Prospective analysis of adrenal function in patients with acute exacerbations of COPD: the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial

OBJECTIVE To analyze prospectively the hypothalamic-pituitary-adrenal (HPA) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease (COPD). DESIGN Prospective observational study. SUBJECTS AND METHODS Patients presenting to the emergency department were randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner. The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline, on day 6 before blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of the test results. Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment. RESULTS A total of 311 patients were included in the analysis. Mean basal and stimulated serum total cortisol levels were highest on admission (496±398 and 816±413 nmol/l respectively) and lowest on day 6 (235±174 and 453±178 nmol/l respectively). Pathological stimulation tests were found in 63, 38, 9, 3, and 2% of patients on day 6, at discharge, and on days 30, 90, and 180 respectively, without significant difference between treatment groups. Clinical indicators of hypocortisolism did not correlate with stimulation test results, but cortisol levels were inversely associated with re-exacerbation risk. There were no hospitalizations or deaths as a result of adrenal crisis. CONCLUSION Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD. In hypocortisolemic patients who were provided with instructions about stress prophylaxis, the abrupt termination of prednisone appeared safe.

The Effect of Incidental Consolidation on Management and Outcomes in COPD Exacerbations: Data from the European COPD Audit

OBJECTIVE There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD). While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice. This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes. PATIENTS AND METHODS The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD. In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph. Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality. RESULTS 14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without. The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change. Previous treatment with inhaled steroids was not associated. Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up. CONCLUSIONS Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis. We recommend that these patients be considered a distinct subset in COPD exacerbation.

COPD-Exazerbation

Das Management der akuten Exazerbation beginnt mit der akuten Situation, hört aber erst nach sorgfältiger Überprüfung und Optimierung des Langzeitmanagements auf. Das Ziel ist, zukünftige Exazerbationen möglichst zu vermeiden, da die Exazerbationsfrequenz mit der Langzeitpro­gnose assoziiert ist.

Ozone and fine particulate matter association with CVD and COPD emergency room visits in Harris County, Texas: Spatiotemporal analysis

This study represents a secondary analysis of the merging of emergency room visits and daily ozone and PM2.5. Although the adverse health effects of ozone and fine particulate matter have been documented in the literature, evidence regarding the health risks of these two pollutants in Harris County, Texas, is limited. Harris County (Houston) has sufficiently unique characteristics that analysis of these relationships in this setting and with the ozone and industry issues in Houston is informative. The objective of this study was to investigate the association between the joint exposure to ozone and fine particulate matter, and emergency room diagnoses of chronic obstructive pulmonary disease and cardiovascular disease in Harris County, Texas, from 2004 to 2009, with zero and one day lags. ^ The study variables were daily emergency room visits for Harris County, Texas, from 2004 to 2009, temperature, relative humidity, east wind component, north wind component, ozone, and fine particulate matter. Information about each patient's age, race, and gender was also included. The two dichotomous outcomes were emergency room visits diagnoses for chronic obstructive pulmonary disease and cardiovascular disease. Estimates of ozone and PM2.5 were interpolated using kriging, in which estimates of the two pollutants were predicted from monitoring data for every case residence zip code for every day of the six years, over 3 million estimates (one of each pollutant for each case in the database). ^ Logistic regressions were conducted to estimate odds ratios of the two outcomes. Three analyses were conducted: one for all records, another for visits during the four months of April and September of 2005 and 2009, and a third one for visits from zip codes that are close to PM2.5 monitoring stations (east area of Harris County). The last two analyses were designed to investigate special temporal and spatial characteristics of the associations. ^ The dataset included all ER visits surveyed by Safety Net from 2004 to 2009, exceeding 3 million visits for all causes. There were 95,765 COPD and 96,596 CVD cases during this six year period. A 1-μg/m3 increase in PM2.5 on the same day was associated with a 1.0% increase in the odds of chronic obstructive pulmonary disease emergency room diagnoses, a 0.4% increase in the odds of cardiovascular disease emergency room diagnoses, and a 0.2% increase in the odds of cardiovascular disease emergency room diagnoses on the following day. A 1-ppb increase in ozone was associated with a 0.1% increase in the odds of chronic obstructive pulmonary disease emergency room diagnoses on the same day. These four percentages add up to 1.7% of ER visits. That is, over the period of six years, one unit increase for both ozone and PM2.5 (joint increase), resulted in about 55,286 (3,252,102 * 0.017) extra ER visits for CVD or COPD, or 9,214 extra ER visits per year. ^ After adjustment for age, race, gender, day of the week, temperature, relative humidity, east wind component, north wind component, and wind speed, there were statistically significant associations between emergency room chronic obstructive pulmonary disease diagnosis in Harris County, Texas, with joint exposure to ozone and fine particulate matter for the same day; and between emergency room cardiovascular disease diagnosis and exposure to PM2.5 of the same day and the previous day. ^ Despite the small association between the two air pollutants and the health outcomes, this study points to important findings. Namely, the need to identify reasons for the increase of CVD and COPD ER visits over the course of the project, the statistical association between humidity (or whatever other variables for which it may serve as a surrogate) and CVD and COPD cases, and the confirmatory finding that males and blacks have higher odds for the two outcomes, as consistent with other studies. ^ An important finding of this research suggests that the number and distribution of PM2.5 monitors in Harris County - although not evenly spaced geographically—are adequate to detect significant association between exposure and the two outcomes. In addition, this study points to other potential factors that contribute to the rising incidence rates of CVD and COPD ER visits in Harris County such as population increases, patient history, life style, and other pollutants. Finally, results of validation, using a subset of the data demonstrate the robustness of the models.^

Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD : results from a national database

Acknowledgments The authors would like to thank Kyungjoo Kim for the confident statistical analyses in this work. This study was supported by a grant (2014P3300300) from the Korea Centers for Disease Control and Prevention. The abstract of this paper was presented at the Asian Pacific Society of Respirology 20th Congress as an oral presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in Respirology

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12

Funding: British Women’s Heart and Health Study is funded by the Department of Health grant no. 90049 and the British Heart Foundation grant no. PG/09/022. British Regional Heart Study is supported by the British Heart Foundation (grant RG/ 13/16/30528). CB (COPDBEAT) received funding from the Medical Research Council UK (grant no. G0601369), CB (COPDBEAT) and AJW (UKCOPD) were supported by the National Institute for Health Research (NIHR Leicester Biomedical Research Unit). MB (COPDBEAT) received funding from the NIHR (grant no. PDF-2013-06-052). Hertfordshire Cohort Study received support from the Medical Research Council, Arthritis Research UK, the International Osteoporosis Foundation and the British Heart Foundation; NIHR Biomedical Research Centre in Nutrition, University of Southampton; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. Generation Scotland: Scottish Family Health Study is funded by the Chief Scientist Office, Scottish Government Health Directorates, grant number CZD/16/6 and the Scottish Funding Council grant HR03006. EU COPD Gene Scan is funded by the European Union, grant no. QLG1-CT-2001-01012. English Longitudinal Study of Aging is funded by the Institute of Aging, NIH grant No. AG1764406S1. GoDARTs is funded by the Wellcome Trust grants 072960, 084726 and 104970. MDT has been supported by MRC fellowship G0902313. UK Biobank Lung Exome Variant Evaluation study was funded by a Medical Research Council strategic award to MDT, IPH, DPS and LVW (MC_PC_12010)

COPD: A stepwise or a hit hard approach?

Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or "hit hard" approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS) are recommended, a step-up or "hit hard" approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications. This paper discusses and proposes stepwise, "hit hard", step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach.

COPD control: Can a consensus be found?

There are currently no reliable instruments for assessing the onset and progression of chronic obstructive pulmonary disease (COPD) or predicting its prognosis. Currently, a comprehensive assessment of COPD including several objective and subjective parameters is recommended. However, the lack of biomarkers precludes a correct assessment of COPD severity, which consequently hampers adequate therapeutic approaches and COPD control. In the absence of a definition of "well-controlled disease", a consensus regarding COPD control will be difficult to reach. However, COPD patient assessment should be multidimensional, and anchored in five points: control of symptoms, decline of pulmonary function, levels of physical activity, exacerbations, and Quality of Life. Several non-pharmacological and pharmacological measures are currently available to achieve disease control. Smoking cessation, vaccination, exercise training programs and pulmonary rehabilitation are recognized as important non-pharmacological measures but bronchodilators are the pivotal therapy in the control of COPD. This paper discusses several objective and subjective parameters that may bridge the gap between disease assessment and disease control. The authors conclude that, at present, it is not possible to reach a consensus regarding COPD control, essentially due to the lack of objective instruments to measure it. Some recommendations are set forth, but true COPD control awaits further objective assessments.

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

Infection frequently causes exacerbations of chronic obstructive pulmonary disease (COPD). Mannose-binding lectin (MBL) is a pattern-recognition receptor that assists in clearing microorganisms. Polymorphisms in the MBL2 gene reduce serum MBL levels and are associated with risk of infection. We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility. Polymorphism frequency was determined by PCR-RFLP in 200 COPD patients and 104 smokers with normal lung function. Serum MBL was measured as mannan-binding activity in a subgroup of 82 stable COPD patients. Frequency of COPD admissions for infective exacerbation was ascertained for a 2-year period. The MBL2 codon 54 B allele reduced serum MBL in COPD patients. In keeping, patients carrying the low MBL-producing B allele had increased risk of admission for infective exacerbation (OR 4.9, P-corrected = 0.011). No association of MBL2 genotype with susceptibility to COPD was detected. In COPD, serum MBL is regulated by polymorphism at codon 54 in its encoding gene. Low MBL-producing genotypes were associated with more frequent admissions to hospital with respiratory infection, suggesting that the MBL2 gene is disease-modifying in COPD. MBL2 genotype should be explored prospectively as a prognostic marker for infection risk in COPD.