Georgios Hillas

C-reactive protein and procalcitonin as predictors of survival and septic shock in ventilator-associated pneumonia

We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development. 45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (ΔPCT, ΔCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables. No difference was found in CRP levels between survivors and nonsurvivors. Nonsurvivors had significantly higher PCT levels on D1 and D7. In the multivariate analysis, the only factors predicting VAP survival were ΔPCT7-1 (OR 7.23, 95% CI 0.008–0.468) and ΔCRP7-4 (OR 4.59, 95% CI 0.013–0.824). VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330–5.715). Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.

Managing comorbidities in COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.

Increased levels of angiopoietins 1 and 2 in sputum supernatant in severe refractory asthma

Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin‐1 (Ang‐1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin‐2 (Ang‐2) acts as its natural inhibitor.

Biomarkers obtained by non-invasive methods in patients with COPD: where do we stand, what do we expect?

Recently, there has been widespread interest in the use of non-invasive methods for the assessment of airway inflammation in a variety of lung diseases including chronic obstructive pulmonary disease (COPD). Sputum induction is a semi-invasive technique the value of which is not restricted to sputum cell counts, as inflammatory mediators can also be measured in the supernatants. However, none of the measurable biomarkers in induced sputum is considered applicable in clinical practice. Despite the predominating sputum neutrophilia, there is increasing evidence that the presence of sputum eosinophilia predicts an objective response to steroid treatment in patients with COPD. The commonly used Exhaled Breath Condensate (EBC) methodologies in COPD patients have considerable variability due to technical issues concerning both sample collection and analysis. Despite the above limitations, biomarkers mainly related to neutrophil derived products and oxidative stress, have been assessed for disease monitoring and response to pharmacological treatment. Endogenous airway acidification, as assessed by EBC pH, represents a measurable marker associated with oxidative stress and sputum neutrophilia. The fraction of exhaled nitric oxide (FeNO) is the most extensively studied exhaled biomarker and increased levels of FeNO have been widely documented in patients with asthma. FeNO measurement in COPD is of limited value due to smoking effect. However, increased values of FeNO have been found in COPD patients with sputum eosinophila. Moreover, measuring FeNO in different exhalation rates may reestablish its value in COPD. Despite the limited use of non-invasive methods, the future direction is a challenge towards new biomarkers or a combination of them that will assist us to move from the research laboratory to daily clinical practice.

Exhaled nitric oxide and exhaled breath condensate pH as predictors of sputum cell counts in optimally treated asthmatic smokers

Background and objective:u2003 Smoking is thought to modify the pattern of airway inflammation. Induced sputum provides useful information on cellular phenotype in inflammatory airways disorders; however, it is time‐consuming and difficult to implement in everyday clinical practice. The aim of this study was to determine whether exhaled NO (FeNO) and exhaled breath condensate (EBC) pH differed in asthmatic smokers compared with asthmatic non‐smokers and healthy subjects, and to evaluate the performance of FeNO and EBC pH for predicting the cellular phenotype of induced sputum.

Persistent airflow obstruction in patients with asthma: Characteristics of a distinct clinical phenotype.

BACKGROUNDnSome patients with asthma present persistent airflow limitation but their clinical and inflammatory characteristics have not been extensively described. In this study we aimed to identify differences in the clinical, functional and inflammatory characteristics between patients with asthma with and without persistent airflow obstruction.nnnMETHODSnPatients (n = 170) were consecutively recruited from two tertiary Asthma Clinics. Patients demographics, pulmonary function tests, inflammatory cells in induced sputum, bronchial hyperresponsiveness (BHR, PD15 to methacholine) and treatment regimens were recorded.nnnRESULTSnSixty patients (35.3%) presented persistent airflow obstruction. Besides differences in lung function, patients with persistent obstruction presented, lower methacholine PD20, higher exhaled NO, and higher eosinophil and neutrophil counts in induced sputum. The majority (71.7%) of the patients with persistent obstruction fulfilled the ATS criteria for severe refractory asthma (SRA), in contrast to 4.5% in the group without persistent obstruction. A cluster analysis identified three clinically relevant clusters: Cluster 1 (n = 56, not related to persistent airflow obstruction) included non-atopic patients, who did not receive high-dose ICS without SRA; Cluster 2 (n = 53, related to persistent airflow obstruction) included atopic patients, receiving high-dose ICS and/or oral CS, fulfilling SRA criteria; Cluster 3 (n = 61, not related to persistent airflow obstruction) included atopic patients not receiving high-dose ICS, without SRA.nnnCONCLUSIONSnAsthma patients with persistent airflow obstruction present a distinct asthma phenotype, with significant differences in clinical, functional and inflammatory characteristics compared to patients without fixed airway obstruction. These patients present more often severe refractory asthma and require more intense treatment.

