Expiratory Airflow Limitation Research Articles

Potential cellular endocrinology mechanisms underlying the effects of Chinese herbal medicine therapy on asthma

Asthma is a complex syndrome with polygenetic tendency and multiple phenotypes, which has variable expiratory airflow limitation and respiratory symptoms that vary over time and in intensity. In recent years, continuous industrial development has seriously impacted the climate and air quality at a global scale. It has been verified that climate change can induce asthma in predisposed individuals and that atmospheric pollution can exacerbate asthma severity. At present, a subset of patients is resistant to the drug therapy for asthma. Hence, it is urgent to find new ideas for asthma prevention and treatment. In this review, we discuss the prescription, composition, formulation, and mechanism of traditional Chinese medicine monomer, traditional Chinese medicine monomer complex, single herbs, and traditional Chinese patent medicine in the treatment of asthma. We also discuss the effects of Chinese herbal medicine on asthma from the perspective of cellular endocrinology in the past decade, emphasizing on the roles as intracellular and extracellular messengers of three substances—hormones, substances secreted by pulmonary neuroendocrine cells, and neuroendocrine-related signaling protein—which provide the theoretical basis for clinical application and new drug development.

Quantitative CT lung densitometry as an obstructive marker for the diagnosis of bronchiolitis obliterans in children.

The purpose of this study is to evaluate the quantitative diagnostic performance of computed tomography (CT) densitometry in pediatric patients with bronchiolitis obliterans (BO). We measured the mean lung density (MLD) and represented the difference of MLD in inspiratory and expiratory phases (MLDD), the ratio of the MLD (E/I MLD), and the relative volume percentage of lung density at 50-Hounsfield unit (HU) interval threshold (E600 to E950). We calculated the sensitivity, specificity, and diagnostic accuracy of the lung density indices for the diagnosis of BO. A total of 81 patients, including 51 patients with BO and 30 controls, were included in this study. In the BO patients, expiratory (EXP) MLD and MLDD were significantly lower, and E/I MLD and expiratory low attenuation areas below the threshold of −850 HU to −950 HU (E850, E900, and E950) were statistically significantly higher than controls. Multivariate logistic regression analysis showed that MLDD (odds ratio [OR] = 0.98, p < .001), E/I MLD (OR = 1.39, p < .001), and E850 to E950 were significant densitometry parameters for BO diagnosis. In a receiver-operating characteristic analysis, E900 (cutoff, 1.4%; AUC = 0.920), E/I MLD (cutoff, 0.87; AUC = 0.887), and MLDD (cutoff, 109 HU; AUC = 0.867) showed high accuracy for the diagnosis of BO. In conclusion, the lung CT densitometry can serve as a quantitative marker providing additional indications of expiratory airflow limitation in pediatric patients with BO.

Pulmonary function tests in children with allergic rhinitis

Background: Allergic Rhinitis is a chronic and common respiratory disorder due to its prevalence, effect on quality of life, performance at school and work place, economic burden and link with asthma. Pulmonary function tests like FEF (25-75%) and PEFR are impaired in allergic rhinitis Expiratory air flow limitation is the hallmark of physiological change in allergic rhinitis. Aims and Objective: The present study aims to study pulmonary function tests such as FVC, FEF, (25-75%) and PEFR in allergic rhinitis cases to evaluate their predilection to the development of asthma. Materials and Methods: The study was carried out in the Department of Physiology at Index Medical College Hospital and Research Center, Indore, Madhya Pradesh. The study was done on 80 male and female subjects of the age group of 6 to 18 years. Forty male and female subjects suffering from allergic rhinitis attending the Ear, Nose and Throat outpatient department of IMCHRC, Indore were taken as cases. Forty males and females were taken as controls after careful selection as per inclusion and exclusion criteria. PFT was done by Digital Spirometer – Helios 401 manufactured by RMS India.

Recent patents in allergy and immunology: A quantitative real-time polymerase chain reaction method for diagnosing asthma and asthma exacerbation.

