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Asthmatics more at risk for related diseases

Asthmatics more at risk for related diseases

The Mayo Clinic recently completed a long-term study of asthma and other inflammatory illnesses, including inflammatory bowel disease (IBS), rheumatoid arthritis, diabetes and coronary heart disease. They found that asthmatics had a greater incidence of these other four inflammatory conditions than non-asthmatics in their study.
There was roughly a 20 percent greater likelihood for these other four illnesses in asthmatics. This is a very strong association that had only previously been suspected.  The Mayo study done in thousands of people indicates just how compelling this association is.
The researchers had two conclusions:
First: Physicians who treat asthmatics should be aware of the greater risk their patients have for other inflammatory diseases.
Second: More basic research needs to be done to ferret out the underlying causes for inflammation as a disease instigator.
White blood cell type counts

White blood cell type counts

An article in The American Journal of Respiratory and Critical Care Medicine discussed recent research of the heterogeneity or diversity of asthma. The thrust of the research project was to try to explain the variable benefit that asthmatics receive from inhaled corticosteroids.

It has been observed for quite some time that while many asthmatics show a marked improvement in their breathing with the use of inhaled steroids, there are others whose response to steroids is modest or nonexistent. Inhaled steroids have been a mainstay in asthma management for years. Because it is known that asthma occurs due to inflammation in the airways, steroids are potent anti-inflammatories and, hence, the predictable nature of their benefit.

Inflammation is defined as the incursion of white blood cells from the blood stream into the inflamed tissue. As it turns out, the type of white blood cell found in asthmatics determines how they respond to steroids. If the white blood cell is an eosinophil, then the patients have greatly benefitted by the inhaled steroids. If the white blood cell is a neutrophil, then steroids have been much less effective.

The researchers used a relatively test called sputum cytology. They collected multiple samples of sputa from a large number of asthmatics. These were sent to a special pathology lab to determine the type of anti-inflammatory cell: eosinophil or neutrophil. The researchers had already separated the asthmatics into groups of “steroid responders” and “steroid non-responders.” The two groups matched up perfectly with the cell type eosinophil or neutrophil respectively.

Food choices vs. kids’ allergy/asthma:

Food choices vs. kids’ allergy/asthma:

The British Medical Journal recently published the results of a huge international study on allergy termed ISAAC (International Study of Allergies and Asthma in Children). The study was undertaken to evaluate the effects of dietary choices on asthma and allergy. The findings were rather startling.

Basically, a healthy diet prevented problems and an unhealthy diet led to problems. There was a very strong preventive benefit from regular consumption of fruits and green vegetables. Both are a rich source of antioxidants which are known to have a beneficial effect on the immune system. Regular fish consumption was also associated with lower incidence of allergy and asthma.

On the other hand, diets rich in fat led to allergy and asthma. Especially bad in this regard were fast foods such as burgers, fries and sodas. Saturated fatty acids destabilize the immune system, whereas N-3-polyunsaturated fatty acids (found in fish) have natural anti-inflammatory properties.  

The investigators concluded that the “Mediterranean diet” is a model diet for general and allergic health. The Mediterranean diet is high in fruits, vegetables, fish, olive oil, tomatoes, grape/raisin products, and nuts.

For millions of asthmatics, hopeful gene therapy studies

For millions of asthmatics, hopeful gene therapy studies

The lead article in The New England Journal of Medicine in September discussed novel research on genetic variation in asthma. More than 300-million people worldwide have asthma, and up to 20 percent of these show poor or no response to corticosteroid medication, which is usually their main controller medicine.

Researchers at Harvard speculated this lack of response to corticosteroid medicines might be genetically linked and they sought to find the gene.

By screening 530,000 single-nucleotide polymorphisms (SNPs – pronounced snips) in a large group of asthmatics they discovered one SNP called rs37973 that showed up in the non-steroid responders. Furthermore, they discovered that rs37973 decreases the effectiveness of gene GLCCI-1, which is the gene that controls response to steroids.

Their hope is that new therapies will soon be discovered that “up-regulate” (turn on) the depressed GLCCI-1 gene.

More lung injury from smoking

More lung injury from smoking

Researchers at the University of Alabama Medical Center have discovered a new reason cigarette smoke causes lung damage.

They found that smoke inhibits leukotriene A4 hydrolase (LTA4A). This molecule is important in shutting down white blood cells following a successful response to inflammation. By not shutting down white blood cells, smokers experience ongoing inflammatory damage to the lung and airways; this leads to COPD and emphysema.

The same researchers also discovered previously unknown substrata of LTA4H called proline-glycine-proline (PGP), which actively recruits white blood cells into lunch tissues.

Discovering these two molecules naturally helps understand how smoking injures lungs, but may also lead to research that allows manipulating these molecules to reduce lung injury.

This could be of benefit not only for smoke-related lung disease, but also for other inflammation problems such as asthma and cystic fibrosis.

LTRA’s

LTRA’s

 

The lead article in a recent issue of the New England Journal of Medicine was on leukotriene antagonists in treating asthma. The lead-article status reflects the importance of this research.

As reported, scientists at the University of Aberdeen, U.K., evaluated leukotriene antagonists in two ways.

