Higher Bronchial Hyperresponsiveness Research Articles

Blood granulocyte patterns as predictors of asthma phenotypes in adults from the EGEA study

To what extent blood granulocyte patterns may predict asthma control remains under-studied. Our aim was to study associations between blood neutrophilia and eosinophilia and asthma control outcomes in adults.Analyses were conducted in 474 asthmatics from the first follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2), including 242 asthmatics who were adults a decade earlier (EGEA1). At EGEA2, asthma control was assessed using the Global Initiative for Asthma definition (2015), and asthma exacerbations by use of urgent care or courses of oral corticosteroids in the past year. Blood EOSlo/EOShi was defined as </≥250 eosinophils·mm-3, respectively, and NEUlo/NEUhi as </≥5000 neutrophils·mm-3, respectively. Estimates were adjusted for age, sex and smoking.At EGEA2, NEUhi was associated with asthma exacerbations and poor asthma control (OR >2.10). EOShi was associated with higher bronchial hyperresponsiveness (BHR) (OR (95% CI) 2.21 (1.24-3.97)), poor lung function (p=0.02) and higher total IgE level (p=0.002). Almost 50% of asthmatics had a persistent pattern between surveys. Persistent NEUhi was associated with poor asthma control at EGEA2 (OR (95% CI) 3.09 (1.18-7.05)). EOShi at EGEA1 and persistent EOShi were associated with higher BHR (OR (95% CI) 2.36 (1.10-5.07) and 3.85 (1.11-13.34), respectively), poor lung function (p<0.06) and higher immunoglobulin E level (p<10-4) at EGEA2.Granulocyte patterns were differently associated with asthma outcomes, suggesting specific roles for each one, which could be tested as predictive signatures.

Importance of concomitant local and systemic eosinophilia in uncontrolled asthma

Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the prevalence and characteristics of patients with concordant and discordant systemic and bronchial eosinophilia. We conducted a retrospective study on 508 asthmatics with successful sputum induction. We assessed the relationship between blood and sputum eosinophils by breaking down the population into four groups according to blood (≥400 cells per mm3) and sputum (≥3%) eosinophils. Then, we prospectively reassessed the link between eosinophils and asthma control (Asthma Control Questionnaire (ACQ)) and exacerbation rate in a new cohort of 250 matched asthmatics. In our retrospective cohort, asthmatics without eosinophilic inflammation were the largest group (49%). The group with isolated sputum eosinophilia (25%) was, compared with noneosinophilic asthma, associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio and higher bronchial hyperresponsiveness and exhaled nitric oxide fraction (FeNO). Asthmatics exhibiting isolated systemic eosinophilia (7%) had similar characteristics as noneosinophilic asthmatics. The group with concordant systemic and airway eosinophilia (19%) showed remarkable male predominance, and had the lowest airway calibre, asthma control and quality of life, and the highest bronchial hyperresponsiveness, FeNO and exacerbation rate. The prospective cohort confirmed the different subgroup proportions and the higher ACQ and exacerbation rates in cases of diffuse eosinophilia compared with noneosinophilic asthmatics. Concomitant systemic and bronchial eosinophilic inflammation contribute to poor asthma control.

The clinical and genetic factors for predicting the response to inhaled corticosteroids

Background It has been reported that a part of asthma patients does not respond well to inhaled corticosteroids (ICS) and the benefit by long term treatment by high-dose ICS is limited in such patients. But the clinical or genetic factors for predicting ICS response have not been fully established especially in adults. The aim of this study is to establish the factor for predicting the response to ICS treatment. Method Patients treated only by ICS for more than 6 months were enrolled and classified into responder group (R group, n=30) if FEV1 improvement ≥ 5% and nonresponder group (NR group, n=40, FEV1 improvement <5%). The relationship between ICS response and pretreatment clinical indices and 21 single nucleotide polymorphism (SNP) were retrospectively analyzed. Results In R group, peripheral blood eosinophil % (R: NR = 7.5: 4.3%) and serum total IgE level (550.4: 497.1 U/ml) was significantly higher as compared to NR group. R group also showed significantly lower %VC (97.5: 114.8%), % FEV1.0 (77.9: 101.3%), FEV1.0% (67.5: 76.4%) and higher bronchial hyperresponsiveness. Bronchial reversibility test was available in 30 patients (R: n=11, NR: n=19) and reversibility was significantly higher in R group (15.9: 5.4%). By logistic multivariate analysis for those 30 patients, bronchial reversibility was significantly related to ICS response. SNP in IFN-g R1 L467P was also related to ICS response. Post/Pre FEV1 ratio was significantly higher in homo/ hetero group as compared to wild group (140.2 v.s 108.8%). Conclusion Pre-treatment bronchial reversibility was identified as a prediction factor for ICS response. It has been reported that SNP in IFN-gR is associated with allergic diseases and serum IgE level and the SNP might be potentially related to ICS response.

The outcome after severe bronchiolitis is related to gender and virus

The association between bronchiolitis in the first year of life and subsequent asthma, atopy, airway obstruction and bronchial hyper-responsiveness (BHR) is unsettled. Genetic predispositions, pre-morbid lung function, environmental interactions and altered immunological responses are risk factors that have been studied. The aim of this study was to assess lung function, BHR and the occurrence of asthma and atopy 11 yr after hospitalization for bronchiolitis in the first year of life, particularly focusing on the role of gender and virus involved. The study included 121 of 131 (92%) children hospitalized for bronchiolitis, 90 (74%) respiratory syncytial virus (RSV)-positive children and 141 children in an age-matched and unselected control group. At follow-up, current asthma was more common after RSV-negative bronchiolitis compared to controls (35.5% vs. 9.2%; p < 0.001), but not after RSV bronchiolitis (15.6%; p = 0.144). Higher BHR and an obstructive lung function pattern were observed after bronchiolitis, the latter most prominent after RSV-negative bronchiolitis. Higher BHR was confined to boys, but present in both the RSV-positive and RSV-negative groups (p = 0.007 and 0.003, respectively). Asthma after bronchiolitis was not associated with atopy. Atopy was similarly distributed between the RSV-positive and RSV-negative bronchiolitis groups and the control group. This study has shown that gender and type of virus are important factors to consider when addressing later development of asthma, BHR and lung function after hospitalization for bronchiolitis in early life.

Benzalkonium Chloride Induced Bronchoconstriction in Patients with Stable Bronchial Asthma

BackgroundAlthough benzalkonium chloride (BAC)-induced bronchoconstriction occurs in patients with bronchial asthma, BAC-containing nebulizer solutions are still being used in daily practice in Korea. The aim of this study was to evaluate the effects of inhaled aqueous solutions containing BAC.MethodsThirty subjects with bronchial asthma and 10 normal controls inhaled up to three 600 µg nebulized doses of BAC using a jet nebulizer. FEV1 (forced expiratory volume at one second) was measured 15 minutes after each dose. Inhalations were repeated every 20 minutes until FEV1 decreased by 15% or more (defined as BAC-induced bronchoconstriction) or the 3 doses were administered. ResultsThe percent fall in FEV1 in response to BAC inhalation was significantly higher in asthmatics than in normal subjects (p<0.05). BAC administration in subjects with asthma reached a plateau (maximal effect). BAC-induced bronchoconstriction was found in 6 asthmatics (20%), with two responders after the 2nd inhalation and after the 3rd inhalation. The percent fall in FEV1 in response to the 1st inhalation of BAC was significantly higher in asthmatics with higher bronchial hyperresponsiveness (BHR) than in those with lower BHR.ConclusionsThis study suggests that the available multi-dose nebulized solution is generally safe. However, significant bronchoconstriction can occur at a relatively low BAC dose in asthmatics with severe airway responsiveness.

Increasing prevalence of bronchial hyperresponsiveness in three selected areas in East Germany. Bitterfeld Study Group.

The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic rhinitis in children was lower in East Germany compared to West Germany. The reasons for this difference are still not understood. This study tested the hypothesis that prevalence of BHR increased in East German children after reunification. Two consecutive cross-sectional surveys of schoolchildren aged 8-14 yrs from three communities in East Germany were carried out in 1992-1993 and 1995-1996. A subsample of 530 and 790 children with complete lung function and cold air challenge data was analysed. The prevalence of BHR increased from 6.4%, in 1992-1993 to 11.6% in 1995-1996 (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.3-3.0, adjusted for age, sex, season, community and parental education). No changes were found for asthma, allergic rhinitis or allergic sensitization. In contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased significantly. The observed increase in the prevalence of BHR was reduced (OR: 1.5, 95% CI: 0.95-2.3) after adjustment for several indoor factors. In conclusion, while the prevalence of nonallergic respiratory diseases seems to decrease, the prevalence of bronchial hyperresponsiveness might be a first indicator of the suspected increase of asthma prevalence in East Germany. The present results give indirect evidence, that less respiratory infections may be associated with higher bronchial hyperresponsiveness.