Use of interrupter technique in assessment of bronchial responsiveness in normal subjects

BACKGROUND: A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD(20 )FEV(1). METHODS: We studied 170 normal subjects, 100 male and 70 female (mean ± SD age, 38 ± 8.5 and 35 ± 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD(100)Rint, EI) as well as by percent dose response ratio (DRR). RESULTS: BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD(20)FEV(1 )(r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 μmol and 1.27 μmol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV(1 )in terms of reactivity (DRR). CONCLUSIONS: Interrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed

Supplementation with vitamins C, E, beta-carotene and selenium has no effect on anti-oxidant status and immune responses in allergic adults: a randomized controlled trial

The definitive version is available at www.blackwell-synergy.comBackground Anti-oxidants are of growing interest in early treatment and prevention of allergic diseases in early life, but the effects on allergen-specific immune responses need to be documented further before intervention studies in infants are undertaken. The aim of this study in adults was to determine the effects of dietary anti-oxidants on allergen-specific immune responses in sensitized individuals. Methods In a randomized controlled trial, 54 allergic adults received an anti-oxidant supplement (n=36) comprising β-carotene (9 mg/day), vitamin C (1500 mg/day), vitamin E (130 mg/day), zinc (45 mg/day), selenium (76 μg/day) and garlic (150 mg/day) or a placebo (n=18) for 4 weeks. Anti-oxidant capacity (AC), serum levels of vitamin C, vitamin E, β-carotene and selenium, peripheral blood responses, exhaled nitric oxide (eNO), as a marker of airway inflammation, and plasma F2 isoprostanes, as a measure of oxidative stress, were measured before and after supplementation. Results Anti-oxidant supplementation resulted in significant increases in serum levels of vitamin C, vitamin E, β-carotene and selenium levels, compared with the placebo group (P<0.001). There was no change in serum AC, plasma F2-isoprostanes, eNO or immune responses following supplementation with anti-oxidants compared with placebo. Conclusion Supplementation with anti-oxidants resulted in significantly increased levels of vitamin C, vitamin E, β-carotene and selenium but no change in immune responses, serum AC or plasma F2-isoprostanes.J. A. Dunstan, L. Breckler, J. Hale, H. Lehmann, P. Franklin, G. Lyons, S. Y. L. Ching, T. A. Mori, A. Barden and S. L. Prescot

Decreased expression of autophagic beclin 1 protein in idiopathic pulmonary fibrosis fibroblasts

Autophagy is the main cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Beclin 1 is a key regulator of this process. In some settings autophagy and apoptosis seem to be interconnected. Recent reports indicate that fibroblasts in idiopathic pulmonary fibrosis (IPF) acquire resistance to apoptosis. Here, we examined the expression of beclin 1, and of the anti apoptotic protein Bcl-2 in human IPF fibroblasts using immunohistochemistry and molecular biology in bioptic sections, in primary cultures of fibroblasts taken from patients with IPF and in fibroblast cell lines. Expression of beclin 1 in fibroblasts from IPF was down-regulated in comparison with fibroblasts from normal lungs while the anti-apoptotic protein Bcl-2 expression was over-expressed. Treatment of fibroblast cell cultures with cisplatin induced a significant increase in beclin 1 and caspase 3 protein levels but a reduction in Bcl-2 expression. These observations were confirmed by the analysis of acid compartments and transmission electron microscopy. Our results demonstrate a modified expression of the apoptotic beclin 1 Bcl-2 proteins in human IPF fibroblasts suggesting the existence of an autophagy/apoptosis system dysfunction.© 2012 Wiley Periodicals, Inc

Non-tuberculous mycobacteria disease as a cause of hospitalization in HIV-infected subjects

The present study characterized and determined the prevalence of mycobacterial diseases (tuberculosis (TB) and non-tuberculous mycobacteria (NTM)) as a cause of hospitalization among HIV-infected subjects consecutively admitted to a large metropolitan hospital during 2001/2002. Hospital discharge diagnoses were established for 521 HIV-positive patients. Respiratory disease accounted for 49% of the admissions. Community acquired pneumonia (CAP) was the main cause of respiratory disease (52%) followed by Pneumocystis carinii (PCP, 24%), non-tuberculous mycobacteria (NTM, 11%) and Mycobacterium tuberculosis (TB, 9%). Mycobacterium tuberculosis disease was established using bacteriological, clinical and radiographic criteria. NTM disease was defined following the American Thoracic Society criteria. NTM was disseminated in the majority of cases (19 Mycobacterium avium complex (MAC), one Mycobacterium kansasii). Nine patients had respiratory disease (seven MAC, one Mycobacterium fortuitum, one Mycobacterium kansasii) and one had gastrointestinal disease caused by MAC. Mortality was 10% for NTM disseminated cases; none of the TB patients died over the course of the study. The length of hospitalization for NTM patients was longer (15 ± 13 days) than for other respiratory cases (10 ± 10, p = 0.04). NTM disease along with its related mortality is a significant pathology as a cause of hospitalization among HIV-infected individuals

Homeodomain-interacting protein kinase2 in human idiopathic pulmonary fibrosis

Homeodomain-interacting protein kinase 2 (Hipk2) is an emerging player in cell response to genotoxic agents that contributes to the cell's decision between cell cycle arrest or apoptosis. HIPK2 acts as co-regulator of an increasing number of transcription factors and modulates many different basic cellular processes such as apoptosis, proliferation, DNA damage response, differentiation. Idiopathic pulmonary fibrosis (IPF) is characterized by an anatomical disarrangement of the lung due to fibroblast proliferation, extracellular matrix deposition and lung function impairment. Although the role of inflammation is still debated, attention has been focused on lung cell functions as fibroblast phenotype and activity. Aim of the present study was to analyze the loss of heterozygosity (LOH) at HIPK2 locus 7q32.34 in human lung fibroblasts and the HIPK2 expression in 15 IPF samples and in four primary fibroblast cell cultures isolated from IPF biopsies using semi-quantitative RT-PCR, Western blots and immunohistochemistry. We demonstrated a frequency of LOH in IPF fibroblasts of 46% for the internal D7S6440 microsatellite and 26.6% for the external D7S2468 microsatellite. Furthermore, we demonstrated low HIPK2 protein expression in those fibroblasts from IPF patients that present the HIPK2 LOH. The restoration of HIPK2 expression in IPF derived cells induced a significant reduction of chemoresistance after treatment with cisplatin. The results obtained allow us to hypothesize that HIPK2 dysfunction may play a role in fibroblasts behavior and in IPF pathogenesis. HIPK2 may be considered as a novel potential target for anti-fibrosis therapy. J. Cell. Physiol. 228: 235241, 2013. (c) 2012 Wiley Periodicals, Inc