Violaine Giraud

Inhaler technique and asthma: Feasability and acceptability of training by pharmacists

Poor inhaler technique is frequent in asthma, but its long-term consequences have been seldom assessed. Pharmacists are ideally positioned to teach inhaler technique. This prospective observational study evaluated the feasibility of inhaler training by pharmacists in patients receiving inhaled corticosteroids by pressurised metered-dose inhaler (pMDI) or breath-actuated MDI. In parallel, the relationships between inhaler technique, adherence, and asthma control, and their modulation one month after training were assessed. Of 727 patients receiving training at pharmacies (n=123), 61% were prescribed a pMDI; 35%, an Autohaler(®); and 5%, an Easi-Breathe(®) inhaler. Poor asthma control (Asthma Control Questionnaire score ≥ 1.5) at baseline was significantly (p<0.05) and independently associated with poor inhaler technique and poor self-reported adherence (Morisky score ≥ 3). The percentage of patients with optimal inhaler technique rose from 24% before to 79% after training (p<0.001). Median training session length was 6 min. At 1 month, mean (SD) ACQ score had improved from a baseline score of 1.8 (1.2) to 1.4 (1.1), (p<0.001). Importantly, greater change was observed in patients with improved inhaler technique versus those without. Similar results were observed for Morisky score. Inhaler technique is associated with adherence and influences asthma control. Inhaler training by pharmacists is feasible and seams to improve inhaler technique, asthma control and adherence.

Anti-IgE Monoclonal Antibody (Omalizumab) in Refractory and Relapsing Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss): Data on Seventeen Patients

To describe the efficacy and safety of omalizumab, an anti‐IgE monoclonal antibody, in patients with refractory and/or relapsing eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA).

Use of a simplified geriatric evaluation in thoracic oncology

Management of elderly patients with bronchial cancer should take into account specific factors linked to the patients age, and the presence of co-morbidities. A geriatric evaluation enables us to use relevant information in the therapeutic decision-making process. However, the Comprehensive Geriatric Assessment described in the literature is tedious and time-consuming. We describe the use of a simplified geriatric evaluation (SGE), in 57 patients aged >/=75 years (mean age: 80.8 years) with thoracic cancer, before discussing therapeutic options with colleagues from various departments. This evaluation enabled us to classify the patients into four groups: group 1 consisted of patients in a good general state; group 2+ comprised patients with no more than two stabilized co-morbidities or one poorly or non-stabilized co-morbidity; group 2- comprised patients with more than two stabilized co-morbidities, or at least two poorly or non-stabilized co-morbidities; group 3 consisted of frail patients. The three patients in group 1 did not have any negative factors that could complicate their management and therefore received anti-tumor therapy. The 15 patients in group 3 were considered to have co-morbidities or functional alterations that were too advanced for them to benefit from anti-tumor therapy, and received symptomatic treatment only. Among the 39 patients in the intermediary groups 2+ and 2-, 24 underwent surgery, chemotherapy or radiotherapy (21 (87.5%) patients in group 2+ and 3 (20.0%) patients in group 2-). These data suggest that the SGE is an important aid to decision-making in the management of elderly patients with bronchial cancer.

Anti‐IgE monoclonal antibody (omalizumab) in refractory and relapsing eosinophilic granulomatosis with polyangiitis (Churg‐Strauss): Data from 17 patients

To describe the efficacy and safety of omalizumab, an anti‐IgE monoclonal antibody, in patients with refractory and/or relapsing eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA).

Delay Between the Initial Symptoms, the Diagnosis and the Onset of Specific Treatment in Elderly Patients With Lung Cancer

INTRODUCTION The proportion of elderly patients with lung cancer is increasing. The objectives of this study were to describe the initial symptoms in elderly patients (≥ 70 years) with lung cancer and to describe the diagnostic and treatment delays. PATIENTS AND METHODS We reviewed all consecutive patients with lung cancer that were diagnosed between 2006 and 2008 in our department. The initial symptoms and delays in the diagnosis and treatment in elderly patients were compared with those of younger patients. RESULTS One hundred ninety-three patients were included (26 small-cell cancers and 167 non-small-cell lung cancers [NSCLCs]). Ninety-two patients (47.7%) were ≥ 70 years old. No statistical differences were identified between the 2 groups concerning initial symptoms. In elderly patients, the delay between the initial symptoms and the first visit with a thoracic oncologist (median 1.6 months [IQR 23 days-3.3 months]), the delay between the first visit and the specific treatment (median 1.1 months [IQR 18 days-1.8 months]), and the delay between initial symptoms and the specific treatment (median 3 months [IQR 2-5.7 months]) were similar to those in the younger patients (P = .101, P = .084, and P = .671, respectively). Eighty-four percent of the elderly patients were actively treated vs. 98% of the younger patients (P = .001). CONCLUSION We identified no differences regarding the initial symptoms in elderly patients with lung cancer compared with those in younger patients. The delays in diagnosis and treatment were similar between the 2 groups.

Role of atmospheric pollution on the natural history of idiopathic pulmonary fibrosis

Introduction Idiopathic pulmonary fibrosis (IPF) has an unpredictable course corresponding to various profiles: stability, physiological disease progression and rapid decline. A minority of patients experience acute exacerbations (AEs). A recent study suggested that ozone and nitrogen dioxide might contribute to the occurrence of AE. We hypothesised that outdoor air pollution might influence the natural history of IPF. Methods Patients were selected from the French cohort COhorte FIbrose (COFI), a national multicentre longitudinal prospective cohort of IPF (n=192). Air pollutant levels were assigned to each patient from the air quality monitoring station closest to the patient’s geocoded residence. Cox proportional hazards model was used to evaluate the impact of air pollution on AE, disease progression and death. Results Onset of AEs was significantly associated with an increased mean level of ozone in the six preceding weeks, with an HR of 1.47 (95% CI 1.13 to 1.92) per 10 µg/m3 (p=0.005). Cumulative levels of exposure to particulate matter PM10 and PM2.5 were above WHO recommendations in 34% and 100% of patients, respectively. Mortality was significantly associated with increased levels of exposure to PM10 (HR=2.01, 95% CI 1.07 to 3.77) per 10 µg/m3 (p=0.03), and PM2.5 (HR=7.93, 95% CI 2.93 to 21.33) per 10 µg/m3 (p<0.001). Conclusion This study suggests that air pollution has a negative impact on IPF outcomes, corroborating the role of ozone on AEs and establishing, for the first time, the potential role of long-term exposure to PM10 and PM2.5 on overall mortality.

Circulating tumor DNA evaluated by Next-Generation Sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer

ABSTRACT Nivolumab is an anti-PD1 antibody, given in second-line or later treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to describe the predictive value of circulating tumor DNA (ctDNA) on the efficacy of nivolumab in advanced NSCLC. We prospectively included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between June 2015 and October 2016. Plasma samples were obtained before the first injection of nivolumab and at the first tumor evaluation with nivolumab. ctDNA was analyzed by Next-Generation Sequencing (NGS), and the predominant somatic mutation was followed for each patient and correlated with tumor response, clinical benefit (administration of nivolumab for more than 6 months), and progression-free survival (PFS). Of 23 patients, 15 had evaluable NGS results at both times of analysis. ctDNA concentration at the first tumor evaluation and ctDNA change correlated with tumor response, clinical benefit and PFS. ROC curve analyses showed good diagnostic performances for tumor response and clinical benefit, both for ctDNA concentration at the first tumor evaluation (tumor response: positive predictive value (PPV) at 100.0% and negative predictive value (NPV) at 71.0%; clinical benefit: PPV at 83.3% and NPV 77.8%) and the ctDNA change (tumor response: PPV 100.0% and NPV 62.5%; clinical benefit: PPV 100.0% and NPV 80.0%). Patients without ctDNA concentration increase >9% at 2 months had a long-term benefit of nivolumab. In conclusion, NGS analysis of ctDNA allows the early detection of tumor response and long-term clinical benefit with nivolumab in NSCLC.

Feasibility of spirometry in primary care to screen for COPD: a pilot study

Background COPD is a frequent but underdiagnosed disease whose diagnosis relies on the spirometric demonstration of bronchial obstruction. Spirometry use by general practitioners could represent the first line in COPD diagnosis. Objective Because duration of spirometry is retarding its development in primary care, we decided to measure the time it requires in the primary-care context in France. Methods Ten volunteer general practitioners were trained during two 3-hour theoretical and practical continuing education sessions. Then, from October 2013 to May 2014, they included patients without any known respiratory disease but at risk of developing COPD (age: ≥40 years, smoker: ≥20 pack-years). The duration of spirometry and its quality were evaluated according to the following acceptability criteria: 1) expiration ≥6 seconds or reaching a plateau; 2) good start with an early peak flow, curve peaked on top and not flat; 3) no artifacts; and 4) reproducibility criteria, ie, forced expiratory volume in 1 second and forced vital capacity differences between the two best spirometry curves ≤0.15 L. Quality of the spirograms was defined as optimal when all the criteria were met and acceptable when all the criteria were satisfied except the reproducibility criterion, otherwise, it was unacceptable. Results For the 152 patients included, the 142 assessable spirometries lasted for 15.2±5.9 minutes. Acceptability criteria 1–3, respectively, were satisfied for 90.1%, 89.4%, and 91.5% of patients and reproducibility criterion 4 for 56.3%. Quality was considered optimal for 58.5% of the curves and acceptable for 30.2%. Conclusion The duration of spirometry renders it poorly compatible with the current primary-care practice in France other than for dedicated consultations. Moreover, the quality of spirometry needs to be improved.

Clinical factors associated with early progression and grade 3–4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab

Introduction The prognosis of advanced non-small-cell lung cancer (NSCLC) has been improved by development of immune checkpoint inhibitors (ICIs) such as nivolumab for second-line treatment. As phase III trials include only selected patients, we here investigated the clinical factors associated with efficacy and safety of nivolumab in ‘real life’ patients with advanced NSCLC. Methods Clinical and histological characteristics, therapies and survival data of all consecutive patients with advanced NSCLC included prospectively and treated by nivolumab in two French academic hospitals between February 2015 and December 2016 were examined. Results Sixty-seven patients were included, mostly male (69%), current or former smokers (87%) with PS <2 (73%). Median age was 68.5 years and 42% were aged ≥70 years. According to uni- and multi-variate analyses, only PS 2 (OR = 0.17, 95% CI 0.03–0.99, p = 0.049) and number of previous treatment lines (OR = 0.33, 95% CI 0.13–0.85, p = 0.022) were significantly negatively associated with tumor control. Worse progression-free survival (PFS) was significantly associated with PS 2 (HR = 5.17, 95% CI 1.99–13.43, p = 0.001) and use of steroids (HR = 3.27, 95% CI 1.39–7.69, p = 0.006). Worse overall survival was associated with symptomatic brain metastasis (HR = 3.15, 95% CI 1.23–8.85, p = 0.029). Treatment-related adverse events occurred in 47 patients (70%), symptomatic brain metastasis being significantly associated with Grade ≥3 toxicity (OR = 8.13, 95% CI 1.21–55.56, p = 0.031). Age and nutritional status were not associated with response, PFS, OS or toxicity. Conclusion Our results suggest that nivolumab is not beneficial or safe for patients with PS 2 and symptomatic brain metastases.

Molecular characterization of circulating tumor cells in lung cancer: moving beyond enumeration

Molecular characterization of tumor cells is a key step in the diagnosis and optimal treatment of lung cancer. However, analysis of tumor samples, often corresponding to small biopsies, can be difficult and does not accurately reflect tumor heterogeneity. Recent studies have shown that isolation of circulating tumor cells (CTCs) is feasible in non-small cell lung cancer patients, even at early disease stages. The amount of CTCs corresponds to the metastatic potential of the tumor and to patient prognosis. Moreover, molecular analyses, even at the single-cell level, can be performed on CTCs. This review describes the technologies currently available for detecting and capturing CTCs, the potential for downstream molecular diagnostics, and the clinical applications of CTCs isolated from lung cancer patients as screening, prognostic, and predictive tools. Main limitations of CTCs are also discussed.