New GOLD classification: longitudinal data on group assignment

Rationale

Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD).

Objective

To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only.

Methods

We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV₁%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data.

Results

At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722).

Conclusions

In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index.     

Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline

Background

To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population.

Methods

Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010. Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping. Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline. And another 9SNPs were selected from HapMap website as HHIP tags. In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses.

Results

We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population. And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations.

Conclusions

These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population. Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0209-3) contains supplementary material, which is available to authorized users.     

Airflow limitation or static hyperinflation: which is more closely related to dyspnea with activities of daily living in patients with COPD?

Background

Dyspnea while performing the activities of daily living has been suggested to be a better measurement than peak dyspnea during exercise. Furthermore, the inspiratory capacity (IC) has been shown to be more closely related to exercise tolerance and dyspnea than the FEV₁, because dynamic hyperinflation is the main cause of shortness of breath in patients with COPD. However, breathlessness during exercise is measured in most studies to evaluate this relationship.

Purpose

To evaluate the correlation between breathlessness during daily activities and airflow limitation or static hyperinflation in COPD.

Methods

We examined 167 consecutive outpatients with stable COPD. The Baseline Dyspnea Index (BDI) was used to evaluate dyspnea with activities of daily living. The relationship between the BDI score and the clinical measurements of pulmonary function was then investigated.

Results

The Spearman rank correlation coefficients (Rs) between the BDI score and the FEV₁(L), FEV₁(%pred) and FEV₁/FVC were 0.60, 0.56 and 0.56, respectively. On the other hand, the BDI score also correlated with the IC, IC/predicted total lung capacity (TLC) and IC/TLC (Rs = 0.45, 0.46 and 0.47, respectively). Although all of the relationships studied were strongly correlated, the correlation coefficients were better between dyspnea and airflow limitation than between dyspnea and static hyperinflation. In stepwise multiple regression analyses, the BDI score was most significantly explained by the FEV₁ (R² = 26.2%) and the diffusion capacity for carbon monoxide (R² = 14.4%) (Cumulative R² = 40.6%). Static hyperinflation was not a significant factor for clinical dyspnea on the stepwise multiple regression analysis.

Conclusion

Both static hyperinflation and airflow limitation contributed greatly to dyspnea in COPD patients.     

Importance of Aspergillus spp. isolation in Acute exacerbations of severe COPD: prevalence,factors and follow-up: the FUNGI-COPD study

Background

Acute exacerbations of COPD (AECOPD) are often associated with infectious agents, some of which may be non-usual, including Aspergillus spp. However, the importance of Aspergillus spp. in the clinical management of AECOPD still remains unclear.

Objectives

The aims of the study were to analyze the prevalence and risk factors associated with Aspergillus spp. isolation in AECOPD, and to investigate the associated clinical outcomes during a 1-year follow-up period.

Methods

Patients presenting with an AECOPD requiring hospitalization were prospectively included from four hospitals across Spain. Clinical, radiological and microbiological data were collected at admission and during the follow-up period (1, 6 and 12 months after discharge), and re-admissions and mortality data collected during the follow-up.

Results

A total of 240 patients with severe AECOPD were included. Valid sputum samples were obtained in 144 (58%) patients, and in this group, the prevalence of Aspergillus spp. isolation was 16.6% on admission and 14.1% at one-year follow-up. Multivariate logistic-regression showed that AECOPD in the previous year (OR 12.35; 95% CI, 1.9-29.1; p < 0.001), concurrent isolation of pathogenic bacteria (OR 3.64; 95% CI 1.65-9.45, p = 0.001) and concomitant isolation of Pseudomonas aeruginosa (OR 2.80; 95% IC, 1.81-11.42; p = 0.001) were the main risk factors for Aspergillus spp. isolation.

Conclusions

The main risk factors for Aspergillus spp. isolation were AECOPD in the previous year and concomitant isolation of Pseudomonas aeruginosa. However, although Aspergillus spp. is often isolated in sputum samples from patients with AECOPD, the pathogenic and clinical significance remains unclear.     

Thrombin-Anti-Thrombin Levels and Patency of Arterio-Venous Fistula in Patients Undergoing Haemodialysis Compared to Healthy Volunteers: A Prospective Analysis

Background

Patients on haemodialysis (HD) are at an increased risk of sustaining thrombotic events especially to their vascular access which is essential for maintenance of HD.

