Daytime Hypoxemia Research Articles

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus.

Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DlCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DlCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DlCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DlCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2] < 90% [T90]). Structural equation models were used to assess associations of impaired DlCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DlCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index ⩾ 30 events/h) and impaired DlCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, -8.2% [95% CI, -11.4% to -4.9%]) and average SpO2 during sleep (median difference, -1.1% [95% CI, -2.1% to -0.01%]) than those with severe SDB and preserved DlCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DlCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DlCO to guide testing and risk stratification strategies.

Nocturnal Hypoxemia Associates With Symptom Progression and Mortality in Patients With Progressive Fibrotic Interstitial Lung Disease

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.

Supplemental oxygen and noninvasive ventilation.

The respiratory system attempts to maintain normal levels of oxygen and carbon dioxide. However, airflow limitation, parenchymal abnormalities and dysfunction of the respiratory pump may be compromised in individuals with advanced COPD, eventually leading to respiratory failure, with reduced arterial oxygen tension (hypoxaemia) and/or increased arterial carbon dioxide tension (P aCO2 ; hypercapnia). Hypoxaemia may persist in individuals with severe COPD despite smoking cessation and optimisation of pharmacotherapy. Long-term oxygen therapy (LTOT) can improve survival in those with severe daytime hypoxaemia, whereas those with less severe hypoxaemia may only have improved exercise capacity and dyspnoea. Changes in respiratory physiology that occur during sleep further predispose to hypoxaemia, particularly in individuals with COPD. However, the major cause of hypoxaemia is hypoventilation. Noninvasive ventilation (NIV) may reduce mortality and need for intubation in individuals with COPD and acute hypercapnic respiratory failure. However, NIV may also improve survival and quality of life in individuals with stable, chronic hypercapnia and is now suggested for those with prolonged hypercapnia (e.g. P aCO2 >55 mmHg 2-6 weeks after hospital discharge) when clinically stable and after optimisation of medical therapy including LTOT if indicated. Many questions remain about the optimal mode, settings and goal of NIV therapy.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Home oxygen for moderate hypoxaemia in chronic obstructive pulmonary disease: a systematic review and meta-analysis

Long-term oxygen therapy (LTOT) improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia. However, the best method of management of moderate hypoxaemia not qualifying for LTOT (including isolated nocturnal desaturation) is uncertain. We examined the effect of home oxygen (either LTOT or nocturnal oxygen therapy) on overall survival in patients with COPD and moderate hypoxaemia. In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINHAL, and Web of Science from database inception to Jan 13, 2022, for parallel-group randomised trials of long-term or nocturnal oxygen in patients with COPD and moderate daytime hypoxaemia or isolated nocturnal desaturation, or both. Control groups received usual care or ambient air through sham concentrators (placebo) throughout the study period. The primary outcome of interest was 3-year mortality. Crossover trials and trials of oxygen in severe hypoxaemia were excluded. Two reviewers applied inclusion and exclusion criteria to titles and abstracts and screened the full-text articles and reference lists of relevant studies. Aggregate data were extracted manually in duplicate using structured data collection forms. Methodological quality was assessed using the Cochrane Risk of Bias tool. Random-effects meta-analysis was used to pool individual studies. We considered the minimal clinically important difference for home oxygen to be a relative risk reduction in mortality at 3-year follow-up of 30-40%. The meta-analysis is registered on PROSPERO, CRD42021225372. We identified 2192 studies and screened 1447 after removal of duplicates, of which 161 were subjected to full-text screening, and six were identified as being eligible for inclusion. These six randomised trials were published between 1992 and 2020 and the quality of evidence was high. In the primary meta-analysis (five trials; 1002 patients), we found the effect of home oxygen in reducing 3-year mortality to be small or absent (relative risk 0·91 [95% CI 0·72-1·16]; τ² = 0·00), hence the lower limit of the 95% CI did not meet the prespecified minimal clinically important difference. The results of our meta-analysis suggest that home oxygen probably makes little or no difference to 3-year mortality in patients with COPD and moderate hypoxaemia. The data do not support the widespread use of home oxygen in this patient population. None.

Long-Term Domiciliary Noninvasive Ventilation for COPD.

COPD can lead to abnormalities in oxygenation as well as ventilation. Thanks to pioneering work by Dr Thomas Petty, supplemental oxygen therapy has been shown to improve morbidity and mortality for individuals with COPD and severe daytime hypoxemia. However, efforts to augment ventilation have been less uniformly successful. Recent studies employing a so-called high-intensity noninvasive ventilation strategy, which used high inspiratory pressures and backup breathing frequency to reduce arterial carbon dioxide levels, have shown improved quality of life and reduced mortality. Thus, efforts are underway to better identify and treat patients with COPD who might benefit from noninvasive ventilation, though many practical questions remain.

Pulmonary complications of sickle cell disease: a narrative clinical review.

Sickle cell disease (SCD) is associated with vaso-occlusive episodes that affect different organs. Pulmonary involvement is a major cause of morbidity and mortality in this patient population. We performed a literature search in the PubMed database for articles addressing SCD and pulmonary diseases. Acute chest syndrome is defined as a new radiodensity on chest radiograph imaging with a history consistent of the disease. Management includes broad spectrum antibiotics, pain control, and blood transfusions. Microvasculature infarcts lead to functional asplenia, which in turn increases the risk of being infected with encapsulated organisms. Universal vaccinations and antibiotic prophylaxis play a significant role in decreasing mortality from pulmonary infections. Venous thromboembolism in patients with SCD should be treated in the same manner as in the general population. Pulmonary hypertension in patients with SCD also increases mortality. The American Thoracic Society treatment modalities are based on the underlying etiology which is either directed at treating SCD itself, using vasodilator medications if the patient is in group 1, or using long-term anticoagulation if the patient is group 4 (in terms of etiology). Patients with SCD are more likely to suffer from asthma in comparison to controls. Sleep disorders of breathing should be considered in patients with unexplained nocturnal and daytime hypoxemia, or recurrentvaso-occlusive events. Lastly, the utility of pulmonary function tests still needs to be established.

Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease

BackgroundLong-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen therapy for the management of isolated nocturnal hypoxemia is uncertain.MethodsWe designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population.ResultsRecruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, −3.0 percentage points; 95% confidence interval, −15.1 to 9.1).ConclusionsOur underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.)

Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients

Background: Despite clinical optimization, many chronic heart failure (CHF) patients remain symptomatic with dyspnea and poor quality of life. Study Objective: While oxygen therapy is prescribed in severe cases, the actual prevalence of different patterns of hypoxemia is unknown. Methods: We analyzed 183 stable CHF patients with optimized medical treatment in the “MARS” database. The patients underwent cardiorespiratory sleep recording and complete daytime pulmonary function tests including arterial blood gases. Results: This prospective cohort was predominately male (86.3%) with a mean age of 67.3 years (59.3; 75.7) and a mean BMI of 26.7 kg/m² (23.7; 31.1). The patients were mainly in NYHA classes II and III with a mean left ventricular ejection fraction of 38%. 102 (55.61%) patients had ischemic cardiomyopathy with multiple comorbidities, and 64 (35.06%) had airflow obstruction. 8 (4.37%) patients had hypoxemia both day and night, and 151 (82.5%) had nocturnal hypoxemia only. All but 3 patients had sleep-disordered breathing (SDB), and either obstructive (59%) or central sleep apnea (39%) with a mean apnea-hypopnea index of 29.59/h (16.48; 48.27), an oxygen desaturation index of 27.09/h (14.09; 45.25), time below 90% saturation of 18 min (2; 64), and a mean nocturnal saturation of 93% (92; 94). Univariate analysis found nocturnal hypoxemia was associated with higher BMI and NT-proBNP levels. In multivariate analysis, only sleep apnea severity (p < 0.0001) and diurnal PaO₂ remained significant. Conclusion: Most stable CHF patients suffer from nocturnal hypoxemia, while daytime hypoxemia is relatively rare. The degree of nocturnal hypoxemia depends on the severity of SDB. Hypoxemia phenotyping and severity could help better evaluate the need for appropriate therapy in CHF patients.

Instability of nocturnal parasympathetic nerve function in patients with chronic lung disease with or without nocturnal desaturation

Objective/backgroundThis study was performed to evaluate the association of nocturnal autonomic nerve (AN) dysfunction, especially parasympathetic nerve (PN) function instability, and nocturnal oxygen desaturation (NOD) in patients with chronic lung diseases (CLD).Patients and methodsTwenty-nine stable CLD patients with irreversible pulmonary dysfunction and mild-to-moderate daytime hypoxemia, 13 CLD patients receiving long-term oxygen therapy (LTOT) with maintained SpO2 >90%, and 17 senior healthy volunteers underwent two-night examinations of nocturnal AN function by pulse rate variability (PRV) instead of heart rate variation using a photoelectrical plethysmograph simultaneously monitoring SpO2 and the presence of sleep disordered breathing at home. AN function was examined by instantaneous time–frequency analysis of PRV using a complex demodulation method.ResultsThere were no significant differences in mean low frequency/high frequency (HF) ratio (index of sympathetic nerve activity) or mean HF amplitude (index of PN activity) among controls and CLD patients with and without NOD (defined as SpO2 <90% for at least 3% of total recording time at night). However, the relative times over which the same main HF peak was sustained for at least 20 seconds (%HF20sec) and 5 minutes in total recording time, indexes of PN function stability, were significantly reduced in CLD patients compared with controls, and further decreased in CLD patients with NOD compared with non-NOD. %HF20sec was significantly higher in the LTOT group than the NOD group. Furthermore, PaO2 at rest and nocturnal hypoxia were significantly correlated with PN function instability in CLD patients.ConclusionPN function is unstable at night associated with nocturnal hypoxemia in CLD patients, which may reflect poor quality of sleep.

Pericardial Effusion in Obstructive Sleep Apnea without Pulmonary Arterial Hypertension and Daily Hypoxemia - is it Unusual?

Background:Pericardial effusion in chronic hypoxemic lung diseases, such as Obstructive Sleep Apnea syndrome, usually occurs after the development of severe pulmonary arterial hypertension. However, data about the frequency of pericardial effusions in Obstructive Sleep Apnea syndrome without pulmonary arterial hypertension and/or daytime hypoxemia are still scarce, and their pathogenesis is unclear.Aims:To assess the prevalence of pericardial effusions and their volume and location in patients with obesity and Obstructive Sleep Apnea syndrome without pulmonary arterial hypertension and/or hypoxemia.Study Design:Cross-sectional study.Methods:We included 279 consecutive patients (162 males) with newly diagnosed Obstructive Sleep Apnea syndrome having a mean age of 42.8±12.4 years and a mean body mass index of 37.3±7.8 kg/m2. Obstructive Sleep Apnea syndrome was confirmed by polysomnography. Main exclusion criteria were concomitant inflammatory diseases, thyroid dysfunction, daytime hypoxemia, nephrotic syndrome, left ventricular systolic dysfunction and pulmonary arterial hypertension.Results:Pericardial effusion was found in 102 (36.56%) -all of them with moderate to severe obstructive Sleep Apnea syndrome. The mean effusion volume was mild to moderate (up to 250 mL). In 36 patients (35.3%) the pericardial effusion was diffuse, in 42 (41.2%), the pericardial effusion was located in front of the right atrium and the right ventricle, and in 24 (23.5%) the pericardial effusion was situated in front of the right cardiac cavities and the left atrium. We found a significant positive correlation between the presence of pericardial effusion and apnea-hypopnea index (r=0.374, p<0.001), body mass index (r=0.473, p<0.001), and desaturation time during sleep (r=0.289, p<0.001).Conclusion:Pericardial effusion in patients with obesity and moderate to severe Obstructive Sleep Apnea syndrome without daily hypoxemia and/or pulmonary hypertension is a relatively common finding. The occurrence of pericardial effusions is dependent mostly on the grade of Obstructive Sleep Apnea syndrome, degree of obesity, and duration of sleep desaturation.

Home Oxygen in Chronic Obstructive Pulmonary Disease.

Two landmark trials conducted more than 35 years ago provided scientific evidence that, under very specific circumstances, long-term oxygen therapy (LTOT) may prolong life. These two trials enrolled 290 patients with chronic obstructive pulmonary disease and severe daytime hypoxemia documented by direct arterial blood gas measurement. From that time, LTOT became a standard of care, and the indications for oxygen therapy expanded to include nocturnal oxygen therapy for isolated nocturnal oxygen desaturation, ambulatory oxygen to correct exercise-induced desaturation, and short-burst oxygen to relieve dyspnea. In most cases, the rationale for broadening the indications for oxygen therapy is that, if hypoxemia exists, correcting it by increasing the FiO2 should help. However, with the exception of LTOT in severely hypoxemic patients with chronic obstructive pulmonary disease, randomized controlled trials of oxygen therapy have failed to demonstrate clinically significant benefits. Also, adherence to LTOT is usually suboptimal. Important areas for future research include improving understanding of the mechanisms of action of supplemental oxygen, the clinical and biochemical predictors of responsiveness to LTOT, the methods for measuring and enhancing adherence to LTOT, and the cost-effectiveness of oxygen therapy. A standardization of terminology to describe the use of supplemental oxygen at home is provided.

Can Daytime Measures of Respiratory Sinus Arrhythmia and Breathing Stability Serve as Biomarkers for OSA?

Obstructive sleep apnea (OSA) is by definition a disorder of nighttime breathing however, there is good evidence that impairments in cognitive and cardiovascular function persist in the day and that adults with OSA exhibit daytime CO2 retention and hypoxemia. Although a diagnosis of OSA requires in‐home or in‐laboratory overnight polysomnography, these types of tests are expensive and, due to health insurance quotas, may be limited in availability. Here, we outline simple methods for assessing daytime respiratory sinus arrhythmia (RSA) and respiratory stability that show promise as potential diagnostic tools to identify adults at risk for OSA. We recorded heart rate (finger oxy‐photoplethysmography) and respiration (inductance plethysmography) in adults with obstructive sleep apnea (N=6) and age and BMI matched healthy adults (N=8). Subjects completed five minutes of eupneic breathing, five minutes of paced breathing (7.5 breaths/minute) and after equilibration, five minutes of hyperoxic, hypercapnia (5% FICO2). Using de‐identified data, we obtained estimates of RSA amplitude, RSA stability, and respiratory stability for each subject in each condition and performed a regression analysis to determine the relationship between each of these variables and subjects' apnea hypopnea index (0–25 AHI). Our preliminary results indicate that daytime measures of respiratory stability and RSA can differentiate healthy adults from adults diagnosed with OSA (p&lt;0.006). Importantly, the analysis requires minimal instrumentation and short sampling periods (~5 minutes). Summary schematics arising from the analysis may prove useful as preliminary clinical/diagnostic biomarkers of RSA and cardio‐respiratory coupling in adults at risk for OSA.Support or Funding InformationThis work was supported by start‐up monies (Department of Physiology, University of Arizona) awarded to EFB and by The Finley and Florence Brown Predoctoral Fellowship (Sarver Heart Center, University of Arizona) awarded to JRV.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Adipose tissue is influenced by hypoxia of obstructive sleep apnea syndrome independent of obesity

AimsObstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular risk and diabetes independent of obesity. We investigated whether adipose tissue dysfunction is exacerbated due to increased tissue hypoxia. MethodsAdipose tissue (AT) oxygenation was measured with a Clarke-type electrode (pATO2) in 16 men with OSAS before and after 4 months of continuous positive airway pressure therapy (CPAP) and in BMI-matched controls. Oxygenation was simultaneously monitored in arterial blood by pulse oximetry (SaO2); mixed blood in AT microcirculation by reflectance spectroscopy (SATO2) along with blood flow. Markers of hypoxia, adipo- and angiogenesis, inflammation and fibrosis were analysed in AT and serum. ResultsOSAS subjects were more insulin resistant. Despite lower arterial SaO2 (95.4±1.3% vs. 97.1±1.6%, P=0.013) in subjects with OSAS, there was no difference in the oxygen content of AT microcirculation (61.6±18.4 vs. 72.2±7.0%, P=0.07) or pATO2 (49.2±7.5 vs. 50.4±14.7mmHg, P=0.83) between groups. Resting AT blood flow was higher in OSAS compared to controls (108.5±22.7 vs. 78.9±24.9au, P<0.005) and strongly associated with inflammation markers IL-6 and MCP-1. AT of OSAS subjects showed increased inflammation (TNFA P=0.049) and fibrosis (COL3A1 P=0.02), a trend of higher HIF1A expression (P=0.06) and reduced adipogenesis (PPARG P=0.006). After CPAP, only expression of the lipid deposition marker LPL increased (30%, P=0.047). ConclusionsAdipose tissue of awake OSAS subjects appears no more hypoxic than adipose tissue of BMI-matched controls despite daytime hypoxaemia. Increased adipose tissue blood flow may be explained by an increased inflammatory response. We observe features of adipose dysfunction in subjects with OSAS, which attribute to increased cardiometabolic risk associated with this condition.

Multi-center, randomized, placebo-controlled trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease: a study protocol for the INOX trial

BackgroundLong-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15–18 h a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT.MethodsThe INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is double blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy. The follow-up period is intended to last at least 3 years.DiscussionThe benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight.Trial registrationCurrent Controlled Trials ISRCTN50085100; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010).

Role of oxygen and continuous positive airway pressure therapy in chronic obstructive pulmonary disease patients with nocturnal oxygen desaturation

Sleep has a significant effect on respiration, even in healthy individuals. Breathing difficulties in chronic obstructive pulmonary disease (COPD) patients during sleep are one of the most common symptoms in these patients. Nocturnal desaturation may occur in COPD in the absence of severe daytime hypoxemia. Nocturnal desaturation may contribute to the development of pulmonary hypertension, nocturnal cardiac arrhythmias, and death during sleep. However, the optimal treatment for patients with isolated nocturnal hypoxemia remains uncertain. The aim of this study was to assess the role of oxygen and continuous positive airway pressure (CPAP) therapy in COPD patients with nocturnal oxygen desaturation (NOD). This study was conducted on 40 male COPD patients. The included patients were classified into two groups: group 1 included normoxic or mildly hypoxic patients with day time SpO2≥91% defined as NOD by fall of greater than 4% from awake SpO2, and group 2 included moderate and severely hypoxic patients with daytime SpO2≤90% who showed a pulse oximetric plot with at least 5 min with SpO2≤90% and a peak of SpO2≤85% and were considered as nocturnal desaturator. The two groups were subjected to full history taking, clinical examination, the Epworth sleepiness scale, anthropometric measurements, pulmonary function tests (spirometry), radiological examination using chest radiograph, and SpO2 using pulse oximetry. SpO2 evaluation using pulse oximetry was carried out for four nights: the first night while breathing room air, the second night while giving low-flow humidified oxygen (2 l/min) overnight, the third night with patients on noninvasive ventilation using autoset CPAP mask, and the fourth night with patients on noninvasive ventilation using autoset CPAP mask with low-flow humidified oxygen (2 l/min). The included patients had moderate, severe, and very severe COPD according to the GOLD spirometric classification. The highest mean value of oxygen saturation was seen in cases that received CPAP with oxygen, followed by cases that received low-flow humidified nasal oxygen, and the lowest mean value was on CPAP. In group 1, there was no significant difference between mean values of oxygen saturation on oxygen and CPAP, but there was a highly significant difference between mean values of oxygen saturation on oxygen and CPAP with oxygen, as well as on CPAP and CPAP with oxygen. In group 2, there was a significant difference between mean values of oxygen saturation on oxygen and CPAP, on nocturnal oxygen and CPAP with oxygen, as well as on CPAP and CPAP with oxygen. In group 1, it is better to prescribe nocturnal CPAP with oxygen than nocturnal oxygen alone or nocturnal CPAP alone to COPD patients with NOD in this group, whereas in group 2 it is better to prescribe nocturnal CPAP with oxygen, followed by nocturnal oxygen alone, compared with nocturnal CPAP alone to COPD patients with NOD in this group.

Contractile capability of the diaphragm assessed by ultrasonography predicts nocturnal oxygen saturation in COPD.

Diaphragm function might be useful to predict nocturnal oxygen desaturation in COPD. Ultrasonography has been widely used for the assessment of the diaphragm. We aimed to investigate the relationship between the contractile capability of the diaphragm assessed by ultrasonography and the nocturnal percutaneous arterial oxygen saturation (NSpO2 ) in COPD. Twenty-eight male patients with COPD (age, 73 ± 7 years; forced expiratory volume in 1 s (FEV1 ), 54.2 ± 17.0% predicted) were included. The thickness of the diaphragm (Tdi) was assessed by ultrasonography. We calculated the change ratio of Tdi at the end of maximal inspiration and expiration (%ΔTdi). The mean value of NSpO2 (NSpO2mean ), the percentage of total sleep time (TST) with desaturation above 4% (DA4%) and the percentage of TST with saturation below 90% (SB90%) were measured by overnight oximetry. Daytime arterial oxygen pressure (PaO2 ) and maximal inspiratory mouth pressure (PImax ) were also measured. All participants had mild or no daytime hypoxaemia (PaO2 , 77.3 ± 8.6 mm Hg). The NSpO2mean , DA4% and SB90% were significantly correlated with %ΔTdi, PaO2 , %PImax of the predicted value and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The %ΔTdi and PaO2 were predictors of NSpO2 mean by multiple regression analysis. This study suggested a close relationship between the NSpO2 and the contractile capability of the diaphragm assessed by ultrasonography in COPD. The %ΔTdi combined with PaO2 might predict NSpO2 in COPD patients with mild or no daytime hypoxaemia.

Dark Adaptation at High Altitude: An Unexpected Pupillary Response to Chronic Hypoxia in Andean Highlanders.

Healy, Katherine, Alain B. Labrique, J. Jaime Miranda, Robert H. Gilman, David Danz, Victor G. Davila-Roman, Luis Huicho, Fabiola León-Velarde, and William Checkley. Dark adaptation at high altitude: an unexpected pupillary response to chronic hypoxia in Andean highlanders. High Alt Med Biol. 17:208-213, 2016.-Chronic mountain sickness is a maladaptive response to high altitude (>2500 m above sea level) and is characterized by excessive erythrocytosis and hypoxemia resulting from long-term hypobaric hypoxia. There is no known early predictor of chronic mountain sickness and the diagnosis is based on the presence of excessive erythrocytosis and clinical features. Impaired dark adaptation, or an inability to visually adjust from high- to low-light settings, occurs in response to mild hypoxia and may serve as an early predictor of hypoxemia and chronic mountain sickness. We aimed to evaluate the association between pupillary response assessed by dark adaptometry and daytime hypoxemia in resident Andean highlanders aged ≥35 years living in Puno, Peru. Oxyhemoglobin saturation (SpO2) was recorded using a handheld pulse oximeter. Dark adaptation was quantitatively assessed as the magnitude of pupillary contraction to light stimuli of varying intensities (-2.9 to 0.1 log-cd/m2) using a portable dark adaptometer. Individual- and stimulus-specific multilevel analyses were conducted using mixed-effect models to elicit the relationship between SpO2 and pupillary responsiveness. Among 93 participants, mean age was 54.9 ± 11.0 years, 48% were male, 44% were night blind, and mean SpO2 was 89.3% ± 3.4%. The magnitude of pupillary contraction was greater with lower SpO2 (p < 0.01), and this dose relationship remained significant in multiple variable analyses (p = 0.047). Pupillary responsiveness to light stimuli under dark-adapted conditions was exaggerated with hypoxemia and may serve as an early predictor of chronic mountain sickness. This unexpected association is potentially explained as an excessive and unregulated sympathetic response to hypoxemia at altitude.

Impact of Continuous Positive Airway Pressure Therapy on Atrial Electromechanical Delay in Obesity-Hypoventilation Syndrome Patients.

Obesity-hypoventilation syndrome (OHS) is defined as daytime hypercapnia and hypoxemia in obese patients with sleep-disordered breathing. We evaluated the electrocardiographic P-wave duration and dispersion (PD) and echocardiographic noninvasive indicators of atrial conduction heterogeneity in OHS patients and the impact of CPAP on atrial conduction and atrial fibrillation incidence. We enrolled 50 OHS patients and 50 sex- and age-matched obese subjects as control. Study population underwent cardiologic evaluation and polysomnography before enrollment, at 1- and 6-month follow-ups after CPAP therapy. The OHS group showed a significant increase in inter-atrial (35.2 ± 8 milliseconds vs. 20.1 ± 2.7 milliseconds, P < 0.0001), intra-left (30.5 ± 7.2 milliseconds vs. 16.5± 2milliseconds, P < 0.0001), and intra-right atrial electromechanical delays (AEMD)(24.8 ± 10 milliseconds vs. 15 ± 2.6 milliseconds, P < 0.0001) as well as in Pmax (130 ± 7.4 milliseconds vs. 97 ± 7.2 milliseconds, P = 0.002) and PD (56.5 ± 8.5 milliseconds vs. 31 ± 7.2 milliseconds, P = 0.002) compared to the control group. Significant improvement was noted after 6 months of CPAP therapy in inter-atrial (35.2 ± 8 milliseconds vs. 24.5 ± 6.3 milliseconds, P < 0.0001), intra-left (30.5 ± 7.2 milliseconds vs. 20.6 ± 5 milliseconds, P = 0.003), and intra-right AEMD (24.8 ± 10 milliseconds vs. 17 ± 7.5 milliseconds, P < 0.0001), as well as in Pmax (130 ± 7.4 milliseconds vs. 95 ± 10 milliseconds, P < 0.0001) and in PD (56.5 ± 8.5 milliseconds vs. 32.5± 6 milliseconds, P < 0.0001) in the OHS group. External loop recorder monitoring detected paroxysmal AF in 19 OHS patients (38%) with significant reduction in paroxysmal AF episodes (12 ± 6 vs. 47 ± 12, P < 0.0001) after 6-month CPAP therapy. Our findings showed a significant increase of electrocardiographic and echocardiographic indexes of atrial conduction heterogeneity in OHS patients. The CPAP therapy, having a positive impact on atrial conduction time, seems to reduce AF incidence in OHS patients.

Treatment of Sleep Disordered Breathing Liberates Obese Hypoxemic Patients from Oxygen.

BackgroundObese hypoxemic patients have a high prevalence of sleep disordered breathing (SDB). It is unclear to what extent treatment of SDB can improve daytime hypoxemia.MethodsWe performed a retrospective cohort study of obese hypoxemic individuals, all of whom underwent polysomnography, arterial blood gas analysis, and subsequent initiation of positive airway pressure (PAP) therapy for SDB. Patients were followed for one year for change in partial pressure of arterial oxygen and the need for supplemental oxygen.ResultsOne hundred and seventeen patients were treated with nocturnal PAP and had follow-up available. Adherence to PAP was satisfactory in 60%, and was associated with a significant improvement in daytime hypoxemia and hypercapnea; 56% of these patients were able to discontinue supplemental oxygen. Adherence to PAP therapy and the baseline severity of OSA predicted improvement in hypoxemia, but only adherence to PAP therapy predicted liberation from supplemental oxygen.ConclusionsThe identification and treatment of SDB in obese hypoxemic patients improves daytime hypoxemia. It is important to identify SDB in these patients, since supplemental oxygen can frequently be discontinued following treatment with PAP therapy.