Recruitment maneuvers (RMs) during invasive mechanical ventilation (IMV) for acute hypoxemic respiratory failure are not characterized in pediatrics. We aimed 1) to describe changes in oxygenation, dynamic compliance, and outcome related to RMs; and 2) to identify which patients may benefit from RMs using machine learning. Single center, retrospective cohort study, 2016-2023. Quaternary PICU in Montreal, Canada. We included all IMV patients between May 2016 and May 2023 who received at least one RM. None. We identified 479 patients who had a total of 8276 RMs. We studied change in Pao2 to Fio2 (Pao2/Fio2) ratio and dynamic compliance data from before and 90 minutes after the RM. In a multivariable model, baseline Pao2/Fio2 ratio (OR, 0.99 [95% CI, 0.99-1.00]; p = 0.004) and initial positive end-expiratory pressure (PEEP) level (OR, 1.14 [95% CI, 1.00-1.31]; p = 0.046) were independently associated with oxygenation response. Recruitment delta in pressure was associated with lower odds of compliance response (OR, 0.93 [95% CI, 0.90-0.97]; p < 0.001). Patients with PEEP lower than that described as "low" in the PEEP-Fio2 tables, vs. those not in this category, had greater odds of oxygen response (OR, 3.33 [95% CI, 1.49-7.73]; p = 0.004). We failed to identify an association between improved oxygenation or dynamic compliance vs. not and ventilator-free days, duration of IMV or PICU length of stay, and PICU mortality. In our 2016-2023 PICU cohort of IMV pediatric cases, we found various associations following RMs. Importantly, there was more than a three-fold greater odds of responsiveness associated with having a lower PEEP relative to Fio2 than that described in the recommended practice tables. These data may help decision-making during IMV when lower PEEP is used.

Biological subphenotypes in severe acute hypoxaemic respiratory failure and acute respiratory distress syndrome using rapid prospective classification (SPARC) in the USA: a multicentre, observational, study.

Although the use of high-flow nasal cannula (HFNC) is recommended for the management of acute hypoxemic respiratory failure and for postextubation respiratory support, the efficacy for other etiologies remains uncertain. This study aimed to examine temporal trends in HFNC utilization and describe variations in clinical practice and clinical course across diverse disease categories and care settings. We conducted a retrospective cohort study using a nationwide in-patient database in Japan. Hospitalized subjects who received HFNC between April 2016 and March 2023 were included. Temporal trends in HFNC use were evaluated by fiscal year using the Cochran-Armitage test. Subjectcharacteristics, disease categories, treatment location at HFNC initiation (ICU, high-dependency unit, or general ward), timing of HFNC initiation, use of invasive mechanical ventilation, and in-hospital mortality were analyzed descriptively. A total of 277,279 subjects received HFNC during the study period. The annual rate of HFNC use per 1,000 admissions increased from 2.0 in 2016 to 8 in 2022 (P < .001). Respiratory diseases were the most common indication (37%), followed by cardiovascular diseases (23%), neonatal conditions (17%), and malignancy (10%). HFNC was frequently used in conjunction with invasive mechanical ventilation, particularly after extubation, among subjects with cardiovascular conditions and neonatal subjects. In contrast, HFNC was more often used without invasive mechanical ventilation in subjects with respiratory diseases or malignancy, frequently in general wards. Overall in-hospital mortality was 25% and varied markedly by disease category and care setting, with particularly high mortality among subjects with interstitial pneumonia or malignancy who initiated HFNC in general wards, approaching 60%. HFNC use increased markedly in Japan and expanded beyond ICUs into general wards. Utilization patterns and outcomes differed considerably by underlying disease and care setting, indicating heterogeneous clinical roles of HFNC across patient populations.

Acute hypoxemic and hypercapnic respiratory failure are among the most common reasons for ICU admission and need for invasive mechanical ventilation. Noninvasive respiratory support (NIRS) strategies-including high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and continuous positive airway pressure (CPAP)-may prevent intubation, improve outcomes, and reduce ICU utilization. However, there is uncertainty regarding optimal patient and modality selection, resulting in variable implementation. There are no clinical practice guidelines comprehensively addressing the use of the different noninvasive respiratory support strategies across the spectrum of acute respiratory failure. To update and develop new evidence-based clinical practice recommendations informing noninvasive respiratory support use, including HFNC, NIV and CPAP, in adults with acute respiratory failure. A multidisciplinary panel used the GRADE approach to address four PICO questions related to the use of NIRS for hypoxemic and hypercapnic respiratory failure, preoxygenation for intubation, and post-extubation respiratory support. Recommendations were informed by several systematic reviews and network meta-analyses. The panel made a strong recommendation for HFNC and a conditional recommendation for NIV or CPAP for adults with acute hypoxemic respiratory failure with close monitoring for the need for escalation of respiratory support, based primarily on effects on need for intubation. For acute hypercapnic respiratory failure, the panel made a strong recommendation for NIV to reduce mortality and need for invasive mechanical ventilation, and a conditional recommendation for HFNC only in patients with less severe hypercapnia and with mild acidemia (eg, pH > 7.25), provided that close monitoring and prompt escalation to NIV are available. The panel made a strong recommendation for HFNC or NIV for preoxygenation prior to endotracheal intubation to prevent peri-intubation hypoxemia. The panel also issued a risk-based recommendation, suggesting HFNC for low-risk patients and NIV for high-risk patients to reduce the need for re-intubation following extubation after critical illness. Noninvasive respiratory support strategies are effective in improving outcomes in a range of clinical scenarios. We provide evidence-based recommendations, which can be further informed by patient risk, institutional capacity, and interface tolerance.

High flow nasal oxygen for acute hypoxaemic respiratory failure in the intensive care unit: An umbrella review.

Visceral leishmaniasis (VL) is a systemic parasitic disease that predominantly involves the reticuloendothelial system, with pulmonary involvement being distinctly uncommon, particularly in individuals who are immunocompetent. We report a case of a middle-aged female who was immunocompetent presenting with acute hypoxaemic respiratory failure, characterised by progressive dyspnoea, bilateral lung consolidation and pleural effusion, initially mimicking severe pulmonary infection or haematological malignancy. The presence of pancytopenia, hypergammaglobulinaemia and massive hepatosplenomegaly raised suspicion of an underlying systemic disorder. Definitive diagnosis was established by demonstration of Leishmania donovani amastigotes in splenic aspirate, with further confirmation of direct pulmonary involvement through identification of intracellular amastigotes within alveolar macrophages on a transbronchial lung biopsy. The patient showed significant clinical and radiological improvement following treatment with liposomal amphotericin B and miltefosine. This case highlights that VL can rarely present with primary pulmonary manifestations even in immunocompetent hosts. It underscores the importance of considering VL in the differential diagnosis of unexplained pulmonary infiltrates with systemic features in endemic regions and demonstrates that histopathological confirmation from lung tissue can be crucial in establishing pulmonary involvement in atypical presentations.

Acute hypoxaemic respiratory failure is frequently attributed to primary pulmonary pathology, particularly in the presence of radiographic abnormalities and inflammatory markers. Cardiac conditions, however, may present with similar features and lead to diagnostic error. We report the case of a man in his early 60s admitted with acute hypoxaemic respiratory failure, initially diagnosed with severe community-acquired pneumonia on the basis of unilateral chest opacity and an apparent inflammatory response. Despite empirical antibiotic therapy, his respiratory status deteriorated. Bedside echocardiography identified acute severe mitral regurgitation due to rupture of the posterior mitral leaflet chordae tendineae. Targeted medical management was initiated, followed by definitive surgical repair with full clinical recovery. This case highlights the potential for acute valvular disease to mimic pulmonary infection and the importance of early echocardiographic assessment in patients with unexplained respiratory failure.

