Non-specific laboratory test indicators of severity in hospitalized adults with swine influenza (H1N1) pneumonia

Letter to the Editor

Introduction

New York was at the epicenter of the “herald wave” of the swine influenza (H1N1) pandemic in the spring of 2009 [1, 2]. Our hospital, Winthrop-University Hospital (WUH), like other hospitals in the area, were inundated with patients with influenza-like illnesses (ILIs) presenting themselves to our Emergency Department (ED) for testing and clinical evaluation. In the majority of patients, the swine influenza (H1N1) was a mild ILI not severe enough to warrant hospitalization. However, 25 adult patients were ill enough to be admitted with definite/probable swine influenza (H1N1) pneumonia during the “herald wave” of the pandemic.

Methods

The diagnoses of swine influenza (H1N1) was problematic and either made on the basis of laboratory confirmation, i.e., a rapid influenza diagnostic test (RIDTs) and/or a positive RT-PCR for H1N1 [3]. Because of restricted RT-PCR testing by the Health Department in July of 2009, the CDC reclassified cases into one diagnostic category, i.e., probable/definite swine influenza (H1N1) [4]. At Winthrop-University Hospital, probable diagnosis was based on the swine influenza diagnostic triad, i.e., an ILI with a temperature of >102°F, severe myalgias plus three of four otherwise unexplained laboratory abnormalities, i.e., relative lymphopenia, elevated serum transaminases (SGOT/SGPT) or an elevated creatinine phosphokinase (CPK) [5].

Of the 25 hospitalized adults with swine influenza (H1N1) pneumonia, three were considered severe and required ventilatory support; two thirds of the severe cases were immunocompetent adults, one had HIV. Two died from swine influenza (H1N1) pneumonia [6, 7]. None of our patients with swine influenza (H1N1) pneumonia presented with or subsequently developed bacterial pneumonia. Unlike in other studies, bacterial pneumonia was not a severity factor in our experience [8, 9, 10]. The swine influenza diagnostic triad correctly identified swine influenza H1N1 patients from those admitted with mimics of swine influenza (H1N1) pneumonia during the pandemic [11]. Twenty two out of 25 of the remaining patients were classified as non-severe, i.e., not requiring ventilatory support, recovered, and were eventually discharged.

Results

We compared non-specific laboratory tests in our cohort of 25 adult hospitalized patients with probable/definite swine influenza (H1N1) pneumonia to determine if there were non-specific laboratory predictors of clinical severity.

The presence of otherwise unexplained relative lymphopenia were a key determining diagnostic marker for hospitalized adults with swine influenza (H1N1) pneumonia [12]. In addition to relative lymphopenia, other non-specific laboratory tests were included, i.e, leukopenia and thrombocytopenia, and CPK elevations [13]. The degree of abnormality at onset as well as the profoundness and duration of relative lymphopenia, thrombocytopenia, and CPK elevations were also compared.

In our patients, we found the degree and duration of relative lymphopenia and thrombocytopenia, while key diagnostic markers, did not predict clinical severity [5, 11, 12]. Very high CPKs, i.e., with rhabdomyolysis, also did not predict clinical severity or adversely affect outcomes (Table 1).
Table 1

Swine influenza (H1N1) in hospitalized adults: non-specific laboratory test predictors of severity

Patient age/gender

Leukopenia (initial) (WBC ≤3.9 K/uL)

Relative Lymphopenia (initial) (≤21%)

Relative Lymphopenia (duration) (≤21%)

Relative Lymphopenia (nadir) (≤21%)

Thrombo-cytopenia duration (initial) (≤160 K/uL)

Thrombo- cytopenia duration (nadir) (≤160 K/uL)

CPK elevation (initial) (≥284 IU/L)

CPK elevation (duration) (≥284 IU/L)

CPK elevation (peak) (≥284 IU/L)

Diagnostic H1N1 tests

A. Severe (requiring ventilatory support)

47 Fa

4.3

11%

9 HDs

HD #5(2%)

2 HDs(138)

HD #2(136)

633

16 HDs

HD #4(2750)

RIDTs: −

VC: NA

FA: −

PCR: − b

40 Fa

3.0

3%

15 HDs

HD #6(1%)

25 HDs(132)

HD #22(56)

2276

9 HDs

HD # 1(2276)

RIDTs: –

VC: −

FA: −

PCR +

81 Ma

10.5

10%

12 HDs

HD # 12(5%)

8 HDs(169)

HD #4(127)

68

1 HDs

HD #16(377)

RIDTs: −

VC: −

FA: −

PCR − b

B. Non−severe (not requiring ventilator support)

45 F

15.3

2%

14 HDs

HD #2(1%)

3 HDs(236)

HD #2(150)

226

NA

NA

RIDTs: +

VC: NA

FA: +

PCR: +

70 F

11.0

38%

1 HD

HD #8(20%)

NA(207)

HD #2(198)

95

NA

HD #4(101)

RIDTs: +

VC: NA

FA –

PCR +

19 M

6.9

10%

NA

NA

NA(177)

NA

NA

NA

NA

RIDTs: −

VC: NA

FA: −

PCR: −

45 F

10.5

2%

3 HDs

HD #1(2%)

NA(200)

HD #3(191)

267

3 HDs

HD #2(519)

RIDTs: NA

VC: NA

FA: NA

PCR: +

76 F

15.1

2%

6 HDs

HD #1(2%)

NA(298)

HD #7(251)

262

NA

NA

RIDTs: −

VC: NA

FA: −

PCR: −

93 M

3.1

20%

12 HDs

HD #6(10%)

18 HDs(133)

HD #2(103)

84

NA

NA

RIDTs: NA

VC: NA

FA: −

PCR: −

80 M

16.9

5%

6 HDs

HD #1(5%)

1 HD(173)

HD #2(150)

58

NA

NA

RIDTs: +

VC: NA

FA: −

PCR: −

44 M

10.8

9%

4 HDs

HD #2(6%)

NA(189)

HD #2(175)

157

NA

NA

RIDTs: −

VC: NA

FA: −

PCR: –

67 M

9.9

8%

4 HDs

HD #1(8%)

1 HD(169)

HD #2(157)

423

2 D

HD #3(426)

RIDTs: −

VC: NA

FA: −

PCR: −

52 M

8.1

4%

5 HDs

HD #4(2%)

6 HDs(123)

HD #2(118)

NA

NA

NA

RIDTs: NA

VC: −

FA: −

PCR: NA

47 F

4.3

11%

9 HDs

HD #5(2%)

2 HDs(138)

HD #2(136)

633

16 D

HD #4(2750)

RIDTs: −

VC: NA

FA: −

PCR: −

71 M

8.1

14%

5 HDs

HD #3(12%)

3 HDs(151)

HD #2(136)

1274

5 D

HD #4(1826)

RIDTs: −

VC: NA

FA: −

PCR: −

34 F

1.4

76%

5 HDs

HD #15(10%)

18 HDs(112)

HD #8(46)

NA

NA

NA

RIDTs: −

VC: NA

FA: −

PCR: −

27 M

2.6

32%

NA

HD #2(30%)

3 HDs(104)

HD #1(104)

4033

4 D

HD #2(5356)

RIDTs: −

VC: NA

FA: −

PCR: −

72 M

17.6

3%

5 HDs

HD #1(3%)

NA(225)

HD #3(185)

NA

NA

NA

RIDTs: −

VC: NA

FA: −

PCR:

77 M

13.3

5%

22 HDs

HD #1(5%)

7 HDs(132)

HD #1(132)

441

1 D

HD #7(441)

RIDTs: −

VC: NA

FA: −

PCR: −

85 F

19.7

3%

20 HDs

HD #11(2%)

NA(282)

HD #2(254)

122

1 D

HD #4(335)

RIDTs: −

VC: −

FA: +

PCR: NA

44 M

8.2

15%

3 HDs

HD #1(15%)

NA(269)

HD #2(224)

124

NA

NA

RIDTs: −

VC: NA

FA: −

PCR: −

35 F

11.7

29%

NA

HD #12(9%)

NA(291)

HD #3(260)

270

1 D

HD #3(313)

RIDTs: −

VC: NA

FA: +

PCR: +

17 M

25.5

17%

3 HDs

HD #2(11%)

NA(210)

HD #3(157)

145

NA

NA

RIDTs: −

VC: NA

FA: −

PCR: −

34 M

2.4

26%

NA

NA

1 HD(159)

HD #1(159)

259

NA

NA

RIDTs: NA

VC: −

FA: −

PCR: NA

89 F

4.9

5%

5 HDs

HD #1(5%)

