RESUMEN
For easy handling and speed of lung diseases diagnostics, approaches based on volatile organic compounds (VOCs), including those emitted by pathogenic microorganisms, are considered but currently require considerable sampling efforts. We tested whether easy-to-handle and fast detection of lung infections is possible using solid-phase microextraction (SPME) of 100 ml of exhaled breath. An analytical procedure for the detection of VOCs from the headspace of epithelial lung cells infected with four human pathogens was developed. The feasibility of this method was tested in a cystic fibrosis (CF) outpatient clinic in vivo. Exhaled breath was extracted by SPME and analyzed by gas chromatography-mass spectrometry (GC-MS). The compositions of VOCs released in the infection model were characteristic for all individual pathogens tested. Exhaled breath of CF patients allowed clear distinction of CF patients and controls by their VOC compositions using multivariate analyses. Interestingly, the major specific VOCs detected in the exhaled breath of infected CF patients in vivo differed from those monitored during bacterial in vitro growth. SPME extraction of VOCs from 100 ml of human breath allowed the distinction between CF patients and healthy probands. Our results highlight the importance of assessing the entire pattern of VOCs instead of selected biomarkers for diagnostic purposes, as well as the need to use clinical samples to identify reliable biomarkers. This study provides the proof-of-concept for the approach using the composition of exhaled VOCs in human breath for the rapid identification of infectious agents in patients with lower respiratory tract infections.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Pruebas Respiratorias/métodos , Fibrosis Quística/complicaciones , Adulto , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Manejo de Especímenes/métodos , Factores de Tiempo , Compuestos Orgánicos Volátiles/análisisRESUMEN
Cystic fibrosis (CF) is a common autosomal-recessive inherited disease, which often results in premature death. Due to treatment advances, life expectancy has however continuously improved in recent years. Currently about half of all patients are adults. There are also "atypical" variants of CF with symptoms occurring in late adulthood. CF is caused by a mutation in the gene coding for a chloride ion channel, known as the cystic fibrosis transmembrane conductance regulator (CFTR). This mutation results in abnormally viscous mucosal secretions, leading to multi-organ disease with particular emphasis in the respiratory and digestive tracts. Impaired mucociliary clearance results in bacterial colonization of the airways (e. g. Pseudomonas aeruginosa) and consequently in chronic pulmonary inflammation, inevitably leading to progressive bronchiectasis and combined ventilatory disorders. Typical acute complications are infective exacerbations - the most frequent cause of death in cystic fibrosis - along with allergic bronchopulmonary aspergillosis, haemoptyses and pneumothoraces. Involvement of the gastrointestinal tract generally manifests as exo- and later endocrine pancreatic insufficiency with diabetes mellitus, malabsorption and sometimes biliary liver cirrhosis. Typical acute complications are pancreatitis and ileus. The article describes epidemiology and pathophysiology of CF and focuses on the signs and symptoms, as well as the diagnostic and multi-modal therapeutic strategies used in adult patients.
Asunto(s)
Fibrosis Quística/complicaciones , Enfermedades Pulmonares/etiología , Proteínas Adaptadoras Transductoras de Señales , Adulto , Aspergilosis Broncopulmonar Alérgica/diagnóstico , Aspergilosis Broncopulmonar Alérgica/etiología , Bronquiectasia/etiología , Proteínas Portadoras/genética , Niño , Aberraciones Cromosómicas , Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Fibrosis Quística/terapia , Análisis Mutacional de ADN , Diagnóstico Diferencial , Genes Recesivos/genética , Proteínas de la Matriz de Golgi , Hemoptisis/etiología , Humanos , Recién Nacido , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/terapia , Proteínas de la Membrana/genética , Proteínas de Transporte de Membrana , Neumonía Bacteriana/etiología , Pronóstico , Infecciones por Pseudomonas/etiología , Pseudomonas aeruginosaRESUMEN
The authors report that 4 out of a series of 56 patients (7.1%) treated with gemcitabine developed an unexplained non-cardiogenic pulmonary distress syndrome most likely related to gemcitabine. One further patient developed ventricular arrhythmia immediately after gemcitabine exposure, leading to cardiac arrest. Between 1995 and 1998 56 patients with locally advanced or metastatic carcinoma were treated with gemcitabine. The patients suffered from breast cancer (n = 17), pancreatic cancer (n = 17), lung cancer (n = 12), cancer of unknown primary (n = 5), ovarian cancer (n = 2), oral cavity cancer (n = 2) and cancer of the bladder (n = 1). Their median age was 55 years, and there were 33 female and 23 male patients. Fifteen patients had been pretreated with radiation therapy: 2 had received radiation therapy involving the mediastinum as treatment for non-small-cell lung cancer and cancer of unknown origin respectively, 11 patients had had prior neoadjuvant or adjuvant radiation therapy of the chest wall for breast cancer and 2 patients had received radiation therapy for head/neck cancer. All patients received gemcitabine on days 1, 8 and 15 and this was repeated on day 29 at a dose of 1000 mg/m(2) as a 30-min infusion in 250 ml isotonic NaCl. In 4 patients gemcitabine treatment was combined with cisplatinum, in 7 patients with a somatostatin analogue and in 1 patient with epirubicin. All other patients received gemcitabine as a single agent. We assume that the pulmonary or cardiac toxicity of 5 patients was related to gemcitabine. In 3 patients re-exposure resulted in repeated toxicity. One patient did not receive gemcitabine again because of the life-threatening nature of the primary response. Two patients had received prior radiation to the mediastinum with 62 Gy and 50 Gy respectively, 3 years and 1 year before gemcitabine application. In our experience pulmonary toxicity after gemcitabine treatment is more common than initially anticipated. Gemcitabine should be used with caution in patients who have received prior radiation to the mediastinum.