SANI Clinical Remission definition: a useful tool in Severe Asthma management.

In the field of severe asthma, the concept of disease control has recently been integrated by the one of clinical remission. With this new concept, we move on to analyze the efficacy of therapy on multiple parameters simultaneously, starting with the mandatory discontinuation of the systemic glucocorticoids, to which is added the effect on exacerbations, respiratory function, and symptoms control. The Italian severe asthma registry SANI (Severe Asthma Network Italy) drafted criteria for the definition of disease remission, allowing patients to be classified into two groups, partial and complete remission. The greater dynamism of the definition, provided by SANI, allows us to hypothesize its practical use, concerning therapy management of severe asthma patients, starting from the level of remission, with the aim to facilitate the clinical decision on replacement, continuation or modulation of patients' therapy.

T2-High Endotype and Response to Biological Treatments in Patients with Bronchiectasis.

Although bronchiectasis pathophysiology has been historically understood around the presence of airway neutrophilic inflammation, recent experiences are consistent with the identification of a type 2 inflammation (T2) high endotype in bronchiectasis. In order to evaluate prevalence and clinical characteristics of bronchiectasis patients with a T2-high endotype and explore their response to biologicals, two studies were carried out. In a cross-sectional study, bronchiectasis adults without asthma underwent clinical, radiological, and microbiological assessment, along with blood eosinophils and oral fractional exhaled nitric oxide (FeNO) evaluation, during stable state. Prevalence and characteristics of patients with a T2- high endotype (defined by the presence of either eosinophils blood count ≥300 cells·µL-1 or oral FeNO ≥ 25 dpp) were reported. A case series of severe asthmatic patients with concomitant bronchiectasis treated with either mepolizumab or benralizumab was evaluated, and patients' clinical data pre- and post-treatment were analyzed up to 2 years of follow up. Among bronchiectasis patients without asthma enrolled in the cross-sectional study, a T2-high endotype was present in 31% of them. These patients exhibited a more severe disease, high dyspnea severity, low respiratory function, and high impact on quality of life. Among the five patients with severe eosinophilic asthma and concomitant bronchiectasis included in the series, treatment with either mepolizumab or benralizumab significantly reduced the exacerbation rate with an effect that persists for up to 2 years of follow up. If validated across different settings, our data suggest the need to design randomized controlled trials on biological treatments targeting the T2-high endotype in bronchiectasis patients.

COVID-19 multidisciplinary high dependency unit: the Milan model.

COVID-19 is a complex and heterogeneous disease. The pathogenesis and the complications of the disease are not fully elucidated, and increasing evidence shows that SARS-CoV-2 causes a systemic inflammatory disease rather than a pulmonary disease. The management of hospitalized patients in COVID-19 dedicated units is advisable for segregation purpose as well as for infection control. In this article we present the standard operating procedures of our COVID-19 high dependency unit of the Policlinico Hospital, in Milan. Our high dependency unit is based on a multidisciplinary approach. We think that the multidisciplinary involvement of several figures can better identify treatable traits of COVID-19 disease, early identify patients who can quickly deteriorate, particularly patients with multiple comorbidities, and better manage complications related to off-label treatments. Although no generalizable to other hospitals and different healthcare settings, we think that our experience and our point of view can be helpful for countries and hospitals that are now starting to face the COVID-19 outbreak.

Once daily aerosolised tobramycin in adult patients with cystic fibrosis in the management of Pseudomonas aeruginosa chronic infection.

It is estimated that about 60-70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection, with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic to be used against P. aeruginosa; inhalatory tobramycin frequency of administration is twice daily and inhalation time is estimated to be 15 to 20 min. From the pharmacokinetic point of view, aminoglycosides are dose-dependent antibiotics and therefore once-daily dosing intravenous regimens have shown to be superior to the conventional multiple daily dosing. Therefore, there is no pharmacological reason to prefer the b.i.d administration as it is usually performed in current clinical practice. Should this be confirmed also for inhalatory route, the use of once-daily dosed aerosolized tobramycin could be an important step in making treatment burden easier in CF patients. The aim of this proof of concept study was to explore the effectiveness of treatment with once daily inhaled tobramycin in reducing P. aeruginos a density in sputum of chronically infected patients.

Cardiovascular autonomic alterations in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Alterations of cardiac autonomic control (CAC) are associated with poor outcomes in patients with infectious and non-infectious diseases. No evaluation of CAC in patients with community-acquired pneumonia (CAP) has been performed so far. The aim of the study was to assess CAC in patients with CAP and evaluate the impact of its alterations on disease severity and clinical outcomes in a multicenter, prospective, observational study. METHODS: Consecutive patients hospitalized for CAP were enrolled between 2011 and 2013 two university hospitals in Italy. CAC was assessed by linear spectral and non-linear symbolic analysis of heart rate variability. The presence of severe CAP was evaluated on hospital admission. The primary study outcome was time to clinical stability (TCS) during hospitalization. RESULTS: Among the 75 patients enrolled (median age: 75 years; 57 % males), a significantly lower total variability and reduction of sympathetic rhythmical component with predominant respiratory modulation was detected in comparison to controls. Among CAP patients affected by a severe CAP on admission, CAC showed a lower sympathetic modulation and predominant parasympathetic oscillatory rhythm. At the multivariate analysis, variables independently correlated with a TCS >7 days were total power, as marker of total variability, [OR (95 % CI): 0.997 (0.994-1.000), p = 0.0454] and sympathetic modulation [OR (95 % CI): 0.964 (0.932-0.998), p = 0.0367]. CONCLUSIONS: Loss of sympathetic rhythmical oscillation is associated with a more severe disease and worse early clinical outcome in hospitalized patients with CAP.

Clinical expression of patients with the D1152H CFTR mutation.

BACKGROUND: Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. METHODS: A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. RESULTS: 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. CONCLUSIONS: The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans.

Rapid on-site evaluation improves needle aspiration sensitivity in the diagnosis of central lung cancers: a randomized trial.

BACKGROUND: Few prospective studies have evaluated the role of endobronchial needle aspiration in diagnosing central airways neoplasms. Rapid on-site evaluation has long been used in transbronchial needle aspiration of adenopathies and peripheral lesions, but its role in sampling central malignancies has not been substantiated yet. OBJECTIVES: In this study we evaluated if endobronchial needle aspiration may increase the sensitivity of bronchoscopy for diagnosing central airways neoplasms when added to conventional diagnostic methods (forceps biopsy, brushing and bronchial washing), and if rapid on-site evaluation may be beneficial in patients undergoing endobronchial needle aspiration. METHODS: 125 patients (77% males, aged 70 ± 7 years; mean ± SD) with central lung cancers were randomized to undergo bronchoscopy including conventional diagnostic methods and needle aspiration, with or without rapid on-site evaluation, stratifying the patients on the basis of the neoplasm growth pattern (exophytic and submucosal/peribronchial disease). RESULTS: Needle aspiration significantly increased the sensitivity of bronchoscopy when added to conventional methods (from 76 to 91%; p < 0.001), primarily resulting from differences in submucosal/peribronchial diseases (68 vs. 90%; p < 0.001) and independently from the presence of rapid on-site evaluation; needle aspiration guided by rapid on-site evaluation guaranteed a higher improvement in bronchoscopy sensitivity than conventional needle aspiration (98 vs. 84%, respectively; p = 0.004). Needle aspiration guided by rapid on-site evaluation showed a significantly higher sensitivity than the conventional method (97 vs. 76%, respectively; p = 0.001). CONCLUSIONS: Needle aspiration increases the sensitivity of bronchoscopy in diagnosing central airways malignancies when added to conventional diagnostic methods, with a further significant improvement when guided by rapid on-site evaluation.

Acute effects of higher than standard doses of salbutamol and ipratropium on tiotropium-induced bronchodilation in patients with stable COPD.

Knowledge on the effects of the additive bronchodilatory effects of short-acting agents on the top of the effect of long-acting bronchodilators is limited. In this trial, we examined the influence of higher than conventional doses of the short-acting inhaled beta(2)-adrenergic agent salbutamol and the short-acting anticholinergic drug ipratropium bromide on bronchodilation induced by a regular treatment with the long-acting anticholinergic drug tiotropium 18 microg/day in 30 patients with stable COPD. On 3 separate days, a dose-response curve to inhaled salbutamol (100 microg puff-1), ipratropium bromide (20 microg puff-1) or placebo was constructed 3h after inhalation of the last dose of tiotropium, using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 microg salbutamol or 120 microg ipratropium bromide. Doses were given at 30-min intervals and measurements made 15 min after each dose. At the highest cumulative dose, salbutamol showed a trend to be more effective than ipratropium bromide in improving FEV(1) (0.157 L vs 0.125 L), and reducing sRaw (-4.52 kPa/s vs 3.57 kPa/s), although the differences between the two treatments were always not significant (p>0.05), whereas there was no substantial difference between the two drugs in changing FVC (0.179 L vs 0.168 L), IC (0.254 L vs 0.240 L), TGV (-0.444 L vs -0.441 L), TLC (-0.334 L vs -0.318 L) and RV (-0.467 L vs -0.498 L). Both drugs did not affect heart rate and SpO2. Our results indicate that there is not much difference in bronchodilation between adding higher than conventional doses of salbutamol or ipratropium bromide to tiotropium in patients with stable COPD. Effective improvement of the pulmonary function may be achieved in such a type of patients by adding salbutamol 600 microg or ipratropium bromide 120 microg to regular tiotropium. These is an interesting finding mainly for those COPD patients suffering from cardiovascular co-morbidities that are at highest risk of myocardial infarction, congestive heart failure, cardiac arrest and sudden cardiac death when treated with elevated doses of a beta(2)-agonist (EudraCT number: 2007-001597-82).