Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis

Bos, Lieuwe D. J.; Schouten, Laura R. A.; Vught, Lonneke A. van; Wiewel, Maryse A.; Ong, David S. Y.; Cremer, Olaf L.; Artigas, Antonio; Martín‐Loeches, Ignacio; Hoogendijk, Arie J.; Poll, Tom van der; Horn, Janneke; Juffermans, Nicole P.; Calfee, Carolyn S.; Schultz, Marcus J.

doi:10.1136/thoraxjnl-2016-209719

Cited by 237 publications

(240 citation statements)

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“…A recent study, using alternative methods to identify subgroup in ARDS, suggests that a hyper-inflammatory subphenotype also exists in observational cohorts. [41] Further studies needed to confirm these findings using LCA.…”

Section: Discussionmentioning

confidence: 99%

Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

et al. 2018

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Purpose: Using latent class analysis (LCA), we have consistently identified two distinct subphenotypes in four randomized controlled trial cohorts of ARDS. One subphenotype has hyper-inflammatory characteristics and is associated with worse clinical outcomes. Further, within 3 negative clinical trials, we observed differential treatment response by subphenotype to randomly assigned interventions. The main purpose of this study was to identify ARDS subphenotypes in a contemporary NHLBI Network trial of infection-associated ARDS (SAILS) using LCA and to test for differential treatment response to rosuvastatin therapy in the subphenotypes. Methods: LCA models were constructed using a combination of biomarker and clinical data at baseline in the SAILS study (n=745). LCA modeling was then repeated using an expanded set of clinical class-defining variables. Subphenotypes were tested for differential treatment response to rosuvastatin. Results: The 2-class LCA model best fit the population. 40% of the patients were classified as the “hyper-inflammatory” subphenotype. Including additional clinical variables in the LCA models did not identify new classes. Mortality at Day 60 and Day 90 was higher in the hyper-inflammatory subphenotype. No differences in outcome were observed between hyper-inflammatory patients randomized to rosuvastatin therapy versus placebo. Conclusions: Using LCA, a 2-subphenotype model best described the SAILS population. The subphenotypes have features consistent with those previously reported in 4 other cohorts. Addition of new class-defining variables in the LCA model did not yield additional subphenotypes. No treatment effect was observed with rosuvastatin. These findings further validate the presence of two subphenotypes and demonstrates their utility for patient stratification in ARDS.

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Section: Discussionmentioning

confidence: 99%

Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

et al. 2018

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“…One of the major disadvantages of such a data-driven approach is the danger of over-fitting to the specific dataset. Importantly, very similar phenotypes were found independently in a group of ARDS patients that was separated in time and place, and analysed using an alternative approach [67]. Progress in the identification of specific phenotypes is not only seen in ARDS, but also in other problems frequently encountered in the intensive care unit, such as sepsis and failure to wean [68][69][70].…”

Section: Ineffective Interventionsmentioning

confidence: 99%

ARDS: challenges in patient care and frontiers in research

2018

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This review discusses the clinical challenges associated with ventilatory support and pharmacological interventions in patients with acute respiratory distress syndrome (ARDS). In addition, it discusses current scientific challenges facing researchers when planning and performing trials of ventilatory support or pharmacological interventions in these patients.Noninvasive mechanical ventilation is used in some patients with ARDS. When intubated and mechanically ventilated, ARDS patients should be ventilated with low tidal volumes. A plateau pressure <30 cmH 2 O is recommended in all patients. It is suggested that a plateau pressure <15 cmH 2 O should be considered safe. Patient with moderate and severe ARDS should receive higher levels of positive endexpiratory pressure (PEEP). Rescue therapies include prone position and neuromuscular blocking agents. Extracorporeal support for decapneisation and oxygenation should only be considered when lungprotective ventilation is no longer possible, or in cases of refractory hypoxaemia, respectively. Tracheotomy is only recommended when prolonged mechanical ventilation is expected.Of all tested pharmacological interventions for ARDS, only treatment with steroids is considered to have benefit.Proper identification of phenotypes, known to respond differently to specific interventions, is increasingly considered important for clinical trials of interventions for ARDS. Such phenotypes could be defined based on clinical parameters, such as the arterial oxygen tension/inspiratory oxygen fraction ratio, but biological marker profiles could be more promising.

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“…Computer algorithms may be of help in translating complex datasets of different variables in distinct ARDS "phenotypes" that are likely to benefit from different therapeutic ventilatory and non-ventilatory strategies. For example, it seems that the "inflammatory" phenotype is likely to respond to higher PEEP and conservative fluid management while the "hypo-inflammatory" phenotype could be harmed by this intervention [13].…”

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confidence: 99%

Highlights in acute respiratory failure

Scala

Heunks

2018

Eur Respir Rev

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@ERSpublications ARF management requires an escalation therapeutic strategy based on application of a wide range of ventilatory and non-ventilatory interventions; there are many unanswered questions that need to be addressed in the near future http://ow.ly/xbPi30iUP2y Acute respiratory failure (ARF) is a devastating condition for patients that results from either impaired function of the respiratory muscle pump or from dysfunction of the lung. ARF is a challenging field for clinicians working both within and outside the intensive care unit (ICU) and respiratory high dependency care unit environment because this heterogeneous syndrome is associated with a high hospital morbidity and mortality rate, ethical issues in managing end of life decisions and increased consumption of healthcare resources.In acute hypercapnic respiratory failure (i.e. pump failure) an imbalance exists between the load imposed on the respiratory muscles and the capacity of the muscle pump [1]. This category mainly includes patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), as well as patients with neuro-miopathies, chest wall deformities and obesity. The in-hospital mortality of patients hospitalised for COPD exacerbation is 2-8% (up to 15% for ICU patients), with a 1-year mortality of 22-43%. Readmissions after hospitalisation for an exacerbation are frequent events, ranging from 14% to 16% in the first month after discharge and 25-58% in the first year [2].Acute hypoxaemic failure covers miscellanea of causes of lung damage including acute cardiogenic pulmonary oedema, pneumonia and trauma. Acute respiratory distress syndrome (ARDS) is a frequent cause of severe hypoxaemia. This clinical syndrome is characterised by acute inflammatory lung injury, associated with increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue [3]. In its most severe form (arterial oxygen tension/inspiratory oxygen fraction <100 mmHg), hospital mortality is ∼42% [3]. The insight in the pathophysiology of acute hypoxaemic failure has improved over the past decade. This has important consequences for treatment and monitoring of patients with ARF.The management of ARF may require an "escalation therapeutic strategy" based on the application of a wide range of ventilatory and non-ventilatory interventions (figure 1) [1, 4]. The rationale for applying these artificial supports is essentially to buy time for the aetiological therapy to reverse the cause of the acute decompensation of the respiratory system while avoiding/minimising the potential lung injuring effects of therapeutic interventions, such as ventilator-induced lung injury. In noninvasive ventilation (NIV) a dedicated interface is used, while with invasive mechanical ventilation (IMV) assistance is provided through an endotracheal tube or tracheostomy. New therapeutic options include high-flow nasal cannula [5], noninvasive and invasive cough assist strategies, high-frequency chest wall oscillation, and

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Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis

Cited by 237 publications

References 41 publications

Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

ARDS: challenges in patient care and frontiers in research

Highlights in acute respiratory failure

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