The genetics of atopy and airway hyperresponsiveness.
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Chromosomes, Human, Pair 12↗
Biomedical subjects
D S Postma
Publications and source records attributed to D S Postma.
Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts.
The glucocorticoid budesonide and the long-acting beta2-adrenoceptor agonist formoterol are used in asthma therapy for their anti-inflammatory and bronchodilating effects, respectively. Since expression of adhesion molecules on resident cells in the lung plays an important role in asthmatic inflammatory responses, the effects of these drugs on the cytokine-induced intercellular adhesion molecule-1 (ICAM)-1 and vascular cell adhesion molecule-1 (VCAM)-1 expression of human lung fibroblasts were investigated. Budesonide and formoterol were added in the absence or presence of interleukin (IL)-1beta, tumour necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma) or IL-4 to human lung fibroblasts; ICAM-1 and VCAM-1 expression were measured after 8 h using a cell surface enzyme linked immunosorbent assay (ELISA). It was found that both budesonide and formoterol significantly inhibited (p<0.05) the increased expression of ICAM-1 and VCAM-1 after stimulation with IL-1beta (maximal inhibition (median (25-75% percentiles) 50 (48-52) and 61% (42-69), respectively, with budesonide and 55 (50-73) and 86% (64-94), respectively, with formoterol (10(-7) M)), TNF-alpha (maximal inhibition 49 (46-57) and 57% (44-68), respectively, with budesonide and 44 (40-75) and 62% (52-83) respectively, with formoterol), IFN-gamma (maximal inhibition 64% (41-67) with budesonide and 39% (29-49) with formoterol for ICAM-1) and IL-4 (maximal inhibition 82% (69-92) with budesonide and 43% (33-67) with formoterol for VCAM-1) in a dose-dependent manner. The results show that budesonide, as well as formoterol, in probably clinically relevant concentrations inhibits cytokine-induced adhesion molecule expression on human lung fibroblasts from a concentration of 10(-9) M. This inhibitory effect on resident cells may have implications for the infiltration of inflammatory cells into pulmonary tissue during therapy with these drugs in asthma.
Adrenergic beta-Agonists↗
Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD.
It is unclear how cellular and soluble inflammatory markers in induced sputum relate to markers in lavage fluid and biopsies in chronic obstructive pulmonary disease (COPD). This was investigated and also the possible differences between subjects with COPD and healthy controls assessed. Eighteen nonatopic subjects with COPD and 11 healthy controls were studied. Sputum was induced by inhalation of hypertonic saline. The airways were lavaged, using the first 50 mL for bronchial wash (BW) and the subsequent 150 mL for bronchoalveolar lavage (BAL), and biopsies were taken from subsegmental carinae. Neutrophils were the predominant cell type in sputum in COPD (median 77.3%) but not in BW (5.5%) and BAL fluid (1.7%). Differential cell counts in sputum did not correlate with the counts in BW or BAL fluid or biopsies, whereas sputum eosinophil cationic protein (ECP) levels correlated with BW fluid ECP levels (p=0.66, p=0.007) and sputum interleukin-8 (IL-8) concentration with BAL fluid IL-8 concentration (p= 0.52, p=0.026). Subjects with COPD had a higher percentage of sputum neutrophils and eosinophils and higher concentrations of ECP and IL-8 than healthy controls. The higher percentages of eosinophils and concentrations of ECP were also seen in BW and BAL fluid. Finally, higher numbers of macrophages and eosinophils were found in biopsies. In conclusion, induced sputum is derived from a different compartment from BW and BAL fluid and biopsies. Induced sputum may be useful for studying the contribution of luminal neutrophils and eosinophils in chronic obstructive pulmonary disease.
Adult↗
Genetics of allergic disease.
Atopy can express itself as asthma, rhinitis and eczema. The presence of atopy can be assessed by increased levels of total serum IgE and specific IgE to common allergens, skin test positivity and increased numbers of peripheral blood eosinophils. Genetic studies indicate that multiple genes are involved in the pathogenesis of atopy and that different genes regulate the presence of increased levels of serum total IgE and specific IgE. Linkage of these traits to chromosomal regions likely to contain atopic susceptibility genes has been replicated in several studies. Genome-wide screens have identified several new chromosomal locations that are likely to contain atopic genes. These regions also contain candidate genes. Moreover, the available literature suggests that multiple, yet different genes may be involved in the translation of atopy to a distinct clinical phenotype. We anticipate that understanding of the genetic basis of atopy will lead to new therapeutic interventions and early diagnosis.
Allergens↗
Bronchiolitis obliterans syndrome and additional costs of lung transplantation.
STUDY OBJECTIVES: The influence of bronchiolitis obliterans syndrome (BOS) on costs after lung transplantation was investigated by comparing the costs of patients with and without this condition. DESIGN: Follow-up costs were prospectively investigated in a medical technology assessment of the Dutch Lung Transplant Program, in relation to the development of the BOS. First, average follow-up costs per week per patient were compared between patients who did or did not develop BOS. Second, in the BOS group, these costs were compared before and after the onset of BOS. SETTING: Dutch Lung Transplant Program, University Hospital of Groningen. RESULTS: Data on 53 patients (37 patients without BOS and 16 with BOS) who underwent transplantation between November 1990 and April 1995 were available. The average follow-up time of these 53 patients was 1.5 years. The follow-up costs amounted to an average (in Dutch guilders [Dfl]) of 1,774/wk for non-BOS patients, compared to 3,072/wk for BOS patients (+ 73%; p = 0.002; one Dfl = 50 cents US currency). This difference in costs was largely accounted for by an increase in used health-care resources, in particular hospitalization and medication. For the BOS patients, the average costs per week before and after the onset of BOS were 1,941 Dfl and 2,422 Dfl, respectively. CONCLUSION: BOS is associated with substantial extra costs. These findings reemphasize the need to focus efforts on prevention of BOS to enhance the cost-effectiveness of lung transplantation.
Adult↗
Disease associated time consumption in early rheumatoid arthritis.
OBJECTIVE: To quantify the disease associated time consumption of normal activities of daily living and of treatment and monitoring activities in a cohort of patients with early rheumatoid arthritis (RA) with followup of at least 6 years. Comparison was made with a group of patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: A prospective and retrospective inventory was carried out, by interview and record investigation, of RA related and RA unrelated items covering the period from the start of the disease. Interviews were also performed in a group of patients with asthma and COPD. RESULTS: For patients with RA there was a mean disease associated time consumption of at least 1.9 h/day during the first 6 years of the disease. The time consumption was mainly due to extra time needed for activities of daily living and daily disease related activities. Patients with the greatest progression of radiographic damage, with the most severe disability, and with the greatest cumulative disease activity had the greatest time consumption. For patients with asthma and COPD the consumption of time was comparable. CONCLUSION: RA is a time consuming disease. Recognition of the disease associated time consumption will have implications for work (dis)ability assessments in patients with chronic diseases such as RA.
Adolescent↗
Computerized medical record in a private neurotology practice.
OBJECTIVE: To develop a computerized medical record for a private neurotology practice using a relational database with templates. BACKGROUND: Computers have been used in the medicine many years for billing, scheduling appointments, and word processing. Neurotology represents a relatively narrow field of medicine, which is particularly suited to a computerized record. A computerized medical record should allow for better data storage and retrieval as well as better documentation of the patient care given. METHODS: Using a commercially available, record-keeping software in a local area computer network. templates were developed for several common neurotologic problems. A template for a neurotologic examination was also developed. These were adapted from templates developed by a group otolaryngology practice in a neighboring city. Data entry templates for vestibular and audiologic tests were also developed. Implementation of the computerized record was accomplished in phases, allowing elimination of the paper record. RESULTS: A fully computerized medical record has been developed and maintained in a private neurotology practice over the past year. Patient response to the computerized record system has been favorable. Office personnel have adapted well to a paperless record, and referring physicians have welcomed the documents generated by the computer. CONCLUSION: Computerizing the medical records of a neurotology practice is possible and allows for improved documentation, ongoing assessment of treatment results, and improved efficiency among office staff.
Humans↗
[Survival and impact of bronchiolitis obliterans syndrome after lung transplantation at the Academic Hospital Groningen, 1990/'98].
