ABSTRACT
Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1-beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-α and minor moisture damage was inversely associated with PI-stimulated IL-1ß. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life.
Subject(s)
Air Pollutants/toxicity , Air Pollution, Indoor/adverse effects , Environmental Exposure/adverse effects , Fungi , Inflammation/blood , Air Pollutants/analysis , Air Pollution, Indoor/analysis , C-Reactive Protein/analysis , Child , Cytokines/blood , Environmental Exposure/analysis , Female , Humans , Infant , Inflammation/etiology , Interleukin-1beta/blood , Interleukin-6/blood , Ionomycin , Leukocyte Count , Leukocytes , Lipopolysaccharides , Male , Peptidoglycan , Prospective Studies , Tetradecanoylphorbol Acetate/analogs & derivatives , Tumor Necrosis Factor-alpha/bloodABSTRACT
BACKGROUND: A new treatment option for persistent cow's milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG4 antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome. METHODS: Seventy-six children (5-17 years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The treatment aimed at reaching a maintenance dose of 200 ml CM (high dose = HD). Those who did not reach target were analysed as a low-dose (LD) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG4 to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT. RESULTS: Fifty-five (72%) patients reached the maintenance dose (HD) during therapy. High specific IgE levels towards the milk allergens α-lactalbumin (P = 0.048), ß-lactoglobulin (P = 0.006) and casein (P = 0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG4 levels to α-lactalbumin (P = 0.034), ß-lactoglobulin (P = 0.010), casein (P = 0.047) and lactoferrin (P = 0.030) during treatment than those who failed. CONCLUSIONS: Component-resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to α-lactalbumin, ß-lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG4 concentration to milk components during treatment indicated effective desensitization.
Subject(s)
Caseins/blood , Immunoglobulin E/blood , Immunotherapy/methods , Lactalbumin/blood , Milk Hypersensitivity/blood , Milk Hypersensitivity/therapy , Administration, Oral , Adolescent , Animals , Biomarkers/blood , Caseins/immunology , Cattle , Child , Child, Preschool , Cohort Studies , Desensitization, Immunologic/methods , Female , Follow-Up Studies , Humans , Lactalbumin/immunology , Male , Milk/adverse effects , Milk/immunology , Milk Hypersensitivity/diagnosis , Predictive Value of Tests , Prospective Studies , Risk Assessment , Statistics, Nonparametric , Treatment OutcomeABSTRACT
Neuroendocrine tumors (NETs) arise from disseminated neuroendocrine cells and express general and specific neuroendocrine markers. Neuropeptide S receptor 1 (NPSR1) is expressed in neuroendocrine cells and its ligand neuropeptide S (NPS) affects cell proliferation. Our aim was to study whether NPS/NPSR1 could be used as a biomarker for neuroendocrine neoplasms and to identify the gene pathways affected by NPS/NPSR1. We collected a cohort of NETs comprised of 91 samples from endocrine glands, digestive tract, skin, and lung. Tumor type was validated by immunostaining of chromogranin-A and synaptophysin expression and tumor grade was analyzed by Ki-67 proliferation index. NPS and NPSR1 expression was quantified by immunohistochemistry using polyclonal antibodies against NPS and monoclonal antibodies against the amino-terminus and carboxy-terminus of NPSR1 isoform A (NPSR1-A). The effects of NPS on downstream signaling were studied in a human SH-SY5Y neuroblastoma cell line which overexpresses NPSR1-A and is of neuroendocrine origin. NPSR1 and NPS were expressed in most NET tissues, with the exception of adrenal pheochromocytomas in which NPS/NPSR1 immunoreactivity was very low. Transcriptome analysis of NPSR1-A overexpressing cells revealed that mitogen-activated protein kinase (MAPK) pathways, circadian activity, focal adhesion, transforming growth factor beta, and cytokine-cytokine interactions were the most altered gene pathways after NPS stimulation. Our results show that NETs are a source of NPS and NPSR1, and that NPS affects cancer-related pathways.
