Does air pollution exacerbate asthma?

A 2007 article in the Annals of Allergy, Asthma & Immunology asked the very salient question: does air pollution exacerbate asthma?

The objective of the article was to investigate associations between traffic and outdoor air pollution levels near residences and poorly controlled asthma among adults diagnosed as having asthma in Los Angeles and San Diego counties.

The authors estimated traffic density (TD) within 500 feet of 2001 California Health Interview Survey (CHIS) respondents' reported residential cross-street intersections. They then assigned annual average concentrations at government monitoring stations within a 5 mile radius of reported residential cross-street intersections of:

1. ozone

2. nitrogen dioxide

3. particulate matter (PM) 2.5 and 10 micrometers or less in diameter

4. carbon monoxide

In order to obtain the study population, 19,664 individuals were interviewed; 2,237 (11.4%) were diagnosed by a physician as having asthma. These individuals’ residence locations were entered into a database. The final study population was 1,609 adults (others were excluded because of missing data).

Exposure evaluation was evaluated by examining traffic density, which was based on a 500 foot buffer around person's probable home street segment. From the nearest measuring station within 5 miles of the respondent, the authors determined annual average concentrations of: ozone, nitrogen dioxide, particulate matter 2.5 micrometers or less or 10 micrometers or less, carbon monoxide.

For the statistical analysis, traffic density was divided into three tiers:

1. Low TD (20th percentile or less)

2. Medium TD (21-80 percentil)

3. High TD (> 80th percentile)

The results can be summarized in the following 4 main points:

1. There was a 2-fold increase in poorly controlled asthma among asthmatic adults (OR 2.11, 95% CI 1.38-3.23) in the highest quintile of traffic density after adjusting for age, sex, race, and poverty.

2. Similar increases were seen for nonelderly adults, men, and women. The strongest associations were seen in elderly adults (OR 3, 95% CI 1.13-7.91).

3. Ozone exposures were associated with poorly controlled asthma among two subgroups:

- elderly adults (OR 1.7, CI 0.91-3.18 per 1 pphm)

- men (OR 1.76, CI 1.05-2.94 per 1 pphm)

4. Particulate matter 10 micrometers or less affected primarily women (OR 2.06, CI 1.17-3.61), even at levels below national air quality standard.

The authors’ conclusion? Heavy traffic and high air pollution levels near residences are associated with poorly controlled asthma.

While this may seem like a relatively straightforward conclusion based on the data, this study had some very significant caveats to keep in mind:

1. Misclassification of exposures from stations:

- Traffic pollutants can have a strong spatial gradient, meaning levels detected at measuring stations might not reflect actual exposure levels of individuals.

2. Resident variability:

- The study did not take into account variables such as personal mobility, occupation-related exposures, or indoor exposures.

3. Temporal ambiguity

- This study was based on cross-sectional survey data, so the length of time any individual lived in a neighborhood was unknown.

4. Medication use

- Individuals’ use of medications was unknown; use could reduce symptoms and lead to underestimated prevalence of poorly controlled asthma.

Y-Y Meng, et al. Traffic and outdoor air pollution levels near residences and poorly controlled asthma in adults. Annals of Allergy, Asthma, & Immunology 2007;98:455-463.

Novel NF-Kb links inflammation and cancer promotion

A recent paper by researchers at the University of California [1] reveals a novel mechanism by which chronic inflammation may play a decisive role in the promotion of cancer. This mechanism is a sort of molecular “cross-talk” between two processes in cells which were thought to be distinct – cell development and inflammation. This cross-talk comes through the actions of a protein, p100, which has been found to be crucial in a cell’s normal developmental metabolic pathways as well as in the cell’s response to inflammation. Novel cancer therapeutic treatments which target developmental pathways linked to chronic inflammation via p100 may prove effective in conjunction with the use of current anti-inflammatories such as NSAIDS.

NF-κB activity is inducible by a diverse range of stimuli including pathogen derived substances and intercellular mediators of inflammation. It is known that NF-κB is normally repressed by three different intracellular inhibitors (IκB-a,b,e proteins),and that during classical inflammatory signaling these inhibitors are released from binding NF-κB, resulting in its activation. A second, independent NF-κB activation pathway is thought to be activated in response to cell developmental signals rather than inflammatory signals. The molecular mechanism of this particular pathway has remained uncertain, but the results of this study show that a fourth IκB inhibitor (p100) is involved in the activation of NF-κB in developmental pathway signaling, such as during lymphoid organogenesis (see included figure).

This diagram reveals the cross-talk between NF-κB activation via inflammatory or developmental signaling – inflammatory signaling can activate developmental (cell reproduction and differentiation) pathways to some extent and vice-verse. And further work by the researchers showed that the “cross-activation” of developmental pathways by classical inflammatory signaling was much stronger, and of longer duration, than the normal developmental activation signal strength. For example, a 1 hr pulse of TNF-a stimulation resulted in an elevation of p100 protein of about 4-fold, that persisted for more than 20 hr. Remarkably, the researchers also showed that the strength of this cross-talk increased with repeated signaling – in other words, the longer cells were exposed to inflammatory signals via TNF-a, the more they were stimulated to reproduce! This is in marked contrast to the normally accepted role of TNF-a in signaling cell death.

The researchers speculate that in epithelial cells that are exposed to prolonged periods of inflammation, such as they might experience during chronic inflammatory diseases, the amount of cross-talk between the classic TNF-a mediated inflammatory cell death pathway and the p100 mediated developmental cell growth pathway may profoundly shift, with the inflammatory signals generating a stronger and stronger cell growth signal in place of the expected cell death signal. This could be the mechanism responsible for chronic inflammations being able to promote the growth of many types of cancers – after prolonged exposure, inflammatory TNF-a signals that were originally responsible for inducing cell death (and resolving inflammation and tissue repair processes) become instead growth stimulating signals that drive epithelial cells toward unrestrained cancerous growth.


1. Basak S, Kim H, Kearns JD, Tergaonkar V, O'Dea E, Werner SL, Benedict CA, Ware CF, Ghosh G, Verma IM, Hoffmann A.(2007) A fourth IkappaB protein within the NF-kappaB signaling module. Cell. Vol 128(2) p369-81.

NSAIDS and Cancer Prevention

Over the last four decades dozens of epidemiological, clinical and experimental studies have established nonsteroidal anti-inflammatory drugs (NSAIDs) as promising epithelial cancer chemopreventive agents. The long-term use of aspirin and other NSAIDs has been shown to reduce the risk of cancer of the colon and other gastrointestinal organs, as well as cancer of the breast, prostate, lung, and skin. In a recent review, Harris[1] et. al. comprehensively reviewed the published research on NSAIDs and cancer incident. Data from 91 epidemiologic studies were analyzed for the dose response of relative cancer risk and level of NSAID intake for ten prevalent human cancers. The results showed a significant exponential decline in the risk with increasing intake of NSAIDs (primarily aspirin or ibuprofen) for 7 out of the 10 cancers, including the four major types: colon, breast, lung, and prostate cancer. Consistent daily intake of NSAIDs (primarily aspirin), produced risk reductions of 73% for stomach, 69% for esophageal, 63% for colon, 47% for ovarian, 39% for breast and prostate, and 36% for lung! NSAID effects became apparent after five or more years of use and were stronger with longer duration.

Despite general consensus as to the effectiveness of NSAIDs for cancer prevention, unresolved questions with regard to safety, efficacy, optimal treatment regimen, and mechanism of action currently limit the clinical application of NSAIDs to the prevention of cancer. Also, the development of safe and effective NSAIDs for chemoprevention is complicated by the potential that rare, serious toxicity may offset the benefit of treatment with these drugs given to healthy individuals who have a low risk of developing cancer. However, I believe there is growing support for the view that a full understanding of the role of NSAIDs in the prevention and treatment of epithelial cancers will be an integral part of the development of effective future treatments for reducing mortality and morbidity from most cancers.


1. Harris RE, Beebe-Donk J, Doss H, Burr Doss D. Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncol Rep. 2005 Apr;13(4):559-83.

Chronic Beryllium Disease --going beyond HLA-DPB1?

