The Pathophysiology of Asthma
Excessive shedding of bronchial epithelium, or outer membrane tissues, is a hallmark of both allergic and non-allergic asthma, and has long been associated with eosinophilia, and specifically the major basic protein of eosinophils, which is toxic to parasitic helminths, such as giardias, but also to bronchial epithelial cells. Eosinophilia is a condition of excess circulating eosinophils, or white blood cells that combat parasites and certain chronic infections. Normally, eosinophils make up only about 1-6 percent of the total white blood cells in circulation, and are found predominantly in the thymus, gastrointestinal tract, lymphatic system, uterus and ovaries, but not in the lung, esophagus, skin or other internal organs. The presence of eosinophils in the lung, bronchioles and esophagus is associated with disease. Following activation by an immune stimulus, such as helminths, and certain types of chronic infection, eosinophils release proteins and enzymes that are cytotoxic, and may damage cells of the lungs, bronchioles and esophagus.
Biopsies of young children with both allergic and non-allergic asthma show that degeneration of the bronchial epithelium has already occurred in asthma, and is associated with eosinophil infiltration. Incidence of Eosinophilic esophagitis, especially in children, is also on the rise, producing symptoms of decreased appetite, difficulty swallowing, esophageal bolus (food obstructing the throat), and heartburn acidity. A 2013 study at the University of Calgary, Alberta, Canada, showed that the incidence of eosinophilic esophagitis has increased significantly in the last 2 decades, and like asthma and COPD, has a geographic variation that is dramatic, demonstrating the adverse effects of environmental factors in the disease. The prevalence geographically ranged up to 43/100,000, but in children receiving an esophagogastroduodenoscopy (imaging test of the throat, stomach and small intestine) for any reason, the incidence was averaged at 24 percent. Studies show that the incidence of giardia and other helminth infection is also much higher than previously thought possible. While this geographic incidence and causative factors in asthma and esophagitis with eosinophil infiltration is still poorly understood, we might assume that proximity to dirty coal-fired power plants and large feedlot animal farming and wastewater are big concerns.
Not only the stimulation of increased eosinophils by helminth and other parasite infections, often low-grade and undetected, but the stimulation of increased eosinophils by medications has become a concern among experts in eosinophil-related diseases such as asthma. A 2007 report by Thomas B. Nutman M.D., of the National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, U.S.A. (see link to the report below in additional information), shows that "medication-related drug reactions are perhaps the most common cause of persistently elevated eosinophil levels in areas where exposure to parasites is uncommon. Medication-associated peripheral blood eosinophilia may present without accompanying symptoms or may be associated with specific signs and symptoms. Asymptomatic eosinophilia has been associated most often with quinine, penicillins, cephalosporins (antibiotics), or quinolones (anti-bacterial antbiotic drugs used to treat urinary tract infections, but are broad spectrum). Pulmonary infiltrates with peripheral eosinophilia have been particularly associated with NSAIDS, sulfas (antibiotics and other drugs), and nitrofurantoin (antibiotic commonly used to treat urinary tract infections)." We clearly see the association with excess use of antibiotics and NSAIDS in children with eosinophil infiltration and rising asthma incidence.
Stimuli of the asthma episodes, or aggravating factors, are perhaps different from the basic causes of the disease. This differentiation appears to be largely overlooked in the medical approach to asthma. Asthmatic stimuli include allergens, common chemicals, including synthetic perfumes, cleaning agents, laundry detergents, fabric softeners, cosmetics, air fresheners, varnishes and paints, medications such as aspirin, acetaminophen, beta-adrenergic agents, and penicillin, common food allergens, sulfite preservatives, sulfur dioxide and other chemicals in smog and air pollution, smokestack emissions from power plants, and chloramines in chlorinated waters. These household agents are getting more and more attention in recent years, both with asthma and COPD. Cold weather, exercise, psychological stress, hormonal changes, and apnea are also associated as triggers or stimuli of asthma episodes. While these numerous asthma stimuli must be avoided with asthma, the underlying pathological factors must not be overlooked when treating the disease.
Besides infiltration of eosinophils and activation of these white blood cells that damges bronchial epithelial cells, other immune infiltrations are also noted in asthma, such as neutrophils, lymphocytes, and mast cells. Neutrophils, the most abundant type of white blood cell in circulation, are part of the innate immune system, are generally first responders to acute infection and inflammatory disease, and follow immune cytokines such as leukotriene B4. Neutrophils are thus associated with acute asthma attacks, and severe or fatal attacks. Hence we use leukotriene inhibitors in standard medicine. Building a stronger innate immune system, and maintaining healthier membrane immune responses would be a good strategy for countering these immune infiltrates. Aiding the maintenance and repair of epithelial tissues in the bronchioles would also be a good strategy to incorporate. Overuse of antibiotics, as well as the standard asthma medications, do not achieve these restorative goals, and in fact stress the immune responses and epithelial membrane tissues. While these standard medications relieve acute symptoms, they do not restore homeostatic health, and in fact, damage the systems that are responsible for the pathology of asthma. An expert panel of the U.S. National Institutes of Health stated in 2007 that "current asthma treatment with anti-inflammatory therapy does not appear to prevent the progression of the underlying disease severity".
Understanding the Mechanisms of Asthma and COPD
Asthma is not a simple problem. Many things may cause the alarming symptoms of subjective shortness of breath (dyspnea), airway constriction (wheezing) and inexplicable chronic coughing episodes. Asthma may be part of chronic obstructive pulmonary disease, or COPD, or it may be a separate problem. COPD is a progressively worsening problem of decreased expiration with the feeling of shortness of breath that causes a deficiency of oxygen and increase in carbon dioxide in the blood. COPD may be seen with or without chronic cough, and may eventually involve emphysema, a disease that involves damage to air sacs, or alveoli, in the lung, decreasing the ability to obtain sufficient oxygen and expel sufficient carbon dioxide from the blood. Emphysema occurs when the alveoli in the lungs are gradually destroyed, and is the end result of a long course of degeneration of the lung membranes, which can be prevented. In emphysema, we see that the alveoli, or small air sacs, gradually are degenerated with holes in the inner membrane, or epithelium. The elastic fibers that hold the bronchioles open also eventually degenerate in emphysema, allowing the airways to collapse when breathing out, and preventing the air from escaping when even mild exertion occurs. Standard medicine may slow the progress of emphysema, but it cannot reverse this damage, leaving the patient disabled and slowly unable to achieve proper regulation of oxygen and carbon dioxide in the body. While stimulating a regrowth of healthy tissues in the lung is not easy, a comprehensive program can accomplish this task, and the utilization of Complementary Medicine presents much hope in this regard. The real emphasis should be on prevention of progression of asthma and COPD, though, and modern medicine readily admits that its treatment protocols do not achieve this important goal.
Asthma may involve acquired allergies and hyperresponsiveness to smoke, mold, mildew, dust, pet hair, pollen, chemicals in the environment, pollution, etc. Asthma episodes may be induced by cold, exercise, emotion, aspirin, Beta-blocking medications, such as blood pressure drugs, viral illnesses, or problems with inflammatory mediators and the immune system. Asthma involves not only problems with the immune response and allergic reaction, but also with the nervous system and autonomic regulation. The autonomic nervous system, a system of balance between the sympathetic and parasympathetic responses, may acquire problems due to variety of health issues, including chronic pain, anxiety, depression and hormonal imbalances. A comprehensive treatment strategy is important, both avoiding triggers to asthmatic episodes, as well as gradually working to restore the bronchiole epithelial membranes, the local and systemic immune homeostasis, and the neurohormonal systems in the body.
Some basic ways to decrease exposure to common allergens include avoiding dust mites, pet dander, fungi, mold and pollens. This could include shaking the bedding out each day outside of the bedroom and dusting surfaces daily. Spraying pillows with a light lemon water mist and exposing them to the sunlight periodically may help. Using a non-electrostatic air filter in the bedroom may help, as well as vacuums designed to eliminate dust mites. Clearing common pollen plants and trees from the yard may be advisable. Getting rid of any old or unecessary carpeting, fixing roof leaks and old water pipes, fixing shower stalls, and having the air tested for mold and fungi if you are suspicious is advisable (refer to the California Home Performance Program to seek out contractors offering The Healthy House Inspection for about $100). These basic methods of decreasing allergens are important, but just one part of the holistic protocol. Decreasing household chemicals that stimulate allergic episodes, such as chemicals in cleaning agents, paints, varnishes, cosmetics, soaps, and perfumes, may be very important, and going green and natural is now much easier, with many products offered routinely. Avoidance of chemicals in the food that may contribute is also important, especially chemical sulfite preservatives, natural sulfites, artificial flavorings and dyes, and transfats. Finally, reversing superantigen responses may be especially important to decrease immune hyper-reactivity. You may go to the article entitled Superantigens, difficult disease and herbal research to learn more about this important subject.
Ozone sources may have to be avoided, such as photochemicals, electrostatic air filters, and as much as possible, carbon monoxide from engines and hydrocarbons from rotting materials. In addition, some people may need to avoid cold drinks and frozen foods, as well as abrupt changes in climate by dressing appropriately in cold weather and planning vacations with care. For many, exercise routines may need to avoid abrupt heavy exercise and exposure to cool dry air with exercise. Swimming may be better than running. Routine low impact exercise should be performed rather than infrequent heavy exercise routines. All of these lifestyle considerations may be important, and only patient education and understanding, and careful evaluation of these numerous asthmatic triggers, can help decrease the frequency of asthmatic attacks by changes in the diet and lifestyle. Keeping a diary of asthmatic episodes and potential triggers is essential. Each individual may have a different set of triggers, and applying universal restrictions is not helpful.
The most important consideration for the patient with asthma and COPD is that avoidance of triggers and aggravating factors, and use of emergency asthma medication, is not the whole picture of health need, though. These are important, but understanding how to restore respiratory and immune health, and work on the array of health problems proven to be associated with the disease is the most important long-term consideration. Simply paying attention of the immediate symptoms, and not working on the underlying health will result in a gradual worsening of the condition. Symptoms are like the tip of an iceberg, but what really sinks the ship is what is concealed under the water.
A number of immune problems are found to be associated with chronic lung diseases. Epigenetic dysfunctions, which could be passed onto children if not corrected, are now being found. A 2013 study in India (cited below in Information Resources) showed that polymorphisms (multiple genetic variants) of the gene that expresses CD-14 (a complement protein messenger in the innate immune system) were significantly more prevalent in patients with chronic lung diseases that survived the Bhopal Disaster, where over 500,000 people were exposed to toxic gases from a pesticide plant operated by Union Carbide in 1984, than healthy controls. The Bhopal Disaster has prompted research in this field that is unprecedented, and reveals much about epigenetic changes passed on to children from chemical pesticides and other chemical toxins. The CD-14 protein acts along with another cell receptor, the Toll-like receptor TLR-4, to detect bacterial lipopolysaccharides (LPS), endotoxins found primarily on the outer membrane of gram-negative bacteria. Low-grade deep bacterial infections could perpetuate these chronic lung diseases when the immune system does not eliminate them. Specific genetic variants, or alleles, of the CD-14, TT and CT types, were noted in 10-20 percent of patients with chronic asthma and COPD that survived the Bhopal Disaster! Such epigenetic variations are believed now to be the result of a combination of environmental, dietary and genetic interactions. As research progresses, more and more of these epigenetic variations associated with these chronic diseases are sure to be found, many of them the result of environmental toxins like the methyl isocyanates of the Bhopal Disaster. A broader, and more holistic, treatment and prevention protocol is able to address these concerns, as well as the numerous other factors that contribute to these complex chronic respiratory diseases. So far, these diseases, asthma and COPD, have eluded allopathic means of reversal of disease progression, and cure, but there is still hope that a more comprehensive treatment strategy will achieve these goals.
The link between Food Allergies, Eczema and Asthma
The National Institute of Allergy and Infectious Diseases, an offshoot of the NIH, convened an Expert Panel on Food Allergy Research in 2006. Dr. Stephen Galli of Stanford co-chaired this committee with Dr. Dean Metcalfe of the NIH. The findings showed that food allergies were frequently accompanied by other allergic diseases, namely asthma and eczema. The prevalence of food allergies appears to be increasing, with greater than 4% of the adult population, and 8% of the children under 4 years of age now affected by serious food allergies. Food allergies account for greater than 50% of emergency room visits for anaphylactic shock in the United States. The asthmatic patients with allergic triggers may be well advised to effect dietary changes, improve gastrointestinal health, and improve the immune health with holistic medicine. The NIAID study found that probiotic regimens and certain Chinese herbal medicines were effective in animal studies in reducing certain immune reactions, and may suppress the adaptive immune responses in a modulatory fashion.
The physiological link between allergic asthma and food allergies concerns the type of immune response. Studies have shown that over 60 percent of the CD4+ leukocytes in the lungs of patients with moderate to severe asthma are not typical helper T-cells, but natural killer T-cells that are activated by antigens/allergens with specific types of lipid and glycolipid components. Most allergens are water soluble, so this finding narrows the suspects in this allergic link to glycolipid pollens (such as cypress tree pollens) and lipid-carbohydrate complexes in foods. This would suggest that the increase consumption in transfats and simple sugars, especially high-fructose corn syrup, presents excess challenge to our immune system, and the development of hyperallergic responses. This would explain the unusual increase in incidence of allergic response to one of our most common fat-carbohydrate combination foods, the peanut, which is not really a nut.
Allergic responses are still not understood fully, and various thresholds of allergen intake trigger allergic responses. Even allergy testing may not reveal fully the extent of foods that you have developed hypersensitivity to. IgE response levels to specific foods in testing predict the likelihood of allergic reaction, but not the severity of that reaction. A simpler approach is to keep a journal and note connections between asthmatic episodes, other allergic responses, and the specific foods that you eat. Avoidance of common allergens for periods of time should be tried and noted in the journal to determine a cause effect relationship. Common allergens include glutens, shellfish, peanuts and dairy. Commercial baked goods often use high gluten flours and should especially be avoided. Endotoxins are found to be a prevalent allergen in asthma eczema, especially in a subset of children that were not exposed to animals at an early age. Not only pets can carry these endotoxins, but meat itself may carry endotoxins, and meat that is less cooked can present as a food allergen. Ground beef and prepared luncheon meats and hotdogs were found to have higher levels in general of these endotoxins. Decreasing meat consumption, or buying local organic meats from smaller cleaner producers may reduce your allergic reactions.
In 2010, much attention is now being directed to the subject of food allergies and the industry built up around the overblown fear of food allergies. As expected, as the public becomes aware of the prevalence of food allergies, which are difficult to understand and detect, there is much fear that food allergies may be responsible for a variety of individual health problems, and consequently, an industry has grown around these fears. The intelligent patient counters this by educating themselves. The key points to understand in allergic and hypersensitivity immune dysfunctions is that they are hard to objectively diagnose, vary intensely in the degree of reactivity, and most importantly, the food is not the problem, but rather the individual immune function. In fact, even patients with extreme allergic and hypersensitivity reactions may eventually consume these foods that cause the reactions without problems once the immune system is, in a sense, reprogrammed. Glutens and gliadins are posing problematic reactivity in a high percentage of people in industrialized countries now, according to the World Health Organization, but these are still healthy food nutrients. The problem is that the commercial use of high gluten flours has stimulated strong antibody responses and negatively impacted the health of the intestinal membranes. Most patients with gluten and gliadin sensitivity, though, will not respond significantly to these nutrients after 6 months of avoidance and restoration of the health of the intestinal tract and immune function. After health is restored, and the immune reaction is quieted, most people will be able to eat these foods without problems. The glutens and gliadins are not the focus, but rather the health of the immune system and gastrointestinal tract. Of course, resuming consumption of high gluten flours in commercial food products will probably again trigger an exagerrated antibody response.
Standard medicine does not have effective holistic therapy to correct this immune function and intestinal health. Many medical doctors are now utilizing tests for allergies, such as blood tests and skin prick challenges, that give some pertinent data, but are not conclusive. The advice to the patient is often to avoid a lot of healthy foods, and the fear of foods generated can be a problem for one's health that is greater than the allergies. The patient can seek help with Complementary Medicine to correct the underlying health problems as they avoid the foods that they may be allergic to, and eventually resume consumption of a variety of healthy foods in their diet. Patients that choose the common path in standard medicine, which generally supports steroid and antihistamine medications with chronic use, avoidance of many foods, and often even the cynical advice to avoid herbal therapy, often find themselves with a deteriorating health problem, even as the harsh medications relieve some of the symptoms. There is a healthier approach that restores health, and Complementary Medicine improves its approach each year with new research.
The Link between Acid Reflux and Asthma
Acid Reflux, or Gastroesophageal Reflux (GERD), are often seen in the same patient. 77% of asthmatics complain of heartburn and 41% complain of reflux associated symptoms. Study of this phenomena has led to greater understanding of both GERD and asthma mechanisms. Acid stress from GERD may initiate asthmatic inflammatory processes, and nocturnal acid reflux may result in stomach acids that stay in the esophagus with likely spillover into the aerodigestive tract and pharyngeal area that are related to asthmatic symptoms and sleep apnea. Upper airway occlusion may in fact create intr-thoracic pressure that induces the acid reflux. This type of acid reflux may have nothing to do with the typical heartburn, and typical medications may not help.
The result of this esophageal acidity and spillover is heightened bronchial reactivity, neurogenic inflammation and acid-induced bronchoconstriction. Studies have found nitric oxide containing neurons, indicating inflamed nerve endings that may trigger asthmatic symptoms, in both the lung and esophagus. Nerve signals from the irritated esophagus were shown to produce substance-P and neurokinin-A release in the lungs, both potent stimulators of the asthmatic responses. One study even showed that esophageal acid exposure could result in decreased blood flow to the coronary artery, causing chest pain.
82% of asthmatics showed abnormal esophageal acid contact times on 24 hour tests, and it is estimated that 24% of patients with asthma that is difficult to control have clinically silent GERD. This association of GERD with asthma is not new. Sir William Osier found that GERD was a potential asthma trigger around 1900. The fear in modern medicine is that asthma medications may potentiate GERD. It was found that theophylline increases gastric acid secretion and lowers esophageal sphincter pressure in a dose-dependant manner, and oral corticosteroids increase esophageal acid times. (Refer to Chest 2002, vol. 121 pp 625-634; Lazenby et al).
Clearly, this shows that present medication management of asthma and GERD may be worsening the clinical condition with chronic use while relieving symptoms. A more holistic and safer approach, with less dosage of both asthma medications and stomach acid medications is warranted. This is where Complementary Medicine comes into play.