Active Asthma and the Prevalence of Physician-Diagnosed COPD

Introduction

Despite the considerable overlap of asthma and chronic obstructive pulmonary disease (COPD), the extent to which the two diagnoses are the manifestations of the same disease remains unresolved. We conducted these analyses to evaluate the role of active asthma in the prevalence of physician-diagnosed COPD.

Methods

From 2006 through 2010, 74,209 adults aged 18–99 years and with a history of asthma participated in the Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-back Survey and responded to interview-administered questionnaires via telephone. We used publicly available data from 71,639 (97%) participants to identify respondents with and without active manifestations of asthma and self-reported, physician-diagnosed COPD. We generated population-weighted estimates of physician-diagnosed COPD prevalence and conducted linear regression to estimate associations between active asthma status and the prevalence of COPD among current smokers, former smokers, and lifetime nonsmokers separately.

Results

Physician-diagnosed COPD was reported in an estimated 29% of the population with any history of asthma, including both active and inactive asthma. Age-specific prevalences of physician-diagnosed COPD were consistently higher among adults with active asthma than adults without active asthma. Compared to inactive asthma, active asthma was associated with an 8.3% [95 % confidence interval (CI) 6.1, 10.5] higher prevalence of physician-diagnosed COPD among lifetime nonsmokers, a 20.6% (95 % CI 18.0, 23.3) higher prevalence among former smokers, and a 26.7% (95 % CI 22.5, 30.9) higher prevalence among current smokers.

Conclusions

Among adults with a history of asthma, active manifestations of asthma may play an important role in the epidemiology of COPD.     

Diabetes mellitus among outpatients with COPD attending a university hospital

Type 2 diabetes mellitus is a common comorbidity of COPD, but there are still many doubts about the relation among diabetes and COPD. We retrospectively collected data from patients afferent to our Respiratory Diseases outpatient clinic at the Tor Vergata University Hospital between 2010 and 2012. The study population was analyzed by clusters of age, gender, body mass index (BMI), smoking status, lung function, concomitant pharmacologic therapies and comorbidities. The values of the association between variables were expressed as odds ratio. Data were adjusted for gender, age and possible confounding variables by Mantel–Haenszel method. We identified 493 patients with COPD. Ninety-two (18.7 %) patients were affected by type 2 diabetes mellitus, with no significant gender differences. The prevalence distribution was similar among the different age clusters, but the association was stronger in patients younger than 65 years. The association was present only in obese subjects in whom it was significant only in patients with moderate-to-severe COPD, but not mild COPD. The presence of cardiovascular diseases was significantly associated with diabetes mellitus in patients with COPD. There was a slight association of inhaled corticosteroid (ICS) use with the presence of diabetes mellitus in COPD, but the combination of an ICS with a β₂-agonist apparently reduced this association. The association with type 2 diabetes mellitus was greater in patients with COPD respect to general population, and correlated with the increase in BMI and the presence of other comorbidities, suggesting that both diseases may be targets of systemic inflammation.     

Clinical characteristics and lung function in chronic obstructive pulmonary disease complicated with impaired peripheral oxygenation

During exercise testing, patients with chronic obstructive pulmonary disease (COPD) often present with ventilatory limitations and various combinations of impaired peripheral oxygenation (IPO) to the exercising muscles. The entities of IPO include anemia, circulation impairment and deconditioning. COPD-IPO is not widely accepted as being a subgroup of COPD. Therefore, the aim of this study was to evaluate the clinical features of COPD-IPO patients. Forty-seven COPD patients underwent cardiopulmonary exercise testing. COPD-IPO was identified when all IPO variables had abnormal values. The patients who did not meet the COPD-IPO criteria were defined as the NIPO group. The variables with abnormal values included peak oxygen uptake ( \( {\dot{\text{V}}\text{O}}_{ 2} \) ) <85 % predicated, anaerobic threshold <40 % \( {\dot{\text{V}}\text{O}}_{{ 2 {\text{max}}}} \) pred, \( {\dot{\text{V}}\text{O}}_{ 2} \) -work rate slope <8.6 ml/watt, oxygen pulse <80 %pred, and ventilatory equivalents for O₂ and CO₂ at nadir (>31 and >34, respectively). Anthropometrics, biochemistry, and lung function were compared between the groups. Forty-six COPD patients were enrolled after excluding one patient who had technical difficulties in performing the exercise tests. Despite FEV₁ and FVC being similarly reduced (p = NS) between the groups, the COPD-IPO (n = 13, 28 %) patients had lower body mass index and were taller, and had impaired diffusing capacity and larger total lung capacity and air-trapping (all p < 0.05). We concluded that COPD patients with all six variables having abnormal values are a unique subgroup and that identification of these patients is worthwhile for further investigations and management such as exercise training and nutritional supplements.     

