Airway Disease Asthma Research Articles

Improving asthma outcomes: Clinicians’ perspectives on peripheral airways

Disease of the peripheral (or small) airways is fundamental in asthma, being closely related to symptoms (or lack of control them), airway hyperresponsiveness, spirometric abnormalities, risk of loss of control or exacerbations and inflammation. Current technology now allows routine measurement of peripheral airway function. Having a working concept of peripheral airways disease in asthma is arguably, very useful to clinicians and beneficial to patients because it allows a more comprehensive assessment of asthma severity (rather than just symptoms alone which is the norm), tracking of progress or deterioration and assessing response to treatment. Oscillometry is a sensitive way to monitor the peripheral airways, while multiple breath nitrogen washout parameters are excellent measures of future risk. In the longer term, physiologic measurements will be crucial in research to define causes and find new, disease modifying treatments.

Silent zone detection in asthma and its relation to T2 inflammation

Abstract Objective Study objectives are to detect small airways disease in asthma and to study T2 inflammatory markers (eosinophil count, IgE, phenotyping) in association with small airways disease. Methods and patients The retrospective study at OPC at Al Qassimi Hospital of EHS included 83 patients with confirmed asthma diagnosis. Based on their ACT scores, patients were divided into two groups. An assessment of demographic data, blood eosinophils, fractional exhaled nitric oxide, IgE, PFE25-75, FEV1%, R5-20, X5 and AX was carried out. Analyzing and collecting data. Results In this study, a significant correlation was found between the R5-20, X5, and AX values of the small airway and the asthma control test. Uncontrolled asthmatics had a higher fractional exhaled nitric oxide level and blood eosinophilic count. Conclusion In asthma management, small airways clinical impact should be investigated actively. Impulse oscillometry is an excellent marker for asthma control.

Small airways in asthma: Pathophysiology, identification and management.

The aim of this review is to summarize the current evidence regarding small airway disease in asthma, focusing on recent advances in small airway pathophysiology, assessment and therapeutic implications. A search in Medline was performed, using the keywords "small airways", "asthma", "oscillometry", "nitrogen washout" and "imaging". Our review was based on studies from adult asthmatic patients, although evidence from pediatric populations is also discussed. In asthma, inflammation in small airways, increased mucus production and airway wall remodelling are the main pathogenetic mechanisms of small airway disease. Small airway dysfunction is a key component of asthma pathophysiology, leading to increased small airway resistance and airway closure, with subsequent ventilation inhomogeneities, hyperresponsiveness and airflow limitation. Classic tests of lung function, such as spirometry and body plethysmography are insensitive to detect small airway disease, providing only indirect measurements. As discussed in our review, both functional and imaging techniques that are more specific for small airways, such as oscillometry and the multiple breath nitrogen washout have delineated the role of small airways in asthma. Small airways disease is prevalent across all asthma disease stages and especially in severe disease, correlating with important clinical outcomes, such as asthma control and exacerbation frequency. Moreover, markers of small airways dysfunction have been used to guide asthma treatment and monitor response to therapy. Assessment of small airway disease provides unique information for asthma diagnosis and monitoring, with potential therapeutic implications.

The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study

Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life. In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed. 773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0·20-0·25, p<0·0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life. Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations. Chiesi Farmaceutici.

Current Needs Assessment for Using Lung Clearance Index for Asthma in Clinical Practice.

Asthma pathophysiology has shown that remodeling of the bronchial airways mainly affects the small rather than large airways. The severity of asthma is conventionally measured by forced expiratory volume 1 (FEV1) but this maneuver is insensitive to changes in distal airways with smaller diameter. The aim of this review is to evaluate the current evidence supporting LCI as a clinical tool for assessing small airways disease in asthma patients, as well as whether it is useful as a treatment response parameter in severe therapy-resistant asthma (STRA) patients. There is an increasing need for novel tests that can assess distal airway disease in asthma. Lung Clearance Index (LCI) may be a useful test for assessing more severe airway obstruction and the persistence of small airway disease. LCI measurement has been shown to be more sensitive than spirometry in cystic fibrosis (CF), but its clinical utility in asthma has not been thoroughly investigated. LCI abnormalities may be a sensitive marker for the persistence of small distal airway disease and may be associated with a more severe asthma endotype unresponsive to inhaled glucocorticoids. There is a need to identify other lung function tests for asthma that can identify early airway remodeling while simultaneously measuring the rate of lung function impairment. When compared to other conventional methods, multiple-breath washout (MBW) measures the lung clearance index (LCI), a more sensitive predictor of early airway disease that is feasible to perform in children. The goal of this review is to evaluate the current evidence of LCI as a clinical tool in asthma patients.

Asthma-COPD-Overlap – diagnostisches und therapeutisches Management

Asthma-COPD Overlap (ACO) is a fuzzy and controversial term intended to characterize patients who have characteristics of asthma and COPD. Since there is no uniform definition, the information on prevalence varies considerably. There is no special diagnostic algorithm and no clear therapy recommendations, as ACO is underrepresented in therapeutic studies. The current clinical consequence of this dilemma should be to differentiate the leading obstructive airway disease asthma or COPD and to treat the predominant phenotype.