Objectives

To assess whether 1) markers of coagulation, fibrinolysis or endothelial activation are increased in patients on HD compared to controls and 2) if measurement of any of these factors could help to identify patients at increased risk of arteriovenous (AVF) access occlusion.

Patients/Methods

Venous blood samples were taken from 70 patients immediately before a session of HD and from 78 resting healthy volunteers. Thrombin-antithrombin (TAT), D-dimer, von Willebrand factor (vWF), plasminogen activator inhibitor-1 antigen (PAI-1) and soluble p-selectin were measured by ELISA. C-reactive protein (hsCRP) was measured by an immunonephelometric kinetic assay. Determination of the patency of the AVF was based upon international standards and was prospectively followed up for a minimum of four years or until the AVF was non-functioning.

Results

A total of 70 patients were studied with a median follow-up of 740 days (range 72-1788 days). TAT, D-dimer, vWF, p-selectin and hsCRP were elevated in patients on HD compared with controls. At one year follow-up, primary patency was 66% (46 patients). In multivariate analysis TAT was inversely associated with primary assisted patency (r= -0.250, p= 0.044) and secondary patency (r = -0.267, p= 0.031).

Conclusions

The novel finding of this study is that in patients on haemodialysis, TAT levels were increased and inversely correlated with primary assisted patency and secondary patency. Further evaluation is required into the possible role of TAT as a biomarker of AVF occlusion.     

Observational study on the impact of initiating tiotropium alone versus tiotropium with fluticasone propionate/salmeterol combination therapy on outcomes and costs in chronic obstructive pulmonary disease

Background

This retrospective cohort study compared the risks of exacerbations and COPD-related healthcare costs between patients with chronic obstructive pulmonary disease (COPD) initiating tiotropium (TIO) alone and patients initiating triple therapy with fluticasone-salmeterol combination (FSC) added to TIO.

Methods

Managed-care enrollees who had an index event of ≥ 1 pharmacy claim for TIO during the study period (January 1, 2003-April 30, 2008) and met other eligibility criteria were categorized into one of two cohorts depending on their medication use. Patients in the TIO+FSC cohort had combination therapy with TIO and FSC, defined as having an FSC claim on the same date as the TIO claim. Patients in the TIO cohort had no such FSC use. The risks of COPD exacerbations and healthcare costs were compared between cohorts during 1 year of follow-up.

Results

The sample comprised 3333 patients (n = 852 TIO+FSC cohort, n = 2481 TIO cohort). Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation (hazard ratio 0.772; 95% confidence interval [CI] 0.641, 0.930) and any exacerbation (hazard ratio 0.763; 95% CI 0.646, 0.949) and a nonsignificant reduction in COPD-related adjusted monthly medical costs.

Conclusions

Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation and any exacerbation over a follow-up period of up to 1 year. These improvements were gained with triple therapy at roughly equal cost of that of TIO alone.     

Prevalence and Burden of Breathlessness in Patients with Chronic Obstructive Pulmonary Disease Managed in Primary Care

Background & Aims

Breathlessness is a primary clinical feature of chronic obstructive pulmonary disease (COPD). We aimed to describe the frequency of and factors associated with breathlessness in a cohort of COPD patients identified from the Clinical Practice Research Datalink (CPRD), a general practice electronic medical records database.

Methods

Patients with a record of COPD diagnosis after January 1 2008 were identified in the CPRD. Breathlessness was assessed using the Medical Research Council (MRC) dyspnoea scale, with scoring ranging from 1–5, which has been routinely administered as a part of the regular assessment of patients with COPD in the general practice since April 2009. Stepwise multivariate logistic regression estimated independent associations with dyspnoea. Negative binomial regression evaluated a relationship between breathlessness and exacerbation rate during follow-up.

Results

The total cohort comprised 49,438 patients diagnosed with COPD; 40,425 (82%) had any MRC dyspnoea grade recorded. Of those, 22,770 (46%) had moderate-to-severe dyspnoea (MRC≥3). Breathlessness increased with increasing airflow limitation; however, moderate-to-severe dyspnoea was also observed in 32% of patients with mild airflow obstruction. Other factors associated with increased dyspnoea grade included female gender, older age (≥70 years), obesity (BMI ≥30), history of moderate-to-severe COPD exacerbations, and frequent visits to the general practitioner. Patients with worse breathlessness were at higher risk of COPD exacerbations during follow-up.

