Biomarker Of Airway Inflammation Research Articles

Particles in Exhaled Air (PExA): Clinical Uses and Future Implications.

Access to distal airway samples to assess respiratory diseases is not straightforward and requires invasive procedures such as bronchoscopy and bronchoalveolar lavage. The particles in exhaled air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles (PEx) sized around 0.5-7 μm and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can count particles and measure particle mass according to their size. The PEx particles can be analysed for metabolites on various analytical platforms to quantitatively measure targeted and untargeted lung specific markers of inflammation. As such, the measurement of distal airway components may help to evaluate acute and chronic inflammatory conditions such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and more recently, acute viral infections such as COVID-19. PExA may provide an alternative to traditional methods of airway sampling, such as induced sputum, tracheal aspirate, or bronchoalveolar lavage. The measurement of specific biomarkers of airway inflammation obtained directly from the RTLF by PExA enables a more accurate and comprehensive understanding of pathophysiological changes at the molecular level in patients with acute and chronic lung diseases.

CDC167 exhibits potential as a biomarker for airway inflammation in asthma.

Current asthma treatments have been discovered to decrease the risk of disease progression. Herein, we aimed to characterize novel potential therapeutic targets for asthma. Differentially expressed genes (DEGs) for GSE64913 and GSE137268 datasets were characterized. Weighted correlation network analysis (WGCNA) was used to identify trait-related module genes within the GSE67472 dataset. The intersection of the module genes of interest, as well as the DEGs, comprised the key module genes that underwent additional candidate gene screening using machine learning. In addition, a bioinformatics-based approach was used to analyze the relative expression levels, diagnostic values, and reverently enriched pathways of the screened candidate genes. Furthermore, the candidate genes were silenced in asthmatic mice, and the inflammation and lung injury in the mice were validated. A total of 1710 DEGs were characterized in GSE64913 and GSE137268 for asthma patients. WGCNA identified 2367 asthma module genes, of which 285 overlapped with 1710 DEGs. Four candidate genes, CDC167, POSTN, SEC14L1, and SERPINB2, were validated using the intersection genes of three machine learning algorithms, including Least Absolute Shrinkage and Selection Operator, Random Forest, and Support Vector Machine. All the candidate genes were significantly upregulated in asthma patients and demonstrated diagnostic utility for asthma. Furthermore, silencing CDC167 reduced the levels of inflammatory cytokines significantly and alleviated lung injury in ovalbumin (OVA)-induced asthmatic mice. Our study demonstrated that CDC167 exhibits potential as diagnostic markers and therapeutic targets for asthma patients.

Specific Ventilation in Severe Asthma Evaluated with Noncontrast Tidal Breathing 1H MRI.

Purpose To determine if proton (1H) MRI-derived specific ventilation is responsive to bronchodilator (BD) therapy and associated with clinical biomarkers of type 2 airway inflammation and airways dysfunction in severe asthma. Materials and Methods In this prospective study, 27 participants with severe asthma (mean age, 52 years ± 9 [SD]; 17 female, 10 male) and seven healthy controls (mean age, 47 years ± 16; five female, two male), recruited between 2018 and 2021, underwent same-day spirometry, respiratory oscillometry, and tidal breathing 1H MRI. Participants with severe asthma underwent all assessments before and after BD therapy, and type 2 airway inflammatory biomarkers were determined (blood eosinophil count, sputum eosinophil percentage, sputum eosinophil-free granules, and fraction of exhaled nitric oxide) to generate a cumulative type 2 biomarker score. Specific ventilation was derived from tidal breathing 1H MRI and its response to BD therapy, and relationships with biomarkers of type 2 airway inflammation and airway dysfunction were evaluated. Results Mean MRI specific ventilation improved with BD inhalation (from 0.07 ± 0.04 to 0.11 ± 0.04, P < .001). Post-BD MRI specific ventilation (P = .046) and post-BD change in MRI specific ventilation (P = .006) were greater in participants with asthma with type 2 low biomarkers compared with participants with type 2 high biomarkers of airway inflammation. Post-BD change in MRI specific ventilation was correlated with change in forced expiratory volume in 1 second (r = 0.40, P = .04), resistance at 5 Hz (r = -0.50, P = .01), resistance at 19 Hz (r = -0.42, P = .01), reactance area (r = -0.54, P < .01), and reactance at 5 Hz (r = 0.48, P = .01). Conclusion Specific ventilation evaluated with tidal breathing 1H MRI was responsive to BD therapy and was associated with clinical biomarkers of airways disease in participants with severe asthma. Keywords: MRI, Severe Asthma, Ventilation, Type 2 Inflammation Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Moore and Chandarana in this issue.

