Anti-TNF-alpha in asthma: Myth or reality

TNF-alpha has been widely studied in asthma and proposed as a possible target for the treatment of severe asthma. Unfortunately, toxic effects of monoclonal antibodies against TNF-alpha have precluded their use in patients with severe disease. Moreover, the clinical benefits have always been very small.

A new trial assessed the efficacy and safety of ethanercept, a biologic against TNF-apha (fusion protein of TNF-alpha receptor), in moderate-to-severe persistent asthma. In a 12-week, randomized, double-blind, placebo-controlled, phase 2 trial, 132 subjects with asthma received subcutaneous injections of etanercept or placebo twice weekly.

Clinical efficacy of etanercept was not shown in any of the outcomes studied over 12 weeks. However, etanercept treatment was well-tolerated.

The authors propose that studies in specific subsets of patients with asthma with longer-term follow-up may be needed to fully evaluate the clinical efficacy of etanercept in asthma.

Is Bisphenol A a risk factor for allergy in children?

Exposure to environmental toxicants is associated with numerous disease outcomes, many of which involve underlying immune and inflammatory dysfunction. The U.S. government declared Bisphenol A (BPA) a hazardous substance in October 2008 and has since placed it on its list of toxic substances. Triclosan (2,4,4’ –trichloro-2’-hydroxydiphenyl ether) is a chlorinated aromatic anti-microbial agent under review by the U.S. Environmental Protection Agency (EPA) using the new National Health and Nutrition Examination Survey (NHANES) 2003-2006 data.

Using data from the 2003-2006 NHANES, a study in the journal Environmental Health Perspectives compared urinary BPA and triclosan with diagnoses of allergies or hayfever in U.S. adults and children age ≥ 6 years.

Triclosan, but not BPA, showed a positive association with allergy/hayfever diagnosis. In the under-18 age group, higher levels of triclosan were associated with greater odds of having been diagnosed with allergies or hayfever (p<0.01).

Although additional studies should be done to investigate these interesting findings, shall we further restrict the use of BPA ?

Osteopontin implicated in maintenance of chronic allergic contact dermatitis

Acute allergic contact dermatitis (ACD) has been previously linked to secreted osteopontin (sOPN), a glycoprotein with cytokine and chemokine functions. OPN is known to attract myeloid dendritic cells (mDCs) to activate naïve T cells in draining lymph nodes in the skin and induce a TH1 phenotype.

Seier et al. (Am J Path 2010, 176:246-258) follow up on their work identifying osteopontin as a principal player in acute ACD with investigations into the pathophysiology that leads to the chronic condition, which is associated with severe eczema. They discover that OPN attracts memory T cells, monocytes, macrophages, and DCs to the skin in acute exposure. Cytokine function of OPN specifically induces IL-12 secretion and suppresses IL-10 production in macrophages. Then, OPN-related IL-12 production establishes Th1 conditions by skewing mDCs toward IL-12 production, which in turn, augments further OPN secretion. The authors also find that IFN-γ from antigen-specific T cells is critical for activation of OPN production in keratinocytes. The Th1 environment in the epidermis is maintained through cybernetic mechanisms involving OPN, IL-12, and antigen-specific T cells, which support persistent, chronic inflammatory conditions in the skin.

Seier et al. also report that anti-OPN antibody treatment can suppress response in established chronic ACD, suggesting possible prevention and intervention possibilities.

Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Inhaled corticosteroids do not increase pneumonia risk in asthma

Previous research has reported an increased risk of pneumonia in patients with COPD who are on inhaled corticosteroids (ICS). This finding was associated with use of fluticasone, but not with budesonide-treated COPD. O’Byrne et al. (Am J Respir Crit Care Med 2010, doi:10.1164/rccm.201005-0694OC) present results from their analyses on pneumonia adverse events [AEs] and serious adverse events [SAE] from budesonide and budesonide/formoterol clinical trials involving asthma subjects. AstraZeneca collected and analyzed the data, which was reviewed by an independent statistician for the purposes of this research.

O’Byrne and co-authors evaluate two datasets, one from studies in subjects 4 years of age and older comparing placebo to Pulmicort® or Symbicort®, and a second dataset from studies of similar design that also include comparative data on fluticasone and high- and low-dosing effects. Pneumonia AEs from the first dataset were 0.5% in the budesonide group and 1.2% in the placebo group. Pneumonia SAEs were lower in the budesonide and placebo groups.

Analyses of the second dataset show pneumonia AEs in the budesonide group were slightly higher, but still lower than in the placebo group from the first dataset. Pneumonia SAEs were similar between the two datasets. The authors note that the risk of pneumonia between high-dose subjects and low-dose subjects was nearly equivalent. In contrast to the findings in COPD, pneumonia risk was similar, low, and not significant between budesonide and fluticasone.

Wrapping up, O’Byrne et al. point out that subjects in the second dataset with the lowest FEV1 values had higher risk of pneumonia. They comment that, in general, COPD subjects have lower baseline FEV1 than asthma subjects, which could account for greater risk of pneumonia in COPD.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Simvastatin provides little help for reducing steroid use in asthma

Statins have shown anti-inflammatory properties in animal models and human tissues, reducing airway hyperreactivity, mast cell degranulation, and inhibition of airway smooth muscle proliferation. Great hopes have been placed in the treatment of asthma by statins, but only two clinical trials have been published, though, using statins in subjects with asthma.

A double-blind, placebo-controlled, crossover study by Cowan et al. (Thorax 2010, 65:891-896) examines whether simvastatin demonstrates steroid-sparing effects across a 6 month period in 43 subjects with stable persistent asthma. All subjects started on 500μg of fluticasone and simvastatin or placebo. Fluticasone was stepped down each month for 6 months or until loss of control (LOC). Subjects were stepped up at the point of LOC until “minimum necessary” ICS dose to achieve control.

Cowan et al report that subjects at the LOC point were not significantly different between simvastatin and placebo. Nevertheless, the authors note that sputum eosinophils were lower on simvastatin than placebo. They conclude that simvastatin did not produce clinically important steroid-sparing effects, though it was associated with improvements in Asthma Control Questionnaire score and FEV1 as well as mitigating eosinophilia.

Tell us what you think. Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Occupation increases risk of severe exacerbation in workers with asthma

Much research has been published on the association of new-onset asthma diagnosis and occupation. Not surprisingly, the association is significant and has implicated both sensitizing and non-sensitizing agents.

Recently, Henneberger et al. (Eur Respir J 2010, 36:743-750) asked another related question: Is severe asthma exacerbation in current asthma patients associated with occupation? Using the European Community Respiratory Health Survey results, they compiled a cohort of workers with current asthma that reported severe exacerbation in a 12 month period. The authors focused on asthma worsening as related to jobs with high risk of exposure to irritants. They found that the relative risk was significant for occupations with high exposure to dust, gas, and fumes and used that to calculate the population-attributable risk percentage. Approximately 15% of severe asthma exacerbations were associated with occupation. Further, the authors found that both sensitizing and non-sensitizing occupational exposures were implicated, which, they pointed out, was consistent with published reports for occupational, new-onset asthma.

Wrapping up, the authors commented that the size of their cohort provided more robust statistical indices and their focus on current asthma exacerbation delineated more clearly the distinction between occupational asthma and work-exacerbated asthma.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Smoking ban in Scotland has greater impact than expected

In a recent issue of the New England Journal of Medicine, Mackay et al. (N Engl J Med 2010, 363:1139-1145) follow up on the outcome of a 2006 smoking ban in enclosed public places in Scotland. The law was enacted to protect workers exposed to occupational smoke, such as bar workers. To examine evidence for a wider impact, data from the Scottish Morbidity Record (SMR) was pulled for asthma-attributed hospital admissions for infants and children up to 14 years.

Banning smoking in public places has been shown to reduce acute myocardial infarction deaths and hospitalizations as well as decrease hospital admissions because of respiratory conditions, but there have been no studies on how the bans affect asthma in children.

In Scotland, prior to the 2006 ban, there was an increasing trend in admissions for childhood asthma symptoms. After the ban, Mackay et al. report a significant reduction in asthma-related admissions by 13%. They discuss previous studies that have reported significant reduction in respiratory symptoms of workers exposed to occupational smoke as well – even if they are smokers.

Of particular interest, Mackay et al. discuss concerns among Scottish public health officials that the ban would cause increased smoking in the home. In fact, studies had found that voluntary smoking bans in the home increased after the legislation based on objective findings of salivary cotinine in children from those homes.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

The Lancet focuses on asthma

To coincide with the European Respiratory Society meeting in Barcelona, which starts on September 18th, The Lancet's September 4 issue highlights asthma in four review articles. The articles cover areas of asthma care in vulnerable populations, areas that are in desperate need of attention as the incidence rises and patients with asthma are living longer.

Gibson et al. (Lancet 2010, Vol 376:803-813) discuss the complexity and lack of research on management of elderly patients with asthma, noting that their age and comorbidities exclude them from most clinical trials. Bush and Saglani (Lancet 2010, Vol. 376:814-825) hit the other age-related knowledge gap; that is, pediatric asthma patients, especially those with severe, refractory asthma. They comment that this population faces the same obstacles to clinical research that elderly patients with asthma have. Moreover, clinical trials in this age group are needed to understand medical needs in young children.

Busse et al. (Lancet 2010, Vol 376:826-834) discuss the need for better understanding of the mechanisms by which respiratory viruses increase risk of asthma as well as increase susceptibility asthma exacerbation in order to more effectively manage and prevent asthma. Finally, Lambrecht and Hammad (Lancet 2010, Vol. 376:835-843) review the state of knowledge about dendritic cells and their collusion with airway epithelium that results in allergic sensitization and asthma.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

NIH Director responds to stem cell research injunction

Francis S. Collins, M.D., Ph.D., Director, National Institutes of Health, released a statement two days after a controversial injunction on stem cell research was issued by the US District Court of the District of Columbia. Dr. Collins stated that “(t)he recent court ruling that halted the federal funding of human embryonic stem cell research could cause irreparable damage and delay potential breakthroughs to improve care for people living with serious diseases and conditions such as spinal cord injury, diabetes, or Parkinson’s disease. The injunction threatens to stop progress in one of the most encouraging areas of biomedical research, just as scientists are gaining momentum—and squander the investment we have already made.” (For the complete statement go to: http://www.nih.gov/about/director/08262010statement_stemcellinjunction.htm.)

The preliminary injunction ordering the temporary halt of all government funding of stem cell research is based on the case Sherley vs. Sebelius. The suit is brought by Christian groups to challenge President Obama’s reversal of the Bush administration’s increased restrictions on NIH funding of stem cell research under the Dickey-Wicker Amendment

The Dickey-Wicker Amendment prohibits federal funding for “(1) the creation of a human embryo or embryos for research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under” applicable federal regulations.

President Bush’s executive order in 2001 permitted funding induced pluripotential stem cell (iPSC) research, but prohibited federal funding for research on embryonic stem cells (ESCs) that were created after the date of the policy statement. Interestingly, federal funding remained available for research on ESCs that were created by private researchers prior to his policy statement.

Two physicians, Drs. James Sherley, of the Boston Biomedical Research Institute, and Theresa Deisher, of Ave Maria Biotechnology Company, are co-plaintiffs with Nightlight Christian Adoptions and the Christian Medical Association. Ave Maria Biomedical Research Institute is a Seattle-based firm co-founded by Dr. Deisher to establish ethical alternatives to embryonic stem cell research.

Tell us what you think. Please feel free to post your comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Vitamin D deficiency implicated in bronchopulmonary allergic aspergillosis

Will a simple, daily dose of sunshine correct the majority of our immune problems? Vitamin D deficiency has been associated with asthma, IgE levels, atopy, and obesity. Now new research has associated vitamin D deficiency with allergic bronchopulmonary aspergillosis (ABPA), which is, in turn, associated with Aspergillus fumigatus colonization in cystic fibrosis (CF) patients; however, only a small percentage of affected CF patients develop ABPA.

Kreindler et al. (J Clin Invest 2010, doi:10.1172/JCI42388) investigated this observation by comparing the Th2 profiles of ABPA CF patients and colonized, non-ABPA CF patients. They found that ABPA CF patients were characterized by a TSLP- & OX40L-driven Th2 environment. In contrast, non-ABPA CF patients did not have an excessive Th2 response and had high levels of TGF-β producing Tregs. Since vitamin D has been associated with Treg development, the authors assessed vitamin D levels in both groups; they found that ABPA patients were significantly deficient relative to the non-ABPA group. They went on to demonstrate that vitamin D deficiency lowered Tgfb mRNA and raised OX40L levels in mice. Treatment with vitamin D reversed these conditions.

Kreindler and coauthors suggested that their data demonstrated that vitamin D increases the proportion of TGF-β to OX40L favoring the induction of Tregs rather than Th2 cells.

Tell us what you think. Please feel free to post your comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Immunotherapy in asthma: a recent Cochrane review says “YES, but”

Specific immunotherapy is widely accepted in allergic rhinitis but it has long been a controversial treatment for asthma. Dr. Michael J. Abramson started the first Cochrane Collaboration review on the subject in the mid 1990s and two updates have since been published. The most recent one was published in the Cochrane Database of Systematic Reviews 2010 Issue 8 (Abramson MJ, Puy RM, Weiner JM, Injection allergen immunotherapy for asthma). The authors searched the Cochrane Airways Group Trials Register up to 2005, Dissertation Abstracts and Current Contents. Their selection criteria focused on “randomized controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome.”
In all, 88 trials were included, of which 13 were new trials. These trials included 42 that looked at immunotherapy for house mite allergy and six that looked at multiple allergens. Their results were as follows:

Concealment of allocation was assessed as clearly adequate in only 16 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardized mean difference -0.59, 95% confidence interval -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to avoid one requiring increased medication. There was no consistent effect on lung function. If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction. If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity).

