YALE JOURNAL OF BIOLOGY AND MEDICINE 90 (2017), pp.165-181.
Original Contribution
Clinical Characteristics of Influenza-Associated Pneumonia of Adults: Clinical Features and Factors Contributing to Severity and Mortality Takashi Ishiguro, MD, PhDa,*, Naho Kagiyama, MD, PhDa, Ryuji Uozumi, MSb, Kyuto Odashima, MDa, Yotaro Takaku, MD, PhDa, Kazuyoshi Kurashima, MD, PhDa, Satoshi Morita, PhDb, and Noboru Takayanagi, MD, PhDa a Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Saitama, Japan; bDepartment of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan
Background: Pneumonia is a major complication of influenza that contributes to mortality. Clinical characteristics and factors of influenza virus contributing to the severity and mortality of pneumonia have not been fully elucidated. Objective: The objective was to clarify clinical characteristics and factors contributing to the severity and mortality of influenza-associated pneumonia (flu-p†). Methods: We retrospectively analyzed patients with flu-p. Results: From December 1999 to March 2016, 210 patients with a median age of 69 (range, 17 to 92) years with flu-p based on positive rapid antigen tests, increased antibody titers of paired sera, or positive results of reverse transcription polymerase chain reaction were admitted to our institution. A multivariate analysis found that advanced age (≥ 65 years), pneumonia subtypes (unclassified), diabetes mellitus, and acute kidney injury complicated with flu-p were independent factors associated with disease severity, whereas pneumonia subtypes (mixed viral and bacterial pneumonia and unclassified), healthcare-associated pneumonia, acute kidney injury complicated with flu-p, and severity on admission (severe) were independent factors associated with non-survival. Conclusion: The clinical characteristics of flu-p are varied, and the contribution of several factors to the severity and mortality of flu-p suggest their importance in either preventing flu-p or managing flu-p after it develops. INTRODUCTION The influenza pandemic in 2009 had a strong effect on clinical practice, and pneumonia is the leading complication of influenza virus infection [1]. Globally, influenza causes significant morbidity and mortality that re-
spectively result in severe illness in 3 to 5 million people and death in up to 500,000 during epidemic years [2]. Of the complications of influenza, pneumonia is the most serious. The excess morbidity and mortality associated with influenza epidemics are generally reflected by high rates of pneumonia and hospitalization associated with
*To whom all correspondence should be addressed: Takashi Ishiguro, MD, PhD, Saitama Cardiovascular and Respiratory Center, 1696 Itai, Kumagaya City, Saitama Pref. 360-0105, Japan. TEL: +81-48-536-9900; FAX: +81-48-536-9920, E-mail: ishiguro.
[email protected]. †Abbreviations: flu-p, influenza-associated pneumonia; HCAP, healthcare-associated pneumonia; CAP, community-acquired pneumonia; NI, neuraminidase inhibitors; PS, performance status; RT-PCR, reverse transcription polymerase chain reaction; COPD, chronic obstructive pulmonary disease. Keywords: influenza associated pneumonia, severity, prognosis, prognostic factor, outcome Author contributions: T. I. is the guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article. N. T., N. K., Y. T., and K. K. aggregated the data, created the tables, and helped draft the discussion of the manuscript. R. U. and S. M. performed the statistical analysis. Copyright © 2017
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Table 1. Patient Characteristics. Characteristic
Total
Primary viral pneumonia
Mixed viral and bacterial pneumonia
Secondary pneumonia
Unclassified
N = 76
N = 71
N = 34
N = 29
Age (years)
66.7 ± 15.63
66.7 ± 15.91
67.4 ± 14.44
61.7 ± 16.91
71.0 ± 15.34
0.118
Male sex
151 (71.9%)
59 (77.6%)
55 (77.5%)
22 (64.7%)
15 (51.7%)
0.029
Smoking history
134 (63.8%)
52 (68.4%)
46 (64.8%)
22 (64.7%)
14 (48.3%)
0.287
Yes
7 (3.3%)
3 (3.9%)
2 (2.8%)
1 (2.9%)
1 (3.4%)
0.555
No
201 (95.7%)
73 (96.1%)
69 (97.2%)
32 (94.1%)
27 (93.1%)
Unknown
2 (1.0%)
0 (0.0%)
0 (0.0%)
1 (2.9%)
1 (3.4%)
Yes
31 (14.8%)
10 (13.2%)
10 (14.1%)
7 (20.6%)
4 (13.8%)
No
129 (61.4%)
57 (75.0%)
44 (62.0%)
15 (44.1%)
13 (44.8%)
Unknown
50 (23.8%)
9 (11.8%)
17 (23.9%)
12 (35.3%)
12 (41.4%)
CAP/HCAP
64 (30.5%)
25 (32.9%)
23 (32.4%)
6 (17.6%)
10 (34.5%)
0.363
pH1N1
48 (22.9%)
19 (25.0%)
21 (29.6%)
6 (17.6%)
2 (6.9%)
0.004
H3N2
8 (3.8%)
1 (1.3%)
2 (2.8%)
3 (8.8%)
2 (6.9%)
sH1N1
23 (11.0%)
16 (21.1%)
5 (7.0%)
2 (5.9%)
0 (0.0%)
Undifferentiated
85 (40.5%)
27 (35.5%)
25 (35.2%)
18 (52.9%)
15 (51.7%)
B
46 (21.9%)
13 (17.1%)
18 (25.4%)
5 (14.7%)
10 (34.5%)
Chronic pulmonary disease
95 (45.2%)
31 (40.8%)
34 (47.9%)
14 (41.2%)
16 (55.2%)
0.534
Chronic obstructive pulmonary disease
41 (19.5%)
11 (14.5%)
22 (31.0%)
4 (11.8%)
4 (13.8%)
0.028
Asthma
20 (9.5%)
11 (14.5%)
2 (2.8%)
4 (11.8%)
3 (10.3%)
0.107
Bronchiectasis
10 (4.8%)
0 (0.0%)
8 (11.3%)
0 (0.0%)
2 (6.9%)
0.006
Nontuberculous mycobacteriosis
4 (1.9%)
0 (0.0%)
3 (4.2%)
0 (0.0%)
1 (3.4%)
0.208
Old pulmonary tuberculosis
14 (6.7%)
5 (6.6%)
1 (1.4%)
5 (14.7%)
3 (10.3%)
0.062
Chronic pulmonary aspergillosis
2 (1.0%)
0 (0.0%)
0 (0.0%)
1 (2.9%)
1 (3.4%)
0.191
Interstitial pneumonia
15 (7.1%)
6 (7.9%)
4 (5.6%)
2 (5.9%)
3 (10.3%)
0.840
Post lung cancer operation
4 (1.9%)
3 (3.9%)
0 (0.0%)
0 (0.0%)
1 (3.4%)
0.250
Hypertension
26 (12.4%)
7 (9.2%)
10 (14.1%)
4 (11.8%)
5 (17.2%)
0.674
Chronic cardiac disease
30 (14.3%)
15 (19.7%)
6 (8.5%)
5 (14.7%)
4 (13.8%)
0.281
Congestive heart failure
12 (5.7%)
5 (6.6%)
3 (4.2%)
1 (2.9%)
3 (10.3%)
0.565
Ischemic heart disease
14 (6.7%)
7 (9.2%)
4 (5.6%)
3 (8.8%)
0 (0.0%)
0.356
Valvular heart disease
5 (2.4%)
4 (5.3%)
0 (0.0%)
1 (2.9%)
0 (0.0%)
0.158
P-value
Vaccination history 23-valent polysaccharide vaccine (within 5 years)
Influenza vaccine (within one year) 0.012
Viral subtypes
Comorbidity
Ishiguro et al.: Influenza-associated pneumonia and prognosis
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Table 1, cont’d. Patient Characteristics. Arrhythmia
6 (2.9%)
3 (3.9%)
1 (1.4%)
1 (2.9%)
1 (3.4%)
0.825
Diabetes mellitus
27 (12.9%)
9 (11.8%)
13 (18.3%)
2 (5.9%)
3 (10.3%)
0.309
Post surgery of upper digestive system
4 (1.9%)
2 (2.6%)
2 (2.8%)
0 (0.0%)
0 (0.0%)
0.625
Chronic liver disease
7 (3.3%)
2 (2.6%)
2 (2.8%)
2 (5.9%)
1 (3.4%)
0.835
Connective tissue disease
9 (4.3%)
3 (3.9%)
4 (5.6%)
2 (5.9%)
0 (0.0%)
0.605
Psychiatric disease
6 (2.9%)
2 (2.6%)
3 (4.2%)
0 (0.0%)
1 (3.4%)
0.676
Malignancy
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
-
Alcoholism
2 (1.0%)
0 (0.0%)
2 (2.8%)
0 (0.0%)
0 (0.0%)
0.267
Steroid or immunosuppressant use
20 (9.5%)
6 (7.9%)
8 (11.3%)
5 (14.7%)
1 (3.4%)
0.426
Chronic kidney disease
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
-
Neurological disorders
17 (8.1%)
5 (6.6%)
8 (11.3%)
0 (0.0%)
4 (13.8%)
0.141
WBC
11202.4 ± 6339.69
10382.9 ± 5636.04
12069.0 ± 7507.49
11985.3 ± 5005.10
10310.3 ± 6260.33
0.298
AST
57.8 ± 169.89
77.8 ± 273.60
53.2 ± 61.10
38.6 ± 39.35
39.1 ± 30.75
0.599
LDH
334.1 ± 406.36
397.0 ± 641.92
312.9 ± 155.89
285.9 ± 174.42
277.0 ± 95.35
0.384
BUN
21.5 ± 17.29
18.7 ± 11.03
26.3 ± 24.82
15.8 ± 6.93
22.9 ± 11.76
0.015
Cre
0.9 ± 0.44
0.9 ± 0.32
1.0 ± 0.61
0.7 ± 0.24
0.9 ± 0.33
0.030
CRP
14.0 ± 10.33
11.8 ± 8.24
18.0 ± 12.14
14.8 ± 10.09
9.4 ± 7.06
BMI≥18
77
15 (19.5%)
Reference
Unknown
2
0 (0.0%)
No
201
54 (26.9%)
Yes
7
2 (28.6%)
Unknown
50
No
129
Body mass index
Reference
Vaccination history 23-valent pneumococcal polysaccharide vaccination within 5 years
Influenza vaccination within one year
0.92 (0.17, 4.87)
0.920
11 (22.0%)
0.81 (0.28, 2.31)
0.695
37 (28.7%)
1.16 (0.47, 2.82)
0.749
Yes
31
8 (25.8%)
Reference
Prior antibiotic treatment
No
142
43 (30.3%)
1.84 (0.91, 3.71)
0.090
Neuraminidase inhibitors by local physicians
No
186
52 (28.0%)
1.94 (0.41, 9.16)
0.402
≥48 h
12
2 (16.7%)
1.00 (0.12, 8.56)
1.000
