Knowing the various conditions that exacerbate asthma is imperative for effective treatment of asthmatic patients.
Remarkable strides have been made in recent years in our understanding of the pathophysiology of asthma with the discovery of a number of cytokines, such as interleukin-5, that greatly exacerbate asthmatic disease by attracting inflammatory cells into the lungs.1 The genes that regulate bronchial hyperresponsiveness and immunoglobulin E (IgE) levels have now been located on chromosome 5. 2 Of even more interest to caregivers of asthmatic patients are the numerous clinical trials now in progress that employ this biotechnology for treatment. At the recent meeting of the joint American Lung Association/American Thoracic Society 1999 International Conference in San Diego, studies were presented on the use of monoclonal antibodies to IgE and to cell surface adhesion receptors to prevent pulmonary inflammation and airway reactivity. The recent introduction of anti-leukotrienes provides a whole new class of drugs that now may be used to treat asthma.
Despite these exciting advances in understanding the mechanisms and treatment of asthma, both the incidence of and deaths from asthma continue to increase in the United States. According to recent Centers for Disease Control reports, the number of persons with asthma by self-report has more than doubled from 1980 to 1994. 3 The greatest increase was seen in children under 4 years where there was an almost fourfold rise. The number of reported deaths due to asthma has tripled from 1978 to 1995 with the greatest death rates occurring in African-American patients.
There has been much discussion as to why the incidence and severity of asthma as well as other allergic diseases have increased around the world despite the scientific progress in fighting the disease. It has been speculated that the Westernization of the lifestyles of many cultures has resulted in more time being spent indoors. 4 This results in greater exposure to indoor allergens such as dust mites, molds, cockroaches, and pet danders. It is sensitization to those perennial allergens, rather than seasonal pollen allergens, that appears to be most associated with the increased incidence of asthma. The lack of seasonal variation makes perennial allergic asthma more difficult to diagnose as the patient has the same symptoms year-round. This problem may be compounded by central heating and air conditioning in homes and offices in which the patient is constantly immersed in the same recirculated air containing potential allergens.
Other factors that have also been suggested as increasing allergic asthma include the decrease in breast-feeding by mothers who must return to work soon after the birth of their child, particularly those in lower economic classes.5 Exposure to foreign proteins such as those in cow milk in the diet may result in food allergies that later increase the likelihood of developing allergies to aeroallergens such as dust mites. Air pollution has also been implicated as changing the severity of asthma by augmenting the inflammation in the lungs, as will be discussed later. It has also been speculated that the overall decrease in childhood infections due to better sanitation and immunization programs has resulted in a shift in T helper lymphocyte populations that makes children more susceptible to allergic disease, although we have no definitive evidence that this occurs.4
In this article I will discuss some of the seasonal and environmental factors that contribute to the increase in the prevalence and severity of asthma. My goal is to provide a better understanding of conditions or agents that exacerbate asthma to assist the health care worker in recognizing these factors when treating asthmatic patients.
I was initially requested to confine my remarks to seasonal effects on asthma. This is challenging to a physician living in Southern California where there is little seasonal variation throughout the year and, indeed, little weather to speak of when compared to other parts of the country. I have broadened my discussion to include other environmental factors as it does appear that exposure to the perennial factors is responsible for the increase in incidence and possibly the increase in mortality of asthma today.
Pollens from trees, grasses, and weeds are the cause of allergic rhinitis and asthma most recognized by the general public and most physicians. This recognition is due primarily to the strong temporal correlation between seasonal occurrence of pollens in the environment and allergic symptoms. The plants most likely to cause symptoms are those that are wind-pollinated because of the large quantities of pollen grain released and their small size that allows them to enter the upper and lower airways. Plants dependent on insects for distribution of pollen grains, such as colorful flowers, have heavier pollen grains that stick to the legs of bees and other insects and are less likely to cause allergic disease.
