Tumour necrosis factor and lymphotoxin A polymorphisms: a relationship with COPD and its progression?
Explore the source record for details and available documents.
Asian People↗
Biomedical subjects
H M Boezen
Publications and source records attributed to H M Boezen.
Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy.
BACKGROUND: It is controversial whether proton pump inhibitor use leads to fundic gland polyp development. AIM: To determine whether fundic gland polyp development is due to proton pump inhibitor use and to investigate mechanisms involved. METHODS: Proton pump inhibitor use and the presence of fundic gland polyps were assessed in consecutive patients undergoing oesophagogastroduodenoscopy. Biopsies from fundic gland polyps and gastric mucosa were taken. Dysplasia was graded as negative, low or high grade. Prevalence of parietal cell hyperplasia and parietal cell protrusions and the proportional cystic area were assessed. RESULTS: 599 patients participated, 322 used proton pump inhibitors, 107 had fundic gland polyps. Long-term proton pump inhibitor use was associated with an increased risk of fundic gland polyps (1-4.9 years use: OR 2.2, 95% CI: 1.3-3.8; > or =5 years: OR 3.8, 95% CI: 2.2-6.7) while short-term therapy (<1 year) was not (OR 1.0, 95% CI: 0.5-1.8). Low-grade dysplasia was found in one fundic gland polyp. Fundic gland polyps associated with long-term proton pump inhibitor use had a larger proportional cystic area and higher frequency of parietal cell hyperplasia and parietal cell protrusion. CONCLUSIONS: Long-term proton pump inhibitor use is associated with an up to fourfold increase in the risk of fundic gland polyps. Risk of dysplasia is negligible. Aetiologically, these polyps seem to arise because of parietal cell hyperplasia and parietal cell protrusions resulting from acid suppression.
Adolescent↗
Preventive intervention possibilities in radiotherapy- and chemotherapy-induced oral mucositis: results of meta-analyses.
The aim of these meta-analyses was to evaluate the effectiveness of interventions for the prevention of oral mucositis in cancer patients treated with head and neck radiotherapy and/or chemotherapy, with a focus on randomized clinical trials. A literature search was performed for reports of randomized controlled clinical studies, published between 1966 and 2004, the aim of which was the prevention of mucositis in cancer patients undergoing head and neck radiation, chemotherapy, or chemoradiation. The control group consisted of a placebo, no intervention, or another intervention group. Mucositis was scored by either the WHO, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) score, or the absence or presence of ulcerations, or the presence or absence of grades 3 and 4 mucositis. The meta-analyses included 45 studies fulfilling the inclusion criteria, in which 8 different interventions were evaluated: i.e., local application of chlorhexidine; iseganan; PTA (polymyxin E, tobramycine, and amphotericin B); granulocyte macrophage-colony-stimulating factor/granulocyte colony-stimulating factor (GM-CSF/G-CSF); oral cooling; sucralfate and glutamine; and systemic administration of amifostine and GM-CSF/G-CSF. Four interventions showed a significant preventive effect on the development or severity of oral mucositis: PTA with an odds ratio (OR) = 0.61 (95% confidence interval [CI], 0.39-0.96); GM-CSF, OR = 0.53 (CI: 0.33-0.87); oral cooling, OR = 0.3 (CI: 0.16-0.56); and amifostine, OR = 0.37 (CI: 0.15-0.89). To date, no single intervention completely prevents oral mucositis, so combined preventive therapy strategies seem to be required to ensure more successful outcomes.
Amifostine↗
Death receptors and ligands in cervical carcinogenesis: an immunohistochemical study.
