Xeroderma pigmentosum patients from Germany: repair capacity of 45 XP fibroblast strains of the Mannheim XP Collection as measured by colony-forming ability and unscheduled DNA synthesis following treatment with methyl methanesulfonate and N-methyl-N-nitrosourea

Summary A total of 45 XP fibroblast strains from the Mannheim XP Collection (representatives of XP complementation groups A, C, D, E, F or G, I, and XP variants) were investigated for colony-forming ability (term: D₀ after treatment with up to ten doses of the methylating carcinogen MeSO₂OMe. As controls 16 fibroblast strains from normal donors were used. Except for 4 XP strains (1 from group C and 3 from group D) which, however, were borderline cases, none of the remaining 41 XP strains was found to be more sensitive than normal controls. This held true within the limits of an experimental accuracy (experimental variability of D₀ values) of ±7%. When weighted means were calculated for XP complementation groups and compared with that of normal donors at a significance level of 5%, no significant difference was detected. In contrast, after exposure of 6 XP group D strains to MeNOUr, a weighted mean D₀ value was obtained which was significantly decreasd by 27%. Unscheduled DNA synthesis (term: G₀ which serves as a measure of excision repair) after exposure to MeNOUr was quantitatively the same (exposure to MeNOUr was quantitatively the same (experimental varability: ±8%) both in the group of normal strains and in most of the XP complementation groups. Exceptions were group E and group F (or G) which had higher, and group I which had lower repair. Analogous G₀ values measured after exposure to MeSO₂OMe (experimental variability: ±13%), however, differed from that of the control strains: they were lower in XP complementation groups A, D, E, F (or G), and I. However, groups A, E, F (or G), and I including only 3 individual strains or less may be considered to be possibly ill-represented. Yet, group D including 11 XP strains did show reduction of the mean G₀ value by 35%. From this it is concluded that there are repair defects in XP group D strains with regrad to MeSO₂OMe-induced adducts. These defects seem to be small.Abbreviations XP xeroderma pigmentosum - MeSO₂OMe methyl methanesulfonate - MeNOUr N-methyl-N-nitrosourea - Me(NO)(NO₂)Gdn N-methyl-N-nitro-N-nitrosoguanidine - HEPES N-2-hydroxyethyl-piperazine-N-2-ethanesulfonic acid This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136     

DNA repair synthesis in fibroblast strains from patients with actinic keratosis,squamous cell carcinoma,basal cell carcinoma,or malignant melanoma after treatment with ultraviolet light,N-acetoxy-2-acetyl-aminofluorene,methyl methanesulfonate,and N-methyl-N-nitrosourea

