Saturday, August 22, 2015
Friday, August 7, 2015
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.
“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.
Sunday, March 29, 2015
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.
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.
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