I have been working for several years with a doctor who does research with chronic beryllium disease (CBD). If you recall from our notes, this is a disease which is caused by inhalation of beryllium dust and an immune response which leads to granuloma formation in the lung. There is a known association between certain HLA-DPB1 alleles and CBD and we are always looking for ways to better understand what this means. The article “Electrostatic Potential on Human Leukocyte Antigen: Implications for Putative Mechanism and Chronic Beryllium Disease” describes how the authors constructed structural models of HLA-DP representing several distinct allotypes and how they calculated the electrostatic potential on the surface of these models. They determine that the higher the negative charge for the HLA-DPB1 alleles the more likely that the person would have chronic beryllium disease. These charges are then related back to certain alleles. I guess I have a question for anyone who may be reading this: Does the electrostatic charge give you any new meaningful information?

The article's link in PubMed.

H1N1 Influenza strains contain H5N1 genetic material...Are the young and healthy at risk of a massive cytokine storm induced by virus infection?

Human infection with highly pathogenic avian influenza A viruses (HPAIV) such as H5N1 subtypes are characterized by inner bleedings and a massive overproduction of cytokines known as cytokine storm (Schmolke et al., 2009). Recent reports have linked the genomes of the last three pandemic influenza viruses as having emerged from gene reassortment events and possessing HA genes of avian influenza origin. Thus, these findings provoke the following question: If existing influenza strains (i.e. 2009 H1N1 influenza) undergo gene reassortment similar to H5N1 strains, is it possible that the resulting human adapted form could manifest itself as a deadly pandemic targeting healthy individuals by the onset of a massive cytokine storm?

Review of what the “cytokine storm” is: when the body’s normal immune system overacts to an intruder such as a virus, by overproduction of signaling chemicals (known as cytokines and chemokines) that help mobilize immune cells capable of removing infectious agents from the body. The extremely high levels of cytokines that are produced as a consequence of a healthy immune system are over-exaggerated and fatally damaging to tissues and organs. Death will usually result from multisystem organ failure.

I came across two articles I’d like to reference in regard to this blog. Below is a brief summary of each paper, highlighting the author’s findings which are relevant to this blog topic.

The first paper published in July 2009 in Science (Rebecca J.Garten et al., 2009) involved a large collaborative effort of many authors representing the WHO, CDC, NIH and various health organizations. The objective of this study was to characterize the antigenic and genetic variations of 2009 H1N1 circulating in humans. In their attempts to do this, they analyzed genome sequences isolated from 2009 H1N1 patients with previous strains of influenza including classical swine, human seasonal, American avian, North American and Eurasian swine strains. This paper examines the antigenic capabilities of influenza and how it has evolved overtime resulting in the emergence of pandemic flu strains. The paper provides the lineages and reassortment events that have taken place overtime and which gave rise to three pandemic influenza viruses (1918 H1N1, 1957 H2N2, and 1968 H3N2). The lineage suggests that all three strains originated from nonhuman reservoirs and the HA genes of all, originated from avian influenza virus. Now the most recent 2009 A/H1N1 strain contains a never before seen combination of gene segments which appear to be derived from Eurasian swine and classical swine lineages (Garten et al., 2009).

The second paper, by Schmolke M. et al., 2009 in the Journal of immunology by a group in Germany presents in accordance with numerous reports, the observation that the high fatality rate of avian influenza is a consequence of lethal cytokine storm induced by A/H5N1 virus both in humans and animals (Deng RM. et al., 2008; Claas EC. et al., 1998). The significance of the study is based on the concern of highly pathogenic avian influenza viruses (HPAIV) being directly transmitted to humans as a possible source of a new influenza pandemic. They performed mRNA profiling on human umbilical vein endothelial cells (HUVEC) infected with H5N1 based on the idea that endothelial cells are a major source of cytokines and chemokines, and relevant for systemic viral dissemination. Their results confirm clustering and upregulation of inflammatory/immune response which are accompanied by a massive systemic production of cytokines and chemokines, characteristic of a cytokine storm.

It’s frightening to acknowledge the ongoing threats of the 2009 H1N1 swine flu and the still present Asian avian flu virus (AAV H5N1) and its pandemic potential. In regards to the influenza strain reassortment and antigenic evolution, sequence variation in the gene segments of the H5N1 strain have been shown to contribute to viral virulence. It will be interesting to compare the updated sequencing of gene segment among the 2009 H1N1 strains with previously pandemic strains which could suggest whether it may or may not be likely to elicit such a strong cytokine response associated with highly virulent strains such as H5N1.