Summary Fibroblast strains derived from skin biopsies of patients with actinic keratosis (6), malignant melanoma (18), squamous cell carcinoma (11), and basal cell carcinoma (12) were investigated for DNA repair synthesis, with 16 fibroblast strains for normal donors as controls. Cells were exposed to UV light, the UV-like carcinogen (Ac)₂ONFln, and the methylating carcinogenes MeSO₂OMe and MeNOUr. Dose-response experiments, which included 10 dose levels, were performed, the data analyzed by linear regression, and the slope of the regression line (term: G ₀) used as a measure of DNA repair synthesis. The mean experimental variability of G ₀ of individual fibroblast strains was 9.5%–15.4%, depending upon exposure. For comparison of all cell strains belonging to the same skin malignancy group with those of the control group, G ₀ values of the individual strains were combined to yield group-specific weighted mean G ₀ values.In addition, the capacity to incise UV-damaged DNA was measured in 24 cell strains from patients with skin tumors using the alkaline elution technique. For quantitating DNA-incising capacity, the initial velocities of the elution curves were plotted versus the UV dose, and the slope of the resulting regression line was used to obtain the characteristic value E ₀. The mean experimental variability of E ₀ of individual strains was ±22%. These E ₀ values were combined to yield weighted mean values of groups.The fibroblast strains in the groups of patients with actinic keratosis and malignant melanoma were found to have normal mean G ₀ values when DNA repair synthesis was challenged with UV light or one of the three carcinogens. However, the squamous cell carcinoma group exhibited significantly lower mean G ₀ values after treatment with UV light (82% that of normal donors), (Ac)₂ONFln (70%), MeSO₂OMe (70%), and MeNOUr (69%). The basal cell carcinoma group showed significantly diminished repair synthesis upon treatment with UV light (81% that of normal donors) and MeSO₂OMe (67%). In contrast to these findings, in no skin malignancy group was post UV DNA-incising capacity (E ₀) significantly diminished, although it should be noted that group sizes were only half as large as for G ₀ determinations.These data may be interpreted as indicating that DNA excision repair is impaired in fibroblast strains from patients with squamous cell carcinoma and — to a lesser extent — basal cell carcinoma. This deficiency seems to pertain to several DNA repair mechanisms, as excision of both alkylation and UV-induced damage is involved. Although the repair impairments are statistically significant, the relative risks at which the investigated patients are do not seem to be high enough as to be of immediate practical value. Our results indicate further studies would be useful.Abbreviations XP xeroderma pigmentosum - UV light ultraviolet light - UVB UV light with the wavelength from 290 nm to 320 nm - (Ac)₂ONFln N-acetoxy-2-acetylaminofluorene - MeSO₂OMe methyl methanesulfonate - MeNOUr N-methyl-N-nitrosourea - ara-C 1--d-arabinofuranosyl cytosine This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136Dedicated to Professor E. Hecker on the occasion of his 60th birthday     

Xeroderma pigmentosum patients from the federal Republic of Germany: Decrease in post-UV colony-forming ability in 30 xeroderma pigmentosum fibroblast strains is quantitatively correlated with a decrease in DNA-incising capacity

Summary A total of 16 normal and 46 XP fibroblast strains from the Mannheim Collection were investigated for colony-forming ability following exposure to both UV light and the UV-like carcinogen (Ac)₂ONFln. The dose-response experiments included up to 13 dose levels. The exponential segments of the curves were analysed by linear regression and the negative reciprocal of the regression coefficient (D₀) was calculated for each cell strain.For quantitating the DNA-incising capacity, DNA elution curves were determined at several UV dose levels. Plotting the initial velocities of the elution curves versus the UV dose yielded a regression line, the slope of which was used to obtain the characteristic value E₀.Comparing D₀ with E₀ values showed that cell strains in which colony-forming ability was reduced suffered a reduction of DNA-incising capacity of the same magnitude. There were only 3 exceptional strains in which reduction of DNA-incising capacity was less pronounced than reduction of colony-forming ability. We have previouly shown (Fischer et al. 1982) that D₀ values from 27 XP strains of the Mannheim Collection were correlated with clinical symptoms. This correlation is now being extended by relating colony-forming ability to the magnitude of the DNA incision defect. From our data we conclude that the best quantitative biochemical denominator to explain the sun sensitivity of XP is that of a defective incision of UV-damaged DNA.A considerable similarity in sensitivity towards both UV light and (Ac)₂ONFln was found in 16 normal and 46 XP strains. This seems to indicate that UV-and (Ac)₂ONFln-induced DNA damage are removed to a large extent by the same pathways in human fibroblasts.Abbreviations XP xeroderma pigmentosum - (Ac)₂ONFln N-acetoxy-2-acetylaminofluorene - UV light ultraviolet light - HEPES N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid - ara-C 1--d-arabinofuranosyl cytosine This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136     

Stimulation of recombination between homologous sequences on plasmid DNA and chromosomal DNA in Escherichia coli by N-acetoxy-2-acetylaminofluorene.

A plasmid containing a wild-type lac operon and a tetracycline-resistance gene was covalently modified by N-acetoxy-2-acetylaminofluorene and used to transform two series of Lac- Escherichia coli cell types. Each set contained wild-type and repair-deficient mutants. One set of cells contained a lacY mutation and the other a deletion of the entire lac operon. Survival and mutagenesis of the plasmid were measured as a function of the N-acetoxy-2-acetylaminofluorene concentration. The results indicate that when no homologous sequences are present in the chromosomal DNA, mutations occur at a low frequency: at 10% survival the frequency was 1-2 X 10(-4) mutants per transformant. When homologous sequences, the lacY allele, are present in the chromosomal DNA, Lac- plasmids are found at a high frequency in a recA-dependent, lexA-independent fashion: at 10% survival the frequency was 5-10 X 10(-2) mutants per transformant. Southern blot analysis of the restriction enzyme profiles of the resulting plasmid and host-cell DNA sequences showed recombinational transfer of host sequences to the N-acetoxy-2-acetylamino-fluorene-treated plasmid had occurred. When the host chromosomes contained Lac+ homologous sequences no mutants were found, indicating that the results were not caused by error-prone recombination.     

Comparison of the healing capacities of sucralfate and cimetidine in the short-term treatment of duodenal ulcer: a double-blind randomized trial

Fifty-nine outpatients with endoscopically proven duodenal ulcer were evaluated for 4-8 wk in a randomized, double-blind trial comparing sucralfate, a sulfated disaccharide, (1 g, 0.5 h before each meal and at bedtime) with cimetidine (300 mg, 0.5 h before each meal and at bedtime). Ulcer symptoms and their relief were recorded by patients in a diary, along with data on cigarette, alcohol, coffee, and drug intake. Duodenoscopy was performed after 4 wk to assess healing, and was repeated after 8 wk if healing had not occurred by the 4-wk evaluation. Twenty-four of 30 patients taking sucralfate (80.0%) and 22 of 29 patients taking cimetidine (75.9%) had their ulcer completely healed after 4 wk. The overall healing rates after 8 wk for the sucralfate and cimetidine groups were 90.0% (27 of 30 patients) and 86.2% (25 of 29 patients), respectively. There were no significant differences between the two treatment groups in ulcer healing, symptom relief, and side effects. Symptoms were relieved equally with respect to time and efficacy. Minor adverse experiences were reported in each treatment group. None of these experiences were serious enough to warrant discontinuation of treatment. These results suggest tha sucralfate is as effective as cimetidine in the short-term treatment of duodenal ulcer.     

原发性高血压716例治疗前后超声心动图检查结果对照研究

目的 探讨原发性高血压（高血压）患者治疗前后的超声心动图结果.方法 对东莞市寮步镇716例高血压患者进行强化治疗干预并行超声心动图检查,比较治疗前后的相关指标.结果 治疗干预后主动脉内径[（26±4） mm vs.（28±4）mm,P＜0.05]及血流速度[（1.06±0.28）m·s-1 vs.（1.12±0.26） m·s-1,P＜0.05]减小;二尖瓣E峰[（0.66±0.22）m ·s-1 vs.（0.61±0.22）m·s-1,P＜0.05]、E/A比值（0.80±0.49vs.0.75±0.26,P＜0.05）、射血分数（69.9％±10.1％ vs.69.0％±11.2％,P＜0.05）、室壁缩短率（39.5％±8.8％vs.38.6％±9.5％,P＜0.05）增加;室壁厚度无明显改变.结论 高血压治疗明显改善患者的心脏功能.     

SV40-induced transformation and T-antigen production is enhanced in normal and repair-deficient human fibroblasts after pretreatment of cells with UV light

Summary Human fibroblasts irradiated with UV light were infected with simian virus 40 and tested either for transformation or T-antigen production. At UV doses that allowed approximately 5–10% of the irradiated cells to survive, the number of surviving transformed colonies increased. This result was confirmed by testing for T-antigen 96 h post infection by means of indirect immunofluorescence. Since these results were obtained for a normal cell line as well as for two UV excision repair-deficient ones (XP groups A and D), it was concluded that excision repair functions cannot play a decisive role in the events leading to increased transformation and T-antigen production. It is proposed that the relative increase of transformation and T-antigen production is the expression of host functions which are induced by DNA damage threatening cell survival.Abbreviations XP Xeroderma pigmentosum - UV light ultraviolet light - p.f.u. plaque-forming unit This work was partly supported by the Deutsche Forschungsgemeinschaft, SFB 136, and partly by a German Cancer Research Center grant for cooperation with the National Council for Research and Development (Jerusalem, Israel)     

Identification and order of sequential mutations in beta-actin genes isolated from increasingly tumorigenic human fibroblast strains.

We have sequenced the mutant beta-actin gene of a tumorigenic human fibroblast cell line (HuT-14T) and found that it carries three mutations that alter the amino acids at positions 36, 83, and 244 as well as a 22-base-pair "insertion" sequence, in the 5' intron, not present in a wild-type gene. The less tumorigenic cell line HuT-14, a progenitor of HuT-14T, has the same codon-244 mutation and the insertion sequence but not the other two mutations. A nontumorigenic cell line that is related to HuT-14 but that has no beta-actin mutations does carry the intron-length polymorphism. We conclude that the mutation at codon 244 occurred first in a beta-actin allele already bearing the 22-base-pair intron insert and that mutations at codons 36 and 83 arose subsequently during the selection for the HuT-14T phenotype. Rat-2 cells synthesize the appropriate charge-variant species of mutant actin protein when transfected with either the singly or the triply mutated beta-actin gene.     

Comparison of human metapneumovirus genotypes from the province of Bolzano in northern Italy with strains from surrounding regions in Italy and Austria

The epidemiology of the genetic sublineages of human metapneumovirus (hMPV) and their clinical relevance are not fully understood. We compared hMPV genotypes isolated in the province of Bolzano in Northern Italy with strains from nearby Italian and Austrian regions by sequencing of NP- and L-gene fragments. Our results suggest that similar strains cycle through adjacent geographic areas, with the respective subtypes replacing each other on a seasonal basis.     

Crystal structures of 2-acetylaminofluorene and 2-aminofluorene in complex with T7 DNA polymerase reveal mechanisms of mutagenesis

The carcinogen 2-acetylaminofluorene forms two major DNA adducts: N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) and its deacetylated derivative, N-(2'-deoxyguanosin-8-yl)-2-aminofluorene (dG-AF). Although the dG-AAF and dG-AF adducts are distinguished only by the presence or absence of an acetyl group, they have profoundly different effects on DNA replication. dG-AAF poses a strong block to DNA synthesis and primarily induces frameshift mutations in bacteria, resulting in the loss of one or two nucleotides during replication past the lesion. dG-AF is less toxic and more easily bypassed by DNA polymerases, albeit with an increased frequency of misincorporation opposite the lesion, primarily resulting in G --> T transversions. We present three crystal structures of bacteriophage T7 DNA polymerase replication complexes, one with dG-AAF in the templating position and two others with dG-AF in the templating position. Our crystallographic data suggest why a dG-AAF adduct blocks replication more strongly than does a dG-AF adduct and provide a possible explanation for frameshift mutagenesis during replication bypass of a dG-AAF adduct. The dG-AAF nucleoside adopts a syn conformation that facilitates the intercalation of its fluorene ring into a hydrophobic pocket on the surface of the fingers subdomain and locks the fingers in an open, inactive conformation. In contrast, the dG-AF base at the templating position is not well defined by the electron density, consistent with weak binding to the polymerase and a possible interchange of this adduct between the syn and anti conformations.     

