Sleep-disordered breathing and idiopathic pulmonary fibrosis--is there an association?

BACKGROUND: Very little data exists on the prevalence and impact of sleep-disordered breathing (SDB) in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the impact of SDB on newly diagnosed IPF patients and explore associations with lung function parameters. METHODS: From 2005 to 2009, a cohort of 27 newly diagnosed patients with IPF underwent unattended polygraphy. All patients were diagnosed according to ATS 2000 diagnostic criteria and were not on supplemental oxygen or other treatment. Standard statistical analysis was undertaken using SPSS v. 19 (IBM). RESULTS: Of the 27 patients, 19 were men. There was no correlation at baseline of apnoea + hypopnoea per time in bed (AH), oxygen desaturation index, or 4% desaturations with any lung function variables, age, or body mass index. Six patients had significant SDB (AH >20). Two patients were started on CPAP following polygraphy. No variables from the original sleep studies at baseline predicted eventual long-term oxygen therapy (LTOT) use. At 5-year follow-up, 18 of 27 patients had died (67%). Cox regression analysis showed no association of time spent at SpO2 <90% on baseline polygraphy with survival (p = 0.39). There was no association with survival for AH >20 (p = 0.4) or LTOT use (p = 0.19). CONCLUSION: Our results do not support the contention that nocturnal upper airway obstruction in steroid-free patients with IPF is a common problem or correlated with lung function. In this cohort of patients, there was no evidence that significant SDB at baseline was a predictor of survival.

Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial.

BACKGROUND: The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. METHODS: We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. RESULTS: Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). CONCLUSIONS: Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.

Sleep-disordered breathing after stroke: a randomised controlled trial of continuous positive airway pressure.

BACKGROUND: Sleep-disordered breathing (SDB) is common after stroke, but it is unclear whether it should be treated. OBJECTIVE: To conduct a randomised controlled trial of continuous positive airway pressure (CPAP) after stroke. METHODS: Patients with stroke with > or = 30 apnoeas and hypopnoeas per hour ((A+H)/h) with predominant obstructive sleep apnoea or hypopnoea were randomised to either CPAP treatment or conservative treatment for 8 weeks. Outcomes were measured blind to treatment allocation at 8 weeks and 6 months after the stroke. The primary outcome was physical function on the Nottingham Extended Activities of Daily Living Scale. RESULTS: Of 658 patients with stroke screened, only 71 (10.7%) were eligible and consented to a sleep study 14-19 days after stroke. 66 patients completed the sleep study (21 women; mean age 72 years), 33 (50%) had > or = 30 (A+H)/h that were predominantly obstructive. 15 were randomised to CPAP treatment and 15 to conventional treatment. Despite intensive efforts, objective use of CPAP was poor, averaging 1.4 h a night. CPAP treatment resulted in no significant improvements (p>0.1) in the primary outcome or in neurological function or sleepiness, and in poorer health status on some measures. CONCLUSIONS: This trial showed no benefit from CPAP treatment, the relevance of the observed detrimental effects is questionable. Even in our highly selected patients with stroke, use of CPAP was poor. At present, CPAP treatment should be advocated for patients with stroke only if they have symptoms of SDB.

Sleep-disordered breathing and upper airway size in pregnancy and post-partum.

Sleep-disordered breathing and snoring are common in pregnancy. The aim of this study was to determine whether pregnancy was associated with upper airway narrowing. One-hundred females in the third trimester of pregnancy were recruited and 50 agreed to be restudied 3 months after delivery. One-hundred nonpregnant females were also recruited. Upper airway dimensions were measured using acoustic reflection. Snoring was less common in nonpregnant (17%) than pregnant females (41%; odds ratio (OR) 3.34; 95% confidence interval (CI) 1.65-6.74) and returned to nonpregnant levels after delivery (18%; OR 0.15; 95% CI 0.06-0.40). Pregnant females had significantly smaller upper airways than nonpregnant females at the oropharyngeal junction when seated (mean difference 0.12; 95% CI 0.008-0.25), and smaller mean pharyngeal areas in the seated (mean difference 0.14; 95% CI 0.001-0.28), supine (mean difference 0.11; 95% CI 0.01-0.22) and lateral postures (mean difference 0.13; 95% CI 0.02-0.24) compared with the nonpregnant females. Pregnant females had smaller mean pharyngeal areas compared with post-partum in the seated (mean difference 0.18; 95% CI 0.02-0.32), supine (mean difference 0.20; 95% CI 0.06-0.35) and lateral postures (mean difference 0.26; 95% CI 0.12-0.39). In conclusion, this study confirmed increased snoring and showed narrower upper airways during the third trimester of pregnancy.

Tumour necrosis factor-alpha (-308) gene polymorphism in obstructive sleep apnoea-hypopnoea syndrome.

Patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) have elevated circulating levels of tumour necrosis factor (TNF)-alpha. The hypothesis in this study was that OSAHS might be associated with the TNF-alpha (-308A) gene polymorphism, which results in increased TNF-alpha production. This hypothesis was examined in OSAHS patients, their siblings and population controls. A total of 206 subjects were recruited. All underwent sleep studies and clinical review, and were subsequently classified as having OSAHS or not depending on apnoea-hypopnoea frequency, sex, age and symptoms. All subjects had blood collected and genotyping was performed on DNA extracted from peripheral leukocytes. Some 192 random UK blood donors were used as population controls. The results demonstrated a significant association for TNF-alpha (-308A) allele carriage with OSAHS (OR=1.8; 95% Confidence interval: 1.18-2.75) when compared with population controls. Siblings with OSAHS were significantly more likely to carry the TNF-alpha (-308A) allele. In addition, 21 pairs of male siblings discordant for carriage of the -308A allele showed a significant level of discordance for the OSAHS phenotype. In conclusion, this study demonstrates an association of tumour necrosis factor-alpha (-308A) carriage with obstructive sleep apnoea-hypopnoea syndrome, suggesting that inflammation may be implicated in the pathogenesis of this condition.

Is there a familial association between obstructive sleep apnoea/hypopnoea and the sudden infant death syndrome?

BACKGROUND: One postulated cause of the sudden infant death syndrome (SIDS) is upper airway obstruction during sleep. Several studies have suggested that SIDS may be more common in families with obstructive sleep apnoea/hypopnoea syndrome (OSAHS), but were limited by uncertainty as to whether the deaths were due to SIDS. We have tested the hypothesis that parents of true SIDS cases have an increased frequency of apnoeas and hypopnoeas during sleep. METHODS: The parents of 269 rigorously determined SIDS cases were invited for single night polysomnography and daytime ventilatory control measurement. RESULTS: Parents of 198 cases were identified but 152 did not respond or declined. Fifty five parents of 34 cases were studied and matched for age, height, and weight to 55 subjects from general practice registers. There was no difference in breathing during sleep between the parents of SIDS cases (median (IQR) 5.9 (3.2, 10.7) apnoeas+hypopnoeas/h) and controls (6.7 (4.0, 12.2) apnoeas+hypopnoeas/h; p = 0.47), but the SIDS parents had lower minimum nocturnal oxygen saturation (median (IQR) 92 (89, 93)%) than controls (92 (90, 94)%; p = 0.048). There were no major differences in control of breathing when awake between SIDS parents and controls. CONCLUSIONS: These results provide no evidence to support an association between SIDS and OSAHS. However, the minor impairment of oxygenation during sleep in SIDS parents requires further study.

Evaluation of a portable device for diagnosing the sleep apnoea/hypopnoea syndrome.

Waiting times for hospital-based monitoring of the obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are rising. This study tested whether Embletta, a new portable device, may accurately diagnose OSAHS at home. A synchronous comparison to polysomnography was performed in 40 patients and a comparison of home Embletta studies with in-laboratory polysomnography was performed in 61 patients. In the synchronous study, the mean difference (polysomnography-Embletta) in apnoeas+hypopnoeas (A+H) x h(-1) in bed was 2 h(-1). In comparison to the apnoea/ hypopnoea index (AHI) x h(-1) slept, the Embletta (A+H) x h(-1) in bed differed by 8 x h(-1). These data were used to construct diagnostic categories in symptomatic patients from their Embletta results: "OSAHS" (> or = 20 (A+H) x h(-1) in bed), "possible OSAHS" (10-20 (A+H) x h(-1) in bed) or "not OSAHS" (<10 (A+H) x h(-1) in bed). In the home study, the mean difference in (A+H) x h(-1) in bed was 3 x h(-1). In comparison to the polysomnographic AHI x h(-1) slept, the Embletta (A+H) x h(-1) in bed differed by 6 +/- 14 x h(-1). Using the above classification, all nine patients categorised as not OSAHS had AHI < 15 x h(-1) slept on polysomnography and all 23 with OSAHS on Embletta had an AHI > or = 15 on polysomnography, but 18 patients fell into the possible OSAHS category potentially requiring further investigation and 11 home studies failed. Most patients were satisfactorily classified by home Embletta studies but 29 out of 61 required further investigation. The study suggested a 42% saving in diagnostic costs over polysomnography if this approach were adopted.

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome.

Some patients with the sleep apnea/hypopnea syndrome (SAHS) remain subjectively and objectively sleepy despite using effective continuous positive airway pressure (CPAP) therapy. The aim of this single center study was to determine the efficacy and safety of the novel wake-promoting medication modafinil in the treatment of CPAP-resistant daytime sleepiness. Thirty sleep apneics receiving effective CPAP therapy (objective use, 6.5 +/- 1.1 h/night) received daily single doses of 400 mg modafinil or placebo for 2 wk in a double-blind randomized crossover design. Outcome measures were assessed at baseline and at the end of both 2-wk treatment periods. Treatment periods were separated by a 1-wk washout. Modafinil had no effect on sleepiness as measured by the Epworth Sleepiness Scale or the Multiple Sleep Latency Test (p > 0.1); however, significant improvements in alertness were found with the Maintenance of Wakefulness Test (modafinil 18.3 +/- 3.9 min; placebo, 16.6 +/- 5.0 min; p < 0.02). No significant treatment-related improvements in cognitive performance or quality of life were found with modafinil (all p > 0.05). There was a significant reduction in CPAP use on modafinil compared to placebo (6.3 +/- 1 h/ night; 6.5 +/- 1, p = 0.03). This study suggests that modafinil may improve some aspects of alertness in patients with SAHS who remain sleepy during CPAP therapy, but further studies are required to assess the significance of the reduction in CPAP use.

Predictors of improvements in daytime function outcomes with CPAP therapy.

Continuous positive airway pressure (CPAP) therapy improves daytime function in the sleep apnea/ hypopnea syndrome (SAHS) but it is unclear which patients benefit and what factors predict this improvement. To test the hypothesis that brief arousals from sleep predict improvements in daytime functioning with CPAP therapy, we prospectively studied 62 patients with polysomnography-defined SAHS. Each underwent daytime function assessments at baseline and after 6 mo of CPAP therapy to measure objective sleepiness, psychological well-being, quality of life, and cognitive performance. The microarousal frequency and AHI were poor predictors of improvements in daytime function with CPAP. Measures of hypoxemia predicted improvements in the mean sleep latency on the maintenance of wakefulness test, SAHS symptoms, quality of life, and reaction time, but such correlations were weak or moderate only explaining between 7% and 22% of variance. Significant relationships were found between CPAP use and improvements in self-ratings of daytime function. Results suggest that standard polysomnographic baseline variables are poor predictors of the response to CPAP therapy.

Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome?

Continuous positive airway pressure (CPAP) therapy is widely prescribed for patients with the sleep apnea/hypopnea syndrome (SAHS), but the use of CPAP for such patients is disappointingly low. We postulated that providing intensive educational programs and nursing support to SAHS patients might improve CPAP use and outcomes. We also examined the hypothesis that CPAP use would be greater among patients who had initiated their own referral than among those asked to seek help by a partner. We randomized 80 consecutive, new patients with SAHS to receive either usual support or additional nursing input including CPAP education at home and involving their partners, a 3-night trial of CPAP in our institution's sleep center, and additional home visits once they had begun CPAP. The primary outcome variable was objective CPAP use; symptoms, mood, and cognitive function were also assessed after 6 mo. CPAP use over 6 mo was greater (p = 0.003) among patients receiving intensive than among those receiving standard support (5.4 +/- 0.3 versus 3.9 +/- 0. 4 h/night [mean +/- SEM]), with greater improvements (p < 0.05) in SAHS symptoms, mood, and reaction time in the intensively supported group. CPAP use was greater (p = 0.002) among patients who initiated their own referrals. CPAP use and outcomes of therapy can be improved by provision of a nurse-led intensive CPAP education and support program. CPAP use is lower among patients whose partners ask them to seek treatment.