Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6, and tumour necrosis factor alpha (TNF-α), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 ± 3 years (mean ± SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1β and IL-6 were found to be 15-fold higher on admission (122 ± 9 pg mL-1 and 60 ± 4 pg mL-1 respectively), whereas TNF-α was three-fold higher (102 ± 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 ± 1 mg L-1), whereas fibronectin levels were reduced (242 ± 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-α serum level (127 ± 7 vs. 86 ± 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-α (-7.2 ± 0.7 vs. -3.8 ± 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 ± 3.0 vs. -54.6 ± 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 ± 1.0 vs. 11.7 ± 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of-cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition

Pathophysiology of evolution of small airways disease to overt COPD

Background: The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; ACT) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFLT) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. Methods: In this cross-sectional study we have assessed for the first time the phase III slope, ACT and EFLT in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. Results: In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800pred in GOLD IV). A close correlation was found of slope with GOLD (r 0.77). ACT was absent in smokers with normal spirometry and in most patients with mild COPD. EFLT first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. Conclusions: Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV1/FVC ratio from GOLD I to IV. A reduction of FEV1 occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of ACT. Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV. © 2010 Informa Healthcare USA, Inc

Driving-related neuropsychological performance in stable COPD patients

Background. Cognitive deterioration may impair COPD patient's ability to perform tasks like driving vehicles. We investigated: (a) whether subclinical neuropsychological deficits occur in stable COPD patients with mild hypoxemia (PaO> 55 mmHg), and (b) whether these deficits affect their driving performance. Methods. We recruited 35 stable COPD patients and 10 normal subjects matched for age, IQ, and level of education. All subjects underwent an attention/alertness battery of tests for assessing driving performance based on the Vienna Test System. Pulmonary function tests, arterial blood gases, and dyspnea severity were also recorded. Results. COPD patients performed significantly worse than normal subjects on tests suitable for evaluating driving ability. Therefore, many (22/35) COPD patients were classified as having inadequate driving ability (failure at least in one of the tests), whereas most (8/10) healthy individuals were classified as safe drivers (P=0.029). PaOand FEV1 were correlated with almost all neuropsychological tests. Conclusions. COPD patients should be warned of the potential danger and risk they face when they drive any kind of vehicle, even when they do not exhibit overt symptoms related to driving inability. This is due to the fact that stable COPD patients may manifest impaired information processing operations. © 2013 Foteini Karakontaki et al

A real-world observational study examining the impact of aclidinium bromide therapy on the quality of life, symptoms, and activity impairment of patients with chronic obstructive pulmonary disease: The greek ON-AIR study

Purpose: This multicenter, prospective, observational study aimed to supplement real-world evidence on the effects of aclidinium bromide on the quality of life (QoL), symptoms, and activity impairment of patients with COPD. Patients and Methods: Eligible patients were ≥40 years of age, newly initiated on aclidinium bromide as monotherapy or add-on therapy according to the product’s approved label. Patient-reported COPD assessment test (CAT), the severity of symptoms and their impact on daily activities, and the features of the Genuair® inhaler device were assessed at enrollment and at 12 weeks post-treatment onset. Results: Between 13 March 2015 and 29 January 2016, 285 eligible consenting patients (76.3% males; median age: 69.0 years; 26.0% newly diagnosed with COPD) were enrolled by 15 hospital-based respiratory medicine specialists in Greece. Aclidinium bromide was initiated as add-on therapy to other inhaled maintenance medications in 73.1% of evaluable patients. The median (interquartile range [IQR]) baseline CAT score decreased from 14.0 (9.0–20.0) to 10.0 (6.0–15.0) points (p<0.001) after 12 weeks of treatment, with 76.5% of the patients achieving a ≥2-point decrease. The severity of night-time and early-morning symptoms, assessed using a 5-point Likert-type scale, decreased from a median (IQR) of 1.0 (0.0–2.0) to 0.0 (0.0–1.0), and from 2.0 (1.0–2.0) to 1.0 (1.0–2.0), respectively (p<0.001 for both). In patients with paired data, the prevalence of at least moderate night-time symptoms, early-morning symptoms, and daily activity impairment decreased from 28.2% to 19.1%, from 63.6% to 34.2%, and from 59.5% to 38.7%, respectively (p<0.001 for all). Inhaler device features were assessed as “very good”/“good” by more than 90% of the patients. The adverse drug reaction rate was 1.4%. Conclusion: The study provides real-world evidence on the beneficial effects of aclidinium bromide on the patients’ QoL, symptom severity, and daily activity impairment, which are complemented by a favorable safety profile and high patient satisfaction with the inhaler device. © 2020 Kostikas et al. This work is published and licensed by Dove Medical Press Limited

Effect of pulmonary rehabilitation on tidal expiratory flow limitation at rest and during exercise in COPD patients

We hypothesized that severe COPD patients who present with the disadvantageous phenomenon of Expiratory Flow Limitation (EFL) may benefit as COPD patients without EFL do after implementation of a Pulmonary Rehabilitation (PR) program. Forty-two stable COPD patients were studied at rest and during exercise. EFL and dynamic hyperinflation (DH) were documented using the negative expiratory pressure (NEP) technique and inspiratory capacity (IC) maneuvers, respectively. Patient centered outcomes were evaluated by the Saint-George's Respiratory Questionnaire (SGRQ) and the mMRC dyspnea scale. Before PR, 16 patients presented with EFL at rest and/or during exercise. After PR, EFL was abolished in 15 out of those 16 EFL patients who exhibited a significant increase in IC values. These were mainly accomplished through a modification of the breathing pattern. In the 26 NFL patients no increase was noted in their IC or a modification of their breathing pattern. However, both NFL and EFL COPD patients improved exercise capacity and patients centered outcomes undergoing the same PR program. © 2017 Elsevier B.V

Dual bronchodilator in the era of triple therapy

Pharmacological medications used for the treatment of COPD patients have increased significantly. Long-acting bronchodilators have been recognized as the mainstay of the treatment of stable COPD, while ICS are usually added in patients with COPD who experience exacerbations, despite bronchodilator treatment. In the latest years, several studies have been published showing the beneficial effect of adding ICS on dual bronchodilation in patients suffering from more severe disease comparing triple therapy with several therapeutic regiments including dual bronchodilation and providing a message that this triple therapy might be more appropriate for COPD patients. However, not all COPD patients have a desirable response to ICS treatment while long-term ICS use in COPD is associated with several side effects. In this report, we aimed to provide a review of the current knowledge on the importance of dual bronchodilation on COPD patients and to compare its use with triple therapy, by covering a wide spectrum of topics. Finally, we propose an algorithm on performing treatment step up from dual bronchodilation to triple therapy and step down from triple to double bronchodilation considering the current evidence. © 2020 Papaioannou et al

PCSK9 inhibitors in clinical practice: Novel directions and new experiences

Background: In randomized clinical trials, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein-cholesterol (LDL-C) with a favorable tolerability and safety profile. Our purpose is to provide real-world data regarding the indications, efficacy and safety of PCSK9i. Methods: The cohort comprised 141 patients who attended the lipid clinic of 3 hospitals in Greece and started using PCSK9i. Patients were requested to attend the lipid clinic at 3 months and at 1 year. Results: Ninety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). A PCSK9i [evolocumab 140 mg/2 weeks (n = 82), alirocumab 75 mg/2 weeks (n = 46) and alirocumab 150 mg/2 weeks (n = 13)] was prescribed due to failure to achieve LDL-C targets despite maximum lipid-lowering therapy (LLT) in 75% of patients, while in the remaining cases, the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2% and remained constant at 12 months (55.8% reduction from baseline). LDL-C target was achieved by 68.1% of patients at 3 months. “Totally” intolerant to statins patients (unable to tolerate any statin dose, n = 23) showed the lowest LDL-C reduction (47.7%). Side effects attributed to treatment were reported by 14 patients (10%). The total number of patients who stopped PCSK9i at 1 year was 14 (10%) but only 2 (1.4%) discontinued treatment because of side effects (myalgias). Conclusions: Our real-world results of PCSK9i showed comparable efficacy and tolerability to those reported in clinical trials and highlighted the value of treatment with PCSK9i heFH patients not achieving LDL-C targets despite maximum LLT and high or very high risk statin intolerant patients. © 2019 Hellenic Society of Cardiolog

Renal Precision Medicine in Neonates and Acute Kidney Injury: How to Convert a Cloud of Creatinine Observations to Support Clinical Decisions

Renal precision medicine in neonates is useful to support decision making on pharmacotherapy, signal detection of adverse (drug) events, and individual prediction of short- and long-term prognosis. To estimate kidney function or glomerular filtration rate (GFR), the most commonly measured and readily accessible biomarker is serum creatinine (Scr). However, there is extensive variability in Scr observations and GFR estimates within the neonatal population, because of developmental physiology and superimposed pathology. Furthermore, assay related differences still matter for Scr, but also exist for Cystatin C. Observations in extreme low birth weight (ELBW) and term asphyxiated neonates will illustrate how renal precision medicine contributes to neonatal precision medicine. When the Kidney Disease Improving Global Outcome (KDIGO) definition of acute kidney injury (AKI) is used, this results in an incidence up to 50% in ELBW neonates, associated with increased mortality and morbidity. However, urine output criteria needed adaptations to broader time intervals or weight trends, while Scr and its trends do not provide sufficient detail on kidney function between ELBW neonates. Instead, we suggest to use assay-specific centile Scr values to better describe postnatal trends and have illustrated its relevance by quantifying an adverse drug event (ibuprofen) and by explaining individual amikacin clearance. Term asphyxiated neonates also commonly display AKI. While oliguria is a specific AKI indicator, the majority of term asphyxiated cases are non-oliguric. Asphyxia results in a clinical significant—commonly transient—mean GFR decrease (−50%) with a lower renal drug elimination. But there is still major (unexplained) inter-individual variability in GFR and subsequent renal drug elimination between these asphyxiated neonates. Recently, the Baby-NINJA (nephrotoxic injury negated by just-in-time action) study provided evidence on the concept that a focus on nephrotoxic injury negation has a significant impact on AKI incidence and severity. It is hereby important to realize that follow-up should not be discontinued at discharge, as there are concerns about long-term renal outcome. These illustrations suggest that integration of renal (patho)physiology into neonatal precision medicine are an important tool to improve contemporary neonatal care, not only for the short-term but also with a positive health impact throughout life