Conclusions

Moderate-to-severe dyspnoea was reported by >40% of patients diagnosed with COPD in primary care. Presence of dyspnoea, including even a perception of mild dyspnoea (MRC = 2), was associated with increased disease severity and a higher risk of COPD exacerbations during follow-up.     

Indocyanine Green-Assisted Internal Limiting Membrane Peeling in Macular Hole Surgery: A Meta-Analysis

Background

The opinion of application of indocyanine green (ICG) in the macular hole surgery was contradictory. Here we conducted a meta-analysis to evaluate the effect of in internal limiting membrane (ILM) peeling for macular hole surgery.

Methods and Findings

We searched electronic databases for comparative studies published before July 2012 of ILM peeling with and without ICG. Twenty-two studies including 1585 eyes were included. Visual acuity (VA) improvement, including the postoperative rate of ≥20/40 VA gained (OR, 0.65; 95% CI, 0.43 to 0.97; P = 0.033) and increased LogMAR (WMD, −0.09; 95% CI, −0.16 to −0.02; P = 0.011), was less in the ICG group. The risk of visual field defects was greater in the ICG group than in the non-ICG group. There was no significant difference in the rate of anatomical outcomes between ILM peeling procedures performed with and without ICG. RPE changes and other postoperative complications were not significantly different between the ICG and non-ICG groups. An additional analysis showed that the VA improvement of the ICG group was less than the non-ICG group only within the first year of follow up. A subgroup analysis showed that the rate of VA improvement was lower in the ICG group than in other adjuncts group. A higher rate of secondary closure and less VA improvement were observed in a high proportion (>0.1%) of the ICG group. A sensitivity analysis after the randomized-controlled trials were excluded from the meta-analysis demonstrated no differences compared with the overall results.

Conclusions

This meta-analysis demonstrated that there is no evidence of clinical superiority in outcomes for ICG-assisted ILM peeling procedure over the non-ICG one. The toxicity of ICG should be considered when choosing the various staining methods.     

Pre-Illness Isoflavone Consumption and Disease Risk of Ulcerative Colitis: A Multicenter Case-Control Study in Japan

Introduction

Previous studies have suggested that estrogens play a role in the development of ulcerative colitis (UC). Because isoflavones have a similar structure to 17β-estradiol, dietary consumption of isoflavones may have similar influences on the development of UC. We examined the association between pre-illness isoflavone consumption and the risk of UC.

Materials and Methods

We conducted a hospital-based case control study, and compared the dietary habits of 126 newly diagnosed UC cases with those of 170 age- and gender-matched hospital controls. Information on dietary factors was collected using a self-administered diet history questionnaire. To consider potential changes in dietary habits due to disease symptoms, the habits were assessed separately during the previous 1 month and at 1 year before the recruitment.

Results

In the assessment of dietary habits during the previous 1 month, the highest tertile of isoflavone consumption revealed an increased odds ratio (OR) for UC (OR = 2.79; 95% confidence interval (CI), 1.39–5.59; Trend P = 0.004). A significant association was also observed for the dietary assessment at 1 year before, when most UC cases had not yet experienced their first disease symptoms (OR = 2.06; 95% CI, 1.05–4.04; Trend P = 0.04). Associations were more pronounced in females (OR in highest tertile of isoflavone consumption at 1 year before = 4.76; 95% CI, 1.30–17.5; Trend P = 0.02) but were obscured in males (corresponding OR = 1.21; 95% CI, 0.49–3.01; Trend P = 0.63).

Conclusions

Dietary isoflavone consumption may be associated with an increased risk of UC, particularly in females. Prospective cohort studies are warranted to confirm these findings.     

Famine in the Young and Risk of Later Hospitalization for COPD and Asthma

Background

Undernutrition during critical periods of growth and development may permanently affect lung physiology and function.

Objectives

To investigate whether acute undernutrition in childhood or young adulthood increases the risk of later hospitalization for obstructive airways disease, chronic obstructive pulmonary disease (COPD), or asthma.

Methods

We studied 7,841 women from Prospect-EPIC who experienced the 1944–45 Dutch famine between ages 0 and 21. Pulmonary outcomes were measured by registered hospital admissions and exposure-blinded computed tomography (CT) in a subgroup of 295 women. With Cox proportional hazard regression we explored effects of famine exposure on risk of hospitalization for obstructive airways disease, COPD, and asthma. With logistic regression we explored effects of famine on risk of CT evidence of pulmonary disease.

