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Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma

P.A.B. Wark, S.L. Johnston, I. Moric, J.L. Simpson, M.J. Hensley, P.G. Gibson
European Respiratory Journal 2002 19: 68-75; DOI: 10.1183/09031936.02.00226302
P.A.B. Wark
1Airways Research Centre, John Hunter Hospital, Newcastle, Australia. 2Dept of Respiratory Medicine, National Heart and Lung Institute at St Marys, Imperial College School of Medicine, London, UK. 3Institute for Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia. 5Faculty of Medicine, University of Newcastle, Newcastle, Australia
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S.L. Johnston
1Airways Research Centre, John Hunter Hospital, Newcastle, Australia. 2Dept of Respiratory Medicine, National Heart and Lung Institute at St Marys, Imperial College School of Medicine, London, UK. 3Institute for Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia. 5Faculty of Medicine, University of Newcastle, Newcastle, Australia
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I. Moric
1Airways Research Centre, John Hunter Hospital, Newcastle, Australia. 2Dept of Respiratory Medicine, National Heart and Lung Institute at St Marys, Imperial College School of Medicine, London, UK. 3Institute for Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia. 5Faculty of Medicine, University of Newcastle, Newcastle, Australia
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J.L. Simpson
1Airways Research Centre, John Hunter Hospital, Newcastle, Australia. 2Dept of Respiratory Medicine, National Heart and Lung Institute at St Marys, Imperial College School of Medicine, London, UK. 3Institute for Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia. 5Faculty of Medicine, University of Newcastle, Newcastle, Australia
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M.J. Hensley
1Airways Research Centre, John Hunter Hospital, Newcastle, Australia. 2Dept of Respiratory Medicine, National Heart and Lung Institute at St Marys, Imperial College School of Medicine, London, UK. 3Institute for Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia. 5Faculty of Medicine, University of Newcastle, Newcastle, Australia
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P.G. Gibson
1Airways Research Centre, John Hunter Hospital, Newcastle, Australia. 2Dept of Respiratory Medicine, National Heart and Lung Institute at St Marys, Imperial College School of Medicine, London, UK. 3Institute for Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia. 5Faculty of Medicine, University of Newcastle, Newcastle, Australia
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Figures

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  • Fig. 1.—
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    Fig. 1.—

    Induced sputum neutrophils (measured as number of cells ×106·mL−1) in subjects with acute asthma (Visit 1) and upon recovery Visit 2). The points represent the geometric mean±1 sem. Subjects with infective asthma (♦) had higher sputum neutrophils at Visit 1 compared to noninfective asthma (▪) (p=0.02). By Visit 2, sputum neutrophils had fallen in subjects with infective asthma (p=0.04), but no significant change was seen in subjects with noninfective asthma.

  • Fig. 2.—
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    Fig. 2.—

    Logistic regression model to predict variables associated with increased sputum neutrophils. An increase in sputum neutrophils was defined as >3.1×106·mL−1. The points represent the odds ratio (OR) and their 95% confidence intervals. ═: the line of unity. The presence of infection and male sex independently predicted the presence of elevated sputum neutrophils at Visit 1.

  • Fig. 3.—
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    Fig. 3.—

    Sputum neutrophil elastase (ng·mL−1) in subjects with acute asthma (Visit 1) and upon recovery (Visit 2). The points represent the geometric mean±1 sem. Subjects with infective asthma (♦) had higher sputum neutrophil elastase at Visit 1 compared to noninfective asthma (▪) (p<0.05). By Visit 2, this had fallen in subjects with infective asthma (p<0.05), but no significant change was seen in subjects with noninfective asthma.

  • Fig. 4.—
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    Fig. 4.—

    Mean sputum lactate dehydrogenase (LDH) in subjects at Visit 1 and Visit 2. The points represent the geometric mean±1 sem. Subjects with infective asthma (♦) had higher sputum LDH at Visit 1 compared to noninfective asthma (▪) (p<0.05). By Visit 2, sputum LDH had fallen significantly in all subjects (p<0.05). IU: international units.

  • Fig. 5.—
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    Fig. 5.—

    Sputum lactate dehydrogenase (LDH) isoenzymes expressed as a per cent of the total LDH activity at the initial visit. Data are presented as medians and interquartile ranges.

Tables

  • Figures
  • Table 1—

    Clinical characteristics

    NoninfectiveInfectiveAnalysis
    Subjects n1237NA
    Male sex3 (25)15 (41)p=0.3
    Age yrs37.3±16.140.5±17.9p=0.2
    Smokers3 (25)2 (17)p=0.2
    Atopy8 (67)21 (57)p=0.4
    Aas score 74.1±1.03.9±1.4p=0.2
    Maintenance ICS¶, µg BDP·day−11475±8611606±826p=0.8
    Admitted4 (33)10 (83)*p<0.01#
    Admitted to ICU02 (17)p=0.2#
    Length of stay in days0.7±1.44.7 (5.9)*p=0.02
    Acute FEV1 % pred70.4±2445.3±31.7*p=0.04
    FEV1 % pred at follow-up86.5±23.170.1±31.2*p=0.04
    Maintenance ICS at follow-up, µg BDP·day−11523±8061865±886p=0.5
    • Data are presented as n (%) or mean±sd unless otherwise stated

    • ICS: inhaled corticosteroids

    • BDP: beclomethasone dipropionate

    • ICU: intensive care unit

    • FEV1: forced expiratory volume in one second

    • NA: not applicable

    • ¶: ICS dose expressed as total daily dose of BDP in µg·day−1, where 1 µg BDP equals 1 µg budesonide and 0.5 µg fluticasone

    • *: p<0.05, significantly different from those with noninfective acute asthma

    • #: analysis using Chi-squared test

  • Table 2—

    Sputum cell counts in acute asthma

    Visit 1Visit 2
    NoninfectiveInfectiveNoninfectiveInfective
    Nebulizer time min2.6±1.72.8±1.94.8±1.64.9±1.6
    TCC×106·mL−12.8±2.98.3±2.5*3.3±2.22.2±1.5***
    Neutrophils×106·mL−10.8±55.1±12.1*1.4±2.20.8±3.4***
    Neutrophils %31.6±2.563.1±3.236.6±239.8±1.6
    Eosinophils×106·mL−10.2±4.50.2±2.50.01±4.50.03±2.5
    Eosinophils %7.2±3.31.5±3.42.5±2***1.2±6.7
    Macrophages %40.5±1.818.2±3.744.7±1.545.7±2
    Lymphocytes %1.1±2.21.1±2.51.7±21±3
    Epithelial cells %2.7±2.73.3±5.51.4±1.32.2±6.1
    Squamous cells %4.9±2.74.6±3.15±3.34.4±1.2
    IL-8 ng·mL−120.9±5.535±3.711.8±6.117.8±6.1
    IL-5 positive cells %15.6±1.88.4±1.62±0.41.4±1.8
    ECP ng·mL−13072±553090±49460±5***398±18
    Neutrophil elastase µg·mL−1169±3.33129±7.4*100±2.5120±9.6***
    LDH IU·mL−1182±2.2550±16*54±12.7***64±1.9***
    • Data are presented as mean±sd

    • TCC: total cell count

    • IL: interleukin

    • ECP: eosinophil cationic protein

    • LDH: lactate dehydrogenase

    • IU: international units. The analysis was carried out using unpaired t-tests on log-transformed data

    • *: p<0.05, significantly higher than subjects with noninfective acute asthma at Visit 1

    • #: p<0.05, significantly higher than subjects with infection and acute asthma at Visit 1

    • ***: p<0.001, significantly lower than Visit 1

  • Table 3—

    Linear regression analysis to predict sputum lactate dehydrogenase (LDH)

    Log LDH IU·mL−1CoefficientStandard errorP>t
    Log neutrophils×106·mL−10.420.1p=0.001
    Log eosinophils×106·mL−1−0.180.09p=0.06
    Log ECP ng·mL−10.210.15p=0.2
    Log neutrophil elastase0.020.08p=0.5
    Log IL-8 ng·mL−10.330.18p=0.09
    Constant2.21.1p=0.059
    • IU: international units

    • ECP: eosinophil cationic protein

    • IL: interleukin. Probability F>0.0001, adjusted R2=0.787

  • Table 4—

    Linear regression analysis to predict length of hospital stay in acute asthma

    Length of stay daysCoefficientStandard errorP>t
    Log neutrophils×106·mL−10.440.37p=0.3
    Log eosinophils×106·mL−1−0.310.25p=0.3
    Log LDH IU·mL−12.560.6p=0.002
    Log ECP ng·mL−11.190.4p=0.02
    Log neutrophil elastase0.100.21p=0.6
    Age yrs0.030.02p=0.3
    Sex−1.30.62p=0.06
    Smoking status1.70.86p=0.08
    Prednisone use0.850.73p=0.3
    Aas severity score 7−0.820.34p=0.04
    Constant−1.973.15p=0.549
    • LDH: lactate dehydrogenase

    • IU: international units

    • ECP: eosinophil cationic protein. Probability F=0.004, adjusted R2=0.797

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Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma
P.A.B. Wark, S.L. Johnston, I. Moric, J.L. Simpson, M.J. Hensley, P.G. Gibson
European Respiratory Journal Jan 2002, 19 (1) 68-75; DOI: 10.1183/09031936.02.00226302

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Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma
P.A.B. Wark, S.L. Johnston, I. Moric, J.L. Simpson, M.J. Hensley, P.G. Gibson
European Respiratory Journal Jan 2002, 19 (1) 68-75; DOI: 10.1183/09031936.02.00226302
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