BackgroundSex-related differences have been consistently reported in the epidemiology of acute hypoxemic respiratory failure (AHRF) and COVID-19. However, whether computed tomography (CT)-derived measures of lung injury differ between sexes and contribute to outcome disparities remains unclear.MethodsIn this large multicenter retrospective cohort study, we analyzed 850 spontaneously breathing patients with COVID-19-related AHRF who underwent early chest CT at hospital admission. Quantitative CT analysis provided measures of lung density, volume, mass, and superimposed pressure (SP), a CT-derived estimate of gravitational stress. Sex-stratified analyses compared morphological, physiological, and outcome variables. Multivariable logistic regression models identified independent predictors of mortality.ResultsAmong 850 patients (35% women), men exhibited larger lung volume (2.91 vs. 2.28 L, p < 0.001), greater lung mass (1.14 vs. 0.93 kg, p < 0.001), and higher SP (5.79 vs. 5.21 cmH₂O, p < 0.001) despite similar fractions of ground-glass opacities and consolidation. In the multivariable model, older age (OR 1.08, 95% CI 1.06–1.11; p < 0.001), lower PaO2/FiO2 (OR 0.99, 95% CI 0.98–0.99; p < 0.001), higher SOFA score (OR 2.67, 95% CI 1.43–4.98; p = 0.002 for SOFA ≥ 2), higher global SP (OR 1.18, 95% CI 1.05–1.34; p = 0.005), and male sex (OR 1.76, 95% CI 1.06–2.92; p = 0.028) were independently associated with an increased risk of mortality. In the mediation analysis, the effect of global SP on mortality does not appear to be mediated by male sex (coefficient 0.00).ConclusionsMale patients with COVID-19-related AHRF exhibited higher global SP than females, reflecting greater gravitational lung load and mechanical disadvantage. Both global SP and male sex were independently associated with mortality, with no evidence of mediation of male sex on mortality. These finding suggest that, beyond anatomical and mechanical differences, biological and hormonal factors likely contribute to the increased disease severity observed in men.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40635-026-00914-4.

High-flow nasal cannula (HFNC) is commonly used for acute hypoxemic respiratory failure and for subjects at risk of postextubation failure. HFNC reduces inspiratory work, but its effects on expiratory muscle activity, including the abdominal wall muscles, are uncertain. We tested whether HFNC decreases expiratory effort in a flow-dependent manner. In this single-center, randomized, crossover trial, we enrolled 30 ICU subjects requiring HFNC. After baseline low-flow oxygen, subjects received HFNC at 30, 40, and 50 L/min in random order for 15 min each. We quantified expiratory muscle activity by ultrasound-derived thickening fractions of the lateral abdominal muscles (TFABD; external oblique + internal oblique + transversus abdominis) and rectus abdominis (TFRA). We also recorded diaphragm thickening fraction (DTF) and hemodynamic variables. Overall, HFNC did not change TFABD, TFRA, or respiratory and hemodynamic variables versus baseline. DTF decreased at 50 L/min (mean 13% vs 25% at baseline; P = .042). In exploratory analyses, subjects with higher baseline expiratory activity (TFABD > 10%) showed reduced TFABD at 40 and 50 L/min, whereas those with baseline TFABD ≤ 10% did not. Baseline TFABD correlated inversely with flow-related changes at all flows (eg, r = -0.867 at 40 L/min; P < .001). HFNC did not uniformly reduce expiratory muscle activity in this relatively stable ICU cohort. Subjects with higher baseline expiratory activity showed abdominal muscle unloading at higher flows. Bedside abdominal ultrasound may help identify subjects more likely to benefit from higher HFNC flow settings.

Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P = .04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P = .34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P = .03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P < .001). In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. ClinicalTrials.gov Identifier: NCT06343545.

BackgroundData are needed on the effect of oxygen delivered through a high-flow nasal cannula, as compared with standard oxygen therapy, on intubation and mortality in patients with acute hypoxemic respiratory failure.MethodsIn this multicenter, open-label trial, we randomly assigned patients who had acute hypoxemic respiratory failure to receive high-flow-oxygen or standard-oxygen therapy. All the patients had a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 or less, a respiratory rate of more than 25 breaths per minute, and pulmonary infiltrate on chest imaging. The primary outcome was death by day 28.ResultsA total of 1116 patients underwent randomization. Of these patients, 1110 (556 in the high-flow-oxygen group and 554 in the standard-oxygen group) were included in the analysis. Mortality at day 28 was 14.6% (in 81 of 556 patients) in the high-flow-oxygen group and 14.6% (in 81 of 554 patients) in the standard-oxygen group (difference, −0.05 percentage points; 95% confidence interval [CI], −4.21 to 4.10; P=0.98). The incidence of intubation by day 28 was 42.4% (in 236 of 556 patients) in the high-flow-oxygen group and 48.4% (in 268 of 554 patients) in the standard-oxygen group (difference, −5.93 percentage points; 95% CI, −11.78 to −0.08). Serious adverse events (cardiac arrest or pneumothorax) occurred during spontaneous breathing in 13 patients (2.3%) in the high-flow-oxygen group and in 6 patients (1.1%) in the standard-oxygen group.ConclusionsAmong patients with acute hypoxemic respiratory failure, the use of oxygen delivered through a high-flow nasal cannula did not significantly reduce mortality at day 28. (Funded by the French Ministry of Health and Fisher and Paykel Healthcare; SOHO ClinicalTrials.gov number, NCT04468126.)