Based on the recent publications mentioned above I think it is obvious that 1) the new swine flu influenza A strain appears to be a combination of previous bird, swine and human genetic make-up. In addition, all three show lineage to have originated from avian flu. 2) H5N1 the highly virulent avian flu strain causes lethal cytokine storm in young and healthy individuals. These ideas together implicate that H1N1 viruses have pandemic potential and historically support the possibility that healthy young adults may be more susceptible to severe infection due to a strong immune system capable of eliciting a lethal cytokine storm. If uncontrolled, such a cytokine storm occurring in vital organs can lead to organ failure and death.

What would be the best approach in preventing an influenza pandemic or in addressing the potential damage it could elicit by inducing a cytokine storm in infected individuals? Should health officials stringently monitor strains of the 2009 A(H1N1) virus for any antigenic and genetic changes? In the case of infected patients, should the use of prophylactics such as immune suppressors or antivirals be used to minimize the possibility of the cytokine storm?

References:

Garten RJ et al., 2009. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 325:197-201.

Schmolke M, Viemann D, Roth J, Ludwig S. 2009. Essential impact of NF-κB signaling on the H5N1 influenza A virus-induced transcriptome. J Immunol. 183:5180-5189.

Deng RM, Korteweg LC, Gao Z, McNutt MA, Ye J, Zhang I, Gu J. 2008. Distinctly different expression of cytokines and chemokines in the lungs of two H5N1 avian influenza patients. J Pathol. 216:328-336.

Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF. 1998. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet. 351:472-477.

Genetic Variation In The Maintenance of HIV Seronegative Status Among High-Risk Populations

Chemokine receptors have proved to be important in maintaining seronegative status among individuals who have a high risk for contracting the HIV virus. Cultures of lymphocytes and macrophages have shown that those who are relatively resistant to HIV infection secrete high levels of co-receptors CCL3, CCL4, and CCL5 when they are inoculated with this virus. It has been discovered that HIV resistant people are homozygous for an allelic, nonfunctional version of the CCR5 co-receptor, D32. In the Caucasian population, the prevalence of this frameshift mutation (coupled with a protein truncation) in the homozygous form is fairly high at about 1%. The heterozygous allelic form of this mutation may provide some modest protection against the sexual transmission of the HIV virus, and could even slow the progression of existing infections. In addition to this, variation in the promoter region of the CCR5 gene has been identified in both Caucasians and African Americans. Differences in promoter regions have also been associated with different rates of progression of the disease. This evidence shows that CCR5 is the major macrophage and T-lymphocyte co-receptor used by HIV to establish initial infection. Interestingly, this also offers hope that primary HIV infection can be blocked by anti-CCR5 receptors.

Janeway, Charles. Janeway's Immunology - 7th Edition / Kenneth Murphy, Paul Travers, Mark Walport. Garland Science. 2008.

Worm therapy available--legally?

Scraping my net over the bottom of the Web, I found Ovamed GmbH, a company in a village near Hamburg that claims to be licensed by the Thai Ministry of Health to sell TSO (Trichuris suis ova) for treatment of Crohn's and UC in those "with a medical recommendation."

And another outfit, Autoimmune Therapies, will sell you a similar product. Here's what they say: "Helminthic therapy, nature's most powerful probiotic, harnesses nature to heal, restoring the helper organisms we co-evolved with and that our immune systems depend on to function correctly, and is based on sound science. Stop treating the symptoms, fix the problem." You can judge for yourselves the accuracy of those statements. They say they sell anywhere except the USA.

There are many more, springing up all over the world, wherever evidence-based medicine is not currently the fashion.

Aquagenic Urticaria (Physical Urticarias)

Physical urticaria refers to a class of chronic urticaria, a hive or wheel type reaction, to a physical stimulus. The literature seems to indicate that for some patients the specific physical trigger results in hives, but in others the stimulus is the only common factor in the otherwise idiopathic condition. A large group of physical stimuli have been characterised and used as diagnostic criteria (1), which include: dermographism, delayed pressure urticarias/ angioedema, cholinergic urticaria, local heat induced urticaria, exercise induced urticaria, solar urticaria, vibrational angioedema, and aquagenic urticaria.