Subject(s)
Endocrine Gland Neoplasms/physiopathology , Gastrointestinal Neoplasms/physiopathology , Neuroendocrine Tumors/physiopathology , Receptors, G-Protein-Coupled/physiology , Signal Transduction/physiology , Skin Neoplasms/physiopathology , Adult , Aged , Antibodies, Monoclonal/immunology , Antibody Specificity , Biomarkers, Tumor/immunology , Biomarkers, Tumor/physiology , Cell Proliferation , Endocrine Gland Neoplasms/pathology , Female , Gastrointestinal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Neuroendocrine Tumors/pathology , Neuropeptides/immunology , Neuropeptides/physiology , Receptors, G-Protein-Coupled/immunology , Retrospective Studies , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Early-life exposure to environmental microbial agents may be associated with the development of allergies. The aim of the study was to identify better ways to characterize microbial exposure as a predictor of respiratory symptoms and allergies. METHODS: A birth cohort of 410 children was followed up until 6 years of age. Bacterial endotoxin, 3-hydroxy fatty acids, N-acetyl-muramic acid, fungal extracellular polysaccharides (EPS) from Penicillium and Aspergillus spp., ß-D-glucan, ergosterol, and bacterial or fungal quantitative polymerase chain reactions (qPCRs) were analyzed from dust samples collected at 2 months of age. Asthma, wheezing, cough, and atopic dermatitis were assessed using repeated questionnaires. Specific IgEs were determined at the age of 1 and 6 years. RESULTS: Only few associations were found between single microbial markers and the studied outcomes. In contrast, a score for the total quantity of microbial exposure, that is, sum of indicators for fungi (ergosterol), Gram-positive (muramic acid) bacteria, and Gram-negative (endotoxin) bacteria, was significantly (inverted-U shape) associated with asthma incidence (P < 0.001): the highest risk was found at medium levels (adjusted odds ratio (aOR) 2.24, 95% confidence interval (95% CI) 0.87-5.75 for 3rd quintile) and the lowest risk at the highest level (aOR 0.34, 95% CI 0.09-1.36 for 5th quintile). The microbial diversity score, that is, sum of detected qPCRs, was inversely associated with risk of wheezing and was significantly (inverted-U shape) associated with sensitization to inhalant allergens. CONCLUSION: Score for quantity of microbial exposure predicted asthma better than single microbial markers independently of microbial diversity and amount of dust. Better indicators of total quantity and diversity of microbial exposure are needed in studies on the development of asthma.
Subject(s)
Asthma/epidemiology , Asthma/etiology , Environmental Exposure , Environmental Microbiology , Allergens/immunology , Asthma/diagnosis , Child , Child, Preschool , Cohort Studies , Dust , Finland/epidemiology , Follow-Up Studies , Humans , Incidence , Infant , Infant, Newborn , Odds Ratio , Population Surveillance , Surveys and QuestionnairesABSTRACT
BACKGROUND: It appears that contacts with furred animals early in life and already during gestation contribute to the immunological development in humans, but the mechanisms and relevant exposures are not clear. OBJECTIVE: To investigate whether exposure to animals during pregnancy and the first year of life is associated with early immune development, determined as stimulated cytokine responses of children at birth and at age 1 year. METHODS: Cord blood (n=228) and peripheral venous blood (n=200) samples 1 year after birth were collected and stimulated with Gram-positive superantigen Staphylococcal enterotoxin B, Gram-negative bacterial lipopolysaccharide (LPS) and the combination of mitogenic phorbol 12-myristate 13-acetate and calcium ionophore ionomycin (P/I) for 24 and 48 h. TNF-α, IFN-γ, IL-5, IL-8 and IL-10 responses were measured by ELISA. For each cytokine, the time-point with the highest response was chosen for further analyses. Animal contacts were surveyed by self-administered questionnaires. RESULTS: Dog ownership was associated with decreased TNF-α-producing capacity at birth (P/I: median 841 vs. 881 pg/10(6) WBC, P=0.05) and 1 year after birth (P/I: 1290 vs. 1530, P=0.01; LPS: 425 vs. 508, P=0.02). Associations remained significant after adjustment for potential confounders. Cat ownership was not associated with cytokine production. CONCLUSION: Having a dog in the household in infancy and already during pregnancy may be associated with reduced innate immune responses in early childhood. The observed attenuation of cytokine production may help in preventing exaggerated immune responses against harmless antigens later in life. Thus, intensive exposure to dogs in early life may be beneficial during normal immune maturation.
Subject(s)
Dogs/immunology , Pets/immunology , Pregnancy/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Cats , Cytokines/biosynthesis , Cytokines/blood , Cytokines/immunology , Enzyme-Linked Immunosorbent Assay , Female , Fetal Blood/immunology , Humans , Infant , Infant, Newborn , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunologyABSTRACT
BACKGROUND: Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment. OBJECTIVE: We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy. METHODS: Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires (n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers. RESULTS: Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17-0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13-0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii. CONCLUSIONS: Maternal immunity to T. gondii and rubella may impact on atopic sensitization in the fetus. A positive T. gondii record explained the previously identified effect of prenatal farm exposure on IgE to seasonal allergens only to a minor extent.
Subject(s)
Allergens/immunology , Fetal Blood/immunology , Hypersensitivity, Immediate/immunology , Immunoglobulin E/blood , Rubella virus/immunology , Rubella/immunology , Toxoplasma/immunology , Toxoplasmosis/immunology , Animals , Female , Humans , Hypersensitivity, Immediate/blood , Hypersensitivity, Immediate/microbiology , Hypersensitivity, Immediate/virology , Pregnancy , Surveys and QuestionnairesABSTRACT
The association between high birth weight and asthma has been suggested. The Northern Finland Birth Cohort 1986, a longitudinal cohort originally including 9479 participants, has been followed up since birth until the age of 16 yr. Using the data of this study, we analyzed the association of high birth weight with asthma and atopic sensitization at the age of 16 yr. The analysis included the 5995 subjects with complete skin prick test data and the 5500 subjects with data on doctor-diagnosed asthma (written questionnaire) at the age of 16 yr. Atopy was defined as at least one positive skin prick test reaction, which definition was also used to separate atopic and non-atopic asthma. There was a significant association between high birth weight (>4510 g) and asthma among the atopic subjects (OR 2.40, 95% CI 1.33-4.32). When looking at atopy, the highest risk was observed among the subjects with highest birth weight category (>4510 g) (OR 1.44, 95% CI 1.05-1.97) and the adjacent (4200-4500 g) birth weight category (OR 1.24, 95% CI 1.01-1.53), when compared with the reference category (2500-3340 g). Our results support the notion that high birth weight is associated with an increased risk of asthma and suggest that the association is mostly explained by an increased risk of atopy. The biological mechanisms behind the associations are unknown, but they could be related to obesity.
Subject(s)
Asthma/epidemiology , Birth Weight , Hypersensitivity, Immediate/epidemiology , Adolescent , Asthma/immunology , Cohort Studies , Female , Follow-Up Studies , Humans , Hypersensitivity, Immediate/immunology , Logistic Models , Longitudinal Studies , Male , Skin TestsABSTRACT
AIMS: The farming environment in childhood has been reported to decrease the risk of sensitisation to allergens. The purpose of the present study was to explore whether later exposure to a farming environment also could affect this sensitisation. METHODS: A population based sample of 202 women who did not live on a farm and 231 who did. The subjects filled in a questionnaire and underwent skin prick tests for several common and farming related allergens. RESULTS: The prevalence of sensitisation to any of the allergens was similar in the two groups (37.1 v 34.6% (p = NS). However, compared with women who did not live on a farm, the women who lived on a dairy farm showed a low prevalence of sensitisation to pollens (4.4 v 17.3%, p = 0.01) and cats (3.5 v 10.4%, p = 0.047). The risk of sensitisation to pollens and pets was lowest among women with both a childhood and adulthood farming environment and was dose dependently associated with current contact with farm animals. However, this contact increased the risk of sensitisation to bovine dander. CONCLUSION: The farming environment may reduce sensitisation to common allergens also after early childhood. However, it may also increase sensitisation to farm allergens.
Subject(s)
Agricultural Workers' Diseases/immunology , Allergens/immunology , Hypersensitivity, Immediate/immunology , Adolescent , Adult , Child , Humans , Male , Skin Tests , Surveys and QuestionnairesABSTRACT
BACKGROUND: Farmers' children are less frequently sensitized to common allergens than the non-farmers' children, but less is known about their sensitization to other allergens and its association with clinical diseases. OBJECTIVE: To examine the association of farm environment with atopic sensitization, allergic diseases, expression of allergen-induced symptoms, and the importance of specific sensitization against 'common' (timothy, dog, cat, birch, Dermatophagoides pteronyssimus, mugwort) and 'other' (cockroach, horse, Lepidoglyphus destructor, cow) allergens for asthma and allergic diseases in children. METHODS: A cross-sectional study including 344 farmers' and 366 non-farmers' children aged 6-13 years in eastern Finland, using a self-administered written questionnaire and skin prick tests against the above-mentioned allergens. RESULTS: Farmers' children had less asthma and allergic diseases and were less often sensitized against common allergens than the non-farmers' children. However, little difference was observed in sensitization against the other allergens between the farmers' (17.2%) and non-farmers (14.5%) children [adjusted odds ratios (aOR) 1.11 (0.71-1.72)]. Being sensitized against only other allergens, without sensitization against common allergens, was unrelated to asthma or allergic diseases. Among the single allergens, sensitization against pets or pollen, or against horse or cow, had the strongest association with asthma, hayfever, and atopic eczema; no such association was seen in D. pteronyssimus, mugwort, cockroach, or L. destructor. Farmers' children had significantly less often symptoms of allergic rhinitis in contact with dog (aOR 0.32%, 95% confidence interval (CI) 0.15-0.67), cat (aOR 0.45, 0.22-0.88), or pollen (aOR 0.58%, 95% CI 0.37-0.90) than the non-farmers' children. CONCLUSION: Farm environment reduces the occurrence of asthma, allergic diseases, and atopic sensitization in children, and also the occurrence of allergen-induced rhinitis. Remarkable differences were observed between single allergens in their association with allergic disease, stressing the importance of allergen selection when defining atopy in epidemiological studies.
