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PubMed2001

Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins.

BACKGROUND: Previous twin studies of asthma and allergy implicate both genetic and environmental factors in disease risk, but few have related the occurrence of clinical disease to objective markers of allergic sensitization in twins. OBJECTIVE: We sought to investigate the concordance and interrelationships of self-reported allergic disease and total and aeroallergen-specific IgE levels within pairs of British adult female twins. METHODS: Three hundred forty monozygotic and 533 dizygotic pairs, aged 18 to 72 years, completed questionnaires about allergic disease. Of these, 282 monozygotic and 270 dizygotic pairs were tested for total IgE and specific IgE to Der p 1, mixed grass pollen, and cat dander by means of fluoroimmunoassay. RESULTS: Concordance rates for all variables were higher for monozygotic than for dizygotic twins, significantly (P < .05) so for hay fever, eczema, and specific IgE positivity but not (P > .05) for self-reported asthma or allergies. Within-pair correlations of log-transformed IgE were 0.59 for monozygotic twins and 0.29 for dizygotic twins, implying heritability of 60%. Within both monozygotic and dizygotic pairs discordant for hay fever or reported allergies, the affected twin had significantly higher total and specific IgE levels. Within pairs who were doubly discordant for 3 allergic diseases, associations between diseases were of similar strength for monozygotic and dizygotic pairs. CONCLUSIONS: These results confirm that genetic factors influence susceptibility to aeroallergen sensitization and clinical allergic disease. However, genetically identical twins are often discordant in their expression of atopy, suggesting a substantial modifying role for environmental factors.

Adolescent↗

PubMed2002

Exposure to birch pollen in infancy and development of atopic disease in childhood.

BACKGROUND: The relationship between early allergen exposure, sensitization, and development of atopic disease remains controversial. In 1993, extremely high levels of birch pollen were recorded in Stockholm, Sweden, creating the unique opportunity to study children with different exposures during infancy. OBJECTIVE: We sought to assess the influence of early high-dose exposure to an inhalant allergen (birch pollen) on sensitization and development of atopic disease in children. METHODS: A total of 583 children with atopic heredity born in Stockholm in February through April 1992, 1993, or 1994 were investigated at age 4.5 to 5 years. The children were examined and underwent skin prick testing with inhalant and food allergens. IgE antibodies (RAST) against birch pollen and recombinant birch pollen allergen (rBet v 1) were analyzed in serum. RESULTS: The children born in 1993 (high-dose exposure at 0-3 months) were more often sensitized (ie, positive skin prick test response) to birch pollen than the children born in 1994 (low-dose exposure; 17.8% and 8.8%, respectively; odds ratio [OR], 2.4; 95% CI, 1.2-4.6). A tendency in the same direction was seen for children born in 1992 (high-dose exposure at 12-15 months; OR, 1.7; 95% CI, 0.9-3.2). The results were supported by the RAST analyses. The prevalence of bronchial asthma, allergic rhinoconjunctivitis, and atopic dermatitis did not differ between the birth-year groups. However, the prevalence of pollen- and animal dander-induced allergic asthma was increased in the children born in 1993 (OR, 2.6; 95% CI, 1.2-5.6). An interaction between early high-dose exposure to birch pollen and cat in the household was suggested for sensitization to cat (P =.06). CONCLUSION: Exposure to high levels of birch pollen in infancy increases the risk of sensitization to the same allergen, as well as the risk of allergic asthma.

Air Pollutants↗

PubMed2002

Eyelid dermatitis: experience in 203 cases.

Allergic contact dermatitis has been considered the most common of the many dermatologic conditions found with eyelid dermatitis. This is a retrospective study of 203 patients who presented with persistent or recurrent eyelid dermatitis with or without dermatitis elsewhere. Almost all underwent patch testing and, when indicated, radioallergosorbent test, skin prick and intradermal tests, and in many cases, usage tests as part of the workup. Relevant allergic contact dermatitis was found in 151 of 203 patients (74.%): 46 (23.%) had protein contact dermatitis, but only 7% had protein contact dermatitis without concurrent allergic contact dermatitis. Less than 1% had irritant dermatitis alone. Twenty-three patients had atopic eczema, of whom 16 also had allergic contact dermatitis, protein contact dermatitis, or both. Other conditions included seborrheic dermatitis (n = 11), psoriasis (n = 7), dry eyes (n = 9), and dermatomyositis or overlapping connective tissue disease (n = 7). Important sources of contact sensitivity include cosmetics, metals, topical medications including corticosteroids, eye medications, dust mites, animal dander, and artificial nails; only 5 cases were caused by nail lacquer. Eyelid dermatitis is a multifaceted clinical problem, but in this group of patients, allergic contact dermatitis was a common cause, even among those with atopic eczema.

Cosmetics↗

PubMed2003

Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli.

Dander from the domestic cat (Felis domesticus) is one of the most common causes of IgE-mediated allergy. Attempts to produce tetrameric folded major allergen Fel d 1 by recombinant methods with structural features similar to the natural allergen have been only partially successful. In this study, a recombinant folded Fel d 1 with molecular and biological properties similar to the natural counterpart was produced. A synthetic gene coding for direct fusion of the Fel d 1 chain 2 N-terminally to chain 1 was constructed by overlapping oligonucleotides in PCR. Escherichia coli expression resulted in a non-covalently associated homodimer with an apparent molecular mass of 30 kDa defined by size exclusion chromatography. Furthermore, each 19,177-Da subunit displayed a disulfide pattern identical to that found in the natural Fel d 1, i.e. Cys3(1) Cys73(2), Cys44(1)-Cys48(2), Cys70(1)-Cys7(2), as determined by electrospray mass spectrometry after tryptic digestion. Circular dichroism analysis showed identical folds of natural and recombinant Fel d 1. Furthermore, recombinant Fel d l reacted specifically with serum IgE, inducing expression of CD203c on basophils and lymphoproliferative responses in cat-allergic patients. The results show that the overall fold and immunological properties of the recombinant Fel d 1 are very similar to those of natural Fel d 1. Moreover, the recombinant Fel d 1 construct provides a tool for defining the three-dimensional structure of Fel d 1 and represents a reagent for diagnosis and allergen-specific immunotherapy of cat allergy.

Allergens↗

PubMed2004

The 1.8-A crystal structure of human tear lipocalin reveals an extended branched cavity with capacity for multiple ligands.

In contrast with earlier assumptions, which classified human tear lipocalin (Tlc) as an outlier member of the lipocalin protein family, the 1.8-A resolution crystal structure of the recombinant apoprotein confirms the typical eight-stranded antiparallel beta-barrel architecture with an alpha-helix attached to it. The fold of Tlc most closely resembles the bovine dander allergen Bos d 2, a well characterized prototypic lipocalin, but also reveals similarity with beta-lactoglobulin. However, compared with other lipocalin structures Tlc exhibits an extremely wide ligand pocket, whose entrance is formed by four partially disordered loops. The cavity deeply extends into the beta-barrel structure, where it ends in two distinct lobes. This unusual structural feature explains the known promiscuity of Tlc for various ligands, with chemical structures ranging from lipids and retinoids to the macrocyclic antibiotic rifampin and even to microbial siderophores. Notably, earlier findings of biological activity as a thiol protease inhibitor have no correspondence in the three-dimensional structure of Tlc, rather it appears that its proteolytic fragments could be responsible for this phenomenon. Hence, the present structural analysis sheds new light on the ligand binding activity of this functionally obscure but abundant human lipocalin.

Amino Acid Sequence↗

PubMed2003

Allergy and irritation: an adverse association in patients with atopic eczema.

