Asthma remission one, none and one-hundred thousand: the relevance of the patient's view.

OBJECTIVE: Achieving remission in severe asthma holds paramount importance in elevating patient quality of life and reducing both individual and societal burdens associated with this chronic condition. This study centers on identifying pivotal patient-relevant endpoints through standardized, reproducible methods, while also developing a patient-centric definition of remission, essential for effective disease management. METHODS: A discrete choice experiment (DCE) was conducted to assess patients' perceptions on the four primary criteria for defining severe asthma remission, as outlined by the SANI survey. Additionally, it investigated the correlation between these perceptions and improvements in the doctor-patient therapeutic alliance during treatment decision-making. RESULTS: 249 patients (70% aged between 31-60, 59% women and 82% without other pathologies requiring corticosteroids) prioritize the use of oral corticosteroids (OCS, 48%) and the Asthma Control Test (ACT, 27%) in defining their condition, ranking these above lung function and exacerbations. This preference for OCS stems from its direct role in treatment, tangible tracking, immediate symptom relief, and being a concrete measure of disease severity compared to the less predictable and quantifiable exacerbations. CONCLUSIONS: This study explores severe asthma remission from patients' perspectives using clinician-evaluated parameters. The DCE revealed that most patients highly value OCS and the ACT, prefer moderate improvement, and avoid cortisone cycles. No definitive preference was found for lung function status. Integrating patient-reported information with professional insights is crucial for effective management and future research. Personalized treatment plans focusing on patient preferences, adherence, and alternative therapies aim to achieve remission and enhance quality of life.

Lung vascular changes as biomarkers of severity in systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features. METHODS: SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted. RESULTS: A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s.d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of <6 mm in diameter. Considering radiological and functional criteria concomitantly, as well as the descriptive trends from the longitudinal evaluations, the normalized PVVs, vessel numbers and densities increased progressively with the increase/worsening of ILD extent and functional impairment. CONCLUSION: In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity.

Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial.

OBJECTIVES: Cardiovascular disease (CVD), lung cancer (LC), and respiratory diseases are main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening. We assessed whether quantification of pulmonary emphysematous changes at baseline LDCT has a predictive value concerning long-term mortality. METHODS: In this longitudinal study, we assessed pulmonary emphysematous changes with densitometry (volume corrected relative area below - 950 Hounsfield units) and coronary artery calcifications (CAC) with a 0-3 visual scale in baseline LDCT of 524 participants in the ITALUNG trial and analyzed their association with mortality after 13.6 years of follow-up using conventional statistics and a machine learning approach. RESULTS: Pulmonary emphysematous changes were present in 32.3% of subjects and were mild (6% ≤ RA950 ≤ 9%) in 14.9% and moderate-severe (RA950 > 9%) in 17.4%. CAC were present in 67% of subjects (mild in 34.7%, moderate-severe in 32.2%). In the follow-up, 81 (15.4%) subjects died (20 of LC, 28 of other cancers, 15 of CVD, 4 of respiratory disease, and 14 of other conditions). After adjusting for age, sex, smoking history, and CAC, moderate-severe emphysema was significantly associated with overall (OR 2.22; 95CI 1.34-3.70) and CVD (OR 3.66; 95CI 1.21-11.04) mortality. Machine learning showed that RA950 was the best single feature predictive of overall and CVD mortality. CONCLUSIONS: Moderate-severe pulmonary emphysematous changes are an independent predictor of long-term overall and CVD mortality in subjects participating in LC screening and should be incorporated in the post-test calculation of the individual mortality risk profile. KEY POINTS: • Densitometry allows quantification of pulmonary emphysematous changes in low-dose CT examinations for lung cancer screening. • Emphysematous lung density changes are an independent predictor of long-term overall and cardio-vascular disease mortality in smokers and former smokers undergoing screening. • Emphysematous changes quantification should be included in the post-test calculation of the individual mortality risk profile.

Mepolizumab Effectiveness and Allergic Status in Real Life.

BACKGROUND: It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life. OBJECTIVE: We tested mepolizumab effectiveness in allergic/nonallergic SEA in real life. A strict criterion to identify the 2 phenotypes was used. METHOD: We retrospectively considered 134 consecutive patients divided into allergic, with a positivity to at least 1 allergen to prick tests and/or IgE values ≥100 UI/mL (severe allergic eosinophilic asthma [SAEA]; n: 97-72.4%), and nonallergic, with no prick test results and normal IgE levels <100 UI/mL (severe nonallergic eosinophilic asthma [SNAEA]; n: 37-27.6%). They had taken mepolizumab for at least 6 months. RESULTS: After 10.9 ± 3.7 months, improvements in FEV1%, FEF25-75%, exacerbation numbers, blood eosinophil (BE) counts, fractional exhaled nitric oxide (FENO) (ppb), percentages of patients that stopped/reduced short-acting ß2-agonists (SABAs) or oral corticosteroid (OC), observed after treatment, were similar in both groups. Only Asthma Control Test (ACT) increases were higher in SNAEA (8 [5-9]) than in SAEA (5 [2.5-8.5]; p = 0.016). However, no differences were found after treatment in percentages of subjects with ACT ≥20, as well as with FEV1 >80%, FEF25-75 >65%, exacerbations ≤2, BE <300 cells/µL, and FENO <25 ppb between SAEA and SNAEA. Besides, no significant relationships were found, comparing SNAEA with SAEA, for FEV1% (ß = -0.110; p = 0.266), FEF25-75% (ß = -0.228; p = 0.06), BE counts (ß = -0.012; p = 0.918), FENO (ß = 0.234; p = 0.085), ACT (ß = 0.046; p = 0.660), and exacerbations (ß = -0.070; p = 0.437). No different associations between lung function and SNAEA occurrence when compared to SAEA condition (FEV1 >80%: OR = 1.04 [95% CI: 0.43-2.55], p = 0.923; FEF25-75 >65%: OR = 0.41 [95% CI: 0.08-2.03], p = 0.272) were detected. Neither all other parameters, such as ACT >20 (OR = 0.73 [95% CI: 0.32-1.63], p = 0.440), presence of exacerbations (OR = 1.35 [95% CI: 0.55-3.27], p = 0.512), SABA discontinuation (OR = 1.16 [95% CI: 0.40-3.39], p = 0.790), and OC cessation/reduction (OR = 3.44 [95% CI: 0.40-29.27], p = 0.258), were differently associated with 1 or the other phenotype. CONCLUSION: Mepolizumab can be considered as a valid therapeutic choice for either allergic or nonallergic SEA in real life.

Discriminant Profiles of Volatile Compounds in the Alveolar Air of Patients with Squamous Cell Lung Cancer, Lung Adenocarcinoma or Colon Cancer.

The objective of the present work was to analyze volatile compounds in alveolar air in patients with squamous cell lung cancer, lung adenocarcinoma or colon cancer, to prepare algorithms able to discriminate such specific pathological conditions. The concentration of 95 volatile com-pounds was measured in the alveolar air of 45 control subjects, 36 patients with lung adenocarci-noma, 25 patients with squamous cell lung cancer and 52 patients with colon cancer. Volatile compounds were measured with ion molecule reaction mass spectrometry (IMR-MS). An iterat-ed least absolute shrinkage and selection operator multivariate logistic regression model was used to generate specific algorithms and discriminate control subjects from patients with differ-ent kinds of cancer. The final predictive models reached the following performance: by using 11 compounds, patients with lung adenocarcinoma were identified with a sensitivity of 86% and specificity of 84%; nine compounds allowed us to identify patients with lung squamous cell car-cinoma with a sensitivity of 88% and specificity of 84%; patients with colon adenocarcinoma could be identified with a sensitivity of 96% and a specificity of 73% using a model comprising 13 volatile compounds. The different alveolar profiles of volatile compounds, obtained from pa-tients with three different kinds of cancer, suggest dissimilar biological-biochemistry condi-tions; each kind of cancer has probably got a specific alveolar profile.

Quantitative analysis of pulmonary vasculature in systemic sclerosis at spirometry-gated chest CT.

OBJECTIVE: To prospectively investigate whether differences in pulmonary vasculature exist in systemic sclerosis (SSc) and how they are distributed in patients with different pulmonary function. METHODS: Seventy-four patients with SSc undergoing chest CT scan for interstitial lung disease (ILD) screening or follow-up were prospectively enrolled. A thorough clinical, laboratory and functional evaluation was performed the same day. Chest CT was spirometry gated at total lung capacity and images were analysed by two automated software programs to quantify emphysema, ILD patterns (ground-glass, reticular, honeycombing), and pulmonary vascular volume (PVV). Patients were divided in restricted (FVC% <80, DLco%<80), isolated DLco% reduction (iDLco- FVC%≥80, DLco%<80) and normals (FVC%≥80, DLco%≥80). Spearman ρ, Mann-Whitney tests and logistic regressions were used to assess for correlations, differences among groups and relationships between continuous variables. RESULTS: Absolute and lung volume normalised PVV (PVV/LV) correlated inversely with functional parameters and positively with all ILD patterns (ρ=0.75 with ground glass, ρ=0.68 with reticular). PVV/LV was the only predictor of DLco at multivariate analysis (p=0.007). Meanwhile, the reticular pattern prevailed in peripheral regions and lower lung thirds, PVV/LV prevailed in central regions and middle lung thirds. iDLco group had a significantly higher PVV/LV (2.2%) than normal (1.6%), but lower than restricted ones (3.8%). CONCLUSIONS: Chest CT in SSc detects a progressive increase in PVV/LV as DLco decreases. Redistribution of perfusion to less affected lung regions rather than angiogenesis nearby fibrotic lung may explain the results. Further studies to ascertain whether the increase in PVV/LV reflects a real increase in blood volume are needed.

Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life.

BACKGROUND: Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life. METHODS: We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV1%:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months). RESULTS: FEV1% improved significantly after MEP. Mean FEF25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/µL (8.4 ± 5.2%) decreasing to 151 ± 384/µL (1.6 ± 1.6%) (p < 0.0001), FENO levels decreased likewise. MEP treatment also led to a significant ACT improvement (mean pre:14.2 ± 4.4; mean post:20.5 ± 28) and exacerbations significantly fell from 3.8 ± 1.9 to 0.8 ± 1.1 (p < 0.0001). 74% of patients were steroid-dependent before MEP. 45.4% and 46.4% of them showed a suspension and dose reduction respectively (p < 0.0001). A significant number reduced also ICS doses. Only 67% of subjects used SABA as needed before MEP, falling to 20% after MEP. About 40% of patients highlighted a maintenance therapy step-down. Subjects showing an omalizumab treatment failure before MEP had a similar positive response when compared with omalizumab untreated patients. CONCLUSION: In real-life, MEP improved significantly all outcomes even small airway obstruction, suggesting its possible role also in distal lung region treatment. Furthermore, it demonstrated its high effectiveness in OC/ICS-sparing, in reducing SABA as needed and in stepping-down maintenance therapy. MEP is a valid alternative for patients with previous omalizumab treatment failure.

Spirometric assessment of emphysema presence and severity as measured by quantitative CT and CT-based radiomics in COPD.

BACKGROUND: The mechanisms underlying airflow obstruction in COPD cannot be distinguished by standard spirometry. We ascertain whether mathematical modeling of airway biomechanical properties, as assessed from spirometry, could provide estimates of emphysema presence and severity, as quantified by computed tomography (CT) metrics and CT-based radiomics. METHODS: We quantified presence and severity of emphysema by standard CT metrics (VIDA) and co-registration analysis (ImbioLDA) of inspiratory-expiratory CT in 194 COPD patients who underwent pulmonary function testing. According to percentages of low attenuation area below - 950 Hounsfield Units (%LAA-950insp) patients were classified as having no emphysema (NE) with %LAA-950insp < 6, moderate emphysema (ME) with %LAA-950insp ≥ 6 and < 14, and severe emphysema (SE) with %LAA-950insp ≥ 14. We also obtained stratified clusters of emphysema CT features by an automated unsupervised radiomics approach (CALIPER). An emphysema severity index (ESI), derived from mathematical modeling of the maximum expiratory flow-volume curve descending limb, was compared with pulmonary function data and the three CT classifications of emphysema presence and severity as derived from CT metrics and radiomics. RESULTS: ESI mean values and pulmonary function data differed significantly in the subgroups with different emphysema degree classified by VIDA, ImbioLDA and CALIPER (p < 0.001 by ANOVA). ESI differentiated NE from ME/SE CT-classified patients (sensitivity 0.80, specificity 0.85, AUC 0.86) and SE from ME CT-classified patients (sensitivity 0.82, specificity 0.87, AUC 0.88). CONCLUSIONS: Presence and severity of emphysema in patients with COPD, as quantified by CT metrics and radiomics can be estimated by mathematical modeling of airway function as derived from standard spirometry.

Emphysematous and Nonemphysematous Gas Trapping in Chronic Obstructive Pulmonary Disease: Quantitative CT Findings and Pulmonary Function.

Purpose To identify a prevalent computed tomography (CT) subtype in patients with chronic obstructive pulmonary disease (COPD) by separating emphysematous from nonemphysematous contributions to total gas trapping and to attempt to predict and grade the emphysematous gas trapping by using clinical and functional data. Materials and Methods Two-hundred and two consecutive eligible patients (159 men and 43 women; mean age, 70 years [age range, 41-85 years]) were prospectively studied. Pulmonary function and CT data were acquired by pulmonologists and radiologists. Noncontrast agent-enhanced thoracic CT scans were acquired at full inspiration and expiration, and were quantitatively analyzed by using two software programs. CT parameters were set as follows: 120 kVp; 200 mAs; rotation time, 0.5 second; pitch, 1.1; section thickness, 0.75 mm; and reconstruction kernels, b31f and b70f. Gas trapping obtained by difference of inspiratory and expiratory CT density thresholds (percentage area with CT attenuation values less than -950 HU at inspiration and percentage area with CT attenuation values less than -856 HU at expiration) was compared with that obtained by coregistration analysis. A logistic regression model on the basis of anthropometric and functional data was cross-validated and trained to classify patients with COPD according to the relative contribution of emphysema to total gas trapping, as assessed at CT. Results Gas trapping obtained by difference of inspiratory and expiratory CT density thresholds was highly correlated (r = 0.99) with that obtained by coregistration analysis. Four groups of patients were distinguished according to the prevalent CT subtype: prevalent emphysematous gas trapping, prevalent functional gas trapping, mixed severe, and mixed mild. The predictive model included predicted forced expiratory volume in 1 second/vital capacity, percentage of predicted forced expiratory volume in 1 second, percentage of diffusing capacity for carbon monoxide, and body mass index as emphysema regressors at CT, with 81% overall accuracy in classifying patients according to its extent. Conclusion The relative contribution of emphysematous and nonemphysematous gas trapping obtained by coregistration of inspiratory and expiratory CT scanning can be determined accurately by difference of CT inspiratory and expiratory density thresholds. CT extent of emphysema can be predicted with accuracy suitable for clinical purposes by pulmonary function data and body mass index. © RSNA, 2018 Online supplemental material is available for this article.

Do COPD subtypes really exist? COPD heterogeneity and clustering in 10 independent cohorts.

BACKGROUND: COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of 'unbiased' data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there has been no systematic assessment of the reproducibility of these subtypes. OBJECTIVE: We performed clustering analyses across 10 cohorts in North America and Europe in order to assess the reproducibility of (1) correlation patterns of key COPD-related clinical characteristics and (2) clustering results. METHODS: We studied 17 146 individuals with COPD using identical methods and common COPD-related characteristics across cohorts (FEV1, FEV1/FVC, FVC, body mass index, Modified Medical Research Council score, asthma and cardiovascular comorbid disease). Correlation patterns between these clinical characteristics were assessed by principal components analysis (PCA). Cluster analysis was performed using k-medoids and hierarchical clustering, and concordance of clustering solutions was quantified with normalised mutual information (NMI), a metric that ranges from 0 to 1 with higher values indicating greater concordance. RESULTS: The reproducibility of COPD clustering subtypes across studies was modest (median NMI range 0.17-0.43). For methods that excluded individuals that did not clearly belong to any cluster, agreement was better but still suboptimal (median NMI range 0.32-0.60). Continuous representations of COPD clinical characteristics derived from PCA were much more consistent across studies. CONCLUSIONS: Identical clustering analyses across multiple COPD cohorts showed modest reproducibility. COPD heterogeneity is better characterised by continuous disease traits coexisting in varying degrees within the same individual, rather than by mutually exclusive COPD subtypes.

Chronic Obstructive Pulmonary Disease: Pulmonary Function and CT Lung Attenuation Do Not Show Linear Correlation.

PURPOSE: To determine whether the relationship between pulmonary function and computed tomographic (CT) lung attenuation in chronic obstructive pulmonary disease (COPD), which is traditionally described with single univariate and multivariate statistical models, could be more accurately described with a multiple model estimation approach. MATERIALS AND METHODS: The study was approved by the local ethics committee. All participants provided written informed consent. The prediction of the percentage area with CT attenuation values less than -950 HU at inspiration (%LAA-950insp) and less than -910 HU at expiration (%LAA-910exp) obtained with single univariate and multivariate models was compared with that obtained with a multiple model estimation approach in 132 patients with COPD. RESULTS: At univariate analysis, %LAA-950insp and %LAA-910exp values higher than the mean value of this cohort (19.1% and 22.0%) showed better correlation with percentage of predicted diffusing capacity of lung for carbon monoxide (Dlco%) than with airflow obstruction (forced expiratory volume in 1 second [FEV1]/vital capacity [VC]). Conversely, %LAA-950insp and %LAA-910exp values lower than the mean value were correlated with FEV1/VC but not with Dlco%. Multiple model estimation performed with two multivariate regressions, each selecting the most appropriate functional variables (FEV1/VC for mild parenchymal destruction, Dlco% and functional residual capacity for severe parenchymal destruction), predicted better than single multivariate regression both %LAA-950insp (R(2) = 0.75 vs 0.46) and %LAA-910exp (R(2) = 0.83 vs 0.63). CONCLUSION: The relationship between pulmonary function data and CT densitometric changes in COPD varies with the level of lung attenuation impairment. The nonlinear profile of this relationship is accurately predicted with a multiple model estimation approach.

Asthma control in severe asthmatics under treatment with omalizumab: a cross-sectional observational study in Italy.

Few data are available on the proportion of asthmatics achieving a good asthma control (according GINA guidelines) and on the level of airway inflammation during omalizumab treatment. The aim of this cross-sectional national observational study was to assess the level of control (according to GINA guidelines) achieved in a group of asthmatics on omalizumab treatment, and to characterize the factors that influence the lack of control. We studied 306 asthmatics under omalizumab treatment for a median of 32 months (range 4-120). The level of control according to GINA was good in 25.2%, partial in 47.1% and poor in 24.5% of patients (data were missing for the remaining 3.2%). Comparison between poorly controlled and partially or well controlled asthmatics showed a statistically significant higher prevalence of some comorbidities in the first group, namely obesity, gastro-oesophageal reflux disease (GORD), aspirin intolerance and mental disorders (all p < 0.001). Similarly, asthmatics with at least one exacerbation in the last year showed a significantly higher prevalence of obesity, chronic rhinosinusitis, nasal polyps, GORD, and aspirin intolerance (all p < 0.05) than patients without exacerbations. When we selected patients without relevant comorbidities (upper airways disease, GORD, obesity, aspirin intolerance) and not currently smoking (N = 73), the percentage of well or partially controlled asthmatics was significantly higher than in patients with comorbidities (84.9% vs 71.1%, p = 0.02); the rate of asthmatics without exacerbations in the last year was also higher (73.6% vs 51.1%, p = 0.001). During omalizumab treatment, a high percentage of asthmatics obtain a good or partial control of asthma. Comorbidities are associated with the lack of asthma control and persistence of exacerbations.

TRITRIAL: The Impact of Fixed Triple Therapy with Beclometasone/Formoterol/Glycopyrronium on Health Status and Adherence in Chronic Obstructive Pulmonary Disease in an Italian Context of Real Life.

Purpose: The TRITRIAL study assessed the effects of beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed combination in patients with chronic obstructive pulmonary disease (COPD) in a real-world setting, focusing on patient's experience and perspective through the use of patients reported outcomes. Patients and Methods: TRITRIAL was a multicenter, prospective, observational study conducted on patients with moderate-severe COPD treated with BDP/FF/G fixed therapy for 12 months. The main objective was to evaluate the impact of BDP/FF/G on health status through the COPD Assessment Test (CAT) score. Additional assessments included adherence and satisfaction, measured by the TAI-10/12 questionnaire and a specifically designed eight-item questionnaire, quality of life through the EQ-5D-5L test, sleep quality through the COPD and Asthma Sleep Impact Scale (CASIS), as well as safety and disease-related outcomes. Results: Data from 655 patients were analyzed in the study. The mean total CAT score significantly improved (from 22.8 at baseline to 18.1 at 6 months and 16.5 at 12 months; p < 0.0001), as well as all the eight CAT sub-items, which decreased on average by 0.5-0.9 points during the study. Adherence and usability of the inhaler also improved during the study, with a decrease in poor compliance (from 30.1% to 18.3%) and an increase in good compliance (from 51.8% to 58.3%) according to the TAI score. Patients also benefited from significantly improved quality of life (EQ Index from 0.70 to 0.80; EQ-5D VAS score from 55.1 to 63.1) and sleep quality (CASIS score from 41.1 to 31.8). Finally, patients reported a significant reduction in exacerbation during the study. Conclusion: TRITRIAL showed that the BDP/FF/G fixed combination is effective and safe in patients with moderate-severe COPD and poorly controlled disease, improving patients' HRQoL, sleep quality, adherence and inhaler usability and reducing COPD symptoms and the risk of exacerbation in a real-life setting.

Pulmonary function and sputum characteristics predict computed tomography phenotype and severity of COPD.

Airway obstruction and parenchymal destruction underlie phenotype and severity in chronic obstructive pulmonary disease (COPD). We aimed to predict, by clinical and pulmonary function data, the predominant type and severity of pathological changes quantitatively assessed by computed tomography (CT). Airway wall thickness (AWT-Pi10) and percentage of lung area with X-ray attenuation values <-950 HU (%LAA-950) were measured in 100 (learning set) out of 473 COPD outpatients undergoing clinical and functional evaluation. Original CT measurements were translated by principal component analysis onto a plane with the novel coordinates CT1 and CT2, depending on the difference (prevalent mechanism of airflow limitation) and on the sum (severity) of AWT-Pi10 and %LAA-950, respectively. CT1 and CT2, estimated in the learning set by cross-validated models of clinical and functional variables, were used to classify 373 patients in the testing set. A model based on diffusing capacity of the lung for carbon monoxide, total lung capacity and purulent sputum predicted CT1 (r = 0.64; p<0.01). A model based on forced expiratory volume in 1 s/vital capacity, functional residual capacity and purulent sputum predicted CT2 (r = 0.77; p<0.01). Classification of patients in the testing set obtained by model-predicted CT1 and CT2 reflected, according to correlations with clinical and functional variables, both COPD phenotype and severity. Multivariate models based on pulmonary function variables and sputum purulence classify patients according to overall severity and predominant phenotype of COPD as assessed quantitatively by CT.

Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.

Low agreement of visual rating for detailed quantification of pulmonary emphysema in whole-lung CT.

BACKGROUND: Multidetector spiral computed tomography (CT) has opened the possibility of quantitative evaluation of emphysema extent in the whole lung. Visual assessment can be used for such a purpose, but its reproducibility has not been established. PURPOSE: To assess agreement of detailed assessment of pulmonary emphysema on whole-lung CT using a visual scale. MATERIAL AND METHODS: Thirty patients with chronic obstructive pulmonary disease underwent whole-lung inspiratory CT. Four chest radiologists rated the same 22 ± 2 thin sections using a visual scale which defines a range of emphysema extent between 0 and 100. Two of them repeated the rating two months later. Inter- and intra-operator agreement was evaluated with the Bland and Altman method. In addition, the percentage of emphysema at -950 Hounsfield units in the whole lung was determined using fully automated commercially available software for 3D densitometry. RESULTS: In three of six operator pairs and in one of two intra-operator pairs the Kendall τ test showed a significant correlation between the difference and the average magnitude of visual scores. Among different operators the half-width of 95% limits of agreement (95% LoA) was wide ranging between a score of 14.2-27.7 for an average visual score of 20 and between 18.5-36.8 for an average visual score of 80. Within the same operator the half-width of 95% LoA ranged between a score of 10.9-21.0 for an average visual score of 20 and between 25.1-30.1 for an average visual score of 80. The visual scores of the four radiologists were correlated with the results of densitometry (P < 0.001; r = 0.65-0.81). CONCLUSION: The inter- and intra-operator agreement of detailed assessment of emphysema in the whole lung using a visual scale is low and decreases with increasing emphysema extent.

BODE-index, modified BODE-index and ADO-score in chronic obstructive pulmonary disease: relationship with COPD phenotypes and CT lung density changes.

COPD is a heterogeneous disorder whose assessment is going to be increasingly multidimensional. Grading systems such as BODE (Body-Mass Index, Obstruction, Dyspnea, Exercise), mBODE (BODE modified in grading of walked distance), ADO (Age, Dyspnea, Obstruction) are proposed to assess COPD severity and outcome. Computed tomography (CT) is deemed to reflect COPD lung pathologic changes. We studied the relationship of multidimensional grading systems (MGS) with clinically determined COPD phenotypes and CT lung density. Seventy-two patients underwent clinical and chest x-ray evaluation, pulmonary function tests (PFT), 6-minute walking test (6MWT) to derive: predominant COPD clinical phenotype, BODE, mBODE, ADO. Inspiratory and expiratory CT was performed to calculate mean lung attenuation (MLA), relative area with density below-950 HU at inspiration (RAI(-950)), and below -910 HU at expiration (RAE(-910)). MGS, PFT, and CT data were compared between bronchial versus emphysematous COPD phenotype. MGS were correlated with CT data. The prediction of CT density by means of MGS was investigated by direct and stepwise multivariate regression. MGS did not differ in clinically determined COPD phenotypes. BODE was more closely related and better predicted CT findings than mBODE and ADO; the better predictive model was obtained for CT expiratory data; stepwise regression models of CT data did not include 6MWT distance; the dyspnea score MRC was included only to predict RA-950 and RA-910 which quantify emphysema extent. BODE reflect COPD severity better than other MGS, but not its clinical heterogeneity. 6MWT does not significantly increase BODE predictivity of CT lung density changes.

Patients and doctors group meetings: an innovative way to explore severe asthma backstage.

Severe asthma patients' life is heavily influenced by the disease, which has impact on personal and professional choices or general lifestyle. Despite the available tools to help physicians investigating the patient-reported outcomes there is a need for a more standardised and structured approach to include the evaluation of quality of life together with the emotions of patients into the routine clinical interaction. We hereby report the use of an active listening and insight approach to understand the emotions of patients with severe asthma through dedicated in-person meetings involving a group of patients with their doctors, caregivers and an external moderator. The initiative "Patients insight meeting" was organized within 17 specialist referral centres for severe asthma in Italy in 2019 and involved 149 patients. Insights related to 4 different items were collected and a task force composed by the external moderators produced a general report including the suggestions from the participating centres. This experience of group-meetings involving both patients and doctors together represents an innovative way to investigate real life experience and the emotions of asthmatic patients, highlighting unmet needs related to patient's experience of his/her disease that need to be included in severe asthmatics' management strategy.

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI).

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

Whole-lung densitometry versus visual assessment of emphysema.

We compared whole-lung densitometry with visual evaluation of pulmonary emphysema. Thirty patients with chronic obstructive pulmonary disease underwent multi-detector CT (150 mAs and 0.75 collimation) with double reconstruction: thick (5-mm) slices with smooth filter for whole-lung densitometry and thin (1 mm) slices with sharp filter for visual assessment (one of every ten slices). Densitometry and visual assessment were performed by three operators each, and the time required for assessment, the inter-observer agreement and the correlation with the results of the diffusion capacity of carbon monoxide (DL(CO)) in the same patients were computed. The average time for densitometry (8.49 +/- 0.13 min) was significantly longer (p < 0.0001) than that for visual evaluation (5.14 +/- 0.11 min). However, the inter-operator agreement ranged between "moderate" to "almost perfect" for densitometry (kappa range 0.58-0.87) and "slight" for visual (kappa = 0.20) assessment. The correlation coefficients of DL(CO) with relative area at -960 and -970 Hounsfield units (HU) (both r = -0.66) and of the first percentile point of lung density (r = 0.66) were slightly stronger than that of the visual score (r = -0.62). Densitometry should be preferred to visual assessment because it enables a more reproducible evaluation of the extent of pulmonary emphysema, which can be carried out on the entire lung in a reasonable amount of time.