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A 71-year-old man with a history of recurrent tonsillar squamous cell carcinoma was admitted to the hospital with oropharyngeal bleeding. He received high-dose radiation therapy with curative intent. On day 4 of hospitalization, he demonstrated hypoxia resulting from an airway mucus plug and was brought to the medical ICU. [ABSTRACT FROM AUTHOR]

A clinically applicable mortality risk prediction system for pulmonary TB may improve treatment outcomes, but no easy-to-calculate and accurate score has yet been reported. The aim of this study was to construct a simple and objective disease severity score for patients with pulmonary TB. Does a clinical score consisting of simple objective factors predict the mortality risk of patients with pulmonary TB? The data set from our previous prospective study that recruited patients newly diagnosed with pulmonary TB was used for the development cohort. Patients for the validation cohort were prospectively recruited between March 2021 and September 2022. The primary end point was all-cause in-hospital mortality. Using Cox proportional hazards regression, a mortality risk prediction model was optimized in the development cohort. The disease severity score was developed by assigning integral points to each variate. The data from 252 patients in the development cohort and 165 patients in the validation cohort were analyzed, of whom 39 (15.5%) and 17 (10.3%), respectively, died in the hospital. The disease severity score (named the AHL score) included three clinical parameters: activities of daily living (semi-dependent, 1 point; totally dependent, 2 points); hypoxemia (1 point), and lymphocytes (< 720/μL, 1 point). This score showed good discrimination with a C statistic of 0.902 in the development cohort and 0.842 in the validation cohort. We stratified the score into three groups (scores of 0, 1-2, and 3-4), which clearly corresponded to low (0% and 1.3%), intermediate (13.5% and 8.9%), and high (55.8% and 39.3%) mortality risk in the development and validation cohorts. The easy-to-calculate AHL disease severity score for patients with pulmonary TB was able to categorize patients into three mortality risk groups with great accuracy. University Hospital Medical Information Network Center; No. UMIN000012727 and No. UMIN000043849; URL: www.umin.ac.jp [ABSTRACT FROM AUTHOR]

A 56-year-old man with a medical history of diabetes, no prior lung disease, and no tobacco exposure presented with exhaustion and a nonproductive cough 7 days after working in an old farmhouse in Vermont. His friend who worked with him exhibited similar symptoms. He was treated as an outpatient with doxycycline; however, his clinical condition deteriorated and necessitated hospitalization and subsequent intubation. [ABSTRACT FROM AUTHOR]

OSA and nocturnal hypoxemia (NH) are common in patients with fibrotic interstitial lung disease (F-ILD), but their relationship with disease outcomes remains unclear. What is the relationship between NH and OSA and clinical outcomes in patients with F-ILD? This was a prospective observational cohort study of patients with F-ILD and without daytime hypoxemia. Patients underwent home sleep study at baseline and were followed up for at least 1 year or until death. NH was defined as ≥ 10% of sleep with oxygen saturation of < 90%. OSA was defined as an apnea-hypopnea index of ≥ 15 events/h. Among 102 participants (male, 74.5%; age, 73.0 ± 8.7 years; FVC, 2.74 ± 0.78 L; 91.1% idiopathic pulmonary fibrosis), 20 patients (19.6%) demonstrated prolonged NH and 32 patients (31.4%) showed OSA. No significant differences were found between those with and without NH or OSA at baseline. Despite this, NH was associated with a more rapid decline in both quality of life as measured by the King's Brief Interstitial Lung Disease questionnaire (change, –11.3 ± 5.3 points in the NH group vs –6.7 ± 6.5 in those without NH; P =.005) and higher all-cause mortality at 1 year (hazard ratio, 8.21; 95% CI, 2.40-28.1; P <.001). No statistically significant difference was seen between the groups in annualized change in measures of pulmonary function testing. Prolonged NH, but not OSA, is associated with worsening disease-related quality of life and increased mortality in patients with F-ILD. [ABSTRACT FROM AUTHOR]