SNPs in FAM13A and IL2RB genes are associated with FeNO in adult subjects with asthma

Nitric oxide has different roles in asthma as both an endogenous modulator of airway function and a pro-inflammatory mediator. Fractional exhaled nitric oxide (FeNO) is a reliable, quantitative, non-invasive, simple, and safe biomarker for assessing airways inflammation in asthma. Previous genome-wide and genetic association studies have shown that different genes and single nucleotide polymorphisms (SNPs) are linked to FeNO. We aimed at identifying SNPs in candidate genes or gene regions that are associated with FeNO in asthma. We evaluated 264 asthma cases (median age 42.8 years, female 47.7%) who had been identified in the general adult population within the Gene Environment Interactions in Respiratory Diseases survey in Verona (Italy; 2008–2010). Two hundred and twenty-one tag-SNPs, which are representative of 50 candidate genes, were genotyped by a custom GoldenGate Genotyping Assay. A two-step association analysis was performed without assuming an a priori genetic model: step (1) a machine learning technique [gradient boosting machine (GBM)] was used to select the 15 SNPs with the highest variable importance measure; step (2) the GBM-selected SNPs were jointly tested in a linear regression model with natural log-transformed FeNO as the normally distributed outcome and with age, sex, and the SNPs as covariates. We replicated our results within an independent sample of 296 patients from the European Community Respiratory Health Survey III. We found that SNP rs987314 in family with sequence similarity 13 member A (FAM13A) and SNP rs3218258 in interleukin 2 receptor subunit beta (IL2RB) gene regions are significantly associated with FeNO in adult subjects with asthma. These genes are involved in different mechanisms that affect smooth muscle constriction and endothelial barrier function responses (FAM13A), or in immune response processes (IL2RB). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation.

Low Serum Levels of Zinc, Selenium, and Vitamin D3 Are Biomarkers of Airway Inflammation and Poor Asthma Control: A Two-Centre Study.

Background Asthma is a chronic inflammatory disease with its control beingaffected by underlying oxidative stress. Trace elements, along with vitamin D3, play an important role in immune alterations leading to an imbalance of Th1/Th2 helper cells. However, their role in asthma pathogenesis and control is inconsistent and inconclusive. The objective of our study was to assess levels of serum trace elementslike zinc, copper, selenium, iron, magnesium,vitamin D3 levels, IgE, and HsCRP in asthmatic children, compare with healthy controls, and assess their association with the level of asthma control. Methods A cross-sectional study was conducted from 2019 to 2021 enrolling 100 asthmatic children and 75 healthy controls. The level of asthma control was assessed as uncontrolled, partly controlled, and controlled asthma as per GINA Guidelines. Mean and standard deviation were calculated for each element and mean differences between groups were analyzed by student t-test. A p-value of <0.05 was considered significant. Results The mean age was 8.75±2.89 yrs in cases and 9.04±2.79 in controls. A total of 57.6% of cases had atopic comorbidities. The mean serum zinc levels were 51±12.8 mg/dl, which was very low in asthmatic children as compared to 60±18.2mg/dl (p-value 0.0002) in healthy controls. Serum selenium was 13±3 µg/dl in asthmatics vs. 15±4 µg/dl (p-value 0.0002) in healthy controls. Serum copper was 115.2±21.92µg/dl vs. 125.3±31.99µg/dl (p-value 0.015), Serum vitamin D3 levels were 13.07±7.82ng/ml vs. 17.82±14.62 ng/ml(p-value 0.006) in both groups, respectively. SIgE and HsCRP were high in asthmatic children suggestive of eosinophilic inflammation. Serum zinc was 49±5.45 mg/dl in the uncontrolled group, 53±6.1 in the partly controlled, and 58±8.0 in the well-controlled group (p<0.0001). Serum selenium was 10± 3.0 µg/dlin the uncontrolled group vs. 13± 2.0 and 14± 2.0 µg/dl in the partly controlled and well-controlled groups, respectively (p-value <0.0001). Vitamin D3 wassignificantly low (9.32±5.95ng/dl) in the uncontrolled group vs. 12.99±4.97 and 13.40±5.92 ng/dl(p<0.005) in the partly controlled and well-controlled groups respectively. Vitamin D3 showed a strong positive correlation with zinc (r=0.4,p< 0.0001) and a negative correlation with inflammatory markers like SIgE and HsCRP. Conclusion Children with asthma had low zinc, selenium, and vitamin D3 levels, and were associated with airway inflammation and poor asthma control.

