Reversible Airway Obstruction Research Articles

Childhood Asthma Awareness in Saudi Arabia: Five-Year Follow-Up Study.

BackgroundBronchial asthma is a chronic inflammatory airway disease that is characterized by reversible airway obstruction due to bronchial hyperresponsiveness. It is one of the most common chronic diseases. In Saudi Arabia, asthma affects 2 million people with asthma frequency in children markedly higher than adults with regional variations ranging from 9% to 33.7%.ObjectiveThe aim of this study is to measure asthma awareness and knowledge of study participants during the ongoing annual Saudi asthma awareness campaigns and compare them with previous survey data conducted in 2014.MethodsA cross-sectional study was carried out in the form of a survey distributed across three major cities in Saudi Arabia, Jeddah, Riyadh and Dammam, during the National Asthma Awareness Campaign in major regional shopping centers in April 2019. Asthma knowledge scores across different demographic groups were generated from surveyed data. Descriptive and correlative statistical analyses were performed to identify factors associated with changes in asthma knowledge. Scores were compared to previous survey results.ResultsThe mean score for asthma knowledge was 15.6 out of 25. Asthma knowledge significantly correlated with age (P=0.002), asthma status of the participants (P=0.001), having children with asthma (P=0.005) or knowing friends or family with asthma (P=0.029) but not with other socioeconomic factors such as gender, marital status, occupation, level of education and number of children in the family (P > 0.05). There was a significant difference in the asthma scores from 2014 (M= 63%, SD=26) to 2019 (M= 70%, SD= 26) conditions; t (24) = −2.106, p=0.046.ConclusionFurther educational campaigns are necessary to enhance and measure general public awareness of asthma, its differential diagnosis against other respiratory infections, environmental triggers, risk factors as well as treatment options.

Respiratory functional phenotypes of severe asthma in cohort of 130 patients

Asthma is a heterogeneous disease divided into clusters that do not consider the type of respiratory functional impairment. The objective was to investigate the association between respiratory functional impairment and main asthma phenotypes. We conducted a retrospective, observational, monocentric study including patients with severe asthma who first consulted at Croix Rousse Hospital, Hospices Civils de Lyon, between January 2015 and June 2018. Patients were divided into 4 respiratory functional groups: reversible proximal airway obstruction (Group 1); fixed proximal airway obstruction (Group 2); exclusive small airway involvement (Group 3); no functional impairment (Group 4). The distribution of these 4 functional groups was analyzed within the main clinical and biological phenotypes of severe asthma: TH2 high allergic, TH2 high eosinophil, mixed TH2 allergic/eosinophil, hypersensitivity to aspirin, and TH2 low. Among 130 patients, 28 patients were included in group 1 (22%), 51 patients in group 2 (39%), 27 patients in group 3 (21%), and 24 patients in group 4 (18%). The distribution of clinical phenotypes was significantly different between the groups (p=0.004). TH2 high eosinophil phenotype patients were higher in groups 1 and 2, compared to other phenotypes (p=0.014), and TH2 allergic phenotype patients were higher in groups 3 and 4, compared to other phenotypes (p=0.0003). Other phenotypes of severe asthma were not associated with a respiratory functional signature. We found heterogenous pulmonary functional impairment in severe asthma. Some functional characteristics are associated to allergic and eosinophilic phenotypes. More studies are needed to determine prognostic or therapeutic value of the functional impairment.

A Study on Serum Immunoglooubin E levels as a marker in childhood asthma

Background: Asthma is a chronic inflammatory of the lungs which causes bronchial hyperresponsiveness and reversible airway obstruction. The disease predominantly affects the children. Bronchial asthma is manifested in response to external trigger of allergens. The most important risk factor is atopy, which produces high amount of IgE, the aim of this study is to evaluate serum IgE levels as a marker for the disease activity and study the correlation with the severity of bronchial asthma. Methods: A prospective study was conducted in peadiatrics department of the tertiary care hospital from March 2019 to February 2019. Children between 6-12yrs admitted with clinical features of asthma as per GINA guidelines was included in the study. IgE levels were taken at the time of the initial presentation. Results: The study showed that all the participants 100% who presented with clinical features suggestive of asthma had high IgE levels irrespective of age, sex and severity of asthma. The mean IgE levels in females were more than males. As the severity of asthma increased the mean IgE levels also increased. Conclusion: The study conclude that the IgE levels are independent of age and sex. IgE levels are directly proportional to severity of asthma.

