An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1, the major cat allergen.

BACKGROUND: Cats are the major source of indoor inhalant allergens after house dust mites. The global incidence of cat allergies is rising sharply, posing a major public health problem. Ten cat allergens have been identified. The major allergen responsible for symptoms is Fel d 1, a secretoglobin and not a lipocalin, making the cat a special case among mammals. MAIN BODY: Given its clinical predominance, it is essential to have a good knowledge of this allergenic fraction, including its basic structure, to understand the new exciting diagnostic and therapeutic applications currently in development. The recent arrival of the component-resolved diagnosis, which uses molecular allergens, represents a unique opportunity to improve our understanding of the disease. Recombinant Fel d 1 is now available for in vitro diagnosis by the anti-Fel d 1 specific IgE assay. The first part of the review will seek to describe the recent advances related to Fel d 1 in terms of positive diagnosis and assessment of disease severity. In daily practice, anti-Fel d 1 IgE tend to replace those directed against the overall extract but is this attitude justified? We will look at the most recent arguments to try to answer this question. In parallel, a second revolution is taking place thanks to molecular engineering, which has allowed the development of various forms of recombinant Fel d 1 and which seeks to modify the immunomodulatory properties of the molecule and thus the clinical history of the disease via various modalities of anti-Fel d 1-specific immunotherapy. We will endeavor to give a clear and practical overview of all these trends.

[Differences and similarities between occupational and tobacco induced COPD]. / BPCO professionnelles et BPCO post-tabagique : similarités et différences.

Chronic obstructive pulmonary disease (COPD) most often results from the inhalation of toxic agents. Cigarette smoking still remains the principal cause but the pertinence of occupational COPD is now clearly established. After a brief overview of the epidemiology of this "other COPD", the clinical and functional characteristics are summarized, taking into account recent advances in this field. The combined effects of occupational exposure and tobacco are also considered, providing evidence of the need to continuously reinforce campaigns of education and prevention in occupational COPD.

Asthma-COPD overlap syndrome (ACOS) vs 'pure' COPD: a distinct phenotype?

BACKGROUND: Some studies suggest that asthma-COPD overlap syndrome (ACOS) is associated with worse outcomes than chronic obstructive pulmonary disease (COPD). The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real-life cohort of patients with COPD. METHODS: Data from the French COPD cohort 'INITIATIVES BronchoPneumopathie Chronique Obstructive' (n = 998 patients) were analyzed to assess the frequency of ACOS defined as a physician diagnosis of asthma before the age of 40 years and to analyze its impact. Univariate analyses were performed to assess the relationship between ACOS and sociodemographic characteristics, risk factors (smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis, dyspnea-modified Medical Research Council scale and baseline dyspnea index), quality of life (QoL), mood disorders, exacerbations, comorbidities, lung function, prescribed treatment, and survival. RESULTS: ACOS was diagnosed in 129 patients (13%). In multivariate analyses, ACOS was associated negatively with cumulative smoking (odds ratio [OR]: 0.992; 95% CI 0.984-1.000 per pack-year) and positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug use (LABA + ICS: 1.86 [1.27-2.74], antileukotrienes 4.83 [1.63-14.34], theophylline: 2.46 [1.23-4.91], and oral corticosteroids: [2.99;.1.26-7.08]). No independent association was found with dyspnea, QoL, exacerbations, and mortality. CONCLUSIONS: Compared to 'pure' COPD patients, patients with ACOS exhibit lower cumulative smoking, suffer more from obesity and atopic diseases, and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations, comorbidities) and prognosis (mortality) are not different from 'pure' COPD patients.

Vitamin D bioavailability: state of the art.

