"Was It Something I Ate?" Asthma and Food Allergies

Food allergies are on people’s minds and in the news. Along with other diseases such as allergic asthma, eczema (aka “atopic dermatitis”), and allergic rhinitis and conjunctivitis (aka “hay fever”), food allergies are common (affecting about 7% of children in the United States) and seem to be on the rise. What are food allergies and how can they relate to asthma? Answering these questions is the goal of this first of a three-part blog entry.

Part 1:

Just what are food allergies? Getting the terms straight.

Studies show that a lot more people think they have food allergies than actually do, but that’s not necessarily because people overcall problems. Rather, it has to do with how the term “food allergy” is defined by western medicine as opposed to its common usage.

In medical parlance, when something unpleasant or harmful happens to a person after eating a particular food, it is referred to as an “adverse food reaction” (AFR). AFR is a broad category, and true food allergy is but one subset of the big AFR group. That is, all food allergies are AFRs, but there are real AFRs that are not allergic reactions. In our more relaxed, common way of speaking, however, we often use the words “food allergy” when we are referring to any kind of AFR.

Here’s an analogy that might help. Consider the set of AFRs to be like the set of motor vehicles. This big group of motor vehicles includes cars, trucks, vans, motorcycles, and mopeds. Maybe it even includes construction vehicles like steamrollers or water craft like speed boats. Now imagine a subgroup of motor vehicles, say trucks. Clearly all trucks are motor vehicles (that is, they belong to that larger set). But there are also motor vehicles that are not trucks (for example, mopeds and steamrollers). So the large category of AFRs is like the large category of motor vehicles, and the subset of true food allergies is analogous to the subset of trucks. The problem arises when someone says “I have a truck” when what that person really meant was “I have a motor vehicle,” because in a colloquial way of speaking we are less rigorous with our terms. That’s why a lot of people report having a food allergy – what they are really saying is “I have an adverse food reaction," and only some of them have a true allergy according to the strict definition.

This is where the analogy above breaks down. Most people who have a motor vehicle can instantly tell whether it is a truck or not – just look at it and one can answer the question, “Is this motor vehicle in the truck family?” Most of us carry around some criteria for answering that question – a truck is the sort of motor vehicle that has at least four wheels, a truck bed, one of a few body shapes, etc.  But how does someone know if his or her AFR is in the family of true food allergies? What are the criteria for that? Turns out it’s not so easy (or impossible) to tell if an AFR is a true food allergy without considering the classic symptoms. And while we’re at it, what does food allergy have to do with asthma anyway?

What are the symptoms of a true food allergy?

After that overly long introduction, it’s time to get down to the real stuff. If food allergies are a subgroup of AFR, exactly what qualifies an AFR to be called accurately a true food allergy? How can we decide if a person is really allergic to a food?

True food allergies are reactions caused by part of the immune system responding to the presence of one or more particular foods taken into the body. These reactions typically occur within a few minutes to a few hours of ingestion of the trigger food(s). So right off the bat, if a person complains of a food allergy causing symptoms a week after he (one time) ate some particular food, we can tell him that he may have had an AFR, but he probably does not have a real allergy to that food

Almost all allergic reactions to a food somehow involve the skin or the moist linings of the body such as the mouth (those moist linings are referred to as “mucous membranes,” “mucosal surfaces,” or “mucosae” for short) with symptoms like itching, flushing, hives, or swelling. Since the food allergen causing the reaction is typically eaten, a lot of food allergic patients have nausea, vomiting, cramping abdominal pain, or diarrhea. When more severe, people may become lightheaded or even faint.

But this blog post wouldn’t be complete if it didn’t mention asthma. People, especially those with known asthma, who experience an allergic reaction to a food can rapidly develop shortness of breath, wheezing, cough, and chest tightness – the classic symptoms of asthma. So while respiratory infections, cold air, exercise, and airborne allergens are among the “most likely suspects” in an asthma attack, add food allergens to the list in some people.

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What Exactly Is "Reactive Airways Disease" Anyway?

