Severe COPD Exacerbations Research Articles

Management of severe acute exacerbations of COPD: an updated narrative review

Background: Patients with chronic obstructive pulmonary disease (COPD) may experience an acute worsening of respiratory symptoms that results in additional therapy; this event is defined as a COPD exacerbation (AECOPD). Hospitalization for AECOPD is accompanied by a rapid decline in health status with a high risk of mortality or other negative outcomes such as need for endotracheal intubation or intensive care unit (ICU) admission. Treatments for AECOPD aim to minimize the negative impact of the current exacerbation and to prevent subsequent events, such as relapse or readmission to hospital. Main body: In this narrative review, we update the scientific evidence about the in-hospital pharmacological and non-pharmacological treatments used in the management of a severe AECOPD. We review inhaled bronchodilators, steroids, and antibiotics for the pharmacological approach, and oxygen, high flow nasal cannulae (HFNC) oxygen therapy, non-invasive mechanical ventilation (NIMV) and pulmonary rehabilitation (PR) as non-pharmacological treatments. We also review some studies of non-conventional drugs that have been proposed for severe AECOPD. Conclusion: Several treatments exist for severe AECOPD patients requiring hospitalization. Some treatments such as steroids and NIMV (in patients admitted with a hypercapnic acute respiratory failure and respiratory acidosis) are supported by strong evidence of their efficacy. HFNC oxygen therapy needs further prospective studies. Although antibiotics are preferred in ICU patients, there is a lack of evidence regarding the preferred drugs and optimal duration of treatment for non-ICU patients. Early rehabilitation, if associated with standard treatment of patients, is recommended due to its feasibility and safety. There are currently few promising new drugs or new applications of existing drugs.

Predictors of mortality in patients with acute exacerbation of chronic obstructive pulmonary disease requiring ICU admission

Background Acute exacerbations are associated with significant morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Identification of mortality predictors in severe COPD exacerbations may be of use in clinical decision making and prognostication. Objective The aim was to determine the in-hospital mortality rate, predictors of 30-day mortality, and duration of mechanical ventilation in patients admitted to the ICU with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Materials and methods This was an observational study conducted in a tertiary care hospital. Patients with acute exacerbation of COPD needing ICU admission were included. A standardized questionnaire was prepared to collect information about included patients. Outcomes of interest were total duration of hospital stay, ICU stay or death. SPSS version 11 was used for the statistical analysis. Results A total of 63 patients were enrolled in the study, out of which 22 (34.9%) died. Sepsis with multiorgan failure was commonest cause of the death. The risk factors associated with increased mortality in univariate analysis were pH less than 7.25, lymphocyte counts of less than 10%, platelet counts less than 1.5 lac, blood urea greater than 40 mg/dl, and need of mechanical ventilation. Multivariate analysis was conducted for those with statistically significant P value in univariate analysis. It showed thrombocytopenia, hypotension, hypercapnea, and uremia were independent predictors of increased mortality. Conclusion The present study revealed a mortality rate of 34.9% in patients with AECOPD needing ICU admission. Thrombocytopenia, hypotension, hypercapnea, and uremia were independent predictors of increased mortality. The results may be useful in the prognostication of patients with AECOPD needing ICU admission.

EFFECT OF ACLIDINIUM BROMIDE ON MAJOR ADVERSE CARDIOVASCULAR EVENTS AND EXACERBATIONS IN PATIENTS WITH COPD AND DIFFERENT CARDIOVASCULAR RISK FACTOR LEVELS

EFFECT OF ACLIDINIUM BROMIDE ON MAJOR ADVERSE CARDIOVASCULAR EVENTS AND EXACERBATIONS IN PATIENTS WITH COPD AND DIFFERENT CARDIOVASCULAR RISK FACTOR LEVELS

Eosinophil counts in first COPD hospitalizations: a comparison of health service utilization.