Results

Risks of hospitalization for obstructive airways disease, COPD, and asthma were increased after moderate famine exposure, and significantly increased after severe famine exposure: hazard ratios for obstructive airways disease were 1.31 (95% CI: 0.97 to 1.77) and 1.57 (95% CI: 1.10 to 2.23) respectively. Associations between famine exposure and hospitalization for COPD were stronger in ever-smokers than in never-smokers.

Conclusions

Acute undernutrition in childhood or young adulthood is associated with an increased risk of later COPD and asthma hospitalization, possibly through increased sensitivity for tobacco smoke.     

Longitudinal inspiratory capacity changes in chronic obstructive pulmonary disease

Background

The changes in inspiratory capacity (IC) over time in chronic obstructive pulmonary disease (COPD) patients are unknown. The Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial included IC measurements.

Methods

IC analysis from UPLIFT® (N = 5992) was performed at 1 and 6 months, and every 6 months through 4 years. Annualized rate of decline in pre- and post-bronchodilator IC and mean differences at each time point were analyzed by mixed-effects models. The relationships between baseline IC and exacerbation rate and mortality were explored using Cox regression analysis.

Results

Baseline characteristics: age, 65 years; 75% men; post-bronchodilator forced expiratory volume in 1 second, 1.32 L (48% predicted); pre- and post-bronchodilator IC, 2.03 and 2.33 L. Mean IC rate of decline (mL/year) was 34 ± 2 (1.7% of baseline) and 50 ± 3 (2.1% of baseline) pre- and post-bronchodilator, respectively, without significant between-group differences. Morning pre-bronchodilator (trough) IC improved with tiotropium versus placebo: 124 mL (1 month), 103 mL (1 year), 107 mL (2 years), 98 mL (3 years), and 97 mL (4 years) (all p < 0.001). Post-bronchodilator improvements were similar between treatment groups. Lower baseline IC values were associated with reduced time to first exacerbation. For the lowest quartile (n = 1413) the values in months were 14.3 (11.7–17.0) for tiotropium and 10.3 (8.8–11.7) for controls (p < 0.01).

Conclusion

IC declines from approximately 34 to 50 mL/year in patients with stage II to IV COPD. Tiotropium treatment does not change the IC decline rate but provides 24-hour improvements in IC sustained over the long term. Trough IC differences suggest that tiotropium provides sustained decrease in end-expiratory lung volume.     

Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients

Background

Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs. Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated. Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD.

Methods

Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year.

Results

Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%). No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline. No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001). In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02]. The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001).

Conclusions

In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D. This association was independent of patients’ characteristics and comorbidities.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0131-0) contains supplementary material, which is available to authorized users.     

Comorbidity and sex-related differences in mortality in oxygen-dependent chronic obstructive pulmonary disease

Background

It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD). The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD.

Methods

National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008. Comorbidities were obtained from the Swedish Hospital Discharge Register. Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion. The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, Pa_O2 breathing air, FEV₁, smoking history and year of inclusion.

Results

In total, 8,712 patients (55% women) were included and 6,729 patients died during the study period. No patient was lost to follow-up. Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P<0.05 for all odds ratios). Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes. Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95% confidence interval, 0.68–0.77; P<0.001).

Conclusions

Comorbidity is different in men and women, but does not explain the sex-related difference in mortality in oxygen-dependent COPD.     

Accelerated extracellular matrix turnover during exacerbations of COPD

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.

Methods

69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up. Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).

Results

Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001). Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001). Pro-C3 levels were unchanged. At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.

Conclusions

Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity. This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression.     

Serum Oxidized Albumin and Cardiovascular Mortality in Normoalbuminemic Hemodialysis Patients: A Cohort Study

Background

Substantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients.

Methods

We conducted a long-term follow-up study in a cohort of normoalbuminemic HD patients to examine the impact of redox state of serum albumin on patients’ survival by measuring the human nonmercaptoalbumin (HNA) fraction of HSA.

Results

After adjusting for potential demographic, anthropometric, and clinical confounders, a positive association of HNA level with the risk of death from cardiovascular disease (CVD) and all-cause mortality was observed in normoalbuminemic HD patients. Using stratified analysis, we found a stronger association between HNA level and the risk of death from CVD and all-cause mortality in patients with pre-existing CVD.

Conclusions

Serum HNA level is a positive predictor of mortality in normoalbuminemic HD patients, especially among those with pre-existing CVD. Increased oxidative stress resulting from biological changes in serum albumin levels could contribute to accelerated atherosclerosis and the development of cardiovascular disease in HD patients.     