“I think that she has a component of reactive airways disease,” the doctor said, describing her otherwise healthy 22-year-old patient with a lingering cough and chest tightness after a respiratory tract infection. “That’s why she has this persistent, wheezy-sounding cough. I’m going to prescribe a bronchodilator and some inhaled steroids.”

“Reactive airways disease.” What is that? I think that I know what the doctor means, but it is hard to be sure. She probably means that following a viral respiratory infection, her patient has sensitized, inflamed bronchial tubes, with asthma-like “twitchiness,” that will benefit from anti-asthmatic medications to relax bronchial smooth muscle (bronchodilators) and suppress airway inflammation (inhaled steroids). And maybe she is correct. But I object to the term, “reactive airways disease,” used to describe what is going on in her patient’s bronchial tubes. Here’s why.

Although I agree that the patient has lingering symptoms and probable airway inflammation following her respiratory infection, I wonder does she really have a “disease” that is being diagnosed other than a viral bronchitis? A disease characterized by “reactive” (that is, constricting more easily than usual) airways? Isn’t that asthma? “Reactive airways disease” sounds to me like “Asthma-like,” or “Asthma-light,” or perhaps “Asthma-but-I’m-not-sure.” But medical providers have the tools available that will allow us to determine whether she has asthma or not. Peak flow measurements, spirometry, exhaled nitric oxide concentration, and bronchoprovocation challenge – there are multiple tools at our disposal.

I understand that in children too young to perform pulmonary function testing, in whom transient wheezing (without asthma) is common and asthma can be difficult to diagnose with certainty early on, the term “reactive airways disease” makes sense as a kind of “place holder,” until the presence or absence of asthma becomes clearer. But the patient we are discussing is 22 years old. Does she have asthma or not? I think that we should be as clear as we can about her diagnosis, rather than slip into the vagueness and ambiguity of “reactive airways disease.”

Why send patients home thinking that they have a newly-diagnosed disease to deal with, when what they have is a lingering cough following a viral respiratory infection, maybe associated with transient bronchial hyperresponsiveness, which will improve with time and/or with our medications?

Yes, but what about that wheezy cough, or wheezing when the patient was asked to breathe out forcefully? Doesn’t that point to something more than an ordinary cough following a cold? Maybe, and maybe not. Let’s check her lung function. If it is normal, then the wheezing is probably not due to asthma with its diffuse airway narrowing involving thousands of bronchial tubes but to central or upper airway narrowing as can be seen in healthy individuals on forceful exhalation and cough, when pressures inside the chest tending to compress bronchial tubes are particularly high. On the other hand, if lung function testing demonstrates airflow obstruction, we have made a diagnosis of asthma (not reactive airways disease). As the maxim goes, “not all that wheezes is asthma” … and not all that wheezes is a disease.

Another reason to avoid the expression, “reactive airways disease,” is that it can easily be confused with reactive airways dysfunction syndrome or RADS, an accepted medical term used to describe a form of occupational asthma. Most occupational asthma develops after many weeks and months of exposure to an inciting inhaled irritant or allergen. On occasion, a single, particularly intense or toxic exposure can cause airway injury and hyperreactivity, referred to as reactive airways dysfunction syndrome, in which the sufferer newly develops asthma after the exposure. I’m not sure that reactive airways dysfunction syndrome is ideal terminology either, but it has a clearer definition and has acquired a more precise meaning than reactive airways disease. The term, RADS, will likely stay, whereas in my opinion we can let the expression “reactive airways disease” go when speaking of adults with cough and wheeze.

New Medications for Asthma

It feels as though there has been a paucity of new medications released for the treatment of asthma. The first of the leukotriene modifiers was made available in 1996; and the anti-IgE monoclonal antibody (omalizumab) came on the market in 2003. There is a short list to mention of newly-released medications since that time, and even then we’ll have to borrow some from the therapeutics of COPD.

