Asthma in the elderly: diagnosis and management.

The National Asthma Education and Prevention Program's "Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma" apply to all ages. This review discusses additional specific points for elderly patients. These patients are very heterogeneous. Their asthma can have begun at any time and can vary greatly in severity. It is frequently associated not only with any of the diseases that affect older persons but also with comorbid lung diseases. Many patients have irreversible airway obstruction, which is due to severe airway remodeling, chronic obstructive pulmonary disease, or bronchiectasis. Diagnosis should include chest radiography and computed tomographic scanning to diagnose other lung diseases if FEV1 remains low after treatment. Asthma pathogenesis includes not only IgE-mediated allergy but also innate immune inflammation from endotoxin and trypsin-like proteases, and therefore evaluation and control of environmental exposures is an important part of management. Pharmacologic treatment, too, is adjusted to achieve and maintain control and is basically the same for all ages, except that elderly patients have reduced response to bronchodilators and increased side effects from beta adrenergic agonists and glucocorticoids. Many elderly patients have difficulty inhaling aerosols, and therefore nebulizers might be a better delivery system. Oral medications have the benefit of greater ease of administration and greater efficacy on the peripheral airways. Leukotriene antagonists and low-dose theophylline are often helpful additives to aerosol glucocorticoids. Oral glucocorticoids might be indicated for severe asthma.

Environmental and occupational allergies.

Airborne allergens are the major cause of allergic rhinitis and asthma. Daily exposure comes from indoor sources, chiefly at home but occasionally at schools or offices. Seasonal exposure to outdoor allergens, pollens, and molds is another important source. Exposure to unusual substances at work causes occupational asthma, accounting for about 5% of asthma in adults. Indoor and outdoor air pollutants trigger airway inflammation and increase the severity of asthma. Diesel exhaust particles increase the production of IgE antibodies. Identification and reduction of exposure to allergens is a very important part of the management of respiratory allergic diseases. The first section of this chapter discusses domestic allergens, arthropods (mites and cockroaches), molds, and mammals (pets and mice). Indoor humidity and water damage are important factors in the production of mite and mold allergens, and discarded human food items are important sources of proliferation of cockroaches and mice. Means of identifying and reducing exposure are presented. The second section discusses outdoor allergens: pollens and molds. The particular plants or molds and the amount of exposure to these allergens is determined by the local climate, and local pollen and mold counts are available to determine the time and amount of exposure. Climate change is already having an important effect on the distribution and amount of outdoor allergens. The third section discusses indoor and outdoor air pollution and methods that individuals can take to reduce indoor pollution in addition to eliminating cigarette smoking. The fourth section discusses the diagnosis and management of occupational asthma.

Inflammatory effect of environmental proteases on airway mucosa.

Proteases--both endogenous proteases from the coagulation cascade, mast cells, and respiratory epithelial trypsin, and exogenous proteases from parasites, insects, mites, molds, pollens, and other aeroallergens--stimulate a tissue response that includes attraction and activation of eosinophils and neutrophils, degranulation of eosinophils and mast cells, increased response of afferent neurons, smooth muscle contraction, angiogenesis, fibrosis, and production of immunoglobulin E. This response to exogenous proteases can be considered a form of innate immunity directed against multicellular organisms. The response of the airways to environmental proteases very closely resembles the response to airborne allergens. Although clinical research in this area is just beginning, the response to environmental proteases appears to be important in the pathogenesis of rhinitis and asthma developing from damp, water-damaged buildings, and intrinsic asthma with its associated rhinosinusitis and polyps.

The natural history of asthma.

Asthma begins most often in infants as wheezing with respiratory infections. If these episodes are mild and infrequent, asthma does not usually persist into the school years. However, if they are more frequent and severe, the asthma is likely to persist. After infancy, incidence falls and continues at about 100/100,000 for the rest of the lifespan. Allergic asthma develops most often in the second decade of life and frequently persists into adult years, but young patients with allergic asthma often enjoy a transient or even a permanent remission. More severe disease and continued allergen exposure cause persistence. Some patients with occupational asthma continue to have asthma long after exposure ceases. Asthma beginning after the fourth decade is usually intrinsic and may include the aspirin triad. Its severity tends to increase with time. Many middle-aged and elderly adults have a persistent decline in lung function that is retarded but not completely prevented by aerosol glucocorticoids. This loss of lung function is often the result of coexisting lung diseases, particularly bronchiectasis and COPD. Patients with asthma have the same overall rate and age of death as the general population, but are more likely to die of lung diseases, including cancer.

The role of protease activation of inflammation in allergic respiratory diseases.

Extracellular endogenous proteases, as well as exogenous proteases from mites and molds, react with cell-surface receptors in the airways to generate leukocyte infiltration and to amplify the response to allergens. Stimulation leads to increased intracellular Ca ++ and gene transcription. The most thoroughly investigated receptors, protease-activated receptors (PARs), are 7-transmembrane proteins coupled to G proteins. PARs are widely distributed on the cells of the airways, where they contribute to the inflammation characteristic of allergic diseases. PAR stimulation of epithelial cells opens tight junctions, causes desquamation, and produces cytokines, chemokines, and growth factors. They degranulate eosinophils and mast cells. Proteases contract bronchial smooth muscle and cause it to proliferate. PARs also promote maturation, proliferation, and collagen production of fibroblast precursors and mature fibroblasts. PAR-2, apparently the most important of the 4 PARs that have been characterized, is increased on the epithelium of patients with asthma. Trypsin, a product of injured epithelial cells, and mast cell tryptase are potent activators of PAR-2. Mast cell chymase activates PAR-1. Proteases from mites and molds appear to act through similar receptors. They amplify IgE production to allergens, degranulate eosinophils, and can generate inflammation, even in the absence of IgE. Proteases produced by Aspergillus species to support its growth are presumably responsible for the exuberant IgE, IgG, and granulomatous response of allergic bronchopulmonary aspergillosis. Similar proteases from molds germinating on the respiratory mucosa have been recently been implicated in the pathogenesis of chronic hyperplastic rhinitis and polyps and, by extension, of intrinsic asthma. Finally, proteases from mites and fungi growing in damp, water-damaged buildings might be the basis for the increased prevalence in these buildings of rhinitis, asthma, and other respiratory diseases. Future research promises to promote our understanding of the pathogenesis of allergic respiratory diseases and point the way to new therapies.

Management of occupational allergy to natural rubber latex in a medical center: the importance of quantitative latex allergen measurement and objective follow-up.

When our employees began coming to the Occupational Health Service, Dermatology, and Allergy Clinics with symptoms of allergy to rubber gloves 12 years ago, the Mayo Clinic initiated 3 responses. (1) The Allergic Disease Research Laboratory adapted well-established technology to measure both the IgE antibody specific to natural rubber allergens, and by use of this IgE antibody, the allergens in rubber products and in the air of the workplace. (2) The Division of Allergic Diseases and Internal Medicine reviewed the prevalence and severity of the problem. (3) The Clinical Practice Committee appointed a multidisciplinary task force to implement measures to reduce exposure. The 3 sections of this article describe the Mayo Clinic's experience of successful control of this occupational health problem. Use of only gloves with low or undetectable allergen content greatly reduced the concentration of allergen in the work site, reduced the number of new cases of occupational allergy to rubber, and allowed individuals with latex allergy to work at their usual jobs.