Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial.

Rationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate. Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax. Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18-50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan. Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026-0.200). The aspiration group experienced less pain overall (mean difference, -1.4; 95% CI, -1.89, -0.91), less pain limiting breathing (frequency difference, -0.18; 95% CI, -0.27, -0.09), and less kinking of the device (frequency difference, -0.05; 95% CI, -0.09, -0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, -0.07; 95% CI, -0.16, +0.02). Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT01008228).

Efficacy of plasma exchange in patients with anti-MDA5 rapidly progressive interstitial lung disease.

BACKGROUND: Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and severe manifestation of anti-MDA5 dermatomyositis (MDA5-DM) associated with poor outcome. The optimal treatment regimen for MDA5-DM RP-ILD is yet to be determined. Specifically, the value of adding plasma exchange (PLEX) to corticosteroids and immunosuppressants remains unclear. We aimed to evaluate the effect of PLEX on the outcome of patients with MDA5-DM RP-ILD. METHODS: This French nationwide multicentre retrospective study included all MDA5-DM RP-ILD patients from 2012 to 2021 admitted to 18 centres. The primary endpoint was one-year transplant-free survival. RESULTS: 51 patients with MDA5-DM RP-ILD (female 67%; mean age at disease onset: 51 ± 11.6 years) were included. Thirty-two (63%) patients required mechanical ventilation and twenty-five (49%) received PLEX. One-year mortality or lung transplant occurred in 63% cases after a median follow-up of 77 [38-264] days. The Cox proportional hazards multivariable model only retained mechanical ventilation but not PLEX (p = 0.7) as independent predictor of the primary endpoint. One-year transplant-free survival rates in PLEX + vs. PLEX-were 20% vs. 54% (p = 0.01), respectively. The Kaplan-Meier estimated probabilities of one-year transplant-free survival was statistically higher in PLEX-compared to PLEX + patients (p = 0.05). PLEX + compared to PLEX-patients more frequently received mechanical ventilation and immunosuppressants suggesting PLEX + patients had a more severe disease. CONCLUSION: MDA5-DM RP-ILD is associated with poor rate of one-year transplant-free survival. The use of PLEX was not associated with a better outcome albeit they were mainly given to more severe patients. While our study reports the largest series of MDA5-DM RP-ILD given PLEX, these results needs to be interpreted with caution owing the numerous selection, indication and interpretation bias. Further studies are needed to evaluate their efficacy in this setting.

Does branched-chain amino acid supplementation improve pulmonary rehabilitation effect in COPD?

BACKGROUND: Muscle wasting is frequent in chronic obstructive lung disease (COPD) and associated with low branched-chain amino acids (BCAA). We hypothesized that BCAA supplementation could potentiate the effect of a pulmonary rehabilitation program (PRP) by inducing muscular change. MATERIALS AND METHODS: Sixty COPD patients (GOLD 2-3) were involved in an ambulatory 4-week PRP either with BCAA oral daily supplementation or placebo daily supplementation in a randomized double-blind design. Maximal exercise test including quadriceps oxygenation measurements, functional exercise test, muscle strength, lung function tests, body composition, dyspnea and quality of life were assessed before and after PRP. RESULTS: Fifty-four patients (64.9 ± 8.3 years) completed the protocol. In both groups, maximal exercise capacity, functional and muscle performances, quality of life and dyspnea were improved after 4-week PRP (p ≤ 0.01). Changes in muscle oxygenation during the maximal exercise and recovery period were not modified after 4-week PRP in BCAA group. Contrarily, in the placebo group the muscle oxygenation kinetic of recovery was slowed down after PRP. CONCLUSION: This study demonstrated that a 4-week PRP with BCAA supplementation is not more beneficial than PRP alone for patients. A longer duration of supplementation or a more precise targeting of patients would need to be investigated to validate an effect on muscle recovery and to demonstrate other beneficial effects.

Mandibular advancement device use in obstructive sleep apnea: ORCADES study 5-year follow-up data.

