Asthma Remission Research Articles

Subcutaneous Immunotherapy for Allergic Asthma in a Single Center of Korea: Efficacy, Safety, and Clinical Response Predictors.

Allergen-specific immunotherapy is the only causal treatment for allergic diseases. However, the efficacy of immunotherapy may vary around the world due to differences in climate, the nature of aero-allergens and their distribution. The aim of this study was to describe the effects of subcutaneous immunotherapy (SCIT) in Korean adults with allergic asthma (AA). As a retrospective cohort study, we reviewed medical records for 627 patients with AA in Korea who were sensitized to house dust mite (HDM) and/or pollens and who underwent SCIT with aluminum hydroxide adsorbed allergen extract from 2000 to 2012. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Herein, 627 asthmatic patients achieved remission within a mean of 4.7 ± 0.2 years. The cumulative incidence rates of remission from AA were 86.9% upon treatment with SCIT. Baseline forced expiratory volume in the first second (FEV1) ≥ 80% (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.79–5.39; P < 0.001), and maintenance of immunotherapy for more than 3 years (HR, 1.82; 95% CI, 1.21–2.72; P = 0.004) were significant predictors of asthma remission during SCIT. In 284 patients on SCIT with HDM alone, initial specific immunoglobulin E (IgE) levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae did not show significant difference between remission and non-remission group after adjusting demographic variables. In conclusion, SCIT was effective and safe treatment modality for patients with AA. Initial FEV1 ≥ 80% and immunotherapy more than 3 years were found to be associated with favorable clinical responses to SCIT.

Влияние фликсотида на электронно-микроскопические изменения ткани легких морских свинок при моделировании бронхиальной астмы

В хронических экспериментах на короткошерстных нелинейных морских свинках показано, что моделирование бронхиальной астмы путем сенсибилизации овальбумином без лечения вызывает электронно-микроскопические изменения в ткани легкого в виде хронического аллергического воспаления. Выявлены существенные изменения аэрогематического барьера с разрыхлением межклеточных контактов и дегенеративными изменениями в альвеолоцитах, нарушения кровообращения с явлениями расширения сосудов и стаза форменных элементов в них. Применение флутиказона пропионата в виде ингаляций («Фликсотид» фирмы GlaxoSmithKline, Великобритания) в течение 3 мес 2 раза в день по 30 – 45 с частично уменьшают нарушения кровообращения и транскапиллярного обмена, отек и дегенеративные изменения в клетках, восстанавливает межклеточные контакты и пиноцитозную активность клеток аэрогематического барьера. Проведенные исследования свидетельствуют о целесообразности дальнейших исследований с целью установления оптимальной длительности базисной терапии в период ремиссии бронхиальной астмы.

Gu-Ben-Fang-Xiao decoction attenuates sustained airway inflammation by suppressing ER stress response in a murine asthma remission model of respiratory syncytial virus infection

Ethnopharmacological relevanceIn recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous. Gubenfangxiao decoction (GBFXD) has been widely used in treating asthma remission stage for decades in the Jiangsu Province Hospital of Chinese Medicine, China. We previously demonstrated that GBFXD could downregulate the asthma susceptibility gene ORMDL3, a trigger of Endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Aim this studyTo investigate the involvement of ER stress and UPR in the anti-inflammatory effects of GBFXD in Respiratory Syncytial Virus (RSV)-OVA-induced asthma remission mice. Materials and methodsMice were orally administered GBFXD at three doses for 30 days after an RSV-OVA challenge. The levels of inflammation mediators in serum were measured using a Luminex assay and the amount of IFN-γ in lung homogenates was detected using ELISA. The splenic CD4+ and CD8+ T lymphocytes were counted using flow cytometric analysis. The mRNA and protein levels of asthma susceptibility gene ORMDL3, ER stress markers (BIP, CHOP), and three canonical UPR branches (PERK-eIF2a-ATF4, IRE1α-XBP1/IRE1α-JNK-AP1 and ATF6-SERCA2b signal pathways) were detected using real-time RT-PCR and western blot. ResultsHistopathological analysis showed that the model group mice still exhibited a sustained airway inflammation even after suspending the OVA-challenge and RSV infections for 30 days. H&E staining results indicated that GBFXD could attenuate sustained airway inflammation. Decreased serum CXCL1 level and increased IFN-γ level in lung homogenate were observed after GBFXD treatment. Reductions in the number of splenic CD4+/CD8+ T lymphocytes were found after DEX treatment. We further confirmed the previous finding that GBFXD could downregulate the expression of ORMDL3. As a result of suppressed UPR, decreased ER stress markers and inhibited UPR branches (PERK and IRE1α signal pathway) were also observed through the significant reduction of signature mRNA and protein expressions after GBFXD treatment. ConclusionGBFXD can significantly attenuate RSV-OVA-induced persistent airway inflammation in murine asthma remission model. These effects may be mediated, at least partially, by inhibiting the activation of ER stress responses.

Infant lung function predicts asthma persistence and remission in young adults.

Asthma in adults is associated with a persistent reduction in lung function from childhood, but this link has not been assessed back to infancy. Reduced infant lung function (ILF), a measure of antenatal and infant lung growth, is associated with asthma into adolescence. Our aim was to assess whether this link persists into adulthood and whether ILF can predict the remission of asthma symptoms in young adults. The study cohort was an unselected full-term birth cohort of 253 subjects enrolled antenatally with lung function assessments at 1, 6 and 12 months (maximum expiratory flow at functional residual capacity, V'maxFRC), and 6, 11, 18 and 24 years (spirometry) of age. Infants with V'maxFRC in the lowest quartile at 1 month had an OR of 5.1 (95% CI: 2-13, P = 0.001) for asthma at 24 years. Subjects with asthma at 24 years had a mean V'maxFRC at 1 month of 69% predicted (95% CI: 48-90%) versus 110% (95% CI: 101-119%) in non-asthmatic patients (P = 0.001). Subjects with current versus resolved asthma symptoms at 24 years had a mean V'maxFRC at 1 month of 69% predicted (95% CI: 53-84%) versus 105% (88-123%), respectively (P = 0.003). Subjects with current asthma at 24 years had persistently lower lung function from infancy with a mean reduction of 16.2% (95% CI: 8.1-24.3%, P < 0.0001). Reduced lung function in early infancy is predictive of persistent asthma in young adults and a persistent reduction in lung function, suggesting abnormal lung development and growth in utero or very early in life.

The Effect of Cigarette Smoking on Lung Function in Young Adults with Asthma.

Life-course persistent asthma and tobacco smoking are risk factors for irreversible airflow obstruction. It is often assumed that smoking and asthma have additive or multiplicative effects on the risk for airflow obstruction, but this has not been demonstrated in prospective studies of children with persistent asthma. To investigate the effects of smoking and asthma on the development of airflow obstruction in a population-based birth cohort followed to age 38 years. Reports of childhood asthma from ages 9, 11, and 13 and self-reports of adult asthma at ages 32 and 38 years were used to define childhood-onset persistent asthma (n = 91), late-onset asthma (n = 93), asthma in remission (n = 85), and nonasthmatic (n = 572) phenotypes. Cumulative tobacco smoking histories and spirometry were obtained at ages 18, 21, 26, 32, and 38 years. Analyses were by generalized estimating equations adjusting for childhood spirometry, body mass index, age, and sex. Smoking history and childhood-onset persistent asthma were both associated with lower FEV1/FVC ratios. Associations between smoking and FEV1/FVC ratios were different between asthma phenotypes (interaction P < 0.001). Smoking was associated with lower prebronchodilator and post-bronchodilator FEV1/FVC ratios among subjects without asthma and those with late-onset or remittent asthma, but smoking was not associated with lower FEV1/FVC ratios among those with childhood-onset persistent asthma. Childhood-onset persistent asthma is associated with airflow obstruction by mid-adult life, but this does not seem to be made worse by tobacco smoking. We found no evidence that smoking and childhood-persistent asthma have additive or multiplicative effects on airflow obstruction.

A 12-year prognosis of adult-onset asthma: Seinäjoki Adult Asthma Study

RationaleLong-term prognosis of adult-onset asthma is poorly known. ObjectiveTo evaluate 12-year prognosis of adult-onset asthma and the factors associated with disease prognosis. MethodsSeinäjoki Adult-onset Asthma Study (SAAS) is a 12-year real-life single-center follow-up study of new-onset asthma diagnosed at adult age and treated in primary and specialized care. Remission was defined by no symptoms and no asthma medication use for 6 months. Asthma control was evaluated according to Global Initiative for Asthma 2010. Factors associated with current asthma control were analyzed by multinomial multivariate logistic regression. Main resultsA total of 203 patients (79% of the baseline population) were followed for 12 years. Remission occurred in 6 (3%) patients. In 34% asthma was controlled, in 36% it was partially controlled and in 30% uncontrolled. Uncontrolled asthma was predicted by elevated body-mass index at baseline, smoking (pack-years) and current allergic or persistent rhinitis. Elevated blood eosinophils and good lung function (FEV1) at baseline protected from uncontrolled asthma. In contrast, gender, age at the onset or baseline symptoms (Airways Questionnaire 20) were not significant predictors of uncontrolled disease. ConclusionsDuring a 12-year follow-up, remission of adult-onset asthma was rare occurring in only 3% of patients. The majority of patients (66%) presented either with uncontrolled or partially controlled asthma.This study is registered at ClinicalTrials.gov with identifier number NCT02733016.