Characterization of changes in serum anti-glycan antibodies in Crohn's disease--a longitudinal analysis

Introduction

Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn''s disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon.

Methods

859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course.

Results

Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed.

Conclusions

While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time.     

Predictors and prevalence of latent tuberculosis infection in patients receiving long-term hemodialysis and peritoneal dialysis

Background

Tuberculosis is a common infectious disease in long-term dialysis patients. The prevalence of latent tuberculosis infection (LTBI) in this population is unclear, particularly in those receiving peritoneal dialysis (PD). This study investigated the prevalence of LTBI in patients receiving either hemodialysis (HD) or PD to determine predictors of LTBI and indeterminate results of interferon-gamma release assay.

Methods

Patients receiving long-term (≥3 months) HD or PD from March 2011 to February 2012 in two medical centers were prospectively enrolled. QuantiFERON-Gold in tube (QFT) test was used to determine the status of LTBI after excluding active tuberculosis. The LTBI prevalence was determined in patients receiving different dialysis modes to obtain predictors of LTBI and QFT-indeterminate results.

Results

Of 427 patients enrolled (124 PD and 303 HD), 91 (21.3%) were QFT-positive, 316 (74.0%) QFT-negative, and 20 (4.7%) QFT-indeterminate. The prevalence of LTBI was similar in the PD and HD groups. Independent predictors of LTBI were old age (OR: 1.034 [1.013–1.056] per year increment), TB history (OR: 6.467 [1.985–21.066]), and current smoker (OR: 2.675 [1.061–6.747]). Factors associated with indeterminate QFT results were HD (OR: 10.535 [1.336–83.093]), dialysis duration (OR: 1.113 [1.015–1.221] per year increment), anemia (OR: 8.760 [1.014–75.651]), and serum albumin level (OR: 0.244 [0.086–0.693] per 1 g/dL increment).

Conclusion

More than one-fifth of dialysis patients have LTBI. The LTBI prevalence is similar in PD and HD patients but is higher in the elderly, current smokers, and those with prior TB history. Such patients require closer follow-up. Repeated or alternative test may be required for malnutrition patients who received long length of HD.     

Readmission rates of patients discharged against medical advice: a matched cohort study

Objective

We compared the readmission rates and the pattern of readmission among patients discharged against medical advice (AMA) to control patients discharged with approval over a one-year follow-up period.

Methods

A retrospective matched-cohort study of 656 patients(328 were discharged AMA) who were followed for one year after their initial hospitalization at an urban university-affiliated teaching hospital in Vancouver, Canada that serves a population with high prevalence of addiction and psychiatric disorders. Multivariate conditional logistic regression was used to examine the independent association of discharge AMA on 14-day related diagnosis hospital readmission. We fit a multivariate conditional negative binomial regression model to examine the readmission frequency ratio between the AMA and non-AMA group.

Principal Findings

AMA patients were more likely to be homeless (32.3% vs. 11%) and have co-morbid conditions such as psychiatric illnesses, injection drug use, HIV, hepatitis C and previous gastrointestinal bleeding. Patients discharged AMA were more likely to be readmitted: 25.6% vs. 3.4%, p<0.001 by day 14. The AMA group were more likely to be readmitted within 14 days with a related diagnosis than the non-AMA group (Adjusted Odds Ratio 12.0; 95% Confidence Interval [CI]: 3.7–38.9). Patients who left AMA were more likely to be readmitted multiple times at one year compared to the non-AMA group (adjusted frequency ratio 1.6; 95% CI: 1.3–2.0). There was also higher all-cause in-hospital mortality during the 12-month follow-up in the AMA group compared to non-AMA group (6.7% vs. 2.4%, p = 0.01).

Conclusions

Patients discharged AMA were more likely to be homeless and have multiple co-morbid conditions. At one year follow-up, the AMA group had higher readmission rates, were predisposed to multiple readmissions and had a higher in-hospital mortality. Interventions to reduce discharges AMA in high-risk groups need to be developed and tested.     

Factors associated with change in exacerbation frequency in COPD

Background

Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.

Methods

1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly. Exacerbations were defined by health care utilisation. Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.

Findings

Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE. More severe disease was associated with changing from IE to FE and less severe disease from FE to IE. Over the preceding year, small falls in FEV₁ and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.

Conclusion

No parameter clearly predicts an imminent change in exacerbation frequency category.

Trial registration

SCO104960, clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00292552","term_id":"NCT00292552"}}NCT00292552