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Posts Tagged ‘asthma’

 

Will treating a fever lead to wheezing?

Monday, November 24th, 2014

By Aric Carroll, PharmD Student

A young child is very susceptible to getting sick, and with that sickness often comes fever. How do most parents treat their child’s fever? The answer for the past few decades has been acetaminophen. In many countries around the world, the first line drug approved for treating fever in children is acetaminophen.1 It has been estimated from one study that up to 75% of all children in Western countries are at some time treated with fever reducing drugs such as acetaminophen.2,3 In the United States acetaminophen use without a physician visit is approved for children as young as 2 years old.4,5 In the past decade, a lot of research has looked at a connection between the rise of acetaminophen use and the rise of asthma in young children.6

A recent study from the Journal of Korean Medical Science (JKMS)9 investigated the relationship between acetaminophen use and asthma prevalence, but took it a step further to try to see why acetaminophen use could be associated with the condition of asthma. The study particularly looked at a specific gene for a receptor in the body called toll-like receptor 4 (TLR4). This is one of the first studies to focus on the combination of TLR4 modification and acetaminophen use and the risk of asthma associated with that combination. In past studies, modification of the gene for TLR4 has been associated with a higher prevalence rate of asthma.7 It has been suggested that modification at this particular gene affects how the TLR4 functions. Modifications may cause the body to work harder at dealing with fine particles that are inhaled leading to physical symptoms associated with asthma.8 The authors of the recent JKMS study acknowledge that TLR4 facilitates the symptoms of asthma by contributing to the release of reactive oxygen species, which are molecules that cause excess stress on the body. This excess stress can then lead to the release of cells that cause inflammation, cause the airways to be inflamed, and cause bronchial hyperresponsiveness (BHR) or tightening of the airways. The study suggests that modification of the TLR4 gene could cause the receptor to be more abundant and lead to greater asthma symptoms.9

The study examined 2, 428 children aged between 8 and 13. The parents of each child were asked to fill out a questionnaire, which included questions about whether the child had used acetaminophen, and whether the child had been diagnosed with asthma. Tests were run on each child to determine a forced expiratory volume after a methocholine challenge, which is an indicator of BHR. Methocholine causes constriction of the airways. BHR to methocholine was defined as a PC20 (the concentration of methocholine re-quired to provoke a 20% reduction in FEV1) ≤ 16 mg/mL. Genetic tests were run on each child to determine modification of the TLR4 gene. The results showed that the use of acetaminophen was associated with risk of BHR; however, it was not associated with actual asthma diagnosis. Modification of the TLR4 receptor was not associated with asthma diagnosis or risk of BHR. A combination of acetaminophen use and TLR4 modification was significantly associated with asthma diagnosis as well as risk for BHR. The study concluded TLR4 gene modification may increase the risk of asthma in children who have used acetaminophen.9

While the study had a very large sample size of children, it had limitations that could have affected the study’s results. The study only looked at acetaminophen use in the past 12 months, but did not take into account whether children had used acetaminophen in earlier years. Also, the study looked at patients with a recall of an actual diagnosis of asthma in the children instead of asking about certain symptoms of asthma such as shortness of breath during physical exercise, wheezing, or increased coughing. Many children may have had symptoms of asthma but had never been diagnosed by a physician. The study also did not in any way establish a relationship between dose or duration of acetaminophen use. Acetaminophen use was defined as if they took acetaminophen longer than 3 days in the last 12 months. This was also solely based on patient recall. These limitations are significant and reduced the generalizability of the study. This type of observational study cannot determine a causative relationship. Thus, this kind of research can only suggest potential risks associated with exposure.

While this study, along with others, have evidence to support a relationship between TLR4 modification and asthma, other similar studies have not found this relationship.10 The conflicting evidence on this specific mechanism makes it hard to conclude one way or another whether TLR4 modification is directly linked to asthma symptoms. Also, at this time there seems to be a lack of sufficient evidence to directly link acetaminophen use to asthma symptoms. More prospective research needs to be done looking at acetaminophen use and its relationship with asthma symptoms specifically in combination with TLR4 gene modification. It may be possible that acetaminophen has a greater adverse effect on children who have a TLR4 gene modification which would increase the risk of asthma specifically in those children. With what evidence is available at this time, it is difficult to say that treating a child with acetaminophen will cause them to develop asthma symptoms.

