Die Rolle von Viren bei tiefen Atemwegsinfektionen des Erwachsenen[]

Zusammenfassung

Infektionen des Respirationstrakts sind in industrialisierten Ländern eine der häufigsten Ursachen für ärztliche Konsultationen, wobei rund ein Drittel dieser Erkrankungen die tiefen Atemwege betreffen. Hierzu zählen neben der akuten Bronchitis auch die akute Exazerbation einer chronisch obstruktiven Lungenerkrankung (COPD), die ambulant oder nosokomial erworbene Pneumonie und als besondere Entität die Influenza, die sämtliche Abschnitte des Respirationstrakt betreffen kann. Über lange Zeit wurde aus Mangel an geeigneten Untersuchungsmethoden die Bedeutung von respiratorischen Viren bei der Genese dieser Infektionen wahrscheinlich unterschätzt. Da bislang oft eine bakterielle Genese vermutet wurde, erfolgte im klinischen Alltag, insbesondere bei der akuten Bronchitis oder der exazerbierten COPD, in vielen Fällen eine antibiotische Behandlung, die wahrscheinlich nicht erforderlich ist und das Risiko einer Resistenzentwicklung beinhaltet. Erst mit der Einführung von sensitiveren Nachweisverfahren für Viren, wie zum Beispiel der Polymerasekettenreaktion (PCR), gelingt ein sicherer und zuverlässiger Nachweis von respiratorischen Viren, der Aussagen über deren Bedeutung bei Infektionen des tiefen Respirationstrakts erlaubt. Im Rahmen dieser dreiteiligen Serie soll deshalb anhand der aktuellen Literatur ein Überblick über den derzeitigen Kenntnisstand zur Bedeutung von respiratorischen Viren bei tiefen Atemwegsinfektionen des Erwachsenen gegeben werden. Der erste Teil befasste sich mit spezifischen Erregern, Pathogenese und Diagnostik. Im aktuellen Teil wird auf die Rolle von Viren bei den häufigsten Formen der tiefen Atemwegsinfekte (s. o.) eingegangen, und der dritte und letzte Teil behandelt Therapie und Prävention.

Abstract

In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2^nd part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options.

1 Gefördert durch die Paul Ehrlich Gesellschaft (PEG).

Literatur

• 1 Holmes W F, Macfarlane J T, Macfarlane R M. et al . Symptoms, signs, and prescribing for acute lower respiratory tract illness.  Br J Gen Pract. 2001;  51 177-181
• 2 Gonzales R, Sande M A. Uncomplicated acute bronchitis.  Ann Intern Med. 2000;  133 981-991
• 3 Braman S S. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines.  Chest. 2006;  129 (Suppl 1) 95S-103S
• 4 Thiadens H A, Postma D S, de Bock G H. et al . Asthma in adult patients presenting with symptoms of acute bronchitis in general practice.  Scand J Prim Health Care. 2000;  18 188-192
• 5 Höffken G, Lorenz J, Kern W. et al . S3-Leitlinie zur Epidemiologie, Diagnostik, antimikrobieller Therapie und Management von erwachsenen Patienten mit ambulant erworbenen tiefen Atemwegsinfektionen (akute Bronchitis, akute Exazerbation einer chronischen Bronchitis, Influenza und andere respiratorische Virusinfektionen) sowie ambulant erworbene Pneumonie.  Pneumologie. 2005;  59 612-664
• 6 Techniker Krankenkasse .Gesundheitsreport 2006. 2006
• 7 Cate T R, Couch R B, Fleet W F. et al . Production of Tracheobronchitis in Volunteers with Rhinovirus in a Small-Particle Aerosol.  Am J Epidemiol. 1965;  81 95-105
• 8 Jonsson J S, Sigurdsson J A, Kristinsson K G. et al . Acute bronchitis in adults. How close do we come to its aetiology in general practice?.  Scand J Prim Health Care. 1997;  15 156-160
• 9 Boldy D A, Skidmore S J, Ayres J G. Acute bronchitis in the community: clinical features, infective factors, changes in pulmonary function and bronchial reactivity to histamine.  Respir Med. 1990;  84 377-385
• 10 Macfarlane J, Holmes W, Gard P. et al . Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community.  Thorax. 2001;  56 109-114
• 11 Freymuth F, Vabret A, Gouarin S. et al . Epidemiology and diagnosis of respiratory syncytial virus in adults.  Rev Mal Respir. 2004;  21 35-42
• 12 Nicholson K G, Kent J, Hammersley V. et al . Risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study.  BMJ. 1996;  313 1119-1123
• 13 Smucny J, Fahey T, Becker L. et al . Antibiotics for acute bronchitis.  Cochrane Database Syst Rev. 2004;  4 CD000245
• 14 Evans A T, Husain S, Durairaj L. et al . Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial.  Lancet. 2002;  359 1648-1654
• 15 Van den Hoogen B G, Osterhaus D M, Fouchier R A. Clinical impact and diagnosis of human metapneumovirus infection.  Pediatr Infect Dis J. 2004;  23 (Suppl 1) 25-32
• 16 Prins J M, Wolthers K C. Human metapneumovirus: a new pathogen in children and adults.  Neth J Med. 2004;  62 177-179
• 17 Kaye M, Skidmore S, Osman H. et al . Surveillance of respiratory virus infections in adult hospital admissions using rapid methods.  Epidemiol Infect. 2006;  134 792-798
• 18 Vabret A, Mourez T, Gouarin S. et al . An outbreak of coronavirus OC43 respiratory infection in Normandy, France.  Clin Infect Dis. 2003;  36 985-989
• 19 Knutson D, Braun C. Diagnosis and management of acute bronchitis.  Am Fam Physician. 2002;  65 2039-2044
• 20 Kardos P, Cegla U, Gillissen A. et al . Leitlinie der Deutschen Gesellschaft für Pneumologie zur Diagnostik und Therapie von Patienten mit akutem und chronischem Husten.  Pneumologie. 2004;  58 570-602
• 21 Melbye H, Kongerud J, Vorland L. Reversible airflow limitation in adults with respiratory infection.  Eur Respir J. 1994;  7 1239-1245
• 22 Macfarlane J, Holmes W, Gard P. et al . Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet.  BMJ. 2002;  324 91-94
• 23 Rabe K F, Beghe B, Luppi F. et al . Update in chronic obstructive pulmonary disease 2006.  Am J Respir Crit Care Med. 2007;  175 1222-1232
• 24 Seemungal T A, Donaldson G C, Paul E A. et al . Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1998;  157 1418-1422
• 25 Burge S, Wedzicha J A. COPD exacerbations: definitions and classifications.  Eur Respir J Suppl. 2003;  41 46s-53s
• 26 Rodriguez-Roisin R. Toward a consensus definition for COPD exacerbations.  Chest. 2000;  117 (Suppl 2) 398S-401S
• 27 Anthonisen N R, Manfreda J, Warren C P. et al . Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease.  Ann Intern Med. 1987;  106 196-204
• 28 WHO .World Health Report 2008. 2008
• 29 Connors A F, Dawson N V, Thomas C. et al . Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments).  Am J Respir Crit Care Med. 1996;  154 959-967
• 30 Groenewegen K H, Schols A M, Wouters E F. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD.  Chest. 2003;  124 459-467
• 31 Kanner R E, Anthonisen N R, Connett J E. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study.  Am J Respir Crit Care Med. 2001;  164 358-364
• 32 Donaldson G C, Seemungal T A, Bhowmik A. et al . Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.  Thorax. 2002;  57 847-852
• 33 Murphy T F, Sethi S, Niederman M. The role of bacteria in exacerbations of COPD. A constructive view.  Chest. 2000;  118 204-209
• 34 Greenberg S B, Allen M, Wilson J. et al . Respiratory viral infections in adults with and without chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2000;  162 167-173
• 35 Bandi V, Apicella M A, Mason E. et al . Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis.  Am J Respir Crit Care Med. 2001;  164 2114-2119
• 36 Patel I S, Seemungal T A, Wilks . et al . Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations.  Thorax. 2002;  57 759-764
• 37 Saint S, Bent S, Vittinghoff E. et al . Antibiotics in chronic obstructive pulmonary disease exacerbations. A meta-analysis.  Jama. 1995;  273 957-960
• 38 MacNee W, Calverley S M. Chronic obstructive pulmonary disease. 7: Management of COPD.  Thorax. 2003;  58 261-265
• 39 Wedzicha J A. Role of viruses in exacerbations of chronic obstructive pulmonary disease.  Proc Am Thorac Soc. 2004;  1 115-120
• 40 Seemungal T, Harper-Owen R, Bhowmik A. et al . Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  164 1618-1623
• 41 Seemungal T A, Donaldson G C, Bhowmik A. et al . Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2000;  161 1608-1613
• 42 Tan W C, Xiang X, Qui D. et al . Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease.  Am J Med. 2003;  115 272-277
• 43 Rohde G, Wiethege A, Borg I. et al . Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study.  Thorax. 2003;  58 37-42
• 44 Papi A, Bellettato C M, Braccioni F. et al . Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations.  Am J Respir Crit Care Med. 2006;  173 1114-1121
• 45 Wilkinson T M, Hurst J R, Perera W R. et al . Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD.  Chest. 2006;  129 317-324
• 46 Barnes P J. Chronic obstructive pulmonary disease.  N Engl J Med. 2000;  343 269-280
• 47 Rohde G, Borg I, Wiethege A. et al . Inflammatory response in acute viral exacerbations of COPD.  Infection. 2008;  36 427-433
• 48 Hogg J C, Chu F, Utokaparch S. et al . The nature of small-airway obstruction in chronic obstructive pulmonary disease.  N Engl J Med. 2004;  350 2645-2653
• 49 Rohde G, Schlosser B, Arinir U. et al . The role of respiratory infections in chronic obstructive pulmonary disease.  Med Klin (München). 2007;  102 893-898
• 50 Borg I, Rohde G, Loseke S. et al . Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases.  Eur Respir J. 2003;  21 944-951
• 51 Rohde G, Wiethege A, Borg I. et al . Influenza A virus in Exacerbation of chronic obstruktive pulmonary disease.  Eur Respir J Suppl. 2001;  18 (Suppl 33) 152
• 52 Worth H, Buhl R, Cegla U. et al . Leitlinie der Deutschen Atemwegsliga und der Deutschen Gesellschaft für Pneumologie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD).  Pneumologie. 2002;  56 704-738
• 53 Ruiz M, Ewig S, Marcos M A. et al . Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity.  Am J Respir Crit Care Med. 1999;  160 397-405
• 54 Lim W S, Macfarlane J T, Boswell T C. et al . Study of community acquired pneumonia aetiology (SCAPA) in adults admitted to hospital: implications for management guidelines.  Thorax. 2001;  56 296-301
• 55 Welte T, Kohnlein T. Global and local epidemiology of community-acquired pneumonia: the experience of the CAPNETZ Network.  Semin Respir Crit Care Med. 2009;  30 127-135
• 56 Fang G D, Fine M, Orloff J. et al . New and emerging etiologies for community-acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases.  Medicine (Baltimore). 1990;  69 307-316
• 57 Dowell S F, Anderson L J, Gary Jr. H E. et al . Respiratory syncytial virus is an important cause of community-acquired lower respiratory infection among hospitalized adults.  J Infect Dis. 1996;  174 456-462
• 58 Almirall J, Bolibar I, Vidal J. et al . Epidemiology of community-acquired pneumonia in adults: a population-based study.  Eur Respir J. 2000;  15 757-763
• 59 Woodhead M. Community-acquired pneumonia guidelines – an international comparison: a view from Europe.  Chest. 1998;  113 (Suppl) 183S-187S
• 60 De Roux A, Marcos M A, Garcia E. et al . Viral community-acquired pneumonia in nonimmunocompromised adults.  Chest. 2004;  125 1343-1351
• 61 Angeles Marcos M, Camps M, Pumarola T. et al . The role of viruses in the aetiology of community-acquired pneumonia in adults.  Antivir Ther. 2006;  11 351-359
• 62 Ewig S. Community-acquired pneumonia: definition, epidemiology, and outcome.  Semin Respir Infect. 1999;  14 94-102
• 63 Krech T, Wegmann T, Martin H. et al . Etiology of atypical pneumonias. A serological study on 1494 patients.  Schweiz Med Wochenschr. 1986;  116 2-7
• 64 Farr B M, Kaiser D L, Harrison B D. et al . Prediction of microbial aetiology at admission to hospital for pneumonia from the presenting clinical features. British Thoracic Society Pneumonia Research Subcommittee.  Thorax. 1989;  44 1031-1035
• 65 Dahmash N S, Chowdhury M N. Re-evaluation of pneumonia requiring admission to an intensive care unit: a prospective study.  Thorax. 1994;  49 71-76
• 66 Bohte R, van Furth R, van den Broek P F. Aetiology of community-acquired pneumonia: a prospective study among adults requiring admission to hospital.  Thorax. 1995;  50 543-547
• 67 Socan M, Marinic-Fiser N, Kraigher A. et al . Microbial aetiology of community-acquired pneumonia in hospitalised patients.  Eur J Clin Microbiol Infect Dis. 1999;  18 777-782
• 68 Hamelin M E, Cote S, Laforge J. et al . Human metapneumovirus infection in adults with community-acquired pneumonia and exacerbation of chronic obstructive pulmonary disease.  Clin Infect Dis. 2005;  41 498-502
• 69 La Scola B, Marrie T J, Auffray J P. et al . Mimivirus in pneumonia patients.  Emerg Infect Dis. 2005;  11 449-452
• 70 Johnstone J, Majumdar S R, Fox J D. et al . Human metapneumovirus pneumonia in adults: results of a prospective study.  Clin Infect Dis. 2008;  46 571-574
• 71 Cebular S, Lee S, Tolaney P. et al . Community-acquired pneumonia in immunocompromised patients. Opportunistic infections to consider in differential diagnosis.  Postgrad Med. 2003;  113 65-66, 69 – 70, 73 – 74
• 72 Duffau P, Moiton M P, Lafon M E. et al . A case of severe community acquired pneumonia and non-respiratory illness induced by Influenza A.  Med Mal Infect. 2006;  36 473-475
• 73 Lee D G, Yoo J H, Choi J H. et al . A fatal case of measles pneumonia complicating an adult recipient of hemopoietic stem cell transplantation during the nationwide epidemic in Korea.  Int J Infect Dis. 2006;  10 410-411
• 74 Kobashi Y, Okimoto N, Matsushima T. et al . Clinical analysis of community-acquired pneumonia in the elderly.  Intern Med. 2001;  40 703-707
• 75 Gutierrez F, Masia M, Mirete C. et al . The influence of age and gender on the population-based incidence of community-acquired pneumonia caused by different microbial pathogens.  J Infect. 2006;  53 166-174
• 76 Johnstone J, Majumdar S R, Fox J D. et al . Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation.  Chest. 2008;  134 1141-1148
• 77 Jennings L C, Anderson T P, Beynon K A. et al . Incidence and characteristics of viral community-acquired pneumonia in adults.  Thorax. 2008;  63 42-48
• 78 Ruiz-Gonzalez A, Falguera M, Nogues A. et al . Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia.  Am J Med. 1999;  106 385-390
• 79 Ishida T, Hasimoto T, Arita M. et al . Efficacy of transthoracic needle aspiration in community-acquired pneumonia.  Intern Med. 2001;  40 873-877
• 80 Nseir S, Di Pompeo C, Pronnier P. et al . Nosocomial tracheobronchitis in mechanically ventilated patients: incidence, aetiology and outcome.  Eur Respir J. 2002;  20 1483-1489
• 81 ATS/IDSA . Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.  Am J Respir Crit Care Med. 2005;  171 388-416
• 82 Louie M, Dyck B, Parker S. et al . Nosocomial pneumonia in a Canadian tertiary care center: a prospective surveillance study.  Infect Control Hosp Epidemiol. 1991;  12 356-363
• 83 Daubin C, Parienti J J, Vincent S. et al . Epidemiology and clinical outcome of virus-positive respiratory samples in ventilated patients: a prospective cohort study.  Crit Care. 2006;  10 R142
• 84 Ong G M, Lowry K, Mahajan S. et al . Herpes simplex type 1 shedding is associated with reduced hospital survival in patients receiving assisted ventilation in a tertiary referral intensive care unit.  J Med Virol. 2004;  72 121-125
• 85 Camps K, Jorens P G, Demey H E. et al . Clinical significance of herpes simplex virus in the lower respiratory tract of critically ill patients.  Eur J Clin Microbiol Infect Dis. 2002;  21 758-759
• 86 De Vos N, Van Hoovels L, Vankeerberghen A. et al . Monitoring of herpes simplex virus in the lower respiratory tract of critically ill patients using real-time PCR: a prospective study.  Clin Microbiol Infect. 2009;  15 358-363
• 87 Daubin C, Vincent S, Vabret A. et al . Nosocomial viral ventilator-associated pneumonia in the intensive care unit: a prospective cohort study.  Intensive Care Med. 2005;  31 1116-1122
• 88 Porteous C, Bradley J A, Hamilton D N. et al . Herpes simplex virus reactivation in surgical patients.  Crit Care Med. 1984;  12 626-628
• 89 Hanley P J, Conaway M M, Halstead D C. et al . Nosocomial herpes simplex virus infection associated with oral endotracheal intubation.  Am J Infect Control. 199;  21 310-316
• 90 Byers R J, Hasleton P S, Quigley A. et al . Pulmonary herpes simplex in burns patients.  Eur Respir J. 1996;  9 2313-2317
• 91 Bruynseels P, Jorens P G, Demey H E. et al . Herpes simplex virus in the respiratory tract of critical care patients: a prospective study.  Lancet. 2003;  362 1536-1541
• 92 Luyt C E, Combea A, Deback C. et al . Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation.  Am J Respir Crit Care Med. 2007;  175 935-942
• 93 Schuller D, Spessert C, Fraser V J. et al . Herpes simplex virus from respiratory tract secretions: epidemiology, clinical characteristics, and outcome in immunocompromised and nonimmunocompromised hosts.  Am J Med. 1993;  94 29-33
• 94 Engelmann I, Gottlieb J, Meier A. et al . Clinical relevance of and risk factors for HSV-related tracheobronchitis or pneumonia: results of an outbreak investigation.  Crit Care. 2007;  11 R119
• 95 Tuxen D V, Wilson J W, Cade J F. Prevention of lower respiratory herpes simplex virus infection with acyclovir in patients with the adult respiratory distress syndrome.  Am Rev Respir Dis. 1987;  136 402-405
• 96 Van den Brink J W, Simoons-Smit A M, Beihuizen A. et al . Respiratory herpes simplex virus type 1 infection/colonisation in the critically ill: marker or mediator?.  J Clin Virol. 2004;  30 68-72
• 97 Ziemann M, Sedemund-Adib B, Reiland P. et al . Increased mortality in long-term intensive care patients with active cytomegalovirus infection.  Crit Care Med. 2008;  36 3145-3150
• 98 Heininger A, Jahn G, Engel C. et al . Human cytomegalovirus infections in nonimmunosuppressed critically ill patients.  Crit Care Med. 2001;  29 541-547
• 99 Jaber S, Chanques G, Borry J. et al . Cytomegalovirus infection in critically ill patients: associated factors and consequences.  Chest. 2005;  127 233-241
• 100 Guidry G G, Black-Payne C A, Payne D K. et al . Respiratory syncytial virus infection among intubated adults in a university medical intensive care unit.  Chest. 1991;  100 1377-1384
• 101 Oliveira E C, Lee B, Colice G L. Influenza in the intensive care unit.  J Intensive Care Med. 2003;  18 80-91
• 102 Malcolm E, Arruda E, Hayden F G. et al . Clinical features of patients with acute respiratory illness and rhinovirus in their bronchoalveolar lavages.  J Clin Virol. 2001;  21 9-16
• 103 Stollenwerk N, Harper R W, Sandrock C E. Bench-to-bedside review: rare and common viral infections in the intensive care unit – linking pathophysiology to clinical presentation.  Crit Care. 2008;  12 219
• 104 Tellier R. Review of aerosol transmission of influenza A virus.  Emerg Infect Dis. 2006;  12 1657-1662
• 105 Brundage J F. Cases and deaths during influenza pandemics in the United States.  Am J Prev Med. 2006;  31 252-256
• 106 Jamieson D J, Honein M A, Rasmussen S A. et al . H1N1 2009 influenza virus infection during pregnancy in the USA.  Lancet. 2009;  374 451-458
• 107 Boivin G, Hardy I, Tellier G. et al . Predicting influenza infections during epidemics with use of a clinical case definition.  Clin Infect Dis. 2000;  31 1166-1169
• 108 Lieberman D, Schlaeffer F, Boldur I. et al . Multiple pathogens in adult patients admitted with community-acquired pneumonia: a one year prospective study of 346 consecutive patients.  Thorax. 1996;  51 179-184

1 Gefördert durch die Paul Ehrlich Gesellschaft (PEG).

2 Alle Autoren haben gleichermaßen zur Erstellung des Manuskriptes beigetragen.