Severe Asthma or Chronic Obstructive Pulmonary Disease with Eosinophilic Inflammation? From Uncertainty to Remission under Anti IL-5R Therapy.

Background and Objectives: Severe adult-onset eosinophilic asthma and COPD with eosinophilic inflammation are two entities with a similar clinical course and are sometimes difficult to differentiate in clinical practice, especially in patients with a history of smoking. Anti-IL-5 or -IL-5R biological therapy has been shown to be highly effective in severe eosinophilic asthma but has not demonstrated significant benefit in patients with COPD with the eosinophilic phenotype. Our aim was to illustrate this issue in the form of a case report. Materials and Methods: We present the case of a 67-year-old patient who is a former smoker with late-onset severe uncontrolled asthma (ACT score < 15) who experienced frequent exacerbations requiring treatment with systemic corticosteroids. The patient's lung function gradually worsened to a nadir FEV1 = 18%, despite a high dose of ICS in combination with a LABA and intermittent courses of OCS, with negative allergic skin-tests, but with high blood eosinophils level. Biological treatment with an anti-IL5R monoclonal antibody (benralizumab) was initiated, despite the difficulty in the differential diagnosis between asthma and COPD with eosinophilic inflammation. Results: The patient's evolution was favorable; clinical remission was effectively achieved with significant improvement in lung function (FEV1 > 100%), but with persistence of residual mild fixed airway obstructive dysfunction (FEV1/FVC < 0.7). The therapeutic response has been maintained to date. Conclusions: Benralizumab was shown to be very effective in a patient with late-onset severe eosinophilic asthma presenting features of chronic obstructive disease-habitual exposure to tobacco and inhaled noxious substances, and persistent airflow limitation on spirometry.

Multivariate analysis and data mining help predict asthma exacerbations.

BACKGROUND: Work-related asthma has become a highly prevalent occupational lung disorder. OBJECTIVE: Our study aims to evaluate occupational exposure as a predictor for asthma exacerbation. METHOD: We performed a retrospective evaluation of 584 consecutive patients diagnosed and treated for asthma between October 2017 and December 2019 in four clinics from Western Romania. We evaluated the enrolled patients for their asthma control level by employing the Asthma Control Test (ACT < 20 represents uncontrolled asthma), the medical record of asthma exacerbations, occupational exposure, and lung function (i.e. spirometry). Then, we used statistical and data mining methods to explore the most important predictors for asthma exacerbations. RESULTS: We identified essential predictors by calculating the odds ratios (OR) for the exacerbation in a logistic regression model. The average age was 45.42 ± 11.74 years (19-85 years), and 422 (72.26%) participants were females. 42.97% of participants had exacerbations in the past year, and 31.16% had a history of occupational exposure. In a multivariate model analysis adjusted for age and gender, the most important predictors for exacerbation were uncontrolled asthma (OR 4.79, p < .001), occupational exposure (OR 4.65, p < .001), and lung function impairment (FEV1 < 80%) (OR 1.15, p = .011). The ensemble machine learning experiments on combined patient features harnessed by our data mining approach reveal that the best predictor is professional exposure, followed by ACT. CONCLUSIONS: Machine learning ensemble methods and statistical analysis concordantly indicate that occupational exposure and ACT < 20 are strong predictors for asthma exacerbation.

Time Spent with Saturation below 80% versus 90% in Patients with Obstructive Sleep Apnoea.

