[Bevacizumab and lung cancer: eligible patients in daily practice]. / Bévacizumab et cancer bronchique: population cible en pratique quotidienne.

BACKGROUND: Combining bevacizumab with platinum-based chemotherapy significantly improves survival for patients with advanced non-squamous non-small cell lung cancer. The objective of this study was to assess the proportion of patients who could receive this combined therapy. METHODS: This was a retrospective single centre analysis of patients treated between 2007 and 2008. Exclusion criteria for bevacizumab included: squamous cell carcinoma, contraindication to platinum-based chemotherapy, uncontrolled hypertension, haemoptysis superior to 2.5 mL, recent surgery, and/or tomodensitometric criteria after independent review by two radiologists (contact with a proximal vessel, tracheobronchial involvement, cavitation). Cardiovascular diseases and central tumour location were not systematically considered as contraindications. RESULTS: Among 194 patients analysed, 21 (10.8%) to 35 (18%) patients were eligible for bevacizumab, whether or not cardiovascular diseases and central tumour location were considered as contraindications. The kappa coefficient was 0.49. CONCLUSION: Even though the proportion of patients who can receive chemotherapy plus bevacizumab may vary according to the eligibility criteria chosen and the interpretation of the CT scan, it is unlikely to exceed 25% of patients in daily practice.

The contribution of CT-guided transthoracic lung biopsy to the diagnosis of organising pneumonia.

BACKGROUND: Organising pneumonia is a pulmonary disease with variable clinical and radiological features and with many differential diagnoses. Diagnosis is based on histology obtained by either transbronchial or surgical lung biopsy but these techniques have several disadvantages. The aim of this study was to evaluate the diagnostic yield of CT-guided transthoracic lung biopsy in organising pneumonia and to compare it to the usual diagnostic tools. METHODS: Six cases of organising pneumonia diagnosed with CT-guided lung biopsy are reported and discussed. The role of CT-guided lung biopsy in the diagnosis of organising pneumonia was also reviewed in the literature. RESULTS: CT-guided transthoracic lung biopsies provided a higher rate of adequate samples than transbronchial biopsies (92-100% versus 77-86%). The samples were larger, which reduced the risks of misdiagnosis and increased the diagnostic yield (88-97% versus 26-55% in pulmonary nodules and 42-100% versus 66-75% in diffuse pulmonary disease). Complications were rare and generally not serious. CONCLUSION: CT-guided transthoracic lung biopsy may be considered in place of transbronchial biopsy in the diagnosis of organising pneumonia. Surgical lung biopsy remains the gold standard method for diagnosis.

[The contribution of CT-guided transthoracic lung biopsy to the diagnosis of organizing pneumonia]. / Apport de la biopsie pulmonaire transthoracique dans le diagnostic de pneumonie organisée.

BACKGROUND: Organizing pneumonia is a pulmonary disease with variable clinical and radiological features and with many differential diagnoses. Diagnosis is based on histology obtained by either transbronchial or surgical lung biopsy but these techniques have several disadvantages. The aim of this study was to evaluate the diagnostic yield of CT-guided transthoracic lung biopsy in organizing pneumonia and to compare it to the usual diagnostic tools. METHODS: Six cases of organizing pneumonia diagnosed with CT-guided lung biopsy are reported and discussed. A review of literature concerning the role of CT-guided lung biopsy in the diagnosis of organizing pneumonia was performed. RESULTS: CT-guided transthoracic lung biopsies provided a higher rate of adequate samples than transbronchial biopsies (92-100% versus 77-86%). The samples were larger, which reduced the risks of misdiagnosis and increased the diagnostic yield (88-97% versus 26-55% in pulmonary nodules and 42-100% versus 66-75% in diffuse pulmonary disease). Complications were rare and generally not serious. CONCLUSION: CT-guided transthoracic lung biopsy may be considered in place of transbronchial biopsy in the diagnosis of organizing pneumonia. Surgical lung biopsy remains the reference method for diagnosis.