The authors conclude that immunotherapy is effective in asthma albeit there is a risk for local or systemic adverse effects (such as anaphylaxis). This indicates that immunotherapy in asthma should be prescribed by specialists and administered with care, in particular in patients with asthma.

Dust from desert storms: Another aggravation for asthma patients

Pollution, ozone, pollen, airborne animal dander, smoke, and now globally distributed mineral dust. These are just a sample of things that are demonstrated to increase the discomfort of asthma sufferers. Dust problems are not just local issues; Saharan dust is distributed across the equatorial zone all the way to Central America as well as southern North American and northern South America. Now there is evidence of significant association between global distribution of dust from these storms and asthma hospitalizations.

This interesting result comes from a study by Kanatani et al. (AJRCCM 2010, doi:10.1164/rccm.201002-0296OC) in which they use optical data from tropospheric monitoring stations in Japan from 2005 to 2009 and compare “heavy dust events,” originating in the Chinese and Mongolian deserts, with asthma hospitalizations in 8 hospitals in Toyama.

They find a significant association between heavy dust events and hospitalizations for asthma exacerbation. This is notable for the higher percentage of boys affected than girls, though the study population had fewer boys than girls. The authors also found that the effect of the dust event persisted up to 6 days after exposure.

Dust mite allergy and perennial allergic rhinitis

The most significant contributor to perennial allergic rhinitis (PAR) is dust mite allergy. Reducing exposure to house dust mite seems like an obvious strategy to minimize symptoms in PAR patients, but does it work? In a 2010 update to a Cochrane Review, Sheikh et al. (Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD001563. DOI: 10.1002/14651858.CD001563.pub3) re-examine the literature to see if anyone else is trying to add more insight into this question. The authors searched the same 4 databases, two Cochrane, Medline and EMBASE, for newly published, randomized trials that evaluate air filtration, pesticides, and barrier bedding as mitigation.

Nine trials of varying quality met inclusion criteria. They didn’t find sufficient numbers and/or rigorously designed trials to permit a meta-analysis, so the authors provide a narrative of their findings. Overall the studies’ results suggest that acaricides along with extensive environmental control via air filtration seem to offer some benefit, but it’s uncertain which method is most effective and to what degree. Sheikh and colleagues are able to state that the evidence is strong that the single intervention of barrier bedding in the patient’s room is not likely to be helpful.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

CoFAR program renewed, expanded

The National Institutes of Health (NIH) announced this week that not only has funding for the Consortium of Food Allergy Research (CoFAR) program been extended for an additional five years, but CoFAR’s scope has also been expanded to include research on eosinophilic gastrointestinal diseases (EGID), which are frequently comorbid with food allergies.

Like food allergies, EGIDs are IgE-mediated. The most common EGID presentation is eosinophilic esophagitis. The EGID studies will be led by Dr. Marc Rothenberg (Cincinnati Children’s Hospital), the co-editor of this section, and include researchers from the University of Colorado, Denver, and Children’s Hospital, Philadelphia.

An additional clinical trial for treatment of peanut allergy has been added to the research program. The new treatment delivers peanut protein transdermally. Further program expansion includes two sites to examine food allergy genetics.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

A new combo product approved for asthma

Last week, Merck & Co.’s Schering Corp. announced that they have received approval from the US Food and Drug Administration for DULERA®, a fixed-dose combination product of mometasone and formoterol, indicated for controller treatment of asthma in patients 12 years and older.

Two controlled studies comparing DULERA® with mometasone and placebo support the FDA’s decision. Merck reports significant increases in FEV1 for the AUC0-12hrs in both trials at week 12, with demonstrated persistence at week 26 in one trial. Side effects were similar to other combination products and include headache, nasopharyngeal irritation, and sinusitis. The black box warning for long-acting β-2 agonists is included in the FDA approval. (For the DULERA® medication guide, click here.) The medication comes in two fixed dose strengths and is expected to be available in the US by the end of this month.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Is specific oral tolerance induction with foods an option in allergic children?

Allergists are talking informally about reports of success in clinical trials employing specific oral tolerance induction (SOTI), also know as "oral immunotherapy," as treatment for food allergy. But where are the published reports?

Fisher et al. (Arch Dis Child 2010, doi:10.1136/adc.2009.172460) looked for those clinical trials reports and ran a meta-analysis to see if SOTI is more effective than avoidance for inducing tolerance. The authors’ pivotal criteria for inclusion in the analysis are double-blind oral food challenge before and after treatment.

Fisher and colleagues found only 3 studies that met all inclusion criteria. All three studies found SOTI significantly better than avoidance/placebo for inducing tolerance. However, one study used the endpoint “any tolerance” rather than food challenge-demonstrated tolerance; reanalysis of the published raw data by Fisher et al did not distinguish SOTI from avoidance for that study.

Editors’ note: 2 of the 3 studies were published in the JACI and can be accessed free of charge from http://www.jacionline.org/article/PIIS0091674907020003/fulltext and http://www.jacionline.org/article/PIIS0091674908017259/fulltext.

The three studies comprised only 127 children, which led the authors to comment that a type II error may account for the overall lack of significance to the results. Two studies that reported significance for SOTI did not measure persistence of tolerance over time, which was measured in the 3rd study for which the authors’ reanalysis found no significant difference.

Fisher et al conclude that SOTI cannot be recommended for routine clinical practice for IgE-mediated food allergy treatment yet. They suggest that future, larger trials need to assess persistence of tolerance over time as well as cost-effectiveness and safety.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Rhinitis and asthma increase the risk of days off work

Allergic rhinitis imposes a substantial economic burden on society, with indirect costs of productivity loss that are larger than the direct healthcare costs. All studies carried out in allergic rhinitis combine to indicate that patients with this disease have an impaired work performance. However, it has not been known whether allergic rhinitis can induce days off work and how its impact compares to asthma.

In a large occupational cohort study recently published online by Kauppi et al. (Respiratory Medicine 2010, doi:10.1016/j.rmed.2010.05.006), the risk of absenteeism due to illness (sick leave) associated with allergic rhinitis with or without asthma was examined in Finland. The study population of over 48,000 subjects was drawn from government employees in 10 towns and 21 public hospitals who consented to link their employer’s sick leave records to a survey they completed on allergic rhinitis and asthma. The study periods were 2000-2002 and 2004 and the survey collected information for the previous calendar year.

Overall, subjects with rhinitis took an average of 3.1 sick days/person/year more than the comparison group, while subjects with asthma took 9.4 days more, and subjects with both took 9.7 additional sick days.

