Familial History Of Asthma Research Articles

Predicting the course of asthma

Asthma is a complex genetic disease that is thought to result from a combination of genetic susceptibility and environmental exposures. Asthma most often develops within the first few years of life and identified risk factors include familial history of asthma, infantile atopic dermatitis, and skin test reactivity to a subgroup of allergens. It still is not clear whether the association with skin test reactivity reveals contributions to pathogenesis by enhanced tendency to produce IgE antibodies or enhanced tendency for T cells to polarize in a Th2 direction or whether these attributes simply act as markers of a condition the origins of which still have not been identified. Currently, severity and persistence have not been unequivocally linked to these (or other) factors. Although clinical remittance is common, recent studies suggest lung function deficits may persist in the absence of symptoms and contribute to risk for chronic obstructive pulmonary disease. Additional studies are needed to establish the mechanisms underlying the development of asthma so that preventive and cure modalities may be rationally developed.

THE PROGNOSIS OF BRONCHIAL ASTHMA FROM ADOLESCENCE TO ADULTHOOD

ISEE-174 Introduction: A rising trend in asthma prevalence and morbidity has been evident throughout the world, and reports on the prognosis of asthma have presented varied outcomes from western countries. Yet, risk factors attributable to the nature and prognosis of bronchial asthma, especially from adolescence to adulthood, have not been under thorough investigation for this part of the world where environmental and genetic influence is of great importance. Methods: From a region-wide questionnaire survey, 704 middle-school students at Chiayi County were identified in 1995 as having had reported wheeze with difficult breathing in the past 12 months. Seven years later in 2002, 369 of them, 211 males and 158 females with mean age of 20 years, were successfully retrieved for questionnaire interviews and physical examinations. Results: There was no statistical significance in gender (p=0.61), mean age (p=0.28), and percentage of physician-diagnosed asthmatic cases (p=0.5) between this sub-group of the follow-up study, and the original population of 704. Among them, 119 subjects (32%) were considered to have asthma persistence into adulthood, and 250 subjects (68%) had not experienced any asthmatic symptoms for at least one year. A majority (60%) of those with inactive asthma were symptom-free for more than 5 years. In addition, 50 active asthmatics and 60 inactive asthmatics were randomly sampled from these 369 subjects, to attend hospital visits for detailed questionnaire interviews, physical examinations, pulmonary function tests, and Immunoglobulin E checks. The presence of mould growth in the residential interiors (OR=5.0, p=0.04), familial history of asthma (OR=2.9, p=0.003), and concomitant allergic rhinitis (OR=3.4, p=0.02) were significantly associated with persistence of asthma into adulthood. Discussion: Our results suggest that environmental and genetic factors both play a vital role on the prognosis of middle-school aged asthmatics. The contribution of indoor mould growth to the persistence of adolescent asthma into adulthood is particularly meaningful for an environment, such as Taiwan, where high humidity and concentrations of airborne microbes have been observed. A future endeavour may focus on the promotion of environmental hygiene along with proper clinical management, for the treatment and control of asthmatics in similar surroundings.

Asthma Questionnaire: Psychometric Properties and Clinical Utility in Pediatric Asthma

We investigated youth and parent knowledge of asthma using the Asthma Questionnaire (AQ), a newly developed measure that targets general asthma-related knowledge and knowledge of techniques often utilized to manage asthma symptoms. Participants included 46 youth with asthma and 126 parents of children with asthma. Also participating in the study was a comparison group consisting of 19 youth and 20 parents with no familial history of asthma. Results provided support for internal consistency and discriminant validity. Unlike knowledge measures previously published, the AQ is supported by its multi-informant versions, item format, and satisfactory initial psychometric properties.

