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Management of primary ciliary dyskinesia in European children: recommendations and clinical practice.

The European Respiratory Society task force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe.

Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median of 4 (IQR 2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analyse by electron microscopy (77%), ciliary function tests (57%) or both (84%). Nasal nitric oxide for screening was used in 46% of centres, saccharine tests in 36%.

Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments.In conclusion, we found substantial heterogeneity in management of PCD within and between countries and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries.

Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.

Environmental Measures in Domicilliary Interventions of Asthmatic Children.

OBJECTIVE: To evaluate the impact of environmental interventions and lifestyle management on respiratory symptoms, concurrent changes in asthma management and whether any observed health benefit could be attributed to these interventions.

METHODS: A longitudinal single cohort pre-post study was conducted on children between 5-14 y with moderate to severe asthma in an outpatient clinic at Jamshedpur over 2 y. History was noted using the pre-intervention questionnaire covering a period of 3 mo prior to enrolment. Participants were followed for 6 mo post- intervention. A childhood asthma severity (CHAS) scale was made and statistical analysis such as Wilcoxon rank sum tests and Mcnemar's test performed to validate the outcomes. Principal component analysis was performed to classify the participants having no, mild and severe symptoms.

RESULTS: There was significant reduction in symptoms and need for medical care post- intervention. Mean of the respiratory symptom score decreased from 7.4 to 2.4 (p < 0.0001) and mean of the health care utilization score decreased from 4.1 to 1.7 (p < 0.0004) in the wilcoxon rank sum tests. Mcnemar's test was used for the analysis of individual item of the asthma symptoms. A significant reduction in wheeze and cough (p < 0.001), slowing down physical activity (p < 0.001), diurnal symptoms (p < 0.000), school absence (p < 0.000), rescue therapy requirement (p < 0.1) and hospitalization (p < 0.000) was seen. PCA was used successfully to classify the participants on the basis of their severity of asthma.

CONCLUSIONS: Respiratory symptoms decreased significantly among asthmatic children following environmental interventions.

Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors.

EGFR screening requires good quality tissue, sensitivity and turn-around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome.

METHODS: Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2.

RESULTS: In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (<2 ng/μL) had more test failures (30% versus 3.9% for [DNA]>2.2 ng/μL), the mutation rate was 9.2%.

CONCLUSION: Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better-differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation.

Diagnosis and management of anaemia and iron deficiency in patients with haematological malignancies or solid tumours in France in 2009-2010: the AnemOnHe study.

OBJECTIVE: To describe the management of anaemia in 2009-2010 in France in patients with haematological malignancies (HM) or solid tumours (ST).
METHODS: Retrospective observational study in 57 centres, enrolling adult patients with HM or ST treated for an episode of anaemia (duration of the episode ≥ 3 months occurring in the last 12 months).

RESULTS: 220 patients with ST (breast, 18%; lung, 18%) and 56 with HM (lymphoma, 60%) were included (median age, 68 years; female, 53%). Mean haemoglobin level at anaemia diagnosis was 9.3 ± 1.4 g/dL (<8 g/dL for 16%) and 9.8 ± 1.1g/dL (<8 g/dL for 6%) in HM and ST patients, respectively. At least one parameter of iron deficiency (ferritin, transferrin saturation) was assessed in 26% of HM and 19% of ST patients. Treatment of anaemia included erythropoiesis-stimulating agents (ESA) for 98% of HM and 89% of ST patients. Iron was prescribed to 14% (oral, 12%; intravenous, 2%) of HM patients and to 42% (oral, 17%; intravenous, 25%) of ST patients. The rates of blood transfusions were high: 70% in HM and 46% in ST patients; transfusions alone or administrated with ESA were more frequent in patients with Hb <8 g/dL.

CONCLUSION: Although recent guidelines recommend evaluating iron deficiency and correcting anaemia by using intravenous iron, our study in cancer patients evidenced that ESA and blood transfusions are still frequently used as the treatment of anaemia in cancer patients. Iron deficiency is insufficiently assessed (only one patient among five) and as a consequence iron deficiency is most likely insufficiently treated.

PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer.

We have previously developed (11)C-erlotinib as a new positron emission tomography (PET) tracer and shown that it accumulates in epidermal growth factor receptor (EGFR)-positive lung cancer xenografts in mice. Here, we present a study in patients with non-small cell lung cancer (NSCLC) investigating the feasibility of (11)C-erlotinib PET as a potential method for the identification of lung tumours accumulating erlotinib.

METHODS: Thirteen patients with NSCLC destined for erlotinib treatment were examined by contrast-enhanced computed tomography (CT), (11)C-erlotinib PET/low-dose CT and (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/low-dose CT before start of the erlotinib treatment. After 12 weeks treatment, they were examined by (18)F-FDG PET/contrast-enhanced CT for the assessment of clinical response.

RESULTS: Of the 13 patients included, 4 accumulated (11)C-erlotinib in one or more of their lung tumours or lymph-node metastases. Moreover, (11)C-erlotinib PET/CT identified lesions that were not visible on (18)F-FDG PET/CT. Of the four patients with accumulation of (11)C-erlotinib, one died before follow-up, whereas the other three showed a positive response to erlotinib treatment. Three of the nine patients with no accumulation died before follow-up, four showed progressive disease while two had stable disease after 12 weeks of treatment.

CONCLUSION: Our data show a potential for (11)C-erlotinib PET/CT for visualizing NSCLC lung tumours, including lymph nodes not identified by (18)F-FDG PET/CT. Large clinical studies are now needed to explore to which extent pre-treatment (11)C-erlotinib PET/CT can predict erlotinib treatment response.

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