Phase angle in assessment and monitoring treatment of individuals with respiratory disease.

Phase angle (PhA) represents a raw variable measured with bioelectrical impedance analysis (BIA) that is used to assess malnutrition in many diseases, including respiratory diseases, mainly chronic obstructive pulmonary disease (COPD). COPD patients with reduced PhA are older, more hypoxic and hypercapnic; patients with more severe COPD have reduced cell mass, evident skeletal muscle depletion, and worsening gas exchange. Malnourished patients with stable COPD in long-term oxygen therapy (LTOT) have more intense dyspnea at rest, greater weight loss over the past 12 months, and more exacerbations per year. Multiple regression analysis highlighted the significance of PhA° in the estimation of muscle strength: hand grip strength (HGS) and in that of respiratory muscles: maximal inspiratory pressure / max. expiratory pressure ratio (MIP/MEP). Furthermore, the relationship between PhA° and all-cause mortality in COPD patients was confirmed with the Cox regression model, Kaplan-Meier test, and log-rank tests. The role of malnutrition in idiopathic pulmonary fibrosis (IPF) is confirmed by the PhA° measurements which, regardless of body weight, is associated with the reduction in muscle mass of these patients, reduces their strength and exercise capacity, and greatly influences the prognosis. In conclusion PhA is a novel biomarker of morbidity and mortality in patients with severe respiratory diseases.

Improving the management of patients with chronic cardiac and respiratory diseases by extending pulse-oximeter uses: the dynamic pulse-oximetry.

Respiratory and cardio-vascular chronic diseases are among the most common noncommunicable diseases (NCDs) worldwide, accounting for a large portion of health-care costs in terms of mortality and disability. Their prevalence is expected to rise further in the coming years as the population ages. The current model of care for diagnosing and monitoring NCDs is out of date because it results in late medical interventions and/or an unfavourable cost-effectiveness balance based on reported symptoms and subsequent inpatient tests and treatments. Health projects and programs are being implemented in an attempt to move the time of an NCD's diagnosis, as well as its monitoring and follow up, out of hospital settings and as close to real life as possible, with the goal of benefiting both patients' quality of life and health system budgets. Following the SARS-CoV-2 pandemic, this implementation received additional impetus. Pulseoximeters (POs) are currently used in a variety of clinical settings, but they can also aid in the telemonitoring of certain patients. POs that can measure activities as well as pulse rate and oxygen saturation as proxies of cardio-vascular and respiratory function are now being introduced to the market. To obtain these data, the devices must be absolutely reliable, that is, accurate and precise, and capable of recording for a long enough period of time to allow for diagnosis. This paper is a review of current pulse-oximetry (POy) use, with the goal of investigating how its current use can be expanded to manage not only cardio-respiratory NCDs, but also acute emergencies with telemonitoring when hospitalization is not required but the patients' situation is debatable. Newly designed devices, both "consumer" and "professional," will be scrutinized, particularly those capable of continuously recording vital parameters on a 24-hour basis and coupling them with daily activities, a practice known as dynamic pulse-oximetry.

Accuracy of a New Pulse Oximetry in Detection of Arterial Oxygen Saturation and Heart Rate Measurements: The SOMBRERO Study.

Early diagnosis and continuous monitoring of respiratory failure (RF) in the course of the most prevalent chronic cardio-vascular (CVD) and respiratory diseases (CRD) are a clinical, unresolved problem because wearable, non-invasive, and user-friendly medical devices, which could grant reliable measures of the oxygen saturation (SpO2) and heart rate (HR) in real-life during daily activities are still lacking. In this study, we investigated the agreement between a new medical wrist-worn device (BrOxy M) and a reference, medical pulseoximeter (Nellcor PM 1000N). Twelve healthy volunteers (aged 20−51 years, 84% males, 33% with black skin, obtaining, during the controlled hypoxia test, the simultaneous registration of 219 data pairs, homogeneously deployed in the levels of Sat.O2 97%, 92%, 87%, 82% [ISO 80601-2-61:2017 standard (paragraph EE.3)]) were included. The paired T test 0 and the Bland-Altman plot were performed to assess bias and accuracy. SpO2 and HR readings by the two devices resulted significantly correlated (r = 0.91 and 0.96, p < 0.001, respectively). Analyses excluded the presence of proportional bias. For SpO2, the mean bias was −0.18% and the accuracy (ARMS) was 2.7%. For HR the mean bias was 0.25 bpm and the ARMS3.7 bpm. The sensitivity to detect SpO2 ≤ 94% was 94.4%. The agreement between BrOxy M and the reference pulse oximeter was "substantial" (for SpO2 cut-off 94% and 90%, k = 0.79 and k = 0.80, respectively). We conclude that BrOxy M demonstrated accuracy, reliability and consistency in measuring SpO2 and HR, being fully comparable with a reference medical pulseoxymeter, with no adverse effects. As a wearable device, Broxy M can measure continually SpO2 and HR in everyday life, helping in detecting and following up CVD and CRD subjects.

