The Editors' Choice

Article Outline

• Synergistic effects of lipid and chemokine mediators on eosinophils
• IL-4–producing basophils in late reactions of the lung
• Allergic and nonallergic eosinophilic rhinitis: More similar than different?
• Medical versus surgical treatment of nasal polyps
• Peanut allergy: Not necessarily a lifelong diagnosis
• Local delivery of SCF antisense oligonucleotides: Promise of a new therapy for asthma?
• Copyright

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Synergistic effects of lipid and chemokine mediators on eosinophils 

Two major classes of eosinophil chemoattractants are peptide CC chemokines, including eotaxins and RANTES, and lipid mediators. Although attention has recently focused primarily on CC chemokines as mediators of tissue infiltration of eosinophils, lipid mediators may also play an important role in regulating this phenomenon. Among this class of substances, 5-oxo-ETE, an arachidonic acid metabolite formed by the 5-lipoxygenase pathway, induces by far the strongest chemotactic response in human eosinophils and has a potency in the range of those of eotaxin and RANTES. In this issue, Powell et al (p 272) demonstrate that CC chemokines and 5-oxo-ETE, as well as acting in their own right as eosinophil chemoattractants, act synergistically to induce enhanced eosinophil migration. Low concentrations of eotaxin and RANTES increase the potency of 5-oxo-ETE by more than 4-fold. The effects of 5-oxo-ETE and eotaxin on activation markers differ somewhat, with L-selectin shedding being more responsive to 5-oxo-ETE, whereas the reverse is true for CD11b expression and actin polymerization. Both mediators have a similar effect on calcium mobilization. The authors conclude that these two classes of chemoattractants may act in concert to induce pulmonary eosinophilia in asthma.

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IL-4–producing basophils in late reactions of the lung 

IL-4 plays a central role in allergic inflammation. Once thought to be made only by a subclass of activated T helper lymphocytes (ie, T_H2 cells), human blood basophils have been shown by more recent studies to be a major source of this cytokine. It is also known that basophils infiltrate allergic reactions along with eosinophils and lymphocytes; however, their role as IL-4–producing cells in these lesions has not been described. In this issue, Schroeder et al (p 265) investigated whether and under what conditions basophils infiltrating the lung 18 to 24 hours after segmental allergen challenge express IL-4 ex vivo. Using cells recovered by bronchoalveolar lavage, they found that IL-4 was spontaneously secreted in cultures containing basophils. For comparison, they found no evidence for the spontaneous secretion of this cytokine by either mononuclear cells or eosinophils recovered from the same subjects. Failure of the bronchoalveolar lavage basophils to release histamine in response to the allergen that provoked the late-phase response, while producing IL-4 in response to calcium ionophore, further supported the belief that these cells were activated in vivo. These findings suggest that basophils, by producing IL-4, play an important role in amplifying allergic inflammation by promoting T_H2 development, eosinophil migration, and IgE synthesis.

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Allergic and nonallergic eosinophilic rhinitis: More similar than different? 

It is a common clinical practice to use the term bronchial asthma without further defining it as allergic or nonallergic. The same practice of nomenclature has not been typically used for the nasal disease that is frequently associated with asthma. In this case the alternative terms of allergic and vasomotor rhinitis are often used depending on the presence or absence of positive skin test results. In this issue, Amin et al (p 249) report on the inflammatory and epithelial characteristics of 27 patients with perennial allergic rhinitis, 12 patients with perennial rhinitis with eosinophils on nasal smear but negative skin test results, and 7 control subjects without rhinitis. They found, in nasal biopsy specimens, that the patients with allergic and nonallergic rhinitis presented similar histologic features of increased numbers of eosinophils and increased and activated mast cells with loss of epithelial integrity. There was a significant negative correlation between the number of eosinophils and epithelial integrity in all patient groups. Their findings support the concept of “eosinophilic rhinitis” as an entity, the nasal equivalent of bronchial asthma. The presence or absence of allergy would then not be the defining characteristic of the condition, but rather a modifying term.

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• Figure. Eosinophil peroxidase staining of a nasal biopsy specimen from a patient with perennial nonallergic rhinitis.

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Medical versus surgical treatment of nasal polyps 

The randomized, double-blind trial is the gold standard for assessing the efficacy of drug therapy. It would be difficult to conduct a double-blind trial for a surgical therapy. Alternatively, a prospective, randomized trial of surgical therapy does not present insurmountable obstacles. In this issue, Blomqvist et al (p 224) demonstrate the feasibility of this approach. They examined the relative effectiveness of medical versus surgical treatment of nasal polyposis. They recruited patients with symmetrical nasal airways and nasal polyposis. All 32 subjects received prednisone for 10 days and nasal budesonide for 30 days. Afterwards, all patients underwent unilateral endoscopic sinus surgery on either the left or right side, by random assignment. After surgery they received topical budesonide bilaterally for a year. At the end of the year the surgically treated side showed significant improvement over the medically treated side. After 1 year, all subjects were offered surgery on the unoperated side. Twenty-five percent requested this additional surgery. For this 25%, the improvement they had experienced with surgery was apparently worth the inconvenience and discomfort of another operation. For most it was not, presumably either because they had experienced such a good response to medical treatment or because they felt that the results with their first surgery did not justify a second operation.

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Peanut allergy: Not necessarily a lifelong diagnosis 

It has traditionally been thought that peanut allergy is not outgrown. In this issue, Skolnick et al (p 367) challenged this notion in a study of children and adolescents with peanut allergy. A total of 223 patients were evaluated, and those who had been reaction free for the past year and had a peanut IgE level below 20 kU_A/L were invited to participate in an oral peanut challenge. Eighty-five of the 223 patients were challenged, and of those, 48 had no reaction (21.5% of all study participants). Characteristics that might help to predict which patients would have reactions were investigated, and it was found that patients who outgrew their peanut allergy were more likely to have outgrown another food allergy as compared with the patients with ongoing peanut allergy. Most importantly, peanut IgE levels were significantly lower in those patients who passed the challenge than in those who failed and those who could not be challenged. In fact, 61% of those with peanut IgE levels below 5 kU_A/L and 67% with levels below 2 kU_A/L had negative challenge results. The authors recommend that children with peanut allergy be re-evaluated at regular intervals and that those with low peanut IgE levels be considered for oral peanut challenge.

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Local delivery of SCF antisense oligonucleotides: Promise of a new therapy for asthma? 

To better understand the role of stem cell factor (SCF) in the pathogenesis of asthma, Finotto et al (p 279) examined the effects of SCF antisense oligonucleotides on allergic inflammatory responses. They demonstrated selective suppression of SCF expression in several cell lines using a specific antisense phosphorothioate oligonucleotide, which overlapped the translation start site of SCF. Next, they tested the effects of SCF antisense phosphorothioate oligonucleotides in a murine model of late-phase allergic inflammation in ovalbumin-sensitized mice. Dexamethasone was used as a comparison treatment. The SCF antisense oligonucleotide treatment produced strong DNA uptake in interstitial lung cells, a striking reduction of intracellular SCF expression (see figure) and a suppression of IL-4 production and eosinophil infiltration.

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• Figure. Lung tissue sections of OVA-immunized mice stained with antibody against SCF after intranasal treatment with control (A) and SCF (B) antisense oligonucleotides.

The authors report that it was at least as effective as the corticosteroid treatment. This article suggests an important functional role for SCF in a murine model of asthma and invites further study of what may be a novel approach to the treatment of asthma and other inflammatory lung diseases.