Fibroproliferative changes on high-resolution CT in the acute respiratory distress syndrome predict mortality and ventilator dependency: a prospective observational cohort study

Kazuya Ichikado, Hiroyuki Muranaka, Yasuhiro Gushima, Toru Kotani, Habashi M Nader, Kiminori Fujimoto, Takeshi Johkoh, Norihiro Iwamoto, Kodai Kawamura, Junji Nagano, Koichiro Fukuda, Naomi Hirata, Takeshi Yoshinaga, Hidenori Ichiyasu, Shinsuke Tsumura, Hirotsugu Kohrogi, Atsushi Kawaguchi, Masakazu Yoshioka, Tsutomu Sakuma, Moritaka Suga, Kazuya Ichikado, Hiroyuki Muranaka, Yasuhiro Gushima, Toru Kotani, Habashi M Nader, Kiminori Fujimoto, Takeshi Johkoh, Norihiro Iwamoto, Kodai Kawamura, Junji Nagano, Koichiro Fukuda, Naomi Hirata, Takeshi Yoshinaga, Hidenori Ichiyasu, Shinsuke Tsumura, Hirotsugu Kohrogi, Atsushi Kawaguchi, Masakazu Yoshioka, Tsutomu Sakuma, Moritaka Suga

Abstract

Objectives: To examine whether the extent of fibroproliferative changes on high-resolution CT (HRCT) scan influences prognosis, ventilator dependency and the associated outcomes in patients with early acute respiratory distress syndrome (ARDS).

Design: A prospective observational cohort study.

Setting: Intensive care unit in a teaching hospital.

Participants: 85 patients with ARDS who met American-European Consensus Conference Criteria and eligible criteria.

Interventions: HRCT scans were performed and prospectively evaluated by two independent observers on the day of diagnosis and graded into six findings according to the extent of fibroproliferation. An overall HRCT score was obtained by previously published method.

Primary and secondary outcomes: The primary outcome was 60-day mortality. Secondary outcomes included the number of ventilator-free days, organ failure-free days, the incidence of barotraumas and the occurrence of ventilator-associated pneumonia.

Results: Higher HRCT scores were associated with statistically significant decreases in organ failure-free days as well as ventilator-free days. Multivariate Cox proportional hazards model showed that the HRCT score remained an independent risk factor for mortality (HR 1.20; 95% CI 1.06 to 1.36; p=0.005). Multivariate analysis also revealed that the CT score had predictive value for ventilator weaning within 28 days (OR 0.63; 95% CI 0.48 to 0.82; p=0.0006) as well as for an incidence of barotraumas (OR 1.61; 95% CI 1.08 to 2.38; p=0.018) and for an occurrence of ventilator-associated pneumonia (OR 1.46; 95% CI 1.13 to 1.89; p=0.004). A HRCT score <210 enabled prediction of 60-day survival with 71% sensitivity and 72% specificity and of ventilator-weaning within 28 days with 75% sensitivity and 76% specificity.

Conclusions: Pulmonary fibroproliferation assessed by HRCT in patients with early ARDS predicts increased mortality with an increased susceptibility to multiple organ failure, including ventilator dependency and its associated outcomes.

Conflict of interest statement

Competing interests: None.

Figures

Figure 1
Figure 1
Outlines of the study.
Figure 2
Figure 2
High-resolution CT findings correlated with pathology. (A) High-resolution CT findings corresponding to exudative phase of acute respiratory distress syndrome (ARDS). HRCT scan at the level of right middle lobe shows dependent airspace consolidation without traction bronchiectasis and non-dependent areas of sparing. The patient was a 68-year-old man with ARDS due to Streptococcus pneumonia. (B) High-resolution CT findings corresponding to fibroproliferative phase of ARDS. HRCT scan at the level of right lower lobe shows extensive airspace consolidation and ground-glass attenuation associated with traction bronchiectasis (arrows). The patient was an 84-year-old woman with ARDS due to sepsis. (C) High-resolution CT findings corresponding to fibrotic phase of ARDS. HRCT scan at the level of right inferior pulmonary vein shows extensive ground-glass attenuation associated with traction bronchiectasis (arrows), coarse reticulation and cystic changes (arrowheads). The patient was a 65-year-old woman with ARDS due to viral pneumonia. (Sequential changes of HRCT findings were shown in the supplemental figure.)
Figure 3
Figure 3
Receiver operator characteristic (ROC) curve of prognostic value of the high-resolution CT score. ROC identified the optimal cut-off value of 210 determined by the Youden Index for prediction of survival at day 60 with 71% sensitivity and 72% specificity (area under the curve, AUC, 0.71; 95% CI 0.61 to 0.82) and for prediction of survival at day 180 with 71% sensitivity and 76% specificity (AUC, 0.73; 95% CI 0.62 to 0.84).
Figure 4
Figure 4
(A) Day 60-mortality rate of each major cause of acute respiratory distress syndrome. (B) Day 60-mortality rate compared between the optimal cut-off value of high-resolution CT score in each cause. Regardless of the cause, the mortality rate of a patient with a lower CT score was significantly lower than that of a patient with a higher CT score.
Figure 5
Figure 5
Receiver operator characteristic (ROC) curve of prediction of the ventilator weaning within 28 days from high-resolution CT score. ROC curve identified the optimal cut-off value of 210 determined by the Youden Index for prediction of ventilator weaning at day 28 with 75% sensitivity and 76% specificity (area under the curve, 0.77; 95% CI 0.67 to 0.88).
Figure 6
Figure 6
Sequential changes of Sequential Organ Failure Assessment (SOFA) scores. The SOFA score of a patient with a lower CT score (

Figure 7

(A) Receiver operator characteristic (ROC)…

Figure 7

(A) Receiver operator characteristic (ROC) curve of prediction of the onset of barotrauma…

Figure 7
(A) Receiver operator characteristic (ROC) curve of prediction of the onset of barotrauma from high-resolution CT score. ROC curve identified the optimal cut-off value of 235 determined by the Youden Index for prediction of barotraumas onset with 73% sensitivity and 77% specificity (area under the curve, 0.77; 95% CI 0.59 to 0.95). (B) Comparison of the incidence of barotraumas between patients with the optimal cut-off value of CT score identified from ROC curve. The incidence of barotrauma of a patient with a lower CT score was significantly lower than that of a patient with a higher CT score.
All figures (7)
Figure 7
Figure 7
(A) Receiver operator characteristic (ROC) curve of prediction of the onset of barotrauma from high-resolution CT score. ROC curve identified the optimal cut-off value of 235 determined by the Youden Index for prediction of barotraumas onset with 73% sensitivity and 77% specificity (area under the curve, 0.77; 95% CI 0.59 to 0.95). (B) Comparison of the incidence of barotraumas between patients with the optimal cut-off value of CT score identified from ROC curve. The incidence of barotrauma of a patient with a lower CT score was significantly lower than that of a patient with a higher CT score.

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