Open research questions in Respiratory Support and Mechanisms

What the literature leaves open

• BACKGROUND High-flow nasal cannula (HFNC) therapy is increasingly used for infants with bronchiolitis on general pediatric wards, yet factors associated with pediatric intensive care unit (PICU) transfer and escalation beyond HFNC remain poorly defined.

  From Floor to Intensive Care Unit: Unpacking the Real Impact of High-Flow Nasal Cannula on Bronchiolitis Triage · 2026 · DOI

• Taken together, although the proportion of evaluable recordings in this validation study was limited, the real-world applicability of the method is likely to be broader; its feasibility and robustness in unselected, spontaneously breathing patients nevertheless remain to be confirmed prospectively.

  Non-invasive estimation of inspiratory muscle pressure and work of breathing by airway pressure extrapolation from the P0.1 maneuver during assisted ventilation · 2026 · DOI

• However, the physiological effects of specific bedside postures, including the hands-on-knees and tripod positions, have not been fully characterized using EIT in spontaneously breathing individuals.

  Effects of Resting Posture on End-Expiratory Lung Impedance and Regional Ventilation Distribution, Assessed Using Electrical Impedance Tomography · 2026 · DOI

• A multidisciplinary team dedicated to physiologic assessment has emerged to support complex ventilatory management, yet factors influencing its recognition, understanding, and utilization within large ICU systems remain unknown.

  Advancing Precision Respiratory Physiology in Critical Care: A 10-Year Survey of the Lung Rescue Team · 2026 · DOI

• Future research should focus on the following priority areas. The nine frugal innovations listed in Table 4 should be validated in larger multi-center trials, and the emerging innovations in supplementary Table 2B require particular attention for validation. The combined effect of FANCAS plus the ABCDEF bundle (Table 5) should be studied in ARDS patients.

  FANCAS nursing framework for ARDS: A systematic review and synthesis · 2026 · DOI

• This review has several limitations. Heterogeneity in nursing outcome definitions precluded quantitative pooling. Most evidence was moderate to low quality. Publication bias may exist because negative studies on nursing interventions are less likely to be published. The framework requires prospective clinical validation. The review was limited to English and Thai language publications, so relevant studies published in Chinese, Spanish, or Portuguese may have been missed. This is particularly relevant for generalizability to East Asia and Latin America. Future systematic reviews should include Chinese databases such as CNKI and Wanfang, as well as Lilacs for Latin American literature. The FAST-HUG-BID-C checklist has not been validated in clinical practice. The original FANCAS framework from 1979 was based on expert opinion rather than empirical evidence.

  FANCAS nursing framework for ARDS: A systematic review and synthesis · 2026 · DOI

• level 11. Exercise intensity: The intensity of exercise should take into account clinical efficacy, individual tolerance, age, and previous conditions (19, 20). 12. The specific intensities are as follows (10, 19, 31, 32). (1) Bed bicycle activity: up to 1 h per day, twice a day.

  Early mobilization to prevent ICU-acquired weakness in mechanically ventilated patients: an integrative review · 2026 · DOI

• This study synthesized evidence on early mobilization to prevent ICU-AW in critically ill patients. However, most of the included evi- dence was derived from studies conducted in different countries and healthcare systems, which may limit its direct applicability to specific clinical settings. The evidence should be adapted to the local clinical context, available resources, and patients’ preferences. Healthcare pro- fessionals are encouraged to use the evidence identified in this review as a flexible framework for context-specific implementation. In addi- tion, this study only included English and Chinese literature, and rel- evant studies in other languages may have been missed.

  Early mobilization to prevent ICU-acquired weakness in mechanically ventilated patients: an integrative review · 2026 · DOI

• Current Limitations and Implementation Challenges: ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT Several limitations and challenges remain to be addressed before patient- specific computational tools can be widely adopted in clinical practice. In the case of data-driven predictive models, the required level of accuracy of the underlying machine learning models is also currently an open question.

