State of the art: Asthma treatment effects on airway remodeling

In this month’s issue, Durrani, Viswanathan, and Busse take a look at what we know – and what we don’t know – about the effects of asthma therapy on airway mesenchymal-epithelial remodeling in asthma (J Allergy Clin Immunol 2011;128:439-448). After summarizing the current information about remodeling mechanisms, Durrani et al. discuss the effects of specific asthma drugs.

Airway remodeling is known to occur in some asthma patients, but the authors point out that it is not linked to any clinical indicators. While remodeling is considered to contribute to the pathology of asthma, the causal relationship has not been confirmed. Typically, remodeling has been considered a response to chronic inflammation and dysregulation of repair mechanisms in the lung, so it has been suggested that treatments aimed at reducing inflammation would impact remodeling. Durrani et al. note that this concept has not held out, in light of evidence that suggests remodeling occurs in parallel with inflammation, as well as clinical data that traditional therapies, such as ICSs, are not effective for all asthma patients. Of interest, they comment that there is new evidence that remodeling is a direct response to increased inflammation during asthma exacerbation, supporting the idea that remodeling and inflammation are concomitant. The authors then focus their review on what is known about effects of asthma therapies on aspects of remodeling, such as airway smooth muscle (ASM) hyperplasia, subepithelial fibrosis, and goblet cell hypertrophy.

Inhaled corticosteroids. Durrani et al. discuss several studies that have reported positive effects of ICSs on elements of airway remodeling, such as decreasing reticular membrane thickening, goblet cell hypertrophy, and vascular remodeling. They note that the same is not true of ASM hyperplasia and epithelial injury and detachment where both positive and negative effects have been observed.

Combination treatments. The authors discuss in vitro studies that have shown that ICS+LABA combination products are more effective than monotherapy with either on matrix deposition in human fibroblasts. Another study reported decreased airway wall thickness and epithelial growth factors in asthma subjects on combination product. The authors are cautiously optimistic about these findings, but note a paucity of research specifically evaluating the effects of ICSs+LABAs and LABAs alone on airway remodeling mechanisms.

Monoclonal antibody therapy. Reviewing studies on omalizumab, mepolizumab, and golimumab, Durrani et al. comment on the lack of direct evidence suggesting that mAb therapy mitigates airway remodeling, even though there are reports of mAb decreasing inflammatory cytokines, eosinophilia, and exacerbations, all of which have been associated with remodeling.

The authors briefly cover other therapies, such as leukotriene antagonists and tyrosine kinase inhibitors, before concluding that pivotal pathways in remodeling need to be identified prior to outcomes research on the clinical impact of remodeling to exacerbation and impairment in asthma.

We asked senior author William W. Busse, MD, from the University of Wisconsin, what he felt the most promising areas are for future research on airway remodeling:

Dr. Busse: As pointed out in our review, there are a number of complicating features which make it difficult to determine the best treatment for processes involved in remodeling. First, as noted, the mechanisms underlying remodeling have not been fully identified making the selection of a target intervention difficult. Second, it is likely for those patients in whom remodeling becomes a part of their disease processes, it begins early in life and is linked to other events in asthma, i.e., injury and repair. Given this information, it is likely that treatment most likely to prevent remodeling will need to begin early in life and in the development of asthma. Since two early life events that are key to asthma development include allergic sensitization and respiratory infections, these two areas are likely to be the best targets. Of these two events, allergic sensitization is emerging to be perhaps the most important and amendable to treatment and, perhaps, prevention.

how was the treatment of and the effects of diseases such as acute congestion changed since the 1880"s ?

Introduction
Acute congestions have changed a lot since the 1880′s. Diseases such as asthma, rhinitis, heart failure have changed over the years cures to these diseases have modernized. doctors have found cures for most of this diseases but some of them just don’t have any cure or people with these diseases have to learn how to live with this problems.

asthma disease
Asthma is a chronic lung condition that causes airway inflammation, the treatment goes on for a long time some people just have to learn how to leave with it. They have to stay on treatment for the rest of their lives. People have to use pumps which inside is made of a sort of oxygen that helps you breathe when you’re doing any kind of exercise asthmatic people don’t tend to do much exercise because of their respiratory system is not strong enough the way that they can fight it is by taking a controller medicine daily, you can have fewer asthma symptoms and fewer asthma attacks if you do not take any of the medications you’re needed . An asthma attack is like all your asthma symptoms coming together as one and it tights the muscles around your airways.

During the asthma attack, the lining of the airways also becomes swollen or inflamed and thicker that’s what makes you not breathe severe breathing and coughing

rhinitis disease
Rhinitis is also a respiratory disease I tend to experience it just never goes away you always have it specially on cold and hot weather. When you’re on cold weather your nose gets congested most of the time and you need a medication which is a liquid that goes into your nose that prevents you from bleeding. On hot weather you experience the same thing but without needing the medication your nose just need to be protected from the hot sunny days. It tends to hurt at first then you just start bleeding. . Instead of sneezing and dripping when you are around a huge amount of dust, your nose doesn’t react to a small amount of dust or whatever you may be allergic to. There is no cure for this disease you just have to learn how to leave with it Allergy is one of the diseases which can be controlled with medicine but can’t be cured by any medicine/operation. Try to find the causative factor & try to avoid it-but it is very difficult.

blindness
As you know There are different types of blindness, such as partial blindness, low visual problems, light perception , and total blindness. The worst one of this diseases is total blindness in which a person has no functional vision whatsoever. The damages that have left the eyes beyond repair can be treated with a surgical operation, which replaces the eyes with another the effectiveness of this operation it depends on the age of the person and at what time the damage of the person’s eye was inflected.

deafness
Deafness is the loss of ability to hear normally. These may occur in both ears or maybe just one. Conductive deafness is due to interference with the conduction of sound across the middle ear to the inner ear. deafness occurs either because the mother has not been immunized or has not previously had German measles. If the mother develops rubella in early pregnancy, there is a high risk of deafness occurring in the baby. Rubella is a common childhood infection. The doctor might want to remove the wax from your ears to see if there’s any possibility If there is no improvement, a referral to a specialist may be considered for sure.

heart failure
Heart failure is a cardiac condition that occurs when a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body’s needs. Heart failure can’t be cured. But they can be treated, often with improvement in symptoms. We tend to think of treatment as something from our doctors like a pill or a surgical procedure. That’s not the case with heart failure.

Conclusion
These diseases might sound horrible and you might think people are weird just because they have them but no these disease are part of their lives. Its alright nobody Is perfect and people shouldn’t judge those that are blind or deaf or cant breathe well. We should be happy that we are alive and that acute congestions cures have changed over the years and more cures have been invented and modernized.

Risky side effects from Singulair

This month, parents in New York publicly accused the drug Singulair to be directly responsible for the death of their 15 year old son. It turns out that Merck, the manufacturer, was aware of the potential for suicidal or depressed thoughts. Instead of publishing this potentially life threatening side effect, they chose to quietly change their package insert during October of 2007. Only the death above brought the change to my attention. The two national allergy societies, the Academy of Allergy, Asthma and Immunology with the American College of Allergy, Asthma and Immunology, have jointly noted that while there have been no prior publicly reported cases associating death with taking Singulair, both societies agreed with the U.S. government’s Food and Drug Administration’s call for more information. The mechanism of this adverse reaction is unclear. I stated publicly, on television and in print, that I had no knowledge of this serious accusation. It turns out that I may have spoken too soon. The next week, one of my patients reported suicidal thoughts while taking Singulair. However, these thoughts ceased after she stopped taking Singulair. I am now questioning my patients whom take Singulair even more closely.

If you are taking Singulair, then I have several recommendations. First, make sure you know why you have been prescribed Singulair. Second, take Singulair only as directed. Third, be on the watch for depressive or suicidal thoughts. Fourth, if you suspect Singulair is causing this, it is okay to stop Singulair suddenly if it is being taken for allergic rhinitis (hay fever). However, if Singulair is being taken for asthma, do not stop it suddenly without contacting your doctor. Recognize that your asthma may flare up and that this could be a potentially life-threatening change also. Finally, if you have questions, ask your doctor.