Continuous positive airway pressure treatment, glycemia, and diabetes risk in obstructive sleep apnea and comorbid cardiovascular disease

OBJECTIVE: Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA. RESEARCH DESIGN AND METHODS: Blood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea cardioVascular Endpoints (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A1c (HbA1c) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded. RESULTS: Median follow-up was 4.3 years. In those with preexisting diabetes (n = 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA1c, or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n = 452) or new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable. CONCLUSIONS: Among patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation.

Continuous Positive Airway Pressure Treatment, Glycemia, and Diabetes Risk in Obstructive Sleep Apnea and Comorbid Cardiovascular Disease.

OBJECTIVE: Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA. RESEARCH DESIGN AND METHODS: Blood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea cardioVascular Endpoints (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A1c (HbA1c) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded. RESULTS: Median follow-up was 4.3 years. In those with preexisting diabetes (n = 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA1c, or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n = 452) or new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable. CONCLUSIONS: Among patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation.

Sleep habits of intermediate-aged students: roles for the students, parents and educators.

AIM: Obtain an overview of the current sleep habits and sleep hygiene practices in a group of intermediate-aged students, and establish whether these students achieve adequate sleep according to the New Zealand education and health guidelines. METHODS: A standardised sleep health questionnaire and seven-day sleep diary were completed by 163 participants (aged 11-13; 62% female) from a cross-section of five Christchurch schools. RESULTS: In this group, 71% of students reported 9-11 hours of sleep per night (averaged over seven days). Total sleep time was independent of gender and the day of the week. Bedtimes and wake-times were earlier from Monday-Thursday compared to the weekend (p<0.0001). Fifty-nine percent of students used a device in the hour before bed. Pre-bedtime device users were more likely to achieve less sleep than non-device users (p<0.001). The majority of students (66%) did not choose their bedtime. CONCLUSIONS: In this group of students, the majority achieved a sleep duration within the advised Ministry of Education and Sleep Health Foundation guidelines, despite non-recommended sleep hygiene practices in the pre-bed routine. Parental guidance, with respect to bed times and reduction in device usage before sleep are two factors that could be employed to improve sleep in this group.

The Effects of Long-term CPAP on Weight Change in Patients With Comorbid OSA and Cardiovascular Disease: Data From the SAVE Trial.

BACKGROUND: Although recent evidence suggests that OSA treatment may cause weight gain, the long-term effects of CPAP on weight are not well established. METHODS: This study was a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) study, a multicenter, randomized trial of CPAP plus standard care vs standard care alone in adults with a history of cardiac or cerebrovascular events and moderate to severe OSA. Participants with weight, BMI, and neck and waist circumferences measured at baseline and during follow-up were included. Linear mixed models were used to examine sex-specific temporal differences, and a sensitivity analysis compared high CPAP adherers (≥ 4 h per night) with propensity-matched control participants. RESULTS: A total of 2,483 adults (1,248 in the CPAP group and 1,235 in the control group) were included (mean 6.1 ± 1.5 measures of weight available). After a mean follow-up of 3.78 years, there was no difference in weight change between the CPAP and control groups, for male subjects (mean [95% CI] between-group difference, 0.07 kg [-0.40 to 0.54]; P = .773) or female subjects (mean [95% CI] between-group difference, -0.14 kg [-0.37 to 0.09]; P = .233). Similarly, there were no significant differences in BMI or other anthropometric measures. Although male participants who used CPAP ≥ 4 h per night gained slightly more weight than matched male control subjects without CPAP (mean difference, 0.38 kg [95% CI, 0.04 to 0.73]; P = .031), there were no between-group differences in other anthropometric variables, nor were there any differences between female high CPAP adherers and matched control subjects. CONCLUSIONS: Long-term CPAP use in patients with comorbid OSA and cardiovascular disease does not result in clinically significant weight change. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00738179; URL: www.clinicaltrials.gov.

Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease.

RATIONALE: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. OBJECTIVES: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease. METHODS: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow-up, and the urinary albumin-to-creatinine ratio was measured at study exit. MEASUREMENTS AND MAIN RESULTS: In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m2), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m2/yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (-4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between-group differences in end-of-study urinary albumin-to-creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings. CONCLUSIONS: CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).

Development and outcomes of a primary care-based sleep assessment service in Canterbury, New Zealand.

Prior to 2007, increasing demand for sleep services, plus inability to adequately triage severity, led to long delays in sleep assessment and accessing continuous positive airway pressure. We established a community sleep assessment service carried out by trained general practices using a standardised tool and overnight oximetry. All cases were discussed at a multi-disciplinary meeting, with four outcomes: severe obstructive sleep apnoea treated with continuous positive airway pressure; investigation with more complex studies; sleep physician appointment; no or non-severe sleep disorder for general practitioner management. Assessment numbers increased steadily (~400 in 2007 vs. 1400 in 2015). Median time from referral to assessment and multi-disciplinary meeting was 28 and 48 days, respectively. After the first multi-disciplinary meeting, 23% of cases were assessed as having severe obstructive sleep apnoea. More complex studies (mostly flow based) were required in 49% of patients, identifying severe obstructive sleep apnoea in a further 13%. Thirty-seven percent of patients had obstructive sleep apnoea severe enough to qualify for funded treatment. Forty-eight percent of patients received a definitive answer from the first multi-disciplinary meeting. Median time from referral to continuous positive airway pressure for 'at risk' patients with severe obstructive sleep apnoea, e.g., commercial drivers, was 49 days, while patients with severe obstructive sleep apnoea but not 'at risk' waited 261 days for continuous positive airway pressure. Ten percent of patients required polysomnography, and 4% saw a sleep specialist. In conclusion, establishment of a community sleep assessment service and sleep multi-disciplinary meeting led to significantly more assessments, with short waiting times for treatment, especially in high-risk patients with severe obstructive sleep apnoea. Most patients can be assessed without more complex studies or face-to-face review by a sleep specialist. SLEEP DISORDERS: MORE ASSESSMENTS, SHORTER WAITS WITH COMMUNITY SLEEP SERVICE: A community-based service for common sleep disorders can provide rapid and easily accessed sleep assessment and treatment. A team led by Michael Hlavac and Michael Epton from Christchurch Hospital describe the creation of a sleep assessment service within the Canterbury district of New Zealand, in which initial assessments are conducted throughout the community by general practice teams under guidance and advice from sleep specialists at the region's largest hospital. Before the service, there were around 300 sleep assessments per year in all of Canterbury, a region with a population of around 510,000. Now, that number has more than tripled, with shorter waiting times for treatment, especially for people with severe sleep apnoea. The authors conclude that most patients can be assessed for a suspected sleep disorder without needing to visit a hospital's sleep unit.

Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness.

STUDY OBJECTIVES: To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. DESIGN: Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. SETTING: Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. PARTICIPANTS: 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. CONCLUSIONS: There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes.

Three families with Perry syndrome from distinct parts of the world.

OBJECTIVES: Perry syndrome consists of autosomal dominant Parkinsonism, depression, weight loss, and central hypoventilation. Eight mutations in 16 families have been reported: p.F52L, p.G67D, p.G71R, p.G71E, p.G71A, p.T72P, p.Q74P, and p.Y78C located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome 2p13.1. METHODS: Genealogical, clinical, genetic, and functional studies were performed in three kindreds from New Zealand, the United States, and Colombia. A diaphragmatic pacemaker was implanted in the proband from the Colombian family to treat her respiratory insufficiency. Dopaminergic therapy was initiated in probands from two families. RESULTS: Besides the probands, 17 symptomatic relatives from all families were identified. The cardinal signs of Perry syndrome were present in all three probands with symptomatic disease onset in their fifth or sixth decade of life. Parkinsonism was moderate with a partial response to dopaminergic treatment. All affected persons but two died of respiratory insufficiency. The proband from the Colombian family is alive most likely due to early diagnosis and implantation of a diaphragmatic pacemaker. Two-and-a-half-year follow-up examination has revealed that the diaphragmatic pacemaker is optimally functioning without any major complications. In the Colombian and US families, the DCTN1 p.G71R and in the New Zealand family the DCTN1 p.Y78C mutations were identified. In functional assays, both mutations altered microtubule binding consistent with a pathogenic role. CONCLUSIONS: Perry syndrome is a rare condition, but new cases are expected to be diagnosed worldwide. Early diagnosis prevents life-threatening acute respiratory failure. Diaphragmatic pacemakers should be considered as an effective symptomatic treatment option.

Sleep disordered breathing in patients with primary Sjögren's syndrome: a group controlled study.

OBJECTIVE: Patients with primary Sjögren's syndrome (pSS) have higher fatigue levels and also suffer from excessive day time sleepiness. The underlying mechanisms for this are not fully understood. Knowing that these patients have higher salivary surface tension, we postulated that sleep disordered breathing (SDB) would be more common and would be a contributor to these symptoms amongst pSS patients. We investigated the prevalence of SDB in pSS patients and its relationship to their symptoms of fatigue and excessive daytime sleepiness. METHODS: This was an observational study of 28 pSS patients (mean±SEM age, 58.7±1.9) and 18 healthy subjects (mean±SEM age, 55.8±3.4) matched for age, sex, and BMI. All the participants underwent an overnight polysomnography. The two groups were compared for fatigue, sleepiness, anxiety, and depression scores, and for the frequency of obstructive apneas and hypopneas during sleep. Correlation analyses were used to explore relationships between sleep study variables and excess sleepiness and fatigue. RESULTS: Fatigue, sleepiness, anxiety and depression symptoms, and sleep onset latency were significantly greater in pSS patients than controls. pSS patients had twice the frequency of obstructive apneas and hypopneas compared with control subjects (median[IQR],18.6/h [10.4-40.1] vs. 9.9/h [6.5-23.4]; p=0.032) and OSA defined as an apnea-hypopnea index >15 events/h of sleep was more prevalent amongst pSS patients than controls (64% vs. 28%; p=0.033). While no significant correlations were found between parameters of sleep disordered breathing and sleepiness scores or fatigue scores in the pSS group, CPAP treatment in a small subset of the pSS who were more severely affected by OSA suggested significant symptomatic benefit. CONCLUSION: OSA appears to be increased in pSS and may be a useful therapeutic target to improve the quality of life of these patients.

Episodic hypoxemia in an airline passenger with chronic respiratory failure on supplemental oxygen.

Assessing the requirements for in-flight oxygen in passengers with pulmonary limitations can be a challenging task for clinicians. Aeromedical guidelines are available to help identify passengers that may require oxygen in flight. However, little is known about the actual in-flight response to passengers on oxygen. We measured the oxygen response (pulse oximetry) of a 67-yr-old female patient with chronic respiratory failure during a trans-Tasman flight (duration 170 min). This patient was assessed at the respiratory clinic before her journey and resting PaO2 (57 mmHg) indicated the requirement for in-flight oxygen. Bottled oxygen delivered at 2 L x min(-1) via nasal cannula was prescribed for her journey. Preflight SpO2 without supplemental oxygen was 92%. Mean in-flight SpO2 was well maintained at 93% while on oxygen at rest. There were four significant hypoxic events, which included light physical activity while on oxygen (three events; SpO2 to 84%) and a visit to the lavatory (off oxygen; SpO2 to 70%). Dyspnea and dizziness were reported during the lavatory visit. This case illustrates the importance of a preflight medical screening for passengers considered at risk during air travel and provides insight into the response of oxygen supplementation during flight.

The effects of hypoxia on load compensation during sustained incremental resistive loading in patients with obstructive sleep apnea.

Inspiratory load compensation is impaired in patients with obstructive sleep apnea (OSA), a condition characterized by hypoxia during sleep. We sought to compare the effects of sustained hypoxia on ventilation during inspiratory resistive loading in OSA patients and matched controls. Ten OSA patients and 10 controls received 30 min of isocapnic hypoxia (arterial oxygen saturation 80%) and normoxia in random order. Following the gas period, subjects were administered six incremental 2-min inspiratory resistive loads while breathing room air. Ventilation was measured throughout the loading period. In both patients and controls, there was a significant increase in inspiratory time with increasing load (P = 0.006 and 0.003, respectively), accompanied by a significant fall in peak inspiratory flow (P = 0.006 and P < 0.001, respectively). The result was a significant fall in minute ventilation in both groups with increasing load (P = 0.003 and P < 0.001, respectively). There was no difference between the two groups for these parameters. The only difference between the two groups was a transient increase in tidal volume in controls (P = 0.02) but not in OSA patients (P = 0.57) during loading. Following hypoxia, there was a significant increase in minute ventilation during loading in both groups (P < 0.001). These results suggest that ventilation during incremental resistive loading is preserved in OSA patients and that it appears relatively impervious to the effects of hypoxia.

Hypoxia impairs the arousal response to external resistive loading and airway occlusion during sleep.

STUDY OBJECTIVES: Sustained hypoxia is a neurocognitive depressant, which has been shown to impair respiratory load sensation. Hypoxia has also been shown to impair arousal in animal models, but the effects of sustained hypoxia on arousal in humans have not been studied. The aim of this study was to assess the effects of sustained hypoxia on arousal from sleep in normal subjects. DESIGN: Twelve normal male subjects (age, 24.3 +/- 1.2 years; body mass index, 24.8 +/- 1.4 kg/m2) were studied during stable stage 2 non-rapid eye movement sleep on 2 separate nights 1 week apart. SETTING: Sleep physiology laboratory. PARTICIPANTS: Normal healthy volunteers. INTERVENTIONS: Arousal responses to external resistive loads (18 cm H2O x L(-1) x sec(-1)) and occlusions were compared during room-air breathing following sustained normoxia and isocapnic hypoxia (SaO2 approximately 85%). MEASUREMENTS AND RESULTS: Time to arousal and minimum esophageal pressure preceding arousal were measured. Time to arousal was significantly increased following hypoxia compared with normoxia for resistive loads (24.6 + 4.4 seconds vs. 12.6 +/- 1.9 seconds, p = .007) but not occlusions. Minimum esophageal pressure prior to arousal was more negative following hypoxia for both external loads (-16.8 +/- 1.2 vs. -13.5 +/- 1.3 cm H2O, p = .035) and occlusions (-19.6 +/- 2.2 vs. -15.1 +/- 1.5 cm H2O, p = .029). CONCLUSIONS: We conclude that sustained isocapnic hypoxia delays arousal to inspiratory loading during sleep and increases the respiratory arousal threshold. This has implications for disorders characterized by sustained nocturnal hypoxia, such as neuromuscular weakness, chronic obstructive pulmonary disease, obesity-hypoventilation syndrome, and severe obstructive sleep apnea.

Acute sustained hypoxia suppresses the cough reflex in healthy subjects.

RATIONALE: An intact cough reflex is important to protect the lung from injurious substances and to clear excess secretions. A blunted cough reflex may be harmful or even fatal in respiratory disease. Hypoxia is common in respiratory disorders and has been shown to have depressant effects on respiratory sensation and ventilation. We hypothesized that it might also suppress the cough reflex. OBJECTIVES: To determine if acute hypoxia increases cough threshold and cough tachyphylaxis to inhaled capsaicin. METHODS: On two occasions, 16 healthy subjects inhaled a saline control followed by doubling doses of capsaicin aerosol (range, 0.49-500 microM) every minute for 15 s during controlled ventilation (approximately 190% baseline) with isocapnic hypoxia (SpO2, approximately 80%) or isocapnic normoxia, in random order. When a subject responded to a dose with five or more coughs, the next doubling dose of capsaicin was administered continuously for 60 s to assess acute tachyphylaxis. MAIN RESULTS: The capsaicin concentration required to elicit five coughs was significantly higher during isocapnic hypoxia compared with normoxia (29.6 +/- 16.0 vs. 23.4 +/- 15.6 microM, p = 0.01). During continuous capsaicin inhalation, significantly more coughs were evoked in the first 10 s compared with the last (2.3 +/- 0.3 vs. 1.3 +/- 0.3, p < 0.01), indicating cough tachyphylaxis. However, the decrease was the same during hypoxia and normoxia (-1.3 +/- 0.4 vs. -0.9 +/- 0.6, p = 0.54). CONCLUSIONS: Acute isocapnic hypoxia suppresses cough reflex sensitivity to inhaled capsaicin. This finding raises the possibility that the cough reflex may be impaired during acute exacerbations of hypoxic-respiratory disorders.

Latex-enhanced immunoassay d-dimer and blood gases can exclude pulmonary embolism in low-risk patients presenting to an acute care setting.

BACKGROUND: Pulmonary embolism (PE) is common, and diagnosis is often difficult. Investigation has traditionally required expensive imaging procedures that are frequently nondiagnostic. Consequently, current practice favors noninvasive diagnosis of PE using algorithms combining risk assessment and d-dimer. Despite the proven safety of this approach, concern persists about such strategies to exclude PE, largely due to variable d-dimer sensitivity. The aim of this study was to prospectively assess the safety of a new algorithm combining a novel, rapid d-dimer test (IL Test; Instrumentation Laboratory; Lexington, MA), Pa(O2) measurement, and risk factor assessment in excluding PE in subjects presenting to an acute care setting. METHODS: All patients aged 18 to 60 years presenting to the emergency department of Christchurch Hospital with suspected PE underwent measurement of d-dimer (IL Test latex-enhanced immunoassay) and Pa(O2), and were assessed for the presence of major clinical risk factors. Those with no risk factors, normal d-dimer findings, and Pa(O2) > or = 80 mm Hg (study arm A) were discharged and followed up by telephone questionnaires over 12 months. Those with elevated d-dimer levels, Pa(O2) < 80 mm Hg, or one or more risk factors (study arm B) were managed as per hospital guidelines. Outcome data were collected on these patients. Our primary outcome was incidence of PE in group A during the first 3-month follow-up period. RESULTS: Three hundred twenty-eight patients were enrolled, of whom 149 were assigned to group A and 179 were assigned to group B. In none of the group A patients was PE diagnosed over the subsequent 3-month period (0%; 95% confidence interval, 0 to 2.1%). PE was diagnosed in 37 group A patients (21%). CONCLUSIONS: The latex-enhanced immunoassay d-dimer and normal arterial oxygen pressure levels can safely exclude PE in a low-risk population presenting to an acute care setting. While these results cannot be extrapolated to all patients with suspected PE, they do confirm the safety of this approach in a population with a low underlying risk of PE.

Home management of mild to moderately severe community-acquired pneumonia: a randomised controlled trial.

OBJECTIVE: To determine whether community management of mild to moderate community-acquired pneumonia (CAP) is as effective and acceptable as standard hospital management of CAP. DESIGN: Randomised controlled trial. SETTING: Christchurch, New Zealand, primary and secondary care. PARTICIPANTS: 55 patients presenting or referred to the emergency department at Christchurch Hospital with mild to moderately severe pneumonia, assessed using a validated pneumonia severity assessment score, from July 2002 to October 2003. INTERVENTIONS: Hospital treatment as usual or comprehensive care in the home delivered by primary care teams. MAIN OUTCOME MEASURES: Primary: days to discharge, days on intravenous (IV) antibiotics, patient-rated symptom scores. Secondary: health status measured using level of functioning at 2 and 6 weeks, patient satisfaction. RESULTS: The median number of days to discharge was higher in the home care group (4 days; range, 1-14) than in the hospital groups (2 days; range, 0-10; P = 0.004). There was no difference in the number of days on IV antibiotics or on subsequent oral antibiotics. Patient-rated symptom scores at 2 and 6 weeks, median change in symptom severity from baseline to 6 weeks, and general functioning at 2 and 6 weeks did not differ between the groups. Patients in both groups were satisfied with their treatment, with a clear preference for community treatment (P < 0.001). CONCLUSIONS: Mild to moderately severe CAP can be managed effectively in the community by primary care teams. This model of comprehensive care at home can be implemented by primary care teams with suitable funding structures.

Sustained hypoxia depresses sensory processing of respiratory resistive loads.

RATIONALE: The combination of acute hypoxia and increased respiratory load is encountered in several respiratory diseases including acute life-threatening asthma and sleep apnea. Hypoxia has been shown to inhibit respiratory load perception in healthy and asthmatic subjects, and could contribute to treatment delays and impaired function of protective reflexes. OBJECTIVES: Using respiratory-related evoked potentials (RREPs) this study aimed to determine the sensory processes mediating hypoxia-induced suppression of respiratory load sensation. METHODS: EEG was measured over the central and parietal cortical regions in 14 healthy subjects. RREPs were elicited by 500-ms midinspiratory resistive load stimuli during and after isocapnic normoxia or hypoxia (blood arterial O2 saturation approximately 80%). On a separate occasion, subjects rated the perceived magnitude of five externally applied inspiratory resistive loads (range, 8.6-43.7 cm H2O x L(-1) x s) under similar experimental conditions. In both experiments subjects voluntarily ventilated approximately 90% above baseline to match ventilatory output between gas conditions. RESULTS: RREP stimulus was matched between gas conditions in 11 subjects (minimum mask pressure -9.7 +/- 0.6 versus -9.2 +/- 0.4 cm H2O). P1 and P2 amplitudes were reduced during isocapnic hypoxia compared with normoxia (maximal at Cz: P1, 2.5 +/- 1.1 versus 3.9 +/- 1.2 microv, p = 0.03; P2, 10.0 +/- 2.2 versus 12.4 +/- 2.1 microv, p < 0.01, respectively). Perceived magnitude of externally applied resistive loads was also reduced during hypoxia compared with normoxia (17.1 +/- 1.1 versus 19.0 +/- 1.1 au, p < 0.01). CONCLUSIONS: These data confirm that isocapnic hypoxia suppresses respiratory load sensation. Decreased amplitude of the earlier (P1) RREP component suggests that this is mediated, at least in part, by suppression of respiratory afferent information before its arrival at the primary sensory cortex.