New inhaled steroids: Some of you may remember the inhaled steroid, flunisolide, marketed as Aerobid. For some people, it had an unpleasant taste, leading to development of a menthol-flavored version, Aerobid-M. Both brands disappeared with the banning of sale of metered-dose inhalers with chlorofluorocarbon (CFC) propellants, but flunisolide has recently re-appeared in a metered-dose inhaler formulation with hydrofluoroalkane (HFA) propellant, called Aerospan. Unlike other inhaled steroids currently on the market, it is available in only one dosage: 80 mcg/puff. The dose is notably less than its predecessor, Aerobid, which was 250 mcg/puff. The unique feature of the new Aerospan inhaler is a built-in, small-volume spacer, reminiscent of the old triamcinolone inhaler with built-in spacer, Azmacort, that was very widely popular in the 1980s and 1990s (before it too succumbed to the ban on CFCs). Aerospan is approved for children age 6 years and older.

A second newly-released inhaled steroid is fluticasone furoate (Arnuity). A variant of the widely used fluticasone propionate (Flovent), it has been approved for once-daily dosing. The only other inhaled steroid approved by the FDA for use once daily is mometasone (Asmanex), although in truth many patients with mild asthma seem to maintain adequate asthma control when taking their inhaled steroid (regardless of which agent) once a day. Fluticasone furoate is available at two doses (100 and 200 mcg/puff), thereby providing a relatively low daily dose. It has been made available in the novel dry-powder device called Ellipta, which seems exceedingly easy to use. The device is fully prepared when the cover is rotated 90 degrees to expose the mouthpiece. The medication is then inhaled with one deep breath … once a day … and the cover rotated back to close the device. There is a built-in dose counter on the Ellipta which displays the number of remaining puffs with large, easily viewed numbers. This medication has been approved for use in children as young as 12 years of age.

Coming soon? And that’s it for new, approved asthma medications. But let me mention in addition two medications currently approved only for the treatment of chronic bronchitis and emphysema (COPD) that may find their way into asthma care in the near future. One is the anticholinergic bronchodilator, tiotropium (Spiriva). We have previously written in this blog about the observation that this once-daily, long-acting bronchodilator can be used in place of or in addition to the long-acting beta-agonist bronchodilators, salmeterol and formoterol, as add-on therapy to an inhaled steroid in patients with difficult-to-control asthma or among those intolerant of the long-acting beta-agonists. Although not an FDA-approved indication for tiotropium, its use in asthma together with an inhaled steroid represents an alternative to the inhaled steroid/long-acting beta-agonist combinations that are Advair, Dulera, and Symbicort. What’s new here is that tiotropium has recently been made available as a soft-mist inhaler rather than the single-dose, dry-powder inhaler using individual capsules of medication loaded into a device (Handihaler) with each use. The soft-mist inhaler (called “Respimat”) has been used to deliver the combination medication, albuterol plus ipratropium (Combivent), and is now available as an alternative to the dry-powder device for delivery of tiotropium. Two inhalations from the soft-mist inhaler are equivalent to one capsule of the dry-powder preparation. Its major advantage is that each canister of the soft-mist inhaler contains 60 doses or a one-month’s supply. Each day’s dose does not need to be prepared separately. Tiotropium’s safety has not been tested or documented in children.

Finally, the once-daily inhaled corticosteroid mentioned above, fluticasone furoate, has been combined with an ultra-long acting inhaled beta-agonist bronchodilator, vilanterol, into a combination called Breo. These medications are delivered from the same multi-dose, dry-powder inhaler used with fluticasone furoate alone, the Ellipta. The once-daily inhaled steroid/long-acting beta agonist combination (Breo) has been approved for use in COPD; its package insert specifically indicates “not for use in asthma.” However, clinical trials in asthma sponsored by its manufacturer (GlaxoSmithKline) have documented the safety and efficacy of Breo in asthma; and an FDA Advisory Panel has recently voted in favor of giving approval to Breo for treatment of asthma.

If approved, Breo will be, in a sense, a once-daily Advair; that is, an inhaled steroid/long-acting beta-agonist combination delivered from a multi-dose, dry-powder inhaler. Although dosing is still to be determined, studies have explored two steroid concentrations: 100 and 200 mcg of fluticasone furoate combined with 25 mcg of vilanterol. Children as young as 12 years of age have been enrolled in these clinical trials.

And stay tuned: clinical trials are underway using a combination once-daily anticholinergic bronchodilator (umeclidium) combined with fluticasone furoate in a multi-dose, dry-powder inhaler in the treatment of asthma. It is a reasonable assumption that persons with asthma will be more faithful to daily medication use if their medications need to be taken only once a day ... as long as they are effective and have few side effects.