STUDY OBJECTIVES: Mandibular advancement devices (MADs) are an alternative to continuous positive airway pressure for the management of obstructive sleep apnea (OSA). The ORthèse d'avanCée mAndibulaire dans le traitement en DEuxième intention du SAHOS sévère (ORCADES) study is investigating the long-term effectiveness of MAD therapy in patients with OSA who refused or were intolerant of continuous positive airway pressure. Five-year follow-up data are presented. METHODS: Data were available in 172 of 331 patients treated with a custom-made computer-aided design/computer-aided manufacturing biblock MAD (Narval CC; ResMed, Saint-Priest, France). The primary end point was treatment success (≥50% decrease in apnea-hypopnea index from baseline). RESULTS: Five-year treatment success rates were 52% overall and 25%, 52%, and 63%, respectively, in patients with mild, moderate, or severe OSA. This reflects a decline over time vs 3-6 months (79% overall) and 2 years (68%). Rates declined in all patient subgroups but to the greatest extent in patients with mild OSA. The slight worsening of respiratory parameters over time was not associated with any relevant changes in sleepiness and symptoms. Moderate or severe OSA at baseline, treatment success at 3-6 months, and no previous continuous positive airway pressure use were significant independent predictors of 5-year treatment success on multivariate analysis. No new safety signals emerged during long-term follow-up. The proportion of patients using their MAD for ≥4 h/night on ≥4 days/wk was 93.3%; 91.3% of patients reported device use of ≥6 h/night at 5 years. At 5-year follow-up, 96.5% of patients reported that they wanted to continue MAD therapy. CONCLUSIONS: Long-term MAD therapy remained effective after 5 years in >50% of patients, with good levels of patient satisfaction and adherence. CITATION: Vecchierini MF, Attali V, Collet JM, et al. Mandibular advancement device use in obstructive sleep apnea: ORCADES study 5-year follow-up data. J Clin Sleep Med. 2021;17(8):1695-1705.

Role of sleep on respiratory failure after extubation in the ICU.

BACKGROUND: Sleep had never been assessed immediately after extubation in patients still in the ICU. However, sleep deprivation may alter respiratory function and may promote respiratory failure. We hypothesized that sleep alterations after extubation could be associated with an increased risk of post-extubation respiratory failure and reintubation. We conducted a prospective observational cohort study performed at the medical ICU of the university hospital of Poitiers in France. Patients at high-risk of extubation failure (> 65 years, with any underlying cardiac or lung disease, or intubated > 7 days) were included. Patients intubated less than 24 h, with central nervous or psychiatric disorders, continuous sedation, neuroleptic medication, or uncooperative were excluded. Sleep was assessed by complete polysomnography just following extubation including the night. The main objective was to compare sleep between patients who developed post-extubation respiratory failure or required reintubation and the others. RESULTS: Over a 3-year period, 52 patients had complete polysomnography among whom 12 (23%) developed post-extubation respiratory failure and 8 (15%) required reintubation. Among them, 10 (19%) had atypical sleep, 15 (29%) had no deep sleep, and 33 (63%) had no rapid eye movement (REM) sleep. Total sleep time was 3.2 h in median [interquartile range, 2.0-4.4] in patients who developed post-extubation respiratory failure vs. 2.0 [1.1-3.8] in those who were successfully extubated (p = 0.34). Total sleep time, and durations of deep and REM sleep stages did not differ between patients who required reintubation and the others. Reintubation rates were 21% (7/33) in patients with no REM sleep and 5% (1/19) in patients with REM sleep (difference, - 16% [95% CI - 33% to 6%]; p = 0.23). CONCLUSIONS: Sleep assessment by polysomnography after extubation showed a dramatically low total, deep and REM sleep time. Sleep did not differ between patients who were successfully extubated and those who developed post-extubation respiratory failure or required reintubation.

Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases.

OBJECTIVES: The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. METHODS: To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5-; n = 190/201) based on selected variables, collected retrospectively, without any missing data. RESULTS: Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis. CONCLUSION: Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.

Efficacy and tolerability of a custom-made Narval mandibular repositioning device for the treatment of obstructive sleep apnea: ORCADES study 2-year follow-up data.

OBJECTIVE/BACKGROUND: Mandibular repositioning device (MRD) therapy is an alternative to continuous positive airway pressure (CPAP). The Orkney Complex Disease Study-ORCADES study is assessing the long-term efficacy and tolerability of MRD therapy in obstructive sleep apnoea syndrome (OSAS); two-year follow-up data are presented. PATIENTS/METHODS: OSAS patients who refused or were noncompliant with CPAP were fitted with a custom-made computer-aided design/computer-aided manufacturing (CAD/CAM) bi-block MRD (ResMed, Narval CC™); mandibular advancement was individually titrated. Sleep and respiratory parameters were determined at baseline, 3-6 months, and two years. The primary endpoint was treatment success (percentage of patients achieving a ≥50% reduction in the apnoea-hypopnoea index [AHI]). RESULTS: Of 315 enrolled patients, 237 remained on MRD treatment at two years, and 197 had follow-up data. The treatment success rate at two years was 67%; AHI <5/h, <10/h and <15/h was achieved in 30%, 56% and 72% of patients, respectively. On multivariate analysis, ≥50% decrease in AHI at 3-6 months and absence of nocturia at 3-6 months were significant predictors of MRD treatment continuation. Adverse events were generally mild, and the majority occurred in the first year of treatment. CONCLUSIONS: Two years' treatment with an MRD was effective and well tolerated in patients with mild to severe OSAS who refused or were intolerant of CPAP.

Women and COPD: do we need more evidence?

The increasingly female face of chronic obstructive pulmonary disease (COPD) prevalence among women has equalled that of men since 2008, due in part to increased tobacco use among women worldwide and exposure to biomass fuels. This finding is supported by a number of characteristics. There is evidence of susceptibility to smoking and other airborne contaminants, along with epidemiological and phenotypic manifestations. COPD has thus become the leading cause of death in women in the USA. The clinical presentation is characterised by increasingly pronounced dyspnoea with a marked tendency towards anxiety and depression, undernutrition, nonsmall cell lung cancer (especially adenocarcinoma) and osteoporosis. Quality of life is also more significantly impacted. The theories advanced to explain these differences involve the role played by oestrogens, impaired gas exchange in the lungs and smoking habits. While these differences require appropriate therapeutic responses (smoking cessation, pulmonary rehabilitation, long-term oxygen therapy), barriers to the treatment of women with COPD include greater under-diagnosis than in men, fewer spirometry tests and medical consultations. Faced with this serious public health problem, we need to update and adapt our knowledge to the epidemiological changes.

Sex differences in mandibular repositioning device therapy effectiveness in patients with obstructive sleep apnea syndrome.

PURPOSE: Mandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS. METHODS: The ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3-6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h). RESULTS: Overall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy. CONCLUSIONS: MRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01326143).

Impact of sleep alterations on weaning duration in mechanically ventilated patients: a prospective study.

Sleep is markedly altered in intensive care unit (ICU) patients and may alter respiratory performance. Our objective was to assess the impact of sleep alterations on weaning duration.We conducted a prospective physiological study at a French teaching hospital. ICU patients intubated for at least 24 h and difficult to wean were included. Complete polysomnography (PSG) was performed after the first spontaneous breathing trial failure. Presence of atypical sleep, duration of sleep stages, particularly rapid eye movement (REM) sleep, and electroencephalogram (EEG) reactivity at eyes opening were assessed by a neurologist.20 out of 45 patients studied (44%) had atypical sleep that could not be classified according to the standard criteria. Duration of weaning between PSG and extubation was significantly longer in patients with atypical sleep (median (interquartile range) 5 (2-8) versus 2 (1-2) days; p=0.001) and in those with no REM sleep compared with the others. Using multivariate logistic regression analysis, atypical sleep remained independently associated with prolonged weaning (>48 h after PSG). Altered EEG reactivity at eyes opening was a good predictor of atypical sleep.Our results suggest for the first time that brain dysfunction may have an influence on the ability to breathe spontaneously.

[Continuous positive airway pressure in obstructive sleep apnea]. / Syndrome d'apnées obstructives du sommeil : le traitement par pression positive continue.

Continuous positive airway pressure (CPAP) is currently the most used and efficient therapy in OSAS. Efficiency of CPAP on sleep respiratory disorders is the same whether in fixed or automatic mode. Larger studies are required to evaluate their respective beneficial impact on cardiovascular or metabolic complications of OSAS. Close medical monitoring is necessary during the first weeks of CPAP therapy. Compliance to CPAP therapy is crucial for efficacy in preventing cardiovascular or metabolic complications of OSAS. As beneficial effects of CPAP in obese patients are modest, on blood pressure levels and metabolic disorders, its use has to be part of a comprehensive care of OSAS and related comorbidities.

Impact of Mandibular Advancement Therapy on Endothelial Function in Severe Obstructive Sleep Apnea.

RATIONALE: Endothelial dysfunction, a major predictor of late cardiovascular events, is linked to the severity of obstructive sleep apnea (OSA). OBJECTIVES: To determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. METHODS: In this trial, we randomized patients with severe OSA and no overt cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on an intention-to-treat basis. An embedded microsensor objectively measured treatment compliance. MEASUREMENTS AND MAIN RESULTS: A total of 150 patients (86% males; mean [SD] age, 54 [10] yr; median [interquartile range] apnea-hypopnea index, 41 [35-53]; mean [SD] Epworth sleepiness scale, 9.3 [4.2]) were randomized to effective mandibular advancement device (n = 75) or sham device (n = 75). On intention-to-treat analysis, effective mandibular advancement device therapy was not associated with improvement of endothelial function compared with the sham device. Office and ambulatory blood pressure outcomes did not differ between the two groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea-hypopnea index (P < 0.001); microarousal index (P = 0.008); and symptoms of snoring, fatigue, and sleepiness (P < 0.001). Mean (SD) objective compliance was 6.6 (1.4) h/night with the effective mandibular advancement device versus 5.6 (2.3) h/night with the sham device (P = 0.006). CONCLUSIONS: In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms but had no effect on endothelial function and blood pressure despite high treatment compliance. Clinical trial registered with www.clinicaltrials.gov (NCT 01426607).

[Smoking, smoking cessation and Crohn's disease]. / Tabagisme, sevrage tabagique et maladie de Crohn.

CONTEXT: Smoking whose prevalence is higher in patients with Crohn's disease (CD) worsens its evolution. Ulcerative colitis mostly affect non- or ex-smokers; smoking may improve the course of the disease. OBJECTIVES: Systematic literature review of data on the relationship between smoking, smoking cessation and Crohn'disease. DOCUMENTARY SOURCES: Medline, on the period 1980-2015 with the keywords "Crohn's disease" or "inflammatory bowel disease" and "smoking" or "smoking cessation"; limits "Title/Abstract"; the selected languages were English or French. STUDY SELECTION: Among 1315 articles, 168 abstracts have given rise to a dual reading to select 69 studies (case-control, retrospective, reviews or meta-analysis). Data were extracted using a reading gate. RESULTS: Smoking increases the risk of complications, recurrences and resort of surgery, corticosteroids or immunosuppressants. These deleterious effects are more common in women. Stopping smoking improves the course of the disease and represents an essential component of its management. LIMITS: Heterogeneity of the studies collected according to the type, population characteristics, definition of smoking status and the validation of smoking cessation. CONCLUSION: Smokers suffering from CD must routinely be made aware of the disadvantages of smoking, benefits of abstinence and helped to quit smoking.

A custom-made mandibular repositioning device for obstructive sleep apnoea-hypopnoea syndrome: the ORCADES study.

BACKGROUND: Mandibular repositioning devices (MRDs) are usually recommended as the first therapy option in patients with mild-to-moderate obstructive sleep apnoea (OSA). However, data on the long-term efficacy of MRDs are limited, not only in OSA patients who are noncompliant with continuous positive airway pressure (CPAP) but also in those with more severe OSA. The ORCADES study aimed to prospectively determine the long-term efficacy and tolerability of two custom-made Narval(™) MRDs for obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients. The interim 3- to 6-month data are reported. METHODS: Eligible patients had OSAHS and had refused or were noncompliant with prescribed CPAP. Outcome measurements after gradual mandibular advancement titration included: apnoea-hypopnoea index (AHI), oxygen saturation, sleepiness, symptoms, quality of life, side effects and compliance. RESULTS: A total of 369 patients were included. Overall, MRD treatment was successful (≥50% decrease in AHI) in 76.2% of the participants; complete response (AHI <10/h) was achieved in 63.5%. Severe OSAHS was effectively treated (AHI <15/h) in about 60% of the participants; 38% had complete symptom resolution. Mandibular repositioning devices significantly decreased subjective sleepiness, eliminated symptoms and improved quality of life. They were well tolerated and compliance was excellent. Only 8% of the participants stopped MRD treatment due to side effects. CONCLUSION: Custom-made Narval(™) MRDs are effective for mild to severe OSA in patients who refuse or are noncompliant with CPAP. They are well tolerated and have excellent compliance.

Cardiovascular comorbidities in obstructive sleep apnoea according to age: a sleep clinic population study.

PURPOSE: To describe the features of obstructive sleep apnoea (OSA) and its association with arterial hypertension (HT), coronary artery disease (CAD), and arrhythmias in elderly (≥65 years) versus younger patients. METHODS: All adult patients referred to our Sleep Research Unit for suspected OSA were included and underwent a thorough medical examination and an in-laboratory polysomnography. The severity of OSA was defined by the apnoea-hypopnoea index (AHI) as mild [5-15/h), moderate [15-30/h), and severe (≥30/h). RESULTS: Elderly patients (n = 136) and really old patients (>75 years) had higher prevalence of OSA (89 %) and severe OSA (36.8 %) as compared to younger patients (n = 439; 79.5 and 27.6 %, respectively, p < 0.05). In patients with OSA, the elderly group had a poorer sleep quality and more severe nocturnal oxygen desaturation than the younger group. Elderly patients presented higher percentages of HT (47.8 %), CAD (19.8 %), and arrhythmias (16.2 %) as compared to younger patients (p < 0.01). The odds ratio (OR) for HT increased with OSA severity from 1.0 to 1.65 (95 % confidence interval 0.83-3.27), 1.0 to 2.5 (95 % CI 1.25-5.00), and 1.0 to 3.77 (1.95-7.29) in younger patients, but not in elderly ones where the OR increased from 1.0 to 0.6 (0.17-2.04), 1.0 to 1.14 (0.34-3.82), and 1.0 to 1.46 (0.46-4.63), respectively. CONCLUSION: Stronger relation of HT and OSA severity in younger patients should encourage us to screen OSA in these patients at very young age. Increased OSA severity without obesity in very old patients needs to be confirmed and further studied.

Comorbidities of COPD.

By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately.