The Association of Normal Range Glycated Hemoglobin with Restrictive Lung Pattern in the General Population

Glycated hemoglobin (HbA1c) is an important diagnostic indicator of diabetes mellitus, and some authors have argued that it is related to impaired lung function in the diabetic population. However, there was rare study for association between lung function and HbA1c in the non-diabetic population. We investigated whether HbA1c below the diagnostic threshold is related to deficits in lung function. We analyzed biochemical and spirometry data from a nation-wide, population-based, case-control study (the KNHANES IV and V). Eligible as cases were all native Koreans aged 40 years or more with no medical illness. A total of 3670 participants were divided into 4 groups according to HbA1c (%) as follows: Group I (n = 842), ≥ 4.0 and ≤ 5.3; Group II (n = 833), > 5.3 and ≤ 5.5; Group III (n = 898), > 5.5 and ≤ 5.7; and Group IV (n = 1097), > 5.7 and ≤ 6.4. Group I had the greatest forced vital capacity (FVC, 96.3 ± 0.5% pred, P < 0.0001), forced expiratory volume per second (FEV₁, 93.8 ± 0.5% pred, P < 0.0001) and FEV₁/FVC (0.792 ± 0.003, P < 0.0001) compared with the other groups. Linear regression showed that HbA1c was closely related to FVC (β = -6.972154, P < 0.0001) and FEV₁ (β = -5.591589, P < 0.0001), but not to FEV₁/FVC. Logistic regression analysis revealed a significant association between HbA1c and a restrictive spirometric pattern (FVC < 80% pred., FEV₁/FVC ≥ 0.70; OR = 3.772, 95% CI = 1.234-11.53), indicating that elevated HbA1c is closely associated with lung impairment in the non-diabetic population. In the healthy population, relatively high HbA1c level is associated with decrements of FVC and FEV₁ and may be a reliable predictor of poor lung function, especially the restrictive pattern.     

Poor Lung Function Has Inverse Relationship with Microalbuminuria,an Early Surrogate Marker of Kidney Damage and Atherosclerosis: The 5th Korea National Health and Nutrition Examination Survey

Background

Despite epidemiological evidences of relationship between poor lung function and atherosclerosis, the relationship between poor lung function and microalbuminuria (MAU), an early surrogate marker of both kidney damage and atherosclerosis, is not well understood. Hence, we plan to investigate the relationship between poor lung function and MAU using multivariate models to adjust for other atherogenic risk factors.

Methods

We used data from the 5^th Korean National Health and Nutrition Examination Survey. Poor lung function is determined by spirometric measurement, primarily through estimation of the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Declines in the percent predicted FVC (<80%) and in the FEV₁/FVC ratio (<0.7) are defined as restrictive and obstructive patterns, respectively. Urine albumin to urine creatinine levels ratio (UACR) were measured in spot urine samples. MAU was defined as UACR >30 mg/g.

Results

Inverse relationship was observed between lung function and UACR. In an age-adjusted regression model, the regression coefficient (B) of 10% lower FVC was 11.09 in men (P = 0.002), which remained significant after adjustment for SBP, FBG, triglyceride level, BMI, smoking history, and heavy alcohol consumption (B = 7.52, P = 0.043). When the restrictive pattern was compared to the normal pattern, the odds ratios (OR) (95% confidence interval, 95%CI) for MAU were 1.90 (1.32–2.72) in men, after adjustment for age, hypertension, diabetes mellitus, triglyceride level, obesity, smoking history, physical activity, and heavy alcohol consumption.

Conclusions

Our study, the first investigation in Asia, demonstrated that the restrictive pattern is related to MAU in men. Furthermore, there was linear relationship between lower FVC and UACR. Thus, our current study suggests that poor lung function, particularly the restrictive pattern, is related to kidney damage as well as atherosclerosis.     

Development and Analysis of Patient-Based Complete Conducting Airways Models

The analysis of high-resolution computed tomography (CT) images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6–10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Other studies have incorporated an algorithmic approach to extrapolate CT segmented airways in order to obtain a complete conducting airway tree down to the level of the acinus. These models have typically been used for mechanistic studies, but also have the potential to be used in a patient-specific setting. In the current study, an image analysis and modelling pipeline was developed and applied to a number of healthy (n = 11) and asthmatic (n = 24) CT patient scans to produce complete patient-based airway models to the acinar level (mean terminal generation 15.8 ± 0.47). The resulting models are analysed in terms of morphometric properties and seen to be consistent with previous work. A number of global clinical lung function measures are compared to resistance predictions in the models to assess their suitability for use in a patient-specific setting. We show a significant difference (p < 0.01) in airways resistance at all tested flow rates in complete airway trees built using CT data from severe asthmatics (GINA 3–5) versus healthy subjects. Further, model predictions of airways resistance at all flow rates are shown to correlate with patient forced expiratory volume in one second (FEV1) (Spearman ρ = −0.65, p < 0.001) and, at low flow rates (0.00017 L/s), FEV1 over forced vital capacity (FEV1/FVC) (ρ = −0.58, p < 0.001). We conclude that the pipeline and anatomical models can be used directly in mechanistic modelling studies and can form the basis for future patient-based modelling studies.     

Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

Background

There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature.

Methods

Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months.

Results

Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV₁] <80% of predicted value). The mean FEV₁ decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV₁>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV₁ decline. Initial FEV₁>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062).

Conclusions

NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.     

The Association of Systemic Microvascular Changes with Lung Function and Lung Density: A Cross-Sectional Study

Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45–84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV₁) (P<0.001) and FEV₁/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV₁ (P = 0.002) but not FEV₁/FVC. Myocardial blood flow (n = 126) was associated with lower FEV₁ (P = 0.02), lower FEV₁/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.     

Effects of seat surface inclination on respiration and speech production in children with spastic cerebral palsy

Background

Respiratory and speech problems are commonly observed in children with cerebral palsy (CP). The purpose of this study was to identify if inclination of seat surface could influence respiratory ability and speech production in children with spastic diplegic CP.

Methods

Sixteen children with spastic diplegic CP, ages 6 to 12 years old, participated in this study. The subjects’ respiratory ability (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximum phonation time (MPT)) were measured in three sitting conditions: a seat surface inclined 0°, anterior 15°, and posterior 15°.

Results

FVC was significantly different across three inclinations of seat surface, F(2, 45) = 3.81, P = 0.03. In particular, the subjects’ FVC at a seat surface inclined anterior 15° was significantly greater than at a seat surface inclined posterior 15° (P < 0.05). However, FEV1, PEF, and MPT were not significantly affected by seat surface inclination (P > 0.05).

Conclusions

The results suggest that anterior inclination of seat surface may provide a positive effect on respiratory function in children with spastic diplegic CP.     

Respiratory Function and Changes in Lung Epithelium Biomarkers after a Short-Training Intervention in Chlorinated vs. Ozone Indoor Pools

Background

Swimming in indoor pools treated with combined chemical treatments (e.g. ozone) may reduce direct exposure to disinfection byproducts and thus have less negative effects on respiratory function compared to chlorinated pools. The aim of this study is to analyze the effects of a short-term training intervention on respiratory function and lung epithelial damage in adults exercising in indoor swimming pool waters treated with different disinfection methods (chlorine vs. ozone with bromine).

Methods

Lung permeability biomakers [surfactant protein D (SP-D) and Clara cell secretory protein (CC16) in plasma] and forced expiratory volumes and flow (FEV1, FVC and FEF_25–75) were measured in 39 healthy adults. Thirteen participants swam during 20 sessions in a chlorinated pool (CP), 13 performed and equivolumic intervention in an ozone pool (OP) and 13 were included in a control group (CG) without exposition.

Results

Median plasma CC16 levels increased in CP swimmers (4.27±3.29 and 6.62±5.51 µg/L, p = 0.01, pre and post intervention respectively) while no significant changes in OP and CG participants were found. No significant changes in median plasma SP-D levels were found in any of the groups after the training period. FVC increased in OP (4.26±0.86 and 4.43±0.92 L, p<0.01) and CP swimmers (4.25±0.86 and 4.35±0.85 L, p<0.01). FEV1 only increased in OP swimmers (3.50±0.65 and 3.59±0.67, p = 0.02) and FEF_25–75 decreased in CP swimmers (3.70±0.87 and 3.37±0.67, p = 0.02).

Conclusion

Despite lung function being similar in both groups, a higher lung permeability in CP compared to OP swimmers was found after a short-term swimming program. Combined chemical treatments for swimming pools such as ozone seem to have less impact on lung epithelial of swimmers compared to chlorinated treated pools.     

Synergistic Impaired Effect between Smoking and Manganese Dust Exposure on Pulmonary Ventilation Function in Guangxi Manganese-Exposed Workers Healthy Cohort (GXMEWHC)

PurposeThe aims of this study were to investigate the effects of manganese (Mn) dust exposure on lung functions and evaluate the potential synergistic effect between smoking and Mn dust exposure among refinery workers.MethodsA retrospective study including 1658 workers in a ferromanganese refinery was conducted, with subjects who were from the Guangxi manganese-exposed workers healthy cohort (GXMEWHC). Based on the Mn manganese cumulative exposure index (Mn-CEI), all subjects were divided into the low exposure group (n = 682) and the high exposure group (n = 976). A pulmonary function test was performed using an electronic spirometer, including the values and percentages of FVC, FEV₁, FEV₁/FVC, MMEF, PEFR, MVV, respectively.ResultsNo significant effect of Mn dust exposure on the pulmonary function was found in the female workers (all p>0.05). However, there was an obvious decrease in the male workers in the high exposure group compared with those in the low exposure group (FVC -60 ml, FEV₁ -120 ml, MMEF -260 ml/s, MVV -5.06 L, all p<0.05). In the high exposure group, the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively. In particular, among the exposed subjects smokers had a statistically significant decrease in lung function compared with non-smokers and the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively (p<0.05). Partial correlation analysis showed that there was also negative correlation between Mn-CEI and decreased changes in MMEF (r = -0.159, p = 0.018) and also MMEF% predicted (r = -0.163, p = 0.015).ConclusionsMn dust can impair the pulmonary ventilation function of male workers but not females, and individual smoking habits and manganese exposure had a synergistic effect on the lung function decrease.     

Eosinophil and T cell markers predict functional decline in COPD patients

Background

The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease.

Methods

Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines.

Results and Discussion

Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05).

Conclusion

These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.     

Associations between lung function and physical and cognitive health in the Canadian Longitudinal Study on Aging (CLSA): A cross-sectional study from a multicenter national cohort

BackgroundLow lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV₁), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population.Methods and findingsFrom the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV₁ with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV₁ (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > −1 SD), 19% (n = 4,353) moderate (z-score −1 to > −2 SD), and 6% (n = 1,329) severely low FEV₁ (z-score = < −2 SD). There was a graded association between lower FEV₁ with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV₁ 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV₁ with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred.ConclusionsWe observed graded associations between lower FEV₁ with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory.

MyLinh Duong and colleagues investigate associations between lung function and self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance.     

Longitudinal associations of adiposity with adult lung function in the Childhood Determinants of Adult Health (CDAH) study

Childhood BMI has been reported to be positively associated with adult lung function. The aim of this study was to investigate the effect of childhood BMI on young adult lung function independently of the effects of lean body mass (LBM). Clinical and questionnaire data were collected from 654 young Australian adults (aged 27-36 years), first studied when age 9, 12, or 15 years. Adult lung function was measured by forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC ratio, and the forced expiratory flow in the middle 50% of FVC (FEF(25-75)). BMI and LBM were derived from anthropometric measures at baseline (1985) and at follow-up (2004-2006). Multivariable models were used to investigate the effect of age and sex standardized BMI in childhood on adult lung function, before and after adjustment for LBM. Adult adiposity had a strong deleterious effect on lung function, irrespective of childhood BMI, and adjustment for childhood LBM eliminated any apparent beneficial effect of childhood BMI on adult FEV(1) or FVC. This suggests that the beneficial effect of increased BMI in childhood on adult FEV(1) and FVC observed in previous longitudinal studies is likely to be attributable to greater childhood LBM not adiposity. Obese children who become obese adults can expect to have poorer lung function than those who maintain healthy weight but large deficits in lung function are also likely for healthy weight children who become obese adults. This highlights the importance of lifetime healthy weight maintenance.     