To our knowledge this is the first prospective longitudinal study reporting sickness absences in public sector employees with allergic rhinitis, asthma or both. This study found an increased risk of sickness absences for those employees who reported physician-diagnosed self-reported allergic rhinitis, asthma or both of these conditions combined.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest for our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

U.S. Department of Transportation considers peanut restrictions on flights

Peanut allergy is one of the most common food allergies and trace amounts can cause threatening symptoms and even death in the most sensitized patients. The U.S. Department of Transportation (DOT) has announced that it will be gathering feedback regarding whether to restrict, or even ban, the serving of peanuts on commercial flights in the U.S. According to an article from the Associated Press (AP), the DOT will be consulting "allergy sufferers, medical experts, the food industry and the public." Supporters of regulations such as these feel that they will reduce fears and the potential of harm for Americans who suffer from a peanut allergy. Opponents, such as peanut farmers and food packagers, feel that such restrictions would be "overreaching" and "unfair."

According to the AP article, the DOT previously considered mandating peanut-free zones on airliners in 1998, but dropped these plans following a "hostile response" from Congress, which threatened to cut its budget. The article also notes that several airlines, including Continental, United, US Airways and JetBlue, have voluntarily stopped serving packaged peanuts.

The proposals regarding peanuts are part of a longer set of proposed protections for travelers. According to the DOT, three options are being considered: completely banning the serving of peanuts, prohibiting peanuts only requested in advance by a passenger, or requiring a "peanut-free zone" when asked for by a passenger. Quoted in the AP article, DOT spokesman Bill Mosely says, "We're just asking for comment on whether we should do any of these three things... We may not do any of them."

On the other hand, the article also quotes Martin Kanan, CEO of the King Nut Companies, which provides the peanuts served on most U.S. flights: "The peanut is such a great snack and such an American snack... What's next? Is it banning peanuts in ballparks?" Armond Morris, a peanut farmer in Georgia, is also quoted: "The peanut industry feels like we're being picked on... If we're going to go targeting food products, maybe we just need to ban all food" on planes.

Comments on the proposal can be submitted at www.regulations.gov, using docket number DOT-OST-2010-0140.

Bone mineral density impaired in children receiving continuous inhaled corticosteroids

Reduced growth induced by inhaled corticosteroid (ICS) use in children with asthma has been, and continues to be, a focus for researchers. Most of the research has been of short duration, and reported no significant differences observed between ICS-treated children and children treated with non-steroidal therapies, such as nedocromil. Moreover, bone mineral density has never been measured in a trial.

The recent online publication by Turpeinen et al. (Pediatric Research 2010, doi: 10.1203/PDR.0b013e69e36), at Helsinki University Hospital, presents findings from the first long-term controlled trial to address the clinical impact of ICS therapy on bone mineral density (BMD). The authors conduct an 18-month blinded randomized trial with three parallel treatment arms: 1) step down, high to moderate budesonide, followed by low-dose maintainace for 12 months; 2) step down, high to moderate budesonide, followed by placebo for a year, with PRN budesonide for worsening; and 3) disodium cromoglycate (DSCG) for all 18 months.

Turpeinen et al. find that BMD was significantly decreased across any BUD treatment as compared to DSCG treatment after 6 months, but more in the continuous BUD group. The difference between all three treatment groups was significant after 12 and 18 months, by pairwise comparison. Overall, all subjects had increased BMD and height across the duration of the study, with the BUD treatment group having the smallest incremental change. They conclude by suggesting that height could be used clinically to monitor ICS effects on bone.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Can a chip help to diagnose food allergies?

Demonstrating clinical food allergy is a double-edged sword; on the one hand, the least risky approach, using skin testing results and specific IgE levels, is allergen-specific, but problematic for sensitivity assessment. On the other, oral food challenge is very sensitive, but is high risk for the subject and has a significant utilization burden.

Research out of MIT, led by J. Christopher Love, PhD, and his team, might hold the solution. Love and his colleagues have produced a microarray chip capable of assessing cytokine production from single leukocytes. The chip is covered in subnanoliter microwells, and is capable of quantitative measure of cytokine secretion by a single cell activated by antigen using a process called microengraving. The chip has much greater sensitivity to the numbers and intensities of responses by stimulated immune cells and can detect up to 4 different cytokines secreted by a single activated cell. Their research is presented in the journal Lab on a Chip.

So how does this help food allergy diagnosis? Love and his team are collaborating with the Children’s Hospital in Boston to correlate cytokine production with allergic response in children receiving oral immunotherapy for milk allergy. In addition, the chip will be used to characterize cytokine production during the desensitization period.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Are cancer and allergy mutually exclusive?: Myths and difficulties

Researchers are asking the question: are there relationships between atopic illnesses and cancer? There are many papers concluding that patients with atopy or asthma have less cancer than those who do not. Unfortunately, almost the same number of papers concludes the contrary. This month we summarize two papers that report on the effort to discover the possible association between atopy and leukemia or ovarian cancer.

In the first of two articles, ElMasri et al. (Archives of Environmental and Occupational Health, 2010, 65:101-105) report the results of a case-control study that looks at association between asthma and ovarian cancer, using a statewide Florida hospital discharge database. The authors started with asthma (present vs. absent) as their risk factor variable, and with ovarian cancer (present vs. absent) as the dependent variable. They found that patients with ovarian cancer were 30% less likely to be diagnosed with asthma compared to limb fracture patients and 38% less likely to be diagnosed with AMI, suggesting that patients with asthma were less likely to develop cancer of the ovary. Based on these results, ElMasri and co-authors suggest an IL-4 link to the apparent protective effect of asthma, which has been shown to have tumor inhibition activity. Zuber Mulla, PhD, CPH, FAAAAI, senior author on the paper, notes, "We originally looked at other allergic conditions during this retrospective study such as hay fever but naturally this condition was probably undercoded in these types of databases so we dropped it and focused on a more serious condition, asthma (but only 40% or so of asthma is allergic asthma--so more work is still needed in this area)."

Linabery et al. (American Journal of Epidemiology 2010, 171:749-764) present findings from a broader scope meta-analysis that examined associations between clinical manifestations of atopy, including allergies, asthma, eczema, “hay fever,” and hives, and childhood/adolescent leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Ten case-control studies were identified from multiple databases. For any atopy/allergies, 31% were less likely to develop ALL. Each individual atopic disease also had a significant inverse association with ALL. The authors find that an inverse relationship exists between any atopy/ allergy and AML, but that it does not reach significance. There was no overall association between any atopy/allergy and any leukemia. They also discuss the controversy over the protective versus predisposing effect of atopy with respect to cancer. On one side, atopy is hypothesized to be protective, pointing to increased immune responses leading to increased immune surveillance. The opposing position argues that increased immune responses lead to hyperproliferation, which increases the likelihood of genetic errors, such as oncogene dysregulation. Linabery et al. point out that the commonality shared by both atopy and leukemia is the working hypothesis that both are linked to the maturation rate of the immune system.

