lobar collapse, and cases of parasitism. The most useful laboratory assays in patients who have immediate cutaneous reactivity. to Aspergillus mixes or A. fumigatus are total serum IgE concentration, elevated serum IgE-A.fumigatus and serum IgG-A.fumigatus. Prednisone remains the drug of choice yet need not be administered indefinitely.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed2003

Amphotericin-induced stridor: a review of stridor, amphotericin preparations, and their immunoregulatory effects.

BACKGROUND: Various adverse effects have been reported with the use of amphotericin B. The respiratory adverse effects include dyspnea, tachypnea, bronchospasm, hemoptysis, and hypoxemia. Stridor has not been previously reported with the use of amphotericin B. OBJECTIVE: To review the mechanism of action and reports of respiratory adverse effects for amphotericin B, the liposomal preparations of amphotericin B, and the differential diagnosis of stridor. DATA SOURCES: A MEDLINE search from 1966 to 2002 was performed to review the current literature for possible mechanisms and immunoregulatory effects related to the infusion of amphotericin B. RESULTS: Amphotericin B has been shown to increase tumor necrosis factor alpha (TNF-alpha) concentrations in macrophages. In addition, it induces prostaglandin E2 synthesis and increases the production of interleukin 1beta (IL-1beta) in mononuclear cells. The immunoregulatory effects of amphotericin B include increases in apoptosis, production of monocyte chemoattractant protein 1, superoxide anion, nitric oxide, and intercellular adhesion molecule 1 expression. CONCLUSIONS: Amphotericin B induces the production of TNF-alpha, interferon-gamma, and IL-1beta, which may potentiate its toxic effects. Some liposomal preparations induced lower levels of TNF-alpha and nitric oxide and may be useful in patients unable to tolerate amphotericin B deoxycholate.

Acute Disease↗
PubMed2002

C-terminal cysteine residues determine the IgE binding of Aspergillus fumigatus allergen Asp f 2.

The knowledge of the structure function relationship of the allergen is essential to design allergenic variants with reduced IgE binding capacity but intact T cell reactivity. Asp f 2 is a major allergen from the fungus Aspergillus fumigatus and >90% of A. fumigatus-sensitized individuals displayed IgE binding to Asp f 2. In the present study, we evaluated the involvement of C-terminal cysteine residues in IgE binding conformation of Asp f 2. The deletion mutants were constructed by adding three C-terminal cysteines of the native Asp f 2 one at a time to the non-IgE binding Asp f 2 (68-203). The point mutants of Asp f 2 (68-268) with C204A and C257A substitutions were constructed to study the role of C-terminal cysteines in IgE binding. Immunological evaluation of reduced and alkylated Asp f 2 and its mutants were conducted to determine the contribution of free sulfhydryl groups as well as the disulfide bonds in allergen Ab interaction. Four-fold increase in IgE Ab binding of Asp f 2 (68-267) compared with Asp f 2 (68-266) and complete loss in IgE binding of C204A mutant of Asp f 2 (68-268) indicate the involvement of C(204) and C(267) in IgE binding conformation of Asp f 2. A significant reduction in IgE binding of wild and mutated Asp f 2 after reduction and alkylation emphasizes the importance of cysteine disulfide bonds in epitope Ab interaction. The hypoallergenic variants may be explored further to develop safe immunotherapeutic strategy for allergic disorders.

Allergens↗
PubMed2002

IgE binding conformational epitopes of Asp f 3, a major allergen of Aspergillus fumigatus.

sp f 3 has been identified as one of the major allergens of Aspergillus fumigatus associated with the sensitization and immune responses in allergic bronchopulmonary aspergillosis (ABPA). In order to understand the structure/function relationship of Asp f 3, we studied synthetic peptides and constructed mutants deleted of specific IgE binding regions. The mutated allergens were obtained by expressing the genes and studied by ELISA for their reactivity with IgE from patients with ABPA. Seven linear IgE binding regions spanning the whole Asp f 3 molecule were demonstrated. The results demonstrated strong binding of IgE from ABPA patients with Asp f 3 and one mutant, Asp f 3(1-150), but not with other mutant constructs. The results identified 12 amino acids at the N-terminal end and 8 amino acids (143-150) at the C-terminal end as significant in the conformational constraints for IgE binding. The Fourier transfer spectra showed comparable beta-sheet structure of Asp f 3(1-150) and Asp f 3, indicating the role of secondary structure in IgE binding. The primary and secondary structures may help understanding of the functional role the allergens play in the disease and may have implications in immunodiagnosis and probably immunotherapy.