Bronchial epithelium in children: a key player in asthma

Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on children. We report physical, chemical and immunological properties from ex vivo and in vitro studies. The responses to various deleterious agents, such as viruses or allergens, may lead to persistent abnormalities orchestrated by bronchial epithelial cells. As epithelium dysfunctions occur early in asthma, reprogramming the epithelium may represent an ambitious goal to induce asthma remission in children.

Predicting Factors for Asthma Remission in Children

Predicting Factors for Asthma Remission in Children

Negative Skin Prick Test Predicts Asthma Remission in Preschool Children

Negative Skin Prick Test Predicts Asthma Remission in Preschool Children

Comparable Function of γ-Tocopherols in Asthma Remission by Affecting Eotaxin and IL-4.

Bronchial asthma is one of the world's most common chronic disorders dangerous to human health. It has been hypothesized that the increased number of asthma sufferers may be due to changing antioxidant intake or vitamin deficiency. However, the influence of vitamins on asthma has rarely been considered. The aim of this study was to explore the effects of γ-tocopherols, a specific form of vitamin E, on asthma remission together with the possible mechanism behind the process. Eosinophil counting was applied to detect the total number of cells, eosinophils and lymphocytes. Meanwhile, HE staining was used for morphological detection. In addition, the eotaxin and IL-4 levels in the serum and bronchoalveolar lavage fluid were measured using ELISA technology. The cell counting results showed that γ-tocopherols possesses the capability to reduce the number of eosinophils. Moreover, the exudation of inflammatory cells together with the hyperplasia of goblet cells was also found to experience significant inhibition when treated with γ-tocopherols. Furthermore, the high levels of eotaxin and IL-4 in the asthma group were evidently reduced under the treatment of γ-tocopherols which was comparable with hexadecadrol. γ-tocopherols can remit asthma by regulating the level of eotaxin and IL-4. Moreover, γ-tocopherols may be regarded as a potential candidate for asthma treatment after much deeper explorations.

CIRCADIAN ARTERIAL TENSION PROFILE IN THE PATIENTS WITH BRONCHIAL ASTHMA AND COMORBID HYPERTENSIVE DISEASE

The aim of research is to study the state of circadian arterial tension profile in the patients with bronchial asthma and hypertensive disease as comorbid disease. Materials and methods. The research has been performed at 76 patients with bronchial asthma and hypertensive disease as comorbid disease (the main group) and 52 patients with hypertensive disease as the comparison group. The groups were comparable with respect to the gender and age sign. Investigation was performed in the period of clinical remission. The main method used in this research was the investigation of day arterial tension profile in the time of its monitoring. Results . It has been revealed the presence of frequent and expressed change from the side of the studied indexes, especially in the patients with comorbid pathology, which were characterized by more frequent and more significant disorders from the side of diastolic blood pressure, especially at night in combination with more considerable and more rapid rise in early morning hours. The day arterial tension profile was characterized either with insufficient decline of arterial pressure at night or, opposite, with its sharp decrease. Specified disorders were increased as far as heaving of main and comorbid diseases, presence of disorders from the side of lipid exchange were not related to the phase of bronchial asthma (remission, exacerbation) and level of its flow control.

Serum IL-17 & eotaxin levels in asthmatic patients with allergic rhinitis.

Objective:To investigate the serum levels of Interleukin (IL)-17 and eotaxin levels and the relationship between serum IL-17, eotaxin and pulmonary function in asthmatic patients with allergic rhinitis.Methods:Serum IL-17 and eotaxin levels in asthmatic patients with allergic rhinitis during attacking and remission and in healthy control subjects were measured using enzyme-linked immunosorbent assay (ELISA) kits. Then we studied the correlation between the serum IL-17, eotaxin levels and pulmonary function in patients.Results:Serum IL-17 and eotaxin levels were significantly elevated in patients during asthma attack and remission compared with healthy control subjects. These levels in patients during asthma attack were much higher than those during remission. Furthermore, serum IL-17 and eotaxin levels were negatively correlated with pulmonary function in asthmatic patients with allergic rhinitis, respectively.Conclusion:Our findings suggest that IL-17 and eotaxin are important factors in asthma with allergic rhinitis, and the correlation between serum IL-17, eotaxin and lung function possibly lead to improvements in the diagnosis and treatment of asthma with allergic rhinitis and related diseases.

Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on Incidence and Remission of Self-Reported Asthma from 1940 to 2010.

BackgroundIt is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma.ObjectiveTo evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010.MethodsThe subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20–84 and born between 1925–1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models.ResultsThe average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1–4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease.ConclusionsAfter 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias.

Interleukin-10 and interleukin-5 balance in patients with active asthma, those in remission, and healthy controls.

BackgroundThe immunological mechanisms of asthma remission remain unclear although several reports have suggested that balance between T helper (Th) 2 cytokines and regulatory cytokines is related.ObjectiveTo study the balance between interleukin (IL) 10 and IL-5 in asthma clinical remission.MethodsWe measured the numbers of IL-5 and IL-10 producing cells in peripheral blood mononuclear cells stimulated with mite antigen obtained from patients with active asthma (group A, n = 18), patients in clinical remission (group R, n = 15) and nonatopic healthy controls (group H, n = 14).ResultsThe numbers of IL-5 producing cells in groups A and R were significantly higher than in group H. The number of IL-5 producing cells was lower in group R than in group A, although the difference was not statistically significant. The number of IL-10 producing cells was higher in group R than in group A, although again the difference was not statistically significant. There was a significant difference in the number of IL-10 producing cells between groups A and H but not between groups R and H. The ratio of the number of IL-10 to IL-5 producing cells was highest in group H followed by groups R and A, and the differences were statistically significant for each pair of groups.ConclusionOur study suggests that the IL-10/IL-5 balance is related to clinical asthma. The balance differs between patients in clinical remission and healthy controls, suggesting that allergic inflammation may continue even after clinical asthma remission.

Diagnostic value of the indices of nonspecific bronchial hyperresponsiveness for verification of bronchial asthma remission in teenagers

The results of an analysis of indices of nonspecific bronchial hyperreactivity in 63 adolescents with asthma in remission are presented in the article. It is established that the absence of bronchial hypersensitivity to inhalation of histamine at a concentration of less than 2,0 mg / ml, with high specificity (89,7 %) and post-test probability (29,8 %) indicates the presence of teenagers complete clinical-instrumental remission with probable ratio chance of this event, equal to 6,0.

Sex-related differences in pulmonary physiologic outcome measures in a high-risk birth cohort

Sex influences the risk of wheezing illnesses and the prevalence of asthma throughout childhood. To better understand the mechanisms of these effects, we analyzed longitudinal relationships between sex, lung physiology, and asthma in the Childhood Origins of ASThma birth cohort study. Childhood Origins of ASThma birth cohort study children were followed prospectively from birth and assessed annually. Results of spirometry, fractional exhaled nitric oxide (Feno), mannitol provocation testing, and (3)He gas magnetic resonance imaging were assessed by sex using multivariate models including age, asthma diagnosis, and wheezing histories. Girls had higher prebronchodilator forced expiratory volume in 0.5 seconds/forced vital capacity values than did boys (mean difference, 0.017; 95% CI, 0.000-0.034; P = .05) of equivalent age. Postbronchodilator findings were more pronounced, with boys demonstrating reduced forced expiratory volume in 0.5 seconds/forced vital capacity values than did girls of equivalent age (mean difference, 0.032; 95% CI, 0.014-0.049; P = .0005). Conversely, girls were noted to have higher ventilation defects on (3)He magnetic resonance imaging than did boys (P = .01). No differences were noted in the rate of positive responses to mannitol provocation or Feno measurements. Lower airflow values are present by spirometry for prepubertal boys than for age-matched girls; however, greater (3)He ventilation defects were noted in girls. This could represent a greater degree of subclinical air trapping in prepubertal girls because residual volumes are not detected on standard spirometric readings. No differences were noted between the 2 sexes with airway hyperresponsiveness (mannitol provocation testing) or inflammation (Feno). Prospective peripubertal follow-up will determine whether these differences persist or change with the de novo expression and remission of asthma based on sex and age.