Relationship of Serum Gamma-Glutamyltransferase Levels with Pulmonary Function and Chronic Obstructive Pulmonary Disease

Background

Gamma-glutamyltransferase (GGT) levels within the normal reference range, possibly a biomarker of oxidative stress and/or exposure to various environmental chemicals, are associated with pulmonary function. However, it is unclear whether it is totally independent of cigarette smoking. Also, the potential interaction between serum GGT and cigarette smoking has not ever been evaluated. Therefore, this study investigated (1) whether serum GGT levels are associated with pulmonary function and chronic obstructive pulmonary disease (COPD), independent of cigarette smoking, and (2) whether there is any interaction between serum GGT and cigarette smoking status on pulmonary function.

Methods

The study subjects were 4,583 participants aged ≥40 in the 2010–2011 Korean National Health and Nutrition Examination Survey. The outcomes were pulmonary function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]) and spirometrically defined COPD.

Results

After adjusting for potential confounders, including cigarette smoking, serum GGT levels were inversely associated with FEV1 and FVC in both genders and positively associated with the risk of COPD in men (all P values <0.01). In men, adjusted odds ratios of COPD were 1.0, 1.69, 1.97, and 2.02 across the quartiles of GGT level (P _trend = 0.002). However, the associations between serum GGT and pulmonary function seemed to differ depending on the smoking status; inverse associations of GGT with FEV1 % and FVC % were clearly observed only among non-current smokers.

Conclusions

In conclusion, in non-smokers serum GGT levels can be used to detect individuals at high risk of decreased pulmonary function and/or COPD.     

Assessment of arterial stiffness in chronic obstructive pulmonary disease by a novel method

Background

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular morbidity and mortality. Increased arterial stiffness is associated with the presence and severity of cardiovascular disease. The cardio-ankle vascular index (CAVI) is a new method for assessment of arterial stiffness that is not influenced by blood pressure at the time of measurement and is significantly correlated with the presence and severity of cardiovascular disease. The aim of the present study was to evaluate whether there is an association between the spirometric severity of COPD, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, with arterial stiffness as assessed by CAVI.

Methods

We enrolled 123 patients with COPD (102 men) followed up by the chest medicine outpatient clinics and 35 healthy subjects (26 men). All patients were assessed with spirometry, CAVI, and clinical history.

Results

Patients with COPD had significantly increased CAVI values compared with control subjects (10.37?±?2.26 vs. 6.74?±?1.42, p?1?% predicted, FEV₁/FVC, and COPD stage (r: ??0.54, p?Conclusion In this study, we have shown that increased arterial stiffness assessed by CAVI is associated with the spirometric severity of COPD.     

Correlations Between Small Airway Function,Ventilation Distribution,and Functional Exercise Capacity in COPD Patients

Background

Interest in using the nitrogen single-breath washout (N₂SBW) test to measure ventilation inhomogeneity and small airway function in COPD patients has grown in recent years. Our aim was to assess the correlation of the measures obtained by the N₂SBW test and other pulmonary function parameters with the six-minute walk distance (6MWD), the degree of dyspnea score, and health status in COPD patients.

Methods

In this cross-sectional study, 31 patients with COPD were subjected to the N₂SBW test, spirometry, whole-body plethysmography, carbon monoxide diffusing capacity measurement, the six-minute walk test, the modified Medical Research Council (mMRC) scale, and the COPD Assessment Test (CAT).

Results

We found a strong correlation between the 6MWD and the phase III slope of the nitrogen single-breath washout (Phase III slope_N2SBW) (r = ?0.796; p = 0.0001). We found moderate correlations between the 6MWD and the residual volume (RV) (r = ?0.651; p = 0.0001) and RV/total lung capacity (RV/TLC) (r = ?0.600; p = 0.0004). We also found moderate correlations between the CAT score and Phase III slope_N2SBW (r = 0.728; p = 0.0001), RV (r = 0.646; p = 0.0001) and RV/TLC (r = 0.603; p = 0.0003). There was a significant difference between the mMRC grades for the following variables: Phase III slope_N2SBW (p = 0.0001), RV (p = 0.0001), and smoking history (p = 0.008). Multivariate analysis showed that Phase III slope_N2SBW was the only independent predictor of the 6MWD (R ²  = 0.703; p = 0.0001), CAT score (R ²  = 0.586; p = 0.0001), and mMRC scale (relative risk = 1.14; p = 0.0001).

Conclusions

In patients with COPD, our findings suggest that the ventilation inhomogeneity impacts the functional exercise capacity, the degree of dyspnea, and health status.     

Significance of relative rib cage and abdomen motion in patients with chronic obstructive pulmonary disease

Changes in intrapleural pressure (ΔPpl) and abdomen pressure (ΔPab) were related to changes in the anterior-posterior diameter of the rib cage (ΔRC) and abdomen (ΔAb) in 17 patients with chronic obstructive pulmonary disease (COPD).ΔPab-ΔPpl equalsΔPdi, the change in transdiaphragmatic pressure. Measurements were made during quiet inspiration in the semierect position.ΔAb/(ΔAb+ΔRC) was used as a measure of relative abdomen motion, andΔPab/ΔPdi was used as a measure of the relative contribution of descent of the diaphragm to the breathing process. Patients with COPD developed greater ΔPdi than normal subjects. This increasedΔPdi was the result of relatively more intercostal and accessory muscle activity rather than increased diaphragm motion. Despite this, patients with COPD showed the same relative abdomen motion as did normal subjects. Observation of relative chest and abdomen motion in patients with COPD is a poor guide to relative use of the rib cage muscles and diaphragm.     

Predictive value of the single-breath nitrogen test for hospitalization due to respiratory disease

The relationship between indices of the single-breath nitrogen test (SBNT) measured in 1974 and hospitalization in the 9 year period 1977–1986 was examined in a random population sample of 876 men aged 46–69 years. Men who could not perform acceptable SBNT tracings had an increased risk of hospitalization due to respiratory disease in general. When age and smoking habits were controlled for, slope of phase III was significantly related to hospitalization due to respiratory disease in general and chronic obstructive pulmonary disease (COPD), whereas closing volume and closing capacity were marginally related to hospitalization due to respiratory disease in general but not to hospitalization due to COPD. The relationship between slope of phase III and hospitalization due to COPD remained significant after the forced expiratory volume in 1 sec (FEV₁) was controlled for: odds ratio 1.4 per % N₂/L (95% confidence interval 1.1–1.7). The effect of the slope of phase III was considered to be clinically insignificant, and we conclude that in a random population sample indices from only 1 SBNT do not provide prognostic information concerning hospitalization in addition to that provided by FEV₁.     

Sociodemographic and disease-related factors are associated with patient-reported anxiety and depression in spondyloarthritis patients in the Swedish SpAScania cohort

Anxiety and depression are common among patients with rheumatic diseases. This study aims to explore which factors are associated with self-reported anxiety and depression in a well-defined cohort of spondyloarthritis (SpA) patients. In 2009, 3,711 patients from the SpAScania cohort were sent a postal questionnaire to assess health-related quality of life (HRQoL) and physical and mental functioning. The Hospital Anxiety and Depression Scale measured anxiety (HADS-A) and depression (HADS-D), subscales 0–21, best–worst. HADS ≥8 indicates possible cases of anxiety or depression. One-way ANOVA (p?HADS scores. Linear regression analysis adjusted for age, gender, and disease duration was used to test for associations between HADS and independent variables. In total, 2,167 (58 %) patients (52 % females, mean age 55.4 years) returned the questionnaire. In total, 683 (32 %) cases were classified as “possible anxiety” and 305 (14 %) as “possible depression” cases with mean (SD) HADS-A 5.9 (4.3) and HADS-D 4.4 (3.6). There were no differences among the SpA subtypes in HADS-A and HADS-D. HADS-A and HADS-D were associated with lower education, lower physical activity (HADS-D only), chronic pain problems, more fatigue, lower general health, lower HRQoL, lower level of functioning, higher disease activity, and lower self-efficacy. Associations with anxiety and/or depression appear multifactorial in patients with SpA including both personal and disease-related factors. Since these comorbidities are increased in SpA and treatable, they should be screened for in clinical practice, possibly with instruments like the HADS.     