Tell us what you think. Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

A new day has begun for the prevention and treatment of chronic respiratory diseases

Last week, the United Nations General Assembly adopted a resolution on the prevention and control of noncommunicable diseases. These diseases, which include chronic respiratory diseases (CRDs, including asthma and rhinitis), cardiovascular diseases, cancers, and diabetes, are responsible for almost 35 million deaths each year.

The resolution is intended to stop global increases in premature deaths and burden attributable to these diseases. It calls for a high-level meeting of the General Assembly in September 2011 to focus on the prevention and control of these diseases, and for the UN Secretary-General to prepare a global status report on noncommunicable diseases, with a particular focus on the challenges faced by developing countries.

A press release from the World Health Organization (WHO) welcomed the resolution. Chronic respiratory diseases have been highlighted by the WHO Global Alliance against Chronic Respiratory Diseases (GARD). Many allergy organizations are part of GARD, including the AAAAI, ACAAI, EAACI, WAO, and many national societies.

This resolution paves the way for a new understanding of CRDs across the world and we hope that all allergists will work together for a world where everyone breathes freely.

Systematic review of food allergy papers highlights need for better studies

Public awareness of food allergy is high, which can be attributed, in part, to the work of advocacy groups. Still, in this setting, clinicians are being frustrated by the lack of reliable diagnostic and management guidelines as the demand for evaluation and intervention grows.

An article in the Journal of the American Medical Association (JAMA), published May 12th, reports rather equivocal results of a systematic literature review of food allergy. Chafen et al. (JAMA 2010, 303:1848-1856) find that there are reasons allergists are struggling to address food allergy; that’s because what is known about food allergy is of limited quality, contradictory, and lacks definitional consistency. Over 12,000 citations were reviewed for the authors’ inclusion criteria, with only 72 making the cut. The authors include prospective research in well-defined, appropriately sized populations employing oral food challenge as the diagnostic standard. Cow’s milk, hen’s egg, peanut, tree nut, fish, and shellfish were the foods represented in the 72 citations. They found that the single most confounding factor in establishing prevalence, optimal management guidelines, and prevention is the lack of a consensus diagnosis. The authors determine that self-report bias and low-quality study design, in addition to variability in diagnostic modality, make it almost impossible to develop useful practice guidelines.

Among several key points reported in the article are: 1) food allergy prevalence is greater than 1-2% but less than 10%, 2) among available tests, i.e., food challenge, food-specific IgE, and skin prick testing, not one is sufficiently easy, sensitive, or specific for recommending over the others, and 3) elimination diets are the empirical therapy, but are not supported by critical research. Of particular concern is the real possibility of over-diagnosing food allergy and exposing individuals to the medical and social stressors associated with it. The authors conclude that diagnostic criteria for food allergy are hampering the development of evidence to support clinical management.

Signature mucosa of allergic rhinitis

How different are persistent allergic rhinitis and intermittent allergic rhinitis? As it turns out, not much and quite a lot. Liu et al (Allergy 2010, doi: 10.1111/j.1398-9995.2010.02340.x) have characterized the nasal mucosa of Chinese subjects with moderate/severe persistent (PER) or intermittent (IAR) allergic rhinitis. Nasal tissue from both subjects with IAR and those with PER showed increased eosinophil and mast cell numbers compared with those seen in nonallergic subjects, with exaggerated conditions in PER tissues compared with those seen in IAR tissues. The authors also demonstrated that eosinophil and mast cell activation markers, such as IL-5 and leukotrienes, respectively, were found in much higher concentration in PER and IAR tissues, implying a distinct Th2 inflammatory profile.

Corresponding author Shixi Liu, PhD, MD, had this to add: “This is the first study to describe the inflammatory cell and mediator signatures in patients with PER versus IAR, using the new ARIA classification. The study shows that PER and IAR can not only be distinguished clinically but also are different in terms of the degree of eosinophilic inflammation and mast cell response to anti-IgE. These observations support the concept of classification.

Tell us what you think. Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

New treatments for asthma and COPD announced last week

For years, no new treatment has been available for asthma and COPD; now, in less than a week, novel therapeutic modalities for each have made progress with regulatory agencies.

On April 27, the U.S. Food and Drug Administration (FDA) approved the first medical device that uses radiofrequency energy to treat severe and persistent asthma in certain adults. The Alair Bronchial Thermoplasty System is intended for patients ages 18 and older whose severe and persistent asthma is not well-controlled with inhaled corticosteroids and long-acting beta agonist medications. “The approval of the Alair system provides adult patients suffering from severe and persistent asthma with an additional treatment option for a disease that is often difficult to manage,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health.

Bronchial thermoplasty is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. In subjects with severe asthma, thermoplasty improved asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the 12-month post-treatment period. The FDA based its approval on data from a clinical trial of 297 patients with severe and persistent asthma. The FDA is requiring a five-year post-approval study of the device to determine its long-term safety and effectiveness.

On April 22, a positive opinion was given by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP), recommending the approval of roflumilast (Daxas®) for the maintenance treatment of severe chronic obstructive pulmonary disease (COPD) in the European Union. Roflumilast reduces the activity of phosphodiesterase 4 (PDE4), an enzyme important to the pathogenesis of COPD. Roflumilast is an anti-inflammatory agent targeting the systemic and pulmonary inflammation associated with COPD. This drug reduces inflammation in the lungs and narrowing of airways, and improves breathing problems in adults with severe COPD. The most common side effects are diarrhea, weight loss, nausea, stomach ache and headache. A post-marketing pharmacovigilance plan for roflumilast will be implemented.

In contrast, an FDA panel last month voted against approval for roflumilast on the grounds that the safety data is not convincing in light of a “modest” increase in lung function, as well as lack of comparative efficacy data. The pharmaceutical company that makes the drug, Forest, submitted an amended application requesting a more restrictive indication. The FDA is expected to make a final decision later this month.

These two treatments may not be devoid of side effects, but the benefit for patients with severe asthma or COPD appears to be of interest.

Another challenge to reported risks of long-acting β2-agonists

The FDA’s position on long-acting β2-agonists has taken another hit, this time in an article reporting results from analysis of a massive database: the UK’s General Practice Research Database.

De Vries et al. (Eur Resp J 2010, published online, doi:10.1183/09031936.00124209) look at SABAs and LABAs prescribed for adults with asthma and associated clinical outcomes of death, asthma death, and hospitalization for status asthmaticus. The authors use a new pattern analysis method to determine absolute hazard rates rather than relative risk, which has the advantage of detecting differential effects independent of changes in exposure to treatment.

Starting with the British Thoracic Society’s guidelines for asthma management, exposure outcomes follow the 5 treatment steps that go from minimal intervention with SABAs to routine use of oral corticosteroids in addition to LABAs and ICS. Hazard rates were highest for the first-step and last-step interventions. These populations are recent starters and heavy, long-term treatment users, respectively. Heterogeneity of asthma medication exposure resulted in substantial variability of risk, but overall, no significant risk increases in all-cause and asthma deaths are associated with LABAs, irrespective of other concomitant therapies.

The finding associated with long-term exposure isn’t entirely surprising, but the high risk for new users is unexpected. De Vries et al. speculate that this effect could derive from excessive use of SABAs when no other treatment is prescribed or treatment of misdiagnosed cardiovascular dyspnoea.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Long-acting β2-agonists effective for acute asthma exacerbations

The FDA has just issued an alert not to use long-acting β2 agonists (LABAs) as single control agents for asthma or for the treatment of acute severe asthma. Yet, a few studies show that LABAs, formoterol in particular, may be used in place of short-acting β2 agonists (SABAs) for acute attacks. This is consistent with discussion in the Global Initiative for Asthma guidelines about the possibility that inhaled formoterol might be just as effective as salbutamol for acute intervention. Formoterol has a rapid effect (within 3 minutes) and, unlike SABAs, has 12-hour duration.

In a recent article published in the Annals of Allergy, Asthma, and Immunology (2010; 104:247-252), Rodrigo et al. report the results of meta-analysis on a literature search for treatment interventions for acute asthma attacks that presented to emergency departments. They report that the number of studies was small, but comprised over 500 subjects. The authors found no difference in spirometric measures between formoterol and SABAs across all time points. Importantly, this shared efficacy was independent of dose ratios, age, severity, sponsorship and analysis method. On the other hand, there was no clear physiologic advantage to formoterol, as both formoterol and SABAs had the same effect on serum potassium, heart rate, QT interval and hospitalization.

The authors suggest, in conclusion, that formoterol is equally effective as SABAs for the treatment of acute asthma. They caution that their findings do not extend to life-threatening asthma since none of the studies analyzed included the very severe population.

These findings appear to challenge the recent FDA recommendation.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Allergy healthcare costs could rise as climate change causes longer pollen seasons

Greenhouse gases, like CO2, have been linked to warming trends across the globe. With increased durations of warmer weather, plants not only have longer growing seasons (and therefore pollen seasons), but agricultural growing zones will be slowly climbing north, allowing trees and plants to move into the zones they don’t currently inhabit, but that have become too warm for growing food crops.

According to an April 14 news item from Reuters, citing a joint Asthma and Allergy Foundation and National Wildlife Federation report, the impact of continued global warming may include higher allergen levels for longer periods in the eastern part of the US. Currently, the costs in the US associated with allergies and allergic asthma are at $32 billion, which includes direct medical care, lost workdays, and lower work productivity.

Plants that are already highly allergenic, such as ragweed, would not only grow and pollinate for longer, but could produce more allergenic pollen proteins as a result. A researcher comments in the news item that there is evidence that ragweed actually grows faster in higher concentrations of atmospheric CO2 and that poison ivy produces a different, more allergenic form of its allergen, urushiol.

(For more on this topic, see the open-access review article by Shea et al. from our September 2008 issue.)

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

FDA pulls CFC-propelled metered dose inhalers from production

In the late 1980s, a variety of legislation was passed to reduce the production and use of chlorofluorocarbons (CFCs) around the world. The concern is that CFCs are damaging to the Earth's ozone layer.

Beginning June 14, 2010, the FDA has mandated a phase-out of 7 metered dose inhalers (MDIs) that use chlorofluorocarbons (CFCs) as propellants. The products, which include Asmacort, Maxair, and Combivent, are prescribed for the treatment of asthma and COPD. Final phase-out will be December 2013.

The FDA has also posted a Consumer Health Information sheet to help clinicians and their patients prepare for the transition to other medications such as MDIs that use hydrofluoroalkanes as propellants.

The FDA news release explains the action as concordant with US obligations under the Montreal Protocol, which initiated the ban on CFCs in all marketed products, and the Clean Air Act. MDIs were excepted from these obligations, pending development of alternative delivery products.

What do you think? Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Vitamin D levels tied to lung function and steroid sensitivity

Is it sunscreen? Or video games? Can we blame it on the weather or overeating? There is mounting evidence that vitamin D deficiency/insufficiency may be a critical factor in healthy lung function and far more common than we know.

Vitamin D and lung function in patients with asthma are the topics of articles by Sutherland et al. (Am J Respir Crit Care Med 2010, 181:699-704) and Freishtat et al. (J Pediatr 2010, doi:10.1016/j.jpeds.2009.12.033).

Sutherland and colleagues look at vitamin D2 and D3 levels, FEV1, and PC20 FEV1 in a small sample comprised of ICS-treated and –untreated asthmatic subjects. They report a significant finding of 22 ml mean increase in FEV1 for each ng/ml increase in vitamin D levels. This effect was most prominent in the ICS-untreated subjects. And there's more. Deficient/insufficient vitamin D levels were correlated to greater airway hyperreactivity and obesity. The authors also show that vitamin D improved in vitro glucocorticoid responses across both groups and suggest that serum vitamin D levels be assessed in adult patients with asthma that have poor response to ICS therapy.

Freishtat et al. present results from a cross-sectional study of African American (AA) youth with and without asthma from inner-city Washington, DC. Confirming previous research that AA individuals are more likely to be vitamin D deficient than other races, they report that vitamin D levels were significantly lower in the subjects with asthma as compared to the subjects without asthma, and prevalence of vitamin D insufficiency was significantly greater. Freishtat and colleagues point out that their AA cohort has lower levels of vitamin D than that reported recently for a Costa Rican cohort. They suggest that many factors could contribute to this, such as dark skin, obesity, high rates of poverty and northern latitude.

Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Keeping children with allergic diseases safe at school

Allergic diseases often occur early in life and many children present severe symptoms while at school. It is important that parents inform schoolteachers and nurses of the possible occurrence of severe allergic reactions (to foods in particular) or severe asthma, and that teachers and staff can act quickly if a reaction occurs.

A task force representing the EAACI and GA2LEN has published a position paper in Allergy that presents the case for adoption of school-based programs that identify allergic children and take responsibility for training staff and implementing appropriate interventions for their well-being (Muraro et al. 25 March 2010, online ahead of print).

The task force consensus presents an allergic child’s bill of rights and outlines the structure of school-based responsibility, physician/parent/teacher roles, and a ground plan for anaphylaxis management.

The platform includes descriptions of asthma, eczema, food allergy and anaphylaxis in the context of school presentation, allergic triggers, challenges facing schools, and suggested intervention actions that schools might enforce. Anaphylaxis management has additional guidance that includes acute management and recommended standing medications for school health clinics.

The task force concludes with a brief discussion of a few nationalized efforts to establish uniform approaches to school-based care of allergic children in the US, UK, and Australia, with attendant identification of liability for school personnel.

[For more on this topic, please see the August 2009 JACI issue, which featured reviews on managing food allergies in schools, indoor allergens in schools and day cares, and school-based asthma programs.

Have a comment? We want to hear from you. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Early work on stem cells for treatment of allergic disease

Therapy using progenitor cells is thought to be of great interest in the future for a variety of diseases including immune-mediated diseases.

Bone marrow stromal cells (mesenchymal stem cells) are thought to “sense” their immune milieu and respond to restore balance. Wow. As the authors of a new article in PNAS comment, “is it possible to imagine a drug doing this?” Nemeth et al. (PNAS 2010 107 (12) 5652-5657; published ahead of print March 15, 2010, doi:10.1073/pnas.0910720107) present results adding to evidence that BMSCs act homeostatically regardless of the direction of immune imbalance.

Nemeth et al. begin with the known inflammation-suppressive effect of BMSC in graft/host disease in humans. This effect is thought to go in the direction of balancing Th1 inflammation toward Th2. The authors decided to look at the effects of BMSCs in a mouse model of allergic asthma to see if BMSCs could re-equilibrate aTh2 environment toward Th1/Th2 balance.

They tested this idea in mice with ragweed-induced asthma, administering syngeneic BMSCs intravenously at the time of challenge. There was virtually global suppression of all asthma-related Th2 inflammatory changes, including a decrease in serum IgE and IgG. Furthermore, the authors demonstrate that BMSCs were recruited specifically to the lung in the mice with asthma.

Looking for possible mechanisms, Nemeth et al. find that up-regulated TGF-β expression by the BMSCs is largely responsible for the anti-inflammatory effects and that this is IL-4R/STAT-6 dependent. The increased TGF-β also positively impacts T-reg numbers in the lung tissue.

Nemeth et al. note that during testing to compare BMSC response from allogeneic and syngeneic sources, they used syngeneic fibroblasts as a control and discover that the fibroblasts had beneficial effects, though the effects were milder.

Is this study going to change the paradigm for the understanding of the treatment of asthma or will it be another experimental study which has little effect in humans with asthma?

Have a comment? Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

British allergy society issues guidelines for investigating anesthesia-related anaphylaxis

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) has published guidelines and algorithms for the systematic investigation of anaphylaxis that occurs during general anesthesia. Identifying the allergen is equally as important as identifying the safe alternatives for the patient. Ewan et al. (Clin Exp Allergy 2010 Jan;40(1):15-31.) pressed the importance of these recommendations for accumulating data on anesthetic drugs because there is no supporting data for most drugs used in general anesthesia and it is impossible to do graded challenges with many anesthetic drugs. Additionally, they recommended that the investigation be conducted at a dedicated drug allergy center, to capitalize on the expertise and volume managed at these centers.

The guidelines begin with the obligations of the anesthetist and the allergist, with the anesthetist being responsible for initiating the investigation. Anesthetist responsibilities start post-resuscitation with serum tryptase levels immediately, 1-2 hours, and >24 hours after recovery. They also inform the patient and refer them to the drug allergist. The allergist then follows up with patients and medical documentation to begin the process of identifying most likely causes of anaphylaxis [and distinguishing them from other complications of general anesthesia] and initiating skin prick testing, intradermal testing, and/or challenge. Detailed recommendations for and reliability of technical aspects of the investigation, such as skin prick and cross-reactivity testing, are also covered by Ewan et al.

The authors noted that the most common reaction was to neuromuscular blocking agents [NMBA], though there is an increase in anaphylaxis cases to latex and antibiotics administered peri-anesthetically. They reported that allergic reactions to local anesthetics are extremely rare and that there are no reports of reaction to inhaled anesthesia.

Have a comment? Tell us what you think by posting your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

FDA announces new safety labeling recommendations for long-acting beta2 agonists

The United States Food and Drug Administration (FDA), after continued analysis of clinical trial data on LABAs, has announced additional labeling requirements on formoterol and salmeterol, as well as the combination products that include these drugs.

Black box warnings are currently in place for both formoterol and salmeterol about the possible increased risk of death and limiting use to those patients whose asthma is not controlled on inhaled corticosteroids (ICS). Current labeling also cautions against use of LABAs as monotherapy for asthma and for management of acute exacerbations.

The new FDA labeling requirements mandate labeling language that LABAs are contraindicated as monotherapy, must be used in conjunction with ICS therapy, should be used for short durations to re-establish control of asthma, then discontinued, and must be used in a combination product for patients who require both LABAs and ICS to manage their asthma to ensure that both medications are used by the patient.

In the latest GINA guidelines (2009), it was proposed that LABAs should not be given as monotherapy, but as adjunct to ICS therapy. These recommendations were based on the paper of Nelson et al (Chest, 2006 Jan;129(1):15-26) and a thorough analysis of the literature. They are in line with the FDA announcement.

What do you think? Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Estrogen Replacement and Asthma Risk

Is a significant risk of developing asthma a fair trade for getting rid of hot flashes and night sweats? An article published in the British journal Thorax reports that French women who used hormone replacement therapy (HRT) were 21% more likely to be diagnosed with asthma than those women who never used HRT. Women who used estrogen-only HRT were 54% more likely to develop asthma compared to their “natural” menopause counterparts.

Estrogen and asthma pathogenesis have been studied, but the findings are equivocal. Estrogen is known to have both inflammatory and anti-inflammatory effects, such as suppressing airway hyperresponsiveness, enhancing nitrous oxide synthetase metabolism, and inhibiting cortisone conversion to cortisol.

The authors suggest that the estrogen effects are likely to be a combination of these mechanisms interacting with the individual’s genetic background. The authors point out that their results on the increased risk associated with estrogen-only HRT must be evaluated in the context of other benefits associated with HRT in menopausal women.

What do you think? Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

To avoid or not to avoid?

The evidence is mounting. Early exposure to potential allergens is critical to the development of tolerance. In this blog, we talk about 3 articles that have appeared recently that basically deliver the same message: when it comes to infant feeding to avoid atopy, the jury is still out.

The leading allergy journal in Europe, Allergy, published an article by the EuroPrevall research consortium (a European Union funded project). Their literature review paper found that there is no overall evidence that supports European infant-feeding guidelines for allergy prevention. There was consensus that breastfeeding for 6 months is best for the infant, but its effect on allergy prevention is unknown.

Two Finnish research groups have come up with similar findings about the timing of introduction of solid foods. One article, in the US journal Pediatrics, shows that introduction of eggs, oats, and wheat after the age of 5 months is associated with food allergies later, and late introduction of potatoes and fish is associated with inhalant allergies.

The other article by Finnish researchers, published in the British Journal of Nutrition, reports on the results of a study of asthma risk, and oatmeal. The researchers followed a large cohort of children and parents for 5 years, and report that children introduced to porridge before 5 months of age were 64% less likely to have wheezing as toddlers compared to children who never ate it or ate it at an older age. It was also shown that infants that were fed fish at an early age had significantly lower incidence of allergic rhinitis by 5 years of age.