Low plasma basic fibroblast growth factor is associated with laser photocoagulation treatment in adult type 2 diabetes mellitus from the Veterans Affairs Diabetes Trial

Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen that does not normally circulate. Yet plasma bFGF-like bioactivity was increased in association with persistent microalbuminuria and retinopathy in adult type 2 diabetes mellitus. In the present study, we tested whether plasma bFGF immunoreactivity (IR) could predict the need for laser treatment of diabetic retinopathy in a baseline subset of advanced type 2 diabetes mellitus from the Veterans Affairs Diabetes Trial (mean: age, 59 years; diabetes duration, 11 years; baseline glycosylated hemoglobin, 9.5%). Plasma bFGF-IR was determined with a sensitive and specific 2-site enzyme-linked immunoassay in 172 patients at the baseline visit. Results were dichotomized at 4.5 pg/mL, the upper limit in healthy men. There was an unexpected significant association between low baseline plasma bFGF-IR level and the interim (4 years) need for laser treatment. First laser treatment was significantly more likely to be required in patients with low compared with high baseline bFGF (19% vs 6%, P = .03 for the difference). After adjusting for clinical risk factors, low vs high bFGF (hazard ratio [HR], 5.01; P = .012), duration of diabetes (HR, 1.05; P = .050), and low-density lipoprotein cholesterol concentration (HR, 0.98; P = .027) were all significantly associated with time to first laser occurrence. These and our prior results suggest that low plasma bFGF-IR may be a marker for the presence of anti-endothelial cell autoantibodies that may contribute to the need for laser photocoagulation treatment in adult men with advanced type 2 diabetes mellitus.     

6-Methylguanine and 6-methylguanosine inhibit colony-forming ability in a malignant xeroderma pigmentosum cell line but not in other xeroderma pigmentosum and normal human fibroblast strains after treatment with 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-urea

Summary The XP cell strain XP29MA, its malignant counterpart XP29MAmal and a normal human fibroblast strain were tested for colony-forming ability after treatment with HECNU in the presence of m⁶G, m⁶Gua, and he⁷G.In XP29MAmal, inhibition of post-HECNU colony-forming ability was 35% when 0.25 mM of either m⁶G or m⁶Gua were present, whereas in XP29MA and the normal fibroblast strain no inhibition was detected. The he⁷G caused a similar but smaller inhibitory effect in XP29MAmal, but failed to do so in XP29MA.HECNU predominantly exerts its killing effect by alkylating O-6 of DNA-bound guanine and causing DNA interstrand crosslinks. Alkylation of O-6 of guanine can be repaired by 6-methylguanine-DNA methyltransferase. From our experiments we conclude that in XP29MAmal this methyltransferase was inhibited in the presence of the 6-alkylguanines, thus leaving more 2-chloroethylated sites in DNA unrepaired. This results in sensitization in terms of decreased colony-forming ability observed only in the malignant cell line.Abbreviations XP xeroderma pigmentosum - HECNU 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-urea - HEPES N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid - m⁶G 6-methylguanosine - m⁶Gua 6-methylguanine - he⁷G 7-(2-hydroxyethyl)-guanosine This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136The publication is dedicated to Professor E. Hecker on the occasion of his 60th birthday     

腹腔镜下输卵管切开取胚加局部MTX注射与药物保守治疗输卵管妊娠后再次妊娠分析

目的探讨两种保守性治疗方法治疗输卵管妊娠后再次妊娠情况。方法回顾性分析2005-03—2008-03该院采用保守性治疗方法治疗的125例未生育输卯管妊娠患者的临床资料,根据治疗方法不同,分为腹腔镜下输卵管切开取胚加局部甲氨蝶呤（MTX）注射65例（A组）和药物保守治疗60例（B组）。比较两组术后宫内妊娠、再次异位妊娠及继发不孕的情况。结果A组宫内妊娠发生率高于B组（P〈0．05）,继发不孕发生率低于B组（P〈0．05）,而两组再次异位妊娠发生率比较差异无统计学意义（P〉0．05）。结论腹腔镜下输卵管切开取胚加局部MTX注射治疗未生育输卵管妊娠患者优于药物保守治疗。     

