Grass Pollen Allergy Research Articles

Ultra-Short-Course Seasonal Allergy Vaccine (Pollinex?? Quattro)

This novel ultra-short-course seasonal allergy vaccine, containing glutaraldehyde-modified allergens and the adjuvants 3-deacylated monophosphoryl lipid A (MPL) and L-tyrosine, requires a preseasonal course of only four injections to be effective in the treatment of seasonal allergic rhinitis. In patients with seasonal allergic rhinitis and/or allergic asthma, a four-injection vaccination course with either the grass pollen or tree pollen allergy vaccine significantly reduced skin prick sensitivity reactions, significantly elevated allergen-specific IgG levels and significantly reduced the seasonally induced boost of IgE. Preseasonal vaccination of adult patients with either grass pollen or tree pollen allergy vaccine significantly reduced the median combined symptom/medication score compared with placebo. Similarly, preseasonal vaccination of children and adolescents with allergies to grass pollen or tree pollen significantly reduced the global symptom and medication use scores compared with the previous pollen season. Postmarketing surveillance indicated that after a course of vaccination, 82% of patients experienced reduced symptoms and 62% reduced their rescue medication use compared with the previous season. The allergy vaccine was generally well tolerated. Local reactions, mainly injection-site redness and swelling, were more common than systemic reactions. There were no serious adverse events.

Primary structure, recombinant expression, and molecular characterization of Phl p 4, a major allergen of timothy grass ( Phleum pratense)

Grass pollen allergy is one of the most important allergic diseases world-wide. Several meadow grasses, like timothy grass and rye grass, contribute to allergic sensitizations, but also allergens from extensively cultivated cereals, especially rye, make a profound contribution. The group 4 allergens are well known as important major allergens of grasses. We have cloned for the first time group 4 sequences from Phleum pratense, Lolium perenne, Secale cereale, Triticum aestivum, and Hordeum vulgare, and investigated the IgE-reactivity of recombinant Phl p 4 as a candidate for allergy diagnostic and therapeutic applications.

Efficacy of Sublingual Immunotherapy in Children With Severe Grass Pollen Allergic Symptoms: A Double-Blind Placebo-Controlled Study

Bufe A, Ziegler-Kirbach E, Stoeckmann E, et al. Allergy . 2004;59:498–504 To determine the clinical efficacy of high-dose sublingual immunotherapy (SLIT) in children with grass-pollen allergy by using a double-blind placebo-controlled study. A total of 161 children with seasonal rhinoconjunctivitis, 82 in the treatment group and 79 in the placebo group, were enrolled from 33 centers in Germany. For the first year, patients were given either treatment …

Group 13 Allergens as Environmental and Immunological Markers for Grass Pollen Allergy: Studies by Immunogold Field Emission Scanning and Transmission Electron Microscopy

Background: Polygalacturonases were recently identified as important grass pollen allergens and designated group 13 allergens. The objective of the present study was to investigate the presence of group 13 grass pollen allergens in different grass species, their release and ultrastructural location in dry and hydrated grass pollen. Methods: Nitrocellulose-blotted allergen extracts from 12 wild and cultivated grass genera were probed with a rabbit antiserum raised against purified recombinant timothy grass pollen allergen, Phl p 13. The release kinetics of Phl p 13 from timothy grass pollen hydrated for 0.5 min to 3 h were analyzed by immunoblotting. Phl p 13 was localized in dry and hydrated grass pollen grains by immunogold field emission scanning and transmission electron microscopy. Results: Group 13 allergens were detected in all 12 wild and cultivated grass genera representing the major subfamilies of the Poaceae. Ultrastructurally, the allergen was located in the wall and in the cytoplasm of timothy grass pollen grains. In the cytoplasm, Phl p 13 was associated with polysaccharide particles and as yet undescribed stacks of microtubule-like structures. After hydration in rain water, pollen grains expel cytoplasmic particles of respirable size containing Phl p 13, which becomes detectable in aqueous supernatants already after 0.5 min. Conclusions: Group 13 allergens represent one set of marker allergens which specifically occur in pollen of the major grass subfamilies and are rapidly released in association with respirable particles after pollen hydration. They may be considered as environmental markers for grass pollen exposure and group 13-specific IgE antibodies as immunological markers for genuine grass pollen sensitization.