These findings stand in sharp contradiction to US and European infant-feeding guidelines that emphasize the introduction of solid foods at discrete developmental stages that begin at 6 months of age. Are we creating – unintentionally – our immune-impaired populations by being too avoidant of allergens?

What do you think? Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Asthma and sports

The 2010 Winter Olympics kicks off on February 12th, in Vancouver, British Columbia, Canada. We’ve found some news items spotlighting issues of allergies and asthma for Olympic athletes.

The New York Times published an article on January 13, 2010, asking why as many as 50% of winter sport Olympians have exercise-induced bronchoconstriction (EIB). Yale University allergist, Christopher Randolph, MD, pointed out that EIB, in the absence of asthma, tends to occur in athletes who train for the greatest number of hours, especially in cold weather. So, does cold weather actually cause EIB?

The conventional wisdom has been that EIB is a constriction/dilation reaction to cold air, like numbing/tingling of the fingertips. More recently, researchers now consider the primary cause to be airway dryness. Abrupt moisture loss in the airways causes mast cell degranulation and cytokine release leading to acute inflammation. Recent research in EIB subjects points to dysregulation of aquaporin water channels (Chan et al., Chest 2008).

But this doesn’t answer the question of EIB prevalence in winter sport athletes. One new theory, mentioned by Dr. Randolph, suggests that EIB in winter sport athletes is a sports injury. Chronic inflammation associated with excessive exercise-related respiration may produce the airway injury.

A Canadian Broadcasting Corporation news article takes up the topic of athletes with allergic rhinitis. Dr. Donald Stark, an allergist in Vancouver, commented that February is alder tree pollen season in southwest B.C. He warned that athletes that are not allergic to alder may cross-react if they are sensitive to birch. This is a particularly problematic issue as over-the-counter medications can produce “doping” results, which would immediately disqualify the athlete. Olympic athletes are allowed to take pseudoephedrine, though blood titers cannot be higher than 150μg/ml.

On a sort of related, summer Olympic event note…
Belgian researchers published results in the European Respiratory Journal on their study of infant swimming and bronchiolitis. They found that infants younger than 2 years that swam in indoor or outdoor pools had increased risk of bronchiolitis compared to their non-swimming peers. The researchers suggested that early exposure to chlorine made the airways more sensitive and reactive to infection as well as allergens.

Children who swam in indoor pools had 3.5 times higher risk and children who swam in outdoor pools had twice the risk of bronchiolitis. Infant swimmers with a history of bronchiolitis also had increased risk of asthma and allergies later in life.

We want to hear from you! Please feel free to post your comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Nut allergies on planes

On January 8, USA Today reported that the Canadian Transportation Authority (CTA) has ordered Air Canada to begin steps to create “nut free zones” (NFZ) in their plane cabins to accommodate passengers with severe nut allergies. The CTA made their decision on the basis of complaints from 2 passengers following what were described as "inconsistent and difficult experiences" when they asked Air Canada to accommodate their nut allergies.

A Canadian newspaper, Toronto’s National Post, reported that the CTA gave Air Canada 30 days to give them a plan to create NFZ for each type of plane. Non-allergic passengers seated in these areas will be advised that they may only bring nut-free food stuffs on board and that they will only be served nut-free foods while in flight.

One of the 2 passengers who filed the complaints with the CTA felt that the ruling could have gone further. Another Canadian newspaper reported that the passenger wanted a global nut ban on all flights.

What do you think? Please feel free to post your own comments on this issue below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Biodiversity and allergy prevalence

Now that one section co-editor has given us a piece of his mind (see our previous post), we asked our other co-editor, Jean Bousquet, MD, PhD, Professor, Montpellier University, to tell us what he thinks is important for allergy/clinical immunology research and practice in 2010, both in Europe and the US:

“The United Nations declared 2010 as the International Year of Biodiversity and launched the event with an appeal to the world to save our ecosystems (http://www.un.org/apps/news/). Saving our ecosystems is a topic very close to my heart; one that prompted me to commission an article on biodiversity and allergy prevalence for Allergy at the end of my tenure as editor-in-chief, and which was recently published (Haahtela, T., Allergy 2009, 64:1799-1803).

The commissioned article by Tari Haahtela of Helsinki University Hospital discusses how butterflies are used as indicators of environment change. Butterfly environments with a lot of diverse species are the healthiest, while environments with few butterfly species indicate disequilibrium. Connecting the increase of atopic disease with poorly stimulated immune systems in childhood, Dr. Haahtela suggests that urban environments have very low microdiversity, compared to non-urban environments, and that the immature immune system doesn’t get exposed to a sufficiently broad pathogen load. He uses the example of a study of butterfly diversity in Karelia, a geographic area that stretches across Finland and Russia. In Finland, the butterfly populations were isolated and made up of just a few species; in Russia, the butterflies were more diverse and widespread. The Finnish habitat was a developed area, and had higher atopy incidence; the Russian habitat was agricultural and overall atopy incidence was low. Dr. Haahtela discusses genetic research involving human populations from Karelia, focusing on single nucleotide polymorphisms associated with atopy. The research showed that alleles correlated with high risk for allergy in the Finnish developed region were protective in the Russian agricultural region. He suggests that the butterfly diversity model can be applied to the decreased micro-organismal diversity in the Finnish developed region, in that tolerance requires challenge by many micro-organisms and the loss of that diverse stimulation is the cause of our illness.”

We want to hear from you! Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.

Predictions for the next decade

Welcome to the JACI’s new News Beyond Our Pages (NBOP) blog. This blog is intended to supplement our monthly News Beyond Our Pages feature, which highlights breaking news and recently published articles of interest to the allergy/immunology community. To launch our new blog, we asked Marc Rothenberg, MD, PhD, NBOP section co-editor, and Director of Allergy/Immunology and Professor of Pediatrics at Cincinnati Children’s Hospital Medical Center to give us his thoughts as we enter a new year and a new decade, and to offer up his predictions for allergy/clinical immunology research and practice during the next ten years:

“As we enter this new decade, our specialty has a special opportunity to truly advance care of patients suffering from a variety of diseases including allergy, immunodeficiency, autoimmunity and a host of inflammatory disorders.

The last decade was marked by deciphering of the human genome and the preliminary assessment of its clinical value. I predict that during the next decade, we will begin to truly use the breakthroughs associated with rapid genome sequencing to identify disease etiology, including the role of occult infections and microbiomes, in the diseases of interest to our specialty. This approach will lead to the design of patient and disease specific therapy.

I hope that our discipline can advance from “allergy shots” to directed tolerance induction protocols truly based immune based mechanisms. This is likely going to be first evident in the food allergy field.

Finally, I predict that biological therapeutics, such as anti-cytokine agents, will be proven to be effective for allergic diseases including asthma and will garner FDA approval.”

We want to hear from you! Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.