Detection of bile acids in bronchoalveolar lavage fluid defines the inflammatory and microbial landscape of the lower airways in infants with cystic fibrosis

BackgroundCystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota.ResultsDetection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage.ConclusionsDetection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties.AFd3CvqLfCjKZ9n4H93NFTVideo

The Potential of Fractional Exhaled Nitric Oxide as a Biomarker in Predicting and Optimizing Use of Treatment in Asthma

Asthma affects the respiratory system and causes airway inflammation. The indication of asthma includes a triad of airway inflammation, hyperresponsiveness, and obstruction. Nitric Oxide (NO) is a gas that is exhaled and is a sign of airway inflammation. NO levels in the exhaled breath of patients with type 2 asthma are elevated, and fractional exhaled nitric oxide (FeNO) is an objective biomarker of airway inflammation. Measurements of FeNO are noninvasive, require minimal patient effort, and are easy to collect in clinical settings. The current review is a systematic review performed using PubMed, Science Direct, and Google Scholar according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) guidelines. This review discusses the entanglement of understanding FeNO measurement and supplementing existing diagnostic and assessment tools for inflammatory lung diseases. Monitoring FeNO can also help identify different asthma phenotypes within the asthma syndrome and suggest the optimal administration of inhaled corticosteroids (ICS) as elevated FeNO levels indicate ICS response. Non-adherence to ICS is a significant contributor to the failure of asthma treatment. A FeNO suppression test can be done to determine non-adherence. FeNO levels should be used with a careful history, conventional spirometric testing with bronchodilator reversibility, measures of bronchial hyperreactivity using methacholine, and other measures of eosinophilic inflammation, such as a peripheral blood eosinophil cell count. FeNO is more sensitive and specific when paired with other lung function tests.

Exploring the Interaction between Fractional Exhaled Nitric Oxide and Biologic Treatment in Severe Asthma: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a biomarker of airway inflammation associated with airway hyper-responsiveness and type-2 inflammation. Its role in the management of severe asthmatic patients undergoing biologic treatment, as well as FeNO dynamics during biologic treatment, is largely unexplored. The aim was to evaluate published data contributing to the following areas: (1) FeNO as a predictive biomarker of response to biologic treatment; (2) the influence of biologic treatment in FeNO values; (3) FeNO as a biomarker for the prediction of exacerbations in patients treated with biologics. The systematic search was conducted on the Medline database through the Pubmed search engine, including all studies from 2009 to the present. Higher baseline values of FeNO are associated with better clinical control in patients treated with omalizumab, dupilumab, and tezepelumab. FeNO dynamics during biologic treatment highlights a clear reduction in FeNO values in patients treated with anti-IL4/13 and anti-IL13, as well as in patients treated with tezepelumab. During the treatment, FeNO may help to predict clinical worsening and to differentiate eosinophilic from non-eosinophilic exacerbations. Higher baseline FeNO levels appear to be associated with a greater benefit in terms of clinical control and reduction of exacerbation rate, while FeNO dynamics during biologic treatment remains a largely unexplored issue since few studies have investigated it as a primary outcome. FeNO remains detectable during biologic treatment, but its potential utility as a biomarker of clinical control is still unclear and represents an interesting research area to be developed.

