[Severe adult asthma and treatment adherence: Results of the FASE-CPHG study]. / Asthme sévère de l'adulte et observance : résultats de l'étude FASE-CPHG.

INTRODUCTION: Data on severe asthma in France are scarce. The aim of this study was to evaluate adherence to asthma treatments and its determinants in a population of severe asthmatics. METHODS: From May 2016 to June 2017, the French Collège des Pneumologues des Hôpitaux Généraux organized a large-scale prospective, cross-sectional, multicenter study on this topic; 1502 patients with severe asthma were included. RESULTS: The average number of substantive treatments was 2.5±1.1. Assessed by self-questionnaire in 1289 patients, overall adherence was 64.8%, in good agreement with the findings of the pneumologist in charge (p<0.0001). Control of asthma according to the GINA criteria was more successful in compliant patients (p<0.01). In univariate analysis, the most compliant participants were frequent exacerbator patients (p=0.02), those with nasal polyposis (p=0.01) and those receiving an anticholinergic agent (p<0.01), anti-IgE biotherapy (p<0.0001) or oral corticosteroids (p<0.01). The least compliant participants were younger (p<0.0001), active smokers (p<0.001), with shorter average disease duration (24.2±15.7 vs 29.1±18.7 years, p<0.0001) and a lower number of substantive asthma treatments (2.2±1 vs 2.6±1, p<0.0001). In multivariate analysis, age, length of disease and anti-IgE treatment were the only factors affecting therapeutic compliance. CONCLUSION: In this large-scale study of severe asthmatic patients, 64.8% were compliant according to the MMAS-4© self-administered questionnaire and appeared to be better monitored according to the criteria defined in our study. Overall, adherence was more satisfactory among older patients and those whose disease had been evolving over a long period of time or were receiving anti-IgE biotherapy.

Effectiveness of Omalizumab in Severe Allergic Asthma and Nasal Polyposis: A Real-Life Study.

BACKGROUND AND OBJECTIVE: Omalizumab is a human anti-IgE antibody approved for the treatment of severe allergic asthma (SAA). However, its effectiveness in SAA associated with chronic rhinosinusitis with nasal polyposis (CRSNP+) is less well documented. Objective: The aim of this study was to evaluate the real-life effectiveness of omalizumab in patients with SAA and CRSNP+ who tolerated and did not tolerate aspirin. METHODS: We performed a retrospective, observational, multicenter, real-life study of patients with SAA and CRSNP+ treated with omalizumab for 6 months. Asthma outcome parameters (symptoms, number of salbutamol rescues/wk, number of moderate/severe exacerbations, Asthma Control Test score, and lung function), sinonasal outcome parameters (symptoms, number of episodes of acute rhinosinusitis, sinus computed tomography images, nasal polyps endoscopy score), and serum eosinophil levels were analyzed 6 months before and after treatment with omalizumab. RESULTS: Twenty-four adult patients were included (9 with documented aspirin intolerance). All respiratory parameters were significantly improved by the treatment. In parallel, a significant improvement was observed in sinonasal clinical outcomes and sinus computed tomography images, with no major effect on the nasal polyps endoscopy score. The serum eosinophil count decreased significantly after 6 months of treatment with omalizumab. CONCLUSION: Treatment of SAA with omalizumab improves the outcome of associated CRSNP+, thus supporting the concept of a "one airway disease".

[Therapeutic strategies in patients undergoing surgery for non-small cell lung cancer. Results of the ESCAP-2011-CPHG study, promoted by the French College of General Hospital Respiratory Physicians (CPHG)]. / Stratégies thérapeutiques chez les patients opérés pour un carcinome bronchique non à petites cellules. Résultats de l'étude ESCAP-2011-CPHG réalisée par le Collège des pneumologues des hôpitaux généraux (CPHG).

BACKGROUND: The aim of ESCAP-2011-CPHG, promoted by the French College of General Hospital Respiratory Physicians, was to describe therapeutic strategies in lung cancer in the first 2 years after diagnosis, in a real-life setting. This article focuses on patients undergoing surgical management of a non-small cell lung cancer (NSCLC). METHODS: A prospective multicentre study was conducted in 53 French general hospitals. For each patient with lung cancer diagnosed in 2010, a standardised form was completed following each change in treatment strategy up to 2 years after diagnosis. RESULTS: Overall, 3418 of the 3943 included patients had NSCLC. 741 patients (21.7%) underwent curative surgery (stage 0-II, IIIA, IIIB, and IV: 65%, 27%, 3% and 5%, respectively). The therapeutic strategy changed less often in surgical than non-surgical patients and average follow-up time was longer: 23.3 months (SD: 9.3) versus 10.4 months (SD: 9.5) for non-surgical patients. Among patients with a surgical first strategy (92.6% of surgical patients as a whole), 56.9% did not receive any other treatment, 34.7% received chemotherapy, 5.9% radio-chemotherapy, 2.6% radiotherapy. At the end of follow-up, 55.8% were still alive without any other strategy, 13.1% had died, and 31.1% had received at least one more strategy. Among patients with a surgical second strategy, 63% had received chemotherapy alone during the first strategy. CONCLUSIONS: ESCAP -2011- CPHG assessed everyday professional practice in the surgical management of NSCLC in general hospitals. It pointed out the discrepancies between current guidelines and the therapeutic strategies applied in real life conditions.

Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†.

BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.

Nerve growth factor levels and localisation in human asthmatic bronchi.

Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa. BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections. The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects. This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo, and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from the increase in nerve growth factor-immunopositive cells determined in the bronchial submucosa.

[Nasosinusal sarcoidosis: 13 cases]. / La sarcoïdose nasosinusienne. A propos de 13 cas.

We report 13 cases of nasosinusal sarcoidosis. Sarcoidosis is a chronic, non caseating granulomatous disease. Nasosinusal involment is rare or exceptional and may be isolated (1 case in our series) or associated (12 cases in our series) with other lesions of the chest, skin, liver, spleen, bone, eyes, salivary glands, peripheral lymph nodes or with neurosarcoidosis. The clinical and CT features are various and often non specific. Nasal biopsy guided by physical examination is easy and constitute the main diagnostic criterion. The course of nasosinusal sarcoidosis is variable and no standard treatment has been established. Response to local or systemic corticosteroid therapy is also variable. The recurrence is frequent after tapering off or interrupting corticosteroids that also have important side effects.

Comparative prognostic value of lactate dehydrogenase and neuron-specific enolase in small-cell lung cancer patients treated with platinum-based chemotherapy.

The influence of pretreatment serum levels of lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) on survival was investigated in a series of 263 consecutive patients with small-cell lung cancer. LDH was elevated in one-half of the patients, NSE in 79%. Both were significantly higher when the disease was considered extensive than when it was limited. The markers were significantly correlated (r= 0.54, P=1.03 x 10(-20)), and both had a significant impact on survival in the univariate analysis. The multivariate survival analysis of the entire population showed that LDH, along with performance status, extent of disease, and albumin, was a more important prognostic factor than NSE. Only when LDH was removed from the model did NSE become an independent prognostic factor. In the separate multivariate survival analyses of limited and extensive disease, LDH remained an independent prognostic factor. For extensive disease, NSE did not even appear in the model when LDH was excluded; for limited stage disease, NSE did become a weak independent prognostic factor when LDH was excluded. In conclusion, LDH, which is less expensive to assay than NSE, is also a stronger independent prognostic factor for small-cell lung cancer and should be part of the initial work-up. In clinical trials, stratification for LDH levels should be considered because of its prognostic weight.

[Radiochemotherapy and radiosensitization for locally advanced non-small-cell bronchial cancer]. / Radiochimiothérapie optimisée pour le cancer bronchique non à petites cellules localement évolué.

Combined chemotherapy and radiotherapy can improve the survival of patients with locally advanced non-small cell lung cancer, when compared to irradiation alone. This survival benefit is essentially due to an increased control of distant micrometastases, whereas local control remains poor. In order to improve local control, new radiotherapy modalities such as 3D conformal treatment, hyperfractionation or accelerated hyperfractionation, are under development. Cytotoxic drugs given at low doses concomitantly to radiotherapy may act as radiosensitizers on the primary tumor. Concomitant chemotherapy at cytotoxic doses and radiotherapy would also allow better control on micrometastases and better local control due to radiosensitization by chemotherapy. However, the concomitant use of chemotherapy and radiotherapy is limited by increased toxicity on normal tissues, more particularly on the esophagus. Randomized comparisons of these modalities versus induction chemotherapy followed by radiotherapy are needed to determine the optimal treatment sequence.