Suddenly Unable to Breathe

A young man came to see me the other day complaining of several episodes of frightening shortness of breath. The first episode developed quickly one day when he was leaving work. He had been tired that week, perhaps with early symptoms of a respiratory tract infection or perhaps his allergies were acting up, but his distress seemed to come on “out of the blue.” Quite abruptly, he recalled, he couldn’t breathe. His symptoms improved relatively quickly, such that by the time he arrived home 30 minutes later he felt all better, although frightened by such a severe attack.

He experienced several similar events over the next few weeks, many waking him from his sleep. He had no prior history of asthma, although he had a history of mild seasonal rhinitis. He experienced occasional post-nasal drip and had no symptoms of heartburn to suggest gastroesophageal reflux. He had never been told of asthma as a child, and he was a lifelong non-smoker.

When questioned more about his difficulty breathing, he was quite clear: he simply could not get air in or out of his chest. It was not that it was hard to empty the air from his chest, he said, it was that no air would move at all. He was given an albuterol inhaler to try, but found it difficult to use and in truth had not tried it.

He reported only minimal cough, no sputum production. He had not experienced wheezing, but recalled a respiratory sound that he made as his episodes gradually resolved. His wife thought that she too had heard a breathing noise, particularly when he tried to breathe in. They have two cats at home but noted no increased likelihood of symptoms when around the cats. In the absence of these attacks, he felt well and was able to work out at the gym without limitation due to his breathing. His only medications were vitamin D and glucosamine chondroitin.

His chest examination was normal. Chest X-ray was normal. Breathing tests (spirometry) performed at a time when he felt well was likewise normal. And the question was: is this asthma?

Asthma causes symptoms that come and go. Between attacks one can feel entirely well with a normal chest exam and normal lung function. However, the history that this young man offered was atypical in several ways, including no prior history of asthma; sudden severe attacks that came on without warning and resolved within a few minutes without treatment; and his sense that during these spells it was not hard to breathe, but impossible to breathe at all – no air movement in or out at all. As the episode abated, there came an inspiratory sound; and when asked if he could localize the site of his distress, he offered that he thought his problem was in his throat more than in his chest.

The diagnosis? Not asthma but laryngospasm – an alternative and more plausible explanation for these sudden attacks of difficulty breathing. Imagine that some irritant triggers the vocal cords to suddenly come together and tightly obstruct the upper airway. One cannot breathe (or talk), and it feels as though one were about to suffocate to death. One tries to inhale or exhale, but no air can pass the closed glottis. After what seems like an eternity but is probably well less than one minute, the laryngeal spasm begins to abate. As the vocal cords begin slowly to move apart, one can start to get air passed, with an inspiratory sound that we recognize as stridor. At first air enters the lungs with increased resistance through the narrowed upper airway, but over several seconds, as the laryngeal muscles further relax and the vocal cords abduct fully, normal breathing is restored. The entire event is over in a minute or two, and no medication is needed (or likely to help). An inhaled bronchodilator might be more irritating to the larynx and should probably be avoided.

What causes some people to develop laryngospasm is not known. Our young man had a normal ENT examination with direct laryngoscopy to exclude a structural abnormality of the glottis. His laryngeal sensitivity developed without prior trauma or other explanation. Potential triggers that may set off spasm of the sensitized larynx include mucus draining from the posterior pharynx, acid refluxed from below, cough with secretions expectorated at high velocity, or oro-pharyngeal aspiration.

Preventing provokers of laryngospasm, such as laryngopharyngeal reflux, is an important treatment, especially in persons with frequent night-time episodes. Other management strategies that have been described include “rescue breathing” techniques taught by speech-language therapists; application of forward and upward pressure behind the earlobes and in front of the mastoid processes in what has been described as the “laryngospasm notch”; and, rarely, botox injections into the larynx.

In most instances, coming to understand the mechanism of the event is key to dealing with it: one needs to try to stay calm, attempt small breaths in through the nose, and perhaps visualize relaxation and separation of the vocal cords. Knowing that the spasm of the larynx will pass in a matter of seconds and that there will be no long-term harmful effect are the reassurances that we have to offer. Distinguishing these episodes from asthma attacks is also crucially important. Treatment with bronchodilators and corticosteroids will not bring relief or prevent episodes of laryngospasm. It only confuses the issue, obscures the diagnosis, and likely frustrates the sufferer.

"... and now I'm hoarse too"

Persons with asthma can have plenty of symptoms that they have to deal with, whether it’s shortness of breath, chest tightness, a noisy chest, or troublesome cough. At the same time nasal allergies can cause a stuffy or drippy nose, sneezing, or frequent throat clearing from post-nasal drip. And then we frequently hear about a hoarse voice. It often comes and goes and can be a considerable frustration, especially for those who do a lot of speaking in their work. The voice quality changes; people notice that your voice doesn’t sound the same, and sometimes it seems like more work to generate a normally loud voice. What is causing this problem on top of everything else?

There are a number of potential causes, just as in persons without asthma, such as trauma from repetitive coughing, gastroesophageal reflux disease (GERD) causing stomach acid to splash onto the vocal cords, or polyps forming along the vocal cords. But an important consideration in persons with asthma is hoarseness as a side effect from use of the medications, inhaled steroids. Examples include the inhaled steroids taken alone (Flovent, Pulmicort, Qvar, Asmanex, Alvesco, and Aerospan) as well as the inhaled steroids taken in combination with long-acting bronchodilator medicines (Advair, Symbicort, and Dulera).

You probably know that it is a good idea to rinse your mouth after using these inhalers in order to prevent a throat infection referred to as “thrush” or oral candidiasis, caused by the yeast, Candida. You cannot, however, rinse down to the level of your vocal cords, which sit behind your “Adam’s apple” in the middle of your neck. Some of the steroid medication that you are inhaling will settle on the vocal cords on its way down onto your bronchial tubes, with the possibility of causing irritation and voice weakness. This is an undesirable effect of the steroid medication – an “inhaled steroid-induced laryngitis.” It is more common when the medication is delivered by metered-dose inhaler rather than dry-powder inhaler, and it is probably more common when the dose of medication is higher. It occurs with all of the inhaled steroids, but not commonly with inhaled bronchodilators alone (such as albuterol), so it seems to be an effect of the medication, not the propellant or powder being inhaled.

No one knows exactly in what way the inhaled steroids affect the vocal cords to cause hoarseness. Some have thought that they cause a weakness of the muscles involved in bringing the cords together during speech; others have thought that there is irritation to the surface membrane that covers the cords. Occasionally, one can find candida infection of the vocal cords. The inhaled steroids do not cause throat cancer or permanent injury to the vocal cords.

Inhaled steroids are the cornerstone of long-term asthma treatment. They reduce symptoms, make the bronchial tubes less hypersensitive to the triggers of asthma, and help to prevent asthma attacks. Their increasingly widespread use is probably the reason for the reduction in asthma hospitalizations and deaths observed in the United States over the last 2 decades. Hoarseness is a frustrating side effect that affects some people who use these highly-effective medicines, even when they are doing everything right in their use.

What can be done? If you can safely omit use of your inhaled steroid for a period of time, your voice quality will return to normal. Sometimes it takes only a few days, sometimes a few weeks. You can try adding a spacer to your metered-dose inhaler or switching from a metered-dose inhaler to a dry-powder inhaler for delivery of your inhaled steroid. There is no good evidence that one inhaled steroid has fewer effects on the voice than any other, although there is some theoretic reasoning to suggest that ciclesonide (Alvesco) might cause less hoarseness. If your hoarseness is severe and persistent, it would be good to have a direct examination of the vocal cords performed by an otolaryngologist (ENT doctor), to exclude alternative reasons for your hoarseness. Meanwhile, we continue to seek better medicines to treat asthma -- effective and free of side effects.

E-cigarettes: smoking cessation aid or new addictive public health hazard?