BackgroundAsthma is diagnosed based on a history of the characteristic symptoms and evidence of expiratory airflow limitation. However, asthma diagnosis using the existing tests is associated with a risk of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 spread. In this study, we developed a quantitative real‐time polymerase chain reaction (qRT‐PCR)‐based asthma diagnosis tool.MethodsWe detected nectin‐4 in the plasma of patients with asthma using qRT‐PCR, explored the relationship of clinical variables.Resultsquantitative real‐time polymerase chain reaction revealed that plasma nectin‐4 mRNA levels were higher in asthmatics than controls. These results correlated with lung function.ConclusionsThose results suggest that qRT‐PCR for nectin‐4 may aid asthma diagnosis and monitoring.

Ferret models of alpha-1 antitrypsin deficiency develop lung and liver disease.

Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause and risk factor for chronic obstructive pulmonary disease, but the field lacks a large-animal model that allows for longitudinal assessment of pulmonary function. We hypothesized that ferrets would model human AATD-related lung and hepatic disease. AAT-knockout (AAT-KO) and PiZZ (E342K, the most common mutation in humans) ferrets were generated and compared with matched controls using custom-designed flexiVent modules to perform pulmonary function tests, quantitative computed tomography (QCT), bronchoalveolar lavage (BAL) proteomics, and alveolar morphometry. Complete loss of AAT (AAT-KO) led to increased pulmonary compliance and expiratory airflow limitation, consistent with obstructive lung disease. QCT and morphometry confirmed emphysema and airspace enlargement, respectively. Pathway analysis of BAL proteomics data revealed inflammatory lung disease and impaired cellular migration. The PiZ mutation resulted in altered AAT protein folding in the liver, hepatic injury, and reduced plasma concentrations of AAT, and PiZZ ferrets developed obstructive lung disease. In summary, AAT-KO and PiZZ ferrets model the progressive obstructive pulmonary disease seen in AAT-deficient patients and may serve as a platform for preclinical testing of therapeutics including gene therapy.

Pulmonary function characteristics in children with symptoms of asthma and its implications for asthma diagnosis

In children with a history suggestive of asthma, diagnosis is usually confirmed with evidence of variable expiratory airflow limitation. This study aimed to evaluate the pulmonary function characteristics in patients suspected of asthma and showing negative bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR).

Physiological aspects of cardiopulmonary dysanapsis on exercise in adults born preterm.

Progressive improvements in perinatal care and respiratory management of preterm infants have resulted in increased survival of newborns of extremely low gestational age over the past few decades. However, the incidence of bronchopulmonary dysplasia, the chronic lung disease after preterm birth, has not changed. Studies of the long-term follow-up of adults born preterm have shown persistent abnormalities of respiratory, cardiovascular and cardiopulmonary function, possibly leading to a lower exercise capacity. The underlying causes of these abnormalities are incompletely known, but we hypothesize that dysanapsis, i.e. discordant growth and development, in the respiratory and cardiovascular systems is a central structural feature that leads to a lower exercise capacity in young adults born preterm than those born at term. We discuss how the hypothesized system dysanapsis underscores the observed respiratory, cardiovascular and cardiopulmonary limitations. Specifically, adults born preterm have: (1) normal lung volumes but smaller airways, which causes expiratory airflow limitation and abnormal respiratory mechanics but without impacts on pulmonary gas exchange efficiency; (2) normal total cardiac size but smaller cardiac chambers; and (3) in some cases, evidence of pulmonary hypertension, particularly during exercise, suggesting a reduced pulmonary vascular capacity despite reduced cardiac output. We speculate that these underlying developmental abnormalities may accelerate the normal age-associated decline in exercise capacity, via an accelerated decline in respiratory, cardiovascular and cardiopulmonary function. Finally, we suggest areas of future research, especially the need for longitudinal and interventional studies from infancy into adulthood to better understand how preterm birth alters exercise capacity across the lifespan.

The annual adult asthma review

Asthma is a chronic inflammatory lung condition characterised by variable respiratory symptoms (wheeze, shortness of breath, cough, and chest tightness) and variable expiratory airflow limitation, usually associated with airway inflammation. It affects 1-in-11 people in the UK and is the cause of over 75 000 hospital admissions per year. Given its prevalence, and the fact that patients are mainly cared for in the community, this article aims to highlight the need for a thorough annual asthma review and what that review entails. When carried out effectively, an asthma review will improve quality of life for those living with the condition, reduce their likelihood of hospital admission and reduce the cost to the NHS as a whole.