The pathomechanism of atopic eczema is complex. Two of the most important exogenous factors for atopic eczema are allergenic and irritant substances. In this study we investigate the combined effect of topical aeroallergens and irritation on the skin of atopic individuals. We performed patch testing with several aeroallergens (atopy patch test) and with an irritant, sodium lauryl sulphate, on clinically unaffected skin of 30 sensitized patients with atopic eczema. Application was conducted alone and as a consecutive application. Healthy volunteers served as controls. Evaluation was made by measurement of transepidermal water loss 2 h after removal of the patches. In atopic patients, we found increased levels of transepidermal water loss induced by the aeroallergens as well as by sodium lauryl sulphate. The most impressive barrier disruption was seen after application of house dust mite, followed by cat dander and grass pollen. However, the consecutive application of aeroallergens and sodium lauryl sulphate led to a highly pronounced increase in transepidermal water loss. Hence, in sensitized atopic subjects the combined effect of aeroallergens and detergents may cause severe skin problems, and this may be relevant in daily practice.

Adolescent↗

PubMed1987

Bronchial asthma. Mechanisms and management of a complex obstructive airway disease.

Airway hyperreactivity to physical, chemical, and pharmacologic stimuli is a hallmark of bronchial asthma. In patients with extrinsic (allergic) asthma, in whom an immunologic mechanism of the IgE type can be demonstrated, specific sensitivity develops to a variety of common environmental substances, including pollen, fungus spores, house dust mites, and animal danders. Persons with intrinsic asthma, in whom immunologic mechanisms are hard to demonstrate, often have chronic sinus disease and nasal polyps and manifest clinical intolerance to nonsteroidal antiinflammatory agents. Evaluation of asthma includes a history and complete physical examination, skin tests, radioallergosorbent tests, pulmonary function tests, blood gas determination, and inhalation challenge tests. Treatment is focused on environmental control, pharmacotherapy, and immunotherapy.

Adrenal Cortex Hormones↗

PubMed1987

Common seasonal and environmental allergens.

House dust represents a complex mixture of individual, clinically important allergens that includes insects, danders, and pollens. Characterization and standardization of each of these allergens will provide significant advancement in our understanding and treatment of allergic respiratory disease.

Allergens↗

PubMed1989

Allergy shots for hay fever.

Although allergy shots have been used for many years, immunotherapy for symptoms of allergic rhinitis has only recently been clearly shown to be effective. Standardization of allergens will provide even better results in the diagnosis and treatment of allergic rhinitis in the future. Success in an individual patient depends on appropriate application. Immunotherapy should be reserved for patients who have allergy to airborne allergens, have significant symptoms after exposure to them, have sensitivity that has been proven by a skin or in vitro test, and cannot avoid the allergen or control symptoms with drugs. Thus, allergy shots are generally not used for allergy to pet dander or food. Immunotherapy is begun with a very dilute concentration of allergen, which is gradually increased to the maximum dose that is safely tolerated. The interval between shots is then increased gradually to once a month. Duration of treatment is usually 3 years in children and longer in adults. Treatment usually fails if the patient cannot free the environment of large amounts of known allergens, if the allergen was not correctly determined during initial evaluation, or if the allergen dose is inadequate. The patient must have realistic expectations: Allergy shots often do not totally eliminate symptoms, and improvement takes time.

Adult↗

PubMed2004

Respiratory outcome in school-aged, very-low-birth-weight children in the surfactant era.

AIM: To assess respiratory outcome and its predictors during the surfactant era in very-low-birth-weight (VLBW, birth weight <1500g) schoolchildren with and without bronchopulmonary dysplasia (BPD). METHODS: At 7-8 years of age, 34 VLBW children with BPD diagnosed at a postnatal age of 28 d underwent flow-volume spirometry, metacholine challenge, bronchodilatation test, whole body plethysmography and diffusion capacity measurement. Fourteen of them had not recovered from BPD by a corrected gestational age of 36 wk (sBPD subgroup). The age- and sex-matched control groups comprised 34 VLBW cases without BPD and 34 term children. RESULTS: Current respiratory symptoms in contact with cold air and/or upon exercise were reported in one-third of the VLBW children. Only half of the symptomatic VLBW cases without BPD had inhaled medications. Compared with term controls, the BPD cases had lower forced expiratory volume in 1 s (FEV1), higher ratio of residual volume to total lung capacity and higher airway resistance. Lower FEV1 and specific conductance were found in the sBPD subgroup compared to both control groups. Additionally, their vital capacity was lower than in term controls. A higher rate of bronchial hyper-reactivity and lower diffusion capacity of the lungs were detected in VLBW as against term cases. Low birth weight, long duration of oxygen therapy, low socio-economic status and exposure to animal dander emerged as predictors of poorer respiratory outcome. CONCLUSION: In the surfactant era, birth weight, neonatal respiratory morbidity, as well as later environmental factors appear to affect the respiratory outcome of VLBW children. However, careful pulmonary follow-up of all VLBW children seems to be indicated regardless of the severity of neonatal respiratory problems.

Bronchopulmonary Dysplasia↗

PubMed2002

Hidden respiratory allergies in voice users: treatment strategies.

The treatment of the allergic voice patient may be somewhat different than other voice patients. Antihistamines are generally avoided, though decongestants with Guaifenesin may be useful. Steroids are more useful in perennial allergic systems. Steroids may be inhaled nasally, inhaled orally, or given systemically. Systemic steroids are especially useful for a performer who needs quick relief. We strongly feel that vocalists with chronic laryngitis and dysphonia should be allergy tested. A hidden dust mite or cat dander allergy is often found. A clean indoor environment can then be established. Immunotherapy injections can also be initiated. Both of these treatments, desensitization injections and environmental control, are especially useful in vocalists. These treatments are helpful in keeping a vocalist's trachea, larynx, and nasal cavity healthy. A careful search for mild asthma should be considered. Establishing good vocal hygiene and voice training may also be necessary.

Combined Modality Therapy↗

PubMed2002

Respiratory symptoms and asthma in relation to cold climate, inhaled allergens, and irritants: a comparison between northern and southern Finland.

We have compared data from northern and southern Finland in a large epidemiological survey on respiratory conditions. The aim was to compare the prevalence of respiratory symptoms, asthma, and chronic bronchitis in northern and southern Finland. The study was a part of comparative studies in Finland, Estonia, and Sweden, the FinEsS studies. Data from a postal survey on subjects aged 20-69 was analyzed. Participation rate was 84% of 7937 invited in Lapland in the north, and 77% of 7877 in Helsinki in the south. Physician-diagnosed asthma was reported by 5.6% in Helsinki, and by 5.5% in Lapland. Symptoms common in asthma were also equally prevalent in the two areas. Hay fever was significantly more common in Helsinki, 36% vs. 26% (p < 0.001). The prevalence for physician-diagnosed chronic bronchitis was not significantly higher in Helsinki (3.4%) than in Lapland (2.9%). Those working outdoors reported more bronchitic symptoms than people working indoors (p < 0.05). Respiratory symptoms provoked by pollen or animal dander were more common in Helsinki, while symptoms provoked by inhaled irritants or cold weather conditions were more prevalent in Lapland. Current smoking was equally prevalent: 37% in Lapland and 38% in Helsinki. Risk factor analysis showed an elevated risk for chronic productive cough for living in Helsinki (OR 1.32), however, increasing age and current smoking were the strongest risk factors. In conclusion, prevalence of asthma and asthma-related symptoms was similar in southern and northern Finland, but chronic bronchitis and bronchitic symptoms were more common in Helsinki, and the highest prevalence was found among current smokers working outdoors. Respiratory symptoms in cold weather were more prevalent in the north, while hay fever and respiratory symptoms provoked by allergens were more common in the south. The results support the view that environmental factors have a substantial effect on respiratory symptoms, but less effect on the prevalence of asthma.

Adult↗

PubMed1990

Dust from carpeted and smooth floors--III. Trials on denaturation of allergenic proteins by household cleaning solutions and chemical detergents.

The effects of detergents on antigens and allergens of birch and timothy grass pollen extracts, codfish, hen egg-white, cat dander and house dust mite were investigated by crossed immunoelectrophoresis (CIE), crossed radio-immunoelectrophoresis (CRIE), radio-allergosorbent test (RAST) inhibition and quantitative precipitation test using laser nephelometry. Nine household cleaning solutions and five chemical detergents were tested. Higher concentrations than recommended for regular cleaning purposes were used as no influence on the antigenic and allergenic activities could be detected using the usual concentrations. Soft soap, guanidine hydrochloride and sodium lauryl sulphate induced most modifications of the antigens and allergens tested. None of the detergents totally destroyed the antigenic and allergenic activities of the selected material, even when used in concentrations up to 10 times that recommended. The materials used for carpet cleaning would not be able to impose any denaturing effects on allergens left on carpets after cleaning.