OBJECTIVE: Increasing imbalance between proliferation and apoptosis is important in cervical carcinogenesis. The death ligands FasL and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis by binding to their cognate cell-surface death receptors Fas or death receptor (DR) 4 and DR5. This study aims to examine if changes in death ligand and death receptor expression during different stages of cervical carcinogenesis are related to an imbalance between proliferation and apoptosis. METHODS: The immunohistochemical expression and localization of Fas/FasL and DR4/DR5/TRAIL were assessed in 11 normal cervices, 15 cervical intraepithelial neoplasia (CIN) grade I, 15 CIN II, 13 CIN III, and 25 (microinvasive) squamous cell cervical cancers. The number of apoptotic cells was determined by morphological criteria and the number of proliferating cells by counting Ki-67-positive cells. RESULTS: A marked increase in proliferation as well as apoptosis percentage was found with increasing severity of neoplasia. In normal cervix and CIN I samples, FasL, DR4, DR5, and TRAIL staining was mainly observed in the basal/parabasal layer, whereas Fas staining was localized in the superficial, more differentiated epithelial layer. Frequency of Fas-positive staining decreased with increasing severity of CIN. In contrast, homogeneous FasL, DR4, DR5, and TRAIL expression throughout the lesions was more frequently observed in CIN III and cervical cancer. FasL, DR4, DR5, and TRAIL staining patterns were correlated, although TRAIL expression was more intense in low-grade lesions. No association was found between death receptor or ligand expression with the percentage of apoptosis or proliferation. CONCLUSION: The loss of Fas and the deregulation of FasL, DR4, DR5, and TRAIL in the CIN-cervical cancer sequence suggest a possible functional role of these death ligands and receptors during cervical carcinogenesis. The frequent expression of DR4 and DR5 presents these receptors as promising targets for innovative therapy modalities in cervical cancer.
Apoptosis↗
A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma.
OBJECTIVE: Will amifostine (A) protect against chemotherapy-induced neuro- and myelotoxicity. PATIENTS AND METHODS: Ninety ovarian cancer patients were randomized to receive standard paclitaxel + carboplatin without (PC) or preceded by amifostine 740 mg/m(2) (PC + A). RESULTS: The mean baseline values of hemoglobin, leukocyte, and platelets were slightly lower in the amifostine group, but the mean percentual decrease of these parameters after each treatment cycle showed no difference between both arms. Symptoms of neurotoxicity remained absent in 40% PC vs. 49% PC + A cycles; sensory neurotoxicity grade I occurred in 45% vs. 48% and grade II in 12% PC vs. 2% of PC + A cycles (overall P < 0.001). Nausea grade II was reported in 2% vs. 6% (P = 0.007) and vomiting grade II in 1% of PC vs. 8% PC + A cycles (P < 0.001). Amifostine was temporarily interrupted in five patients due to hypotension, but no dose reductions were indicated. Quality of life questionnaires showed no difference in neurotoxicity scores between both study arms at treatment completion. The median progression-free survival was 16 vs. 22 months (n.s.) for PC and PC + A patients. In a pooled analysis of four randomized studies, amifostine diminished the risk of developing neurotoxicity grade II-III (Odds Ratio 0.3, 95% confidence interval 0.15-0.63, P < 0.05), but had no effect on the risk for bone marrow toxicity. CONCLUSION: Amifostine shows only minor but significant activity in diminishing neurotoxicity without preventing paclitaxel + carboplatin-induced bone marrow toxicity.
Adult↗
Susceptibility to air pollution in elderly males and females.