Functional diagnostics of the respiratory system in chronic obstructive pulmonary disease

The article deals with the pathophysiology of chronic obstructive pulmonary disease (COPD), modern possibilities of functional methods in COPD, including the diagnosis of small airway dysfunction and expiratory air flow limitation with quiet breathing by impulse oscillometry, and also describes the characteristic changes in the indicators of pulmonary functional tests in COPD.

Asthma phenotypes and endotypes.

Asthma is a complex disorder characterized by expiratory airflow limitation, wheeze, shortness of breath, chest tightness and cough, which can vary over time and in intensity. Being highly heterogeneous, asthma was characterized and classified in several asthma phenotypes and endotypes from 1947 until today. The present systematic review aims to summarize and describe evidence that was published in the last ten years in the field of asthma phenotyping and endotyping. The systematic review resumed high-quality evidence (clinical trials and randomized control trials) retrieved on MEDLINE and EMBASE databanks and involving adult asthmatic populations. Analyses of literature were conducted according to PRISMA and CASP guidelines. Querying MEDLINE and EMBASE databanks, 5019 and 12261 entries were retrieved, respectively. Applying limitations for year of publication, age of participants, and type of publication, the search results were reduced to 98 and 132 articles, respectively. After data abstraction and resolution of duplications, only 50 articles were further evaluated. The research products were then classified first in macro-areas of interest (phenotypes or endotypes) and then in detailed micro-areas. This systematic review overviews the principal findings available from high-quality literature in the last decade concerning asthma phenotypes and endotypes. Asthma has been described from different points of view, characterizing symptoms, microbiota composition, comorbidities, viral infections, and airway and/or systemic inflammatory status. The comprehension of precise mechanisms underlying asthma pathogenesis is thereby the basis for the development of novel therapeutic strategies, likely essential to the development of precision medicine.

Identifying miRNA-mRNA Networks Associated With COPD Phenotypes.

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory airflow limitation and symptoms such as shortness of breath. Although many studies have demonstrated dysregulated microRNA (miRNA) and gene (mRNA) expression in the pathogenesis of COPD, how miRNAs and mRNAs systematically interact and contribute to COPD development is still not clear. To gain a deeper understanding of the gene regulatory network underlying COPD pathogenesis, we used Sparse Multiple Canonical Correlation Network (SmCCNet) to integrate whole blood miRNA and RNA-sequencing data from 404 participants in the COPDGene study to identify novel miRNA–mRNA networks associated with COPD-related phenotypes including lung function and emphysema. We hypothesized that phenotype-directed interpretable miRNA–mRNA networks from SmCCNet would assist in the discovery of novel biomarkers that traditional single biomarker discovery methods (such as differential expression) might fail to discover. Additionally, we investigated whether adjusting -omics and clinical phenotypes data for covariates prior to integration would increase the statistical power for network identification. Our study demonstrated that partial covariate adjustment for age, sex, race, and CT scanner model (in the quantitative emphysema networks) improved network identification when compared with no covariate adjustment. However, further adjustment for current smoking status and relative white blood cell (WBC) proportions sometimes weakened the power for identifying lung function and emphysema networks, a phenomenon which may be due to the correlation of smoking status and WBC counts with the COPD-related phenotypes. With partial covariate adjustment, we found six miRNA–mRNA networks associated with COPD-related phenotypes. One network consists of 2 miRNAs and 28 mRNAs which had a 0.33 correlation (p = 5.40E-12) to forced expiratory volume in 1 s (FEV1) percent predicted. We also found a network of 5 miRNAs and 81 mRNAs that had a 0.45 correlation (p = 8.80E-22) to percent emphysema. The miRNA–mRNA networks associated with COPD traits provide a systems view of COPD pathogenesis and complements biomarker identification with individual miRNA or mRNA expression data.

Pharmacological Rationale for Targeting IL-17 in Asthma.

