Normal Lung Function Research Articles

Posttranscriptional Gene Regulatory Networks in Chronic Airway Inflammatory Diseases: In silico Mapping of RNA-Binding Protein Expression in Airway Epithelium.

Background: Posttranscriptional gene regulation (PTGR) contributes to inflammation through alterations in messenger RNA (mRNA) turnover and translation rates. RNA-binding proteins (RBPs) coordinate these processes but their role in lung inflammatory diseases is ill-defined. We evaluated the expression of a curated list of mRNA-binding RBPs (mRBPs) in selected Gene Expression Omnibus (GEO) transcriptomic databases of airway epithelium isolated from chronic obstructive pulmonary disease (COPD), severe asthma (SA) and matched control subjects, hypothesizing that global changes in mRBPs expression could be used to infer their pathogenetic roles and identify novel disease-related regulatory networks.Methods: A published list of 692 mRBPs [Nat Rev Genet 2014] was searched in GEO datasets originated from bronchial brushings of stable COPD patients (C), smokers (S), non-smokers (NS) controls with normal lung function (n = 6/12/12) (GEO ID: GSE5058) and of (SA) and healthy control (HC) (n = 6/12) (GSE63142). Fluorescence intensity data were extracted and normalized on the medians for fold change (FC) comparisons. FCs were set at ≥ |1.5| with a false discovery rate (FDR) of ≤ 0.05. Pearson correlation maps and heatmaps were generated using tMEV tools v4_9_0.45. DNA sequence motifs were searched using PScan-ChIP. Gene Ontology (GO) was performed with Ingenuity Pathway Analysis (IPA) tool.Results: Significant mRBP expression changes were detected for S/NS, COPD/NS and COPD/S (n = 41, 391, 382, respectively). Of those, 32% of genes changed by FC ≥ |1.5| in S/NS but more than 60% in COPD/NS and COPD/S (n = 13, 267, 257, respectively). Genes were predominantly downregulated in COPD/NS (n = 194, 73%) and COPD/S (n = 202, 79%), less so in S/NS (n = 4, 31%). Unsupervised cluster analysis identified in 4 out of 12 S the same mRBP pattern seen in C, postulating subclinical COPD. Significant DNA motifs enrichment for transcriptional regulation was found for downregulated RBPs. Correlation analysis identified five clusters of co-expressed mRBPs. GO analysis revealed significant enrichments in canonical pathways both specific and shared among comparisons. Unexpectedly, no significant mRBPs modulation was found in SA compared to controls.Conclusions: Airway epithelial mRBPs profiling reveals a COPD-specific global downregulation of RBPs shared by a subset of control smokers, the potential of functional cooperation by coexpressed RBPs and significant impact on relevant pathogenetic pathways in COPD. Elucidation of PTGR in COPD could identify disease biomarkers or pathways for therapeutic targeting.

Asthma‐chronic obstructive pulmonary disease overlap: A clinical entity?

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.

Pulmonary Functions and Factors Affecting Them in Patients with Chronic Kidney Disease

To determine the pulmonary functions in patients with chronic kidney diseases (CKD) and factors affecting them. Observational study. Nephrology Department, Mayo Hospital, Lahore, from October 2018 to April 2019. All patients of CKD, coming in Nephrology OPD, were included. Patients on maintenance hemodialysis (HD), chronic obstructive pulmonary disease (COPD), smokers, chronic heart disease, and neuromuscular diseases were excluded from the study. Demographic data, physical examination findings and laboratory parameters were taken. Patients underwent spirometry at Pulmonology Department for measurement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and FEV1/FVC. One hundred and forty patients were included in the study. Mean GFR was 27.75 ± 17.49 ml/min/1.73m2 and 7(5%) patients belonged to stage 2 CKD, 48 (34.3%) belonged to stage 3 CKD, 45 (32.1%) belonged to stage 4 CKD and rest 40 (28.6%) were from stage 5 CKD. Pulmonary functions were FEV1 (90.81±25.84), FVC (88.91±28.54), and FEV1/FVC (108.57±13.0). According to laid down criteria, 62 (44.3%) cases had restrictive lung disease (RLD), 5 (3.6%) cases had mixed and 78 (55.7%) cases normal lung function status. Important factors affecting pulmonary functions were GFR (p=0.038), monthly income (p=0.017) and education (p=0.041). Drop in GFR and anemia have negative correlation and age has positive correlation with pulmonary dysfunctions. Pulmonary functions were abnormal in almost half of the patients and restrictive lung disease was the most common pattern in these patients. Factors affecting the pulmonary functions were progression of CKD, falling hemoglobin level, monthly income and education. Drop in GFR and anemia had negative correlation and age had positive correlation with pulmonary functions. Key Words: CKD, Pulmonary functions, Restrictive lung disease, GFR, Anemia.

Aryl hydrocarbon receptor deficiency enhanced airway inflammation and remodeling in a murine chronic asthma model

The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Recent studies have shown that AhR is a novel master regulator of the mucosal immune system, including lungs and intestine. To elucidate the role of AhR in chronic severe asthma, AhR wild-type and knockout mice (AhR-/- ) were sensitized and challenged with ovalbumin for 4weeks. To uncover the underlying mechanisms, inflammatory cells profile and cytokines production were analyzed in bronchial lavage fluid (BALF) and lung tissue. Compared to wild-type mice, AhR-/- mice had exacerbated asthma symptoms, including airway inflammation, mucus production, airway hyperresponsiveness, and airway remodeling. BALF monocytes, neutrophils, eosinophils, and lymphocytes were all enhanced in OVA-immunized AhR-/- mice. In OVA-immunized AhR-/- mice, T helper (Th) 17 cell-specific cytokine IL-17A, as well as airway remodeling factors, including epithelial-mesenchymal transition (EMT) markers and vascular endothelial growth factor (VEGF), were all enhanced in lung tissue. Moreover, human cohort studies showed that AhR gene expression in bronchial epithelial cells decreases in severe asthma patients. Loss of AhR leads to worsening of allergic asthma symptoms, indicating its importance in maintaining normal lung function and mediating disease severity.

Smoking-associated increase in mucins 1 and 4 in human airways

RationaleSmoking-related chronic obstructive pulmonary disease (COPD) is associated with dysregulated production of mucus. Mucins (MUC) are important both for mucus secretion and epithelial defense. We have examined the distribution of MUC1 and MUC4 in the airway epithelial cells of never-smokers and smokers with and without COPD.MethodsMucosal biopsies and bronchial wash samples were obtained by bronchoscopy from age- and sex-matched COPD-patients (n = 38; GOLD I-II/A-B), healthy never-smokers (n = 40) and current smokers with normal lung function (n = 40) from the Karolinska COSMIC cohort (NCT02627872). Cell-specific expressions of MUC1, MUC4 and regulating factors, i.e., epithelial growth factor receptor (EGFR) 1 and 2, were analyzed by immunohistochemistry. Soluble MUC1 was measured by quantitative immunodetection on slot blot.ResultsThe levels of cell-bound MUC1 expression in basal cells and in soluble MUC1 in bronchial wash were increased in smokers, regardless of airway obstruction. Patients with chronic bronchitis had higher MUC1 expression. The expression of MUC4 in cells with goblet cell phenotype was increased in smokers. The expression of EGFR2, but not that of EGFR1, was higher in never-smokers than in smokers.ConclusionsSmoking history and the presence of chronic bronchitis, regardless of airway obstruction, affect both cellular and soluble MUC1 in human airways. Therefore, MUC1 may be a novel marker for smoking- associated airway disease.

The Interplay of the Genetic Architecture, Aging, and Environmental Factors in the Pathogenesis of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease of indeterminate etiology and limited therapeutic options. The initiation, development, and progression of IPF are influenced by genetic predisposition, aging, and host and environmental factors, but the magnitude of the contribution of each of them and the sequence of the pathogenic events are uncertain. Current evidence indicates that accumulated environmental exposures in a genetically predisposed individual, usually over 60 years of age, leads to phenotypic and functional alterations of the lung epithelium. Aberrant activation of epithelial cells results, through a complex release of numerous mediators, in the local expansion of peculiar subsets of aggressive fibroblasts and myofibroblasts, which are crucial effector cells of fibrotic remodeling and loss of the normal lung architecture and function. Progressive increase of the mechanical stiffness activates cell-autonomous and matrix-dependent processes contributing to the perpetuation of the fibrotic response. This Perspective provides an integral overview of the major risk factors underpinning the pathogenesis of IPF, including gene variants, aging alterations, environmental factors, host risk factors, and epigenetic reprogramming.

Long-Term Inhalative Sedation in Children With Pulmonary Diseases.

To describe safety and feasibility of long-term inhalative sedation (LTIS) in children with severe respiratory diseases compared to patients with normal lung function with respect to recent studies that showed beneficial effects in adult patients with acute respiratory distress syndrome (ARDS). Single-center retrospective study. 12-bed pediatric intensive care unit (PICU) in a tertiary-care academic medical center in Germany. All patients treated in our PICU with LTIS using the AnaConDa® device between July 2011 and July 2019. Thirty-seven courses of LTIS in 29 patients were analyzed. LTIS was feasible in both groups, but concomitant intravenous sedatives could be reduced more rapidly in children with lung diseases. Cardiocirculatory depression requiring vasopressors was observed in all patients. However, severe side effects only rarely occured. In this largest cohort of children treated with LTIS reported so far, LTIS was feasible even in children with severely impaired lung function. From our data, a prospective trial on the use of LTIS in children with ARDS seems justified. However, a thorough monitoring of cardiocirculatory side effects is mandatory.

Prescient Model for Identifying COPD

Chronic Obstructive Pulmonary Disease is a disease of lungs that involves gradual decrease of normal functioning of lungs. This paper aims at specifying the work done to predict chronic obstructive pulmonary disease at an early stage. As lung disease has become a very prevalent problem all over the world where the patients don’t even come to know that they have severe lung disease at an early stage as there are no proper disease specific symptoms in an early stage it is quite difficult to predict the disease. If the problem is not detected in time it may prove to be fatal as there might be inflammation in lungs due to which the patient might suffer severe breathlessness. This paper aims to specify the methods and techniques used previously to determine chronic obstructive pulmonary disease in its early stage so that the patient’s quality of life can be improved with the proper medication, healthy diet and exercise. This paper intends to study technological advancement that includes machine learning algorithms to analyze the disease. It was observed that many machine learning algorithms are being used such as Convolutional neural network, K-nearest neighbor, random forest, regression, support vector machine and many more. The experts have used deep learning based ResNet with convolutional neural networks to classify the infected features in High Resolution Computed Tomography scans of lungs.

The Healthy Airway Mycobiome in Individuals of Asian Descent

The Healthy Airway Mycobiome in Individuals of Asian Descent

S100A9/CD163 Expression in Circulating Classical Monocytes in Chronic Obstructive Pulmonary Disease

Although many studies have characterized polarity of macrophages in chronic obstructive pulmonary disease (COPD), limited information is available regarding cellular phenotypes of circulating monocytes in this condition. This study aimed to determine the influence of cigarette smoking and COPD on the cellular phenotype of circulating monocytes. Thirty-two patients with COPD and 36 healthy volunteers (n = 17 and 19 in nonsmokers and smokers with normal lung functions, respectively) were enrolled in this study. The expression of two cell surface markers, pro-inflammatory-related S100A9 and anti-inflammatory-related CD163, on classical monocytes was analyzed by flow cytometry. The percentage of CD14strongCD16− classical monocytes in circulating monocytes showed no difference among the three groups. The percentage of S100A9+, S100A9+CD163−, and S100A9+CD163+ cells in classical monocytes was significantly increased in COPD patients relative to nonsmoker controls. In contrast, the levels of S100A9−CD163+ cells were significantly decreased in smokers with normal lung functions and in COPD patients relative to that in nonsmokers. Multivariate analyses revealed an independent association between S100A9+ cell rates and COPD (exponent 1.0336, 95% confidence interval [CI] 1.0063–1.0617, p value < 0.05). In Receiver operating characteristic (ROC) analyses, the ratio of S100A9+CD163−/S100A9−CD163+ cells yielded a receiver operating characteristic-area under the curve of 0.719 (95% CI = 0.567–0.871) for discrimination between smokers with normal lung functions and COPD patients. In conclusion, our results demonstrated increased pro-inflammatory phenotypes in circulating classical monocytes in COPD, providing novel insights to elucidate their roles in the pathogenesis of COPD.

Correlation between level of autophagy and frequency of CD8+ T cells in patients with chronic obstructive pulmonary disease.

ObjectiveThe pathogenesis of chronic obstructive pulmonary disease (COPD) remains elusive. Here, we assessed the correlation between CD8+ T cell frequencies and autophagy in COPD patients.MethodsSubjects were divided into three groups (n = 30 patients/group): (1) COPD patients in the stable phase; (2) smokers with normal lung function; and (3) non-smokers with normal lung function. Flow cytometry was used to enumerate CD8+ T cell subsets (CD8+, CD8+ effector, and CD8+ memory T cells) and quantitate T-cell apoptosis. RT-PCR and western blotting were used to measure levels of LC3 and p62.ResultsFrequencies of CD8+ T cell subsets and expression of p62 and LC3 II/I were significantly higher in COPD patients compared with the other two groups, while the rate of apoptosis was lower. In COPD patients, LC3 II/I and p62 expression were positively correlated with CD8+ T cell subset frequencies. Moreover, a significant correlation was observed between LC3 II/I and p62 expression and T cell subset frequencies.ConclusionAutophagy level is positively correlated with the frequencies of CD8+ T cells, suggesting that autophagy might be involved in COPD pathogenesis.

Effect of family with sequence similarity 13 member A gene interference on apoptosis and proliferation of human airway epithelial cells and its relationship with small airway remodeling in patients with chronic obstructive pulmonary disease

Objective: To explore the relationship between family with sequence similarity 13 member A (FAM13A) gene and small airway remodeling in chronic obstructive pulmonary disease (COPD), and the effect of interference with FAM13A gene expression on the apoptosis and proliferation phenotype of human airway epithelial cells (16HBE). Methods: From January 2018 to January 2020, 74 patients in the Department of Thoracic Surgery of General Hospital of Ningxia Medical University were treated by surgery for lung tumors or pulmonary bullae. According to the lung function and smoking history, the 74 patients were divided into four groups: non-smoking group with normal lung function (normal group, 23 patients), smoking group with normal lung function (smoking group, 24 patients), non-smoking group with COPD (11 patients) and smoking group with COPD (16 patients). The expression of FAM13A in small airway of each group was detected by immunohistochemistry, and the correlation between FAM13A and the airflow restriction indexes by pulmonary function was analyzed. The shRNA fragment of FAM13A gene was designed, and the shRNA lentivirus vector of FAM13A gene was constructed and packaged. The expression level of FAM13A gene was detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blot, and the best shRNA sequence was screened. Flow cytometry was used to detect apoptosis rate and the fluorescence intensity of proliferation marker Ki-67 in 16HBE cells. Results: FAM13A was mainly expressed in the cytoplasm of small airway epithelial cells. The levels of FAM13A absorbance (A) of small airway epithelial cells in non-smoking group and smoking group with COPD were higher than those in normal group and smoking group (0.365±0.026, 0.412±0.053 to 0.113±0.018, 0.105±0.009, all P<0.05), and they were negatively correlated with forced expiratory volume in 1s/forced vital capacity (FEV(1)/FVC) and FEV(1)% pre (r=-0.48 and r=-0.40, all P<0.05). The FAM13A shRNA lentiviral vector was successfully constructed, and FAM13A interference was successfully achieved in the 16HBE cell line. After infection of 16HBE cells, the results of qRT-PCR and Western blot showed that the expression of FAM13A in shRNA-target-2 group decreased (all P<0.01). Compared with the negative control group (shRNA-NC), the apoptosis rate of FAM13A shRNA group decreased (P=0.023), and the fluorescence intensity of Ki-67 also decreased (P=0.042). Conclusions: FAM13A gene expression is increased in COPD small airway epithelial cells, and it is related to COPD airflow limitation. FAM13A gene may participate in the process of COPD remodeling by affecting the apoptosis and proliferation of human airway epithelial cells.

Vascular Pruning on CT and Interstitial Lung Abnormalities in the Framingham Heart Study

Pulmonary vascular disease is associated with poor outcomes in individuals affected by interstitial lung disease. The pulmonary vessels can be quantified with noninvasive imaging, but whether radiographic indicators of vasculopathy are associated with early interstitial changes is not known. Are pulmonary vascular volumes, quantified from CT scans, associated with interstitial lung abnormalities (ILA) in a community-based sample with a low burden of lung disease? In 2,386 participants of the Framingham Heart Study, we used CT imaging to calculate pulmonary vascular volumes, including the small vessel fraction (a surrogate of vascular pruning). We constructed multivariable logistic regression models to investigate associations of vascular volumes with ILA, progression of ILA, and restrictive pattern on spirometry. In secondary analyses, we additionally adjusted for diffusing capacity and emphysema, and performed a sensitivity analysis restricted to participants with normal FVC and diffusing capacity. In adjusted models, we found that lower pulmonary vascular volumes on CT were associated with greater odds of ILA, antecedent ILA progression, and restrictive pattern on spirometry. For example, each SD lower small vessel fraction was associated with 1.81-fold greater odds of ILA (95%CI, 1.41-2.31; P< .0001), and 1.63-fold greater odds of restriction on spirometry (95%CI, 1.18-2.24; P= .003). Similar patterns were seen after adjustment for diffusing capacity for carbon monoxide, emphysema, and among participants with normal lung function. In this cohort of community-dwelling adults not selected on the basis of lung disease, more severe vascular pruning on CT was associated with greater odds of ILA, ILA progression, and restrictive pattern on spirometry. Pruning on CT may be an indicator of early pulmonary vasculopathy associated with interstitial lung disease.