The first part of the study compared the adding of inhaled steroids to the adding of leukotriene antagonists as add-on therapy for control of asthma. In the hundreds of patients they studied, the researchers found the two therapies to be equally effective. Both restored asthma control so that symptoms improved and the need for rescue medication was reduced.

The second prong of the study looked at patients who were already on an inhaled steroid but still needed more controller help. Again the patients had additional therapy either in the form of a leukotriene antagonist or a long-acting bronchodilator (Salmeterol).

Both groups improved with the add-on medication, and the improvement was similar in both groups.

The leukotriene antagonist used in this study was montelukast (Singulair), but there are two other drugs in this family – Accolate and Xyflo. They work by reducing the inflammation that causes asthma. This is also how steroids work.

Bitter Might Be Good!

Bitter Might Be Good!

The University of Maryland Medical School has discovered taste receptors found on the tongue are also in human lungs. The specific receptor in the lungs is for tasting bitterness.

Of exceeding interest is the lung receptor being connected with the muscle that regulates airway contraction and relaxation.

The Maryland scientists feel they can help treat asthma by manipulating the bitterness receptor.

Perhaps this will mean lemon or rhubarb inhalers!

Effective therapy; no increased risk with asthma

Effective therapy; no increased risk with asthma

Inhaled corticosteroids are an important therapy for a variety of lung conditions, especially Chronic Obstructive Pulmonary Disease (COPD) and asthma.

It has been known for several years that inhaled steroids increase the risk of pneumonia in patients with COPD. Whether this is also true in asthmatics has not been studied.

A recent research paper in the Journal of Respiratory and Critical Care Medicine indicates that inhaled steroids do not raise the risk for pneumonia in asthmatics. In the cited clinical trial involving 15,000 children and adults with asthma there was no increased risk for pneumonia.

A second study looked at low-dose versus higher-dose inhaled steroids in asthmatics and there was no increase in risk in the high-dose group.

Asthma study shows common airway barrier, adds to bank of asthma knowledge

Asthma study shows common airway barrier, adds to bank of asthma knowledge

Last month the lead article in the New England Journal of Medicine was titled “A Large-Scale, Consortium-Based Genome-Wide Association Study of Asthma”, and was from work done by the National Heart and Lung Institute in the U.K.

It was a detailed, in-depth study that led to two major findings: First, asthma is genetically heterogenous.  This fact accounts for the variability in the illness itself, and also to the variability in response to treatments.  That is, when an inhaler that works beautifully in one asthmatic fails to help a second person, the reason may well be that they have two different asthmatic illnesses based on genetics.

On thing in common for all the asthma genes is that they all seem to lead to a defect in the epithelial barrier of the airways.  This faulty barrier leads to damage from the adaptive immune system, and the resultant airway inflammation.  Reason?  Because viruses, bacteria and allergens can more easily invade these porous airways.

The second finding was that elevated levels of IgE are not the seminal cause for asthma, but rather occur in response to this airway porosity with resultant greater exposure to allergens.

Still, this finding does not negate the fact that therapies directed at elevated IgE are exceedingly helpful in treating asthma.

This research will lead to greater efforts at altering gene defects, and also at means to improve the airway epithelail barrier function.

Asthma Research: Steps to New Treatment

Asthma Research: Steps to New Treatment

The National Institutes of Health (NIH) just finished a study on poorly controlled asthmatics. Asthma by its very nature is a condition that tends to wax and wane. When asthma worsens the standard medical approach is called step therapy; that is, whatever the current therapy is, additional steps are taken to regain control. These steps involve the addition of extra controller medicines.
Over the past few years a common step that’s been taken is to add a long-acting bronchodilator (LABA) to the use of an inhaled steroid. For example, someone on Flovent inhaler would step up to Advair (Flovent plus the LABA Salmeterol), or someone on Pulmicort inhaler would step up to Symbicort (Pulmicort plus the LABA Fomoterol).
Another approach is to double the inhaled steroid. If someone is on two puffs of an inhaled steroid twice a day, he or she is told to increase to four puffs twice a day, or a different, stronger inhaled steroid is used.
The NIH study compared these two standard options to a novel one, which is the addition of Tio tropium bromide to an inhaled steroid. Tio tropium is an anti-cholinergic medicine that has been used for years to help people with Chronic Obstructive Pulmonary Disease (COPD). The cholinergic nerves that innervate the lungs cause broncho constriction (airway narrowing) and excess mucus production. Blocking these nerves through an anti-cholinergic dilates airways and reduces excess mucus.
The NIH compared the three different steph in terms of regaining asthma control. All three steps worked. The mildest benefit came from doubling the steroid dose. The best effect came from adding a LABA or Tio tropium, with the latter being the more effective step.
The reason this study was done is that although LABA therapy has been extremely effective over the years, some people have not tolerated the medicine due to side effects such as tremor, anxiety, and rapid heart rate. Also, doubling the inhaled steroid works, but there is greater likelihood of systemic steroid effect from using higher doses.
As of now, the Food and Drug Administration has not approved Tio tropium for asthma, but experts expect this approval to be forthcoming.