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Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

Background: Safety and efficacy of benralizumab (BEN) for severe eosinophilic asthma (SEA) have been demonstrated in Phase III clinical trials. Obesity is a risk factor for SEA and might affect the beneficial effect of asthma medication. ANANKE is part of AstraZeneca’s global XALOC real-world evidence program for benralizumab. Aims: To explore whether benralizumab efficacy is affected by body mass index (BMI) in SEA patients. Methods: Post-hoc analysis of an observational, multicenter, retrospective Italian study of SEA patients with at least 12 weeks of BEN treatment. Patients were stratified according to BMI: normal/underweight (Nr) (BMI Results: 182 patients were included, Nr=70 (68.6% female, mean age 55±12.8, median BEN duration 9.2 months), OW=79 (48.1% female, mean age 56.6±12.9, median BEN duration 9.4 months), Ob=33 (75.8% female, mean age 56.5±14.7, median BEN duration 10.2 months). Any AER passed from 4.49 to 0.18 (-96%) in Nr (N=66), from 3.99 to 0.32 (-92%) in OW (N=76) and from 3.72 to 0.34 (-90.9%) in Ob (N=30). Severe AER changed from 1.32 to 0.04 (-97%) in Nr, from 1.12 to 0.10 (-91.1%) in OW and from 1.13 to 0.08 (-92.9%) in Ob. ACT increased from a median of 15 in Nr (N=57), 14 in OW (N=61) and 13 in Ob (N=25) to 22 in Nr (N=29) and Ob (N=11) and 23 in Ow (N=35) at week 48. Conclusions: In an Italian real-world setting, the efficacy of BEN in SEA patients seems not to be affected by obesity, leading to asthma control al >90% reduction of AER and severe AER regardless of BMI.

Introductions: Safety and efficacy of benralizumab for severe eosinophilic asthma (SEA) have been demonstrated in Phase III clinical trials. However real-word evidence in Italy is limited. ANANKE is part of AstraZeneca’s global XALOC RWE program for benralizumab. Objects: To describe the clinical impact of benralizumab on adult patients with SEA in a real-life setting. Methods: This is an ongoing observational, multicentre, retrospective study of the clinical characteristics and asthma exacerbations for SEA patients in Italy with at least 12 weeks of benralizumab treatment. Clinical (including comorbidities and atopic status) and laboratory (blood eosinophil count and total IgE) data have been collected. Annualized exacerbation rates (AER) before and after the first benralizumab injection (index date) were analysed. Results: 61 patients were included in this interim analysis [70.5% female, mean age 52.8 ± 13.9, median duration of disease 9.5 years (IQR 3.7-23.1), median eosinophil count (N=41) 410/mm3 (IQR 300-680/mm3), median total IgE (N=39) 215 IU/L (IQR 83-477 IU/L), atopic status 55.7%]. Comorbidities were frequent (44/61 patients, 72.1%), and 34.4% reported chronic rhinosinusitis with nasal polyps (CRSwNP) in the past year. Patients were treated with benralizumab for a median of 9.3 months (IQR 6.1-11.7).During the year prior to index date, AER was 4.98 for any exacerbation and 1.25 for severe exacerbations (N=52). After index date, AER was reduced to 0.38 for any exacerbation(92.4% reduction) and 0.08 for severe exacerbations (93.6% reduction). Conclusion: benralizumab has been prescribe to adult-onset SEA patients, with high prevalence of CRSwNP, indipendent of atopy. Benralizumab led to 93.6% reduction in severe AER

