Occupational asthma follow-up — which markers are elevated in exhaled breath condensate and plasma?

Objectives: To search for optimal markers in the exhaled breath condensate (EBC), plasma and urine that would reflect the activity/ severity of occupational asthma (OA) after the withdrawal from the exposure to the allergen. Material and Methods: Markers of oxidative stress: 8-iso-prostaglandin F2α (8-isoprostane, 8-ISO), malondialdehyde (MDA), 4-hydroxy-trans-2-nonenale (HNE), cysteinyl leukotrienes (LT) and LTB4 were determined using liquid chromatography and mass spectrometry in 43 subjects with immunological OA (49.3±11.8 years), removed from the exposure to the sensitizing agent 10.5±6.5 years ago; and in 20 healthy subjects (49.0±14.9 years). EBC was harvested both before and after the methacholine challenge test. In parallel, identical markers were collected in plasma and urine. The results were analyzed together with forced expiratory volume in one second (FEV1), blood eosinophils, immunoglobulin E (IgE) and eosinophilic cationic protein (ECP) and statistically evaluated (Spearman rank correlation rS, two- or one-sample t tests and alternatively Kruskal Wallis or pair Wilcoxon tests). Results: Several parameters of lung functions were lower in the patients (FEV1% predicted, MEF25% and MEF50%, Rtot%, p < 0.001). Shorter time interval since the removal from the allergen exposure correlated with higher ECP (rS = 0.375) and lower FEV1%, MEF25% and MEF50% after methacholine challenge (rS = -0.404, -0.425 and -0.532, respectively). In the patients, IgE (p < 0.001) and ECP (p = 0.009) was increased compared to controls. In EBC, 8-ISO and cysteinyl LTs were elevated in the asthmatics initially and after the challenge. Initial 8-ISO in plasma correlated negatively with FEV1 (rS = -0.409) and with methacholine PD20 (rS = -0.474). 8-ISO in plasma after the challenge correlated with IgE (rS = 0.396). Conclusions: The improvement in OA is very slow and objective impairments persist years after removal from the exposure. Cysteinyl LTs and 8-ISO in EBC and 8-ISO in plasma might enrich the spectrum of useful objective tests for the follow-up of OA

Recent Advancements in the LC- and GC-Based Analysis of Malondialdehyde (MDA): A Brief Overview

Malondialdehyde (MDA) is an end-product of lipid peroxidation and a side product of thromboxane A2 synthesis. Moreover, it is not only a frequently measured biomarker of oxidative stress, but its high reactivity and toxicity underline the fact that this molecule is more than “just” a biomarker. Additionally, MDA was proven to be a mutagenic substance. Having said this, it is evident that there is a major interest in the highly selective and sensitive analysis of this molecule in various matrices. In this review, we will provide a brief overview of the most recent developments and techniques for the liquid chromatography (LC) and gas chromatography (GC)-based analysis of MDA in different matrices. While the 2-thiobarbituric acid assay still is the most prominent methodology for determining MDA, several advanced techniques have evolved, including GC–MS(MS), LC–MS(MS) as well as several derivatization-based strategies

Temperatura do ar exalado, um novo biomarcador no controle da asma: um estudo piloto Exhaled breath temperature, a new biomarker in asthma control: a pilot study

OBJETIVO: Avaliar se a temperatura do ar exalado (TAE), medida por um método não invasivo, é efetiva no monitoramento de pacientes com asma não controlada. MÉTODOS: Estudo piloto com nove pacientes (sete mulheres e dois homens; média de idade: 39 anos) com diagnóstico de asma por pelo menos um ano e sem uso de tratamento de manutenção por pelo menos três meses antes do início do estudo. Na primeira visita, os pacientes foram submetidos à espirometria e à medida da TAE. Todos os pacientes foram orientados a iniciar tratamento com budesonida/formoterol (200/6 µg) inalatório a cada 12 h por seis semanas. Além disso, os pacientes com asma grave (VEF1 < 60% do previsto) foram orientados a utilizar prednisolona oral (40 mg/dia) por cinco dias. Após seis semanas, os pacientes foram submetidos aos mesmos testes. RESULTADOS: Todos os pacientes relataram melhora dos sintomas de asma; confirmada por um aumento significativo de VEF1 da primeira para a segunda visita (média de VEF1: 56,1% vs. 88,7% do previsto; p < 0,05). Cinco pacientes utilizaram prednisolona oral, mas somente nos cinco dias iniciais do tratamento. Seis pacientes utilizaram doses extras da medicação inalatória (média de tempo de uso de medicação adicional = 2,5 semanas). Houve uma diminuição significativa da TAE entre os momentos de avaliação (média de TAE: 35,1ºC vs. 34,1ºC; p < 0,05). CONCLUSÕES: A asma não controlada, sobretudo durante exacerbações, é acompanhada pela elevação da TAE, que se reduz após o controle adequado da asma, demonstrado pela melhora do VEF1 e dos sintomas referidos. Esses resultados preliminares apontam para o monitoramento da TAE como um parâmetro possível na avaliação do controle da asma.<br>OBJECTIVE: To evaluate whether the exhaled breath temperature (EBT), measured by a noninvasive method, is an effective means of monitoring patients with uncontrolled asthma. METHODS: A pilot study comprising nine patients (seven women and two men; mean age: 39 years) diagnosed with asthma at least one year prior to the beginning of the study and not having been under maintenance therapy for the last three months. In the first visit, the patients underwent spirometry and measurement of EBT. The patients were then instructed to use inhaled budesonide/formoterol (200/6 µg) every 12 h for six weeks. In addition, the patients with severe asthma (FEV1 < 60% of predicted) were instructed to use oral prednisolone (40 mg/day) for five days. After six weeks, the patients underwent the same tests. RESULTS: All of the patients reported an improvement in the symptoms of asthma, as confirmed by a statistically significant increase in FEV1 from the first to the second visit (mean, 56.1% vs. 88.7% of predicted; p < 0.05). Five patients used oral prednisolone for the first five days of the treatment period. Six patients used additional doses of inhaled budesonide/formoterol (mean duration, 2.5 weeks). The EBT decreased significantly from the first to the second visit (mean EBT: 35.1ºC vs. 34.1ºC; p < 0.05). CONCLUSIONS: Uncontrolled asthma, especially during exacerbations, is followed by an increase in EBT, which decreases after appropriate asthma control, as demonstrated by an increase in FEV1 and an improvement of the reported symptoms. These preliminary results suggest that EBT can be used as a parameter for the assessment of asthma control