Breathomics and treatable traits for chronic airway diseases.

The long-term management goals of the inflammatory airway diseases asthma and chronic obstructive pulmonary disease (COPD) are similar and focus on symptom control and reduction of exacerbation frequency and severity. Treatable traits have recently been postulated as a management concept which complements the traditional diagnostic labels 'asthma' and 'COPD', thereby focusing on therapy targeted to a patients' individual disease-associated characteristics. Exhaled volatile organic compounds (VOCs) may be utilized as noninvasive biomarker for disease activity or manifestation in asthma and COPD. In this review, we provide an overview of the current achievements concerning exhaled breath analysis in the field of uncontrolled chronic airways diseases. Monitoring of (airway) inflammation and identification of (molecular) phenotypic characteristics in asthma and COPD through exhaled VOC analysis by either mass spectrometry (MS) based or sensor-driven electronic nose technology (eNose) seems to be feasible, however pending confirmation could hamper the valorization of breathomics into clinical tests. Exhaled VOC analysis and the management of asthma and COPD through the concept of pulmonary treatable traits are an interesting match. To develop exhaled breath analysis into an added value for pulmonary treatable traits, multicentre studies are required following international standards for study populations, sampling methods and analytical strategies enabling external validation.

Effect of intranasal corticosteroids on allergic airway disease in asthma

Effect of intranasal corticosteroids on allergic airway disease in asthma

Small airway disease in asthma: a new target for better asthma control?

Small airway disease in asthma: a new target for better asthma control?

Small airway disease in asthma: pathophysiological and diagnostic considerations.

The aim of the current review is to summarize the evidence of small airway abnormalities in asthma, the proposed diagnostic tools for small airway abnormalities and the clinical implications of small airway abnormalities in asthma. Pathological abnormalities in the peripheral membranous bronchioles less than 2 mm in diameter (i.e. small airways) can be very frequently detected in asthma patients across severity: from mild to the more severe clinical manifestations of the disease. Interestingly, not only are small airway abnormalities present in asthma, but there is evidence that the magnitude of small airway abnormalities correlates with the severity of the disease. So far no unanimously accepted method and/or algorithm is available for small airway abnormality detection; however, some functional techniques and inflammatory markers have been used as surrogates of small airway dysfunction. Clinicians, and not only researchers, must consider small airways when approaching asthma patients, particularly when dealing with patients with a 'difficult-to-treat phenotype'. The identification of subgroups of asthma patients with prominent small airway disease is not merely speculative, and carries pathophysiological and therapeutic implications.

Clinical application of inert gas Multiple Breath Washout in children and adolescents with asthma

Children with asthma often have normal spirometry despite significant disease. The pathology of the small airways in asthma may be assessed using Multiple Breath Washout (MBW) and calculating the Lung Clearance Index (LCI). There are only few studies using MBW in children with asthma and existing data regarding bronchodilator effect are contradictory. The aim of the present pilot study was to compare LCI in asthma and controls and assess the effect of salbutamol in children with asthma on the LCI. Unselected patients with a diagnosis of asthma visiting the outpatient department of our hospital between 04-2010 and 03-2011 were recruited and compared to a healthy control group. MBW was performed as inert gas MBW using sulfurhexafluorid (SF6) as the tracer gas. Clinical data were documented and spirometry and MBW (EasyOne Pro, MBW module, NDD Switzerland) were performed before and after the use of salbutamol (200-400μg). Healthy controls performed baseline MBW only. 32 children diagnosed with asthma (4.7-17.4 years) and 42 controls (5.3-20.8) were included in the analysis. LCI differed between patients and controls, with a mean LCI (SD) of 6.48 (0.48) and 6.21 (0.38) (P=0.008). Use of salbutamol had no significant effect on LCI for the group. These pilot data show that clinically stable asthma patients and controls both have a LCI in the normal range. However, in patients the LCI is significantly higher indicating that MBW may have a role in assessing small airways disease in asthma.

Airway surface mycosis in chronic TH2-associated airway disease

Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with TH2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients.

The role of small airway disease in asthma

This review provides an update on the importance of the peripheral 'small' airways in asthma. As the small airways account for less than 10% of total airway resistance, thus having little impact on standard lung function measures such as forced expiratory volume and peak flow, they have been referred to as the 'silent zone'. The study has revealed that small airway involvement is present in all stages of asthmatic disease, being related to important clinical phenotypes such as nocturnal asthma, exercise-induced asthma, and difficult-to-control asthma, including those with the risk of repeated asthma exacerbations. Uncontrolled small airway inflammation is related to airway remodeling and progression of the disease, with a more rapid decline in the lung function. Moreover, studies on both children and adults have shown that the involvement of the small airways represents a crucial step in asthma development. New tools have been developed and old tools have been refined, providing an opportunity to better understand small airway inflammation and dysfunction. Small airway inflammation is present in all stages of asthmatic disease and plays an important role in many key clinical conditions/phenotypes. In order to control the disease, we need to target small airway inflammation, which is not only difficult to reach by standard inhaled medications but also to some extent different. A better understanding of the important role small airways are playing in asthma will show that the 'silent zone' is by far not silent at all.

Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: A systematic review

Traditionally, asthma has been considered a disease that predominantly involves the large airways. Today, this concept is being challenged, and increasing evidence has become available showing that abnormalities in the small airways also contribute to the clinical expression of asthma. The small airways can be affected by inflammation, remodeling, and changes in the surrounding tissue, all contributing to small-airways dysfunction. In this article we have performed a systematic review of the literature on the association between small-airways dysfunction and clinical signs and symptoms of asthma. This review shows that small-airways dysfunction associates with worse control of asthma, higher numbers of exacerbations, the presence of nocturnal asthma, more severe bronchial hyperresponsiveness, exercise-induced asthma, and the late-phase allergic response. Importantly, small-airways dysfunction can already be present in patients with mild asthma. Our review provides suggestive evidence that a better response of the small airways to inhaled steroids or montelukast associates with better asthma control. For this reason, an early recognition of small-airways dysfunction is important because it enables the physician to start timely treatment to target the small airways. It is important to develop simpler and more reliable tools (eg, questionnaires or bronchial provocation tests with small-particle stimuli) to assess the presence and extent of small-airways dysfunction in daily clinical practice.

WAO-1 The assessment and importance of small airway disease in asthma

WAO-1 The assessment and importance of small airway disease in asthma

Small airways disease in asthma: a review

Small airways disease in asthma: a review

Phenotyping airways disease: an A to E approach

The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic.

Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma

The regional pattern and extent of airway closure measured by three-dimensional ventilation imaging may relate to airway hyperresponsiveness (AHR) and peripheral airways disease in asthmatic subjects. We hypothesized that asthmatic airways are predisposed to closure during bronchoconstriction in the presence of ventilation heterogeneity and AHR. Fourteen asthmatic subjects (6 women) underwent combined ventilation single photon emission computed tomography/computed tomography scans before and after methacholine challenge. Regional airway closure was determined by complete loss of ventilation following methacholine challenge. Peripheral airway disease was measured by multiple-breath nitrogen washout from which S(cond) (index of peripheral conductive airway abnormality) was derived. Relationships between airway closure and lung function were examined by multiple-linear regression. Forced expiratory volume in 1 s was 87.5 ± 15.8% predicted, and seven subjects had AHR. Methacholine challenge decreased forced expiratory volume in 1 s by 23 ± 5% and increased nonventilated volume from 16 ± 4 to 29 ± 13% of computed tomography lung volume. The increase in airway closure measured by nonventilated volume correlated independently with both S(cond) (partial R(2) = 0.22) and with AHR (partial R(2) = 0.38). The extent of airway closure induced by methacholine inhalation in asthmatic subjects is greater with increasing peripheral airways disease, as measured by ventilation heterogeneity, and with worse AHR.

P78 Lung clearance index in children with acute exacerbation of asthma

IntroductionLung clearance index (LCI) can detect small airways disease in asthma; however there is no published LCI data collected during acute exacerbation. We aimed to investigate LCI in asthmatic children...

Relationship of Adipokines with Immune Response and Lung Function in Obese Asthmatic and Non-Asthmatic Women

Background. Obesity is a risk factor for asthma. Studies in mice suggest that the adipokines leptin and adiponectin affect asthmatic responses. The purpose of this study was to determine if adipokines associated with obesity are (1) altered in obese women with asthma compared to controls and (2) associated with increased cytokines and chemokines involved in allergic inflammation. Methods. We performed a cross-sectional study of asthmatic and non-asthmatic obese premenopausal women. Participants answered questionnaires and performed lung function tests. Serum and peripheral blood mononuclear cells (PBMCs) were collected for analysis of cytokines and adipokines. Results. A total of 22 asthmatic (mean body mass index 40.0 ± 5.1 kg/m2) and 20 non-asthmatic women (mean body mass index 41.3 ± 5.6 kg/m2) participated. We found no difference in serum adipokine concentrations between asthmatics and non-asthmatics. Serum adiponectin correlated positively with PBMC eotaxin (rs = 0.55, p = .0003) and RANTES (regulated upon activation, normal T-cell expressed, and secreted) (rs = 0.36, p = .03), whereas serum leptin correlated negatively with PBMC eotaxin (rs = −0.34, p = .04). There was a negative correlation between serum adiponectin and PBMC interferon-γ (rs = −0.41, p = .01). Conclusions. Perturbations of adipokines that occur in obesity were correlated with decreased cytokine production typically associated with allergic responses in PBMC of obese premenopausal women. This study suggests that although obese asthmatics may have elements of Th2-mediated inflammation, adipokine derangements in obesity are associated with Th1 rather than Th2 bias. Obesity has complex effects on allergic inflammation and is likely to be important modifier of the pathogenesis of airway disease in asthma.