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PubMed1998

Asthma-like symptoms, atopy, and bronchial responsiveness in furniture workers.

OBJECTIVES: To study the role of individual and occupational risk factors for asthma in furniture workers. METHODS: 296 workers were examined (258 men, 38 women) with a questionnaire of respiratory symptoms and diseases, baseline spirometry, bronchial provocative test with methacholine, and skin prick tests. Non-specific bronchial hyperreactivity was defined as when a provocative dose with a fall of 20% in forced expiratory volume in 1 second (PD20FEV1) was < 0.8 mg and atopy in the presence of at least one positive response to skin prick tests. Workers were subdivided into spray painters (exposed to low concentrations of diisocyanates and solvents), woodworkers (exposed to wood dusts), and assemblers (control group). RESULTS: The prevalences of attacks of shortness of breath with wheezing and dyspnoea were higher in spray painters (13.5% and 11.5% respectively) than in woodworkers (7.7% and 6.3%) or in assemblers (1.6% and 1.6%); prevalences of chronic cough, asthma, and rhinitis were also slightly but not significantly higher in spray painters and in woodworkers than in assemblers. The difference in the prevalence of respiratory symptoms among the job titles was due to the atopic subjects, who showed a higher prevalence of chronic cough, wheeze, shortness of breath with wheeze, dyspnoea, and asthma in spray painters than in the other groups. The prevalence of non-specific bronchial hyperreactivity in subjects who performed bronchial provocative tests was 17.7%, with no significant difference among groups. Asthma symptoms were significantly associated with non-specific bronchial hyperreactivity. Asthma-like symptoms plus non-specific bronchial hyperreactivity was found in 4% of assemblers, 10% of woodworkers, and 13.3% of spray painters (chi 2 = 2.6, NS). Multiple logistic analysis taking into account individual (smoke, atopy, age) and occupational (job titles) risk factors confirmed that spray painters had higher prevalence of chronic cough than assemblers, and a trend in increasing the prevalence of shortness of breath with wheeze, dyspnoea, and asthma. CONCLUSIONS: Painters in the furniture industry, particularly atopic subjects, are at higher risk of asthma-like symptoms than other job titles. In these workers asthma-like symptoms are more sensitive than non-specific bronchial hyperreactivity in detecting a negative effect of the occupational exposure.

Adult↗
PubMed2000

Atopy, lung function, and obstructive airways disease after prenatal exposure to famine.

BACKGROUND: Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. METHODS: Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). RESULTS: Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI 0. 9 to 2.6). CONCLUSIONS: The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.

Birth Weight↗
PubMed1980

Atopy and bronchial reactivity in older patients with cystic fibrosis.

We studied 25 adolescent and adult patients with cystic fibrosis (CF) and 25 control subjects to determine if the prevalence of atopy and bronchial hyperreactivity was increased in this disease. Results showed that atopic symptoms, as defined by history, were more frequently present in the CF patients. Prick testing of the skin produced positive reactions in 88% of the CF group and 36% of the control subjects (p less than 0.001), and the mean number of reactions per subject was significantly higher in the former group (p less than 0.001); reactions to fungal antigens were strikingly positive in the CF group. The CF patients had a significantly higher mean serum IgG4 (p less than 0.001), IgE (p less than 0.01), and higher mean eosinophil count (p less than 0.05). Clear-cut bronchial hyperreactivity was demonstrated in the CF group compared with control subjects. Bronchial provocation with 400 micrograms of histamine led to a greater than 15% fall in the preinhalation FEV1 in 35% of the CF subjects compared with 4% of the control group, with a mean percentage fall of 15% and 3% respectively (p less than 0.001). In the CF group a greater than 15% rise in PEFR occurred in 32% after inhalation of the parasympatholytic, ipratropium bromide (54 micrograms), and in 27% after inhalation of the sympathomimetic, fenoterol (400 micrograms). No correlation was found between bronchial reactivity and atopic status, HLA phenotype pattern, or disease severity. The cause of the increased prevalence of atopy and bronchial reactivity in CF patients remains unknown. However, it is clear that a trial of bronchodilator therapy is warranted in adolescents and young adults with CF.