There has been renewed interest in vitamin D since numerous recent studies have suggested that besides its well-established roles in bone metabolism and immunity, vitamin D status is inversely associated with the incidence of several diseases, e.g., cancers, cardio-vascular diseases, and neurodegenerative diseases. Surprisingly, there is very little data on factors that affect absorption of this fat-soluble vitamin, although it is acknowledged that dietary vitamin D could help to fight against the subdeficient vitamin D status that is common in several populations. This review describes the state of the art concerning the fate of vitamin D in the human upper gastrointestinal tract and on the factors assumed to affect its absorption efficiency. The main conclusions are: (i) ergocalciferol (vitamin D2), the form mostly used in supplements and fortified foods, is apparently absorbed with similar efficiency to cholecalciferol (vitamin D3, the main dietary form), (ii) 25-hydroxyvitamin D (25OHD), the metabolite produced in the liver, and which can be found in foods, is better absorbed than the nonhydroxy vitamin D forms cholecalciferol and ergocalciferol, (iii) the amount of fat with which vitamin D is ingested does not seem to significantly modify the bioavailability of vitamin D3, (iv) the food matrix has apparently little effect on vitamin D bioavailability, (v) sucrose polyesters (Olestra) and tetrahydrolipstatin (orlistat) probably diminish vitamin D absorption, and (vi) there is apparently no effect of aging on vitamin D absorption efficiency. We also find that there is insufficient, or even no data on the following factors suspected of affecting vitamin D bioavailability: (i) effect of type and amount of dietary fiber, (ii) effect of vitamin D status, and (iii) effect of genetic variation in proteins involved in its intestinal absorption. In conclusion, further studies are needed to improve our knowledge of factors affecting vitamin D absorption efficiency. Clinical studies with labeled vitamin D, e.g., deuterated or (13)C, are needed to accurately and definitively assess the effect of various factors on its bioavailability.

[The epidemiology of pollen allergy]. / Épidémiologie de l'allergie pollinique.

The prevalence of seasonal allergic rhinitis can be established through surveys performed in a sample of the general population. These surveys are based on a questionnaire, which could lead to an overestimate of prevalence rates, and on measurements of specific IgE, which need to be interpreted in the light of the responses to the questionnaire. Such surveys are few in France and need to be updated. Risk factors for seasonal allergic rhinitis are genetic, epigenetic and environmental. Relationships between exposure to pollen and health can be documented through ecological and panel surveys. Panel surveys may give information on threshold levels and dose-response relationships. In addition to pollen exposure, global warming and air pollutants act as cofactors. Monitoring of both pollen exposure and its health effects should be encouraged and strengthened.

Urinary S-PMA related to indoor benzene and asthma in children.

INTRODUCTION: Benzene is a ubiquitous pollutant of both indoor and outdoor environments which impacts on respiratory health. Our aim was to relate urinary S-phenylmercapturic acid (S-PMA), a biomarker of benzene exposure, to benzene concentrations and related sources at home and asthma in a population-based sample of children. METHODS: Exposure to benzene was assessed in the dwellings of 63 children (32 asthmatics and 31 controls) through the identification of sources of benzene and in situ assessments with passive samplers. The determination of urinary S-PMA was obtained by liquid chromatography-mass spectrometry. RESULTS: At home, asthmatics were significantly more polluted by benzene levels from ambient sampling than controls (p ≤ 0.05). Benzene exposure significantly aggravated asthma symptoms overall in non-atopic children (OR = 10.10; 95% confidence interval: 10.10). Urinary S-PMA was significantly associated with benzene concentrations in the entire population (regression coefficient = 0.28, 95% CI: 0.07-0.49; p < 0.05) and asthma (OR = 7.69; 95% CI: 1.37-42.52 for an increase of 1 µg/g creatinine of urinary S-PMA). However, after adjustment for environmental tobacco smoking exposure, familial allergy, age and sex, the latter relationship was no more significant (OR = 4.95; 95% CI: 0.91-27.4, p < 0.10). Both benzene concentrations and urinary S-PMA concentrations were higher in dwelling built after 1948 and in flats. CONCLUSIONS: Our study suggests a relationship between childhood asthma and benzene concentrations at home, even at low levels of this pollutant. This was confirmed when considering urinary S-PMA, which was related to both benzene concentrations and asthma. Further epidemiological and toxicological studies are needed to confirm our results.

Clinical COPD phenotypes: a novel approach using principal component and cluster analyses.

Classification of chronic obstructive pulmonary disease (COPD) is usually based on the severity of airflow limitation, which may not reflect phenotypic heterogeneity. Here, we sought to identify COPD phenotypes using multiple clinical variables. COPD subjects recruited in a French multicentre cohort were characterised using a standardised process. Principal component analysis (PCA) was performed using eight variables selected for their relevance to COPD: age, cumulative smoking, forced expiratory volume in 1 s (FEV(1)) (% predicted), body mass index, exacerbations, dyspnoea (modified Medical Research Council scale), health status (St George's Respiratory Questionnaire) and depressive symptoms (hospital anxiety and depression scale). Patient classification was performed using cluster analysis based on PCA-transformed data. 322 COPD subjects were analysed: 77% were male; median (interquartile range) age was 65.0 (58.0-73.0) yrs; FEV(1) was 48.9 (34.1-66.3)% pred; and 21, 135, 107 and 59 subjects were classified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1, 2, 3 and 4, respectively. PCA showed that three independent components accounted for 61% of variance. PCA-based cluster analysis resulted in the classification of subjects into four clinical phenotypes that could not be identified using GOLD classification. Importantly, subjects with comparable airflow limitation (FEV(1)) belonged to different phenotypes and had marked differences in age, symptoms, comorbidities and predicted mortality. These analyses underscore the need for novel multidimensional COPD classification for improving patient care and quality of clinical trials.

[Exposure to fine air particles and occurrence of allergic diseases: results of ISAAC-France phase 2]. / Exposition aux particules atmosphériques fines et développement des maladies allergiques de l'enfant. Résultats épidémiologiques issus de l'étude des six villes (ISAAC-2 France).

To evaluate whether fine air particles could be involved in the occurrence of atopy and allergic diseases, we performed a cross-sectional epidemiological survey involving primary schoolchildren living in six French towns with contrasted air pollution levels. Air pollution was measured during a week in the school yards and by standard air monitoring networks. Children get an examination in school looking for atopic dermatitis and bronchial hyperresponsiveness assessed by a standardized run test. Besides, parents or guardians provided past medical history and environmental data, especially on passive smoking. Overall, 5,338 children, aged 10.4 (+/-0.7) years, coming from 108 different schools and 401 different classes were included in the survey. Taking into account potential confounders, high exposure to proximity PM(2.5) was linked to a higher point prevalence of atopic dermatitis and hyperresponsiveness, to a higher cumulative prevalence of allergic asthma and a higher sensitization rate to common indoor allergens. Thus, these data suggest that chronic exposure to urban fine particles could be a risk factor for atopy, hyperresponsiveness and asthma.

[An unusual cause of chylothorax: primary amyloidosis]. / Une cause exceptionnelle de chylothorax: l'amylose primitive.

BACKGROUND: Amyloidosis is a large family of diseases defined by the presence of extra cellular protein deposits which can remain localised but are generally diffuse. Pleural involvement with effusion is rare (6% only), and difficult to diagnose because the clinical signs are non-specific. OBSERVATION: We report the case of a 77 year old man, hospitalized for anasarca, with recurring pleural effusions despite two drainages and talcage. Pleural aspiration revealed a chylothorax. ProBNP was high: 24000 ng/l. Echocardiography revealed a restrictive cardiomyopathy and suggested the diagnosis of a systemic disease. Negative peripheral biopsies led us to perform an endomyocardial biopsy, which confirmed the diagnosis of amyloidosis AL. CONCLUSION: We report an original case of primary amyloidosis presenting as a chylothorax and confirmed by an endomyocardial biopsy. We highlight the multi factorial character of pleural effusions associated with amyloidosis. This explains the delay in treatment and the disease's critical nature (median survival 2 months). The prognostic value of proBNP is also emphasised.

[Pulmonary artery intimal sarcoma]. / Sarcome intimal de l'artère pulmonaire.

Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.

[Indoor radon exposure and lung cancer risk. Results of an epidemiological study carried out in France]. / Exposition domestique au radon et risque de cancer du poumon.

INTRODUCTION: Several epidemiological studies have indicated an increased risk of lung cancer associated with indoor radon exposure. As part of a large European project, a hospital based case-control study was carried out in four regions of France: Auvergne, Brittany, Languedoc-Roussillon and Limousin. MATERIAL AND METHODS: Individual data on demographic characteristics, residential history, smoking and occupational exposures were collected during face-to-face interviews. Radon concentrations were measured in each dwelling occupied by the subject during the 30-year period prior to the interview. RESULTS: 486 cases and 984 controls were included in the study. After adjustment for age, sex, region, smoking history and occupational exposure, the risk of lung cancer increased by 4% per 100 Bq/m(3), when considering cumulative exposure in the 30 years prior to diagnosis. CONCLUSION: The study indicates a positive association between lung cancer risk and indoor radon exposure. The risk estimate per unit of exposure is in agreement with other recently published indoor case-control studies.

Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel-cisplatin versus vinorelbine-cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study.

BACKGROUND: This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC). METHODS: Overall, 115 patients received DC (docetaxel 75 mg/m(2) and cisplatin 100 mg/m(2) both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m(2)/week on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m(2) days 1 and 8 (A2), or docetaxel 100 mg/m(2), day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR). RESULTS: Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms A1 and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC. CONCLUSIONS: The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of long-term survivors, despite the absence of efficacy of the second-line in our study.

Early CYFRA 21-1 variation predicts tumor response to chemotherapy and survival in locally advanced non-small cell lung cancer patients.

We have evaluated CYFRA 21-1 serum level variations as an indicator of tumor response and survival in 44 consecutive patients with locally advanced non-small cell lung cancer (NSCLC) treated with induction chemotherapy (IC). Irrespective of the initial CYFRA 21-1 serum concentration, a more than 65% decrease in the serum level after the first chemotherapy course was significantly predictive of an objective tumor response (p = 0.0022). In addition, a more than 80% decrease in this level significantly predicted a better disease-free survival (p = 0.039). In patients with initial CYFRA 21-1 serum levels > 3.3 ng/mL (n = 29), a more than 80% decrease after the first IC course was the most significant predictor of overall survival (p = 0.025) in a Cox analysis including initial staging, tumor response and surgery. We conclude that early monitoring of CYFRA 21-1 serum levels may be a useful prognostic tool for tumor response and survival in stage III NSCLC patients treated by induction chemotherapy.

[Pulmonary nodules: dosimetric and clinical studies at low dose multidetector CT]. / Evaluation dosimétrique en exploration TDM thoracique multibarrette faible dose dans la détection des nodules pulmonaires.

PURPOSE: To measure breast radiation dose from multidetector CT using three different low dose protocols and compare it to a standard two view chest examination. To compare the number of pulmonary nodules detected at low and standard dose. MATERIALS AND METHODS: Thermoluminescent dosimetry was used to measure the absorbed dose on a phantom (Rando) and 10 patients. Then, we compared the standard dose to the low dose examinations. The Wilcoxon rank test and the kappa test were used to assess differences in the detection of nodules. RESULTS: The absorbed dose of these low dose protocols correspond to the radiation dose for the acquisition of two to ten chest radiographs (two views). This study suggests that only the 30 mA protocol is sufficient for the detection of all pulmonary nodules; nodules smaller than 5 mm were overlooked at 10 mA. CONCLUSION: A good image quality can be obtained with low dose protocols at multidetector CT (correspond to 2 to 10 chest radiographs).

[Analysis of nasal and exhaled nitric oxide concentration in nasal polyposis]. / Analyse des concentrations nasales et dans l'air expiré du monoxyde d'azote (NO) dans la polypose naso-sinusienne.

UNLABELLED: Nitric oxide (NO) is implicated in the pathophysiology of inflammatory airway diseases. It has been identified as a potential marker of airway inflammation. OBJECTIVE: The purpose of the study was to assess the concentrations of nasal NO in upper and lower airways in nasal polyposis patients. PATIENTS: 18 nasal polyposis patients (14 men, 4 women) and 21 control subjects (7 men, 14 women), all non asthmatic non smokers, without respiratory infections were prospectively studied. METHODS: They included nasal obstruction scoring, nasal endoscopic grading, allergy testing, nasal cytology, flow-volume spirometry and measurement of nasal (NNO) and exhaled NO (ENO) concentrations. NO was measured by a chemiluminescence NO Analyser (Sievers 280). NNO was analysed by aspiration with a constant flow of 3 l/mn. ENO was analysed during a slow expiration (50 ml/s) against a constant resistance of 10 cm H2O. RESULTS: NNO was significantly (p<0,001) decreased in NP group (596.4 +/- 102.06 ppb) compared to control group (2 251.6 +/- 288.6 ppb). ENO was significantly (p<0.05) increased in NP group (45.4 +/- 14.1 ppb) compared to control group (11.2 +/- 1.16 ppb). NNO and ENO were not significantly different between atopic and non-atopic NP patients. NNO concentrations was inversely correlated with the values of nasal endoscopic grading. No correlation was found between NNO concentrations and respectively nasal obstruction scoring and eosinophil count in nasal mucosa. CONCLUSION: Further studies are necessary to understand the pathophysiology of decreasing NNO and increasing ENO in nasal polyposis. In particular, ENO could be consider as a biologic marker of lower airway inflammation in nasal polyposis.

Basal production of pentane in expired gas from healthy humans.

BACKGROUND: Pentane in exhaled gas is often used as an index of lipoperoxidation, but today, there is no standardization for its measurement. In this study, with our technical experience, we determined basal production of pentane in healthy subjects, and we evaluated variability of pentane flow 1 month later. METHODS: 18 subjects inhaled hydrocarbon-free air (HCFA) in order to realize a lung washout. Ambient air and three samples (at T0, T10, T30 min) of expired gas were concentrated using a "trap-and-purge" procedure. For the analysis of pentane, an Al(2)O(3)/KCl plot column contained in a gas chromatograph equipped with a flame ionization detector was used. RESULTS: After 10 min of washout, mean (+/-SD) exhalation rate of pentane was 1+/-0.6 pmol min(-1) kg(-1). After 30 min of washout, mean (+/-SD) exhalation rate of pentane was 0.7+/-0.5 pmol min(-1) kg(-1). No significant difference in pentane flow was shown 1 month later for eight subjects who repeated the protocol. CONCLUSION: With our results and data of the literature, exhalation rates of pentane from healthy adults appear to range between 0.3 and 2 pmol min(-1) kg(-1). The variability of pentane flow 1 month later seems not very important.

Clinical characteristics and outcome of patients with invasive pneumococcal disease, Puy-de-Dôme, France, 1994-1998.

A surveillance program for invasive pneumococcal disease was undertaken in Puyde-Djme, an administrative district of the region Auvergne in France, from 1 January 1994 to 31 December 1998. A total of 214 cases were identified. The annual incidence of invasive pneumococcal disease increased (P=0.04) from 5.5 in 1994 to 9.3 cases per 10(5) person-years in 1998. The highest incidences were for children <2 years of age (59.2 cases per 10(5) person-years) and for adults > or = 65 years (18 cases per 10(5) person-years). Clinical diagnoses, available in 200 patients, included acute pneumonia (62%), meningitis (10%), sepsis without focus (20%), and others (8%). The most frequent chronic medical conditions of the patients included smoking, alcoholism, cardiovascular and pulmonary diseases, and malignancies. Thirty-one percent of the isolates were nonsusceptible to penicillin. Penicillin resistance (MIC > or = 0.1 mg/l) was more frequent (P=0.02) in cancer patients. The overall case-fatality rate was 21.5%. Risk factors for death were age, sex, and underlying diseases of the patients, along with the severity of illness. These population-based findings should convince clinicians to offer pneumococcal vaccine to patients at high risk for invasive pneumococcal disease, thereby increasing vaccination coverage levels in France.

[Solid pleural-based mass as initial manifestation of non-Hodgkin's lymphoma]. / Localisation tumorale solide sous-pleurale revelatrice d'un lymphome non-Hodgkinien.

Subpleural involvement is a well-known site of advanced or recurrent lymphoma. But, to our knowledge, it has never been described as an initial manifestation of this disease. We report the case of a patient with solid subpleural mass revealing a non-Hodgkin's lymphoma.

[Nasal soluble levels of ICAM-1 in allergic rhinitis]. / Taux d'ICAM-1 soluble nasal dans les rhinites allergiques.

UNLABELLED: Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), play an important role in the development of the inflammatory allergic response in the nose. ICAM-1 expression on nasal epithelial cells during allergic reaction is regarded as a major hallmark of allergic inflammation. OBJECTIVE: The aim of the study was to evaluate the levels of soluble ICAM-1 (sICAM-1) in nasal epithelial lining fluid (ELF) in patients with allergic rhinitis. PATIENTS: Seventeen patients with perennial allergic rhinitis (age: 34,6 +/- 14,6) were screened and the results were compared with those from 11 seasonal allergic rhinitis patients (age: 25.9 +/- 7.4) and 10 non-allergic patients. METHODS: The study was performed outside the pollen season. The scores of subjective symptoms were estimated by two differents methods. First, on the basis of a visual analog scale for the symptoms including nasal obstruction, rhinorrhea, sneezing and pruritus. This score was called "Autoscore" (fullmark =40 points). Second, on the basis of a four mark scale for each symptom defined (0 =no symptom, 1 =mild, 2 =moderate, 3 =severe). This score was called "Heteroscore" (fullmark =12 points). Specimens of nasal mucosa were collected by brushing the surface of nasal cavity. Levels of sICAM-1 and sECP (soluble Eosinophilic cationic protein) were measured by specific enzyme-linked immunosorbent assay. RESULTS: The levels of sICAM-1 in ELF were significantly higher (p <0.01) in patients with perennial rhinitis compared to patients with seasonal rhinitis outside the pollen season and to non allergic patients. Levels of sICAM-1 in patients with perennial allergic rhinitis were correlated with levels of sECP (p <0.003) and with the four mark scale scores (p <0. 03) but did not correlate with the visual analog scale scores. CONCLUSIONS: sICAM-1 increased in nasal secretions during natural perennial rhinitis and could be considered as a representative hallmark for clinical severity and follow-up evaluation in perennial allergic rhinitis.