Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report.

Rhinitis is an umbrella term that encompasses many different subtypes, several of which still elude complete characterization. The concept of phenotyping, being the definition of disease subtypes on the basis of clinical presentation, has been well established in the last decade. Classification of rhinitis entities on the basis of phenotypes has facilitated their characterization and has helped practicing clinicians to efficiently approach rhinitis patients. Recently, the concept of endotypes, that is, the definition of disease subtypes on the basis of underlying pathophysiology, has emerged. Phenotypes/endotypes are dynamic, overlapping, and may evolve into one another, thus rendering clear-cut definitions difficult. Nevertheless, a phenotype-/endotype-based classification approach could lead toward the application of stratified and personalized medicine in the rhinitis field. In this PRACTALL document, rhinitis phenotypes and endotypes are described, and rhinitis diagnosis and management approaches focusing on those phenotypes/endotypes are presented and discussed. We emphasize the concept of control-based management, which transcends all rhinitis subtypes.

Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study.

A radiolabeled murine monoclonal antibody (T101) was used for imaging and therapy of six patients with cutaneous T cell lymphoma (CTCL). Radioimmunodetection was performed with a 5.6 to 13.1 mCi 131I-T101 preparation (9.6 to 10.5 mg). A therapeutic dose of 100.5 to 150.1 mCi 131I on 9.9 to 16.9 mg of antibody was administered to five patients, with subsequent retreatment following plasmapheresis in three patients at the time of disease progression. All patients responded to their initial therapy and two patients responded to retreatment. Regression of skin lesions and peripheral adenopathy was witnessed. All patients reported resolution of their chronic pruritus. The duration of response ranged from 3 weeks to 3 months. Acute toxicity included fevers, pruritus, and mild dyspnea in two instances. Myelosuppression was seen in patients receiving the 144.7 mCi, 145.0 mCi, and 150.1 mCi 131I-T101 doses. Radioimmunodiagnostic and therapy studies included gamma scintigraphy, plasma, urinary, and wholebody antibody clearances, and biodistribution determined from skin, bone marrow, and liver biopsies. Immunologic studies included immunoperoxidase staining of target tissues, immunofluorescent flow cytometric analysis on peripheral blood and bone marrow, assays for serum blocking factors, determination of a human antimouse antibody (HAMA) response, and quantitation of circulating T101 levels. These preliminary data suggest that 131I-T101 has therapeutic potential in CTCL and that myelosuppression will be the limiting toxicity.

Asbestos-induced injury to cultured human pulmonary epithelial-like cells: role of neutrophil elastase.

The mechanisms responsible for asbestos-induced pulmonary epithelial cell cytotoxicity, especially oxidant-independent mechanisms, are not established. We determined whether human polymorphonuclear leukocyte (PMN) proteases contribute to asbestos-induced damage to human pulmonary epithelial-like cells (PECs) assessed using an in vitro chromium-51 release assay. Serine antiproteases, phenylmethylsulfonyl fluoride and alpha 1-antitrypsin, each ameliorated PEC injury induced by amosite asbestos and PMNs. A role for a specific proteinase, human neutrophil elastase (HNE), is supported by the facts that (1) asbestos increased HNE release assessed by an enzyme-linked immunosorbent assay technique (1.7 +/- 0.5 vs. 2.8 +/- 0.5 micrograms/ml; P < .025), (2) purified HNE or porcine pancreatic elastase (PPE) each alone caused PEC detachment, (3) asbestos plus either HNE or PPE caused PEC lysis similar to that mediated by asbestos and PMNs, and (4) cationic agents released from PMNs were unlikely to be involved because polyanions did not ameliorate injury resulting from asbestos and PMNs. Compared to elastase, cathepsin G caused less PEC detachment and negligible augmentation in asbestos-induced PEC lysis. Asbestos increased the association of 125I-labeled elastase with PECs nearly 50-fold compared with PPE alone (14.4% vs. 0.3%, respectively; P < .01) and nearly 10-fold compared with another particle, opsonized zymosan. We conclude that PMN-derived proteases, especially elastase, may contribute to asbestos-induced lung damage by augmenting pulmonary epithelial cell injury.