A 68-year-old patient with obesity (BMI, 4 7 kg/m2) was transferred to the ED of our hospital because of dyspnea and pronounced hypoxemia. The patient underwent total right hip arthroplasty in an outside hospital because of osteoarthritis; there was no history of trauma. After 48 h, she experienced dyspnea with severe hypoxemia. The next day she was transferred to our hospital. Her history was notable for arterial hypertension and depression, but not heart failure. Her medications included candesartan (16 mg once daily) and sertraline (100 mg once daily). Perioperatively, she received enoxaparin 4.000 International Units subcutaneously once daily. There was no family history of respiratory diseases. The patient currently smokes (50 pack-years) with no recent increase in her habit and denied vaping, alcohol consumption, illicit drug use, and any home or occupational exposures. Prior to surgery, the family of the patient reported that she maintained modest mobility despite her osteoarthritis and was able to fulfill her daily activities. Interestingly, she reported a similar event of severe dyspnea and hypoxemia after total knee arthroplasty 3 years earlier; however, no further details were available [ABSTRACT FROM AUTHOR]

An otherwise healthy 17-year-old male patient presented to a periphery hospital with a compound fracture of the right distal tibia and fibula after a traumatic accident on a ski trip. He was treated empirically with IV cefazolin before undergoing open reduction with internal fixation with intramedullary nail for surgical fixation. Postoperatively, he became febrile, tachypneic, and hypoxemic, requiring up to 6 L/min supplemental oxygen by nasal prongs. He reported mild chest discomfort but denied productive cough, hemoptysis, or calf tenderness. Because of nonresolving oxygen demands, on postoperative day (POD) 4, he was transferred to a tertiary care center for further management. [ABSTRACT FROM AUTHOR]

An 80-year-old man came to the ED with fever, hematuria, and overall discomfort for 1 week. His medical history included a superficial urothelial carcinoma of the bladder for which he was adjunctively treated with intravesical Mycobacterium bovis BCG (bacillus Calmette-Guérin) immunotherapy for several months. The patient was admitted to the hospital and was initially treated with cephalosporins for a suspected complicated urinary tract infection, but his symptoms did not improve. Ten days after the initial admission, the patient developed hypoxemic respiratory failure during an episode of fever and cold chills and was admitted to the ICU. [ABSTRACT FROM AUTHOR]

Hypoxia is encountered frequently in the ICU as a result of a wide range of pathologic characteristics. The oxygen-hemoglobin dissociation curve describes hemoglobin's affinity for a given P o 2 and factors affecting uptake and offload. Research in manipulating this relationship between hemoglobin and oxygen is sparing. Voxelotor is a hemoglobin oxygen-affinity modulator that is approved by the US Food and Drug Association for use in the management of sickle cell disease. We present two patients without sickle cell disease who underwent treatment with this novel agent to assist with chronic hypoxia and weaning of mechanical support. [ABSTRACT FROM AUTHOR]

Prone positioning is an immediately accessible, readily implementable intervention that was proposed initially as a method for improvement in gas exchange > 50 years ago. Initially implemented clinically as an empiric therapy for refractory hypoxemia, multiple clinical trials were performed on the use of prone positioning in various respiratory conditions, cumulating in the landmark Proning Severe ARDS Patients trial, which demonstrated mortality benefit in patients with severe ARDS. After this trial and the corresponding meta-analysis, expert consensus and societal guidelines recommended the use of prone positioning for the management of severe ARDS. The ongoing COVID-19 pandemic has brought prone positioning to the forefront of medicine, including widespread implementation of prone positioning in awake, spontaneously breathing, nonintubated patients with acute hypoxemic respiratory failure. Multiple clinical trials now have been performed to investigate the safety and effectiveness of prone positioning in these patients and have enhanced our understanding of the effects of the prone position in respiratory failure. In this review, we discuss the physiologic features, clinical outcome data, practical considerations, and lingering questions of prone positioning. [ABSTRACT FROM AUTHOR]

