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Anti-Tissue Antibodies Are Related to Lung Function in Chronic Obstructive Pulmonary Disease

RATIONALE Chronic obstructive pulmonary disease (COPD) is a multicomponent disease. Autoimmunity can contribute to the pathogenesis of COPD. OBJECTIVES This study investigates the prevalence of circulating antinuclear antibodies (ANA) and anti-tissue (AT) antibodies, two common markers of autoimmunity, in COPD and their relationship with several components of the disease. METHODS We determined lung function, the serum titers of ANA and AT by immunofluorescence, and the serum levels of C-reactive protein (CRP) by high sensitivity nephelometry in 328 patients with clinically stable COPD and in 67 healthy controls recruited in the PAC-COPD study. Multiple linear and logistic regression analysis was used to analyze results. MEASUREMENTS AND MAIN RESULTS The prevalence of abnormal ANA and AT titers was 34% and 26% in patients and 3% and 6% in controls, respectively. Levels of AT greater than or equal to 1:320 were seen in 21% of patients with COPD and were independently associated with the severity of airflow limitation and gas transfer impairment (P < 0.05). Neither ANA or AT titers was related to body mass index, current smoking status, use of inhaled steroids, the Charlson index, or serum C-reactive protein values. CONCLUSIONS Between a quarter and a third of patients with clinically stable COPD present abnormal titers of circulating ANA and AT. The observed relationship between AT and lung function supports a role for autoimmunity in the pathogenesis of COPD.

Low erythropoietin plasma levels during exacerbations of COPD.

Background: It is known that pro-inflammatory cytokines suppress in vitro the gene expression and protein production of erythropoietin (Epo). We hypothesized that systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) may influence Epo production, particularly during episodes of exacerbation of the disease (ECOPD) where an inflammatory burst is known to occur. Objectives: We compared the plasma levels of Epo and high-sensitivity (hs) C-reactive protein (hsC-RP) in patients hospitalized because of ECOPD (n = 26; FEV1: 48 ± 15% predicted), patients with clinically stable COPD (n = 31; FEV1: 49 ± 17% predicted), smokers with normal lung function (n = 9), and healthy never smokers (n = 9). Methods: Venous blood samples were taken between 9 and 10 a.m. after an overnight fast into tubes with EDTA (10 ml) or without EDTA (10 ml). Plasma levels of Epo (R&D Systems Inc., Minneapolis, Minn., USA) and hsC-RP (BioSource, Belgium) were determined by ELISA. Results: Log-Epo plasma levels were significantly lower (0.46 ± 0.32 mU/ml) in ECOPD than in stable COPD (1.05 ± 0.23 mU/ml), smokers (0.95 ± 0.11 mU/ml) and never smokers with normal lung function (0.92 ± 0.19 mU/ml) (p < 0.01, each). In a subset of 8 COPD patients who could be studied both during ECOPD and clinical stability, log-Epo increased from 0.49 ± 0.42 mU/ml during ECOPD to 0.97 ± 0.19 mU/ml during stability (p < 0.01). In patients with COPD log-Epo was significantly related to hsC-RP (r = –0.55, p < 0.0001) and circulating neutrophils (r = –0.48, p < 0.0001). Conclusions: These results show that the plasma levels of Epo are reduced during ECOPD likely in relation to a burst of systemic inflammation.

Differential effects of smoking and COPD upon circulating myeloid derived suppressor cells

BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor ζ chain (TCR ζ) through the catabolism of l-arginine. The effects of smoking on MDSCs and their potential participation in COPD immunopathogenesis have not been explored so far. METHODS To investigate it, we compared the level of circulating Lineage-/HLA-DR-/CD33+/CD11b+ MDSCs, the serum concentration of arginase I (ARG I) and the expression of peripheral T-cell receptor ζ chain (TCR ζ) in never smokers, smokers with normal spirometry and COPD patients. Flow cytometry was used to quantify circulating MDSCs and TCR ζ expression. Serum ARG I levels were determined by ELISA. RESULTS The main findings of this study were that: (1) current smoking upregulates and activates circulating MDSCs both in smoker controls and COPD patients; and, (2) at variance with the smokers with normal spirometry, in patients with COPD this effect persists after quitting smoking and is accompanied by a significant and specific down-regulation of the TCR ζ chain expression in circulating T lymphocytes. CONCLUSION Smoking modulates circulating MDSCs. Their regulation appears altered in patients with COPD.