It is important to know which individuals in the general population have increased susceptibility to air pollution. The aim of this study was to identify susceptible subgroups by studying airways hyperresponsiveness (AHR), high total immunoglobulin (Ig)E and sex. Diary data on lower and upper respiratory symptoms (LRS and URS, respectively), cough, and morning and evening peak expiratory flow (PEF) were collected in 327 elderly patients (50-70 yrs) for a period of 3 months. Acute effects of particulate matter with a diameter <10 microm, black smoke, sulphur dioxide and nitrogen dioxide on symptoms and PEF were estimated using logistic regression. In total, 48 (14.7%) subjects had AHR+/IgE+, 112 (34.3%) had AHR-/IgE+, 42 (12.8%) had AHR+/IgE- and 125 (38.2%) had AHR-/IgE-. In the AHR+/IgE+ group, each 10 microg x m(-3) increase in air pollution was associated with a significant increase in prevalence of URS (odds ratio ranging 1.03-1.19), cough (1.03-1.08) and fall in morning PEF (1.04-1.26). In the AHR+/IgE+ group, males responded predominantly with symptoms and females with a fall in morning PEF. In conclusion, elderly individuals with both airway hyperresponsiveness and high total immunoglobulin E are especially susceptible to air pollution. Identifying susceptible subgroups might enlarge insight into the actual mechanisms by which air pollution evokes specific modes of response.
Age Factors↗
Life expectancy in differentiated thyroid cancer: a novel approach to survival analysis.
In differentiated thyroid carcinoma 10-year survival rates amount to 80-95%. Because age at diagnosis varies widely, these survival rates strongly depend on age at presentation. The aim of the present study was to analyse the attributable risk factors, including therapy per se, on survival in thyroid cancer after proper adjustment for the baseline mortality rate in the general population and to elucidate the adverse treatment effects on survival. Initial treatment in 504 patients consisted of thyroidectomy and 131I ablation. High-dose 131I was administered for residual disease. Patients in complete remission underwent an annual physical examination and thyroglobulin measurements during TSH suppression. Survival time was studied after transformation to standardised survival time to adjust for the baseline mortality rate in the general population. Median follow-up since diagnosis was 9 years. The 10-year overall survival was 83% and disease-specific survival 91%. After initial treatment, persistent disease occurred in 75 patients (15%). In univariate analysis, T4, N1, M1 status and Hürthle cell type were prognostic for persistent and recurrent disease. Age was not prognostic for recurrent disease in multivariate analysis. The standardised survival time was not altered in disease-free patients. However, patients with persistent disease had a median standardised survival time of only 0.60 (95% confidence interval 0.47;0.72), ranging from 0 to above 1, independent of initial tumour status or age. The cumulative proportion of persistent disease was at least 20% of the whole group. Disease-free patients after thyroid carcinoma have a normal residual life span. In contrast, in cases of persistent disease the life expectancy ranges widely with its median being reduced to 60%. Overall, treatment including radioiodine is safe but unsuccessful in 20% of the patients. Age is not a disease-specific risk factor and should not be used as an independent factor in treatment algorithms.
Adult↗
Development of an optimal sampling strategy for clinical pharmacokinetic studies of the novel anthracycline disaccharide analogue MEN-10755.
AIM: MEN-10755 is a novel anthracycline analogue that has shown an improved therapeutic efficacy over doxorubicin in animal models, especially in gynaecological and lung cancers and is currently under clinical development for the treatment of solid tumours. The aim of the project was to develop an optimal sampling strategy for MEN-10755 to provide an efficient basis for future pharmacokinetic/pharmacodynamic investigations. METHODS: Data from 24 patients who participated in a phase I clinical pharmacokinetic study of MEN-10755 administered as a short i.v. infusion were included. Individual pharmacokinetic values were calculated by fitting the plasma concentration data to a two-compartment model using nonlinear least-squared regression (KINFIT, Ed 3.5). Population pharmacokinetic analysis was carried out using (a) the traditional standard two-stage method (STS) based on all data (KINFIT-ALL), (b) the iterative two-stage Bayesian (IT(2)B) population modelling algorithm (KINPOP), and (c) the STS method using KINFIT and using four optimally timed plasma concentrations (KINFIT-OSS4). Determinant (D) optimal sampling strategy (OSS) was used to evaluate the four most information-rich sampling times. The pharmacokinetic parameters V(c) (l), k(el) (h(-1)), k(12) (h(-1)) and k(21) (h(-1)) calculated using KINPOP served as a model for calculation of four D-optimal sampling times. D-optimal sampling data sets were analysed using KINFIT-OSS4 and compared with the population model obtained by the traditional standard two-stage approach for all data sets (KINFIT-ALL). RESULTS: The optimal sampling times were: the end of the infusion, and 1.5 h, 3.8 h and 24 h after the start of the infusion. The four-point D-optimal sampling design determined in this study gave individual parameter estimates close to the basic standard estimates using the full data set. CONCLUSION: Because accurate estimates of pharmacokinetic parameters were achieved, the four-point D-optimal sampling design may be very useful in future studies with MEN-10755.