Multivariate analysis of factors predictive of brain metastases in localised non-small cell lung carcinoma.

Brain metastases are a frequent feature of the course of non-small cell lung carcinoma (NSCLC). The potential usefulness of prophylactic cranial irradiation (PCI) has led to the search for target groups likely to derive benefit. This multivariate analysis looked for factors predictive of brain metastases in a group of stages I-III NSCLC patients under care of the thoracic oncology unit of Besançon University Hospital from 1977 to 2001. All the patients had the same follow-up. They were divided into two groups: BM+ when they had a brain metastasis as the first site of progression, whether solitary or not, and BM(-) otherwise. Variables analysed were age, gender, performance status (0-1 versus 2-3), weight-loss stage T-status, N-status, pathological type, type of treatment, administration of chemotherapy, use of cisplatin and response to treatment. Three hundred and five patients were eligible and there were 77 patients (25.25%) in the BM+ group. Median time to onset of brain metastases was 12 months (1-163 months) and median survival from the diagnosis of brain metastases was 6 months (1-65 months). Factors predictive of brain progression were age < or =62 years (RR: 2.5, 95% CI: 1.33-4.76 and P = 0.004), T4 tumour status (RR: 3.75, 95% CI: 1.72-8.21 and P = 0.0009), N2-3 (RR: 2.61, 95% CI: 1.32-5.15 and P = 0.0057), and adenocarcinoma (RR: 3.39, 95% CI: 1.78-6.46 and P = 0.0002). No aspect of treatment plays a role in the frequency of this type of metastasis. These factors predictive of brain progression could serve as a basis for the selection of patients with the aim of sitting of studies on prophylactic cranial irradiation in NSCLC.

Respiratory status in dairy farmers in France; cross sectional and longitudinal analyses.

AIMS: To compare respiratory status in dairy farmers with that of non-farming controls. METHODS: Longitudinal study in the Doubs (France). From a cohort constituted in 1994 (T1), 215 (81.1%) dairy farmers and 110 (73.8%) controls were reevaluated in 1999 (T2). The protocol comprised a medical and occupational questionnaire, spirometric tests at both evaluations, allergological tests at T1, and a non-invasive measure of blood oxygen saturation (SpO2) at T2. RESULTS: In 1999 analyses, the prevalence of chronic bronchitis was higher (p = 0.013), and FEV1/VC (p < 0.025) and SpO2 (-0.7%, p < 0.01) lower in dairy farmers than in controls. In a multiple linear regression model, farming, age, and smoking were significantly and inversely correlated with SpO2. In the whole population, the mean annual decline in FEV1 and FEV1/VC was -13.4 ml and -0.30%, respectively. Farming was associated with an accelerated decline in FEV1/VC (p < 0.025) after adjustment for covariates. No relation between allergy and respiratory function changes was observed, except for FEF25-75. CONCLUSIONS: This prospective study shows that dairy farming is associated with an excess of chronic bronchitis, with a moderate degree of bronchial obstruction and a mild decrease in SpO2.

Respiratory morbidity in a population of French dental technicians.

AIMS: To compare wage earner dental technicians with non-exposed salaried subjects for the prevalence of respiratory symptoms and function, and chest x ray abnormalities. METHODS: A total of 134 dental technicians and 131 non-exposed subjects participated. A medical and an occupational questionnaire were filled in to evaluate the prevalence of respiratory symptoms and occupational exposures. Subjects underwent respiratory tests and chest x ray examination. RESULTS: Mean age of the dental technicians was 36.6 years with a mean duration of dental work of 16.5 years. There was a significant risk of cough (day and night) and usual phlegm in dental technicians. Respiratory function parameters were lower in dental technicians with a significant difference between exposed and non-exposed groups for % FVC (forced vital capacity), % FEF(25) (forced mid expiratory flow), and % FEF(50). The prevalence of small opacities increased with age. Small opacities were significantly related to an exposure to asbestos in the past. CONCLUSIONS: Our young population of dental technicians is at risk of respiratory morbidity. They should benefit from adequate technical prevention measures.

Prevalence of asthma and respiratory symptoms in dairy farmers in the French province of the Doubs.

With the aim of determining whether dairy farming is associated with an excess of asthma and respiratory symptoms, we compared the respiratory status in a sample of dairy farmers (n = 265) and a control group of nonexposed subjects (n = 149). The study protocol comprised a questionnaire, spirometry, and a bronchodilatation test (400 micrograms salbutamol powder), and an allergological evaluation: serum total IgE level, Phadiatop test, and skin prick tests (SPT) for seven inhalant allergens. Cumulative prevalences of self-reported asthma and of current asthma were respectively 5.3% and 1.5% in farmers, and respectively 3.4% and 1.3% in control subjects (both NS). Prevalences of all the respiratory symptoms studied were higher in farmers, with statistically significant differences after adjusting for age, sex, and smoking, for wheezing ever (OR: 2.7, p < 0.05), wheezing within the last year (OR: 5.2, p < 0.025), usual morning cough (OR: 5, p < 10(-)3), usual morning phlegm (OR: 11.3, p < 10(-)4), and chronic bronchitis (OR: 11.8, p < 0.01). The effect of exposure on these symptoms was more pronounced than, or of the same magnitude as that of smoking. Smoking and exposure had an additive effect except for chronic cough for which a positive interaction was observed (p = 0.05). Mean FEV1/VC (percentage of predicted) was statistically negatively correlated to dairy farming (p < 0.025) after adjusting for confounders. Bronchial obstruction was reversible in about 10% of subjects in both groups. In conclusion, this study mainly demonstrated an excess of respiratory symptoms in dairy farmers which is weak and nonsignificant for asthma, and high for cough, phlegm, and chronic bronchitis. It also suggested that the combined effect of farming and smoking was synergistic on chronic cough.

Six year longitudinal study of respiratory function in dairy farmers in the Doubs province.

A previous study, carried out in 1986 in France, showed the prevalence of respiratory symptoms and of respiratory function impairment to be higher in dairy farmers than in a control group of nonexposed subjects living in a rural zone. In order to confirm the harmful effect of dairy farming, the two groups were re-studied 6 yrs later at the same period of the year. One hundred and ninety-four (77.6%) farmers and 155 (62%) control subjects were available for re-examination. Non-re-evaluated subjects were comparable to re-evaluated subjects for age, sex, smoking and respiratory symptoms and function at initial evaluation. Dairy farmers consistently had more respiratory symptoms and lower levels of respiratory function than did control subjects. In the study populations as a whole, the mean annual decline in vital capacity (VC) and forced expiratory volume in one second (FEV1) was slightly, but nonsignificantly, higher in farmers than in control subjects: in mL x yr(-1) (SD), -43.1 (68.2) versus -37.9 (60.2) for VC and -32.8 (56.7) versus -30 (47.2) for FEV1. There was a positive interaction between farming and age (i.e. duration of exposure in this cohort) on respiratory function decline, and in male subjects aged > or = 45 yrs, dairy farming was associated with an accelerated loss in VC (p<0.05) and FEV1 (p<0.05) after controlling for age, smoking, height and geographic location in a multiple linear regression model. Initial values of respiratory function, age and pack-years smoked (only for VC) were the other variables found to be significant determinants of decline in lung function. In conclusion, this study mainly suggests that dairy farming is associated to a very moderate accelerated loss in respiratory function that increases with duration of exposure and is significant in older male subjects.

[Respective influence of occupational and personal factors on respiratory function in dairy farmers]. / Influence respective des facteurs professionnels et personnels sur la fonction respiratoire en milieu agricole de production laitière.

Occupational and individual factors influencing respiratory function were analysed in a sample of dairy farmers. The study protocol included a medical questionnaire, an occupational questionnaire, spirometry and allergological tests (skin prick tests for a panel of inhalant allergens, serum total IgE level and Phadiatop (CAP System). Two hundred and forty-five farmers were studied (140 men, 105 women with an average age of 45.9 (11.3) years, 35 were smokers, 27 ex-smokers and 183 non-smokers). A multiple linear regression model was used to analyse the correlations between respiratory function and the different independent variables. There was a statistically significant negative correlations between smoking (expressed in pack-years) and all the respiratory function parameters (p < 0.01). Respiratory function was significantly impaired in farmers working on traditional farms (p < 0.05 for VC and for FEV1), and the respiratory function values increased proportionally with the modernisation of the farms (notably using an artificial barn drying system for hay and a ventilation system for the cow byres). No significant relationship between respiratory function and quantitative indicators of exposure (size of farm, amount of livestock, quantity of hay handled during professional lifetime) or indicators of IgE-mediated allergy was observed. In conclusion, this study suggests that traditional work conditions in farms which have little mechanisation are, along with tobacco, the determining factors for the respiratory function impairment in dairy farmers.

[Second line chemotherapy in patients with refractory and resistant non small cell lung cancer]. / Chimiothérapie de deuxième ligne chez les patients réfractaires et résistants atteints de cancers du poumon non à petites cellules.

Effectiveness of chemotherapy has been demonstrated in stage IV non small cell lung cancer as well as in stage IIIb disease when combined with radiotherapy. A significant improvement of both survival and quality of life was shown and is thought to be associated with higher efficiency. Therefore, treatment of relapses is now a question of practical interest. Ninety-seven non small cell lung cancer patients who were delivered a second line chemotherapy following primary chemotherapy alone were reviewed. Sixty-five patients were administered a 2 drug cisplatin-based regimen (with etoposide, bleomycin or vinorelbine). Twenty eight patients received no cisplatin but the cyclophosphamide, epirubicin combination or any 2-drug regimen assembled from the following agents: etoposide, mitomycin, ifosfamide. The last 4 patients were given single-agent vinorelbine. Fifteen objective responses (15.2%) (95% CI: 9-24%) were observed. The median response duration was 27 weeks. Response rates were 18.4% (95% CI 9-28%) and 9.3% (95% CI: 0-19%) in cisplatin-based combinations and in other regimens, respectively. No difference in response rates was observed between primary responsive and non responsive patients but response rates were influenced by the choice of the first line combination chemotherapy.

Longitudinal study of respiratory health in dairy farmers: influence of artificial barn fodder drying.

Factors influencing respiratory consequences of dairy farming have not been extensively investigated to date. To evaluate the effects of barn fodder drying on respiratory symptoms and lung function, a 5 yr follow-up study was performed in the Doubs (France). A cohort of male dairy farmers was analysed in 1990. The initial cross-sectional results suggested that barn-drying fodder may protect dairy farmers from lung function impairment. In 1995, 113 barn-drying farmers (92%) and 231 traditional-drying farmers (84%) were re-analysed. Barn and traditional fodder-drying farmers were compared for prevalence of symptoms and spirometric measures of lung function. After controlling for age, smoking status, altitude and cumulative exposure, barn-drying farmers compared to traditional-drying farmers had a lower prevalence of chronic bronchitis (4 versus 10%; p<0.05) and slightly higher values of forced expiratory volume in one second (FEV1) (p=0.06) and FEV1/vital capacity (VC) (p<0.01). Nevertheless, decline of the respiratory function parameters was not significantly different between the two groups. Variables positively and significantly associated to longitudinal decline of lung function parameters were: age (FEV1, FEV1/VC); altitude (VC, FEV1) and chronic bronchitis and dyspnoea at the initial survey (FEV1/VC). Persistence and emergence of chronic bronchitis, dyspnoea and symptoms at exposure were also significantly associated to an acceleration in the annual decline of the respiratory function. In conclusion, the mode of fodder drying does not seem to significantly influence the decline in lung function. Nevertheless, this study confirms the results of the initial cross-sectional analysis and supports the hypothesis that barn drying fodder may have a protective effect on respiratory health in dairy farming.

[Prevalence of immediate allergy to respiratory allergens in fodder farmers in Doubs]. / Prévalence de l'allergie immédiate aux pneumallergènes chez les agriculteurs fourragers du Doubs.

The Doubs is a damp, semi-mountainous fodder farming department in which occupational respiratory diseases (including asthma) are common in farmers. We studied the prevalence of IgE-mediated allergy (total IgE, Phadiatop and skin prick tests) in a group of 265 exclusive dairy farmers of both sexes of the department and in a control group of non exposed, administrative workers living in the same area. Skin prick tests were: Dermatophagoides pteronyssinus, Acarus siro, cat hair, cow danders, grass pollens, betullacea pollens (trees from the East of France), and hay extracts from the Doubs. Total IgE were higher than 180 KUI/l in 26 (9.9%) farmers and in 15 (10.5%) controls (NS). Phadiatop was positive in 41 (15.7%) farmers and in 27 (19%) controls (NS). Prevalence of positive skin prick tests (at least one) in farmers and controls was respectively 36% and 40% (NS). Farmers were more frequently sensitized to hay extracts (OR = 1.7), cow danders (OR = 1.3) and less frequently to cat hair (OR = 0.63) than controls but the differences were not statistically significant. In conclusion, this study fails to give evidence of a risk of IgE-mediated allergy to work-related and other common inhalation allergens in dairy farmers the Doubs.

Farmer's lung precipitins in Doubs (a department of France): prevalence and diagnostic value.

In a French region where farmer's lung (FL) is common, we determined the prevalence of FL precipitins in dairy farmers and analyzed the relation between the presence of FL precipitins and the clinical probability of the disease. All the exposed dairy farmers of both sexes (n = 2555) from five districts of the Doubs department were asked to respond to a medical and professional questionnaire. A total of 1763 (69%) farmers agreed to participate. Precipitins tests were conducted in 551 (31%) farmers who showed any respiratory symptom and in a random sample of 100 asymptomatic farmers. Serum for each farmer was analyzed by both double diffusion and immunoelectrophoresis against Micropolyspora faeni (MF) and extracts of moldy hay (HE) from Doubs. The 651 farmers were then divided into four groups (G 1-4) with a decreasing probability of FL (G1: typical FL symptoms; G4: asymptomatic farmers). The estimated prevalence of precipitins in the whole population was as follows: 1) by double diffusion, against HE: 83%, against MF: 27%; 2) by immunoelectrophoresis, against HE: 26%, against MF: 19%. There was a close "linear" relation between the prevalence of precipitins detected by immunoelectrophoresis against HE and the symptoms: 51% in G1, 36% in G2, 29% in G3, and 13% in G4. Precipitins detected by immunoelectrophoresis were also related to exposure and geography (more immunization in tableland area than in plain or mountain area). Presence of precipitins detected by double diffusion was not related to symptoms, exposure, or geography.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of barn drying of fodder on respiratory symptoms and function in dairy farmers of the Doubs region of France.

BACKGROUND: A previous study showed there to be fewer microorganisms (especially thermophilic actinomycetes) on farms with artificial barn drying of fodder than on those using traditional storage methods. A cross sectional study was performed to see whether barn drying provides protection against respiratory problems in dairy farmers. METHODS: The respiratory symptoms and function of a group of 123 farmers with daily exposure to cattle foddering from farms which had had a barn drying system for at least three years were compared with those of a representative sample of 274 farmers working in farms with traditional storage in five districts in the Doubs region of France. RESULTS: Both groups were comparable for mean age, weight, height, smoking habits, alcohol consumption, past history of respiratory disease, history of allergy, geographical location of the farm, and length of exposure. Retrospectively estimated exposure to fodder was greater in the group using a barn drying system than in the group working with traditional storage. Acute symptoms at exposure (rhinitis, eye irritation, dry cough, asthma symptoms) and chronic symptoms all tended to be less frequent in the barn drying group, although not individually significantly so. Mean (SD) respiratory function parameters were higher in the barn drying group than in the traditional group: % vital capacity (VC) 104 (14) v 102 (15); % forced expiratory volume in one second (FEV1) 99 (14) v 94 (18); % FEV1/VC 96 (11) v 92 (16); % forced mid expiratory flow (FEF25-75) 87 (24) v 79 (25). CONCLUSION: The results of this cross sectional study suggest that barn drying of fodder may protect respiratory function in dairy farmers.

Prevalence and risk factors for chronic bronchitis and farmer's lung in French dairy farmers.

The prevalence of chronic bronchitis and of clinical farmer's lung was studied in 30 districts of the French Doubs province in relation to individual (age, sex, smoking) and geographical (altitude) factors. 5703 exclusively dairy farmers (response rate 83%) participated in the study by answering a medical questionnaire. Prevalences of chronic bronchitis and clinical farmer's lung were 9.3% and 1.4% respectively. A logistic regression model was used to evaluate risk factors for chronic bronchitis and clinical farmer's lung. A risk of chronic bronchitis was associated with male sex (p < 10(-4)), age (p < 10(-4)), smoker category (p < 10(-4)), and altitude (p < 10(-4)). A risk of clinical farmer's lung was associated with non-smokers (p < 0.05), and linearly with altitude (p < 10(-4)). Also there was a strong positive relation between chronic bronchitis and clinical farmer's lung (odds ratio 19.5 (95% confidence interval 12.1-31.4) after adjustment for confounding variables. The main finding of this study is the highly significant increase of prevalence of the diseases in relation to altitude.

Etiologic factors of chronic bronchitis in dairy farmers. Case control study in the Doubs region of France.

Relationships were investigated between chronic bronchitis and plant dust exposure assessed by quantification of barn threshing and cattle foddering and chronic bronchitis and acute respiratory syndromes after plant mold dust exposure. Two groups of male dairy farmers were studied in the Doubs region, France: 197 with chronic bronchitis and 163 control subjects without chronic bronchitis. There was no relationship between chronic bronchitis and exposure. Thirty-three chronic bronchitis patients had semidelayed respiratory syndromes (SDRS) vs two control subjects. Twenty-seven times out of 33 (16 of 17 in the nonsmokers), the SDRS preceded chronic bronchitis. Past history of acute respiratory syndromes during barn threshing (RSBT) was more frequent in chronic bronchitis; RSBT always preceded chronic bronchitis. It is concluded that host factors are important in chronic bronchitis and that acute effects after exposure may be predisposing factors to chronic bronchitis.

Effects of ultrasonic and sonic scalers on dental plaque microflora in vitro and in vivo.

The effects of ultrasonic and sonic scalers on the subgingival microflora were investigated in vitro and in vivo. In the in vitro investigation, 27 plaque samples collected from periodontal pockets were submitted to ultrasonic and sonic vibrations for 10, 30 and 60 s. Bacterial suspensions were examined by darkfield microscopy to detect qualitative changes and cultured to evaluate the total number of cultivable bacteria. Microscopic counts following both instrumentations showed a decrease in the proportions of spirochetes and motile rods and an increase in the % of coccoids and rods. The changes were directly related to the time-period of instrumentation. Comparison between both types of instrumentation showed significant differences and more pronounced changes were observed with the ultrasonic than the sonic scaler. Spirochetes and motile rods were reduced to approximately 0.1% after ultrasonic treatment versus 24.7% after sonic instrumentation. Cultural observations showed a marked increase in total number of colony-forming units following both treatments. The clinical investigation included 66 periodontal pockets which were instrumented subgingivally for 10 and 30 s with ultrasonic or sonic scalers. Qualitative changes were similar to those observed in vitro, i.e., reduction in spirochete and motile rod counts as well as the other morphotypes with an increase in coccoid cells. Total counts of bacteria were reduced following debridement. No difference in the microscopic or cultural data was found between ultrasonic and sonic instrumentation.