TNFSF14 (LIGHT) Induces Airway Smooth Muscle Contraction

Abstract Asthma is a chronic inflammatory disorder characterized by reversible airway obstruction and airway hyperresponsiveness (AHR). The precise mechanism responsible for AHR is not known but it may involve excess mucus production and alterations in airway smooth muscle cell (SMC) activity. SMC from asthmatic patients are thought to generate more force and contract to a greater extent to allergens or certain inflammatory stimuli, but which inflammatory stimuli in asthmatics drive contraction is still not clear. Previously, we showed that the tumor necrosis factor superfamily member LIGHT (TNFSF14) promotes airway remodeling and AHR in mouse models of chronic asthma, despite having little effect on airway eosinophilia. Exogenous administration of rLIGHT to the mouse airways also induced smooth muscle hyperplasia. We found that LTβR and HVEM, the receptors for LIGHT, are expressed on both human and mouse SMC from the lungs, with LTbR primarily expressed on human cells, suggesting a direct effect of this T cell-derived cytokine. From studies in vitro with primary human SMC, we found that rLIGHT administration induced contraction of SMC in collagen-gels in 3D structures, and migration of SMC in monolayers. rLIGHT induced both actin polymerization and phosphorylation of myosin light chain which leads to actomyosin formation to induce contraction. rLIGHT promoted both canonical and non-canonical NF-kB in airway SMC, and these signals activated the small GTPase Rac1 and P21-Activated Kinase 1 (PAK1) which are involved in actin rearrangement and myosin light chain kinase activity. These results reveal direct evidence that LIGHT can drive SMC contraction and may directly regulate airway hyperresponsiveness relevant to asthma pathogenesis.

Infant respiratory syncytial virus prophylaxis and nasopharyngeal microbiota until 6 years of life: a subanalysis of the MAKI randomised controlled trial