Subject(s)
Agricultural Workers' Diseases/immunology , Allergens/immunology , Asthma/immunology , Adolescent , Agricultural Workers' Diseases/diagnosis , Animals , Animals, Domestic , Asthma/diagnosis , Case-Control Studies , Chi-Square Distribution , Child , Cockroaches , Cross-Sectional Studies , Environmental Exposure , Female , Finland , Humans , Hypersensitivity/diagnosis , Hypersensitivity/immunology , Male , Skin TestsABSTRACT
Epidemiological data suggest that respiratory syncytial virus (RSV) infection in early life is a risk factor for later asthma. There are no prospective studies on RSV infection starting from infancy progressing through childhood into adulthood. We followed up a cohort of children, hospitalized for RSV bronchiolitis or RSV pneumonia before age 24 months, until age 18-20 years. The aim of the study was to evaluate early RSV infection as a risk factor for asthma, bronchial reactivity, and lung function abnormalities in young adults. The participants filled in a questionnaire on asthma and asthma-like symptoms. The clinical study included flow-volume spirometry (FVS), methacholine inhalation challenge (MIC), home PEF (peak expiratory flow) monitoring, and skin prick tests (SPT) to common allergens. Asthma was present in 17-22% of 36 index subjects, depending on asthma definition, compared to 11% of 45 controls. Furthermore, FEV% and MEF25 were lower, and MEF50 tended to be lower, in index than in control subjects. One or more abnormal lung function results were found in 16 (44%) index subjects, but only in 5 (11%) controls (P < 0.01). Bronchial reactivity (PD20 <4,900 microg methacholine) was demonstrated in 16 (46%) index subjects and 14 (32%) controls (NS). At least one positive SPT result was present in 21 (60%) index subjects; 6 (29%) had asthma (NS vs. nonatopic index subjects); 13 (62%) had abnormal lung function (P < 0.05); and 14 (67%) had bronchial reactivity (P < 0.01). In the logistic regression adjusted for atopy, as defined by SPT positivity, RSV infection in infancy was an independent risk factor for lung function abnormality (one or more abnormal results in FVS; OR, 5.27; 95% CI, 1.60-17.36), and also for decreased FEV% and MEF50 when these were analyzed separately. However, RSV infection in infancy was not a significant risk factor for asthma or bronchial reactivity. In young adults, lung function abnormalities may be associated with RSV infection which required hospitalization in infancy.
Subject(s)
Asthma/etiology , Bronchiolitis/complications , Pneumonia, Viral/complications , Respiratory Syncytial Virus Infections/complications , Adult , Asthma/epidemiology , Bronchiolitis/virology , Case-Control Studies , Cohort Studies , Female , Follow-Up Studies , Humans , Logistic Models , Male , Morbidity , Pneumonia, Viral/virology , Risk Factors , Surveys and QuestionnairesABSTRACT
The effect of farming on the risk of upper airway symptoms is not clear. In this cross-sectional, population-based study, 198 female farmers, 50 nonfarmers living on a farm, and 218 nonfarmers not living on a farm, filled in a symptom questionnaire and underwent skin-prick testing with common and agricultural allergens. In the logistic regression analysis, the latter group served as a control. Several adjustments were made, including childhood farming environment. Current farming was found to decrease the risks of pet- and pollen-induced upper airway symptoms, dose-dependently with the intensity and duration of animal husbandry. Including skin-test positivity to pets in the regression models did not affect the negative association between farming and pet-induced symptoms. In contrast, animal husbandry increased the risk of farm work-induced upper airway symptoms. Animal husbandry often induces work-related upper airway symptoms. However, the present study among female adults suggests that it may also decrease the risk of pet- and pollen-induced upper airway symptoms.
Subject(s)
Agricultural Workers' Diseases/etiology , Animals, Domestic , Pollen/adverse effects , Respiratory Tract Diseases/etiology , Agricultural Workers' Diseases/epidemiology , Animals , Chi-Square Distribution , Cross-Sectional Studies , Female , Finland/epidemiology , Humans , Logistic Models , Prevalence , Respiratory Tract Diseases/epidemiology , Risk Factors , Skin Tests , Surveys and QuestionnairesABSTRACT
BACKGROUND: The inverse association between farming and atopy in children has been attributed to microbial exposure, especially through livestock. Very little is known about other potential explanatory factors. OBJECTIVE: To explore potential differences in lifestyle and environmental factors between farmer and non-farmer families, and whether these factors could explain the association between farming and childhood atopy. METHODS: A cross-sectional study, including 366 farmers' and 344 non-farmers' children in eastern Finland. Information regarding exposure and background characteristics was gathered by a written questionnaire. Atopy was defined as having one or more positive skin prick test reactions (> 3 mm) against the six common aeroallergens. RESULTS: Regardless of the current farming type, atopy was less frequent among the farmers' children than the non-farmers' children (aOR 0.56, 95% CI 0.40-0.78). Remarkable differences were seen in many lifestyle factors (including diet) between the farmer and non-farmer families, but only a few of the explored factors were associated with atopy. The frequency of current livestock contacts seemed to have an inverse, dose-dependent association with atopy (aOR 0.46, 95% CI 0.22-0.97 for daily vs. no contact). Having lived on a dairy farm in infancy (aOR 0.51, 95% CI 0.28-0.93), or having had cats or dogs in infancy (aOR 0.60, 95% CI 0.42-0.85), decreased the risk of atopy at school age. The inverse association between farming and atopy was not explained by the sociodemographic factors, or by differences in conventional risk factors of atopy. Animal contacts explained partially, but not completely, the association. CONCLUSION: Higher frequency of animal contacts is one factor, but probably not the only one, explaining the inverse association of farming and atopy in children. The importance of early life exposures may have recently been over-emphasized, and current exposures discounted, when studying the risk factors of childhood atopy.