To the Editor, Severe asthma (SA) is a chronic disease affecting around 3-8% of adult asthma population in Europe, with the refractory form estimated to occur in 0.1% of the general population (1,2). SA is characterized by increased use of healthcare resources (i.e. emergency room/hospital admissions, access to intensive care units (ICU), use of biologics) due to exacerbations compared to the less severe form. In the current SARS-CoV-2 pandemic, there is an ongoing debate on the role of asthma and use of immunomodulating drugs, like corticosteroids and biologics, on COVID-19 outcomes. According to available data on COVID-19 hospitalizations, asthma seems to play little role on the clinical severity or access to health resources, unlike other chronic conditions such as hypertension, obesity and chronic obstructive pulmonary disease (3). However, to date, no information is available on the burden of SA on COVID-19 severity and hospitalization rates.A questionnaire was submitted to the Italian Registry of Severe Asthma (IRSA) network (4), assessing the prevalence and clinical characteristics of patients with SA who contracted COVID-19 during the outbreak in Italy (February 24th - May 18th 2020), and 41 out of 78 centers distributed evenly among different Italian regions participated to the survey (Figure 1a).Among the 558 subjects surveyed, 7 subjects contracted COVID-19 (1.25% of the national sample), with an average age of 54.5 years: 5 isolated at home/received home care (71.5%), while 2 subjects were admitted to the hospital (28.5%), none required accessed to ICU and no deaths were reported. All COVID-19 subjects with SA came from 2 regions of Northern Italy (6 Lombardy, 1 Emilia-Romagna, 3.7% of the regional population), all showing one or more comorbidities, and were treated with high-dose inhaled corticosteroids plus long-acting beta-2 agonists (ICS-LABA) and biologics (see Table 1).We then compared our results with data provided by the Italian Department for Civil Protection in the same time period from the affected geographic areas (5), and we observed that the frequency of COVID-19 among subjects referred to IRSA centers strongly correlated with the prevalence of SARS-CoV-2 infection in the corresponding province (Figure 1b). Furthermore, the hospitalization rate in COVID-19-SA subjects was not significantly different from the general population (24.1%, 23.6-24.6 95% C.I.; p=0.25, Chi-squared test). Lastly, we could not observe a significantly increased COVID-19 frequency in subjects undergoing high-dose ICS-LABA and biologics compared to SA treated with ICS-LABA alone (p=0.09, Fisher exact test).These findings from the IRSA registry offer some insights on the susceptibility to SARS-CoV-2 infection, access to healthcare resources and mortality by SA patients.Given the low prevalence of SA in Italy (2), we expected less COVID-19-SA cases per region than what reported by the IRSA survey. However, we observed that the geographic location of COVID-19-SA patients mostly reflected the bimodal distribution of the COVID-19 outbreak in Italy, mainly clustered in Lombardy and neighboring regions, where the highest cumulative COVID-19 cases were recorded (>500/100000 cases per inhabitants) (5). In these areas, the prevalence of positive cases by province also strongly correlated with the frequency of COVID-19-SA patients observed in each IRSA center (Figure 1b), suggesting that patients with SA most likely contract the infection when high circulation of the virus within the area of residence is present. The lack of positive cases reported in Southern regions further proves this hypothesis, and demonstrates the efficacy of the lockdown measures adopted to contain the further spread of the virus.Our results also suggest no increased risk of contracting COVID-19 in SA treated with biologics compared to ICS-LABA alone. Although there is currently no strong evidence that biologics used in asthma might affect the risk of contracting COVID-19, new evidence suggests a protective effect of inhaled corticosteroids against viral entry by ACE2 receptor downregulation, that are usually prescribed at a high dose in SA (6), thus a possible explanation to the lack of observed differences in our cohort.Despite the severity of asthma and reported comorbidities, no ICU admissions were reported, and hospital admissions in COVID-19-SA subjects did not differ from the median rate observed in the same geographic areas (5). Furthermore, we could observe no difference in the median monthly hospitalization rate of SA patients in 2019 compared to 2020 in Lombardy region where both hospital-admitted subjects reside (0.97 vs 0.9%, IRSA data).Our result is consistent with recent literature, showing that asthma in Western countries was not associated with an increased hospitalization rate and ICU admissions due to COVID-19 (3,8). It is still debated if a protective effect of Th2-inflammation in a significant proportion of asthma sufferers (7), or concomitant anti-inflammatory therapy could be the reasons for such outcomes (6). However, if asthma patients with COVID-19 require intubation, the duration of hospitalization was shown to be longer than average (8).As for the role of biologics in COVID-19 disease progression, we could not observe an increase in hospital admissions in patients with SA treated with biologics compared to the general population, with the majority isolating at home and requiring no additional treatment. Considering that, in areas with high prevalence of SARS-CoV-2 infection, 68.2% of SA subjects were treated with either omalizumab or mepolizumab, our observations further prove the safety of biologics during the COVID-19 pandemic.Lastly, we did not observe any deaths in our cohort, but we speculate that this outcome is most likely due to the small sample size and younger average age. In fact, advanced age seems to be the most determining risk factor on mortality due to COVID-19 compared to other causes. (9)Taken together, our results point at a neutral role of SA in the COVID-19 disease course and hospital admissions. One major strengths of our study is that, by using a fast and inexpensive tool, we could outline the salient features of severe asthma and COVID-19 at a national level, while the major weakness is the limited number of SA subjects diagnosed with COVID-19, that could lead to sampling bias and low accuracy. Further confirmation of these results with an increased sample size is therefore warranted

Background Even after publication of the 2011 update of GOLD report, some fundamental questions in the management of COPD are still open and this may weaken the applicability of these guidelines in everyday clinical practice. Objective To assess the level of consensus amongst Italian respirologists on different topics related to diagnosis, monitoring and role of bronchodilator therapy in COPD, by using the Delphi technique. Methods A Delphi study was undertaken between July and November 2011, when two questionnaires were consecutively sent to a panel of experts to be answered anonymously. After each round, the data were aggregated at group level of question topics and structured feedback was given to the panel. Results A first-round questionnaire was sent to 208 pulmonologists randomly selected from different Italian regions. The 132 respondents (63% of those initially selected) were from northern (53%), central (19%) and southern (28%) Italy. A second-round questionnaire was sent to all the first-round respondents, and a response was received from 110 of them (83%). The main topics that reached the pre-defined cut off for consensus (67% or more) were: a) bronchodilator therapy with long-acting bronchodilators could be beneficial in patients with airflow limitation even in the absence of symptoms, b) in patients not fully controlled with one long-acting bronchodilator, maximizing bronchodilation (i.e. adding another bronchodilator with a different mechanism of action) is the preferable option; and c) the use of inhaled corticosteroids (ICSs) as add on therapy should be considered in severe patients with frequent exacerbations. Conclusions Italian specialists agree on several aspects of the diagnosis and treatment of COPD and expert opinion could support everyday decision process in the management of COPD.

Background LOPD is a metabolic, autosomal recessive disease due to a reduced functionality of protein α-glucosidase (GAA), which leads to an accumulation of glycogen in skeletal muscle tissue and in other organs. 70% of LOPD patients develops progressive respiratory failure (RF) with vital capacity reduction and risk of mechanical ventilation. Recent data suggest the importance of an early LOPD diagnosis. Aims Prevalence of LOPD suspect in patients with RF. Optimizing the diagnostic process encouraging early diagnosis. Methods 12 months real-life study, conducted in 18 Pulmonology Italian Centers, aimed to enroll 500 adult patients with unexplained RF and follow the diagnostic algorithm for suspected LOPD. For each patient, clinicians collected a drop of blood on Dried Blood Spot (DBS) for the measurement of GAA. Muscular disability was assessed with Walton Gardner Medwin Scale (WGMS). Results 38 patients enrolled: characteristics and preliminary data in Figure 1. 68% acceded for respiratory reasons, 32% for other causes. 42% was hospitalized and 24% needed mechanical ventilation. Hyperckemia was reported in 34% of patients. The majority of cases (76%) presented a WGMS between 0 and 5. 1 case resulted positive for LOPD suspect (GAA = 0,48 micromol/L/h). Conclusions PneumoLoped could provide original data to focus the role of pulmonologists in LOPD early diagnosis in patients with unexplained RF.

Background: The present study reports the results of a survey jointly carried out by three Italian respiratory scientific associations (AIMAR, AIPO, SIMeR) together with an important Federation of elderly patients (FederAnziani) during the National Conference of Italian Court for Health Right held in Rimini from November 29th to December 1st, 2013. The survey, based on a spirometric examination preceded by a questionnaire on respiratory health, was conducted on elderly people coming from all Italian regions to attend the Conference. Methods: Nine hundred forty-nine subjects (574 females and 375 males), mean age 66.2 ± 10.1 years, were interviewed and performed spirometric examination. There were 137 smokers (14.4 %). Mean value of Body Mass Index (BMI) was significantly higher in males (27.6 ± 6.6) than in females (26.3 ± 4.3). Results: 17.1 % (N = 143) of the studied subjects reported to be suffering from respiratory disease and the prevalent illnesses were asthma (31.5 %) and COPD/emphysema (24.5 %), but only 3.3 % of the whole surveyed group was able to identify COPD as a pulmonary disease, however without knowing its characteristics, while these were known by 0.5 % of the interviewed subjects only. A high number of subjects, 22 % of whom were smokers, declared chronic sputum production. 10.2 % of the study group showed an obstructive defect at spirometry when the criterium of lower limit of the normal (LLN) was considered, whereas it was 12.4 % if the fixed limit of 0.70 was chosen. 64 % of the obstructed people thought they did not have any respiratory disease. Conclusions: The results of this survey, able to spread the knowledge of respiratory diseases and spirometry in a wide sample of subjects for the most part scarcely aware of them, emphasize the need for a greater divulgation of respiratory issues among the general population.

Objective Unfavourable effects of sleep-disordered breathing (SDB) in heart failure (HF) are mainly mediated by impaired sympathetic activity. Few data are available on SDB and cardiac adrenergic impairment evaluated at myocardial level. The aim of the study was to assess the relationship between SDB, cardiac sympathetic innervation assessed by 123 I-metaiodobenzylguanidine ( 123 I-MIBG) imaging and prognosis in HF. Methods Observational, prospective study enrolling patients with HF and reduced systolic function. Patients underwent nocturnal cardiorespiratory monitoring to assess SDB presence by apnoea/hypopnoea index (AHI), and 123 I-MIBG imaging to calculate heart-to-mediastinum (H/M) ratios and washout rate. Patients were prospectively followed for 29±18 months for the combined endpoint of cardiovascular death and HF hospitalisation. Results Ninety-four patients (66.1±9.8 years; left ventricular ejection fraction 32±7%) were enrolled; 72 (77%) showed SDB and, compared with non-SDB, significantly reduced early (1.67±0.22 vs 1.77±0.13; p=0.019) and late H/M ratios (1.50±0.22 vs 1.61±0.23; p=0.038). Dividing patients into two groups according to SDB severity, patients with a moderate–severe disturbance (AHI >15; n=43) showed significantly worse survival for the composite study outcome (log-rank test, p=0.001) with respect to patients with mild or no disorder (AHI ≤15; n=51). Adding SDB variables to the already known prognostic role of 123 I-MIBG imaging, we observed a worse survival in patients with both SDB and H/M impairment. Conclusions Patients with systolic HF and SDB show more impaired cardiac adrenergic innervation assessed by 123 I-MIBG imaging, and more adverse prognosis compared with HF patients without SDB.

La terapia farmacologica e non dei pazienti con enfisema polmonare da deficit di alfa1-antitripsina è illustrata per quanto riguarda tutto ciò che non è terapia aggiuntiva con alfa1-antitripsina esogeno. Similitudini e differenze rispetto alla terapia della BPCO sono analizzate in questo lavoro di revisione.

Diese Studie untersucht systematisch die Rezeption der Figur des Capitano der Commedia dell’Arte im deutschsprachigen Theater des 16. und 17. Jahrhunderts. Um von anderen Studien hervorgerufene Missverständnisse zu vermeiden, wird für diesen Typus der neue Begriff ‘lächerlicher Krieger’ eingeführt. Das erste nennenswerte Beispiel kommt aus der Tradition der Fastnachtspiele und aus der Feder eines Schweizers: Pamphilus Gengenbach. Es folgt ein interessantes Beispiel aus den Werken des Herzogs Heinrich Julius von Braunschweig-Wolfenbüttel. In der Zeit der escalation der Kriege in Zentraleuropa setzen die Autoren die Figur viel engagierter ein. Dies kann bei den Werken von Johan Rist und Andreas Gryphius beobachtet werden. Mit der Ende des Dreißigjährigen Krieges, verliert die Figur des lächerlichen Kriegers wieder an Vitalität, und wird nur noch als steriler Stereotyp eingesetzt, wie das Beispiel vom Prahlhans Don Alfanzo von Christian Weise zeigt, um schließlich ganz in Vergessenheit zu geraten.

Obesity is a risk factor for sleep disordered breathing (SDB) in children. Plasma levels of high-sensitivity C-reactive protein (Hs-CRP) are predictive of cardiovascular morbidity in adults, and CRP levels are associated with over-weight. Increased carotid intima-media thickness (IMT) is associated with several cardiovascular risk factors. We evaluated the effect of SDB on CRP levels and IMT in lean and obese children not selected for snoring.101 children (age 5-15 years) attending a weight clinic or scheduled for routine visit. IMT was measured with quantitative B-mode ultrasound scans. The apnea-hypopnea index (AHI) was measured overnight: AHI1 defined controls, AHI ≥ 1 to5 = mild SDB, and AHI ≥ 5 = obstructive sleep apnea (OSA).AHI was significantly associated with Hs-CRP concentration (r = 0.32, p = 0.002) in all 101 children irrespective of age and sex. Body mass index (BMI) was higher in OSA children than controls (25.5 ± 7.0 vs 22.1 ± 6.9, p = 0.05). Obese children had 3.3 times more probability of having OSA (HR 3.3, 95% CI 1.2-9.3, p = 0.02) than lean children. Hs-CRP values were significantly higher in children with OSA than in children without (p = 0.011), but not when BMI z-score was added as covariate. IMT was not associated with AHI or SDB.The results of this study suggest an association between OSA and Hs-CRP concentrations (mainly mediated by overweight and obesity), but not between OSA and subclinical atherosclerosis. There is scope for prevention in childhood before OSA syndrome causes the irreversible damage to arteries observed in adult patients.

COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD “a preventable and treatable disease”. The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60% predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2 < 88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with “severe” or “very severe” COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneously published in Sarcoidosis Vasc Diffuse Lung Dis 2014, 31(Suppl. 1);3-21.

Sleep apnea (SA) has been reported to worsen prognosis in patients with heart failure, likely through enhanced sympathetic drive arising from nocturnal arousals. However, very few studies have evaluated the association between SA and cardiac sympathetic innervation in heart failure patients. We