Subscribe to RSS
DOI: 10.1055/s-2001-14676
Nichtinvasive Emphysemdiagnostik: Eine Standortbestimmung
Non-Invasive Emphysema Diagnostics: Defining the Present PositionPublication History
Publication Date:
31 December 2001 (online)
Einleitung
Die Entwicklung neuer Methoden der Emphysemdiagnostik steht heute im Mittelpunkt des Interesses [4] [79] [102], da sich durch aktuelle Erkenntnisse zur Rolle molekularer und zellulärer Prozesse in der Pathogenese des Lungenemphysems über eine rein symptomatische Therapie hinaus erstmals spezifische Möglichkeiten der Lungenemphysemtherapie und -prävention eröffnen [4] [90] [91]. Aktuelle tierexperimentelle Ergebnisse konnten pharmakologisch induzierte Heilungsmechanismen beim Papain-induzierten Lungenemphysem mittels Gabe von Retinol (Vitamin A) belegen [5] [55]. Bislang galt die emphysematöse Lungendestruktion als irreversibler und die Prognose bestimmender Prozess bei Patienten mit COPD (engl.: chronic obstructive pulmonary disease) [12] [59] [86]. Die Definition des Lungenemphysems basiert auf morphologischen Kriterien, die durch eine irreversible Zerstörung des Alveolarraumes gekennzeichnet ist [87]. Weltweit wird mit einer Zunahme der Inzidenz und Mortalität des Lungenemphysems in den kommenden Jahrzehnten gerechnet [37]. Etwa 400 000 Menschen leiden in der BRD an einem klinisch relevanten Lungenemphysem. Jährlich sterben ca. 3000 Menschen an einem Lungenemphysem [49]. Die in Zukunft erforderlichen Interventionsstudien stellen hohe Anforderungen an Sensitivität und Spezifität in der COPD-Diagnostik. In aktuellen Leitlinien zur Diagnostik und Therapie der COPD [2] [84] fehlt jedoch eine kritische Wertung der differenzialdiagnostischen Trennschärfe verfügbarer Methoden in Bezug auf die wichtige Subklassifikation der unter COPD subsummierten Lungenerkrankungen. Sowohl auf nationaler [101] als auch auf internationaler Ebene [38] [83] [91] werden vermehrte Forschungsaktivitäten in der Lungenemphysemdiagnostik gefordert. Nach einer Stellungnahme der „American Thoracic Society” genügt keine der derzeit routinemäßig eingesetzten Methoden den Erfordernissen zu Filteruntersuchungen (Screening) auf chronisch obstruktive Atemwegserkrankungen (COPD) [100]. Filteruntersuchungen umfassen Vorsorgeuntersuchungen und Untersuchungen zur Krankheitsfrüherkennung (sekundäre Prävention). Früherkennung der COPD bedeutet Früherkennung von chronisch-obstruktiver Bronchitis und Lungenemphysem mit und ohne obstruktive Ventilationsstörung. Nach den Kriterien von Wilson u. Mitarb. [103] ist eine Lungenfunktionsmessmethode für Filteruntersuchungen dann geeignet, wenn folgende Vorbedingungen erfüllt sind:
Die Zielkrankheit muss wegen ihrer Schwere und/oder Häufigkeit eine große Bedeutung für die Volksgesundheit haben. Ausreichende Ressourcen für die weiterführende Diagnostik und Therapie müssen vorhanden sein. Die Zielkrankheit muss ein erfassbares Latenzstadium oder eine symptomarme Frühphase aufweisen. Der Test muss den Teilnehmern wiederholt zugemutet werden können.
Nach Ulmer [101] wird in Zukunft eine differenzierte Therapie nur möglich sein, wenn es gelingt Subgruppen der heterogenen Gruppe der chronisch obstruktiven Lungenerkrankungen lungenfunktionell besser zu charakterisieren als
chronische Bronchitis mit/ohne Atemwegsobstruktion, Emphysem mit/ohne Atemwegsobstruktion und chronisch obstruktive Bronchitis mit Lungenemphysem.