The effects of high-flow nasal cannula (HFNC) and continuous positive airway pressure (CPAP) in patients with acute hypoxemic respiratory failure (AHRF) on respiratory mechanics and inspiratory efforts are not entirely understood. To compare the physiologic effects of HFNC and helmet CPAP with respect to conventional oxygen therapy (COT) in terms of respiratory mechanics, inspiratory effort, gas exchange, and hemodynamics during AHRF. Crossover study. General surgical-medical ICU of San Paolo University Hospital, Milan, Italy. Thirty-three adult patients with AHRF, defined as an Pa o2 less than 60 mm Hg or an Pa o2 /F io2 less than 300 with a positive end-expiratory pressure (PEEP) level greater than or equal to 5 cm H 2 O, along with an Pa co2 less than 45 mm Hg. After support with COT, three types of respiratory support were applied in random order: HFNC with 60 L/min of flow and helmet CPAP with 5 or 10 cm H 2 O of PEEP. Tidal volume, respiratory rate, inspiratory esophageal (ΔPes), and airway pressure swings were measured and an arterial blood gas analysis, along with hemodynamic data, was obtained after 20 minutes from the application of each respiratory support device. The application of HFNC and helmet CPAP at both 5 and 10 cm H 2 O of PEEP reduced minute ventilation (9.2 ± 3.2, 8.8 ± 2.3, and 9.3 ± 2.7 vs. 10.9 ± 3.3 L/min; p < 0.001) and ΔPes (-6.0 cm H 2 O [-7.8 to -4.0 cm H 2 O], -5.8 cm H 2 O [-7.2 to -4.5 cm H 2 O], and -5.9 cm H 2 O [-8.0 to -4.0 cm H 2 O] vs. -7.5 cm H 2 O [-10.8 to -6.5 cm H 2 O]; p < 0.001) while increasing Pa o2 /F io2 (188 ± 57, 208 ± 62, and 213 ± 69 vs. 129 ± 32; p < 0.001) with respect to COT; the application of 10 cm H 2 O of PEEP with helmet CPAP did not reduce inspiratory effort indices or increased oxygenation, but worsened mechanical power compared with HFNC and helmet CPAP with 5 cm H 2 O of PEEP. In patients with mild and moderate AHRF, HFNC and helmet CPAP ameliorated minute ventilation and respiratory rate, reduced inspiratory effort, and increased oxygenation compared with COT; the application of 10 cm H 2 O of PEEP during CPAP support worsened mechanical power.

Patient self-inflicted lung injury (P-SILI) describes a pathophysiological concept in which patients with acute hypoxemic respiratory failure (AHRF) may exacerbate lung injury through excessive respiratory drive and vigorous spontaneous breathing efforts, thereby perpetuating respiratory failure. Spontaneous breathing-related lung injury is thought to be mediated by 4 main mechanisms: 1. increased mechanical stress on lung tissue, 2. heterogeneous ventilation with intrapulmonary gas redistribution (pendelluft), 3. augmented pulmonary blood flow leading to microvascular injury, and 4. Patient-ventilator asynchrony (PVA) in the setting of non-invasive ventilation (NIV). All of these mechanisms are closely linked to an elevated respiratory drive, which primarily arises from the underlying lung pathology, particularly alveolar flooding due to plasma leakage. Clinical monitoring of respiratory effort and neural respiratory drive is possible using techniques such as esophageal pressure measurement. However, these methods are often invasive, not fully validated, time- and resource-intensive, costly, and may be associated with reduced patient comfort.In the management of acute respiratory failure, including acute respiratory distress syndrome (ARDS) and AHRF, prevention of P-SILI is essential. Recent evidence suggests that late failure of NIV followed by delayed intubation is associated with the highest mortality rates. Consequently, the choice of ventilatory support must be individualized and continuously reassessed, taking into account the risk of both P-SILI and ventilator-induced lung injury. Non-invasive ventilation, high-flow nasal cannula therapy, pharmacological interventions, and prone positioning during spontaneous breathing all have therapeutic limits that require continuous, round-the-clock evaluation. To date, robust evidence from large clinical trials regarding their impact on the prevention and treatment of P-SILI, as well as the optimal timing of intubation, remains lacking.