BACKGROUND: Nocturnal hypoxaemia measured as the percentage of total sleep time spent with saturation below 90% (TST90%) may better predict cardiovascular consequences of obstructive sleep apnoea (OSA) than the number of obstructive respiratory events measured with the apnoea-hypopnea index (AHI). Deeper hypoxaemia may potentially induce more severe pathophysiological consequences. However, the additional value of the percentage of total sleep time spent with saturation below 80% (TST80%) to TST90% is not fully explored. METHODS: Comprehensive medical history was taken and fasting lipid and C-reactive protein levels were measured in 797 volunteers participating in two cohort studies in Hungary and Romania. Sleep parameters, including AHI, TST90% and TST80%, were recorded following a polysomnography (PSG, n = 598) or an inpatient cardiorespiratory polygraphy (n = 199). The performance of TST80% to predict cardiovascular risk was compared with TST90% using linear and logistic regression analyses as well receiver operating characteristics curves. Sensitivity analyses were performed in patients who had PSG, separately. RESULTS: Both parameters are significantly related to cardiovascular risk factors; however, TST80% did not show better predictive value for cardiovascular risk than TST90%. On the other hand, patients with more severe hypoxaemia reported more excessive daytime sleepiness. CONCLUSIONS: TST80% has limited additional clinical value compared to TST90% when evaluating cardiovascular risk in patients with OSA.

Comparison of Composite Lipid Indices in Patients with Obstructive Sleep Apnoea.

Purpose: Obstructive sleep apnoea (OSA) is a recognised risk factor for cardiovascular disease. However, it is difficult to evaluate the risk of cardiovascular disease in patients with OSA due to multiple shared risk factors. Composite lipid indices, such as atherogenic index of plasma (AIP), visceral adiposity index (VAI) and lipid accumulation product (LAP) have been shown to predict cardiovascular disease better than their individual lipid components. This study aimed to evaluate these indices in patients with OSA. Patients and Methods: Six hundred sixty-seven (667) patients with OSA and 139 non-OSA control volunteers participated in the study. Fasting serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) levels were measured, and AIP, LAP and VAI were calculated following cardiorespiratory polygraphy. The relationship between lipid parameters, OSA and its comorbidities was evaluated using receiver operating curve (ROC) analysis. Results: We found a significant difference in all lipid parameters between OSA patients and controls. Comparing ROCs, LAP was significantly more strongly associated with OSA compared to all the other parameters. The optimal cut-off value for LAP to detect OSA was 76.4, with a sensitivity of 63% and a specificity of 76%. In addition, LAP was the best parameter to predict hypertension and diabetes in patients with OSA, and it was predictive for ischaemic heart disease together with HDL-C. Conclusion: Our results support the use of LAP in clinical practice when evaluating cardiovascular risk in patients with OSA. However, the optimal cut-off value should be determined in large-scale follow-up studies.

Liver Impairment and Hematological Changes in Patients with Chronic Hepatitis C and COVID-19: A Retrospective Study after One Year of Pandemic.

Background and Objectives: The COVID-19 pandemic is an ongoing public health emergency. Patients with chronic diseases are at greater risk for complications and poor outcomes. The objective of this study was to investigate the liver function abnormalities and clinical outcomes in patients with COVID-19 and chronic hepatitis C. Materials and Methods: This retrospective, single-center study was conducted on a cohort of 126 patients with a history of hepatitis C, confirmed with COVID-19 between 01 April 2020 and 30 December 2020. Several clinical outcomes were compared between patients with active and non-active HCV infection, and the risks of liver impairment and all-cause mortality in active HCV patients were analyzed using a multivariate logistic regression model. Results: Among 1057 patients under follow-up for chronic HCV infection, 126 (11.9%) were confirmed with COVID-19; of these, 95 (75.4%) were under treatment or achieved SVR, while in the other 31 (24.6%), we found active HCV replication. There was a significantly higher proportion of severe COVID-19 cases in the active HCV group as compared to the non-active HCV group (32.2 vs. 7.3%, p < 0.001). Multivariate analysis showed that age, sex, alanine aminotransferase, C-reactive protein, procalcitonin, and HCV viral load were significant independent risk factors for liver impairment and all-cause mortality. The length of stay in hospital and intensive care unit for COVID-19 was significantly higher in patients with active HCV infection (p-value < 0.001), and a higher proportion of these patients required mechanical ventilation. Conclusions: Active HCV infection is an independent risk factor for all-cause mortality in COVID-19 patients.

