Transitioning from hospital to home with non-invasive ventilation: who benefits? Results of a cohort study.

BACKGROUND: Non-invasive ventilation (NIV) is effective in a variety of acute respiratory illnesses in hospitalised patients. Home NIV is effective for stable patients with hypercapnia due to neuromuscular or chronic pulmonary disease. However, there are little data to guide which patients may benefit from NIV immediately following hospitalisation with hypercapnia. OBJECTIVE: To evaluate outcomes of patients with daytime hypercapnia at the end of an acute hospital admission. DESIGN: Retrospective cohort study. PARTICIPANTS: Entry into the cohort was by querying the hospital electronic medical system for consultations regarding NIV after discharge. Cases received NIV and controls did not. We extracted data on demographics, ICD-9 diagnoses and medications coded at admission, blood gas measurements and dates of discharge, first readmission and death. INTERVENTION: None. MAIN MEASUREMENT: Time from hospital discharge to mortality or readmission. KEY RESULTS: We identified 585 cases and 53 controls who survived to discharge at the index admission. Cases and controls were broadly similar in age and Charlson Comorbidity Index. In the whole cohort, cases treated with home NIV were at increased risk of death compared with controls (HR 1.88 95% CI 1.17 to 3.03). In multivariate Cox regression for all-cause mortality, poor prognostic factors were increasing age (HR 1.03 per year, 95% CI 1.02 to 1.04), cardiac failure (HR 1.31, 95% CI 1.01 to 1.67) and failure to attend NIV follow-up (HR 2.33, 95% CI 1.33 to 4.10). In contrast, chronic respiratory disease was associated with improved prognosis (HR 0.77, 95% CI 0.61 to 0.97) as was sleep apnoea (HR 0.44, 95% CI 0.23 to 0.83). Cases did not have different time-to-readmission compared with controls (HR 1.42 95% CI 0.99 to 2.02). CONCLUSION: Transitioning to home NIV after a hypercapnic hospitalisation may be useful in younger, co-operative patients with chronic respiratory disease. For older patients or those with cardiac failure, home NIV may not be beneficial and may potentially be harmful.

Pressure pulsations enhance penetration index in COPD.

This study was done in order to evaluate the effect of a novel pressure pulsation device (Pulsehaler™, Respinova Ltd., Israel) on the deposition pattern of inhaled aerosol in the lungs of COPD patients. Fifteen COPD patients were recruited to undergo spirometry and SPECT-CT lung scan following nebulization of radioactively labeled albuterol in saline solution with a jet nebulizer ("NEB") and with a combined Pulsehaler™/jet nebulizer ("PH + NEB") treatment. Central and peripheral segments of the coronal and transverse SPECT scans were evaluated for total counts and for the ratios between peripheral counts and central counts (penetration Index, "PI"). There was a significant improvement in FEV1 from before to after albuterol treatment in the PH + NEB group (151 ml ± 187, p < 0.008), but not in the NEB only group (66 ml ± 125, p = 0.06). FVC, FEF25-75, FEV1%, FVC%, FEF25, FEF50, and FEF75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF25-75 (PH + NEB > NEB, p = 0.0176), FEF75 (PH + NEB > NEB, p = 0.0028), but not for the other spirometry measures. Borg scores also were improved significantly improved in PH + NEB vs NEB (p = 0.0006). Total lung deposition and total body deposition were lower in the PH + NEB treatments vs the NEB treatments. However, PI values were 3.08 ± 0.67 times greater on average with the PH + NEB (p = 0.026) as compared to NEB only. The magnitude of the increased penetration index observed in this study indicates that pressure pulsations should be further explored as means to improve drug delivery into the distal small airways of the bronchial tree. Effects of the pressure pulsations on small airway patency could be the mechanism by which the effect was achieved.

Continuous positive airway pressure alters brain microstructure and perfusion patterns in patients with obstructive sleep apnea.

OBJECTIVES: To assess the effects of continuous positive airway pressure (CPAP) treatment on brain structure and function in patients with obstructive sleep apnea (OSA). METHODS: A prospective study of seven OSA patients recruited from the sleep center at our institution was carried out. Patients were treated with six weeks of CPAP treatment. Pre-treatment and post-treatment magnetic resonance imaging (MRI) perfusion scans were obtained and compared to assess for treatment-induced changes. Microstructural changes were quantified using functional anistrophy (FA) and mean diffusivity (MD), and brain perfusion was quantified using cerebral blood flow (CBF) and cerebral blood volume (CBV). RESULTS: Of the seven patients included the in study, six (85.7%) were male, and the mean age was 51 years (standard deviation = 13.14). Increased FA and decreased MD were found in the hippocampus, temporal lobes, fusiform gyrus, and occipital lobes. Decreased FA and increased MD were found in frontal regions for all patients (p < 0.05). Increased CBF and CBV were also observed following treatment (p < 0.05). CONCLUSION: In addition to symptom resolution, CPAP treatment may allow for healing of OSA-induced brain damage as seen by restoration of brain structure and perfusion.

Decreased nocturnal glucose variability in non-diabetic patients with sleep apnea: a pilot study.

BACKGROUND: Obstructive sleep apnea has been sho be associated with impaired glucose metabolism and overt diabetes mellitus. However, the effect of hypoxic episodes on nocturnal glucose regulation in non-diabetic patients is unknown. OBJECTIVES: To investigate the effect of hypoxemia and nocturnal glucose homeosatsis in non-diabetic patients with sleep apnea. METHODS: Seven non-diabetic patients with moderate to severe sleep apnea were connected to a continuous glucose-monitoring sensor while undergoing overnight polysomnography. Mean SpO2 and percentage of time spent at SpO2 90% were recorded. The correlation between mean glucose levels, the difference between consecutive mean glucose measurements (glucose variability) and the corresponding oxygen saturation variables were determined in each patient during REM and non-REM sleep. RESULTS: No consistent correlation was found forthe individual patient between oxygen saturation variables and glucose levels during sleep. However, a lower mean SpO2 correlated with decreased glucose variability during sleep (r = 0.79, P = 0.034). This effect was primarily evident during REM sleep in patients with significant, compared to those with mild, oxygen desaturations during sleep (> 30% vs. < 10% of sleeping tim spent with SpO2 < 90%) (P = 0.03). CONCLUSIONS: Severe nocturnal hypoxemia in non-diabetic patients with moderate to severe sleep apnea might affect glucose regulation primarily during REM sleep.

Genetics and the history of the Samaritans: Y-chromosomal microsatellites and genetic affinity between Samaritans and Cohanim.

The Samaritans are a group of some 750 indigenous Middle Eastern people, about half of whom live in Holon, a suburb of Tel Aviv, and the other half near Nablus. The Samaritan population is believed to have numbered more than a million in late Roman times but less than 150 in 1917. The ancestry of the Samaritans has been subject to controversy from late Biblical times to the present. In this study, liquid chromatography/electrospray ionization/quadrupole ion trap mass spectrometry was used to allelotype 13 Y-chromosomal and 15 autosomal microsatellites in a sample of 12 Samaritans chosen to have as low a level of relationship as possible, and 461 Jews and non-Jews. Estimation of genetic distances between the Samaritans and seven Jewish and three non-Jewish populations from Israel, as well as populations from Africa, Pakistan, Turkey, and Europe, revealed that the Samaritans were closely related to Cohanim. This result supports the position of the Samaritans that they are descendants from the tribes of Israel dating to before the Assyrian exile in 722-720 BCE. In concordance with previously published single-nucleotide polymorphism haplotypes, each Samaritan family, with the exception of the Samaritan Cohen lineage, was observed to carry a distinctive Y-chromosome short tandem repeat haplotype that was not more than one mutation removed from the six-marker Cohen modal haplotype.

Normal and elevated HbA1C levels correlate with severity of hypoxemia in patients with obstructive sleep apnea and decrease following CPAP treatment.

PURPOSE: Sleep apnea is associated with higher HbA1C levels in patients with and without diabetes but whether its severity correlates with HbA1C levels ranging from normal to abnormal is less clear. Also, the effect of continuous positive airway pressure (CPAP) treatment on HbA1C levels in patients with sleep apnea is controversial. METHODS: Thirty consecutive patients with obstructive sleep apnea were studied. None of the patients was previously diagnosed with diabetes. All patients underwent overnight polysomnography and HbA1C levels were determined. Patients were subdivided into three groups according to their HbA1C levels: <6% (n = 10), 6-6.5% (n = 10), and ≥6.5% (n = 10). Polysomnography and determination of HbA1C level were repeated in patients with severe sleep apnea (n = 12) following 3-5 months of CPAP treatment. RESULTS: HbA1C levels across the spectrum from normal to abnormal correlated with severity of hypoxemia (average SpO(2), r = -0.43, p = 0.019 and percent time with SpO(2) < 90%, r = 0.48, p = 0.007). HbA1C levels decreased from a mean of 6.47 ± 0.67% to a mean of 6.28 ± 0.51%, p = 0.038 in 12 patients with severe sleep apnea following 3-5 months of CPAP treatment. CONCLUSIONS: The severity of hypoxemia in patients with sleep apnea correlates with HbA1C levels ranging from normal to pre-diabetes and diabetes. CPAP treatment for 3-5 months decreases HbA1C levels in patients with severe sleep apnea.

Hypoxemia correlates with attentional dysfunction in patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea is associated with cognitive impairment, but whether hypoxemia or repeated arousals and sleepiness are the underlying mechanism is controversial. Studies using a wide range of attention and executive functions tests in patients with severe sleep apnea are lacking. METHODS: In a prospective cohort study, 40 patients aged 30-70 years, diagnosed with obstructive sleep apnea (apnea-hypopnea index ≥5) were recruited. Patients with known cardiovascular, pulmonary, psychiatric, or neurological disease, and or patients receiving anti-psychotic, sedatives, or stimulant medications were excluded. Patients underwent full overnight polysomnography including continuous oxygen saturation measurements followed by extensive neuropsychological testings in attention and executive function domains. The correlation between sleep apnea severity and patients' performance on the neuropsychological tests was examined. RESULTS: The patients' performance on measures of attention and executive function was significantly worse compared to the average in a normal population. Attention, as reflected by the number of omissions and by the reaction time on the Conners' Continuous Performance Test correlated significantly with the apnea-hypopnea index (r = 0.6, p < 0.001 and r = 0.48, p = 0.003, respectively) and with parameters of hypoxemia, namely the average SpO(2) (r = -0.51, p = 0.002 and r = -0.39, p = 0.02, respectively) and the percent time spent with SpO(2) < 90% (r = 0.57, p < 0.001 and r = 0.39, p = 0.02, respectively), but not with the degree of sleepiness. Executive dysfunction did not correlate with sleep parameters. DISCUSSION: Attention is the predominant cognitive function affected in patients with obstructive sleep apnea and correlates primarily with nocturnal hypoxemia rather than daytime sleepiness or sleep fragmentation. Executive functions, while below average in some patients, do not correlate with polysomnographic parameters.

Continuous positive airway pressure improves sleep apnea associated fatty liver.

Treatment of sleep apnea can improve liver enzyme abnormalities in patients with nonalcoholic fatty liver disease. However, the effect of continuous positive airway pressure therapy for sleep apnea on liver fat accumulation was not assessed. Liver biopsy is the "gold standard" for determining and quantifying liver fat accumulation; however, obtaining two separate liver biopsies is challenging. We examined, using a newly described computerized tomography method to quantify liver fat accumulation, whether treatment of sleep apnea improves liver steatosis. In a prospective cohort study, patients diagnosed with obstructive sleep apnea, at Assaf Harofeh Medical Center's sleep laboratory, were identified. Patients completed a questionnaire and underwent blood tests for liver enzymes and lipid profile, and computed tomography scans to determine the liver attenuation index. Patients with liver attenuation index or=30%) were treated with continuous positive airway pressure for 2-3 years. Subsequently, patients underwent repeat blood tests and tomography scans. Of 47 patients who were analyzed, 16 had a low liver attenuation index (

Three years of pulmonary rehabilitation: inhibit the decline in airflow obstruction, improves exercise endurance time, and body-mass index, in chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary rehabilitation is known to be a beneficial treatment for COPD patients. To date, however, there is no agreement for how long a rehabilitation program should be implemented. In addition, current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients. The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation (PR) program for COPD patients on pulmonary function, exercise capability, and body mass index (BMI). METHODS: A matched controlled trial was performed with outcome assessments evaluated at 6, 12, 18, 24, 30, and 36 months. Eighty patients with moderate to severe COPD (age 63 +/- 7 years; FEV1 48% +/- 14) were recruited. The control group received standard care only, while in addition, the case study group received PR for duration of three years. These groups were matched for age, sex, BMI, FEV1% and number of pack-years smoked. RESULTS: The decline in FEV1 after the three years was significantly lower in the PR group compared to control, 74 ml versus 149 ml, respectively (p < 0.001). Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study, in contrast to the control group (p < 0.01). A decreased BMI was noted in the control group after three years, while in the PR group a mild improvement was seen (p < 0.05). CONCLUSION: Three years of outpatient pulmonary rehabilitation resulted in modifying the disease progression of COPD, as well as improving physical performance in these patients.

Excessive daytime sleepiness in patients with Parkinson's disease: a polysomnography study.

To investigate excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD), the reasons for which have not yet been clarified, polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT) were performed in 46 patients with PD, and, in addition, PSG was performed in 30 healthy controls. Assessment included Epworth Sleepiness Score (ESS), Mini-Mental State Examination (MMSE), and Hamilton Test (HT) for depression. Fifty percent of PD patients reported EDS (ESS, 10 +/- 4.5 vs. 6.9 +/- 3.7; P = 0.01). Compared with controls, PD patients as a group had lower sleep efficiency (65 +/- 22 vs. 77 +/- 14; P = 0.03), a longer Stage 2 (73 +/- 12 vs. 67 +/- 12; P = 0.03), and a shorter rapid eye movement stage (8 +/- 8 vs. 17 +/- 8; P < 0.001). Clinical data and sleep characteristics were similar in PD with/without EDS. Of interest, patients treated with clonazepam (CLNZ) had lower EDS than those without CLNZ (ESS, 7.9 +/- 4.7 vs. 11.3 +/- 4.0; P = 0.03). These patients suffered less periodic leg movement during sleep (2.1 +/- 2.7 vs. 12.4 +/- 28; P = 0.04), which might explain the finding. No correlation was found between ESS, MSLT, and all other clinical features analyzed. In PD patients, according to the data obtained, severity of EDS does not depend on any specific clinical factor and the etiology is probably multifactorial. Paradoxically, PD patients treated with CLNZ were less sleepy than patients not treated with CLNZ.

A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in acute asthmatic attack.

STUDY OBJECTIVE: Noninvasive ventilation has been shown to be effective in patients with acute respiratory failure due to pulmonary edema and exacerbations of COPD. Its role in an acute asthmatic attack, however, is uncertain. The purpose of this pilot study was to compare conventional asthma treatment with nasal bilevel pressure ventilation (BPV) [BiPAP; Respironics; Murrysville, PA] plus conventional treatment in patients with a severe asthmatic attack admitted to the emergency department. DESIGN: A prospective, randomized, placebo-controlled study. SETTING: An emergency department at a university hospital. PATIENTS: Thirty patients with a severe asthma attack were recruited from a larger group of 124 asthmatic patients seen in the emergency department. Fifteen patients were randomly assigned to BPV plus conventional therapy and 15 patients to conventional therapy alone. The two groups had similar clinical characteristics on hospital admission. Mean (+/- SD) FEV(1) on recruitment was 37.3 +/- 10.7% in the BPV group and 33.8 +/- 10.2% in the control group (p = not significant). INTERVENTIONS AND MEASUREMENTS: BPV with predetermined inspiratory and expiratory pressures was applied for 3 h in the BPV group; in the control group, a similar sham device with subtherapeutic pressures was applied for 3 h. Bedside lung function test results and vital signs were obtained at baseline, and during and at the completion of the study protocol. RESULTS: The use of BPV significantly improved lung function test results. Eighty percents of the patients in the BPV group reached the predetermined primary end points (an increase of at least 50% in FEV(1) as compared to baseline), vs 20% of control patients (p < 0.004). Mean rise in FEV(1) was 53.5 +/- 23.4% in the BPV group and 28.5 +/- 22.6% in the conventional treatment group (p = 0.006). The intention-to-treat analysis of the secondary end point rate of hospitalization included 33 patients. Hospitalization was required for 3 of 17 patients (17.6%) in the BPV group, as compared with 10 of 16 patients (62.5%) in the control group (p = 0.0134). CONCLUSION: In selected patients with a severe asthma attack, the addition of BPV to conventional treatment can improve lung function, alleviate the attack faster, and significantly reduce the need for hospitalization.