Gut-lung Microbiota Interactions in Chronic Obstructive Pulmonary Disease (COPD): Potential Mechanisms Driving Progression to COPD and Epidemiological Data.

This paper focuses on the gut-lung axis in the context of Inflammatory Bowel Disease (IBD) and Chronic Obstructive Pulmonary Disease (COPD), highlighting the key role played by microbial dysbiosis and the impact of environmental and genetic factors on the innate and acquired immune system and on chronic inflammation in the intestinal and pulmonary tracts. Recent evidence indicates that Antigen-Presenting Cells (APCs) perform regulatory activity influencing the composition of the microbiota. APCs (macrophages, dendritic cells, B cells) possess membrane receptors known as Pattern Recognition Receptors (PRRs), a category of toll-like receptors (TLRs). PRRs recognise distinct microbial structures and microbial metabolites called Signals, which modulate the saprophytic microbial equilibrium of the healthy microbiota by recognising molecular profiles associated with commensal microbes (Microbe-Associated Molecular Patterns, MAMPs). During dysbiosis, pathogenic bacteria can prompt an inflammatory response, producing PAMPs (Pathogen-Associated Molecular Patterns) thereby activating the proliferation of inflammatory response cells, both local and systemic. This series of regulatory and immune-response events is responsible (together with chronic infection, incorrect diet, obesity, etc.) for the systemic chronic inflammation (SCI) known as "low-grade inflammation" typical of COPD and IBD. This review looks at immunological research and explores the role of the microbiota, looking at two recent clinical studies, SPIROMICS and AERIS. There is a need for further clinical studies to characterize the pulmonary microbiota and to obtain new information about the pathogenesis of lung disease to improve our knowledge and treatment strategies and identify new therapeutic targets.

A New Berlin Questionnaire Simplified by Machine Learning Techniques in a Population of Italian Healthcare Workers to Highlight the Suspicion of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) syndrome is a condition characterized by the presence of repeated complete or partial collapse of the upper airways during sleep associated with episodes of intermittent hypoxia, leading to fragmentation of sleep, sympathetic nervous system activation, and oxidative stress. To date, one of the major aims of research is to find out a simplified non-invasive screening system for this still underdiagnosed disease. The Berlin questionnaire (BQ) is the most widely used questionnaire for OSA and is a beneficial screening tool devised to select subjects with a high likelihood of having OSA. We administered the original ten-question Berlin questionnaire, enriched with a set of questions purposely prepared by our team and completing the socio-demographic, clinical, and anamnestic picture, to a sample of Italian professional nurses in order to investigate the possible impact of OSA disease on healthcare systems. According to the Berlin questionnaire, respondents were categorized as high-risk and low-risk of having OSA. For both risk groups, baseline characteristics, work information, clinical factors, and symptoms were assessed. Anthropometric data, work information, health status, and symptoms were significantly different between OSA high-risk and low-risk groups. Through supervised feature selection and Machine Learning, we also reduced the original BQ to a very limited set of items which seem capable of reproducing the outcome of the full BQ: this reduced group of questions may be useful to determine the risk of sleep apnea in screening cases where questionnaire compilation time must be kept as short as possible.

Effects of inhaled corticosteroids (ICS) on lung microbiota and local immune response in long-term treatment of chronic obstructive pulmonary disease (COPD): utility of titration and therapeutic index.

Administration of inhaled corticosteroids (ICS) is one of the most controversial issues in the treatment of stable chronic obstructive pulmonary disease (COPD). Associations between these drugs and increased incidence of severe pneumonia and other respiratory infections have already been reported in literature, as well as effects on the immune system and on the lung microbiota. ICS vary in their pharmacodynamic and pharmacokinetic properties, despite being widely considered therapeutically similar. The use of ICS requires, therefore, a deep knowledge of their pharmacokinetics and pharmacodynamics to obtain the maximum benefit and the least side effects. Defining new phenotypes-endotypes of COPD may lead to novel pharmacological and therapeutic scenarios while define the correct indications for prescription of ICS. Titration is certainly an important means by which these objectives can be achieved.