Studying the Role of Alveolar Exhaled Nitric Oxide in Combination with Bronchial Nitric Oxide to Predict Asthma Control in Children with Asthma: A Real-Life Prospective Study

Background: Fractional exhaled nitric oxide (FENO) is currently used as a biomarker of airway inflammation in patients with asthma. However, the role of alveolar nitric oxide (CANO) in asthmatic children has not been clearly demonstrated Methods: It was a prospective and descriptive study. The measurement of FENO and CANO, spirometry, blood eosinophil counts (BEC), and total IgE levels were performed for each study subject. Results: This study included 109 uncontrolled asthmatic children without inhaled corticosteroid (ICS) treatment. The exhaled NO level in asthmatic patients was significantly higher than in control subjects: FENO: 22.5 vs. 8.4 ppb; CANO: 5.9 vs. 2.8 ppb; J’awNO (maximum airway nitric oxide flux): 56.9 vs. 18.7 ppb; respectively. The sensitivities and specificities for asthma diagnosis with the cut-off of CANO at 3.5 ppb and 5.0 ppb were 74.3% and 73.3%, and 46.0% and 83.3%, respectively. There were the moderate and the weak correlations between CANO with FENO and CANO with IgE in asthmatic patients (r = 0.465, 95%CI (0.133-0.659), P=0.001; r=0.133, 95%CI (0.068- 0.497), P=0.184; respectively). The percentage of controlled asthma in patients with CANO ≥5 ppb at inclusion was higher than that in CANO &lt;5 ppb group. Conclusion: Exhaled NO is a relevant biomarker of allergic asthma. The level of FENO and CANO might be used to predict asthma control in children.

ROLE OF HIGH- SENSITIVITY C REACTIVE PROTEIN (hs-CRP) IN ASSESSMENT OF ASTHMA CONTROL IN CHILDREN

Introduction: Data are scarce on hs-CRP as a biomarker for airway inflammation in pediatric asthma. We aimed to examine correlation between hs-CRP and asthma control levels. Methods: Children with physician- diagnosed asthma, ages 6 to 15 years, were enrolled. GINA-2016 criteria were used to assess the level of asthma control. The relationships between serum hs-CRP and each of asthma control measures (Asthma control criteria, spirometry, impulse oscillometry, eosinophil counts and Fractional exhaled nitric oxide (FeNO) were assessed. Results: 150 asthmatic children were enrolled; 52 (35%) had well controlled asthma, 76 (51%), and 22 (14%) children had partly controlled and uncontrolled asthma, respectively. Median (IQR) values of hs-CRP were 0.47 (0.1, 1.67) mg/L in well controlled, 0.30 (0.1, 1.83) mg/L in partly controlled, and 2.74 (0.55, 3.74) mg/L in uncontrolled asthma (p = 0.029). Using Receiver Operator Characteristic (ROC) curve analysis, area under curve for hs-CRP mg/L to discriminate between uncontrolled and (controlled + partly controlled) asthma was 0.67 (95% CI 0.55, 0.80) and a cutoff 1.1 mg/L of serum hs-CRP level had a sensitivity of 68.1% with specificity of 67.97%. In two groups of hs-CRP (< 3 mg/L) and hs-CRP (≥ 3 mg/L), high hs-CRP group had higher proportion of uncontrolled asthmatic children (p = 0.03). Conclusion: We observed higher serum hs-CRP values in children with uncontrolled asthma suggesting its potential role as a biomarker of asthma control.

Clinically relevant effects of Mindfulness-Based Stress Reduction in individuals with asthma

BackgroundPsychological distress and comorbid psychopathology contribute to exacerbation risk in patients with asthma. Thus, interventions designed to reduce stress and improve emotion regulation, such as Mindfulness-Based Stress Reduction (MBSR), may augment standard care. Few studies have addressed this question and a paucity of data exists to determine the ability of MBSR to impact clinical outcomes in asthma. MethodsThis randomized controlled trial investigated effects of MBSR training on asthma control and airway inflammation, in relation to psychological symptoms, in adults with asthma. Participants were randomized to an 8-week MBSR training (n = 35) or wait-list control group (n = 34). Clinically relevant asthma assessments, including Asthma Control Questionnaire and inflammatory biomarkers, were collected at baseline and six approximately-monthly follow-ups. Self-reported mindfulness, distress, depression, and anxiety symptoms were assessed at baseline, post-intervention, and study completion. Chronic stress level was determined at baseline only. ResultsAsthma control improved significantly in individuals randomized to MBSR, relative to wait-list controls (p = .01; effect size d = 0.76), which was maintained at 4mo post-intervention. 32% of MBSR participants achieved a clinically significant improvement, based on the ACQ6 Minimally Important Difference, relative to 12% of wait-list participants. Moreover, MBSR-related improvement in asthma control was associated with a reduction in distress (p = .043) and the intervention was most efficacious for those with the highest baseline depressive symptoms (p = .023). Importantly, MBSR also reduced levels of exhaled nitric oxide, a biomarker of airway inflammation, relative to wait-list controls (p < .05). ConclusionSupporting and extending extant evidence of mind-body relationships in asthma and the benefits of stress reduction for these patients, this is, to the best of our knowledge, the first RCT to demonstrate that training in MBSR improves clinically relevant asthma outcomes. MBSR may thus be a valuable addition to optimal asthma management, particularly for those with comorbid psychopathology. Clinical trial registrationNCT02157766.

Status of TNF-α and IL-6 as pro-inflammatory cytokines in exhaled breath condensate of late adolescents with asthma and healthy in the dust storm and non-dust storm conditions.

Exposure to airborne particulate matter (PM) can be considered as an important risk factor for human health. Some cytokines have been recognized as the biomarkers of exposure to air pollution. Experimental studies indicate that PM exposure could be associated with inflammation. Thus, the purpose of this study was to evaluate whether the exposure to air PM is associated with biomarkers of inflammation. The specific aim of this study was to determine the correlation between airborne PM levels and IL-6 and TNF-α as airway inflammation biomarkers among two groups of late adolescents in northwest of Iran. This study included 46 subjects, comprising 23 asthmatic subjects and 23 non-asthmatic persons. Environmental PM (PM10, PM2.5 and PM1) levels were measured in dust storm and non-dust storm days during both cold and warm seasons. Following the sampling of PM, Two pro-inflammatory cytokines of IL-6 and TNF-α in exhaled breath condensate (EBC) were also determined in the EBC samples via commercial ELISA kits. Daily mean ambient air PM10, PM2.5 and PM1 concentrations during the dust storm days was 221.79, 93.13 and 25.52 μg m-3 and in non-dusty days 48.37, 18.54 and 6.1 μg m-3, respectively. Biomarkers levels were significantly (p < 0.001) higher in asthmatic students compared to the non-asthmatic subjects. EBC cytokines levels were increased in dust storm days compared to the non-dusty days (p < 0.001) and were positively correlated with different size of ambient PM concentration. Dust storm conditions can increase the pro-inflammatory cytokines and cause adverse effects on pulmonary health and lung tissue damage.

Short-term effects of personal exposure to temperature variability on cardiorespiratory health based on subclinical non-invasive biomarkers

Growing literatures have explored the cardiorespiratory health effects of the daily temperature, but such effects of temperature variability remain unclear. We investigated the acute associations of personal levels of temperature variability with cardiorespiratory biomarkers. This is a panel study with four repeated measurements among forty eligible college students in Hefei, Anhui Province, China. We collected personal-level temperature data using temperature/humidity data loggers. Temperature variability parameters included diurnal temperature range (DTR), the standard-deviation of temperature (SDT) and temperature variability (TV). Cardiorespiratory health indicators included three BP parameters [systolic BP (SBP), diastolic BP (DBP) and mean article pressure (MAP)], fractional exhaled nitric oxide (FeNO), and four saliva biomarkers [C-reactive protein (CRP), cortisol, alpha-amylase and lysozyme]. Linear mixed-effect models were then used to assess the associations of temperature variability with these cardiorespiratory biomarkers. We found that short-term exposure to the three temperature variability parameters was associated with these cardiorespiratory biomarkers. The magnitude, direction and significance of these associations varied by temperature variability parameters, by biomarkers and by lags of exposure. Specifically, temperature variability parameters were inversely associated with BP and saliva lysozyme; positively associated with airway inflammation biomarkers (FeNO and saliva CRP) and stress response biomarkers (saliva cortisol and alpha-amylase). The results were robust to further control for air pollutants, and these associations were more prominent in females and in subjects with abnormal body mass index. Our findings suggested that acute exposure to temperature variability could significantly alter cardiorespiratory biomarker profiles among healthy young adults in China.

