Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome.

STUDY OBJECTIVES: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. METHODS: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. RESULTS: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.

OSA Upper Airways Surgery: A Targeted Approach.

Obstructive sleep apnea syndrome (OSA) is a multi-factorial disorder, with quite complex endotypes, consisting of anatomical and non-anatomical pathophysiological factors. Continuous positive airway pressure (CPAP) is recognized as the first-line standard treatment for OSA, whereas upper airway (UA) surgery is often recommended for treating OSA patients who have refused or cannot tolerate CPAP. The main results achievable by the surgery are UA expansion, and/or stabilization, and/or removal of the obstructive tissue to different UA levels. The site and pattern of UA collapse identification is of upmost importance in selecting the customized surgical procedure to perform, as well as the identification of the relation between anatomical and non-anatomical factors in each patient. Medical history, sleep studies, clinical examination, UA endoscopy in awake and drug-induced sedation, and imaging help the otorhinolaryngologist in selecting the surgical candidate, identifying OSA patients with mild UA collapsibility or tissue UA obstruction, which allow achievement of the best surgical outcomes. Literature data reported that the latest palatal surgical procedures, such as expansion sphincter palatoplasty or barbed reposition palatoplasty, which achieve soft palatal and lateral pharyngeal wall remodeling and stiffening, improved the Apnea Hypopnea Index, but the outcome analyses are still limited by methodological bias and the limited number of patients' in each study. Otherwise, the latest literature data have also demonstrated the role of UA surgery in the improvement of non-anatomical factors, confirming that a multidisciplinary and multimodality diagnostic and therapeutical approach to OSA patients could allow the best selection of customized treatment options and outcomes.

Post-sigh sleep apneas in mice: Systematic review and data-driven definition.

Sleep apneas can be categorized as post-sigh (prevailing in non-rapid eye movement sleep) or spontaneous (prevailing in rapid eye movement sleep) according to whether or not they are preceded by an augmented breath (sigh). Notably, the occurrence of these apnea subtypes changes differently in hypoxic/hypercapnic environments and in some genetic diseases, highlighting the importance of an objective discrimination. We aim to: (a) systematically review the literature comparing the criteria used in categorizing mouse sleep apneas; and (b) provide data-driven criteria for this categorization, with the final goal of reducing experimental variability in future studies. Twenty-two wild-type mice, instrumented with electroencephalographic/electromyographic electrodes, were placed inside a whole-body plethysmographic chamber to quantify sleep apneas and sighs. Wake-sleep states were scored on 4-s epochs based on electroencephalographic/electromyographic signals. Literature revision showed that highly different criteria were used for post-sigh apnea definition, the intervals for apnea occurrence after sigh ranging from 1 breath up to 20 s. In our data, the apnea occurrence rate during non-rapid eye movement sleep was significantly higher than that calculated before the sigh only in the 1st and 2nd 4-s epochs following a sigh. These data suggest that, in mice, apneas should be categorized as post-sigh only if they start within 8 s from a sigh; the choice of shorter or longer time windows might underestimate or slightly overestimate their occurrence rate, respectively.

Diagnostic yield and risk/benefit analysis of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases: a large cohort of 699 patients.

BACKGROUND: Standardization of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases is imminent; however, the majority of published series on cryobiopsy include a limited number of patients and are characterized by several differences in procedural technical details. METHODS: This is an observational, retrospective cohort study. Aim of the study was to suggest some sampling strategies related to transbronchial cryobiopsy in the diagnostic work-up of patients with diffuse parenchymal lung diseases. RESULTS: Six hundred ninety-nine patients with suspected diffuse parenchymal lung disease were recruited. A specific pathological diagnosis was achieved in 614/699 cases (87.8%) and a multidisciplinary diagnosis was obtained in 630/699 cases (90.1%). Diagnostic yield was significantly influenced by the number of samples taken (1 vs ≥ 2 biopsies, p < 0.005). In 60.4% of patients, biopsies were taken from one site and in 39.6% from different sites (in the same lobe or in two different lobes), with a significant increase in diagnostic yield, specifically in patients with fibrotic lung diseases (65.5% vs 93.4%, p < 0.0001). The 2.4 mm or 1.9 mm probes were used, with no differences in terms of diagnostic yield. Regarding safety, pneumothorax occurred in 19.2% and was influenced by baseline lung function; in all patients Fogarty balloon has been used and severe haemorrhage occurred in 0.7% of cases. Three patients (0.4% of cases) died within 30 days after the procedure. CONCLUSIONS: We propose some sampling strategies of cryobiopsy which seem to be associated with a higher diagnostic yield and a favorable risk/benefit ratio: sampling at least two samples in different sites, using either the 2.4 mm or the 1.9 mm probe, intubating the patients and using bronchial blockers/catheters.

Arousal responses to respiratory events during sleep: the role of pulse wave amplitude.

The study aims at assessing the changes in electroencephalography (as measured by the A-phases of cyclic alternating pattern) and autonomic activity (based on pulse wave amplitude) at the recovery of airway patency in patients with obstructive sleep apnea syndrome. Analysis of polysomnographic recordings from 20 male individuals with obstructive sleep apnea syndrome was carried out in total sleep time, non-rapid eye movement and rapid eye movement sleep. Scoring quantified the combined occurrence (time range of 4 s before and 4 s after respiratory recovery) or separate occurrence of A-phases (cortical activation), and pulse wave amplitude drops (below 30%) to apneas, hypopneas or flow limitation events. A dual response (A-phase associated with a pulse wave amplitude drop) was the most frequent response (71.8% in total sleep time) for all types of respiratory events, with a progressive reduction from apneas to hypopneas and flow limitation events. The highly significant correlation in total sleep time (r = 0.9351; P < 0.0001) between respiratory events combined with A-phases and respiratory events combined with pulse wave amplitude drops was confirmed both in non-rapid eye movement (r = 0.9622; P < 0.0001) and rapid eye movement sleep (r = 0.7162; P < 0.0006). In conclusion, a dual cortical and autonomic activation is the most common manifestation at the recovery of airway patency. The significant correlation between A-phases and relevant pulse wave amplitude drops suggests a possible role of pulse wave amplitude as a marker of cerebral response to respiratory events.

Phenotyping the pathophysiology of obstructive sleep apnea using polygraphy/polysomnography: a review of the literature.

Continuous positive airway pressure (CPAP) is the first-line treatment for the majority of patients affected by obstructive sleep apnea syndrome (OSA). However, long-term compliance with CPAP therapy may result limited and alternatives to CPAP therapy are required to address the increasing need to provide tailored therapeutic options. Understanding the pathophysiological traits (PTs) of OSA patients [upper airway (UA) anatomical collapsibility, loop gain (LG), arousal threshold (AT), and UA gain (UAG)] lies at the heart of the customized OSA treatment. However, sleep research laboratories capable to phenotype OSA patients are sparse and the diagnostic procedures time-consuming, costly, and requiring significant expertise. The question arises whether the use of routine clinical polysomnography or nocturnal portable multi-channel monitoring (PSG/PM) can provide sufficient information to characterize the above traits. The aim of the present review is to deduce if the information obtainable from the clinical PSG/PM analysis, independently of the scope and context of the original studies, is clinically useful to define qualitatively the PTs of individual OSA patients. In summary, it is possible to identify four patterns using PSG/PM that are consistent with an altered UA collapsibility, three that are consistent with altered LG, two with altered AT, and three consistent with flow limitation/UA muscle response. Furthermore, some PSG/PM indexes and patterns, useful for the suitable management of OSA patient, have been discussed. The delivery of this clinical approach to phenotype pathophysiological traits will allow patients to benefit in a wider range of sleep services by facilitating tailored therapeutic options.

European position paper on drug-induced sleep endoscopy: 2017 Update.