Allergens↗
PubMed2002

Churg-Strauss syndrome: survival for 26 years.

BACKGROUND: Churg-Strauss syndrome (CSS), a necrotizing vasculitis characterized by asthma and eosinophilia, was described initially in 1951. Before the use of oral corticosteroids, the average patient survived for only a few months. Today with the use of oral corticosteroids and immunosuppressants, survival has increased significantly. METHODS: We report the case of a patient with CSS treated with prednisone and azathioprine. A review of the English literature was performed with MEDLINE from 1966 to the present using these keywords: Churg-Strauss syndrome, survival, prognosis, morbidity, mortality, and treatment. RESULTS: This patient survived 26 years after the diagnosis of CSS and died without autopsy findings of active vasculitis. This is the longest reported survival with CSS in the English literature to our knowledge. The patient's disease course was marked by two acute (vasculitic) episodes, with intermittent subacute disease, and finally a state of disease remission. CONCLUSIONS: Survival in patients with CSS can be prolonged with early initiation of corticosteroids and immunosuppressants, close outpatient followup, and prompt, aggressive treatment of relapses. This case exemplifies the disease progression and remission as reported by other authors. We propose that CSS can be classified into acute (vasculitic), subacute, and remittable stages.

Anti-Inflammatory Agents↗
PubMed2002

Allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) complicates asthma and cystic fibrosis. The survival factors in Aspergillus fumigatus that support saprophytic growth in bronchial mucus are not understood. Prednisone remains the most definitive treatment but need not be administered indefinitely. MHC II -restricted CD4(+) T( H)2 clones have been derived from patients with ABPA. The total serum IgE concentration is elevated sharply but is "nonspecific. " IgE serum isotypic antibodies to A fumigatus are useful in diagnosis; this is in contrast to the situation for patients with asthma without ABPA. High-resolution computed tomography of the chest demonstrates multiple areas of bronchiectasis in most patients with ABPA and is a useful radiologic tool. Some asthma control patients might have a few bronchiectatic airways, but not to the extent seen in or of the same character as those in ABPA. This review discusses clinical, radiologic, investigational, pathogenetic, and treatment issues of ABPA.

Adult↗
PubMedDate not supplied

Psychogenic cough in adults: a report of two cases and review of the literature.

Psychogenic cough, also known as "habit cough," is a well-documented condition in the pediatric and adolescent population, with numerous cases reported in the medical literature. Many of these patients are strikingly similar in their clinical characteristics and, although the data are limited, a variety of treatment options may be successful in terminating this form of cough. However, psychogenic cough in adults has been reported infrequently and is less well defined. We report two cases of psychogenic cough in adult patients referred to our service for an evaluation of refractory, chronic cough and review the relevant medical literature. Our patients seemingly represent the first cases of psychogenic cough reported in the geriatric population and share clinical features with children, adolescents, and young adults. One case is unique in the sense that the cough responded to a distracter in the form of a throat lozenge, and this patient consumed > or = 20 lozenges/day for approximately 13 years. Psychogenic cough should be considered in adult patients who present with a chronic cough of no obvious organic basis that has failed therapy directed at postnasal drip, asthma, and gastroesophageal reflux. We propose criteria to assist in making a diagnosis of psychogenic cough in adult patients and review the limited information that exists concerning treatment modalities.

Aged↗
PubMedDate not supplied

Long-term evaluation of hypersensitivity pneumonitis: a case study follow-up and literature review.

