Asthma Complications: Long- and Short-Term Effects

Complications Of Asthma Ten Early Warning Signs

While nearly everyone who has asthma can lead a near-normal lifestyle with proper guidance and treatment, some patients can and do develop serious complications from asthma. Sometimes these problems are minor setbacks easily managed with basic asthma treatment.

On other occasions, patients may experience serious breathing difficulties that require acute emergency care, hospitalization, or even admittance to an intensive-care unit.

Many severe asthma setbacks can be minimized or even prevented by asthmatic patients and their families learning to recognize the following ten early warning signs of deteriorating asthma:

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1. Excessive school or work loss
2. Cough and wheezing unresponsive to medications
3. Wheezing with minimal exertion
4. Need for inhaler every two or three hours
5. Constant wheezing during sleep
6. Persistent high fever
7. Severe neck or chest pain
8. Persistent vomiting
9. Difficulty speaking because of wheezing
10. Cyanosis (blue color) of the lips and hands

The presence of one or more of these ten early warning signs is a clear-cut medical alert that out-of-control asthma requires im- mediate attention from a primary doctor, emergency room, or asthma specialist.

The Acute Asthma Attack

• When the acute attack persists or is accompanied by any early warning signs of deteriorating asthma, the patient should contact her or his doctor or go to the nearest (or best-equipped) hospital emergency room for further evaluation and care.
• Adult asthma tends to be more chronic and less episodic, which means that adults are less likely to experience acute attacks of asthma. Many adults who come to the office or hospital with “acute asthma” have been gasping for days or even weeks.
• Those adults who are subject to severe and explosive asthma are often sensitive to aspirin-like drugs or potent bisulfite preservatives.

Changing Patterns Of Care

In previous years most patients with acute asthma were sent to their local emergency room, where oxygen, X-ray facilities, and lab tests such as blood theophylline levels and arterial blood gases were readily available.

• Those patients with severe wheezing, cyanosis, an inability to talk, or a previous history of life-threatening asthma should always be referred to a fully equipped emergency facility. However, most patients with acute bronchospasm are not that seriously ill.
• Many patients have been wheezing for several days or even weeks before they contact their healthcare provider. There is a growing tendency on the part of primary physicians and asthma specialists to treat acutely ill asthmatic patients in their office or clinic and not send them to the local emergency room.
• There are several valid reasons for this emerging trend. First, chest X-rays and blood gas studies are not needed in most cases of acute asthma. Secondly, acute asthma care is undoubtedly more cost-effective in a clinic or office setting.

Studies have shown that acute asthma care delivered by asthma specialists reduces the rate of hospitalization and asthma relapses. Busy emergency room physicians may have neither the time nor the expertise to competently resolve an acute asthma episode or prevent a relapse.

• The asthma doctor also is more likely to have a peak flow meter or spirometer readily available to monitor the patient’s breathing capacity closely. Lastly, the availability of office-based laboratory tests that measure blood theophylline levels gives the doctor a new weapon in evaluating acute asthma.
• One blood theophylline test, the AccuLevel, requires only a small drop of blood from a prick of the finger. When a wheezing patient is initially seen in the office or out-patient setting, the doctor should quickly evaluate the severity of the acute asthma episode by noting the patient’s appearance, listening to the chest, and performing a breathing test.
• The doctor will then order an inhalation treatment with a beta-agonist aerosol Fortunately, the time-honored practice of administering repeated injections of adrenaline, or Susphrine (long-acting adrenaline), has given way to the more judicious modern-day nebulization or inhalation therapy.

Patients no longer have to endure the pallor, tremors, rapid heart rates, and vomiting often associated with adrenaline injections. When the blood theophylline test reveals a low blood theo- phylline level, theophylline-tolerant patients can be given an appropriate dose of a short-acting theophylline drug.

• It is often necessary to administer a pulse of prednisone and to avoid any delay in starting prednisone. I usually give the first day’s dose of prednisone in the office.
• Patients who respond to the above treatment program should have their total asthma program reviewed, and a follow-up visit should be scheduled within one to two weeks.
• Patients and families need to be reminded constantly that proper use of their peak flow meter may enable them to detect an asthma relapse in its early stages and prevent a sick call or an emergency visit.
• Those few patients who do not respond to routine office or clinic therapy should be referred to the local emergency room, where they may be given more inhalation treatments along with an intravenous form of theophylline, called aminophylline.

