Schools are quite paranoid about giving any medication on their watch. The liability for giving sunscreen when you don’t need it? Zero. This is very similar to the use of epinephrine in a school aged child with food allergy. You certainly don’t want to withhold epi and risk anaphylaxis or death, when the risk of giving the EpiPen is negligible even if you don’t need the drug. Maybe our policies in schools will change after a large malpractice case gets media attention for NOT giving epinephrine at the appropriate time for peanut allergy.
Ok, another study about the dangers of food allergy (yesterday in USA Today). You would think the occurrence of food allergy to KNOWN allergens (peanut & milk) would decrease given all the attention given to accidental ingestion. Evidently, this is not the case. Explanations? Maybe we’re afraid of giving epinephrine. In my personal experience, giving epinephrine is analogous to “waving the white flag.” It doesn’t have to be nor should it be when treating children with suspected food allergy. As I tell my nurses, “give the epi, then call the doctor!”
Truly remarkable how cancer survival has improved in children WITHOUT the addition of new drugs. There is so much more to health than just taking more medication! Allergy operates in the same way–good avoidance is first, followed by other aggressive medications.
Purpose of review To update safety information regarding allergen-specific immunotherapy (ASIT) in clinical practice and highlight the risk factors associated with the adverse reactions, product and each dose. Recent findings Efforts in recent years have focused on increasing our understanding of the efficacy and safety of ASIT, especially the sublingual variety (SLIT), in multicenter studies. Moreover, new Clinical Practice Guidelines (CPGs) and an international consensus concerning ASIT have been published recently. Although no deaths as a result of subcutaneous immunotherapy or SLIT have been reported in the last 2 years, systemic reactions mainly arising from administration errors still appear. Recent studies support the safety of new forms of specific immunotherapy. Summary An understanding of the risk factors for each patient, product and dose, and the implementation of CPGs are the main factors that could improve the safety of ASIT. The standardization of all procedures for prescribing and administering ASIT, and the systematic collection of standardized safety data in a multicenter database (postmarketing surveillance), may be required to generate new information on the safety of ASIT.
Why Do We Even Care About Safety of Allergy Shots?
Allergen-specific immunotherapy (ASIT), both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been shown to be effective for the treatment of allergic respiratory disease in randomized controlled trials and meta-analyses. Indeed, SCIT is the treatment of choice for preventing anaphylaxis in patients with systemic reactions to hymenoptera (bee stings).
The greatest drawback to the more widespread use of ASIT is the associated risk of severe side-effects, as the dose which has been shown to be well tolerated and effective in a group of patients may not be so for a specific patient. Here again, everyone is different and what may be the best dose for one patient, may cause an adverse reaction for someone else.
Systemic reactions are those which produce symptoms and signs far from the administration site. They may be immediate systemic reaction (ISR), appearing in the first 30 min postadministration, or delayed systemic reaction (DSR), occurring after the first 30 min, with the former tending to be more severe.
The incidence of systemic reactions has been estimated at between 1 and 34% of patients and around 0.2–0.3% of doses, depending on the type of study, patient, diagnosis, extract or treatment scheme.
Historical reviews of ASIT-related mortalityhighlighted severe or poorly controlled asthma and administration errors as the main causes of fatal systemic reactions. These findings led to the drafting of Clinical Practice Guidelines (CPGs) for ASIT treatment,and their subsequent updates, in the 1990s. Adherence to such guidelines is the main reason behind the reduced frequency and severity of systemic reactions in the past 20 years. The statistics regarding mortality and systemic reactions prior to these CPGs are no longer applicable.
Let’s look at some individual factors that increase your chances of a systemic reaction to an allergy shot!
What do you put in my serum? No specific allergen is currently thought to produce higher mortality or a greater chance of a large local reaction.
Very few fatal reactions to pure hymenoptera venom immunotherapy (VIT) have been reported. Indeed, several studieshave found a lower incidence of systemic reactions with hymenoptera vaccines, with bee vaccines being tolerated worse than wasp vaccines.
Systemic reactions appear to be more frequent when aqueous extracts are used. This is presumably due to the fact that the allergen is absorbed very quickly after it’s injected.
Dose-related Risk Factors
Administration errors are the main identifiable and avoidable cause of ASIT-related systemic reactions, including SLIT. (SLIT is the oral allergy drops)
Any delay in the treatment of a systemic reaction increases its severity. This is why I instruct my nurses to give epinephrine first, then call.
Although CPGs provide recommendations to avoid such errors, they continue to occur with a greater than expected frequency.
I could write a book on the types of errors that occur with the dose of allergy shots. Would this be a best-seller or what?