Sputum and BAL Clara cell secretory protein and surfactant protein D levels in asthma

Clara cell secretory protein (CC16) is associated with Th2 modulation. Surfactant protein D (SPD) plays an important role in surfactant homeostasis and eosinophil chemotaxis. We measured CC16 and SPD in sputum supernatants of 84 asthmatic patients and 12 healthy controls. In 22 asthmatics, we additionally measured CC16 and SPD levels in BAL and assessed smooth muscle area (SMA), reticular basement membrane (RBM) thickness, and epithelial detachment (ED) in bronchial biopsies. Induced sputum CC16 and SPD were significantly higher in patients with severe asthma (SRA) compared to mild–moderate and healthy controls. BAL CC16 and SPD levels were also higher in SRA compared to mild–moderate asthma. CC16 BAL levels correlated with ED, while SPD BAL levels correlated with SMA and RBM. Severity represented a significant covariate for these associations. CC16 and SPD levels are upregulated in SRA and correlate with remodeling indices, suggesting a possible role of these biomarkers in the remodeling process.

Sputum interleukin-13 as a biomarker for the evaluation of asthma control.

Asthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin‐13 (IL‐13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control.

Activin A and follistatin in patients with asthma. Does severity make the difference

Activin A is a pleiotropic cytokine holding a fundamental role in inflammation and tissue remodelling. Follistatin can modulate the bioactivity of activin. We aimed to measure activin A and follistatin in sputum supernatants and bronchoalveolar lavage (BAL) of asthmatic patients and to determine the possible associations with severity as well as with inflammatory and remodelling indices.

The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis

Introduction Bronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non‐cystic fibrosis (non‐CF) bronchiectasis, little is known about non‐invasive techniques used for evaluating airway inflammation in obstructive airway diseases. Objectives We sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non‐CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD. Methods We evaluated prospectively collected data from subjects with bronchiectasis. Comparisons were made between clinical, radiographic and physiologic characteristics, as well as induced sputum markers using appropriate statistical tools. We compared the levels of sputum markers with those of a previously studied cohort of asthma and COPD patients. Results We enrolled 40 subjects (21 men, mean age 63.5 yrs) with bronchiectasis. Fifteen subjects (37.5%) had a neutrophilic phenotype, 7 (17.5%) had an eosinophilic phenotype, 3 (12.5%) had a mixed neutrophilic‐eosinophilic phenotype and 15 (37.5%) had a paucigranulocytic phenotype. Subjects with sputum neutrophilia had more severe bronchiectasis in HRCT and higher levels of IL‐8 in sputum, whereas subjects with eosinophilia had higher levels of FeNO, greater bronchodilator reversibility and higher sputum IL‐13. Sputum IL‐8 levels were higher in subjects exhibiting frequent exacerbations and correlated with neutrophils in sputum (r = 0.799), the extent of bronchiectasis in HRCT (r = 0.765) and post‐bronchodilator FEV1 (r = −0.416). Sputum IL‐13 levels correlated with sputum eosinophils (r = 0.656) and bronchodilator reversibility (r = 0.441). Neutrophilic bronchiectasis exhibited comparable IL‐8 levels to COPD, whereas eosinophilic bronchiectasis showed significantly lower IL‐13 levels compared to asthma. Conclusions Sputum cell counts and IL‐8 and IL‐13 correlate with distinct clinical and functional measurements of disease severity and therefore may have a role for non‐invasively assessing inflammation in non‐cystic fibrosis bronchiectasis. HighlightsInduced sputum is used for assessing airway inflammation in non‐CF bronchiectasis.Interleukin levels in induced sputum may correlate with disease severity.IL‐8 and IL‐13 levels were compared with clinical and laboratory characteristics.IL‐8 was associated with sputum neutrophilia and greater disease severity.IL‐13 was associated with sputum eosinophilia and bronchodilator reversibility.