Palliative care and end of life management in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with an unknown etiology that causes deterioration of the structure of the lung parenchyma, resulting in a severe and progressive decline in respiratory function and early mortality. IPF is essentially an incurable disease, with a mean overall survival of 5 years in approximately 20% of patients without treatment. The combination of a poor prognosis, uncertainty about the disease's progression, and the severity of symptoms has a significant impact on the quality of life of patients and their families. New antifibrotic drugs have been shown to slow disease progression, but their impact on health-related quality of life (HRQoL) has to be proven yet. To date, studies have shown that palliative care can improve symptom management, HRQoL, and end-of-life care (EoL) in patients with IPF, reducing critical events, hospitalization, and health costs. As a result, it is essential for proper health planning and patient management to establish palliative care early and in conjunction with other therapies, beginning with the initial diagnosis of the disease.

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.

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.

Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial.

BACKGROUND: Increased oxidative stress is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). We postulated that treatment with the antioxidant N-acetylcysteine would reduce the rate of lung-function decline, reduce yearly exacerbation rate, and improve outcomes. METHODS: In a randomised placebo-controlled study in 50 centres, 523 patients with COPD were randomly assigned to 600 mg daily N-acetylcysteine or placebo. Patients were followed for 3 years. Primary outcomes were yearly reduction in forced expiratory volume in 1 s (FEV1) and the number of exacerbations per year. Analysis was by intention to treat. FINDINGS: The yearly rate of decline in FEV1 did not differ between patients assigned N-acetylcysteine and those assigned placebo (54 mL [SE 6] vs 47 mL [6]; difference in slope between groups 8 mL [9]; 95% CI -25 to 10). The number of exacerbations per year did not differ between groups (1.25 [SD 1.35] vs 1.29 [SD 1.46]; hazard ratio 0.99 [95% CI 0.89-1.10, p=0.85]). Subgroup analysis suggested that the exacerbation rate might be reduced with N acetylcysteine in patients not treated with inhaled corticosteroids and secondary analysis was suggestive of an effect on hyperinflation. INTERPRETATION: N-acetylcysteine is ineffective at prevention of deterioration in lung function and prevention of exacerbations in patients with COPD.

[Inhaled corticosteroid therapy in adults with asthma. Current evidences]. / Attuali concetti sull'uso dei corticosteroidi per via inalatoria nella terapia dell'asma dell'adulto.

Different international guidelines recommend the early introduction of inhaled corticosteroids (ICS) and their regular use to gain clinical and functional control of persistent asthma. There is now evidence that the starting dose of all ICS is lower than previously regarded. Initial moderate ICS doses appear to be more effective than an initial low ICS dose. The lowest effective dose should always be seeked by a step-down procedure. More than 90% of benefit is achieved by approximately a daily regular dose of 200 microg of fluticasone or 400 microg of beclomethasone or budesonide. The beneficial effects of increasing the dose of ICS alone appear to be modest in most cases. Intermittent ICS therapy has been successfully used in the long term treatment of mild asthma. In general, twice-daily administration of ICS provides greater therapeutic benefit than a once-daily regimen in moderate asthma. When asthma control has been obtained, a once-daily regimen can be tried. In clinical practice, this has the potential advantage of increasing patients' compliance. Chlorofluorocarbon-free formulations of old ICS have also remarkably improved their clinical efficacy mainly through an increased peripheral deposition pattern. Despite some limitations due to poor response in neutrophilic asthma and to potential systemic side effects, ICS will certainly be the cornerstone of asthma therapy even the next future.

The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*.

Respiratory diseases in Italy already now represent an emergency (they are the 3(rd) ranking cause of death in the world, and the 2(nd) if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual's risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable to the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document "Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)" of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document - produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise -after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,'case-finding'approach; assessment of the individual's level of risk of COPD; use of short questionnaires for an initial screening based on symptoms; use of simple spirometry for the second level of screening); b) it identifies possible ways of including these activities within primary care practice; c) it places early diagnosis within the "systemic", consequential management of chronic respiratory diseases, which will be briefly described with the aid of schemes taken from the Italian and international reference documents.

Inhaler mishandling is very common in patients with chronic airflow obstruction and long-term home nebuliser use.

Inhalers and nebulisers are devices used for delivering aerosolised drugs in subjects with Chronic Airflow Obstruction (CAO). This multicentre, cross-sectional observational study was performed in a large population of outpatients with CAO regularly using home aerosol therapy and referring to chest clinics. The aims of the study were to compare the characteristics of the group of subjects with CAO who were using home nebulisers but also experienced with inhalers vs. those only using inhalers and to investigate whether the first group of subjects was particularly prone to inhaler misuse. Information was gained evaluating the responses to a standardised questionnaire on home aerosol therapy and the observations of inhaler technique. We enrolled 1527 patients (58% males; mean ± SE; aged 61.1 ± 0.4 years; FEV1% pred 69.9 ± 0.6; 51% and 44% respectively suffering from COPD and asthma) who were only inhaler users (OIU group) and 137 (85% males; aged 67.7 ± 1.3 years; FEV1% pred 62.3 ± 2.9; 60% and 23% respectively suffering from COPD and asthma) who were using both nebulisers and inhalers (NIU group). Nebuliser users were older, had more severe obstruction, related symptoms and health care resources utilisation. Nebulisers users performed more critical inhalers errors than those of the OIU group (49% vs. 36%; p = 0.009). We conclude that our patients with CAO and regular nebuliser treatment had advanced age, severe respiratory conditions and common inhaler misuse.

Smoking cessation in patients requiring bronchoscopy: the Bronchoscopy AntiSmoking Study (BASIS).

We investigated the readiness to quit and the smoking cessation rates of smokers requiring bronchoscopy and receiving advice quitting. This randomized controlled trial evaluated the effectiveness of two smoking cessation interventions, either a brief advice (control group), or a longer support, delivered at the time of bronchoscopy. We consecutively enrolled 233 adult smokers, regardless of the initial level of motivation to quit. Their mean (SD) age was 57 (12) years; males were 192. They had smoked a median of 44.5 pack-years. Their mean (SD) Fagerstrom score was 8 (2). There was no difference between groups. Surprisingly, 45% of participants were in the action stage at baseline; these 105 subjects had quit in the week immediately prior to the bronchoscopy. At 6- and 12-months follow-up visits, respectively 41% and 29% of participants in the intervention group and 27% and 13% in the control group objectively showed a 1-week point prevalence abstinence. The difference was significant at 6 months (p<0.05) but not at 1-year visit (p=0.052), even if there was a trend towards greater cessation rate in the intervention group. In multivariable logistic models, at the final visit being a quitter was positively associated with having been in the action stage at baseline and negatively with the Fagerstrom score and the presence of smokers in household. We conclude that the time of bronchoscopy may possibly predispose smokers to quit. Further efforts are needed to clear whether more protracted support might achieve higher long-term smoking cessation rates.

Changes in lung function and respiratory muscle strength after sternotomy vs. laparotomy in patients without ventilatory limitation.

A relevant ventilatory defect occurs after sternotomy, a very common thoracic surgical opening. The mechanism of the ventilatory impairment is unclear. Moreover, until now, the effect of sternotomy on pulmonary gas exchange has scarcely been investigated. We evaluated the time-course up to recovery and changes in spirometry, maximum static inspiratory (PI(max)) and expiratory (PE(max)) mouth pressures and pulmonary gas exchange in 6 patients after sternotomy and in 8 patients after laparotomy. All patients were free of cardiopulmonary diseases and had normal preoperative lung function. Sternotomy and laparotomy decreased forced vital capacity (FVC) by 67 and 49%, respectively. Moreover, the percent decreases in PI(max), PE(max) and PaO(2) after sternotomy vs. laparotomy were respectively 54 vs. 57%, 54 vs. 60%, and 22.6 vs. 7.5% (p < 0.05). Following sternotomy, the percent decreases in FVC correlated with the percent decreases in PI(max) (p < 0.05) and PE(max) (p < 0.01). The return to baseline values occurred after approximately 2 weeks. The present study shows that sternotomy can induce greater respiratory effects than laparotomy and suggests a relevant involvement of respiratory muscle weakness after surgical opening of the thorax. The study also supports the view that the evaluation of patient's lung function before sternotomy can be clinically relevant.

Assessment of breathlessness perception by Borg scale in asthmatic patients: reproducibility and applicability to different stimuli.

In asthmatics, the score of bronchoconstriction-associated breathlessness at 20% fall in forced expiratory volume at first second (FEV1) evaluated on a Borg scale (PS20) is a tool successfully used to measure the perception of symptoms. This prospective laboratory study evaluated the applicability of PS20 to assess the breathlessness induced by ultrasonically nebulized distilled water (UNDW) and methacholine (M) and its reproducibility. Twenty-two mild and clinically stable asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated by linear interpolation of the last two points of the perception/fall in FEV1 curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did not differ and were respectively 1.82 +/- 1.85 and 2.03 +/- 1.86. They were significantly related (rs=0.63; p<0.01) and the bias between PS20 UNDW and PS20 M was -0.21 with the limits of agreement ranging from -3.2 to 3.6. The intraclass correlation coefficient for repeated measurement of PS20 M was 0.82; the bias between the two measurements was 0.2 with the limits of agreement ranging from -2.8 to 3.2. All patients had a measurable breathlessness perception degree on a Borg scale during both distilled water challenges and methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness perception were also similar for both stimuli. In addition, PS20 showed a good reproducibility and this allows the serial evaluation of patient's breathlessness perception by this technique in clinical settings and in the physiology laboratory.

Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone.

We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 microg twice a day) or high-dose (500 microg twice a day) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 patients with mild to moderate asthma. We also studied the effect on the inflammatory cells and the basement membrane thickness, and we compared findings from bronchial biopsies taken in patients with asthma with those in eight control subjects. Bronchial responsiveness to methacholine and asthma symptom score were measured before and after treatments. Eight patients in the low-dose FP group and eight patients in high-dose FP group completed the study. At baseline, patients with asthma showed an increase in the number of vessels and in vascular area as compared with control subjects. In the subjects with asthma, number of vessels correlated with vascular area (p < 0.01) and with number of mast cells (p < 0.01). Bronchial responsiveness to methacholine, asthma symptom score, and inflammatory cells decreased significantly after both low- and high-dose FP (p < 0.05). However, the number of vessels, the vascular area, and the basement membrane thickness decreased only after high-dose FP (p < 0.05). In conclusion, this study shows that in patients with mild to moderate asthma, high dose of inhaled FP given over 6 weeks can significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.