Obstructive Sleep Apnea in Adults: Common Questions and Answers.

Obstructive sleep apnea (OSA) is a common disorder that affects quality of life and is associated with comorbidities such as hypertension, atrial fibrillation, heart failure, coronary heart disease, type 2 diabetes mellitus, and stroke. OSA is characterized by a reduction or cessation of breathing during sleep, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. The U.S. Preventive Services Task Force states that there is insufficient evidence to recommend routine screening for OSA in the absence of symptoms. OSA should be considered in patients with excessive daytime fatigue, unrestful sleep, persistent snoring, and nocturnal awakenings with gasping or choking. The STOP-BANG questionnaire is the most sensitive screening tool for OSA, and the diagnostic standard is polysomnography with an observed apnea-hypopnea index greater than 5 in the presence of symptoms or greater than 15 without symptoms. Home sleep apnea testing is a useful diagnostic option in patients who have symptoms consistent with moderate to severe OSA without significant cardiopulmonary comorbidities. Positive airway pressure, with a humidified nasal or facial mask, is the first-line treatment for adults with OSA. Weight loss is a beneficial adjunct to treatment through intensive lifestyle modification, medications, or bariatric surgery. Alternatives for patients intolerant of or nonadherent to positive airway pressure include changing the type of mask used, mandibular advancement devices, hypoglossal nerve stimulation, and other surgical interventions. Although many OSA therapies effectively improve daytime sleepiness and blood pressure, none have demonstrated a mortality benefit in randomized controlled trials.

Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial - the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study.

RATIONALE: Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting. METHODS: This is a prospective, multicentre, randomised, controlled, stepped wedge trial, in which patients presenting with AHRF in Uganda will be randomly assigned to standard oxygen therapy delivered through a face mask, HFNC oxygen or CPAP. The primary outcome is all-cause mortality at 28 days. Secondary outcomes include the number of patients with criteria for intubation at day 7, the number of patients intubated at day 28, ventilator-free days at day 28 and tolerance of each respiratory support. ETHICS AND DISSEMINATION: The study has obtained ethical approval from the Research and Ethics Committee, School of Biomedical Sciences, College of Health Sciences, Makerere University as well as the Uganda National Council for Science and Technology. Patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04693403. PROTOCOL VERSION: 8 September 2023; version 5.

Continuous Positive Airway Pressure versus Differential Lung Ventilation during One Lung Ventilation for Thoracic Surgery.

INTRODUCTION: One lung ventilation (OLV) is a technique used during lung resection surgery to facilitate optimal surgical conditions. However, this may result in severe hypoxemia due to the right-to-left shunt created in the collapsed lung. Several techniques are used to overcome hypoxemia, one of which is continuous positive airway pressure (CPAP) to the non-dependent lung. Another technique is ventilating the non-dependent lung with a minimal volume, thus creating differential lung ventilation (DLV) or split lung ventilation (SLV). In this study, we compared the efficacy of CPAP to DLV during video-assisted thoracoscopic (VATS) lung resection. MATERIALS AND METHODS: In this single-center randomized controlled, cross-over study, each patient acted as his control as well as the study. Patients crossed over from SLV to CPAP (or vice versa) with an interval period during which only OLV was used (control period). The primary objective of the study was to observe the changes in oxygenation, ventilation, and the surgeons' perception of the surgical field using CPAP or SLV to the non-ventilated lung during the period of OLV in patients undergoing thoracic surgery. RESULTS: The study revealed that oxygenation was significantly better when using SLV to the non-ventilated lung during the period of OLV (P = 0.03). However, the surgeon found a significantly better surgical field when applying CPAP to the surgical field. CONCLUSIONS: The study showed that using SLV to the non-ventilated lung during the period of OLV was superior in terms of oxygenation, although it interfered more with the surgical field.

Cardio-metabolic health effects of CPAP treatment for sleep apnoea during weight loss: A randomised controlled pilot trial.

BACKGROUND AND AIMS: This study assessed whether the addition of continuous positive airway pressure (CPAP) during weight loss would enhance cardiometabolic health improvements in patients with obesity and Obstructive Sleep Apnoea (OSA). METHODS AND RESULTS: Patients with overweight or obesity, pre-diabetes and moderatesevere OSA were randomised to receive CPAP therapy with a weight loss programme (CPAP+WL) or a weight loss programme alone (WL alone). PRIMARY OUTCOME: 2-hour glucose assessed by an oral glucose tolerance test. SECONDARY OUTCOMES: 24 hr blood pressure, body composition (DEXA) and fasting blood markers. 17 patients completed 3-month follow-up assessments (8 CPAP+WL and 9 WL alone). Overall, participants in both groups lost ∼12 kg which reduced polysomnography determined OSA severity by ∼45 %. In the CPAP+WL group, CPAP use (compliance 5.29 hrs/night) did not improve any outcome above WL alone. There was no improvement in 2-hour glucose in either group. However, in the pooled (n = 17) analysis there were overall improvements in most outcomes including insulin sensitivity (.000965 units, p = .008), sleep systolic BP (- 16.2 mmHg, p = .0003), sleep diastolic BP (-9.8 mmHg, p = 0.02), wake diastolic BP (- 4.3 mmHg, p = .03) and sleepiness (Epworth Sleepiness Score -3.2, p = .0003). In addition, there were reductions in glucose area under the curve (-230 units, p = .009), total (-0.86 mmol/L, p = 0.006) and LDL cholesterol (-0.58 mmol/L, p = 0.007), triglycerides (-0.75 mmol/L, p = 0.004), fat mass (-7.6 kg, p < .0001) and abdominal fat (-310 cm3, p < .0001). CONCLUSION: Weight loss reduced OSA and improved sleepiness and cardiometabolic health. These improvements were not further enhanced by using CPAP. Results suggest weight loss should be the primary focus of treatment for patients with OSA and obesity.

Sleep health primary care clinical resource.

BACKGROUND: Obstructive sleep apnoea (OSA) and insomnia are the two most common sleep disorders and are frequent reasons for presentation in Australian general practice. OBJECTIVE: This article describes the development, content and suggested uses of the online sleep health primary care clinical resource, which provides general practitioners and other primary healthcare professionals with evidence-based information on the aetiology, assessment, management, referral and ongoing care for OSA and chronic insomnia. DISCUSSION: The Royal Australian College of General Practitioners-accepted clinical resource for the management of OSA and chronic insomnia in primary care was developed by the Australian National Centre for Sleep Health Services Research. The resource is designed to be used during consultations (eg following the steps in assessment and management and the use of online questionnaires for the assessment of OSA [Epworth Sleepiness Scale/OSA50/STOP-Bang] and insomnia [Sleep Condition Indicator/and Insomnia Severity Index]) and as an education/training tool (eg evidence on the role of continuous positive airway pressure/mandibular advancement splints for management of OSA and brief behavioural therapy for insomnia/cognitive behavioural therapy for insomnia for the management of insomnia).

Management of obstructive sleep apnoea in primary care.

BACKGROUND: Obstructive sleep apnoea (OSA) is common in the community and is increasing in prevalence. Primary care plays a pivotal role in the diagnosis and management of OSA. OBJECTIVE: This article focuses on the management options for a patient with an established diagnosis of OSA and provides a guide for driving licensing requirements. Indications for continuous positive airway pressure (CPAP) are discussed and tips provided to consider when conducting a review appointment, including trouble shooting. DISCUSSION: There are several treatment options available for patients with an established diagnosis of OSA. Selecting the optimal therapy involves aligning the symptoms and severity of OSA with the presence of comorbidities. CPAP is a highly effective therapy for symptomatic adults with moderate-to-severe OSA and for some symptomatic patients with mild OSA. Early trouble shooting of side effects and using supportive interventions increases the probability of long-term adherence, which is key to symptomatic improvement.

Validity, reliability, and responsiveness of the Brazilian version of the instrument World Health Organization Disability Assessment Schedule (WHODAS 2.0) for individuals with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a disabling health condition, and there is no disease-specific patient-reported outcome instrument to assess individuals with OSA. OBJECTIVES: To evaluate the psychometric properties of the Brazilian version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0) in individuals with OSA. METHODS: One hundred individuals with OSA responded to the WHODAS 2.0 version of 36 items, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the 12-item health survey (SF-12). Internal consistency, convergent and discriminative validity, and responsiveness to continuous positive airway pressure (CPAP) were the psychometric properties tested. RESULTS: Cronbach's α values indicate good internal consistency (0.91 - 0.73), except for the self-care domain (α = 0.52). Convergent validity indicated an excellent correlation (r = -0.80) between the domains of functioning and quality of life. Discriminative validity showed no association between OSA severity and functioning (p = 0.90). The responsiveness to CPAP treatment showed a large effect size (r = 0.82; p < 0.05) CONCLUSIONS: The WHODAS 2.0 instrument is valid, reliable, and responsive for assessing individuals with OSA.

Treating sleep-disordered breathing of idiopathic pulmonary fibrosis patients with CPAP and nocturnal oxygen treatment. A pilot study : Sleep-disordered breathing treatment in IPF.

INTRODUCTION: Sleep-disordered breathing (SDB) is a major comorbidity in idiopathic pulmonary fibrosis (IPF) and is associated with a poor outcome. There is a lack of knowledge regarding the impact of SDB treatment on IPF. We assessed at one year: (1) the effect of CPAP and/or nocturnal oxygen therapy on IPF regarding lung function, blood mediators, and quality of life; (2) adherence to SDB treatment and SDB changes. METHODOLOGY: This is a prospective study of consecutive newly diagnosed IPF patients initiating anti-fibrotic treatment. Lung function, polysomnography, blood tests and quality of life questionnaires were performed at inclusion and after one year. Patients were classified as obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and sleep-sustained hypoxemia (SSH). SDB therapy (CPAP and/or nocturnal oxygen therapy) was initiated if needed. RESULTS: Fifty patients were enrolled (36% had OSA, 22% CSA, and 12% SSH). CPAP was started in 54% of patients and nocturnal oxygen therapy in 16%. At one-year, polysomnography found improved parameters, though 17% of patients had to add nocturnal oxygen therapy or CPAP, while 33% presented SDB onset at this second polysomnography. CPAP compliance at one year was 6.74 h/night (SD 0.74). After one year, matrix metalloproteinase-1 decreased in OSA and CSA (p = 0.029; p = 0.027), C-reactive protein in OSA (p = 0.045), and surfactant protein D in CSA group (p = 0.074). There was no significant change in lung function. CONCLUSIONS: Treatment of SBD with CPAP and NOT can be well tolerated with a high compliance. IPF patients may exhibit SDB progression and require periodic re-assessment. Further studies to evaluate the impact of SDB treatment on lung function and serological mediators are needed.

Automated oxygen titration with non-invasive ventilation in hypoxaemic adults with cardiorespiratory disease: a randomised cross-over trial.

BACKGROUND: Closed-loop oxygen control systems automatically adjust the fraction of inspired oxygen (FiO2) to maintain oxygen saturation (SpO2) within a predetermined target range. Their performance with low and high-flow oxygen therapies, but not with non-invasive ventilation, has been established. We compared the effect of automated oxygen on achieving and maintaining a target SpO2 range with nasal high flow (NHF), bilevel positive airway pressure (bilevel) and continuous positive airway pressure (CPAP), in stable hypoxaemic patients with chronic cardiorespiratory disease. METHODS: In this open-label, three-way cross-over trial, participants with resting hypoxaemia (n=12) received each of NHF, bilevel and CPAP treatments, in random order, with automated oxygen titrated for 10 min, followed by 36 min of standardised manual oxygen adjustments. The primary outcome was the time taken to reach target SpO2 range (92%-96%). Secondary outcomes included time spent within target range and physiological responses to automated and manual oxygen adjustments. RESULTS: Two participants were randomised to each of six possible treatment orders. During automated oxygen control (n=12), the mean (±SD) time to reach target range was 114.8 (±87.9), 56.6 (±47.7) and 67.3 (±61) seconds for NHF, bilevel and CPAP, respectively, mean difference 58.3 (95% CI 25.0 to 91.5; p=0.002) and 47.5 (95% CI 14.3 to 80.7; p=0.007) seconds for bilevel and CPAP versus NHF, respectively. Proportions of time spent within target range were 68.5% (±16.3), 65.6% (±28.7) and 74.7% (±22.6) for NHF, bilevel and CPAP, respectively.Manually increasing, then decreasing, the FiO2 resulted in similar increases and then decreases in SpO2 and transcutaneous carbon dioxide (PtCO2) with NHF, bilevel and CPAP. CONCLUSION: The target SpO2 range was achieved more quickly when automated oxygen control was initiated with bilevel and CPAP compared with NHF while time spent within the range across the three therapies was similar. Manually changing the FiO2 had similar effects on SpO2 and PtCO2 across each of the three therapies. TRIAL REGISTRATION NUMBER: ACTRN12622000433707.

Comparison of the effect of two recruitment manoeuvres to conventional ventilation on lung atelectasis in paediatric laparoscopic surgery- a prospective randomised controlled trial.

BACKGROUND: There is a high incidence of pulmonary atelectasis during paediatric laparoscopic surgeries. The authors hypothesised that utilising a recruitment manoeuvre or using continuous positive airway pressure may prevent atelectasis compared to conventional ventilation. OBJECTIVE: The primary objective was to compare the degree of lung atelectasis diagnosed by lung ultrasound (LUS) using three different ventilation techniques in children undergoing laparoscopic surgeries. DESIGN: Randomised, prospective three-arm trial. SETTING: Single institute, tertiary care, teaching hospital. PATIENTS: Children of ASA PS 1 and 2 up to the age of 10 years undergoing laparoscopic surgery with pneumoperitoneum lasting for more than 30 min. INTERVENTION: Random allocation to one of the three study groups: CG group: Inspiratory pressure adjusted to achieve a TV of 5-8 ml/kg, PEEP of 5 cm H2O, respiratory rate adjusted to maintain end-tidal carbon dioxide (ETCO2) between 30-40 mm Hg with manual ventilation and no PEEP at induction. RM group: A recruitment manoeuvre of providing a constant pressure of 30 cm H2O for ten seconds following intubation was applied. A PEEP of 10 cm H2O was maintained intraoperatively. CPAP group: Intraoperative maintenance with PEEP 10 cm H2O with CPAP of 10 cm H2O at induction using mechanical ventilation was done. OUTCOME MEASURES: Lung atelectasis score at closure assessed by LUS. RESULTS: Post induction, LUS was comparable in all three groups. At the time of closure, the LUS for the RM group (8.6 ± 4.9) and the CPAP group (8.8 ± 6.8) were significantly lower (p < 0.05) than the CG group (13.3 ± 3.8). In CG and CPAP groups, the score at closure was significantly higher than post-induction. The PaO2/FiO2 ratio was significantly higher (p < 0.05) for the RM group (437.1 ± 44.9) and CPAP group (421.6 ± 57.5) than the CG group (361.3 ± 59.4) at the time of pneumoperitoneum. CONCLUSION: Application of a recruitment manoeuvre post-intubation or CPAP during induction and maintenance with a high PEEP leads to less atelectasis than conventional ventilation during laparoscopic surgery in paediatric patients. TRIAL REGISTRY: CTRI/2019/08/02058.

Ventilatory Assistance Before Umbilical Cord Clamping in Extremely Preterm Infants: A Randomized Clinical Trial.

Importance: Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. Objective: To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death. Design, Setting, and Participants: This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth. Intervention: After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation. Main Outcomes and Measures: The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs. Results: Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort. Conclusions and Relevance: This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight. Trial Registration: ClinicalTrials.gov Identifier: NCT02742454.

Effect of positive airway pressure treatment on excessive fragmentary myoclonus in 100 sleep-related breathing disorder patients.

STUDY OBJECTIVES: Excessive fragmentary myoclonus (EFM) is a frequent finding in patients undergoing video-polysomnography (VPSG). We aimed to evaluate the potential effect of sleep-related breathing disorder's treatment with positive airway pressure (PAP) therapy on EFM. METHODS: One hundred consecutive patients with EFM and sleep-related breathing disorder subsequently treated with PAP at the sleep lab of the Medical University of Innsbruck, Department of Neurology, Austria, were included. Each patient underwent two nights of VPSG: the first night without and the second night with PAP therapy. Fragmentary myoclonus was automatically scored with validated software, and fragmentary myoclonus index (FMI) and minutes of non-rapid eye movement (NREM) sleep with EFM (minNREM+EFM) were calculated. RESULTS: Under PAP therapy there was a significant decrease in the minNREM+EFM - 60.5 (9.5-161.8) at baseline vs. 37.5 (6.3-168.8) minutes under PAP, p = 0.025. No significant differences were observed for FMI between the two nights. Sleep variables, sleep diagnoses, comorbidities, and medication did not influence FMI or the minNREM+EFM. CONCLUSIONS: The initiation of PAP treatment led to a significant reduction of minNREM+EFM, but not of FMI. The results suggest that PAP therapy might influence the distribution of FM potentials.