Allergens↗

PubMed2004

Longitudinal study of sensitization to natural rubber latex among dental school students using powder-free gloves.

BACKGROUND: A high rate of sensitization and clinical allergy to latex proteins has been reported in health care personnel. This is thought to be due to increased occupational exposure especially to natural rubber latex (NRL) gloves with an estimated prevalence varying widely (2.8-18%). OBJECTIVE: This was a longitudinal study to monitor a cohort of first-year dental students throughout 4 study years during exposure to powder-free gloves. Their atopic status was determined by skin prick testing using a panel of common allergens, and any sensitivity to latex proteins and the cross-reacting food allergens assessed. METHODS: Skin prick testing was carried out on the volunteers using latex, avocado, kiwi, banana, grass pollens, tree pollen, house dust mite and cat dander. Each volunteer completed a questionnaire detailing allergic history and any previous latex exposure. RESULTS: Skin prick testing showed a 65% incidence of atopy in the longitudinal study group. Initial latex skin testing was positive in 3 of the 63 students followed throughout their period of study. Subsequent testing gave a negative result in one student and one declined retesting. The third continued to give a positive response on each testing; she wore only nitrile gloves and remained free of clinical NRL allergy symptoms. No student developed latex sensitivity during the 5 yr of this study. CONCLUSION: Exposure to powder-free latex gloves was not associated with subsequent sensitization over 5 yr in a population with a high atopic incidence.

Allergens↗

PubMed2025

Sex-dependent influence of LMAN1 on allergen-induced airway hyperresponsiveness.

Allergic asthma is a chronic inflammatory disease of the airways characterized by a type 2-high adaptive immune response towards common aeroantigens such as dust mite, pollen, and animal dander. Despite the advances made toward translation of various biologics into the clinic, the limited efficacy of these therapies in certain populations, combined with the ineligibility of some patients for treatment (clinically or economically), have led to the continued need for the development of more widely effective allergic asthma therapies. Our lab previously identified lectin mannose-binding 1 (LMAN1) as a novel receptor for house dust mite (HDM) and showed that in vitro, LMAN1 downregulated inflammatory NF-κB signaling in DCs in response to HDM. In this follow-up work, we investigated the in vivo relevance of LMAN1 by subjecting LMAN1 knockout (KO) mice and wild type (WT) littermate controls to a model of HDM-induced allergic asthma. Surprisingly, we discovered that loss of LMAN1 led to opposing effects on airway hyperresponsiveness (AHR), which were dependent on the sex of the mice. HDM-treated female LMAN1 KO mice showed increased AHR, while HDM-treated male KO mice showed decreased AHR, compared with their WT counterparts. We further identified the features of HDM-induced asthma which may account for the gender-biased effects of LMAN1 on lung function. This work not only highlights the complexity of the loss of LMAN1 in vivo but also suggests that such sex-dependent responses should be taken into consideration when pursuing LMAN1 as a therapeutic target for treatment of allergic asthma.

Animals↗

PubMed1990

Enzyme-linked immunosorbent assay for quantifying antigens of Dermatophagoides farinae and D. pteronyssinus (Acari: Pyroglyphidae) in house dust samples.

Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody as capture and detector antibodies was developed for quantifying antigens of Dermatophagoides farinae Hughes and D. pteronyssinus (Trouessart) mites contained in house dust samples. This monoclonal antibody was directed against mite antigens that were also reactive to immunoglobulin E antibody in all of 10 serum samples obtained from patients allergic to mites. Histological study using fluorescent antibody revealed that the monoclonal antibody was bound to the major part of the D. farinae mite body section including fecal matter and cuticles. The detection limit of the assay system was 0.17 microgram of soluble antigens of both mite species and the antigen amount corresponding to 0.5 mites per microplate well, whether in live or dead mites. This system did not react to antigens of Tyrophagus putrescentiae (Schrank) and Cheyletus malaccensis Oudemans. Slight inhibition of less than or equal to 21.3% was observed with nonspecific substances contained in house dust, such as wool, cotton, human dander, human hair, soil, and biscuit, but no direct ELISA reactions were obtained with any of these materials. In 49 house dust samples, ELISA was significantly correlated with the conventional microscopic observation method.