Literatur
- 1 American Thoracic Society . Single-breath carbon monoxide diffusing capacity (transfer factor). Am J Respir Crit Care Med. 1995; 152 2185-2198
- 1b American Thoracic Society . Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995; 152 2185-2198
- 2 Badget R C, Tanaka D V, Hunt D K, Jelley M JH, Feinberg L E, Steiner J F, Petty T L. Can moderate chronic obstructive pulmonary disease be diagnosed by historical and physical findings alone?. Am J Med. 1993; 94 188-196
- 3 Barnes P J. Chronic obstructive pulmonary disease: new opportunities for drug development. TiPS. 1998; 19 415-423
- 4 Belloni P N, Garvin L, Mao C-P, Bailey-Healy I, Leaffer D. Effects of all-trans-retinoic acid in promoting alveolar repair. Chest. 2000; 117 235S-241S
- 5 Bergin C, Müller N, Nichols D M, Lillington G, Hogg J C, Mullen B, Grymaloski M R, Osborne S, Paré P D. The diagnosis of emphysema. A computed tomographic-pathologic correlation. Am Rev Respir Dis. 1986; 133 541-546
- 6 Bernhardt J, Veit R, Bauer B. Erhebungen zur Strahlenexposition der Patienten bei der Röntgendiagnostik. Z Med Phys. 1995; 5 33-39
- 7 Bessis L, Callard P, Gotheil C, Biaggi A, Grenier Ph. High-resolution CT of parenchymal lung disease: precise correlation with histologic findings. RadioGraphics. 1992; 12 45-58
- 8 Boushy S F, Aboumrad M H, North L B, Helgason A H. Lung recoil pressure, airway resistance, and forced flows related to morphologic emphysema. Am Rev Respir Dis. 1971; 104 551-561
- 9 Brand P, Rieger C, Beinert T, Heyder J. Aerosol derived airway morphometry in healthy subjects. Eur Respir J. 1995; 8 1639-1646
- 10 Brand P, Rieger C, Schulz H, Beinert T, Heyder J. Aerosol bolus dispersion in healthy subjects. Eur Respir J. 1997; 10 460-467
- 11 Burrows B, Bloom J W, Raver G A, Cline M G. The course and prognosis of different forms of chronic airways obstruction in a sample from the general population. N Engl J Med. 1987; 317 1309-1314
- 12 Colp C, Park S S, Williams M H. Emphysema with little airway obstruction. Am Rev Respir Dis. 1970; 101 615-619
- 13 Fabbri M, Fasano L, Zompatori M, Rimondi M R, Brighi N, Gavelli G P, Cinti C, Bassein L. Assessment of emphysema using high resolution CT, CT expiratory density mask and plain chest films. Monaldi Arch Chest Dis. 1994; 49 375-379
- 14 Flenley D C. Diagnosis and follow-up of emphysema. Eur Respir J. 1990; 3 (Suppl 9) 5s-8s
- 15 Foster W L, Pratt P C, Roggli V L, Godwin J D, Halvorsen R A, Putman C E. Centrilobular emphysema: CT-pathologic correlation. Radiology. 1986; 159 27-32
- 16 Gelb A F, Gold W M, Wright R R, Bruch H R, Nadel J A. Physiologic diagnosis of subclinical emphysema. Am Rev Respir Dis. 1973; 107 50-63
- 17 Gelb A F, Schein M, Kuei J, Tashkin D P, Müller N L, Hogg J C, Epstein J D, Zamel N. Limited contribution of emphysema in advanced chronic obstructive pulmonary disease. Am Rev Respir Dis. 1993; 147 1157-1161
- 18 Gelb A F, Hogg J C, Müller N L, Schein M J, Kuei J, Tashkin D P, Epstein J D, Kollin J, Green R H, Zamel N, Elliott W M, Hadjiaghai L. Contribution of emphysema and small airways in COPD. Chest. 1996; 109 353-359
- 19 Gelb A F, Zamel N, Hogg J C, Müller N L, Schein M J. Pseudophysiologic emphysema resulting from severe airway disease. Am J Respir Crit Care Med. 1998; 158 815-819
- 20 Gevenois P A, de Maertelaer V, De Vuyst P, Zanen J, Yernault J-C. Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1995; 152 653-657
- 21 Gevenois P A, De Vuyst P, de Maertelaer V, Zanen J, Jacobovitz D J, Cosio M G, Yernault J-C. Comparison of computed density and microscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1996; 154 187-192
- 22 Greaves J A, Colebatch H JH. Elastic behaviour and structure of normal and emphysematous lungs port-mortem. Am Rev Respir Dis. 1980; 121 127-136
- 23 Gould G A, MacNee W, McLean A, Warren P M, Redpath A, Best J JK, Lamb D, Flenley D C. CT measurements of lung density in life can quantitate distal airspace enlargement - an essential defining feature of human emphysema. Am Rev Respir Dis. 1988; 137 380-392
- 24 Guest P J, Hansell D M. High resolution computed tomography (HRCT) in emphysema associated with alpha-1-antitrypsin deficiency. Clin Radiol. 1992; 45 260-266
- 25 Gurney J W, Jones K K, Robbins R A, Gossman G L, Nelson K J, Daughton D, Spurzem J R, Rennard S I. Regional distribution of emphysema: correlation of high-resolution CT with pulmonary function tests in unselected smokers. Radiology. 1992; 183 457-463
- 26 Hale K A, Ewing W L, Gosnell B A, Niewoehner D E. Lung disease in long-term cigarette smokers with and without chronic airflow obstruction. Am Rev Respir Dis. 1984; 130 716-721
- 27 Hamada T, Sasaguri T, Hisaoka M, Hirakata K, Tanimoto A, Nakata H, Sasaguri Y, Hashimoto H. Mild emphysema: a novel method using formalin-fixed lungs for computed tomography and pathological analysis. Virchows Arch. 1995; 426 597-602
- 28 Hayhurst M D, Flenley D C, McLean A, Wightman A JA, MacNee W, Wright D, Lamb E, Best J. Diagnosis of pulmonary emphysema by computerised tomography. Lancet. 1984; 2 320-323
- 29 Heremans A, Verschakelen J A, van Fraeyenhoven L, Demedts M. Measurement of lung density by means of quantitative CT scanning. A study of correlations with pulmonary function. Chest. 1992; 102 805-811
- 30 Heyder J. Gravitational deposition of aerosol particles within a system of randomly orientated tubes. J Aerosol Sci. 1975; 6 133-137
- 31 Heyder J. Charting human thoracic airways by aerosols. Clin Phys Physiol Meas. 1983; 4 29-37
- 32 Heyder J, Blanchard D, Feldman H A, Brain J D. Convective mixing in human respiratory tract: estimates with aerosol boli. J Appl Physiol. 1988; 64 1273-1278
- 33 Heyder J, Davies C N. The breathing of half-micron aerosols. III. Dispersion of particles in the respiratory tract. J Aerosol Sci. 1971; 2 437-452
- 34 Hogg J C, Wright J L, Wiggs B R, Coxson H O, Saez A O, Paré P D. Lung structure and function in cigarette smokers. Thorax. 1994; 49 473-478
- 35 Hruban R H, Meziane M A, Zerhouni E A, Khouri N F, Fishman E K, Wheeler P S, Dumler J S, Hutchins G M. High resolution computed tomography of inflation-fixed lungs. Am Rev Respir Dis. 1987; 136 935-940
- 36 Hurd S. The impact of COPD on lung health worldwide. Chest. 2000; 117 1S-4S
- 37 Jefferey P K. Inflammation in chronic obstructive lung disease. Am J Respir Crit Care Med. 1999; 160 S3-S4
- 38 Jenkins D E, Greenberg S D, Boushy S F, Schweppe H I, O'Neal R M. Correlation of morphologic emphysema with pulmonary parameters. Trans Assoc Am Physicians. 1965; 78 218-230
- 39 Klose K J, Leppek R, Michalik-Himmelmann R. Die Bedeutung der Computertomographie in der pneumologischen bildgebenden Diagnostik. Internist. 1993; 34 1026-1037
- 40 Kohlhäufl M, Brand P, Häußinger K, Scheuch G, Schulz H, Heyder J. Pneumologische Diagnostik mit Modellaerosolen - 1. Teil: Intrapulmonale Morphometrie. Pneumologie. 1997; 51 40-46
- 41 Kohlhäufl M, Brand P, Meyer Th, Scheuch G, Weber N, Schulz H, Häußinger K, Schulz H, Heyder J. Detection of impaired intrapulmonary convective mixing by aerosol bolus dispersion in patients with emphysema. Eur J Med Res. 1997; 2 121-128