When emergency room care does not break the asthma attack, the patient should be admitted to the hospital for additional treatment. The six telltale signs that signal the need for hospitalization are

1. Fast heart rate and rapid respiration
2. Use of the neck and rib muscles to breathe
3. Severe wheezing or inability to speak
4. Persistent sweating
5. Blue lips and fingernails or cyanosis
6. A disturbed or confused mental state

While children and young adults are more prone to acute asthma requiring emergency care, they are also more likely to respond to treatment and avoid unwanted hospitalization.

• Many adult asthmatics who come to an emergency room with acute asthma can be very difficult to treat, as adults are more likely to put off calling their doctor or seeking emergency care.
• Delays in seeking care make it harder for doctors to reverse the asthma relapse. As for asthma, doctors are fond of saying, “The time to treat your acute asthma relapse and prevent you from being hospitalized was yesterday.
• ” When a patient does require a hospital stay, doctors use the term status asthmaticus to describe the patient’s medical condition. Once hospitalized, the patient in “status” is given oxygen, inhalation therapy, intravenous aminophylline, and intravenous cortisone drugs.

Most hospitalized asthmatics improve within twenty-four to forty-eight hours and are discharged after a three- to seven-day hospital stay.

Life Threatening Asthma

A very small percentage of patients who do not respond to in-hospital treatment develop a life-threatening condition called “acute respiratory failure.” In respiratory failure, the bronchial tubes are almost totally blocked.

• The lungs are deprived of life-sustaining oxygen and cannot eliminate the body’s toxic waste gas, carbon dioxide. Picture this as a form of very slow suffocation. Machines must take over the control of breathing, and these patients are connected to a breathing machine called a ventilator.
• A tube is inserted into the trachea (windpipe), and the respiratory muscles are deliberately paralyzed. Dials on the machine are adjusted to deliver the proper amounts of oxygen and remove carbon dioxide. This procedure, called assisted ventilation, may continue for two to three days.
• Once the ventilated patient begins to improve, the machine is gradually turned down, and the patient is slowly weaned from the ventilator. Thanks to the development of intensive-care units devoted to respiratory care and the ready availability of intensivists (intensive-care doctors) and pulmonary.
• For specialists in larger community hospitals, assisted ventilation has a very low complication and mortality rate. An inpatient asthma death is a very rare event in well-staffed hospitals. Most asthma deaths now occur suddenly and unexpectedly outside of the hospital.
• It is my impression and that of my pulmonary colleagues that the overall incidence of acute respiratory failure is decreasing. Our practice used to see two or three asthmatic patients a year who ended up on a ventilator.
• Now only one patient every two or three years needs this type of intensive treatment. More aggressive use of anti-inflammatory drugs and prompt intervention with prednisone in the early stages of relapsing asthma may be the reason for this apparent decline in acute respiratory failure in patients with asthma.

Deaths From Asthma

Doctors know that Oliver Wendell Holmes was wrong when he stated, “Asthma is a slight ailment that promotes longevity.” Sir William Osler also erred when he wrote that “asthmatics pant on into old age.

• ” The extremely low asthma death rate in Holmes’s and Osler’s era was undoubtedly the result of inaccurate statistics and poor record keeping. The United States did not begin to gather accurate death records from individual states until 1930.
• From 1930 to 1953 the number of recorded asthma deaths in the United States ranged between five thousand and six thousand per year. After 1953 asthma deaths slowly declined to a low point of two thousand in 1979.
• In 1968 English investigators reported a sudden increase in the asthma death rate from 1959 to 1966 in England and Wales. A similar pattern was seen in Australia and New Zealand, but not in the United States or Canada.
• Initially, this acute rise in asthma mortality in Great Britain was attributed to misuse of the MDIS (pocket inhalers). In 1981 a second epidemic of asthma deaths was observed in young New Zealanders.
• Confirmation of these findings spawned additional surveys, which concluded that very inadequate care and adverse psychosocial factors were the two major causes of the rise in asthma mortality in New Zealand.
• In 1984 Dr. Michael Sly of George Washington University reviewed data from the National Center for Health Statistics and found a progressive increase in asthma mortality in the United States after 1979, which reached 3,790 deaths in 1984.
• Regional U.S. studies found an 82 percent increase in asthma mortality rates in Washington and Oregon. In 1987 California investigators reported a 145 percent increase in asthma deaths from 1976 to 1983.