Inhibition of transient receptor potential melastatin 7 (TRPM7) channel induces RA FLSs apoptosis through endoplasmic reticulum (ER) stress

Transient receptor potential melastatin 7 (TRPM7) is involved in both normal physiological processes and pathology of various diseases. The purpose of this study was to explore the function and underlying mechanisms of TRPM7 channels in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) apoptosis induced by thapsigargin in vitro. In this study, using a combination of Western blotting, RT-PCR, and nuclear morphology analysis, we investigated the influence and potential function of TRPM7 channels on the apoptosis induced by thapsigargin in RA FLSs. Chemical inhibitors (Gd³⁺ and 2-APB) and specific siRNA for TRPM7 were used to study the role of TRPM7 in RA FLSs apoptosis. The expression of TRPM7 was significantly potentiated in RA FLSs. Co-incubation of RA FLSs with Gd³⁺, 2-APB, or TRPM7-siRNA increased cell apoptosis. Furthermore, we found that suppression of TRPM7 channels also increased the expression CHOP and calpain and decreased the expression caspase-3. We conclude that suppression of TRPM7 channels may increase RA FLSs apoptosis in vitro, and this is associated with endoplasmic reticulum (ER) stress. Therefore, inhibition of TRPM7 could activate ER stress and induce RA FLSs apoptosis.     

EGFR Mutation Testing Practice in Advanced Non-Small Cell Lung Cancer

Purpose

Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients.

Methods

An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients.

Results

24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79 % of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60 % of participants recommend waiting for EGFR test results prior to initiation of first-line therapy.

Conclusions

EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.     

Endovascular Versus Medical Therapy for Atherosclerotic Renovascular Disease

The diagnosis of renal artery stenosis (RAS) has become increasingly common in part due to greater awareness of ischemic renal disease and increased use of diagnostic techniques. Over 90 % of RAS cases are caused by atherosclerotic renovascular disease (ARVD). Patients with ARVD are at high risk for fatal and nonfatal cardiovascular and renal events. The mortality rate in patients with ARVD is high, especially with other cardiovascular or renal comorbidities. Recent clinical studies have provided substantial evidence concerning medical therapy and endovascular interventional therapeutic approaches for ARVD. Despite previous randomized clinical trials, the optimal therapy for ARVD remained uncertain until the results of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial were released recently. CORAL demonstrated that optimal medical therapy was equally effective to endovascular therapy in the treatment of ARVD. Clinicians can now practice with more evidence-based medicine to treat ARVD and potentially decrease mortality in patients with ARVD using optimal medical therapy.     

VEGF neutralization can prevent and normalize arteriovenous malformations in an animal model for hereditary hemorrhagic telangiectasia 2

Arteriovenous malformation (AVM) refers to a vascular anomaly where arteries and veins are directly connected through a complex, tangled web of abnormal AV fistulae without a normal capillary network. Hereditary hemorrhagic telangiectasia (HHT) types 1 and 2 arise from heterozygous mutations in endoglin (ENG) and activin receptor-like kinase 1 (ALK1), respectively. HHT patients possess AVMs in various organs, and telangiectases (small AVMs) along the mucocutaneous surface. Understanding why and how AVMs develop is crucial for developing therapies to inhibit the formation, growth, or maintenance of AVMs in HHT patients. Previously, we have shown that secondary factors such as wounding are required for Alk1-deficient vessels to develop skin AVMs. Here, we present evidences that AVMs establish from nascent arteries and veins rather than from remodeling of a preexistent capillary network in the wound-induced skin AVM model. We also show that VEGF can mimic the wound effect on skin AVM formation, and VEGF-neutralizing antibody can prevent skin AVM formation and ameliorate internal bleeding in Alk1-deficient adult mice. With topical applications at different stages of AVM development, we demonstrate that the VEGF blockade can prevent the formation of AVM and cease the progression of AVM development. Taken together, the presented experimental model is an invaluable system for precise molecular mechanism of action of VEGF blockades as well as for preclinical screening of drug candidates for epistaxis and gastrointestinal bleedings.     

Heterogeneous models for an early discrimination between sepsis and non-infective SIRS in medical ward patients: a pilot study