Respiratory syncytial virus (RSV) infection during infancy is suggested to cause long-term wheeze. In turn, wheeze has been associated with bacterial dysbiosis of the respiratory tract. We investigated the effects of RSV prophylaxis with palivizumab in otherwise healthy preterm infants on respiratory microbiota composition at 1 year and 6 years of age. In a multicentre, single-blind, randomised, placebo-controlled trial (the MAKI trial), infants born between 32-35 weeks of gestation, in one university and in 15 regional hospitals in the the Netherlands, were randomly assigned (1:1) to receive palivizumab or placebo during the RSV season of their first year of life. Intramuscular injections of palivizumab 15 mg/kg or placebo were given during one RSV season: either from Oct 1, or from discharge from the neonatal unit until March 10 (minimun of 2 and maximum of 5 injections were given). Children were 6 months old or younger at the start of the RSV season; exclusion criteria included congenital heart disease, bronchopulmonary dysplasia, Down's syndrome, or other serious congenital disorders, use of mechanical ventilation at birth, treatment with surfactant, or physician-diagnosed wheeze before the start of the RSV season. Children were followed up for clinical symptoms until 6 years of age. For this subanalysis, we obtained nasopharyngeal swabs from children aged 1 year and 6 years and analysed them using 16S-rRNA sequencing. At 6 years we also measured reversible airway obstruction. The primary outcome was the effect of palivizumab during infancy on the respiratory microbiota composition at age 1 year and 6 years (intention-to-treat analysis). The trial is registered in the ISRCTN registry, number ISRCTN73641710. From April 1, 2008, to Dec 31, 2010, 429 infants were enrolled in the MAKI trial (n=214 to the palivizumab group; n=215 to the placebo group). At 1 year, we collected swabs and sequenced DNA from 170 (40%) of 429 children, of which 145 (85%) samples had high-quality DNA. The overall microbiota composition was significantly different (R2 1·3%; p=0·0185) between the palivizumab group and the placebo group at 1 year of life; children in the palivizumab group had a significantly lower abundance of the Staphylococcus-dominated cluster (odds ratio 0·28 [95% CI 0·11-0·68]; p=0·00394), an increased abundance of biomarker species, such as Klebsiella, and a more diverse set of oral taxa, including Streptococcus spp, compared with children in the placebo group. At 6 years, we collected swabs and sequenced DNA from 349 (88%) of 395 children who completed follow-up, of which 342 (98%) samples had high-quality DNA. The overall microbiota composition was not significantly different between groups at 6 years (R2 0·6%; p=0·0575); however, children in the palivizumab group had a significantly increased abundance of Haemophilus spp and lower abundance of Moraxella and Neisseriaceae spp compared with children in the placebo group. Absence of PCR-confirmed RSV infection at 1 year was significantly associated with a higher abundance of Haemophilus spp at age 6 years and a significantly lower abundance of Moraxella and Neisseriaceae than children with RSV infection at 1 year. Reversible airway obstruction at 6 years was also positively associated with Haemophilus abundance and negatively associated with the abundance of health-associated taxa, such as Moraxella, Corynebacterium, Dolosigranulum, and Staphylococcus, even after correction for RSV immunoprophylaxis (all: p<0·05). Additionally, reversible airway instruction was associated with significantly higher Streptococcus pneumoniae abundance. Palivizumab in infancy in otherwise healthy preterm infants is associated with persistent effects on the abundance of specific, potentially pathogenic, microbial taxa in the respiratory tract. Several of the palivizumab-associated biomarker species were associated with reversible airway obstruction at age 6 years. These results warrant further studies to establish the long-term ecological effects and health consequences of palivizumab in infancy. MedImmune.

Assessment of levels of asthma control among adult patients with asthma at Chitungwiza Central Hospital, Zimbabwe

BackgroundThe management of the reversible airways obstruction forms the cornerstone of quality asthma management. The aim of this study was to assess the level of control for asthma in adult patients, using a cross sectional study design. The assessment of control for asthma was based on the ACQ.MethodsWe conducted a cross-sectional study to measure the level of control for asthma among patients with asthma who volunteered and were reporting to Chitungwiza Central Hospital. We interviewed and conducted spirometry (lung function testing) on 400 adult patients with asthma. We used the ACQ questions to interview patients. A trained health care provider performed spirometry using the Koko Legend spirometer after meeting all the ambient conditions as outlined in the American Thoracic Society guidelines.ResultsOur study assessed levels of asthma control among 400 adult patients with physician-diagnosed asthma. The results showed that 248 (62%) participants had uncontrolled asthma. The median age of the adult patients who had uncontrolled asthma was 35 years (IQR: 27–44). Using the clinical practice cut-point of 0.75 for controlled asthma, only 152 (38%) were controlled, while 72 (18.8%), 50 (12.5%) and 123 (30.7%) were mildly uncontrolled, moderately uncontrolled and very uncontrolled respectively. Among participants who were widowed had uncontrolled asthma (p = 0.003) while most of the married 103 (67.8%) had controlled asthma (p = 0.018). The findings of the study showed that all the items on the ACQ were significantly different in asthma mean scores (p ≤ 0.0001).ConclusionWe concluded that most asthma patients that participated in the study were uncontrolled. We therefore, recommend an evaluation of factors associated with poor asthma control in order to improve asthma care and achieve good asthma control outcomes.

Inhaled Corticosteroids Prescribed for COPD Patients with Mild or Moderate Airflow Limitation: Who Warrants a Trial of Withdrawal?

COPD patients prescribed inhaled corticosteroids (ICS) outside guidelines should be targeted for ICS withdrawal. Within a primary care population of 209,618 we used a combination of digital search algorithm, individual record review, and clinical review to identify COPD patients suitable for a trial of ICS withdrawal. At most, 39% of COPD patients with mild or moderate airflow limitation prescribed ICS were suitable for withdrawal according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Recurrent exacerbations and reversible airway obstruction were the main reasons for patients’ unsuitability for withdrawal. Identifying COPD patients in whom ICS withdrawal should be considered presents a challenge to primary care clinicians.

Association between chronic arsenic exposure and the characteristic features of asthma.

Widespread contamination of arsenic (As) has become a global public health concern. Exposure to As causes respiratory complications. Asthma, a major respiratory complication, is increasing worldwide. However, the effect of chronic As exposure on the risk of asthma remains to be clarified. This study aims to examine the associations between As exposure (water, hair and nail As) and the risk of asthma among 842 individuals exposed to a wide range of As concentrations through drinking water in Bangladesh. Subjects' As exposure levels were measured with ICP-MS. Lung function was examined by a handheld spirometer. Characteristic features of asthma were evaluated by bronchodilator-mediated reversibility in airway obstruction and asthma-like symptoms through a structured questionnaire. Total serum immunoglobulin E (sIgE) levels were measured by immunoassay. As exposure metrics showed inverse associations with lung function measures (FEV1, FEV6, and FEV1/FEV6 ratio) and positive associations with the risks of airway obstruction (AO), reversible airway obstruction (RAO), and asthma-like symptoms. The majority of AO patients (70 of 97) were RAO with one or more characteristic symptoms of asthma. Intriguingly, subjects' As exposure levels showed positive associations with total sIgE levels. Total sIgE in RAO patients was significantly (p<0.001) higher than that in the control group. Thus the results revealed that chronic As exposure was associated with the risk of the characteristic features of asthma. Additionally the association between As exposure and subjects' total sIgE levels and an elevated level of total sIgE in RAO group suggested that As exposure-related asthma might be allergic in nature.

Plasma based targeted metabolomic analysis reveals alterations of phosphatidylcholines and oxidative stress markers in guinea pig model of allergic asthma

Bronchial asthma is one of the most common, chronic respiratory diseases, characterized by reversible airway obstruction, eosinophil and Th2 infiltration, airway hyperresponsiveness and airway remodelling; with many cells and mediators involved. Metabolomics is a relatively new field in “omics” sciences enabling the identification of metabolome for better diagnostics and studying of diseases phenotype.The aim of this study was to investigate the role of targeted metabolomics study for better understanding of the bronchial asthma pathophysiology and finding potential biomarkers in experimental models of eosinophilic inflammation.Plasma level of 185 metabolites was measured with the AbsoluteIDQ™ p180 kit in guinea pigs with experimentally-induced allergic inflammation (n = 15) compared to naïve non-sensitised and non-challenged controls (n = 18).Of the 185 metabolites identified in plasma, 22 were significantly different and changed in ovalbumin sensitised animals. Plasma level of 13 phosphatidylcholines with saturated and unsaturated long-chain fatty acids, total phosphatidylcholines count, carnitine, symmetric dimethylarginine and its ratio to total unmodified arginine, and kynurenine to tryptophan ratio were found to be decreased, while phospholipase A2 activity indicator, tryptophan, taurine and ratio of methionine sulfoxide to unmodified methionine were found to be increased in sensitised guinea pigs compared to naïve controls.Targeted metabolomic analysis revealed significant differences in plasma metabolome of sensitised guinea pigs. Our observations point to the activation of inflammatory and immune pathways, as well as the involvement of oxidative stress.

Relationship between Blood and Induced Sputum Eosinophils, Bronchial Hyperresponsiveness and Reversibility of Airway Obstruction in Mild-to-Moderate Chronic Obstructive Pulmonary Disease

Blood eosinophilia has been proposed as a surrogate marker for airway eosinophilia and as a predictor of treatment response in chronic obstructive pulmonary disease (COPD). The aim of the study was to assess the relationship between blood and sputum eosinophils and to investigate the association between blood and sputum eosinophil count and clinical features of mild-to-moderate COPD. We performed a retrospective analysis of blood and sputum eosinophil count, as well as demographic and lung function data in a cohort of 90 stable, steroid-naive (Global Initiative for Chronic Obstructive Lung Disease 1 or 2) COPD patients and 20 control subjects. Blood and sputum eosinophil count did not correlate both in patients with COPD (r = –0.04 p = 0.705) and in controls (r = 0.05, p = 0.838). Sputum eosinophilia (≥3%) was present in 40% of COPD patients. The median blood eosinophil count in patients with COPD was 180 (interquartile range 90–270)/μL; patients with low blood eosinophils (<180/μL) did not differ from those with high blood eosinophils (≥180/μL) in terms of forced expiratory volume in 1 second, bronchial reversibility or hyperresponsiveness. This was also the case when COPD patients with and without sputum eosinophilia were compared. At the same time, positive bronchial reversibility and positive bronchial hyperresponsiveness were observed in 2 (11%) COPD patients with high blood eosinophils and in 1 (5%) patient with sputum eosinophilia. There was a weak, albeit significant correlation (r = 0.22 p = 0.041) between blood eosinophil count and age in patients with COPD. Peripheral eosinophil count poorly reflects sputum eosinophils and lung function in stable steroid-naive mild-to-moderate COPD patients.

Virus-Induced Asthma/Wheeze in Preschool Children: Longitudinal Assessment of Airflow Limitation Using Impulse Oscillometry.

Several researchers have assessed the utility of Impulse Oscillometry System (IOS) in diagnosing and evaluating the severity of respiratory diseases in childhood, but none has investigated the impact of the fluctuations of IOS parameters in an individualized manner. In this two-year prospective study, we aimed to longitudinally evaluate changes in airflow limitation and bronchodilator responsiveness in steroid-naïve four- to six-year-old children during a virus-induced wheezing episode, with IOS pulmonary resistance parameters set at 5 (R5) and 20 (R20) Hz. Moreover, feasibility and reproducibility, in addition to the diagnostic properties of these parameters were examined. Lung function was assessed every six weeks (baseline), within the first 48 h following an acute wheezing episode (Day 0), after 10, and after 30 days. Forty-three out of 93 recruited children (4.5 ± 0.4 years old) experienced a wheezing episode during the study period. All children were able to perform the IOS effort in an acceptable and highly reproducible manner. R5 and R20 fluctuated independently of atopy, age, height, and weight. On Day 0, R5 values were significantly lower than the respective baseline values and returned to individual baseline levels within 10 days. Post-bronchodilation R5 values were similar to the baseline ones, reflecting a reversible airway obstruction on Day 0. Response to bronchodilation (ΔR5) was significantly more pronounced on Day 0. ΔR5 values lower than −20.5% had a sensitivity of 70% and a specificity of 76% and could accurately identify up to 75% of the examined preschoolers. This study provides evidence in favor of the objective utility of IOS as an easy, highly reproducible, and sensitive technique to assess clinically significant fluctuations and bronchodilation responses suggestive of airflow limitation. Reference values although necessary are suboptimal, utilizing the personal best values as personal reference is useful and reliable.

Ciprofibrate attenuates airway remodeling in cigarette smoke-exposed rats

Airway remodeling is a key pathological lesion in chronic obstructive pulmonary disease (COPD), and it leads to poorly reversible airway obstruction. Current pharmacological interventions are ineffective at controlling airway remodeling. To address this issue, we queried the Connectivity Map (cMap) database to screen for drug candidates that had the potential to dilate the bronchus and inhibit airway smooth muscle (ASM) proliferation. We identified ciprofibrate as a drug candidate. Ciprofibrate inhibited cigarette smoke extract-induced rat ASM cell contraction and proliferation in vitro. We exposed Sprague-Dawley (SD) rats to clean air or cigarette smoke (CS) and treated the rats with ciprofibrate. Ciprofibrate improved pulmonary function, inhibited airway hypercontraction, and ameliorated morphological small airway remodeling, including airway smooth muscle proliferation, in CS-exposed rats. Ciprofibrate also significantly reduced IL-1β, IL-12p70, IL-17A and IL-18 expression, which are related to airway remodeling, in the sera of CS-exposed rats. These findings indicate that ciprofibrate could attenuate airway remodeling in CS-exposed rats.

A clinical study to determine the threshold of bronchodilator response for diagnosing asthma in Chinese children

BackgroundThere is few objective, clinically feasible and inexpensive test for diagnosing childhood asthma. We want to find an ideal way to solve it.MethodsThe control group was 301 non-asthmatic children, and the asthma group was 286 asthmatic children. The asthmatic children were divided into three groups according to the severity of their disease. Pre- and post-bronchodilator spirometer tests were performed, and the main spirometer parameters were compared. The bronchodilator response (BDR) [BDR is used to determine the reversibility of airway obstruction by measuring the changes of forced expiratory volume in the first second (FEV1) before and after inhalation of bronchodilators] was then determined, and the optimal threshold of BDR for diagnosing childhood asthma was found.Results301 non-asthmatic children and 286 asthmatic children participated in the study, the demographics were similar. FEV1 for pre-bronchodilator of asthmatic children was significantly lower than that of non-asthmatic children (P ≤ 0.01). BDR of non-asthmatic children was 3.30 ± 3.85%. BDR of asthmatic children was 9.45 ± 9.15%. There was no significant difference in BDR for patients with different severities of asthma within the group. BDR had no statistical correlation with gender, age, height, weight in neither non-asthmatic children nor asthmatic children. On the receiver-operating characteristic curve, a BDR threshold of ≥ 7.5% offered an optimal balance in asthma diagnosis with a sensitivity rate of 50.7% and specificity rate of 87.7%. Meanwhile, with a BDR threshold of ≥ 12%, the sensitivity rate was 28.7% and the specificity rate was 96.3%.ConclusionA BDR threshold of ≥ 7.5% has more value in childhood asthma diagnosis as compared to ≥ 12%.

Cross-sectional study of reversible airway obstruction in LAM: better evidence is needed for bronchodilator and inhaled steroid use

Lymphangioleiomyomatosis can be associated with reversible airflow obstruction and although no guidelines around reversibility testing or inhaled therapy exist, many patients receive bronchodilators and inhaled corticosteroids. To better identify those...

Effect of various topical anti glaucoma drugs on cardiopulmonary system. A prospective study

Purpose: To quantitatively evaluate the cardiopulmonary effects of various topical antiglaucoma drugs. Material & method: In this study, forty consecutive cases of newly diagnosed primary open angle glaucoma were recruited. After taking a detailed history, an ophthalmological examination and a systemic examination including resting pulse rate, blood pressure, ECG, auscultation of the chest and spirometry were performed. Then the patients were randomly divided into four groups and one of the four topical anti glaucoma medication (Timolol, Latanoprost, Brimonidine, and Dorzolamide) prescribed. Patients were reviewed 4 weeks later and the same ocular and systemic examinations were performed. Result: Timolol therapy reduced all the spirometry parameters that are statistically significant difference with the P value of less than 0.1. Timolol therapy resulted in the mean reduction of pulse rate by 3.2 beats/ minute and a mean reduction of systolic and diastolic blood pressure by 5.8 mmHg and 5.6 mmHg, respectively all the spirometry & cardiovascular parameters remained unchanged in the other three groups after 4 weeks of treatment. Conclusion: Timolol significantly affects the cardiopulmonary status. Therefore, we could advice the assessment of cardiopulmonary status mandatory in patients receiving topical beta-blockers. Bronchospasm may be of clinical significance in the elderly, who commonly have undiagnosed reversible airway obstruction.

Potential Mechanisms of T Cell-Mediated and Eosinophil-Independent Bronchial Hyperresponsiveness.

Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of patients with bronchial asthma, recent studies suggest the possible development of Th2-independent airway inflammation and BHR. These non-Th2 endotype patients seem to consist of multiple subgroups, and often do not respond to inhaled corticosteroids. Therefore, to understand the pathogenesis of asthma, it is important to characterize these non-Th2 subgroups. Recently, we demonstrated that Th9 cells induce eosinophil infiltration and eosinophil-independent BHR, and Th9 cells-mediated BHR may be resistant to glucocorticoid. In this review, we summarize the contribution of several T cell subsets in the development of bronchial asthma and introduce our recent study demonstrating Th9 cell-mediated and eosinophil-independent BHR.

Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation.

Background: Pasture-associated severe equine asthma is a warm season, environmentally-induced respiratory disease characterized by reversible airway obstruction, persistent and non-specific airway hyper-responsiveness, and chronic neutrophilic airway inflammation. During seasonal exacerbation, signs vary from mild to life-threatening episodes of wheezing, coughing, and chronic debilitating labored breathing.Purpose: In human asthma, neutrophilic airway inflammation is associated with more severe and steroid-refractory asthma phenotypes, highlighting a need to decipher the mechanistic basis of this disease characteristic. We hypothesize that the collective biological activities of proteins in bronchoalveolar lavage fluid (BALF) of horses with pasture-associated severe asthma predict changes in neutrophil functions that contribute to airway neutrophilic inflammation.Methods: Using shotgun proteomics, we identified 1,003 unique proteins in cell-free BALF from six horses experiencing asthma exacerbation and six control herdmates. Contributions of each protein to ten neutrophil functions were modeled using manual biocuration to determine each protein’s net effect on the respective neutrophil functions.Results: A total of 417 proteins were unique to asthmatic horses, 472 proteins were unique to control horses (p<0.05), and 114 proteins were common in both groups. Proteins whose biological activities are responsible for increasing neutrophil migration, chemotaxis, cell spreading, transmigration, and infiltration, which would collectively bring neutrophils to airways, were over-represented in the BALF of asthmatic relative to control horses. By contrast, proteins whose biological activities support neutrophil activation, adhesion, phagocytosis, respiratory burst, and apoptosis, which would collectively shorten neutrophil lifespan, were under-represented in BALF of asthmatic relative to control horses. Interaction networks generated using Ingenuity® Pathways Analysis further support the results of our biocuration.Conclusion: Congruent with our hypothesis, the collective biological functions represented in differentially expressed proteins of BALF from horses with pasture-associated severe asthma support neutrophilic airway inflammation. This illustrates the utility of systems modeling to organize functional genomics data in a manner that characterizes complex molecular events associated with clinically relevant disease.

COPD patients with peripheral airway obstruction reversibility identified by exhaled nitric oxide

Rationale: Besides its role as an inflammatory marker in asthma, fractional exhaled nitric oxide (FENO) provides information on the extent of the airway obstruction process through evaluating its change after bronchodilation. Objective: To investigate whether FENO change after bronchodilation can identify different sites of airway obstruction in COPD patients. Methods: FENO, FEV1 and the slopes (S) of the alveolar plateau of the single breath washout test (SBWT) were measured in 61 stable COPD patients (FEV1 34.5% predicted) before and after the inhalation of 400 μg salbutamol. SBWT used Helium (He), and sulfur-hexafluoride (SF6). Obstruction relief occurring in pre-acinar and intra-acinar small airways is expected to decrease SHe and SSF6, respectively. Indices changes (Δ) after bronchodilation were expressed as a percentage of pre-bronchodilation values. Results: FENO stability (∣ΔFENO∣ ≤ 11%) was observed in 19 patients [−2.7(6.7)%] [mean (SD)] (NO = group); ΔFENO > 11% [+37.4(27.7)%] in 20 patients (NO+ group) and ΔFENO < −11% in 22 patients [−31.2(9.8)%] (NO− group). A similar ΔFEV1 (p = 0.583; [+9.4(9.6)%]) was found in the three groups. In NO = and NO+ groups, neither SHe nor SSF6 changed; in NO− both SHe [−12.4(27.5)%, p = 0.007] and SSF6 [−20.2(20.4)%, p < 0.001] significantly decreased. Conclusion: Different patterns of FENO response to β2-agonists were observed in COPD most likely depending on the extent of the dilation process. A profile of airway obstruction with an extensive β2-agonist response down to lung periphery is identified by FENO reduction after acute bronchodilation in 30% of COPD patients. The clinical relevance of this profile requires further investigation.

Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study.

Background:Omalizumab may modulate airway remodeling in severe asthma. Using forced expiratory volume in 1 second (FEV1) as a surrogate of airway remodeling, we aimed to investigate if an omalizumab add-on in severe allergic asthma may lead to a persistent reversal of airway obstruction and to evaluate the potential biomarkers of airway obstruction reversibility.Methods:Data were collected before (T0) and after omalizumab add-on for 1 year (T1, 32 patients), 2 years (T2, 26 patients) and 4 years (T4, 13 patients). All patients had baseline FEV1 below 80 % predicted (60.5 ± 12.5 %). After omalizumab, 18 patients showed FEV1 normalization (reversible airway obstruction; RAO+) already at T1 (88.7 ± 14.9 %, p < 0.0001) that persisted up to T4 (83.2 ± 7.9, p < 0.01), while 14 patients (RAO−) had FEV1 persistently decreased, from T1 (65.2 ± 8.4%, p < 0.05) up to T4 (61.4 ± 6.2%, not significant). Both groups had significant improvement of symptoms and exacerbations after omalizumab at T1, which persisted up to T4. The comparison between pretreatment characteristics of the two groups showed that RAO+ patients, had higher values of circulating eosinophils, exhaled nitric oxide (FENO), prevalence of rhinitis and nasal polyps, need of oral corticosteroids, shorter asthma duration, higher FEV1 and response to albuterol test. The optimal cut-off points predicting FEV1 normalization after omalizumab add-on were 30.5 ppb for FENO and 305 cells/µl for eosinophils.Conclusions:This study suggests that omalizumab add-on contributes to the persistent reversal of airway obstruction in a consistent number of patients with severe allergic asthma, and this beneficial effect is predicted by elevated pretreatment FENO and circulating eosinophils.

Determining the optimal time to assess the reversibility of airway obstruction.

Context:The optimal time to interpret bronchodilator reversibility remains controversial. This time may affect a positive diagnosis and manage asthma and chronic obstructive pulmonary disease (COPD).Aims:We sought to document the time when maximum respiratory function is reached after inhalation of salbutamol and to define the optimal time of bronchodilator response to assess the reversibility or non reversibility of airway obstruction.Subjects and Methods:This prospective analytical study was spread over 8 months and included 58 patients with asthma or COPD with airway obstruction. Spirometry was performed before and at 5, 10, 15, 20, and 30 min after salbutamol inhalation (200 mcg) administered through pressurized metered-dose inhalers and large volume spacer.Results:After salbutamol inhalation, the mean individual peak bronchodilation occurred at 20 min for the forced vital capacity and at 30 min for the forced expiratory volume in 1 s. The percentage of reversible patients in our sample was guideline dependent. It increased from 53% to 67.2% when using the American Thoracic Society/European Respiratory Society definition compared to using the Global Initiative for Chronic Obstructive Lung Disease. The maximum number of reversible patients was significantly different at 20 min compared to 5 and 10 min.Conclusions:Interpreting bronchodilator reversibility after 20 min was the ideal time to judge the reversibility or nonreversibility in obstructive ventilatory disorders in adults.