OBJECTIVE: To describe the results of the lung transplantation programme in Groningen in relation to the bronchiolitis obliterans syndrome (BOS), in the first 118 consecutive patients. DESIGN: Retrospective. METHOD: Data were collected on the 118 patients subjected to lung transplantation in November 1990 to June 1998 in the University Hospital Groningen, the Netherlands, regarding the prevalence of chronic transplant dysfunction (BOS) and survival. RESULTS: 117 lung transplantations (95 bilateral lung transplantations including 2 retransplants, and 22 single lung transplantations) and 1 heart-lung transplantation had been performed. The patients were 70 males and 48 females with a mean age of 42 years (range: 9-64). The mean (SD) survival at 1, 2, 3 and 5 years post transplantation was 83% (3), 70% (4), 66% (5) and 61% (5) respectively. The median survival amounted to 2447 days. The mean (SD) prevalence of BOS at respectively 1, 2, 3 and 5 years post transplantation was 32% (5), 36% (5), 44% (5) en 54% (6). After a diagnosis of BOS stage I the median survival was 649 days. CONCLUSION: The survival of the lung transplant programme of the University Hospital Groningen is considered to compare favourably with other centres. The prevalence of BOS is considerable, and comparable with the prevalence of BOS reported by other programmes. BOS is associated with a decreased life expectancy.
Academic Medical Centers↗
Eosinophilia and positive skin tests predict cardiovascular mortality in a general population sample followed for 30 years.
The authors investigated whether two objective allergy markers, peripheral blood eosinophilia and skin tests for common aeroallergens, were associated with cardiovascular death. Of 5,382 subjects in the Vlagtwedde-Vlaardingen Study (the Netherlands) with data on allergy markers in 1965-1972, 507 subjects died from cardiovascular disease during 30 years of follow-up. Subjects with eosinophilia had an increased risk of cardiovascular death (relative risk (RR) = 1.7; 95% confidence interval (CI): 1.4, 2.2), including ischemic heart disease death (RR = 1.6; 95% CI: 1.2, 2.2) and cerebrovascular death (RR = 2.3; 95% CI: 1.4, 3.8), independent of major risk factors. This association was limited to subjects with a percentage of the predicted forced expiratory volume in 1 second (FEV1 % predicted) of <100%. Positive skin tests were associated with a significantly reduced cardiovascular mortality in subjects with normal lung function and weight who did not smoke (RR = 0.15; 95% CI: 0.05, 0.46). Conversely, when subjects with positive skin tests had a body mass index of > or =25 kg/m2, had an FEV1 % predicted of <80%, or smoked, they had an increased risk for cardiovascular mortality. These results were not restricted to asthmatics. Our data suggest a possible link between eosinophilia and positive skin tests and cardiovascular mortality, especially in combination with other risk factors associated with its mortality.
Asthma↗
[Nitric oxide and asthma].
Nitric oxide (NO) is a universal signalling molecule, involved in many physiological and pathophysiological processes, including asthmatic airway inflammation. Nitric oxide synthases (NOS) are newly identified enzyme systems active in airway epithelial cells, macrophages, neutrophils, mast cells, non-adrenergic non-cholinergic neurons, smooth muscle cells and endothelial cells. Two functional classes of NOS can be identified: the inducible form temporarily leading to large amounts of NO, and the constitutive form continuously leading to small amounts of NO. Large amounts of NO contribute to airway inflammation and killing of micro-organism, whereas small amounts of NO lead to smooth muscle relaxation. Asthmatic airway obstruction is induced by various bronchoconstricting factors (like allergens, pharmacological spasmogens, physical stimuli, infectious disease state) and is inhibited by NO. The development of specific inhibitors for the inducible form of NOS might open up a new era of antiasthmatic drugs.
Asthma↗
Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.
BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. RESULTS: Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups. CONCLUSIONS: In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.
Administration, Inhalation↗
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↗
[The place of long-acting beta 2 adrenergic agonists in the treatment of asthma and chronic obstructive lung disease (COPD)].