BACKGROUND: The first edition of the European position paper (EPP) on drug-induced sleep endoscopy (DISE) was published in 2014 with the aim to standardise the procedure, to provide an in-depth insight into the main aspects of this technique and to have a basis for future research. Since 2014, new studies have been published concerning new sedative agents or new insights into the pattern/levels of the obstruction depending on the depth of sedation. Therefore, an enlarged group of European experts in the field of sleep breathing disorders (SBD), including the most of the first DISE EPP main authors, has decided to publish an update of the European position paper on DISE, in order to include new evidence and to find a common language useful for reporting the findings of this endoscopic evaluation in adult population affected by SBD. METHODS: The authors have evaluated all the available evidence reported in the literature and have compared experience among various departments in leading European centres in order to provide an update regarding the standardisation of the DISE procedure and an in-depth insight into the main aspects of this technique. RESULTS: After the first European Position Consensus Meeting on DISE and its update, consensus was confirmed for indications, required preliminary examinations, where to perform DISE, technical equipment required, staffing, local anaesthesia, nasal decongestion, other medications, patient positioning, basics and special diagnostic manoeuvres, drugs and observation windows. So far, no consensus could be reached on a scoring and classification system. However, regarding this aim, the idea of an essential classification, such as VOTE with the possibility of its graded implementation of information and descriptions, seems to be the best way to reach a universal consensus on DISE classification at this stage. A common DISE language is mandatory, and attempts to come to a generally accepted system should be pursued.

OSA and Prolonged Oxygen Desaturation During Sleep are Strong Predictors of Poor Outcome in IPF.

PURPOSE: Sleep Breathing Disorders (SBD) are frequently found in idiopathic pulmonary fibrosis (IPF) and they are associated with worse quality of sleep and life and with higher mortality. The study aimed at evaluating the impact of SBD on prognosis (mortality or disease progression) in 35 patients with mild to moderate IPF. METHODS AND RESULTS: Obstructive sleep apnea (OSA) was diagnosed in 25/35 patients with IPF: 14/35 mild, 7/35 moderate, and 4/35 severe. According to the American Academy of Sleep Medicine (AASM) definition, sleep-related hypoxemia was found in 9/35 patients with IPF. According to the presence/absence of SBD, IPF patients were divided into 4 groups: NO-SBD group (Group A, 25.7%), OSA without sleep-related hypoxemia (Group B, 48.5%), OSA with sleep-related hypoxemia group (Group C, 22.8%), and only 1/35 had sleep-related hypoxemia without OSA(Group D, 2.8%). Statistical analysis was focused only on group A, B, and C. Patients with OSAS and sleep-related hypoxemia (Group C) had the worse prognosis, both in terms of mortality or clinical deterioration. SBD were the only independent risk factor (Cox Proportional Hazards Multiple Regression Analysis) for mortality (HR 7.6% IC 1.2-36.3; p = 0.029) and disease progression (HR 9.95% IC 1.8-644.9; p = 0.007). CONCLUSIONS: SBD are associated with a worse prognosis, both in terms of mortality or clinical progression. The presence of SBD should be explored in all IPF patients.

The role of compact polysomnography/polygraphy in sleep breathing disorder patients' management.

While managing obstructive sleep apnea (OSA) or suspicious OSA patients, the otorhinolaryngologist frequently has to deal with patients undergoing repeated polysomnography (PSG) or portable monitoring (PM) and, on the other hand, should be confident about the quality and consistency of the polysomnographic diagnosis. The main polysomnographic traces compressed in a unique epoch, defined as compact PSG/PM (CP), which should be reported in all PSG/PM report, could represent an efficient tool to confirm the quality of PSG/PM diagnosis and to recognize the sleep breathing disorders (SBD): OSA, no-OSA SBD and overlap of OSA with no-OSA SBD. In this study, a synthetic and clear guided iconography and an easy decision-making algorithm based on desaturation patterns (phasic, prolonged and overlap desaturation patterns) identifiable on the CP are suggested for a quick check of the quality of PSG/PM diagnosis and to achieve an improvement in the patient's clinical management.

The importance of obstructive sleep apnoea and hypopnea pathophysiology for customized therapy.

The objective of this study is to highlight the importance of anatomical and not-anatomical factors' identification for customized therapy in OSAHS patients. The data sources are: MEDLINE, The Cochrane Library and EMBASE. A systematic review was performed to identify studies that analyze the role of multiple interacting factors involved in the OSAHS pathophysiology. 85 out of 1242 abstracts were selected for full-text review. A variable combinations pathophysiological factors contribute to realize differentiated OSAHS phenotypes: a small pharyngeal airway with a low resistance to collapse (increased critical closing pressure), an inadequate responses of pharyngeal dilator muscles (wakefulness drive to breathe), an unstable ventilator responsiveness to hypercapnia (high loop gain), and an increased propensity to wake related to upper airway obstruction (low arousal threshold). Identifying if the anatomical or not-anatomical factors are predominant in each OSAHS patient represents the current challenge in clinical practice, moreover for the treatment decision-making. In the future, if a reliable and accurate pathophysiological pattern for each OSAHS patient can be identified, a customized therapy will be feasible, with a significant improvement of surgical success in sleep surgery and a better understanding of surgical failure.

The interpretation of compact polysomnography/polygraphy in sleep breathing disorders patients: a validation's study.

The Otorhinolaryngologist (ENT) frequently has to deal with OSA or suspicious OSA patients and undergone polysomnography (PSG) or portable monitoring (PM) and should be confident about the quality and consistency of the polysomnographic diagnosis. The main polysomnographic traces compressed in a unique epoch, defined as compact PSG/PM (CP), could represent an efficient tool to confirm the quality of PSG/PM Sleep Breathing Disorders diagnosis. This is a validation's study of a CP interpretation's method, analyzing the learning curve, the level of diagnostic accuracy, and the inter-operator agreement in interpreting the CP pattern between a group of ENT specialists not skilled in PSG/PM scoring, but managing SBD patients during daily practice. Seven ENT specialists have been enrolled in the study. 50 CP traces (ranging from normal to all main SBD patterns) have been showed to each participant for the interpretation and scoring process, before and after a 2-h theoretical-practical interactive lesson, focusing on the recognition of the four main oximetric patterns on CP traces (normal, phasic, prolonged, and overlap patterns). RESULTS: before and after the theoretical-practical interactive lesson, the whole diagnostic accuracy in interpreting the 50 CP has been reported improved from 0.12 to 0.80 (median 0.52) to 0.82-0.96 (median 0.92) (p = 0.006) and the inter-scorers' agreement showed a kappa value increased from of 0.18 to 0.75 (p < 0.0001). A complete clinical diagnostic evaluation is essential in OSA patients and the ENT specialist should be concerned to verify if the patient, suitable for surgical therapy, is affected really by an isolated form of OSA. The CP interpretation allows a checking of the proper nosographic SBD framework and could be significantly important for all ENT specialists not skilled in PSG/PM scoring, but managing SBD patients during daily practice. The data reported in our validation's study showed that the CP interpretation's method is easy to apply, with a rapid learning curve. The level of diagnostic accuracy is high with a high inter-scorer agreement in interpreting the CP patterns.

Can sleep microstructure improve diagnosis of OSAS? Integrative information from CAP parameters.

PURPOSE: The scoring of American Academy of Sleep Medicine (AASM) arousal is mandatory for the definition of respiratory event-related arousal (RERA). However there are other EEG activation phenomena, such as A phases of cyclic alternating pattern (CAP) which are associated with respiratory events in non rapid eye movements (NREM) sleep. This study aims at quantifying the additional value of CAP for the definition of respiratory events and sleep alterations in OSAS. METHODS: Analysis of polysomnographic recordings from nineteen OSAS patients was carried out. Scoring was focused on investigation of the cerebral response to flow limitation (FL) events. For this purpose we used both CAP rules and AASM arousal criteria. MAIN RESULTS: While no difference was demonstrated in the arousal index between mild and moderate-severe OSAS patients, CAP time showed a progressive enhancement from normal subjects (152.5±20.76) to mild (180.64±34.76) and moderate-severe (282.27±58.02) OSAS patients. In NREM sleep, only 41.1% of FL events met the criteria for the definition of RERA, while, 75.5% of FL events ended with a CAP A phase and most FL CAP (69.1%) terminated with a CAP phase A3 subtype. CONCLUSIONS: Our data indicate that the RERA scoring has a limited accuracy in the detection of FL events. In NREM sleep, CAP rules provided more information than AASM arousal for the definition of respiratory events and sleep alterations in OSAS.

European position paper on drug-induced sedation endoscopy (DISE).

BACKGROUND: Although drug-induced sedation endoscopy (DISE) represents the most widespread diagnostic tool for upper airway endoscopic evaluation of snoring and obstructive sleep apnea hypopnea syndrome (OSAHS), many controversies exist about how to perform the sedation, the indications for DISE, and how to report DISE findings. The present position paper reports on a consensus as proposed by a group of European experts in the field of DISE after discussion during a recent dedicated meeting. METHODS: The authors have evaluated all the available evidence reported in the literature and have compared experience among various departments in leading European centers in order to provide a standardization of the DISE procedure and an in-depth insight in the main aspects of this technique. RESULTS: A proposal of the DISE procedure standardization has been achieved with a general agreement concerning the terminology, indications, contraindications, required preliminary examinations, setting, technical equipment required, staffing, local anesthesia and nasal decongestion, patient positioning, basis and special diagnostic maneuvers, and the applied sedation drugs and observation windows. Otherwise, no consensus has been reached on a scoring and classification system. CONCLUSIONS: Although consensus has been reached on several aspects of the DISE procedure, some topics remain open to future research, such as a better analysis of the importance of positional aspects during DISE and a further comparison of the differences in degree, level and pattern of upper airway collapse observed during DISE versus during natural sleep and awake endoscopy. Finally, a universally accepted scoring and classification system is lacking.

Atypical patterns in portable monitoring for sleep apnoea: features of nocturnal epilepsy?

Atypical cardiorespiratory patterns can be found during routine clinical use of portable monitoring for diagnosis of sleep-disordered breathing (SDB). Over 1,000 consecutive portable recordings were analysed to study the potential ictal nature of stereotyped cardiorespiratory and motor patterns. Snoring, airflow, thoracic effort, pulse rate, body position, oxygen saturation and activity of the anterior tibialis muscles were quantified. Recordings showing stereotyped polygraphic patterns recurring throughout the night, but without the features of sleep apnoea (apnoea/hypopnoea index <5 events·h(-1)), were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography. A total of 15 recordings showing repeated polygraphic patterns characterised by a sequence of microphone activation, respiratory activity atypical for sleep and wakefulness, heart rate acceleration and limb movements, followed by body position change, were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography that showed frontal epileptic discharges triggering periodic electroencephalographic arousals, autonomic activation and stereotyped motor patterns. A diagnosis of nocturnal frontal lobe epilepsy (NFLE) was established for all patients. NFLE should be taken into consideration in patients with stereotyped and recurrent behavioural features during portable monitoring carried out for diagnosis of SDB.

The predictive value of Muller's maneuvre for CPAP titration in OSAHS patients.

To investigate the role of awake upper airways (UA) endoscopy assessment as a parameter of prediction for CPAP titration in OSAHS patient therapy. Retrospective analysis of UA endoscopic assessment with Mueller's maneuvre and the application of the nose oropharynx hypopharynx score (NOHs) was conducted to obtain a numeric score representing the grade of severity of UA obstruction. Other commonly used predictive parameters for CPAP titration were also included in the study: anthropometric [BMI, neck circumference (NC)] and polysomnographic parameters (AHI, ODI). 3 groups of patients were identified: (1) 67/90 patients requiring intermediate CPAP values, (2) 13/90 patients requiring high CPAP values, and (3) 10/90 patients requiring low pressure values. BMI (p = 0.0013) was the only monitored parameter to show significant statistical value as a CPAP titration predictor. However, higher values of anthropometric parameters (NOHs ≥9, BMI >35, NC >45) showed a sensitivity of 69.2% as a single parameter and 76.9% as combined parameters, and specificity between 66.2 and 72.7% as a single parameter and 43.4% as combined parameters, unequivocally identifying patients requiring high therapeutic CPAP value. A lower cut-off of anthropometric parameters (NOHs ≤6, BMI ≤29, NC <42) showed sensitivity between 40 and 60% as a single parameter and of 90% as combined parameters, and specificity between 68.7 and 80.2% as a single parameter which increased to 93.7% as combined parameters, identifying patients requiring a low therapeutic CPAP value. The results show that anthropometric and polygraphic parameters have no significant independent predictive value for CPAP titration, with the exception of BMI. However, anthropometric parameters showed good levels of sensitivity and specificity in OSAHS patients requiring high or low levels of CPAP therapy.