The increase in asthma deaths in California was highest in blacks, females, and patients over fifty-five years of age.

The Massachusetts Experience

After participating in the International Asthma Mortality Task Force in November 1986 at the National Institutes of Health, I reviewed asthma mortality data in my home state, Massachusetts. I initially found an increase in asthma deaths in Massachusetts from 1970 through 1986.

• Unlike other studies in the United States, England, New Zealand, France, and Germany, I found no increase in asthma mortality rates in children and adults under age sixty-five. The rise in asthma deaths in Massachusetts was concentrated in the elderly, especially females over age eighty.
• I recently extended this research into 1987 and 1988 and found a more than twofold increase in the asthma death rate in Massachusetts in the late 1980s. This increase was most apparent in adults between thirty-five and forty-nine years of age.
• There was only a slight rise in asthma deaths in patients ages fifteen to thirty-five, and no increase was noted in children under age fourteen. Massachusetts females are more at risk in all age groups, including children, especially young, innercity black females.
• Young asthmatics who did die from asthma were more likely to succumb suddenly and unexpectedly outside the hospital. Additional studies on asthma deaths are needed to determine the cause of these alarming trends.

Near-Fatal Asthma

Published articles in the medical literature have addressed the fact that the majority of asthma-related deaths now occur at home or on the way to the hospital.

• The lack of a doctor’s physical examination or medical records during the terminal event makes it difficult or impossible to determine what is triggering these fatal asthma episodes.
• In a concerted effort to identify terminal triggers, asthma researchers have begun to study those patients who make it to the hospital and survive a life-threatening asthma attack. The terms near-fatal asthma and sudden asphyxia asthma are now used to describe these survivors.
• Claude H. Perret and his colleagues from the University Hospital in Lausanne, Switzerland, analyzed the history and clinical characteristics of thirty-four patients who presented to their hospital with sudden severe (asphyxic) or near-fatal asthma that required intubation and mechanical ventilation with a respirator.
• Approximately one-third of Perret’s patients developed severe asthma “out of a clear blue sky,” fifteen out of thirty-four gradually decompensated, and nine patients came to the hospital after experiencing three to four days of unstable asthma.
• After analyzing the age, sex, and potential allergen exposure in this group, Perret concluded that near-fatal asthma was more likely to be triggered by allergens or emotions and that “out of a clear blue sky” life-threatening asthma was more common in young men.

A study of near-fatal asthma from Argentina looked at ten patients who required intubation and mechanical ventilation within twenty minutes after arriving at the hospital. Nine of these ten patients experienced a sudden deterioration of their asthma.

• The purpose of this study was to determine if an abnormal heartbeat (cardiac arrhythmia) or administration of oxygen was responsible for the sudden deterioration of asthma. The authors found that oxygen administration did not lead to respiratory arrest, and only one of the ten patients had an abnormal cardiac rhythm.
• The study concluded that near-fatal asthma was a result of severe oxygen deprivation rather than abnormal heart rate, suggesting that undertreatment rather than overtreatment was contributing to the increase in near-fatal and fatal asthma.
• In 1991 Dr. Mark O’Hollaren and his associates from the Mayo Clinic in Rochester, Minnesota, reported in the New England Journal of Medicine on the potential exposure to mold allergens as a precipitating factor in near-fatal asthma.
• O’Hollaren’s group reviewed eleven patients (two of whom eventually died) who had eighteen episodes of near-fatal asthma. Most of these patients developed acute respiratory failure within one to two hours after the onset of asthma symptoms.

Four patients had seizures, although none had a prior history of seizure disorder. Surprisingly, ten of these eleven patients had positive skin tests for the alternaria mold, and all these episodes of near-fatal asthma occurred during the peak of the Alternaria, or mold season.

• This is the first study that provides some evidence, albeit circumstantial, that exposure to aeroallergens such as outdoor molds might be a significant risk factor for sudden near-fatal or fatal asthma episodes.
• This report suggests that seasonal or perennial exposure to allergens should be added to the list of risk factors for sudden near-fatal asthma.
• An accompanying editorial to this paper by Dr. Regis McFadden wisely cautioned that the Mayo Clinic study did not conclusively prove a cause-and-effect relationship between mold exposure and near-fatal asthma attacks.
• McFadden pointed out that more studies are needed to unravel the mystery of fatal and near-fatal asthma attacks. Dr. Richard E. Ruffin of South Australia recently conducted a follow-up study of forty-five patients with near-fatal asthma ranging in age from twelve to sixty-five years.

These Australians who had experienced a near-fatal asthma episode were carefully followed at monthly intervals over one year. Near-fatal asthma was twice as common in females as in males. There was no obvious seasonal pattern to these episodes, and more than one-third of the near-fatal episodes occurred at home.

• The important message of this Australian study was that none of the forty-five patients died in the ensuing year, clearly pointing out the need for close assessment and frequent follow-up visits for patients with near-fatal asthma.
• Dr. Roy Patterson of Northwestern University recently classified ten near-fatal asthma patients according to their psychological profiles and specifically studied the issue of noncompliance by these ten patients.
• Patterson’s patients exhibited multiple personality disorders and significant psychiatric problems, all of which resulted in a bottom line of noncompliance. The message of Patterson’s report was clear. Noncompliance issues are of utmost importance and should be addressed thoroughly by healthcare providers in all cases of near-fatal asthma.
• A recent JAMA report described a seventy-six-year-old woman with chronic steroid-dependent asthma who, several minutes before her sudden death, was exposed to a sulfite-containing de-rusting agent, Super Iron- out, which was placed in her dishwasher to open a clogged drain.

After the dishwasher was run for a few minutes, this unfortunate woman opened the dishwasher door and inhaled the emerging hot, steamy vapors. She immediately gasped, began to wheeze, and died within a few minutes.

• Subsequent analysis of the de-rusting agent showed that it emits a high concentration of sulfur dioxide, a well-known asthma trigger, suggesting that nonspecific asthma irritants and common air pollutants may be triggering near-fatal or fatal asthma.
• Before continuing with this rather morbid discussion of asthma deaths, I want to emphasize that even though asthma deaths are increasing, they are very rare when one considers that millions of children and adults have asthma.
• Approximately two hundred American children die from asthma each year, yet between four and five million children have asthma. This makes the odds of dying from childhood asthma about twenty-five thousand to one.
• In Massachusetts, there were fourteen asthma deaths in children under age fourteen from 1974 to 1989, an average of one childhood death per year. There were only two deaths in children in this age group from 1984 to 1989.

The reason for discussing asthma deaths in detail is not to scare the reader but to point out that many, if not most, asthma deaths are preventable.

• I believe the most common cause of asthma death in children and adults is a failure by the patient or family to recognize the severity of a serious asthma attack. Doctors at the Aberdeen Royal Infirmary in Scotland found that most asthmatics who died had a very poor understanding of their asthma.
• Patients and their families failed to recognize the danger signs of deteriorating asthma and delayed seeking care until the patient was critically ill. Studies at the Royal Hospital for Sick Children in Bristol, England.
• Found that most of the children who died from asthma did so in the middle of the night before they reached a hospital. Tragically, the parents of these children failed to recognize the severity of the nocturnal attacks, and many did not want to bother their family doctor in the middle of the night.
• Unlike other asthma death studies, the Bristol report did not find that asthma deaths were sudden and unexpected. In most cases, there was ample time to treat and save the child. The high risk of nocturnal asthma has been pointed out in subsequent studies. Seventy percent of all fatal asthma attacks occur between midnight and 8:00 A.M.

Who Is At Risk For Near Fatal Or Fatal Asthma

In 1985 Drs. Robert Strunk and David Mrazek, from Denver’s National Jewish Center for Immunology and Respiratory Medicine, published a very important paper reviewing the records of twenty-one patients who died after they were discharged from this world-renowned asthma center and comparing them to a similar number who survived.

Drs. Strunk and Mrazek found that the survivors were very different from those who died from asthma. All asthmatics who died suffered from severe physical and psychological problems not found in the surviving group.