Familial Risk of Asthma Among Adolescents and Their Relatives in Taiwan

Although family studies have established that asthma has a hereditary basis, little evidence has been presented about the family risk of simple asthma (AS or nonatopic asthma) and asthma with other atopic diseases (AWAD or atopic asthma) after adjusting for potential risk factors. In this study, data were collected on demographic variables and a wide range of known risk factors for asthma. Study participants were asthmatic adolescents and controls, and their relatives. The role of a familial history of asthma and atopic diseases in predicting asthma risk among asthmatic adolescents and their relatives was evaluated in a population-based family study conducted in southern Taiwan. Asthma risk factor data were collected through telephone interviews with students' parents for 207 asthmatic adolescents 11–16 years of age, their 1600 relatives, and 207 nonasthmatic adolescents in the control group and their 1638 relatives. The results show (after adjusting potential confounders) that a family history of asthma is highly associated with asthma in adolescents. Having two or more family members with asthma was associated with a 3.4-fold (95% confidence interval [CI]=1.0–12.0) increased risk of asthma among adolescents. Logistic regression was used to assess the effects of having an asthmatic relative and the effect of atopic diseases among relatives of cases. Having a family history of asthma and other atopic conditions, such as rhinitis and atopic dermatitis (adjusted odds ratio [AOR]=3.64, 95% CI=2.29–5.74 and AOR=1.94, 95% CI=1.53–2.46, respectively), was found to be a significant predictor of asthma in children. Along with a history of allergic rhinitis or atopic dermatitis, familial risks of asthma occurring in adolescents with and without other atopic diseases will be analyzed separately. A critical finding was the significant difference in a risk of asthma and atopic diseases among the relatives of asthma cases with atopic diseases and controls. However, for relatives of asthma cases without atopic diseases compared to control probands, AORs were highly significant for family history of asthma, but not for the family history of atopic diseases. These findings suggest that both forms of asthma may be hereditary, but there are differences in their modes of inheritance. Atopic status itself did not predispose a child to AS. A concomitant inheritance of a predisposition to asthma and atopic condition for AWAD cases was suggested.

Relationships of active and passive smoking to total IgE in adults of the Epidemiological Study of the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA).

The increase of total IgE in relation to active smoking has been shown in the general population, but little is known about subjects with a personal or family history of asthma. The objective of this report is to analyze the relationships of active and passive smoking to total IgE in the Epidemiological Study of the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). The sample studied includes 122 asthmatic probands, 430 first-degree relatives, and 190 control subjects, age 25 to 54 yr. As expected, first-degree relatives had total IgE intermediate between cases and control subjects and men had higher values than women. Current smokers had significantly higher IgE than never smokers. The relationship was statistically significant restricting the analysis in asthmatic probands. In a model taking into account gender, personal and familial history of asthma, socio- occupational class, and the nonindependence of subjects from the same family, IgE were in current smokers, ex-smokers, and never smokers 128, 61, and 76 IU/ml and 77, 41, and 55 IU/ml in men (p = 0.01) and women (p = 0. 05), respectively. The relation was independent of skin test response. Some increase in IgE was observed in both men and women first-degree relatives in relation to passive smoking. That relation was statistically significant in women only (adjusted for asthma values: 103 IU/ml versus 48 IU/ ml, p = 0.02). Results show that an increase in total IgE in relation to active smoking may be evidenced even in asthmatics despite the healthy smoker effect. Susceptible subjects, such as women who are first-degree relatives of asthmatics, may increase total IgE in relation to passive smoking.

Genetics and specific immune response in allergy to birch pollen and food: Evidence of a strong, positive association between atopy and the HLA class II allele HLA-DR7

Background: In some geographic areas birch pollen represents the most prominent cause for airborne allergic diseases. Up to 70% of patients allergic to birch pollen are hypersensitive to fruits, especially apples. Associations have been found, in some instances, with a sensitivity to aeroallergens and HLA class II genes. Objectives: We investigated whether susceptibility or resistance to birch pollen allergy with and without food allergy was associated with HLA class II genes. Methods: Blood samples were obtained from 2 groups of unrelated European-born white adults: 42 atopic patients (31 of them with asthma) and 42 healthy control subjects with no personal or familial history of asthma or atopy. Their antibody responses to birch pollen, apples, grass, and weed pollens were evaluated by skin tests, RASTs, and immunoprints. Genomic DNA was extracted from PBLs. The exons of DQA1 , DQB1 , DRB1 , and DPB1 genes were selectively amplified by using the PCR method. Genotyping was carried out by digestion of the amplified DNA products with allele-specific endonucleases (PCR-RFLP), which recognize allelic variations in the polymorphic exon. Results: We found no significant differences in the frequency of DPB1 alleles between patients and control subjects. HLA class II DR4 and/or DR7 alleles were present in 42.6% of the patients and in only 2.4% of the healthy subjects. These results confirm a previous study of a group of polysensitized atopic patients, which showed that DR4 and DR7 alleles were rare in healthy control subjects and frequently observed in atopic subjects with or without concomitant asthma. Conclusion: We conclude that the allele HLA-DR7 is significantly involved in the presentation of apple and pollen allergens. However, we suggest that this susceptibility is more related to atopy than to specific responses to allergens. (J Allergy Clin Immunol 1999;104:395-401.)

Rhinitis alone or rhinitis plus asthma: what makes the difference?