Research has shown that a large local reaction does not predict the occurance of a more severe systemic reaction; a concept that can be difficult to grasp for patients. (see below)
Dosing Scheme
In the case of SCIT with airborne allergens, the use of fast regimens (rush and cluster) has been associated with a higher number of systemic reactions, although more recent studies have shown their safety to be similar to that of conventional schemes. Patients tend to like the rapid schedule because they can avoid the prolonged build-up of conventional treatment.
Omalizumab (Xolair) has been used to reduce the systemic reaction incidence in patients receiving SCIT with inhaled allergens and VIT (venom shots), with good results.
It is possible, but not confirmed, that systemic reactions increase during the pollen season, but patients generally do not decrease their dose at this time.
Prior Reactions
Together with poorly controlled asthma, the presence of a prior systemic reaction during AIT is the main risk factor associated with a new systemic reaction.
There is currently no evidence that the dose adjustments recommended in clinical guidelines reduce recurrent systemic reaction in a patient.
Premedication with antihistamines or omalizumab has been shown to be useful in some studies, although such treatment is not recommended as standard.
Local reactions do not predict the appearance of a systemic reaction, although some studies have suggested them to be a risk factor.The dose adjustments subsequent to major local reactions recommended in the clinical guidelines do not reduce the frequency of future systemic reactions. For additional information regarding the safety of allergy shots, refer to the reference below:
Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127:S1-S55.
•• Latest and extended update of the Joint Task Force (AAAAI-ACAAI) on Practice Parameters concerning all aspects of allergen-specific immunotherapy.
Vitamin D deficiency is associated with exercise-induced paradoxical vocal cord dysfunction (VCD) in young athletes, according to research presented here at the World Allergy Organization XXII World Allergy Conference (WAC). The study was conducted during the winter in a town above 45 degrees latitude.Exercise can be associated with exercise-induced bronchospasm (EIB) or laryngospasm, which can be mistaken for asthma. The researchers had previously demonstrated that vitamin D deficiency is associated with VCD during a hyperventilation test, especially in hypocapnic conditions.Of the participants, 16 (43%) were atopic and 6 (16%) reported that they had previously been diagnosed with asthma. None used drugs or had had respiratory infections in the previous month, and all had normal results on lung function tests. In isocapnic conditions on hyperventilation testing, 10 participants experienced EIB and 12 experienced exercise-induced VCD. Under hypocapnic conditions, 8 participants experienced EIB and 15 had exercise-induced VCD.Vitamin D deficiency (serum 25-hydroxycholecalciferol < 25 ng/mL) was recorded in 18 participants (49%). Athletes with exercise-induced VCD had significantly lower serum levels of vitamin D than those without it, in both isocapnic (19.1 ± 1.8 vs 25.7 ± 1.5 ng/mL; P = .013) and hypocapnic (20.2 ± 1.9 vs. 26.2 ± 1.8 ng/mL; P = .029) conditions.
The researchers found no correlation between vitamin D and EIB.
“I think the role of vitamin D and other micronutrients [in respiratory problems] is still poorly understood, and for sure they have a role both in this particular syndrome, but also in airway inflammation and so also asthma. I think it’s an interesting field to be expanded,” Enrico Heffler, MD, PhD, from the University of Torino, Italy, who presented the research at a poster session here, told Medscape Medical News.
Dr. Heffler also related a previous case study of a patient with severe vitamin D deficiency who experienced VCD and bronchospasm; symptoms and lung function were significantly improved after vitamin D supplementation.
“This study is fascinating because it links vitamin D deficiency to something new. [The researchers] need to do a double-blind placebo-controlled trial in these individuals,” Glenis Scadding, MD, a consultant allergist and rhinologist at the Royal National Throat, Nose and Ear Hospital, London, United Kingdom, who attended the session, told Medscape Medical News.
Dr. Heffler and Dr. Scadding have disclose no relevant financial relationships.
World Allergy Organization XXII World Allergy Conference (WAC); Abstract 3018. Presented December 6, 2011.
If patients don’t think you as a doctor are open to discussion about complementary medicine, guess what?
Ask your doctor about complementary medicine–don’t be silent any longer!
They won’t talk! This web site is to prove that the Federal Government is interested in “bridging the gap” between traditional medicine and the complementary approach. I would advise you to visit with your doctor about complementary medicines and treatment for allergies & asthma.
Thanks Dr Pedersen for your insight! The bottom line: maybe combination Advair, Symbicort, or Dulera aren’t as bad as they are put out to be.
Over the last decade, the aims of asthma management have altered to focus on achieving and maintaining good asthma control and reducing future risks, such as decrease in lung function, asthma exacerbations, hospitalizations, death, and adverse effects from treatment. The benefits of good asthma control include a variety of asthma outcomes that are important to both patients and society.
These include:
No restriction in lifestyle
Better physical fitness and quality of life
Reductions in patients’ perception of the asthma burden, health care resource use, and lower risk of exacerbations, hospitalizations, and death.
Inhaled corticosteroids (ICSs) or combination therapy with an ICS and a long-acting β2-agonist (LABA) have become established as cornerstones in guideline-recommended asthma treatment because these therapies have been the most successful in achieving asthma control and reducing future risks in the vast majority of patients with asthma.
Changes in the goals of asthma management, as well as treatment recommendations, have revolutionized management from both the patient’s perspective and a societal perspective. The main question that remains is whether the clinical benefits balance or outweigh the risks of the treatments?
When regular ICS treatment was introduced 4 decades ago, safety concerns were common, and initially, the treatment was reserved for patients with severe disease. The concerns were based on fears generated by the side effects of oral corticosteroids rather than data generated by using ICSs, but with increasing knowledge and experience, the concerns decreased, and ICSs became a first-line therapy for asthma because the benefits of the treatment clearly outweighed the risks. Fast foward to 2012 and our concern is overuse of combination therapy with LABAs/ICS as a risk factor for severe, albeit rare, severe asthma exacerbations.
In this issue of the Journal of Allergy and Clinical Immunology, Wells et al add to the paucity of real-world data by reporting the findings from a large, population-based, real-world observational study comparing the effects of ICSs and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population of 1828 patients with a total of 3791 person years of follow-up. Data were obtained longitudinally from a managed care organization, and LABA exposure was estimated from pharmacy data. It was found that ICS/LABA combination therapy had an overall protective effect on asthma exacerbations that was as good as or better than that for ICSs alone. The protective effects of ICS/LABA combination therapy seemed particularly marked in patients older than 18 years, male subjects, patients with moderate and severe asthma at baseline, and reassuringly, African Americans (who have been suggested to be at greater risk).
Although the study is well executed, carefully analyzed, and uses sound methodology, it was not of a sufficient size to make any firm conclusions about severe but rare asthma-related events, such as intubations, death, or both. Yet it is an important contribution to the literature on the perceived risk of serious adverse effects of LABAs. It is reassuring that the results from a carefully executed observational study, mimicking real-world study conditions, are in such good agreement with the findings in the randomized, controlled efficacy trials comparing ICS use alone with a fixed LABA/ICS combination. In addition to significant improvements in asthma control, such studies consistently report reductions in asthma exacerbations, need for oral steroid bursts, and asthma-related emergency department visits compared with ICS treatment alone. Because such events normally precede more serious outcomes, such as intubations, death, or both, these findings make it unlikely (but do not prove) that treatment with fixed LABA/ICS combinations per se should be associated with an increased risk of these serious outcomes.
The US Food and Drug Administration has requested a series of very large postmarketing clinical trials to evaluate LABA/ICS combination safety, (see reference below) but the most serious asthma outcomes are so rare that even these studies might not be able to provide a definite conclusion. Moreover, the results from these studies will not be available until 2017 at the earliest. What should clinicians do in the meantime?
It would be a disservice to our patients if we, in the fear of doing harm to our patients, waited for the perfect. The study by Wells et al supports that a better option would be to follow the recommendations of the asthma guidelines, which unanimously have taken the stand that there is no convincing evidence that LABA/ICS combinations administered in a single inhaler are associated with serious adverse effects. Their benefits on asthma control and reduction of asthma exacerbations outweigh their risk, and we should be careful not to let the perfect become the enemy of the good.
Chowdhury BA, Seymour SM, Michele TM, Durmowicz AG, Liu D, Rosebraugh CJ. The risks and benefits of indacaterol—the FDA’s review. N Engl J Med. 2011;365:2247–2249
Or at least as sexy as you can get for a vitamin. Of all the vitamins out there, vitamin D has the most PROVEN benefit for allergies & asthma. Remember the cod liver oil? Of course you don’t….you’re not that old!
The importance of vitamin D as an essential nutrient is well known, given its role in calcium and phosphate homeostasis. Over the past two decades, the influence of vitamin D on the immune system has become increasingly clear.Recent work has elucidated that vitamin D harbors actions more akin to hormones and pro-hormones. The discovery of the vitamin D receptor (VDR) has stimulated more research into the nature of this vitamin which has, subsequently, been shown to be a steroid hormone. This steroid constitutes a component of a complex endocrine pathway termed the ‘Vitamin D endocrine system’.Investigators have found that vitamin D plays an integral role in the induction of cell differentiation, inhibition of cell growth, immunomodulation, and regulation of other hormonal systems.This review seeks to highlight the recent research with respect to vitamin D and its role in chronic rhinitis and chronic rhinosinusitis (CRS). The results show higher levels of Vit D are associated with fewer problems with allergy and sinusitis.
The effects of Vitamin D
Although these results are extremely compelling, the Mulligan study suffers from a small sample size. Future work may extrapolate these data to a larger patient set, ideally through a prospective study, which would help clarify the role of vitamin D in the pathophysiology of CRS. Systemic vitamin D levels could, potentially, be added to the routine workup of patients suffering from CRS and these data could be used to help determine the disease severity and possibly even treatment. To this end, a recent Polish study evaluated the role of vitamin D in the reduction of fibroblast proliferation in vitro from nasal polyps in patients with CRS. A statistically significant decrease in fibroblast proliferation was noted with calcitriol and tacalcitol treatment. Furthermore, increasingly higher doses induced a greater suppressive effect on fibroblast proliferation. This study is a first step towards investigating the utility of topical vitamin D analogs for the treatment of CRS. Wow–topical Vitamin D for treatment of sinusitis?!
Conclusions from this work:
Early research suggests that vitamin D is involved in the pathophysiology of chronic rhinitis and chronic rhinosinusitis (CRS).
It is intriguing to consider the possibility that abnormal vitamin D blood levels – or even the local tissue concentration of vitamin D – could be a critical influencing factor in chronic rhinitis and CRS pathophysiology.
The concept of the unified airway “one airway, one disease” would suggest that similar associations from the asthma literature will be found with regards to allergic rhinitis, chronic rhinitis, and CRS.
Randomized controlled trials are needed to further evaluate vitamin D and its relationship to allergic rhinitis, chronic rhinitis, and CRS.
These findings may then direct researchers to pursue clinical trials aimed at evaluating vitamin D and its analogs as potential therapeutic interventions.
The practice of medicine is just that….I advise the recommended treatment based on the information available at the time. If I look back to the time during my fellowship in the early 90′s, much of what we thought was true and now 20 years later, been disproven. As an example, the following study from a respected medical journal cautions against the use of PPI medication for reflux in children. It’s worth your attention, but first some background information.
Children have a high prevalence of asthma and gastroesophageal reflux (GER). Children with asthma often report symptoms of GER and also have a high prevalence of asymptomatic GER. We call this “silent reflux”.
Some experts have suggested that untreated GER may cause persistent asthma control problems in children refractory to treatment with inhaled corticosteroids. However, whether treatment with proton pump inhibitors (PPIs) improves asthma control has not previously been determined. The objective of this study by Holbrook and colleagues was to determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER. (ie, Prevacid for “silent reflux”)
Study Synopsis and Perspective
Use of PPIs in children with poorly controlled asthma who were using inhaled corticosteroids and who had no symptoms of GER was not found to improve asthma control and was, in fact, associated with an increase in adverse effects, according to results of a study published in the January 25 issue of JAMA. (PPIs Produce Negative Outcomes in Children With Poor Asthma Control)
PPIs ”are often prescribed for poorly controlled asthma regardless of reflux symptoms, and there have been large increases in the use of PPIs among children between 2000 and 2005…. Hence, it is of clinical importance to determine whether antireflux therapy, the most common of which are PPIs, improves control of asthma in children,” write Janet T. Holbrook, MPH, PhD, from the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues from the Writing Committee for the American Lung Association Asthma Clinical Research Centers.
The goal of this placebo-controlled, double-masked, randomized study was to determine whether the PPI lansoprazole was effective in controlling asthma symptoms in children with asthma, but no overt GER. The researchers also investigated whether pH testing would identify children with GER who responded to PPI therapy.
The children were randomly assigned to receive either lansoprazole (15 mg/day for those weighing <30 kg; 30 mg/day for those weighing ≥30 kg; n = 149) or a matching placebo (n = 157). The researchers found that the mean difference in the Asthma Control Questionnaire (ACQ) score between the 2 groups was 0.2 units (95% confidence interval [CI], 0.0 – 0.3 units), which was not statistically significant (P = .12).
There also was no significant difference in the forced expiratory volume in the first second (FEV1; 0.0 L; 95% CI, −0.1 to 0.1 L), and no change in the rate of episodes of poor asthma control (relative risk [RR], 1.2; 95% CI, 0.9 – 1.5) or asthma-related quality of life (−0.1; 95% CI, −0.3 to 0.1). In addition, children treated with lansoprazole developed more respiratory infections (RR, 1.3; 95% CI, 1.1 – 1.6; P = .02) than those in the placebo group.
A subgroup of children in the study (n = 115) underwent esophageal pH studies before randomization; the prevalence of GER among this group was found to be 43%. In those children with a positive pH study, there was no positive treatment effect with lansoprazole vs placebo for any asthma outcome.
The most common adverse event reported among both groups was asthma exacerbation.
This is the exact opposite of what I would expect!
A higher prevalence of upper respiratory tract infections, sore throats, and episodes of bronchitis was noted among patients in the lansoprazole group. The study authors speculate that this may be a result of loss of host defense against bacterial colonization as a result of higher gastric pH levels.
“The results of this clinical trial are uniformly negative regarding the benefit of acid suppression therapy on symptom relief, lung function, airway reactivity, or quality of life,” write the authors. The results also “indicate that PPI therapy for poorly controlled asthma is not warranted.”
In an accompanying editorial, Fernando Martinez, MD, from the Arizona Respiratory Center, University of Arizona, Tucson, notes that although it is not a statistically significant difference, the increase in activity-related bone fractures in the lansoprazole group also raises concerns. This potential complication has prompted an advisory from the US Food and Drug Administration about the risk for fractures in adults receiving chronic PPI therapy.
Overall, however, Dr. Martinez praises the work of Dr. Holbrook and colleagues and concludes that “[g]iven their potential adverse effects, these medications should thus be used with great restraint for treatment of GER/[gastroesophageal reflux disease] during childhood. The substantial increase in use of PPIs in children during the last decade is worrisome and unwarranted.”
Support for this study was provided by the American Lung Association Asthma Clinical Research Centers Infrastructure Award and National Institutes of Health/National Heart, Lung, and Blood Institute grants. Dr. Holbrook and colleagues have disclosed no relevant financial relationships. Dr. Martinez has served as a consultant to MedImmune and has presented at an Abbott-sponsored seminar.
The Study of Acid Reflux in Children With Asthma was a randomized, masked, placebo-controlled, parallel clinical trial comparing lansoprazole vs placebo in children without overt GER but with poor asthma control despite treatment with inhaled corticosteroids.
Lung function measures, such as FEV1, asthma-related quality of life, and episodes of poor asthma control, were secondary endpoints.
In the subgroup with a positive pH study result, there was no apparent treatment effect for lansoprazole vs placebo for any asthma outcome, including asthma-related quality of life or lung function.
Lansoprazole was also ineffective in subgroups defined by markers of asthma severity (either FEV1 at baseline or oral corticosteroid use in the past year).
At least 1 serious adverse event occurred in 10 participants in the lansoprazole group and 9 in the placebo group.
Asthma exacerbation was the most common serious adverse event in both groups (15 of 25 reports).
The investigators concluded that in children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole did not reduce symptoms or improve lung function but was associated with increased adverse events.
The findings do not support routine esophageal pH testing to identify children who respond to PPIs, nor do they support trials of PPIs for poorly controlled asthma.
An accompanying editorial notes that the overuse of PPIs in childhood asthma is an example of “therapeutic creep,” or extending the use of a treatment with real or suggestive therapeutic effects in selected patients to other patients in whom the efficacy of that treatment has never been demonstrated.
The editorial also notes that therapeutic creep increases the risk for potential adverse effects without any added advantage for patients and may have significantly added to the marked increase in asthma drug costs.
Clinical Implications
Findings of a randomized, placebo-controlled trial suggest that PPI treatment of children with poorly controlled asthma but without symptomatic GER is not effective in reducing asthma symptoms or improving lung function.
In this randomized, placebo-controlled trial, the addition of lansoprazole was associated with increased adverse events, particularly respiratory tract infections. There may be significant safety concerns for long-term PPI use in children, meriting further research
I personally wonder if more aggressive use of Vitamin D replacement would be helpful for the increase in risk of fractures for the patients taking PPI medication. Yes indeed, further research is warranted.
Often allergy patients have sleep disordered breathing and want to know if allergies contribute. Most of the time, interruptions in your sleep due to allergy consist of congestion, snoring, sneezing, and possibly apnea. Anything other than those symptoms should be evaluated for alternative causes. Specialists dealing with sleep disorders are allergists, ENT (otolaryngologists) and pulmonologists. There is a board-certification for sleep medicine, so you might want to check for this on listed credentials. Good night!
Of course you don’t….you’re not that old!