Though fewer than 50 cases of aquagenic urticaria have been documented in medical journals, relatively recent online tabloids and blogs have written articles about the condition (2,3). The clinical features of the condition include small perifollicular wheels on any skin region after contact with water (distilled, tap, or saline). For some patients characteristics of the water effected the condition, salinity, pH, and others factors (4,5). Many patients suffering from aquagenic urticaria have also been diagnosed with cholinergic urticaria or dermographism (6,7).

From the known mechanism of the immune system we have learned about this year it seems unlikely that water itself could be recognized by the immune system. However, a few hypothesis for the mechanism of the condition have been proposed. It is possible that the water acts to carry an antigen (possibly sebum) through from the epidermis to the dermis where it is recognized by mast cells causing the localized reaction (8). Further studies with this hypothesis demonstrated that organic solvents increased sensitivity to the reaction, and removal of the stratum corneum layer of the skin produced similar results. Another theory suggested cholinergic activation resulted in the reaction, scopolamine was shown to decrease reactions in two patients, but pre-treatment with atropine did not suppress reactions. The injection of methacholine, which usually elucidates cholinergic reactions for diagnostics was negative when tested on aquagenic urticaria patients (9). It may also be possible that the activation or involvement of the sensory neurons, perhaps presenting antigens from a latent virus could provide a possible mechanism, though no research has been done in this vein. Similarly, it is possible that ions in the water change an already present molecule of self into a recognizable antigen.

Elucidating a mechanism, or further understanding of aquagenic urticaria and other types of physical urticaria may provide immunologists new insights into antigen presentation, and inflammation.


1. Kontou-Fili, K, Borici-Mazi, R, Kapp, A, et al. Physical urticaria: classification and diagnostic guidelines. An EAACI position paper. Allergy 1997; 52:504.
2. http://www.dailymail.co.uk/news/article-520329/The-teenage-girl-allergic-WATER.html
3. http://abcnews.go.com/Health/AllergiesNews/story?id=7401149&page=2
4. Gallo, R, Cacciapuoti, M, Cozzani, E, Guarrera, M. Localized aquagenic urticaria dependent on saline concentration. Contact Dermatitis 2001; 44:110
5. Tkach, JR. Aquagenic urticaria. Cutis 1981; 28:454
6. Parker RK, Crowe MJ, Guin JD. Aquagenic urticaria. Cutis. 1992 Oct;50(4):283-4
7. Luong KV; Nguyen LT. Aquagenic urticaria: report of a case and review of the literature. Ann Allergy Asthma Immunol. 1998 Jun;80(6):483-5.
8. SHELLEY, WB, RAWNSLEY, HM. AQUAGENIC URTICARIA. CONTACT SENSITIVITY REACTION TO WATER. JAMA 1964; 189:895
9. utdol.com

CRP and COPD

I found this article to be very interesting as I currently work in research looking at the association between COPD (chronic obstructive pulmonary disease) and CVD (cardiovascular disease). I found this article in the European Journal of Internal Medicine 19 (2008) 104–108.
Authors: Fisun Karadag, Sevin Kirdar, Aslihan B. Karul, Emel Ceylan

Title: The value of C-reactive protein as a marker of systemic inflammation in stable chronic obstructive pulmonary disease


In this article the authors sought to evaluate circulating CRP levels in order to determine the value of CRPas a biomarker of systemic inflammation and as an indicator of malnutrition or severity of COPD in stable COPD patients in comparison to the proinflammatory cytokines TNF-α and IL-6.

The study consisted of 35 male patients with stable COPD and 30 age and sex matched controls with normal pulmonary function. Serum CRP, TNF-α, IL-6. levels were taken from the subjects. It was found that CRP levels were significantly higher in stable COPD subjects than in control subjects however, TNF-α and IL-6 were not significantly different. When BMI was taken into account then it was found that COPD subjects with low BMI had a higher serum CRP and TNF-α levels compared to COPD subjects with normal to high BMI.

