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STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF) is associated with worse mortality and clinical outcome. We aimed to assess differences between patients with IPF with and without OSA and the effect of positive airway pressure treatment on sleep and overall life quality, morbidity, and mortality in these patients. METHODS: Forty-five patients with newly diagnosed IPF underwent polysomnography. Using an apnea-hypopnea index ≥ 15 events/h for OSA diagnosis resulted in 16 patients with IPF and 29 with IPF-OSA. The patients completed the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Functional Outcomes in Sleep Questionnaire, Fatigue Severity Scale, Short Form-36 life questionnaire, and Beck Depression Inventory before and at the end of the follow-up period. RESULTS: Patients with IPF-OSA showed the most severe functional impairments in questionnaires, especially for General Health component of the Short Form-36 life questionnaire (37 vs 58, P = .03). At the 7-year follow-up, 16 (36%) patients had died, 6 (38%) in the IPF group and 10 (35%) in IPF-OSA group. Patients with ≥6-hour positive airway pressure use had better survival compared with patients with

STUDY OBJECTIVES: To evaluate the influence of sex on obstructive sleep apnea (OSA)-related symptoms and prevalent cardiovascular disease (CVD) in a large clinical population of patients. METHODS: A total of 6,716 patients (mean age 52 years, 24% women) had undergone diagnostic polysomnography and completed the Epworth Sleepiness Scale (ESS), Athens Insomnia Scale, and Beck Depression Inventory. We investigated the predictive value of sex on associated symptoms and prevalent cardiovascular disease, after adjustment for relevant confounding factors including age, obesity, and comorbidities. RESULTS: Most of the patients (90%) had OSA (apnea-hypopnea index [AHI] ≥ 5 events/h), and 66% were obese. Women were older than men and had a higher body mass index; however, men had a thicker neck circumference, a higher waist-to-hip ratio, and increased OSA severity (AHI 36 versus 27 events/h, P < .001). Female sex independently predicted prevalent CVD after adjustment for confounders (odds ratio [95% CI] 1.476 [1.154–1.887], P = .002). Men independently were more likely to report driving problems (3.359 [2.470–4.569], P < .001) and excessive daytime sleepiness (ESS ≥ 16) (1.355 [1.036–1.773], P = .027). Furthermore, female sex was an independent predictive factor for depressive symptoms (2.473 [1.831–3.340], P < .001), frequent awakenings (1.703 [1.323–2.192], P < .001), nocturia (1.727 [1.340–2.226], P < .001) and morning headaches (1.855 [1.488–2.326], P < .001). CONCLUSIONS: Females referred for sleep studies were more likely to exhibit CVD and less likely to complain of typical OSA symptoms than males in this large clinical patient cohort. CITATION: Bouloukaki I, Mermigkis C, Markakis M, Pataka A, Alexaki I, Ermidou C, Moniaki V, Mauroudi E, Michelakis S, Schiza SE. Cardiovascular effect and symptom profile of obstructive sleep apnea: does sex matter? J Clin Sleep Med. 2019;15(12):1737–1745.

STUDY OBJECTIVES: To assess the role of different levels of adherence and long-term effects of positive airway pressure (PAP) therapy on gas exchange, sleepiness, quality of life, depressive symptoms, and all-cause mortality in patients with obesity hypoventilation syndrome (OHS). METHODS: A total of 252 patients with newly diagnosed OHS were followed up for a minimum of 2 years after PAP initiation. PAP adherence (h/night) was monitored. Arterial blood gas samples were taken with patients being alert for more than 4 hours after morning awakening. Subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]), quality of life (Short Form 36 [SF-36]) and patient's depressive symptoms (Beck Depression Inventory [BDI]) were assessed before and at the end of the follow-up period, along with all-cause mortality. RESULTS: At the end of the follow-up period (median duration [25th–75th percentile], 30 [24–52] months), PaO(2) increased from baseline (72.7 ± 10.3 versus 63.2 ± 10.6, P < .001) and both PaCO(2) and HCO(3)(−) decreased (43.0 [39.2–45.0] versus 50.0 [46.7–55.4] and 27.5 ± 3.2 versus 31.4 ± 4.2, respectively, P < .001). In addition, PAP therapy significantly improved ESS (7 [4–9] versus 14 [11–16], P < .001), BDI (8.8 ± 4.9 versus 15.5 ± 7.3, P < .001) and SF-36 (82 [78–87] versus 74 [67–79], P < .001) scores. Over the follow-up period 11 patients died. Patients who used PAP for > 6 h/night had significant improvements (P < .05) in blood gases and SF-36 scores than less adherent patients. CONCLUSIONS: Increased hours of use and long-term therapy with PAP are effective in the treatment of patients with OHS. Clinicians should encourage adherence to PAP therapy in order to provide a significant improvement in clinical status and gas exchange in these patients. COMMENTARY: A commenary on this article appears in this issue on page 1455. CLINICAL TRIAL REGISTRATION: Title: PAP Therapy in Patients With Obesity Hypoventilation Syndrome, Registry: ClinicalTrials.gov, Identifier: NCT03449641, URL: https://clinicaltrials.gov/ct2/show/NCT03449641 CITATION: Bouloukaki I, Mermigkis C, Michelakis S, Moniaki V, Mauroudi E, Tzanakis N, Schiza SE. The association between adherence to positive airway pressure therapy and long-term outcomes in patients with obesity hypoventilation syndrome: a prospective observational study. J Clin Sleep Med. 2018;14(9):1539–1550.

Patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality as a result of various alterations in oxygenation parameters and sleep macro- and micro-architecture. There is a shortage of data to support the efficacy of long-acting inhaled anticholinergic agents in improving these adverse effects, which are known to have a negative impact on clinical outcomes. We aimed to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO2) and sleep quality in patients with COPD.In a randomized, open-label, parallel-group trial involving 200 patients with mild to moderate COPD (resting arterial oxygen tension60 mmHg while awake), we compared the effects of 6 months' treatment with the two devices on sleeping SaO2 and sleep quality. Overnight polysomnography and pulmonary function testing were performed at baseline and after 6 months' treatment.A total of 188 patients completed the trial. Both groups showed significant improvement in minimum sleep SaO2 and time of sleep spent with SaO2 below 90 (TST90) compared to baseline. The patients using the Respimat had significantly better TST90 than did those using the HandiHaler. Sleep disturbance was highly variable in these patients, but the sleep stage durations were significantly better in the Respimat group.Sleeping SaO2 can be improved by tiotropium delivered using either the HandiHaler device or the Respimat Soft Mist Inhaler. However, the patients who used the Respimat device had significantly better TST90 and sleep architecture parameters.

We aimed to compare the effect of intensiveversusstandard interventions on continuous positive airway pressure (CPAP) adherence 2 years after CPAP initiation, as well as on sleepiness, quality of life, depression, hospitalisation and death rate due to cardiovascular disease (CVD).3100 patients with newly diagnosed sleep apnoea were randomised into the standard group, with usual follow-up care, or the intensive group, with additional visits, telephone calls and education. Subjective daytime sleepiness (Epworth Sleepiness Scale; ESS), quality of life (36-item Short Form Health Survey; SF-36) and the patient’s level of depression (Beck Depression Inventory; BDI) were recorded before and 2 years after CPAP initiation, together with CVD hospitalisations and death rate.2 years after CPAP initiation, the intensive group used CPAP significantly more than the standard group (6.9versus5.2 h per night; pCPAP usage can be improved by both intensive and standard patient support. However, the patients who received intensive CPAP support had significantly better ESS, BDI and SF-36 scores, and lower cardiovascular morbidity and mortality, suggesting that an intensive programme could be worthwhile.

Circulating KL6 has been recognized as a biomarker of subclinical lung injury induced by oxidative stress in idiopathic pulmonary fibrosis (IPF) and in obstructive sleep apnoea (OSA). The proportion of coexistence of OSA and IPF is remarkable and IPF guidelines recently recognize OSA as a serious problem affected survival. The aim of this study was to investigate potential additive effects in serum and BALF KL6 levels, of the coexistence of OSA in IPF patients. 25 patients with IPF (Group A) and 22 patients with IPF-OSA(Group B) were included in the study. BALF KL6 was available in 13 patients from group A and in 10 patients from group B. We investigated the correlation of KL6 levels with several parameters from the sleep study, such as apnoea-hypopnoea index (AHI), REM apnoea-hypopnoea index (REM-AHI) and desaturation indexes. Both serum and BALF KL6 levels were non-significantly between two groups. However, a negative correlation was found between KL6 serum levels and severity of IPF, assessed by DLCO (r=-0.504, p=0.017) and KCO (r=-0.548, p=0.01), only in group with IPF plus OSAS. Our preliminary findings showed a negative association of serum KL6 and lung diffusion parameters only in IPF-OSA subgroup of patients. This evidence could support the hypothesis that KL6 levels probably reflect the additional oxidative stress OSA provides in IPF patients. Further studies are needed to clarify this observation.

Background: There is limited data concerning long-term effects of positive airway pressure (PAP) therapy on survival and functional status in patients with obesity hypoventilation syndrome (OHS). Aims: To assess the role of different levels of compliance and long-term effects of PAP therapy on gas exchange, sleepiness, quality of life, depression and death rate in patients with OHS. Methods: Two hundred fifty two OHS patients, newly diagnosed, who have been recommended PAP therapy, were followed up for a minimum of 2 years. Arterial blood samples were taken for gas level measurements with patients awake, for more than 4 h since wakening.The hours/day and percentage of days PAP was used were monitored. Epworth sleepiness scale (ESS), quality of life (Short Form 36-SF-36) and Beck Depression Inventory (BDI) were recorded together with the death rate before and at the end of the follow up period. Results: At the end of thefollow-up period (mean duration, 50 months), PaO 2 had increased from baseline (p 2 and HCO 3 − had decreased (p 6 hours/day had a considerably greater improvement in blood gases and questionnaires scores than less adherent patients. Conclusions: Increased hours of use and long-term therapy with PAP are effective in the treatment of patients with OHS. Clinicians should encourage adherence to PAP therapy in order to provide a significant improvement in clinical status and gas exchange in these patients.