Subject(s)
Agriculture , Animals, Domestic , Hypersensitivity/immunology , Life Style , Animals , Child , Child, Preschool , Cross-Sectional Studies , Diet , Female , Humans , Hypersensitivity/diagnosis , Infant , Infant, Newborn , Male , Prevalence , Risk Factors , Skin Tests , Tobacco Smoke PollutionABSTRACT
AIM: It has been suggested that living on a farm decreases the risk of childhood allergy, especially if farming involves livestock. The aim of this study was to examine the association between farming and allergy in children, and the influence of atopic heredity in this association. METHODS: The cross-sectional data of the 7981 children aged 13-14 y who participated in the Finnish ISAAC study between the years 1994 and 1995 were used to evaluate the association between farming and allergy. RESULTS: Living on a farm was associated with a decreased risk of current symptoms of allergic rhinoconjunctivitis among all children (aOR 0.79; 95% CI 0.63, 0.99), and with a decreased risk of hay fever, especially among those children with a parental history of hayfever (aOR 0.60; 95% CI 0.40-0.89, p = 0.072 for interaction). The children of farmers with a history of hay fever also had a decreased risk of current wheeze (aOR 0.38; 95% CI 0.12-1.24, p = 0.040 for interaction). No significant association was found between farming and either asthma or eczema. Children living on a farm with livestock had the lowest risk of allergic rhinoconjunctivitis (aOR 0.69), followed by those living on a farm without livestock (aOR 0.89) compared with the non-farming children (p-value for trend 0.024). CONCLUSION: Our results support the recent findings on a decreased risk of allergy among the children living on farms. A possible differential effect of parental history of hay fever on the relation of farming environment and the risk of allergic symptoms warrant further investigation.
Subject(s)
Agriculture , Asthma/epidemiology , Hypersensitivity/epidemiology , Adolescent , Asthma/genetics , Cross-Sectional Studies , Eczema/epidemiology , Female , Finland/epidemiology , Humans , Hypersensitivity/genetics , Male , Odds Ratio , Prevalence , Rhinitis, Allergic, Seasonal/epidemiology , Rhinitis, Allergic, Seasonal/genetics , SmokingABSTRACT
BACKGROUND: Although peripheral blood eosinophilia is associated with risk of asthma, the relation with atopy has not been established. OBJECTIVE: To assess the relationship between eosinophils and chronic asthma in childhood, and to determine the factors associated with eosinophil levels over time. METHODS: Percent eosinophils/300 white blood cell (WBC) count ('eos') was measured at 9 months, 6 years and 11 years in subjects participating in the prospective Tucson Children's Respiratory Study. Children were classified based on the number of measurements in which they had low (< or = 2%) or high (>5%) eosinophils, as follows: (1) Persistently low eos (n = 130); (2) Low eos (intermittently low or consistently moderate, but never high, n = 317); (3) Intermittently high eos (n = 192); and (4) Persistently high eos (n = 17). Only children with > or = 2 eos measurements were included in the analysis. Chronic asthma was defined as medical doctor (MD)-diagnosed asthma with reports of wheezing during the previous year, on > or = 3 questionnaires completed between 2 and 13 years of age. Children with at least one positive skin prick test (SPT; > or = 3 mm) at age 6 or 11 were considered 'atopic'. RESULTS: Chronic asthma was linearly related to longitudinally ascertained eosinophils (trend chi2 P<0.001) with prevalence ranging from 5.8% among children with persistently low eos to 37.5% among children with persistently high eos. This relation was independent of atopy. Parental history of asthma was associated with both chronic asthma (P <0.001) and with longitudinal eosinophil status (P < 0.001). After adjusting for atopy and gender, there was a 70% increase in asthma risk with each increase in longitudinal eosinophil level. This stepwise increase was reduced to 48% when parental asthma was added to the model. CONCLUSION: Longitudinal eosinophil levels are linearly associated with chronic asthma in childhood, independent of atopy. The strong association between parental asthma and eosinophil status suggests that genetic background may be an important determinant of eosinophilic response.