• As a result of their study, Strunk and Mrazek were able to develop a precise profile of the high-risk asthma patient that includes
• A history of seizures associated with asthma
• A recent decrease in prednisone doses
• Wheezing at the time of hospital discharge
• A disregard for wheezing and other symptoms poor self-care while in the hospital
• Conflicts with staff and parents
• Use of their asthma to manipulate people
• Emotional disturbance
• Symptoms of depression
• Severe family disruption

Emotional factors are strong predictors of fatal asthma. Asthma specialists now have a specific profile of the high-risk patient, who is often an outwardly hostile, angry, rebellious, depressed patient who comes from a severely disrupted family.

Even though it is now easier to identify such patients, preventing fatal asthma can be an enormous task. No episode of asthma in a high-risk patient should be taken lightly, and prompt use of oral cortisone drugs is essential and life-saving.

Most if not all of these patients should be evaluated at a specialized asthma center.

New Studies On Asthma Morbidity And Mortality

Asthma morbidity (the need for emergency room visits or hospitalization) and asthma mortality increased dramatically in the 1980s in all developed countries, including the United States.

• What is causing this trend? Several possibilities include a rise in the prevalence or number of cases of asthma, an increase in the severity of asthma, a toxic effect of asthma medications, and widespread poor or neglected asthma care.
• Data from the National Center for Health Statistics suggest that the prevalence rate for asthma remained stable in the 1970s. After 1980 the prevalence rate for asthma in children, particularly those under age seventeen.
• Early doubled in some populations Hospitalization rates of children and adolescents have risen approximately 5 percent per year, with the largest increase found in children under age five.
• During the 1970s the asthma mortality rate of children and young adults ages five through thirty-four declined by approximately 8 percent per year. During the 1980s this trend reversed, and a 6 percent increase was noted annually.
• Asthma is more prevalent among black children ages six to eleven than among white children the same age. Nonwhites are three times more likely than whites to die from asthma. Until recently, there was little information dealing with these astonishing racial and geographic differences in asthma mortality and morbidity.

Dr. Kevin Weiss has identified four distinct geographic areas with higher rates of asthma mortality. These four geographic areas, New York City; Cook County, Illinois; Maricopa County, Arizona; and Fresno County, California, are very different locales.

• The first two are northern cities with heavy industry, Maricopa County surrounds Phoenix and Tucson, and Fresno County is an area with lots of farming and suburban activity. Surprisingly, Los Angeles, known for its large inner-city Hispanic population, was not one of the areas with a high asthma mortality rate.
• In Cook County (Chicago), 90 percent of all asthma deaths within one five-year period occurred in minority individuals, who comprise forty percent of the city’s population. In New York City, asthma hospitalization rates are much higher for Hispanics and Afro-Americans.
• New York City investigators have found a six- tenfold difference between asthma hospitalization rates and a twenty-fivefold difference in the asthma mortality rate from neighborhood to neighborhood. The highest hospitalization rates and the most asthma deaths are found in New York City’s poorest neighborhoods.
• Asthma morbidity and mortality are major health problems in Detroit, where asthma mortality increased in the 1980s despite a 20 percent decline in that city’s population. At one Detroit hospital, asthma admissions more than doubled, from 184 admissions, in 1985 to 409 admissions in 1988.
• Afro-American children comprised the majority of these admissions. Boston, or Suffolk County, which has the highest asthma mortality rate within Massachusetts, also has the highest percentage (25 percent) of nonwhite residents within the state.
• In February 1991 the NIAID launched a new five-year National Cooperative Inner City Study to study these alarming inner-city trends. This national cooperative effort will be conducted at eight medical centers in seven major U.S. cities.

The purpose of this study will be to determine the cause of increasing morbidity and mortality in urban children and develop a model for inner-city asthma care.

International Studies

The rise in asthma mortality is not confined to the United States. One Australian study analyzed 163 asthma deaths in Victoria, Australia. Surprisingly, one-third of these Australian patients had mild to moderate asthma, and only 60 percent had previously required hospitalization for asthma.

• Only thirteen of 163 deaths occurred in a hospital, and the terminal outside-of-hospital episode was sudden in nearly two-thirds of decedents. One-third of these asthma deaths were thought to be preventable.
• The causes of death included poor patient compliance, delay in seeking medical help, geographic isolation, and inadequate treatment of the final episode.
• The observations that one in every three asthma deaths occurred in patients with mild to moderate asthma and that 90 percent of the patients died outside the hospital indicate the importance of close follow-up and management in all patients with asthma, regardless of its severity.
• European investigators have demonstrated that the number of asthma deaths can be decreased if the patients are allowed to admit themselves to the hospital.
• In Paris, the number of asthma deaths went down sixfold when local ambulance services instituted a policy of immediately answering all asthma-related calls and transporting patients with relapsing asthma to a local hospital.

The Beta Agonist Debate

Are asthma drugs, especially beta-agonist drugs, contributing to the rise in asthma mortality rates? The debate over the role of inhaled beta-agonists in asthma deaths is a long and controversial one dating back to the late 1960s, when asthma mortality increased significantly in Western Europe, particularly in England and Wales.

• Investigators found that this increase in asthma deaths in England shortly followed the introduction of a high-potency pressurized beta agonist aerosol called Isoproterenol Forte.
• In 1967 United Kingdom authorities issued a warning on this pressurized aerosol, and asthma mortality rates declined significantly after it was removed from over-the-counter sales. English studies found that sudden and unexplained asthma deaths in young people were often associated with the excessive use of pressurized aerosols.
• Was this a direct effect of the drug, or did overreliance on the aerosol create a false sense of security and a delay in seeking medical care? This argument has continued for nearly twenty-five years.
• In 1979 an editorial in the Lancet stated, “There is a growing realization that pressurized aerosols were probably not the main culprit in the asthma epidemic of the 1960s.” This editorial went on to state that undertreatment of asthma and a delay in seeking care were the main causes of asthma mortality.
• In the early 1980s, a second asthma mortality epidemic was reported by New Zealand investigators. Like the English epidemic, the New Zealand epidemic also saw an increase in asthma deaths in young asthmatics.

Reports again implied that overuse of the inhaled beta agonist drugs may be playing a role in asthma deaths, particularly when they were used with theophylline medications.

• One review suggested that the widespread use of home nebulizers using high-dose beta agonists could be the culprit in this New Zealand asthma death epidemic.
• The New Zealand Asthma Mortality Study Group, which thoroughly reviewed 271 asthma deaths in 1985, could identify only nine cases in which excess use of beta-agonists may have triggered the death.
• This report again emphasized the risks of underutilization of effective treatment, particularly oral corticosteroids. The most likely explanation for the New Zealand epidemic was again that excessive reliance on modern-day inhalers resulted in a delay in seeking appropriate treatment during relapsing asthma.
• However, some authorities disagreed with these conclusions. Dr. Neil Pearce and his group from Wallington, New Zealand, proposed that the introduction of a newer, longer-acting, more potent beta agonist called fenoterol was a potential element in the second.
• New Zealand’s asthma death epidemic, as the increase in asthma deaths, coincided with the introduction of fenoterol to New Zea land.

Fenoterol, or Berotec, a much more potent beta agonist than those currently available in the United States, has 200 micrograms per puff, compared with the commonly used albuterol drugs, which deliver 100 micrograms per spray.

• Fenoterol is also a more potent stimulator of the beta-1 receptor and is more likely than albuterol to cause a rise in pulse rates or blood pressure.
• Additional fuel was added to this fire by a December 1990 publication in the Lancet by Dr. Malcolm Sears. This well-designed placebo-controlled study evaluated sixty-four asthmatic New Zealanders for six months.
• One group took their inhaled beta agonist (fenoterol) regularly; the other group used it strictly as needed or upon demand. The as-needed or on-demand group had fewer bouts of nocturnal asthma, less need for prednisone, lower bronchial reactivity, and better peak flow rates than those patients who used their beta-agonists regularly.
• Sears concluded that patients who use regular, round-the-clock inhalation of a beta-agonist drug have poorer control of their asthma than patients who use their inhaler only on demand or as needed.
• One attractive explanation for the poor control in the round-the-clock users was that patients using beta-agonists regularly may experience higher exposures to allergens and other inhalants that trigger asthma.

Sears strongly recommended that inhaled beta agonist drugs be used only on demand to relieve acute asthma. This paper generated heated discussions Editorial letters pointed out that findings should not be applied to all beta agonist drugs.

• Fenoterol is a much more potent beta agonist than shorter-acting drugs such as albuterol. In August 1991 another study involving beta-agonist drugs and asthma deaths was reported to the FDA and released to the public.
• This Canadian study, led by Dr. Walter Spitzer of McGill University, examined records of 12,031 asthmatics who took asthma drugs between 1978 and 1987 in the province of Saskatchewan.
• Spitzer found that the forty-four Saskatchewan patients who died from asthma were using twice as many beta agon: st inhalers as those who did not die from asthma. Patients using two canisters a month were 2.6 times more likely to die from asthma.
• Dr. Spitzer and his colleagues and the study’s sponsor, Boehringer-Ingelheim, felt that the potential cause-and-effect relationship between excess use of beta-agonists and increased death justified the release of these findings before his study was published in the medical literature.
• This report was widely covered by radio, television, and the national press, Critics of this report pointed out that many of the Canadian patients studied were using fenoterol, a drug not available in the United States.

Fenoterol is the same drug that alarmed investigators in New Zealand in the 1980s. Concerns generated by the media created justifiable anxiety among asthmatic patients and their families.

• The two major allergy organizations in the United States, the American College of Allergy and Immunology and the American Academy of Allergy and Immunology, responded by issuing news releases stating that there were not enough data to justify sweeping changes in the current beta agonist dosing recommendations.
• Dr. Edward O’Connell, then president of the American College of Allergy and Immunology, appropriately noted that doctors had been successfully and safely using beta-agonist drugs to treat asthma for more than ten years.
• The FDA also addressed this issue at a special hearing in December 1992. Experts at this hearing concluded that more studies were needed before recommending any changes in dosing guidelines.
• This Canadian study was eventually published in the New England Journal of Medicine (NEJM) in February 1992. Again, the results were widely and somewhat inaccurately reported by radio, television, and the national press.
• In their conclusions, the authors of this study stated that the possible explanations for the association between beta-agonists and asthma deaths include the following facts:

Patients with severe asthma are more likely to take more asthma inhalers,

• Beta-agonists may have adverse effects on the cardiovascular system,
• Beta-agonists may open up the airways too much and increase bronchial hyperreactivity, and
• Overreliance on beta-agonists may mislead the patient into thinking his or her asthma is under control and lead to a delay in seeking care.
• The editorial that accompanied this article pointed out that the study’s control group probably had less severe asthma than those who died from their asthma.
• The NEJM editorial notes that if patients with asthma become overly fearful of their beta-agonist inhalers, emergency rooms will soon become flooded with patients with acute asthma.

The first drug these patients will receive after they enter the emergency room will be an inhaled betà agonist! Inhaled beta-agonist drugs are still the most effective drugs for relieving acute asthma attacks and preventing exercise-induced asthma.

• These studies raise one important question: should physicians prescribe beta-agonist drugs, especially inhalers, on a round-the-clock or as-needed basis? I believe the answer to this question will fall into a gray zone.
• Many asthma-care providers now recommend cutting back on the around-the-clock use of inhaled bronchodilators in relatively stable patients with normal peak flow rates.
• Some patients with unstable asthma with wide fluctuations in peak flow rates will require more regular use of bronchodilators, particularly in the morning and at bedtime.
• The concerns raised about a drug such as fenoterol make it highly unlikely that this drug or others like it will receive FDA approval any time shortly until they have shown to be safe and effective in additional well-controlled studies.
• Preliminary studies with two newer beta-agonists, formoterol (Foratidyl) and salmeterol (Sero- vent), offer promise, as these drugs have a twelve-hour duration of action and may eliminate the need for the four to six-hour dosing of the shorter-acting beta-agonists.

The causes of asthma death are multiple. I do not feel that overuse of any one asthma drug itself is a major cause of asthma mortality. In this day and age, it is rare for patients to die in the hospital, where they receive aggressive high-dose drug therapy with all categories of asthma drugs.

• Patients develop a false sense of security when they repeatedly use bronchodilator drugs to reverse relapsing asthma, leading to a tragic delay in seeking care.
• Retrospective analysis of asthma deaths has shown that all too many patients stayed at home taking medications for hours and hours before they decided to go to their local hospital. Patients with home nebulizers may be at special risk in that they can develop an even stronger but equally false sense of security.
• I feel that overreliance on bronchodilators such as inhaled beta-agonists and oral theophylline, underutilization of corticosteroids, and a lack of appropriate environmental controls are the three major causes of the increase in asthma morbidity and mortality.