Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (30)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oliveira, E. C.
Right arrow Articles by Colice, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oliveira, E. C.
Right arrow Articles by Colice, G.
(Chest. 2001;119:1717-1723.)
© 2001 American College of Chest Physicians

Influenza Pneumonia*

A Descriptive Study

Eduardo C. Oliveira, MD; Paul E. Marik, MD, FCCP and Gene Colice, MD, FCCP

* From the Division of Critical Care Medicine, Washington Hospital Center, Washington, DC.

Correspondence to: Paul Marik, MD, FCCP, Critical Care Medicine, Mercy Hospital of Pittsburgh, 1400 Locust St, Pittsburgh, PA 15219-5166; e-mail: pmarik{at}mercy.pmhs.org


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objective: To describe the clinical features and complications of patients hospitalized with influenza during the 1999–2000 influenza season.

Methods: We reviewed all cases of patients with influenza admitted to a large metropolitan referral hospital during the 1999–2000 season.

Results: Thirty-five adult patients (15 men and 20 women) tested positive for influenza A by direct enzyme immunoassay. A fourfold to sevenfold increase in the number of influenza cases was observed over previous years. Most patients had serious comorbid illnesses (88%), such as diabetes and chronic respiratory and heart disease. Seventeen patients developed pneumonia; these patients tended to be older (mean ± SD, 63 ± 13 years vs 51 ± 19 years, respectively; p = 0.04) and had a higher incidence of chronic lung disease (41% vs 6%, respectively; p = 0.02) than the patients without pneumonia. Shortness of breath was the only symptom that distinguished patients with pneumonia from those with an upper respiratory tract illness alone. Antiviral treatment was begun 4 ± 3 days from initiation of symptoms in patients with pneumonia and consisted of oseltamivir (35.2%), rimantadine (5.8%), or a combination of both (17.6%). Respiratory and/or blood culture results were positive in five patients (29%), Staphylococcus aureus was isolated in five patients, and Streptococcus pneumoniae was isolated in one patient. Ten of the patients with pneumonia (58.8%) were admitted to the ICU, and 5 patients (29%) died. The length of ICU stay and mechanical ventilation were 28 ± 26 days and 21.5 ± 20.5 days, respectively. Death in most pneumonia patients was attributed to respiratory failure.

Conclusion: The recognized number of hospital admissions for influenza increased fourfold to sevenfold over previous years, most likely due to the implementation of rapid diagnostic tests for influenza. Patients with signs and symptoms of influenza and shortness of breath should undergo chest radiography. Hospitalization of patients with influenza pneumonia occurred in both previously healthy and immunocompromised patients and had a high mortality. S aureus was the most common bacterial isolate in patients with influenza pneumonia. Empiric antibiotics with staphylococcal activity should be used pending culture results in patients with influenza pneumonia. The effectiveness of oseltamivir and rimantadine in treating patients with influenza pneumonia remains to be determined.

Key Words: influenza • pneumonia • mechanical ventilation


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Influenza A virus accounts for significant morbidity and mortality despite major efforts in prevention and treatment.1 Thousands of deaths occur and billions of dollars are spent each year for influenza-related illnesses.1 2 3 Morbidity and mortality have largely been attributed to the development of respiratory complications, and management has mainly consisted of supportive care and treatment of superimposed bacterial infections.1 2 3 The difficulty in confirming the diagnosis of influenza A infection in patients with community-acquired pneumonia has limited the use of antiviral agents in these patients. Recently, rapid diagnostic tests have become available for the diagnosis of influenza, and a new class of therapeutic agents (neuraminidase inhibitors) has been approved for use in patients with influenza. The impact of these advances on the recognition and treatment of influenza pneumonia is unclear. We therefore reviewed all cases of patients with influenza admitted to a large metropolitan referral hospital in Washington, DC from December 1999 to February 2000. Clinical course, treatment, and associated morbidity and mortality are described in detail on cases complicated by pneumonia. The results are compared to previous studies.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Subjects
One hundred thirty-nine patients between the ages of 25 years and 92 years admitted to Washington Hospital Center, Washington, DC from December 1999 to February 2000 with upper or lower respiratory tract symptoms were tested for influenza A. The hospital charts of the patients with positive findings for influenza A were reviewed. Influenza pneumonia was defined by a new pulmonary infiltrate on the chest radiograph. Influenza upper respiratory tract illness (URI) was defined by fever, chills, nasal discharge, and cough with or without sputum, but with a clear chest radiograph. In addition, the hospital records of all medical admissions from December to February for the last 5 years were reviewed to identify patients with diagnosed influenza. The number of cases of influenza patients admitted to the hospital during each influenza "season" was recorded.

