Socioeconomic Status and Longitudinal Lung Function of Healthy Mexican Children

Introduction

Our aim was to estimate the longitudinal effect of Socioeconomic status (SES) on lung function growth of Mexican children and adolescents.

Materials and Methods

A cohort of Mexican children in third grade of primary school was followed with spirometry twice a year for 6 years through secondary school. Multilevel mixed-effects lineal models were fitted for the spirometric variables of 2,641 respiratory-healthy Mexican children. Monthly family income (in 2002 U.S. dollars [USD]) and parents’ years completed at school were used as proxies of SES.

Results

Individuals with higher SES tended to have greater height for age, and smaller sitting height/standing height and crude lung function. For each 1-year increase of parents’ schooling, Forced expiratory volume in 1 sec (FEV₁) and Forced vital capacity (FVC) increased 8.5 (0.4%) and 10.6 mL (0.4%), respectively (p <0.05) when models were adjusted for gender. Impact of education on lung function was reduced drastically or abolished on adjusting by anthropometric variables and ozone.

Conclusions

Higher parental schooling and higher monthly family income were associated with higher lung function in healthy Mexican children, with the majority of the effect likely due to the increase in height-for-age.     

Dietary intake,lung function and airway inflammation in Mexico City school children exposed to air pollutants

Introduction

Air pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children. Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants.

Methods

A total of 158 asthmatic children recruited at the Children''s Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks. Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks. Dietary intake was evaluated using a 108-item food frequency questionnaire and a fruit and vegetable index (FVI) and a Mediterranean diet index (MDI) were constructed. The impact of these indices on lung function and interleukin-8 (IL-8) and their interaction with air pollutants were determined using mixed regression models with random intercept and random slope.

Results

FVI was inversely related to IL-8 levels in nasal lavage (p < 0.02) with a significant inverse trend (test for trend p < 0.001), MDI was positively related to lung function (p < 0.05), and children in the highest category of MDI had a higher FEV₁ (test for trend p < 0.12) and FVC (test for trend p < 0.06) than children in the lowest category. A significant interaction was observed between FVI and ozone for FEV₁ and FVC as was with MDI and ozone for FVC. No effect of diet was observed among healthy children.

Conclusion

Our results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City.     

Instability in the COPD Diagnosis upon Repeat Testing Vary with the Definition of COPD

Background

A low FEV₁/FVC from post-bronchodilator spirometry is required to diagnose COPD. Both the FEV₁ and the FVC can vary over time; therefore, individuals can be given a diagnosis of mild COPD at one visit, but have normal spirometry during the next appointment, even without an intervention.

Methods

We analyzed two population-based surveys of adults with spirometry carried out for the same individuals 5-9 years after their baseline examination. We determined the factors associated with a change in the spirometry interpretation from one exam to the next utilizing different criteria commonly used to diagnose COPD.

Results

The rate of an inconsistent diagnosis of mild COPD was 11.7% using FEV₁/FVC <0.70, 5.9% using FEV₁/FEV₆ <the lower limit of the normal range, LLN and 4.1% using the GOLD stage 2-4 criterion. The most important factor associated with diagnostic inconsistency was the closeness of the ratio to the LLN during the first examination. Inconsistency decreased with a lower FEV₁.

Conclusions

Using FEV₁/FEV₆ <LLN or GOLD stage 2-4 as the criterion for airflow obstruction reduces inconsistencies in the diagnosis of mild COPD. Further improvement could be obtained by defining a borderline zone around the LLN (e.g. plus or minus 0.6 SD), or repeating the test in patients with borderline results.     

Clinical Implications of Having Reduced Mid Forced Expiratory Flow Rates (FEF25-75), Independently of FEV1, in Adult Patients with Asthma

Introduction

FEF_25-75 is one of the standard results provided in spirometry reports; however, in adult asthmatics there is limited information on how this physiological measure relates to clinical or biological outcomes independently of the FEV₁ or the FEV₁/FVC ratio.

Purpose

To determine the association between Hankinson’s percent-predicted FEF_25-75 (FEF_25-75%) levels with changes in healthcare utilization, respiratory symptom frequency, and biomarkers of distal airway inflammation.

Methods

In participants enrolled in the Severe Asthma Research Program 1–2, we compared outcomes across FEF_25-75% quartiles. Multivariable analyses were done to avoid confounding by demographic characteristics, FEV₁, and the FEV₁/FVC ratio. In a sensitivity analysis, we also compared outcomes across participants with FEF_25-75% below the lower limit of normal (LLN) and FEV₁/FVC above LLN.

Results

Subjects in the lowest FEF_25-75% quartile had greater rates of healthcare utilization and higher exhaled nitric oxide and sputum eosinophils. In multivariable analysis, being in the lowest FEF_25-75% quartile remained significantly associated with nocturnal symptoms (OR 3.0 [95%CI 1.3–6.9]), persistent symptoms (OR 3.3 [95%CI 1–11], ICU admission for asthma (3.7 [1.3–10.8]) and blood eosinophil % (0.18 [0.07, 0.29]). In the sensitivity analysis, those with FEF_25-75% <LLN had significantly more nocturnal and persistent symptoms, emergency room visits, higher serum eosinophil levels and increased methacholine responsiveness.

Conclusions

After controlling for demographic variables, FEV₁ and FEV₁/FVC, a reduced FEF_25-75% is independently associated with previous ICU admission, persistent symptoms, nocturnal symptoms, blood eosinophilia and bronchial hyperreactivity. This suggests that in some asthmatics, a reduced FEF_25-75% is an independent biomarker for more severe asthma.     

Investigation of Hydrogen Sulfide Exposure and Lung Function,Asthma and Chronic Obstructive Pulmonary Disease in a Geothermal Area of New Zealand

Background

Results have been conflicting whether long-term ambient hydrogen sulfide (H₂S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world’s largest population exposed to ambient H₂S—from geothermal sources.

Objectives

We investigated associations of H₂S with lung function, COPD and asthma in this population.

Methods

1,204 of 1,639 study participants, aged 18–65 years during 2008–2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H₂S monitoring networks across Rotorua. Four metrics for H₂S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H₂S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV₁/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV₁ response to bronchodilator) with H₂S exposure quartiles.

Results

None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H₂S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H₂S exposures were beneficially associated with lung function parameters.

Conclusions

The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H₂S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H₂S exposures require confirmation in other studies.     

Long-Term Once-Daily Tiotropium Respimat? Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised,Placebo-Controlled Study

Background

This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β₂-agonist (LABA).

Methods

285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209). Primary objective: to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV₁) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.

Results

At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV₁ and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.

Conclusions

The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.

Trial Registration

ClinicalTrials.gov NCT01340209     

Association between Air Pollutants and Asthma Emergency Room Visits and Hospital Admissions in Time Series Studies: A Systematic Review and Meta-Analysis

Background

Air pollution constitutes a significant stimulus of asthma exacerbations; however, the impacts of exposure to major air pollutants on asthma-related hospital admissions and emergency room visits (ERVs) have not been fully determined.

Objective

We sought to quantify the associations between short-term exposure to air pollutants [ozone (O₃), carbon monoxide (CO), nitrogen dioxide (NO₂), sulfur dioxide (SO₂), and particulate matter ≤10μm (PM₁₀) and PM_2.5] and the asthma-related emergency room visits (ERV) and hospitalizations.

Methods

Systematic computerized searches without language limitation were performed. Pooled relative risks (RRs) and 95% confidence intervals (95%CIs) were estimated using the random-effect models. Sensitivity analyses and subgroup analyses were also performed.

Results

After screening of 246 studies, 87 were included in our analyses. Air pollutants were associated with significantly increased risks of asthma ERVs and hospitalizations [O₃: RR(95%CI), 1.009 (1.006, 1.011); I² = 87.8%, population-attributable fraction (PAF) (95%CI): 0.8 (0.6, 1.1); CO: RR(95%CI), 1.045 (1.029, 1.061); I² = 85.7%, PAF (95%CI): 4.3 (2.8, 5.7); NO₂: RR(95%CI), 1.018 (1.014, 1.022); I² = 87.6%, PAF (95%CI): 1.8 (1.4, 2.2); SO₂: RR(95%CI), 1.011 (1.007, 1.015); I² = 77.1%, PAF (95%CI): 1.1 (0.7, 1.5); PM₁₀: RR(95%CI), 1.010 (1.008, 1.013); I² = 69.1%, PAF (95%CI): 1.1 (0.8, 1.3); PM_2.5: RR(95%CI), 1.023 (1.015, 1.031); I² = 82.8%, PAF (95%CI): 2.3 (1.5, 3.1)]. Sensitivity analyses yielded compatible findings as compared with the overall analyses without publication bias. Stronger associations were found in hospitalized males, children and elderly patients in warm seasons with lag of 2 days or greater.

Conclusion

Short-term exposures to air pollutants account for increased risks of asthma-related ERVs and hospitalizations that constitute a considerable healthcare utilization and socioeconomic burden.     

COPD phenotype description using principal components analysis

Background

Airway inflammation in COPD can be measured using biomarkers such as induced sputum and Fe_NO. This study set out to explore the heterogeneity of COPD using biomarkers of airway and systemic inflammation and pulmonary function by principal components analysis (PCA).

Subjects and Methods

In 127 COPD patients (mean FEV₁ 61%), pulmonary function, Fe_NO, plasma CRP and TNF-α, sputum differential cell counts and sputum IL8 (pg/ml) were measured. Principal components analysis as well as multivariate analysis was performed.

Results

PCA identified four main components (% variance): (1) sputum neutrophil cell count and supernatant IL8 and plasma TNF-α (20.2%), (2) Sputum eosinophils % and Fe_NO (18.2%), (3) Bronchodilator reversibility, FEV₁ and IC (15.1%) and (4) CRP (11.4%). These results were confirmed by linear regression multivariate analyses which showed strong associations between the variables within components 1 and 2.

Conclusion

COPD is a multi dimensional disease. Unrelated components of disease were identified, including neutrophilic airway inflammation which was associated with systemic inflammation, and sputum eosinophils which were related to increased Fe_NO. We confirm dissociation between airway inflammation and lung function in this cohort of patients.     

Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

Background

Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.

Methods

We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV₁) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV₁ by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.

Results

The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10^-7). In addition, meta-analysis using the five cohorts with ≥3 FEV₁ measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10^-8) at genome-wide significance. Neither locus was associated with FEV₁ decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV₁ decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.

Conclusions

In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV₁ that harbor candidate genes with biologically plausible functional links to lung function.     

Long-term air pollution exposure and living close to busy roads are associated with COPD in women

Background

Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution. However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far. Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women. We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.

Methods

In consecutive cross sectional studies conducted between 1985–1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany. NO₂ and PM₁₀ exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data. Lung function was determined and COPD was defined by using the GOLD criteria. Chronic respiratory symptoms and possible confounders were defined by questionnaire data. Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.

Results

The prevalence of COPD (GOLD stages 1–4) was 4.5%. COPD and pulmonary function were strongest affected by PM₁₀ and traffic related exposure. A 7 μg/m₃ increase in five year means of PM₁₀ (interquartile range) was associated with a 5.1% (95% CI 2.5%–7.7%) decrease in FEV₁, a 3.7% (95% CI 1.8%–5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03–1.72) for COPD. Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06–3.02) than for those living farther away. Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.

Conclusion

Chronic exposure to PM₁₀, NO₂ and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function.     

Lacrimal Cytokines Assessment in Subjects Exposed to Different Levels of Ambient Air Pollution in a Large Metropolitan Area

Background

Air pollution is one of the most environmental health concerns in the world and has serious impact on human health, particularly in the mucous membranes of the respiratory tract and eyes. However, ocular hazardous effects to air pollutants are scarcely found in the literature.

Design

Panel study to evaluate the effect of different levels of ambient air pollution on lacrimal film cytokine levels of outdoor workers from a large metropolitan area.

Methods

Thirty healthy male workers, among them nineteen professionals who work on streets (taxi drivers and traffic controllers, high pollutants exposure, Group 1) and eleven workers of a Forest Institute (Group 2, lower pollutants exposure compared to group 1) were evaluated twice, 15 days apart. Exposure to ambient PM_2.5 (particulate matter equal or smaller than 2.5 μm) was 24 hour individually collected and the collection of tears was performed to measure interleukins (IL) 2, 4, 5 and 10 and interferon gamma (IFN-γ) levels. Data from both groups were compared using Student’s t test or Mann- Whitney test for cytokines. Individual PM_2.5 levels were categorized in tertiles (lower, middle and upper) and compared using one-way ANOVA. Relationship between PM_2.5 and cytokine levels was evaluated using generalized estimating equations (GEE).

Results

PM_2.5 levels in the three categories differed significantly (lower: ≤22 μg/m³; middle: 23–37.5 μg/m³; upper: >37.5 μg/m³; p<0.001). The subjects from the two groups were distributed unevenly in the lower category (Group 1 = 8%; Group 2 = 92%), the middle category (Group 1 = 89%; Group 2 = 11%) and the upper category (Group 1 = 100%). A significant relationship was found between IL-5 and IL-10 and PM_2.5 levels of the group 1, with an average decrease of 1.65 pg/mL of IL-5 level and of 0.78 pg/mL of IL-10 level in tear samples for each increment of 50 μg/m3 of PM_2.5 (p = 0.01 and p = 0.003, respectively).