9 HD(180)

HD #9(142)

104

NA

NA

RIDTs: +

VC: NA

FA: +

PCR: +

Values in bold are abnormal

F female, M male, D days, HD hospital day, CPK creatinine phosphokinase, FA viral fluorescent antibody panel (influenza A, influenza B, parainfluenza, adenovirus, RSV, metapneumoviruses), RIDTs rapid influenza diagnostic tests, VC respiratory viral culture (influenza A, influenza B, parainfluenza, adenovirus, RSV, metapneumoviruses), PCR polymerase chain reaction for H1N1, NA not applicable

aVentilated patients

bH1N1 pneumonia at autopsy

In human seasonal influenza A, leukopenia is an important severity marker [13, 14, 15] (Tables 2 and 3).
Table 2

Swine influenza (H1N1) in hospitalized adults: summary of non-specific laboratory test predictors of severity

4/25 patients

25/25 patients

16/25 patients

11/25 patients

% Leukopenia (WBC ≤3.9 K/uL)

% Relative Lymphopenia (L ≤ 21%)

% Thrombo-cytopenia (P ≤ 160 K/uL)

% CPK elevation (CPK ≥284 IU/L)

16%

10%a

64%

44%

Leukopenia (mean) (WBC ≤3.9 K/uL)

Relative Lymphopenia (mean) (L ≤ 21%)

Thrombocytopenia (mean) (P ≤ 160 K/uL)

CPK elevation (mean) (CPK ≥284 IU/L)

2.5

9%

123

1,579

# Days with Leukopenia (mean) (WBC ≤3.9 K/uL)

# Days with relative Lymphopenia (mean) (L ≤ 21%)

# Days with Thrombocytopenia (mean) (P ≤ 160 K/uL)

# Days with CPK elevation (mean) (CPK ≥284 IU/L)

12 days

8 days

7 days

5 days

Lowest Leukopenia day # (mean)

Lowest relative lymphopenia day # (mean)

Lowest Thrombocytopenia day # (mean)

Highest CPK elevation day # (mean)

Day # 7

Day # 4

Day # 4

Day # 5

aFour of 25 patients did not have relative lymphopenia on admission

Table 3

Swine influenza (H1N1) in hospitalized adults: leukopenia as a predictors of severity

Patient age/gender

Leukopenia (initial) (WBC ≤3.9 K/uL)

Leukopenia duration(days) (WBC ≤3.9 K/uL)

Lowest leukopenia (day/value) (WBC ≤3.9 K/uL)

Relative lymphopenia (L ≤ 21%)

Thrombocytopenia (P ≤ 160 K/uL)

CPK elevation (CPK ≥284 IU/L)

40 Fa

3.0

10 D

Day 9

+

+

+

0.8

93 M

3.1

11 D

Day 9

+

+

na

2.3

34 F

1.4

21 D

Day 6

+

+

na

0.8

27 M

2.6

4 D

Day 2

+

+

+

1.7

F female, M male, D days, na not applicable, L lymphocytes, P platelets, CPK creatinine phosphokinase

1/25 with fatal outcome; 3/25 with good outcomes

aVentilated patients

In our experience with swine influenza (H1N1) pneumonia, leukopenia was present in only 4/25 of patients. In swine influenza (H1N1) pneumonia, when leukopenia when present, thrombocytopenia usually occurred in concert with relative lymphopenia [11]. In our cohort of hospitalized adults with swine influenza (H1N1) pneumonia, leukopenia, when present, occurred on HD #7 (mean) and persisted for 12 days (mean). Unlike human seasonal influenza A, leukopenia was not diagnostic of swine influenza (H1N1) pneumonia [13, 14, 15]. The lung defense against influenza is by cell-mediated immunity (CMI), i.e., T-lymphocyte function [16, 17, 18]. Patients with severe swine influenza (H1N1) have profoundly impaired T-cell function vs. non-severe patients [19]. It has also been shown that influenza is absent in the lungs of patients with fatal influenza [20].

From our experience with 25 hospitalized adults during the “herald wave” of the swine influenza (H1N1) pandemic, we conclude that non-specific laboratory tests, while useful diagnostically, were not predictive of swine influenza (H1N1) pneumonia severity.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Infectious Disease DivisionWinthrop-University HospitalMineolaUSA
  2. 2.State University of New York School of MedicineStony BrookUSA

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