Subject(s)
Asthma/complications , Eosinophilia/etiology , Hypersensitivity/complications , Asthma/genetics , Child , Child, Preschool , Chronic Disease , Eosinophilia/epidemiology , Female , Humans , Male , Multivariate Analysis , Prevalence , Risk FactorsABSTRACT
BACKGROUND: The definition or diagnosis of asthma is a challenge for both clinicians and epidemiologists. Symptom history is usually supplemented with tests of bronchial hyperresponsiveness (BHR) in spite of their uncertainty in improving diagnostic accuracy. METHODS: To assess the interrelationship between respiratory symptoms, BHR, and clinical diagnosis of asthma, the respiratory symptoms of 1633 schoolchildren were screened using a questionnaire (response rate 81.2%) and a clinical study was conducted in a subsample of 247 children. Data from a free running test and a methacholine inhalation challenge test were available in 218 children. The diagnosis of asthma was confirmed by a paediatric allergist. RESULTS: Despite their high specificity (>0.97), BHR tests did not significantly improve the diagnostic accuracy after the symptom history: area under the receiver operator characteristic (ROC) curve was 0.90 for a logistic regression model with four symptoms and 0.94 for the symptoms with free running test and methacholine inhalation challenge results. On the other hand, BHR tests had low sensitivity (0.35-0.47), whereas several symptoms had both high specificity (>0.97) and sensitivity (>0.7) in relation to clinical asthma, which makes them a better tool for asthma epidemiology than BHR. CONCLUSIONS: Symptom history still forms the basis for defining asthma in both clinical and epidemiological settings. BHR tests only marginally increased the diagnostic accuracy after symptom history had been taken into account. The diagnosis of childhood asthma should not therefore be overlooked in symptomatic cases with no objective evidence of BHR. Moreover, BHR should not be required for defining asthma in epidemiological studies.
Subject(s)
Asthma/diagnosis , Bronchial Hyperreactivity/diagnosis , Bronchial Provocation Tests/standards , Bronchoconstrictor Agents , Child , Diagnosis, Differential , Exercise Test/standards , Humans , Methacholine Chloride , Sensitivity and Specificity , Spirometry/standards , Surveys and QuestionnairesABSTRACT
BACKGROUND: Influence of household pets in the development of childhood asthma or atopy has been controversial. OBJECTIVE: The purpose of this study was to investigate whether pet exposure in early life decreases the subsequent risk of frequent wheezing and/or allergic sensitization. METHODS: This was a prospective observational birth cohort study. The setting was a large health maintenance organization in Tucson, Ariz; the subjects were a population sample of 1246 newborns enrolled at birth and followed prospectively to age 13 years. The main outcome measures were as follows: time to first report of frequent wheezing (>3 episodes in the past year), skin prick test reactivity at 6 years and 11 years of age, and total serum IgE at 9 months, 6 years, and 11 years of age. RESULTS: Children living in households with > or =1 indoor dogs at birth were less likely to develop frequent wheeze than those not having indoor dogs (P =.004). This inverse association was confined to children without parental asthma (hazard ratio = 0.47; P <.001 [Cox regression]) and was not evident for children with parental asthma (hazard ratio = 0.96; P =.87). Adjustment by potential confounders did not change the results. Indoor cat exposure was not significantly associated with the risk of frequent wheezing. Neither cat exposure in early life nor dog exposure in early life was associated with skin prick test reactivity or total serum IgE at any age. CONCLUSION: Dog exposure in early life might prevent the development of asthma-like symptoms, at least in low-risk children with no family history of asthma. Nevertheless, early pet exposure does not seem to significantly influence the development of allergic sensitization.