HLA distribution in COPD patients.

Abstract Background: Auto-immunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), particularly to the presence of emphysema. Auto-immune diseases are characterized by an abnormal distribution of HLA class II alleles (DR and DQ). The distribution of DRB1 and DQB1 alleles has not been investigated in COPD. Methods: To this end, HLA medium-low resolution typing was performed following standardized protocols in 320 clinically stable COPD patients included in the PAC-COPD study. Results were compared with controls of the same geographical and ethnic origin, and potential relationships with the severity of airflow limitation and lung diffusing capacity impairment were explored in patients with COPD. Results: The distribution of DRB1 and DQB1 alleles in COPD was similar to that of controls except for a significantly higher prevalence of DRB1*14 in patients with severe airflow limitation and low diffusing capacity. Conclusions: By and large, HLA distribution was similar in COPD patients and controls, but the HLA class II allele DRB1*14 may contribute to the pathogenesis of severe COPD with emphysema.

Características de pacientes asmáticos ingresados en una unidad de cuidados respiratorios intermedios

INTRODUCTION Intermediate respiratory care units (IRCU) provide continuous monitoring and non-invasive mechanical ventilation (NIMV) in patients with severe respiratory failure who are usually admitted to intensive care units (ICU). The usefulness of IRCU in managing severe asthma exacerbations has never been evaluated. METHODS Clinical data were prospectively and systematically compiled from patients admitted to the IRCU with a principal diagnosis of bronchial asthma exacerbation. We assessed therapeutic failure (intubation or exitus) and patient evolution up until 6 months after discharge compared with a group of patients admitted to a conventional hospital ward, paired for age and sex, and with the same principal diagnosis. RESULTS A total of 74 asthma patients were included (37 admitted to IRCU and 37 to the hospital ward) with a mean age (±SD) of 58±20, who were predominantly women (67%), with previous diagnosis of asthma and persistent asthma treatment. The main cause of admittance to the IRCU was severe respiratory failure. The patients who were admitted to the IRCU presented more radiological affectation (alveolar infiltrates) and had significantly higher pCO(2). Ten patients admitted to the IRCU required NIMV. There were no differences between the two groups regarding either therapeutic failure or the 6-month follow-up after discharge. CONCLUSIONS Patients with severe asthma exacerbations can be managed in an IRCU while avoiding hospitalization in an ICU and demonstrating a prognosis similar to milder exacerbations treated in conventional hospital wards.

Transbronchial cryobiopsy in the diagnosis of the idiopathic interstitial pneumonias

Background Histology is crucial for the multidisciplinary diagnosis of idiopathic interstitial pneumonias (IIP). Transbronchial cryobiopsy (TBC) has been demonstrated to be useful for obtaining lung parenchyma; however its experience in the diagnosis of IIP is limited. Objectives To describe the diagnostic yield and safety of TBC in the study of IIP. Method Prospective study of 23 outpatients of TBC. All cases had the typical clinical and radiological features of IIP. The endoscopic procedure was performed in the operating theatre using a flexible bronchoscope obtaining 3-5 biopsies of lung parenchyma with radiological control. Biopsies were reviewed by the reference pathologist. Results The patients were 65±10-year-old (57% men). The length range of biopsies was 2-7 mm. The sample was adequate (at least 20 alveolar spaces) in 20 patients (87%). The specific diagnosis (confirmed by Multidisciplinary discussion) was obtained in 12 patients (52%): usual interstitial pneumonia (UIP n=9) and nonspecific interstitial pneumonia (NSIP n=3). The complications were: pneumothorax in 2 patients (both required drainage), 4 patients showed significant bleeding (>100 ml), one of them severe with respiratory failure but the patient recovered 3 days after. In the remaining patients the diagnosis was reached by VATS (9 patients: UIP [n=5], unclassifiable interstitial pneumonia [n=2], NSIP [n=1] and respiratory bronchiolitis associated to interstitial pneumonia [n=1]), or by clinical and radiological parameters (1 organising pneumonia, 1 UIP). Conclusions In patients with suspected IIP, TBC is useful to obtain lung parenchyma with good yield and avoids in 52% of open biopsies in our population.