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Background We aimed to assess the efficacy of a closed-loop oxygen control in critically ill patients with moderate to severe acute hypoxemic respiratory failure (AHRF) treated with high flow nasal oxygen (HFNO). Methods In this single-centre, single-blinded, randomized crossover study, adult patients with moderate to severe AHRF who were treated with HFNO (flow rate ≥ 40 L/min with FiO 2  ≥ 0.30) were randomly assigned to start with a 4-h period of closed-loop oxygen control or 4-h period of manual oxygen titration, after which each patient was switched to the alternate therapy. The primary outcome was the percentage of time spent in the individualized optimal SpO 2 range. Results Forty-five patients were included. Patients spent more time in the optimal SpO 2 range with closed-loop oxygen control compared with manual titrations of oxygen (96.5 [93.5 to 98.9] % vs. 89 [77.4 to 95.9] %; p  < 0.0001) (difference estimate, 10.4 (95% confidence interval 5.2 to 17.2). Patients spent less time in the suboptimal range during closed-loop oxygen control, both above and below the cut-offs of the optimal SpO 2 range, and less time above the suboptimal range. Fewer number of manual adjustments per hour were needed with closed-loop oxygen control. The number of events of SpO 2  < 88% and < 85% were not significantly different between groups. Conclusions Closed-loop oxygen control improves oxygen administration in patients with moderate-to-severe AHRF treated with HFNO, increasing the percentage of time in the optimal oxygenation range and decreasing the workload of healthcare personnel. These results are especially relevant in a context of limited oxygen supply and high medical demand, such as the COVID-19 pandemic. Trial registration The HILOOP study was registered at www.clinicaltrials.gov under the identifier NCT04965844 .

Bronchiectasis (BE) is a long-term, chronic lung condition featured by widened and scarred airways. These can alter the physiological mucociliary clearance, making it difficult to clear mucus and microorganisms, leading to frequent exacerbations. High flow sal therapy (HFNT) is a noninvasive respiratory support that delivers heated and humidified gas eventually enriched with oxygen, through a sal cannula. Humidification is crucial for adequate airways mucociliary clearance, improving ciliary function and consequently reducing airways inflammation and recurrent infections. HFNT has been mostly used in patients with acute hypoxemic respiratory failure and in selected patients with chronic respiratory failure due to COPD. Still, evidence about its use in acute and long-term home setting in patients with clinically relevant BE are lacking. We report a case of severe widespread BE, already on top medical therapy and pulmory rehabilitation, still suffering from difficult mucus expectoration and recurrent exacerbations, who has been additiolly treated with HFNT, both in hospital and domiciliary, reporting significant improvements on relevant clinical and patient-centered outcomes. Thus, HFNT may confer additiol benefits as an add-on treatment of patients with severe BE and respiratory failure.

Background Standard high-flow nasal cannula (HFNC) is a respiratory support device widely used to manage post-extubation hypoxemic acute respiratory failure (hARF) due to greater comfort, oxygenation, alveolar recruitment, humidification, and reduction of dead space, as compared to conventional oxygen therapy. On the contrary, the effects of the new asymmetrical HFNC interface (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) is still under discussion. Our aim is investigating whether the use of asymmetrical HFNC interface presents any relevant difference, compared with the standard configuration, on lung aeration (as assessed by end-expiratory lung impedance (EELI) measured by electrical impedance tomography (EIT)), diaphragm ultrasound thickening fraction (TFdi) and excursion (DE), ventilatory efficiency (estimated by corrected minute ventilation (MV)), gas exchange, dyspnea, and comfort. Methods Pilot physiological crossover randomized controlled study enrolling 20 adults admitted to the Intensive Care unit, invasively ventilated for at least 24 h, and developing post-extubation hARF, i.e., PaO 2 /set FiO 2  < 300 mmHg during Venturi mask (VM) within 120 min after extubation. Each HFNC configuration was applied in a randomized 60 min sequence at a flow rate of 60 L/min. Results Global EELI, TFdi, DE, ventilatory efficiency, gas exchange and dyspnea were not significantly different, while comfort was greater during asymmetrical HFNC support, as compared to standard interface (10 [7–10] and 8 [7–9], p-value 0.044). Conclusions In post-extubation hARF, the use of the asymmetrical HFNC, as compared to standard HFNC interface, slightly improved patient comfort without affecting lung aeration, diaphragm activity, ventilatory efficiency, dyspnea and gas exchange. Clinical trial number ClinicalTrial.gov. Registration number: NCT05838326 (01/05/2023). New & noteworthy The asymmetrical high-flow nasal cannula oxygen therapy (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) provides greater comfort as compared to standard interface; while their performance in term of lung aeration, diaphragm activity, ventilatory efficiency, dyspnea, and gas exchange is similar.

Long-term High Flow Nasal Cannula (LT-HFNC), defined as High Flow Nasal Cannula treatment provided to patients with chronic pulmonary conditions during stable phases, has emerged as a home treatment in different categories of patients with chronic lung diseases in recent years. This paper summarizes the physiological effects of LT-HFNC and evaluates the clinical knowledge to date about treatment in patients with chronic obstructive lung disease, interstitial lung disease and bronchiectasis. The guideline is translated and summarized in this paper and presented unabridged as an appendix to the paper. The paper describes the working process behind the Danish Respiratory Society's National guideline for treatment of stable disease, which has been written to support clinicians in both evidence-based decision making and practical issues concerning the treatment.

Abstract Rationale One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation. Objectives To validate the diagnostic accuracy of an index (termed ROX and defined as the ratio of oxygen saturation as measured by pulse oximetry/FiO2 to respiratory rate) for determining HFNC outcome (need or not for intubation). Methods This was a 2-year multicenter prospective observational cohort study including patients with pneumonia treated with HFNC. Identification was through Cox proportional hazards modeling of ROX association with HFNC outcome. The most specific cutoff of the ROX index to predict HFNC failure and success was assessed. Measurements and Main Results Among the 191 patients treated with HFNC in the validation cohort, 68 (35.6%) required intubation. The prediction accuracy of the ROX index increased over time (area under the receiver operating characteristic curve: 2 h, 0.679; 6 h, 0.703; 12 h, 0.759). ROX greater than or equal to 4.88 measured at 2 (hazard ratio, 0.434; 95% confidence interval, 0.264–0.715; P = 0.001), 6 (hazard ratio, 0.304; 95% confidence interval, 0.182–0.509; P < 0.001), or 12 hours (hazard ratio, 0.291; 95% confidence interval, 0.161–0.524; P < 0.001) after HFNC initiation was consistently associated with a lower risk for intubation. A ROX less than 2.85, less than 3.47, and less than 3.85 at 2, 6, and 12 hours of HFNC initiation, respectively, were predictors of HFNC failure. Patients who failed presented a lower increase in the values of the ROX index over the 12 hours. Among components of the index, oxygen saturation as measured by pulse oximetry/FiO2 had a greater weight than respiratory rate. Conclusions In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation. Clinical trial registered with www.clinicaltrials.gov (NCT 02845128).

The purpose of the study is to describe early predictors and to develop a prediction tool that accurately identifies the need for mechanical ventilation (MV) in pneumonia patients with hypoxemic acute respiratory failure (ARF) treated with high-flow nasal cannula (HFNC). This is a 4-year prospective observational 2-center cohort study including patients with severe pneumonia treated with HFNC. High-flow nasal cannula failure was defined as need for MV. ROX index was defined as the ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate. One hundred fifty-seven patients were included, of whom 44 (28.0%) eventually required MV (HFNC failure). After 12 hours of HFNC treatment, the ROX index demonstrated the best prediction accuracy (area under the receiver operating characteristic curve 0.74 [95% confidence interval, 0.64-0.84]; P<.002). The best cutoff point for the ROX index was estimated to be 4.88. In the Cox proportional hazards model, a ROX index greater than or equal to 4.88 measured after 12 hours of HFNC was significantly associated with a lower risk for MV (hazard ratio, 0.273 [95% confidence interval, 0.121-0.618]; P=.002), even after adjusting for potential confounding. In patients with ARF and pneumonia, the ROX index can identify patients at low risk for HFNC failure in whom therapy can be continued after 12 hours.

Background The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO 2 clearance after 2 h of treatment. Methods We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO 2  ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO 2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO 2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. Results Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO 2 reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group ( p  = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO 2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p  = 0.0003). Both treatments had a significant effect on PaCO 2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. Conclusions HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO 2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. Trial registration : The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Background Acute respiratory distress syndrome (ARDS) subphenotypes differ in outcomes and treatment responses. Subphenotypes in high-flow nasal oxygen (HFNO)-treated ARDS patients have not been investigated. Objectives To identify biological subphenotypes in HFNO-treated ARDS patients. Methods Secondary analysis of a prospective multicenter observational study including ARDS patients supported with HFNO. Plasma inflammation markers (interleukin [IL]-6, IL-8, and IL-33 and soluble suppression of tumorigenicity-2 [sST2]) and lung epithelial (receptor for advanced glycation end products [RAGE] and surfactant protein D [SP-D]) and endothelial (angiopoietin-2 [Ang-2]) injury were measured. These biomarkers and bicarbonate were used in K-means cluster analysis to identify subphenotypes. Logistic regression was performed on biomarker combinations to predict clustering. We chose the model with the best AUROC and the lowest number of variables. This model was used to describe the HAIS (High-flow ARDS Inflammatory Subphenotype) score. Results Among 41 HFNO patients, two subphenotypes were identified. Hyperinflammatory subphenotype ( n  = 17) showed higher biomarker levels than hypoinflammatory ( n  = 24). Despite similar baseline characteristics, the hyperinflammatory subphenotype had higher 60-day mortality (47 vs 8.3% p  = 0.014) and longer ICU length of stay (22.0 days [18.0–30.0] vs 39.5 [25.5–60.0], p  = 0.034). The HAIS score, based on IL-8 and sST2, accurately distinguished subphenotypes (AUROC 0.96 [95%CI: 0.90–1.00]). A HAIS score ≥ 7.45 was predictor of hyperinflammatory subphenotype. Conclusion ARDS patients treated with HFNO exhibit two biological subphenotypes that have similar clinical characteristics, but hyperinflammatory patients have worse outcomes. The HAIS score may identify patients with hyperinflammatory subphenotype and might be used for enrichment strategies in future clinical trials.

High flow nasal cannula (HFNC) therapy has been previously shown to produce positive upper airway pressures in adult and child patients. This work aimed to evaluate and quantify the effects of HFNC flowrate and gas type on airway pressures measured in vitro in infant airway replicas. Ten realistic infant airway replicas, extending from nares to trachea, were connected in turn to a lung simulator and were supplied gas flows through HFNC. Air and heliox were each provided at two weight-indexed flowrates, 1 l/min/kg and 2 l/min/kg. Pressure and lung volume were continuously measured during simulated breathing. For constant simulated patient effort, no statistically significant change in tidal volume was measured between baseline and lower or higher HFNC flowrates, nor was there any significant difference in tidal volume between air and heliox. Tracheal pressure increased with increasing HFNC flow rate, and was highly variable between airway replicas. Higher pressures were measured for air versus heliox. For air supplied at 2 l/min/kg, average airway pressures in excess of 4 cm H2O were generated, with positive end-expiratory pressure (PEEP) ranging from 2.5 to nearly 12 cm H2O across the replicas. A predictive correlation for PEEP was proposed based on supplied gas density and flow velocities exiting the cannula and nares, and was able to account for a portion of variability between airway replicas (R2 = 0.913). Additionally, PEEP was well correlated with, and predictive of, expiratory peak pressure (R2 = 0.939) and average inspiratory pressure (R2 = 0.944).

BackgroundHigh-flow nasal oxygen (HFNO), also known as high-flow nasal cannula, is an important noninvasive respiratory support strategy in perioperative and critical care practice. As the literature has expanded across multiple clinical contexts, a structured overview is needed to clarify the development, knowledge base, and emerging priorities of the field.MethodsWe conducted a bibliometric and visual analysis of HFNO research using English-language articles and reviews retrieved from the Web of Science Core Collection, Scopus, and PubMed for the period 2000–2025. After screening, merging, and deduplication, 2,314 unique publications were included. Bibliometrix in R was used for performance analysis, thematic mapping, and thematic evolution; VOSviewer for collaboration analysis; and CiteSpace for co-citation analysis, keyword clustering, timeline visualization, burst detection, and dual-map overlay.ResultsHFNO research showed sustained exponential growth, with marked acceleration after 2018 and especially after 2020. The literature was concentrated in respiratory medicine, critical care, and anesthesiology journals, with Respiratory Care ranking first in publication output. The United States and China were the leading contributors, while several French institutions, particularly Assistance Publique-Hôpitaux de Paris, were prominent in the institutional network. Co-citation analysis identified major clusters related to acute respiratory failure, perioperative oxygen therapy, preoxygenation strategies, and coronavirus disease. Keyword and thematic analyses indicated a shift from early emphasis on perioperative oxygenation and postoperative respiratory support toward broader critical care application and, more recently, toward context-specific deployment, acute hypoxemic respiratory failure, awake prone positioning, treatment monitoring, and the ROX index.ConclusionHFNO research has evolved from a focused literature on oxygenation support into a broader and more clinically differentiated field spanning perioperative and critical care practice. Current hotspots are increasingly centered on context-specific use, monitoring, failure prediction, and escalation decisions. Future research should prioritize clinically actionable patient stratification, standardized outcome definitions, and protocol-based integration of HFNO across different care pathways.