Precision Medicine in Targeted Therapies for Severe Asthma:Is There Any Place for "omics" Technology?

According to the current guidelines, severe asthma still represents a controversial topic in terms of definition and management. The introduction of novel biological therapies as a treatment option for severe asthmatic patients paved the way to a personalized approach, which aims at matching the appropriate therapy with the different asthma phenotypes. Traditional asthma phenotypes have been decomposing by an increasing number of asthma subclasses based on functional and physiopathological mechanisms. This is possible thanks to the development and application of different omics technologies. The new asthma classification patterns, particularly concerning severe asthma, include an increasing number of endotypes that have been identified using new omics technologies. The identification of endotypes provides new opportunities for the management of asthma symptoms, but this implies that biological therapies which target inflammatory mediators in the frame of specific patterns of inflammation should be developed. However, the pathway leading to a precision approach in asthma treatment is still at its beginning. The aim of this review is providing a synthetic overview of the current asthma management, with a particular focus on severe asthma, in the light of phenotype and endotype approach, and summarizing the current knowledge about “omics” science and their therapeutic relevance in the field of bronchial asthma

Bronchial Thermoplasty Global Registry (BTGR): 2-year results

Asma; Broncoscòpia; Termoplàstia bronquialAsma; Broncoscopia; Termoplastia bronquialAsthma; Bronchoscopy; Bronchial ThermoplastyObjectives: Bronchial thermoplasty (BT) is a device-based treatment for subjects ≥18 years with severe asthma not well controlled with inhaled corticosteroids and long-acting beta-agonists. The Bronchial Thermoplasty Global Registry (BTGR) collected real-world data on subjects undergoing this procedure. Design: The BTGR is an all-comer, prospective, open-label, multicentre study enrolling adult subjects indicated for and treated with BT. Setting: Eighteen centres in Spain, Italy, Germany, the UK, the Netherlands, the Czech Republic, South Africa and Australia PARTICIPANTS: One hundred fifty-seven subjects aged 18 years and older who were scheduled to undergo BT treatment for asthma. Subjects diagnosed with other medical conditions which, in the investigator's opinion, made them inappropriate for BT treatment were excluded. Primary and secondary outcome measures: Baseline characteristics collected included demographics, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT), medication usage, forced expiratory volume in one second and forced vital capacity, medical history, comorbidities and 12-month baseline recall data (severe exacerbations (SE) and healthcare utilisation). SE incidence and healthcare utilisation were summarised at 1 and 2 years post-BT. Results: Subjects' baseline characteristics were representative of persons with severe asthma. A comparison of the proportion of subjects experiencing events during the 12 months prior to BT to the 2-year follow-up showed a reduction in SE (90.3% vs 56.1%, p<0.0001), emergency room visits (53.8% vs 25.5%, p<0.0001) and hospitalisations (42.9% vs 23.5 %, p=0.0019). Reductions in asthma maintenance medication dosage were also observed. AQLQ and ACT scores improved from 3.26 and 11.18 at baseline to 4.39 and 15.54 at 2 years, respectively (p<0.0001 for both AQLQ and ACT). Conclusions: The BTGR demonstrates sustained improvement in clinical outcomes and reduction in asthma medication usage 2 years after BT in a real-world population. This is consistent with results from other BT randomised controlled trials and registries and further supports improvement in asthma control after BT.This study was sponsored by Boston Scientific Corporation, Marlborough, MA, USA

Endobronchial ultrasound-guided transbronchial needle aspiration under conscious sedation with meperidine and midazolam

Endobronchial Ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is usually performed under general anesthesia or deep sedation with drugs such as Propofol that, at least in Italy, can be administered only by an anesthesiologist. Aim of the study was to assess conscious sedation feasibility, safety and tolerability using Meperidine and Midazolam as administered by Pulmonologist and relevant impact on the efficiency of the sampling procedures. All patients undergoing EBUS-TBNA from February 2013 to July 2014 were examined retrospectively. Efficiency using Meperidine and Midazolam during EBUS-TBNA has been assessed: completion of lymph-nodal sampling, sampling adequacy, diagnostic yield, cough during endoscopic procedure complications and need for procedure repetition with Anesthesiology assistance. Patient satisfaction and cost/effectiveness were also evaluated. One hundred and thirty-four consecutive patients were considered; 97.7% completed the procedure. In 96.9% of cases the prefixed program of lymph-nodal sampling was accomplished. Sampling adequacy was 92,4%. Diagnostic yield was 55%. In 94.7% of cases cough was absent or did not interfere with EBUS-TBNA. The need to repeat the endoscopic procedure occurred in 6 cases but only in 2 the presence of an Anesthesiologist was required. Patient satisfaction was very high, with 95.9% of subjects reporting they would “definitely return”. A 27% cost reduction was calculated. EBUS-TBNA under conscious sedation using Meperidine and Midazolam prescribed and administered by pulmonologist without the Anesthesiologist assistance, revealed to be a safe, well tolerated and cost saving procedure. The efficiency of sampling was good, apart from a relatively low diagnostic yield due to different expertise of operators

Towards precision medicine: The application of omics technologies in asthma management

Asthma is a chronic obstructive respiratory disease characterised by bronchial inflammation. Its biological and clinical features have been widely explored and a number of pharmacological treatments are currently available. Currently several aspects of asthma pathophysiological background remain unclear, and this is represent a limitation for the traditional asthma phenotype approach. In this scenario, the identification of new molecular and clinical biomarkers may be helpful in order to better understand the disease, define specific diagnostic tools and highlight relevant novel targets for pharmacological treatments. Omics technologies offer innovative research tools for addressing the above mentioned goals. However, there is still a lot to do both in the fields of basic research and in the clinical application. Recently, genome-wide association studies, microRNAs and proteomics are contributing to enrich the available data for the identification of new asthma biomarkers. A precise approach to the patient with asthma, particularly with severe uncontrolled asthma, requires new and specific therapeutic targets, but also proper tools able to drive the clinician in tailoring the treatment. On the other hand, there is a need of predictors to treatment’s response, particularly in the field of biological drugs, whose sustainability implies a correct and precise selection of the patients. Translating acquired omics knowledge in clinical practice may address the unmet needs described above, but large-scale studies are required in order to confirm their relevance and effectiveness in daily practice. Thus in our opinion the application of omics is still lagging in the real-life setting

Long-term benefits of omalizumab in a patient with severe non-allergic asthma

<p>Abstract</p> <p>Introduction</p> <p>Currently, omalizumab is indicated for the treatment of patients with severe allergic uncontrolled asthma despite optimal therapy.</p> <p>Case presentation</p> <p>We studied a 52-year-old man who has been suffering from severe non allergic steroid-resistant asthma with increased levels of total IgE and a lot of comorbidity. After a 3 years long treatment with omalizumab, he presented a significant improvement in disease control in terms of hospitalizations, exacerbation, quality of life and lung function with good safety profile.</p> <p>Conclusion</p> <p>Our case shows, after a long follow-up, how omalizumab can be effective in a severe form of non-atopic asthma. It is therefore hoped that further studies can identify indicators that are able to give to clinicians information about patients who can be responsive to monoclonal anti-IgE antibody even if non allergic.</p