Sleep disordered breathing: management update

The term sleep disordered breathing encompasses a spectrum of abnormalities, including snoring, obstructive sleep apnoea (OSA), central sleep apnoea (CSA), respiratory‐related arousals and hypoventilation. This review focuses on both OSA and CSA. It provides a clinical update of recent advances in the diagnosis, management and prognosis of these two conditions. An increasing array of treatment modalities, particularly for OSA, broadens the opportunity for personalised therapy tailored to the individual patient.     

Automatic CPAP Performance in Patients with Sleep Apnea Plus COPD

Abstract

Background: Automatic CPAP devices have demonstrated good results in obtaining optimal fixed CPAP pressure to eliminate respiratory events in patients with sleep apnea-hypopnea syndrome (SAHS). However, automatic CPAP has not been fully studied in patients with COPD plus SAHS. Objectives: To analyse the performance of an automatic CPAP in severe COPD patients compared with SAHS patients with no associated co-morbidity. Methods: We compared 10 consecutive patients with SAHS and no associated co-morbidity and 10 patients with SAHS plus severe COPD who required CPAP titration. Automatic CPAP performance was studied during full-night PSG. Inadequate pressure increase periods, absence of pressure increases in reaction to respiratory events, air leak periods, and pressure behaviour in the face of erratic breathing periods were analysed. Results: The SAHS patients without co-morbidities vs. SAHS plus COPD patients presented: mean sleep efficiency, 80.2 (11.5)% vs. 76.5 (12.1)%; residual AHI, 6.3 (5.2) vs. 5.1 (7.7); residual CT90, 1 (3)% vs. 14 (1)%. The device´s performance demonstrates a mean of 1.2 (1.5) vs. 1.3 (1.2) periods of inadequate pressure increases; absence of pressure increases in reaction to respiratory events, 4.1 (5.4) vs. 0.6 (0.7) times; periods of air leaks, 1.3 (3.8) vs. 13.9 (11.7); mean optimal pressure, 9.1 (1.4) vs. 9.0 (1.9) cm H₂O. Conclusion: Titration with automatic CPAP could be as effective in patients with SAHS plus severe COPD as in patients with SAHS without COPD. However, the presence of more leakages must be taken into account.     

Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer

Higher epidermal growth factor receptor (EGFR) signaling can contribute to tumor metastasis and resistance to therapies in oral squamous cell carcinoma (OSCC). EGFR signaling can promote epithelial-mesenchymal transition (EMT) in OSCC. EMT is a process by which epithelial cells acquire invasive properties and it can contribute to tumor metastasis. Not only do the abnormal functions of microtubule and microtubule-organizing centers (MTOC) such as centrosomes lead to cancers, but also the malignant tissues are characterized by aberrant centriolar features and amplified centrosomes. Microtubule inhibition therapies increase the sensitivity to EGFR targeting drugs in various cancers. In this study, we show that the loss of expression of a microtubule/tubulin binding protein, centrosomal protein 4.1-associated protein (CPAP), which is critical for centriole biogenesis and normal functioning of the centrosome, caused an increase in the EGFR levels and its signaling and, enhanced the EMT features and invasiveness of OSCC cells. Further, depletion of CPAP enhanced the tumorigenicity of these cells in a xeno-transplant model. Importantly, CPAP loss-associated EMT features and invasiveness of multiple OSCC cells were attenuated upon depletion of EGFR in them. On the other hand, we found that CPAP protein levels were higher in EGF treated OSCC cells as well as in oral cancer tissues, suggesting that the frequently reported aberrant centriolar features of tumors are potentially a consequence, but not the cause, of tumor progression. Overall, our novel observations show that, in addition to its known indispensable role in centrosome biogenesis, CPAP also plays a vital role in suppressing tumorigenesis in OSCC by facilitating EGFR homeostasis.     

Patients’ preference of established and emerging treatment options for obstructive sleep apnoea

Background

Obstructive sleep apnoea (OSA) is the most common form of sleep-disordered breathing. The standard treatment, continuous positive airway pressure (CPAP), has limited long-term compliance. Alternative treatment options are required and new methods, including hypoglossal nerve stimulation (HNS) and continuous transcutaneous electrical stimulation (CTES), are currently emerging. We report on patients’ preference for different treatments of OSA.

Methods

We recorded patients’ age, gender, body mass index (BMI), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire with 10 questions (FOSQ10), severity of OSA, and current treatment. We showed pictures of existing [CPAP, mandibular advancement device (MAD)] and emerging treatments (HNS and CTES). We then asked (I) whether participants were interested in further information about HNS/CTES; (II) if they would be willing to try HNS/CTES; and (III) if they were to choose only one of the four listed treatments, which one would they prefer to use every night.

Results

One hundred sixty-two patients completed the survey {81 males, mean age 52 [12] years, BMI 34 [7] kg/m², ESS 10.2 (6.0) points, FOSQ10 28.5 (8.1) points}. The majority of the respondents (89.5%) had been diagnosed with OSA. A total of 91.3% of the respondents were interested in more information and were willing to try HNS/CTES. Most respondents preferred the potential use of CTES (56.7%), while 21.7% chose HNS, 17.8% CPAP, and 3.8% the MAD. There were no differences in the characteristics of the patients who preferred CTES compared to those who preferred other treatments, but a regression analysis revealed that a low ESS score was an independent predictor of patients choosing CTES (P<0.05).

Conclusions

More than 9 out of 10 of the respondents were interested in trying emerging technologies to treat OSA, most preferring CTES. Less sleepy patients were more likely to choose less invasive treatments. These findings will likely impact on future research and development of therapies for sleep-disordered breathing.     

Enzyme-replacement therapy in perinatal hypophosphatasia: Case report and review of the literature

Hypophosphatasia (HPP) is a rare disease resulting from alterations of the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). Perinatal HPP is mainly characterized by bone hypomineralization and severe respiratory insufficiency. We describe a full-term boy diagnosed with perinatal HPP after birth, showing dramatic improvement after treatment with Asfotase Alfa, an enzyme-replacement therapy (ERT) prescribed in HPP cases. He initially presented with respiratory insufficiency due to bone hypomineralization, and severe pulmonary hypoplasia that required tracheostomy and invasive ventilation for 8 months. He was taken off ventilation at 41 weeks of age. He also presented complications including hypercalcemia, craniosynostosis, nephrocalcinosis, hypotonia, and a severe feeding disorder. He is still alive at 30 months of age, and his respiratory status and tonus is steadily improving. This case reflects the progression of HPP patients with specific therapy added to symptomatic management. Some aspects of the disease are now well known, such as nephrocalcinosis and craniosynostosis, related to the natural course of the disease, which persisted despite the ERT. The long-term prognosis and outcome for this newborn child remain unknown.