Small airway morphology and lung function in the transition from normality to chronic airway obstruction.

This study investigated the relationships between pathological changes in small airways (<6 mm perimeter) and lung function in 22 nonasthmatic subjects (20 smokers) undergoing lung resection for peripheral lesions. Preoperative pulmonary function tests revealed airway obstruction [ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) < 70%] in 12 subjects and normal lung function in 10. When all subjects were considered together, total airway wall thickness was significantly correlated with FEV1/FVC (r2 = 0.25), reactivity to methacholine (r2 = 0.26), and slope of linear regression of FVC against FEV1 values recorded during the methacholine challenge (r2 = 0.56). Loss of peribronchiolar alveolar attachments was significantly associated (r2 = 0.25) with a bronchoconstrictor effect of deep inhalation, as assessed from a maximal-to-partial expiratory flow ratio <1, but not with airway responses to methacholine. No significant correlation was found between airway smooth muscle thickness and lung function measurements. In conclusion, this study suggests that thickening of the airway wall is a major mechanism for airway closure, whereas loss of airway-to-lung interdependence may contribute to the bronchoconstrictor effect of deep inhalation in the transition from normal lung function to airway obstruction in nonasthmatic smokers.     

Impact of Emphysema Heterogeneity on Pulmonary Function

Objectives

To investigate the association between emphysema heterogeneity in spatial distribution, pulmonary function and disease severity.

Methods and Materials

We ascertained a dataset of anonymized Computed Tomography (CT) examinations acquired on 565 participants in a COPD study. Subjects with chronic bronchitis (CB) and/or bronchodilator response were excluded resulting in 190 cases without COPD and 160 cases with COPD. Low attenuations areas (LAAs) (≤950 Hounsfield Unit (HU)) were identified and quantified at the level of individual lobes. Emphysema heterogeneity was defined in a manner that ranged in value from −100% to 100%. The association between emphysema heterogeneity and pulmonary function measures (e.g., FEV1% predicted, RV/TLC, and DLco% predicted) adjusted for age, sex, and smoking history (pack-years) was assessed using multiple linear regression analysis.

Results

The majority (128/160) of the subjects with COPD had a heterogeneity greater than zero. After adjusting for age, gender, smoking history, and extent of emphysema, heterogeneity in depicted disease in upper lobe dominant cases was positively associated with pulmonary function measures, such as FEV1 Predicted (p<.001) and FEV1/FVC (p<.001), as well as disease severity (p<0.05). We found a negative association between HI% , RV/TLC (p<0.001), and DLco% (albeit not a statistically significant one, p = 0.06) in this group of patients.

Conclusion

Subjects with more homogeneous distribution of emphysema and/or lower lung dominant emphysema tend to have worse pulmonary function.     

Higher Lipoprotein (a) Levels Are Associated with Better Pulmonary Function in Community-Dwelling Older People – Data from the Berlin Aging Study II

Reduced pulmonary function and elevated serum cholesterol levels are recognized risk factors for cardiovascular disease. Currently, there is some controversy concerning relationships between cholesterol, LDL-cholesterol, HDL-cholesterol, serum triglycerides and lung function. However, most previous studies compared patients suffering from chronic obstructive pulmonary disease (COPD) with healthy controls, and only a small number examined this relationship in population-based cohorts. Moreover, lipoprotein a [Lp(a)], another lipid parameter independently associated with cardiovascular diseases, appears not to have been addressed at all in studies of lung function at the population level. Here, we determined relationships between lung function and several lipid parameters including Lp(a) in 606 older community-dwelling participants (55.1% women, 68±4 years old) from the Berlin Aging Study II (BASE-II). We found a significantly lower forced expiration volume in 1 second (FEV1) in men with low Lp(a) concentrations (t-test). This finding was further substantiated by linear regression models adjusting for known covariates, showing that these associations are statistically significant in both men and women. According to the highest adjusted model, men and women with Lp(a) levels below the 20^th percentile had 217.3ml and 124.2ml less FEV1 and 239.0ml and 135.2ml less FVC, respectively, compared to participants with higher Lp(a) levels. The adjusted models also suggest that the known strong correlation between pro-inflammatory parameters and lung function has only a marginal impact on the Lp(a)-pulmonary function association. Our results do not support the hypothesis that higher Lp(a) levels are responsible for the increased CVD risk in people with reduced lung function, at least not in the group of community-dwelling older people studied here.     