Obstructive Sleep Apnea Effects on Chronic Airway Disease Exacerbations-Missed Opportunities for Improving Outcomes in Chronic Obstructive Pulmonary Disease and Asthma.

In patients with chronic obstructive pulmonary disease (COPD) and asthma, exacerbations determine the natural history of both diseases. Patients with both respiratory diseases who suffer from obstructive sleep apnea (OSA) as a comorbidity (overlap syndromes) have a higher risk of exacerbations and hospitalization. In cases of OSA/COPD and OSA/asthma, continuous positive airway pressure treatment is indicated. Adequate adherence to therapy appears to reduce exacerbations and their severity, especially in OSA/COPD overlap. However, there is a lack of randomized trials that definitively demonstrate this evidence.

Targeting Hypercapnia in Chronic Lung Disease and Obesity Hypoventilation: Benefits and Challenges.

Hypoventilation is a complication that is not uncommon in chronic obstructive pulmonary disease and calls for both medical treatment of the underlying disease and, frequently, noninvasive ventilation either during exacerbations requiring hospitalization or in a chronic state in the patient at home. Obesity hypoventilation syndrome by definition is associated with ventilatory failure and hypercapnia. It may or may not be accompanied by obstructive sleep apnea, which when detected becomes an additional target for positive airway pressure treatment. Intensive research has not completely resolved the best choice of treatment, and the simplest modality, continuous positive airway pressure, may still be entertained.

Early pathophysiology-driven airway pressure release ventilation versus low tidal volume ventilation strategy for patients with moderate-severe ARDS: study protocol for a randomized, multicenter, controlled trial.

BACKGROUND: Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS. METHODS: The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation. The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated. TRIAL ETHICS AND DISSEMINATION: The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION: The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018.

Impact of neonatal noninvasive resuscitation strategies on lung mechanics, tracheal pressure, and tidal volume in preterm lambs.

This study investigated the relationship between three respiratory support approaches on lung volume recruitment during the first 2 h of postnatal life in preterm lambs. We estimated changes in lung aeration, measuring respiratory resistance and reactance by oscillometry at 5 Hz. We also measured intratracheal pressure in subsets of lambs. The first main finding is that sustained inflation (SI) applied noninvasively (Mask SI; n = 7) or invasively [endotracheal tube (ETT) SI; n = 6] led to similar rapid lung volume recruitment (∼6 min). In contrast, Mask continuous positive airway pressure (CPAP) without SI (n = 6) resuscitation took longer (∼30-45 min) to reach similar lung volume recruitment. The second main finding is that, in the first 15 min of postnatal life, the Mask CPAP without SI group closed their larynx during custom ventilator-driven expiration, leading to intratracheal positive end-expiratory pressure of ∼17 cmH2O (instead of 8 cmH2O provided by the ventilator). In contrast, the Mask SI group used the larynx to limit inspiratory pressure to ∼26 cmH2O (instead of 30 cmH2O provided by the ventilator). These different responses affected tidal volume, being larger in the Mask CPAP without SI group [8.4 mL/kg; 6.7-9.3 interquartile range (IQR)] compared to the Mask SI (5.0 mL/kg; 4.4-5.2 IQR) and ETT SI groups (3.3 mL/kg; 2.6-3.7 IQR). Distinct physiological responses suggest that spontaneous respiratory activity of the larynx of preterm lambs at birth can uncouple pressure applied by the ventilator to that applied to the lung, leading to unpredictable lung pressure and tidal volume delivery independently from the ventilator settings.NEW & NOTEWORTHY We compared invasive and noninvasive resuscitation on lambs at birth, including or not sustained inflation (SI). Lung volume recruitment was faster in those receiving SI. During noninvasive resuscitation, larynx modulation reduced tracheal pressure from that applied to the mask in lambs receiving SI, while it led to increased auto-positive end-expiratory pressure and very large tidal volumes in lambs not receiving SI. Our results highlight the need for individualizing pressures and monitoring tidal volumes during resuscitation at birth.