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

Childhood asthma: A best-practice strategy for the diagnosis and assessment of control in South Africa

The South African (SA) Childhood Asthma Working Group of the Allergy Society of SA (ALLSA) advises on best-practice strategy for childhood asthma management. The strategy is in accordance with current evidence and consensus. The aim of this review is to inform on a best-practice strategy for asthma diagnosis and the assessment of asthma control in SA children who attend public and private healthcare services. The diagnosis of asthma is more difficult in preschool-aged than school-aged children. This review proposes a four-step diagnostic approach in both groups, with an added obligation to objectively measure variable expiratory airflow limitation in school-aged children. Asthma control refers to the degree to which the effects of asthma can be seen in patients, or to which these have been reduced by treatment. After initiation of treatment, it is essential to assess asthma control at regular follow-up visits, and to adjust treatment accordingly. Patient education is key to attaining control.

Role of peak expiratory flow in the assessment and management of asthma in children

Peak expiratory flow (PEF) is a portable, reliable, and inexpensive method for lung function assessment. PEF can reflect expiratory airflow limitation and its variability can document reversibility, which provides an objective basis for the diagnosis of asthma in children. Short-term PEF monitoring can be an important aid in the management of acute asthma exacerbations, identification of possible triggers, and assessment of response to treatment. Long-term PEF monitoring can assist in the assessment of asthma control and warning of acute exacerbations, and this is useful for children with severe asthma. This article reviews the measurements, influencing factors, interpretation, and application of PEF, and its role in the diagnosis and management of asthma in children, to provide references for the clinical application of PEF in children.

Incidental Diagnosis of Swyer-James-MacLeod Syndrome in a Military Pilot

BACKGROUND: Swyer-James-MacLeod syndrome (SJMS) is a specific form of bronchiolitis obliterans that occurs rarely, but represents recognized sequelae of common pediatric respiratory illness, and presents as unilateral hyperlucency on chest imaging. This case study describes such an incidental radiographic finding identified during the assessment of chest wall discomfort in a military pilot.CASE REPORT: A 35-yr-old military pilot presented to his flight surgeon with vague intermittent chest discomfort. Initial evaluation revealed an abnormal chest radiograph with unilateral hyperlucency and mild expiratory airflow limitation on pulmonary function testing. The evaluation also included computed tomography imaging with contrast infusion and echocardiography, though the presenting complaint had resolved. The airman was referred to our clinic for further evaluation and aeromedical recommendations regarding returning to flight duties. He was diagnosed with SJMS and recommended to be returned to flight duties.DISCUSSION: SJMS can be challenging to recognize to the untrained eye. An inflammatory response from viral or bacterial infection in childhood results in dysfunctional growth of the affected region of the lung, causing radiographic asymmetry. Although destruction of the alveoli and emphysema may occur, for most cases, there are minimal clinical sequelae. SJMS is not known to be progressive and is not associated with systemic conditions. The pilot likely had the abnormal chest radiograph at the time of commission and had not experienced any in-flight complications. His chest pain had resolved without intervention and SJMS was determined to be unlikely to impact his flight performance (such as response to supplemental oxygen) or life expectancy.Harrison MF, Cowl CT. Incidental diagnosis of Swyer-James-MacLeod syndrome in a military pilot. Aerosp Med Hum Perform. 2021; 92(4):281285.

Comparative evaluation of expiratory airflow limitation between patients with COPD and BE using IOS

Impulse oscillometry (IOS) allows evaluation of the compartmentalized resistance and reactance of the respiratory system, distinguishing central and peripheral obstruction. The IOS measurements are getting attention in the diagnosis and differentiation of chronic respiratory diseases. However, no data are available in the literature to differentiate between COPD and BE using IOS parameters. We aimed to evaluate the feasibility of IOS in the diagnosis of bronchiectasis non-cystic fibrosis (BE) in comparison to COPD. Whole breath, inspiration, expiration, and inspiratory-expiratory difference (Δ) were evaluated based on the IOS parameters: total resistance (R5), central airway resistance (R20), peripheral airway resistance (R5-R20), reactance (X5), reactance area (AX), and resonance frequency (Fres). Fifty-nine subjects (21 Healthy, 19 BE, and 19 COPD) participated in this study. It was observed a significant difference in the comparison of healthy and pulmonary disease groups (BE and COPD) for total breathing (R5-R20, X5, AX, and Fres), inspiratory phase (R5 and R5-R5), and expiratory phase (R5-R20 and X5). The comparison between BE and COPD groups showed significant difference in the expiratory phase for resistance at 5 and 20 Hz and, ΔR5 and ΔR20. The IOS evidenced an increase of R5, R20 and R5-R20 in patients with BE and COPD when compared to healthy subjects. Expiratory measures of IOS revealed increased airway resistance in COPD compared to BE patients who had similar FEV1 measured by spirometry, however, further studies are needed to confirm these differences.

Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date.

Asthma is a complex heterogeneous disease defined by chronic inflammation of the airways. Patients present with wheezing, chest tightness, cough and shortness of breath. Bronchial hyperresponsiveness and variable expiratory airflow limitation are hallmark features. About 3.6–6.1% of patients, despite receiving high-dose inhaled corticosteroids (ICS) and a second controller medication, report persistent symptoms referred to as severe asthma. Uncontrolled severe asthma is associated with increased mortality, morbidity, diminished quality of life and increased health expenditures. The development of modern biological therapy has revolutionized severe asthma treatment. By targeting specific chemokines, asthma control has drastically improved, resulting in better quality of life, less emergency department visits and inpatient admissions, and decreased chronic systemic corticosteroid utilization. Despite these advances, there remains a subset of asthma patients who remain symptomatic with poor quality of life and heavy utilization of the healthcare system. Recently attention has been given to pharmaceutical therapy directed at receptors and cytokines on the epithelial layer of the lung referred to as “alarmins”. Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like receptor family found on the epithelial layer of the lung that releases a cytokine cascade inducing eosinophilic inflammation, mucus production and airflow obstruction in asthmatics. Tezepelumab is the first investigational monoclonal antibody that inhibits TSLP. Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV1 and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.

Physiological tests of small airways function in diagnosing asthma: a systematic review

BackgroundAsthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed...

Clinical Characteristics and Outcomes of Patients with Asthma-COPD Overlap in Japanese Patients with COPD.

PurposeAsthma–COPD overlap (ACO) has been reported as an association with a lower quality of life, frequent exacerbations, and higher mortality than those with COPD alone. However, clinical characteristics and outcomes of ACO remain controversial.Patients and MethodsWe conducted a prospective observational study analyzing data of patients with stable COPD enrolled from the Ishinomaki COPD Network Registry. Patients with features of asthma who had a history of respiratory symptoms that vary over time and intensity, together with documented variable expiratory airflow limitation, were identified, and then defined as having ACO. The characteristics, frequency of exacerbations, and mortality during the 3-year follow-up were compared between patients with ACO and patients with COPD alone.ResultsAmong 387 patients with COPD, 41 (10.6%) were identified as having ACO. Patients with ACO tended to be younger, have higher BMI, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids. Inflammatory biomarkers including fractional exhaled nitric oxide, blood eosinophil count, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were significantly higher in patients with ACO than in those with COPD alone. Lung function, mMRC score, CAT score, and comorbidity index were not different between the groups. The annual rate of all exacerbations and severe exacerbations required hospital admission were not different between ACO and COPD alone (0.20 vs 0.14, 0.12 vs 0.10, events per person, respectively). Mortality was significantly higher in patients with COPD alone compared with those with ACO during the study period (P=0.037).ConclusionThe results of our study indicate that ACO is not associated with poor clinical features nor outcomes in an outpatient COPD cohort receiving appropriate treatment.

The use of a direct bronchial challenge test in primary care to diagnose asthma

Many asthmatics in primary care have mild symptoms and lack airflow obstruction. If variable expiratory airflow limitation cannot be determined by spirometry or peak expiratory flow, despite a history of respiratory symptoms, a positive bronchial challenge test (BCT) can confirm the diagnosis of asthma. However, BCT is traditionally performed in secondary care. In this observational real-life study, we retrospectively analyze 5-year data of a primary care diagnostic center carrying out BCT by histamine provocation. In total, 998 primary care patients aged ≥16 years underwent BCT, without any adverse events reported. To explore diagnostic accuracy, we examine 584 patients with a high pretest probability of asthma. Fifty-seven percent of these patients have a positive BCT result and can be accurately diagnosed with asthma. Our real-life data show BCT is safe and feasible in a suitably equipped primary care diagnostic center. Furthermore, it could potentially reduce diagnostic referrals to secondary care.