M. Sofia

Increased Endothelin-Like Immunoreactive Material on Bronchoalveolar Lavage Fluid from Patients with Bronchial Asthma and Patients with Interstitial Lung Disease

Endothelin (ET) is an endothelial regulatory peptide present also in pulmonary tissue where it exerts several biological actions both on bronchial and vascular smooth muscle cells. It has been shown to increase in bronchoalveolar lavage fluid (BALF) from asthmatic patients; but changes in other chronic respiratory disease have not been well studied. We measured by a radioimmunoassay (RIA) ET-immunoreactive (IR) levels on BALF (BALF-ETIR, pg/ml) from 5 normal subjects (NS), 5 patients with chronic extrapulmonary disease (ED) without signs of lung involvement, 5 patients with allergic bronchial asthma (BA), 10 patients with idiopathic lung fibrosis (ILF) and 9 patients with miscellaneous interstitial lung disease (MILD). In 5/5 NS and 4/5 ED BALF-ETIR was lower than sensibility of RIA test used (0.8 pg/ml). BALF-ETIR was dosable in all patients with bronchopulmonary disease; means were 2.45 pg/ml in BA, 12.37 pg/ml in ILF, 2.90 pg/ml in MILD--Wilcoxons rank test (two tailed) versus NS, p < 0.05. There was an inverse correlation between BALF-ETIR values and the degree of ventilatory impairment (forced vital capacity % of predicted value, r = -0.61 p < 0.01; forced expiratory volume in 1 s % of predicted value, r = -0.71 p < 0.01) and the level of arterial pressure of O2 (PaO2; r = -0.75 p < 0.01); a positive correlation was found with number of neutrophils/ml of BALF (r = 0.52 p < 0.01)--Spearmans rank correlation. Though rarely detected on BALF from normal lungs, ET increases on BALF in patients with bronchopulmonary disease, raising the question of its involvement in pathogenic mechanisms or evolution of bronchial asthma and interstitial lung disease.

Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis

Background Nitric oxide has been detected by chemiluminescence in the lumen of nasal airway, which is increased in nasal breathing in patients with seasonal rhinitis during a chronic exposure. The purpose of this study was to determinate the effect of a NO‐synthase inhibitor NGL‐arginine methyl ester (L‐NAME) on nasal airway resistance (NAR) in patients with seasonal allergic rhinitis after an acute challenge to the allergen.

Endothelin-1 Induces Proliferation of Human Lung Fibroblasts and IL-11 Secretion Through an ET A Receptor-Dependent Activation of Map Kinases

Endothelin‐1 (ET‐1) is implicated in the fibrotic responses characterizing interstitial lung diseases, as well as in the airway remodeling process occurring in asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal human lung fibroblasts (NHLFs), the ET‐1 receptor subtypes, and the intracellular signal transduction pathways involved in the proliferative effects of this peptide. Therefore, cells were exposed to ET‐1 in the presence or absence of an overnight pre‐treatment with either ETA or ETB selective receptor antagonists. After cell lysis, immunoblotting was performed using monoclonal antibodies against the phosphorylated, active forms of mitogen‐activated protein kinases (MAPK). ET‐1 induced a significant increase in MAPK phosphorylation pattern, and also stimulated fibroblast proliferation and IL‐6/IL‐11 release into cell culture supernatants. All these effects were inhibited by the selective ETA antagonist BQ‐123, but not by the specific ETB antagonist BQ‐788. The stimulatory influence of ET‐1 on IL‐11, but not on IL‐6 secretion, was prevented by MAPK inhibitors. Therefore, such results suggest that in human lung fibroblasts ET‐1 exerts a profibrogenic action via an ETA receptor‐dependent, MAPK‐mediated induction of IL‐11 release and cell proliferation.

Detection of IgG and IgA against the mycobacterial antigen A60 in patients with extrapulmonary tuberculosis

BACKGROUND Diagnosis of extrapulmonary tuberculosis is often difficult to establish using standard methods. Serological techniques based on detection of antibodies against mycobacterial antigen A60 have shown good sensitivity and specificity in pulmonary tuberculosis. The present study was undertaken to define the diagnostic accuracy of testing for IgG and IgA against A60 in extrapulmonary tuberculosis. METHODS One hundred and ninety eight subjects were studied: 42 patients with extrapulmonary tuberculosis confirmed by microbiology and/or histology, 24 subjects with healed pulmonary or extrapulmonary tuberculosis, 44 patients with a defined non-tuberculous disease, and 88 healthy volunteers (44 PPD negative and 44 PPD positive). Detection of IgG and IgA against A60 antigen was carried out by enzyme-linked immunosorbent assay. Cut off values were determined by receiver operating characteristic curves. RESULTS Sensitivity of the IgG test was 73.8% in extrapulmonary tuberculosis, while the specificity was 96.1%. The IgA test showed a sensitivity of 69.0% with a specificity of 93.6%. Combination of the IgG and IgA tests showed a sensitivity of 80.9% and a specificity of 92.3%. Patients with extrapulmonary tuberculosis showed significantly higher titres of both IgG and IgA against A60 than other groups. CONCLUSIONS Anti-A60 IgG or IgA tests are characterised by good sensitivity and specificity. The combined use of both tests allows an increase in diagnostic accuracy of extrapulmonary tuberculosis.