The authors came to the conclusion that the present study confirms that because circulating CRP levels are higher in stable COPD patients this may be regarded as a valid biomarker of low-grade systemic inflammation. Also, because CRP and TNF-α were higher in the COPD patients with a low BMI then this could be considered an indicator of malnutrition in COPD patients.
The results of this study could be applied to the current study in which I am working looking at COPD and CVD. Using CRP as an indicator of low grade systemic inflammation could be utilized when we are looking at the occurrence of coronary calcium development in those with varying severity of COPD and outcomes such as stroke or heart attacks. Based on these results, I would expect those with lower COPD severity (goldstage 1) to still be at increased risk for heart attacks and stroke. This would be contradictory to the current notion that goldstage 1’s are not really COPD thus the lack of contribution to cardiovascular disease. The other results identifying higher CRP and TNF-α indicating malnutrition could e applicable to studies looking at muscle/tissue wasting in COPD subjects.

Food allergies--peanut/tree nut

Being one of the clinicians in this course, I thought I would share some information about food allergy (which is an issue we encounter with increasing frequency):

Food allergies are adverse immunologic reactions to food proteins and run the spectrum of IgE mediated reactions to cell mediated reactions such as food protein induced enterocolitis or contact dermatitis. However, IgE mediated food reactions are the most common.

Food allergies are prevalent with reproducible symptoms in 5% of young children and 1-2% of adults. More than 90% of food allergies are caused by milk, egg, fish/shellfish, wheat, soy, peanut/tree nuts. It is estimated that 1-2% of the U.S. and European population is allergic to peanuts and/or tree nuts.

Furthermore, reactions to nuts, particularly peanut are severe and often fatal. In fact, per the United States Food Allergy & Anaphylaxis Network (FAAN) registry, peanuts are responsible for a significant percentage of food-associated deaths. Unfortunately, accidental exposure to peanuts is common, noted to occur in 14.3% of Montreal schoolchildren, and exposure to doses as small as 100 micrograms may provoke symptoms (an average peanut weighs 300-500 milligrams). Approximately 20% of children will outgrow a peanut allergy (approximately 10% outgrow tree nut allergy).

Interestingly, nearly one-third of peanut allergic patients will become tree nut allergic and this trend seems to be true of tree nut allergic patients becoming peanut allergic, at least for some tree nuts, such as cashew. So, is it that nut allergic persons are predisposed to develop allergies to multiple different nut proteins? Or are they reacting to similar epitopes in the various types of nuts? The answer is unclear for several reasons. First, and most obviously, not enough work has been done between peanut and tree nut cross reactivity. Second, how do we assess cross-reactivity? Do we use methods that denature the protein and exposure linear, but not necessarily functional epitopes, such as Western blotting? Or do we use functional assays that use structurally intact proteins such as histamine release assays (human basophils or immortalized rat basophils)? Also, how do these studies correlate with the clinical history as well as measurements of peanut or tree nut specific IgE? This is the subject of some ongoing research being conducted here as well as a few other sites in the U.S. and Europe, and perhaps elsewhere.

As a final note, there are a few articles that demonstrate transfer of allergies in the context of transplantation. The first article by Bellou et al. involves bone marrow transplantion. The second article by Phan et al. involves liver transplantation. The third article, which did not have an abstract available online reports peanut hypersensitivity transfer via fresh frozen plasma. The mechanism responsible for the transfer of allergy is undetermined but ideas include adoptive transfer of primed donor B-cells or T-cells, or the transfer of donor mast cells sensitized to peanut specific-IgE or passive transfer of donor peanut specific-IgE.

Articles:

Bellou A, et al. Tranfer of atopy following bone marrow transplantation. Ann Allergy Asthma Immunol. 1997 May;78(5):513-6.

Phan TG, et al. Passive transfer of nut allergy after liver transplantation. Arch Intern Med. 2003 Jan 27;163(2):237-9.

Arnold DM, et al. Passive transfer of peanut hypersensitivity by fresh frozen plasma. Arch Intern Med. 2007 Apr 23;167(8):853-4.

References:

Sampson H. Update on food allergy. J Allergy Clin Immunol 2004;113:805-9.

Bock S. Prospective appraisal of complaints of adverse reactions to foods in children during the first three years of life. Pediatrics 1987;79:683-8.

