Influence of low temperature on bronchodilatation induced by terbutaline administered by metered dose or dry powder inhalers in asthmatics.

Low temperatures may affect dose delivery efficacy and clinical effectiveness of medication aerosols. In this study we examine the effect of cold ambient temperature on the bronchodilatation produced by terbutaline delivered from a chlorofluorocarbon pressurized metered dose inhaler (pMDI) compared to a multi-dose dry powder inhaler (DPI). Fourteen stable asthmatics were studied on two consecutive days. On day 1, after measuring FEV1 at room temperature (22 degrees C), each patient was randomized to receive 500 microg of terbutaline delivered from pMDI or DPI stored for 24 h at 22 degrees C with FEV1 recorded 20 min post-dose; then, patients were placed in a chamber at -10 degrees C, and af…

Neumorreducción en el tratamiento del enfisema: resultados preliminares

Se presentan los resultados de las primeras 3 neumorre-ducciones que se han realizado en nuestro hospital como tratamiento paliativo del enfisema pulmonar. Se reseco el tercio superior del LSD y parte del medio en 2 pacientes y se hizo lobectomia superior derecha en el otro. Se utilizo autosutura recubierta de goretex, se hizo pleurodesis con talco del tercio superior del hemitorax y se colocaron drenajes con aspiracion a -5 cmH2O. Se resalta lo evolucionados que estaban los pacientes y los buenos resultados obtenidos en cuanto a mortalidad, estancia hospitalaria y mejoria funcional y clinica. Se propone considerar la mejoria que produce la neumorreduccion, cuando se valore funcionalmente u…

Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

Background: Inhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD patients were used to compare the anti-inflammatory effects of aclidinium bromide (a long-acting muscarinic antagonist) with corticosteroids and their potential additive effect. Methods: Human sputum and blood neutrophils were isolated from healthy individuals ( n = 37), patients with stable COPD ( n = 52) and th…

Vascular effects of sildenafil in patients with pulmonary fibrosis and pulmonary hypertension: an ex vivo/in vitro study

Sildenafil improves the 6-min walking distance in patients with idiopathic pulmonary fibrosis (IPF) and right-sided ventricular systolic dysfunction.We analysed the previously unexplored role of sildenafil on vasoconstriction and remodelling of pulmonary arteries from patients with IPF and pulmonary hypertension (PH) ex vivo. Pulmonary arteries from 18 donors without lung disease, nine IPF, eight PH+IPF and four PH patients were isolated to measure vasodilator and anti-contractile effects of sildenafil in isometric organ bath. Ventilation/perfusion was explored in an animal model of bleomycin lung fibrosis.Sildenafil relaxed serotonin (5-HT) pre-contracted pulmonary arteries in healthy dono…

Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences

BACKGROUND AND PURPOSE Pulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ETB) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction. EXPERIMENTAL APPROACH ETB receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca2+, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A2 and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phal…

Cigarette smoke-induced pulmonary endothelial dysfunction is partially suppressed by sildenafil.

Abstract Cigarette smoke mediated oxidative stress and endothelial dysfunction are important processes in the pathogenesis of several lung disorders. In this study we evaluated the effect of PDE5 inhibition on pulmonary artery endothelial dysfunction induced by cigarette smoke in vitro . Human pulmonary artery endothelial cells (HPAEC) were incubated in the absence or presence of PDE5 inhibitor sildenafil (10 nM–1 μM), PKG agonist 8-Br-cGMP (1 mM), or the antioxidants dyphenyleneiodonium (DPI 1 μM) and N -acetylcysteine (NAC 1 mM) for 30 min. Then, cigarette smoke extract (CSE) was added for 24 h. CSE (2.5–10%)-induced ROS generation was suppressed by DPI, and partially reversed by sildenaf…

Cigarette Smoke-Induced Fibroblast Activation Is Attenuated By Aclidinium In Vitro

Neutrophil activation in severe, early-onset COPD patients versus healthy non-smoker subjects in vitro: effects of antioxidant therapy.

<i>Background:</i> Neutrophils and oxidative stress have been implicated in the pathogenesis of COPD. Severe, early-onset COPD is characterized by a rapid decline in the lung function at an early age; however, nothing is known about neutrophil activation in COPD patients. <i>Objectives:</i> The aim of this study was to evaluate peripheral blood neutrophil activation in severe, early-onset COPD patients versus healthy non-smokers and the effect of N-acetyl-<i>L</i>-cysteine (NAC) on neutrophil activation in vitro. <i>Methods:</i> Neutrophils were isolated from 15 severe, early-onset COPD patients and 15 age-matched healthy subjects and stimulat…

Direct effect of cigarette smoke on human pulmonary artery tension.

