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Exhaled Metallic Elements and Serum Pneumoproteins in Asymptomatic Smokers and Patients With COPD or Asthma Antonio Mutti, Massimo Corradi, Matteo Goldoni, Maria Vittoria Vettori, Alfred Bernard and Pietro Apostoli Chest 2006;129;1288-1297 DOI 10.1378/chest.129.5.1288 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournals.org/cgi/content/abstract/129/5/1288 by the American College of Chest Physicians, 3300 Dundee Road, Northbrook IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder ( http://www.chestjournal.org/misc/reprints.shtml). ISSN: 0012-3692. 2007 CHEST is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright Downloaded from chestjournals.org on May 23, 2007 Copyright © 2006 by American College of Chest Physicians
CHEST Original Research Exhaled Metallic Elements and Serum Pneumoproteins in Asymptomatic Smokers and Patients With COPD or Asthma* Antonio Mutti, MD; Massimo Corradi, MD; Matteo Goldoni, Phys; Maria Vittoria Vettori, PhD; Alfred Bernard, PhD; and Pietro Apostoli, MD Study objectives: The aim of this study was to characterize the elemental composition of exhaled breath condensate (EBC) in order to identify new biomarkers of exposure and susceptibility in COPD patients. Serum pneumoproteins were used as lung-specific biomarkers of effect. Design: EBC was obtained from 50 healthy subjects, 30 healthy smokers, 30 asthmatics, and 50 patients with stable COPD, and was collected by cooling exhaled air. Trace elements and toxic metals in the samples were measured by means of inductively coupled plasma-mass spectrometry and electrothermal atomic absorption spectroscopy. The serum pneumoproteins were immunoassayed. Results: The EBC of COPD subjects had higher levels of such toxic elements as lead, cadmium, and aluminum, and lower levels of iron and copper, than that of the nonsmoking control subjects. There were no between-group differences in surfactant protein (SP)-A and SP-B levels. Clara-cell protein and SP-D levels were negatively and positively influenced, respectively, by tobacco smoke. Conclusions: Our results show that toxic metals and transition elements are detectable in the EBC of studied subjects. We propose new biomarkers of exposure as a means of assessing the target tissue dose of carcinogenic and pneumotoxic substances from tobacco smoke or polluted workplaces, and the use of the transition elements involved in redox systems of oxidative stress as disease biomarkers associated with effect or susceptibility. Together with biomarkers of effect, such as serum pneumoproteins, the elemental composition of EBC may be clinically useful in distinguishing similar diseases. (CHEST 2006; 129:1288–1297) Key words: COPD; exhaled breath condensate; metals; pneumoproteins; trace elements Abbreviations: ANOVA analysis of variance; CC16 Clara-cell secretary protein; EBC exhaled breath condensate; ETAAS electrothermal atomic absorption spectroscopy; ICP-MS inductively coupled plasma-mass spectrometry; LOD limit of detection; PM particulate matter; SOD superoxide dismutase; SP surfactant protein COPD is one of the leading causes of morbidity and mortality worldwide, and represents a substantial economic burden on global health. 1 It is characterized by small airways disease, mucus hypersecretion, and chronic bronchitis, which lead to an obstructed airflow that impairs ventilatory capacity and gas exchange, and causes shortness of breath. 1 Various instruments have been developed for diagnosing, monitoring, and evaluating COPD. Lung function tests offer insights into changes in airway caliber, exhaled air flow, lung volumes, and gas exchange, 2 and imaging techniques (especially highresolution CT) offer insight into the loss of lung COPD tissue 3 ; both provide indirect measurements of the adverse effects occurring in a biological system as a consequence of exposure to toxic or noxious agents. More direct evaluation of biological lung events can be obtained using more or less invasive measurements (bronchoscopy, induced sputum). These have improved our understanding of the biological processes occurring in lung diseases and still represent the “gold standard” for evaluating the diseases themselves, 4 but their applicability is limited mainly because the invasiveness of the sampling procedures makes them unsuitable for routine clinical use. Modern research relies on biomarkers, which are 1288 Original Research Downloaded from chestjournals.org on May 23, 2007 Copyright © 2006 by American College of Chest Physicians
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UNIVERSITÀ DEGLI STUDI DI PARMA DO
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Riassunto La raccolta e l’analisi
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Sommario CAPITOLO 1: Introduzione .
