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Asymmetry in acute exacerbation of idiopathic pulmonary fibrosis

Akihiko Sokai, Kiminobu Tanizawa, Tomohiro Handa, Takeshi Kubo, Seishu Hashimoto, Kohei Ikezoe, Yoshinari Nakatsuka, Kensaku Aihara, Yoshio Taguchi, Shigeo Muro, Toru Oga, Sonoko Nagai, Takateru Izumi, Toyohiro Hirai, Kazuo Chin, Michiaki Mishima
ERJ Open Research 2017 3: 00036-2016; DOI: 10.1183/23120541.00036-2016
Akihiko Sokai
1Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Kiminobu Tanizawa
2Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • For correspondence: tanizawa@kuhp.kyoto-u.ac.jp
Tomohiro Handa
1Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Takeshi Kubo
3Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Seishu Hashimoto
4Respiratory Medicine, Tenri Hospital, Tenri, Japan
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Kohei Ikezoe
1Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Yoshinari Nakatsuka
1Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Kensaku Aihara
5Respiratory Medicine, Saiseikai Noe Hospital, Osaka, Japan
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Yoshio Taguchi
4Respiratory Medicine, Tenri Hospital, Tenri, Japan
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Shigeo Muro
1Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Toru Oga
2Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Sonoko Nagai
6Respiratory Medicine, Kyoto Central Clinic/Clinical Research Center, Kyoto, Japan
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Takateru Izumi
6Respiratory Medicine, Kyoto Central Clinic/Clinical Research Center, Kyoto, Japan
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Toyohiro Hirai
1Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Kazuo Chin
2Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Michiaki Mishima
1Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • FIGURE 1
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    FIGURE 1

    Evaluation by high-resolution computed tomography (HRCT). The extents of emphysema, ground-glass opacities (GGOs), consolidation, and reticulation and honeycombing (R/HC) were scored to the nearest 10% in each of the five HRCT slices. The scores of 10 zones were averaged to obtain the mean scores for each lung. The right-to-left ratio of the parenchymal opacities consisting of GGOs and consolidation was calculated. This case, in which the ratio was 0.42, was an example of asymmetrical acute exacerbation.

  • FIGURE 2
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    FIGURE 2

    A comparison of 180-day survival curves between patients with idiopathic pulmonary fibrosis with asymmetrical acute exacerbation (AE) and those with symmetrical AE.

Tables

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  • TABLE 1

    Patient characteristics and clinical data

    Characteristic
    Subjects n59
    Males54 (91.5)
    Age years71.7±8.2
    Smoking history49 (86.0)
    FVC before AE % predicted71.0±21.9
    DLCO before AE % predicted37.0±17.3
    Treatment before AE
     LTOT23 (39.0)
     Corticosteroids20 (33.9)
     Immunosuppressive agents10 (16.9)
    WBC µL−110 490±4150
    D-dimer µg·mL−15.1±6.3
    CRP mg·dL−16.5±6.4
    LDH IU·L−1380±226
    KL-6 U·mL−11763±1278
    P/F<20026 (47.3)
    BAL performed11 (18.6)
    Treatment of AE
     High-dose corticosteroids59 (100)
     Antibiotics58 (98.3)
     Immunosuppressive agents30 (50.8)
     Noninvasive ventilation14 (23.7)
    180-day mortality %59.2

    The data are presented as mean±sd or n (%), unless otherwise indicated. FVC: forced vital capacity; AE: acute exacerbation; DLCO: diffusing capacity of the lung for carbon monoxide; LTOT: long-term oxygen therapy; WBC: white blood cell; CRP: C-reactive protein; LDH: lactate dehydrogenase; KL-6: Krebs von den Lungen-6; P/F: the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen; BAL: bronchoalveolar lavage.

    • TABLE 2

      Chest high-resolution computed tomography indices at diagnosis

      IndicesExtent or number
      Parenchymal opacities %40.5±15.1
      Ground-glass opacities %34.1±15.1
      Consolidation %6.4±7.6
      Reticulation/honeycombing %14.8±12.1
      Emphysema %7.0±10.2
      Bronchiectasis in parenchymal opacities28 (47.5)
      Asymmetrical acute exacerbation13 (22.0)

      The data are presented as mean±sd or n (%).

      • TABLE 3

        Univariate and multivariate analyses of 180-day mortality

        Univariate analysisMultivariate analysis
        HR95% CIp-valueHR95% CIp-value
        Age1.000.95–1.050.96
        Male1.970.59–12.20.30
        Smoking history0.440.20–1.110.080.510.23–1.310.15
        LTOT2.101.06–4.250.03*2.341.04–5.280.04*
        FVC before AE % predicted0.990.97–1.010.43
        DLCO before AE % predicted0.980.94–1.010.16
        P/F <2000.690.33–1.400.30
        CRP1.030.96–1.950.36
        LDH 10 IU·L−1 per unit1.021.01–1.03<0.01*1.021.00–1.050.02*
        KL-6 100 U·mL−1 per unit1.021.00–1.040.100.990.96–1.020.69
        Parenchymal opacities1.021.00–1.040.090.990.96–1.020.51
        Ground-glass opacities1.010.99–1.030.27
        Consolidation1.020.98–1.060.26
        Reticulation/honeycombing0.980.95–1.020.31
        Emphysema1.020.98–1.050.34
        Bronchiectasis in parenchymal opacities1.190.60–2.380.62
        Asymmetrical AE0.330.10–0.850.02*0.360.10–0.990.047*

        HR: hazard ratio; LTOT: long-term oxygen therapy; FVC: forced vital capacity; AE: acute exacerbation; DLCO: diffusing capacity of the lung for carbon monoxide; P/F: the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen; CRP: C-reactive protein; LDH: lactate dehydrogenase; KL-6: Krebs von den Lungen-6. *: p<0.05.

        • TABLE 4

          Patient characteristics between asymmetrical and symmetrical acute exacerbation

          Asymmetrical AESymmetrical AEp-value
          Subjects n1346
          Age years74.2±8.171.0±8.10.21
          Male10 (76.9)44 (95.7)0.07
          Smoking history3 (60.0)21 (91.3)0.14
          FVC before AE % predicted70.2±17.671.3±23.30.70
          DLCO before AE % predicted34.6±20.538.0±16.20.32
          Treatment before AE
           LTOT4 (30.8)19 (41.3)0.54
           Corticosteroids2 (15.4)18 (39.1)0.18
           Immunosuppressive agents0 (0.0)10 (21.7)0.10
          WBC ×103·µL−110 120±472010 590±40200.43
          D-dimer µg·mL−14.7±5.35.3±6.71.00
          CRP mg·dL−15.7±4.66.7±6.80.96
          LDH IU·L−1347±88389±2520.82
          KL-6 U·mL−11607±10741805±13350.54
          P/F<2008 (61.5)18 (42.9)0.34
          BAL performed1 (7.7)10 (21.7)0.43
          Parenchymal opacities %32.6±14.542.7±14.60.04*
          Ground-glass opacities %24.1±14.437.0±14.2<0.01*
          Consolidation %8.6±9.25.7±7.00.18
          Reticulation/honeycombing %16.5±11.314.3±12.40.41
          Emphysema %11.7±13.15.7±9.00.07
          Bronchiectasis in parenchymal opacities6 (47.5)22 (47.8)1.00
          Treatment of AE
           High-dose corticosteroids13 (100)46 (100)–
           Antibiotics13 (100)45 (97.8)1.00
           Immunosuppressive agents4 (30.8)26 (56.5)0.13
           Non-invasive ventilation3 (23.1)11 (23.9)1.00
          180-day mortality %30.868.20.03*

          The data are presented as mean±sd or n (%), unless otherwise indicated. AE: acute exacerbation; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; LTOT: long-term oxygen therapy; WBC: white blood cell; CRP: C-reactive protein; LDH: lactate dehydrogenase; KL-6: Krebs von den Lungen-6; P/F: the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen; BAL: bronchoalveolar lavage. *: p<0.05.

          Supplementary Materials

          • Figures
          • Tables
          • Supplementary Material

            K. Chin 00036-2016_Chin

            T. Handa 00036-2016_Handa

            T. Oga 00036-2016_Oga

            K. Tanizawa 00036-2016_Tanizawa

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          Asymmetry in acute exacerbation of idiopathic pulmonary fibrosis
          Akihiko Sokai, Kiminobu Tanizawa, Tomohiro Handa, Takeshi Kubo, Seishu Hashimoto, Kohei Ikezoe, Yoshinari Nakatsuka, Kensaku Aihara, Yoshio Taguchi, Shigeo Muro, Toru Oga, Sonoko Nagai, Takateru Izumi, Toyohiro Hirai, Kazuo Chin, Michiaki Mishima
          ERJ Open Research Apr 2017, 3 (2) 00036-2016; DOI: 10.1183/23120541.00036-2016

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          Asymmetry in acute exacerbation of idiopathic pulmonary fibrosis
          Akihiko Sokai, Kiminobu Tanizawa, Tomohiro Handa, Takeshi Kubo, Seishu Hashimoto, Kohei Ikezoe, Yoshinari Nakatsuka, Kensaku Aihara, Yoshio Taguchi, Shigeo Muro, Toru Oga, Sonoko Nagai, Takateru Izumi, Toyohiro Hirai, Kazuo Chin, Michiaki Mishima
          ERJ Open Research Apr 2017, 3 (2) 00036-2016; DOI: 10.1183/23120541.00036-2016
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