Subject(s)
Animals, Domestic , Dogs , Environmental Exposure , Environmental Illness/prevention & control , Hypersensitivity/prevention & control , Adolescent , Animals , Arizona , Asthma/etiology , Asthma/genetics , Asthma/prevention & control , Cats , Child , Child, Preschool , Environment, Controlled , Environmental Illness/etiology , Environmental Illness/genetics , Female , Humans , Hypersensitivity/etiology , Hypersensitivity/genetics , Immunoglobulin E/blood , Male , Prospective Studies , Respiratory Hypersensitivity/etiology , Respiratory Hypersensitivity/genetics , Respiratory Hypersensitivity/prevention & control , Respiratory SoundsABSTRACT
Serum procalcitonin (PCT), a marker of bacterial infection, was measured in children with pneumonia to examine whether PCT can be used to screen pneumococcal (PNC) from viral pneumonia. The number of patients was 132; mean age 3.0 yrs, and 64% were males. In all cases, pneumonia was radiologically confirmed, being alveolar in 46 and interstitial in 86 cases. The aetiology of infection was studied by a panel of serological tests for PNC, for five other respiratory bacteria and for seven common respiratory viruses. PNC infection was found in 25, mixed viral-PNC infections in 13 and viral infection in 17 cases. In general, serum PCT was not associated with the type or aetiology of pneumonia. PCT values were >1.0 mg.L(-1) in 40% of PNC cases, as compared to 12-15% in viral or mixed cases, respectively (p<0.05). PCT values were significantly higher in >2 yrs old children than in younger ones. The cut-off limits of 0.5 ng.mL(-1), 1.0 ng.mL(-1) and 2.0 ng.mL(-1) were tested for screening between PNC and viral pneumonia. The highest sensitivity of 55% was found at the 0.5 ng.mL(-1) cut-off level, whereas the highest specificity of 88% was reached at the level of 1.0 ng.mL(-1). The likelihood ratios, however, were far from optimal for both the positive and negative results. Although marginally higher in pneumococcal pneumonia than in viral pneumonia, serum procalcitonin cannot be used to discriminate between these two types of pneumonia.
Subject(s)
Biomarkers/blood , Calcitonin/blood , Pneumonia, Pneumococcal/diagnosis , Protein Precursors/blood , Calcitonin Gene-Related Peptide , Child, Preschool , Diagnosis, Differential , Female , Humans , Male , Pneumonia, Pneumococcal/blood , Pneumonia, Viral/diagnosis , Prospective Studies , Sensitivity and SpecificityABSTRACT
Antimicrobial screening against selected Gram-positive and Gram-negative bacteria, yeasts, mold, as well as plant pathogenic fungi, with emphasis on method optimization was carried out on methanol extracts prepared from seven plants grown in Finland. Sensitivity to the extracts was found to vary considerably among the micro-organisms, the extract from Petroselinum crispum and Ruta graveolens showing the highest toxicity against Rhizoctonia solani. The growth of Heterobasidium annosum was inhibited, whereas that of Phytophtora (cactorum) was promoted by all the extracts. The antibacterial and antifungal activities of six natural coumarin compounds were weak, except for the inhibitory effect against Fusarium culmorum.