COVID-19 IgG/IgM patterns, early IL-6 elevation and long-term radiological sequelae in 75 patients hospitalized due to interstitial pneumonia followed up from 3 to 12 months.

BACKGROUND: COVID-19 pandemic resulted in about 165 million infections and 3.4 million deaths all over the world across 15 months. The most severe clinical presentation of COVID-19 diseases is interstitial pneumonia. METHODS: In this paper we describe clinical outcomes based on radiological features as well as the pattern of haematochemical parameters and IgG/IgM antibodies in 75 patients hospitalized due to COVID-related interstitial pneumonia not requiring intensive care assistance. Each patient underwent routine laboratory tests, including inflammatory markers and coagulation profile at baseline. Computed Tomography (CT) was performed at baseline and after 3 months to assess the persistence of radiological sequelae. A Generalized Linear Model (GLM) was used to test for each patient the association between individual haematochemical parameters at the time of hospital admission and the subsequent radiological features after three months. The presence of IgG antibodies was quantitatively determined in 70 patients at the time of hospital admission and after 3 months. A subgroup of 49 and 21 patients underwent additional dosage of IgG after 6 and 12 months, respectively. IgM serological antibodies were available for 17 patients at baseline and 61 at T3, with additional follow-up for 51 and 20 subjects after 6 and 12 months, respectively. RESULTS: Only 28 out of 75 patients discharged from the hospital were totally healed after 3 months, while 47 patients (62.7%) still presented radiological sequelae. According to the GLM model, specific haematochemical baseline parameters-such as IL-6, GPT, platelets and eosinophil count-showed a statistically significant association with the presence of radiological sequelae at month 3 highlighting an OR = 0.5, thus meaning that subjects completely healed after 3 months presented half levels of IL-6 at baseline compared to patients with sequelae. In general, IgG serum levels were always higher than IgM at the time of hospitalization (75% at T0; n = 12 out of 16 patients with data available in both visits), after 3 months (72.1%; n = 44 out of 61 pts.), after 6 months (56.8%; 25 out of 44 pts.), and one year after hospitalization (60%; 12 out of 20 pts.). Overall, IgG and IgM serum levels presented a statistically significant decreasing trend from the baseline to month 3, 6 and 12. One patient presented an increase in IgM between baseline and month 3 but negative PCR test for SARS-COV2 on throat swab. CONCLUSIONS: As supported by our findings on 75 patients, COVID-related interstitial pneumonia triggers early IgG levels (higher than IgM) that gradually decrease over 12 months. Mid-term sequelae are still detectable at lung Computed Tomography after 3 months from the hospital admission. Occasionally, it is possible to observe increase of IgM levels in presence of low concentrations of IgG and negative PCR ELISA tests for SARS-COV2 RNA. Baseline levels of IL-6 could be proposed as predictor of radiological mid/long-term sequelae after COVID-related interstitial pneumonia.

Neuropsychological and socio-cognitive deficits in patients with obstructive sleep apnea.

Introduction: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive deficits. We investigated the cognitive and socio-cognitive profiles of patients with severe OSA, controlling for potentially relevant mediating variables (i.e. age, body-mass index, cognitive reserve and depression). Moreover, we studied the neuropsychological profile of a high-risk OSA phenotype characterized by severe OSA and severe nocturnal hypoxemia.Method: We assessed 29 previously untreated severe OSA patients with a mean age of 55.6 (± 9.9 years) and a mean apnea-hypopnea index (AHI) of 53.1 (± 17.4). A control group of 34 healthy participants was also enrolled. Participants completed an extensive neuropsychological battery that included social cognition, a relatively new investigation area among OSA patients.Data analysis: Data were analyzed with a Bayesian approach. Specifically, Bayesian ANCOVA was used to investigate whether the grouping variable could predict test performance. Age, body-mass index, cognitive reserve and state of depression were added as covariates to the null model to weight the effects of these potential confounding factors. Three groups were analyzed: healthy controls (H), OSA with severe apnea and severe nocturnal oxygen desaturation (D+), and OSA with severe apnea non-desaturators (D-). Performances on the various neuropsychological tests were treated as the dependent variables.Results: The results indicate that non-verbal reasoning, the theory of mind skills, and mental shifting ability were impaired in OSA patients. Patients with severe nocturnal hypoxemia underperformed compared to patients with the same severity of apnea but non-desaturators. Additionally, we observed a trend toward a worse performance among OSA desaturator patients in the following abilities: constructional ability, short term verbal memory, phonological fluency, and the ability to inhibit automatic and dominant responses.Conclusion: The data suggest a key role of hypoxemia in affecting cognitive functioning in OSA patients. Executive functions and the concomitant involvement of social cognition are particularly affected.

Association Between Severity of COVID-19 Respiratory Disease and Risk of Obstructive Sleep Apnea.

OBJECTIVES: The purpose of this observational retrospective study was to evaluate, in patients with a severe acute respiratory syndrome coronavirus 2 infection, the association between the severity of coronavirus disease 2019 (COVID-19) respiratory illness and the risk of infected patients to develop obstructive sleep apnea (OSA). METHODS: Ninety-six patients with confirmed COVID-19 infection were enrolled in the study. The STOP-BANG questionnaire to investigate the risk of the OSA syndrome was filled in by the patients at admission. The enrolled patients were divided into 2 groups according to the respiratory disease: group 1 (72 patients), hospitalized patients undergoing conventional oxygen therapy; group 2 (24 patients), patients requiring enhanced respiratory support. STOP-BANG results of these 2 groups were compared to observe whether patients with high OSA risk more frequently presented a severe form of COVID-19. RESULTS: 41.6% of the patients in group 2 had a STOP-BANG score between 5 and 8 (high risk of having apnea); in contrast, 20.8% of the patients in group 1 had a STOP-BANG score between 5 and 8, with a statistically significant difference between the 2 groups (P = .05). A complementary trend was observed regarding the proportion of patients in the range 0 to 2, which classifies patients at a low risk of OSA (48.6% vs 20.8% for groups 1 and 2, P = .01). CONCLUSIONS: According to our data, the chances of having a severe case of COVID-19 should be considered in patients at high risk of OSA. CURRENT KNOWLEDGE/STUDY RATIONALE: Emerging research suggests that OSA could represent a potentially important risk factor for the severe forms of COVID-19. The purpose of this observational retrospective study was to evaluate the potential association between OSA and the severity of COVID-19 disease. STUDY IMPACT: According to our data, the likelihood of contracting a severe form of COVID-19 disease should be considered in patients at high risk of OSA.

Targeting the gut-lung microbiota axis by means of a high-fibre diet and probiotics may have anti-inflammatory effects in COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 is a 2019 novel coronavirus, which only in the European area has led to more than 300,000 cases with at least 21,000 deaths. This manuscript aims to speculate that the manipulation of the microbial patterns through the use of probiotics and dietary fibers consumption may contribute to reduce inflammation and strengthen the immune system response in COVID-19 infection. The reviews of this paper are available via the supplemental material section.

The Neuropsychological Profile of Attention Deficits of Patients with Obstructive Sleep Apnea: An Update on the Daytime Attentional Impairment.

INTRODUCTION: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive disturbances. One of the neuropsychological processes most investigated in OSA patients is attention, but the results have been controversial. Here, we update the attention profile of OSA patients with the final aim to improve attention assessment, with a possible impact on clinical and medical-legal practices, in terms of which attention subdomains and parameters need consideration and which one is a high-risk OSA phenotype for attention dysfunctions. METHOD: For this purpose, we assessed 32 previously untreated OSA patients (26 men and 6 women) under 65 years of age (mean age 53.2 ± 7.3; mean education level 10.4 ± 3.4 years) suffering from moderate to severe sleep apnea and hypopnea (mean apnea-hypopnea index (AHI) 45.3 ± 22.9, range 16.1-69.6). A control group of 34 healthy participants matched with OSA patients for age, education level, and general cognitive functioning were also enrolled. The OSA patients and healthy participants were tested through an extensive computerized battery (Test of Attentional Performance, TAP) that evaluated intensive (i.e., alertness and vigilance) and selective (i.e., divided and selective) dimensions of attention and returned different outcome parameters (i.e., reaction time, stability of performance, and various types of errors). Data analysis: The data were analyzed by ANCOVA which compared the speed and accuracy performance of the OSA and control participants (cognitive reserve was treated as a covariate). The possible mechanisms underlying attention deficits in OSA patients were examined through correlation analysis among AHI, oxygenation parameters, sleepiness scores, and TAP outcomes and by comparing the following three phenotypes of patients: severe OSA and severe nocturnal desaturators (AHI++D+), severe OSA nondesaturators (AHI++D-), and moderate OSA nondesaturators (AHI+D-). RESULTS: The results suggest that the OSA patients manifest deficits in both intensive and selective attention processes and that reaction time (RT) alone is ineffective for detecting and characterizing their problems, for which error analysis and stability of performance also have to be considered. Patients with severe OSA and severe hypoxemia underperformed on alertness and vigilance attention subtests. CONCLUSIONS: The data suggest the importance of evaluating attention deficits among OSA patients through several parameters (including performance instability). Moreover, the data suggest a multifaceted mechanism underlying attention dysfunction in OSA patients.

Influence of the Lung Microbiota Dysbiosis in Chronic Obstructive Pulmonary Disease Exacerbations: The Controversial Use of Corticosteroid and Antibiotic Treatments and the Role of Eosinophils as a Disease Marker.

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease associated with loss of lung function, poorer quality of life, co-morbidities, significant mortality, and higher health care costs. Frequent acute exacerbations of COPD are sudden worsening of symptoms, the nature of which is associated with bacterial or viral infections. However, one-third of exacerbations remain of undetermined origin. Although it is largely discussed and controversial, current guidelines recommend treatment of exacerbations with bronchodilators, antibiotics, and systemic corticosteroids; this is despite being associated with limited benefits in term of reducing mortality, side effects and without paying attention to the heterogeneity of these exacerbations. Increasing evidence suggests that the lung microbiota plays an important role in COPD and numerous studies have reported differences in the microbiota between healthy and disease states, as well as between exacerbations and stable COPD, leading to the hypothesis that frequent acute exacerbation is more likely to experience significant changes in lung microbiota composition. These findings will need further examination to explain the causes of lung dysbiosis, namely microbial composition, the host response, including the recruitment of eosinophils, lifestyle, diet, cigarette smoking and the use of antibiotics and corticosteroids. It is now important to assess: 1) Whether alterations in the lung microbiota contribute to disease pathogenesis, especially in exacerbations of unknown origin; 2) The role of eosinophils; and 3) Whether the microbiota of the lung can be manipulated therapeutically to improve COPD exacerbation event and disease progression. In summary, we hypothesize that the alterations of the lung microbiota may explain the undetermined origins of exacerbations and that there is an urgent need to facilitate the design of intervention studies that aim at conserving the lung microbial flora.

Role of Diet in Chronic Obstructive Pulmonary Disease Prevention and Treatment.

Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem. Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment. This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action. Several dietary options can be considered in terms of COPD prevention and/or progression. Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD. Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health.

Obstructive sleep apnea syndrome and olfactory perception: An OERP study.

Obstructive Sleep Apnea Syndrome (OSA) is characterized by snoring associated with repeated apnea and/or obstructive hypopnea. The nasal airways of OSA patients, measured via acoustic rhinometry, could be significantly narrower than healthy subjects and this reduced nasal structure can impair olfactory function. The relationship between nasal structure and olfactory function, assessed via behavioral test results, indicates that there is a high prevalence of nasal airflow problems. Based on these assumptions, the purpose of this study was to carry out an assessment of olfactory perception in OSA patients through the Chemosensory Event-Related Potentials (CSERP), investigating the N1 component and the Late Positive Component (LPC). Twelve OSA patients, non-smokers, were recruited in the Pulmonary Rehabilitation Unit, scored with the Epworth Sleepiness Scales, after Polygraphic Recording, Apnea Hypopnea Index and Body Mass Index evaluation. The control group consisted of twelve healthy controls, non-smokers, recruited as volunteers. Subjects, during an EEG recording, performed an oddball olfactory recognition task based on two scents: rose and eucalyptus. Main results highlighted differences in N1 and LPC between OSA and controls. OSA patients presented faster N1 latencies and greater amplitude. The same trend was found in LPC, where OSA showed decreased latency and increased amplitude during rose stimulation, in the right inferior frontal cortex. and faster latencies in left centroparietal cortex OERP results can suggest an impairment in endogenous components. This result could be the consequence of the exogenous perceptual difficulty highlighted in N1 component. The increased arousal could also be related to the respiratory activity involved during the olfactory task.

The Clinical Use of Stem Cell Research in Chronic Obstructive Pulmonary Disease: A Critical Analysis of Current Policies.

Chronic obstructive pulmonary disease (COPD) is a disorder affecting more than 200 million people around the world, resulting in three million deaths per year. COPD is characterized by the loss of lung tissue and airway remodelling, with chronic inflammation of the airways and progressive destruction of lung parenchyma. The use of stem cells may lead to regenerative processes that address biological damage. However, this approach raises ethical issues that need to be considered in clinical trials using stem cell therapy, such as informed consent, patient recruitment and harm minimization, as well as the inherent uncertainty of these medical procedures on human beings. Indeed, up to now, these experiments have been performed in preclinical studies using animal models, with few studies involving humans. Additional efforts should be made to assess this promising procedure.

Statins May Prevent Atherosclerotic Disease in OSA Patients without Co-Morbidities?

Obstructive sleep apnoea (OSA) is characterized by repetitive interruptions of breathing, causing Chronic Intermittent Hypoxia (CIH) that can be involved in the development and progression of cardiovascular diseases. There is evidence showing a close relationship between OSA and atherosclerosis, even in patients who do not show co-morbidities such as hypertension, diabetes, high levels of lowdensity lipoprotein cholesterol (LDL-C), cigarette smoking and obesity, which can activate the endothelium. This endothelium activation due to CIH and specific to OSA seems to be dependent on a different pathway. The current first line therapy for OSA is the application of the continuous positive airway pressure (CPAP), but it alone is not enough to reduce cardiometabolic risk in patients with OSA. In contrast, statins, via their pleiotropic property, might be able to change inflammation and early atherosclerosis, lipid profile and cardiovascular outcomes in OSA. The role of statins in OSA patients with or without any co-morbidities could potentially prevent coronary vascular risk and stroke and in the future, represent an additional treatment option along with CPAP therapy. Strengthening the prevention strategies against atherosclerosis in OSA should be one of the focal aims for healthcare programs of the future.

Obstructive sleep apnea syndrome: coagulation anomalies and treatment with continuous positive airway pressure.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder associated with severe cardiovascular events, morbidity and mortality. Recent evidence has highlighted OSAS as an independent risk factor for an excessive platelet activation and arterial thrombosis, but the underlying mechanisms have not yet been determined. Studies in cell culture and animal models have significantly increased our understanding of the mechanisms of inflammation in OSAS. Hypoxia is a critical pathophysiological element that leads to an intense sympathetic activity, in association with systemic inflammation, oxidative stress and procoagulant activity. While platelet dysfunction and/or hypercoagulability play an important role in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS. CONCLUSION: Further studies are required to determine the precise role of hypercoagulability in the cardiovascular pathogenesis of OSAS, particularly its interaction with oxidative stress, thrombotic tendency and endothelial dysfunction. Nasal continuous positive airway pressure (nCPAP), the gold standard treatment for OSAS, not only significantly reduced apnea-hypopnoea indices but also markers of hypercoagulability, thus representing a potential mechanisms by which CPAP reduces the rate of cardiovascular morbidity and mortality in OSAS patients.

Diagnostic Accuracy of Obstructive Airway Adult Test for Diagnosis of Obstructive Sleep Apnea.

RATIONALE: The gold standard for the diagnosis of Obstructive Sleep Apnea (OSA) is polysomnography, whose access is however reduced by costs and limited availability, so that additional diagnostic tests are needed. OBJECTIVES: To analyze the diagnostic accuracy of the Obstructive Airway Adult Test (OAAT) compared to polysomnography for the diagnosis of OSA in adult patients. METHODS: Ninety patients affected by OSA verified with polysomnography (AHI ≥ 5) and ten healthy patients, randomly selected, were included and all were interviewed by one blind examiner with OAAT questions. MEASUREMENTS AND MAIN RESULTS: The Spearman rho, evaluated to measure the correlation between OAAT and polysomnography, was 0.72 (p < 0.01). The area under the ROC curve (95% CI) was the parameter to evaluate the accuracy of the OAAT: it was 0.91 (0.81-1.00) for the diagnosis of OSA (AHI ≥ 5), 0.90 (0.82-0.98) for moderate OSA (AHI ≥ 15), and 0.84 (0.76-0.92) for severe OSA (AHI ≥ 30). CONCLUSIONS: The OAAT has shown a high correlation with polysomnography and also a high diagnostic accuracy for the diagnosis of OSA. It has also been shown to be able to discriminate among the different degrees of severity of OSA. Additional large studies aiming to validate this questionnaire as a screening or diagnostic test are needed.

Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis.

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis and arterial thrombosis, which are associated with high cardiovascular (CV) morbidity and mortality. In studies performed in clinical populations with elevated CV event risk profiles, the occurrence of moderate to severe OSAS was very often accompanied by a worsened vascular function and increased prevalence of structural abnormalities. Recent investigations of atherosclerosis in OSAS have focused on thrombotic tendency and blood viscosity, providing new insight into mechanisms of the disease. Despite that knowledge about the mechanisms of development of CV disease in patients with OSAS is still incomplete, observations confirm a relationship between sleep-disordered breathing and the rheological properties (flow properties) of blood. While platelet dysfunction and hypercoagulability (PDMPs, PaI-1, and SF) play important roles in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS.

Chronic obstructive pulmonary disease phenotype desaturator with hypoxic vascular remodelling and pulmonary hypertension obtained by cluster analysis.

Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). This article discusses and refines the concept of desaturator phenotypes in COPD with pulmonary hypertension (PH) obtained by cluster analysis and presents a pattern of phenotypic markers that could be used as a framework for future diagnosis and research. Nocturnal oxygen desaturation results in sleep disturbances which predispose to nocturnal cardiac dysrhythmias, PH and possibly nocturnal death, particularly during acute exacerbations. We assume that in patients with COPD at least two factors play a role in PH: the severity of pulmonary impairment, and the severity of systemic nocturnal hypoxaemia due to reduced pulmonary functions. Establishing a common language for future research will facilitate our understanding and management of such a disease. This knowledge could lead to different pharmacological treatments and other interventions directed at specific phenotypic groups.

Use of cluster analysis to describe desaturator phenotypes in COPD: correlations between pulmonary function tests and nocturnal oxygen desaturation.

BACKGROUND: Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although forced expiratory volume in 1 second (FEV(1)) inadequately describes this heterogeneity, a clear alternative has not emerged. This article discusses and refines the concept of phenotyping desaturators in COPD and shows a possible pattern which could be used as a framework for future research. RECENT FINDINGS: COPD is a complex condition with pulmonary and extrapulmonary manifestations. We suggest that COPD phenotypes should be associated with clinically meaningful outcomes. The innovation of COPD phenotyping is defined as COPD desaturators. Sleep-related hypoxemia and hypercapnia are well recognized in COPD and the development of systemic inflammation during sleep. These sleep-related changes predispose to nocturnal cardiac arrhythmias, pulmonary hypertension, and possibly death, particularly during acute exacerbations. CONCLUSION: A more focused definition makes possible a classification of patients into two distinct subgroups for both clinical and research purposes. Establishing a common language for future research will facilitate our understanding and management of such diseases. Even if different treatment strategies have different outcomes for these groups, we will have confirmation, or otherwise, of the clinical value of cluster analysis. This knowledge could lead to pharmacological treatment and other interventions directed to specific phenotypic groups.