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A series of five adult cases of respiratory syncytial virus-related acute respiratory distress syndrome.


Respiratory syncytial virus is a common cause of respiratory tract disease in children, predominantly presenting with mild symptoms. We present five cases of respiratory syncytial virus infection of the lower respiratory tract in immunocompromised adults suffering from severe respiratory insufficiency leading to bilateral pneumonia and fulfilling the criteria for acute respiratory distress syndrome. Respiratory syncytial virus was cultured as the only pathogen in the bronchoalveolar lavage fluid in four of these patients. Despite various therapeutic interventions, only one patient survived. Respiratory syncytial virus was implicated as a direct cause of respiratory failure. Respiratory syncytial virus may be an underestimated cause of severe respiratory failure and acute respiratory distress syndrome in the immunocompromised adult admitted to the intensive care unit.

Key Words: RSV, respiratory syncytial virus, pneumonia, ARDS, acute respiratory distress syndrome, respiratory failure, BAL, bronchoalveolar lavage


Respiratory syncytial virus (RSV) infection is an important but rarely lethal respiratory tract disease in infants and young children. In adult patients RSV may be a cause of respiratory failure in the immunocompromised and non-immunocompromised host (1-5), but most reports still focus on the very young patient. We report five cases of RSV infection in adults, all leading to severe respiratory failure and meeting the criteria for acute respiratory distress syndrome (ARDS) (6). RSV was therefore implicated as a direct cause of severe respiratory failure. Despite several therapeutic interventions, only one of these patients survived. This report suggests that RSV might be an underestimated cause of respiratory insufficiency in the intensive care unit (ICU) and may present as ARDS in the adult.


Case 1

A 64-year-old male had a history of mucosal associated lymphoid tissue lymphoma of the colon, surgically treated at the age of 60 years. There was a relapse one year later and chemotherapy was administered with proven complete remission. At his second relapse, he underwent autologous bone marrow transplantation during the period of bone marrow aplasia. Three weeks after transplantation, he was admitted to the ICU with signs of respiratory failure.


The chest X-ray showed massive alveolar infiltrates (Figure 1). No evidence for left cardiac failure was observed by echocardiography. Culture of the bronchoalveolar lavage (BAL) fluid was only positive for RSV and no evidence of other sites of infection were found. The patient was treated with continuous ribavirin aerosol at a daily dosage of 6 g/18 h. Despite these efforts, he died of multiple organ failure three weeks after admission to the ICU.

Case 2

A 52-year-old woman with a medical history of depression, alcohol and nicotine abuse developed an invasive spinocellular epithelioma of the lower oesophagus. Prior to surgery she was treated with a combination of radio- and chemotherapy, causing neutropenia. Overall, she recovered well and oesophagectomy was performed. An endotracheal aspirate taken four days after surgery was positive for RSV All other cultures remained sterile. The chest X-ray as well as the CT scan (Figure 2) showed bilateral infiltrates meeting the criteria for ARDS. No specific antiviral treatment was given. Swan-Ganz monitoring excluded left heart failure. She remained in the ICU for several weeks suffering from respiratory insufficiency. She recovered from this episode and left the ICU in an acceptable condition. One week later she was readmitted with a relapse of respiratory insufficiency. She died 10 days later due to severe septic shock and multiple organ failure: no other pathogen was found.


Case 3

A 78-year-old female with a medical history of chronic renal failure and previously diagnosed with Wegener's granulomatosis was admitted to the ICU with respiratory failure. The diagnostic criteria for ARDS were again present. Culture of BAL collected on admission demonstrated RSV Transthoracic echocardiography did not suggest left heart failure. She was treated with ribavirin aerosols at a daily dosage of 6 g/18 h. Ten days later, RSV could no longer be detected in a repeat BAL. She relapsed with a second episode of respiratory failure. Cultures were now positive for Aspergillus fumigatus, Xanthomonas maltophilia and Enterobacter species. Despite therapy with antibiotics, an antifungal agent and maximal ventilatory support, she died of septic shock 30 days after the initial admission.

Case 4

A 63-year-old male with a medical history of appendicectomy and epididymitis was diagnosed with a progressive follicular B-cell non-Hodgkin lymphoma at the age of 62. One year later, there was a transformation towards a large-cell lymphoma and he underwent an autologous peripheral blood stem cell transplantation after high-dose chemotherapy. Soon afterwards, he was admitted to the ICU with respiratory insufficiency and signs of bilateral alveolar infiltrates on chest X-ray. Haemodynamic monitoring by Swan-Ganz catheter showed no evidence of left heart failure or hydrostatic oedema. In the BAL, collected on admission, the only agent detected was RSV The patient died 48 hours after admission.

Case 5

A 62-year-old female with a history of mitral valvuloplasty, atrial fibrillation, cerebrovascular accident, epilepsy, cholecystitis complicated by peritonitis, pneumonia and ARDS three years earlier, was admitted to the ICU with respiratory insufficiency. At the time of her admission to the ICU she had already been hospitalised for three weeks because of acute pancreatitis. Chest X-ray on admission showed bilateral alveolar infiltrates. Enterobacter aerogenes and Enterococcus faecalis were isolated from a bronchus aspirate on admission. However, BAL one day later only demonstrated RSV She required ventilatory support during 12 days but recovered from a second episode of ARDS and left the ICU one month after admission. No specific antiviral therapy was administered. Despite a history of valvuloplasty, echocardiography showed a good left ventricular function.

Culture of BAL fluid

The University Hospital of Antwerp is a 600-bed tertiary care hospital with a 39-bed ICU. The number of admissions in this unit is approximately 2000 per year including surgical, medical and trauma patients. In our ICU, BAL is routinely performed in patients with persistent or unexplained hypoxaemia and with radiographic bilateral alveolar infiltrates not responding to standard antibiotic therapy. We observed these five cases of RSV related ARDS in an observation period of eight years (1999 to 2006) during which period BAL was performed in approximately 1200 patients. BAL samples are routinely cultured for bacteria, fungi and respiratory viruses (enteroviruses, rhinoviruses, parainfluenza and influenza viruses, adenoviruses, herpes simplex virus, cytomegalovirus and RSV) (7). The BAL samples are inoculated in VERO, MDCK, MRC-5 and HEP-2 cells. Viral identification is made by indirect immunofluorescence on centrifuged cell cultures using monoclonal antibodies (influenza virus, parainfluenza virus, adenovirus, cytomegalovirus and RSV). The cultures are observed for 14 to 21 days for appearance of a cytopathic effect characteristic of the other viruses (enterovirus, rhinovirus and herpes simplex virus). In four of the five patients presented, RSV was cultured from the BAL fluid. Bronchoalveolar lavage did not reveal any other additional bacterial, viral or fungal isolates as a cause of the observed bilateral infiltrates in these individuals.


The respiratory syncytial virus is named after the giant syncytia produced in tissue cultures with this virus (8). RSV is a major cause of lower respiratory tract infection in infants and young children, causing both bronchiolitis and pneumonia: these children usually present with severe wheezing (9). It affects 90% of infants and young children by the age of two. Natural immunity however, is incomplete and repeated infections may occur throughout life (10).

Among adults, RSV infections usually present as a self-limiting upper respiratory tract illness or tracheobronchitis. The infection rate is variable, with outbreaks mainly occurring during winter months (11). RSV infection may however be an important cause of hospitalisation in elderly patients, accounting for up to 10.6% of hospitalisations for pneumonia in one series (2). It may have a disease burden similar to that of nonpandemic Influenzavirus A (2). RSV may also be detected in a high percentage of patients with chronic obstructive pulmonary disease (12). In a series of 132 elderly and high-risk hospitalised patients, this viral infection resulted in admission to the ICU in 15% of cases and a mortality of 8.5% (2)

An increasing number of reports stress the importance of RSV in the immunocompromised host, especially transplant patients (bone marrow, liver or lung transplants and patients with a medical history of leukaemia) (2,3,13-16). Cellular immunity seems to play an important role in the defence mechanism, explaining why RSV infections in the immunocompromised host occur more frequently and more seriously. RSV infection in the adult may also lead to different presentations ranging from bronchitis to pneumonia but full-blown respiratory failure is rarely observed. In our series, three out of five patients had an underlying malignant or haematological disease. Wegener's granulomatosis was the underlying diagnosis in the fourth case. The association between RSV infection and Wegener's granulomatosis has been reported once (17). In our series, bilateral alveolar infiltrates were observed both on chest X-ray and/or CT scan of the chest. Moreover, all patients met ARDS criteria characterised by profound hypoxaemia, diffuse alveolar infiltrates on chest X-ray (not due to left ventricular failure) and decreased compliance (6). Severe bilateral pneumonia leading to ARDS has been described only occasionally in RSV-infected adults (18).

A successful identification of RSV depends on appropriate collection of respiratory samples. Identification can be attempted by viral culture, nucleic acid amplification, histopathology or serology (19). In our patient group, the gold standard of culturing the virus was performed on all respiratory samples.

Preventive measures to limit nosocomial transmission include the use of masks, wearing gloves and proper hand hygiene after removing them. It also includes avoiding patient contact whenever possible and, if not, wearing a gown (20). The outcome of patients with RSV infection after allogenic peripheral blood stem cell transplantation has been studied retrospectively: 6.3% of the allogenic peripheral blood stem cell recipients were identified as infected with RSV, 19.2% died as a direct result of this RSV infection'. Studies have been published of RSV patients in the ICU, also showing that the immunocompromised patient is at the greatest risk of dying".

Aerosolised ribavirin was approved by the U.S. Food and Drug Administration in 1986 for the therapy of young children with severe RSV pneumonia. Its efficacy in children remains controversial. Conflicting results also exist on the effect of ribavirin in adult bone marrow transplantation patients with RSV infection. RSV treatment did not correlate with the outcome in one study (4). Others observed that treatment with the antiviral agent ribavirin for RSV infection is well tolerated when administered both intravenously and orally and may reduce morbidity and mortality in bone marrow transplant recipients (22). Survival of patients treated with aerosolised ribavirin therapy generally was associated with earlier diagnosis of RSV, a treatment duration longer than five days and early treatment initiation prior to respiratory failure (23). Thus the effectiveness of treatment may largely depend upon the stage of the disease as well as the overall condition of the patient. This seems to be confirmed by our data, with only one survivor in five cases who all had severe respiratory failure and ARDS at the time of diagnosis. One trial reported the apparent efficacy of a combination of aerosolised ribavirin and intravenous immunoglobulin at a dosage of 500 mg/kg every other day in RSV related upper respiratory tract illness in adult blood and bone marrow transplant recipients: only two lethal cases were observed in 14 patients treated (24). In only two of our five patients were we able to initiate a treatment with aerosolised ribavarin, mostly due to limited availability.

Hospitalisation of the immunocompromised (especially haematological) patient in the ICU is still accompanied by high morbidity and mortality". Multiple organ failure and ARDS are frequently observed. Our report of five cases with fulminant ARDS in whom RSV was the only initially isolated causative agent in the lower respiratory tract, emphasises that RSV infection may be an underestimated cause of virus-related ARDS in the immunocompromised host admitted to the ICU. It stresses the need to detect RSV in respiratory samples in these patients and to search for new antiviral agents.

Accepted for publication on August 22, 2007.


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(22.) Stretton M, Ajizian SJ, Mitchell I, Newth CJ. Intensive care course and outcome of patients infected with respiratory syncytial virus. Pediatr Pulmonol 1992; 13:143-150.

(23.) Dominguez KD, Mercier RC. Treatment of RSV pneumonia in adults-evidence of ribavirin effectiveness? Ann Pharmacother 1999; 33:739-741.

(24.) Ghosh S, Champlin RE, Englund J, Giralt SA, Rolston K, Raad I et al. Respiratory syncytial virus upper respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with aerosolized ribavirin and intravenous immunoglobulin. Bone Marrow Transplant 2000; 25:751-755.

(25.) Benoit DD, Depuydt PO, Vandewoude KH, Offner FC, Boterberg T, De Cock CA. Outcome in severely ill patients with hematological malignancies who received intravenous chemotherapy in the intensive care unit. Intensive Care Med 2006; 32:93-99.

D. ROBERT *, D. VERBIEST ([dagger]), H. DEMEY *, M. IEVEN ([double dagger]), H. JANSENS ([section]), P.G. JORENS ** Department of Critical Care Medicine, University Hospital of Antwerp, University of Antwerp and Department of Microbiology, University Hospital of Antwerp, Edegem, Belgium and Department of Critical Care Medicine, Oosterschelde Ziekenhuizen Goes, Goes, The Netherlands

* M.D., Intensivist, Department of Critical Care Medicine, University Hospital of Antwerp, University of Antwerp. ([dagger]) M.D., Intensivist, Department of Critical Care Medicine, University Hospital of Antwerp, University of Antwerp and Department of Critical Care Medicine, Oosterschelde Ziekenhuizen Goes. ([double dagger]) Ph.D., Professor, Microbiologist, Department of Microbiology, University Hospital of Antwerp. ([section]) M.D., Microbiologist, Department of Microbiology, University Hospital of Antwerp. ** M.D., Ph.D., Professor, Intensivist, Department of Critical Care Medicine, University Hospital of Antwerp, University of Antwerp.

Address for reprints: Dr P G. Jorens, University Hospital of Antwerp (UZA), Wilrijkstraat 10, B 2650 Edegem, Belgium.
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Article Details
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Title Annotation:Case Reports
Author:Robert, D.; Verbiest, D.; Demey, H.; Ieven, M.; Jansens, H.; Jorens, P.G.
Publication:Anaesthesia and Intensive Care
Article Type:Clinical report
Geographic Code:4EUBL
Date:Mar 1, 2008
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