Microbiological Methods
Either a direct enzyme immunoassay (Directigen; BD Diagnostic Systems; Sparks, MD) or an endogenous viral-encoded enzyme assay (ZstatFlu; ZymeTx; Oklahoma City, OK) was used to test for influenza A. The sensitivities and specificities for these tests have been reported to range from 65 to 96% and 90 to 99%, respectively.4 5 6 7 8 Samples from suspected patients were obtained by a nasopharyngeal wash as recommended by the test manufacturer. Bronchial washings were also tested in selected cases. The first five tests performed had culture confirmation by centrifugation-enhanced rapid viral culture,9 which confirmed the test results in all five cases (three positive and two negative results). Tracheal aspirates and blind protected specimen brush (PSB) sampling with quantitative bacterial culture were performed in intubated patients. A quantitative threshold of 500 cfu/mL was used for the PSB. Bronchoscopy with BAL was performed as clinically indicated. A quantitative threshold of 5,000 cfu/mL was used for the BAL specimens. Complicating bacterial pneumonia was diagnosed in patients with quantitative cultures above these predefined thresholds.

Data Collection and Analysis
The patients’ demographic and clinical data were recorded in an electronic spreadsheet (Excel 2000; Microsoft; Redmond, WA). At the end of the data collection, summary statistics were compiled to allow a description of the patients with and without pneumonia. Statistical analysis was done using NCSS 2000 (NCSS Statistical Software; Kaysville, UT). {chi}2 analysis with Fisher’s Exact Test (when appropriate) was used to compare categorical data. Continuous data were compared using Student’s t test. Unless otherwise stated, all data are expressed as mean (with range) or percentages, with statistical significance declared for probability values of <= 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
During each of the past five influenza seasons, influenza was diagnosed in five to eight patients. Thirty-five of the 139 patients (25%) tested between December 1999 and February 2000 had positive findings for influenza A. Of the 35 patients, 17 patients (48.5%) developed influenza pneumonia and the other 18 patients had influenza URI. Demographics and baseline characteristics of the influenza patients with and without pneumonia are shown in Table 1 . The male/female ratio was 1:1.3 (15 men and 20 women); most patients were black (29 patients; 82.9%). The mean age was 57 years (range, 25 to 94 years). The characteristics of the patients who developed influenza pneumonia were similar to those with URI except they tended to be older (63 ± 13 years vs 51 ± 19 years, respectively; p = 0.04). Serious comorbid illnesses, such as heart disease, diabetes, and renal disease, and organ transplantation were found frequently in both the pneumonia group and the URI group; however, a history of chronic respiratory disease was more common in the pneumonia group (41% vs 6%, respectively; p = 0.02). AIDS, lymphoma, smoking, and alcohol abuse did not appear to be important factors in this study. The mean durations of symptoms prior to hospital admission for the pneumonia group and the URI group were 2 days (range, 1 to 7 days) and 3.3 days (range, 1 to 10 days), respectively (not significant). Although small, this difference suggests that patients with pneumonia were more symptomatic, as seen by their more frequent complaints of shortness of breath (82.3% vs 17%, respectively; p = 0.002), and sought medical attention earlier in the disease course. Other complaints, such as cough (82%), fever or chills (80%), and myalgias (31%), were equally seen in both groups. Fever was the most frequent physical finding (mean hospital admission temperature of 38.3°C). No consistent laboratory abnormalities were noted except for a high serum lactate dehydrogenase level (mean, 304 U/L; range, 130 to 711 U/L). Influenza vaccination data were available in 24 of the 35 patients (68.6%) included in this study, 14 in the URI group and 10 in the pneumonia group. Seven of the 14 patients (50%) in the URI group and 2 of the 10 patients (20%) in the pneumonia group had been vaccinated in the fall of 1999. Vaccination data were available in two of the five patients who died, and both had not been vaccinated. High morbidity was associated with both vaccinated and unvaccinated patients in whom pneumonia developed. No significant difference was observed in length of stay (LOS) between vaccinated and unvaccinated patients (mean, 4.6 days and 4.7 days, respectively); however, only two of the nine vaccinated patients (22.2%) developed pneumonia.


View this table:
[in this window]
[in a new window]

  		Table 1.. Demographic and Baseline Clinical Characteristics*

 
The hospital features of the patients with influenza pneumonia are presented in Table 2 . The number of days (mean ± SD) between the onset of symptoms and start of antiviral treatment was similar between the patients who died (4.5 ± 2.5 days) and survived (4.1 ± 3.0 days). Antiviral treatment was administered to 14 of the 17 patients (82%) with pneumonia, and consisted of oseltamivir (35%), rimantadine (6%), or a combination of both (41%). Antiviral medications were well tolerated and administered for a total of 5 days in most patients. Bilateral diffuse interstitial/alveolar infiltrates were seen as the most common radiographic abnormality (nine patients; 52%), followed by right lower lobe consolidation in six patients (35%). Blood cultures were obtained from all 17 patients; 4 of the ICU patients had positive culture findings (Staphylococcus aureus in 3 patients and Streptococcus pneumoniae in 1 patient). Respiratory tract cultures were obtained from all ICU patients (n = 10; Table 2 ). Respiratory tract culture findings were positive in five of these patients, four of whom were also bacteremic. S aureus was isolated in five patients, and S pneumoniae was isolated in one patient. Of the five patients with positive culture findings for S aureus, four patients (80%) had methicillin-resistant strains.


View this table:
[in this window]
[in a new window]

  		Table 2.. Characteristics of Patients With Pneumonia*

 
Of the 17 patients with influenza pneumoniae, 10 patients (58.8%) were admitted to the ICU; 5 of these patients died (Table 2) . Overall, there was a 29.4% mortality rate. Patients who died had similar APACHE (acute physiology and chronic health evaluation) II scores as survivors (18.5 ± 8.5 vs 16.5 ± 14.5, respectively). Of the five patients who died, four patients had bilateral infiltrates observed on their chest radiographs. Although most patients who died had serious comorbid illnesses (four patients), of the two patients with no comorbid illness who developed pneumonia, one patient died. Ten patients (58.8%) received mechanical ventilation for a mean of 20.4 days (range, 1 to 42 days), and tracheostomy was performed in four patients (23%) due to failure to wean. The lowest PaO2/fraction of inspired oxygen was 230 (90 to 280) in the survivors, compared to 91 (54 to 185) in the nonsurvivors (p = 0.005). The number of ventilator days was 18.4 (range, 10 to 42 days) in the survivors, compared to 22.4 days (range, 1 to 39 days) in the nonsurvivors (not significant). All patients were treated with broad-spectrum antibiotics from day 1. The mean hospital LOS was 19.1 days (range, 2 to 4 days), and death was attributed to respiratory failure and/or multiple-organ system failure (MOSF). No deaths were recorded in the URI group. Levofloxacin, vancomycin, and cephalosporins were the most commonly administered antibiotics. The mean antibiotic days (the number of antibiotic medications times the number of days of treatment) was 17.4 days (range, 0 to 42 days), and levofloxacin was the most commonly administered antibiotic for empiric coverage (14 patients; 82%).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this article, we describe our experience with influenza A virus respiratory complications during the 1999–2000 influenza season. An important observations in this study was the increased (fourfold to seven fold) recognition of influenza A infection. This is likely due to the availability of the recently marketed influenza antigen tests that allow for the rapid diagnosis of influenza, and the increased public awareness of influenza due to the intense media coverage of this subject. Other findings of this study include the association of influenza pneumonia with serious comorbid illnesses and the development of complicating S aureus bacterial pneumonias. Despite optimal medical treatment, the mortality of influenza pneumonia was high and similar to that of the 1919 outbreak (Table 3 ). Due to the small sample size, the uncontrolled nature of our study, and the delay in initiating specific antiviral therapy, the impact of the neuraminidase inhibitors on the outcome of influenza pneumonia could not be determined.


