Ernest Sala

Systemic effects of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterised by an inappropriate/excessive inflammatory response of the lungs to respiratory pollutants, mainly tobacco smoking. Recently, besides the typical pulmonary pathology of COPD (i.e. chronic bronchitis and emphysema), several effects occurring outside the lungs have been described, the so-called systemic effects of COPD. These effects are clinically relevant because they modify and can help in the classification and management of the disease. The present review discusses the following systemic effects of chronic obstructive pulmonary disease: 1) systemic inflammation; 2) nutritional abnormalities and weight loss; 3) skeletal muscle dysfunction; and 4) other potential systemic effects. For each of these, the potential mechanisms and clinical implications are discussed and areas requiring further research are highlighted.

Low-dose theophylline enhances the anti- inflammatory effects of steroids during exacerbations of COPD

Background: Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease (ECOPD). Reduced activity of histone deacetylases (HDAC) contributes to enhanced inflammation in stable COPD. It was hypothesised that HDAC activity is further reduced during ECOPD and that theophylline, an HDAC activator, potentiates the anti-inflammatory effect of steroids in these patients. A study was performed to investigate HDAC activity during ECOPD and the effects of theophylline on the anti-inflammatory effects of steroids in a randomised single-blind controlled study. Methods: 35 patients hospitalised with ECOPD and treated according to international guidelines (including systemic steroids) were randomised to receive or not to receive low-dose oral theophylline (100 mg twice daily). Before treatment and 3 months after discharge, HDAC and nuclear factor-κB (NF-κB) activity in sputum macrophages, the concentration of nitric oxide in exhaled air (eNO) and total antioxidant status (TAS), tumour necrosis factor α (TNFα), interleukin (IL)-6 and IL8 levels in sputum supernatants were measured. Results: Patients receiving standard therapy showed decreased NF-κB activity, eNO concentration and sputum levels of TNFα, IL6 and IL8, as well as increased TAS during recovery of ECOPD, but HDAC activity did not change. The addition of low-dose theophylline increased HDAC activity and further reduced IL8 and TNFα concentrations. Conclusions: During ECOPD, low-dose theophylline increases HDAC activity and improves the anti-inflammatory effects of steroids. Trial registration number: NCT00671151

Prevalence of and risk factors for pulmonary abnormalities in HIV‐infected patients treated with antiretroviral therapy

Pulmonary abnormalities are often present in patients infected with the human immunodeficiency virus (HIV).

A controlled trial of noninvasive ventilation for chronic obstructive pulmonary disease exacerbations

PURPOSE This prospective, multicenter, double-blind, placebo-controlled study tested the hypothesis that noninvasive positive pressure ventilation reduces the need for endotracheal intubation in patients hospitalized in a pulmonary ward because of acute exacerbation of chronic obstructive pulmonary disease. MATERIALS AND METHODS Seventy-five consecutive patients with exacerbation (pH, 7.31 +/- 0.02; Pao(2), 45 +/- 9 mm Hg; Paco(2), 69 +/- 13 mm Hg) were randomly assigned to receive noninvasive ventilation or sham noninvasive ventilation during the first 3 days of hospitalization on top of standard medical treatment. RESULTS The need for intubation (according to predefined criteria) was lower in the noninvasive ventilation group (13.5% vs 34%, P < .01); in 31 patients with pH not exceeding 7.30, these percentages were 22% and 77%, respectively (P < .001). Arterial pH and Paco(2) improved in both groups, but changes were enhanced by noninvasive ventilation. Length of stay was lower in the noninvasive ventilation group (10 +/- 5 vs 12 +/- 6 days, P = .06). In-hospital mortality was similar in both groups. CONCLUSIONS These results demonstrate that noninvasive positive pressure ventilation, in a pulmonary ward, reduces the need for endotracheal intubation, particularly in the more severe patients, and leads to a faster recovery in patients with acute exacerbation of chronic obstructive pulmonary disease.

Pulmonary gas exchange responses to histamine and methacholine challenges in mild asthma

Histamine (HIST) produces greater changes in bronchial and pulmonary vasculature, and so may produce more gas exchange abnormalities, than methacholine (MTH) after inhalational challenge. The goals of this study were to compare the effects of HIST and MTH challenge on pulmonary gas exchange in patients with mild asthma at an equivalent degree of bronchoconstriction. Eleven patients were studied (mean+/-SEM age, 22+/-1 yr; forced expiratory volume in one second (FEV1), 91+/-5% pred) using a randomized, double-blind cross-over design. Respiratory system resistance (Rrs), arterial blood gases, and ventilation-perfusion distributions were measured before and after HIST/MTH challenges when cumulative doses caused a 30% fall in FEV1. Compared with baseline, HIST and MTH provoked similar moderate to severe increases in Rrs (p<0.005 each), and mild to moderate decreases in arterial oxygen tension (Pa,O2) due to ventilation-perfusion abnormalities (dispersion of pulmonary blood flow -log SDQ-, 0.40+/-0.03-0.71+/-0.08 and 0.47+/-0.04-0.89+/-0.06; normal values <0.60-0.65), respectively, similar to those shown in mild to moderate acute asthma, without differences between them. For the same degree of airflow obstruction, both histamine and methacholine bronchoprovocations induce, in patients with mild asthma, very similar disturbances in ventilation-perfusion distribution and respiratory system resistance, suggesting similar mechanisms of airway narrowing.

Tratamiento hospitalario de los episodios de agudización de la EPOC. Una revisión basada en la evidencia

Este artículo presenta una visión integrada del tratamiento de los pacientes hospitalizados por agudización de enfermedad pulmonar obstructiva crónica (AEPOC)1-5, basada en la mejor evidencia médica disponible (tabla I). El tratamiento hospitalario de la AEPOC persigue varios objetivos2,5: a) la estabilización respiratoria y hemodinámica del paciente; b) la mejoría o, si es posible, normalización del estado clínico basal del paciente; c) el diagnóstico de la(s) causa(s) de la AEPOC; d) la evaluación de la gravedad de la EPOC y la identificación de cualquier posible comorbilidad presente; e) la educación del paciente en el correcto uso de la medicación y los equipos terapéuticos (nebulizadores, inhaladores, oxigenoterapia, etc.), así como la promoción de un estilo de vida saludable antes del alta, y f) por último, la evaluación de la necesidad de tratamiento adicional en el domicilio, como rehabilitación respiratoria y/u oxigenoterapia domiciliaria. La consecución de estos objetivos requiere el manejo del paciente en diferentes niveles asistenciales del hospital: área de urgencias, sala de hospitalización, unidad de cuidados intensivos (UCI). En esta revisión se abordarán: a) el manejo clínico inicial del paciente con AEPOC en el área de urgencias; b) los criterios de ingreso hospitalario; c) el tratamiento de la AEPOC en la sala de hospitalización convencional; d) el manejo de la AEPOC en la UCI, y e) los criterios de alta desde cada uno de estos niveles asistenciales. Tras ello, se identificarán los aspectos que a juicio de los autores no están resueltos y precisan más investigación.

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.

Actividad de una unidad de cuidados respiratorios intermedios dependiente de un servicio de neumología

BACKGROUND AND OBJECTIVE With the development of noninvasive ventilation (NIV), patients with increasingly complex needs have been admitted to respiratory medicine departments. For this reason, such departments in Spain and throughout Europe have been adding specialized respiratory intermediate care units (RICUs) for monitoring and treating patients with severe respiratory diseases. The aim of the present study was to describe the activity of such a RICU. The description may be of use in facilitating the setting up of RICUs in other hospitals of the Spanish National Health Service. METHODS A systematic record of activity carried out in the RICU of the Hospital Universitario Son Dureta between January and December 2006 was kept prospectively. RESULTS Of 206 patients with a mean (SD) age of 65 (14) years admitted to the unit, 67% came from the emergency department, 14% from the respiratory medicine department, and 12% from the intensive care unit (ICU). The most common admission diagnoses were exacerbated chronic obstructive pulmonary disease (COPD) (n=97, 47.1%), pneumonia (n=39, 18.9%), heart failure (n=17, 8.2%), and pulmonary vascular diseases (n=18, 8.7%). One hundred twenty-one patients (59%) required NIV. Mean length of stay in the RICU was 5 (5) days. Patients were discharged to the conventional respiratory ward in 79.1% of the cases; 7.8% required subsequent admission to the ICU, and 9.7% died. Of the patients with exacerbated COPD (mean age, 66.5 [10] years; mean length of stay, 4.6 [4.5] days), 67% required NIV, 7.2% required subsequent admission to the ICU, and 8.2% died. CONCLUSIONS The creation of a RICU by a respiratory medicine department is viable in Spain. Such units make it possible to treat a large number of patients with a low rate of therapeutic failures. Exacerbated COPD was the most common diagnosis on admission to our RICU, and the need for NIV the most common criterion for admission.

Airway Mucin 2 Is Decreased in Patients with Severe Chronic Obstructive Pulmonary Disease with Bacterial Colonization

RATIONALE Mucins are essential for airway defense against bacteria. We hypothesized that abnormal secreted airway mucin levels would be associated with bacterial colonization in patients with severe chronic obstructive pulmonary disease (COPD) Objectives: To investigate the relationship between mucin levels and the presence of potentially pathogenic micro-organisms in the airways of stable patients with severe COPD Methods: Clinically stable patients with severe COPD were examined prospectively. All patients underwent a computerized tomography scan, lung function tests, induced sputum collection, and bronchoscopy with bronchoalveolar lavage (BAL) and protected specimen brush. Patients with bronchiectasis were excluded. Secreted mucins (MUC2, MUC5AC, and MUC5B) and inflammatory markers were assessed in BAL and sputum by ELISA. MEASUREMENTS AND MAIN RESULTS We enrolled 45 patients, with mean age (±SD) of 67 (±8) years and mean FEV1 of 41 (±10) % predicted. A total of 31% (n = 14) of patients had potentially pathogenic micro-organisms in quantitative bacterial cultures of samples obtained by protected specimen brush. Patients with COPD with positive cultures had lower levels of MUC2 both in BAL (P = 0.02) and in sputum (P = 0.01). No differences in MUC5B or MUC5AC levels were observed among the groups. Lower MUC2 levels were correlated with lower FEV1 (r = 0.32, P = 0.04) and higher sputum IL-6 (r = -0.40, P = 0.01). CONCLUSIONS Airway MUC2 levels are decreased in patients with severe COPD colonized by potentially pathogenic micro-organisms. These findings may indicate one of the mechanisms underlying airway colonization in patients with severe COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01976117).

[Hospital treatment of chronic obstructive pulmonary disease exacerbations: an evidence-based review].

This article presents an integrated overview of treatment of patients admitted to hospital for chronic obstructive pulmonary disease (COPD) exacerbations,1-5 based on the best scientific evidence available (Table 1). Hospital treatment of COPD exacerbations has several aims,2,5 namely: a) to stabilize the patient’s respiration and hemodynamics; b) to improve or, if possible, normalize the clinical state of the patient; c) to diagnose the cause or causes of the exacerbation; d) to assess the severity of COPD and identify other concurrent diseases; e) to educate the patient on how to take medication and use therapeutic equipment (nebulizers, inhalers, oxygen therapy devices, etc) correctly, and to promote a healthy lifestyle before discharge; and, finally, f) to evaluate the need for additional home treatment such as respiratory rehabilitation and/or home oxygen therapy. If these aims are to be achieved, the patient must be managed at different levels of care, that is, in the emergency room, the hospital ward, and the intensive care unit (ICU). This review will cover the following: a) initial clinical management of patients with COPD exacerbations in the emergency room; b) the criteria for admission to hospital; c) treatment for COPD exacerbations in a conventional hospital ward; d) management of COPD exacerbations in the ICU; and e) the criteria for discharge from each of these levels of care. We will then identify aspects that we consider unresolved and in need of further investigation.