Quantitative Analysis of Fibroblastic Foci in Usual Interstitial Pneumonia: Correlation Between the Quantitative %FF Score and Clinical Data

Quantitative Analysis of Fibroblastic Foci in Usual Interstitial Pneumonia: Correlation Between the Quantitative %FF Score and Clinical DataNo significant correlation was found between the quantitative %FF score and FVC or resting Pa02 at surgical lung biopsy in CVD-UIP or IPF/UIP (data not shown). There was no correlation between the quantitative %FF score and BAL findings in CVD-UIP (data not shown), while a significant correlation was found between the quantitative %FF score and the percentage of neutrophils (p = 0.026, r = 0.55) and eosinophils (p = 0.046, r = 0.50) in IPF/UIP. Comparison of survival between IPF/UIP and CVD-UIP is shown in Figure 4.

Consistent with the study of Flaherty et al and our previous data, patients with CVD-UIP had significantly better survival than those with IPF/UIP (log-rank test, p = 0.045). Univariate Cox proportional hazards regression models showed that the quantitative %FF score (hazard ratio, 3.03; p = 0.004) and period from symptom onset (hazard ratio, 1.07; p = 0.019) were significant predictors of survival (Table 2). Multivariate Cox proportional hazards regression models, which were adjusted for age, percentage of predicted FVC at surgical lung biopsy, and IPF/UIP diagnosis, showed that the quantitative %FF score was a significant predictor of survival in all UIP patients (hazard ratio, 7.24, p = 0.010; Table 3). Period from symptom onset (hazard ratio, 1.07; p = 0.026) and resting Pa02 (hazard ratio, 0.91; p = 0.046) were also significant predictors (Table 3). Even in IPF patients alone, the quantitative %FF score was an independent predictor of survival (hazard ratio, 5.53; p = 0.032; Table 4). Source

Comparison Between the Quantitative Scoring Method and Semiquantitative Scoring Methods
We compared our quantitative scoring method with three previously reported semiquantitative scoring methods. With the use of к coefficient, interobserver agreement was found to be moderate with the Michigan FF scoring method (unweighted к coefficient, 0.53; p < 0.001), whereas the agreement was relatively low with the Denver FF scoring method (unweighted к coefficient, 0.33; p < 0.001) and with the Brompton FF method (unweighted к coefficient, 0.27; p < 0.001). The quantitative %FF score had a significant correlation with the Michigan FF score (p = 0.794, p < 0.001; Fig; 5, top, A), Denver FF score (p = 0.601, p = 0.001; Fig 5, center, B), and Brompton FF score (p = 0.608, p < 0.001; Fig 5, bottom, C), but patients with the same score assessed by the semiquantitative methods had widely varying scores assessed by our method.

Figure-4

Figure 4. Comparison of survival between CVD-UIP and IPF/UIP. Kaplan-Meier analysis shows that patients with CVD-UIP had significantly better survival than those with IPF/UIP (log-rank test, p = 0.045).

Figure-5

Figure 5. Correlation between the quantitative scoring method and semiquantitative scoring methods. The quantitative %FF score had a significant correlation with Michigan FF score (top, A; p = 0.794, p < 0.001), Denver FF score (center, B; p = 0.601, p = 0.001), and Brompton FF score (bottom, C; p = 0.608, p < 0.001), whereas patients with the same score assessed by the semiquantitative methods had widely varying scores as assessed by the quantitative method.

Table 2—Univariate Cox Proportional Hazards Models of Survival in All UIP Patients

Variables HazardRatio 95% Confidence Interval p Value
Lower Upper
Age at biopsy, yr 1.04 0.94 1.16 0.468
Male gender 0.45 0.11 1.93 0.286
Symptom onset, mo 1.07 1.01 1.13 0.019
IPF/UIP diagnosis 4.72 0.89 24.9 0.068
FVC, % predicted 0.98 0.95 1.02 0.394
Resting Pao2, mm Hg 0.93 0.86 1.01 0.071
Quantitative FF score, % 3.03 1.42 6.48 0.004

Table 3—Multivariate Cox Proportional Hazards Models of Survival Adjusting for Age, FVC at Surgical Lung Biopsy, and IPF/UIP Diagnosis in All UIP Patients

Variables HazardRatio 95% Confidence Interval p Value
Lower Upper
Male gender 0.12 0.02 0.79 0.028
Symptom onset, mo 1.07 1.01 1.14 0.026
Resting Pao2, mm Hg 0.91 0.83 1.00 0.046
Quantitative FF score, % 7.24 1.59 32.9 0.010

Table 4—Multivariate Cox Proportional Hazards Models of Survival Adjusting for FVC at Surgical Lung Biopsy in IPF/UIP Patients

Variables HazardRatio 95% Confidence Interval p Value
Lower Upper
Age at biopsy, yr 1.04 0.90 1.19 0.598
Male gender 0.28 0.44 1.77 0.175
Symptom onset, mo 1.06 1.00 1.13 0.057
Resting Pao2, mm Hg 0.94 0.85 1.03 0.178
Quantitative FF score, % 5.53 1.16 26.3 0.032
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