This study reports the results of pulmonary assessment performed 1 year after PICUD of a group of children survivors of ARDS, with a clear distinction being made between p-ARDS and ep-ARDS. This is the first study describing CT abnormalities of lung parenchyma in children < 17 years old, with a relatively large study population compared to the available literature on adults [13,14,15,16,17]. The majority of children who were mechanically ventilated for ARDS expressed respiratory symptoms and presented CT-scan and PFT abnormalities. The severity of ARDS as indicated by physiologic parameters/ventilator settings during the PICU stay was correlated with CT scan and PFTs abnormalities at the 1-year assessment. Respiratory symptoms were reported in as much as 74% of children surviving to p-ARDS, and, sequelae observed on thoracic CT scan were important in some children, all in the p-ARDS group.
Based on the oxygen deficit (oxygenation index collected at H24 after admission for ARDS in PICU) our population consisted of mild-to-severe paediatric ARDS [3, 6]. Sixty-two percent of the 37 children in whom VTE was reported were ventilated with VTE within the 5–8 ml/kg recommended VTE range, 38% of the 37 children with VTE within the 3–6 ml/kg recommended VTE range for patients with poor Crs [12] in order to tend to a lung-protective ventilation strategy. A trend to lower VTE in the patients with poorer Crs was observed in our study. Fourteen out of the 37 children (38%) were ventilated within the 9–15 ml/kg range. In this latter group, the possibility cannot be ruled out that these high volumes contributed to some degree of volutrauma. Ventilator setting in the patients of our study did not perfectly follow the recommendations for lung-protective ventilation strategy, but were in agreement with usual care mechanical ventilation practice for paediatric ARDS [18]. Indeed, maximal VTE values/kg (using actual body weight) during the whole PICU stay were slightly lower than those observed during the first 72 h of mechanical ventilation in a multicentre study assessing variability in usual care mechanical ventilation practice for paediatric ARDS [18]. Median maximal PEEP was within the recommended ranges [12] and median maximal plateau pressure (Pplat) was higher than recommended limit value (28 cmH2O) [12]. Mean highest PEEP in p-ARDS and ep-ARDS groups were 1 cmH2O higher and 4 cmH2O higher, respectively, than those reported in the previous study [18] and maximal PImax was ≤ 40 cmH2O in 42% children in our study versus 99% in that study [18].
We must underline that the number of children with ep-ARDS is small, however respiratory symptoms at rest or exercise and/or requirement for respiratory maintenance treatment during the year following the PICU hospitalization were sixfold more frequent in children with p-ARDS, than in those with ep-ARDS with more frequent wheezing episodes in the former group. Lower respiratory tract infections and wheezing episodes persisted up to a median time after PICUD of, respectively, 10 months and 12 months. Boucher et al. reported abnormal respiratory symptoms (cough, wheezing with or without upper respiratory infections, respiratory symptoms on exertion) in fewer (37%) of children 3 months after PICUD though the majority of children (76%) had suffered from ARDS of respiratory infectious aetiology [2]. Chakdour et al. noticed respiratory symptoms (chronic cough ± dyspnoea) in a similar percentage (68%) of children, all with p-ARDS, 3 months after discharge [19] though none had respiratory symptoms 9–12 months after discharge. It should be noted that both studies included patients with less-severe ARDS, as assessed by PALICC criteria and patients’ characteristics.
On CT scan at 1-year follow-up, in our group of ep-ARDS, all abnormalities were observed in the anterior lung parenchyma, with septal reticulations pattern in 13% of children and ground glass opacities pattern in 13% of children. Nöbauer et al., in adults with primary thoracic trauma, also observed that CT scan lesions were predominantly located in the ventral zone [17]. Desai et al. assessing adult ARDS survivors, 6.5 months after the acute phase, underlined that the most common abnormality observed in thoracic CT scan of ARDS survivors (mostly ep-ARDS) was a reticular pattern with predilection in the anterior nondependent zone, and that its extent was related to the duration of mechanical ventilation [16]. A reticular pattern was observed by these authors in a higher proportion of patients (85%) than in our study, but the mean duration of mechanical ventilation was longer in their population [16].
Ground glass opacification in survivors is supposed to represent fine intralobular fibrosis below the resolutions limits of CT scans [16]. In another study by Desai et al., in adults, the extent of reticular pattern and ground glass opacification were negatively correlated with FVC, but positively correlated with the ratio of residual volume to total lung capacity [20].
Howling et al. in adults ARDS reported that dilated bronchi observed during the acute phase in 68% of the analysed lobes persisted in the majority (92%) at 6-month follow-up, often (88%) accompanied by CT features of supervening pulmonary fibrosis (reticular distorting pattern) [14]. Reticular pattern were observed in less than 20% of our cohort of child ARDS survivors. Bronchiectasis was also less likely in our cohort (21%) than in adults.
In our study, CT-scan abnormalities of p-ARDS were diffuse (both anterior and posterior). This less classical diffuse distribution of abnormalities, with areas of reticular pattern and ground-glass opacification, was observed in adults after ARDS (63% of intrapulmonary origin) [15].
In 5 of our children, all with p-ARDS, the ground glass opacities pattern and the mosaic perfusion pattern were more widespread. Kim et al. in adults also observed that, although the mean extent of lesions in all patients was mild (averaging 15.3% of the total lung volume), the lesions were more extensive in the p-ARDS than the ep-ARDS group [4]. They speculated that, due to differences in lung mechanics in the early stage of ARDS and the refractory nature of p-ARDS with respect to alveolar recruitment, p-ARDS may be more vulnerable to ventilator-induced lung injury compared with ep-ARDS, leading to more important sequelae in the long-term [4].
We found a mosaic perfusion pattern in 23% of children with p-ARDS but in none of ep-ARDS cases. Decreased attenuation consistent with a mosaic pattern was observed in 13% of ARDS adults [13], and decreased attenuation due to small airway disease in 11% of ARDS patients [16]. Disease of the lung prior to ARDS may have contributed to the observed anomalies. In 2 of the previously mentioned studies 33% and 42% of patients were smokers, respectively [13, 17]. The authors underlined that pre-existing diseases of the lung, such as smoking-related emphysema or post-infection scarring, were excluded by clinical history only not by imaging modality in their study. In other studies in adults [4, 15] and the present study, patients with previous respiratory disease or neurologic injury have been excluded in an attempt to better isolate the contribution of ARDS itself to morbidity.
PFT abnormalities were observed in 86% of this cohort including a lung hyperinflation and/or an obstructive pattern, restrictive abnormalities, a mild decrease in diffusing capacity. Important abnormalities were observed in 7 children, all with p-ARDS.
Adult survivors of ARDS may have abnormalities in pulmonary function and exercise endurance which can persist for up to 5 years [21]. A decreased 6-min-walking distance was observed at 3 months; though this last improved at 1 year [22]. In our cohort, a decrease in the 6-min-walking distance was observed in 11/15 children, desaturation at the end of the 6-min-walk test was observed in 1 child and decrease in inspiratory muscle strength in 2/13 children.
Few paediatric studies report the long-term pulmonary function of ARDS survivors [19, 23, 24] and they are often of a smaller size than our study. Abnormalities in PFT were observed in a larger proportion of our cohort (86%) than in the study of Ward et al. (37% of children), 10.7 months after p- or ep-ARDS, but ARDS in their cohort was less severe (based on the PaO2/FiO2 ratio and the PICU length of stay) [23].
Contrary to our study, Ward et al. [23] observed some obstructive—but no restrictive abnormalities in children with p- and ep-ARDS. In Chakdour et al.’s study, conducted at 9–12 months after discharge, 19% of children exhibited a restrictive pattern [19]. In a smaller sample study of 7 children with ARDS, followed up for a mean duration of 5.6 years after PICUD, PFT were within normal limits except for one child with mildly reduced TLCO and another with exercise-induced hypoxemia [24]. In none of the above-mentioned paediatric studies evaluating PFT was a CT scan performed.
Strength and limitations
The strengths of our study include its prospective design, its consistent follow-up time, the inclusion of children covering a large range of ages at the 1-year assessment, its inclusion of a significant proportion of severe paediatric ARDS with greater potential for persistent pulmonary dysfunction, and its screening for thoracic CT-scan abnormalities—to our knowledge, this is the first study describing CT abnormalities of lung parenchyma in children < 17 years of age surviving ARDS. Our study also discriminates respiratory sequelae deriving from p-ARDS and ep-ARDS—it has been shown in an adult group of patients that p-ARDS were more likely to develop pulmonary fibrosis [4]. The respiratory sequelae observed in the group of children with ep-ARDS need further confirmation as the number of children in this group was small.
Limitations of our study are that PFT outcome measures differed in older and younger children, since PFT assessment was adapted to developmental ability and cooperation (for example, in children less than 7 years of age, tests requiring no active cooperation were used in 2.5–6-year-old children or were performed during sleep in less than 2.5 years of age patients), and that dynamic lung compliance was not assessed in all children.
In conclusion, children surviving ARDS requiring mechanical ventilation present frequent respiratory symptoms, significant CT-scan and PFT abnormalities 1 year after PICUD. This strongly highlights the need for a systematic pulmonary assessment at 1 year of these children.
