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Objective: To determine the impact of endobronchial coils on health-related quality-of-life (HRQoL). This paper utilizes trial data to identify the predictors of HRQoL in patients with severe emphysema, and subsequently estimates the impact of a new treatment on HRQoL (measured by utilities). These utility estimates are used to generate indicative long-term QALY estimates for a range of clinically plausible scenarios as a precursor to cost-effectiveness analyses.Methods: Patient level HRQoL data from RENEW and the National Emphysema Treatment Trial (NETT) were combined and mapped to generic EuroQol 5-dimension health utility questionnaire (EQ-5D) values using a published algorithm. Multilevel statistical models were developed using treatment, time, response, and baseline characteristics (EQ-5D, age, gender, FEV1, lung RV) to predict EQ-5D over time. Lifetime QALY estimates were generated using published survival data from NETT (assuming no impact of treatment on mortality) and four clinically plausible response profiles. Each response profile was combined with assumptions around treatment impact (constant or time varying).Results: After controlling for baseline characteristics, both treatment and response had a statistically significant impact (p Conclusions: Coils and SoC resulted in statistically significant improvements in HRQoL compared to SoC alone in patients with severe emphysema.

Electrosyneresis and double diffusion are immunoprecipitation techniques commonly used in the serological diagnosis of Farmer's lung disease (FLD). These techniques are reliable but lack standardization. The aim of this study was to evaluate Western blotting for the serodiagnosis of FLD. We carried out Western blotting with an antigenic extract of Lichtheimia corymbifera, an important aetiological agent of the disease. The membranes were probed with sera from 21 patients with FLD and 21 healthy exposed controls to examine the IgG antibody responses against purified somatic antigens. Given the low prevalence of the disease, 21 patients could be considered as a relevant series. Four bands were significantly more frequently represented in membranes probed with FLD sera (bands at 27.7, 40.5, 44.0 and 50.5 kDa) than those probed with control sera. We assessed the diagnostic value of different criteria alone or in combination. The diagnostic accuracy of the test was highest with the inclusion of at least two of the following criteria: at least five bands on the strip and the presence of one band at 40.5 or 44.0 kDa. Sensitivity, specificity and positive and negative predictive values were all 81%, and the odds ratio was 18.06. Inclusion of bands of high intensity diminished rather than improved the diagnostic value of the test. We concluded that Western blotting is a valuable technique for the serodiagnosis of FLD. The industrial production of ready-to-use membranes would enable the routine use of this technique in laboratories, and provide reliable and standardized diagnostic results within a few hours.

Background: There is a need to improve the safety and efficacy of allergen-specific immunotherapy. Long synthetic peptide-based immunotherapy was proven safe, immunogenic, and protective in preclinical trials. Objective: To evaluate the safety and immunogenicity of an allergen-derived long synthetic overlapping peptide (LSP) immunotherapy, we designed a double-blind, placebo-controlled phase I clinical trial in patients hypersensitive to bee venom. Methods: Patients from the active group were injected at day 0 with a mixture of 3 LSPs mapping the entire PLA2 molecule, a major bee venom allergen, in a dose-escalating protocol to a maintenance dose of 100 μg per peptide repeated at days 4, 7, 14, 42, and 70. The control group was injected with human albumin. Results: Whereas specific T-cell proliferation in the peptide group increased up to day 14, a sharp decline was observed thereafter, ending in specific T-cell hyporesponsiveness at day 80. Serum-specific IgG4 response was enhanced, in contrast to anti-PLA2 IgE. Specific T-cell cytokine modulation was marked by increased IL-10 and IFN-γ secretion. LSP injections were well tolerated in all patients except for mild, late allergic reactions in 2 patients at day 70. Conclusions: The results of this short-term study demonstrate that LSP-based allergen immunotherapy was safe and able to induce T H 1-type immune deviation, allergen-specific IL-10 production, and T-cell hyporesponsiveness. LSPs, which offer the advantage of covering all possible T-cell epitopes for any HLA genotype, can be considered candidates for a novel and safe approach of specific immunotherapy. (J Allergy Clin Immunol 2003;111:854-61.)

PURPOSE: Saccharopolyspora rectivirgula is the principal cause of farmer's lung disease (FLD). Serodiagnosis is based on immunoprecipitation techniques or enzyme immunoassays with homemade crude antigens and is not standardized. We aimed to produce specific recombinant antigens for the development of a standardized ELISA. EXPERIMENTAL DESIGN: We recruited 41 patients and 43 healthy exposed controls from five university hospital pneumology departments in France and Switzerland. S. rectivirgula proteins were extracted, separated by 2D electrophoresis, and subjected to Western blotting, with sera from FLD patients or controls. FLD-specific proteins were identified by MS and were produced as recombinant antigens. The diagnostic performance of ELISA tests using the recombinant antigens was assessed with all the sera from FLD patients and controls. RESULTS: We identified 25 FLD-specific proteins, some of which play important roles in transport, nutrition, or virulence. We produced 17 of these proteins as recombinant antigens and assessed their suitability for inclusion in the ELISA test. A combination of three of these proteins (SR1FA, SR17, and SR22) proved remarkably effective at discriminating between patients and controls, with a sensitivity of 83% and a specificity of 77%. CONCLUSIONS AND CLINICAL RELEVANCE: The recombinant antigens produced in this study constitute a major step toward the improvement of diagnostic performance and the standardization of FLD serodiagnosis.

Background: Fexofenadine, the hydrochloride salt of terfenadine active metabolite, is a nonsedative, noncardiotoxic antihistamine derivative for the treatment of allergic rhinitis. Objective: We sought to compare the effects of terfenadine and fexofenadine on nasal provocation tests with allergen. Methods: A preliminary provocation test (screening phase) was performed in 25 patients with a history of seasonal allergic rhinitis to grass pollen to determine the combined nasal reaction threshold, which was defined as 2 of the 3 following criteria: (1) at least a 40% decrease in peak nasal inspiratory flow and/or a 30% decrease in minimal cross-sectional area as measured by acoustic rhinometry, nasal secretions of 0.5 g, and 5 to 10 sneezes per minute. Patients were then included into a double-blind, randomized, 2-way crossover study to receive terfenadine or fexofenadine 120 mg 2 hours before provocation. Rhinorrhea, sneezing, peak nasal flow, and minimal nasal cross-sectional area, as well as symptom scores for nasal congestion and itchiness, were recorded at each allergen concentration up to the reaction threshold. The whole study was performed out of allergy season. Results: Fexofenadine was as potent as terfenadine in limiting pruritus and nasal congestion. Rhinorrhea and sneezing were better controlled by fexofenadine than by terfenadine. Overall, the allergen concentration necessary to reach the combined reaction threshold was increased after treatment with both drugs. Comparison between screening and each treatment phase indicated that the shift in allergen concentration to reach the reaction threshold was significantly greater after fexofenadine than after terfenadine ( P = .033). Conclusion: After oral administration, fexofenadine provided better protection than terfenadine against the immediate allergic reaction. (J Allergy Clin Immunol 1999;103:1025-30.)

In France and Finland, farmer's lung disease (FLD), a hypersensitivity pneumonitis common in agricultural areas, is mainly caused by Eurotium species. The presence of antibodies in patients' serum is an important criterion for diagnosis. Our study aimed to improve the serological diagnosis of FLD by using common fungal particles that pollute the farm environment as antigens. Fungal particles of the Eurotium species were observed in handled hay. A strain of Eurotium amstelodami was grown in vitro using selected culture media; and antigen extracts from sexual (ascospores), asexual (conidia), and vegetative (hyphae) forms were made. Antigens were tested by enzyme-linked immunosorbent assay (ELISA), which was used to test for immunoglobulin G antibodies from the sera of 17 FLD patients, 40 healthy exposed farmers, and 20 nonexposed controls. The antigens were compared by receiver operating characteristic analysis, and a threshold was then established. The ascospores contained in asci enclosed within cleistothecia were present in 38% of the hay blades observed; conidial heads of aspergillus were less prevalent. The same protocol was followed to make the three antigen extracts. A comparison of the results for FLD patients and exposed controls showed the area under the curve to be 0.850 for the ascospore antigen, 0.731 for the conidia, and 0.690 for the hyphae. The cutoffs that we determined, with the standard deviation for measures being taken into account, showed 67% for sensitivity and 92% for specificity with the ascospore antigen. In conclusion, the serological diagnosis of FLD by ELISA was improved by the adjunction of ascospore antigen.

The diagnostic approach to diffuse parenchymal lung disease (DPLD) and especially to the idiopathic interstitial pneumonias has changed over the last two decades, mostly thanks to the development of high resolution CT. Though far from replacing pathology, this additional tool has contributed to the definition of new and more precise diagnostic criteria especially for idiopathic interstitial pneumonias, integrating data provided by the three main contributors: lung specialist, radiologist and pathologist. The purpose of this article is to review the role of histopathology in the multidisciplinary approach of the diagnosis of DPLD and idiopathic interstitial pneumonias.

To date, insufficient evidence is available to recommend serum soluble interleukin-2 receptor (sIL-2R) measurement as a routine test in the assessment of sarcoidosis. Therefore, we evaluated the clinical value of this test.Forty-seven patients with sarcoidosis, all presenting with active disease, were included in the study. Initial serum sIL-2R levels were determined by enzyme-linked immunosorbent assay, and clinical data at presentation and follow-up were collected retrospectively.The median follow-up period of all patients was 44 months (range, 6 to 100 months), and 38 patients had follow-up data present over at least 24 months. The median sIL-2R level was 1,068 U/mL (range, 248 to 4,410 U/mL; upper limit of normal, 710 U/mL). A positive correlation was found between serum sIL-2R levels and the number of CD4+ T lymphocytes in BAL (rs = 0.53, p0.001). In accordance with this result, both sIL-2R level and the number of CD4+ T lymphocytes were elevated in stage I compared to stage III disease (p0.05). Patients with extrapulmonary disease (ED) [excluding Löfgren's syndrome] showed higher sIL-2R levels than those presenting with only pulmonary sarcoidosis (p = 0.001). No relation was found between sIL-2R level and response to treatment, and there was no association between sIL-2R levels and radiographic evolution and lung function outcome.Our data suggest a role for serum sIL-2R as marker of pulmonary disease activity and ED in patients with sarcoidosis.