Systemic Inflammation in Young Adults Is Associated with Abnormal Lung Function in Middle Age

Background

Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain.

Methodology/Principal Findings

We evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001) and forced expiratory volume in 1 second (FEV₁) (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001) independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001) and FEV₁ (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001). Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR) per standard deviation 1.51 (95% confidence interval (CI): 1.30–1.75) for fibrinogen and 1.35 (95% CI: 1.14–1.59) for CRP). Higher year 5 fibrinogen was additionally associated with abnormal FEV₁. A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08–2.16).

Conclusion/Significance

Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00005130","term_id":"NCT00005130"}}NCT00005130     

Relation between fat mass, fat free mass and ventilatory function in children and adolescents

The aim of the present study was to evaluate the relation between fat mass (FM), fat free mass (FFM) and ventilatory function in children and adolescents. 1 174 healthy children and adolescents (583 males and 591 females) aged 10-18 years were selected from Heilongjiang Province through random sampling by means of questionnaire and physical examination, and measured for height, weight, waist to hip ratio (WHR), FM, FFM and ventilatory function. The data were analyzed by means of independent-samples t test, Pearson correlation analysis and multi-factors regression analysis. Regardless of sex, an independent positive correlation was found (P<0.001) between age and FFM index (FFMI). FM index (FMI) correlated negatively with age in males (P<0.001), but positively with age in females (P<0.001). Regardless of sex, FFMI correlated positively with forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), forced expiratory flow at 25% of forced vital capacity (FEF25%), FEF50%, and maximal mid-expiratory flow (MMEF) (P<0.05), while negatively with FEV1/FVC (P<0.01). FFMI was correlated positively with FEF75% in males (P<0.05), but not correlated in females. In males, FMI correlated negatively with FEV1, FEV1/FVC, PEF, FEF25%, FEF50%, FEF75% and MMEF (P<0.05), but not correlated with FVC. No correlation was found between the ventilatory function indices and FMI in females. Except FEV1/FVC and FEF75% in males, the effect of FFMI in predicting ventilatory function was higher than FMI regardless of sex. Moreover, the predicting effect of FFMI was higher in males than that in females. Growth spurt of lung function occurred in the ages of 12-15 years in males, while in the ages of 12, 13 and 18 years in females. During the period of growth spurt of lung function, regardless of sex, the effect of FFMI in predicting the lung function was higher than that of age. In conclusion, regardless of sex, FFMI correlates positively with ventilatory function, as a reflection of muscle mass. The effect of FFM in predicting ventilatory function is higher in males than that in females. FM correlates negatively with ventilatory function in males, but not in females. The rapid growth of height and FFM are possibly the main reasons for growth spurt of lung function.     

The vitamin E isoforms α-tocopherol and γ-tocopherol have opposite associations with spirometric parameters: the CARDIA study

Background

Clinical studies of the associations of vitamin E with lung function have reported conflicting results. However, these reports primarily examine the α-tocopherol isoform of vitamin E and have not included the isoform γ-tocopherol which we recently demonstrated in vitro opposes the function of α-tocopherol. We previously demonstrated, in vitro and in animal studies, that the vitamin E isoform α-tocopherol protects, but the isoform γ-tocopherol promotes lung inflammation and airway hyperresponsiveness.

Methods

To translate these findings to humans, we conducted analysis of 4526 adults in the Coronary Artery Risk Development in Young Adults (CARDIA) multi-center cohort with available spirometry and tocopherol data in blacks and whites. Spirometry was obtained at years 0, 5, 10, and 20 and serum tocopherol was from years 0, 7 and 15 of CARDIA.

