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.

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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.

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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.

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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.

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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.