Hefle S, Nordlee J, Taylor S. Allergenic Foods. Crit Rev Food Sci Nutr 1996; 36:S69–S89.

Sicherer S, Furlong T, et al. A voluntary registry for peanut and tree nut allergy: Characteristics of the first 5149 registrants. J Allergy Clin Immunol 2001;108:128-32.

Sicherer S, Sampson H. Peanut allergy: Emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol 2007;120:491-503.

Yu JW, Kagan R, Verreault N, Nicolas N, Joseph L, St Pierre Y, et al. Accidental ingestions in children with peanut allergy. J Allergy Clin Immunol 2006;118:466-72.

Roux K, Teuber S, et al. Tree nut allergens. Int Arch Allergy Immunol 2003;131:234-44.

Fleischer D, Conover-Walker M, et al. The natural history of tree nut allergy. J Allergy Clin Immunol 2005;116:1087-93.

Burks K, Bock S. Natural History of Peanut and Tree Nut Allergy: Development of Tree Nut Allergy/Sensitization. J Allergy Clin Immunol 2008;121:S235.

Nicotine, Anti-Inflammatory H1N1 Cure

With the recent global outbreak of H1N1, there have been many theories for different vaccines to cure H1N1. Lucky for us some of those theories have been approved by medical researchers and the FDA and vaccines have been produced to cure the people who are affected with the disease. Ironically, there is another theory that you all may find controversial, which I find interesting to blog about and read your comments.

Doing some research on Anti-Inflammatory drugs/remedies using the world wide web, I came across this article stating that Nicotine from tobacco has an anti-inflammatory affect via the vagus nerve which can block a variety of cytokines of the H1N1 virus. Last week in discussion, we talked about the "risk/benefit" theory, where taking an Anti-Inflammatory drug can initially be beneficial, but if that drug is overused, the risk is damage to the GI tract, liver, and can raise blood pressure.

In regards to this article, the "risk/benefit" theory can be applied as well. The article does mentioned that smoking is very toxic to the body, but the nicotine in tobacco can act as an anti-inflammatory and as long as nicotine is present in tobacco, the degenerative effects from inflammatory diseases will be moderately controlled.

Nicotine stimulates the cholinergic anti-inflammatory pathway. At the end of this pathway are immune cells that produce anti-inflammatory cytokines that block inflammation. Thus, nicotine, although one of the most addictive chemicals, can have beneficial effects on inflammatory diseases, such as arthritis, asthma, cancer, inflammatory bowel diseases and perhaps, H1N1.

Tobacco Smoke Is Toxic but also Anti-Inflammatory
Paradoxically tobacco smoke contains hundreds of toxic and carcinogenic chemicals that produce inflammatory reactions and numerous degenerative diseases, but it also contains nicotine that is anti-inflammatory. Smokers assault their bodies, but moderate and obscure the inflammatory degeneration and disease, until they stop the nicotine exposure.

Nicotine Withdrawal Is Inflammatory
The anti-inflammatory benefits of nicotine reveal the inflammatory basis of many unexpected diseases. Nicotine withdrawal is severe, partly because it leads to rebound release of inflammatory cytokines, inflammation and inflammatory disease symptoms that include depression and obesity. Smoking cessation may contribute to more severe symptoms of H1N1 infections.

Nicotine Acts via the Vagus Nerve
Attempts to augment bypass surgery for weight reduction have encountered the anti-inflammatory benefits of stimulating the vagus nerve. Vagus nerve stimulation via an electrode attached to the left branch in the neck by a device implanted behind the clavicle, reduces inflammatory cytokine production and is an effective treatment for obesity. Other types of vagus stimulation are being tested for efficacy in treatment of numerous inflammatory diseases, including arthritis, allergy, asthma, Alzheimer’s, etc.