Investigations into the relationship between respiratory disorders and excessive body weight in the adolescents presenting with bronchial asthma treated based at a specialized health resort facility

A total of 71 patients with bronchial asthma (BA) were examined and treated based at a specialized health facility of whom 43 ones presented with mild asthma and 26 patients with moderately severe asthma in remission. The median age of the patients was 12,04 ± 2,08 years. Spirometry parameters: MOS50, MOS75, and PSV, proved to be of high informative value combined with high enough sensitivity and specificity. The significant difference between the groups as a whole (p < 0.05) were documented based on the serum leptin levels that were higher in the overweight patients and especially in the girls (p < 0.05). The leptin level was a similarly sensitive/specific (AUROC > 0.5) and informative (SCDFC > 0.5) parameter which confirms its diagnostic value given it is employed in combination with overweight for the evaluation of the status of the patients suffering from asthma. Negative linear and non-parametric correlation between the functional parameters and the serum leptin levels in the overweight patients with bronchial asthma suggests that the enhanced leptin concentration may serve as a marker of strong obstruction and severe inflammation at all levels of the respiratory tract in the patients presenting with a combination of the two conditions.

Early risk factors for pubertal asthma.

Early life risk factors are previously described for childhood asthma, but less is known related to asthma in adolescence. We aimed to investigate early risk factors (before 2 years) for pubertal asthma and secondarily for pubertal asthma phenotypes based upon allergic comorbidities. Based on data from 550 adolescents in the prospective birth cohort 'Environment and Childhood Asthma' study, subjects were categorized by recurrent bronchial obstruction (rBO) 0-2 years, asthma 2-10 years, and pubertal asthma from 10 to 16 years including incident asthma in puberty and asthma in remission from 10 to 16 years or as never rBO/asthma 0-16 years. Asthma in puberty was further classified based on the comorbidities atopic dermatitis and allergic rhinitis (AR) from 10 to 16 years. Twenty-three common asthma risk factors identified by 2 years of age, including frequency and persistence of bronchial obstruction (severity score), were analysed by weighted logistic regression for each phenotype. In adjusted models, the risk of pubertal asthma increased significantly with higher severity score, parental rhinitis, being the firstborn child, and familial stress around birth. Pubertal asthma in remission was significantly associated with severity score and number of lower respiratory tract infections and inversely associated with breastfeeding beyond 4 months. Pubertal incident asthma was more common among firstborn children. All asthma phenotypes with allergic diseases were significantly associated with severity score, whereas familial perinatal stress increased the risk of asthma only. Asthma combined with AR was associated with parental asthma and being firstborn, whereas the risk of asthma with both atopic dermatitis and AR increased with higher paternal education, atopic dermatitis, being firstborn, and familial perinatal stress. Important early risk factors for pubertal asthma were early airways obstruction, parental rhinitis, being the firstborn child, and perinatal familial stress.

Asthma incidence, remission, relapse and persistence: a population-based study in southern Taiwan.

BackgroundIn western countries, late-onset asthmatics are more severe than early-onset asthmatics in clinic-based studies. However, whether asthma occurrence rates were higher in late ages than in younger ages was inconclusive. This information is essentially lacking in Asian population.MethodsThe participants were schoolchildren’s parents recruited from 94 elementary and middle schools in 2004. A cross-sectional self-administered questionnaire was sent through the children to their parents to survey their respiratory health. We investigated typical asthma symptoms occurring at different ages and subsequent remission or relapse after the first asthma event. Person-years of the participants from birth to the time of survey were used as the denominator.ResultsAmong the 25,377 participants consisting of 949,807 total person-years, 860 reported ever having asthma. Highest incidences occurred at ages 0–12 and 36–40 years. The incidence of asthma was higher in males before puberty, and higher in females after puberty, with overall incidences 1.00 and 0.77 per 1000 person-years for females and males, respectively. Participants with late-onset asthma (onset age >12 years) comprised a large portion of adult current asthmatics. More than 52% of persistence or relapse was observed in early-onset asthma (onset age ≤12 years). The younger birth cohort had a more prominent later peak of asthma incidence than the older one.ConclusionsIn Asian population, asthma occurrence showed a U-shape age distribution with a prominent second peak in the thirties. A high proportion of early-onset asthma relapsed and most of late-onset asthma persisted or relapsed in adulthood.

Remission and persistence of asthma followed from 7 to 19 years of age.

M Andersson, L Hedman, A Bjerg, B Forsberg, B Lundback, E Ronmark. Pediatrics. 2013;132(2). Available at: www.pediatrics.org/cgi/content/full/132/2/e435 The goal of this study was to analyze the remission and persistence of childhood asthma in adolescents. The study population included 205 subjects with asthma studied from age 7 to 8 years up until the study end-point age of 19 years. Subjects with asthma were identified by distributing an extended International Study of Asthma and Allergies in Childhood questionnaire to the families of all children in the first and second grade in 3 municipalities in northern …