Results

In cross-sectional regression analysis at year 0, higher γ-tocopherol associated with lower FEV₁ (p = 0.03 in blacks and p = 0.01 in all participants) and FVC (p = 0.01 in blacks, p = 0.05 in whites, and p = 0.005 in all participants), whereas higher α-tocopherol associated with higher FVC (p = 0.04 in blacks and whites and p = 0.01 in all participants). In the lowest quartile of α-tocopherol, higher γ-tocopherol associated with a lower FEV₁ (p = 0.05 in blacks and p = 0.02 in all participants). In contrast, in the lowest quartile of γ-tocopherol, higher α-tocopherol associated with a higher FEV₁ (p = 0.03) in blacks. Serum γ-tocopherol >10 μM was associated with a 175–545 ml lower FEV₁ and FVC at ages 21–55 years.

Conclusion

Increasing serum concentrations of γ-tocopherol were associated with lower FEV1 or FVC, whereas increasing serum concentrations of α-tocopherol was associated with higher FEV1 or FVC. Based on the prevalence of serum γ-tocopherol >10 μM in adults in CARDIA and the adult U.S. population in the 2011 census, we expect that the lower FEV₁ and FVC at these concentrations of serum γ-tocopherol occur in up to 4.5 million adults in the population.     

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

Background

Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes.

Objectives

We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures.

Methods

For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV₁), FEV₁ over forced vital capacity (FEV₁/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF_25-75) was regressed on interval exposure to particulate matter <10 µm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p_interaction<0.05). Replication was attempted for SNPs with MAF>10% in 3320 SAPALDIA participants without GWAS.

Results

On the SNP-level, rs2035268 in gene SNCA accelerated FEV₁/FVC decline by 3.8% (p_interaction = 2.5×10⁻⁶), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p_interaction = 9.7×10⁻⁸) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p_interaction = 3.0×10⁻⁴) on FEV₁/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful.

Conclusions

Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobacco smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challenging.     

稳定期慢性阻塞性肺疾病患者营养不良与甲状腺激素、肺功能及血清IL-6、IL-18的关系研究

目的:观察稳定期慢性阻塞性肺疾病(COPD)患者营养不良与甲状腺激素、肺功能及血清白细胞介素(IL)-6、IL-18的关系。方法:选择2019年1月~2020年12月我院收治的稳定期COPD患者76例作为研究对象。根据患者的微型营养评定(MNA)评分将其分为营养不良组(n=31)和非营养不良组(n=45),比较两组患者的人口学资料、疾病相关因素,甲状腺激素[三碘甲状腺原氨酸(T3)、甲状腺激素(T4)、促甲状腺激素(TSH)]水平,肺功能[第1秒用力呼气量占预测值百分比(FEV1%pred)、第1秒用力呼气量与用力肺活量比值(FEV1/FVC)],血清IL-6、IL-18水平。分析MNA评分与甲状腺激素水平、肺功能及血清IL-6、IL-18水平的相关性。分析患者发生营养不良的危险因素。结果:营养不良组年龄高于非营养不良组(P<0.05)。营养不良组T3、T4、TSH、FEV1%pred、FEV1/FVC显著低于非营养不良组,血清IL-6、IL-18水平显著高于非营养不良组(P<0.05)。稳定期COPD患者的MNA评分与T3、T4、TSH、FEV1%pred、FEV1/FVC呈正相关,与IL-6、IL-18呈负相关(P<0.05)。多因素Logistic回归分析显示,年龄>60岁、T3≤1.60 nmol/L、T4≤73.00 nmol/L、TSH≤1.50 nmol/L、FEV1%pred≤60.00%、FEV1/FVC≤0.54、IL-6≥8.00 pg/mL、IL-18≥47.00 pg/mL是稳定期COPD患者营养不良的危险因素(P<0.05)。结论:稳定期COPD患者营养不良受多种因素影响,临床应针对相关因素给予有效干预,降低此类患者营养不良风险。