Conclusion

High levels of PM_2.5 exposure is associated with decrease of IL-5 and IL-10 levels suggesting a possible modulatory action of ambient air pollution on ocular surface immune response.     

Pulmonary Impairment in Tuberculosis Survivors: The Korean National Health and Nutrition Examination Survey 2008-2012

Objectives

Pulmonary tuberculosis (TB) can affect lung function, but studies regarding long-term follow-up in patients with no sequelae on chest X-ray (CXR) have not been performed. We evaluated lung functional impairment and persistent respiratory symptoms in those with prior pulmonary TB and those with prior pulmonary TB with no residual sequelae on CXR, and determined risk factors for airflow obstruction.

Methods

We used data from adults aged ≥ 40 years from the annual Korean National Health and Nutrition Examination Surveys conducted between 2008 and 2012. P values for comparisons were adjusted for age, sex, and smoking status.

Results

In total of 14,967 adults, 822 subjects (5.5%) had diagnosed and treated pulmonary TB (mean 29.0 years ago). The FVC% (84.9 vs. 92.6), FEV₁% (83.4 vs. 92.4), and FEV₁/FVC% (73.4 vs. 77.9) were significantly decreased in subjects with prior pulmonary TB compared to those without (p < 0.001, each). In 12,885 subjects with no sequalae on CXR, those with prior pulmonary TB (296, 2.3%) had significantly lower FEV₁% (90.9 vs. 93.4, p = 0.001) and FEV₁/FVC% (76.6 vs. 78.4, p < 0.001) than those without. Subjects with prior pulmonary TB as well as subjects with no sequalae on CXR were more likely to experience cough and physical activity limitations due to pulmonary symptoms than those without prior pulmonary TB (p < 0.001, each). In total subjects, prior pulmonary TB (OR, 2.314; 95% CI, 1.922–2.785), along with age, male, asthma, and smoking mount was risk factor for airflow obstruction. In subjects with prior pulmonary tuberculosis, inactive TB lesion on chest x-ray (OR, 2.300; 95% CI, 1.606–3.294) were risk factors of airflow obstruction.

Conclusion

In addition to subjects with inactive TB lesion on CXR, subjects with no sequelae on CXR can show impaired pulmonary function and respiratory symptoms. Prior TB is a risk factor for airflow obstruction and that the risk is more important when they have inactive lesions on chest X-ray. Hence, the patients with treated TB should need to have regular follow-up of lung function and stop smoking for early detection and prevention of the chronic airway disease.     

Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis

Background

Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis.

Method

Studies were identified by an electronic search of PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang databases, including publications prior toAugust 2014. Pooled hazard ratios (HR) for overall survival (OS) were aggregated and quantitatively analyzed by meta-analysis.

Results

Twenty-two studies (n = 2154) were evaluated in the meta-analysis. Combined HR suggested that bFGF overexpression had an adverse impact on survival of patients with lung cancer(HR = 1.202,95%CI, 1.022–1.382). Our subgroup analysis revealed that the combined HR evaluating bFGF expression on OS in operable non-small cell lung cancer (NSCLC) was 1.553 (95%CI, 1.120–1.986); the combined HR in small cell lung cancer (SCLC) was 1.667 (95%CI, 1.035–2.299). There was no significant impact of bFGF expression on survival in advanced NSCLC.

Conclusion

This meta-analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC, but is not associated with outcome in advanced NSCLC. The data suggests that high bFGF expression is highly related to poor prognosis. Nevertheless,more high-quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer.     

Decreased Histone Deacetylase 2 (HDAC2) in Peripheral Blood Monocytes (PBMCs) of COPD Patients

Background

Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD). However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear.

Methods

PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers. The HDAC2 and NF-κB p65 expression were quantified by Western Blot. HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit. Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA.

Results

HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers. Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers. The FEV₁%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients. Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers.

Conclusions

HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity. The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation. Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function.     

Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers – Is There a Specific Role for Mast Cells?

Background

Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath.

Methods

Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test), measurement of fractional exhaled nitric oxide (FeNO) and pH/8-isoprostane in exhaled breath condensate (EBC). Lung tissue sections containing cancer-free large (LA) and small airways (SA) were stained for inflammatory cells. Mucosal (MC_T) respectively connective tissue mast cells (MC_TC) and interleukin-17A (IL-17A) expression by mast cells was analysed using a double-staining protocol.

Results

The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MC_T were higher in the lamina propria of SA compared to LA (MC_TC: 49 vs. 27.4 cells/mm²; MC_T: 162.5 vs. 35.4 cells/mm²; P<0.005 for both instances). IL-17A expression was predominantly detected in MC_TC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (r_s= -0.39), for the FEV₁% pred. (r_s= 0.37) and for FEV₁/FVC ratio (r_s=0.38) with MC_T in SA (P<0.05 for all instances). 8-isoprostane concentration correlated with the mast cells in the SA (r_s=0.44), there was no correlation for pH or FeNO with cellular distribution in SA.

Conclusions

Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the lack of correlation with lung function and exhaled breath parameters.     

Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease

Background

Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT.

Methods

One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results.

Results

Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV₁/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV₁ (%predicted), FEV₁/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R² = 0.51, p<0.0001). These results were replicated in the Vietnamese population.

Conclusions

The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD.     

Effects of PM2.5 and NO2 on the 8-isoprostane and lung function indices of FVC and FEV1 in students of Ahvaz city,Iran

The aim of this study was to determine the correlation between PM_2.5 and NO₂ pollutants and oxidative stress marker (8-isoprostane) and lung function tests (FVC and FEV₁) in healthy children who were living and studying in three different areas of Ahvaz city including A₁: Naderi site with high traffic, A₂: Alavi Alley site with average traffic, and A₃: Ein 2 site with low traffic (a rural area on the suburb of Ahvaz). 30 students in the 12–13 year-old range were selected from each studied zone (1, 2 and 3 sites) during three months of year. Of each student, one sample was taken every two weeks to measure 8-isoprostane of exhaled breath condensate (EBC). Air pollution data were collected from three air quality monitoring stations. Also, the relationship between air pollution and 8-isoprostane as well as lung function tests were determined using generalized estimating equations (GEE). The mean concentration of PM_2.5 and NO₂ in A₁, A₂ and A₃ areas were 116, 92 and 45 (μg/m³) also 77, 53 and 14 (ppb) respectively. Among all studied students, there was a significant correlation between the increase of mean concentration of PM_2.5 and NO₂ in 1–4 before sampling day, increased 8-isoprostane concentration and decreased FEV₁, while there was no significant correlation between them and decreased FVC. In A₁ site, an increase in IQR (13 μg/m³) PM_2.5 and IQR (6.5 ppb) NO₂ on 1–4 days before sampling was associated with 0.38 unit (95% CI: 0.11, 0.65) and 1.1 unit (95% CI: 0.85, 1.35) increase in 8-isoprostane concentration, also decreased 121 ml and 190 ml FEV₁, respectively. Results showed that the short-term exposure to traffic-related air pollution can decrease the values of lung function indices and increase the oxidative stress. It may adversely affect children’s lungs.     

Parathyroid Hormone as a Novel Biomarker for Chronic Obstructive Pulmonary Disease: Korean National Health and Nutrition Examination Survey

Objective

To understand and predict chronic obstructive pulmonary disease (COPD), a biomarker that reflects disease severity is needed.

Research Design and Methods

Data from 10269 adults aged over 40 years of age were retrieved from the Korea National Health and Nutrition Examination Survey (KNHANES), and 1302 patients met the criteria for COPD. The association between values of vitamin D and parathyroid hormone (PTH), and COPD severity including lung function and quality of life, were analyzed.

Results

In COPD patients, lung function was inversely related to PTH values (P = 0.02 for FVC [% predicted]; P < 0.001 for FEV₁ [% predicted]); however, the association of lung function with vitamin D levels was not statistically significant in a multivariable analysis. Value of PTH was independently associated with EQ5D-index (P = 0.04), but vitamin D level showed no significant relationship with EQ5D-index (P = 0.59) or EQ5D-VAS (P = 0.81).

Conclusions

Elevation of PTH, unlike vitamin D, is independently associated with COPD severity, and may be a better biomarker for COPD.     

Positive Association between APOA5 rs662799 Polymorphism and Coronary Heart Disease: A Case-Control Study and Meta-Analysis

Objective

Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism.

Methods

We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software.

Results

Significant differences were observed between CHD cases and controls at the level of both genotype (χ² = 8.964, df = 2, P = 0.011) and allele (χ² = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089–1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ² = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088–1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001).

Conclusion

Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.