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.

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 The current model of care for diagnosing and monitoring NCDs is out of date because it results in late medical interventions and/or an unfavourable cost-effectiveness balance based on reported symptoms and subsequent inpatient tests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.

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.

Targeting the COPD exacerbation.

Exacerbations of COPD have a profound detrimental effect on the patient and impose a significant burden on healthcare resource utilization. Prevention and treatment of exacerbations are major objectives of the clinical management of COPD. For this approach to be successful, clinicians must combine both pharmacologic approaches and non-pharmacologic strategies aimed at improving the patient's disease management. Non-pharmacologic approaches include those that can be incorporated into the office setting as well as intervention strategies that are integrated into the lifelong management of COPD. These strategies include developing a partnership with the patient and their social supports, encouraging and facilitating smoking cessation, immunizations, proper use of supplemental oxygen, and most importantly, giving the patient the tools to manage their illness appropriately. Moreover there is clear evidence of an irrevocable decline in pulmonary function after each exacerbation, usually resulting in reduced physical activity and impaired skeletal muscle function. Not surprisingly, pulmonary rehabilitation after such events has been shown to prevent relapse, improve survival and enhance patients' overall function after acute exacerbations.

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.

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.

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.

N-acetylcysteine in COPD: why, how, and when?

Oxidants have long been recognized to have an important role in the pathogenesis of COPD, and in this cigarette smoke has a strong responsibility, because it generates a conspicuous amount of oxidant radicals able to modify the structure of the respiratory tract and to enhance several mechanisms that sustain lung inflammation in COPD. In fact, oxidative stress is highly increased in COPD and natural antioxidant capacities, mainly afforded by reduced glutathione, are often overcome. Thus an exogenous supplementation of antioxidant compounds is mandatory to at least partially counteract the oxidative stress. For this purpose N-acetylcysteine has great potentialities due to its capacity of directly contrasting oxidants with its free thiols, and to the possibility it has of acting as donor of cysteine precursors aimed at glutathione restoration. Many studies in vitro and in vivo have already demonstrated the antioxidant capacity of NAC. Many clinical studies have long been performed to explore the efficacy of NAC in COPD with altern results, especially when the drug was used at very low dosage and/or for a short period of time. More recently, several trials have been conducted to verify the appropriateness of using high-dose NAC in COPD, above all to decrease the exacerbations rate. The results have been encouraging, even if some of the data come from the most widely sized trials that have been conducted in Chinese populations. Although other evidence should be necessary to confirm the results in other populations of patients, high-dose oral NAC nevertheless offers interesting perspectives as add-on therapy for COPD patients.

INDACO project: COPD and link between comorbidities, lung function and inhalation therapy.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by respiratory and extrarespiratory components referring both to systemic complications of COPD, like skeletal muscle myopathy, weight loss and others, and frequently associated comorbidities, interesting various organs and systems (cardiovascular diseases, malignancies, osteoporosis, diabetes, etc.). These comorbidities may increase the rate of hospitalization of COPD patients and have a huge effect on the outcomes of the respiratory disease. Inhalation therapy of COPD with bronchodilators and steroid is primary driven by airflow obstruction, symptoms like dyspnoea, and acute exacerbations. INDACO project has been developed in 2013 to assess the prevalence and type of comorbidities in COPD patients referred to the outpatient wards of some hospitals in Central and South Italy and a preliminary report has recently been published. In the present study, after widening that database, we evaluate the prevalence of comorbidities and the relationships between comorbidities and sex, age, symptoms, lung function and inhalation therapy in COPD patients. METHODS: In each enrolled patient, anthropometric and anamnestic data, smoking habits, respiratory function, GOLD (Global initiative for Chronic Obstructive Lung Disease) severity stage, Body Mass Index (BMI), number of acute COPD exacerbations in previous years, presence and type of comorbidities, and the Charlson Comorbidity Index (CCI) were recorded. RESULTS: We collected data of 569 patients (395 males and 174 females, mean age 73 ± 8.5 yrs). The prevalence of patients with comorbidities was 81.2%. Overall number of comorbidities was not related to airflow obstruction and age, but to acute exacerbation of COPD, dyspnoea measured with MRC scale, and male gender. A subgroup analysis revealed that ischaemic heart disease was predominant in males, whereas mood disorders in females. The use of a more complex (multi-drug) inhalation therapy was related with bronchial obstruction measured by FEV1/FVC (p for trend = 0.003) and number of comorbidities (p for trend = 0.001). In multivariate analysis, only airflow obstruction and number of comorbidities were determinant of complexity of therapy, but not MRC and acute exacerbation of COPD. However, the statistical model reached an extreme low degree of significance (r^2 = 0.07). CONCLUSIONS: Our study showed a high prevalence of comorbidities in COPD, with some differences related to gender. Number of comorbidities and airflow obstruction represent the determinant of inhalation therapy prescription. Dyspnoea and acute exacerbation of COPD, unlikely suggested by guidelines, are not significant drivers of therapy in the real life setting of our study.

The lungs need to be deflated: effects of glycopyrronium on lung hyperinflation in COPD patients.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation caused by bronchial alterations, small airways disease and parenchymal destruction. In patients with COPD the structural and functional lung alterations can progress more or less rapidly from the initial small airways disease to an overt COPD where a severe expiratory flow limitation takes place. In these conditions, lung hyperinflation develops characterized by increase in functional residual capacity (FRC) and decrease in inspiratory capacity (IC). Thus, IC is an easy and reliable index to monitor lung hyperinflation and to assess the efficacy of bronchodilator drugs. When FRC increases, tidal volume (VT) is located in a more flatted upper part of the P -V curve of the respiratory system and respiratory muscles must sustain a greater elastic workload. Furthermore, due to inadequate time for expiration, there is a positive alveolar pressure at the end of expiration (PEEPi). This represents a further elastic workload for the inspiratory muscles. This impairment of ventilatory mechanics generates dyspnea that in most severely compromised patients occurs also for small efforts causing activity limitation and worst health-related quality of life (HRQoL). Due to these respiratory alterations, bronchodilators are the cornerstone of the long-term treatment of COPD in order to decrease airways resistances, lung hyperinflation and exacerbation rate, and improve patient's symptoms, exercise tolerance and health status. Long-acting antimuscarinic bronchodilators (LAMAs) have proven to be very useful in terms of lung deflation and exercise tolerance. Recently, new LAMAs with several positive characteristics have been introduced into clinical use among which glycopyrronium bromide has shown to be particularly effective. Glycopyrronium has a longer-lasting effect compared to other anticholinergic drugs, therefore it allows a single daily administration and facilitates the therapy of a disease that needs a chronic bronchodilation by decreasing the mechanic stress of the airways determined by repeated bronchoconstriction and increasing patient's adherence to treatment plan with better clinical results. Several studies demonstrated that glycopyrronium is able to positively and significantly decrease lung hyperinflation, symptoms, and improve psycho-physical status of COPD patients, with a low rate of adverse events, similar to that of placebo.

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.

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.

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.

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.

Idiopathic pulmonary fibrosis: the need for early diagnosis.

Idiopathic pulmonary fibrosis (IPF), a chronic fibrosing lung disease of a progressive nature and unknown etiology, has the largest epidemiological impact and the worst prognosis among the idiopathic interstitial pneumonias (IIP). Despite the progress in pathogenetic knowledge, many aspects are still dubious, in particular the biomolecular mechanisms activated in the early stages of the disease. Early diagnosis is desirable not only to better define aspects of the natural history of the disease, but also to customize treatment protocols. An early diagnosis of IPF should necessarily be based on the ability to highlight a number of features drawn not only from a careful composition of specific anamnestic data with clinical, functional and radiological parameters, but also from biological markers that, in a proper context, can provide guidance and confirm a clinical-anamnestic suspicion. The identification of specific biomarkers for IPF is a modern and attractive look for the potential clinical implications in terms of diagnosis, prediction of disease progression and prognosis. Biomolecular investigations on IPF were performed selectively on tissue samples, bronchoalveolar lavage (BAL), or blood: nowadays the "multi-omic" approach may allow studying individual constitutional profiles resorting to a series of biomolecular disciplines, the so-called "omics", which focuses on responses of the entire genomic complex, in line with the current trend to quantitatively analyze the interactions of all components of a biological system. Such refined investigations are an essential base for research now, but they might become a routine in the near future, allowing a more precise classification of patients suffering from a disease of unclear taxonomy.

Cryptogenic organizing pneumonia after radiotherapy for breast cancer.

We report a case of fever, dyspnea, respiratory failure and migratory, recurrent and bilateral lung opacities 4 months after radiotherapy and hormone therapy following surgery for breast cancer. Computerized tomography (CT) scans showed infiltrates outside the radiation fields. Bronchoalveolar lavage revealed lymphocytic alveolitis, whereas laboratory analysis demonstrated a mild systemic inflammation. Systemic steroids resulted in clinical and radiological improvement, but a disease relapse was evident at withdrawal of therapy, with definitive clinical and radiological normalization after a second cycle of therapy. This is a case of cryptogenic organizing pneumonia (COP) (previously known as bronchiolitis obliterans organizing pneumonia) primed by radiotherapy, as in previously reported cases. It is extremely important to be aware of the possibility of this complication, in order to optimize radiation and hormone treatment of breast cancer.

Respiratory involvement in inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD) and are due to a dysregulation of the antimicrobial defense normally provided by the intestinal mucosa. This inflammatory process may extend outside the bowel to many organs and also to the respiratory tract. The respiratory involvement in IBD may be completely asymptomatic and detected only at lung function assessment, or it may present as bronchial disease or lung parenchymal alterations. Corticosteroids, both systemic and aerosolized, are the mainstay of the therapeutical approach, while antibiotics must be also administered in the case of infectious and suppurative processes, whose sequels sometimes require surgical intervention. The relatively high incidence of bronchopulmonary complications in IBD suggests the need for a careful investigation of these patients in order to detect a possible respiratory involvement, even when they are asymptomatic.

Methotrexate-induced pneumonitis in Crohn's disease. Case report and review of the literature.

Methotrexate (MTX) is a folate-antagonist used in several neoplastic and inflammatory diseases. Reports of pulmonary complications in patients given low-dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable frequency and can present with different forms. Most often MTX-induced pneumonia in patients affected by rheumatoid arthritis (RA) is reported.In this paper we describe a case of MTX-related pneumonitis in a relatively young woman affected by Crohn's disease who presented non-productive cough, fever and dyspnea on exercise. Chest X-ray demonstrated bilateral interstitial infiltrates and at computed tomography (CT) ground-glass opacities appeared in both lungs. At spirometry an obstructive defect was demonstrated. A rapid improvement of symptoms and the regression of radiographic and spirometric alterations was achieved through MTX withdrawal and the introduction of corticosteroid therapy.