View this table:
[in this window]
[in a new window]

  		Table 3.. Comparison of Selected Published Series on Influenza Pneumonia*

 
Official reports for influenza activity in the United States in 1999–2000 revealed that most cases (99.7%) were due to influenza A (H3N2) viruses. According to the Centers for Disease Control and Prevention, the percentage of physician visits for an influenza-like illness during the 1999–2000 season was similar to that of the previous 5 years.1 However, despite the release of the neuraminidase inhibitors, the peak mortality due to pneumonia and influenza during the 1999–2000 season was 2% higher than the peak during the last two seasons (9.1% vs 11.2%, respectively).1 In our institution, the recognized number of hospital admissions for influenza increased fourfold to sevenfold over previous years, much beyond what would be expected considering official reports for influenza activity in the United States. We believe that the increase in the number of influenza cases seen in our institution was due to improvements in diagnosis with the availability of rapid diagnostic techniques. In addition, it is likely that increased public awareness of influenza due to the intense media coverage during the 1999–2000 season may have impacted on the number of patients tested for influenza. It is unlikely that false-positive results were included in our series since specificities for the rapid viral tests are high (range, 90 to 99%).5 6 7 8 9 It is more likely that the total number of influenza cases was underestimated, because sensitivities can be as low as 65% (range, 65 to 96%). In our study, rapid diagnosis was helpful in the institution of antiviral treatment and control measures, such as respiratory isolation. The latter is of major importance since intrahospital outbreaks of influenza have been reported.10

Characteristics of patients in this series are similar to those reported in previous studies (Table 3) .11 12 13 14 15 16 17 18 19 In almost all series, the majority of the patients who developed pneumonia were old and had severe comorbid conditions, such as heart disease, COPD, renal disease, diabetes, and immunosuppression.11 12 13 14 15 16 17 18 19 20 However, serious influenza pneumonia has also occurred in previously healthy patients. In this series, 2 of the 17 patients (11.7%) who developed influenza pneumonia had no reported comorbid illness. One of those patients was an unvaccinated 33-year-old woman who developed an initial right lower lobe infiltrate followed by superimposed bacterial infections, respiratory failure, and death. Shortness of breath was the only symptom that distinguished patients with pneumonia from those with a URI alone. Consequently, patients with features of influenza and shortness of breath should undergo chest radiography to exclude pneumonia. As seen in Table 3 , as well as several other autopsy series,11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 S pneumoniae (29 to 48%) and S aureus (7 to 40%) have been the most common bacterial isolates causing superimposed infections in patients with influenza pneumonia. Haemophilus influenzae,16 24 Pseudomonas aeruginosa,15 and herpes virus26 are less commonly implicated. In this series, S aureus was the most common bacterial pathogen isolated. The high prevalence of methicillin-resistant S aureus (MRSA) was rather surprising. However, this finding may be related to the fact that these patients had serious comorbid diseases and/or it may reflect local resistance patterns. Based on these findings, antistaphylococcal antibiotic therapy (with MRSA activity in MRSA endemic regions) should be initiated in hospitalized cases of influenza pneumonia while culture and sensitivity data are pending.

The theories proposed for the high incidence of superimposed bacterial infections in influenza pneumonia emphasize the synergistic effects of viral and bacterial pathogens to produce lung injury. Hers and Mulder27 suggested that influenza virus can directly damage the respiratory epithelium, allowing free access to invading bacteria. It has also been demonstrated that some Staphylococcus and Streptococcus strains may increase viral replication and pathogenicity, contributing to influenza viral pneumonia.28 29 The findings of premortem and postmortem lung specimens also suggest a combined role for both bacterial and viral pathogens, although lesions compatible with an uncomplicated viral pneumonia have been widely described.27 30 31 32 33