Prehospital high-flow nasal canula oxygen therapy in hypoxemic acute respiratory failure: an open-label, randomized controlled pilot study (PRHOXY-1).

A 75-year-old man with interstitial lung disease was admitted with an acute exacerbation and severe hypoxemic respiratory failure. During intensive care management, he developed acute myocardial infarction, required veno-venous extracorporeal membrane oxygenation and later underwent continuous haemodiafiltration for an acute kidney injury. A pulmonary embolism, gastrointestinal bleeding and intestinal perforation subsequently occurred, and the patient died of septic shock on day 40 of hospitalisation. An autopsy showed diffuse alveolar damage superimposed on a usual interstitial pneumonia pattern, intra-alveolar haemorrhage, a subacute myocardial infarction, pulmonary arterial thrombi, a terminal ileal perforation with transmural necrosis and microthrombi in the intestinal wall. This case illustrates the difficulty of balancing thrombosis and bleeding during and after extracorporeal support for an acute exacerbation of interstitial lung disease and highlights the need for early suspicion of intestinal ischaemia in patients receiving extracorporeal membrane oxygenation who exhibit unexplained anaemia, gastrointestinal bleeding, worsening sepsis, or rising lactate levels, particularly during deep sedation.

Acute hypoxemic respiratory failure (AHRF) is a major cause of morbidity and mortality and often requires advanced respiratory support. Awake prone positioning (APP) has emerged as a simple, low-cost intervention to improve oxygenation in non-intubated patients; however, its clinical effectiveness and safety remain uncertain. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of awake prone positioning in non-intubated adult patients with acute hypoxemic respiratory failure. A systematic search of PubMed, Scopus, and Web of Science was conducted from database inception to February 2026. Randomized controlled trials and observational comparative studies evaluating APP versus usual care were included. Primary outcomes were mortality, intubation, and length of hospital stay. Secondary outcomes included ICU stay, invasive mechanical ventilation, ICU admission, escalation of respiratory support, time to invasive ventilation, and adverse events. Risk of bias was assessed using ROB 2 for randomized trials and the Newcastle-Ottawa Scale for observational studies. Meta-analysis was performed using a random-effects model. Twenty-four studies involving 6,164 patients were included. APP significantly reduced mortality (OR = 0.60, 95% CI 0.42-0.86, p = 0.005), intubation (OR = 0.69, 95% CI 0.60-0.79, p < 0.00001), length of hospital stay (MD = - 0.70 days, 95% CI - 1.07 to - 0.32, p = 0.0003), ICU stay (MD = - 2.84 days, 95% CI - 5.44 to - 0.24, p = 0.03), and invasive mechanical ventilation (OR = 0.42, 95% CI 0.31-0.58, p < 0.00001). No significant differences were observed in ICU admission, escalation of respiratory support, or adverse events. Awake prone positioning was associated with improved clinical outcomes, including reduced mortality, intubation, and hospital stay, without an apparent increase in adverse events. However, these findings should be interpreted cautiously given the observed heterogeneity and potential publication bias. Further high-quality randomized trials are needed to confirm these results.

PurposeIdentifying physiological clusters in acute hypoxemic respiratory failure (AHRF) may help to personalize non-invasive respiratory support (NIRS). Electrical impedance tomography (EIT) provides real-time, regional information on tidal ventilation, but its value for clustering AHRF patients undergoing NIRS has not been established.MethodsWe conducted a single-center observational study including adults with AHRF monitored with EIT during NIRS. Tidal ventilation images were pre-processed, normalized, and embedded into a 2-dimensional space using t-SNE. Spectral clustering was applied to identify distinct imaging patterns. Clinical, physiological and laboratory variables were compared across clusters. The association between cluster membership and intubation at 7 days was assessed using penalized Cox regression adjusted for age, BMI, PaCO₂ and ROX index.ResultsThirty-two patients were enrolled. Spectral clustering identified three distinct clusters of tidal images. Clusters differed in clinical severity and physiological profile: Cluster 1 was characterized by shorter stature and higher SAPS II; Cluster 2 showed the highest pendelluft; Cluster 3 exhibited symmetric ventilation with low pendelluft. These phenotypes also differed in hemodynamics, including heart rate and shock index. Cluster membership was independently associated with intubation at 7 days. Compared with Cluster 3, both Cluster 1 and Cluster 2 showed a significantly lower hazard of intubation (HR 0.115, p = 0.017 and 0.042, p = 0.002, respectively).ConclusionsUnsupervised clustering of EIT tidal images is feasible in AHRF and identifies distinct physiological clusters with different short-term outcomes. These findings support the potential role of EIT-based imaging patterns for early stratification of patients undergoing NIRS.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40635-026-00912-6.

A middle-aged man with a history of polysubstance abuse presented with acute hypoxemic respiratory failure following self-reported ingestion of kratom and tianeptine. Initial evaluation showed significant respiratory depression, hypoxia, bilateral pulmonary infiltrates, and acute encephalopathy. Symptomatic management, naloxone administration, and ICU-level supportive care led to gradual clinical improvement. This case highlights the potential for severe respiratory and neurological compromise with combined kratom and tianeptine toxicity.

Background: Non-invasive respiratory supports (High-Flow Nasal Oxygen, HFNO; Continuous Positive Airway Pressure, CPAP; Non-Invasive Ventilation, NIV) are frequently used in Acute Hypoxemic Respiratory Failure (AHRF). However, the experience of assisted breathing may profoundly affect patients’ psychological balance, particularly during acute critical illness and subsequent rehabilitation. Aims and objectives: This longitudinal study investigated the psychological burden associated with non-invasive respiratory support use in patients with COVID-19-related AHRF, exploring changes in psychological functioning from acute hospitalization (RICU/ICU) (T0) to follow-up, conducted at a mean of 6.0 ± 3.1 months after respiratory rehabilitation (T1). Methods: Fifty-two patients (mean age = 66.9 ± 9.17 years) were assessed at T0 and T1. Standardized measures evaluated anxiety, psychological distress, post-traumatic stress symptoms, depression, and resilience, in relation to perceived illness severity and subjective experience of non-invasive respiratory support. Results: During acute care, patients reported high levels of fear and anxiety related to illness severity and uncertainty. The experience of non-invasive respiratory support, often perceived as a marker of critical condition, was associated with increased fear and anxiety (t(14) = 2.79, p = 0.014) compared to the recovery phase, leading to feelings of loss of control and diminished psychological well-being (t(17) = 2.35, p = 0.031). However, resilience significantly improved over time (t(16) = −4.78, p < 0.001). Conclusions: Non-invasive respiratory support may represent a psychologically demanding experience, often perceived as challenging to patients’ sense of safety and control. Encouragingly, psychological adaptation and resilience can improve during rehabilitation. Integrating structured psychological support within respiratory rehabilitation pathways may promote recovery and restore psychological balance in patients requiring assisted ventilation.

Acute hypoxemic respiratory failure (AHRF) is common and biologically heterogeneous. Static phenotyping at a single time point does not capture illness evolution and risks stage-mixing; reproducible clinical course archetypes may address this. We aimed to identify, externally validate, and predict trajectory classes (TCs) of persistent AHRF. We analyzed MIMIC-IV (derivation; n = 3938) and two external validation cohorts (UK/Netherlands; n = 6480) comprising adults with PaO2/FiO2 < 300mmHg and PEEP ≥ 5 cmH2O for ≥ 72h. Daily mean PaO2/FiO2 to day 14 and time to ICU discharge/death were jointly modelled using a competing-risk latent class mixed model. Early TC prediction used a 12-variable XGBoost model. We explored prevalence of ARDS and hyperinflammatory subphenotypes between TCs. A four-class model provided optimal fit: (TC1) early recovery (0.3% 14-day mortality); (TC2) stable persistence (8% 14-day mortality); (TC3) biphasic improvement-deterioration (17% 14-day mortality); and (TC4) rapid decline (100% 14-day mortality). These archetypes generalized to external cohorts with high assignment certainty. TCs demonstrated distinct patterns in other clinical biomarker trajectories. TC4 was enriched for the hyperinflammatory subphenotype (41-53%), while TC2 was most common in patients with ARDS (50%). Early TC prediction models achieved mean AUCs ≥ 0.78 (0.70-0.86) by day 3 in external validation. Four reproducible oxygenation archetypes capture the 14-day course of persistent respiratory failure. By providing early prognostic value distinct from static baseline severity, these trajectories have the potential to guide therapeutic strategies, reduce patient heterogeneity in trials, and direct biological phenotyping.