Background: Functional capacity, as measured by the 6-min walk test (6MWT), is often reduced in fibrotic interstitial lung disease (ILD). This study evaluated longitudinal changes and the prognostic significance of 6MWT parameters, and explored change in oxygenation status as a physiological criterion to define disease progression in patients with fibrotic ILD.Research Questions: What are the trajectories and prognostic value of 6MWT parameters in patients with fibrotic ILD?Study Design and Methods: Using prospective registries in Australia and Canada, patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD were stratified by the presence of criteria for progressive pulmonary fibrosis (PPF). The cumulative incidence of exertional and resting hypoxemia and changes in 6-min walk distance (6MWD) and composite indices (distance-saturation product and distance-saturation-oxygen product) were determined, with prognostic significance evaluated at the time of meeting criteria for PPF. New-onset exertional or resting hypoxemia was evaluated as another potential criterion for PPF.Results: Patients with IPF/PPF (n = 126) and non-IPF/PPF (n = 227) had a similar cumulative incidence of exertional hypoxemia and annualized decline in 6MWD and composite indices, which varied across each PPF criterion. Patients with IPF/non-PPF (n = 231) and non-IPF/non-PPF (n = 531) had a significantly lower incidence of hypoxemia than those with IPF/PPF, with an annualized increase in 6MWD and composite indices in the non-IPF/non-PPF group. Exertional or resting hypoxemia at the time of meeting criteria for PPF was independently associated with reduced transplant-free survival in IPF and non-IPF, adjusting for patient demographics and lung function. Adding new-onset exertional or resting hypoxemia as a physiological criterion reduced the median time to development of PPF from 11.2 to 6.7 months in IPF and from 11.7 to 5.6 months in non-IPF in patients who eventually met both definitions (P < .001 for both).Interpretation: Patients with IPF/PPF and non-IPF/PPF have comparable deterioration in functional capacity. Oxygenation status provides prognostic information in PPF and may assist in defining disease progression in fibrotic ILD. [ABSTRACT FROM AUTHOR]

A 77-year-old woman with asthma, hypothyroidism, irritable bowel syndrome, overactive bladder, and multiple rheumatologic conditions was sent from the clinic to the ED for evaluation of hypoxia. In the clinic, she reported dizziness without shortness of breath and was noted to have perioral cyanosis with an oxygen saturation measured by pulse oximetry (Sp o 2) of 80%. She was given a nonrebreather mask delivering oxygen at 8 L/min, but the Sp o 2 remained at 77% to 82%. In the ED, the patient reported intermittent shortness of breath, 2 to 3 days of mild left lower extremity swelling, and a brief episode of lightheadedness earlier in the day that had since resolved. She denied fevers/chills, upper respiratory symptoms, and chest pain. She had been referred to the pulmonology clinic 3 years earlier to evaluate mild hypoxia with Sp o 2 readings in the low 90% range, but pulmonary function testing failed to identify an etiology. There was no history of VTE. Her rheumatologic conditions included osteoarthritis, rheumatoid arthritis, Sjögren's syndrome, and fibromyalgia. [ABSTRACT FROM AUTHOR]

Mortality historically has been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome, and focusing solely on mortality fails to recognize the importance that reducing morbidity can have on patients' lives. The COVID-19 pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury: mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs typically is greater than that for other clinical trial outcomes, such as mortality and ventilator-free days. OFDs is the primary outcome for the Fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This article outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome. [ABSTRACT FROM AUTHOR]

Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiological mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proved challenging; several contemporary trials showed no major clinical benefits with prone positioning. By optimizing patient selection and treatment protocols, the recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS.

Background: Pulse oximeters may produce less accurate results in non-White patients.Research Question: Do pulse oximeters detect arterial hypoxemia less effectively in Black, Hispanic, and/or Asian patients than in White patients in respiratory failure and about to undergo extracorporeal membrane oxygenation (ECMO)?Study Design and Methods: Data on adult patients with respiratory failure readings 6 h before ECMO were provided by the Extracorporeal Life Support Organization registry. Data was collected from 324 centers between January 2019 and July 2020. Our primary analysis was of rates of occult hypoxemia-low arterial oxygen saturation (Sao2 ≤ 88%) on arterial blood gas measurement despite a pulse oximetry reading in the range of 92% to 96%.Results: The rate of pre-ECMO occult hypoxemia, that is, arterial oxygen saturation (Sao2) ≤ 88%, was 10.2% (95% CI, 6.2%-15.3%) for 186 White patients with peripheral oxygen saturation (Spo2) of 92% to 96%; 21.5% (95% CI, 11.3%-35.3%) for 51 Black patients (P = .031 vs White); 8.6% (95% CI, 3.2%-17.7%) for 70 Hispanic patients (P = .693 vs White); and 9.2% (95% CI, 3.5%-19.0%) for 65 Asian patients (P = .820 vs White). Black patients with respiratory failure had a statistically significantly higher risk of occult hypoxemia with an OR of 2.57 (95% CI, 1.12-5.92) compared with White patients (P = .026). The risk of occult hypoxemia for Hispanic and Asian patients was equivalent to that of White patients. In a secondary analysis of patients with Sao2 ≤ 88% despite Spo2 > 96%, Black patients had more than three times the risk compared with White patients (OR, 3.52; 95% CI, 1.12-11.10; P = .032).Interpretation: Compared with White patients, the prevalence of occult hypoxemia was higher in Black patients than in White patients about to undergo ECMO for respiratory failure, but it was comparable in Hispanic and Asian patients compared with White patients. [ABSTRACT FROM AUTHOR]

Case Presentation: An 84-year-old woman with a medical history of hypertension, hypothyroidism, and transient ischemic attacks presented with right-sided upper and lower extremity weakness for 1 day. She was a lifetime nonsmoker with no known heart disease or chronic lung disease. She had no occupational exposure or pertinent family history. She denied any fevers, chills, rashes, or shortness of breath. There was no history of recent travel. [ABSTRACT FROM AUTHOR]

Case Presentation: A 37-year-old man presented with breathlessness and wheeze of 3 weeks' duration. There was no chest pain, cough, palpitation, pedal edema, or fever. For the past 12 years, he had been experiencing episodic breathlessness and wheeze, which improved with inhaled salbutamol. He also had symptoms of nasal obstruction, nasal discharge, and sneezing. There was no history of smoking, substance abuse, or the use of any over-the-counter medication. The current episode of bronchial asthma exacerbation was managed with bronchodilators and systemic glucocorticoids. Despite symptomatic relief and clinical improvement, his oxygen saturation remained at 75% to 80%, and he was referred to our facility for further evaluation. [ABSTRACT FROM AUTHOR]

Background: Limited evidence is available regarding the association between OSA and coronary plaque assessed by using quantitative coronary CT angiography.Research Question: Are there any associations between OSA severity-related indexes and the presence and burden of coronary plaque?Study Design and Methods: Cross-sectional data from 692 patients who underwent sleep monitoring and coronary CT angiography were used for this study. Of these patients, 120 (17.3%) underwent polysomnography, and 572 (82.7%) underwent respiratory polygraphy. Multivariable logistic and linear regression analyses were used to investigate the associations of OSA severity-related indexes with the presence, volume, and composition of plaque.Results: In multivariable analyses, patients with moderate to severe OSA were more likely to have coronary plaques (P = .037), and plaques were more likely to contain a noncalcified plaque (NCP) component (P = .032) and a low-density NCP (LD NCP) component (P = .030). Furthermore, the apnea-hypopnea index and oxygen desaturation index as continuous variables were both associated with the presence of plaque, NCP, and LD NCP (all, P < .05). Multivariable linear regression models showed that moderate to severe OSA was associated with NCP volume (β = 50.328; P = .042) and LD NCP volume (β = 15.707; P = .011). Moreover, the apnea-hypopnea index (P = .015), oxygen desaturation index (P = .005), and percentage of nighttime with oxygen saturation < 90% (P = .017) were all significant predictors of LD NCP volume. Compared with those with no or mild OSA, patients with severe OSA had a significantly higher total plaque volume (P = .036), NCP volume (P = .036), and LD NCP volume (P = .013).Interpretation: OSA was independently associated with the presence and burden of coronary plaque, which suggests an increased risk of coronary events.Clinical Trial Registration: Chinese Clinical Trial Registry; No. ChiCTR-ROC-17011027; http://chictr.org.cn. [ABSTRACT FROM AUTHOR]

Case Presentation: A 70-year-old woman was transferred to our ED from an outside ED for hypoxemia. Three weeks earlier, an inpatient evaluation for syncope revealed a right intraventricular filling defect, multiple pulmonary nodules, pulmonary emboli, and a left breast mass. She underwent breast biopsy, was started on rivaroxaban, and was discharged with outpatient follow-up. She experienced progressively worsening dyspnea, prompting a return to the outside ED, where she was found to be severely hypoxemic and was intubated. Her medical history included diabetes, hypertension, hyperlipidemia, COPD, hypothyroidism, diastolic heart failure, and a 40+ pack-year smoking history. [ABSTRACT FROM AUTHOR]

Background: Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD currently is unknown.Research Question: What are the epidemiologic features of hypoxemia and its additive prognostic value in a current risk prediction model of fibrotic ILD?Methods: We identified 848 patients with fibrotic ILD (258 with idiopathic pulmonary fibrosis [IPF]) in five prospective ILD registries from Australia, Canada, and Switzerland. Cumulative incidence of exertional and resting hypoxemia from the time of diagnosis was estimated at 1-year intervals in patients with baseline 6-min walk tests, adjusted for competing risks of death and lung transplantation. Likelihood ratio tests were used to determine the prognostic significance of exertional and resting hypoxemia for 1-year mortality or transplantation when added to the ILD-GAP model. The cohort was divided into derivation and validation subsets to evaluate performance characteristics of the extended model (the ILD-GAP-O2 model), which included oxygenation status as a predictor.Results: The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1%, respectively, for exertional hypoxemia and 2.4%, 5.6%, and 16.5%, respectively, for resting hypoxemia, which were significantly higher in patients with IPF compared with patients without IPF (P < .001 for both). Addition of exertional or resting hypoxemia to the ILD-GAP model improved 1-year mortality and transplantation prediction (P < .001 for both). The ILD-GAP-O2 model showed improved discrimination (C-index, 0.80 vs 0.75) and model fit (Akaike information criteria, 400 vs 422) in the validation cohort, with comparable calibration.Interpretation: Patients with IPF have higher cumulative incidence of exertional and resting hypoxemia than patients without IPF. The extended ILD-GAP-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD. [ABSTRACT FROM AUTHOR]

Background: Many patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PH) wish to travel to altitude or by airplane, but their risk of hypoxia-related adverse health effects is insufficiently explored.Research Question: How does hypoxia, compared with normoxia, affect constant work-rate exercise test (CWRET) time in patients with PH, and which physiologic mechanisms are involved?Study Design and Methods: Stable patients with PH with resting Pao2 ≥ 7.3 kPa underwent symptom-limited cycling CWRET (60% of maximal workload) while breathing normobaric hypoxic air (hypoxia; Fio2, 15%) and ambient air (normoxia; Fio2, 21%) in a randomized cross-over design. Borg dyspnea score, arterial blood gases, tricuspid regurgitation pressure gradient, and mean pulmonary artery pressure/cardiac output ratio (mean PAP/CO) by echocardiography were assessed before and during end-CWRET.Results: Twenty-eight patients (13 women) were included: median (quartiles) age, 66 (54; 74) years; mean pulmonary artery pressure, 41 (29; 49) mm Hg; and pulmonary vascular resistance, 5.4 (4; 8) Wood units. Under normoxia and hypoxia, CWRET times were 16.9 (8.0; 30.0) and 6.7 (5.5; 27.3) min, respectively, with a median difference (95% CI) of -0.7 (-3.1 to 0.0) min corresponding to -7 (-32 to 0.0)% (P = .006). At end-exercise in normoxia and hypoxia, respectively, median values and differences in corresponding variables were as follows: Pao2: 8.0 vs 6.4, -1.7 (-2.7 to -1.1) kPa; arterial oxygen content: 19.2 vs 17.2, -1.7 (-3 to -0.1) mL/dL; Paco2: 4.7 vs 4.3, -0.3 (-0.5 to -0.1) kPa; lactate: 3.7 vs 3.7, 0.9 (0.1 to 1.6) mM (P < .05 all differences). Values for Borg scale score: 7 vs 6, 0.5 (0 to 1); tricuspid pressure gradient: 89 vs 77, -3 (-9 to 16) mm Hg; and mean PAP/CO: 4.5 vs 3.3, 0.3 (-0.8 to 1.4) Wood units remained unchanged. In multivariable regression, baseline pulmonary vascular resistance was the sole predictor of hypoxia-induced change in CWRET time.Interpretation: In patients with PH, short-time exposure to hypoxia was well tolerated but reduced CWRET time compared with normoxia in association with hypoxemia, lactacidemia, and hypocapnia. Because pulmonary hemodynamics and dyspnea at end-exercise remained unaltered, the hypoxia-induced exercise limitation may be due to a reduced oxygen delivery causing peripheral tissue hypoxia, augmented lactic acid loading and hyperventilation.Trial Registry: ClinicalTrials.gov; No.: NCT03592927; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk.Research Question: Do novel nocturnal oxygen saturation (Spo2) metrics have prognostic value in patients with OSA and high cardiovascular event risk?Study Design and Methods: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo2, average Spo2 for the entire recording (mean Spo2), average Spo2 during desaturation events (desaturation Spo2), average baseline Spo2 interpolated across episodic desaturation events (baseline Spo2), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate.Results: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93).Interpretation: Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management. [ABSTRACT FROM AUTHOR]

Background: Previous studies have yielded inconsistent findings regarding the association between OSA and cancer in humans.Research Question: Is there an association between indexes of sleep-disordered breathing severity and cancer incidence in patients investigated for suspected OSA?Study Design and Methods: Data from a large multicenter cohort of cancer-free patients investigated for OSA were linked to health administrative data to identify new-onset cancer. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association of cancer incidence with OSA severity and nocturnal hypoxemia.Results: After a median follow-up period of 5.8 years (interquartile range, 3.8-7.8), 718 of 8,748 patients (8.2%) had received a diagnosis of cancer. On unadjusted Kaplan-Meier survival analyses, cancer incidence was associated with increasing severity of OSA (log-rank test, P < .0005) and nocturnal hypoxemia (log-rank test, P < .0001 for both oxygen desaturation index and percent night time with oxygen saturation < 90% [T90]). After adjustment for anthropomorphic data, smoking and alcohol consumption, comorbid cardiac, metabolic, and respiratory diseases, marital status, type of sleep study, and study site, only T90 was associated with cancer incidence (adjusted hazard ratio, 1.33; 95% CI, 1.05-1.68 for T90 ≥ 13% vs < 0.01%; P = .02). On stratified analyses, the association between T90 and cancer appeared stronger in older patients with obesity and no adequate OSA therapy. Among the most frequent cancer sites, nocturnal hypoxemia was associated with lung and breast malignancies.Interpretation: Nocturnal hypoxemia was associated with all-cancer incidence in patients investigated for OSA. Whether OSA therapy might reduce the risk of cancer needs further evaluation. [ABSTRACT FROM AUTHOR]

Background: OSA, a common comorbidity in interstitial lung disease (ILD), could contribute to a worsened course if untreated. It is unclear if adherence to CPAP therapy improves outcomes.Research Question: Does adherence to CPAP therapy improve outcomes in patients with concurrent interstitial lung disease and OSA?Study Design and Methods: We conducted a 10-year retrospective observational multicenter cohort study, assessing adult patients with ILD who had undergone polysomnography. Subjects were categorized based on OSA severity into no/mild OSA (apnea-hypopnea index score < 15) or moderate/severe OSA (apnea-hypopnea index score ≥ 15). All subjects prescribed and adherent to CPAP were deemed to have treated OSA. Cox regression models were used to examine the association of OSA severity and CPAP adherence with all-cause mortality risk and progression-free survival (PFS).Results: Of 160 subjects that met inclusion criteria, 131 had OSA and were prescribed CPAP. Sixty-six patients (41%) had no/mild untreated OSA, 51 (32%) had moderate/severe untreated OSA, and 43 (27%) had treated OSA. Subjects with no/mild untreated OSA did not differ from those with moderate/severe untreated OSA in mean survival time (127 ± 56 vs 138 ± 93 months, respectively; P = .61) and crude mortality rate (2.9 per 100 person-years vs 2.9 per 100 person-years, respectively; P = .60). Adherence to CPAP was not associated with improvement in all-cause mortality risk (hazard ratio [HR], 1.1; 95% CI, 0.4-2.9; P = .79) or PFS (HR, 0.9; 95% CI, 0.5-1.5; P = .66) compared with those that were nonadherent or untreated. Among subjects requiring supplemental oxygen, those adherent to CPAP had improved PFS (HR, 0.3; 95% CI, 0.1-0.9; P = .03) compared with nonadherent or untreated subjects.Interpretation: Neither OSA severity nor adherence to CPAP was associated with improved outcomes in patients with ILD except those requiring supplemental oxygen. [ABSTRACT FROM AUTHOR]

Background: Pulmonary gas exchange efficiency, determined by the alveolar-to-arterial Po2 difference (A-aDo2), progressively worsens during exercise at sea-level; this response is further elevated during exercise in hypoxia. Traditionally, pulmonary gas exchange efficiency is assessed through measurements of ventilation and end-tidal gases paired with direct arterial blood gas (ABG) sampling. Because these measures have a number of caveats, particularly invasive blood sampling, the development of new approaches for the noninvasive assessment of pulmonary gas exchange is needed.Research Question: Is a noninvasive method of assessing pulmonary gas exchange valid during rest and exercise in acute hypoxia?Study Design and Methods: Twenty-five healthy participants (10 female) completed a staged maximal exercise test on a cycle ergometer in a hypoxic chamber (Fio2 = 0.11). Simultaneous ABGs via a radial arterial catheter and noninvasive gas-exchange measurements (AGM100) were obtained in 2-minute intervals. Noninvasive gas exchange, termed the O2 deficit, was calculated from the difference between the end-tidal and the calculated Pao2 (via pulse oximetry and corrected for the Bohr effect by using the end-tidal Pco2). Noninvasive O2 deficit was compared with the traditional alveolar to arterial oxygen difference (A-aDo2), using the traditional Riley analysis.Results: Under conditions of rest at room air, hypoxic rest, and hypoxic exercise, strong correlations between the calculated gPao2 and directly measured Pao2 (R2 = 0.97; P < .001; mean bias = 1.70 mm Hg) were observed. At hypoxic rest and exercise, strong relationships between the estimated and directly measured Pao2 (R2 = 0.68; P < .001; mean bias = 1.01 mm Hg) and O2 deficit with the traditional A-aDo2 (R2 = 0.70; P < .001; mean bias = 5.24 mm Hg) remained.Interpretations: Our findings support the use of a noninvasive measure of gas exchange during acute hypoxic exercise in heathy humans. Further studies are required to determine whether this approach can be used clinically as a tool during normoxic exercise in patients with preexisting impairments in gas exchange efficiency. [ABSTRACT FROM AUTHOR]

Background: Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia (ie, a significant fall in hemoglobin oxygen saturation [Spo2]) during sea level exercise in endurance-trained athletes. It is unknown whether there are specific properties of pulmonary vascular function in athletes exhibiting oxygen desaturation.Methods: Ten endurance-trained athletes with exercise-induced hypoxemia (EIH), nine endurance-trained athletes with no exercise-induced hypoxemia (NEIH), and 10 untrained control subjects underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for carbon monoxide (Dlco) and lung diffusion capacity for nitric oxide (Dlno) testing. Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure, pulmonary vascular resistance (PVR), cardiac output (Qc), and pulmonary vascular distensibility (alpha) mathematically determined from the curvilinearity of the multi-point mPAP/Qc relation.Results: EIH athletes exhibited a lower exercise-induced PVR decrease compared with the untrained and NEIH groups (P < .001). EIH athletes showed higher maximal mPAP compared with NEIH athletes (45.4 ± 0.9 mm Hg vs 41.6 ± 0.9 mm Hg, respectively; P = .003); there was no difference between the NEIH and untrained subjects. Alpha was lower in the EIH group compared with the NEIH group (P < .05). Maximal mPAP, Pcap, and alpha were correlated with the fall of Spo2 during exercise (P < .01, P < .01, and P < .05). Dlno and Dlco increased with exercise in all groups, with no differences between groups. Dlno/Qc was correlated to the exercise-induced Spo2 changes (P < .05).Conclusions: EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility, or exercise-induced changes in PVR compared with NEIH subjects, in keeping with pulmonary capillary stress failure or intrapulmonary shunting hypotheses. [ABSTRACT FROM AUTHOR]

Lobar atelectasis (or collapse) is an exceedingly common, rather predictable, and potentially pathogenic companion to many forms of acute illness, postoperative care, and chronic debility. Readily diagnosed by using routine chest imaging and bedside ultrasound, the consequences from lobar collapse may be minor or serious, depending on extent, mechanism, patient vulnerability, abruptness of onset, effectiveness of hypoxic vasoconstriction, and compensatory reserves. Measures taken to reduce secretion burden, assure adequate secretion clearance, maintain upright positioning, reverse lung compression, and sustain lung expansion accord with a logical physiologic rationale. Both classification and logical approaches to prophylaxis and treatment of lobar atelectasis derive from a sound mechanistic knowledge of its causation. [ABSTRACT FROM AUTHOR]

Case Presentation: A 49-year-old woman with a medical history of epilepsy presented to the ED 1 h after a single, 15-min, witnessed, tonic-clonic seizure. Over the preceding 6 months, she had experienced five similar seizures of shorter duration. There were no recent changes to her phenytoin dose nor had she started any new medications. The patient had traveled to Jamaica 3 weeks before presentation, where she smoked marijuana once but otherwise had not used illicit substances nor had she used tobacco or alcohol. She states she felt well during and after the trip until this presentation. While being evaluated by the neurology service, the patient complained of sudden-onset chest pain and cough with associated hypoxemia. She denied changes in her sleep habits, she had not experienced any fevers, and she had no changes in her exercise tolerance. The patient was admitted to the general medicine floor for further workup. [ABSTRACT FROM AUTHOR]

In the surgical setting, OSA is associated with an increased risk of postoperative complications. At present, risk stratification using OSA-associated parameters derived from polysomnography (PSG) or overnight oximetry to predict postoperative complications has not been established. The objective of this narrative review is to evaluate the literature to determine the association between parameters extracted from in-laboratory PSG, portable PSG, or overnight oximetry and postoperative adverse events. We obtained pertinent articles from Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, and Embase (2008 to December 2017). The search included studies with adult patients undergoing surgery who had OSA diagnosed with portable PSG, in-laboratory PSG, or overnight oximetry that reported on specific sleep parameters and at least one adverse outcome. The search was restricted to English-language articles. The search yielded 1,810 articles, of which 21 were included in the review. Preoperative apnea-hypopnea index (AHI) and measurements of nocturnal hypoxemia such as oxygen desaturation index (ODI), cumulative sleep time percentage with oxyhemoglobin saturation (Spo2) < 90% (CT90), minimum Spo2, mean Spo2, and longest apnea duration were associated with postoperative complications. OSA is associated with postoperative complications in the population undergoing surgery. Clinically and statistically significant associations between AHI and postoperative adverse events exists. Complications may be more likely to occur in the category of moderate to severe OSA (AHI ≥ 15). Other parameters from PSG or overnight oximetry such as ODI, CT90, mean and minimal Spo2, and longest apnea duration can be associated with postoperative complications and may provide additional value in risk stratification and minimization. [ABSTRACT FROM AUTHOR]

Individuals living with spinal cord injury or disease (SCI/D) are at increased risk for sleep-disordered breathing (SDB), with a prevalence that is three- to fourfold higher than the general population. The main features of SDB, including intermittent hypoxemia and sleep fragmentation, have been linked to adverse cardiovascular outcomes including nocturnal hypertension in patients with SCI/D. The relationship between SDB and SCI/D may be multifactorial in nature given that level and completeness of injury can affect central control of respiration and upper airway collapsibility differently, promoting central and/or obstructive types of SDB. Despite the strong association between SDB and SCI/D, access to diagnosis and management remains limited. This review explores the role of SCI/D in the pathogenesis of SDB, poor sleep quality, the barriers in diagnosing and managing SDB in SCI/D, and the alternative approaches and future directions in the treatment of SDB, such as novel pharmacologic and nonpharmacologic treatments. [ABSTRACT FROM AUTHOR]