Mortality associated with influenza pneumonia is high. The mortality rate in this series of 29.4% is similar to rates reported in other series over the past 100 years. There was also significant morbidity associated with influenza pneumonia, as seen by the number of ventilator days and the hospital LOS (Table 3) . The persistently high morbidity and mortality associated with influenza pneumonia, despite advances in diagnosis and treatment, can be partially explained by the increased number of people at risk for the development of influenza respiratory complications (aging, etc). Although vaccination among elderly and other high-risk groups has been shown to reduce hospitalization, pneumonia, and death,34 35 36 the benefits of vaccination are not universal. In this study, none of the vaccinated patients died, but significant morbidity was seen in two vaccinated patients in whom pneumonia developed. The role of specific influenza antiviral agents in reducing mortality is uncertain. In the past, treatment has been limited to amantadine and rimantadine,37 but more recently, inhaled zanamivir and oral oseltamivir, two new neuraminidase inhibitors, have been approved for the treatment of mild influenza infection.38 39 40 41 To date and to our knowledge, the efficacy of these new antiviral agents in patients with influenza pneumonia is unknown and no information is available on their bioavailability in critically ill patients. In this study, oral oseltamivir and rimantadine were the preferred antiviral medications due to easier administration in critically ill patients and in patients receiving mechanical ventilation. Due to the small number of patients and the uncontrolled nature of our study, we were not able to assess the efficacy of treatment with oseltamivir. Furthermore, there was a delay (on average 4 days) between the onset of symptoms and the initiation of antiviral therapy in the patients with influenza pneumonia. The neuraminidase inhibitors are approved for use within the first 48 h of the onset of symptoms. The rapid identification and treatment (within 48 h) of patients with an influenza-like illness who are at risk of developing influenza pneumonia (the elderly and those with comorbid diseases, especially COPD) with the new neuraminidase inhibitors may reduce the incidence and/or severity of influenza pneumonia.

In summary, we describe our experience with influenza A respiratory complications in the 1999–2000 season. The recognized number of hospital admissions for influenza to our hospital increased fourfold to sevenfold over previous years, likely due to the implementation of rapid diagnostic tests and heightened awareness of the disease. S aureus was the most common bacterial isolate associated with influenza pneumonia, and appropriate coverage for this organism should be given to patients hospitalized with influenza pneumonia. Hospitalization of patients with influenza with pneumonia occurred in both previously healthy and immunocompromised patients and had a high morbidity and mortality. The effectiveness of specific antiviral agents in treating influenza pneumonia remains to be determined.


   Footnotes
 
Abbreviations: LOS = length of stay; MOSF = multiple-organ system failure; MRSA = methicillin-resistant Staphylococcus aureus; PSB = protected specimen brush; URI = upper respiratory tract illness

Received for publication September 5, 2000. Accepted for publication January 3, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. CDC update: influenza activity–United States, 1999–2000 season. MMWR Morb Mortal Wkly Rep 2000; 49:173–177
  2. Neuzil, MK, Reed, GW, Mitchel, FE, et al (1999) Influenza-associated morbidity and mortality in young and middle-aged women. JAMA 281,901-907[Abstract/Free Full Text]
  3. Barker, WH, Mullooly, JP (1992) Pneumonia and influenza during epidemics. Arch Intern Med 142,85-89
  4. Leonardi, GP, Leib, H, Birkhead, GS, et al (1994) Comparison of rapid detection methods for influenza A virus and their value in health-care management of institutionalized geriatric patients. J Clin Microbiol 32,70-74[Abstract/Free Full Text]
  5. Doller, G, Schuy, W, Tjhen, KY, et al (1992) Direct detection of influenza virus antigen in nasopharyngeal specimens by direct enzyme immunoassay in comparison with quantitating virus shedding. J Clin Microbiol 30,886-889
  6. Ryan-Poirier, KA, Katz, JM, Webster, RG, et al (1992) Application of Directigen Flu-A for the detection of influenza A virus in human and nonhuman specimens. J Clin Microbiol 30,1072-1075[Abstract/Free Full Text]
  7. Kaiser, L, Brioles, MS, Hayden, FG (1999) Performance of virus isolation and Directigen Flu-A to detect influenza A virus in experimental human infection. J Clin Virol 14,191-197[CrossRef][ISI][Medline]
  8. Carrat, F, Tachet, A, Housset, B, et al (1997) Influenza and influenza-like illness in general practice: drawing lessons for surveillance from a pilot study in Paris, France. Br J Gen Pract 47,217-220[ISI][Medline]
  9. Waris, M, Ziegler, T, Kivivirta, M, et al (1999) Rapid detection of respiratory syncytial virus and influenza A virus in cell cultures by immunoperoxidase staining with monoclonal antibodies. J Clin Microbiol 28,1159-1162
  10. Blumenfeld, HL, Kilbourne, ED, Louria, DB, et al (1959) Studies on influenza in the pandemic of 1957–1958: I. An epidemiologic, clinical and serologic investigation of an intra-hospital epidemic, with a note on vaccination efficacy. J Clin Invest 38,199-212
  11. Chickering, HT, Park, JH (1919) Staphylococcus aureus pneumonia. JAMA 72,617-626
  12. Kilbourne, ED (1959) Studies on influenza in the pandemic of 1957–1958: III. Isolation of influenza A (Asian strain) viruses from influenza patients with pulmonary complications; details of virus isolation and characterization of isolates with quantitative comparison of isolation methods. J Clin Invest 38,266-273
  13. Louria, DB, Blummenfeld, HL, Ellis, JT, et al (1959) Studies in the pandemic of 1957–1958: II. Pulmonary complications of influenza. J Clin Invest 38,213-265
  14. Petersdorf, RG, Fusco, JJ, Harter, DH, et al (1959) Pulmonary infections complicating Asian influenza. Arch Intern Med 103,262-272
  15. Lindsay, MI, Hermann, EC, Morrow, GW, et al (1970) Hong Kong influenza: clinical, microbiologic, and pathologic features in 127 cases. JAMA 214,1825-1832[CrossRef][Medline]
  16. Schwarzmann, SW, Adler, JL, Sullivan, RJ, et al (1971) Bacterial pneumonia during the Hong Kong influenza epidemic of 1968–1969. Arch Intern Med 127,1037-1041[CrossRef][ISI][Medline]
  17. Ljungman, P, Andersson, J, Aschan, J, et al (1993) Influenza A in immunocompromised patients. Clin Infect Dis 17,244-247[ISI][Medline]
  18. Yousuf, HM, Englund, J, Couch, R, et al (1997) Influenza among hospitalized adults with leukemia. Clin Infect Dis 24,1095-1099[ISI][Medline]
  19. Yuen, KY, Chan, PKS, Tsang, DNC, et al (1998) Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1. Lancet 351,467-471[CrossRef][ISI][Medline]
  20. Martin, CM, Kunin, CM, Gottlieb, LS, et al (1959) Asian influenza A in Boston, 1957–1958: II. Severe staphylococcal pneumonia complicating influenza. Arch Intern Med 103,532-541
  21. Oseasohn, R, Adelson, L, Kaji, M (1959) Clinicopathologic study of thirty-three fatal cases of Asian influenza. N Engl J Med 269,510-518
  22. Martin, CM, Kunin, CM, Gottlieb, LS, et al (1959) Asian influenza A in Boston, 1957–1958: I. Observation in thirty-two influenza-associated fatal cases. Arch Intern Med 103,515-531
  23. Whimbey, E, Elting, LS, Couch, RB, et al (1994) Influenza A virus infections among hospitalized adult bone marrow transplant patients. Bone Marrow Transplant 13,437-440[ISI][Medline]
  24. Giles, C, Shuttleworth, EM (1957) Post-mortem findings in 46 influenza deaths. Lancet 2,1224-1225
  25. Feldman, PS, Cohan, MA, Hierholzer, WJ (1972) Fatal Hong Kong influenza: a clinical, microbiological and pathological analysis of nine cases. Yale J Biol Med 45,49-63[ISI][Medline]
  26. Klimek, JJ, Lindenberg, LB, Cole, S, et al (1976) Fatal case of influenza pneumonia with suprainfection by multiple bacteria and herpes simplex virus. Am Rev Respir Dis 113,683-688[ISI][Medline]
  27. Hers, JF, Mulder, J (1961) Broad aspects of the pathology and pathogenesis of human influenza. Am Rev Respir Dis 83,84-94
  28. Scheiblauer, H, Reinacher, M, Tashiro, M, et al (1992) Interactions between bacteria and influenza A virus in the development of influenza pneumonia. J Infect Dis 166,783-791[ISI][Medline]
  29. Tashiro, M, Ciborowski, P, Klenk, HD, et al (1987) Role of Staphylococcus protease in the development of influenza pneumonia. Nature 325,536-537[CrossRef][Medline]
  30. Katzenstein, AA (1997) Katzenstein and Askin’s surgical pathology of non-neoplastic lung disease 3rd ed. ,248-260 WB Saunders Company Philadelphia, PA.
  31. Noble, R, Lillington, GA, Kempson, RL (1973) Fatal influenza pneumonia: premortem diagnosis by lung biopsy. Chest 63,644-646[Abstract/Free Full Text]
  32. Yeldandi, AV, Colby, TV (1994) Pathologic features of lung biopsy specimens from influenza pneumonia cases. Hum Pathol 25,47-53[CrossRef][ISI][Medline]
  33. Tamura, H, Aronson, BE (1978) Intranuclear fibrillary inclusions in influenza pneumonia. Arch Pathol Lab Med 102,252-257[ISI][Medline]
  34. Palache, AM (1997) Influenza vaccines: a reappraisal of their use. Drugs 54,841-856[ISI][Medline]
  35. Mullooly, JP, Bennett, MD, Hornbrook, MC, et al (1994) Influenza vaccination programs for elderly persons: cost-effectiveness in a health maintenance organization. Ann Intern Med 121,947-952[Abstract/Free Full Text]
  36. Nichol, KL, Margolis, KL, Wourema, J, et al (1994) The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med 331,778-784[Abstract/Free Full Text]
  37. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999; 46(RR-4):1–28
  38. Neuraminidase inhibitors for the treatment of influenza A and B infections. MMWR Morb Mortal Wkly Rep 1999; 48(RR-6):1–9
  39. Hayden, FG, Atmar, RL, Schilling, M, et al (1999) Use of the selective neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 341,1336-1343[Abstract/Free Full Text]
  40. Hayden, FG, Treanor, JJ, Fritz, RS, et al (1999) Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA 282,1240-1206[Abstract/Free Full Text]
  41. Monto, AS, Fleming, DM, Henry, D, et al (1999) Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza A and B virus infections. J Infect Dis 180,254-261[CrossRef][ISI][Medline]



This article has been cited by other articles:


Home page
 Arch Intern MedHome page
A. R. Falsey, Y. Murata, and E. E. Walsh
Impact of Rapid Diagnosis on Management of Adults Hospitalized With Influenza
Arch Intern Med, February 26, 2007; 167(4): 354 - 360.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
N. Hupert, G. M.L. Bearman, A. I. Mushlin, and M. A. Callahan
Accuracy of Screening for Inhalational Anthrax after a Bioterrorist Attack
Ann Intern Med, September 2, 2003; 139(5_Part_1): 337 - 345.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Roentgenol.Home page
A. Oikonomou, N. L. Muller, and S. Nantel
Radiographic and High-Resolution CT Findings of Influenza Virus Pneumonia in Patients with Hematologic Malignancies
Am. J. Roentgenol., August 1, 2003; 181(2): 507 - 511.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
R. A. Fowler, S. E. Lapinsky, D. Hallett, A. S. Detsky, W. J. Sibbald, A. S. Slutsky, and T. E. Stewart
Critically Ill Patients With Severe Acute Respiratory Syndrome
JAMA, July 16, 2003; 290(3): 367 - 373.
[Abstract] [Full Text] [PDF]

Home page
 J Intensive Care MedHome page
E. C. Oliveira, B. Lee, and G. L. Colice
Influenza in the Intensive Care Unit
J Intensive Care Med, March 1, 2003; 18(2): 80 - 91.
[Abstract] [PDF]

Home page
 ChestHome page
A. L. Gabry, X. Ledoux, M. Mozziconacci, and C. Martin
High-Altitude Pulmonary Edema at Moderate Altitude (< 2,400 m; 7,870 feet): A Series of 52 Patients
Chest, January 1, 2003; 123(1): 49 - 53.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (30)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oliveira, E. C.
Right arrow Articles by Colice, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oliveira, E. C.
Right arrow Articles by Colice, G.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS