Severe uncontrolled asthma with bronchiectasis: A pilot study of an emerging phenotype that responds to mepolizumab

Background: Asthma and bronchiectasis are different conditions that frequently coexist. The prevalence of bronchiectasis rises considerably in subjects with severe asthma (25%-51%). Objective: We evaluated the clinical and biological efficacy of mepolizumab on our pilot population of severe uncontrolled asthmatics with bronchiectasis not related to other pathologies. Patients and methods: Four patients with severe uncontrolled asthma and diagnosed as bronchiectasis were recruited and started biological treatment with mepolizumab. Standard investigations were performed in all four patients at baseline (T0), after 3 months (T1) and after 1 year (T2) of treatment. Results: After 1 year (T2) of therapy with mepolizumab, patients showed a significant increment of asthma control test value (12±1.1 vs 24.5±0.3, P<0.01), a reduction of the number of exacerbations/year (5±0.7 vs 0.75±0.75, P<0.01), an increase of pre-bronchodilator FEV 1 (1,680±500 vs 1,860±550 mL, P<0.01) and a reduction of eosinophils in blood (0.75±0.14 vs 0.12±0.02 cells/μL, P<0.01), in the sputum (9.6%±2.1% vs 5.6%±2.7%, P<0.05) and in nasal cytology (++ vs +). Conclusion: The efficacy of mepolizumab in terms of reduction of inflammation and increase of control that we observed in our patients might suggest that targeting the IL-5 in severe eosinophilic asthma with bronchiectasis may be a good therapeutic strategy

A case of cryptogenic organizing pneumonia occurring in Crohn's disease.

A 29 year-old-man with Crohn's disease, who developed diffuse pulmonary infiltrates and hypoxemia two months following oral administration of mesalazine, was examined. Clinical findings and computed tomography were suggestive of, and lung histology was diagnostic of, bronchiolitis obliterans organizing pneumonia, also known as cryptogenic organizing pneumonia. Although the data did not allow for definitive conclusions, they did suggest that the pulmonary disease was an extraintestinal manifestation of Crohn's disease, rather than an adverse reaction to mesalazine. In fact, the patient showed clinical, radiological and functional improvements, despite the treatment with mesalazine and the withdrawal of steroid therapy

Sleep apnea risk in subjects with asthma with or without comorbid rhinitis

BACKGROUND: As many as 80% of patients with asthma suffer from allergic rhinitis (AR), and rhinitis symptoms are associated with sleep complaints The aim of this cross-sectional study was to assess the prevalence of obstructive sleep apnea syndrome risk in patients with asthma and to explore the association between comorbid rhinitis and obstructive sleep apnea syndrome risk. METHODS: Subjects with asthma were recruited by general practitioners during a control visit. Physicians compiled a questionnaire that assessed the presence of AR according to ARIA (Allergic Rhinitis and Its Impact on Asthma) guidelines and factors influencing the risk of obstructive sleep apnea syndrome (gastroesophageal reflux disease, obesity, smoking). Subjects completed a questionnaire evaluating the presence and severity of AR and the STOP-BANG questionnaire (snoring, tiredness during daytime, observed apnea, high blood pressure, body mass index, age, neck circumference, gender), a validated screening method to identify obstructive sleep apnea syndrome risk. Physicians were blinded to the subjects\u2019 questionnaires, ensuring objectivity of the method. RESULTS: The analyses were conducted on 1,941 subjects (males 58%, mean age 48.2 \ub1 15.2 y): 740 with asthma alone and 1,201 with asthma and AR. STOP-BANG revealed that 52.6% of the subjects were at increased risk of obstructive sleep apnea syndrome: 47.3% of subjects with asthma alone and 55.9% of patients with asthma and AR. Rhinitis was associated with a 1.44 times higher odds ratio for having obstructive sleep apnea syndrome risk. Rhinitis duration and severity were associated with obstructive sleep apnea syndrome risk, although the latter deserved greater importance. The results showed that, once a correction for each of these factors was performed, subjects with AR with an odds ratio of 1.99 were reported to be at risk of obstructive sleep apnea syndrome. CONCLUSIONS: The probable increased risk of obstructive sleep apnea syndrome is associated with the concomitant presence of rhinitis, independent of obesity and other contributors to risk of obstructive sleep apnea syndrome

Transthoracic Ultrasound in Infectious Organizing Pneumonia: A Useful Guide for Percutaneous Needle Biopsy

In patients presenting with classical features of CAP (i.e., new peripheral pulmonary consolidations and symptoms including fever, cough, and dyspnea), a clinical response to the appropriate therapy occurs in few days. When clinical improvement has not occurred and chest imaging findings are unchanged or worse, a more aggressive approach is needed in order to exclude other non-infective lesions (including neoplasms). International guidelines do not currently recommend the use of transthoracic ultrasound (TUS) as an alternative to chest X-ray (CXR) or chest computed tomography (CT) scan for the diagnosis of CAP. However, a fundamental role for TUS has been established as a guide for percutaneous needle biopsy (US-PNB) in pleural and subpleural lesions. In this retrospective study, we included 36 consecutive patients whose final diagnosis, made by a US-guided percutaneous needle biopsy (US-PTNB), was infectious organizing pneumonia (OP). Infective etiology was confirmed by additional information from microbiological and cultural studies or with a clinical follow-up of 6-12 months after a second-line antibiotic therapy plus corticosteroids. All patients have been subjected to a chest CT and a systematic TUS examination before biopsy. This gave us the opportunity to explore TUS performance in assessing CT findings of infective OP. TUS sensitivity and specificity in detecting air bronchogram and necrotic areas were far lower than those of CT scan. Conversely, TUS showed superiority in the detection of pleural effusion. Although ultrasound findings did not allow the characterization of chronic subpleural lesions, TUS confirmed to be a valid diagnostic aid for guiding percutaneous needle biopsy of subpleural consolidations

Diagnostic Performance of CLEIA Versus FEIA for KL-6 Peripheral and Alveolar Concentrations in Fibrotic Interstitial Lung Diseases: A Multicentre Study

Background: Interstitial lung diseases (ILD) is a group of lung disorders characterized by interstitial lung thickening due to in-flammatory and fibrotic processes. Krebs von den Lungen-6 (KL-6) is a molecule secreted by damaged type II alveolar pneumo-cytes in the alveolar space. The goal of the present study was to compare two detection methods of KL-6 in both bronchoalveolar lavage (BAL) and serum from ILD patients at the moment of diagnosis. Methods: Patients with suspicious of ILD and followed at two Italian referral centres for rare lung diseases were included in the study. BAL fluid and serum were collected and analysed by chemiluminescent enzyme immunoassay (CLEIA) and fluorescent enzyme immunoassay (FEIA) methods provided by Tosoh Biosciences. Results: A total of 158 (mean age +/- standard deviation, 61.5 +/- 13.7, 65 females) patients were enrolled. A total of, 36 had diagnosis of idiopathic pulmonary fibrosis (IPF), 74 sarcoidosis, 15 connective tissue disease-ILD (CTD-ILD) and 33 other ILD. Diagnostic agreement between two methods was demonstrated for both BAL (r = 0.707, p < 0.0001) and serum (r = 0.816, p < 0.0001). BAL KL-6 values were lower than serum (p < 0.0001). IPF patients had higher serum KL-6 concentration than other ILDs (p = 0.0294), while BAL KL-6 values were lower in IPF than in non-IPF (p = 0.0023). Conclusion: This study explored KL-6 concentrations through the CLEIA method in serum and BAL of patients with various ILDs, showing significant differences of biomarkers concentrations between IPF and other non-IPF ILDs. Our findings are promising as they provided further knowledge concerning KL-6 expression across different ILDs and may suggest its utility in differential diagnosi

Effectiveness and Safety of Transthoracic Ultrasound in Guiding Percutaneous Needle Biopsy in the Lung and Comparison vs. CT Scan in Assessing Morphology of Subpleural Consolidations

(1) Background: The aim of this study was to conduct a prospective analysis on the diagnostic accuracy of transthoracic ultrasound-guided percutaneous needle biopsy (TUS-PNB) for the histological assessment of peripheral lung lesions and to assess the performance of transthoracic ultrasound (TUS) examination vs. chest CT (gold standard) in the differentiation between malignant and benign peripheral lung lesions. (2) Methods: A total of 961 consecutive patients with subpleural pulmonary lesions were enrolled. All the patients received a CT scan with contrast; 762 patients underwent TUS-PTNB for suspicion of malignancy, and the remaining 199 enrolled patients underwent only TUS examination as a part of routine follow-up for known non-malignant subpleural consolidations. (3) Results: Among the 762 TUS-guided biopsies, there were 627 (82.28%) malignant lesions, 82 (10.76%) benign lesions, and 53 (6.96%) indeterminate lesions. The overall diagnostic accuracy was 93.04%. The rates of pneumothorax not requiring chest-tube insertion and self-limited hemoptysis were 0.79 and 0.26%, respectively. Patients were divided into two groups based on the benign or malignant nature of the subpleural consolidations. On TUS, both malignant and benign lesions showed mostly irregular margins and a hypoechoic pattern, but no differences were assessed in terms of sonographic margins and pattern between the two groups. There was poor agreement between TUS and chest CT in assessing air bronchograms and necrotic areas. The only finding in the detection of which TUS showed superiority compared to chest-CT was pleural effusion. (4) Conclusions: TUS-PNB was confirmed to be an effective and safe diagnostic method for peripheral pulmonary consolidation, but their sonographic pattern did not allow to rule out a malignant nature. A pre-operative evaluation on CT images, combined with the possibility of performing additional immunohistochemical and cytological investigations and the experience of the medical staff, may improve the diagnostic yield of TUS-guided biopsies

SARS-CoV-2 serological profile in healthcare professionals of a Southern Italy hospital

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the first coronavirus that has caused a pandemic. Assessing the prevalence of anti-SARS-CoV-2 in healthcare worker groups offers a unique opportunity to study the correlation between seroconversion and immunization because of their occupational exposure and a higher risk of contagion. The study enrolled 3242 asymptomatic employees of “Policlinico Riuniti”, Foggia. After the first screening, we collected sequential serum samples for up to 23 weeks from the same subjects. In order to perform a longitudinal follow-up study and get information about the titration of IgG levels, we analyzed data from subjects (33) with at least two consecutive serological IgG—positive tests; 62 (1.9%; 95% CI: 1.4–2.3) tested positive for at least one anti-SARS-CoV-2 antibody. The seroprevalence was lower in the high-risk group 1.4% (6/428; 95% CI: 0.5–2.6) vs. the intermediate-risk group 2.0% (55/2736; 95% CI: 1.5–2.5). Overall, within eight weeks, we detected a mean reduction of –17% in IgG levels. Our data suggest a reduction of about 9.27 AU/mL every week (R2 = 0.35, p = 0.0003). This study revealed the prevalence of SARS-CoV-2 antibodies among Foggia’s hospital healthcare staff (1.9%). Moreover, the IgG level reduction suggests that the serological response fades fast in asymptomatic infections

Tiotropium inhibits proinflammatory microparticle generation by human bronchial and endothelial cells

Tiotropium is a muscarinic antagonist that reduces the risk of acute exacerbations of chronic obstructive pulmonary disease, possibly through an as yet incompletely characterized anti-inflammatory activity. We hypothesized that muscarinic activation of bronchial epithelial cells and endothelial cells causes the release of proinflammatory microparticles and that tiotropium inhibits the phenomenon. Microparticle generation was assessed by a functional assay, by flow cytometry and by NanoSight technology. Immortalized bronchial epithelial cells (16HBE) and umbilical vein endothelial cells were treated with acetylcholine in the presence of varying concentrations of tiotropium. Intracellular calcium concentration, extracellular regulated kinase phosphorylation and chemokine content in the conditioned media were assessed by commercial kits. Acetylcholine causes microparticle generation that is completely inhibited by tiotropium (50 pM). Microparticles generated by acetylcholine-stimulated cells increase the synthesis of proinflammatory mediators in an autocrine fashion. Acetylcholine-induced upregulation of microparticle generation is inhibited by an inhibitor of extracellular regulated kinase phosphorylation and by a phospholipase C inhibitor. Tiotropium blocks both extracellular regulated kinase phosphorylation and calcium mobilization, consistent with the hypothesis that the drug prevents microparticle generation through inhibition of these critical pathways. These results might contribute to explain the effect of tiotropium in reducing acute exacerbations of chronic obstructive pulmonary disease

A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis

Background: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. Objectives: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. Methods: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. Results: Forty-one patients with a forced vital capacity (FVC) 6450% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) 6435% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. Conclusions: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters