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1.
Background
In the backdrop of conflicting reports (some studies reported adverse outcomes of biomass fuel use whereas few studies reported absence of any association between adverse health effect and fuel use, may be due to presence of large number of confounding variables) on the respiratory health effects of biomass fuel use, this cross sectional survey was undertaken to understand the role of fuel use on pulmonary function.Method
This study was conducted in a village of western India involving 369 randomly selected adult subjects (165 male and 204 female). All the subjects were interviewed and were subjected to pulmonary function test. Analysis of covariance was performed to compare the levels of different pulmonary function test parameters in relation to different fuel use taking care of the role of possible confounding factors.Results
This study showed that biomass fuel use (especially wood) is an important factor for deterioration of pulmonary function (particularly in female). FEV1 (p < .05), FEV1 % (p < .01), PEFR (p < .05) and FEF25–75 (p < .01) values were significantly lower in biomass fuel using females than nonusers. Comparison of only biomass fuel use vs. only LPG (Liquefied Petroleum Gas) use and only wood vs. only LPG use has showed that LPG is a safer fuel so far as deterioration of pulmonary function is concerned. This study observes some deterioration of pulmonary function in the male subjects also, who came from biomass fuel using families.Conclusion
This study concluded that traditional biomass fuels like wood have adverse effects on pulmonary function. 相似文献2.
Fabrice Paganin Martine Prevot Jean Baptiste Noel Marie Frejeville Claude Arvin-Berod Arnaud Bourdin 《BMC pulmonary medicine》2009,9(1):1-5
Background
Pulmonary rehabilitation is known to be a beneficial treatment for COPD patients. To date, however, there is no agreement for how long a rehabilitation program should be implemented. In addition, current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients. The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation (PR) program for COPD patients on pulmonary function, exercise capability, and body mass index (BMI).Methods
A matched controlled trial was performed with outcome assessments evaluated at 6, 12, 18, 24, 30, and 36 months. Eighty patients with moderate to severe COPD (age 63 ± 7 years; FEV1 48% ± 14) were recruited. The control group received standard care only, while in addition, the case study group received PR for duration of three years. These groups were matched for age, sex, BMI, FEV1% and number of pack-years smoked.Results
The decline in FEV1 after the three years was significantly lower in the PR group compared to control, 74 ml versus 149 ml, respectively (p < 0.001). Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study, in contrast to the control group (p < 0.01). A decreased BMI was noted in the control group after three years, while in the PR group a mild improvement was seen (p < 0.05).Conclusion
Three years of outpatient pulmonary rehabilitation resulted in modifying the disease progression of COPD, as well as improving physical performance in these patients. 相似文献3.
Background
HTLV-I infection has been linked to lung pathology and HTLV-II has been associated with an increased incidence of pneumonia and acute bronchitis. However it is unknown whether HTLV-I or -II infection alters pulmonary function.Methods
We performed pulmonary function testing on HTLV-I, HTLV-II and HTLV seronegative subjects from the HTLV outcomes study (HOST), including vital capacity (VC), forced expiratory volume in one second (FEV1), and diffusing lung capacity for carbon monoxide (DLCO) corrected for hemoglobin and lung volume. Multivariable analysis adjusted for differences in age, gender, race/ethnicity, height and smoking history.Results
Mean (standard deviation) pulmonary function values among the 257 subjects were as follows: FVC = 3.74 (0.89) L, FEV1 = 2.93 (0.67) L, DLCOcorr = 23.82 (5.89) ml/min/mmHg, alveolar ventilation (VA) = 5.25 (1.20) L and DLCOcorr/VA = 4.54 (0.87) ml/min/mmHg/L. There were no differences in FVC, FEV1 and DLCOcorr/VA by HTLV status. For DLCOcorr, HTLV-I and HTLV-II subjects had slightly lower values than seronegatives, but neither difference was statistically significant after adjustment for confounding.Conclusions
There was no difference in measured pulmonary function and diffusing capacity in generally healthy HTLV-I and HTLV-II subjects compared to seronegatives. These results suggest that previously described HTLV-associated abnormalities in bronchoalveolar cells and fluid may not affect pulmonary function. 相似文献4.
Brian J O’Connor Sara Collarini Gianluigi Poli Caterina Brindicci Monica Spinola Daniela Acerbi Peter J Barnes Brian Leaker 《BMC pulmonary medicine》2011,11(1):1-8
Background
Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612).Methods/Design
The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1≤50% of predicted or FEV1 < 1 liter, RV/TLC≥0.65 at screening, marked dyspnea score ≥2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥1 point at the 6-month follow-up visit.Discussion
If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit.Trial Registration
ClinicalTrials.gov: NCT00391612 相似文献5.
Charlie Strange Felix JF Herth Kevin L Kovitz Geoffrey McLennan Armin Ernst Jonathan Goldin Marc Noppen Gerard J Criner Frank C Sciurba 《BMC pulmonary medicine》2007,7(1):1-12
Background
Lung volume reduction surgery is effective at improving lung function, quality of life, and mortality in carefully selected individuals with advanced emphysema. Recently, less invasive bronchoscopic approaches have been designed to utilize these principles while avoiding the associated perioperative risks. The Endobronchial Valve for Emphysema PalliatioN Trial (VENT) posits that occlusion of a single pulmonary lobe through bronchoscopically placed Zephyr® endobronchial valves will effect significant improvements in lung function and exercise tolerance with an acceptable risk profile in advanced emphysema.Methods
The trial design posted on Clinical trials.gov, on August 10, 2005 proposed an enrollment of 270 subjects. Inclusion criteria included: diagnosis of emphysema with forced expiratory volume in one second (FEV1) < 45% of predicted, hyperinflation (total lung capacity measured by body plethysmography > 100%; residual volume > 150% predicted), and heterogeneous emphysema defined using a quantitative chest computed tomography algorithm. Following standardized pulmonary rehabilitation, patients were randomized 2:1 to receive unilateral lobar placement of endobronchial valves plus optimal medical management or optimal medical management alone. The co-primary endpoint was the mean percent change in FEV1 and six minute walk distance at 180 days. Secondary end-points included mean percent change in St. George's Respiratory Questionnaire score and the mean absolute changes in the maximal work load measured by cycle ergometry, dyspnea (mMRC) score, and total oxygen use per day. Per patient response rates in clinically significant improvement/maintenance of FEV1 and six minute walk distance and technical success rates of valve placement were recorded. Apriori response predictors based on quantitative CT and lung physiology were defined.Conclusion
If endobronchial valves improve FEV1 and health status with an acceptable safety profile in advanced emphysema, they would offer a novel intervention for this progressive and debilitating disease.Trial Registration
ClinicalTrials.gov: NCT00129584 相似文献6.
Ali Reza Hosseini-khalili Julian Thompson Anthony Kehoe Nicholas S Hopkinson A Khoshbaten Mohammad Reza Soroush Steve E Humphries Hugh Montgomery Mostafa Ghanei 《BMC pulmonary medicine》2008,8(1):1-5
Background
Exposure to mustard gas frequently results in long-term respiratory complications. However the factors which drive the development and progression of these complications remain unclear. The Renin Angiotensin System (RAS) has been implicated in lung inflammatory and fibrotic responses. Genetic variation within the gene coding for the Angiotensin Converting Enzyme (ACE), specifically the Insertion/Deletion polymorphism (I/D), is associated with variable levels of ACE and with the severity of several acute and chronic respiratory diseases. We hypothesized that the ACE genotype might influence the severity of late respiratory complications of mustard gas exposure.Methods
208 Kurdish patients who had suffered high exposure to mustard gas, as defined by cutaneous lesions at initial assessment, in Sardasht, Iran on June 29 1987, underwent clinical examination, spirometric evaluation and ACE Insertion/Deletion genotyping in September 2005.Results
ACE genotype was determined in 207 subjects. As a continuous variable, FEV1 % predicted tended to be higher in association with the D allele 68.03 ± 20.5%, 69.4 ± 21.4% and 74.8 ± 20.1% for II, ID and DD genotypes respectively. Median FEV1 % predicted was 73 and this was taken as a cut off between groups defined as having better or worse lung function. The ACE DD genotype was overrepresented in the better spirometry group (Chi2 4.9 p = 0.03). Increasing age at the time of exposure was associated with reduced FEV1 %predicted (p = 0.001), whereas gender was not (p = 0.43).Conclusion
The ACE D allele is associated with higher FEV1 % predicted when assessed 18 years after high exposure to mustard gas. 相似文献7.
Guan-Hong Shang Dian-Jie Lin Wei Xiao Chong-Qi Jia Yu Li Ai-Hua Wang Liang Dong 《Respiratory research》2009,10(1):1-7
Background
Desmosine and Isodesmosine (D/I) are cross-linking amino acids which are present only in mature elastin. Changes in their concentration in body fluids indicate changes in elastin degradation and can be a reflection of tissue elastase activity. This study was undertaken to determine whether continuous therapy with the long-acting bronchodilator Tiotropium bromide (TTP) could result in reductions in D/I as measured by mass spectrometry in plasma, urine and sputum.Methods
Twelve not currently smoking patients with chronic obstructive pulmonary disease (COPD), never on TTP, were selected for study. Levels of D/I, along with measurements of FVC, FEV1 and FEV1/FVC. were determined before starting TTP daily, and then one and two months after.Results
D/I decreased in plasma (10 of 12 patients), in sputum all (12 of 12), and in the percentage of free D/I in urine (10 of 12). Most patients showed slight increases in FVC and FEV1 percent predicted over two months.Conclusion
The results are consistent with an effect of prolonged bronchodilitation by anti-cholinergic blockade to also result in reduced lung elastin degradation. 相似文献8.
Hiroyuki Taniguchi Yasuhiro Kondoh Masahito Ebina Arata Azuma Takashi Ogura Yoshio Taguchi Moritaka Suga Hiroki Takahashi Koichiro Nakata Atsuhiko Sato Yukihiko Sugiyama Shoji Kudoh Toshihiro Nukiwa 《Respiratory research》2011,12(1):1-9
Background
The rate of decline in forced expiratory volume in 1 second (FEV1) is representative of the natural history of COPD. Sparse information exists regarding the associations between the magnitude of annualised loss of FEV1 with other endpoints.Methods
Retrospective analysis of UPLIFT® trial (four-year, randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily in chronic obstructive pulmonary disease [COPD], n = 5993). Decline of FEV1 was analysed with random co-efficient regression. Patients were categorised according to quartiles based on the rate of decline (RoD) in post-bronchodilator FEV1. The St George's Respiratory Questionnaire (SGRQ) total score, exacerbations and mortality were assessed within each quartile.Results
Mean (standard error [SE]) post-bronchodilator FEV1 increased in the first quartile (Q1) by 37 (1) mL/year. The other quartiles showed annualised declines in FEV1 (mL/year) as follows: Q2 = 24 (1), Q3 = 59 (1) and Q4 = 125 (2). Age, gender, respiratory medication use at baseline and SGRQ did not distinguish groups. The patient subgroup with the largest RoD had less severe lung disease at baseline and contained a higher proportion of current smokers. The percentage of patients with ≥ 1 exacerbation showed a minimal difference from the lowest to the largest RoD, but exacerbation rates increased with increasing RoD. The highest proportion of patients with ≥ 1 hospitalised exacerbation was in Q4 (Q1 = 19.5% [tiotropium], 26% [control]; Q4 = 33.8% [tiotropium] and 33.1% [control]). Time to first exacerbation and hospitalised exacerbation was shorter with increasing RoD. Rate of decline in SGRQ increased in direct proportion to each quartile. The group with the largest RoD had the highest mortality.Conclusion
Patients can be grouped into different RoD quartiles with the observation of different clinical outcomes indicating that specific (or more aggressive) approaches to management may be needed.Trial Registration
ClinicalTrials.gov number, NCT00144339 相似文献9.
Punam Singh Haripriya Gundimeda Matthias Stucki 《The International Journal of Life Cycle Assessment》2014,19(5):1036-1048
Purpose
Cooking energy is an essential requirement of any human dwelling. With the recent upsurge in petroleum prices coupled with intrinsic volatility of international oil markets, it is fast turning into a politico-socio-economic dilemma for countries like India to sustain future subsidies on liquefied petroleum gas (LPG) and kerosene. The aim of this paper is to evaluate and compare the environmental performance of various cooking fuel options, namely LPG (NG), LPG (CO), kerosene, coal, electricity, firewood, crop residue, dung cake, charcoal, and biogas, in the Indian context. The purpose of this study is to find environmentally suitable alternatives to LPG and kerosene for rural and urban areas of the country.Methods
The study assessed the cooking fuel performance on 13 ReCiPe environmental impact categories using the life cycle assessment methodology. The study modeled the system boundary for each fuel based on the Indian scenario and prepared a detailed life cycle inventory for each cooking fuel taking 1 GJ of heat energy transferred to cooking pot as the functional unit.Results and discussion
The cooking fuels with the lowest life cycle environmental impacts are biogas followed by LPG, kerosene, and charcoal. The environmental impacts of using LPG are about 15 to 18 % lower than kerosene for most environmental impact categories. LPG derived from natural gas has about 20 to 30 % lower environmental impact than LPG derived from crude oil. Coal and dung cake have the highest environmental impacts because of significant contributions to climate change and particulate formation, respectively. Charcoal produced from renewable wood supply performs better than kerosene on most impact categories except photochemical oxidation, where its contribution is 19 times higher than kerosene.Conclusions
Biogas and charcoal can be viewed as potentially sustainable cooking fuel options in the Indian context because of their environmental benefits and other associated co-benefits such as land farming, local employment opportunities, and skill development. The study concluded that kerosene, biogas, and charcoal for rural areas and LPG, kerosene, and biogas for urban areas have the lower environmental footprint among the chosen household cooking fuels in the study. 相似文献10.
Katrin Morenz Heike Biller Frank Wolfram Steffen Leonhadt Dirk Rüter Thomas Glaab Stefan Uhlig Jens M Hohlfeld 《BMC pulmonary medicine》2012,12(1):1-7
Background
The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD. Data derived from population studies can advance our understanding of the true burden of COPD. The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.Methods
All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV1/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004. Mortality was observed until the end of year 2007. Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV1 % predicted) and reported heart disease.Results
The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001). Mortality was associated with higher age, being a current smoker, male gender, and COPD. Replacing COPD with FEV1 % predicted in the multivariate model resulted in the decreasing level of FEV1 being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.Conclusions
In this cohort COPD and decreased FEV1 were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease. 相似文献11.
Harriet Corvol Nadia Nathan Celine Charlier Katarina Chadelat Philippe Le Rouzic Olivier Tabary Brigitte Fauroux Alexandra Henrion-Caude Josue Feingold Pierre-Yves Boelle Annick Clement 《Respiratory research》2007,8(1):88-9
Background
The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to variations in the inflammatory response.Methods
We evaluated the association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and BclI, and disease progression in a cohort of 255 young patients with CF. Genotypes were tested for association with changes in lung function tests, infection with Pseudomonas aeruginosa and nutritional status by multivariable analysis.Results
A significant non-corrected for multiple tests association was found between BclI genotypes and decline in lung function measured as the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). Deterioration in FEV1 and FVC was more pronounced in patients with the BclI GG genotype compared to the group of patients with BclI CG and CC genotypes (p = 0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02 respectively for F508del homozygous patients).Conclusion
The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function. 相似文献12.
Riza Hakan Erbay Ata Nevzat Yalcin Mehmet Zencir Simay Serin Habip Atalay 《BMC pulmonary medicine》2004,4(1):1-7
Background
Prophylactic treatment with N-acetylcysteine (NAC) for 3 months or more is associated with a reduction in the frequency of exacerbations of chronic obstructive pulmonary disease (COPD). This raises the question of whether treatment with NAC during an acute exacerbation will hasten recovery from the exacerbation.Methods
We have examined this in a randomised, double-blind, placebo controlled trial. Subjects, admitted to hospital with an acute exacerbation of COPD, were randomised within 24 h of admission to treatment with NAC 600 mg b.d. (n = 25) or matching placebo (n = 25). Treatment continued for 7 days or until discharge (whichever occurred first). To be eligible subjects had to be ≥ 50 years, have an FEV1 ≤ 60% predicted, FEV1/VC ≤ 70% and ≥ 10 pack year smoking history. Subjects with asthma, heart failure, pneumonia and other respiratory diseases were excluded. All subjects received concurrent treatment with prednisone 40 mg/day, nebulised salbutamol 5 mg q.i.d and where appropriate antibiotics. FEV1, VC, SaO2 and breathlessness were measured 2 hours after a dose of nebulised salbutamol, at the same time each day. Breathlessness was measured on a seven point Likert scale.Results
At baseline FEV1 (% predicted) was 22% in the NAC group and 24% in the control group. There was no difference between the groups in the rate of change of FEV1, VC, SaO2 or breathlessness. Nor did the groups differ in the median length of stay in hospital (6 days for both groups).Conclusions
Addition of NAC to treatment with corticosteroids and bronchodilators does not modify the outcome in acute exacerbations of COPD. 相似文献13.
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 PD20 FEV1.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% (PD100Rint, 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 PD20FEV1 (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 FEV1 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. 相似文献14.
Juan P de Torres Ciro Casanova Angela Montejo de Garcini Armando Aguirre-Jaime Bartolome R Celli 《Respiratory research》2007,8(1):18-7
Rationale
We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction.Objectives
Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients.Methods
In a FEV1 % matched population of 100 men and women with COPD we measured: age, MMRC, FEV1, FVC, TLC, IC/TLC, PaO2, PaCO2, DLCO, Pimax, P0.1, Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations.Results
MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:-0.39, p = 0.01), FEV1 % (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO2 (men:-0.59, p < 0.001), PaCO2 (men:0.27, p = 0.05), DLCO (men:-0.54, p < 0.001), P0.1/Pimax (men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P0.1/Pimax in women (r2 = 0.30) and BMI, DLCO, PaO2 and P0.1/Pimax in men (r2 = 0.81) were the strongest predictors of MMRC scores.Conclusion
In mild to severe COPD patients attending a pulmonary clinic, P0.1/Pimax was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD. 相似文献15.
James F. Donohue Thomas Goodin Robert Tosiello Alistair Wheeler 《Respiratory research》2017,18(1):202
Background
Long-acting muscarinic antagonists (LAMAs) are recommended for the treatment of chronic obstructive pulmonary disease (COPD). Glycopyrrolate/eFlow® is an investigational drug–device combination of the LAMA glycopyrrolate administered by an eFlow® Closed System (eFlow® CS) nebulizer. The GOLDEN 2 (NCT01706536) and GOLDEN 6 (NCT02038829) Phase II, multicenter studies were conducted to inform dose selection for the GOLDEN Phase III clinical trials. Bronchodilator responses and safety assessments supported dose selection.Methods
Subjects with moderate-to-severe COPD were randomized into 28-day parallel-group (GOLDEN 2) or 7-day crossover (GOLDEN 6) studies and received placebo, glycopyrrolate (3, 6.25, 12.5, 25, 50 or 100 μg twice daily [BID]) or aclidinium bromide 400 μg BID. The primary endpoint of both studies was change from baseline in trough forced expiratory volume in 1 s (FEV1). Safety assessments included the incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events, and discontinuation due to TEAE. Lung function data collected in both studies were pooled.Results
The combined GOLDEN 2 (n?=?282) and GOLDEN 6 (n?=?96) studies included 378 subjects. On Days 7 and 28 there were dose-ordered, statistically significant and clinically important lung function improvements in glycopyrrolate treatment groups. Specifically, on Day 7, glycopyrrolate produced >0.100 L placebo-adjusted changes from baseline in trough FEV1 (12.5 μg BID: 0.122 L; 25 μg BID: 0.123 L; 50 μg BID: 0.137 L) and FEV1 AUC0–12 (12.5 μg BID: 0.145 L; 25 μg BID: 0.178 L; 50 μg BID: 0.180 L). The improvements in lung function for the glycopyrrolate 25 and 50 μg BID doses were comparable to those with aclidinium bromide 400 μg BID (FEV1: 0.149 L; FEV1 AUC0?12: 0.172 L). Acceptable safety profiles were observed across all groups in both studies.Conclusions
The efficacy and safety findings supported selection of glycopyrrolate 25 and 50 μg BID doses for the Phase III GOLDEN studies and provided preliminary evidence for the use of nebulized glycopyrrolate as a maintenance therapy for COPD.16.
Background
Asthmatics treated with long-acting beta-agonists have a reduced bronchodilator response to moderate doses of inhaled short acting beta-agonists during acute bronchoconstriction. It is not known if the response to higher doses of nebulised beta-agonists or other bronchodilators is impaired. We assessed the effect of long-acting beta-agonist treatment on the response to 5 mg nebulised salbutamol and to ipratropium bromide.Methods
Two double-blind, placebo-controlled, crossover studies of inhaled formoterol 12 μg twice daily in patients with asthma. High-dose salbutamol: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 5 mg was then administered via nebuliser and the FEV1 was monitored for 20 minutes. Ipratropium: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled 4.5% saline to produce a 20% fall in FEV1. Salbutamol 200 μg or ipratropium bromide 40 μg was then inhaled and the FEV1 was monitored for 30 minutes. Four study arms compared the response to each bronchodilator after formoterol and placebo. Analyses compared the area under the bronchodilator response curves, adjusting for changes in pre-challenge FEV1, dose of provocational agent and FEV1 fall during the challenge procedure.Results
The response to nebulised salbutamol was 15% lower after formoterol therapy compared to placebo (95% confidence 5 to 25%, p = 0.008). The response to ipratropium was unchanged.Conclusion
Long-acting beta-agonist treatment induces tolerance to the bronchodilator effect of beta-agonists, which is not overcome by higher dose nebulised salbutamol. However, the bronchodilator response to ipratropium bromide is unaffected. 相似文献17.
Yumin Zhou Yimin Zou Xiaochen Li Shuyun Chen Zhuxiang Zhao Fang He Weifeng Zou Qiuping Luo Wenxi Li Yiling Pan Xiaoliang Deng Xiaoping Wang Rong Qiu Shiliang Liu Jingping Zheng Nanshan Zhong Pixin Ran 《PLoS medicine》2014,11(3)
Background
Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning. The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD.Methods and Findings
A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China. Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011. That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants'' homes. Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions.Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders. The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y). The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05). The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements.Conclusions
Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD.Trial Registration
Chinese Clinical Trial Register ChiCTR-OCH-12002398 Please see later in the article for the Editors'' Summary 相似文献18.
Seth Thomas Scanlon Tatyana Milovanova Sonja Kierstein Yang Cao Elena N Atochina Yaniv Tomer Scott J Russo Michael F Beers Angela Haczku 《Respiratory research》2005,6(1):1-11
Background
Recent studies suggest that HCV infection is associated with progressive declines in pulmonary function in patients with underlying pulmonary diseases such as asthma and chronic obstructive pulmonary disease. Few molecular studies have addressed the inflammatory aspects of HCV-associated pulmonary disease. Because IL-8 plays a fundamental role in reactive airway diseases, we examined IL-8 signaling in normal human lung fibroblasts (NHLF) in response to the HCV nucleocapsid core protein, a viral antigen shown to modulate intracellular signaling pathways involved in cell proliferation, apoptosis and inflammation.Methods
NHLF were treated with HCV core protein and assayed for IL-8 expression, phosphorylation of the p38 MAPK pathway, and for the effect of p38 inhibition.Results
Our studies demonstrate that soluble HCV core protein induces significant increases in both IL-8 mRNA and protein expression in a dose- and time-dependent manner. Treatment with HCV core led to phosphorylation of p38 MAPK, and expression of IL-8 was dependent upon p38 activation. Using TNFα as a co-stimulant, we observed additive increases in IL-8 expression. HCV core-mediated expression of IL-8 was inhibited by blocking gC1qR, a known receptor for soluble HCV core linked to MAPK signaling.Conclusion
These studies suggest that HCV core protein can lead to enhanced p38- and gC1qR-dependent IL-8 expression. Such a pro-inflammatory role may contribute to the progressive deterioration in pulmonary function recently recognized in individuals chronically infected with HCV. 相似文献19.
Nicholas S Hopkinson Rachel C Tennant Mark J Dayer Elisabeth B Swallow Trevor T Hansel John Moxham Michael I Polkey 《Respiratory research》2007,8(1):25-8
Background
Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development. We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year.Methods
64 patients with stable COPD (FEV1 mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart. Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation.Results
QMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04). The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment. Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001). Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs. +1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs. +0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026).Conclusion
Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations. Factors predicting progression of quadriceps weakness could not be identified from the present cohort. 相似文献20.
Khaled Al-shair Umme Kolsum Rachel Dockry Julie Morris Dave Singh Jørgen Vestbo 《Respiratory research》2011,12(1):1-6