Lung cancer configures as one of the deadliest types of cancer. The future implementation of early screening methods such as exhaled breath condensate analysis and low dose computed tomography (CT) as an alternative to current chest imaging based screening will lead to an increased burden on bronchoscopy units. New approaches for improvement of diagnosis in bronchoscopy units, regarding patient management, are likely to have clinical impact in the future. Diagnostic approaches to address mortality of lung cancer include improved early detection and stratification of the cancers according to its prognosis and further response to drug treatment. In this study, we performed a detailed mass spectrometry based proteome analysis of acellular bronchoalveolar lavage (BAL) fluid samples on an observational prospective cohort consisting of 90 suspected lung cancer cases which were followed during two years. The thirteen new lung cancer cases diagnosed during the follow up time period clustered, based on liquid chromatography-mass spectrometry (LC-MS) data, with lung cancer cases at the time of BAL collection. Hundred and thirty-tree potential biomarkers were identified showing significantly differential expression when comparing lung cancer versus non-lung cancer. The regulated biomarkers showed a large overlap with biomarkers detected in tissue samples.
Acta Med Port 2015 Nov-Dec;28(6):702-707 RESUMOIntrodução: A doença pulmonar obstrutiva crónica e a asma afectam quase 300 milhões de indivíduos em todo o mundo. A terapêutica inalatória associa-se frequentemente a erros na técnica realizada reduzindo a eficácia e adesão. Objectivo: Avaliar a técnica inalatória e sua relação com o controlo clínico e funcional em asma e doença pulmonar obstrutiva crónica. Material e Métodos: Estudo transversal analítico incluindo doentes com asma e doença pulmonar obstrutiva crónica medicados com dispositivos inalatórios. Recolheram-se dados demográficos e existência de ensino prévio da técnica. Avaliou-se a técnica inalatória em: Passo 1 -expiração prévia; Passo 2 -activação do dispositivo; Passo 3 -inspiração; Passo Step 1 -device activation;Step 2 -previous expiration;Step 3 -inspiration;Step 4 -end inspiratory pause. Teaching inhalation technique has a positive impact on its future performance. Most patients make mistakes, affecting clinical control in asthma, although in chronic obstructive pulmonary isease no relation was found. This is an ongoing work that aims to reevaluate inhalation technique after patients' education and its further impact.
To assess the impact that educational interventions to improve inhaler techniques have on the clinical and functional control of asthma and COPD, we evaluated 44 participants before and after such an intervention. There was a significant decrease in the number of errors, and 20 patients (46%) significantly improved their technique regarding prior exhalation and breath hold. In the asthma group, there were significant improvements in the mean FEV1, FVC, and PEF (of 6.4%, 8.6%, and 8.3% respectively). Those improvements were accompanied by improvements in Control of Allergic Rhinitis and Asthma Test scores but not in Asthma Control Test scores. In the COPD group, there were no significant variations. In asthma patients, educational interventions appear to improve inhaler technique, clinical control, and functional control.
Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.
α-1 Antitrypsin deficiency (AATD) caused by null alleles is associated with the total lack of protein and generally it translates into more severe clinical features of pulmonary disease. This is the case of Q0(Ourém) , a rare variant found in several families of Central Portugal caused by the L353fsX376 mutation. A total of 41 patients carrying at least one copy of Q0(Ourém) were evaluated for SERPINA1 levels, respiratory function values and lung parenchyma status (chest X-ray and computerized tomography scan). Q0(Ourém) haplotype background was characterized using seven microsatellites flanking SERPINA1 and Q0(Ourém) age was estimated by a statistical method relying on the decay of haplotype sharing at linked markers (DHSMAP). Homozygous patients showed a compromised lung function and extensive emphysema. SQ0(Ourém) , although having serum levels below the 11 µM threshold, did not necessarily result in signs of disease. MQ0(Ourém) were found to be a heterogeneous group, mainly composed of normal individuals. Eight Q0(Ourém) haplotypes were identified and the allele was estimated to have arisen 650 years ago. Q0(Ourém) was associated with mild to severe AATD and has a single origin, probably linked to the major Ourém settlements where the occurrence of severe AATD may not be explained by recent consanguinity.
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