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Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis

Yaniv Dotan, William B. Shapiro, Eneida Male, Eduardo C. Dominguez, Amandeep Aneja, Zhao Huaqing, Chandra Dass, Kartik Shenoy, Nathaniel Marchetti, Francis C. Cordova, Gerard J. Criner, A. James Mamary
ERJ Open Research 2020 6: 00261-2019; DOI: 10.1183/23120541.00261-2019
Yaniv Dotan
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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  • ORCID record for Yaniv Dotan
  • For correspondence: yaniv.dotan@sluhn.org
William B. Shapiro
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Eneida Male
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Eduardo C. Dominguez
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Amandeep Aneja
2Pathology and Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Zhao Huaqing
3Dept of Clinical Science, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Chandra Dass
4Dept of Clinical Radiology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Kartik Shenoy
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Nathaniel Marchetti
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Francis C. Cordova
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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Gerard J. Criner
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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A. James Mamary
1Dept of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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  • Article
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  • FIGURE 1
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    FIGURE 1

    Study design. IPF: idiopathic pulmonary fibrosis; AE-IPF: acute exacerbation of IPF.

  • FIGURE 2
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    FIGURE 2

    Prevalence of explanted lung pathology patterns in patients a) without (n=52) and b) with (n=28) acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). UIP: usual interstitial pneumonia; COP: cryptogenic organising pneumonia; DIP: desquamative interstitial pneumonia; DAD: diffuse alveolar damage.

Tables

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  • TABLE 1

    Baseline characteristics and pre-evaluation data at time of lung transplantation listing for patients without acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) before lung transplantation and patients with AE-IPF before lung transplantation

    No AE-IPF groupAE-IPF groupp-value
    Subjects5237
    Baseline characteristics
     Age66±767±50.42
     Male/female39/1322/150.17
     BMI kg·m−228±428±40.28
    Comorbidities and smoking history
     Diabetes mellitus11 (21)12 (32)0.33
     Hypertension18 (35)21 (57)0.051
     Coronary artery disease25 (48)22 (59)0.39
     Congestive heart failure (systolic)01 (3)0.42
     Smoking history38 (73)25 (68)0.65
     Ever-smoker pack-years23±1116±290.42
    Pulmonary function tests
     FEV1/FVC84±786±80.17
     FEV1 % pred52±1550±150.42
     FVC % pred47±1343±120.2
     TLC % pred48±946±90.41
     RV % pred44±1533±100.004
     DLCO % pred28±1124±100.17
     Baseline oxygen saturation %90±688±60.09
     6-min walk distance m254±99218±740.08
     Lowest oxygen saturation %83±1381±60.61
    Blood tests
     Creatinine mg·dL−10.91±0.20.82±0.30.096
     Albumin g·dL−13.4±0.532.95±0.540.0002¶
     WBC cells·mm−312.8±6.514±50.23
     Platelets cells·mm−3222±71212±1130.63
     PCO2 mmHg43±944±110.54
    Right heart catheterisation data
     mPAP mmHg23±827±110.028¶
     PCWP mmHg8±47.5±50.46
     Cardiac index L·min−1·m−23±2.72.7±0.70.53
     PVR WU3.4±2.64.4±2.90.11
    Oesophageal pH and manometry data
     Number of total reflux episodes#36±2530±260.34
     Time with pH <4# %16±2517±240.96
     GORD score#10±159±130.76

    Data are presented as n, mean±sd or n (%), unless otherwise stated. BMI: body mass index; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TLC: total lung capacity; RV: residual volume; DLCO: diffusing capacity of the lung for carbon monoxide; WBC: white blood cells; PCO2: partial pressure of CO2; mPAP: mean pulmonary artery pressure; PCWP: pulmonary capillary wedge pressure; PVR: pulmonary vascular resistance; WU: Wood units; GORD: gastro-oesophageal reflux disease. #: based on 24-h oesophageal multichannel intraluminal impedance and pH monitoring: eight patients from the no AE-IPF and 10 patients from the AE-IPF groups did not complete the studies and were excluded from the GORD data analysis; ¶: not statistically significant when excluding patients evaluated and listed during AE-IPF.

    • TABLE 2

      Absolute forced vital capacity (FVC) decline and hazard ratios (HR) for developing acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on FVC decline (compared to <5% absolute decline)

      No AE-IPFAE-IPFAE-IPF HR (95% CI)p-value
      Subjects#4822
      Absolute FVC decline
       <5% pred26 (54)4 (18)Reference
       5–10% pred12 (25)5 (23)3.2 (0.77–13.5)0.11
       10–15% pred4 (8)5 (23)5.6 (1.33–23.8)0.019
       >15% pred6 (13)8 (34)7.3 (1.91–27.6)0.004

      Data are presented as n or n (%), unless otherwise stated. #: data were not available for four and 15 patients from the no-AE-IPF and AE-IPF groups, respectively.

      • TABLE 3

        High-resolution computed tomography (HRCT) findings, timing, ground-glass opacities (GGO) and correlation to pathologic findings in both groups

        No AE-IPFAE-IPF
        Subjects5237
        Baseline HRCT UIP pattern (typical/probable/indeterminate)33/14/525/9/3
        GGO in chest HRCT at any time before lung transplantation17/52 (33)19/37 (51)
        GGO severity in chest HRCT at any time scored by thoracic radiologist (mild/moderate/severe#)5/2/103/0/16
        Had chest HRCT 30 days prior to lung transplantation2/52 (4)13/28¶ (46)
        Had GGO in chest HRCT 30 days prior to lung transplantation1/2 (50)9/13 (69)
        Had GGO in chest HRCT 30 days prior to lung transplantation and acute pathological process in explant lung0/19/9 (100)

        Data are presented as n or n (%). AE-IPF: acute exacerbation of idiopathic pulmonary fibrosis; UIP: usual interstitial pneumonia. #: mild: focal/patchy involvement, moderate: neither mild nor severe, severe: bilateral extensive; ¶: nine out of 37 patients died before receiving lung transplantation.

        • TABLE 4

          Timing of listing, hospitalisation and lung transplantation or death for both groups

          No AE-IPFAE-IPF
          Subjects n5237
          Time from hospitalisation to lung transplantation# days0.4±0.521.6±24
          Time from listing to transplantation days164+175
          Listed during AE-IPF¶ 20±30.8
          Listed before AE-IPF¶ 167±146
          Time from AE-IPF to death before getting lung transplantation (n=9) daysNA37.8±32.7
          Time from lung transplantation to discharge days15.9+14.731.9±28.6

          AE-IPF: acute exacerbation of idiopathic pulmonary fibrosis; NA: not applicable. #: time from hospitalisation for AE-IPF to lung transplantation; ¶: n=14.

          • TABLE 5

            Microbiological data for patients with acute exacerbation of idiopathic pulmonary fibrosis before mechanical ventilation

            Patients examinedPositive results
            Sputum bacterial culture184# (22)
            Sputum viral culture or PCR171 (6)

            Data are presented as n or n (%). #: all four patients with positive bacterial cultures died before being transplanted.

            Supplementary Materials

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              Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

              TABLE S1 Study definitions 00261-2019.tableS1

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            Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis
            Yaniv Dotan, William B. Shapiro, Eneida Male, Eduardo C. Dominguez, Amandeep Aneja, Zhao Huaqing, Chandra Dass, Kartik Shenoy, Nathaniel Marchetti, Francis C. Cordova, Gerard J. Criner, A. James Mamary
            ERJ Open Research Oct 2020, 6 (4) 00261-2019; DOI: 10.1183/23120541.00261-2019

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            Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis
            Yaniv Dotan, William B. Shapiro, Eneida Male, Eduardo C. Dominguez, Amandeep Aneja, Zhao Huaqing, Chandra Dass, Kartik Shenoy, Nathaniel Marchetti, Francis C. Cordova, Gerard J. Criner, A. James Mamary
            ERJ Open Research Oct 2020, 6 (4) 00261-2019; DOI: 10.1183/23120541.00261-2019
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