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5.3.1 Scopi dello studio ..........
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Congressi Nazionali ed Internaziona
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ischio consiste nel caratterizzare
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1.1 I biomarcatori Il termine “bi
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Forschungsgemainschaft (DFG, 2004).
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elettrotermico (ETAAS) fino ad arri
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E’ possibile studiare la cinetica
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Tra le molecole dosate con maggior
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circostanze, sarebbe più appropria
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3.3.2 Miscele di inquinanti comples
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3.3.3.3 Elementi metallici nel BAL
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- Cromatura galvanica, che prevede
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Molti studi in vivo e in vitro hann
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tra tessuto sano e malato (Raithel
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4.3.2 Cd e il fumo di sigaretta Le
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sulla sintesi dell’eme. I valori
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- Smontaggio, pulitura e deposito n
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5.2.2.3 Le misure ambientali Le mis
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5.2.3 Risultati I livelli di Cr mis
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di DPC in 1-butanolo e 100 μl di H
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5.4 Un terzo studio confermativo ne
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5.5 Cr nel tessuto polmonare e nel
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I livelli di Cromo erano 0.14 (0.04
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- Monitoraggio ambientale: è stato
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6.2 Nichel, Cadmio e Piombo esalati
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CAPITOLO 5: Discussione 7. Esposizi
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Cr(VI) nel CAE rinforza l’ipotesi
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Se nell’urina viene escreta una m
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sigaretta (Rustemeier et al., 2002;
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Cr(VI) nell’indurre risposte corr
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sul passaggio di Cr nei due stati d
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depositarsi ad alte concentrazioni
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Poiché il volume esalato non è al
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11.8 Conclusioni Il sistema appare
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Amorim, L.C., de Cardeal, L.Z., 200
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Bernard, A., 2004. Renal dysfunctio
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Coogan, T.P., Squibb, K.S., Motz, J
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Effros, R.M., Hoagland, K.W., Bosbo
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Hazelwood, K.J., Drake, P.L., Ashle
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Microscopic analysis of chromium ac
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McGarvey, L.P., Dunbar, K., Martin,
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NIOSH, 2003. NIOSH Method 7703: Hex
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Rahman, I., Kelly, F., 2003. Biomar
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Tatrai, E., Kovacikova, Z., Hudak,
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13. Tabelle 86
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Controlli Lavoratori N° soggetti 2
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N° soggetti 10 Sesso (M/F) 10/0 La
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Cr-Plasma (μg/L) Cr-RC (ng/10 9 ce
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Controlli NSCLC tempo 1 NSCLC tempo
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Ni-Aria Lunedì (μg/m 3 ) Ni-U Lun
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Composizione SERETIDE® 0.3-0.5 mic
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Figura 1: Tavola periodica degli el
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Figura 3. Meccanismi di tossicità
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Figura 5. (A) Cromatura Galvanica -
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Cr-CAE (μg/L) 100 10 1 0.1 r=0.25,
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mAbs a 540/545 nm : r = 0.9999, int
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A Cr-CAE (μg/L) Cr(VI)/Cr TOT B 10
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Cr-U (μg/g creat.) 7 6 5 4 3 2 1 0
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1 0.1 Cr-CAE (μg/L) log(Cr-CAE) =
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Page 129 and 130: Ni-CAE (μg/L) Cd-CAE (μg/L) Pb-CA
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Page 151 and 152: • Goldoni Matteo, Caglieri A, Pol
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Page 185 and 186: dedicated to elemental analysis, an
Page 187 and 188: Exhaled Metallic Elements and Serum
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