SARS-CoV-2 pandemic in Italy: ethical and organizational considerations.

The current SARS-CoV-2 pandemic is still raging in Italy. The country is currently plagued by a huge burden of virusrelated cases and deaths. So far, the disease has highlighted a number of problems, some in common with other Countries and others peculiar to Italy which has suffered from a mortality rate higher than that observed in China and in most Countries in the world. The causes must be sought not only in the average age of the population (one of the oldest in the world), but also in the inconsistencies of the regional health systems (into which the National Health System is divided) and their delayed response, at least in some areas. Ethical issues emerged from the beginning, ranging from restrictions on freedom of movements and restrictions on personal privacy due to the lockdown, further to the dilemma for healthcare professionals to select people for ICU hospitalization in a shortage of beds in Intensive Care Unit (ICU). Organizational problems also emerged, although an official 2007 document from the Ministry of Health had planned not only what measures had to be taken during an epidemic caused by respiratory viruses, but also what had to be done in the inter-epidemic period (including the establishment of DPIs stocks and ventilators), vast areas of Italy were totally unprepared to cope with the disease, as a line of that document was not implemented. Since organizational problems can worsen (and even cause) ethical dilemmas, every effort should be made in the near future to prepare the health system to respond to a similar emergency in a joint, coherent, and homogeneous way across the Country, as planned in the 2007 document. In this perspective, Pulmonary Units and specialists can play a fundamental role in coping with the disease not only in hospitals, as intermediate care units, but also at a territorial level in an integrated network with GPs.

Accuracy of diagnosis of COPD and factors associated with misdiagnosis in primary care setting. E-DIAL (Early DIAgnosis of obstructive lung disease) study group.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and results in both substantial and increasing socioeconomic burden. Guidelines on COPD encourage primary care physicians to detect the disease at an early stage. Our main aim was to evaluate the accuracy of the diagnosis of COPD at the primary health care. METHODS: 6466 patients were randomly selected in 22 Italian primary care practices (46% males, mean age 56 ±â€¯16 years) and were asked about respiratory symptoms and risk for any chronic respiratory disease including COPD. After a prior evaluation, 701 patients (51% males, mean age 59 ±â€¯15 years) were sent by General Practitioners (GPs) to Pulmonary Units (PU) for confirming the diagnosis. The agreement in diagnosing COPD between GPs and pulmonary diseases specialists was assessed by using Cohen's kappa (k) statistic. RESULTS: Lack of precision in COPD diagnosis resulted in 13% of over-diagnosis and 59% of under-diagnosis. GPs were quite good in correctly excluding the patients who did not have COPD (specificity = 87%), but less good in diagnosing the patients with COPD (sensitivity = 41%). The risk of under-diagnosis was higher in people with age >62 years and in current/ex-smokers, when compared to no COPD, whereas it was higher in subject <62 years old and in those with no previous spirometry when compared to correctly diagnosed COPD. CONCLUSION: Our results confirm that COPD misdiagnosis is common in primary care and that under-diagnosis is a major problem. It is necessary to enhance COPD diagnosis and to reduce misdiagnosis in primary care settings.

Supplementation with Qter® and Creatine improves functional performance in COPD patients on long term oxygen therapy.

BACKGROUND: Skeletal muscle dysfunction and poor functional capacity are important extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), especially in COPD patients on long-term O2 therapy (LTOT). Beside the role of pulmonary rehabilitation, the effect of nutritional interventions is still controversial, and there are knowledge gaps on the effective role of nutraceutical supplementation on hard endpoints. The aim of this study was to investigate the effects of nutritional supplementation with Coenzyme Q10 (QTer®) - a powerful antioxidant with the potential to reduce oxidative stress and improve mitochondrial function - and Creatine on functional, nutritional, and metabolomic profile in COPD patients on long-term O2 therapy. METHODS: One-hundred and eight patients with COPD from 9 Italian hospitals were enrolled in this double-blinded randomized placebo-controlled clinical study. At baseline and after 2 months of therapy, the patients underwent spirometry, 6-minute walk test (6MWT), bioelectrical impedance analysis, and activities of daily living questionnaire (ADL). Also, dyspnea scores and BODE index were calculated. At both time points, plasma concentration of CoQ10 and metabolomic profiling were measured. FINDINGS: Ninety patients, who randomly received supplementation with QTer® and Creatine or placebo, completed the study. Compared with placebo, supplemented patients showed improvements in 6MWT (51 ±â€¯69 versus 15 ±â€¯91 m, p < 0.05), body cell mass and phase angle, sodium/potassium ratio, dyspnea indices and ADL score. The CoQ10 plasma concentration increased in the supplementation group whereas it did not change in the placebo group. The metabolomics profile also differed between groups. Adverse events were similar in both groups. INTERPRETATION: These results show that in patients with COPD, dietary supplementation with CoQ10 and Creatine improves functional performance, body composition and perception of dyspnea. A systemic increase in some anti-inflammatory metabolites supports a pathobiological mechanism as a reason for these benefits. Further trials should help clarifying the role of QTer® and Creatine supplementation in patients with COPD.

COPD management as a model for all chronic respiratory conditions: report of the 4th Consensus Conference in Respiratory Medicine.

BACKGROUND: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. METHODS: These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3-4 November 2016. RESULTS AND CONCLUSIONS: Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role.

Most Italians attending a congress on health of elderly people do not know and do not recognize respiratory diseases.

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 29(th) to December 1(st), 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.

The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use: Results from an Observational Study (ASSESS).

This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p < 0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (both p < 0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (all p < 0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (all p ≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (both p < 0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk.

Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study.

BACKGROUND: Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes. METHODS: The study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded. RESULTS: The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%. In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001). Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between symptoms and a patient's physical activity level (p < 0.05 for each period). CONCLUSIONS: More than half of patients experienced COPD symptoms throughout the whole 24-hour day. There was a significant relationship between night-time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.

Audit on the appropriateness of integrated COPD management: the "ALT-BPCO" project.

BACKGROUND: Non communicable chronic diseases (including respiratory ones) are the leading cause of death and disability. To cope with them we need to redesign the health system, improving primary prevention, screening, and outpatient services, while fully integrating different branches of the health service. The Italian Ministry of Health published extended guidelines on integrated COPD management (COPD-GL) in 2010. In2011 a condensed version was produced. These documents define appropriateness of management regarding both the specialist and the health service. METHODS: An internal audit on how clinical practice conforms to COPD-GL standards was implemented in one Italian region involving 29 respiratory units (RU) (65.8% of the total regional RU): data were collected from the clinical database at time zero and after 6 months. In the meantime, specialists of RU underwent education on COPD-GL. RESULTS: At time zero, significant gaps between current practice and recommendations emerged both in medical practice (mean agreement 25%) and in the health organization (48%). At month 6 the gaps were reduced more in clinical practice (60.7%) than in organization (54.7%). CONCLUSIONS: It is easier to resolve the gaps in specialist clinical practice than the organizational gaps, changing which is the politicians' task. Correcting specialists' inappropriateness may be worthless if this is not accompanied by improvement of the organizational obstacles. The search for appropriateness should not be limited only to specialists or to a strict control of drug prescription but should include all the organizational aspects. Implementation of COPD-GL calls for actions on the part of both specialists and the health system.

The clinical and integrated management of COPD. An official document of AIMAR (Interdisciplinary Association for Research in Lung Disease), AIPO (Italian Association of Hospital Pulmonologists), SIMER (Italian Society of Respiratory Medicine), SIMG (Italian Society of General Medicine).

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.

Pneumocafé project: an inquiry on current COPD diagnosis and management among General Practitioners in Italy through a novel tool for professional education.

BACKGROUND: Symptoms of COPD are frequently disregarded by patients and also by general practitioners (GPs) in early stages of the disease, that consequently is diagnosed when already at an advanced grade of severity. Underdiagnosis and undertreatment of COPD and scarce use of spirometry are widely recurrent, while a better knowledge of the disease and a wider use of spirometry would be critical to diagnose more patients still neglected, do it at an earlier stage and properly treat established COPD. The aim of Pneumocafè project is to improve, through an innovative approach, the diagnosis and management of COPD at primary care level increasing the awareness of issues pertaining to early diagnosis, adequate prevention and correct treatment of the disease. METHODS: Pneumocafè is based on informal meetings between GPs of various geographical zones of Italy and their reference respiratory specialist (RS), aimed at discussing the current practice in comparison to suggestions of official guidelines, analyzing the actual problems in diagnosing and managing COPD patients and sharing the possible solution at the community level. In these meetings RSs faced many issues including patho-physiological mechanisms of bronchial obstruction, significance of clinical symptoms, patients' phenotyping, and clinical approach to diagnosis and long-term treatment, also reinforcing the importance of a timely diagnosis, proper long term treatment and the compliance to treatment. At the end of each meeting GPs had to fill in a questionnaire arranged by the scientific board of the Project that included 18 multiple-choice questions concerning their approach to COPD management. The results of the analysis of these questionnaires are here presented. RESULTS: 1, 964 questionnaires were returned from 49 RSs. 1,864 questionnaires out of those received (94.91% of the total) resulted properly compiled and form the object of the present analysis. The 49 RSs, 37 males and 12 females, were distributed all over the Italian country and practiced their profession both in public and private hospitals and in territorial sanitary facilities. GPs were 1,330 males (71.35%) and 534 females (28.64%), mean age 56,29 years (range 27-70 yrs). Mean duration of general practice was 25.56 years (range: 0,5-40 yrs) with a mean of 1,302.43 patients assisted by each GP and 2,427,741 patients assisted in all. The majority of GPs affirmed that in their patients COPD has a mean-to-great prevalence and a mean/high impact on their practice, preceded only by diabetes and heart failure. Three-quarters of GPs refer to COPD guidelines and most of them believe that a screening on their assisted patients at risk would enhance early diagnosis of COPD. Tobacco smoking is the main recognized cause of COPD but the actions carried out by GPs to help a patient to give up smoking result still insufficient. The majority of GPs recognize spirometry as necessary to early COPD diagnosis, but the main obstacle pointed out to its wider use was the too long time for the spirometry to be performed. GPs' main reason for prescribing a bronchodilator is dyspnea and bronchodilators preferably prescribed are LABA and LAMA. Control of patient's adherence to therapy is mainly carried out by GPs checking the number of drugs annually prescribed or asking the patient during a control visit. Finally, about how many COPD patients GPs believe are in their group of assisted patients, a mean range of 25-40 patients was reported, that is consistently below the forecast based on epidemiological data and number of patients assisted by each GP. CONCLUSIONS: The results obtained with this project confirm the validity of this informal approach to professional education. Furthermore, this inquiry provided important insights about the general management of COPD and the process of integration between RS and GPs activities on this disease condition in the long run.

ISMAR-study presentation: in-hospital epidemiology and clinical management of respiratory and cardiac comorbidities in cardiac and respiratory disease units.

BACKGROUND: Cardiovascular and respiratory diseases are leading causes of morbidity and their co-occurrence has important implications in mortality and other outcomes. Even the most recent guidelines do not reliably address clinical, prognostic, and therapeutic concerns due to the overlap of respiratory and cardiac diseases. STUDY OBJECTIVES AND DESIGN: In order to evaluate in the reality of clinical practice the epidemiology and the reciprocal impact of cardio-pulmonary comorbidity on the clinical management, diagnostic workup and treatment, 1,500 cardiac and 1,500 respiratory inpatients, admitted in acute and rehabilitation units, will be enrolled in a multicenter, nationwide, prospective observational study. For this purpose, each center will enroll at least 50 consecutive patients. At discharge, data analysis will be aimed at the definition of cardiac and pulmonary inpatient comorbidity prevalence, demographic characteristics, length of hospital stay, and risk factors, taking into account also procedures, pharmacological and non-pharmacological treatment, and follow up in patients with cardio-respiratory comorbidity. CONCLUSIONS: The purely observational design of the study aims to give new relevant information on the assessment and management of overlapping patients in real life clinical practice, and new insight for improvement and implementation of current guidelines on the management of individual diseases.

Standards of suitability for the management of chronic obstructive respiratory diseases.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) ranks third as cause of mortality and disability-adjusted life years (DALY) worldwide and also in Italy it imposes a huge health, social and economic load. Early symptoms of COPD are often disregarded by patients and physicians, spirometry is underutilized, and the diagnosis is delayed till the disease has reached a distinct severity level. Despite the availability of various guidelines, the behavior of health workers involved in the management of COPD is still rather unlike. These considerations are the reason why in October 2013 AIMAR (Interdisciplinary Scientific Association for Research in Lung Disease) devised and organized a "Third Consensus Conference", aimed at pointing out the standards of suitability for COPD management. In this context three important topics of discussion were identified: early and more widespread diagnosis, management of acute and subacute phases, long-term assistance to chronic patients. METHODS: The procedure recommended by the Italian Health Superior Institute (ISS) for Consensus Conferences organization was applied. The Conference was structured in three sessions, each dealing with one of the above mentioned topics and including a short update of the subject-matter and presentation, discussion and voting of some statements with a choice ranging from total agreement to total disagreement or no knowledge. The results of voting were eventually recorded in the document, reviewed by an independent jury, that forms the substance of this paper. RESULTS: The essential role of spirometry, the need for distinguish between different COPD phenotypes, and the obligatoriness to base on the blood gas analysis findings the long-term oxygen therapy, were largely agreed, as well as the need for interventions aimed at decreasing the rate of acute exacerbations. More specific topics like the use of noninvasive ventilation, recognizing the factors affecting outcome and mortality, the choice of pharmacological and non pharmacological treatments in COPD patients led to lively discussing, but they did not always reach the total agreement, probably because of insufficient familiarity with these problems and of diversities in organization and instruments availability. The chronic respiratory assistance was treated with particular regard to smoking cessation, whose implementation is still insufficient. Many doubts rose due to uncertainty, lack of ability and standardization of procedures, insufficient institutional support, and difficulties to realize a network for assistance to chronic patients. CONCLUSIONS: The results of this Third Consensus Conference revealed some certainties and many doubts and diversities of view also on topics whose importance is well demonstrated in scientific literature. Thus, there is still a long distance to cover before reaching a suitable standardization of COPD management and such situation urges the need for improving not only the health professional's operativeness but also the organizational support by competent institutions. In this context some initiatives organized by AIMAR in cooperation with other respiratory scientific societies and patients' associations are going on.

Clinical efficacy and tolerability of an immune-stimulant(*) constituted by inactivated bacterial bodies in the prophylaxis of infectious episodes of airways: a double blind, placebo-controlled, randomized, multicentre study.

BACKGROUND: (Buccalin ®) is a Bacterial Lysates (BL) that belongs to a family of immune-stimulators, developed more than 30 years ago and it still has a role in the prophylaxis of Recurrent Respiratory Tract Infections (RRTI). However, original studies were conducted with an approach that does not seem to be aligned with the present methodologies. In addition, concomitant therapies substantially improved in the last decades. These two reasons strongly suggested to update our knowledge on the capacity of this bacterial lysate (Buccalin ®) to reduce the number of days with infectious episodes in patients with RRTI. METHODS: A double blind, placebo-controlled, randomized, multicentre study was programmed (EudraCT code: 2011-005187-25). The reduction of the number of days with infectious episodes (IE) was the primary endpoint. Secondary endpoints were the number of IE, the use of concomitant drugs, the efficacy on signs and symptoms of RRTI and the safety of the drug. Patients were treated according to the registered schedule and were followed up for a period of 6 months. RESULTS: From a cohort of 188 patients eligible for the study, 90 were included in the active group and 88 in the placebo group. The study was completed in 170 patients. A significant reduction of the number of days with IE was observed (6.57 days in the active group and 7.47 in the placebo group). Secondary endpoints were only partially achieved. No virtual adverse events related to the treatment were recorded. CONCLUSION: The administration of bacterial lysate (Buccalin ®) in patients with RRTI had the capacity to significantly reduce the number of days with IE in a multicentre, randomized, placebo controlled, clinical study. The treatment was safe. Of note, all patients were free to be treated with the best concomitant therapies. In these conditions, the positive results observed demonstrated that this bacterial lysate has maintained its capacity of reducing the days with infections in patients with RRTI, also in association to the concomitant therapies available nowadays.

Effects of nutraceutical diet integration, with coenzyme Q10 (Q-Ter multicomposite) and creatine, on dyspnea, exercise tolerance, and quality of life in COPD patients with chronic respiratory failure.

BACKGROUND: The protein-calorie malnutrition, resulting in muscle mass loss, frequently occurs in severe COPD patients with chronic respiratory failure (CRF), causing dyspnea, reduced exercise tolerance and impaired quality of life.The cause of this occurrence is an intake-output energy imbalance. A documented deficit of phosphocreatine and reduced mithocondrial energy production can contribute to this imbalance.Aim of this study is to verify whether a dietary supplementation with creatine and coenzyme Q10, important mitochondrial function factors, is able to influence this mechanism leading to a dyspnea reduction and improving exercise tolerance and quality of life. METHODS: 55 COPD patients with chronic respiratory failure (in long term O2 therapy), in stable phase of the disease and without severe comorbidities were assigned (double-blind, randomized) to: group A (30 patients) with daily dietary supplementation with Creatine 340 mg + 320 mg Coenzyme Q-Ter (Eufortyn®, Scharper Therapeutics Srl) for 2 months whereas Group B (25 patients) received placebo.All patients continued the same diet, rehabilitation and therapy during the study. At recruitment (T0) and after 2 months (T1), patients were submitted to medical history, anthropometry (BMI), bioelectrical impedance, arterial blood gas analysis, evaluation of dyspnea (VAS, Borg, BDI, MRC) and functional independence (ADL), 6-minute walk test (6MWT) and quality of life questionnaire (SGRQ). At 6 months and 1 year, a telephone follow up was conducted on exacerbations number. RESULTS: No significant difference was detected at baseline (T0) in the 2 groups. After 2 months of therapy (T1) the FFMI increased in the daily dietary supplementation group (+ 3.7 %) and decreased in the placebo group (- 0.6 %), resulting in a statistically significant (p < 0.001) treatment difference. Statistically significant treatment differences, favouring daily dietary supplementation group, were also seen for the 6MWT comparison. Group A patients also showed significant: 1) improvement in the degree of dyspnea (VAS: p < 0.05; Borg: p < 0.05; MRC: p < 0.001; BDI1: p < 0.05; BDI3: p < 0.03), and independence level in activities of daily living (p < 0.03); 2) improvement in quality of life in activity section (- 6.63 pt) and in total score (- 5.43 pt); 3) exacerbation number decrease (p < 0.02). No significant differences were found (end of study vs baseline) in group B. CONCLUSIONS: The nutraceutical diet integration with Q-Ter and creatine, in COPD patients with CRF in O2TLT induced an increasing lean body mass and exercise tolerance, reducing dyspnea, quality of life and exacerbations. These results provide a first demonstration that acting on protein synthesis and muscular efficiency can significantly modify the systemic consequences of the disease.

Prevention of respiratory tract infections with bacterial lysate OM-85 bronchomunal in children and adults: a state of the art.

Respiratory tract infections (RTIs) are a leading cause of morbidity and also represent a cause of death in some parts of the world. The treatment of RTIs implies a continuous search for stronger therapies and represents an economical burden for health services and society. In this context the prevention of infections is absolutely required. The use of bacterial lysates as immuno-modulators to boost immunological response is widely debated. Aim of this review is to summarize the main clinical studies on the effect of the bacterial lysate OM-85 in treating RTIs in susceptible subjects - namely children and chronic obstructive pulmonary disease (COPD)-affected adults. Results from clinical trials and recent systematic reviews are reported.The results show that mean number of RTIs decreases upon treatment with OM-85, as measured by frequency of exacerbations or number of antibiotic courses. Data from systematic reviews indicated that OM-85 is particularly beneficial in children at high risk of RTIs. In COPD-affected adults, clinical studies showed that treatment with OM-85 reduced exacerbations, although systematic reviews did not legitimate the protective effect of OM-85 toward COPD as significant.The use of OM-85 could be efficacious in reducing exacerbation frequency of RTIs in children and adults at risk. However further high-quality studies are needed to better explain the mechanism of action and confirm the beneficial results of OM85.

A randomized controlled trial on office spirometry in asthma and COPD in standard general practice: data from spirometry in Asthma and COPD: a comparative evaluation Italian study.

STUDY OBJECTIVES: To evaluate whether office spirometry by general practitioners (GPs) is feasible and may improve the diagnosis of asthma and COPD. METHODS: A prospective, randomized, comparative trial was planned involving 57 Italian pulmonology centers and 570 GPs who had to enroll consecutive subjects aged 18 to 65 years with symptoms of asthma or COPD without a previous diagnosis. Patients were randomized 1:1 into two groups with an interactive voice responding system: conventional evaluation alone vs conventional evaluation and spirometry. Office spirometry was performed by GPs who were trained by reference specialists using a portable electronic spirometer (Spirobank Office; MIR; Rome, Italy). Diagnosis was confirmed by the reference specialist center in blind fashion. RESULTS: Seventy-four GPs complied to the trial. Of 333 patients enrolled, 136 nonrandom violators completed the protocol. Per-protocol analysis showed a concordant diagnosis between GPs and specialists in 78.6% of cases in the conventional evaluation-plus-spirometry group vs 69.2% in the conventional evaluation group (p = 0.35). In the intention-to-treat analysis, the respective percentages of concordant diagnosis were 57.9 and 56.7 (p = 0.87). CONCLUSIONS: Office spirometry by GPs is feasible, but frequent protocol violation and inadequate sample size did not allow us to prove a significant advantage of office spirometry in improving the diagnosis of asthma and COPD in standard general practice as organized at present in Italy, thus reinforcing the need for close cooperation between GPs and specialists in respiratory medicine.

Systemic effects of COPD.

Chronic obstructive pulmonary disease (COPD) is characterised by a range of pathological changes of the respiratory system, including airflow limitation secondary to structural changes of the small airways and loss of alveolar attachments, inflammation, ciliary dysfunction, and increased mucous production. COPD also has significant systemic consequences. The relationships between these pulmonary and nonpulmonary morbidities are not fully understood, and this further complicates the assessment of disease severity and prognosis. Although improving lung function and disease symptoms have been the main focus of COPD management, these parameters alone do not reflect the full burden of disease. More recent endeavours have highlighted the potential role of addressing physical limitations imposed by systemic alterations. It is evident that systemic manifestations are common in COPD. Indeed, many patients demonstrate a gradual and significant weight loss that exacerbates the course and prognosis of disease. This weight loss is often accompanied by peripheral muscle dysfunction and weakness, which markedly contribute to exercise limitation and impaired quality of life. Weight loss has been postulated to be the result of a high metabolic rate that is not compensated for by increased dietary intake. The cause of this elevated metabolism is a matter of much debate, and several factors have been implicated. Similarly, the processes underlying depletion of muscle mass and function have not been fully delineated. The impact of the systemic manifestations of COPD is substantial, and although many attempts have been made to elucidate the mechanisms underlying these manifestations, there are important questions, which remain to be answered. An increase in our understanding in this field will doubtless highlight potential therapeutic targets, and assist in guiding future therapeutic development.