HAE drug works for ACE problem

It is hoped that recent research into expanding the use of a targeted, expensive drug could bring financial relief to many who share symptoms with those covered by the drug’s current restrictive application.

At issue are serious symptoms caused by ACE-inhibitor-induced angioedema. The drug studied is Icatibant (brand name Firazyr), but its only approved application at present is for Hereditary Angioneurotic Edema, or HAE — a rare, but significant disease.

People with HAE suffer repeated bouts of swelling (angioedema) of different body parts, from lips and tongue to throat and even the intestines. The attacks can be severe and occasionally life-threatening when the airway is compromised. They are caused by the build-up and release of bradykinin, a powerful vasodilator. Icatibant works by blocking the tissue receptor where bradykinin exerts its mischief.

Not so rare is ACE-inhibitor-induced angioedema, which also occurs because of a build-up and release of bradykinin. Unlike HAE in which any part of the body is susceptible to swelling, ACE angioedema tends to occur primarily around the head and neck — lips, tongue, face, palate and throat.

Also unlike HAE which is caused by a genetic deficiency in an enzyme, ACE angioedema is caused in susceptible individuals by the medications called ACE-inhibitors, which are antihypertensives. At the current time the only FDA-approved use of Icatibant is in HAE; therefore, using it in ACE-angioedema would be an “off-label” use.

Which comes around to the crazy world of insurance. At this point insurance carriers will only cover the cost (roughly $8,000 per dose) for people with HAE. Hopefully, this research study will change things, as ACE-angioedema is a common reason for emergency room visits.

Dear Doc: Wheezing when exercising? Learn facts

Dear Dr. K: I wheeze when I exercise. Does that mean I should stop aerobic activities?

 The unequivocal answer to your question is “no” — and I’m sure Roger Bannister would second my answer.

Roger Bannister was the first runner to break the 4-minute mile. What many people don’t know is that he was a medical student when he performed that feat. (Pun intended.) In fact, in the 1950s when he broke four minutes the physicians at that time were mistakenly telling asthmatics not to exercise. Bannister actually changed that approach because of research he did in exercise physiology. He learned that exercise itself might stimulate wheezing with the activity but in the long run (pun intended), it helped lessen the asthma tendency.

Exercise can bring on wheezing for several reasons: airway cooling, airway dehydration and inhalation of allergens and pollutants. The latter is not surprising as the mouth breathing associated with aerobic exercise leads to inhalation of non-filtered air (bypassing the nose and sinuses).

Certain situations are more likely to elicit wheezing: running in cold/dry air, swimming in heavily chlorinated pools and biking along exhaust-laden roadways.

Sometimes exercise-induced asthma manifests as a cough rather than wheezing. This cough can happen during the activity or afterward (when it is known as “locker-room cough”).

The most important fact about exercise-related asthma is that improved aerobic conditioning lessens the asthmatic tendency and, in effect, “strengthens the lungs.”

General measures to manage the problem include identifying triggers such as high chlorine levels or pollutants, and avoiding them. Avoid exercising in extreme cold or dryness and engage in pre-exercise warm-up. For runners, if the asthma occurs while running fast, slowing the pace for a while can allow you to “run through” the asthma.

Finally, using an inhaled bronchodilator prior to exercise often eliminates the problem entirely.

Sleep apnea in asthmatics needs closer attention

Tough news reported in research results recently published in The Journal of the American Medical Association that persons with asthma were twice as likely to develop sleep apnea as non-asthmatics.

The study was done at the University of Wisconsin and involved thousands of people over a 25-year period. Sleep studies were done every four years in order to observe the frequency with which sleep apnea developed.

The striking outcome was compelling because asthma itself is a frequent cause of disturbed sleep. Hence, if the asthma gets blamed as the sole cause for nighttime wakening, the sleep apnea will go undetected and therefore, untreated.

The Wisconsin researchers suggested greater awareness of this possibility in asthmatics, their families and their doctors. If family members report snoring or apneic episodes, or if the patient has daytime somnolence, a sleep study should be considered.

Xolair in pregnancy studied

The University of North Carolina recently completed a study of the use of Xolair (Omalizumab) in pregnancy.

Xolair is a monoclonal, anti-IgE antibody that is used as an add-on-therapy for moderate to severe asthmatics not adequately controlled with inhaled steroids.

Asthma is a common condition affecting roughly 10 percent of pregnant women. It is well known that poorly controlled asthma during pregnancy increases the risk for congenital anomalies, perinatal mortality, low birth weight and prematurity.

Xolair has been a welcome addition to the asthma treatment tool box, but up until now its safety in pregnancy was not known.

Although the study group was small — 191 women — the outcome indicated that Xolair does not appear to increase the risk for the fetus beyond that seen in the general asthmatic population.

Q – Tips: Smoking

  • A recent study by the CDC (Center for Disease Control) reveals greater risk for death from smoking as related to diseases not previously tied to tobacco use: renal failure, intestinal ischemia, hypertensive heart disease and breast and prostate cancer.

Perhaps shared therapies can ease double suffering

What’s known as the Asthma-COPD overlap syndrome was reviewed recently in the Allergy and Asthma Proceedings.

The authors adroitly point out that even though physicians try to pigeon-hole diagnoses, many times people’s health problems don’t fit neatly into a single diagnostic category. This is especially true in the spectrum of chronic airway disorders.

More and more people are being seen by physicians who have both asthma and COPD. The conditions are both similar and different.

In general, asthma (also called reversible airways disease — RADS) is completely reversible with therapies, while COPD (chronic obstructive pulmonary disease) is never (by definition) completely reversible; hence, the adjective “chronic.”

Both conditions are caused by inflammation in the airways. In asthma, the inflammatory cell is the eosinophil, while in COPD it is the neutrophil.

Both conditions tend to have genetic links. In asthma it is the genes that cause allergy. In COPD it is the genes that control alpha-1-antitrypsin (an enzyme that protects the lungs from oxidative stresses).

In general, asthma tends to have onset in childhood, whereas COPD occurs in adults.

Asthma is caused primarily by allergy to inhaled pollens, molds, danders and dust mites. COPD is caused primarily by cigarette smoke and biomass pollutants.

Finally, diffusion capacity is normal or high in asthma, but always reduced in COPD. Diffusion capacity is a measurement of the transfer of oxygen from the lungs into the blood stream.

The most important take-home message is that therapies that were previously used exclusively for one diagnosis may work in both because of the overlap. For instance, inhaled steroids which are a mainstay in the treatment of asthma often benefit patients with COPD.

Also, anticholinergics such as Atrovent, Combivent and Spiriva – originally designed exclusively for COPD – may also benefit people with the overlap syndrome. The bottom line is for patients and physicians to be aware of the overlap, and to look for therapies that are individually stylized to a given person’s need.

Dear Doc: Will oral doses replace allergy shots?

Dear Dr. K:

I’ve read about the newly available oral drops for allergy. Could that replace my current allergy shot?

A quick answer for you is “no;” a longer answer to your question is “perhaps in the future.”

The reason I say “no” is that your current allergy shot contains extracts for nine different grasses, including, Bahia; seven different molds, ragweed and three other Florida weeds; plus seven different trees, including oak.

Right now drop therapy is only available for single allergens and these are extremely limited in their spectrum. For instance, the only serum for grass is for Timothy grass. We have Timothy grass in Florida, but it is a minor contributor to our grass pollen burden, as opposed to the Bahia Grass family and Bermuda grass. The only weed extract available is for short ragweed, one type we have in Florida. More prominent, however, are the giant and southern ragweed plants. And so it goes . . .

It has been known for more than 100 years that allergy immunotherapy works best when all the relevant allergens are addressed.

Another issue is cost. At present, the oral therapy is quite expensive and is not being covered by insurance companies. Part of the reason for the expense is that drug therapy must be done daily requiring a lot of allergy serum.

Finally, like any new modality “the bugs need to be worked out.” One “bug” is that up to 50 percent of people taking oral treatments have unpleasant side effects of mouth and tongue itching, along with stomach upset. These side effects are occurring with just one allergen in the serum so when multiple allergens are available, these problems could become greater nuisances.

Technology always seems to improve current standards, so I have no doubt oral therapy will eventually join allergy shot therapy and perhaps replace it, but there is a long way to go.

GI Tract – gut flora’s humble abode


A recent review article in the Journal of Allergy and Clinical Immunology addressed the role of gut microbiota in health and illness.

The author pointed out that the GI tract serves two main functions: 1. Digestion and absorption of foods and nutrients; 2. Immune function. He also pointed out that these don’t operate independently, but rather, are fully intertwined.

The GI tract is the home for the majority of our immune system cells and proteins. This is so because the GI tract is home to billions of microbes that require immune surveillance. Disruptions in these microbes can impact both digestion and immune function.

One example is celiac disease. It is an inherited condition caused by autoimmunity directed against gluten. New research is finding that despite the inherited tendency, many individuals won’t develop the disease if their gut bacteria are normal.

On the other hand, the more disrupted the gut flora, the more likely that the immune system will cause the inflammation that leads to the disease. Sadly, once the disease starts, it leads to greater alteration in the gut flora, which in turn leads to more inflammation – a bad synergism.

Another example is obesity and metabolic syndrome (insulin resistance and high lipids). Two broad observations are relevant: 1. Children who receive multiple courses of antibiotics are more likely to become obese than children who don’t (antibiotics alter gut flora.) 2. Societies whose cows, beef, chickens and pigs receive antibiotics with their food are also more likely to become obese than those who don’t.

In a similar vein, gastric bypass surgery is more effective at both weight loss and improvement in metabolic syndrome than is lap-band surgery. The former leads to a positive improvement in gut flora not seen with lap-banding.

Even more interesting is the fact that in gastric bypass, patients the metabolic syndrome improves even before there is any noticeable weight loss. The bad gut bacteria breakdown fats into more easy-to-absorb particles, hence greater weight gain and higher cholesterol levels.

Finally, in mice experiments: Transfer of healthy gut bacteria from lean mice to obese mice leads to weight reduction in the latter without reduction in caloric content.  

Q – Tips: Exercise as important as medication

  • An editorial in the American Journal of Medicine was titled “Exercise is Just as Important as Your Medication.”

The article was very detailed in extolling the numerous health benefits of exercise, but one comment struck me most of all: The editorialist pointed out that unfortunately, physicians or patients themselves set too high a benchmark for the activities. He recommended an approach that was moderate in nature and stylized for each person’s health constraints and abilities.

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