Asthma management: A new phenotype-based approach using presence of eosinophilia and allergy.

Asthma is a heterogeneous disease. The Czech Pneumology and Allergology Societies commissioned 10 experts to review the literature and create joint national guidelines for managing asthma, reflecting this heterogeneity. The aim was to develop an easy-to-use diagnostic strategy as a rational approach to the widening opportunities for the use of phenotype-targeted therapy. The guidelines were presented on websites for public comments by members of both the societies. The reviewers' comments contributed to creating the final version of the guidelines. The key hallmark of the diagnostic approach is the pragmatic concept, which assesses the presence of allergy and eosinophilia in each asthmatic patient. The guidelines define three clinically relevant asthma phenotypes: eosinophilic allergic asthma, eosinophilic nonallergic asthma and noneosinophilic nonallergic asthma. The resulting multifunctional classification describing the severity, level of control and phenotype is the starting point for a comprehensive treatment strategy. The level of control is constantly confronted with the intensity of the common stepwise pharmacotherapy, and the concurrently included phenotyping is essential for phenotype-specific therapy. The concept of the asthma approach with assessing the presence of eosinophilia and allergy provides a way for more precise diagnosis, which is a prerequisite for using widening options of personalized therapy.

Correlation of IL-1alpha and IL-4 gene polymorphisms and clinical parameters in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a serious disease characterized with progressive scarring of the lungs in which a genetic background is supposed. We have tested correlation of promotor regions of IL-1alpha and IL-4 gene polymorphisms with clinical parameters in IPF. We investigated the group of 30 patients with IPF. The correlations of vital capacity (VC) and diffusing capacity for carbon monoxide (DL(CO)), bronchoalveolar lavage (BAL) fluid cell counts and high resolution computed tomography (HRCT) alveolar and interstitial scores with different genotypes of IL-4 at (-1098), (-590) and (-33) positions and IL-1 alpha at (-889) position were tested. The PCR method was used for genotyping. The carriers of CT genotype at IL-1 alpha (-889) position had higher VC at the time of diagnosis. The CC genotype at this position was more frequent in patients with higher counts of HLADR+ T lymphocytes in BAL. The GT genotype at IL-4 (-1098) position correlated with higher counts of CD4(+) T lymphocytes, and inversely the TT genotype with higher counts of CD8(+) T lymphocytes in BAL fluid. According to dynamic changes of HRCT score the CT genotype at IL-4 (-33) was more frequent in patients with progressive disease compared to that with stable disease. We assume from our data that the gene polymorphisms of the promotor region of IL-4 at position (-1098) and (-33) and IL-1 alpha at position (-889) are likely to play a pathogenic role in IPF and in modification of its clinical presentation and severity.

Non-invasive assessment of respiratory muscle function and its relationship to exercise tolerance in patients with chronic obstructive pulmonary disease.

Most patients with chronic obstructive pulmonary disease (COPD) have impaired respiratory muscle function. Maximal oesophageal pressure correlates closely with exercise tolerance and seems to predict the distance walked during the 6-min walk test. This study assessed the non-invasive parameters of respiratory muscle function in 41 patients with COPD to investigate their relationship to pulmonary function tests and exercise tolerance. The COPD patients, who demonstrated the full range of airway obstruction severity, had a mean forced expiratory volume in 1 s of 42.5% predicted (range, 20 - 79% predicted). Both the maximal inspiratory muscle strength and non-invasive tension-time index were significantly correlated with the degree of lung hyperinflation, as expressed by the ratio of residual volume to total lung capacity, and the distance walked in 6 min. We conclude that respiratory muscle function was influenced mainly by lung hyperinflation and that it had an important effect on exercise tolerance in COPD patients.

[Videothoracoscopy in local anesthesia diagnosis and therapy of pleural effusions]. / Videotorakoskopie v lokální anestezii v diagnostice a lécbe pohrudnicních výpotku.

Videothoracoscopy (VTS) has been performed in the Department of Pneumology in Plzen since the year 2001. Up to-September 2005 there were realized 75 videothoracoscopies, all under local anaesthesia with analgosedation and during the spontaneous ventilation. The objective of the present work is to demonstrate that the so called "medical" videothoracoscopy is very well tolerated, quick and accurate miniinvasive method of examination of pleural pathological states, which has a high diagnostic effect and minimal complications. During the exploration it is possible to carry out, besides the collection of bioptic samples from parietal as well as visceral pleura, a whole range of therapeutical acts - evacuation of effusion, mechanical disruption of adhesions in case of empyema with its subsequent drainage or pleurodesis with talc in case of malignant exudates. As for the basic indication of the medica VTS, we consider it to be the differential diagnosis of a pleural effusion of unclear etiology, consisting mostly in the confirmation or exclusion of malignant exudates. The differential diagnosis with the help of VTS between the nonmalignant (mostly inflammatory) and malignant exudate was successful, in our group of patients, in 96 %. The operation was well tolerated by all patients and in none of them occurred significant complications or consequences.

Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma.

Under Global Initiative for Asthma guidelines, the clinical control of disease activity and the adjustment of treatment in patients with asthma are based on symptoms, use of rescue medication, lung function and peak expiratory flow measurement (standard strategy). We investigated whether a strategy to reduce the number of sputum eosinophils (EOS strategy) gives better clinical control and a lower exacerbation rate compared with the standard strategy. Fifty-five patients with moderate to severe asthma entered this open, randomized, parallel-group study and visited the out-patient department every 3 months for 18 months. The dose of corticosteroids was adjusted according to the standard strategy or the percentage of sputum eosinophils (EOS strategy). During the study period, the EOS strategy led to a significantly lower incidence of asthma exacerbations compared with the standard strategy group (0.22 and 0.78 exacerbations per year per patient, respectively). There were significant differences between the strategies in time to first exacerbation.

Pleural fluids associated with metastatic lung tumors are rich in progelatinase B/proMMP-9.

Gelatinase B/MMP-9 is a member of matrix metalloproteinases with a major role in extracellular matrix degradation, cell proliferation and migration. Its proenzyme form has also been reported in pleural fluids as an inducible species, but its relation to pleural pathology has not yet been fully clarified. The primary goal of this study was to evaluate proMMP-9 as a potential marker for differentiating pleural effusions of both malignant and non-malignant origin. Pleural fluid samples were studied from 194 patients, including tumor etiology in 133 cases, inflammatory disorders in 33, transudates in 12, and unspecified disorders in 16 patients. The concentrations of proMMP-9 were estimated by means of immunoassays and/or by scanning zymography. Samples were also examined for C-reactive protein (CRP). The analysis of proMMP-9 showed significant differences among the etiological groups with the highest concentrations in para-inflammatory exudates, intermediate in para-neoplastic exudates, and the lowest in transudates. However, the analysis of the para-neoplastic group revealed a distinct heterogeneity with a minor portion of fluids reaching values typical for para-inflammatory effusions. A subsequent sorting based on tumor histology showed increased levels particularly in exudates associated with metastatic tumors. Interestingly, proMMP-9 values in general correlated with CRP, a systemic marker of inflammation. Thus, MMP-9 proenzyme appears to complement traditional markers distinguishing pleural fluids of different origin. Yet, the differentiation between paraneoplastic and para-inflammatory exudates must be regarded with caution due to the presence of a high-expressive paraneoplastic sub-population, including effusions associated with metastatic tumors.

[Non-alcoholic risks of alcoholic beverages]. / Nealkoholická rizika alkoholických nápoju.

Alcoholic beverages are a potential source of numerous health risks. The general risks are well known; first of all they result from the contents of the alcohol and their degree is directly proportional to the amount consumed. However, alcoholic beverages contain also a wide range of non-alcoholic components, which can be a source of health risks as well. Some of these substances work through allergic or pseudoallergic mechanisms and such undesired response can appear early after the consumption of a small amount of beverage. The article offers a basic survey of alcoholic beverages; it mentions important technological procedures of their production stating also the most significant resulting components of their individual types. A special attention is paid to the non-alcoholic components, which can be the cause of undesired effects on the human health.

A new HFA-134a propellant in the administration of inhaled BDP via the Jet spacer: controlled clinical trial vs the conventional CFC.

This study was carried out with the aim of demonstrating the efficacy and tolerability of beclomethasone dipropionate (BDP) aerosol spray 500 microg b.i.d. via a spacer device (Jet, Chiesi Farmaceutici S.p.A.) using a new HFA-134a formulation or chlorofluorocarbon (CFC) propellant. After having completed a 2-week run-in period, 154 adult patients (77 in each group) with mild-to-moderate persistent asthma were randomised into two groups to receive the study treatment for a duration of 12 weeks in a double-blind, multinational, multicentre, parallel-group design. Morning and evening peak expiratory flow rate (PEFR), use of rescue salbutamol, number of day- and night-time asthma attacks, number of night-time awakenings due to asthma and clinical symptoms were recorded daily by patients on diary cards. Pulmonary function tests (FEV1, FVC, PEFR, FEF25-75%, MEF50 and FEF25) and vital signs were measured at the clinic at study entry, at the start of treatment and every 2 weeks thereafter. Morning serum cortisol (8.00-10.00 a.m.) was measured at the start and at the end of the treatment period. Adverse events were recorded throughout the total study period. Significant improvements over baseline were reported in both groups in terms of lung function, symptoms and use of rescue inhaled salbutamol. Equivalence between groups was demonstrated for the primary end-point morning PEFR, as well as for evening PEFR and FEV1. No statistically significant differences in the comparisons between groups, except for FEF25 (P=0.044), were observed in any of the other efficacy variables. Adverse events were reported in 31% of patients in the BDP-HFA group and in 32% in the CFC group. Adverse drug reactions were 4 and 2 in the two groups, respectively. No drug-related serious adverse events were reported in either of the groups. No signs of relevant adrenal suppression were observed in both groups: 2 patients in each group had final values below the normal range. In conclusion, the BDP-HFA-134a formulation proved to be equivalent in efficacy and comparable in safety to the standard BDP-CFC product over 12 weeks in adult patients with mild-to-moderate persistent asthma.