Risk Of Persistent Asthma Research Articles

Disadvantage in early-life and persistent asthma in adolescents: a UK cohort study

ObjectiveTo determine how early-life risk factors explain socioeconomic inequalities in persistent asthma in adolescence.MethodsWe did a causal mediation analysis using data from 7487 children and young people in the UK...

Механізми формування гіперреактивності бронхів з урахуванням фенотипової неоднорідності та клінічної девіації бронхіальної астми в підлітковому віці (огляд літератури)

Bronchial asthma is a disease characterized by recurrent episodes of variable bronchial obstruction, chronic bronchial inflammation, bronchial hypersensitivity and remodulation. Modern therapy of the disease was aimed at these links of pathogenesis, and this concept postulated the need for long-term use of anti-inflammatory drugs and, above all, topical inhaled corticosteroids. However, it should be recognized that the coherent inflammatory theory currently requires revision and new understanding, or even replacement with a new theory, which, considering these characteristics of the disease as an epiphenomenon, will serve as a basis for new approaches in treatment and prevention. The aim of our work — to analyze the mechanisms of formation of bronchial hyperreactivity, taking into account the phenotypic heterogeneity and clinical deviation of bronchial asthma in adolescence (based on the analysis of scientific sources). It is extremely important to determine the risk of transition of the adolescents' bronchial asthma into adulthood, when chronic obstructive pulmonary diseases might develop. Among the main predictors of this risk such factors as age, obesity, early puberty, body weight at birth and in the newborn period and sex can be distin guished. Thus, some authors associate the risk of persistence of the disease with its onset in early childhood, and others — at the age of 6 years old. High body mass index and early onset of puberty are considered to be the predictors of persistent bronchial asthma. It is noted that low and extremely low birth weight of premature infants or rapid weight gain in the neonatal period are associated with a decrease in lung ventilation and the risk of persistent asthma in the future. It is believed that bronchial asthma in children is more common in boys than in girls, in contrast, during puberty, allergic diseases and asthma are more common in girls. Conclusions. The above mentioned literature data give reason to believe that, despite advances in the scientific understanding of the pathogenesis of the main characteristics of bronchial asthma, there are great difficulties in using them in practice. Moreover, current inflammatory paradigm of bronchial asthma needs to be revised because it being a dogma becomes unproductive from a clinical point of view. No conflict of interest was declared by the authors. Key words: asthma, adolescents, hyperreactivity, remission.

ASSOCIATION OF CORTICOTROPHIN RELEASING HORMONE RECEPTOR 1 GENE POLYMORPHISMS (RS242941 AND RS242939) WITH PERSISTENT ASTHMA AND ITS PHENOTYPE IN NORTHERN INDIAN ASTHMATIC CHILDREN: A CROSS‑SECTIONAL STUDY

<p><strong>INTRODUCTION:</strong> Asthma is a common, chronic, relapsing disease in children. Corticotrophin‑releasing hormone receptor 1 (CRHR1) gene is identified as a potential marker for steroid responsiveness. Genetic variations in CRHR1 are expected to diminish the capacity to secrete endogenous cortisol. <strong>OBJECTIVE:</strong> This study aimed to find out association of CRHR1 gene polymorphisms namely, rs242941 (G > T) and rs242939 (A > G) with persistent asthma and its phenotype in Northern Indian asthmatic children. <strong>MATERIALS AND METHODS:</strong> This was a hospital‑based cross‑sectional study. Genotyping was done for 250 asthmatic children, aged 1‑12 years, using polymerase chain reaction restriction fragment length polymorphisms method.<strong> RESULTS:</strong> Mutant homozygous genotype (TT) and mutant allele (T) of single nucleotide polymorphism (SNP) rs242941 were found to be associated with increased risk for persistent asthma (odds ratio [OR] =4.2; 95% confidence interval [CI] =1.6‑10.9; P = 0.00 and OR = 1.8; 95% CI = 1.2‑2.8; P = 0.00, respectively). On analyzing genotypic and phenotypic associations, factors such as urban residence (OR = 2.01; 95% CI = 1.11‑3.63; P = 0.01), family history of asthma (OR = 1.80; 95% CI = 1.00‑3.24; P = 0.05), previous hospitalization (OR = 2.12; 95% CI = 1.14‑3.96; P = 0.01), previous use of bronchodilators (OR = 3.64; 95% CI = 1.68‑7.94; P = 0.00), previous use of inhaled corticosteroids (OR = 2.37; 95% CI = 1.15‑4.93; P = 0.01), visit to doctor in last 1 year (OR = 1.82; 95% CI = 1.01‑3.28; P = 0.04), seasonal variation in exacerbation (OR = 2.66; 95% CI = 1.16‑6.12; P = 0.01), and lower pulmonary functions ( P = 0.00) were found to be associated with SNP rs242941. Genotypes of SNP rs242939 showed no association with persistent asthma and its phenotype. Minor allele frequency for SNP rs242941 and SNP rs242939 was 43.20% and 11.00%, respectively, in Northern Indian asthmatic children. <strong>CONCLUSION:</strong> In conclusion, we observed an association of SNP rs242941 with persistent asthma and its phenotype in Northern Indian asthmatic children. </p>

Predicting persistence of asthma in preschool wheezers: crystal balls or muddy waters?