Extracorporeal Shock Waves Increase Markers of Cellular Proliferation in Bronchial Epithelium and in Primary Bronchial Fibroblasts of COPD Patients.

Chronic obstructive pulmonary disease (COPD) is due to structural changes and narrowing of small airways and parenchymal destruction (loss of the alveolar attachment as a result of pulmonary emphysema), which all lead to airflow limitation. Extracorporeal shock waves (ESW) increase cell proliferation and differentiation of connective tissue fibroblasts. To date no studies are available on ESW treatment of human bronchial fibroblasts and epithelial cells from COPD and control subjects. We obtained primary bronchial fibroblasts from bronchial biopsies of 3 patients with mild/moderate COPD and 3 control smokers with normal lung function. 16HBE cells were also studied. Cells were treated with a piezoelectric shock wave generator at low energy (0.3 mJ/mm2, 500 pulses). After treatment, viability was evaluated and cells were recultured and followed up for 4, 24, 48, and 72 h. Cell growth (WST-1 test) was assessed, and proliferation markers were analyzed by qRT-PCR in cell lysates and by ELISA tests in cell supernatants and cell lysates. After ESW treatment, we observed a significant increase of cell proliferation in all cell types. C-Kit (CD117) mRNA was significantly increased in 16HBE cells at 4 h. Protein levels were significantly increased for c-Kit (CD117) at 4 h in 16HBE (p < 0.0001) and at 24 h in COPD-fibroblasts (p = 0.037); for PCNA at 4 h in 16HBE (p = 0.046); for Thy1 (CD90) at 24 and 72 h in CS-fibroblasts (p = 0.031 and p = 0.041); for TGFβ1 at 72 h in CS-fibroblasts (p = 0.038); for procollagen-1 at 4 h in COPD-fibroblasts (p = 0.020); and for NF-κB-p65 at 4 and 24 h in 16HBE (p = 0.015 and p = 0.0002). In the peripheral lung tissue of a representative COPD patient, alveolar type II epithelial cells (TTF‐1+) coexpressing c-Kit (CD117) and PCNA were occasionally observed. These data show an increase of cell proliferation induced by a low dosage of extracorporeal shock waves in 16HBE cells and primary bronchial fibroblasts of COPD and control smoking subjects.

Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, more than 25% of COPD patients are non-smokers, and gene-by-smoking interactions are expected to affect COPD onset. We aimed to identify the common genetic variants interacting with pack-years of smoking on FEV1/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV1/FVC was performed for individuals with FEV1/FVC ratio ≥ 70 in the Korea Associated Resource cohort data, and significant SNPs were validated using data from two other Korean cohorts. The GWIS revealed that rs10947231 and rs8192575 met genome-wide significant levels; For {text{H}}_{0} :beta_{SNP} = beta_{SNP*pack - years} = 0{text{ vs H}}_{1} : not {text{H}}_{0} , the likelihood ratio (LR) test was conducted, and its P values, PLR, for rs10947231 and rs8192575 were 2.23 × 10–12 and 1.18 × 10–8, respectively. Interaction between rs8192575 and smoking is significantly replicated with two additional data (PINT = 0.0454, 0.0131). Expression quantitative trait loci, topologically associated domains, and PrediXcan analyses revealed that rs8192575 is significantly associated with AGER expression. SNPs on the 6p21 region are associated with FEV1/FVC, and the effect of smoking on FEV1/FVC differs among the associated genotypes.

Airway mechanical compression: its role in asthma pathogenesis and progression.

The lung is a mechanically active organ, but uncontrolled or excessive mechanical forces disrupt normal lung function and can contribute to the development of disease. In asthma, bronchoconstriction leads to airway narrowing and airway wall buckling. A growing body of evidence suggests that pathological mechanical forces induced by airway buckling alone can perpetuate disease processes in asthma. Here, we review the data obtained from a variety of experimental models, including in vitro, ex vivo and in vivo approaches, which have been used to study the impact of mechanical forces in asthma pathogenesis. We review the evidence showing that mechanical compression alters the biological and biophysical properties of the airway epithelium, including activation of the epidermal growth factor receptor pathway, overproduction of asthma-associated mediators, goblet cell hyperplasia, and a phase transition of epithelium from a static jammed phase to a mobile unjammed phase. We also define questions regarding the impact of mechanical forces on the pathology of asthma, with a focus on known triggers of asthma exacerbations such as viral infection.