Animals↗

PubMed2006

Reliability and validity of the Asthma Trigger Inventory applied to a pediatric population.

OBJECTIVE: To test the reliability and validity of the Asthma Trigger Inventory (ATI) applied to a pediatric population. METHOD: Children with asthma (N = 272, 56% male, age 7-17) and their primary caregivers answered together an asthma trigger inventory, ATI (Ritz, Steptoe, Bobb, Harris, & Edwards, 2006) developed for adults. Cronbach's alpha, principal component analysis (PCA), hierarchical regression, and correlations of the ATI subscales with skin prick tests, psychological questionnaires, and disease severity were used to assess the psychometric properties of the ATI. RESULTS: The ATI subscales demonstrated excellent reliability regardless of gender, race, socioeconomic status (SES), or age. PCA confirmed and replicated the theoretical structure of the ATI. Hierarchical multiple regressions illuminated the association of ATI subscales with demographics and asthma history. Evidence in support of construct validity was found in associations between ratings of triggering and disease severity and asthma-related quality of life (PAQLQ). Criterion validity for allergy triggering was partially supported by correlations between ATI animal allergens subscale and the cat dander skin prick test, and construct validity for emotional triggering by associations between the emotional trigger subscale score and the anxiety (STAIC) and depression (CDI, CDI-P, CDRS-R, and CBCL-I) scores. CONCLUSION: The ATI holds promise as a reliable, valid, and useful clinical and research tool to assess the type and degree of asthma triggering in a pediatric population (age 7-17) of varied gender, race, and SES.

Asthma↗

PubMed2002

Effect of cage vs. floor litter environments on the pulmonary hypertensive response to intravenous endotoxin and on blood-gas values in broilers.

Intravenous endotoxin has been shown to trigger a delayed pulmonary hypertensive response that varies widely in magnitude and duration among individual broilers. It was proposed that this individual variability may reflect immunological differences acquired during previous respiratory challenges that might have subsequently altered the endotoxin-initiated biochemical cascade. In Experiment 1, we tested the hypothesis that, when compared with broilers reared in clean stainless steel cages (Cage group), broilers reared on floor litter (Floor group) should experience a greater respiratory challenge and therefore may consistently exhibit a more enhanced pulmonary hypertensive response to intravenous endotoxin. Birds in the Cage group were grown in stainless steel cages at a low density (72 birds/8 m2 chamber), and fecal and dander materials were removed daily. Birds in the Floor group were reared on wood-shavings litter at a higher density (110 birds/8 m2 chamber). Pulmonary and systemic mean arterial pressures and blood-gas values were evaluated prior to and following the intravenous administration of 1 mg Salmonella typhimurium endotoxin. Broilers in the Floor and Cage groups exhibited pulmonary hypertensive responses to endotoxin that were very similar in terms of time of onset, duration, and magnitude, as well as variability in the response among individuals. Systemic hypotension also developed similarly in both groups following endotoxin injection. Blood-gas values indicated that the partial pressure of CO2 and the HCO3- concentration in arterial blood were higher (P < 0.05) in the Floor group than in the Cage group prior to and subsequent to the endotoxin injection. In Experiment 2, we reevaluated the effect of a dirty vs. a clean environment on blood-gas values using a different strain of broilers, and confirmed the negative impact of floor rearing on blood-gas values. We conclude that broilers reared on the floor inhaled litter dust and noxious fumes, which impaired pulmonary gas exchange and increased the arterial partial pressure of CO2 when compared with broilers reared in clean stainless steel cages. Nevertheless, the pulmonary hypertensive response to endotoxin did not differ between broilers reared on the floor and those in cages.

Animal Husbandry↗