“Vaping” is taking off in the U.S. and elsewhere around the world. With the encouragement of big tobacco companies, more and more people are trying electronic cigarettes as an alternative to tobacco-filled cigarettes. Should we be encouraged by the availability of a safe alternative to conventional cigarettes or dismayed by a new, addictive nicotine-containing product unleashed to the general public, including children, without regulatory oversight?

Why do we offer our opinion about e-cigarettes in a blog about asthma? We do so because: 1) many people with asthma smoke cigarettes, probably similar in frequency to the 19-20% of the general population who continue to smoke in the United States; and 2) we hate cigarette smoking! Our medical lives are filled to overflowing with smoking-related medical disasters, whether the slow suffocation of advanced emphysema or the horrible, inexorable death from incurable lung cancer (the cause of more cancer deaths in the United States than the next 3 most common cancer killers – colon, breast, and pancreas -- combined). Persons with asthma who smoke cigarettes put themselves in “double jeopardy,” with airway disease due to asthma combined with airway disease and emphysema due to cigarette smoking (chronic obstructive pulmonary disease or “COPD”), while at the same time interfering with the beneficial effects of some of the asthma medications (the inhaled steroids).

At first blush, then, we are inclined to embrace the idea of an alternative to cigarettes without the tar and other products of combustion that predispose to the development of cancer and other diseases, like heart attacks and strokes. As physicians, we are constantly seeking aids that can help persons who are addicted to cigarettes stop smoking. We have nicotine-containing patches, gum, nasal spray, and lozenges that we can recommend, even a small, nicotine-containing cartridge that can be placed in a plastic cigarette holder to inhale nicotine to the lungs (Nicotrol®). What’s wrong with a novel nicotine delivery system, the e-cigarette, which mimics smoking more closely, with a warm mist to inhale and a visible puff of smoke to enjoy “guilt-free?”

Well, here’s our list of what’s wrong with the e-cigarette:

• We don’t know exactly what is in the e-cigarette vapor. It contains nicotine, propylene glycol, often flavoring, and perhaps other chemicals. The amount of nicotine (and other chemicals) in each cartridge is not closely regulated. The long-term effects of inhaling this vapor into the lungs are unknown. Wouldn’t you like to know this information before promoting “vaping” as a safe alternative to cigarette smoking?

• One could imagine that widespread availability of e-cigarettes, aggressively marketed to children and young adults, could lead to an increase in persons addicted to nicotine and going on to take up cigarette smoking, rather than a decrease. We have witnessed over the last few decades a national change in attitude toward cigarette smoking, restricting smoking at work, in public places, in and around schools, restaurants, bars, airplanes, some hotels, etc. It is no longer the norm. What would the implication be of unrestricted use of e-cigarettes … at the workspace or restaurant table next to yours? What’s the risk of second-hand e-cigarette vapor exposure, anyway? We don’t know.

• Nicotine is highly addictive, even without all the other poisons in tobacco smoke. Do we as a nation need to offer inhaled nicotine as an unregulated drug, including to children, pregnant women, nursing mothers, persons with heart disease, and the elderly? Several countries around the world have banned the sale of e-cigarettes. Britain plans to regulate it as a medicine.

What should the U.S. Food and Drug Administration do, on our behalf?

We would favor making e-cigarettes available like the Nicotrol® inhalation system, with a prescription, to be used for the medical indication of smoking cessation. The FDA could closely monitor and control the contents of e-cigarettes and insist that the chemical components be clearly displayed on the product, like ingredients in a skin cream. The agency could also insist that medical studies be performed to ensure the short-term and long-term safety of the medication, or to develop clear labeling warnings about the potential health risks … as for other drugs. The manufacture and sale of e-cigarettes has already become a multi-billion dollar industry; there should be plenty of money to spare to do safety testing on the product, along with assessment of its effectiveness as a smoking-cessation aid.

The Forum of International Respiratory Societies, a consortium of professional respiratory societies and experts in respiratory medicine from around the world, recently released a position statement regarding electronic cigarettes. They recommended a ban on the sales of e-cigarettes; or if not a ban, regulation as medicines; or if not regulated as medicines, regulation as tobacco products. The publication is in press; an abstract is available at the following link: http://www.atsjournals.org/doi/abs/10.1164/rccm.201407-1198PP