Extracellular Traps: A Novel Therapeutic Target for Severe Asthma.

Asthma is a complicated disease defined by a combination of clinical symptoms and physiological characteristics. Typically, asthma is diagnosed by the presence of episodic cough, wheezing, or dyspnea triggered by variable environmental factors (allergens and respiratory infections), and reversible airflow obstruction. To date, the majority of asthmatic patients have been adequately controlled by anti-inflammatory/bronchodilating agents, but those with severe asthma (SA) have not been sufficiently controlled by high-dose inhaled corticosteroids-long-acting beta-agonists plus additional controllers including leukotriene modifiers. Accordingly, these uncontrolled patients provoke a special issue, because they consume high healthcare resources, requiring innovative precision medicine solutions. Recently, phenotyping based on biomarkers of airway inflammation has led to elucidating the pathophysiological mechanism of SA, where emerging evidence has highlighted the significance of eosinophil or neutrophil extracellular traps contributing to the development of SA. Here, we aimed to provide current findings about extracellular traps as a novel therapeutic target for asthma to address medical unmet needs.

Biomarkers of airway inflammation and immunotherapy

Biomarkers of airway inflammation and immunotherapy

Associations between outdoor air pollution, ambient temperature and fraction of exhaled nitric oxide (FeNO) in university students in northern China - A panel study

BackgroundNorthern China has severe air pollution, especially in winter. Fractional exhaled nitric oxide (FeNO) is an established biomarker of airway inflammation. AimTo study associations between ambient temperature, air pollution and FeNO in university students in northern China. MethodsWe performed a panel study in 67 university students without asthma diagnosis in the city of Taiyuan. FeNO was measured 6 times, over one heating season. Outdoor PM10, PM2.5, SO2, NO2 and O3 were measured at a fixed location in the campus. SO2, NO2 and O3 were measured 7 days (24 h/day) before the FeNO test. PM2.5 and PM10 were measured at different lag times (lag 1 day to lag 7 days). Temperature and carbon monoxide (CO) data were collected from a nearby monitoring station (lag 7). Linear mixed models were applied to study associations between exposure and FeNO, adjusting for gender, age, current smoking, height and furry pet or pollen allergy. ResultsThe overall geometric mean (GM) of FeNO was 17.2 ppb. GM of FeNO was lowest (12.9 ppb) in January and highest (20.0 ppb) in April. The range of lag 7 pollution was 105.0–339.0 μg/m3 for PM10, 72.0–180.0 μg/m3 for PM2.5, 36.0–347.0 μg/m3 for SO2, 26.0–69.0 μg/m3 for NO2, 31.0–163.0 μg/m3 for O3 and 0.93–3.14 mg/m3 for CO. The lag 7 temperature ranged from −4.5 to 20.1 °C. FeNO was consistently higher at higher outdoor temperature (p < 0.001). In multi-pollutant models with temperature adjustment, PM10, PM2.5 and SO2 were associated with FeNO (all p-values <0.001). In contrast, CO was negatively associated (protective) with FeNO (p < 0.001). Associations between exposure and FeNO were similar in men and women. ConclusionPM10, PM2.5 and SO2 and outdoor temperature can be associated with airway inflammation, measured as FeNO, in young adults in northern China while CO could be negatively associated with FeNO.

Comprehensive assessment of the relation between clinical symptoms, functional parameters and biomarkers of airway inflammation

Background: Asthma is a chronic inflammatory disorder of the airways causing bronchial hyper-responsiveness that is characterized by variable and recurring symptoms and airflow obstruction. Asthma is characterized by multiple biomarkers measurable in biological fluids. To become useful, these biomarkers need to be quantifiable by reliable systems, reproducible in the clinical setting, easy to obtain and cost-effective. bjective: The current study aimed to assess the relation between clinical symptoms, functional parameters and biomarkers of airway inflammation. Materials and Methods: This prospective, observational and single-center study carried out in the outpatient and inpatient department of Thoracic medicine, Tirunelveli Medical College Hospital, Tamil Nadu, India from June-2017 to June-2018 was aimed to assess the relation between clinical symptoms, functional parameters and biomarkers of airway inflammation in all stable asthmatic patients of 18–60 years of age. The severity of asthma was assessed according to the GINA criteria, based on clinical symptoms and pulmonary function test. Blood samples were collected for absolute eosinophil count and induced sputum samples for eosinophil count. Data was entered in Microsoft Excel and statistical analysis was performed by t-test. p&lt;0.05 was considered statistically significant.

FeNO in Asthma.

Asthma is a common disease affecting 350 million people worldwide, which is characterized by airways inflammation and hyperreactivity. Historically diagnosis and treatment have been mainly based on symptoms, which have the potential to result in misdiagnosis and inappropriate treatment. Nitric oxide (NO) is exhaled in human breath and is a marker of airways inflammation. Levels of NO are increased in the exhaled breath of patients with type 2 asthma and fractional exhaled nitric oxide (FeNO) provides an objective biomarker of airway inflammation. FeNO testing is an accessible, noninvasive, and easy-to-use test. Cut-off values have been established by the American Thoracic Society (ATS), the Global Initiative for Asthma (GINA), and the National Institute for Health and Care Excellence (NICE) but vary between guidance. FeNO levels have been shown to be predictive of blood and sputum eosinophil levels but should not be used in isolation and current guidance emphasizes the importance of incorporating clinical symptoms and testing when utilizing FeNO results. The inclusion of FeNO testing can increase diagnostic accuracy of asthma, while high levels in asthmatic patients can help predict response to inhaled corticosteroids (ICS) and suppression of levels with ICS to monitor adherence. FeNO levels are also a predictor of asthma risk with increased exacerbation rates and accelerated decline in lung function associated with high levels as well as having an emerging role in predicting response to some biologic therapies in severe asthma. FeNO testing is cost-effective and has been shown, when combined with clinical assessment, to improve asthma management.

Chronic air pollution-induced subclinical airway inflammation and polygenic susceptibility

BackgroundAir pollutants can activate low-grade subclinical inflammation which further impairs respiratory health. We aimed to investigate the role of polygenic susceptibility to chronic air pollution-induced subclinical airway inflammation.MethodsWe used data from 296 women (69–79 years) enrolled in the population-based SALIA cohort (Study on the influence of Air pollution on Lung function, Inflammation and Aging). Biomarkers of airway inflammation were measured in induced-sputum samples at follow-up investigation in 2007–2010. Chronic air pollution exposures at residential addresses within 15 years prior to the biomarker assessments were used to estimate main environmental effects on subclinical airway inflammation. Furthermore, we calculated internally weighted polygenic risk scores based on genome-wide derived single nucleotide polymorphisms. Polygenic main and gene-environment interaction (GxE) effects were investigated by adjusted linear regression models.ResultsHigher exposures to nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter with aerodynamic diameters of ≤ 2.5 μm, ≤ 10 μm, and 2.5–10 µm significantly increased the levels of leukotriene (LT)B4 by 19.7% (p-value = 0.005), 20.9% (p = 0.002), 22.1% (p = 0.004), 17.4% (p = 0.004), and 23.4% (p = 0.001), respectively. We found significant effects of NO2 (25.9%, p = 0.008) and NOx (25.9%, p-value = 0.004) on the total number of cells. No significant GxE effects were observed. The trends were mostly robust in sensitivity analyses.ConclusionsWhile this study confirms that higher chronic exposures to air pollution increase the risk of subclinical airway inflammation in elderly women, we could not demonstrate a significant role of polygenic susceptibility on this pathway. Further studies are required to investigate the role of polygenic susceptibility.Graphical

Role of air pollutants mediated oxidative stress in respiratory diseases.

Airborne particulate (PM) components from fossil fuel combustion can induce oxidative stress initiated by reactive oxygen species (ROS) that are strongly correlated with airway inflammation and asthma. A valid biomarker of airway inflammation is fractionated exhaled nitric oxide (FENO). The oxidative potential of PM2.5 can be evaluated with the dithiothreitol (DTT) dosage, which represents both ROS chemically produced and intracellular ROS of macrophages. This correlates with quality indicators of the internal environment and ventilation strategies such as dilution and removal of airborne contaminants.