PurposeCurrent evidence suggests that a higher blood eosinophil cell count at admission for acute exacerbation of COPD (AECOPD) is associated with a favorable response to systemic steroids. However, the impact of blood eosinophil counts at admission on post-hospitalization outcomes is still unclear. The main objective of this study is to investigate readmission outcomes associated with blood eosinophilia following severe COPD exacerbation in patients with infrequent COPD hospitalizations.Patients and methodsThis is an observational cohort study design. We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013. Patients were stratified into the eosinophilic group if the blood eosinophil count on admission was ≥200 cells/µL and/or ≥2% of the total white blood cell (WBC) count. The primary outcome was 1-year COPD-related readmission. Secondary outcomes included 1-year all-cause mortality, 1-year all-cause readmission, length of stay, time to COPD-related readmission, and number of 1-year COPD-associated emergency department (ED) and ambulatory visits.ResultsA total of 479 patients were included. Of whom, 173 were stratified into the eosinophilic group. Higher blood eosinophil cell count was associated with an increased risk of 1-year COPD-related readmission (OR, 1.83 [95% CI, 1.16–2.89]; P<0.01), a shorter time to first COPD-related readmission (HR, 1.64 [95% CI, 1.14–2.36]; P<0.01), and an increased number of 1-year COPD-related ED visits (incidence rate ratio, 1.78 [95% CI, 1.21–2.61]; P<0.01). All-cause mortality, all-cause readmission, length of stay, and number of ambulatory visits did not differ between groups.ConclusionHigher blood eosinophil cell count at admission for a COPD exacerbation is associated with increased COPD readmission rates in patients with infrequent COPD hospitalizations.

Ischemic Heart Disease during Acute Exacerbations of COPD.

Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of acute cardiovascular events, and around 30% die from cardiovascular diseases. Recent data suggest an increased risk of myocardial infarction in the following days of a severe exacerbation of COPD. Disruption in the balance during the exacerbation with tachycardia, increased inflammation and systemic oxidative stress as well as some other factors may confer an increased risk of subsequent cardiovascular events. A number of investigations may be useful to an early diagnosis, including electrocardiography, imaging techniques and blood test for biomarkers. Some drugs that have changed prognosis in the cardiovascular setting such as cardioselective beta-blockers may be underused in patients with COPD despite its demonstrated benefits. This review focuses on several aspects of exacerbation of COPD and cardiovascular events including epidemiology, possible mechanism, diagnosis and treatment.

The Clinical Implications of Carbon Dioxide Increased Level in Arterial Blood Related to Severe Exacerbations of Chronic Obstructive Pulmonary Disease

In the evolution of patients with chronic obstructive pulmonary disease (COPD), exacerbations occur, especially, in severe stages, determining aggravated respiratory failure and decreased survival. In order to evaluate the implications of COPD exacerbations in patients with second type of chronic respiratory failure and hypercapnic encephalopathy, a prospective observational study was done among 195 COPD in patients of Targu Mures Clinical County Hospital, Romania. Inclusion criteria consisted in severe exacerbations of COPD, complicated by hypercapnia, defined by an increased level of arterial blood gas carbon dioxide (PaCO2) �45 mmHg, suggestive for the second type of respiratory failure. The increased values of PaCO2 ranged between 45 and 112 mmHg among 95 patients. The prevalence of hypercapnia in COPD patients, admitted in hospital for severe exacerbations, was high (n=91/195; 46.66%). The majority of COPD patients (93.4%) were initially hospitalized in the intensive care unit (ICU) department because of hypercapnic encephalopathy. The mortality rate was higher among patients with endotracheal tube insertion than in patients treated by noninvasive mechanical ventilation. High levels of hypercapnia, conscience disorders and respiratory acidosis may be considered factors of severity in COPD exacerbation.

Bispectral index in hypercapnic encephalopathy associated with COPD exacerbation: a pilot study.

BackgroundHypercapnic encephalopathy is relatively frequent in severe exacerbations of COPD (ECOPDs), with its intensity usually being evaluated through clinical scales. Bispectral index (BIS) is a relatively new technique, based on the analysis of the electroencephalographic signal, which provides a good approximation to the level of consciousness, having already been validated in anesthesia.ObjectiveThe objective of the study was to evaluate the utility of BIS in the assessment of the intensity of hypercapnic encephalopathy in ECOPD patients.Patients and methodsA total of ten ECOPD patients were included, and the level of brain activity was assessed using BIS and different scales: Glasgow Coma Scale, Ramsay Sedation Scale (RSS), and Richmond Agitation–Sedation Scale. The evaluation was performed both in the acute phase and 3 months after discharge.ResultsBIS was recorded for a total of about 600 minutes. During ECOPD, BIS values ranged from 58.8 (95% CI: 48.6–69) for RSS score of 4 to 92.2 (95% CI: 90.1–94.3) for RSS score of 2. A significant correlation was observed between values obtained with BIS and those from the three scales, although the best fit was for RSS, followed by Glasgow and Richmond (r=−0.757, r=0.701, and r=0.615, respectively; P<0.001 for all). In the stable phase after discharge, BIS showed values considered as normal for a wake state (94.6; 95% CI: 91.7–97.9).ConclusionBIS may be useful for the objective early detection and automatic monitoring of the intensity of hypercapnic encephalopathy in ECOPD, facilitating the early detection and follow-up of this condition, which may avoid management problems in these patients.

Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial.

There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations. To evaluate the efficacy and safety of direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease (COPD). This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50 μg once daily) or continuation of triple therapy (tiotropium [18 μg] once daily plus combination of salmeterol/fluticasone propionate [50/500 μg] twice daily) in nonfrequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was noninferiority on change from baseline in trough FEV1. Moderate or severe exacerbations were predefined secondary endpoints. A total of 527 patients were randomized to indacaterol/glycopyrronium and 526 to triple therapy. Inhaled corticosteroids withdrawal led to a reduction in trough FEV1 of -26 ml (95% confidence interval, -53 to 1 ml) with confidence limits exceeding the noninferiority margin of -50 ml. The annualized rate of moderate or severe COPD exacerbations did not differ between treatments (rate ratio, 1.08; 95% confidence interval, 0.83 to 1.40). Patients with ≥300 blood eosinophils/μl at baseline presented greater lung function loss and higher exacerbation risk. Adverse events were similar in the two groups. In patients with COPD without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with ≥300 blood eosinophils/μl suggests that these patients are likely to benefit from triple therapy. Clinical trial registered with www.clinicaltrials.gov (NCT 02603393).

Development and validation of a predictive model to identify patients at risk of severe COPD exacerbations using administrative claims data.

BackgroundPatients with COPD often experience severe exacerbations involving hospitalization, which accelerate lung function decline and reduce quality of life. This study aimed to develop and validate a predictive model to identify patients at risk of developing severe COPD exacerbations using administrative claims data, to facilitate appropriate disease management programs.MethodsA predictive model was developed using a retrospective cohort of COPD patients aged 55–89 years identified between July 1, 2010 and June 30, 2013 using Humana’s claims data. The baseline period was 12 months postdiagnosis, and the prediction period covered months 12–24. Patients with and without severe exacerbations in the prediction period were compared to identify characteristics associated with severe COPD exacerbations. Models were developed using stepwise logistic regression, and a final model was chosen to optimize sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV).ResultsOf 45,722 patients, 5,317 had severe exacerbations in the prediction period. Patients with severe exacerbations had significantly higher comorbidity burden, use of respiratory medications, and tobacco-cessation counseling compared to those without severe exacerbations in the baseline period. The predictive model included 29 variables that were significantly associated with severe exacerbations. The strongest predictors were prior severe exacerbations and higher Deyo–Charlson comorbidity score (OR 1.50 and 1.47, respectively). The best-performing predictive model had an area under the curve of 0.77. A receiver operating characteristic cutoff of 0.4 was chosen to optimize PPV, and the model had sensitivity of 17%, specificity of 98%, PPV of 48%, and NPV of 90%.ConclusionThis study found that of every two patients identified by the predictive model to be at risk of severe exacerbation, one patient may have a severe exacerbation. Once at-risk patients are identified, appropriate maintenance medication, implementation of disease-management programs, and education may prevent future exacerbations.

Circulating eosinophil levels do not predict severe exacerbations in COPD: a retrospective study.

Whether the level of circulating eosinophils in chronic obstructive pulmonary disease (COPD) patients can predict the risk of exacerbations of COPD (ECOPD) or response to treatment is debated. Here, we evaluate the prevalence of elevated eosinophils in COPD patients and its relationship with severe ECOPD requiring hospitalisation.We retrospectively reviewed the charts of COPD patients hospitalised in our centre between January 1, 2005 and November 30, 2015 because of ECOPD or other reasons (controls). In a second analysis, the ECOPD patients were divided into two subgroups based on having ECOPD in the next year after the index event or not. Circulating eosinophils, both during clinical stability and hospitalisation, as well as clinical and functional data and the relation to recurrent exacerbations were analysed.We studied 992 COPD patients (318 ECOPD patients and 674 controls). Among ECOPD patients, 121 had one or more ECOPD during the year after the index event. The prevalence of eosinophils ≥2% was 72% in ECOPD patients and 71% in controls (p=0.93). Among ECOPD patients, eosinophil levels ≥2%, ≥4% or ≥300 cells·μL−1, either when clinically stable or during hospitalisation, did not show a significant association with the rate of recurrent severe exacerbations. The severity of airflow limitation was associated with recurrent exacerbations, but inhaled corticosteroid treatment was not.The majority of COPD patients have circulating eosinophils >2% and a significant association with the risk of severe ECOPD or response to inhaled corticosteroids was not demonstrated.

Management of severe COPD exacerbations: focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide.

The major determinant of the decline in lung function, quality of life, and the increased mortality risk in patients with COPD is represented by severe acute exacerbations of the disease, that is, those requiring patients’ hospitalization, constituting a substantial social and health care burden in terms of morbidity and medical resource utilization. Different long-term therapeutic strategies have been proposed so far in order to prevent and/or reduce the clinical and social impact of these events, the majority of which were extrapolated from trials initially focused on the effect of long-acting muscarinic antagonist and subsequently on the efficacy of long-acting β2-agonists in combination or not with inhaled corticosteroids. The option to employ all three classes of molecules combined, despite the limited amount of evidence in our possession, represents a choice currently proposed by international guidelines; however, current recommendations are often based mainly on observational studies or on the results of secondary outcomes in randomized controlled trials. The present narrative review evaluates the available trials that investigated the efficacy of inhaled therapy to prevent COPD exacerbations and especially severe ones, with a particular focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide fixed dose combination, which is the first treatment that comprises all the three drug classes, specifically tested for the prevention of moderate and severe COPD exacerbations.

Adjuvant acetazolamide in patients with acute severe exacerbation of COPD and noninvasive ventilation

The aim of the study was to investigate an efficacy of short-term treatment with acetazolamide (ACET) in patients with acute exacerbation of COPD (AECOPD) and noninvasive ventilation (NIV). Methods. This was a prospective case-control study. The study involved 20 patients. Inclusion criteria were as follows: AECOPD; pH > 7.33; PaCO2 > 48 mmHg; HCO 3 – > 26 mmol/L; and treatment with NIV. Clinical characteristics, Charlson comorbidity index, APACHE II score, arterial blood gases, and serum electrolytes were recorded before inclusion. Patients were defined as cases when they had received ACET (500 mg per day) for 3 days; they were compared to a matched control group who did not receive ACET. Clinical parameters, arterial blood gases, serum electrolytes, potential adverse effects, and length of hospital stay were monitored daily. Results. No significant differences in baseline characteristics, comorbidities, or concomitant drugs used were found between the groups. Mean duration of hospital stay was significantly shorter in the ACET group (16.2 ± 8.4 days vs 19.1 ± 2.8 days; p = 0.023). An iIntra-group analysis showed a significant improvement in clinical and arterial blood gas parameters in both groups already in the first day of the treatment. In the ACET group, systolic blood pressure (SBP), respiratory rate (RR), and SpO2 significantly improved at day 4 (112.5 ± 4.9 mmHg vs 125 ± 7.1 mmHg (p = 0.001); 15.2 ± 1.1 min –1 vs 17.1 ± 0.9 min –1 (p = 0.001) and 94.7 ± 1.1% vs 92.3 ± 0.8% (p = 0.0001), respectively). There was a significant decrease in PaCO2, pH and HCO 3 – at day 3 (48 ± 3.8 mmHg vs 52.4 ± 5.3 mmHg (p = 0.0288); 7.374 ± 0.4 vs 7.502 ± 0.17 (p = 0.0015) and 26.4 ± 2.8 mmol/L vs 36.9 ± 4.1 mmol/L (p = 0.00001), respectively) and day 4 (44 ± 2.4 mmHg vs 48.4 ± 4.6 mmHg (p = 0.0115); 7.387 ± 0.02 vs 7.480 ± 0.02 (p = 0.00001) and 24.2 ± 2.1 mmol/L vs 35.6 ± 3.0 mmol/L (p = 0.00001), respectively) in the ACET group. No adverse events were recorded in both groups. Conclusions. ACET adjuvant to NIV appears to be effective and could prevent post-NIV alkalosis occurrence and could reduce the length of hospital stay in patients with AECOPD and mixed metabolic disorders (respiratory acidosis and metabolic alkalosis).

Shall We Focus on the Eosinophil to Guide Treatment with Systemic Corticosteroids during Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)? CON.

The employment of systemic corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) has been shown to improve airway limitation, decrease treatment failure and risk of relapse, and may improve symptoms in addition to decreasing the length of hospital stay. Nowadays, all clinical guidelines recommend systemic corticosteroids to treat moderate or severe COPD exacerbations. However, their use is associated with potential side effects, mainly hyperglycemia. In the era of precision medicine, the possibility of employing blood eosinophil count has emerged as a potential way of optimizing therapy. Issues regarding the intra-individual variability of blood eosinophil count determination, a lack of clear data regarding the real prevalence of eosinophilic acute exacerbations, the fact that previously published studies have demonstrated the benefit of systemic corticosteroids irrespective of eosinophil levels, and especially the fact that there is only one well-designed study justifying this approach have led us to think that we are not ready to use eosinophil count to guide treatment with systemic corticosteroids during acute exacerbations of COPD.

Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD

BackgroundThe benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid–LABA or LAMA–LABA), are uncertain.MethodsIn this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate–vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium–vilanterol (at doses of 62.5 μg and 25 μg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.ResultsThe rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate–vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium–vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium–vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium–vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium–vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).ConclusionsTriple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate–vilanterol or umeclidinium–vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium–vilanterol. (Funded by GlaxoSmithKline; IMPACT ClinicalTrials.gov number, NCT02164513.)

Acute exacerbations as a poor prognostic factor of chronic obstructive pulmonary disease

This review presents information on severe acute exacerbation of COPD (AECOPD) as an independent negative prognostic factor. Mortality risk increases with the frequency of severe exacerbations, particularly if these require admission to a hospital. Large epidemiological studies in the field of COPD provided sufficient data on potential indicators of increased mortality in COPD. Key predictors of poor prognosis in COPD are the patient’s age, lower forced expiratory volume in 1 second (FEV1), lung hyperinflation, respiratory failure (low PaO2, high PaCO2), pulmonary hypertension, low body mass index, decreased physical tolerance, frequent exacerbations, and comorbidity. Thus, the management of patients with acute exacerbation of COPD still remains as an actual clinical problem.

Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial

Combinations of long-acting bronchodilators are recommended to reduce the rate of chronic obstructive pulmonary disease (COPD) exacerbations. It is unclear whether combining olodaterol, a long-acting beta-agonist, with tiotropium, a long-acting anti-muscarinic, reduces the rate of exacerbations compared with tiotropium alone. This 52-week, double-blind, randomised, parallel-group, active-controlled trial randomly assigned (1:1) patients with COPD with a history of exacerbations using a randomised block design to receive tiotropium-olodaterol 5 μg-5 μg or tiotropium 5 μg once daily. Patients using inhaled corticosteroids continued this therapy. Treatment was masked to patients, investigators, and those involved in analysing the data. The primary endpoint was the rate of moderate and severe COPD exacerbations from the first dose of medication until 1 day after last drug administration. The primary analysis included all randomly assigned patients who received any dose of study medication but were not from a site excluded due to on-site protocol violations. The trial is registered with ClinicalTrials.gov, number NCT02296138. Overall, 9009 patients were screened from 818 centres in 51 countries. We recruited 7880 patients between Jan 22, 2015 and March 7, 2016 (mean age 66·4 years [SD 8·5], 5626 [71%] were men, mean FEV1 percent predicted 44·5% [SD 27·7]): 3939 received tiotropium-olodaterol and 3941 tiotropium. The rate of moderate and severe exacerbations was lower with tiotropium-olodaterol than tiotropium (rate ratio [RR] 0·93, 99% CI 0·85-1·02; p=0·0498), not meeting the targeted 0·01 significance level. The proportion of patients reporting adverse events was similar between treatments. Combining tiotropium and olodaterol did not reduce exacerbation rate as much as expected compared with tiotropium alone. Boehringer Ingelheim International GmbH.

Static and dynamic hyperinflation during severe acute exacerbations of chronic obstructive pulmonary disease.

BackgroundStatic hyperinflation is known to be increased during moderate acute exacerbations of chronic obstructive pulmonary disease (COPD) (AECOPD), but few data exist in patients with severe exacerbations of COPD. The role of dynamic hyperinflation during exacerbations is unclear.MethodsIn a prospective, observational cohort study, we recruited patients admitted to hospital for AECOPD. The following measurements were performed upon admission and again after resolution (stable state) at least 42 days later: inspiratory capacity (IC), body plethysmography, dynamic hyperinflation by metronome-paced IC measurement, health-related quality of life and dyspnea.ResultsForty COPD patients were included of whom 28 attended follow-up. The IC was low at admission (2.05±0.11 L) and increased again during resolution by 15.6%±23.1% or 0.28±0.08 L (mean ± standard error of the mean, p<0.01). Testing of metronome-paced changes in IC was feasible, and it decreased by 0.74±0.06 L at admission, similarly to at stable state. Clinical COPD Questionnaire score was 3.7±0.2 at admission and improved by 1.7±0.2 points (p<0.01), and the Borg dyspnea score improved by 2.2±0.5 points from 4.4±0.4 at admission (p<0.01).ConclusionStatic hyperinflation is increased during severe AECOPD requiring hospitalization compared with stable state. We could measure metronome-paced dynamic hyperinflation during severe AECOPD but found no increase.

Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: a randomized multicenter study

PurposeTo compare the efficacy of an antibiotic protocol guided by serum procalcitonin (PCT) with that of standard antibiotic therapy in severe acute exacerbations of COPD (AECOPDs) admitted to the intensive care unit (ICU).MethodsWe conducted a multicenter, randomized trial in France. Patients experiencing severe AECOPDs were assigned to groups whose antibiotic therapy was guided by (1) a 5-day PCT algorithm with predefined cutoff values for the initiation or stoppage of antibiotics (PCT group) or (2) standard guidelines (control group). The primary endpoint was 3-month mortality. The predefined noninferiority margin was 12%.ResultsA total of 302 patients were randomized into the PCT (n = 151) and control (n = 151) groups. Thirty patients (20%) in the PCT group and 21 patients (14%) in the control group died within 3 months of admission (adjusted difference, 6.6%; 90% CI − 0.3 to 13.5%). Among patients without antibiotic therapy at baseline (n = 119), the use of PCT significantly increased 3-month mortality [19/61 (31%) vs. 7/58 (12%), p = 0.015]. The in-ICU and in-hospital antibiotic exposure durations, were similar between the PCT and control group (5.2 ± 6.5 days in the PCT group vs. 5.4 ± 4.4 days in the control group, p = 0.85 and 7.9 ± 8 days in the PCT group vs. 7.7 ± 5.7 days in the control group, p = 0.75, respectively).ConclusionThe PCT group failed to demonstrate non-inferiority with respect to 3-month mortality and failed to reduce in-ICU and in-hospital antibiotic exposure in AECOPDs admitted to the ICU.

Supplemental oxygen in patients with stable chronic obstructive pulmonary disease: evidence from Nocturnal Oxygen Treatment Trial to Long-term Oxygen Treatment Trial.

Oxygen therapy was the first treatment shown to prolong life in patients with chronic obstructive pulmonary disease (COPD) and has been joined by lung volume reduction surgery in selected patients with emphysema, smoking cessation, and potentially noninvasive ventilation in chronic hypercapneic respiratory failure. Although there is consensus around the survival-enhancing effect of supplemental oxygen (SupplO2) for patients with chronic severe hypoxemia at rest, the impact of SupplO2 for COPD patients with moderate hypoxemia and exertional desaturation had been less clear. The recently published Long-term Oxygen Treatment Trial (LOTT) showed no benefit of SupplO2 for the composite outcome of survival and all-cause hospitalizations, or for component outcomes, severe COPD exacerbations, or quality of life in COPD patients with moderate resting hypoxemia or room air normoxemia with exercise desaturation. Results of the LOTT challenge the practice of prescribing SupplO2 for patients with COPD and moderate resting hypoxemia or isolated exertional desaturation. In the context that LOTT may not have recruited patients for whom SupplO2 conferred subjective benefit, there may be a role for short-term trials of SupplO2 with assessment of subjective benefit in such patients.

Relationship between the presence of bronchiectasis and acute exacerbation in Thai COPD patients.

BackgroundThe prevalence rate of bronchiectasis in COPD is variable. Coexisting bronchiectasis and COPD may influence COPD severity and exacerbation.ObjectiveWe investigated whether bronchiectasis is associated with frequent or severe COPD exacerbation. Lower airway bacterial and mycobacterial infections are a possible mechanism for bronchiectasis.Materials and methodsA cross-sectional study was conducted in 2013–2014. COPD exacerbations and hospitalizations were reviewed. Spirometry and CT were performed. COPD symptoms were assessed by using the COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Sputum inductions were performed and specimens were sent for microbiology.ResultsWe recruited 72 patients. Global Initiative for Chronic Obstructive Lung Disease (GOLD) A, B, C, and D, were noted in 20%, 27.1%, 14.3%, and 38.6% of the patients, respectively. Frequent exacerbations (≥2) and/or ≥1 hospitalization in the previous year were observed in 40.3% of patients. Median mMRC of COPD with frequent and non-frequent exacerbations was 1.0 (range 1–2) and 2.0 (range 1–3), (p=0.002), respectively. Median CAT of COPD with frequent and non-frequent exacerbations was 20.5 (3–37) and 11.0 (2–32), (p=0.004), respectively. CT-detected bronchiectasis was observed in 47.2% of patients. Median mMRC of COPD with and without bronchiectasis was 1.0 (0–4) and 1.0 (0–4) (p=0.22), respectively. Median CAT of COPD with and without bronchiectasis was 16.2 (95% CI: 12.9–19.6) and 13.0 (3–37), (p=0.49), respectively. The lower post-bronchodilator forced expiratory volume in 1 second (FEV1) of COPD with frequent exacerbations than those without was noted (p=0.007). The post-bronchodilator forced expiratory volume at 1 second percent in patients with and without bronchiectasis was not different (p=0.91). After adjusting for gender, severity of airflow obstruction, severity of COPD symptoms, the odds ratio for bronchiectasis with frequent and/or severe exacerbation was 4.99 (95% CI: 1.31–18.94), (p=0.018). Neither bacterial nor mycobacterial airway infection was associated with bronchiectasis or frequent exacerbation.ConclusionsBronchiectasis is common in Thai COPD. It was associated with frequent exacerbation or hospitalization. Mycobacterial tuberculosis in COPD patients with bronchiectasis was uncommon.