Predictive Value of Comorbid Conditions for COVID-19 Mortality.

In this paper, we aim at understanding the broad spectrum of factors influencing the survival of infected patients and the correlations between these factors to create a predictive probabilistic score for surviving the COVID-19 disease. Initially, 510 hospital admissions were counted in the study, out of which 310 patients did not survive. A prediction model was developed based on this data by using a Bayesian approach. Following the data collection process for the development study, the second cohort of patients totaling 541 was built to validate the risk matrix previously created. The final model has an area under the curve of 0.773 and predicts the mortality risk of SARS-CoV-2 infection based on nine disease groups while considering the gender and age of the patient as distinct risk groups. To ease medical workers' assessment of patients, we created a visual risk matrix based on a probabilistic model, ranging from a score of 1 (very low mortality risk) to 5 (very high mortality risk). Each score comprises a correlation between existing comorbid conditions, the number of comorbid conditions, gender, and age group category. This clinical model can be generalized in a hospital context and can be used to identify patients at high risk for whom immediate intervention might be required.

Triglyceride-Glucose Index in Non-Diabetic, Non-Obese Patients with Obstructive Sleep Apnoea.

Obstructive sleep apnoea (OSA) is associated with increased insulin resistance. Triglyceride-glucose index (TyG) is a simple marker of insulin resistance; however, it has been investigated only by two studies in OSA. The aim of this study was to evaluate TyG in non-diabetic, non-obese patients with OSA. A total of 132 patients with OSA and 49 non-OSA control subjects were included. Following a diagnostic sleep test, fasting blood was taken for the analysis of the lipid profile and glucose concentrations. TyG was calculated as ln(triglyceride [mg/dL] × glucose [mg/dL]/2). Comparison analyses between OSA and control groups were adjusted for age, gender, body mass index (BMI) and smoking. TyG was higher in men (p < 0.01) and in ever-smokers (p = 0.02) and it was related to BMI (ρ = 0.33), cigarette pack-years (ρ = 0.17), apnoea-hypopnoea index (ρ = 0.38), oxygen desaturation index (ρ = 0.40), percentage of total sleep time spent with oxygen saturation below 90% (ρ = 0.34), and minimal oxygen saturation (ρ = -0.29; all p < 0.05). TyG values were significantly higher in OSA (p = 0.02) following adjustment for covariates. OSA is independently associated with higher TyG values which are related to disease severity in non-obese, non-diabetic subjects. However, the value of TyG in clinical practice should be evaluated in follow-up studies in patients with OSA.

ERS International Congress 2020: highlights from the Respiratory Infections assembly.

In the coronavirus disease 2019 (COVID-19) pandemic year 2020, the 30th European Respiratory Society (ERS) International Congress took place for the first time in a fully virtual format. Despite the challenging nature of the task to create and deliver an online event of this size and scope, it turned out to be a great success, welcoming over 33 000 delegates to the specially designed online platform and offering more than 450 scientific and educational sessions. Somewhat predictably, this year's ERS International Congress dedicated a full day to the topic of COVID-19, highlighting that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease that is particularly important this year. In this article, the Early Career Members of the Assembly 10 (Respiratory Infections and Tuberculosis) review some of the most interesting sessions including presentations and posters on respiratory infections and tuberculosis that were deemed as important.

Atherogenic Index of Plasma in Obstructive Sleep Apnoea.

BACKGROUND: Dyslipidaemia is well recognised in obstructive sleep apnoea (OSA) and could contribute to the development of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) predicts cardiovascular morbidity and mortality better than the individual lipid levels. The aim of this study was to investigate the AIP in patients with OSA in relation with disease severity. METHODS: Four hundred sixty-one patients with OSA and 99 controls participated in this study. AIP was assessed in the morning following a diagnostic sleep study. The association between lipid values and OSA were adjusted for age, gender, and body mass index. RESULTS: Patients with OSA had higher AIP and triglyceride, and lower high-density lipoprotein cholesterol (HDL-C) levels (all p < 0.05). AIP significantly correlated with the Epworth Sleepiness Scale score (ρ = 0.19), the apnoea-hypopnoea index (ρ = 0.40) and oxygen desaturation index (ρ = 0.43, all p < 0.05). However, there was no relationship between the AIP and markers of sleep quality such as total sleep time, sleep period time, sleep efficiency, arousal index or percentage of REM sleep (all p > 0.05). AIP was not a better predictor for self-reported cardiovascular disease or diabetes than HDL-C. CONCLUSIONS: AIP is elevated in OSA and is related to disease severity. However, it does not seem to have an additional clinical value compared to HDL-C.

Clinical Profile of 24 AIDS Patients with Cryptococcal Meningitis in the HAART Era: A Report from an Infectious Diseases Tertiary Hospital in Western Romania.

Management of cryptococcal infections among patients suffering from acquired immunodeficiency syndrome (AIDS) represents a medical challenge. This retrospective study aims to describe the disease management and outcomes among 24 AIDS patients who suffered from Cryptococcus neoformans meningitis. The parameters evaluated from our patients' database records include epidemiological data, clinical manifestations, biochemical and microbiological analysis of patients' cerebrospinal fluid (CSF), treatment profiles, and disease outcomes. All patients included in the study had a lymphocyte count of less than 200 CD4/mm3. Of the 24 patients included in this study, five had been diagnosed with HIV infection since childhood, after receiving HIV-infected blood transfusions. The most prominent symptom was fatigue in 62.5% of patients, followed by nausea/vomiting and headache. Seven patients had liver cirrhosis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, while Kaposi sarcoma and cerebral toxoplasmosis were found in two patients. Six out of 24 patients died due to bacterial sepsis and acute respiratory distress syndrome (ARDS). High intracranial pressure was the strongest predictive factor for mortality (OR = 2.9), followed by ARDS (OR = 1.8), seizures at disease onset (OR = 1.4), and diabetes mellitus (OR = 1.2). Interestingly, patients younger than 40 years old had a significantly lower survival rate than that of the older patients. Before developing Cryptococcal meningitis, all patients had low adherence to the early ART treatment scheme and skipped the follow-up visits. All patients received a combination of amphotericin B and flucytosine as induction therapy, adding fluconazole for maintenance. Simultaneously, AIDS HAART was initiated at diagnosis of the cryptococcal infection. A combined regimen of antifungals and highly active antiretroviral therapy showed improved patient recovery with minor side effects.

The Burden of Associated Comorbidities in Patients with Obstructive Sleep Apnea-Regional Differences in Two Central-Eastern European Sleep Centers.

BACKGROUND: Obstructive sleep apnea (OSA) is usually associated with cardiovascular and cerebrovascular disease, metabolic syndrome and depression. Data on relevant OSA-associated comorbidities in Central-European populations are scarce. The aim of this study was to compare the prevalence of comorbidities in two OSA cohorts from Hungary and Romania. METHODS: Data from 588 (282 from Hungary, 306 from Romania) untreated patients with OSA were retrospectively analyzed. The prevalence rates of hypertension, diabetes, dyslipidemia, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), osteoporosis, cerebrovascular and cardiovascular disease, arrhythmia and depression were compared between the two populations following adjustment for demographics, body mass index, smoking history, comorbidities and sleep parameters. RESULTS: The prevalence rates of hypertension, arrhythmia, cerebrovascular and cardiovascular disease, diabetes and COPD in the whole study population were directly related to the severity of OSA. We found an inverse correlation between the prevalence of osteoporosis and OSA severity (all p < 0.05). Following adjustment, the prevalence of dyslipidemia was higher in the Hungarian cohort, whilst the prevalence of asthma, cardiovascular and cerebrovascular diseases was higher in the Romanian cohort (all p < 0.05). CONCLUSIONS: There was no difference in the prevalence rate of most comorbidities in patients with OSA from the two cohorts, except for dyslipidemia, asthma, cardiovascular and cerebrovascular disease.

