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Friday, May 21, 2010

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

Monday, May 17, 2010

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.

Friday, May 14, 2010

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.

Friday, May 7, 2010

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

Tuesday, May 4, 2010

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.