Idiopathic anaphylaxis. A clinical summary of 175 patients.

One hundred seventy-five patients with idiopathic anaphylaxis, treated by the same team of physicians, were retrospectively evaluated. The diagnosis of idiopathic anaphylaxis was made only after a careful evaluation had failed to identify an allergen or underlying disease. Before our care of these patients, there were a total of 76 hospital admissions, including 21 intensive care unit admissions and 291 emergency department visits. Prophylactic treatment with maintenance antihistamines and prednisone was appropriate for frequent episodes, and short-term treatment was given for infrequent episodes. No fatalities were reported from idiopathic anaphylaxis in the 124 patients who were available for follow-up. With the appropriate treatment, remissions can be induced in a substantial number of patients. Significant reductions in the frequency of emergency department visits and hospitalizations have been shown, which, in turn, are accompanied by decreases in overall medical costs. In this disease, the period before treatment serves as a control period for comparison after therapy.

Natural history of asthma in patients requiring long-term systemic corticosteroids.

To study the natural history of corticosteroid-dependent asthma, we evaluated 40 randomly selected adult patients with severe asthma who were refractory to management with inhaled corticosteroids and bronchodilators and who required long-term prednisone therapy (mean duration, 6.2 +/- 5.1 years). During long-term observation, 13 patients (32.5%) significantly improved; ten (25%) of these tolerated discontinuation of long-term prednisone use and three (7.5%) had decreased prednisone requirements. Three patients (7.5%) had increased requirements for prednisone. Twenty-four patients (60%) had generally unchanged, long-term prednisone requirements; of note, eight of these had significant, but temporary intervals (mean, 3.2 years) when they could be managed without prednisone. Patients with mixed asthma were more likely to tolerate discontinuation of long-term prednisone; no other factors studied were predictive of the course of asthma. Although prior to our care many patients had a history of numerous emergency room visits and hospitalizations (some for life-threatening episodes of status asthmaticus), there were few emergency room visits and hospitalizations while under strict management by our service. Variations observed in the natural history of corticosteroid requirements in asthma must be considered in designing studies seeking to evaluate efficacy of new experimental therapies for asthma.

Identification of patients at risk for anaphylaxis due to streptokinase.

To identify patients at risk for immediate-type allergic reactions to streptokinase, we performed streptokinase skin tests on patients immediately before planned administration of intravenous streptokinase for treatment of acute myocardial infarction. Forty-five patients had negative skin tests and received streptokinase without allergic reaction. One patient had a positive skin test and was given urokinase instead, without incident. Positive skin tests were also present in a patient who had recently had an anaphylactic reaction to streptokinase, and in two physician volunteers who had been sensitized to streptokinase during initial determination of the optimal skin testing dose. Immunoassays for IgE to streptokinase were performed on serum samples from skin-tested patients and volunteers, and on 16 other patients who had not been skin tested but had previously received streptokinase without allergic reactions. The skin test was a sensitive and specific indicator of elevated levels of IgE to streptokinase. We propose that skin testing immediately before streptokinase administration is a practical approach for identifying patients at risk for immediate-type allergic reactions to streptokinase, and its use may possibly prevent anaphylaxis and death.

Potentially fatal asthma and syncope. A new variant of Munchausen's syndrome in sports medicine.

We report a case of Munchausen's syndrome in a 19-year-old female college athlete who presented with potentially fatal asthma and recurrent syncopal episodes. Failure to control her asthma with the appropriate medications and the lack of objective findings on both physical examination and diagnostic testing raised the possibility of factitious disease. Munchausen's syndrome, although not described with any frequency in asthmatic patients, should be considered in the differential diagnosis of those patients refractory to aggressive medical management.

Erythema multiforme and Stevens-Johnson syndrome. Descriptive and therapeutic controversy.

Diagnosis and particularly the management of erythema multiforme and Stevens-Johnson syndrome are controversial in medical textbooks and thus in individual cases. In these diseases, fatalities may result from various causes, including secondary infection or visceral organ damage to lung, liver, or kidneys. We present a series of 13 cases managed by one group of physicians which demonstrates the controversy in certain cases, and we review the controversy in the medical literature. Corticosteroid therapy used in this series was considered beneficial in every case by the managing physician and lifesaving in some cases. There were no fatalities in this series. Although the summation may be considered as our opinion only, the frequently suggested "controlled trial of corticosteroid therapy" can probably never be done for ethical reasons, and series such as this will have to establish the standard of therapy.

Occupational respiratory and dermatologic disease.

Many diseases caused by occupational exposures may have an allergic or immunopathogenetic basis. These include asthma, hypersensitivity pneumonitis, the pulmonary disease-anemia syndrome, allergic contact dermatitis, and contact urticaria. This article discusses concepts important to the understanding of occupational forms of these diseases and provides approaches to their diagnosis, treatment, and prevention.

Recent findings in asthma likely to impact patient care.

The management of asthma is becoming increasingly complex as more pharmacologic agents become available and we gain increased understanding of the pathogenetic processes of asthma and the risks for potentially irreversible airway remodeling that might be increased by suboptimal management and interactions with concomitant disease states such as gastroesophageal reflux. Although physicians now have greater responsibility to make use of this increasing knowledge to provide more effective management for their asthma patients, they also have a greater opportunity to increase the overall quality of life of patients under their care.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2016 revision

BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

Occupational asthma: a practical approach.

Although evaluation of possible occupational asthma may be complex, it can be pursued systematically by first assessing whether asthma is present, and then determining whether asthma is caused or triggered by the workplace or by alternative or confounding nonoccupational explanations. A detailed history is of great importance in raising suspicion of occupational asthma, but studies have shown that even detailed histories obtained by experienced specialists can lead to inaccurate conclusions about the presence or absence of occupational asthma. Consequently, objective measurements should be performed to establish the diagnosis of occupational asthma whenever possible. If the patient is still working in the workplace, work-related changes in spirometry or peak flow measurements can confirm the diagnosis. For occupational asthma from some airborne sensitizers, immediate-type skin testing or in vitro tests for specific IgE may establish sensitization. However, there is evidence that for some isocyanates, in vitro tests for specific IgG serum antibody levels correlate better with documented bronchospasm from isocyanate exposure, even though the IgG antibody is not thought to be pathogenic. Controlled, specific inhalation tests may be valuable, but they should be performed only under experienced medical supervision. Intervention should be focused on reducing or avoiding harmful workplace exposures so that permanent lung impairment and need for chronic medical treatment are avoided. Assessment of permanent impairment/disability from occupational asthma optimally should be determined 2 years after the removal from occupational exposure, when improvement has been shown to plateau and the patient will likely have reached maximal medical improvement.

Newer and alternative non-steroidal treatments for asthmatic inflammation.

Although most patients with asthma can be effectively managed with minimal toxicity using available treatments, some patients are relatively resistant to treatment or are at risk for adverse effects from treatment, such as high-dose systemic corticosteroids. In considering new or alternative therapeutic candidates for asthma treatment, those possessing anti-inflammatory properties are of greatest interest because inflammation is recognized as having central importance in the pathogenesis of persistent asthma. Of non-steroidal agents that have well-established positions in asthma treatment, nedocromil and cromolyn possess significant anti-inflammatory effects, and theophylline and beta agonists possess some anti-inflammatory effects of potential relevance to asthma. In addition, there are a number of newer or alternative therapies that have theorized or demonstrated anti-inflammatory effects in asthma, including leukotriene modifier agents, anti-IgE, gold, nebulized lidocaine, cyclosporine, intravenous immunoglobulin, methotrexate, hydroxychloroquine, dapsone, and troleandomycin. This review summarizes available data about these agents for asthma, focusing on their putative or proven mechanisms of action, evidence for clinical benefit, and their potential role as corticosteroid sparing agents, and principal toxicities. The review also discusses factors that confound assessment of the clinical benefit of agents in asthma, including variability in the natural history of asthma, heterogeneity of airway inflammation, and varying responses to treatment in different subsets of asthmatics.