At the introduction of long-acting beta 2-adrenergic agonists physicians were reluctant to prescribe them for prolonged use, as they might increase mortality due to asthma. In national and international guidelines beta 2-agonists are reserved for moderate to severe asthma. Well-controlled studies have shown, however, that long-acting beta 2-agonists are effective bronchodilators, able to improve symptoms and lung function and to decrease the number of exacerbations. As long as these bronchodilators are combined with inhaled steroids, they may be beneficial in early stages of asthma of low severity. In the treatment of COPD the place of long-acting beta 2-agonists is not clear yet. First experiences show, however, that these drugs deserve a place in the treatment of COPD, notably against nocturnal dyspnoea. Use of long-acting beta 2-agonists is often associated with clear improvement in quality of life and walking distance of COPD patients, which does not appear to be accompanied by distinct improvement in pulmonary function (FEV1), however.
Adrenal Cortex Hormones↗
Interferon-gamma and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts.
The expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and more specifically vascular adhesion molecule-1 (VCAM-1) on lung fibroblasts may be important for migration of inflammatory cells through the submucosa to the airway lumen in the asthmatic inflammatory response. This study aimed to assess which cytokines are regulating ICAM-1 and VCAM-1 expression on human lung fibroblasts. For this purpose, confluent fibroblast cultures (derived from lung tissue from a nonasthmatic donor) were stimulated for 4 h with interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha, interferon (IFN)gamma, IL-4, IL-5 or transforming growth factor (TGF)beta. IL-1beta (optimal concentration (OC) 1 U x mL(-1)) and TNFalpha (OC 100 U x mL(-1)) both increased ICAM-1 and VCAM-1 expression. IFNgamma (OC 2 U x mL(-1)) increased only ICAM-1 expression and IL-4 (OC 5 ng x mL(-1)) increased only VCAM-1 expression, whereas IL-5 (20 ng x mL(-1)) and TGFbeta (10 ng x mL(-1)) did not influence ICAM-1 or VCAM-1 expression. ICAM-1 expression reached a plateau at 8-12 h after cytokine stimulation and remained constant for at least 24 h. VCAM-1 showed a transient increased expression within 24 h after IL-1beta and TNFalpha stimulation. In contrast, VCAM-1 expression did not decrease after maximal expression at 4 h upon IL-4 stimulation. It is concluded that the Helper-1T-cell, type cytokine interferon gamma and the Helper-2 T-cell type cytokine interleukin-4 differentially regulate intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on human lung fibroblasts. The proinflammatory cytokines interleukin-1beta and tumour necrosis factor alpha increase both intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, without differential regulation of the expression of these adhesion molecules.
Cell Movement↗
Genetics of allergy and bronchial hyperresponsiveness.
Allergy and asthma are closely related complex diseases caused by a combination of both genetic and environmental influences. Two common genetic approaches, candidate gene studies and genome-wide screens, have been used to localize and evaluate potential genetic factors that confer susceptibility or modify the phenotype of these diseases. Four genome screens suggest multiple chromosomal locations likely to contain asthma and allergy genes and many potential candidate genes exist in these regions. These screens were performed in six different populations and identified many common susceptibility regions as well as novel regions for each population. Ideally, these genes may point towards key biological pathways that will eventually serve as targets for therapeutic agents.
Asthma↗
Peripheral blood T lymphocytes from asthmatic patients are primed for enhanced expression of interleukin (IL)-4 and IL-5 mRNA: associations with lung function and serum IgE.
BACKGROUND: The TH2-like cytokines interleukin (IL)-4 and IL-5 play a pivotal role in airway wall inflammation in asthma and these cytokines are increased in peripheral blood and bronchoalveolar lavage fluid from asthmatic patients. It is unclear why specifically TH2-like cytokines are increased in asthmatic patients. A possible explanation may be an impaired adenylyl cyclase activity, which has been observed in peripheral blood mononuclear cells of asthmatics. OBJECTIVE: To assess interferon (IFN)-gamma, IL-4 and IL-5 mRNA expressions and their control by prostaglandin E2 (PGE2), which activates adenylyl cyclases, of peripheral T lymphocytes from patients with moderately severe asthma and healthy controls. METHODS: Peripheral blood T lymphocytes from asthmatics and healthy controls were isolated and stimulated with antibodies against CD3 plus CD28 in the absence and presence of increasing concentrations of PGE2. IFN-gamma, IL-4 and IL-5 mRNA levels were detected by reverse transcription-polymerase chain reaction. RESULTS: In contrast to IFN-gamma mRNA, IL-4 (P = 0.03, n = 8) and IL-5 (P < 0. 05, n = 5) mRNAs in the asthma group were significantly higher than in controls (n = 4). In addition, IL-5 showed a significant inverse correlation with forced expiratory volume (FEV1) (P < 0.04, n = 5), whereas IL-4 positively correlated with PC20adenosine-monophosphate (AMP) (P < 0.02, n = 8). Accumulation of mRNA for IFN-gamma, IL-4 and IL-5 mRNA were significantly diminished by 10-5 m PGE2 in both asthmatics and controls. In contrast, 10-6 m PGE2 significantly down-regulated IFN-gamma and IL-4 mRNAs (P < 0.05 for both IFN-gamma and IL-4, n = 4) in the control group, whereas this was not observed for IL-4 mRNA in the asthma group (n = 7). CONCLUSIONS: Activated peripheral blood T lymphocytes from asthma patients display higher levels of IL-4 and IL-5 mRNA in vitro, which may be due to a diminished activity of adenylyl cyclase. A new observation is that higher IL-4 mRNA levels are associated with less severe AMP responsiveness, which might be due to a negative feedback loop of IL-4 production by mast cells.
Adult↗
Allergen challenge primes for IL-5 mRNA production and abrogates beta-adrenergic function in peripheral blood T lymphocytes from asthmatics.
BACKGROUND: In previous studies, we have found a dysfunctional adenylyl cyclase (AC) system in patients with asthma after allergen provocation, which resulted in a 40-50% decreased generation of intracellular cAMP. In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN-gamma (TH1-like cytokine) and IL-5 (TH2-like cytokine) are differentially regulated by the AC system. Therefore, we postulate that an increased IL-5/IFN-gamma ratio as observed in asthmatics might be due to a dysfunctional AC system. OBJECTIVE: To assess whether a dysfunctional AC system as observed in asthmatics after allergen provocation, is responsible for an increased IL-5/IFN-gamma cytokine ratio. METHODS: Peripheral blood T lymphocytes of seven asthma patients were stimulated with anti-CD3 plus anti-CD28 MoAbs in the absence and presence of isoproterenol (ISO) and prostaglandin E2 (PGE2) to activate the AC system. Before, 3 h and 24 h after allergen provocation, IFN-gamma and IL-5 mRNAs were detected by semiquantitative RT-PCR. RESULTS: Before allergen provocation, ISO (10-5 mol/L) significantly downregulated IFN-gamma mRNA (P < 0.03, n = 6), and showed a trend to upregulate IL-5 mRNA (P = 0.138, n = 5). Three and 24 h after allergen provocation, ISO was not longer able to modulate IFN-gamma and IL-5. In contrast with the observations with ISO, PGE2 still dose-dependently inhibited IFN-gamma mRNA, both before, 3 h and 24 h after allergen provocation (n = 7). IL-5 mRNA, but not IFN-gamma mRNA, was significantly upregulated in anti-CD3 plus anti-CD28-activated T cells (P < 0.05, n = 5) 24 h after allergen provocation, compared with before allergen provocation. CONCLUSION: Twenty-four hours after allergen provocation, a significant reduction of beta-adrenergic control on IFN-gamma and IL-5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selective priming of IL-5 mRNA production.
Adenylyl Cyclases↗
Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5'-monophosphate-induced bronchoconstriction in patients with COPD.
BACKGROUND: Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP. OBJECTIVE: To investigate the mechanism of AMP-induced bronchoconstriction in COPD. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60+/-7 years, FEV1 61+/-12% of predicted and FEV1/VC 51+/-8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 microg of inhaled ipratropium bromide, or placebo. RESULTS: GM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P<0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P<0.0001). CONCLUSION: These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.
Adenosine Monophosphate↗