In most parts of the United States tree pollens are most prevalent in the months of April and May. Grass pollens are present from May through August, often peaking in June. Pollens from weeds peak in the fall, and are usually highest in late August and September. The pollen count, which is often reported by local news agencies, is based on the number of pollen grains per cubic meter of air as calculated by various collecting devices; most patients develop symptoms when the pollen count reaches 25-50 grains/m3. Obviously, pollen exposure varies greatly over the United States with regard to plant species, months of the year that the pollen count is the greatest, and the concentration of pollen grains in the air. The reader can find this information for their local area by referring to a standard allergy textbook as listed at the end of this article6,7 or by contacting a local allergy or asthma society.
- Tree pollens: Deciduous trees are more likely than conifers to cause allergic disease. Pollination usually occurs in the spring and may result in very high pollen counts. Birch is the most important cause of pollen allergy in North America and northern Europe and Asia. Birch may cross-react with hazelnut and alder as well as various foods including apple, peach, walnut, pear, almond, kiwi, cashew, tomato, and carrot. Oak and elm also may produce allergic responses in some patients whereas beech and chestnut are not likely to cause allergies. The olive tree is a major pollen allergen in Mediterranean countries, and we have found a large number of patients in Southern California with strong allergic reactions to olive trees, particularly in our affiliated county hospital, Olive View-UCLA Medical Center, Sylmar, in a more agricultural area north of downtown Los Angeles.
Pine trees may produce vast quantities of pollen but usually are not responsible for causing allergic reactions. Among the conifers, mountain cedar and cypresses may produce allergies in some patients.
- Grass pollens: Grasses are the most common cause of pollen allergy worldwide, and there is extensive antigenic cross-reactivity between species (timothy, rye, orchard, blue, sweet vernal). This cross-reactivity makes it easier to do allergy skin testing for grasses, as patients that react to one grass species are likely to react to other grass species as well. However, Bermudagrass and johnsongrass belong to a different family that does not cross-react to the above-mentioned species, and must be tested for separately.
Weather conditions greatly affect the distribution of grass pollen grains, with counts being low on cold, rainy days and high on hot, dry days. Wind is also a very important factor for distributing pollens, and can spread them over several miles. In Southern California the occurrence of the warm Santa Ana winds that originate over desert areas correlates with an increase in asthmatic attacks. Grass pollen counts are usually highest in earlier morning and late afternoon as the pollens tend to be carried into the higher atmosphere during the middle of the day.
- Weed pollen: Ragweed holds the dubious distinction as being the most recognized plant species associated with allergies. There are six cross-reacting species of ragweed distributed across North America, but they are rare in Europe. Ragweed tends to flourish in land areas altered by industrial or agricultural activities such as along roadways, at construction sites, and in grain fields. Pollen from ragweed is usually highest in August and September, occurring later in Southern states. Other weeds may also act as important aeroallergens but the species vary over the United States. The distribution of weed pollen grains is affected by the same factors that influence the distribution of grass pollens.
Molds or fungi release spores into the air for reproduction that are usually smaller (2-5 microns) than pollen grain (15-50 microns), making it easier for fungal spores to enter the lower airways. Molds require a high relative humidity, making them much more prevalent in wet climates or following the rainy season of dryer climates. The El Ni¤o weather conditions experienced in 1997-1998 have been blamed for an increased incidence of mold allergy. Indoor mold growth is associated with areas of the house where moisture is present, such as bathrooms, leaky roofs, humidifiers, and potted plants. Warmer temperatures also favor mold growth.
Cladosporium and Alternaria are the mold species often found in decaying plant materials, and spore counts are highest in late summer. Spores from the fungi Aspergillus and Penicillium may occur year-round, and are often found indoors because of potted plants and humidifiers. It should be noted that patients with allergies to Penicillium are not more likely to be allergic to the drug penicillin. Aspergillus spores may provoke a severe allergic response in some patients, resulting in allergic bronchopulmonary aspergillosis (ABPA), requiring intensive therapy with steroids. Cystic fibrosis patients are particularly susceptible to ABPA. Occupational exposure and subsequent sensitization to fungi may occur in individuals involved in the production of bread, cheese, beer, and wine.
DUST MITE ALLERGY
Dust mites were first reported to be present in house dust in 1964, and the major dust mite antigen, Der p1, in the feces of dust mites was purified in 1986. Dust mites feed primarily on human skin dander, making mattresses and pillows an ideal site for mite growth. Other sites of mite infestation include carpets, upholstered furniture, and stuffed toys. Mite growth is also favored by warmer temperatures (17-32øC) and high humidity (55-80percent relative humidity). Mites also do not grow at high altitudes, above 3,000 meters elevation.
There are two major species of dust mite in the United States, Dermatophagoides pteronyssinus and Dermatophagoides farinae, that strongly cross-react. Seasonal changes can affect the numbers of mites present, with the lowest numbers occurring in temperate climates during the winter because of cold temperatures and indoor drying of air. In warmer climates, more mites are present during the rainy season.
As the mite fecal particles are large, most human exposure occurs at night when the patient is in bed and in close contact with pillows and mattresses. Therefore, control measures include completely covering the pillows and mattresses with fabrics that exclude mite penetration. Removal of carpeting and stuffed animals may be required in more severe cases.
A major study was reported in the New England Journal of Medicine in 1997, finding a high correlation between cockroach allergy and asthma-related health problems in inner-city children. Of the 476 children with asthma that were tested, 37percent had positive skin tests for cockroach. When samples of house dust from these children’s bedrooms were tested, more than 50percent had high levels of cockroach antigen. The children with cockroach allergy had higher rates of hospitalization and emergency department visits for asthma. High levels of cockroach antigen are also found in food in kitchens and food storage areas.9 Aggressive extermination of cockroaches is recommended for sensitive individuals.
The number of pet cats now exceeds the number of pet dogs in the United States, and, unfortunately, the number of patients with cat allergy also outnumber those with dog allergy. The source of the major cat allergen is now believed to be the skin of the cat rather than cat saliva. Cats’ behavior of licking their fur to bathe themselves probably contributes to the spread of antigen when the fur dries.
Patients with cat allergy often experience symptoms within a few minutes of entering a room where a cat had been staying. Cat allergens may be present for several months after the animal has left, because of the adhesion of the sticky particles to carpets, walls, and furniture and their small size, which allows them to enter the airways.
Dog allergens tend to be more varied, and may occur in saliva, skin, and urine. Various dog breeds differ in their expression of allergens, and antigen exposure may be decreased by regular bathing of the dog.
NONALLERGIC ENVIRONMENTAL FACTORS
The major outdoor pollutants associated with respiratory disease are sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and particulate matter less than 10 micrometers in diameter. The distribution of these pollutants varies greatly with the geography of the land, weather, and population density.
SO2 is emitted from coal-burning power plants, refineries, and pulp mills. Patients with asthma are particularly susceptible to SO2, and will experience a drop in pulmonary function at concentrations as low as 1.0 ppm SO2. The effects of SO2 are aggravated by cold air and exercise in sensitive patients. NO2 results from combustion from automobiles and stationary sources. NO2 increases bronchial hyperresponsiveness and may increase susceptibility to pulmonary infections.
Ozone is produced by the interaction of sunlight with chemical precursors such as volatile hydrocarbons. Children living in areas with elevated ozone levels have increased bronchial hyperresponsiveness and were also found to have decreased numbers of helper T cells that may alter immunity. Particulate matter (<10 microns) occurs from a variety of sources, including diesel exhaust, and high levels have been associated with increased emergency department visits as well as an increase in pulmonary and cardiac deaths due to asthma. These particles also stimulate production of cytokines in epithelial cells found in the airway.10 Cigarette smoking should be considered in any discussion of air pollution, and there is strong evidence that adults who smoke in the home contribute to exacerbations of asthma in their children.11
Seasonal changes may have significant effects on asthmatic patients, particularly those with pollen allergies. Increases in relative humidity may have an adverse effect on patients with dust mite and mold allergies as mites and molds thrive in more humid environments. Identifying the seasonal and environmental factors that may exacerbate asthma is the first step in eliminating or modifying them for the patient’s benefit.
Robert L. Roberts, MD, PhD, is associate professor of pediatrics at UCLA Medical Center in Los Angeles in the Division of Pediatric Immunology/Allergy/ Rheumatology.
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