Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

[Early diagnosis of lung cancer: impact of autofluorescence bronchoscopy]. / Diagnostic précoce du cancer bronchique : apport de la bronchoscopie en autofluorescence.

INTRODUCTION: Less than 15% of all patients survive five years after a diagnosis of lung cancer. This poor prognosis is attributed to a lack of early detection. Among the methods of early diagnosis of bronchial cancer, autofluorescence bronchoscopy allows for the early identification of preinvasive bronchial lesions. The goal of this prospective study is to evaluate the contribution of the autofluorescence bronchoscopy, on a hospital site, over a period of one year. METHODS: All patients with an indication of autofluorescence bronchoscopy were included in the study. The following parameters were collected: age, sex, smoking status, FEV1, FVC, biopsy sites, histology, duration of examination. RESULTS: Two hundred and seventy-four patients were included. The average age was 63.8 years (+/-12), the smoking status was 35 packs/year (+/-19). A fluorescence abnormality was detected in 131 patients and 165 sites were biopsied. An histological abnormality was found in 76% of the samples, with 34 hyperplasia (28%), 56 squamous metaplasia (46%), three mild dysplasia (3%), two moderate dysplasia (2%), one severe dysplasia (1%), two carcinomas in situ (2%) and 21 invasive carcinomas (18%). CONCLUSION: Autofluorescence bronchoscopy is an effective examination for the detection of the preinvasive neoplasic lesions and may be proposed when lung cancer is suspected.

T-cell activation in occupational asthma and rhinitis.

BACKGROUND: Allergic asthma and rhinitis are described as associated with a Th2 activation. However, recent works indicate that a Th1 activation can also be associated with these diseases, concomitantly to a defect in regulatory T (Treg) cell activation. Occupational asthma (OA) and occupational rhinitis (OR) are peculiar cases of these diseases in which the T-cell activation profile is largely unknown. OBJECTIVE: To characterize T-cell activation induced after a specific inhalation test (SIT) in OA and OR. MATERIAL AND METHODS: A total of 21 subjects with OA, 10 subjects with OR, 10 exposed nonallergic (ENA) subjects, and 14 healthy volunteers were included. The SIT with the incriminated substance was performed in patients and ENA subjects. Blood and induced sputum were obtained before and after SIT. T cells were analysed for CD69, CD25, IL-13, and IFN-gamma expression by flow cytometry. IL-4 and IFN-gamma were assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Treg cells were identified as CD4(+)CD25(+high)CD45RO(+)CD69(-) T cells in peripheral blood. RESULTS: Baseline IFN-gamma production was decreased in OA and OR compared with controls. The SIT induced an increase in both Th1 and Th2 cells in blood and sputum from OA. In this group, the proportion of peripheral Treg cells decreased after SIT. Similar results were found in the CD8(+) population. ELISA assays were concordant with flow cytometry. In OR, an attenuated activation profile was found, with an increase in the proportion of IL-13-producing T cells after SIT. By contrast, in ENA subjects, SIT induced Th2 activation, with an increase in Treg cells and a decrease in Th1 cells. CONCLUSIONS: Our results demonstrate a gradient of T-cell activation from a tolerating profile in ENA subjects to an inflammatory profile in OA, with an intermediate stage in OR.

Variation of T-cell activation in allergic subjects during natural pollen exposure.

BACKGROUND: Allergic inflammation is characterized by a Th2 activation. However, little is known about dynamics of T-cell cytokine production during natural allergen exposure. The aim of this study was to assess the Th1/Th2 balance in cypress allergic patients compared with controls, and variations of this balance over the pollen season. METHODS: Twenty cypress allergic patients and 10 controls were studied, distributed during two consecutive pollen seasons. Cytokine production was assessed by flow cytometry and ELISA. The variation of cytokine production during the pollen season was analyzed among patients in four occasions, and the preseason values were compared with controls. IL-13 and IFN-gamma-containing T cells were assessed among whole blood cells and PBMC. In addition the effect of specific stimulation by Juniperus ashei pollen extract was studied. RESULTS: Compared with controls, IL-13-producing T cells were increased in allergics in any case. By contrast, compared with controls, allergic IFN-gamma-producing T cells were decreased in whole blood, but not in PBMC, and were increased after specific stimulation. During the season, an increase in IFN-gamma- and a decrease in IL-13-producing T cells occurred in patients, whatever the culture conditions. CONCLUSION: These results show that the allergic T-cell activation is not limited to a Th2 profile: allergen-stimulated T cells are able to produce IFN-gamma at baseline, and the Th1/Th2 ratio increases during the pollen season.

[Bronchial obstruction by an aberrant left pulmonary artery misdiagnosed as asthma in a 7 year old child]. / Un faux asthme lié à une compression bronchique par une artère pulmonaire gauche à trajet aberrant chez une enfant de 7 ans.

INTRODUCTION: Wheezing is common symptom in infants and is usually due to asthma. However an alternative diagnosis should be sought if there is no reversibility to B2-agonist. CASE REPORT: This case report describes a 7 years old child who had been treated for poorly controlled asthma for several years. The absence of B2-agonist reversibility, indirect signs of thoracic straining on spirometry and evidence of right heart decompensation raised doubts about the diagnosis. CT angiography demonstrated a pulmonary artery malformation. Formal pulmonary angiography confirmed the diagnosis of pulmonary artery sling. This malformation had been causing intermittent bronchial compression and the symptoms resolved after surgical intervention. CONCLUSION: Wheezing symptoms over two Years in a child, misdiagnosed as asthma, is an unusual presentation of this pulmonary vascular anomaly.

T cell activation, from atopy to asthma: more a paradox than a paradigm.

During the last 15 years, it was largely shown that allergic inflammation was orchestrated by activated Th2 lymphocytes, leading to IgE production and eosinophil activation. Indeed, Th2 activation was shown to be necessary to induce allergic sensitization in animal models. In humans, a Th2 skewing was shown in atopic children soon after birth. In asthma, descriptive studies showed that Th2 cells were more numerous in patients than in controls. In addition, during specific allergen stimulation, an increase of Th2 cells was described in most cases. According to this Th2 paradigm, it was proposed that early avoidance of microbial exposure could explain the increase of atopic diseases seen in the last 20 years in developed countries, as the "hygiene hypothesis". Recently, it was proposed that early exposure to lipopolysaccharide (LPS) could be protective against atopic diseases. However, it is well established that exposure to LPS can induce asthma symptoms, both in animals and humans, although it induces a Th1 inflammatory response. In addition, most infections induce asthma exacerbations and Th1 responses. Recently, some studies have showed that some Th1 cells were present in asthmatic patients, which could be related to bronchial hyperreactivity. There is therefore an "infectious paradox" in asthma, which contributes to show that the Th2 paradigm is insufficient to explain the whole inflammatory reaction of this disease. We propose that the Th2paradigm is relevant to atopy and inception of asthma albeit a Th1 activation would account at least in part for bronchial hyperreactivity and asthma symptoms.