This paper examines the clinical expression of asthma in a group of patients displaying rhinitis according to age, sex, associated symptoms, smoking, familial history of asthma, atopy, type of sensitization to aeroallergens (pollens and/or indoor allergens), total serum immunoglobulin E (IgE), and blood eosinophils. A total of 117 adults with rhinitis were analysed on the basis of symptoms. Among them, 51 also displayed asthma, defined as a history of recurrent episodes of dyspnoea with a reversible airflow obstruction or a positive methacholine challenge. The logistic regression analysis carried out in a stepwise approach, combining several factors, showed that various parameters affected the risk of having asthma associated with rhinitis. A further analysis was made in 74 rhinitis patients comparing 42 subjects without nonallergic airway hyperresponsiveness (NAAH) to 32 patients with asthma and NAAH. Atopy, high total serum IgE levels, elevated blood eosinophil count and maternal asthma were associated with asthma. Furthermore, in atopic patients, pollen sensitization was more closely related to rhinitis alone, whereas sensitization to indoor allergens was a major determinant for the association of asthma with the symptoms of rhinitis. The same risk factors as those found in the clinical part of the study discriminated the patients with rhinitis without NAAH from those with rhinitis, asthma and NAAH. In conclusion, this study gives new insights into the relationships between asthma and rhinitis.

Evidence of a strong, positive association between atopy and the HLA class II alleles DR4 and DR7

Atopy, with or without associated asthma, provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class II gene products are involved in the control of immune responses. We investigated whether susceptibility or resistance to the disease was associated with HLA class II genes. Blood samples were obtained from two groups of unrelated European-born white adults: 56 atopic patients (52 of them with asthma) and 39 healthy controls with no personal or familial history of asthma or atopy. Genomic DNA was extracted from peripheral blood lymphocytes. The exons of DQA1, DQB1, DRB and DPB1 genes were selectively amplified by the polymerase chain reaction (PCR) method. Genotyping was carried out by digestion of the amplified DNA products with allele-specific endonucleases (PCR-RFLP), which can recognize allelic variations in the polymorphic exon. We found no significant differences in the frequency of DPB1 alleles between patients and controls. HLA class II DR4 and DR7 alleles were present in 39.2% of the patients and in 2.5% of the healthy subjects (Pc*2 < or = 3.9 10(-3)). Conversely, DQA1*0103 and DQB1*0502 alleles were more frequent in the control subjects. These results confirm a previous study of an extended pedigree, which showed that DR4 and DR7 alleles were absent in all healthy members of the family and were frequently observed in atopic and/or in asthmatic subjects. We observed that HLA-DR 4 and DR7 alleles are significantly implicated in their susceptibility to the disease and suggest that this susceptibility is more related to atopy than to specific responses to allergens. According to previous studies, we could also submit that in atopic patients with asthma, DR4 alleles at the least, could be more closely associated with atopy than with asthma per se. Conversely, we suggest that some allelic DQA1 and DQB1 sequences might confer protection against the disease.

Reference values of the provocative concentrations of methacholine that cause 6% and 20% changes in forced expiratory volume in one second in a normal population.

The provocative concentrations of inhaled methacholine that cause 6% (PC6) and 20% (PC20) falls in forced expiratory volume in one second (FEV1) were assessed in a population of 100 nonsmoking persons, equally distributed for sex, who ranged uniformly from 20 to 60 yr of age. These subjects had no respiratory symptoms, rhinitis, atopic history, or familial history of asthma. Single twofold dilutions of methacholine from 2 to 128 mg/ml were used; 81 and 34 subjects, respectively, showed PC6 and PC20 values less than 128 mg/ml. Eight subjects had PC20 values less than 16 mg/ml. In these subjects, the test had a good reproducibility (r = 0.92) when we repeated it, and serial measurements of peak expiratory flow rates did not suggest asthma. The fact that PC6 was related, although loosely, to baseline FEV, FEV/FVC, and forced expiratory flow during the middle half of the FVC (FEF) and that 4 of the 8 subjects with PC20 values less than 16 mg/ml had lower values of FEF might suggest that responsiveness to methacholine is partially linked with baseline airway caliber.

Fatal aplastic anemia associated with chloramphenicol (chloromycetin) therapy; report of two cases.

Two cases of fatal aplastic anemia in patients receiving chloramphenicol (chloromycetin®) are reported, and the literature is reviewed briefly. In both patients, a 71-year-old widow and a 92-year-old man, an initial course of treatment with the antibiotic was uneventful, but resumption of therapy after an interval of several weeks was associated with hematological complications. <h3>REPORT OF CASES</h3><h3>Case 1.—</h3> R. C. B., a 71-year-old white physician's wife, complained of weakness and a rash on her legs in January, 1952. When examined by one of us (A. A. H.), who had attended her for 15 years, discrete and confluent petechiae and ecchymoses were found in widespread distribution, including the oral mucosa. Except for the purpura, her physical condition was the same as it had been for years. There was no history or familial history of asthma, hay fever, urticaria, or blood dyscrasia. Since 1932 the patient had intermittently followed a dietary