[Epidemiological study of genetic and environmental factors in asthma, bronchial hyperresponsiveness and atopy. Protocol and potential selection bias]. / Etude épidémiologique des facteurs génétiques et environnementaux de l'asthme, l'hyperréactivité bronchique et l'atopie (EGEA). Protocole et biais de sélection potentiels.

BACKGROUND: The EGEA study combines a case-control study and a family study to assess genetic and environmental risk factors and their interactions for asthma, bronchial hyperresponsiveness and atopy. Information is scanty regarding potential selection biases, in particular regarding familial ressemblance in epidemiological surveys of this kind. METHODS: Asthmatic probands (adult and paediatric) were recruited in chest clinics of six clinical centres. Controls were mostly population-based (electoral rolls) for adults and recruited in surgery departments for children. RESULTS: The population examined includes 348 nuclear families ascertained by one asthmatic and 416 controls, totalling 1847 subjects (EGEA I) and an additional sample of 40 families ascertained by two asthmatic siblings (EGEA II). Potential biases for the various types of analyses have been studied. Quantification of the consequences of the greater participation of probands with a parental history of asthma shows it does not introduce a major bias in the estimates of familial resemblance. Cases and controls showed a good comparability regarding sex, age, area of residence and familial geographical origin, allowing proper associations studies for environmental and candidate genetic factors. CONCLUSIONS: The case-control component of the study will allow to perform studies on environmental factors and association studies for various genetic polymorphisms. Using the family base collected, segregation and genetic linkage/association analyses with DNA markers may be performed.

EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy)-- descriptive characteristics.

The Epidemiological study on the Genetics and Environment of Asthma (EGEA) was planned to assess genetic, environmental risk factors and their interactions for asthma and for the two related traits of bronchial hyperresponsiveness and atopy. The population examined includes 348 nuclear families ascertained by one asthmatic (213 adult and 135 paediatric probands) and 416 controls, totalling 1,847 subjects (EGEA I). Prevalences of asthma, skin prick test response, high IgE and bronchial hyperresponsiveness were for parents, siblings, and offspring of cases intermediate between cases and spouses or controls, both in adults and children, confirming the familial resemblance for asthma and related traits. With an additional sample of 40 families ascertained by two asthmatic siblings (EGEA II), a total of 119 families with two asthmatic siblings has been ascertained for a genome screening.

The limits of chemotherapy dose intensification using granulocyte colony stimulating factor alone in extensive small cell lung cancer.

Human Recombinant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung cancer, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m2 day 1, Etoposide 120 mg/m2 day 1-3 and Ifosfamide 2 g/m2 (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (Neupogen, Amgen Roche 5 micrograms/kg/day s.c. day 4-14). Twenty-seven (50%) patients could not receive the total of six courses, seven because of severe septic complication, 10 because of Grade 4 thrombopenia, seven because of non-response and three because of patient refusal. Chemotherapy had to be delayed in 58 out of the 244 administered courses and this was due to thrombopenia in 48% of cases. The probability of optimal dose-on-time administration was 64% at three courses. The mean actually received dose intensity was 93% at six courses (27 patients treated). It was increased by 76% compared to our previously published conventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. The overall response rate after three courses was 77% in the 48 evaluable patients. The median survival is 8 months overall and 5 months disease free. The actuarial survival is 22% at 2 years. We conclude that substantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growth factors active on the megacaryocytic lineage or haematological rescue with peripheral blood stem cells might be useful in this setting.

From granuloma to fibrosis in interstitial lung diseases: molecular and cellular interactions.

Granuloma is a feature of many chronic interstitial lung diseases, and may serve as a focus for subsequent fibrosis. Granulomas are composed of structured masses of cells of the macrophage lineage, which adopt an epithelioid aspect, interspersed with lymphocytes. They are formed around local centres of irritation. During their resolution, fibroblasts congregate around the structures and may penetrate the interior. In many cases, granulomas can disappear without leaving lasting traces. However, especially when damage has occurred to the surrounding tissue, permanent scarring and fibrosis may occur. Both types of cell present in the granuloma are capable of secreting a number of factors influencing the accumulation and proliferation of fibroblasts, both positively and negatively. The possible roles played by the different factors and, especially, interactions between them are discussed in the light of fibrosis formation. Possible therapeutic interventions are summarized.

[Cutaneous Kaposi's sarcoma with pulmonary carcinomatous lymphangitis in patient with heart transplantation]. / Sarcome de Kaposi cutané avec lymphangite carcinomateuse pulmonaire chez un transplanté cardiaque.

The great strides in organ transplantation have been accompanied by some specific pathologies, notably, neoplasia, including Kaposi's sarcoma which occupies the third place in frequency after cutaneous tumours and malignant lymphomas. We report a case of cutaneous Kaposi's sarcoma developing some six months after a cardiac transplant. The modulation of immuno-suppression and treatment with Alpha interferon allowed an initial stabilisation of the cutaneous lesions. However, there were secondary developments of the lesions and, 21 months after the initial presentation, the patient developed a diffuse infiltrating pneumonia leading to death. The autopsy revealed lymphangitis carcinomatosis of Kaposi's sarcoma type. This observation underlines the therapeutic difficulties seen in Kaposi's sarcoma after organ transplantation when there is no alternative to allow a significant reduction or cessation of immuno-suppression.

[Clinical and economic evaluation of the initial assessment of small cell cancer of the lung. Alternatives to classic evaluation. LGTO. The Lyon Group of Thoracic Oncology]. / Evaluation clinique et économique du bilan initial des cancers du poumon à petites cellules. Alternatives à un bilan classique. GLOT. Groupe Lyonnais d'Oncologie Thoracique.

Alternatively to the usual evaluation summary, a characteristic of small cell lung cancer, is the probability of significant diffuse metastases; the prognosis is directly linked to the extent of these metastases. Moreover, the assessment of the initial extension becomes heavier and more costly as investigations continue and each new technology appears. In order to evaluate the contribution of each examination, a classification has been established as a function of the time-scale to obtain the results, of the technology involved, or whether the investigation is painful or not and any likelihood of iatrogenic side-effects. An assessment in three stages is proposed to achieve the most effective and cheapest diagnosis possible. In relation to the usual technique of assessment this sequential approach allows for a 27% reduction in the time-scale for the diagnosis of diffuse disease, 51.3% in terms of technical involvement, 46.3% in terms of pain and discomfort and 53.9% in terms of iatrogenic potential. At the same time a reduction in cost of 47.5% is observed.

[Alveolar proteinosis. Prolonged favorable course after total pulmonary lavage]. / Protéinose alvéolaire. Evolution favorable prolongée après lavage pulmonaire total.

We report the outcome in a case of alveolar proteinosis diagnosed histologically in a 43 year old female. The increase in dyspnoea and the deterioration in the pulmonary function tests have lead to the realisation that a total pulmonary lavage was required under general anaesthesia. This was performed in two stages. A biochemical analysis of the lavage liquid showed an accumulation of phospholipids, proteins, and LDH. A subjective improvement was obtained in a few weeks followed by a slow radiological improvement as well as on CT scanning, and in respiratory function. Radiological and blood gas improvement was noted 19 months after total bilateral pulmonary lavage. Broncho-alveolar lavage is thus able to induce long-term improvement in pulmonary alveolar proteinosis.

[T-lymphocytes disorders in pulmonary sarcoidosis]. / Perturbations lymphocytaires T au cours de la sarcoïdose pulmonaire.

Sarcoidosis is a granulomatous disorder of unknown aetiology accompanied by variable immunological changes which concern both the monocyte and lymphocyte cell line. During the course of this disease anomalies of distribution (with accumulation in the disease tissue contrasting with a peripheral lymphopenia) and also of T cell functions (a predominance of CD4 T lymphocytes within the lesions and spontaneous expression of activation criteria) have been described. Recent works show some disturbances of T cell function and evoke the possibility of the initial pathology being related to this cell. Some current hypotheses place the T cell receptor for the antigen and the interleukin 2 receptor whose dysfunction will lead to an anomaly of the transduction of the activating signal of the T lymphocyte. The intrinsic origin (genetically determined) or extrinsically (retroviral) of these disturbances remains however to be determined.

[Diffuse interstitial pneumopathies caused by lentivirus (HIV-1) in humans and animals]. / Pneumopathies interstitielles diffuses dues aux lentivirus chez l'homme (HIV-1) et chez l'animal.

Lentiviruses belong to the retroviruses family (ie RNA viruses with reverse transcriptase activity); they induce inflammatory and/or degenerative slowly progressive diseases, affecting various organs. Some lentiviruses preferentially infect lymphocytes (HIV-1 and HIV-2, SIV and FIV) and are associated with infectious and tumoral disorders. Most lentiviruses induce a pulmonary disease, typically diffuse interstitial pneumonia. The visna/maedi-virus of sheep infects monocyte macrophage cells and the pulmonary lesions are macrophagic and neutrophilic alveolitis, lymphoid infiltration, myomatosis and interstitial fibrosis. Such pulmonary lesions are also induced by the goat and equine lentiviruses. In humans infected by HIV-1 or HIV-2, a diffuse interstitial lung disease also occurs; the histological findings are of alveolitis associated with lymphoid peribronchovascular infiltrates. The mechanism of formation of the lesions involves complex cellular interactions (especially between macrophage and lymphocyte, via cytokine production). These interactions are well modelled by small ruminant lentivirus induction of interstitial pneumonia.