Accuracy of positive airway pressure titration through telemonitoring of auto-adjusting positive airway pressure device connected to a pulse oximetry in patients with obstructive sleep apnea.

PURPOSE: In COVID-19 era, all forms of access of patients to the sleep units should be reduced as much as possible when implementing telemedicine. In the field of obstructive sleep apnea (OSA) therapy with positive airway pressure (PAP) devices, telemedicine includes the use of built-in software (BIS) and storage of PAPs and remote-controlled data (BISrc data) that are processed and transmitted daily to sleep units. We compared two methods of evaluating the final residual severity of OSA patients in home PAP titration: BISrc data versus nocturnal portable multichannel monitoring (PM) data in PAP (reference method) and to verify whether the efficacy PAP therapy guided by BISrc data was clinically adequate. METHODS: We conducted a real-life prospective study in newly diagnosed patients with OSA. Patients used an auto-adjusting positive airway pressure (AirSense 10 ResMed) with a pulse oximeter that allows daily transfer of BISrc data (apnea hypopnea index [AHI] and SaO2 ) and remote changes in ventilator setting. Once the PAP titration was completed, the pressure value or ranges were kept constant for 3 days and home PM was repeated. RESULTS: There were 41 patients with moderate to severe OSA who completed the study. When considering AHI only, the diagnostic accuracy of BISrc on the third day was equal to 97.5%; when considering AHI > 10/h, ODI > 10/h, and SaO2 < 90%, the diagnostic accuracy slightly decreased to 90.2%. CONCLUSION: In clinical practice, the two measurement methods are equivalent. The use of BISrc data for home titration would reduce the access to sleep units. We urge that widespread use of BISrc be promoted in the current practice of management of OSA.

Clinical implications of interstitial pneumonia with autoimmune features diagnostic criteria in idiopathic pulmonary fibrosis: A case control study.

Background: A subgroup of IPF patients can meet IPAF criteria (features suggesting an underlying autoimmune process without fulfilling established criteria for a CTD). This study was aimed to evaluate whether IPAF/IPF patients compared to IPF patients differ in clinical profile, prognosis and disease course. Methods: This is a retrospective, single center, case-control study. We evaluated 360 consecutive IPF patients (Forlì Hospital, between 1/1/2002 and 28/12/2016) and compared characteristics and outcome of IPAF/IPF to IPF. Results: Twenty-two (6%) patients met IPAF criteria. IPAF/IPF patients compared to IPF were more frequently females (N = 9/22, 40.9% vs. N = 68/338, 20.1%, p = 0.02), suffered more frequently from gastroesophageal reflux (54.5% vs. 28.4%, p = 0.01), and showed a higher prevalence of arthralgias (86.4% vs. 4.8%, p < 0.0001), myalgias (14.3% vs. 0.3%, p = 0.001) and fever (18.2% vs. 1.9%, p = 0.002). The serologic domain was detected in all cases (the most frequent were ANA in 17 and RF in nine cases) and morphologic domain (histology features) was positive in 6 out of 10 lung biopsies (lymphoid aggregates). Only patients with IPAF/IPF evolved to CTD at follow-up (10/22, 45.5%; six rheumatoid arthritis, one Sjögren's and three scleroderma). The presence of IPAF was a positive prognostic determinant (HR 0.22, 95% CI 0.08-0.61, p = 0.003), whereas the isolated presence of circulating autoantibody did not impact prognosis (HR 1.00, 95% CI 0.67-1.49, p = 0.99). Conclusion: The presence of IPAF criteria in IPF has a major clinical impact correlating with the risk of evolution to full blown-CTD during follow-up and identifying a subgroup of patients with a better prognosis.

Non-continuous positive airway pressure treatment options in obstructive sleep apnoea: A pathophysiological perspective.

The phenotyping of the pathophysiology of obstructive sleep apnoea (OSA) lies at the core of tailored treatments and it is one of the most debated topics in sleep medicine research. Recent sophisticated techniques have broadened the horizon for gaining insight into the variability of the endotypic traits in patients with OSA which account for the heterogeneity in the clinical presentation of the disease and consequently, in the outcome of treatment. However, the implementation of these concepts into clinical practice is still a major challenge for both researchers and clinicians in order to develop tailored therapies targeted to specific endotypic traits that contribute to OSA in each individual patient. This review summarizes available scientific evidence in order to point out the links between endotypic traits (pharyngeal airway collapsibility, upper airway neuromuscular compensation, loop gain and arousal threshold) and the most common non-continuous positive airway pressure (CPAP) treatment options for OSA (mandibular advancement device, upper airway surgery, medication therapy, positional therapy) and to clarify to what extent endotypic traits could help to better predict the success of these therapies. A narrative guide is provided; current design limitations and future avenues of research are discussed, with clinical and research perspectives.

Surgery vs ventilation in adult severe obstructive sleep apnea syndrome.

BACKGROUND AND PURPOSE: Management of severe obstructive sleep apnea-hypopnea syndrome (OSAHS) is challenging and needs multidisciplinary cooperation. Ventilation is considered the gold standard of treatment in severe OSAHS. The aim of the study was to compare the therapeutical efficacy of a type of surgery (maxillomandibular advancement [MMA]) vs a ventilatory treatment modality (autotitrating positive airway pressure [APAP]). MATERIALS AND METHODS: At the ENT Department of Forlì Hospital (University of Pavia), in strict cooperation with the Sleep Lab of the University of Bologna, a prospective randomized controlled trial was designed and performed. After fully informing them, 50 consecutive patients who have severe OSAHS were enrolled and randomized into a conservative (APAP) or surgical (MMA) section. Demographic, biometric, polysomnogram (PSG) and Epworth Sleepiness Scale profiles of the 2 groups were statistically not significantly different. RESULTS: One year after surgery or continuous APAP treatment, both groups showed a remarkable improvement of mean Apnea-Hypopnea Index (AHI) and Epworth Sleepiness Scale levels; the degree of improvement was not statistically different. CONCLUSIONS: Given the relatively small sample of subjects studied and the relatively brief follow-up, MMA proved to be a valuable alternative therapeutical tool in our adult and severe OSAHS patient group, with a success rate not inferior to APAP.

Upper airway collapsibility in patients with OSA treated with continuous positive airway pressure: a retrospective preliminary study.

STUDY OBJECTIVES: To investigate the prevalence of mildly collapsible upper airways (defined by therapeutic continuous positive airway pressure [CPAP] values ≤ 8 cm H2O) in moderate to severe obstructive sleep apnea patients treated with CPAP and to determine their clinical, functional, and nocturnal polysomnographic characteristics. METHODS: Eighty-seven patients with moderate to severe obstructive sleep apnea consecutively treated with CPAP were retrospectively investigated. Two nocturnal home sleep portable monitoring studies were performed at baseline and during treatment. Participants were categorized according to therapeutic CPAP values: ≤ 8 cm H2O (group 1), 8-12 cm H2O (group 2), ≥ 12 cm H2O (group 3). Anthropometric, awake respiratory function, symptoms, comorbidities, and nocturnal home sleep portable monitoring studies data were collected. RESULTS: Mild upper airway collapsibility (therapeutic CPAP values ≤ 8 cm H2O) was present in 25.3% of patients. They showed more favorable apnea-hypopnea index, oxygen desaturation index, mean nocturnal saturation, sleep time with oxygen saturation < 90%, desaturation nadir, and supine position. Oxygen desaturation index showed a weak association with anatomical collapsibility. Using the receiver operating characteristic curve, the area under the curve for the oxygen desaturation index vs CPAP pressure requirements ≤ 8 cm H2O was low and oxygen desaturation index ≤ 40.8/h showed a sensitivity of 63.3% and a specificity of 69.2% to detect patients with mild collapsibility. CONCLUSIONS: A quarter of moderate to severe patients under CPAP therapy had mild collapsibility and were likely to also be good candidates for alternative and better tolerated non-CPAP therapies. Baseline anthropometric, clinical, and respiratory function characteristics did not predict mild upper airway collapsibility determined by CPAP pressure requirements ≤ 8 cm H2O.