Yes. Asthma in childhood, if neglected, can lead to serious, dis­abling lung disease in adult life. Unfortunately, the notion that an asthmatic child will outgrow the condition is not true. Asthma that is not diagnosed early and treated effectively can lead to physical retardation and personality problems that will handicap the child throughout life. Early diagnosis and treatment, not only in children but in adults as well, can prevent serious complications later on.

Evidence is increasing that various weather phenomena, including changes in barometric pressure, have a significant effect on human health. With regard to your particular problem, it is best to seek a physician’s advice and help in administering nasal decongestants when the weather changes, to minimize the effects of the changes.

Adrenalin is a brand name for epinephrine, an extract of the hormone secreted by the adrenal gland; it is used as a treatment in some allergy emergencies.

Sensitivity to soybean is an increasingly apparent problem. Most children outgrow this sensitivity. While they remain sensitive, though, soybean should be avoided in any form. Soybean-containing foods can be avoided by reading labels.

The chemical coating of many artificial fibers, rather than the fibers themselves, can provoke allergic reactions. Most of these reac­tions are caused by direct contact, which produces a form of contact dermatitis. The best approach is to wash new clothes repeatedly be­fore wearing them, to leach out the allergenic coating.

A lymphocyte is a white blood cell important in im­munity; of the two major types (both types have several subclasses), T lymphocytes are processed in the thymus and are involved in cell-mediated immunity, and В lymphocytes are derived from the bone marrow and are precursors of plasma cells, which produce antibody.

This is a special category of intrinsic asthma induced by the ingestion of aspirin. It may occur as a triad of asthma, nasal polyps, and increased eosinophils, associated with severe potentially fatal reactions to aspirin. Aspirin intolerance can also be associated with chronic urticaria (see Table 2.1). The cause of aspirin-induced asthma may involve arachidonic acid, since aspirin may inhibit its cyclooxygenase products (see Arachidonic Acid) and allow selective breaking down of arachidonic acid via the Iipooxy-genase pathway.

The measurement of serum IgE levels, first made possible by the discovery in 1967 of a patient with IgE myeloma, is of interest to physicians because elevations in serum IgE levels occur more fre­quently in allergic individuals. The reader should remember, though, that the total serum IgE measurement is not a specific diagnostic test for allergy. Subsequent purification of IgE, and the preparation of antibody specific for human IgE (anti-IgE), led to the development of labora­tory procedures for measuring total IgE and allergen-specific IgE. These new diagnostic methods supplement the traditional skin test, which gives only partially complete quantitative information about specific IgE antibody. Several methods, called radioimmunoassay methods, are now available for measuring total serum IgE. The competitive radioimmunosorbent test (RIST) is a competitive-binding assay in which IgE in the test sample competes with IgE that has been tagged with radio­active iodine. In this test, the IgE content of the serum is inversely proportional to the radioactivity bound by the anti-IgE. The absolute level of IgE is obtained by comparing it with a standard curve derived from a serum containing a known amount of IgE. The RIST method has limited sensitivity, however, primarily because of the variability among samples containing less than 100 nanograms of IgE per milliliter. In the noncompetitive RIST method, a sample of test serum is incubated with solid-phase anti-IgE in the absence of labeled IgE. The solid-phase anti-IgE is then washed and incubated with anti-IgE labeled with radioactive iodine, which, in turn, binds to the IgE on the solid phase. The radioactivity binds in proportion to the amount of IgE bound during the first incubation, and is directly proportional to the IgE content of the serum sample. Because of improvements in sensitivity and precision, this procedure is now the method of choice for measuring serum IgE. Of perhaps greater interest is the measurement of specific IgE antibody using the radioallergosorbent test (RAST). This test is similar to the noncompetitive RIST, except that allergen, rather than anti-IgE, is bound to the solid-phase matrix. After incubation of solid-phase allergen (allergosorbent) with serum, the matrix is washed and then incubated with labeled anti-IgE. The amount of radioactivity that binds to the allergosorbent is directly proportional to the allergen-specific IgE antibody in the serum sample. The result is expressed as "antibody titer" relative to that of a designated reference serum. Re­cent modifications of the RAST method permit quantification of abso­lute amounts of IgE antibody specific for several purified allergens. But interpretation of the results is still uncertain, especially when the values obtained are not highly elevated because of a fairly wide over­lap of nonallergic and allergic individuals in the lower range of values. RAST, therefore, is still mainly a semiquantitative, diagnostic screen­ing procedure. The more sensitive skin test still has greater diagnostic significance, particularly when the test results are borderline. Two types of cell must be considered in discussing allergic reac­tions: mast cells and basophil leukocytes. Mast cells, located near the small blood vessels, are found in connective tissue throughout the body. This is clearly a convenient location for cells associated with the functioning of the blood vessels. We do not yet know exactly where mast cells originate, although evidence recently uncovered sug­gests that some mast cells come from the bone marrow, while others are derived from lymphocytes. If we are to understand the role of mast cells in allergic reactions, we must learn more about their origin. One thing we do know is that mast cells are long-lived, though just how long is uncertain. Basophil leukocytes are the progeny of the same stem cells (located in the bone marrow) that produce such other types of white blood cell as neutrophils and eosinophils. As basophils mature (perhaps under the influence of T cells), they leave the bone marrow and enter the blood, where they appear to remain for only one or two days. Then the basophils leave the blood and enter the extravascular spaces, most often at sites of allergic reactions or where parasites have lodged. Many apparently exit the body by moving into the respiratory or the gastrointestinal tract. Both mast cells and basophils have an abundance of dense granules in their cytoplasm. These cells can be identified in the light microscope only when the granules are specially stained. Each granule is sur­rounded by a membrane that effectively insulates the contents of the granule from the rest of the cell. Granules contain a high concentra­tion of histamine, which is held there because it is bound to the anti­coagulant heparin and to a protein matrix. IgE molecules have a rather high affinity for the surface of mast cells and basophils. This affinity is due to the presence of molecules (receptors) on the cell’s surface, which recognize certain unique structural features of the constant region of the IgE molecule. In both normal and allergic people, IgE molecules are bound to mast cells and basophils. In allergic individuals, however, some of these molecules are antibody molecules specific to one or more allergens. Thus the cells in an allergic person are said to be sensitized; when allergen reaches them, they respond characteristically. An allergic reaction is said to begin when an allergen molecule interacts with two specific IgE antibody molecules on the surface of a sensitized mast cell or a basophil. Exactly how the bridging of two antibody molecules by an allergen induces the cell to respond is still not known. What is known is that the cell can be triggered in the absence of either antigen or antibody. All that must be done is to bridge two of the surface receptor molecules; this is true even when IgE is not present. The triggering process has recently been accom­plished with antibody specific for the mast cell receptor itself. A number of biochemical changes have been detected in mast cells and basophils immediately after they are triggered by the interaction of allergen with IgE antibody. The change most thoroughly studied oc­curs in the cyclic nucleotide system, in which the cyclic adenosine monophosphate (cAMP) concentration falls, while that of the cyclic guanosine monophosphate (cGMP) rises. A fall in the cAMP-cGMP
ratio favors the entry of calcium ions into the cell. In a process called degranulation, an increase in the concentration of intracellular cal­cium leads immediately to secretion of the contents of the granule from the cell into the surrounding body fluid. This process, however, does not result in destruction of the cell. Degranulation operates thus: triggering of the cell causes the cell’s surface membrane to move up against the membrane surrounding the granules (which are just be­neath the surface). The two membranes quickly fuse, and an opening forms at the site. As the opening enlarges, the interior of the granule is exposed to the fluid outside the cell. The contents of the granule are now effectively outside the cell. Note that the membrane of the cell remains intact, with the membrane of the granule now incorporated in it. At this point, the histamine quickly dissolves out of the granule and diffuses into the surrounding tissue. There it acts directly on ad­jacent small blood vessels, making them leaky to the fluid of the blood. This, in turn, leads to edema, or swelling of the tissues, and acts on the nerve endings, causing an itching sensation. When this happens in the skin, it is called hives. The process is the same that occurs when a doctor performs a skin test on an allergic patient, using a dilute solution of allergenic extract. A local reaction appears within a few minutes, then fades within
twenty to thirty minutes. This is an immediate hypersensitivity reaction. Histamine also acts on smooth, or nonskeletal, muscle —for exam­ple, on the tiny muscles in the bronchial tree—causing them to con­tract and making the air passages in the lungs narrower. This condition is called bronchospasm, or asthma. Histamine can also act on mucous glands, causing the secretion of thin, watery mucus—a condition that usually occurs in the noses of allergic people during the hay fever season. Histamine is only one of the "mediators" of anaphylaxis released when mast cells or basophils are triggered by the interaction of aller­gens and IgE. Other substances that are released, for which there is evidence of a role in allergic inflammation, are: 1. SRS-A, a slow-reaction substance of anaphylaxis, known as leukotriene, that was recently identified as a product of arachidonic acid metabolism. It acts on smooth muscles. 2. ECF-A, an eosinophil chemotactic factor of anaphylaxis that consists of several different short peptide chains. It acts as an attrac-tant to eosinophils. 3. PAF, a factor recently identified as an acetyl glycerylether compound. It activates platelets, small blood corpuscles that con­tain additional mediators, and anticoagulants.
Other mediators (see Figure 5.7) may be involved in allergic re­actions, but their role is unclear. The explosive release of mediators from mast cells and basophils depends on where the reaction occurs. Most allergic reactions occur in the eyes, nose and throat, lungs, intestines, or skin. In a condition known as anaphylactic shock, the entire body is affected. The intensity of an allergic reaction depends somewhat on the concentration of mediators that reach their targets in the tissues and on how long-acting they are. Powerful inactivators of each mediator occur in the blood and the tissues, limiting this concentration and duration. To a certain degree, the intensity and duration of a particular allergic reaction depend on the number of mast cells and basophils in the tissues at the time of the allergen-IgE antibody interaction. Their number is not constant in the target tissues. During the ragweed-pollen season, for example, mast cells and basophils appear in greater numbers in the membrane that lines the nasal cavity, as well as in the abundant mucus typical of hay fever. When these cells are con­centrated in the nose, much more mediator exists to be released after pollen is inhaled. This condition may have something to do with the fact that symptoms of ragweed hay fever can continue for days or weeks after the actual ragweed pollen season has ended. We do not know exactly what causes the influx of these cells during the pollen season, or what accounts for their disappearance after the season. It will not be surprising, though, if it turns out that T cells have some­thing to do with the influx of mast cells and basophils.

Aside from the recognized fact that perfume and smoke are irri­tants, little is known about what causes respiratory difficulties or the blisters. Until researchers discover an effective means of desensitizing a patient against the effect of such agents, the best advice is to stay away from them.