Omalizumab is efficacious for management of recalcitrant, antihistamine-resistant chronic urticaria.

Chronic urticaria continues to be a challenging condition for both patients and physicians. Despite improved understanding of chronic urticaria, many patients continue to experience ongoing symptoms and impaired quality of life. Omalizumab is a recombinant humanized monoclonal antibody that binds to the domain at which IgE binds to the high-affinity IgE receptor on mast cells and basophils. The efficacy of omalizumab for antihistamine-resistant chronic urticaria has been demonstrated in several randomized controlled trials as well as observational studies. Omalizumab is generally well tolerated, and is associated with less potential for harm compared with other therapeutic alternatives (e.g., calcineurin inhibitors) for recalcitrant chronic urticaria. Omalizumab has become the best-studied agent for treatment of antihistamine-resistant chronic urticaria, and the agent for which the data in support of its efficacy is most methodologically sound. Omalizumab is an effective therapeutic option for patients with recalcitrant chronic urticaria.

International Consensus on drug allergy.

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.

Resveratrol extends lifespan and preserves glia but not neurons of the Nothobranchius guentheri optic tectum.

Resveratrol is reported as having neuroprotective properties, however, much of this reputation has come from research using disease and injury models of neurodegeneration and not neurodegenerative-ageing. The results published here pertain to the affect resveratrol has on neurodegenerative-ageing. Resveratrol had previously been used to extend the lifespan of Nothobranchius furzeri wherein it preserved cognition and reduced ageing-associated neurodegeneration. No cell-type specific antibodies were then identified which could be used to investigate the nature of the neurodegeneration or resveratrols effect on CNS cells. Using wholemounts stained with SMI31 anti-phospho-neurolament, GA-5 and DAKO Z0334 anti-GFAP antibodies, E587 antiserum against NCAMs and anti-tenascin-R antibodies we determined what cellular changes occurred with age in the optic tectum of Nothobranchius guentheri. We show that resveratrol-treatment extended the lifespan of N. guentheri but did not preserve neuron density of the optic tectum stratum griseum superciale even though it did reduce the proportion of degenerate (SMI31 antigen accumulating) neurons in the optic tectum. Resveratrol-treatment did prevent the ageing-dependent loss of radial glia lining the optic tectum of N. guentheri. The ageing-related loss of NCAM expression and tenascin-R expressing perineuronal nets was also prevented by resveratrol-treatment. Glial and perineuronal density as well as NCAM expression appear to correlate well with age. These results suggest that the anti-ageing properties of resveratrol in vertebrates may be unrelated to the protection of neurons.

Neuronal and glial differentiation during lizard (Gallotia galloti) visual system ontogeny.

We studied the histogenesis of the lizard visual system (E30 to adulthood) by using a selection of immunohistochemical markers that had proved relevant for other vertebrates. By E30, the Pax6(+) pseudostratified retinal epithelium shows few newborn retinal ganglion cells (RGCs) in the centrodorsal region expressing neuron- and synaptic-specific markers such as betaIII-tubulin (Tuj1), synaptic vesicle protein-2 (SV2), and vesicular glutamate transporter-1 (VGLUT1). Concurrently, pioneer RGC axons run among the Pax2(+) astroglia in the optic nerve and reach the superficial optic tectum. Between E30 and E35, the optic chiasm and optic tract remain acellular, but the latter contains radial processes with subpial endfeet expressing vimentin (Vim). From E35, neuron- and synaptic-specific stainings spread in the retina and optic tectum, whereas retinal Pax6, and Tuj1/SV2 in RGC axons decrease. Müller glia and abundant optic nerve glia express a variety of glia-specific markers until adulthood. Subpopulations of optic nerve glia are also VGLUT1(+) and cluster differentiation-44 (CD44)-positive but cytokeratin-negative, unlike the case in other regeneration-competent species. Specifically, coexpression of CD44/Vim and glutamine synthetase (GS)/VGLUT1 reflects glial specialization, insofar as most CD44(+) glia are GS(-). In the adult optic tract and tectum, radial glia and free astroglia coexist. The latter show different immunocharacterization (Pax2(-)/CD44(-) /Vim(-)) compared with that in the optic nerve. We conclude that upregulation of Tuj1 and SV2 is required for axonal outgrowth and search for appropriate targets, whereas Pax2(+) optic nerve astroglia and Vim(+) radial glia may aid in early axonal guidance. Spontaneous axonal regrowth seems to succeed despite the heterogeneous mammalian-like glial environment in the lizard optic nerve.

Expression of BDNF and NT-3 during the ontogeny and regeneration of the lacertidian (Gallotia galloti) visual system.

Retinal ganglion cell (RGC) axons regrow spontaneously after optic nerve (ON) transection in G. galloti. Because brain-derived neurotrophic factor (BDNF) is considered the major neurotrophin participating in vertebrate visual system development and promotes RGC survival, we investigated its distribution using dual-labeling immunohistochemistry for neuronal and glial markers. We examined the developing and regenerating lizard visual system at 1, 3, 6, 9, and 12 months postlesion to comparatively evaluate BDNF expression patterns. BDNF was detected from midembryonic stages (E35) in both retinal plexiform layers, and in radial glial processes in the tectum. Moreover, RGC axon staining was detected at late prenatal stages (E39), showing a transient punctate staining which progressed in a temporo-spatial pattern that was similar to myelination. Strong expression in RGC axons was maintained in adults. However, transient downregulation of BDNF staining occurred on the experimental side one month after ON transection followed by a gradual recovery with extensive punctate/swelling distribution and persistent upregulation at 12 months. Conversely, quantitative PCR analysis for 1 and 12 months regenerate lizards showed downregulation of the ratio of BDNF mRNA expression at 12 months and nonsignificant changes of NT-3 transcripts. In summary, we demonstrate that BDNF and NT-3 are abundantly expressed during lizard visual system ontogeny and regeneration suggesting their participation in the development, maintenance and plasticity of the system.

Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations.

This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients' values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients' values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. The GRADE approach to grading quality of evidence about diagnostic tests and strategies.

The GRADE approach to grading the quality of evidence and strength of recommendations provides a comprehensive and transparent approach for developing clinical recommendations about using diagnostic tests or diagnostic strategies. Although grading the quality of evidence and strength of recommendations about using tests shares the logic of grading recommendations for treatment, it presents unique challenges. Guideline panels and clinicians should be alert to these special challenges when using the evidence about the accuracy of tests as the basis for clinical decisions. In the GRADE system, valid diagnostic accuracy studies can provide high quality evidence of test accuracy. However, such studies often provide only low quality evidence for the development of recommendations about diagnostic testing, as test accuracy is a surrogate for patient-important outcomes at best. Inferring from data on accuracy that using a test improves outcomes that are important to patients requires availability of an effective treatment, improved patients' wellbeing through prognostic information, or - by excluding an ominous diagnosis - reduction of anxiety and the opportunity for earlier search for an alternative diagnosis for which beneficial treatment can be available. Assessing the directness of evidence supporting the use of a diagnostic test requires judgments about the relationship between test results and patient-important consequences. Well-designed and conducted studies of allergy tests in parallel with efforts to evaluate allergy treatments critically will encourage improved guideline development for allergic diseases.

Localisation and expression of a myelin associated neurite inhibitor, Nogo-A and its receptor Nogo-receptor by mammalian CNS cells.

Axon regeneration failure in the adult mammalian central nervous system (CNS) is partly due to inhibitory molecules associated with myelin. The Nogo receptor (NgR) plays a role in this process through an extraordinary degree of cross reactivity with three structurally unrelated myelin-associated inhibitory ligands namely; Nogo-A, myelin associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp). The major aim of the study was to investigate and explore the cellular localisation and expression pattern of NgR and Nogo-A in the mammalian nervous system. We therefore generated a rabbit polyclonal anti-NgR antibody from the leucine rich repeat (LRR) No. 9 domain of the NgR polypeptide chain. Together with a commercially available polyclonal antibody specific for NgR, and in conjunction with double labeling immunofluorescence methods on cryosections and cell cultures, NgR immunoreactivity was observed in the CNS and dorsal root ganglia (DRG). In cellular populations, it was confined to neuronal cell bodies and their processes. NgR was also localised on the surface of extending DRG intact axons and growth cones in live staining experiments. Nogo-A, a member of the reticulon family protein, was widely distributed in the mammalian brain, spinal cord, and DRG. Intense Nogo-A immunoreactivity was also detected in oligodendrocyte cell bodies and their myelin sheaths in nerve fibre tracts of the CNS. Furthermore, numerous populations of neurons in the brain and spinal cord expressed Nogo-A to a variable extent in their cell bodies and neurites, suggesting additional, as-yet-unknown, functions of this protein. These results confirm results obtained by other researchers with different sets of antibodies. However, they also raise the question of the mechanism and circumstances under which NgR interacts with Nogo-A, as the latter appears to be confined to the cytoplasm and can therefore not be expected to bind NgR on the axon surface.

Treatment of osteoporosis: missed opportunities in the hospital fracture clinic.

AIM: To identify what proportion of patients who, having sustained an initial distal radial fragility fracture and a subsequent femoral neck fracture, had had their osteoporosis addressed in the interval between the two events. PATIENTS AND METHODS: The hospital electronic information system was used to identify all patients aged over 50 years treated for a distal radial fracture, in our fracture clinic, between 1995-2000. In addition all patients admitted to our hospital, during the same time period, with a femoral neck fracture were identified. RESULTS: A study cohort of 74 patients were identified. The proportion of patients who received investigation of, or treatment for, osteoporosis between their wrist and femoral neck fracture was 8% whereas 84% did not. CONCLUSIONS: Current mechanisms for identifying patients with osteoporosis before they sustain a femoral neck fracture are inadequate.

Glycosylphosphatidyl inositol-anchored proteins and fyn kinase assemble in noncaveolar plasma membrane microdomains defined by reggie-1 and -2.

Using confocal laser scanning and double immunogold electron microscopy, we demonstrate that reggie-1 and -2 are colocalized in < or =0.1-microm plasma membrane microdomains of neurons and astrocytes. In astrocytes, reggie-1 and -2 do not occur in caveolae but clearly outside these structures. Microscopy and coimmunoprecipitation show that reggie-1 and -2 are associated with fyn kinase and with the glycosylphosphatidyl inositol-anchored proteins Thy-1 and F3 that, when activated by antibody cross-linking, selectively copatch with reggie. Jurkat cells, after cross-linking of Thy-1 or GM1 (with the use of cholera toxin), exhibit substantial colocalization of reggie-1 and -2 with Thy-1, GM1, the T-cell receptor complex and fyn. This, and the accumulation of reggie proteins in detergent-resistant membrane fractions containing F3, Thy-1, and fyn imparts to reggie-1 and -2 properties of raft-associated proteins. It also suggests that reggie-1 and -2 participate in the formation of signal transduction centers. In addition, we find reggie-1 and -2 in endolysosomes. In Jurkat cells, reggie-1 and -2 together with fyn and Thy-1 increase in endolysosomes concurrent with a decrease at the plasma membrane. Thus, reggie-1 and -2 define raft-related microdomain signaling centers in neurons and T cells, and the protein complex involved in signaling becomes subject to degradation.

Topographic restriction of TAG-1 expression in the developing retinotectal pathway and target dependent reexpression during axon regeneration.

TAG-1, a glycosylphosphatidyl inositol (GPI)-anchored protein of the immunoglobulin (Ig) superfamily, exhibits an unusual spatiotemporal expression pattern in the fish visual pathway. Using in situ hybridization and new antibodies (Abs) against fish TAG-1 we show that TAG-1 mRNA and anti-TAG-1 staining is restricted to nasal retinal ganglion cells (RGCs) in 24- to 72-h-old zebrafish embryos and in the adult, continuously growing goldfish retina. Anti-TAG-1 Abs selectively label nasal RGC axons in the nerve, optic tract, and tectum. Axotomized RGCs reexpress TAG-1, which occurs as late as 12 days after optic nerve lesion, when regenerating RGC axons arrive in the tectum, suggesting TAG-1 reexpression is target contact-dependent. Accordingly, TAG-1 reexpression ceases upon interruption of the regenerating projection by a second lesion. The topographic restriction of TAG-1 expression and its target dependency during regeneration suggests that TAG-1 might play a role in the retinotopic organization and restoration of the retinotectal pathway.

Survey of the extent and nature of care for adults and older adults by allergy/immunology practitioners.

BACKGROUND: The proportion of older adults in the US population will increase dramatically in the near future, yet the frequency and nature of care furnished to older adults by Allergy/Immunology practitioners has not been described. OBJECTIVE: To determine the extent and nature of care being provided to adults and older adults by Allergy/Immunology practitioners. METHODS: ACAAI members and fellows were surveyed to obtain information regarding certification and training as well as their practice patterns. RESULTS: The distribution of diagnoses among patients aged 40 to 54 years were very similar to distributions found among adults age 55 to 69 years and > or = 70 years of age. Virtually all respondents indicated they provide inhalant allergen immunotherapy for patients age 40 to 54 years with asthma and/or allergic rhinitis; administration of inhalant allergen immunotherapy for asthma and allergic rhinitis was also frequently reported for adults > or = 55 years. The proportions of respondents providing venom immunotherapy for adults aged 40 to 54, 55 to 69, and > or = 70 years were 82%, 70%, and 39%, respectively. CONCLUSION: ACAAI members and fellows commonly provide care to older adults. Our survey findings highlight the need to develop strategies for successful management of Allergy/Immunology conditions specifically pertaining to older adults, including studies to determine the therapeutic utility of inhalant allergen and venom immunotherapy in this age group.

Net nearest neighbor analysis (NNNA) summarizes non-compensated dinucleotides within gene sequences.

MOTIVATION: Net Nearest Neighbor Analysis (NNNA) measures a previously unexamined aspect of dinucleotide frequency-the non-compensated, non-repetitive dinucleotides in a sequence. Non-compensated dinucleotides are those in excess of their corresponding reverse dinucleotides. RESULTS: NNNA regards dinucleotides as vector quantities, making it possible to summarize any sequence as a group of circuits and tags. The results of NNNA are found to be consistent with traditional analytic methods, yet reveal additional characteristics of the sequences. The NNNA circuits and tags uniquely identify each tRNA in Escherichia coli K-12 and certain structural components of each tRNA, extract function-specific characteristics for each of the sequences involved in the formation of insulin from preinsulin, and exhibit species-specific phylogenetic characterization (demonstrated with MONILINIA:). AVAILABILITY: Nearest neighbor analysis software has been available for many years and is a component of most gene analysis software packages, including the Staden Package which is available at no charge to academic users (http://www.mrc-1mb.cam.ac. uk/pubseq/).

Osteoid osteoma of the lunate--a case report.

We report a rare case of an osteoid osteoma of the lunate bone in a young lady who presented to us with chronic wrist pain. She was treated by excision and cancellous bone grafting of the lesion with complete resolution of symptoms.

Identification of reggie-1 and reggie-2 as plasmamembrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons.

Neurons are believed to possess plasmalemmal microdomains and proteins analogous to the caveolae and caveolin of nonneuronal cells. Caveolae are plasmalemmal invaginations where activated glycosyl-phosphatidylinositol (GPI)-anchored proteins preferentially assemble and where transmembrane signaling may occur. Molecular cloning of rat reggie-1 and -2 (80% identical to goldfish reggie proteins) shows that reggie-2 is practically identical to mouse flotillin-1. Flotillin-1 and epidermal surface antigen (ESA) (flotillin-2) are suggested to represent possible membrane proteins in caveolae. Rat reggie-1 is 99% homologous to ESA in overlapping sequences but has a 49-amino-acid N-terminus not present in ESA. Antibodies (ABs) which recognize reggie-1 or -2 reveal that both proteins cluster at the plasmamembrane and occur in micropatches in neurons [dorsal root ganglia (DRGs), retinal ganglion, and PC-12 cells] and in nonneuronal cells. In neurons, reggie micropatches occur along the axon and in lamellipodia and filopodia of growth cones, but they do not occur in caveolae. By quantitative electronmicroscopic analysis we demonstrate the absence of caveolae in (anti-caveolin negative) neurons and show anti-reggie-1 immunogold-labeled clusters at the plasmamembrane of DRGs. When ABs against the GPI-anchored cell adhesion molecules (CAMs) F3 and Thy-1 are applied to live DRGs, the GPI-linked CAMs sequester into micropatches. Double immunofluorescence shows a colocalization of the CAMs with micropatches of anti-reggie antibodies. Thus, reggie-1 and reggie-2 identify sites where activated GPI-linked CAMs preferentially accumulate and which may represent noncaveolar micropatches (domains).

Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol.

The effects of dietary cholesterol on brain amyloid precursor protein (APP) processing were examined using an APP gene-targeted mouse, genetically humanized in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial Alzheimer's disease mutations. These mice express endogenous levels of APP holoprotein and abundant human Abeta. Increased dietary cholesterol led to significant reductions in brain levels of secreted APP derivatives, including sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect on cell-associated species, including full-length APP and the COOH-terminal APP processing derivatives. The changes in levels of sAPP and Abeta in brain all were negatively correlated with serum cholesterol levels and levels of serum and brain apoE. These results demonstrate that secreted APP processing derivatives and Abeta can be modulated in the brain of an animal by diet and provide evidence that cholesterol plays a role in the modulation of APP processing in vivo. APP gene-targeted mice lacking apoE, also have high serum cholesterol levels but do not show alterations in APP processing, suggesting that effects of cholesterol on APP processing require the presence of apoE.

Retinal axon regeneration in the lizard Gallotia galloti in the presence of CNS myelin and oligodendrocytes.

Retinal ganglion cell (RGC) axons in lizards (reptiles) were found to regenerate after optic nerve injury. To determine whether regeneration occurs because the visual pathway has growth-supporting glia cells or whether RGC axons regrow despite the presence of neurite growth-inhibitory components, the substrate properties of lizard optic nerve myelin and of oligodendrocytes were analyzed in vitro, using rat dorsal root ganglion (DRG) neurons. In addition, the response of lizard RGC axons upon contact with rat and reptilian oligodendrocytes or with myelin proteins from the mammalian central nervous system (CNS) was monitored. Lizard optic nerve myelin inhibited extension of rat DRG neurites, and lizard oligodendrocytes elicited DRG growth cone collapse. Both effects were partially reversed by antibody IN-1 against mammalian 35/250 kD neurite growth inhibitors, and IN-1 stained myelinated fiber tracts in the lizard CNS. However, lizard RGC growth cones grew freely across oligodendrocytes from the rat and the reptilian CNS. Mammalian CNS myelin proteins reconstituted into liposomes and added to elongating lizard RGC axons caused at most a transient collapse reaction. Growth cones always recovered within an hour and regrew. Thus, lizard CNS myelin and oligodendrocytes possess nonpermissive substrate properties for DRG neurons--like corresponding structures and cells in the mammalian CNS, including mammalian-like neurite growth inhibitors. Lizard RGC axons, however, appear to be far less sensitive to these inhibitory substrate components and therefore may be able to regenerate through the visual pathway despite the presence of myelin and oligodendrocytes that block growth of DRG neurites.

Exercise-induced bronchospasm in high school athletes via a free running test: incidence and epidemiology.

BACKGROUND: Exercise-induced bronchospasm (EIB) affects up to 35% of athletes and up to 90% of asthmatics. Asthma morbidity and mortality have increased over the past several decades among residents of Philadelphia, PA. It is possible that a simple free running test for EIB may serve as a tool to study the factors contributing to recent trends in asthma, and to screen for asthma in athletes in the urban setting. OBJECTIVES: The purposes of this study were to (1) assess a free running test to screen for EIB, and (2) examine prevalence of and epidemiologic factors associated with EIB in high school athletes. DESIGN: Cross-sectional observational study on the incidence and risk factors for EIB. To validate our method and criteria for the diagnosis of EIB, a repeat test was performed on a portion of the athletes. In a randomized single-blinded fashion, 15 athletes who had demonstrated EIB initially received albuterol or placebo prior to a repeat exercise test. SETTING: Community high school athletic facilities. PARTICIPANTS: We studied 238 male high school varsity football players. INTERVENTION: All athletes underwent an acquaintance session with a questionnaire, followed by a 1-mile outdoor run (6 to 8 mins). MEASUREMENTS: Peak expiratory flow (PEF) measurements were determined prior to and 5, 15, and 30 min after exercise. Heart rates (HRs) and dyspnea scores were measured. EIB was defined as a decrease of 15% in PEF at any time point after exercise. Associations of EIB with demographic factors were assessed by univariate and multivariate analyses. RESULTS: Two hundred thirty-eight athletes participated: 92 European-Americans (EA), 140 African-Americans (AA), 5 Hispanics, and 1 Native American. Mean age was 16+/-1 years. Average HR postexercise was 156+/-24 beats/min. Twenty-four (10%) reported a history of treated asthma. The prevalence of EIB among the remaining 214 athletes was 19 of 214 (9%). The rate of EIB among AA athletes was higher than among EA athletes: (17/126 [13%] AA vs 2/82 [2%] EA, p = 0.01). During the validation portion of the study, the placebo-treated group (n = 7) demonstrated a consistent drop in PEF after exercise on repeat testing, with a 16+/-5% fall in PEF on initial testing and a 14+/-13 drop with placebo. In contrast, the fall in airflow in the albuterol-treated athletes (n = 8) following exercise reversed with albuterol treatment, from a 15+/-6% fall in PEF at initial testing to an increase in PEF of 6+/-9% from baseline following albuterol administration. A history of wheezing (p < 0.001), residence in a poverty area (p < 0.0001), race (p = 0.01), remote history of asthma (p < 0.001), and absolute water content of the air on the day tested (p = 0.04) were significantly associated with EIB. By stepwise regression, EIB was most closely associated with a history of wheezing (p = 0.001) and poverty area residence (p = 0.003). CONCLUSIONS: Our findings indicate a substantial rate of unrecognized EIB exists among urban varsity athletes, and suggest that active screening for EIB, especially for students residing in poverty areas, may be indicated to identify individuals at risk for EIB and asthma.