Asthma affects millions of people worldwide. The pathophysiology is complex but involves exaggerated smooth muscle contraction in the airways along with inflammation that in a chronic state causes airway remodeling (narrowing). The majority of current therapies for asthma address these two issues. Bronchodilators relax the smooth muscles and anti-inflammatories treat the inflammation. Despite the panoply of these medications there are still many asthmatics who either don’t respond as well as desired or have untoward side effects from the medications.
Recent research at our local USF has uncovered a new potentially unique mechanism via bitter taste receptors (TAS2R). Bitter taste receptors are found in many animals, including humans, and are thought to have evolved as a survival mechanism to both sense and avoid potentially harmful food sources. As it turns out, stimulating these receptors causes airway smooth muscles to relax by a mechanism completely different from currently available bronchodilators.
It also seems that stimulating TAS2R receptors in the nose and lungs can promote an innate immune response against inhaled irritants and microbes, and can also improve clinical function. Remember that cilia are the microscopic hairs whose motion helps remove allergens, irritants and microbes from our respiratory system. So, having the cilia beat more quickly is a good thing.
Of course, this research is very preliminary but the exciting aspect is it may prove to be an extremely safe new approach to treating asthma. Perhaps Mary Poppins was wrong about “the spoonful of sugar”.
For many years now, asthma has been referred to as “The Nocturnal Predator” because of its tendency to exacerbate at night. The traditional explanation given was due to our normal circadian variation in adrenal gland output. Our adrenal glands produce two hormones that are an innate treatment for asthma: adrenalin and cortisone. In fact, many of the pharmaceutical therapies for asthma mimic the body in that they contain forms of adrenalin and cortisone.
Our adrenal glands “wake up” about an hour before we do and release surges of adrenalin and cortisone until about 4 or 5 pm. Then they “shut down” so we can be prepared for our sleep quietude. It is this dramatic drop in adrenal output at night that can allow asthma and other allergies to exacerbate. For many years this physiology was felt to be the total story. But science always moves forward and new research is showing that adrenal variation is just part of the equation.
One very new understanding is that in addition to our brains circadian clock, individual cells including the immune cells also have circadian clocks. When these clocks are disrupted the immune cells do not function optimally and therefore are less able to respond to allergic threats or microbial (virus & bacteria) invasion. As small a clock disruption as that which impacts many students: their school/work schedule versus their weekend schedule can lead to greater difficulty with allergies and infection.
For years, the phenomenon of “everyone getting sick” at the beginning of fall semester has been blamed on the gathering effect of the “herd” that had been separated during the summer. Certainly, this still plays a role, but the clock paradigm is equally important.
This clock effect also helps explain why shift workers and people who travel one or more time zones distant tend to have more allergies and more infections. When bed time versus wake-up times have been studied it turns out that wake-up time is the critical factor. You didn’t hear it from me but tell your teenage children not to sleep in until noon on Saturdays.
A recent study in Europe was done on people with mild-persistent asthma. The study compared daily use of a combination inhaler with long lasting bronchodilator and steroid versus just using the inhaler when the asthma started to flare up. The rate of severe exacerbation of the asthma requiring either an ER visit or treatment with oral steroids was the same in both groups.
Nine people died and 8,500 more recently were hospitalized with severe asthma in Australia in a single week of thunderstorms. Said storms occurred during the peak of rye grass pollen season. The rain caused the pollen to become saturated, and the electrical discharges caused fragmentation of the pollen grains into tiny particles. More typically, pollen grains are filtered out by the nose/sinus area, leading to hay fever symptoms. But tiny fragments created by the storms were able to slip right through the upper airways, landing in the lungs, precipitating sudden, severe allergic asthma. In addition, many of the victims had no prior history of asthma, just allergic hay fever.
John Hopkins Epidemiologists have found that asthmatics who live in areas of the country where fracking is done have an increased incidence of hospital/ER-requiring flare-ups — that is four times greater than their counterparts not exposed to the environmental leak of natural gas.
Dear Dr. K: Dear Dr. K.: My husband and I both have allergies and we are both triathletes. When we exercise my husband’s nasal congestion always improves, while mine seems to get worse. What’s going on?
The answer to your question is statistics.
Your husband is on the good side of statistics and you are on the bad side. What I mean is that in the majority of people with allergies exercise helps open the nasal passages. It does this by two main mechanisms: neurologic and chemical. In most persons, exercise increases preferentially the sympathetic nerves that control blood vessel size, constricting these blood vessels, and thus, improving nasal patency (being open or expanded).
Exercise also releases “adrenal-like” chemicals that exert the same effect on the nasal blood vessels.
In a small number of people, exercise preferentially stimulates the parasympathetic nerves, which dilate nasal blood vessels and cause congestion. This phenomenon is called exercise-induced rhinitis. It is similar to a related phenomenon in asthmatics called exercise-induced-bronchospasm.
One predisposing factor to exercise-induced-rhinitis is deviation of the nasal septum. Apparently, people with septal deviation have a chronic disparity in air flow through the two nostrils. For some reason, this makes the parasympathetic nerves more sensitive, and thus their adverse response to exercise.
An amazing 96 percent of patients with lung conditions attending a “Singing for Breathing” program in the United Kingdom (UK) report improvement.
Research done by UK scientists has shown that singing therapy can improve lung function in a variety of conditions including asthma, COPD and cystic fibrosis.
The program consists of six weeks of twice-weekly voice lessons, followed by once-a-week maintenance classes. It is sponsored by the British Lung Foundation and is held at 55 clinics across Great Britain.
The British scientists feel that singing improves lung function in a variety of ways:
First of all, it strengthens the muscles of respiration: the diaphragm, the intercostal muscles and the chest wall muscles. Secondly, it helps dilate the airways by substantial exhalation and greater air movement. Thirdly, training the laryngeal muscles helps prevent laryngospasm that often occurs in asthmatics and COPD patients. Fourthly, the positive effects associated with singing help both airway patency (openness) and chest wall muscle function. Finally, participants were trained to try singing a sustained note as a mechanism to stop a coughing/wheezing attack prior to reaching for a rescue inhaler. More often than not, the sustained note was therapeutic.
Asthma worse? Being female and a list of other factors might be the cause — based on Columbia University’s recently published data on research about women and asthma. They found that a number of factors led to greater difficulty with asthma including: hormones, obesity, stress, depression and PTSD (Post Traumatic Stress Disorder).
The researchers note that hormone levels (especially estrogen) impact the Th-2/ Th-1 balance that has been previously discussed in this newsletter. High estrogen leads to Th-2 predominance, which promotes allergy. Increased estrogen can come from the normal wax and wane of the menstrual cycle, pregnancy, hormone replacement or oral contraceptives.
Obesity is also pro-inflammatory via the Th-2 mechanism. Columbia found that as little as a 15pound weight loss by obese women asthmatics resulted in 20 percent improvement in their asthma.
The issue of stress and depression is a double bind. In general, women experience depression more frequently than men. The asthmatic condition itself can cause life stress and depression, but the opposite is also true: stress and depression cause worsening of asthma. The Columbia group found that upwards of 15 percent of women with poorly controlled asthma had unresolved issues from childhood sexual trauma. They consider this a form of PTSD.
Interestingly, they found strong correlation of PTSD and worsening asthma in military women who had service-related traumas. Stress, depression and PTSD all lead to a number of stress hormone changes by way of the adrenal glands, along with production of inflammatory molecules such as interleukins, substance-P, and natural killer-cell function.
African-American women seemed more prone to depression and PTSD than their Caucasian, Asian and Hispanic sisters. In yet another fallout from racial discrimination, Columbia found a strong correlation between African-American asthmatics who had experienced significant racial bias versus women who had not, in terms of severity of asthma and frequency of exacerbation.
The researchers’ take-home message is that both patients and doctors should be aware of the interplay and dynamic force of stress/depression and asthma.
Mayo Clinic researchers have found that having asthma increases the risk for developing shingles almost two-fold. This is true both in children and adults.
For quite some time it has been known that calcium plays a major role in muscle contraction. A number of calcium-altering medicines are used to help heart problems and hypertension by relaxing the smooth muscle found in the heart and arteries. Now there may be an application to asthma.
Smooth muscle is also found in our bronchial tubes; constriction of this muscle that occurs through proteins called calcium-sensing receptors causes asthma.
A recent British study examined the use of a class of drugs used to treat osteoporosis called calcilytics. These drugs were administered to asthmatic mice with dramatic results: the drugs blocked the action of calcium-sensing receptors and thus, prevented the smooth muscle constriction.
The scientists are now starting human studies. This research is very compelling as it offers a mechanism to control asthma that has never before been available.