Long-Term Effects of Continuous Positive Airway Pressure (CPAP) Therapy on Obesity and Cardiovascular Comorbidities in Patients with Obstructive Sleep Apnea and Resistant Hypertension-An Observational Study.

BACKGROUND: We sought to investigate whether long-term continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA) and resistant hypertension (RHTN) could attenuate the cardiovascular disease risk by lowering their body-mass index (BMI). METHODS: This was a long-term observational study of RHTN patients diagnosed with OSA. Patients were evaluated with polysomnography initially and after a mean follow-up period of four years. The patients were divided into two groups based on their compliance to CPAP therapy. RESULTS: 33 patients (aged 54.67 ± 7.5, 18 men, 54.5%) were included in the study, of which 12 were compliant to CPAP therapy. A significant reduction in BMI at follow-up was noted in patients compliant to CPAP therapy (1.4 ± 3.5 vs. -1.6 ± 2.5, p = 0.006). We also noted a large effect size reduction in abdominal circumference at follow-up in the CPAP group. At follow-up evaluation, the mean heart rate (b/min) was lower in the CPAP group (58.6 ± 9.5 vs. 67.8 ± 7.8), while arrhythmia prevalence increased between initial (28.6%) and follow-up (42.9%) evaluation with an intermediate effect size in non-compliant patients. CONCLUSIONS: In our cohort of OSA patients with RHTN, long-term adherence to CPAP therapy was associated with weight loss and improvement in cardiac rhythm outcomes.

Early Clinically Important Improvement (ECII) and Exacerbation Outcomes in COPD Patients.

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are difficult outcomes to measure in clinical trials. It would be valuable to be able to predict which patients are likely to benefit in terms of exacerbation prevention based on their early response in lung function and symptoms. Methods: This was a post-hoc analysis from the 52-week, randomized, double-blind, double-dummy, non-inferiority FLAME trial. Early clinically important improvement (ECII) was defined as achievement of minimal clinically important difference in trough forced expiratory volume in 1 second (FEV1; ≥100 mL increase) and one patient-reported outcome (PRO): either St. George's Respiratory Questionnaire for COPD (≥4-unit reduction; D1), or COPD assessment test (≥2-point reduction; D2) at Week 4 or 12. Results: Approximately 18-20% of patients achieved ECII at Week 4 or 12 post-randomization according to any of the two definitions. The rate of subsequent exacerbations was lower in patients who achieved ECII at Week 4 (D1: ratio of rates [95% CI], 0.85 [0.74 to 0.98]; D2, 0.88 [0.77 to 1.00]) or at Week 12 (D1, 0.85 [0.74 to 0.98]; D2, 0.86 [0.75 to 1.00]) versus patients not achieving ECII. Patients who achieved ECII experienced longer time-to-first exacerbation between Week 4 or 12 to end of study. More patients achieved ECII with indacaterol/glycopyrronium versus salmeterol/fluticasone according to both definitions at Week 4 (D1, odds ratio [95% CI], 1.69 [1.40 to 2.04]; D2, 1.61 [1.34 to 1.93]), and 12 (D1, 2.01 [1.66 to 2.44]; D2, 1.80 [1.48 to 2.18]). Conclusion: ECII is a novel composite endpoint, based on clinically relevant improvement in lung function and PROs in the early phase of treatment intervention that may predict subsequent exacerbation risk and may be used in clinical trials.

ERS International Congress, Madrid, 2019: highlights from the Respiratory Infections Assembly.