The objective of the study was to determine the accuracy of phospholipase A2 group II (PLA2-II), interferon-gamma-inducible protein 10 (IP-10), angiopoietin-2 (Ang-2), and procalcitonin (PCT) plasma levels in early ruling in/out of sepsis among systemic inflammatory response syndrome (SIRS) patients. Biomarker levels were determined in 80 SIRS patients during the first 4 h of admission to the medical ward. The final diagnosis of sepsis or non-infective SIRS was issued according to good clinical practice. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for sepsis diagnosis were assessed. The optimal biomarker combinations with clinical variables were investigated by logistic regression and decision tree (CART). PLA2-II, IP-10 and PCT, but not Ang-2, were significantly higher in septic (n = 60) than in non-infective SIRS (n = 20) patients (P ≤ 0.001, 0.027, and 0.002, respectively). PLA2-II PPV and NPV were 88 and 86 %, respectively. The corresponding figures were 100 and 31 % for IP-10, and 93 and 35 % for PCT. Binary logistic regression model had 100 % PPV and NPV, while manual and software-generated CART reached an overall accuracy of 95 and 98 %, respectively, both with 100 % NPV. PLA2-II and IP-10 associated with clinical variables in regression or decision tree heterogeneous models may be valuable biomarkers for sepsis diagnosis in SIRS patients admitted to medical ward (MW). Further studies are needed to introduce them into clinical practice.     

Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?

Aims/hypothesis

South Asians are up to four times more likely to develop type 2 diabetes than white Europeans. It is postulated that the higher prevalence results from greater genetic risk. To evaluate this hypothesis, we: (1) systematically reviewed the literature for single nucleotide polymorphisms (SNPs) predisposing to type 2 diabetes in South Asians; (2) compared risk estimates, risk alleles and risk allele frequencies of predisposing SNPs between South Asians and white Europeans; and (3) tested the association of novel SNPs discovered from South Asians in white Europeans.

Methods

MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry were searched for studies of genetic variants associated with type 2 diabetes in South Asians. Meta-analysis estimates for common and novel bi-allelic SNPs in South Asians were compared with white Europeans from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. The population burden from predisposing SNPs was assessed using a genotype score.

Results

Twenty-four SNPs from 21 loci were associated with type 2 diabetes in South Asians after meta-analysis. The majority of SNPs increase odds of the disorder by 15–35% per risk allele. No substantial differences appear to exist in risk estimates between South Asians and white Europeans from SNPs common to both groups, and the population burden also does not differ. Eight of the 24 are novel SNPs discovered from South Asian genome-wide association studies, some of which show nominal associations with type 2 diabetes in white Europeans.

Conclusions/interpretation

Based on current literature there is no strong evidence to indicate that South Asians possess a greater genetic risk of type 2 diabetes than white Europeans.     

Is early postpartum HbA1c an appropriate risk predictor after pregnancy with gestational diabetes mellitus?

Compared to the 2-h oral glucose tolerance test (OGTT), the assessment of HbA1c was proposed as a less time-consuming alternative to detect pathologies in carbohydrate metabolism. This report aims to assess the predictive accuracy of HbA1c to detect alterations in glucose disposition early after gestational diabetes mellitus (GDM) pregnancy. A detailed metabolic characterization was performed in 77 women with previous GDM (pGDM) and 41 controls 3–6 month after delivery: 3-h OGTT, frequently sampled intravenous glucose tolerance test. Follow-up examinations of pGDMs were performed up to 10 years. HbA1c (venous samples, HPLC) was assessed at baseline as well as during the follow-up period (475 patient contacts). Moderate associations were observed between HbA1c and measurements of plasma glucose during the OGTT at the baseline examination: The strongest correlation was found for FPG (r = 0.40, p < 0.001), decreasing after ingestion. No associations were detected between HbA1c and OGTT dynamics of insulin or C-peptide. Moreover, baseline HbA1c showed only modest correlation with insulin sensitivity (r = ?0.25, p = 0.010) and disposition index (r = ?0.26, p = 0.007). A linear model including fasting as well as post-load glucose levels was not improved by HbA1c. However, pGDM females with overt diabetes manifestation during the follow-up period showed more pronounced increasing HbA1c in contrast to females remaining normal glucose tolerant or developing prediabetes. It is suggested that the performance of HbA1c assessed early after delivery is inferior to the OGTT for the detection of early alterations in glucose metabolism. However, an increase in HbA1c levels could be used as an indicator of risk for diabetes manifestation.     

The coactivator PGC-1α regulates skeletal muscle oxidative metabolism independently of the nuclear receptor PPARβ/δ in sedentary mice fed a regular chow diet

Aims/hypothesis

Physical activity improves oxidative capacity and exerts therapeutic beneficial effects, particularly in the context of metabolic diseases. The peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α) and the nuclear receptor PPARβ/δ have both been independently discovered to play a pivotal role in the regulation of oxidative metabolism in skeletal muscle, though their interdependence remains unclear. Hence, our aim was to determine the functional interaction between these two factors in mouse skeletal muscle in vivo.