Algorithms↗
Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma.
BACKGROUND: Asthma is a genetically complex disease characterized by respiratory symptoms, intermittent airway obstruction and airway hyper-responsiveness due to airway inflammation and remodelling. The ADAM33 gene is associated with asthma and airway hyper-responsiveness and is postulated as a gene for airway remodelling. OBJECTIVE: To investigate whether polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in patients with asthma. METHODS: In a cohort of 200 asthma patients followed over 20 years, eight single nucleotide polymorphisms of the ADAM33 gene were analysed to estimate their effect on annual FEV(1) decline. RESULTS: The rare allele of the S_2 polymorphism was significantly associated with excess decline in FEV(1) (P<0.05). CONCLUSION: These findings suggest that a variant in ADAM33 is not only important in the development of asthma but also in disease progression, possibly related to enhanced airway remodelling.
ADAM Proteins↗
Childhood factors associated with asthma remission after 30 year follow up.
BACKGROUND: Factors contributing to either "complete" or "clinical" remission of asthma are important to know since there is no cure for the disease. METHODS: A cohort of 119 allergic asthmatic children was examined three times with a mean follow up of 30 years. They were aged 5-14 years at visit 1 (1966-9), 21-33 years at visit 2 (1983-6), and 32-42 years at visit 3 (1995-6). Complete remission of asthma at visit 3 was defined as no asthma symptoms, no use of inhaled corticosteroids, normal lung function (FEV1 >90% predicted), and no bronchial hyperresponsiveness (PC10 >16 mg/ml). Clinical remission was defined as no asthma symptoms and no use of inhaled corticosteroids. RESULTS: 22% of the group was in complete remission of asthma at visit 3 and a further 30% was in clinical remission (total 52%); 57% of subjects in clinical remission had bronchial hyperresponsiveness and/or a low lung function. Logistic regression analyses showed that a higher FEV1 in childhood and more improvement in FEV1 from age 5-14 to 21-33 were associated with both complete and clinical asthma remission at age 32-42. CONCLUSIONS: Complete remission of asthma was present in a small subset of asthmatics while half the subjects showed clinical remission. Both complete and clinical remission were associated with a higher lung function level in childhood and a higher subsequent increase in FEV1. These results support the view that defining remission only on the basis of symptoms and medication use will overlook subjects with subclinical active disease and possibly associated airway remodelling.
Adolescent↗
First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial.
The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin-gemcitabine (CG) or epirubicin-gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n=240) were randomised to receive gemcitabine 1125 mg x m(-2) (days 1 and 8) plus either cisplatin 80 mg x m(-2) (day 2) or epirubicin 100 mg x m(-2) (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status <or=2. QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 questionnaires. There were no significant differences in median progression-free survival (CG 26 weeks, EG 23 weeks), median overall survival (CG 43 weeks, EG 36 weeks), or tumour response rates (CG 46%, EG 36%). Toxicity was mainly haematologic. In the EG arm granulocytopenia occurred more frequently, leading to more febrile neutropenia. Also, elevation of serum transaminases, mucositis, fever, and decline in LVEF were more common in the EG arm. In the CG arm, more patients experienced elevated serum creatinine levels, sensory neuropathy, nausea, and vomiting. Global QOL was not different in both arms. Progression-free survival, overall survival, response rate, and QOL were not different between both arms; however, overall toxicity was more severe in the EG arm.
Adenocarcinoma↗
Detection of telomerase, its components, and human papillomavirus in cervical scrapings as a tool for triage in women with cervical dysplasia.
AIM: To examine whether the detection of either telomerase and its components or high risk human papillomavirus (HPV) are of value in predicting the presence of cervical intraepithelial neoplasia (CIN) grade II/III in women referred because of cervical cytology reports showing at most moderate dyskaryosis. METHODS: Cervical scrapings of 50 women referred with cytological borderline, mild, or moderate dyskaryosis were analysed. Telomerase activity was assessed by a commercially available telomere repeat amplification protocol assay and its components human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) were assessed by reverse transcriptase polymerase chain reaction (PCR). HPV was detected by GP5+/6+ PCR enzyme immunosassay. Histological findings on colposcopy guided biopsies or excised cervical tissue were regarded as the final pathological diagnosis. The sensitivity and specificity for detecting CIN II/III were calculated. RESULTS: Twenty eight women were diagnosed with CIN II/III. Telomerase activity was detected in none, hTR in 88%, hTERT in 23%, and high risk HPV was detected in 79% of these women. As a diagnostic test none of the described analyses combined a sensitivity of at least 90% with a specificity >or= 90%. Despite the small numbers, calculation of the 95% confidence intervals excluded a combined sensitivity and specificity of at least 90% for all of the evaluated parameters. CONCLUSIONS: Neither detection of telomerase or its components, nor detection of high risk HPV seem suitable for the triage of women with borderline, mild, and moderate cytological dyskaryosis.
Adult↗
Effect of intravenous hydrocortisone on nocturnal airflow limitation in childhood asthma.
Low endogenous cortisol levels appear to contribute to the pathophysiology of nocturnal asthma. Lower cortisol levels are associated with lower forced expiratory volume in one second (FEV1) levels in children with asthma. The aim of the present study was to identify whether substitution of low serum cortisol with intravenous hydrocortisone decreases 24-h FEV1 variation and/or indirect measures of airway inflammation. Hydrocortisone was given over 24 h in a double-blind randomised crossover design to 26 subjects. FEV1 was measured every 4 h during 24 h; blood eosinophils and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured at 04:00 h and 16:00 h. Cortisol levels increased during the night and morning hours. FEV1 values were higher at all time points in children with nocturnal asthma (n=10; 24-h FEV1 variation > or = 15%) which was significant at 08:00 h, unlike in the non-nocturnal asthma (NA-) group (n=16). Numbers of eosinophils (10(9) x L(-1)) at 04:00 h decreased in the asthma group (median 0.61 (range 0.05-1.42) versus 0.52 (0.05-1.79)). Provocative dose causing a 20% fall in FEV1 (PD20) methacholine did not change, whereas PD20 AMP improved only at 16:00 h in the NA- group (72.0 (0.13-144.0) versus 144.0 (2.25-144.0) mg x mL(-1)). These results show that substitution of lower endogenous 24-h values of cortisol contribute to higher forced expiratory volume in one second values and a decrease of blood eosinophils as an inflammatory marker in more severe airway obstruction.
Adolescent↗
Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin.
BACKGROUND: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative (131)I diagnostic whole-body scan (WBS) is advocated. However, the therapeutic benefit of this "blind" treatment is not clear. OBJECTIVE: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic (131)I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose (131)I. DESIGN: Retrospective single-center study. METHODS: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi (131)I. Median follow-up from this treatment until the end of observation was 4.2 Years (range 0.5-13.5 Years). RESULTS: The post-treatment WBS revealed (131)I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive post-treatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P=0.001). CONCLUSIONS: High-dose iodine treatment in diagnostically negative patients who have a negative post-treatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.
Adenoma, Oxyphilic↗
Clinical and immunologic factors associated with the presence or absence of airways hyper-responsiveness in childhood asthma.
BACKGROUND: During the baseline period of a clinical trial comparing different dosage schedules of inhaled steroids, asthmatic children (aged 6-10 years) were expected to meet the inclusion criterion of airways hyper-responsiveness (PD(20) methacholine < 80 micro g) after withdrawal of inhaled corticosteroids for 2-8 weeks. However, many children failed to do so. OBJECTIVE: It has been shown that young wheezing children may outgrow their symptoms. We investigated if differences between children with and without airways hyper-responsiveness after withdrawal of inhaled corticosteroids were compatible with differences between transient and persistent wheezers found in other studies. METHODS: Seventy-eight children entered the study, of which 41 developed airways hyper- responsiveness after withdrawal of inhaled corticosteroids, and 37 did not. These two groups of children were compared with respect to differences in demographic, clinical, and immunological features (IL-4, IL-5, IL-10, and IFN-gamma produced by Con A stimulated peripheral mononuclear cells (PBMCs) and serum IL-4, IL-5 and soluble intercellular adhesion molecule-1 (sICAM-1)). RESULTS: Hyper-responsive children had more atopic features (positive RAST, high IgE, eczema), lower levels of FEV1 and lower concentrations of sICAM-1 than non-hyper-responsive children. Apart from a borderline significantly higher IL-4 production in the hyper-responsive group, other immunologic parameters were comparable. Multivariate logistic regression analysis showed that high serum IgE, low FEV1, and low sICAM-1 levels were independently associated with the presence of airways hyper-responsiveness after stopping inhaled corticosteroids. Atopy was associated with higher concentrations of IL-4 in the hyper-responsive group. CONCLUSION: After withdrawal of inhaled corticosteroids many children previously diagnosed with asthma did not develop airways hyper-responsiveness. We conclude that hyper-responsive children share features with persistent wheezers as found in previous studies, whereas the non-hyper- responsive children may represent transient wheezers.
Animals↗
Perinatal predictors of respiratory symptoms and lung function at a young adult age.
A longitudinal cohort of 2,957 babies, born in 1975-1978, was used to investigate whether perinatal factors predict respiratory morbidity at a young adult age. In 1997, the presence of asthmatic (wheeze, nocturnal dyspnoea) and bronchitic (cough, phlegm, dyspnoea grade 3) symptoms and the level of lung function was determined in this cohort. The independent association between smoking during pregnancy, being first-born, birth weight and respiratory symptoms and lung function at young adult age was investigated using multiple regression models, taking other potential risk factors into account. Of 1,568 responders, 608 (39%, aged 18-22 yrs) had at least one respiratory symptom. The young adults who had a mother that smoked during pregnancy had a significantly lower level of lung function than their nonintra-uterine exposed peers (regression coefficient (B) (standard error): peak expiratory flow (PEF) -0.257 (0.131) L x s(-1); forced expiratory flow when 25% of the forced vital capacity has been exhaled (FEF25) -0.290 (0.129) L x s(-1)), although they were not at increased risk of having respiratory symptoms. Young adults who were first-born had better levels of lung function (B (SE): forced expiratory volume in one second (FEV1) 0.090 (0.042) L) and were less likely to have asthmatic symptoms (odds ratio (95%, confidence interval): 0.58 (0.35-0.95)) than those not first-born. Low birth weight (FEV1 -0.013 (0.004) L for a reduction of 100 g) was also predictive of reduced achieved levels of lung function at young adult age, independent of other potential risk factors, e.g. current smoking habits or familial predisposition. This study adds to the knowledge of the role of perinatal factors, such as smoking during pregnancy, as important predictors of respiratory morbidity.
Adolescent↗
Eosinophilic granulocytes and interleukin-6 level in bronchoalveolar lavage fluid are associated with the development of obliterative bronchiolitis after lung transplantation.
In a prospective cohort study, we assessed whether changes in total cell counts and differentiation and interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) concentrations in bronchoalveolar lavage fluid (BALF) are associated with a higher risk to develop obliterative bronchiolitis (OB). We investigated 60 lung transplant patients (follow-up of 2 to 8 yr) with either histologic evidence of OB within 1 yr after lung transplantation (n = 19) or no pathology, good outcome (GO) for at least 24 mo and well-preserved lung function, i.e., FEV > or = 80% of baseline (n = 41). Median time between lung transplantation and the first BAL was 42 d for the GO group and 41 d for the OB group (p > 0.05). In the bronchial fraction, median total cell counts (0.06 x 10(3)/ml versus 0.04 x 10(3)/ml), lymphocyte (9 x 10(3)/ml versus 2 x 10(3)/ml), and eosinophilic granulocyte counts (1 x 10(3)/ml versus 0) were significantly higher in the OB group than in the GO group (p < 0.05). In the alveolar fraction, this was the case for the median value of neutrophilic granulocyte counts (19 x 10(3)/ml versus 4 x 10(3)/ml), respectively. Median values of IL-6 and IL-8 concentrations in both bronchial (IL-6: 23 versus 6 pg/ml, IL-8: 744 versus 102 pg/ml) and alveolar fractions (IL-6: 13 versus 3 pg/ml, IL-8: 110 versus 30 pg/ml) of the BALF were significantly higher in the OB group than in the GO group. By means of logistic regression, we showed that higher total cell, neutrophilic granulocyte, and lymphocyte counts, the presence of eosinophilic granulocytes, and higher concentrations of IL-6 and IL-8 were significantly associated with an increased risk to develop OB. We conclude that monitoring cell counts, neutrophilic and eosinophilic granulocytes, IL-6, and IL-8 in BALF within 2 mo after lung transplantation in addition to the transbronchial lung biopsy (TBB) pathology will contribute to a better identification and management of the group of patients at risk for developing OB within a year.
Adult↗
Effects of ambient air pollution on upper and lower respiratory symptoms and peak expiratory flow in children.
BACKGROUND: Previous epidemiological studies have shown acute effects of increased amounts of ambient air pollution on the prevalence of respiratory symptoms in children with respiratory disorders. We investigated whether children with bronchial hyperresponsiveness (BHR) and relatively high serum concentrations of total IgE (>60 kU/L, the median value) are susceptible to air pollution. METHODS: We collected data from children during three winters (1992-95) in rural and urban areas of the Netherlands. Lower respiratory symptoms (wheeze, attacks of wheezing, shortness of breath), upper respiratory symptoms (sore throat, runny or blocked nose), and peak expiratory flow were recorded daily for 3 months. The acute effects of airborne particulate matter with a diameter of less than 10 microm, black smoke, sulphur dioxide, and nitrogen dioxide were estimated by logistic regression. FINDINGS: 459 (73%) of 632 children had complete data. Of these, 26% had BHR and relatively high (above median) serum total IgE, 36% had no BHR and total IgE of 60 kU/L or less, 15% had BHR and total IgE of 60 kU/L or less, and 23% had a total IgE of more than 60 kU/L but no BHR. In children with BHR and relatively high serum total IgE the prevalence of lower respiratory symptoms increased significantly by between 32% and 139% for each 100 microm/m3 increase in particulate matter, and between 16% and 131% for each 40 microm/m3 increase in black smoke, SO2, or NO2. Decrease in peak expiratory flow of more than 10% in that group was more common with increased airborne particulate matter and black smoke. There were no consistent positive or negative associations between increased air pollution and prevalence of respiratory symptoms or decrease in peak expiratory flow in the other three groups of children. INTERPRETATION: Children with BHR and relatively high concentrations of serum total IgE are susceptible to air pollution. Although our odds ratios were rather low (range 1.16-2.39) the overall effect of air pollution on public health is likely to be substantial since these odds ratios refer to large numbers of people.
Air Pollutants↗