Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients

Abstract Background Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. Methods In this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC 100% - FEF 25–75% Results Treatment with extrafine BDP/FF(200/6 μg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. Conclusions Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 μg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP

Changes in sputum composition during 15min of sputum induction in healthy subjects and patients with asthma and chronic obstructive pulmonary disease

SummaryIntroductionThe use of sputum induction by inhalation of hypertonic saline to study the cellular and biochemical composition of the airways allows noninvasive sampling of the airways content and identification of markers of airways inflammation.ObjectiveThe present study aimed to identify possible changes in the cellular composition of induced sputum between samples obtained sequentially (three periods of 5min each) during one sputum induction. Moreover, difference between these samples and the mixed one (mixture of samples obtained after 5, 10 and 15min of induction) was investigated.MethodsForty-six subjects (10 healthy volunteers, 12 patients with chronic obstructive pulmonary disease (COPD) and 24 patients with asthma) (mean age 53.0±14.0yr, forced expiratory volume in one second (FEV1) 71.8±19.0% pred) produced sputum after three consecutive 5min periods of hypertonic (4.5%) saline inhalation. Stained cytospins from the three periods separately and from the mixed sample were produced and analyzed.ResultsThe mean percentage of neutrophils, eosinophils, lymphocytes and epithelial cells did not change significantly in samples obtained consecutively after 5, 10 and 15min of the induction procedure. There was no significant difference in the cellular composition of samples obtained after 5, 10 and 15min of induction and the cellular composition of the mixed sample (P=0.06).ConclusionThe separate analysis of induced sputum from three consecutive sampling and the mixed sample did not demonstrate significant changes in their cellular composition. Fifteen minutes induction procedure with the fixed concentration of hypertonic saline and processing of the mixed sample can be recommended for clinical settings and clinical trials

Neutrophilic airways inflammation in lung cancer: the role of exhaled LTB-4 and IL-8

Background: Recent advances in lung cancer biology presuppose its inflammatory origin. In this regard, LTB-4 and IL-8 are recognized to play a crucial role in neutrophil recruitment into airways during lung cancer.Notwithstanding the intriguing hypothesis, the exact role of neutrophilic inflammation in tumour biology remains complex and not completely known.The aim of this study was to give our contribution in this field by investigating LTB-4 and IL-8 in the breath condensate of NSCLC patients and verifying their role in cancer development and progression.Method: We enrolled 50 NSCLC patients and 35 controls. LTB-4 and IL-8 concentrations were measured in the breath condensate and the blood of all the subjects under study using EIA kits. Thirty NSCLC patients and ten controls underwent induced sputum collection and analysis.Results: LTB-4 and IL-8 resulted higher in breath condensate and the blood of NSCLC patients compared to controls. Significantly higher concentrations were found as the cancer stages progressed. A positive correlation was observed between exhaled IL-8 and LTB-4 and the percentage of neutrophils in the induced sputum.Conclusion: The high concentrations of exhaled LTB-4 and IL-8 showed the presence of a neutrophilic inflammation in the airways of NSCLC patients and gave a further support to the inflammatory signalling in lung cancer. These exhaled proteins could represent a suitable non-invasive marker in the diagnosis and monitoring of lung cancer. © 2011 Carpagnano et al; licensee BioMed Central Ltd

Patient and physician perspectives on biological treatment in severe asthma: a Severe Asthma Network Italy survey

: Patients with severe asthma perceive beneficial effects of biologics and good self-reported adherence to treatment, even when self-administered at home https://bit.ly/48vP70w

Beliefs and preferences regarding biological treatments for severe asthma

Background: Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers’ specialty and experience. Methods: We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared. Results: Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05). Conclusions: Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice

Exhaled Breath Analysis and Sleep

It is currently estimated that the economic burden for obstructive sleep apnea syndrome (OSAS) cases not coming to medical attention is steadily increasing, thus making OSAS a major public health concern. For its increasing incidence among the common population, the interest of researchers and clinicians has been recently directed to the study of pathological mechanisms underlying sleep disorders. Current opinion is that airway inflammation and oxidative stress play a crucial role in the pathophysiology of OSAS. Recently there has been increasing interest in the investigation of lungs by non-invasive means measuring the exhaled breath volatile mediators, such as nitric oxide (NO), carbon monoxide (CO), ethane and pentane and finally the non-volatile substances in the liquid phase of exhalate, termed breath condensate. The non-invasiveness of these techniques for the study of airways affected by different respiratory disorders and among those, the OSAS, makes these ideally suited for the evaluation and serial monitoring of patients. Notwithstanding the increasing number of scientific contributions on the use of the exhaled markers in sleep disorders, at the moment, their use is not completely suitable for clinical application. An important contribution to the increase of our knowledge on exhaled markers and for their possible concrete application in clinical practice may come from future studies using proteomics, genomics and metabolomics. In this review, we focus on exhaled breath analysis giving an update on its general aspects, its application in OSAS, and finally its actual clinical applicability and areas for future direction

Is it feasible to collect exhaled breath condensate in COVID-19 patients undergoing noninvasive ventilatory support?

In patients with #COVID19-related acute hypoxic respiratory failure requiring noninvasive ventilatory support, EBC collection with adequate precautions may be feasible and future studies will be needed to explore this research field https://bit.ly/39OxufF

New panel of microsatellite alterations detectable in the EBC for lung cancer prognosis

Our research group demonstrated, in a precedent study, the prognostic power of the 3p microsatellites alterations (MAs) detectable in exhaled breath condensate (EBC) in NSCLC patients. The analysis of genetic markers in the EBC might have precious clinical and economic consequences when inserted in diagnostic and follow up programs for lung cancer.The aim of this study was to evaluate the prognostic value of a new panel of MAs in the EBC of patients with NSCLC.We enrolled 45 NSCLC patients during a period of 36 months and the follow-up period was 156 weeks. We analyzed MAs for eight markers in EBC samples: D3S2338, D3S1266, D3S1300, D3S1304, D3S1289, D5S2094, D3S1313, and AFMa305ye1. Our study showed that the presence of more than 2 simultaneous MAs reduces outcome in NSCLC patients. The new panel of eight microsatellites markers proposed in EBC samples could have a potential clinical role in assessing survival in lung cancer patients