  Computational tools for personalizing treatment of acute respiratory failure, from machine learning to digital twins: a narrative review · 2026 · DOI

• This study has several limitations. First, double trigger- ing was identified by ventilator waveform analysis alone, without concurrent esophageal pressure (Pes) or electri- cal activity of the diaphragm (EAdi) monitoring, which are the gold standards for physiologic confirmation of patient–ventilator asynchrony. Therefore, misclassifi- cation cannot be excluded, and the findings should be interpreted as applying to waveform-defined double trig- gering rather than physiologically confirmed asynchrony. Second, the sample size was small, which limits statis- tical power, reduces the stability of ROC-derived cutoff values, and restricts generalizability. Therefore, the pro- posed thresholds should be considered exploratory and should not be extrapolated to broader ICU populations without external validation. Third, the correction of double triggering was not stan- dardized. Different ventilator adjustments, with addi- tional sedation and/or analgesia titration when clinically indicated, were applied according to bedside judgment, often in combination. As a result, the observed changes in diaphragmatic ultrasound parameters should be inter- preted as reflecting overall restoration of synchrony rather than the isolated effect of any single intervention. Fourth, sedation and analgesia remain potential con- founders because they may influence diaphragmatic contractility, inspiratory drive, thickening fraction, and excursion duration, thereby affecting diaphragmatic ultrasound measurements and their interpretation. Fifth, driving pressure was not systematically calcu- lated in this study. In the pressure-control subgroup, PEEP was fixed and applied inspiratory pressures did not differ significantly between states, rendering any calcu- lated airway driving pressure essentially unchanged. In the volume-control subgroup, accurate plateau pressure measurements were unavailable at both time points due to severe patient-ventilator asynchrony and spontaneous respiratory efforts. Consequently, our findings lack data on transpulmonary or airway driving pressures, which could have provided additional physiological insights into the transition from asynchrony to synchrony.

  Diaphragmatic ultrasonography parameters during waveform-defined double triggering asynchrony in mechanically ventilated critically ill patients · 2026 · DOI

• Based on the findings of the present study, the following recommendations are proposed: 1. Similar studies may be conducted with larger sample sizes to enhance the generalizability of the findings. 2. Multi-center studies may be undertaken in different hospitals and clinical settings to compare outcomes across institutions. 3. Randomized controlled trials may be conducted to compare the effectiveness of various teaching strategies, such as individual teaching, group teaching, and audiovisual methods. 4. Longitudinal studies may be carried out to assess long-term retention of knowledge and sustained adherence to incentive spirometry. 5. Future research may evaluate the effect of planned teaching programs on clinical outcomes such as incidence of postoperative pulmonary complications, duration of hospital stay, and patient satisfaction. 6. Educational materials such as videos, illustrated booklets, and multilingual handouts may be developed and tested to improve patient understanding and engagement. IJFMR260378814 Volume 8, Issue 3, May-June 2026 15 International Journal for Multidisciplinary Research (IJFMR) E-ISSN: 2582-2160 ● Website: www.ijfmr.com ● Email: [email protected] 7. Similar interventions may be evaluated among patients undergoing other major surgeries, such as thoracic, abdominal, and orthopedic procedures.

  Effectiveness of a Planned Teaching Program on Knowledge and Practice Regarding the Use of Incentive Spirometry Among Patients Undergoing Cardiac Surgery at Apollo Excelcare Hospital · 2026 · DOI

• Finally, given the observational nature of the study, causality cannot be inferred, and the clinical integration of EIT-based clustering remains to be tested in properly designed trials.

  Identification of physiological clusters in acute hypoxemic respiratory failure patients undergoing non-invasive respiratory support using EIT-based t-SNE and spectral clustering · 2026 · DOI

• Several limitations should be considered when interpret- ing these findings. The observational design does not allow causal inference regarding the relationship between mechan- ical power and mortality, and residual confounding cannot be excluded despite multivariable adjustment. In addition, the relatively limited number of outcome events compared with the number of covariates may have reduced the preci- sion of the multivariable estimates, as reflected by the wide confidence intervals observed in some models. This may also have affected model stability and the reliability of the estimated effect sizes. Accordingly, the observed independ- ent associations should be interpreted with caution and are best considered hypothesis-generating rather than definitive. Physiological and ventilatory measurements were obtained at a single early time point. Mechanical power represents a dynamic exposure that may evolve over the course of ill- ness, and this analysis does not account for cumulative or time-weighted exposure or changes in ventilatory manage- ment over time. This may attenuate the strength of observed associations and preclude a more precise evaluation of tem- poral relationships between mechanical power and clinical outcomes. Ventilator-free days represent a composite out- come influenced by the competing risk of mortality, and correlation-based analyses should therefore be interpreted with caution. The number of subjects with severe PARDS in the present cohort was relatively small, which may partly explain the lower mortality observed in this subgroup com- pared with previously reported PARDS cohorts. Although the direction of the associations remained consistent across analyses, external validation in larger and independent pedi- atric cohorts is required. Mechanical power was calculated using a simplified equation for pressure-controlled ventila- tion, which may not fully capture the complexity of pressure and flow waveforms. Normalization of mechanical power to body surface area was prespecified as exploratory; although this approach demonstrated consistent associations in uni- variable and physiological analyses, its clinical relevance and generalizability require confirmation across broader age ranges and ventilatory strategies. Finally, the study was conducted in tertiary pediatric intensive care units with advanced monitoring capabilities. European Journal of Pediatrics (2026) 185:393 Page 11 of 12 393 Therefore, the applicability of transpulmonary-based indi- ces may be limited in centers without routine esophageal manometry. Although esophageal pressure measurements were part of routine practice at the participating centers, exclusion of patients without reliable measurements or complete datasets may have introduced selection bias. While transpulmonary measurements provide a more direct assessment of lung-specific mechanics, their rou- tine use remains limited in many clinical settings. In this context, airway compliance-normalized mechanical power, derived from routinely available ventilator parameters, may represent a more broadly applicable surrogate for estimating ventilatory stress. The consistency of findings between airway and transpulmonary indices supports the potential clinical utility of airway-based measures, while transpulmonary measurements may offer additional physi- ological refinement in specialized centers.

  Association of compliance-normalized airway and transpulmonary mechanical power with mortality in PARDS · 2026 · DOI

• National leadership ■ The Department of Health should provide clear, consistent and sustained Ministerial and Board level leadership on the use of technology in health care.

  Cost-Effectiveness of Internet of Things-Based Management of Home Noninvasive Positive Pressure Ventilation in Patients With Chronic Obstructive Pulmonary Disease and Hypercapnic Chronic Respiratory Failure: Trial-Based Economic Evaluation. · 2026 · DOI

• While the existing classes and rules support therapy recom- mendations and outcomes, the scope of the NIRS ontology is limited to acute and decompensated chronic conditions.

  Development and evaluation of an ontology for non-invasive respiratory support in acute care · 2026 · DOI

• Our study has several limitations. First, the definition of the SWRL rule relies on guideline-based clinical scenarios, with expert review by an intensivist. However, the ontology has not been tested with retrospective analysis to measure its PLOS One | https://doi.org/10.1371/journal.pone.0348199 May 4, 2026 12 / 15 predictive accuracy. Second, although our ontology captures basic temporal concepts (e.g., duration), it does not fully rep- resent complex, continuous time-series trends such as rapid desaturation over minutes, which are vital for real-time mon- itoring. Third, the thresholds in our rules (e.g., FiO₂ ≥ 0.40 for COPD) are derived from specific guidelines listed in the S1 Appendix and may not align with local protocols or clinical gray zones. These thresholds are flexible and can be updated as new information becomes available. Fourth, the ontology was internally validated using eICU data from 2014–2015. While the clinical concepts are still relevant, new modalities or interfaces developed after 2015 may require updates to the class hierarchy.

  Development and evaluation of an ontology for non-invasive respiratory support in acute care · 2026 · DOI

• The persistent inflammation, immunosuppression, and catabolism (PIICS) syndrome has been described in trauma patients, but specific interventions targeting the compensatory anti-inflammatory response (CARS) phase to prevent secondary pneumonia in this population require clinical trial development and validation.

  The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia · 2026 · DOI

• Supine body positioning has been identified as a risk factor for ventilator-associated pneumonia in mechanically ventilated patients, but the specific effects of patient positioning on microaspiration and bacterial colonization in trauma patients with multiple rib fractures and altered chest wall mechanics have not been rigorously studied.

  The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia · 2026 · DOI

• The molecular fingerprint of lung inflammation following blunt chest trauma has been partially characterized, but longitudinal profiling of danger-associated molecular patterns (DAMPs), inflammatory mediators, and their kinetics in relation to pneumonia development requires systematic investigation in trauma cohorts.

  The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia · 2026 · DOI

• Early mobilization has shown promise in reducing pneumonia incidence in traumatic brain injury patients, but optimal mobilization protocols, timing of intervention initiation, and efficacy in polytrauma patients with multiple thoracic injuries remain undefined and require prospective randomized controlled trials.

  The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia · 2026 · DOI

• Diaphragm injuries represent a diagnostic challenge in trauma patients with rib fractures, yet the relationship between diaphragmatic dysfunction and pneumonia development in the context of blunt chest trauma has not been systematically investigated with standardized diagnostic protocols.

  The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia · 2026 · DOI

• The brain-lung axis has been identified as a potential contributor to trauma-associated pneumonia following isolated brain injury, but the specific neuroimmune pathways linking acute brain trauma to altered respiratory immune function and pneumonia development have not been systematically characterized in clinical cohorts.

  The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia · 2026 · DOI

• While neutrophil dysfunction and neutrophil extracellular trap (NET) formation have been implicated in trauma-associated pneumonia pathogenesis, the specific molecular mechanisms linking extrathoracic multiple trauma-induced neutrophil dysregulation to gram-negative pneumonia susceptibility require further mechanistic characterization in animal models of combined trauma and secondary lung infection.

  The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia · 2026 · DOI

• The study presents SI distribution data (60% linear, 20% downward concave, 20% upward concave) from a single pediatric critical illness cohort but does not stratify findings by underlying etiology (neurological insult 36%, pneumonia 30%, septic shock 22%, CHD 12%). Research should examine whether stress index curve phenotypes differ across specific disease etiologies to enable etiology-tailored ventilation strategies.

  Stress Index in Pediatric Critical Illness: A Tool from Ventilator Graphics · 2026 · DOI

• The paper references a real-time stress index estimation tool for low-cost mechanical ventilators (Caballero et al., 2022) but does not validate this automated approach against visual SI inspection in the pediatric population. Implementation studies are needed to test whether real-time SI estimation software on bedside ventilator displays improves timely identification of harmful ventilator settings and reduces VILI in mechanically ventilated children.

  Stress Index in Pediatric Critical Illness: A Tool from Ventilator Graphics · 2026 · DOI

Most-cited papers in Respiratory Support and Mechanisms

• Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries · JAMA · 2016 · 4,709 citations
• Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy · JAMA · 2020 · 1,731 citations
• A Randomized Trial Comparing Lung-Volume–Reduction Surgery with Medical Therapy for Severe Emphysema · New England Journal of Medicine · 2003 · 1,543 citations
• Characteristics and Outcomes in Adult Patients Receiving Mechanical Ventilation<SUBTITLE>A 28-Day International Study</SUBTITLE> · JAMA · 2002 · 1,363 citations
• Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19 · JAMA · 2020 · 1,086 citations
• Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome · JAMA · 2008 · 1,080 citations
• Management of COVID-19 Respiratory Distress · JAMA · 2020 · 879 citations
• Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome · JAMA · 2017 · 798 citations
• Acute Lung Injury – From Pathophysiology to Treatment · Physiological Research · 2021 · 113 citations
• Individualized Treatment Effects of Oxygen Targets in Mechanically Ventilated Critically Ill Adults · JAMA · 2024 · 111 citations

Most recent work

• Prophylactic noninvasive ventilation after extubation in high-risk patients without hypercapnia · Intensive Care Medicine · 2026
• Safety principles of lowering inspiratory pressure · Journal of Clinical Sleep Medicine · 2026
• Risk heterogeneity within hypoinflammatory acute respiratory failure: continuous probabilities identify high-risk patients masked by binary classification · Intensive Care Medicine · 2026
• The Association Between Mechanical Power and Mortality in Critically Ill Patients Receiving Invasive Mechanical Ventilation: A Systematic Review and Meta-Analysis · Critical Care Medicine · 2026
• Prone Positioning in Infants With Acute Bronchiolitis · JAMA · 2026
• The Role of Duffy Antigen Receptor for Chemokines in Acute Respiratory Distress Syndrome · Journal of Leukocyte Biology · 2026
• Physiological dissociation between ventilatory ratio and ventilatory efficiency in patients with ARDS · Intensive Care Medicine Experimental · 2026
• Positive end-expiratory pressure increases intracranial pressure but does not affect PRx, regardless of body position, in a porcine ARDS model · Frontiers in Physiology · 2026
• Transferability and integration of physics-informed neural network models for scalable multi-zone occupant-centric ventilation control · Building and Environment · 2026
• Continuous-flow ventilation with VENTIJET in moderate ARDS: a pilot safety and feasibility study · Intensive Care Medicine Experimental · 2026

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