Since preschool wheezing is the common expression of several heterogeneous disorders, identification of children at risk for persistent asthma is particularly challenging. To date, efforts to predict the outcome of preschool wheeze have mainly relied on predictive rules consisting of simple clinical and laboratory parameters. Among these tools, the asthma predictive index (API) has been introduced in international guidelines and position papers and is recommended for use in clinical practice. This article reviews the currently available asthma predictive models focusing on their validity and performance characteristics. Although these tools are generally simple and easy to apply, they suffer important intrinsic and practical limitations and they have been insufficiently validated to allow for widespread use in clinical settings. We also present evidence that their ability to predict the long-term outcome of preschool wheeze is limited in general populations, and even poorer in high-risk children in which prediction of asthma persistence might have important clinical and prognostic implications. Due to the complex and multifactorial nature of asthma, prediction of asthma persistence based on simple clinical models is practically impossible.

Association of CFTR gene mutation with bronchial asthma and its severity in Indian children: A case-control study

Background: Asthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them.Aim: To assess the association of CFTR gene mutation with asthma and its severity as per GINA guidelines.Subjects and methods: This was a hospital-based case-control study. Excluded from cases and controls were those with clinically suspected cystic fibrosis or sweat chloride level>60 mmol/L or suffering from other respiratory diseases. Included were 200 cases and 180 controls, aged 5 months to 15 years. Screening was done for CFTR gene mutations; ΔF508, G542X, G551D, R117H and W1282X using the ARMS-PCR method.Results: ΔF508 was found in three (1.5%) cases and two (1.1%) controls (p = 0.739), G542X in nine (4.5%) cases and five (2.8%) controls (p = 0.374), R117H in one (0.5%) case and one (0.6%) control (p = 0.940) and G551D in twelve (6.0%) cases and two (1.1%) controls (p = 0.012). Individuals carrier for G551D mutation had increased risk for persistent asthma (p = 0.006). Percent predicted FEV1 (p = 0.014) and FVC (p = 0.028) were significantly lower among carriers as compared to non-carriers.Conclusion: Significantly higher frequency of G551D mutation among asthma patients compared with controls suggests that this mutation may increase risk for the disease and also its severity.

Mite component–specific IgE repertoire and phenotypes of allergic disease in childhood: The tropical perspective

Sensitization to perennial aeroallergens correlates with the risk of persistent asthma (AS) in children. In tropical Singapore, multiple codominant species of mites abound in the indoor environment, and preferential species-specific sensitization has been associated with different phenotypes of allergic disease. We investigated the pattern of mite component-specific IgE (mcsIgE) in children with different phenotypes of clinical allergic disease in an environment with multiple mite species exposure. A prospective evaluation of newly diagnosed patients with clinical diagnosis of allergic rhinitis (AR), atopic dermatitis (AD), or AS and sensitization to one or more aeroallergens were performed. Sera were tested for specific IgE against an extensive panel of Dermatophagoides pteronyssinus and Blomia tropicalis allergens. A total of 253 children were included, mean age 7.3 yr, 79% fulfilled criteria for AR, 46% AS, 71% AD, and 31% for all three. Sensitization to one or both mites was observed in 91% of children, 89% were sensitized to D. pteronyssinus, and 70% to B. tropicalis. The most common mite allergens recognized by these atopic children were Der p 1 (64%), Der p 2 (71%), Blo t 5 (45%), Blo t 7 (44%), and Blo t 21 (56%). Specific IgE responses to an increased number of distinct mite allergens correlated with the complexity of the allergic phenotype. In multivariate analysis, an increased risk for the multi-systemic phenotype (AR + AS + AD) was associated with sensitization to an increased repertoire of mite components (three or more) (OR 4.3, 95% CI 2.1-8.8, p = 0.001) and a positive parental history of AS (OR 2.4, 95% CI 1.2-2.9, p = 0.013). A highly pleiomorphic IgE response to the prevalent indoor mites is associated with the presence of a multi-systemic allergic phenotype in childhood in a tropical environment.

Do risk factors for persistent asthma modify lung function in infants and young children with recurrent wheeze?

There is very limited information on how the risk of persistent asthma in recurrent wheezing (RW) infants modifies their lung function early in life. The aim of this study is to compare lung function of RW infants and young children with a positive or negative asthma predictive index (API), an index previously used to anticipate asthma persistence into childhood and adolescence. Two groups of RW infants and young children were recruited in two centres in Spain (Palma de Mallorca and Murcia). Lung function was measured according to the thoracho-abdominal compression technique (RCT), and values of the maximal flow at functional residual capacity (V'FRC) were expressed as Z-scores. Other variables included in the study, as independent factors, were: gender, age, length, weight, and parental smoking habits together with information regarding API. Expressed as mean +/- SD, API+ RW infants (n = 50; age in months 11.9 +/- 4.9) had a lower V'FRC Z-score than API- RW ones (n = 41; age in months 12.3 +/- 6.2; -2.01 +/- 0.79 vs. -1.64 +/- 0.77, P = 0.026, respectively). Centre and tobacco exposition did not have an effect on lung function. Among RW infants and young children, those having a positive API have a significant lower lung function as measured by V'FRC at an early age.

Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-old children at risk for persistent asthma

Background: Objective lung function measurements are routinely used to diagnose and manage asthma, but their utility for young children has not been defined. Objective: Bronchodilator responses were measured by means of impulse oscillometry (IOS) and compared with conventional spirometry to determine the value of lung function measures in 4-year-old asthma-prone children. Methods: The study participants were in the Childhood Asthma Prevention Study (National Institute of Health/National Institute of Allergy and Infectious Diseases) and at risk for asthma. At age 4 years, concurrent asthma was determined by using a previously validated modified American Thoracic Society questionnaire. Children performed IOS and spirometry before and after albuterol administration and underwent skin prick testing to 13 common allergens to assess atopy. IOS measures were as follows: airways resistance at 5 Hz and 10 Hz, airways reactance at 5 Hz and 10 Hz, and resonant frequency. Results: Asthmatic patients versus nonasthmatic patients significantly differed in their IOS-assessed bronchodilator responses through Δ resistance at 5 Hz (medians, 27% vs 17%; P = .02) and Δ resistance at 10 Hz (24% vs 16%; P = .03). Because atopic children who have frequent wheezing are at risk for persistent asthma, the data were analyzed in regard to atopic patients with or without asthma. IOS strongly distinguished atopic asthmatic children through Δ resistance at 5 Hz (36% vs 13%, P = .007), Δ resistance at 10 Hz (25% vs 11%, P = .02), and Δ reactance at 10 Hz (47% vs 12%, P = .03). Conventional spirometry did not establish similar statistically significant findings. Conclusion: IOS bronchodilator responses are remarkably abnormal in 4-year-old children, who are most likely to have persistent asthma. IOS is a useful diagnostic tool in early asthma development and might be a helpful objective outcome measure of early interventions. (J Allergy Clin Immunol 2003;112:317-22.)

The burden of asthma as reflected by the prevalence defined by doctor's diagnosis and the use of healthcare services by preschool children in a Swedish region

Aim: Epidemiological data and reports on the prevalence and burden of preschool asthma are mainly based on questionnaires and generally give a prevalence of above 6% in Sweden. In this study we used other ways of studying the prevalence, risk factors and the use of healthcare services in a defined region. Methods: The catchment area included 9410 children aged 0‐6 y. All outpatient clinics had computerized records of patients and visits to the outpatient clinic could be studied as well as admissions to hospital for asthma between 1988 and 1998. Results: According to patients’record data, the prevalence of doctor‐diagnosed asthma was 4.5% in 1998. Seventy‐nine percent of recorded patients are seen outside the hospital, thus the burden of asthma for the health system is mainly on the outpatient clinics. Admissions and especially readmissions to the hospital have decreased during the past decade. One‐third of the children with newly diagnosed asthma had recurring exacerbations and risk for persistent asthma. Conclusions: The prevalence of doctor‐diagnosed asthma as measured by total mapping in a region is lower than that reported from questionnaire‐based studies. Hospital admissions for preschool asthma have decreased possibly as a result of improved medical care in the paediatric outpatient clinics where asthma is a dominating diagnose. In one‐third of identified new asthmatics, there is a high risk of developing persistent asthma.

Development of Wheezing Disorders and Asthma in Preschool Children

Recent longitudinal studies have shed light on the pathogenesis and progression of asthma. The patterns of expression of childhood asthma that persist into adult life have been explored. Distinct asthma phenotypes (transient wheezing, nonatopic wheezing, and atopy-associated asthma) have been identified. Defining which children are at risk for persistent asthma could allow for better management and, potentially, for reduced morbidity and mortality.

Childhood asthma: New insights into management

Recently, a concerted effort has been made to reverse the trend of increasing asthma mortality and morbidity. One additional strategy might be to recognize patients at risk for persistent asthma and to intervene early. This review summarizes new information on asthma pathogenesis that has helped shape a new direction in managing childhood asthma. At the core is the recognition that asthma is a chronic inflammatory disease. Subsequently, inhaled steroids, the most potent anti-inflammatory asthma medications, have emerged as the cornerstone of the management of persistent asthma. The recent report of the National Heart, Lung, and Blood Institute’s Childhood Asthma Management Program provides a comprehensive “profile of performance” for 3 treatment choices for the management of persistent asthma. This study answers questions regarding the benefits and shortcomings of the medications evaluated and prompts a closer evaluation of the long-term effects of other treatment strategies, including medications currently being developed. Although intervention with inhaled steroids offers new opportunities to control the development of asthma, one must be cognizant of potential risks in early and long-term therapeutic intervention. This review provides a perspective on our present knowledge, the rationale for early intervention, and opportunities for more aggressive therapy, as well as speculation on how ongoing clinical research will continue to play a role in advancing asthma care and moving toward a “cure” for this life-threatening disease. (J Allergy Clin Immunol 2002;109:3-13.)