BACKGROUND:Asthma can present in early childhood or de novo in adulthood. Our understanding of the burden of comorbidities in adult asthmatic patients stratified by age at onset is incomplete. OBJECTIVES:To evaluate how different comorbidities may affect symptom control in two distinct groups of patients with early- and late-onset asthma (EOA and LOA, respectively) and to explore whether reported comorbidities are associated with lung function and inflammatory parameters. METHODS:We conducted a cross-sectional study of 175 adult asthmatic patients (aged 57.5 ± 17.1 years) recruited at our university asthma clinic. We defined EOA as asthma onset less than 12 years, and LOA as onset greater than 40 years. The primary outcome was symptom control and main comorbidities evaluated were rhinitis, gastroesophageal reflux, obesity, cardiovascular conditions, and bronchiectasis. We used multivariable regression analysis to identify potential predictors of poor control in EOA and LOA. RESULTS:Of 175 subjects, 77 had EOA (44%), 98 had LOA (56%), and comorbidities had a differential impact in the two groups. Rhinitis was more frequent in EOA (76 vs 53%; P = .02) and was associated with uncontrolled asthma (P < .001), reduced FEV1/FVC (P = .01), increased eosinophils (P = .003) and total IgE (P < .01). Conversely, in LOA, rhinitis was associated with more controlled asthma and higher FEV1/FVC (both P < .01). In EOA, only, IgE levels were directly related to blood eosinophils (r = 0.42; P <.001) and inversely to FEV1/FVC (r = -0.35; P = .002). Obesity was present in 20% of patients in both groups, but only in LOA was it associated with uncontrolled disease (P = .009), reduced FEV1/FVC (P = .009), and blood neutrophils (P = .03). In multivariable regression analysis, rhinitis in EOA and obesity in LOA were the risk factors most closely associated with poor control. Gastroesophageal reflux, cardiovascular comorbidities, and bronchiectasis did not affect control. CONCLUSIONS:Early-onset persistent asthma and late-onset asthma are distinct phenotypes with different underlying inflammatory patterns and different comorbidities affecting symptom control.

Background: Age of asthma onset may have significant pathogenetic implications. While early and late phenotypes have been well studied, intermediate onset-asthma is not well understood. Aim: To investigate the impact of comorbidities, smoking history and inflammatory phenotypes on asthma control (GINA) in patients stratified by age of onset. Methods: In a cohort of 250 patients(54±16 yr) followed at the asthma clinic 3 clusters were defined: early-onset asthma(EA)<12 yr; intermediate asthma(IA) 12-40 yr; late-onset asthma(LA)>40 yr. Results: 77/250 (30%) subjects had EA, 76 (30%) IA and 98 (39%) LA. EA was different from LA, with more rhinitis (76vs53%, p=0.02) which was associated to worse asthma control (p=0.01) and lower FEV1/FVC (74±10vs83±7%;p=0.01); EA also had more eosinophils (0.36±0.3 vs 0.14±0.1 x109/L;p<0.01) and IgE (441±635vs71±76KU/L;p<0.01). LA patients had more neutrophils (4.2±1.5vs3.3±1.1x109/L;p=0.01) particularly when obese. Obesity in LA was associated to worse control (p=0.009) and lower FEV1/FVC (73±9vs80±10;p=0.009). IA was an intermediate phenotype, with both eosinophilic (0.31±0.3x109/L) and neutrophilic (4±1.4x109/L) patterns. In IA obesity, but not rhinitis, was associated to worse control (p=0.003), lower FEV1/FVC (71±10vs79±10; p=0.03) and neutrophilic inflammation. Of note, smoking history and environmental exposure were associated to worse control in IA (p<0.001, p=0.04) but not in EA and LA. Conclusions: Early, intermediate and late-onset asthma are distinct phenotypes. In our population IA showed a combination of EA and LA features and a mixed eosinophilic/neutrophilic pattern. Differently from EA and LA, in IA asthma control is influenced by smoking and environmental exposure.

Introduction: Acute cellular rejection (ACR) and infection are significant causes of morbidity and mortality in transplanted recipients. The use of scheduled post-transplant biopsies (SPB) remains controversial because of its risk-benefit ratio compared to biopsies on clinical demand. Cystic fibrosis (CF) recipients have a higher risk of early immunological complications (ACR and antibody mediated rejection) compared to other diseases. Few studies have evaluated the effectiveness and safety of SPB in CF, with special regard to the time period elapsed from lung transplantation (LTx). Aim: To investigate the incidence of ACR and microbial infection in CF recipients, the safety and adequacy of SPB in detecting ACR and whether the time after LTx may influence these results. Methods: A single-centre retrospective analysis was performed on CF patients who underwent SPB for LTx between January 2019 and December 2020. The time after LTx was recorded in each patient. Results: 92 SPB were performed with a median time after LTx of 24 months (range 1-148). 89(97%) had adequate samples, and ACR was diagnosed in 13 procedures (11%). 3(3.2%) pneumothorax and 3(3.2%) major bleeding were reported. ACR and complication incidence were similar when considering the different time period elapsed from LTx (0-1, 1-2, 2-3, 3-4 and >4 years). CF transplanted from >2 years had a significantly higher number of ACR that required treatment [8/8(100%) vs 2/5(46%), p=0.03] and a lower incidence of infections [5/46(11%) vs 14/46(30%), p=0.03] than those transplanted <2 years. Conclusions: In CF recipients, SPB is a safe and accurate procedure to identify ACR that should be routinely performed in transplant recipient follow-up.

Introduction: Malignant pleural effusion (PE) is a common complication of advanced malignancy, especially lung and breast cancer (BC). The incidence of pleural metastasis in BC is known to be higher within the first years from diagnosis and rarer after 10-12 years. Aim: To evaluate the incidence of ultra-late pleural metastasis in patients with breast cancer-related PE, and whether clinical aspects may be associated with this late recurrence. Methods: A single-centre retrospective study of all patients that underwent medical thoracoscopy for suspected malignant PE from 2013 to 2019 was performed. Ultra-late metastasis were defined as recurrence appearing later than 10 years from BC diagnosis. Data regarding BC histotype (Luminal A, Luminal B, HER2+ and triple negative), macroscopic pleural appearance (nodules or diffuse thickening), amount of PE (litres) and side of PE compared to primary BC were recorded. Results: Of the 491 patients evaluated, 40 (8%) had BC pleural involvement. Four (10%) had a first diagnosis of BC after thoracoscopy. Of the other 36 patients, 19 (52%) had BC diagnosed more than 10 years before, and 7 of them even more than 20. The amount of PE, macroscopic appearance, side of PE involvement and histotype were similar between those < or >10 years from BC. There was a significantly higher time to recurrence (months) in Luminal B compared to triple negative (166±101 vs 76±74; p=0.02) and a trend in diffuse pleural involvement compared to nodules (175.6±105.6 vs 114.3±84.5; p=0.08). Conclusions: Ultra-late pleural BC metastasis are not uncommon in our cohort of patients with breast cancer-related PE. Longer time to recurrence was found in Luminal B histotype and in diffuse pleural involvement.

Introduction: Surveillance bronchoscopy (SB) represents an important diagnostic tool in the follow-up and management of lung transplant (LTx) complications. Propofol, a short acting non‐opioid sedative–hypnotic, provides safe and effective sedation during bronchoscopy. However, the sedation requirements in transplanted patients and specially in cystic fibrosis (CF) have not been well determined. Aim: To evaluate whether CF recipients may require different amounts of intravenous propofol during SB compared to non-CF. Methods: A single-centre retrospective study of all transplanted patients undergoing SB from January to December 2019 was performed. Propofol was the only drug administered to achieve deep sedation. CF and non-CF recipients were compared regarding age, BMI and mean propofol dose. Results: 121 patients, 51 CF and 70 non-CF, were evaluated. Non-CF included patients with idiopathic pulmonary fibrosis (IPF, n=23), Chronic Obstructive Pulmonary Disease (COPD, n=17) and other diseases (n=30). CF patients were younger (33±11 vs 55±9; p<0.0001) and had lower BMI (23±3 vs 25±4; p=0.003) than non-CF. Moreover, the mean propofol dose per weight required in CF was significantly higher than non-CF (6±2 vs 3±1 mg/kg; p<0.0001), even when considered as single diseases (IPF p<0.0001, COPD p=0.0001 and OD p<0.0001). Multiple linear regression analysis including BMI, age and years from transplantation showed that having CF independently predicts propofol dosage (β=0.3; p=0.01). Conclusions: CF recipients required higher dosages of propofol during surveillance bronchoscopy compared to non-CF. The known enhanced clearances of many drugs, to which propofol should be added, very likely explain our results.

Background: Asthma can present in early age and progress through adulthood or de novo in adulthood. Aim: to investigate possible differences in pathogenetic and clinical features of early-onset asthma persisting into adulthood and late-onset asthma. Method: We conducted a cross-sectional study of 250 adult patients (54±16 years-old) recruited at our asthma clinic. We defined early-onset persistent asthma (EOA) as onset <12 years and late-onset asthma (LOA) as >40 years. Severity was graded by GINA steps (STEP1, 2, 3 controlled; STEP3 uncontrolled, 4 and 5). Results: 76/250 (30%) subjects had EOA and 98/250 (39%) LOA. Rhinitis was more frequent in EOA (76 vs 53%; p=0.02) and was associated with increased severity (p=0.01), reduced FEV1/FVC (74±10 vs 83±7%; p=0.01), increased eosinophils (0.36±0.3 vs 0.14±0.1 x109/L; p<0.01) and IgE (441±635 vs 71±76KU/L; p<0.01). IgE were directly related to blood eosinophils (r=0.42; p=0.005) and inversely to FEV1/FVC (r=-0.34;p=0.02) in EOA, but not in LOA. Conversely, LOA patients with rhinitis were less severe and had higher FEV1/FVC (82±9vs74±9%;p<0.01). Obesity was present in 20% of the 250 patients regardless onset time, but obesity in LOA was associated to a more severe disease (p=0.009), reduced FEV1/FVC (73±9 vs 80±10;p=0.009) and increased blood neutrophils (4.2±1.1 vs 3.7±1.6x109/L;p=0.03) when compared to non-obese LOA. GERD was highly prevalent (60%) but had no impact on disease severity or lung function. Bronchiectasis were rare and more predominant in LOA (9vs3%). Conclusions: Early-onset persistent and late-onset asthma are distinct phenotypes, with different underlying inflammatory patterns and different comorbidities which impact on the outcome.