The European Respiratory Society (ERS) International Congress organised in Madrid, Spain, in 2019 welcomed >22 000 participants from 134 countries. For each ERS assembly, an impressive number of abstracts were submitted. The topics covered by Assembly 10 (Respiratory Infections and Tuberculosis) were included this year in the top five research areas with the most submitted abstracts, with a total of 424 abstracts accepted for presentation. As it would be difficult for any delegate to stay up to date with all the scientific advances in the field, we wanted to highlight three of the Congress sessions that included presentations on respiratory infections and tuberculosis that we deemed as important and we hope the readers will consider this material of great interest.

Impact of baseline symptoms and health status on COPD exacerbations in the FLAME study.

BACKGROUND: COPD is a heterogeneous disease and patients may respond differently to therapies depending on baseline symptom burden. METHODS: This post-hoc analysis from the 52-week FLAME study investigated the impact of baseline symptom burden in terms of health status, dyspnoea, bronchitis status, eosinophil levels and smoking status on the subsequent risk of moderate or severe exacerbations. Health status was measured by St. George's Respiratory Questionnaire (SGRQ) score (higher ≥46.6 and lower < 46.6) and COPD Assessment Test (CAT) score (higher ≥17 and lower < 17); dyspnoea and bronchitis were assessed via an electronic diary (eDiary). Differential response to once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 µg versus twice-daily salmeterol/fluticasone (SFC) 50/500 µg was assessed. RESULTS: Data from 3354 patients was analysed. The risk of exacerbations was lower in patients who had less severe health impairment (rate ratio [RR] [95% CI]): SGRQ-C, (0.88 [0.78, 0.99]); CAT, 0.85 [0.75, 0.96]) and lower dyspnoea (0.79 [0.69, 0.90]) at baseline versus those with more severe health impairment and higher dyspnoea, respectively. Compared with SFC, IND/GLY led to better prevention of moderate-to-severe exacerbations in the majority of groups studied. CONCLUSION: Patients with more severe health status impairment and greater symptom burden at baseline subsequently experienced more exacerbations in the FLAME study. IND/GLY was overall more effective in preventing exacerbations versus SFC, regardless of baseline symptom burden. Our results suggest that future studies on novel exacerbation therapies should consider targeting patients with higher symptom burden at baseline. CLINICAL TRIAL IDENTIFIER: NCT01782326.

Capturing Exacerbations of Chronic Obstructive Pulmonary Disease with EXACT. A Subanalysis of FLAME.

RATIONALE: Chronic obstructive pulmonary disease exacerbations accelerate lung function decline, reduce quality of life, and increase mortality. A subset of patients (n = 457) from the FLAME (Effect of Indacaterol Glycopyrronium vs. Fluticasone Salmeterol on COPD Exacerbations) study used the Exacerbations of COPD Tool (EXACT) to capture symptom-defined exacerbations. OBJECTIVES: To evaluate the effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on symptom-defined exacerbations measured using EXACT, and to assess differences between these events and exacerbations requiring healthcare resource use (HCRU). METHODS: All patients in FLAME used an electronic diary to record and detect symptom deteriorations; HCRU-related exacerbations were confirmed by investigators. In patients using the EXACT questionnaire, the onset, recovery, and magnitude of symptom-defined exacerbations were identified by changes in total scores relative to baseline. We analyzed the annualized rate and time to first symptom-defined (EXACT) exacerbation and assessed differences between symptom-defined and HCRU events in terms of number, severity, and concordance. MEASUREMENTS AND MAIN RESULTS: A nonsignificant 17% reduction in the annualized rate of symptom-defined (EXACT) exacerbations (rate ratio, 0.83; 95% confidence interval [CI], 0.60-1.14; P = 0.242) and a numerically longer time to first symptom-defined exacerbation were observed with indacaterol/glycopyrronium versus salmeterol/fluticasone (hazard ratio, 0.76; 95% CI, 0.56-1.03; P = 0.075). These results were consistent with data from the overall FLAME population. Of the symptom-defined (EXACT) events, 23.5% corresponded to HCRU events, and 22.2% of HRCU events were captured by EXACT (κ index, 0.24; 95% CI, 0.15-0.33). CONCLUSIONS: Regardless of the exacerbation definition used, our findings support the use of long-acting ß2 agonists/long-acting muscarinic receptor antagonists as the preferred treatment option for patients at risk of future exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).

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.

RATIONALE: There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations. OBJECTIVES: 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). METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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).

The ERS-industry fellowship: a tale of two experiences.

Recipients of the ERS Fellowship in Industry discuss their experiences http://ow.ly/1gcE30hMe89.

Rates and predictors of uncontrolled bronchial asthma in elderly patients from western Romania.

PURPOSE: Bronchial asthma (BA) is a chronic inflammatory disorder of the airways, featuring variable and often reversible airflow limitations. An accurate assessment of BA control is difficult in practice, especially in the elderly, requiring the assessment of several clinical and paraclinical parameters that are influenced not only by asthma, but also by comorbidities. The purpose of this study was to evaluate the predictors of uncontrolled BA in a group of elderly patients from western Romania. PATIENTS AND METHODS: We retrospectively evaluated 126 elderly patients (aged $ 65 years), who were consecutively evaluated in the Pulmonology Department of Victor Babes Hospital, Timisoara, Romania, between March 2009 and July 2012. We collected demographic data, performed pulmonary function testing and an asthma control test (ACT), and evaluated the level of BA control based on the 2012 Global Initiative for Asthma guidelines. Statistical processing of the data was done using the Epi Info and STATA programs. RESULTS: In our study group, 36 (29%) patients were men and 90 (71%) were women; their mean age was 74.42±8.32 years (range: 65-85 years). A total of 14.28% of patients were smokers. About 30.15% of patients had an ACT score <19, 54.76% had an ACT score 20-24, and 15.09% had an ACT of 25. Moreover, 59.52% had normal spirometry results. Infectious exacerbations were found in 58.73% of patients. A history of allergies was demonstrated in 48.41% of patients, 34.12% had occupational exposure, and 82.53% of patients were treated with inhaled corticosteroids. Our results showed that 30.15% of patients had uncontrolled BA. We found six predictive factors for uncontrolled BA: infectious exacerbation, occupational exposure, mixed (obstructive and restrictive) ventilatory dysfunction, persistent airway obstruction on spirometry, duration of disease in months, and current smoking status. Infectious exacerbations, persistent airway obstructions, and occupational exposure were the most powerful predictors. CONCLUSION: Elderly patients represent an important group that is at risk for developing uncontrolled BA. Predictors may identify those elderly patients with uncontrolled BA and facilitate early medical interventions.

Long-term effects of nocturnal continuous positive airway pressure therapy in patients with resistant hypertension and obstructive sleep apnea.

Obstructive sleep apnea (OSA) is often linked to high blood pressure and has a particularly high prevalence in patients with resistant hypertension. The effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) values has been evaluated in several short-term clinical trials with conflicting results. Our aim was to investigate the role of long-term CPAP treatment in achieving BP control in patients who associate OSA and resistant hypertension. We have included in the study 33 patients with resistant hypertension, diagnosed with OSA in our sleep lab. Data was collected initially and after a mean follow-up period of 4 years. Patients were divided into 2 groups according to the use of CPAP therapy. Patients under CPAP therapy (n = 12) exhibited a higher reduction in both systolic and diastolic pressure and BP control was achieved in 75% of cases, while patients without CPAP treatment (n = 21) remained with refractory hypertension in proportion of 90.5%. A de-escalation of antihypertensive drug regimen by discontinuation of 1 or more drugs was observed in 41.6% (n = 5) of patients from CPAP group and in the other 33.4% (n = 4) the medication remained unchanged, but BP control was reached. Using a direct logistic regression model for examining the impact of different confounders on the probability of diagnosis of resistant hypertension at follow-up, the only statistically significant predictor found was the lack of CPAP usage.