A hybrid molecule resembling the epitope spectrum of grass pollen for allergy vaccination

Allergy vaccines based on natural allergen extracts contain greatly varying amounts of individual allergens with different immunogenicity. To develop a novel type of allergy vaccine for complex allergen sources that combines defined amounts of the major allergens in the form of single hybrid molecules. A hybrid molecule was engineered by PCR-based mending and expression of the cDNAs coding for the 4 major grass pollen allergens and compared with its single components by circular dichroism analysis, T-cell proliferation, ELISA competition, and histamine release assays. Immune responses to the hybrid molecule were studied in BALB/c mice and rat basophil leukemia assays. The hybrid contained most of the B-cell epitopes of grass pollen and could be used to diagnose allergy in 98% (n = 652) of patients allergic to grass pollen. Immunization of mice and rabbits with the hybrid induced stronger and earlier IgG antibody responses than equimolar mixtures of the components, which can be explained by the induction of stronger T-cell responses by the hybrid versus the individual components. IgG antibodies induced by vaccination with the hybrid blocked immediate allergic reactions, as demonstrated by rat basophil degranulation assays in a murine model of grass pollen allergy. We demonstrate for grass pollen allergy that recombinant hybrid molecules covering the spectrum of the disease-eliciting epitopes of complex allergen sources can be engineered.

Safety and immunological changes during tablet based specific immunotherapy

RATIONALE: The ALK Grass tablet is a new preparation for sublingual immunotherapy of grass pollen allergy. We aimed at determining a safe dose-range, and subsequently confirming the safety during daily sublingual administration. Simultaneously, immunological changes were measured.

Clinical and patient based evaluation of immunotherapy for grass pollen and mite allergy

Background Treatment of allergic disease can be done by pharmacological intervention by allergen avoidance – in the following called standard care (SC), or by specific treatment with allergy vaccination; Specific Immunotherapy (SIT). The aim of this study were to evaluate the effects of subcutaneously administrated SIT compared to SC by objective (clinical/medical records) and subjective parameters (patient's opinion) in a before/after SIT study. Methods The study included retrospectively all grass- and mite allergic 16-60 year old patients (N = 253) who had started SIT for grass pollen or mite allergy during the period 1.1.1996-1.1.2002 at The Allergy Unit, Aarhus University Hospital, or at a specialist practice in Aarhus. Relevant data were collected before/after treatment from medical records and from a specific designed questionnaire. The following indicators for effect were applied: Success of immunotherapy expressed as completion of up dosing phase, change in symptoms, a comparison of overall rhinoconjunctivitis symptoms, number of symptom free days per year, effect of pharmaceuticals, change in physical and psychological wellbeing and number of lost days from work/education and leisure activities. Results Compliance for completed up dosing for SIT was 94 % (95 % CI 90-97). The questionnaire revealed that after SIT there were a significant reduction in degree of symptoms, 84 % (95 % CI 79-89) of the respondents achieved a reduction in over all rhinoconjunctivitis score, there were an increase in symptom free days per year, a decrease in days off/incapacity from work/education and leisure activities, an improved effect of the pharmaceuticals used for allergic symptoms and an improvement in physical and psychological wellbeing. The study also showed that SIT was more effective treating rhinoconjunctivitis symptoms than lung symptoms. Conclusion The study revealed great advantages of SIT compared to SC and a high compliance for SIT during the up dosing period.

Health-Economic Analyses of subcutaneous Specific Immunotherapy for grass pollen and mite allergy

Objective To investigate the health and monetary consequences of treating allergy with specific immunotherapy (SIT) compared with symptomatic treatment/standard care among patients with grass pollen or mite allergy. Methods We performed an economic analysis based on 253 grass- and/or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit, Aarhus University Hospital and at a specialist practice in Aarhus. Relevant data were collected before, during and after SIT treatment from the national health service based on each patient's personal identification number and medical records and from a specifically designed questionnaire. A cost-benefit analysis including direct and indirect costs before, during and after SIT was performed. In addition direct costs were related to the clinical effect (improvement in well-being) in the form of a cost-effectiveness analysis. Results The direct cost per patient/year before SIT (equivalent to standard care) was DKK 2,580. The investment in SIT was DKK 27,545 (in present values) per patient over a 4-year period. After SIT the cost was reduced to DKK 1,072 per patient/year. In the long term, prospective introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/ year of improved well-being. However, when indirect costs were included in the economic evaluation SIT was shown to be net beneficial. Conclusion This study reveals that SIT is associated with initial resource investments and subsequent resource savings in the long term compared with standard care. When all consequences are measured in monetary terms, and assuming that sick days are associated with a loss of productivity, this analysis suggests that SIT increases societal welfare. This conclusion also holds if there is no loss of productivity.

Mapping of conformational IgE epitopes on Phl p 5a by using mimotopes from a phage display library

Phl p 5 represents a major allergen of timothy grass pollen (Phleum pratense). Detailed knowledge about the structures responsible for IgE binding would allow the design of a novel generation of allergy vaccines. We aimed to characterize the IgE epitopes of Phl p 5a using phage display combined with a molecular modeling approach. Phl p 5a-specific IgE from sera of patients with grass pollen allergy was used for screening of a random peptide phage library displaying constrained decamers. Fifteen phage clones that shared sequence motifs and could be grouped into families were selected by using Phl p 5a-specific IgE. Peptide alignment with the solvent-accessible amino acids of Phl p 5a revealed 3 sequence sections with frequent hits of identical or similar amino acids. On the surface of Phl p 5a, these sections assembled in compact patches, most likely representing conformational IgE epitopes, whereas no matching clusters were found on the back sides of the 2 Phl p 5a halves. In surface plasmon resonance experiments, the high-affinity interaction between IgE and Phl p 5 could be competed by phage-displayed peptides up to 24%, indicating that they represent true epitope mimics (ie, mimotopes). Allergen-specific immunogenicity of the mimotopes was proved in Biozzi mice. The selected mimotopes facilitated the localization of conformational IgE epitopes of Phl p 5. We suggest them to be suitable candidates for the development of an epitope-specific immunotherapy.

Safety evaluation of a new allergy vaccine containing the adjuvant monophosphoryl lipid A (MPL) for the treatment of grass pollen allergy.

A novel allergy vaccine (Pollinex Quattro) has been developed for the prevention or relief of allergic symptoms caused by a variety of pollens. Within this range, the grass pollen allergy vaccine contains extracts of 12 grass pollens and rye cereal (all chemically modified by glutaraldehyde) that are adsorbed onto L-tyrosine with addition of the immunostimulatory adjuvant monophosphoryl lipid A (MPL). A specific preclinical safety testing strategy was developed to support clinical use, comprising single-dose toxicity, repeat-dose toxicity and local tolerance studies. Dose levels of up to 0.5 ml per animal (mouse) and up to 1.0 ml per animal (rat and rabbit) were used with vaccines containing 2000 or 12 000 standardized units (SU) ml(-1) of grass pollen allergoids, 50 micro g ml(-1) of MPL adjuvant and 20 mg ml(-1) of tyrosine. Overall, the product showed no toxicological findings of significance at levels greatly in excess of those proposed for clinical use. A not unexpected, but relatively minor, immunostimulatory effect was seen following repeated dosing (once weekly for 3 weeks) at 1.0 ml per rat.

Levocetirizine better protects than desloratadine in a nasal provocation with allergen

BackgroundDirect comparisons of antihistamines are rare but very much needed. Newly available antihistamine preparations, levocetirizine, the R-enantiomer of racemate cetirizine, and desloratadine, an active metabolite of loratadine, have been recently released for allergic rhinitis. ObjectiveWe sought to compare levocetirizine and desloratadine in a nasal provocation test (NPT) with grass pollen. MethodsTwenty-four volunteers with grass pollen allergy and a history of rhinitis were enrolled in a double-blind, placebo-controlled, crossover study. Three NPTs were performed in a dose-escalating manner during the out-of-season period 4 hours after a single dose of levocetirizine (5 mg), desloratadine (5 mg), or placebo. ResultsDifferences in the mean allergen dose level (primary end point) necessary to reach the NPT threshold indicated improved protection provided by levocetirizine compared with that provided by desloratadine (P=.02). Sneezing and rhinorrhea were better inhibited by levocetirizine than desloratadine. Nasal congestion, as assessed by using objective methods, was not limited by either active substances or placebo. In nasal lavage fluid, IL-5, IL-8, eotaxin, and eosinophil cationic protein levels increased at 24 hours, without differences between the groups. In contrast, levocetirizine, but not desloratadine, significantly limited albumin extravasation into nasal lavage fluid in the early-phase response. ConclusionsThis study demonstrates a better overall protection of a single dose of levocetirizine compared with desloratadine in an NPT with grass pollen allergen. In contrast to late-phase inflammatory markers, which were unaffected, extravascular leakage of the early-phase marker albumin was significantly limited by levocetirizine.

Double-masked, randomized, parallel-group study comparing olopatadine 0.1% ophthalmic solution with cromolyn sodium 2% and levocabastine 0.05% ophthalmic preparations in children with seasonal allergic conjunctivitis

Background: It is estimated that >50% of medications have not been tested in children. Physicians need pediatric data to guide them in treating children. Olopatadine hydrochloride ophthalmic solution 0.1% is a topical antiallergic agent that is both an antihistamine with high affinity and selectivity for the histamine H 1 receptor and a mast cell stabilizer that inhibits the release of histamine and other proinflammatory mediators from human conjunctival mast cells. The efficacy and tolerability of olopatadine has been demonstrated by comparative studies in adults and children with seasonal allergic conjunctivitis (SAC). Objective: Pediatric patient data were extracted from 2 clinical trials to assess the efficacy and tolerability of olopatadine hydrochloride ophthalmic solution 0.1% compared with those of cromolyn sodium ophthalmic solution 2% and levocabastine ophthalmic solution 0.05% as treatment for SAC in children. Methods: In study 1, conducted at 15 centers in 7 countries (Europe and Australia) from October 1995 to December 1997, olopatadine was instilled BID and placebo (vehicle) BID for 6 weeks and compared with cromolyn instilled QID. Study 2, conducted at 17 centers in 8 countries (Europe and Australia) from November 1998 to June 2000, compared olopatadine BID with levocabastine BID. In both studies, children of either sex and any race, aged 4 to 11 years, and having proven grass pollen allergies were assigned to treatment in a double-masked, randomized fashion. Slit-lamp examination, the physician's impression scale, and self-ratings were used to obtain efficacy data. Data analyses were based on pollen concentrations. The tolerability assessments were based on visual acuity, pupil diameter, intraocular pressure, and a dilated fundus examination. Results: Study 1 comprised 30 children (olopatadine [n = 13] and cromolyn sodium [n = 17]; 18 boys, 12 girls; mean age, 7.9 years [range, 4–11 years]). Study 2 comprised 22 children (olopatadine [n = 10] and levocabastine [n = 12]; 12 boys, 10 girls; mean age, 8.6 years [range, 5–11 years]). In study 1, ocular itching ( P = 0.010), redness seen on slit-lamp examination (P = 0.003), and eyelid swelling ( P = 0.034) were significantly less intense with olopatadine than with cromolyn sodium during the peak pollen period. In study 2, redness seen on slit-lamp examination ( P = 0.040) and self-rated ocular redness ( P = 0.024) were significantly less intense with olopatadine than levocabastine during the peak pollen period. Olopatadine was well tolerated. Conclusion: Olopatadine hydrochloride ophthalmic solution 0.1% was more effective than both cromolyn sodium 2% and levocabastine 0.05% ophthalmic preparations in controlling ocular signs and symptoms of SAC in children and was well tolerated when administered twice daily for 6 weeks.

VH gene usage in immunoglobulin E responses of seasonal rhinitis patients allergic to grass pollen is oligoclonal and antigen driven.

IgE is the pivotal-specific effector molecule of allergic reactions yet it remains unclear whether the elevated production of IgE in atopic individuals is due to superantigen activation of B cell populations, increased antibody class switching to IgE or oligoclonal allergen-driven IgE responses. To increase our understanding of the mechanisms driving IgE responses in allergic disease we examined immunoglobulin variable regions of IgE heavy chain transcripts from three patients with seasonal rhinitis due to grass pollen allergy. Variable domain of heavy chain-epsilon constant domain 1 cDNAs were amplified from peripheral blood using a two-step semi-nested PCR, cloned and sequenced. The VH gene family usage in subject A was broadly based, but there were two clusters of sequences using genes VH 3-9 and 3-11 with unusually low levels of somatic mutations, 0-3%. Subject B repeatedly used VH 1-69 and subject C repeatedly used VH 1-02, 1-46 and 5a genes. Most clones were highly mutated being only 86-95% homologous to their germline VH gene counterparts and somatic mutations were more abundant at the complementarity determining rather than framework regions. Multiple sequence alignment revealed both repeated use of particular VH genes as well as clonal relatedness among clusters of IgE transcripts. In contrast to previous studies we observed no preferred VH gene common to IgE transcripts of the three subjects allergic to grass pollen. Moreover, most of the VH gene characteristics of the IgE transcripts were consistent with oligoclonal antigen-driven IgE responses.

Clinical efficacy of microencapsulated timothy grass pollen extract in grass-allergic individuals

Conventional allergen immunotherapy is clinically effective in reducing the symptoms of allergic rhinitis and asthma. It differs from other pharmacotherapies in that it can induce long-term clinical remission of these diseases. However, it requires years of treatment and is associated with serious allergic reactions. To evaluate the safety, clinical efficacy, and immunologic mechanisms of immunotherapy with an oral, microencapsulated form of timothy grass allergen. In this double-blind, placebo-controlled study, 24 patients aged 19 to 55 years with grass pollen allergy were randomized to receive either microencapsulated timothy grass pollen extract or placebo once a day for 10 weeks. The dose of study drug was doubled weekly. Safety was evaluated through weekly visits, daily symptom diaries, and routine laboratory tests. Efficacy was evaluated by comparing medication use and symptoms scores during peak grass pollen season before and after treatment. Allergen-specific T-cell responses, cytokine production, and IgG, IgE, and skin reactivity were measured to evaluate immunologic mechanisms. Eleven of 12 patients in the active treatment group had a decrease in the combined medication and symptom score, but only 4 of 10 patients in the placebo group had a decrease in scores. The proliferative response to timothy grass was reduced by at least 30% in 9 of the 12 grass-treated patients, but only 3 of 11 placebo patients had a proliferative response reduction. Timothy grass-induced interleukin-5 messenger RNA was reduced in the active group, but not in the placebo group. There were no significant changes in either group in IgG, IgE, and skin reactivity. Oral immunotherapy with microencapsulated allergen induces a form of immunologic tolerance to the allergen and is a safe, efficient, and effective method of allergen immunotherapy.

Polygalacturonase (pectinase), a new oilseed rape allergen.

Type I hypersensitivity to rapeseed pollen allergens was described as the result of a cross-sensitization with various pollens that could constitute an aggravating factor in birch or grass pollen allergies. Recently, a few rapeseed pollen allergens were described. The aim of the present work was to identify new rapeseed pollen allergens by using two-dimensional gel analysis, microsequencing, and mass spectrometry. Water extractable proteins from oilseed rape pollen or stamen were separated by two-dimensional gel electrophoresis. The proteins were then electroblotted onto a nitrocellulose (NC) sheet. The NC sheets were successively incubated with (1) individual human sera pre-selected for their immunoglobulin E (IgE) reactivity to rapeseed pollen proteins, (2) alkaline phosphatase (AP)-conjugated goat anti-human IgE and (3) AP substrate. The allergens localized by this method were then identified by microsequencing and MALDI-TOF mass spectrometry analysis. Of the 18 sera studied, five recognized a wide multispot zone with a molecular mass around 43 kD and pIs between 6.5 and 8.5. The results obtained with two representative sera are shown. From this zone, two isoforms of the polygalacturonase enzyme were identified by microsequencing. Confirmation was obtained through MALDI-TOF mass spectrometry analysis. The present results allow the identification of a new rapeseed allergen that can be the main allergen for some patients.

Characterization of immunoglobulin E responses in Balb/c mice against the major allergens of timothy grass (Phleum pratense) pollen.

Grass pollen, such as that from timothy grass (Phleum pratense), represents a major cause of type I allergy. To characterize the IgE immune response and to identify the major allergens eliciting an IgE response in a mouse model using pollen extract of P. pratense for sensitization, in order to assess analogies to human hyperreactivity and to gain information on the allergenic potential as determined by the IgE-reactivity kinetics of defined allergens. Balb/c mice were sensitized with pollen extract or with purified natural allergens. Serum IgE levels, the induction of specific IgE antibodies and immediate hypersensitivity were monitored by ELISA, Western blot and a skin test, respectively. The sensitized mice mounted a strong IgE response and showed IgE-reactivity first against Phl p 5a and 5b, then Phl p 4 and 13 and lastly against Phl p 6. No IgE response was mounted against Phl p 1. However, all purified fractions examined (Phl p 5a, 5b, 6 and 1) induced specific IgE and showed similar kinetics of IgE induction as pollen extract (first Phl p 5a and 5b, then Phl p 6). Skin test experiments demonstrated positive reactivity only in sensitized mice. The IgE reactivity induced by the major allergens in Balb/c mice was very similar to that found in allergic patients, with the exception of Phl p 1. The kinetics of the specific IgE response was comparable using either pollen extract or the purified major allergens, indicating that the intrinsic properties of the allergens are of importance rather than their proportionate amounts in pollen extract. This model should prove to be suitable for investigations regarding the mechanisms of induction and manifestation of timothy grass pollen allergy and for the evaluation of therapeutic strategies.

A randomized, double-blind, parallel-group comparison of olopatadine 0.1% ophthalmic solution versus placebo for controlling the signs and symptoms of seasonal allergic conjuctivitis and rhinoconjunctivitis

Background: The most common form of allergic ocular disease is seasonal allergic conjunctivities, coinciding with the pollen season and generally associated with rhinitis. Symptoms of allergic conjunctivitis include ocular itching, hyperemia, tearing, mucus production, foreign body sensation, chemosis, and lid edema. Similarly, the primary symptoms of allergic rhinoconjunctivitis are nasal itching, irritation, sneezing, watery rhinorrhea, and congestion combined with ocular itching, tearing, and swelling. Objective: This study compared olopatadine 0.1% ophthalmic solution with placebo eyedrops (over-the-counter artificial tear product), instilled in the eye, with regard to the prevention and relief of the ocular and nasal symptoms of seasonal allergic conjunctivitis and rhinoconjunctivitis. Methods: This was a randomized, double-blind, parallel-group study, conducted at 7 US centers, to instill either olopatadine 0.1% ophthalmic solution or placebo eyedrops (artificial tears) in both eyes twice daily for 10 weeks. Patients were evaluated for efficacy (intent-to-treat) and safety. Only patients with proven grass pollen allergy (dermal and conjunctival allergen challenge tests) were selected; all patients were studied during the same period, historically shown to be grass season; and grass pollen counts were obtained. Results: A total of 131 patients (64 olopatadine; 67 placebo) were assessed for efficacy (intent-to-treat); 132 patients were assessed for safety. The mean (SD) age of participants was 38.53 (11.61) years (range, 18 to 87 years), and 58.0% were women ( 76 131 ), with no significant differences between groups for age or sex. In the olopatadine group, 1.6% of patients were black ( 1 64 ), compared with 14.9% of the placebo group ( 10 67 ) ( P = 0.005). Mean scores of ocular itching and hyperemia were lower at all assessment times with olopatadine than placebo. The difference was statistically significant ( P < 0.05) for itching on days 7, 14, 35, 63, and 70, and for hyperemia on days 14, 28, 42, and 63, after correction for multiplicity. Linear regression slopes predicting ocular itching and hyperemia from the pollen count were significantly lower ( P < 0.003 and P < 0.035, respectively) with olopatadine than with placebo. Similar results were obtained for rhinorrhea, sneezing, and nasal itching ( P < 0.006, P < 0.012, and P < 0.034, respectively). With placebo, the proportion of patients with frequent ocular itching and hyperemia increased as a function of pollen level; however, with olopatadine, the proportions remained low and virtually constant. Conclusion: In the population studied, olopatadine 0.1% ophthalmic solution controlled ocular and nasal symptoms of allergic conjunctivitis and rhinoconjunctivitis and was well tolerated when administered twice daily for 10 weeks.

Development of a quality-of-life assessment for the allergic child or teenager with multisystem allergic disease

Background: Health-related quality of life (HRQOL) questionnaires currently being used to evaluate allergic disease are organ-specific. They therefore fail to take account of the systemic aspects of allergic disease. Objective: To develop and validate a pediatric HRQOL questionnaire for allergic disease (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ) that encapsulates problems related to the eyes, ears, nose, lungs, skin, emotions, and everyday activities. Methods: In the development phase, 77 subjects (6 to 16 years of age), with seasonal or perennial allergic problems, were asked how much they were bothered by each different area of HRQOL impairment. The highest scoring areas were used to construct the PADQLQ. In the validation phase of the study, 36 subjects (8 to 16 years of age) with seasonal allergic rhinoconjunctivitis, seasonal allergic asthma, and/or cutaneous manifestations of grass pollen allergy were assessed before and during the pollen season. Results: The PADQLQ contains 26 questions. In addition to standard symptoms (eg, rhinitis), it incorporates multiorgan symptoms that are usually overlooked (eg, hearing problems). The PADQLQ demonstrated good cross-sectional and longitudinal validity, showing a high degree of correlation with symptom scores and quality of life as measured by a visual analogue scale and two-organ specific questionnaires. The PADQLQ showed good within-subject reliability and a small minimal important difference (0.33; 95% CI, 0.11 to 0.54 on a 7-point scale). Conclusions: The PADQLQ has good cross-sectional and longitudinal validity, making it a potentially useful outcome measure in the evaluation of systemic treatments such as antihistamine medications and immunotherapy in children with multisystem allergic disease. (J Allergy Clin Immunol 2003;111:491-7.)

Efficacy of sublingual immunotherapy in grass pollen allergy.

Sublingual immunotherapy (SLIT) was developed to improve the safety of specific immunotherapy; however, its effectiveness is still subject to discussion although the balance sheet for SLIT is improving. In SLIT laboratory parameters and objective measures of allergen reactivity are nonuniform even in studies showing clinical effectiveness, thus subjective symptom scores remain the principal end points. For allergic rhinitis an expert panel collaborating with the WHO recently proposed that SLIT was a viable alternative for injectable immunotherapy (SIT) since a multitude of double-blind placebo-controlled studies had proved the effectiveness of SLIT. Unfortunately, there are only a small number of studies comparing effectiveness of SLIT directly with subcutaneous SIT. These studies demonstrated comparable effectiveness of both therapies. According to the data so far SLIT can be recommended for the therapy of allergic rhinitis in adults and children refusing injectable therapy. For the treatment of allergic asthma both positive and disappointing results have been published. Effectiveness in preventing the onset of allergic asthma in patients with allergic rhinitis has been demonstrated for SIT, while for SLIT this question cannot yet be answered.

Airway inflammation in thunderstorm asthma

Epidemics of acute asthma associated with thunderstorms occur intermittently worldwide, though airway inflammation during these acute episodes has not been characterized. The aim of this study was to characterize airway inflammation in thunderstorm asthma. Cases were recruited after presentation to the emergency room with acute asthma immediately following a thunderstorm (n = 6). They were compared to two control groups: a group of atopic asthmatics that had presented with acute asthma to the emergency room prior to the thunderstorm (n = 12), and a second group of corticosteroid naive asthmatics who presented to the emergency room in the prior 12 months (n = 6). Subjects had spirometry, sputum induction and allergy skin tests acutely and at review 4 weeks later. Thunderstorm (TS) cases were more likely to have a history of hay fever and grass pollen allergy, and less likely to be on inhaled corticosteroids (ICS) prior to presentation. Cases and control groups had a similar degree of moderate to severe acute airway obstruction (P = 1.0). TS cases had elevated sputum eosinophils (14.8% of total cell count) compared to controls (1%, 2.6%, P < 0.01). TS cases had higher sputum eosinophil cationic protein (ECP; 11,686 ng/mL) compared to controls (1,883, 3,300, P = 0.02) acutely. TS cases had more cells positive for IL-5 (30%) compared to controls (1, 1.5%, P = 0.02). When adjusted for ICS use, TS cases had a risk ratio for elevated sputum eosinophils of 2.4 (1.23-4.69). Thunderstorm asthma is characterized by airway inflammation with IL-5-mediated sputum eosinophilia and eosinophil degranulation. These results are consistent with allergen exposure as the cause of the exacerbation, and are consistent with the thunderstorm-induced grass pollen deluge as the cause of epidemic asthma after thunderstorms.