Increased 24-Hour Endothelin-1 Urinary Excretion in Patients with Chronic Obstructive Pulmonary Disease

Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in patients with pulmonary hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this study we have evaluated the 24-hour urinary excretion of ET-1 in COPD patients both during acute exacerbation and stable phase of the disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on admission to the hospital for an acute exacerbation and at the recovery period. Ten healthy volunteers were also studied. Determination of plasma and 24-Hour urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1 levels in COPD patients were similar during exacerbation and recovery and were not significantly different from those in the healthy subjects. 24-hour urinary excretion of ET-1 was increased in COPD patients during acute exacerbation; it decreased during recovery, but remained elevated when compared to normal subjects. A negative correlation was found between arterial oxygen pressure and ET-1 excretion; no correlation was found between plasma and urinary ET-1 values. In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy subjects. Urinary ET-1 values are further increased during acute exacerbation of the disease.

Right ventricular performance in severe obesity. Effect of weight loss.

Backgroundu2002 The effects of severe obesity on right ventricular function in the absence of associated cardiopulmonary disease are not well known. Right myocardial performance index (R‐MPI) is an echocardiographic index to non‐invasively assess the right ventricular function.

The effect of platelet‐activating factor (PAF) on nasal airway resistance in healthy subjects is not mediated by nitric oxide

Background: The nose is an important source of nitric oxide (NO) in man, but the relevance of NO production to the response to inflammatory mediators is not clear.

Lack of effect of nitric oxide inhibition on bronchial tone and methacholine-induced bronchoconstriction in man

The role of nitric oxide (NO) as a bronchodilator has been studied in humans with controversial results. The aim of the present study was to investigate the role of endogenous NO on bronchial tone by studying whether nitric oxide synthase (NOS) inhibition with NGnitro-L-arginine-methyl-ester (L-NAME) influences basal bronchial tone, or potentiates methacholine-induced bronchoconstriction. In a preliminary experiment in five subjects, a significant reduction in exhaled NO was found after delivering L-NAME (15 mg in saline) (from 3.9 +/- 1.2 to 2.4 +/- 1.1 nmol min-1, P < 0.05). In nine healthy non-smokers, specific airway conductance (SGAW), as a measure of airway calibre, was recorded after delivering, in a double-blind, controlled vs. placebo fashion, both nebulized L-NAME and saline, at baseline and after methacholine-induced bronchoconstriction. There was no significant difference between the baseline SGAW values before and after delivering L-NAME (0.264 +/- 0.04 and 0.267 +/- 0.05 cm H2O-1 s-1, respectively). After pre-treatment with L-NAME, SGAW values during methacholine-induced bronchoconstriction were not different in comparison to values obtained after saline inhalation. It is concluded that decreased endogenous NO does not influence bronchial tone in healthy people, nor does it modify methacholine-induced bronchoconstriction.

Nitric oxide attenuates platelet-activating factor induced nasal airway plasma extravasation in healthy subjects.

Background Paranasal sinuses and the nose are important sources of nitric oxide (NO) in humans but the relevance of NO production to the control of nasal airway plasma exudation and its response to inflammatory mediators such as platelet‐activating factor (PAF) in healthy subjects is not well known.

Inhaled ultrasonically nebulized distilled water decreases exhaled nitric oxide in asthma.

Exhaled nitric oxide (eNO) is increasingly used as a marker of disease activity in asthma. Inhaled hypertonic saline has been shown to induce bronchoconstriction and to decrease eNO in asthmatic subjects, whereas the effects of hypotonic solutions on eNO in these patients have not been studied. To evaluate the effect of ultrasonically nebulized distilled water (UNDW), an indirect hypotonic stimulus, on eNO, 17 asthmatic patients were enrolled and eNO from lower airways was measured by chemiluminescence. UNDW significantly reduced FEV1 ≥ 20% in 9 subjects (UNDW+), but had no effect in eight patients (UNDW−). Baseline eNO concentration were found to be 51.3 ± 11.1 ppb in UNDW+ and 32.9 ± 7.5 ppb in UNDW− patients, respectively (p = 0.199, NS). UNDW inhalation significantly decreased eNO (from 51.3 ± 11.1 ppb to 31.0 ± 7.1 ppb in UNDW+ (p < 0.020, n = 9) and from 32.9 ± 7.5 ppb to 26.2 ± 7.3 ppb in UNDW− subjects (p < 0.024, n = 8), respectively). eNO percentage reduction in UNDW+ patients was significantly higher compared with UNDW− subjects (−37 ± 4% vs −23 ± 3%, p = 0.021). There was no correlation between FEV1 changes and eNO percentage decreases in both UNDW+ and UNDW− subjects. In UNDW+ patients, acute bronchodilation induced by salbutamol caused a recovery in both FEV1 and eNO, though eNO levels remained lower than baseline values. We concluded that UNDW inhalation can significantly decrease eNO in asthmatic patients, either responders or nonresponders to this indirect osmotic challenge; the reduction in eNO levels was only partly dependent on acute changes in airway caliber.