Executive Summary of Joint Task Force Practice Parameters on Diagnosis and Management of Rhinitis.

Rhinitis is a significant cause of widespread morbidity, medical treatment costs, reduced work productivity and lost school days. Although sometimes mistakenly viewed as a trivial disease, symptoms of allergic and non-allergic rhinitis may significantly impact a patient's quality of life, by causing fatigue, headache, cognitive impairment and other systemic symptoms. In addition, many antihistamines commonly used for treatment can themselves cause performance impairment that may contribute to fatal automobile accidents, work place accidents, decreased work productivity and in children, impaired school performance. Appropriate management of rhinitis may be an important component in effective management of coexisting or complicating respiratory conditions, such as asthma, sinusitis, or chronic otitis media. Rhinitis may be caused by allergic, non-allergic, infectious, hormonal, occupational, and other factors. Defining the causes of rhinitis in an individual is important because different rhinitis syndromes may require different therapeutic approaches for optimal management, an important consideration as more treatment options become available. This Executive Summary reviews key points about diagnosis and management of rhinitis contained in the comprehensive document, Diagnosis and Management of Rhinitis: Complete Guidelines of Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, and Joint Task Force Algorithm and Annotations for Diagnosis and Management of Rhinitis. These documents represent a consensus opinion of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, a national panel co-sponsored by the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council on Allergy, Asthma and Immunology.

Extensive subcutaneous fibrosis in a patient treated with alum precipitated allergenic extract.

BACKGROUND: Alum-precipitated allergenic extract (Allpyral) used for immunotherapy has been associated with subcutaneous nodule formation at injection sites. OBJECTIVE: We describe a severe localized reaction at the site of Allpyral injections and evaluate possible mechanisms for this reaction. METHODS: Case report with cutaneous patch testing and CAT scan imaging. RESULTS: The patient developed extensive subcutaneous inflammation and fibrosis with overlying skin changes which appear to be permanent. CAT scan findings were corroborative and cutaneous patch testing to aluminium was positive. CONCLUSIONS: Alum-precipitated allergenic extract used for immunotherapy caused extensive subcutaneous fibrosis with overlying skin changes at the site of injections. The lesions are disfiguring and appear to be permanent. This may be due in part to a type IV hypersensitivity response to the aluminum component of Allpyral extract. A CAT scan was valuable in demonstrating structural changes associated with this lesion.

Induction of antigen-specific bronchial reactivity to trimellityl-human serum albumin by passive transfer of serum from humans to rhesus monkeys.

A rhesus monkey model was developed to demonstrate the pathogenetic role of IgE to chemical hapten-protein conjugates in causing human occupational asthma from reactive chemicals. Serum from a worker with trimellitic anhydride (TMA) asthma that contained high titers of IgE, IgG, IgM, and IgA to trimellityl-human serum albumin (TM-HSA) was aerosolized into the lungs of two monkeys to afford passive airway sensitization. After the monkeys were challenged with aerosolized TM-HSA, pulmonary functions demonstrated acute airway responses similar to that of Ascaris antigen-induced, IgE-mediated bronchospasm in Ascaris-sensitive monkeys. The monkeys had no airway reactivity when challenged with TM-HSA 1 week after the first positive TM-HSA response elicited with passive sensitization. Passive cutaneous reactivity to TM-HSA was also elicited by the donor serum, but heat-treated donor serum failed to confer cutaneous or bronchial reactivity. These results indicate that airway reactivity in this passive-transfer monkey model of TMA asthma is an antigen-specific response mediated by heat-labile serum factors, presumably IgE to TM-HSA, and does not occur by irritant mechanisms. This experimental model could become a valuable system for evaluating the role of IgE to hapten-protein conjugates in the immunopathogenesis of asthma caused by other reactive chemicals capable of acting as haptens. We postulate that immunologic and clinical features should be consistent with asthma caused by such reactive chemicals and mediated by such mechanisms.