Immunoglobulin E- (IgE) and non-IgE-mediated reactions in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS).

AEDS is a chronic, relapsing, highly pruritic inflammatory skin disease that commonly begins in childhood. Two forms of this disorder exist, i.e. an allergic (extrinsic) form and a nonallergic (intrinsic) form. There are clear genetic, humoral and cellular differences between the allergic and nonallergic forms of AEDS. The allergic variants express local IgE production in affected tissue and both allergic and nonallergic triggers play a major role in the expression of disease. The role of allergens is very important in the immunopathogenesis of AEDS. Nonimmunological triggers play a secondary modulatory role often hampering treatment effort and optimal response to therapeutic efforts.

Indoor pollution and its impact on respiratory health.

LEARNING OBJECTIVES: This overview discusses the respiratory complications of indoor air pollution, emphasizing the most common pollutants that individuals are likely to encounter outside the workplace. DATA SOURCES: Data were obtained from a review of the recent literature. STUDY SELECTION: The expert opinion of the author was used to select and synthesize relevant data on this multifaceted subject. RESULTS: There have been a number of studies documenting an association between exposure to indoor allergens and development of both sensitization and asthma in children. In addition to classic allergens, chemical indoor air pollution may also exert an adverse effect on both the upper and lower respiratory tract by a variety of nonimmunologic, irritative mechanisms. CONCLUSIONS: Our understanding of the adverse effects of indoor air pollution on health and comfort has broadened in recent years. It has supplied a credible framework for developing and implementing a variety of control strategies.

Reactive airways dysfunction syndrome (RADS): guidelines for diagnosis and treatment and insight into likely prognosis.

Reactive airways dysfunction syndrome (RADS) is defined as the sudden onset of asthma following a high level exposure to a corrosive gas, vapor, or fume. This variant of occupational asthma continues to generate controversy regarding the criteria for its diagnosis. There is also some disagreement as to the likely prognosis with this disorder. Currently, the diagnosis requires the assumption of normal premorbid pulmonary physiology and absence of bronchial hyperreactivity. Criteria for the diagnosis of RADS are discussed with a proposal for both major and minor criteria to increase the confidence of an accurate diagnosis. The pathology of RADS involves a primarily lymphocytic inflammatory response with some evidence of subepithelial thickening and fibrosis. Most patients with this condition who survive the short-term exposure to a toxicant recover completely without significant clinical or physiologic sequelae. The issue of low-level RADs remains controversial and problematic as a tenable diagnosis, and will require further careful investigation to evaluate the premise that chronic, low-level toxicants are capable of leading to such a condition. More likely, most of the cases which have been reported represent preexisting asthma and/or expressions of an atopic predisposition.

Reactive airways dysfunction syndrome (RADS): fact or fantasy?

Most evidence suggests that RADS is a distinct syndrome and not simply an exacerbation of pre-existing hyperresponsiveness. There is no doubt that much remains to be explained regarding pathogenesis. On the other hand, I urge caution about the claims of "low-level RADS". Here the data are much more anecdotal and leave much to be desired.

Sick building syndrome--a wolf in sheep's clothing.

OBJECTIVE: Reading this article will acquaint the reader with possible outcomes associated with the diagnosis of "sick building syndrome." The definition, epidemiology, and precipitating events of this symptom complex are distinguished from other defined building-related illnesses. DATA SOURCE: The author's experience with many patients presenting with this diagnostic label and selected studies on indoor pollution and "sick building syndrome" are carefully reviewed. STUDY SELECTION: Pertinent scientific investigations on "sick building syndrome" and previously published reviews on this and related subjects that met the educational objectives were critically reviewed. RESULTS: "Sick building syndrome" is a pseudodiagnosis composed of nonspecific, transient symptoms without proven biologic markers. Its application in the clinical setting invites frequent subsequent linkage to other similar vague diagnoses associated with chronic debility and lack of therapeutic intervention. CONCLUSION: The reader is encouraged to avoid the use of this term in favor of a simpler, descriptive diagnosis (e.g., transient office-related annoyance and/or irritation) or if this seems inadequate, adoption of the diagnostic label of "idiopathic building intolerance."

Seasonal variation in bronchial hyperreactivity (BHR) in allergic patients.

As summarized in Table 1, the literature consistently supports the hypothesis that allergic asthmatic patients have seasonal BHR changes that parallel allergen exposure. These seasonal changes appear to be preventable by treatment with corticosteroids (systemic, inhaled, or nasal), disodium cromoglycate, and immunotherapy. Studies have almost exclusively focused on pollens, though similar limited data exist for dust mites. Though the dust mite is a perennial allergen, mite levels are well known to fluctuate with seasonal temperature and humidity trends (44-46), and therefore, seasonal BHR variation in mite-sensitive asthmatic patients is not surprising. Allergenic mold species have not been studied in this regard. In allergic rhinitis patients, the data are less consistent (see Table 2). However, the studies that failed to identify a seasonal BHR difference were either small or had other design limitations. The seasonal changes identified by the larger analyses were similar to those identified for asthmatic patients. Thus, although confirmatory studies would be helpful, it seems likely that in the absence of clinical asthma, allergic rhinitis patients with baseline BHR have allergen-related seasonal changes in BHR. The BHR effects of seasonal changes in air pollution and viral URIs are not known, since they have not yet been directly studied. However, interesting recent reports have identified possible synergistic effects of air pollution exposure on BHR and allergic responses. Similarly, the availability of new viral identification techniques has resulted in the discovery that viral infection may be more prevalent during clinical asthma exacerbation than previously realized. Therefore, air pollution and viral infections may well influence BHR seasonally, and (along with allergens) may contribute to seasonal asthma morbidity and mortality peaks. The mechanism(s) underlying seasonal BHR changes is (are) not known. One plausible possibility with regard to allergen-driven BHR changes involves a type I hypersensitivity late-phase reaction. Characterized by recruitment of eosinophils, lymphocytes, and other cells that are central components of allergic inflammation and are not normally found in the lower airways, this reversible inflammatory process could in turn act, presumably via chemical mediators, on the airway smooth muscle. This may cause bronchoconstriction, but may also increase responsiveness to bronchoconstrictive stimuli independent of bronchoconstriction. This explanation for seasonal BHR changes is supported by findings of blood eosinophil (31,47) and BAL eosinophilic cationic protein (31) level changes that parallel BHR. Prevention of seasonal BHR changes using anti-inflammatory medications (32,33,35) also supports this hypothesis (30) however, and the complex potential interactions between infectious agents and air pollutants on seasonal BHR changes have yet to be studied directly. Therefore, although BHR indeed may predictably vary season to season in allergic individuals, additional investigation is needed to better characterize the reasons for this phenomenon. Further insight in this area may help address the reasons why there are often seasonal epidemics in asthma morbidity and mortality.

Occupational asthma and related respiratory disorders.

Occupational rhinitis is a common but generally underreported entity. Although it may occur alone, it is frequently associated with occupational asthma. Occupational asthma may have one of several presentations that are difficult to distinguish from non-work conditions. The respiratory tract acts as the final common pathway for all inhaled environmental pollutants, whether encountered in the home or at work. More than 200 chemicals have been incriminated as a cause of work-related asthma. It is said that about 2% of the 10 million Americans who have asthma acquired it as a result of some chemical irritant or immunogen in their work environment. A number of predisposing factors facilitate the development of work-related asthma. These include industrial conditions, climatic factors, atopic predisposition, smoking, recreational drug use, viral infection, nonspecific bronchial hyperreactivity, and a variety of miscellaneous factors. Pathogenetically, occupational asthma may be immunologic or nonimmunologic in nature. The immunologic variants involve sensitization to a variety of large-molecular-weight constituents. The major nonimmune variant is referred to as inflammatory bronchoconstriction or reactive airways dysfunction syndrome (RADS). There are well-defined criteria for the diagnosis of immunologic and nonimmunologic asthma. The several clinical variations of occupational asthma can be difficult to distinguish from nonindustrial disorders. The most common presentation in practice involves the worker with preexistent asthma who has been adversely affected by work exposures. Occasionally these industrial exposures precipitate permanent impairment. It is clear, however, that occupational asthma is not a single, simple, or homogeneous entity, even when a single specific causal factor can be identified in the workplace. Therefore the physician must be aware of the patient's entire medical history and the precise occupational exposures and must have convincing physiologic evidence that demonstrates a cause-and-effect relationship before making a definitive diagnosis of work-related asthma. Once the diagnosis is established, the worker should be removed from the work-place. If the diagnosis is made in a timely fashion, the patient should experience a significant improvement. The major factor in determining a poor prognosis in occupational asthma is the duration of exposure before the diagnosis is established. Prevention of the disorder is the best therapeutic intervention.

A model for faculty practice teaching clinics developed at the Oregon Health Sciences University.

In 1988 the Oregon Health Sciences University established its first faculty practice teaching clinic wherein physicians in training were incorporated into a faculty private practice clinic; this pilot project proved very successful and has been subsequently adopted as the model for essentially all outpatient clinics (both medical and surgery) in the university system. The model encourages efficiency, overhead control, and appropriate staffing; it also compensates faculty members for their additional time spent teaching. The authors conclude this model may help other academic training centers adapt to the changing demands of medical education.

Formaldehyde: an analysis of its respiratory, cutaneous, and immunologic effects.

Formaldehyde is truly ubiquitous in our ecology and continuing important commercial applications. Most of us have daily contact with this chemical. The most significant outdoor source of this chemical is gasoline and diesel fuel combustion. The primary indoor source is combustion of tobacco products. Formaldehyde is associated with a disagreeable odor that can produce "annoyance" symptoms and at higher concentrations can be a transient and completely reversible irritant to the eyes and mucous membranes of the respiratory tract. It is so soluble and rapidly metabolized that it rarely reaches the lower respiratory tract to inflict damage. The exception is in cigarette smokers who actively inhale. Formaldehyde may on rare occasions induce bronchial asthma at relatively high exposure doses. There are no conclusive studies that prove the development of de novo IgE-mediated respiratory tract symptoms secondary to inhalation of formaldehyde vapors. The approach to formaldehyde-induced symptoms should be one of careful documentation of objective physiologic changes.

Dietary amino acid-induced systemic lupus erythematosus.

The effects of dietary manipulations on autoimmune disease are understood poorly. In this article, we detail our experience with a human subject who developed autoimmune hemolytic anemia while participating in a research study that required the ingestion of alfalfa seeds. Subsequent experimental studies in primates ingesting alfalfa sprout seeds and L-canavanine (a prominent amino acid constituent of alfalfa) is presented. The results of these studies indicate a potential toxic and immunoregulatory role of L-canavanine in the induction of a systemic lupus-like disease in primates.

Sjogren's syndrome: a rheumatic disorder with prominent respiratory manifestations.

Sjogren's syndrome is an autoimmune condition with extraordinary and unique involvement in the eyes and respiratory tract. These patients frequently present or are referred to an allergist for evaluation. Recognition of the syndrome is critical for effective management.

Potential adverse health effects of wood smoke.

The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo[a]pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal.