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RATIONALE: Acetazolamide and atomoxetine-plus-oxybutynin ('AtoOxy') can improve obstructive sleep apnoea (OSA) by stabilising ventilatory control and improving dilator muscle responsiveness respectively. Given the different pathophysiological mechanisms targeted by each intervention, we tested whether AtoOxy-plus-acetazolamide would be more efficacious than AtoOxy alone. METHODS: In a multicentre randomised crossover trial, 19 patients with moderate-to-severe OSA received AtoOxy (80/5 mg), acetazolamide (500 mg), combined AtoOxy-plus-acetazolamide or placebo at bedtime for three nights (half doses on first night) with a 4-day washout between conditions. Outcomes were assessed at baseline and night 3 of each treatment period. Mixed model analysis compared the reduction in Apnoea-Hypopnoea Index (AHI) from baseline between AtoOxy-plus-acetazolamide and AtoOxy (primary outcome). Secondary outcomes included hypoxic burden and arousal index. RESULTS: Although AtoOxy lowered AHI by 49 (33, 62)%baseline (estimate (95% CI)) vs placebo, and acetazolamide lowered AHI by+34 (14, 50)%baseline vs placebo, AtoOxy-plus-acetazolamide was not superior to AtoOxy alone (difference: -2 (-18, 11)%baseline, primary outcome p=0.8). Likewise, the hypoxic burden was lowered with AtoOxy (+58 (37, 71)%baseline) and acetazolamide (+37 (5, 58)%baseline), but no added benefit versus AtoOxy occurred when combined (difference: -13 (-5, 39)%baseline). Arousal index was also modestly reduced with each intervention (11%baseline-16%baseline). Mechanistic analyses revealed that similar traits (ie, higher baseline compensation, lower loop gain) were associated with both AtoOxy and acetazolamide efficacy. CONCLUSIONS: While AtoOxy halved AHI, and acetazolamide lowered AHI by a third, the combination of these leading experimental interventions provided no greater efficacy than AtoOxy alone. Failure of acetazolamide to further increase efficacy suggests overlapping physiological mechanisms. TRIAL REGISTRATION NUMBER: NCT03892772.
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Acetazolamida , Apneia Obstrutiva do Sono , Humanos , Estudos Cross-Over , Acetazolamida/uso terapêutico , Apneia Obstrutiva do Sono/terapia , Quimioterapia Combinada , Cloridrato de Atomoxetina/uso terapêuticoRESUMO
PURPOSE: Obstructive sleep apnea (OSA) severity varies considerably depending on the body position during sleep in certain subjects. Such variability may be underpinned by specific, body position-related changes in OSA pathophysiological determinants, or endotypes. Also head position relative to trunk may influence OSA endotypes. However, no studies to our knowledge have reviewed the endotype variations according to head or body position up to now. RECENT FINDINGS: Several findings illustrate that supine OSA is mostly attributable to unfavorable upper airway anatomy compared to lateral position. However, a reduced lung volume, with consequent ventilatory instability (or elevated loop gain), may also play a role. Furthermore, preliminary findings suggest that prone and reclined positions may have a beneficial effect on collapsibility and loop gain. SUMMARY: Sleeping supine induces many unfavorable pathophysiological changes, especially in certain predisposed OSA patients. Little is known on the influence of other sleep positions on key endotypic traits.
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BACKGROUND: Healthcare workers (HCWs) are at risk from aerosol transmission of severe acute respiratory syndrome coronavirus 2. The aims of this study were to (1) quantify the protection provided by masks (surgical, fit-testFAILED N95, fit-testPASSED N95) and personal protective equipment (PPE), and (2) determine if a portable high-efficiency particulate air (HEPA) filter can enhance the benefit of PPE. METHODS: Virus aerosol exposure experiments using bacteriophage PhiX174 were performed. An HCW wearing PPE (mask, gloves, gown, face shield) was exposed to nebulized viruses (108 copies/mL) for 40â minutes in a sealed clinical room. Virus exposure was quantified via skin swabs applied to the face, nostrils, forearms, neck, and forehead. Experiments were repeated with a HEPA filter (13.4 volume-filtrations/hour). RESULTS: Significant virus counts were detected on the face while the participants were wearing either surgical or N95 masks. Only the fit-testPASSED N95 resulted in lower virus counts compared to control (P = .007). Nasal swabs demonstrated high virus exposure, which was not mitigated by the surgical/fit-testFAILED N95 masks, although there was a trend for the fit-testPASSED N95 mask to reduce virus counts (P = .058). HEPA filtration reduced virus to near-zero levels when combined with fit-testPASSED N95 mask, gloves, gown, and face shield. CONCLUSIONS: N95 masks that have passed a quantitative fit-test combined with HEPA filtration protects against high virus aerosol loads at close range and for prolonged periods of time.
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COVID-19 , Respiradores N95 , COVID-19/prevenção & controle , Filtração , Humanos , Máscaras , Aerossóis e Gotículas Respiratórios , Carga ViralRESUMO
BACKGROUND AND OBJECTIVE: Right ventricular (RV) volumes are crucial outcome determinants in pulmonary diseases. Little is known about the associations of RV volumes during hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We aimed to ascertain associations of RV end-diastolic volume indexed to body surface area (RVEDVI) during hospitalized AECOPD and its relationship with mortality in long-term follow-up. METHODS: This is a prospective observational cohort study (December 2013-November 2019, ACTRN12617001562369) using dynamic retrospective ECG-gated computed tomography during hospitalized AECOPD. RVEDVI was defined as normal or high using Framingham Offspring Cohort values. Cox regression determined the prognostic relevance of RVEDVI for death. RESULTS: A total of 148 participants (70 ± 10 years [mean ± SD], 88 [59%] men) were included, of whom 75 (51%) had high RVEDVI. This was associated with more frequent hospital admissions in the 12 months before admission (52/75 [69%] vs. 38/73 [52%], p = 0.04) and higher breathlessness (modified Medical Research Council score, 2.9 ± 1.3 vs. 2.4 ± 1.2, p = 0.007). During follow-up, high RVEDVI was associated with greater mortality (log-rank p = 0.001). In univariable Cox regression, increasing RVEDVI was associated with higher mortality (hazard ratio [HR]: 1.02 per ml/m2 ; 95% CI: 1.01, 1.03; p = 0.001). In multivariable Cox regression, RVEDVI was independently associated with mortality (HR: 1.01 per ml/m2 ; 95% CI: 1.00, 1.03; p = 0.050) at a borderline significance level. Adding RVEDVI to three COPD mortality prediction systems improved model fit (pooled chi-square test [BODE: p = 0.05, ADO: p = 0.04, DOSE: p = 0.02]). CONCLUSION: In patients with hospitalized AECOPD, higher RV end-diastolic volume was associated with worse acute clinical parameters and greater mortality.
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Doença Pulmonar Obstrutiva Crônica , Tetralogia de Fallot , Humanos , Masculino , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Estudos Retrospectivos , Volume SistólicoRESUMO
BACKGROUND AND OBJECTIVE: Upper airway surgery for obstructive sleep apnoea (OSA) is an alternative treatment for patients who are intolerant of continuous positive airway pressure (CPAP). However, upper airway surgery has variable treatment efficacy with no reliable predictors of response. While we now know that there are several endotypes contributing to OSA (i.e., upper airway collapsibility, airway muscle response/compensation, respiratory arousal threshold and loop gain), no study to date has examined: (i) how upper airway surgery affects all four OSA endotypes, (ii) whether knowledge of baseline OSA endotypes predicts response to surgery and (iii) whether there are any differences when OSA endotypes are measured using the CPAP dial-down or clinical polysomnographic (PSG) methods. METHODS: We prospectively studied 23 OSA patients before and ≥3 months after multilevel upper airway surgery. Participants underwent clinical and research PSG to measure OSA severity (apnoea-hypopnoea index [AHI]) and endotypes (measured in supine non-rapid eye movement [NREM]). Values are presented as mean ± SD or median (interquartile range). RESULTS: Surgery reduced the AHITotal (38.7 [23.4 to 79.2] vs. 22.0 [13.3 to 53.5] events/h; p = 0.009). There were no significant changes in OSA endotypes, however, large but variable improvements in collapsibility were observed (CPAP dial-down method: ∆1.9 ± 4.9 L/min, p = 0.09, n = 21; PSG method: ∆3.4 [-2.8 to 49.0]%Veupnoea , p = 0.06, n = 20). Improvement in collapsibility strongly correlated with improvement in AHI (%∆AHISupineNREM vs. ∆collapsibility: p < 0.005; R2 = 0.46-0.48). None of the baseline OSA endotypes predicted response to surgery. CONCLUSION: Surgery unpredictably alters upper airway collapsibility but does not alter the non-anatomical endotypes. There are no baseline predictors of response to surgery.
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Apneia Obstrutiva do Sono , Nível de Alerta/fisiologia , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Sistema Respiratório/cirurgia , Resultado do TratamentoRESUMO
INTRODUCTION: Nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major feature of the COVID-19 pandemic. Evidence suggests patients can auto-emit aerosols containing viable viruses; these aerosols could be further propagated when patients undergo certain treatments, including continuous positive airway pressure (PAP) therapy. Our aim was to assess 1) the degree of viable virus propagated from PAP circuit mask leak and 2) the efficacy of a ventilated plastic canopy to mitigate virus propagation. METHODS: Bacteriophage phiX174 (108â copies·mL-1) was nebulised into a custom PAP circuit. Mask leak was systematically varied at the mask interface. Plates containing Escherichia coli host quantified viable virus (via plaque forming unit) settling on surfaces around the room. The efficacy of a low-cost ventilated headboard created from a tarpaulin hood and a high-efficiency particulate air (HEPA) filter was tested. RESULTS: Mask leak was associated with virus contamination in a dose-dependent manner (χ2=58.24, df=4, p<0.001). Moderate mask leak (≥21â L·min-1) was associated with virus counts equivalent to using PAP with a vented mask. The highest frequency of viruses was detected on surfaces <1â m away; however, viable viruses were recorded up to 3.86â m from the source. A plastic hood with HEPA filtration significantly reduced viable viruses on all plates. HEPA exchange rates ≥170â m3·h-1 eradicated all evidence of virus contamination. CONCLUSIONS: Mask leak from PAP may be a major source of environmental contamination and nosocomial spread of infectious respiratory diseases. Subclinical mask leak levels should be treated as an infectious risk. Low-cost patient hoods with HEPA filtration are an effective countermeasure.
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COVID-19 , Pandemias , Aerossóis , Humanos , Máscaras , Respiração Artificial , SARS-CoV-2RESUMO
BACKGROUND: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). METHODS: Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. RESULTS: The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. CONCLUSIONS: Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.
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COVID-19/fisiopatologia , Dióxido de Carbono/análise , Hipercapnia/fisiopatologia , Adulto , Estudos de Casos e Controles , Humanos , Hipercapnia/complicações , Capacidade Inspiratória , Medidas de Volume Pulmonar/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
Ample evidence supports an association between acute oxygen over-administration and harm. Australian and international guidelines consistently recommend lower oxygen saturation aims in populations with chronic obstructive pulmonary disease (COPD). We assessed adherence to acute oxygen use guidelines and outcomes in hospitalised patients with COPD at a large Australian metropolitan hospital network.
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Oxigênio , Doença Pulmonar Obstrutiva Crônica , Austrália/epidemiologia , Fidelidade a Diretrizes , Humanos , Doença Pulmonar Obstrutiva Crônica/terapiaRESUMO
Surgery for adult obstructive sleep apnoea (OSA) plays a key role in contemporary management paradigms, most frequently as either a second-line treatment or in a facilitatory capacity. This committee, comprising two sleep surgeons and three sleep physicians, was established to give clarity to that role and expand upon its appropriate use in Australasia. This position statement has been reviewed and approved by the Australasian Sleep Association (ASA) Clinical Committee.
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Endoscopia/métodos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias , Apneia Obstrutiva do Sono , Adulto , Australásia/epidemiologia , Humanos , Comunicação Interdisciplinar , Administração dos Cuidados ao Paciente/métodos , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/etiologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/cirurgiaAssuntos
Doenças Pulmonares Intersticiais , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Comorbidade , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is typically worse in the supine versus lateral sleeping position. One potential factor driving this observation is a decrease in lung volume in the supine position which is expected by theory to increase a key OSA pathogenic factor: dynamic ventilatory control instability (i.e. loop gain). We aimed to quantify dynamic loop gain in OSA patients in the lateral and supine positions, and to explore the relationship between change in dynamic loop gain and change in lung volume with position. METHODS: Data from 20 patients enrolled in previous studies on the effect of body position on OSA pathogenesis were retrospectively analysed. Dynamic loop gain was calculated from routinely collected polysomnographic signals using a previously validated mathematical model. Lung volumes were measured in the awake state with a nitrogen washout technique. RESULTS: Dynamic loop gain was significantly higher in the supine than in the lateral position (0.77 ± 0.15 vs 0.68 ± 0.14, P = 0.012). Supine functional residual capacity (FRC) was significantly lower than lateral FRC (81.0 ± 15.4% vs 87.3 ± 18.4% of the seated FRC, P = 0.021). The reduced FRC we observed on moving to the supine position was predicted by theory to increase loop gain by 10.2 (0.6, 17.1)%, a value similar to the observed increase of 8.4 (-1.5, 31.0)%. CONCLUSION: Dynamic loop gain increased by a small but statistically significant amount when moving from the lateral to supine position and this may, in part, contribute to the worsening of OSA in the supine sleeping position.
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Pulmão/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Sono/fisiologia , Adulto , Feminino , Capacidade Residual Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Postura , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Estatística como Assunto , Decúbito Dorsal/fisiologiaRESUMO
BACKGROUND AND OBJECTIVE: Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility. METHODS: Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHI<15 events/h on-therapy. RESULTS: Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies. CONCLUSION: Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and eszopiclone) for OSA.
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Pressão Positiva Contínua nas Vias Aéreas , Oxigenoterapia , Apneia Obstrutiva do Sono/terapia , Zopiclona/uso terapêutico , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Faringe/fisiopatologia , Valor Preditivo dos Testes , Pressão , Estudos RetrospectivosRESUMO
RATIONALE: Oral appliances (OAs) are commonly used as an alternative treatment to continuous positive airway pressure for patients with obstructive sleep apnea (OSA). However, OAs have variable success at reducing the apnea-hypopnea index (AHI), and predicting responders is challenging. Understanding this variability may lie with the recognition that OSA is a multifactorial disorder and that OAs may affect more than just upper-airway anatomy/collapsibility. OBJECTIVES: The objectives of this study were to determine how OA alters AHI and four phenotypic traits (upper-airway anatomy/collapsibility and muscle function, loop gain, and arousal threshold), and baseline predictors of which patients gain the greatest benefit from therapy. METHODS: In a randomized crossover study, 14 patients with OSA attended two sleep studies with and without their OA. Under each condition, AHI and the phenotypic traits were assessed. Multiple linear regression was used to determine independent predictors of the reduction in AHI. MEASUREMENTS AND MAIN RESULTS: OA therapy reduced the AHI (30 ± 5 vs. 11 ± 2 events/h; P < 0.05), which was driven by improvements in upper-airway anatomy/collapsibility under passive (1.9 ± 0.7 vs. 4.7 ± 0.6 L/min; P < 0.005) and active conditions (2.4 ± 0.9 vs. 6.2 ± 0.4 L/min; P < 0.001). No changes were seen in muscle function, loop gain, or the arousal threshold. Using multivariate analysis, baseline passive upper-airway collapsibility and loop gain were independent predictors of the reduction in AHI (r2 = 0.70; P = 0.001). CONCLUSIONS: Our findings suggest that OA therapy improves the upper-airway collapsibility under passive and active conditions. Importantly, a greater response to therapy occurred in those patients with a mild anatomic compromise and a lower loop gain.
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Obstrução das Vias Respiratórias/fisiopatologia , Resistência das Vias Respiratórias/fisiologia , Aparelhos Ortodônticos , Faringe/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Resultado do TratamentoRESUMO
BACKGROUND: Obstructive sleep apnoea (OSA) and obesity are two common conditions affecting the Australian population; obesity is the major risk factor for OSA. OBJECTIVE: The objectives of this article are to review the interactions between obesity and OSA, including the increased cardiovascular risk, and highlight the importance of using OSA diagnosis as a critical time to address obesity itself and other cardiovascular risk factors. DISCUSSION: Snoring and symptoms of OSA frequently worsen during periods of rapid weight gain. Obesity and metabolic factors (eg hypertension, hyperlipidaemia, insulin resistance) are commonly present at the time of OSA diagnosis. Severe OSA is an independent risk factor for cardiovascular disease and stroke. Continuous positive airway pressure (CPAP) treatment is safe and effective, reduces sleepiness, and improves mood and quality of life; however, the cardiovascular benefits of CPAP are uncertain. Weight loss leads to variable improvement in OSA, is most effective in milder OSA, and has a greater benefit on cardiovascular risk than CPAP.
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Obesidade/complicações , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/terapia , Austrália , Doenças Cardiovasculares/prevenção & controle , Pressão Positiva Contínua nas Vias Aéreas/métodos , Pressão Positiva Contínua nas Vias Aéreas/normas , Humanos , Qualidade de Vida/psicologia , Fatores de RiscoAssuntos
Nível de Alerta/fisiologia , Polissonografia/métodos , Taxa Respiratória/fisiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Sono/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
BACKGROUND AND OBJECTIVE: This study aimed to evaluate the involvement of airway cross-sectional area and shape, and functional residual capacity (FRC), in the genesis of obstructive sleep apnoea (OSA) in patients with supine-predominant OSA. METHODS: Three groups were recruited: (i) supine OSA, defined as a supine apnoea-hyponoea index (AHI) at least twice that of the non-supine AHI; (ii) rapid eye movement (REM) OSA, defined as REM AHI at least twice the non-REM AHI and also selected to have supine AHI less than twice that of the non-supine AHI (i.e. to be non-positional); and (iii) no OSA, defined as an AHI less than five events per hour. The groups were matched for age, gender and body mass index. Patients underwent four-dimensional computed tomography scanning of the upper airway in the supine and lateral decubitus positions. FRC was measured in the seated, supine and lateral decubitus positions. RESULTS: Patients with supine OSA demonstrated a significant decrease in FRC of 340 mL (P = 0.026) when moving from the lateral to supine position compared to controls with no OSA, and REM OSA patients. We found no differences between groups in upper airway size and shape. However, all groups showed a significant change in airway shape with the velopharyngeal airway adopting a more elliptoid shape (with the long axis laterally oriented), with reduced anteroposterior diameter in the supine position. CONCLUSIONS: A fall in FRC when moving lateral to supine in supine OSA patients may be an important triggering factor in the generation of OSA in this patient group.