Diagnostic usefulness of impulse oscillometry in adult asthmatics with normal lung function

Although conventional spirometry has been used for diagnosing asthma. Clinician should have to serially follow up spirometry during management to confirm variable airflow limitation. However, spirometry have limitations to evaluate asthmatics who have normal lung function. We evaluated diagnostic usefulness of impulse oscillometry (IOS) that could detect peripheral airway impairment relatively early in these patients. Six hundred-eight patients who have had chronic cough over two months were enrolled. All patients underwent spirometry and IOS. Among them, 48 patients were excluded due to underlying lung disease or chronic obstructive lung disease. One hundred-two patients of asthma were excluded due to decreased lung function (predicted forced expiratory volume in 1 second < 80%). Two-hundred sixty asthmatics with normal lung function were compared with 195 non-asthmatic patients. Diagnosis of asthma was made by allergy specialists. Mean values of AX (reactance area) (non-asthmatics vs. asthmatics with normal lung function, 0.36+/-0.21 vs. 0.88+/-0.81), Fres (resonance frequency) (13.21+/-2.91 vs. 15.83+/-6.98), R5 (resistance at 5 Hz) (0.30+/-0.09 vs. 0.39+/-0.14), R20 (resistance at 20 Hz) (0.23+/-0.07 vs. 0.27+/-0.08), R5-R20 (difference between R5 and R20) (0.27+/-0.07 vs. 0.33+/-0.10), X5 (reactance at 5 Hz) (-0.1+/-0.04 vs. -0.15+/-0.09)and Z5 (respiratory impedance at 5 Hz) (0.32+/-0.09 vs. 0.42+/-0.15) were significantly higher in asthmatics than non-asthmatic patients. AX was the most appropriate value for predicting asthma (the area under a receiver operating characteristic curve = 0.745). Optimal cut-off value for AX to diagnose asthma was 0.85. Its sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 39.23%, 97.44%, 95.33%, and 54.60%, respectively. AX also showed significant relationship with asthma in logistic regression (odds ratio: 41.24, p < 0.001). One-point measure of AX (over 0.85) could assist to diagnosis of asthma when patient showed normal lung function at initial visit.

Impact of the COVID-19 pandemic in children with allergic asthma

Impact of the COVID-19 pandemic in children with allergic asthma

The sputum microbiome is distinct between COPD and health, independent of smoking history

BackgroundAirway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.MethodsWe compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.ResultsIn healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera. Haemophilus formed only 3% of the healthy microbiome. In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively. There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history. Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).ConclusionThe healthy and COPD sputum microbiomes are distinct and independent of smoking history. Our results underline the important role for Gammaproteobacteria in COPD.

Oil supplementation with a special combination of n-3 and n-6 long-chain polyunsaturated fatty acids does not protect for exercise induced asthma: a double-blind placebo-controlled trial

BackgroundMany patients suffering from exercise-induced asthma (EIA) have normal lung function at rest and show symptoms and a decline in FEV1 when they do sports or during exercise-challenge. It has been described that long-chain polyunsaturated fatty acids (LCPUFA) could exert a protective effect on EIA.MethodsIn this study the protective effect of supplementation with a special combination of n-3 and n-6 LCPUFA (sc-LCPUFA) (total 1.19 g/ day) were investigated in an EIA cold air provocation model. Primary outcome measure: Decrease in FEV1 after exercise challenge and secondary outcome measure: anti-inflammatory effects monitored by exhaled NO (eNO) before and after sc-LCPUFA supplementation versus placebo.ResultsNinety-nine patients with exercise-induced symptoms aged 10 to 45 were screened by a standardized exercise challenge in a cold air chamber at 4 °C. Seventy-three patients fulfilled the inclusion criteria of a FEV1 decrease > 15% and were treated double-blind placebo-controlled for 4 weeks either with sc-LCPUFA or placebo. Thirty-two patients in each group completed the study. Mean FEV1 decrease after cold air exercise challenge and eNO were unchanged after 4 weeks sc-LCPUFA supplementation.ConclusionSupplementation with sc-LCPUFA at a dose of 1.19 g/d did not have any broncho-protective and anti-inflammatory effects on EIA.Trial registrationClinical trial registration number: NCT02410096. Registered 7 February 2015 at Clinicaltrial.gov