Adolescent↗
PubMed1999

Relationship between fetal growth and the development of asthma and atopy in childhood.

BACKGROUND: A study was undertaken to investigate the relationship between birth anthropometric measures and the subsequent development of asthma, airway hyperresponsiveness, and atopy in later childhood. METHODS: A longitudinal study was performed on 734 subjects (71%) from a cohort of children born in Dunedin, New Zealand in 1972-73. The birth anthropometric measures were available from hospital records and the main outcome measures of reported asthma, skin prick tests, and methacholine hyperresponsiveness were measured at the age of 13 years, while the serum total IgE was measured at 11 years. RESULTS: After adjustment for other factors, infants with a larger head circumference at birth tended to have higher serum total IgE at 11 years of age (p = 0.02) but IgE was not associated significantly with birth length or birth weight. The adjusted odds ratio for raised serum IgE (>150 IU/ml) in infants with a head circumference of 37 cm or more was 3.4 (95% CI 1.4 to 7.9). In contrast, recent asthma symptoms were positively associated with birth length (p = 0. 04) but not with head circumference. The adjusted odds ratio for asthma in the previous two years in infants with a birth length of 56 cm or more was 6.4 (95% CI 2.0 to 19.8). Infants with a birth weight of less than 3.0 kg had an odds ratio for reported asthma of 0.2 (95% CI 0.0-0.6). There were no significant associations of any of the birth parameters with skin prick positivity, reported hay fever, or eczema. CONCLUSIONS: These results suggest that increased fetal growth is related to an increased risk of asthma and atopy in childhood. The precision of the findings is limited by the small numbers in the extreme categories of each birth parameter, but the results are consistent with intrauterine programming of the developing respiratory and immune systems.

Adolescent↗
PubMed2001

B-cell isotype control in atopy and asthma assessed with cDNA array technology.

B-cell isotype switching and the production of IgE is regulated by a variety of gene products through different mechanisms. A better understanding of these processes has the potential to identify markers of disease and new therapeutic targets. The aim of the study was to investigate human B-cell isotype control and IgE production in atopy and asthma with cDNA array technology. Eighteen atopic asthmatic, eight atopic nonasthmatic, and fourteen healthy control subjects were included. Peripheral blood mononuclear cells were separated by gradient centrifugation, mRNA was purified, and the reverse-transcribed probes were hybridized to cDNA membranes. Group differences were assessed with the Mann-Whitney U-test. Twenty-three of seventy-eight tested IgE-related genes had significantly altered expression in atopy and asthma compared with that in the healthy subjects. The differentially expressed genes include surface molecules involved in T- and B-cell interaction and activation, cytokines, intracellular signaling products, and transcription factors. In conclusion, both atopic nonasthmatic and atopic asthmatic individuals had activated proinflammatory pathways, a minimal requirement for B-cell isotype switching, and a clear net pro-IgE cytokine climate.

Adolescent↗
PubMed1998

Two common polymorphisms in the coding part of the CD43 gene are not associated with atopy.

BACKGROUND: Recently linkage and association of the chromosomal region 16p12-11 with enhanced IgE responsiveness have been shown. The gene coding for CD43 (sialophorin) has been localized to this region. Sialophorin represents a major sialoglycoprotein on the surface of human lymphocytes, monocytes and granulocytes. It is supposed to play an important role in human mast cell, T- and B-cell regulation and activation and has been described in connection with immunodeficiency diseases such as the Wiskott-Aldrich syndrome. Therefore, it can be designated as a candidate gene for atopy. METHODS: Using SSCP analysis and direct genomic sequencing, polymorphisms in the CD43 gene have been looked for and their association with atopy has been tested in a population of 260 largely atopic children and young adults. RESULTS: Three common polymorphisms in the coding part of the CD43 gene were found. Two of them are leading to amino acid exchanges, one from argine to cysteine at amino acid position 337 of the mature gene product and one from leucine to phenylalanine at amino acid position 341. Subsequent association studies revealed no obvious influence of R337C or L341F on IgE regulation (p = 0.47 and 0.43), neither in a cognate nor in an uncognate fashion. CONCLUSION: We conclude that CD43 polymorphisms are unlikely to account for the observed linkage effect at 16p12-11. Whether the polymorphisms R337C and L341F adjacent to phosphorylation sites in the intracellular region of the protein alter the normal functioning of CD43 remains to be elucidated.

Adolescent↗
PubMedDate not supplied

Candidate gene and mutational analysis in asthma and atopy.

BACKGROUND: Using quantitative phenotype scores, we have genotyped four markers close to the FcepsilonRI-beta gene on chromosome 11q and 17 markers on chromosome 12. We have also determined the frequency of the I181L/V183L and E237G polymorphisms in our population. METHODS: 131 randomly ascertained families and 109 families with an asthmatic proband were recruited. Written and video questionnaires, bronchial challenge, and skinprick tests were administered and IgE levels measured. Phenotype scores were derived using principal-component analysis. The asthma score incorporated the questionnaire data reduced to two variables (wheeze and video), the ratio of predicted to observed FEV1, and bronchial hyperresponsiveness calculated as the slope of the dose-response curve. Total IgE, with the highest heritability of the atopy variables, was used as the atopy score. I181L/V183L polymorphism was determined by sequencing and E237G polymorphism by the amplification refractory mutation system. The data were analyzed using the BETA programme. RESULTS: No examples of the I181L/V183L polymorphism were identified. The E237G polymorphism was identified with a frequency of 3.5% with weak evidence for linkage (lod 1.522) to asthma. Linkage was found to markers on chromosome 12 and asthma. The largest single locus lod was achieved for D12S366 and wheeze (lod 3. 307). Using multipoint analysis, a maximum lod score of 2.29 centres around D12S97 at location 173.5 cM for the asthma score. CONCLUSION: The linkage results for chromosome 12 justify further interest in this region. Future endeavours will be directed towards fine mapping in the hope of identifying novel candidate genes.

Asthma↗
PubMedDate not supplied

Environmental risk factors for respiratory and skin atopy: results from epidemiological studies in former East and West Germany.

The fall of the Berlin wall in 1989 offered the unique opportunity to compare populations of a similar genetic and geographic background which had been living under quite different environmental exposure conditions for over 40 years. Since 1990 comparative epidemiological studies were performed between various regions in former East and West Germany with yearly questionnaires and 3 years' physical, dermatological, allergological and exposure examination in a total of about 30,000 preschool children. There were striking differences between the various German regions with higher prevalence rates of respiratory atopy (hay fever, asthma) and atopic sensitization (prick test, RAST) in West Germany, while atopic eczema was significantly higher in East Germany (17.5 vs. 11.4% in West Germany). Total serum IgE levels were markedly higher in children in the east of Germany, similarly to the prevalence of parasitic infestation (questionnaire data as well as positive ascaris RAST). In multivariate logistic regression analysis the following factors were significantly associated with atopic eczema: animal contact (odds ratio, OR 2.9), animal furs in the bedroom (OR 2.2), use of gas without ventilation (OR 1.7) and living near road with heavy traffic (OR 1.7). Furthermore, socioeconomic factors measured as parental educational status (university vs. elementary school) were significantly associated (OR 2.3) with atopy. Respiratory tract infections and irritant responses decreased together with decreasing SO2 and suspended particulate air pollution in East Germany from 1991 to 1997. It is concluded that environmental factors from the physical, chemical, biological, and psychological environment (characteristic of a 'modern' or 'western' society) do influence the development of atopic sensitization and disease.

Allergens↗
PubMedDate not supplied

Modulation of atopy patch test reactions by topical treatment of human skin with a fatty acid-rich emollient.

Measures directed at improving the skin barrier function are thought to be effective in preventing reexacerbation of atopic dermatitis, but direct proof of a prophylactic effect of emollients has been elusive. In the present study, the atopy patch test has been employed as a model for the initiation phase of atopic dermatitis in order to assess whether pretreatment of non-lesional skin with a fatty acid-rich emollient (Eucerin Omega Creme) has a prophylactic effect in patients with atopic dermatitis. Pretreatment of test sites with Eucerin Omega Creme either prevented or diminished the development of eczema, as compared with untreated control test sites in the same patients (n = 38). These studies indicate that the use of fatty acid-rich emollients prevents the development of atopic eczema. They also demonstrate that the atopy patch test can be used to assess the capacity of a given regimen to exert prophylactic effects in this disease.

Adult↗
PubMed2006

Genetic impact of functional single nucleotide polymorphisms in the 3'-UTR region of the chemoattractant receptor expressed on Th2 cells (CRTH2) gene on asthma and atopy in a Japanese population.

BACKGROUND: The human chemoattractant receptor expressed on Th2 cells (CRTH2), the receptor for prostaglandin D2, induces cell migration in eosinophils, basophils, and Th2 cells. The gene encoding CRTH2 is located on chromosome 11q13. Several groups, including ours, have reported significant associations between this region and various traits associated with allergic diseases such as asthma and atopy. Two single nucleotide polymorphisms in the 3'-UTR of the CRTH2 gene (1544G-->C and 1651G-->A) are associated with the mRNA stability of the gene; they have also been associated with asthma in both African American and Chinese populations. METHODS: Because CRTH2 is a biologically important candidate gene on chromosome 11q13, we conducted a case-control analysis using 787 Japanese subjects (384 asthmatics and 403 controls) to evaluate the genetic impact of the CRTH2 gene on asthma and asthma-related traits. Four polymorphisms [1544G-->C (rs11571288), 1651G-->A (rs545659), 11336T-->C (rs2074422), and 12375G-->T (rs561285)] were studied. RESULTS: The allele, genotype, or haplotype frequencies for 2 functional polymorphisms in our Japanese population were significantly different from those in the Chinese or African American populations. No association was found between any polymorphisms or haplotypes in the CRTH2 gene and asthma, atopy, or total serum IgE levels in a Japanese population. CONCLUSIONS: Our data failed to support previous associations of functional polymorphisms at the 3'-UTR of the CRTH2 gene implicated in asthma. We did show a significant difference in the allele and genotype frequencies as well as different haplotype frequencies among African American, Chinese, and Japanese populations, suggesting that the genetic impacts of these functional polymorphisms on asthma and asthma-related phenotypes may vary in different populations.

Adolescent↗
PubMed2007

Genetic predisposition to asthma and atopy.

A large number of studies have tried to identify heritable components in the susceptibility to asthma and atopy phenotypes. This review examines the evidence of multigenetic inheritance for these conditions. We identified in the literature at least 372 gene-disease association studies for asthma and 124 for atopy published in the last 6 years. Gene-environment analyses were performed in 41 and 14 articles, respectively, in the same time period. Many postulated associations have been probed with limited sample sizes and will require more extensive replication and large-scale evidence. Meta-analyses have been performed for polymorphisms in 5 genes and provide modest evidence for genetic association of asthma with ADAM33 and TNFA gene polymorphisms. Meta-analyses of linkage studies show that it is unlikely to detect strong linkage peaks for asthma susceptibility. However, linkage was claimed between loci on chromosomes 2, 4, 6, 9, 10, 11 and 15 and total serum IgE levels. Careful definitions and standardization of phenotypes across teams of investigators are important to endorse. New large-scale testing platforms may offer new opportunities for discovering susceptibility gene variants, but they need to be coupled with careful study design, international collaboration, and possibly also dissection of gene-environment interactions.

Asthma↗
PubMed1985

Lymphocyte subsets in infants: relationships to feeding, atopy, atopic heredity and infections.

Numbers of T and B lymphocytes and T cell subsets were measured longitudinally in blood samples of 68 healthy infants from 1 month to 28 months of age. Monoclonal antibodies against cell surface antigens (OKT3, OKT4, OKT8, and OKIal) and antibodies to immunoglobulin heavy chains (gamma, mu, alpha and delta) were used for immunofluorescent staining. The absolute number of T lymphocytes (OKT3) was found to be highest at the age of 6-7 months, reflecting the greater numbers of both helper (OKT4) and suppressor (OKT8) cells. The percentages of OKT4 and OKT8 positive cells and hence the ratios of these cells were very stable throughout the study period. Relatively, breast-fed infants had more suppressor (OKT8) cells than infants on formula, but the difference was not apparent in absolute counts. Change to formula feeding caused an increase in B cells. The heredity for atopy did not influence the total numbers of T cells or cell numbers in the different subgroups. At the age of 4 months an altered helper/suppressor ratio was noted in infants who later developed a severe atopy. At the age of 28 months the relative number of T cells was lower in atopic than nonatopic infants. The rate of respiratory infections did not affect these numbers.

Age Factors↗
PubMed1986

Analysis of histamine-binding lymphocytes in atopy.

Using flow cytofluorimetry, the histamine-binding properties and T cell subclass distribution of peripheral blood lymphocytes in normal and atopic subjects were investigated. In the case of active (or symptomatic) atopy, the levels of histamine-binding lymphocytes were significantly reduced. However, none of these parameters distinguished between normal individuals and patient groups when the atopics were asymptomatic except the OKT3 marker; in the atopic group, the proportion of OKT3-positive cells was lower. These results indicate that the decreased levels of histamine-binding lymphocytes in atopy are a secondary phenomenon, and that the ratio of T helper to T suppressor/cytotoxic cells is not significantly altered in atopic patients. The changes in histamine-binding lymphocytes appear to be unrelated to the decreased numbers of OKT3-positive cells, since the latter changes were evident in active and asymptomatic atopics.

Antibodies, Monoclonal↗
PubMed1996

Lack of association between atopy and the Ile181Leu variant of the beta-subunit of the high-affinity immunoglobulin E receptor.

A previous study has reported a strong association of a variant (Ile181Leu) of the beta-subunit of the high-affinity IgE receptor (Fc epsilon RI-beta) with allergic asthma bronchiale in a random patient sample. Based on their results the authors concluded that Fc epsilon RI-beta may be the maternally inherited, atopy-causing locus. We have investigated 40 unrelated atopic patients, 30 with allergic asthma and 10 with atopic dermatitis or allergic rhinoconjunctivitis along with some of their relatives for the presence of Ile181Leu by nucleic acid sequence analysis and/or hybridization with mutation-specific oligonucleotide probes. None of the probands showed this mutation suggesting that its association with atopy may be restricted to certain populations or occur at lower frequency than reported.

Adolescent↗
PubMed1997

Role of IL-13 in CD4 T cell-dependent IgE production in atopy.

IgE isotype switching of human B cells requires physical interaction of T and B cells via surface molecules, and either IL-4 or IL-13 secreted by T cells. In this study we analyzed the role of IL-4 versus IL-13 in IgE production in atopy. We found that peripheral blood mononuclear cells (PBMC) from atopic individuals but not from nonatopic subjects secreted IgE without addition of IL-4 or IL-13, if T and B cells were simultaneously activated by anti-CD3 mAb and soluble CD40L, respectively. IgE production by atopic PBMC was dependent on endogenously secreted IL-4 and IL-13, since it could be blocked by a combination of anti-IL-4 plus anti-IL-13 antibodies. No differences in the B cell compartment of nonatopics and atopics were detectable, since PBMC from both donor populations secreted comparable amounts of IgE, if only the B cells were activated by soluble CD40L plus either exogenous IL-4 or IL-13. Further phenotypic analysis of T cells from atopics revealed that activated CD4+45RO- secreted IL-4 but no IL-13, whereas CD4+45RO+ memory T cells secreted low amounts of IL-4, but large amounts of IL-13. Accordingly, prolonged activation of native CD4+45RO- T cells in vitro induced expression of CD45RO, and strongly favored secretion of IL-13 rather than IL-4. Addition of exogenous IL-4 during activation further increased both IL-4 and IL-13 production to a similar degree. However, the potential of CD4 T cells from atopics to deliver contact-dependent activation signals to B cells and to induce IgE production (in the absence of soluble CD40L) increased with prolonged activation, and coincided with IL-13 rather than IL-4 production. Under similar conditions, CD8 effector cells secreted IL-13 but no IL-4, did not express CD40L, and could not help Ig(E) production by B cells. These results suggest that, in atopy, persistently stimulated CD4+45RO+memory/effector T cells provide contact-dependent activation signals to B cells, and that these cells may induce IgE switching largely via secretion of IL-13.

Adult↗
PubMed1996

The role of atopy in grain dust-induced airway disease.

To determine whether atopy influences the physiologic or inflammatory response to grain dust, we compared spirometric measures of airflow and bronchoalveolar lavage (BAL) measures of lower respiratory tract inflammation between demographically similar nonatopic (n = 10) and atopic (n = 10) study subjects after each of two inhalation exposures: Hanks' balanced salt solution (HBSS) and corn dust extract (CDE; 0.4 microgram of endotoxin/kg body weight). Subjects were healthy nonsmokers with similar baseline pulmonary function, without bronchial hyperreactivity, and had not participated in agriculture. Atopic subjects had two or more positive skin responses to 10 common environmental allergens. Both groups developed significant airflow obstruction and lower airway inflammation after CDE inhalation. Importantly, the magnitude of the post-CDE exposure airflow decrements, BAL cellularity, and BAL concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, and IL-8 did not significantly differ between atopics and nonatopics. The concentrations of histamine and eosinophils in the BAL fluid were unaffected by CDE inhalation and did not significantly differ between atopics and nonatopics. Atopic status does not appear to be a significant determinant of airflow obstruction or lower airway inflammation following CDE inhalation. Our findings suggest that atopy may play, at most, a minor role in the development of grain dust-induced airway disease.

Adult↗
PubMed2000

Relative scarcity of asthma and atopy among rural adolescents raised on a farm.

We determined the prevalence of markers of atopy and asthma among 1, 199 rural secondary school students ages 12 to 19 yr. Subjects identified as having been raised on a farm and half as many subjects without regular exposure to a farming environment from the same school class completed a respiratory symptom questionnaire and underwent allergy skin tests and a methacholine bronchoprovocation test. Current wheeze, airways hyperresponsiveness (AHR), and skin test positivity to inhaled allergens were all significantly less common among adolescents raised on the farm and these differences were especially pronounced in girls. After adjusting for gender and current smoking, the odds ratios for being raised on a farm were: 0. 70 (95% CI 0.52 to 0.95) for current wheeze; 0.59 (95% CI 0.37 to 0. 95) for asthma, defined as the concomitant occurrence of wheeze and AHR; and 0.58 (95% CI 0.46 to 0.75) for atopy defined as a positive reaction to any one of 24 common inhaled allergens. These associations were also not significantly altered by adjusting for the difference in the number of siblings.

Adolescent↗
PubMed2000

Evidence for genetic associations between asthma, atopy, and bronchial hyperresponsiveness: a study of 8- to 18-yr-old twins.

We measured asthma in the last 12 mo, diagnosed by a respiratory physician at interview; atopy, defined by a positive skin prick test to any of eight common allergens; and bronchial hyperresponsiveness (BHR) to hypertonic saline, in 381 twin pairs aged 8 to 18 yr selected from the Australian Twin Registry-183 monozygous (MZ) and 198 dizygous (DZ). The associations between twins, as measured by an odds ratio, were greater in MZ pairs compared with DZ pairs for asthma: 25.6 (95% confidence interval 11.3- 57.8) versus 1.9 (1.0-3. 5); atopy: 14.6 (7.1-30.1) versus 2.5 (1.4- 4.5); and BHR: 14.1 (6. 4-31.0) versus 4.2 (2.1-8.6) (all p < 0.002). The associations between each pair of traits within an individual were slightly greater than the association between one trait in a twin and the other trait in the cotwin (cross-trait cross-pair) in MZ pairs. Further, the associations in MZ pairs were greater than in DZ pairs (p < 0.05). Under the assumptions of the classic twin model, these data suggest that the strong cross-sectional associations between these three traits are due to an overlap between the genetic factors involved in each of these three traits.

Adolescent↗