Methods

Adult male control mice, PGC-1α muscle-specific transgenic (mTg) mice, PPARβ/δ muscle-specific knockout (mKO) mice and the combination PPARβ/δ mKO + PGC-1α mTg mice were studied under basal conditions and following PPARβ/δ agonist administration and acute exercise. Whole-body metabolism was assessed by indirect calorimetry and blood analysis, while magnetic resonance was used to measure body composition. Quantitative PCR and western blot were used to determine gene expression and intracellular signalling. The proportion of oxidative muscle fibre was determined by NADH staining.

Results

Agonist-induced PPARβ/δ activation was only disrupted by PPARβ/δ knockout. We also found that the disruption of the PGC-1α–PPARβ/δ axis did not affect whole-body metabolism under basal conditions. As expected, PGC-1α mTg mice exhibited higher exercise performance, peak oxygen consumption and lower blood lactate levels following exercise, though PPARβ/δ mKO + PGC-1α mTg mice showed a similar phenotype. Similarly, we found that PPARβ/δ was dispensable for PGC-1α-mediated enhancement of an oxidative phenotype in skeletal muscle.

Conclusions/interpretation

Collectively, these results indicate that PPARβ/δ is not an essential partner of PGC-1α in the control of skeletal muscle energy metabolism.     

Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies

Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen κ = 0.962) and moderate agreement between the IgM aPS/PT assays (κ = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods.     

Mitochondrial function and mitochondrial DNA maintenance with advancing age

We review the impact of mitochondrial DNA (mtDNA) maintenance and mitochondrial function on the aging process. Mitochondrial function and mtDNA integrity are closely related. In order to create a protective barrier against reactive oxygen and nitrogen species (RONS) attacks and ensure mtDNA integrity, multiple cellular mtDNA copies are packaged together with various proteins in nucleoids. Regulation of antioxidant and RONS balance, DNA base excision repair, and selective degradation of damaged mtDNA copies preserves normal mtDNA quantities. Oxidative damage to mtDNA molecules does not substantially contribute to increased mtDNA mutation frequency; rather, mtDNA replication errors of DNA PolG are the main source of mtDNA mutations. Mitochondrial turnover is the major contributor to maintenance of mtDNA and functionally active mitochondria. Mitochondrial turnover involves mitochondrial biogenesis, mitochondrial dynamics, and selective autophagic removal of dysfunctional mitochondria (i.e., mitophagy). All of these processes exhibit decreased activity during aging and fall under greater nuclear genome control, possibly coincident with the emergence of nuclear genome instability. We suggest that the age-dependent accumulation of mutated mtDNA copies and dysfunctional mitochondria is associated primarily with decreased cellular autophagic and mitophagic activity.     

Hospital Readmissions with Exacerbation of Obstructive Pulmonary Disease in Illicit Drug Smokers

Purpose

Patients with obstructive pulmonary disease (asthma or chronic obstructive pulmonary disease—COPD) who smoke illicit drugs are at an increased risk of hospital admissions. We compared hospital readmission rates due to exacerbations of obstructive pulmonary disease amongst patients who were current/ex-illicit drug smokers versus current/ex-tobacco smokers.

Methods

We reviewed all the admissions between January 2009 and September 2011 with a presumptive diagnosis of an ‘exacerbation of COPD’ retrospectively from our COPD admission database.

Results

There were 950 sequential hospital admissions in 709 patients over a 33-month period; 250 ex-tobacco smokers, 370 current tobacco smokers and 89 current/ex-illicit drug smokers. Recurrent hospital admission rates with exacerbation of obstructive pulmonary disease were higher in the illicit drug smokers compared with current/ex-tobacco smokers (1.00 versus 0.22/0.26, p < 0.001). Illicit drug smokers were younger [50 versus 72.9/69.9 (mean 71.2) years, p < 0.001] and had shorter length of hospital stay [7.44 versus 9.28/10.69 (mean 9.87) days, p = 0.038]. Illicit drug smokers with FEV₁ < 1 litre (L) had higher readmissions than ex/current tobacco smokers with FEV₁ < 1 L (p < 0.001). Admissions requiring non-invasive ventilation for type 2 respiratory failure were more common in illicit drug smokers (8.4 versus 3 %, p < 0.002).

Conclusion

We have shown that readmission rates in illicit drug smokers with FEV₁ < 1 L are higher than in tobacco smokers. Studies are needed to determine whether targeting these illicit drug users with an intensive community intervention package (to include early therapy, pulmonary rehabilitation) will reduce readmission rates in this often neglected population.