Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases.

BACKGROUND: Heritable forms of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH) diverge by lung histopathological lesions, clinical and para-clinical presentation, their responsible genes, and mode of transmission. Since the identification of the BMPR2 gene in families affected by PAH, mutations in several other genes have been discovered for both forms. The mutation landscape in these new genes is not yet well known. METHODS: We set up a next-generation sequencing-based targeted sequencing gene panel allowing known genes for PAH and PVOD/PCH to be analysed simultaneously. Genetic analysis was prospectively performed on 263 PAH and PVOD/PCH patients (adult and paediatric cases). RESULTS: Pathogenic mutations were identified in 19.5% of sporadic PAH patients (n=180), 54.5% of familial PAH patients and 13.3% of PVOD/PCH patients. BMPR2 was the most frequently mutated gene, followed by TBX4 in both paediatric and adult PAH. BMP9 mutations were identified in 1.2% of adult PAH cases. EIF2AK4 biallelic mutations were restricted to PVOD/PCH. A truncating mutation and a predicted loss-of-function variant were also identified in BMP10 in two severely affected sporadic PAH female patients. CONCLUSION: Our results confirm that mutations are found in genes beyond BMPR2 in heritable PAH, emphasise the role of TBX4 and BMP9, and designate BMP10 as a new PAH gene.

The "one airway, one disease" concept in light of Th2 inflammation.

In line with the pathophysiological continuum described between nose and bronchus in allergic respiratory diseases, we assessed whether nasal epithelium could mirror the Type 2 T-helper cell (Th2) status of bronchial epithelium.Nasal and bronchial cells were collected by brushing from healthy controls (C, n=13), patients with allergic rhinitis and asthma (AR, n=12), and patients with isolated allergic rhinitis (R, n=14). Cellular composition was assessed by flow cytometry, gene expression was analysed by RNA sequencing and Th2, Type 17 T-helper cell (Th17) and interferon (IFN) signatures were derived from the literature.Infiltration by polymorphonuclear neutrophils (PMN) in the nose excluded 30% of the initial cohort. All bronchial samples from the AR group were Th2-high. The gene expression profile of nasal samples from the AR group correctly predicted the paired bronchial sample Th2 status in 71% of cases. Nevertheless, nasal cells did not appear to be a reliable surrogate for the Th2 response, in particular due to a more robust influence of the IFN response in 14 out of 26 nasal samples. The Th2 scores in the nose and bronchi correlated with mast cell count (both p<0.001) and number of sensitisations (p=0.006 and 0.002), while the Th17 scores correlated with PMN count (p=0.006 and 0.003).The large variability in nasal cell composition and type of inflammation restricts its use as a surrogate for assessing bronchial Th2 inflammation in AR patients.

Outpatient management of primary spontaneous pneumothorax: a prospective study.

We prospectively assessed the safety and cost saving of a small-bore drain based procedure for outpatient management of first episodes of primary spontaneous pneumothorax. Patients were managed by observation alone or insertion of an 8.5-F "pig-tail" drain connected to a one-way valve, according to size and clinical tolerance of the pneumothorax. All patients were reassessed after 4 h, on the first working day after discharge and on day 7. Patients still exhibiting air leak on day 4 underwent thoracoscopy. The primary end-point was complete lung re-expansion at day 7. 60 consecutive patients entered the study. 48 (80%) met the definition of large pneumothorax. The success rate was 83%. The 1-year recurrence rate was 17%. 36 (60%) patients were discharged after 4 h and 50% had full outpatient management. No severe complication was observed. The mean ± SD length of hospitalisation was 2.3 ± 3.1 days. This policy resulted in about a 40% reduction in hospital stay-related costs. The present study supports the use of a single system combined with a well-defined management algorithm including safe discharge criteria, as an alternative to manual aspiration or chest tube drainage. This approach participates in healthcare cost-savings.

Two panels of plasma microRNAs as non-invasive biomarkers for prediction of recurrence in resectable NSCLC.

The diagnosis of non-small cell lung carcinoma (NSCLC) at an early stage, as well as better prediction of outcome remains clinically challenging due to the lack of specific and robust non-invasive markers. The discovery of microRNAs (miRNAs), particularly those found in the bloodstream, has opened up new perspectives for tumor diagnosis and prognosis. The aim of our study was to determine whether expression profiles of specific miRNAs in plasma could accurately discriminate between NSCLC patients and controls, and whether they are able to predict the prognosis of resectable NSCLC patients. We therefore evaluated a series of seventeen NSCLC-related miRNAs by quantitative real-time (qRT)-PCR in plasma from 52 patients with I-IIIA stages NSCLC, 10 patients with chronic obstructive pulmonary disease (COPD) and 20-age, sex and smoking status-matched healthy individuals. We identified an eleven-plasma miRNA panel that could distinguish NSCLC patients from healthy subjects (AUC = 0.879). A six-plasma miRNA panel was able to discriminate between NSCLC patients and COPD patients (AUC = 0.944). Furthermore, we identified a three-miRNA plasma signature (high miR-155-5p, high miR-223-3p, and low miR-126-3p) that significantly associated with a higher risk for progression in adenocarcinoma patients. In addition, a three-miRNA plasma panel (high miR-20a-5p, low miR-152-3p, and low miR-199a-5p) significantly predicted survival of squamous cell carcinoma patients. In conclusion, we identified two plasma miRNA expression profiles that may be useful for predicting the outcome of patients with resectable NSCLC.

Comprehensive allergy work-up is mandatory in cystic fibrosis patients who report a history suggestive of drug allergy to beta-lactam antibiotics.

BACKGROUND: In the general population, reports on suspected ß-lactam hypersensitivity are common. After a drug allergy work-up at best 20% of the selected patients are positive. However, these considerations have not been explored in cystic fibrosis patients for whom antibiotics are even more crucial. METHODS: The study, part of the Drug Allergy and Hypersensitivity (DAHD) cohort, was performed in the regional cystic fibrosis center of Montpellier, France. After identifying patients with a clinical history suggestive of drug allergy to ß-lactams, a complete drug allergy work-up, was carried out according to the EAACI recommendations. RESULTS: Among the 171 patients involved, 23 reported clinical manifestations potentially compatible with a drug allergy to ß-lactams. After performing the complete drug-allergy work-up, 7 were considered as drug hypersensitive (3 had positive skin tests, 1 a positive provocation test, 3 declined the tests). Excluding the latter 3 patients with incomplete drug allergy work-up, the rate of proven drug allergy was 2.3%. CONCLUSIONS: Drug allergy to ß-lactams in cystic fibrosis patients is of importance. A full drug allergy work-up is mandatory in case of suspicion, because ß-lactam responsibility is often ruled out.

Idiopathic acute eosinophilic pneumonia requiring ECMO in a teenager smoking tobacco and cannabis.

We describe what we believe is an entirely novel case of a 15-year-old boy with idiopathic acute eosinophilic pneumonia and unusual, resistant hypoxemia which necessitated extracorporeal membrane oxygenation. Response to corticosteroids was excellent and a full recovery was observed. Smoking cigarettes and cannabis on the day the symptoms began may have contributed to the occurrence of this rare disease.