The effect of chronic cigarette smoke on pulmonary artery (PA) tension has been studied extensively; nevertheless, the direct effect of cigarette smoke is poorly understood. We investigated the direct effect of cigarette smoke extract (CSE) on PA tension in non-smokers, smokers, and COPD patients in vitro. PA samples from 35 patients who underwent lung resection were examined by measuring isometric tension in response to increasing serotonin concentrations. CSE dose dependently inhibited the response to serotonin in smokers and COPD patients, and to a lesser extent in non-smokers. CSE-induced relaxation was similarly inhibited by the nonspecific nitric oxide synthase (NOS) inhibitor l-NOARG…

Insuficiencia respiratoria aguda como primera manifestación de lesiones del tronco cerebral

We describe three patients with different brainstem lesions (bulbar angioma, bulbar infarct, and Arnold-Chiari malformation) who debuted with acute respiratory insufficiency. Other neurological manifestations had gone unobserved in all three cases. Respiratory insufficiency worsened notably during sleep to the point that mechanical ventilation was required or death occurred (Ondine s curse). The patient with a bulbar angioma is stable with only assisted ventilation by a nasal route at night, with good quality of life. Our conclusions are that: a) central nervous system anomalies need to be investigated as possible causes of respiratory insufficiency when lungs are normal; b) the respiratory…

Cirugía combinada para cáncer de pulmón y reducción de volumen en pacientes con enfisema avanzado

Authors' Reply to “Lung Volume Reduction Surgery in Patients With Enphysema: the Spanish Experience

Diaphragmatic paralysis following minor cervical trauma.

Two asthmatic patients developed unilateral diaphragmatic paralysis from phrenic nerve injury, in one case following cervical chiropractic manipulation and in the other after a motorcycle accident. Both presented with increased dyspnea and orthopnea. Diagnosis, severity, and level of the lesion were established by neurophysiological methods, which are preferred to chest radiography and diaphragmatic ultrasonography. In spite of only partial electrophysiological recovery of the nerve, both patients were asymptomatic 1 year later.

Inhibitory effects of N-acetylcysteine on the functional responses of human eosinophils in vitro

Background Oxidative stress appears to be relevant in the pathogenesis of inflammation in allergic diseases like bronchial asthma. Eosinophils are oxidant-sensitive cells considered as key effectors in allergic inflammation. Objective The aim of this work was to study the effects of the clinically used antioxidant N-acetyl-L-cysteine (NAC) on the functional responses of human-isolated eosinophils. Methods Human eosinophils were purified from the blood of healthy donors by a magnetic bead separation system. The effects of NAC were investigated on the generation of reactive oxygen species (chemiluminescence and flow cytometry), Ca2+ signal (fluorimetry), intracellular glutathione (GSH; flow c…

Electrophysiologic evaluation of phrenic nerve and diaphragm function after coronary bypass surgery: Prospective study of diabetes and other risk factors

Objective Phrenic neuropathy after coronary artery bypass grafting has been related to various risk factors with conflicting results. The aim of this study was to assess the incidence, characteristics, and clinical consequences of phrenic neuropathy and the influence of diabetes and other risk factors. Methods We conducted an observational, prospective study of parallel groups including 94 consecutive patients subjected to coronary artery bypass grafting, half of them with diabetes and associated polyneuropathy . Electrophysiologic study of phrenic nerve conduction as the reference method, chest radiography, diaphragm ultrasound, and functional respiratory tests were performed 24 to 48 hour…

PGC-1α Induction in Pulmonary Arterial Hypertension

Idiopathic Pulmonary arterial hypertension (IPAH) is characterized by the obstructive remodelling of pulmonary arteries, and a progressive elevation in pulmonary arterial pressure (PAP) with subsequent right-sided heart failure and dead. Hypoxia induces the expression of peroxisome proliferator activated receptorγcoactivator-1α(PGC-1α) which regulates oxidative metabolism and mitochondrial biogenesis. We have analysed the expression of PGC-1α, cytochrome C (CYTC), superoxide dismutase (SOD), the total antioxidant status (TAS) and the activity of glutathione peroxidase (GPX) in blood samples of IPAH patients. Expression of PGC-1αwas detected in IPAH patients but not in healthy volunteers. Th…

Additional file 1: of Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

Supplementary Table S1. Maximal percentage of inhibition of IL-8, MMP-9, CCL-5, GM-CSF and IL-1β release from neutrophils of healthy subjects and COPD patients. Neutrophils were incubated with aclidinium (Acl; 0.1nM-1 μM), fluticasone (Flut; 0.1nM-1 μM), formoterol (Form; 0.01nM-100nM) or salmeterol (Salm; 0.1nM-1 μM) in response to LPS (1 μg/ml) or cigarette smoke extract (CSE 5 %). The levels of different cytokines in the cell supernatant were determined and the maximal percent of inhibitions were calculated. Values are mean ± SD of 3 independent experiments run in triplicate. *p 

Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a

Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients’ …

Additional file 2: of Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

Supplementary Figure E1. Effects of formoterol and salmeterol on pro-inflammatory markers. Concentration-dependent inhibition of lipopolysaccharide (LPS)-induced cytokines or MMP-9 release by formoterol (Form) and salmeterol (Salm) from peripheral blood neutrophils of healthy subjects and COPD patients. Neutrophils were preincubated with Salm (0.1nM-1 μM) or form (0.01nM-100nM) for 1 h followed by cell stimulation with LPS (1 μg/ml) for 6 h. Results are expressed as means ± SD of n = 3 (3 cell healthy and 3 cell COPD populations run in triplicate) independent experiments. Two-way ANOVA was followed by the post hoc Bonferroni test. *p