Nicotine Blocks Cytokine Storms
Cytokine storms are a deadly consequence of inflammation that is out of control. These exaggerated host responses are targets for bioterrorism, because it takes very little toxin or a very minimal infection to be lethal, if it produces a cytokine storm. In mice, the ricin toxin, a bioterrorism agent, induces a cytokine storm that kills by multiple organ failure. Ricin-treated mice can be protected by nicotine prior or after the cytokine storm begins.Read more: http://diseases-viruses.suite101.com/article.cfm/nicotine_antiinflammatory_h1n1_cure#ixzz0YMYaYMWp

In my opinion from a person who does not smoke, I think when it comes to using tobacco whether it be from cigarettes or chewing to receive a source of nicotine to fight inflammation, the risks of smoking to receive a source of nicotine out weigh the benefits. Smoking can cause lung cancer, throat cancer, severely raise a person's blood pressure, effect a person's physical appearance, and can become addicting to where a person can't go through a day without having a smoke. There are other ways to fight inflammation that are less harmful to a person than using nicotine and I believe a person who smokes to fight inflammation should reconsider and look at other healthier treatments like changing their diet, exercising, etc.

Mabley JG, Pacher P, Szabo C. Activation of the cholinergic anti-inflammatory pathway reduces ricin-induced mortality and organ failure in mice. Mol Med. 2009 Feb 11. [Epub ahead of print]
Gwilt CR, Donnelly LE, Rogers DF. The non-neuronal cholinergic system in the airways: an unappreciated regulatory role in pulmonary inflammation? Pharmacol Ther. 2007 Aug;115(2):208-22.
Johnston GR, Webster NR. Cytokines and the immunomodulatory function of the vagus nerve. Br J Anaesth. 2009 Apr;102(4):453-62.Read more: http://diseases-viruses.suite101.com/article.cfm/nicotine_antiinflammatory_h1n1_cure#ixzz0YMchF3PY

Electro-acupuncture

In our acupuncture discussion last week, I had briefly mentioned about “electroacupuncture”. It was my first time hearing this term so I looked up for more detailed information on this subject…if anyone’s interested in it as well!

We all have a general idea of how traditional acupuncture works…
Electroacupuncture stem from the same idea of using needles on the acupoints but with the needles attached to a device that generates continuous electric stimulation. Another term for electroacupunture is “Percutaneous Electrical Nerve Stimulations (PENS)”

There are three main benefits of using electroacupunture:
1. It substitutes for prolonged hand manoeuvring. It helps to assure that the patient gets the amount of stimulation needed in case of the acupunturist’s pause due to fatigue. It also helps to reduce the total treatment time by providing continuous stimulus as well as the chances for the acupuncturist to attend other patients.
2. It can provide a stronger stimulation without causing tissue damage. Strong stimulation may be necessary in difficult cases such as neuralgia or paralysis.
3. Electroacupunture makes it easier to control the frequency and the amount of stimulus in comparison with hand manipulation of the needles.

There is one disadvantage of electroacupunture --- the lack of direct acupuncturist participation. It limits the opportunity for the acpunturist to respond to changes that are taking place during treatment.
According to the Chinese literature, good results are expected from electroacupunture especially in treatment of neurological diseases, including chronic pain, spasm, and paralysis. However, the method should be used with caution in patients with serious cardiac disease. It’s generally recommended to avoid placing electrodes near the heart to prevent the adverse responses of the heart to electrical impulses. In addition, the path between any two electrodes should not cross the heart area as well. Some have also suggested avoiding placing electrodes to needles on both sides of the spinal cord no matter how low the current that’s being used, because of the possible effect of the electrical stimulus on the nervous system.

Similar to the traditional acupuncture treatments, the electroacupunture treatment experiments also revealed conflicting outcomes. The majority of journal articles from China on electroacupunture are devoted to laboratory animal studies. Those studies have limited relevance to humans due to the difficulties matching points on these animals with those on humans. Therefore, electroacupunture animal studies mainly provide a means of using an animal model to study acupuncture therapy in general.

This following short video provides the basic idea as well as demonstratio of both traditional and electroacupuncture!



Here is the link if the short video does not show on your computer.
http://www.youtube.com/watch?v=bvlxggeIG4E&feature=related





References

http://www.itmonline.org/arts/electro.htm Electro-acupuncture Subhuti Dharmananda, Ph.D, Director, Institute for Tranditional Medicine, Portland, Oregon
http://en.wikipedia.org/wiki/Electroacupuncture Electro acupuncture
http://www.youtube.com/watch?v=bvlxggeIG4E&feature=related Acupuncture treatment - the basics. Tom Kennedy