This study reports a 3-year follow-up of a classic presentation of hypersensitivity pneumonitis (HP), originally reported elsewhere, after removal of the causative antigens. The literature is reviewed and this case is compared with outcomes of series previously reported. The patient was reevaluated by clinical, serologic, radiographic, and pulmonary function testing 3 years after removal of her home's contaminated humidifier, cleaning of the home, and administration of a course of prednisone. Repeat serologic measurements revealed positive serum precipitins only for Aspergillus flavus and Phoma herbarum, significantly fewer than her original panel, which revealed precipitating antibodies to her humidifier water and 10 other specific antigens. Pulmonary function tests remained stable. Physical exam revealed bibasilar rales. Computed tomography scan revealed pulmonary fibrosis, bronchiectasis, and honeycombing that was compared with 3 years earlier. Although most of the data obtained on reevaluation suggest remission, radiographic findings have not remitted. Long-term follow-up of parameters of HP disease activity do not always reveal consistent findings. This patient appears to be in a category of HP between the classic subacute and chronic stages.

Aged↗
PubMedDate not supplied

Immunotherapy update: mechanisms of action.

Allergen immunotherapy (IT) results in reduction of symptoms of allergic rhinitis and asthma. There still is not satisfactory evidence as to the best marker that explains clinical responses. IT inhibits the early and late nasal, bronchial, and cutaneous responses to allergen challenge. There are increases in antiallergen immunoglobulin G (IgG; 2- to 10-fold) and IgG4 (10- to 100-fold), a gradual decline in antiallergen IgE antibodies, and reduced numbers of nasal or bronchial mast cells, eosinophils, and CD4+ T-helper 2 (TH2) lymphocytes. Cytokine changes include reductions in serum interleukin (IL)-4 and in vitro lymphocyte-derived IL-4 as compared with a lack of increases in interferon gamma or IL-2. In a study in which skin biopsy specimens were obtained 24 hours after intradermal grass injection, the IT-treated patients had sharply increased numbers of macrophages which had messenger RNA for IL-12. This cytokine supports development of TH0 into TH1 CD4+ lymphocytes. Allergen immunotherapy results in a profound IgG and IgA antibody response with down-regulation of TH2 and possibly up-regulation of TH1 responses.

Asthma↗
PubMedDate not supplied

Therapy in the management of the rhinitis/asthma complex.

Allergic rhinitis is a risk factor for the development of asthma, and, conversely, asthma often is present in patients with rhinitis (17-25% in children and 20-50% in adults). Up to 80% of patients with asthma have allergic, nonallergic, or mixed rhinitis. Gastroesophageal reflux can be identified in 25-50% of patients with asthma and may be asymptomatic. Topical nasal corticosteroids typically reduce rhinitis symptoms more effectively than oral or topically administered histamine 1 antagonists but are similar in terms of ocular symptom reduction. The leukotriene D4 antagonist montelukast, as well as loratadine (29%), has been found to reduce nasal symptoms (27%) but the combination (33%) provided little additional benefit. Subcutaneous injections with a monoclonal anti-immunoglobulin E antibody for ragweed or birch allergic rhinitis have produced few anaphylactic reactions but when reactions occur, they appear 90-120 minutes after the injection. In the patients who received 300 mg of omalizumab every 3 or 4 weeks for ragweed allergic rhinitis, there were 23% fewer mean nasal symptoms than in placebo-treated subjects. In that study, antihistamines but not nasal corticosteroids were used during the study period. Overall, 70.7% of patients reported treatment as good or excellent compared with 40.8% in placebo-treated patients. The impact of omalizumab or other anti-immunoglobulin E therapies on rhinitis and asthma is being investigated. In patients experiencing acute, purulent, rhinosinusitis, treatment with a nasal corticosteroid helps relieve symptoms sooner than antibiotic and decongestant therapy alone. Treatment of rhinitis or rhinosinusitis and gastroesophageal reflux should be part of the management of patients with asthma.

Acetates↗