Figures
- Figure 1–
Design of the study. IPF: idiopathic pulmonary fibrosis; VATS: video-assisted thoracoscopy; UIP: usual interstitial pneumonia; ATS: American Thoracic Society; ERS: European Respiratory Society.
- Figure 2–
a) Prospective cohort: 3-yr survival form the time of diagnosis. b) Prospective cohort: 3-yr incidence of acute exacerbations.
- Figure 3–
Prospective cohort, receiver operating characteristics curve of different variables at the time of diagnosis versus 3-yr survival (see table S3 for more details). a) Body mass index; b) Medical Research Council dyspnoea score; c) 6-min walking distance (6MWD; m); d) 6MWD (% predicted); e) alveolar–arterial oxygen tension difference; f) forced vital capacity; g) diffusing capacity of the lung for carbon monoxide; h) composite physiologic index; i) high-resolution computed tomography fibrosis score; and j) bronchoalveolar lavage total cell count.
- Figure 4–
a) Prospective cohort, Kaplan–Meier survival analysis grouped by Risk stratificatiOn ScorE (ROSE). Low risk: Medical Research Council dyspnoea score (MRCDS) ≤3, 6-min walking distance (6MWD) >72% predicted (% pred) and composite physiologic index (CPI) <41; intermediate risk: MRCDS >3, 6MWD <72% pred or CPI >41; and high risk: MRCDS >3, 6MWD <72% pred and CPI >41. p<0.0001. b) Prospective cohort, receiver operating characteristics curve of ROSE at the time of diagnosis versus 3-yr survival. Refer to table S3 for more details. c) Prospective cohort, intermediate risk group, Kaplan–Meier survival analysis grouped by 6-month changes of ROSE. p<0.0001. d) Prospective cohort, intermediate risk group, receiver operating characteristics curve of 6-month change of ROSE versus 3-yr survival; area under the curve 0.77, standard error 0.055, sensitivity 94% (95% CI 73–100%), specificity 41% (95% CI 25–58%). p-value <0.0001.
Tables
- Table 1– Demographic, clinical, functional and radiographic characteristics of the two cohorts# at the time of diagnosis
Variable Prospective cohort Retrospective cohort p-value Subjects n 70 68 M/F (% male) 57/13 (81) 50/18 (74) ns Age yrs 67±8 62±9 0.0011 BMI m·kg−2 28±4 27±5 ns Time to diagnosis months 23±20 NA NA Biopsy-based diagnosis yes/no (%) 23/47 (33) 22/46 (32) ns Smokers/never-smokers (%) 44/26 (63) 34/34 (50) ns Smoking pack-yrs 33±18 24±17 0.028 Concomitant emphysema yes/no (%) 24/46 (34) 13/55 (19) 0.044 MRC dyspnoea score 2.5±1.1 NA NA 6MWD¶ m 372±146 350±116 ns 6MWD¶ % pred 79±29 68±24 0.049 PA–a,O2 mmHg 32±14 26±10 ns FVC % pred 75±22 75±21 ns DL,CO+ % pred 46±19 55±17 0.013 CPI 48±15 42±12 0.038 HRCT disease extent§ % of total lung volume 36±12 NA NA BAL total cell countƒ cells·mL−1 596130±502073 NA NA Data are presented as mean±sd, unless otherwise stated. M: male; F: female; BMI: body mass index; MRC: Medical Research Council; 6MWD: 6-min walking distance; % pred: % predicted; PA–a,O2: alveolar–arterial oxygen tension difference; FVC: forced vital capacity; DL,CO: diffusing capacity of the lung for carbon monoxide; CPI: composite physiologic index; HRCT: high-resolution computed tomography; BAL: bronchoalveolar lavage; ns: not significant; NA: not available. #: a prospective cohort at the Pulmonary Unit, University of Rome “Tor Vergata”, Rome, Italy and a retrospective cohort at the pulmonary unit, University of Siena, Siena, Italy; ¶: n=64; +: n=65; §: mean of the scores from each of the three core radiologists; ƒ: n=28. p-value: Chi-squared, unpaired t-test or Mann–Whitney U-test, where required.
- Table 2– Prospective cohort: demographic, clinical, functional and radiographic characteristics at the time of diagnosis of 3-yr survivors and nonsurvivors
Variable Survivors Nonsurvivors p-value Subjects n 37 33 Age yrs 66±4 67±9 ns BMI m·kg−2 29±4 27±3 0.0384 Time to diagnosis months 20±19 27±22 ns Smoking pack-yrs 32±16 34±22 ns Concomitant emphysema yes/no (%) 9/28 (24) 15/18 (45) 0.0267 MRC dyspnoea score 2.1±0.8 3.3±1.1 <0.0001 6MWD m 412±128 319±153 0.0184 6MWD % pred 89±27 66±27 0.0018 Desaturation at 6MWT# yes/no (%) 19/16 (54) 25/4 (86) 0.0061 PA–a,O2 mmHg 28±13 36±17 0.0392 FVC % pred 81±21 68±23 0.0027 DL,CO % pred 53±17 37±17 0.0005 CPI 43±15 55±13 0.0006 HRCT disease extent % of total lung volume 33±11 41±11 0.0098 BAL total cell count cells·mL−1 417972±319004 952444±623505 0.0037 Data are presented as mean±sd, unless otherwise stated. BMI: body mass index; MRC: Medical Research Council; 6MWD: 6-min walking distance; % pred: % predicted; 6MWT: 6-min walking test; PA–a,O2: alveolar–arterial oxygen tension difference; FVC: forced vital capacity; DL,CO: diffusing capacity of the lung for carbon monoxide; CPI: composite physiologic index; HRCT: high-resolution computed tomography; BAL: bronchoalveolar lavage; ns: not significant. p-value: Chi-squared, unpaired t-test or Mann–Whitney U-test, where required. #: arterial oxygen saturation ≤88%.
- Table 3– Prospective cohort: 3-yr survival, univariate analysis of variables at the time of diagnosis
Variable Hazard ratio (95% CI) p-value Age yrs 1.02 (0.98–1.07) ns Smoking pack-yrs 0.99 (0.97–1.02) ns Time to diagnosis months 1.01 (0.99–1.03) ns BMI m·kg−2 0.89 (0.80–0.98) 0.0155 MRC dyspnoea score 2.52 (1.76–3.62) <0.0001 6MWD m 1.00 (1.00–1.00) ns 6MWD % pred 0.98 (0.96–0.99) 0.0007 Desaturation at 6MWT# 0.54 (0.32–0.84) 0.0052 PA-a,O2 mmHg 1.03 (1.01–1.05) 0.0063 FVC % pred 0.97 (0.95–0.99) 0.0039 DL,CO % pred 0.94 (0.92–0.97) <0.0001 CPI 1.06 (1.03–1.10) <0.0001 HRCT fibrosis score % of total lung volume 1.03 (1.00–1.07) 0.0497 BAL total cell count cells·mL−1 1.00 (1.00–1.00) 0.0009 Concomitant emphysema 1.82 (0.90–3.66) 0.096 BMI: body mass index; MRC: Medical Research Council; 6MWD: 6-min walking distance; % pred: % predicted; 6MWT: 6-min walking test; PA–a,O2: alveolar–arterial oxygen tension difference; FVC: forced vital capacity; DL,CO: diffusing capacity of the lung for carbon monoxide; CPI: composite physiologic index; HRCT: high-resolution computed tomography; BAL: bronchoalveolar lavage; ns: not significant. #: no desaturation (arterial oxygen saturation ≤88%) during the 6MWT.
- Table 4– Prospective and retrospective cohorts: 3-yr survival Cox proportional hazard analysis of variables at the time of diagnosis
Variable Hazard ratio (95% CI) p-value Prospective cohort# MRC dyspnoea score >3 6.77 (2.37–19.41) 0.0005 6MWD <72% pred 3.27 (1.25–8.82) 0.0162 CPI >41 5.36 (1.50–34.15) 0.0071 Retrospective cohort¶ 6MWD <72% pred 5.43 (1.35–36.17) 0.016 CPI >41 4.20 (1.05–27.93) 0.042 MRC: Medical Research Council; 6MWD: 6-min walking distance; % pred: % predicted; CPI: composite physiologic index. #: p-value of the model <0.0001; ¶: p-value of the model 0.0053.
- Table 5– Prospective cohort: acute exacerbations, univariate analysis of variables at the time of diagnosis
Variable Hazard ratio (95% CI) p-value Age at diagnosis yrs 1.02 (0.96–1.10) ns Smoking pack-yrs 0.99 (0.95–1.03) ns Time to diagnosis months 1.01 (0.98–1.04) ns BMI m·kg−2 0.92 (0.79–1.07) ns MRC dyspnoea score 1.96 (1.18–3.30) 0.0095 6MWD m 1.00 (1.00–1.00) ns 6MWD % pred 0.98 (0.96–1.00) ns Desaturation at 6MWT# 0.43(0.10–0.97) 0.040 PA–a,O2 mmHg 1.03(1.00–1.07) 0.053 FVC % pred 0.98 (0.95–1.01) ns DL,CO % pred 0.94 (0.90–0.98) 0.0007 CPI 1.05 (1.01–1.10) 0.022 HRCT fibrosis score % of total lung volume 1.05 (1.00–1.10) 0.063 BAL total cell count cells·mL−1 1.00 (1.00–1.00) ns Concomitant emphysema 3.37 (1.12–11.17) 0.030 BMI: body mass index; MRC: Medical Research Council; 6MWD: 6-min walking distance; % pred: % predicted; 6MWT: 6-min walking test; PA–a,O2: alveolar–arterial oxygen tension difference; FVC: forced vital capacity; DL,CO: diffusing capacity of the lung for carbon monoxide; CPI: composite physiologic index; HRCT: high-resolution computed tomography; BAL: bronchoalveolar lavage; ns: not significant. #: no desaturation (arterial oxygen saturation ≤88%) during the 6MWT.
- Table 6– Prospective cohort: acute exacerbations, Cox proportional hazard analysis of variables at the time of diagnosis
Variable Hazard ratio (95% CI) p-value DL,CO % pred 0.93 (0.89–0.97) 0.0008 Concomitant emphysema 3.20 (1.06–10.67) 0.040 DL,CO: diffusing capacity of the lung for carbon monoxide; % pred: % predicted. Model 1 (cut-off), p-value of the model 0.0004.
Supplementary material
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Methods
Results
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Figure legends - Figure S1
- Figure S2a
- Figure S2b
- Figure S3
- Figure S4
- Figure S5a
- Figure S5b
- Supplementary material -