So, what are your thoughts? Even with this possibility of acetaminophen use in children leading to asthma symptoms, do you think it’s still reasonable for acetaminophen to be used to treat a child’s fever?

References

  1. Gonzalez-Barcala F, Pertega S, Silvarrey A, et al. Exposure to paracetamol and asthma symptoms. European Journal Of Public Health [serial online]. August 2013;23(4):706-710. Available from: Food Science Source, Ipswich, MA. Accessed October 15, 2014.
  2. Jensen J, Tønnesen L, Söderström M, Thorsen H, Siersma V. Paracetamol for feverish children: parental motives and experiences. Scandinavian Journal Of Primary Health Care [serial online]. June 2010;28(2):115-120. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed October 16, 2014.
  3. Sullivan J, Farrar H. Fever and antipyretic use in children. Pediatrics [serial online]. March 2011;127(3):580-587. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed October 16, 2014.
  4. Reducing fever in children: safe use of acetaminophen. FDA Consumer Health Information. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm263989.htm. Published July 21, 2011. Updated June 6, 2014. Accessed October 15, 2014.
  5. Krinsky, D. L., Berardi, R. R., & Ferreri, S. P. (2011). Handbook of nonprescription drugs: An interactive approach to self-care (17th ed.). Washington, D.C: American Pharmacists Association.
  6. Farquhar H, Stewart A, Beasley R, et al. The role of paracetamol in the pathogenesis of asthma. Clinical & Experimental Allergy [serial online]. January 2010;40(1):32-41. Available from: Academic Search Complete, Ipswich, MA. Accessed October 15, 2014.
  7. Fagerås Böttcher M, Hmani-Aifa M, Vaarala O, et al. A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children. The Journal Of Allergy And Clinical Immunology. September 2004;114(3):561-567. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed October 16, 2014.
  8. Kerkhof M, Postma D, Koppelman G, et al. Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma. Thorax [serial online]. August 2010;65(8):690-697. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed October 18, 2014.
  9. Lee S, Kang M, Hong S, et al. Association between Recent Acetaminophen Use and Asthma: Modification by Polymorphism at TLR4. Journal Of Korean Medical Science. March 2014;29(5):662-668. Available from: Science Citation Index, Ipswich, MA. Accessed October 10, 2014.
  10. Hussein Y, Awad H, Shalaby S, Ali A, Alzahrani S. Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and susceptibility to asthma and allergic rhinitis: A case-control analysis. Cellular Immunology [serial online]. 2012;274(1-2):34-38. Available from: Science Citation Index, Ipswich, MA. Accessed October 18, 2014.

Vitamin D: A New Option in the Fight Against Asthma?

Monday, October 27th, 2014

By Charles Snyder, PharmD Student Cedarville University

Most people are either affected by asthma or know of someone close to them who struggles with the condition, which has increased in prevalence in America an estimated 25% every decade since 1960.[1] Asthma is a chronic disease that affects the airways of the body, leading to increased sensitivity, soreness, and swelling of these inner airways and ultimately less air into the lungs. Common symptoms include but are not limited to; wheezing, cough, tightness of the chest and difficulty breathing. Since there is currently no cure for asthma, the goal of treatment is to relieve these chronic symptoms. This is achieved by avoiding common things that can trigger asthmatic attacks such as exposure to pollen, dander and other allergens and by taking inhaled medications. Inhaled corticosteroids, such as Advair®, are aimed at preventing inflammation and swelling of the airways in a long-term capacity. Other anti-asthmatic medications are inhaled at the time of an asthmatic flare up, with a goal of immediately reducing symptoms.[2] As a whole, the current treatments for asthma are fairly effective; however, many patients still struggle to manage their chronic asthmatic symptoms on a day to day basis.

Fox news recently highlighted a new research study that suggests taking vitamin D may have an influence in combating the chronic effects of asthma. [3] The idea that vitamin D levels can affect asthma is a fairly common one. Rates of asthma incidence are statistically higher in northern regions, so it appears that there could be a connection between the northern environment and asthma. Many researchers suspect that the decreased sunlight in these regions, which is responsible for producing the majority of the body’s vitamin D, is leading to the increased asthma rates.[4] It is hypothesized that vitamin D helps to protect against asthma by regulating the immune system. This is accomplished by reducing the number of inflammatory cells (Helper T cells) that produce the symptoms of asthma. These inflammatory cells are also thought to produce another negative effect by reducing the effect of inhaled steroids.[5]

The study was performed by Dr. Saba Arshi at the Medical University of Tehran. This study involved one-hundred and thirty children and adults who were diagnosed with mild to severe asthma. The participants were divided into two groups. One group received treatment for their asthma using a dry powder inhaler, the control group, while the other group was treated with both the dry powder inhaler as well as high doses (100,000 units initially and then 50,000 units per week) of vitamin D for six months. After 28 weeks the researchers conducting the study measured the amount of air that patients could exhale. They found that the group who received the vitamin D, along with the inhaler, had improved by about twenty percent, while the dry powder inhaler only group had improved by seven percent.

There were, however, some limitations to this particular study. First, patients’ adherence to the medications was not measured over the course of the study. This means the regularity of the participants actually taking their assigned treatments is unknown. Second, the number of participants in the study was quite small, one hundred and thirty. Finally, the study only measured the volume of air patients were able to exhale, it did not test whether any asthma specific symptoms were improved over the course of the study.

The Fox news article had this to say about the study’s results, “I think it’s a reasonable hypothesis and their study and some other studies provide evidence it might be true. But I don’t think it’s proven yet.”3 This is a fair analysis of the study. Unfortunately, there simply has not been enough testing done on the relationship between vitamin D levels and asthma incidence to make a definitive statement. Much of the research that has been done has shown conflicting results on the topic4. A recent study published in The Journal of the American Medical Association (JAMA) provided results disagreeing with the study previously discussed. The JAMA article tested whether oral vitamin D supplements increased the effect of an inhaled corticosteroid. However, using variables similar to Dr. Arshi’s study, they found that there was no significant difference in treatment when paired with taking vitamin D.[6] Also worth noting is that a recent systematic review, produced by the Journal of Allergy, Asthma and Clinical Immunology, examined 1081 studies. Out of those studies, only three met the systematic reviews criteria and those three all had conflicting results on whether vitamin D levels played a role in Asthma development and treatment.5 This shows that there is still a lot of discussion occurring about the effect of vitamin D in asthma, and further, definitive data is still needed.

However, vitamin D has a wide range of health benefits such as treating conditions that cause weak bones, helping to raise calcium levels in the blood, and treatment of psoriasis, among others. When taken within the recommended daily dose (approximately 600 international units daily depending on age and weight),[7] there are very few side effects traditionally associated with vitamin D. The described study as well as other studies have not been able to present enough evidence to support using vitamin D to treat asthma. However I feel that vitamin D provides such a wide range of benefits, with no major side effects to asthmatics, that it would be worth trying for people struggling with asthma symptoms. Would you be willing to try vitamin D to see what benefits it could have for you or recommend it to asthma patients?

[1] Brown SD, Calvert HH, Fitzpatrick AM. Vitamin D and Asthma. Dermato-Endocrinology. 2012;2(4):137-145 Accessed September 20, 2014.

[2] National Heart, Lung and Blood Institute. How is asthma treated and controlled. NIH.gov Web site. http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/treatment.html. Published August 4,2014. Updated 2014. Accessed September 20, 2014.

[3] Does vitamin D help with asthma? Fox News Web site. http://www.foxnews.com/health/2014/08/19/does-vitamin-d-help-with-asthma/. Published August 19, 2014. Updated 2014. Accessed September 20, 2014.

[4] Mason R, Sequeira V, Gordon-Thomson C. Vitamin D: the light side of sunshine Eur J Cin Nutr. September 2011;65(9):986-993. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed September 20, 2014.

[5] Rajabbik MH, Lotfi T, Alkhaled L, et al. Association between low vitamin D levels and the diagnosis of asthma in children: A systematic review of cohort studies. Allergy, Asthma & Clinical Immunology. 2014;10(1):1-16.

Therapeutic Research Faculty. Vitamin D. Medline Plus Web site.

[6] Castro M, King TS,Kunselman SJ, et al. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: The Vida randomized clinical trial. JAMA. 2014;311(20):2083-2091. Accessed September 20, 2014

[7] Therapeutic Research Faculty. Vitamin D. Medline Plus Web site. http://www.nlm.nih.gov/medlineplus/druginfo/natural/929.html. Published July 30, 2014. Updated 2014. Accessed September 20, 2014.