- 42 Kohlhäufl M, Brand P, Meyer Th, Scheuch G, Weber N, Schulz H, Häußinger K, Schulz H, Heyder J. Diagnosis of emphysema in patients with chronic bronchitis - a new approach. Eur Respir J. 1998; 12 793-798
- 43 Kohlhäufl M, Brand P, Scheuch G, Schulz H, Häußinger K, Heyder J. Pneumologische Diagnostik mit Modellaerosolen. II. Teil: Aerosolbolusdispersion - ein Marker für den konvektiven Gastransport. Penumologie. 1999; 53 50-56
- 44 Kohlhäufl M, Brand P, Rock C, Radons Th, Scheuch G, Meyer T, Schulz H, Pfeifer K J, Häußinger K, Heyder J. Noninvasive diagnosis of emphysema. Aerosolmorphometry and aerosol bolus dispersion in comparison to HRCT. Am J Respir Crit Care Med. 1999; 160 913-918
- 45 Kohlhäufl M, Brand P, Scheuch G, Häußinger K, Heyder J. Aerosolmorphometrie und Aerosolbolusdispersion. Dtsch med Wschr. 1999; 124 1399-1400
- 46 Kohlhäufl M, Brand P, Scheuch G, Meyer T, Schulz H, Häußinger K, Heyder J. Aerosol morphometry and aerosol bolus dispersion in patients with CT-determined combined pulmonary emphysema and lung fibrosis. J Aerosol Med. 2000; 13 117-124
- 47 Kohlhäufl M, Brand P, Meyer Th, Scheuch G, Häußinger K, Schulz H, Heyder J. Neue Methoden in der Diagnostik chronisch obstruktiver Lungenerkrankungen. In: Scheuch G (Hrsg). Aerosole in der Inhalationstherapie München-Deisenhofen: Dustri 2001: 53-74
- 48 Konietzko N, Fabel F (Hrsg). Weißbuch Lunge 2000. Stuttgart, New York: Thieme 2000: 19
- 49 Kuwano K, Matsuba K, Ikeda T, Murakami J, Araki A, Nishitani H, Ishida T. The diagnosis of mild emphysema. Am Rev Respir Dis. 1990; 141 169-178
- 50 Liedtke M, Hoffarth H P, Ulmer W T. Die Fluss-Volumen-Kurve bei Lungenemphysem. Atemw.-Lungenkrkh. 1991; 17 157-161
- 51 Lohela P, Sutinen S, Pääko P, Lahti R, Tienari J. Diagnosis of emphysema on chest radiography. Fortschr Röntgenstr. 1984; 141 395-402
- 52 Loubeyre P, Paret M, Revel D, Wiesendanger T, Brune J. Thin-section CT detection of emphysema associated with bronchiectasis and correlation with pulmonary function tests. Chest. 1996; 109 360-365
- 53 Macklem P T, Becklake M R. The relationship between the mechanical and diffusing properties of the lung in health and disease. Am Rev Respir Dis. 1963; 87 47-56
- 54 Massaro G D, Massaro D. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nature Med. 1997; 3 675-677
- 55 McLean A, Warren P M, Gillooly M, MacNee W, Lamb D. Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer. Thorax. 1992; 47 144-149
- 56 Miller R R, Müller N L, Vedal S, Morrison N J, Staples C A. Limitations of computed tomography in the assessment of emphysema. Am Rev Respir Dis. 1989; 139 980-983
- 57 Milne E NC, Bass H. The roentgenographic diagnosis of early chronic obstructive pulmonary disease. J Can Assoc Radiol. 1969; 20 3-15
- 58 Mitchell R S, Standford R E, Johnson J M, Silvers G W, Dart G, George M S. The morphological features of the bronchi, bronchioles, and alveoli in chronic airway obstruction: a clinicopathologic study. Am Rev Respir Dis. 1976; 114 137-145
- 59 Morrison N J, Abboud R T, Ramadan F, Miller R R, Gibson N N, Evans K G, Nelems B, Müller N L. Comparison of single breath carbon monoxide diffusing capacity and pressure-volume curves in detecting emphysema. Am Rev Respir Dis. 1989; 139 1179-1187
- 60 Müller N L. CT diagnosis of emphysema. It may be accurate, but is it relevant?. Chest. 1993; 2 329-330
- 61 Müller N L, Staples C A, Miller R R, Abboud R T. “Density mask”. An objective method to quantitate emphysema using computed tomography. Chest. 1988; 94 782-787
- 62 Nagai A, Inano H, Matsuba K, Thurlbeck W M. Scanning electromicroscopic morphometry of emphysema in humans. Am J Respir Crit Care Med. 1994; 150 1411-1415
- 63 Nagai A, West W W, Thurlbeck W M. The National Institutes of Health intermittent positive-pressure breathing trial: pathology studies. II. Correlation between morphologic findings, clinical findings, and evidence of expiratory airflow obstruction. Am Rev Respir Dis. 1985; 132 946-953
- 64 Nakano Y, Muro S, Sakai H, Hirai T, Chin K, Tsukino M, Nishimura K, Itoh H, Paré P D, Hogg J C, Mishima M. Computed tomographic measurements of airway dimensions and emphysema in smokers. Am J Respir Crit Care Med. 2000; 162 1102-1108
- 65 Nicklaus T M, Stowell D W, Christiansen W R, Renzeit Jr A D. The accuracy of the roentgenologic diagnosis of chronic pulmonary emphysema. Am Rev Respir Dis. 1966; 93 889-899
- 66 Nikiforov A L, Lippmann M, Palmes F D. Validation of an in vivo aerosol probe technique by measurements of deposition and morphometry in excised human lungs. Ann Occup Hyg. 1988; 32 33-39
- 67 O'Connor G T, Sparrow D, Weiss S T. A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: the normative aging study. Am J Respir Crit Care Med. 1995; 152 87-92
- 68 Otto H, Zeilhofer R. Lungenfunktion und Strukturbefund unter besonderer Berücksichtigung der obstruktiven Ventilationsstörung und des Lungenemphysems. Respiration. 1969; 26 262-286
- 69 Pratt P C. Role of conventional chest radiography in diagnosis and exclusion of emphysema. Am J Med. 1987; 82 998-1006
- 70 Pratt P C, Jutabha O, Klugh G A. Quantitative relationship between structural extent of centrilobular emphysema and postmortem volume and flow characteristics of lungs. Med Thorac. 1965; 22 197-208
- 71 Remy-Jardin M, Remy J, Boulenguez Ch, Sobaszek A, Edme J-L, Furon D. Morphologic effects of cigarette smoking on airways and pulmonary parenchyma in healthy adult volunteers: CT evaluation and correlation with pulmonary function tests. Radiology. 1993; 186 107-115
- 72 Remy-Jardin M, Remy J, Gosselin B, Becette V, Edme J-L. Lung parenchymal changes secondary to cigarette smoking: pathologic-CT correlations. Radiology. 1993; 186 643-651
- 73 Robins A G. Pathophysiology of emphysema. Clin Chest Med. 1983; 4 413-420
- 74 Rosenthal F S. Aerosol recovery following breathholding derived from distribution of chordlengths in pulmonary tissue. J Aerosol Sci. 1989; 2 267-277
- 75 Rosenthal F S. The effect of nonuniform ventilation on the dispersion of inspired aerosol boluses - a modelling study. J Aerosol Med. 1993; 6 177-197
- 76 Rosenthal F S, Wright S. Aerosol deposition and dispersion characterize lung injury in a canine model of emphysema. J Appl Physiol. 1995; 78 1585-1595
- 77 Ryder R, Lyons J, Campbell H, Gough J. Emphysema in coal workers pneumoconiosis. BMJ. 1970; 3 481-487
- 78 Saetta M, Finkelstein R, Cosio M G. Morphological and cellular basis for airflow limitation in smokers. Eur Respir J. 1994; 7 1505-1515
- 79 Sakai F, Gamsu G, Im J-G, Ray C S. Pulmonary function abnormalities in patients with CT-determined emphysema. J Comput assist Tomogr. 1987; 11 963-968
- 80 Sanders C. Imaging of emphysema. Sem Resp Med. 1992; 13 318-331
- 81 Sanders C, Hrudaya P N, Bailey W C. Detection of emphysema with computed tomography. Correlation with pulmonary function tests and chest radiography. Invest Radiol. 1988; 23 262-266
- 82 Siafakas N M, Postma D S. Future research in chronic obstructive pulmonary disease. Eur Respir Mon. 1998; 3 288-296