Quantification of viral inactivation by photochemical treatment with amotosalen and UV A light, using a novel polymerase chain reaction inhibition method with preamplification

BACKGROUND: In evaluating a photochemical treatment process for inactivating parvovirus B19, there lacked simple culture methods to measure infectivity. The recently developed enzyme-linked immunospot (ELISpot) infectivity assay uses late-stage erythropoietic progenitor cells and is labor intensive and time consuming. We evaluated a novel, efficient polymerase chain reaction (PCR) inhibition assay and examined correlations with reductions in infectivity. METHODS: Contaminated plasma was treated with 150 micromol/L amotosalen and 3 J/cm(2) ultraviolet A light and then tested for DNA modification using conventional PCR inhibition and a novel preamplification approach. The novel assay subjected the samples to preamplification cycles using long-template PCR, followed by quantitative PCR (QPCR) inhibition detection. Both approaches were tested for correlations with reductions in viral infectivity by comparing ELISpot assay results of identical samples. RESULTS: The B19 preamplification inhibition assay showed detection ranges of 2-2.5 log and demonstrated quantitative correlation with up to a 5.8-log reduction in viral infectivity in ELISpot results. Conventional PCR detected a >5 log reduction in amplification, correlated with a 4.4-log reduction in viral infectivity. A range of 4-log inhibition of hepatitis B virus DNA amplification was also achieved. CONCLUSIONS: The results demonstrated that a novel preamplification QPCR assay is a useful tool for predicting reductions in infectivity after photochemical treatment. This assay was extended to show utility in circumstances where practical in vitro assays are unavailable for the determination of the efficacy of pathogen inactivation.     

Phase-shifts in melatonin, 6-sulphatoxymelatonin and alertness rhythms after treatment with moderately bright light at night

OBJECTIVES Shift work and rapid travel across several time zones leads to desynchronization of internal circadian rhythms from the external environment and from each other with consequent problems of behaviour, physiology and performance. Field studies of travellers and shift workers are expensive and difficult to control. This investigation concerns the simulation of such rhythm disturbance in a laboratory environment. The main objectives are to assess the ability of controlled exposure to moderately bright light and darkness/sleep to delay circadian rhythms in volunteers without environmental isolation and, secondly, to evaluate the use of different indices of melatonin (MT) secretion together with self-rated alertness as marker rhythms. PATIENTS Six normal volunteers aged 22–26 years (mean ± SD 24·3 ± 1·4). DESIGN Subjects were exposed to the following periods of moderately bright light (1200 lux) on three consecutive days in early December 1991: Day (D)1: 2000-0200 h, D2: 2200-0400 h and D3: 2400-0600 h. Each period was followed by 8 hours of darkness (< 1 lux). Hourly blood, sequential 4-hourly urine (8-hourly when asleep) and hourly saliva (except when asleep) samples were taken throughout a 24-hour period on D0 (baseline), D4 (1 day post-light treatment) and D7 (4 days post-light treatment). During waking hours, subjective alertness was rated every 2 hours on a visual analogue scale. MEASUREMENTS MT was measured in plasma and saliva, and its metabolite, 6-sulphatoxymelatonin (aMT6s), was measured in urine. MT, aMT6s and alertness scores were analysed by ANOVA and a cosinor analysis program. RESULTS A delay shift was present in the aMT6s, plasma MT and salivary MT rhythms (degree of shift: 2·67 ± 0.3 h (P<0·001, n = 5); 2·35±0·29 h (P<0·001, n = 6); and 1·97 ± 0·32 h (P < 0·01, n = 6), mean ± SEM, respectively) 1 day post-light treatment compared to baseline. Adaptation to the initial phase position was apparent by the 4th post-treatment day. Significant correlations were obtained between plasma MT onset (degree of shift: 3·12 ± 0·74 h (P < 0·001, n = 6, mean ± SEM)) and the acrophases (calculated peak times) of plasma MT (P<0·001), salivary MT (P < 0·05) and urinary aMT6s (P < 0·01). A significant phase delay in the alertness rhythm was also evident 1 day post-treatment (3·08 ± 0·67 h (P < 0·01, n = 6, mean ± SEM)) with adaptation by the 2nd post-treatment day. CONCLUSIONS This study suggests that these methods of determining MT secretion are comparable and give reliable assessments of the MT circadian phase position even after a phase-shift. Significant phase-shifts of similar magnitude can be induced in both MT and alertness rhythms using moderate intensity bright light at night.     

Comparison of the lung function change in patients with COPD and bronchial asthma before and after treatment with budesonide/formoterol

Objective

This study investigated the rapid onset of bronchodilation effect and compared lung function changes following budesonide/formoterol (Symbicort Turbuhaler®) inhalation in Chinese patients with moderate-severe chronic obstructive pulmonary disease (COPD) and bronchial asthma.

Methods

In this open-label, parallel-group clinical study, patients eligible for study were divided into COPD group (n=62, mean age 68.16±8.75 years) and asthma group (n=30, mean age 45.80±12.35 years). Lung function tests (include FEV1, FVC, FEV1/FVC, and IC) were performed at baseline (t=0 min time point, value before inhalation of budesonide/formoterol), and then eligible patients received two inhalations of budesonide/formoterol (160/4.5 μg). Lung function tests were reassessed at t=3, 10 and 30 min time point. The primary end-point was lung function change 3 min after drug inhalation, and the secondary end-points were comparison of the gas flow rate (ΔFEV1) and volume responses (ΔFVC, ΔIC) between COPD and asthma patients after inhalation of budesonide/formoterol.

Results

Compared with the baseline, all patients significantly improved their lung function (included FEV1, FVC, FEV1/FVC, and IC) at 3 min (P<0.05). Greater bronchodilation efficacy was found in the asthma group compared with the COPD group (P<0.05). In the asthmatic patients, the curves of FEV1, FVC, FEV1/FVC, IC, showed improvement with an ascending trend at all time points from 3 to 30 min. Whereas in the COPD patients, only the curves of FEV1, FVC, IC showed similar pattern. We found that ΔFVC was significantly higher than ΔFEV1 in both groups (P<0.05), but no significant difference between ΔIC and ΔFEV1 (P>0.05). Compared with COPD group, asthma group had higher level of ΔFEV1 and ΔIC (P<0.05), but no significant difference for ΔFVC can be found.

Conclusions

Budesonide/formoterol has a fast onset of bronchodilation effect in patients with moderate-severe COPD and asthma. Greater efficacy was found in the asthma group compared with the COPD group. The gas flow rate and volume responses in patients with COPD differ from those with asthma after inhalation of Budesonide/formoterol.KEY WORDS : Budesonide/formoterol, chronic obstructive pulmonary disease, bronchial asthma, lung function testChronic obstructive pulmonary disease (COPD) and bronchial asthma (asthma) have important similarities and differences. Both are chronic inflammatory diseases that cause airflow limitation (1,2). However, there are great difference between the two in terms of genetic basis, idiosyncratic reaction, airway hyper-responsiveness, inflammatory mediators and response to the treatment (3). There is neither study about the rapid onset of effect of ICS/LABA combination therapy (budesonide/formoterol) in China nor report about the differences of lung function change before and after treatment between patients with COPD and asthma all over the world.It is traditionally thought that the responses in bronchodilatation test of asthma and COPD are “gas flow rate responses” and “volume responses” respectively (1). But yet no report about the “gas flow rate responses” and “volume responses” of ICS/LABA such as budesonide/formoterol in patients with COPD and asthma is available.In this trial, we will determine the rapid onset of effect of budesonide/formoterol in patients with COPD and asthma by testing the lung function in several time points in a short time. In addition, we will discuss the differences of the gas flow rate and volume responses in patients with asthma and COPD after budesonide/formoterol inhalation.