- 83 Siafakas N M, Vermeire P, Pride N B, Paoletti P, Gibson J, Howard J, Yernault J C, Decramer M, Higenbottam T, Postma D S, . Rees J on behalf of the Task Force . Optimal assessment and management of chronic obstructive pulmonary disease. Eur Respir Mon. 1995; 8 1398-1420
- 84 Snider G L, Brody J S, Doctor L. Subclinical emphysema. Am Rev Respir Dis. 1962; 85 666-683
- 85 Snider G L. Chronic obstructive pulmonary disease: a definition and implications of structural determinant of airflow obstruction for epidemiology. Am Rev Respir Dis. 1989; 140 S3-S8
- 86 Snider G L, Kleinerman J, Thurlbeck W M, Bengali Z H. The definition of emphysema. Report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases Workshop. Am Rev Respir Dis. 1985; 132 182-185
- 87 Spector D M, Hunt P R, Rosenthal F, Lippmann M. Influence of airway and airspace size on particle deposition in excised donkey lungs. Exp Lung Res. 1985; 9 363-387
- 88 Spouge D, Mayo J R, Cardoso W, Müller N L. Panacinar emphysema: CT and pathologic findings. J Comput assist Tomogr. 1993; 17 710-713
- 89 Stockley R A. New perspectives on the protease/antiprotease balance. Eur Respir Rev. 1997; 7 128-130
- 90 Stockley R A. New approaches to the management of COPD. Chest. 2000; 117 58S-62S
- 91 Sutinen S, Christoforidis A J, Klugh G A, Pratt P C. Roentgenologic criteria for the recognition of nonsymptomatic pulmonary emphysema. Am Rev Respir Dis. 1965; 91 69-76
- 92 Sweet H C, Wyatt J P, Fritsch A, Kinsella P W. Panlobular and centrilobular emphysema: Correlations of clinical findings with pathologic patterns. Ann Intern Med. 1961; 55 565-581
- 93 Thurlbeck W M. The incidence of pulmonary emphysema. Am Rev Respir Dis. 1963; 87 206-215
- 94 Thurlbeck W M. Pathophysiology of chronic obstructive pulmonary disease. Clin Chest Med. 1990; 3 389-403
- 95 Thurlbeck W M, Henderson J A, Fraser R G, Bates D V. Chronic obstructive lung disease: a comparison between clinical, roentgenologic functional and morphologic criteria in chronic bronchitis, emphysema, asthma, and bronchiectasis. Medicine. 1970; 49 81-145
- 96 Thurlbeck W M, Müller N L. Definition, imaging, and quantification. Am J Radiol. 1994; 163 1017-1025
- 97 Thurlbeck W M, Simon G. Radiographic appearance of the chest in emphysema. Am J Radiol. 1978; 130 429-440
- 98 Thurlbeck W M, Wright J L. Thurlbeck's chronic airflow obstruction. Hamilton: Decker 1999
- 99 Tockmann M S, Becklake M R, Clausen J L, Cox Jr P M, O'Brien R J, Permutt S, Petty Th L, Reed Ch, Reichmann L B, Stead W W. Screening for adult respiratory disease. Am Rev Respir Dis. 1983; 128 768-774
- 100 Ulmer W T. Lungenemphysem - Forschungsprogramm: Möglichkeiten und Erfordernisse. Pneumologie. 1991; 45 488-490
- 101 Ulmer W T, Reichel G, Nolte D, Islam M S. Die Lungenfunktion. New York: Thieme 1983: 14
- 102 Wilson J MG, Jungner G. Principles and practice of screening for disease. Publ Hlth Papers. Geneva: WHO 1968: 34-18
- 103 Woodring J H, Philips B A, West J, Ulmer J, Cooper J K. A prospective evaluation of plain radiographic signs of chronic obstructive pulmonary disease. J Thorac Imaging.. 1991; 6 14-21
- 104 Worth H. Zur Diagnose des Lungenemphysems. Stuttgart: Thieme 1985
- 105 Yoshioka A, Betsuyaku T, Nishimura M, Miyamoto K, Kondo T, Kawakami Y. Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. Am J Respir Crit Care Med. 1995; 152 2127-2132
Dr. M. Kohlhäufl
Asklepios Fachklinik München-Gauting
Robert-Koch-Allee 2
82131 Gauting
Email: E-mail: kohlhaeufl@gsf.de