Search PubMed⌕ Search

Biomedical subjects

D S Postma

Publications and source records attributed to D S Postma.

At least 253 records · Page 14Linked to original sources
PubMed1994

Clinical evaluation of lymphocyte sub-populations and oxygen radical production in sarcoidosis and idiopathic pulmonary fibrosis.

The purpose of this study was to investigate the relationship between bronchoalveolar lavage (BAL)-derived parameters of interstitial lung disease and clinical and lung function parameters in 34 patients with sarcoidosis and 23 patients with idiopathic pulmonary fibrosis (IPF). BAL findings of healthy individuals served as controls. Cell content and differentiation of BAL fluid were determined. Oxygen radical (O2-) production of BAL cells and of blood polymorphonuclear (PMN) cells was measured. Phenotypes of lung and blood lymphocytes were determined by immunoperoxidase staining. In addition, lung function was assessed, chest X-rays were made and serum ACE was measured. Lymphocyte alveolitis in sarcoidosis was associated with increased alveolar macrophage (AM) O2- production (P < 0.025 vs. sarcoidosis with normal lymphocyte counts). Patients with extrapulmonary sarcoidosis had higher CD4/CD8 ratios in BAL (P < 0.025) and shorter disease duration (P < 0.01) than those with strictly pulmonary sarcoidosis. Disease duration in sarcoidosis correlated inversely with the number of BAL cells (r = -0.38, P < 0.05), the relative and absolute number of lymphocytes in BAL fluid (r = -0.34, P < 0.05 and r = -0.44, P < 0.01, respectively) and the percentage of CD4-positive cells and the CD4/CD8 ratio (r = -0.43, P < 0.05 and r = -0.48, P < 0.025, respectively). Although significant increases in O2- production by BAL cells were observed in both IPF and sarcoidosis, only in sarcoidosis was a higher AM O2- production associated with a significantly lower total lung capacity (r = -0.67, P < 0.005) and pulmonary diffusing capacity TLCO (r = -0.50, P < 0.05). In conclusion, our findings show that lung lymphocyte phenotypes differ among patients with pulmonary and extrapulmonary sarcoidosis and that O2- production is upregulated in active sarcoidosis. In addition, our findings suggest that different relationships between BAL data and lung function in patients with sarcoidosis and IPF may be explained by differences in disease duration. In IPF, disease duration is likely to be underestimated because of its insidious onset. In sarcoidosis, the presence of extrapulmonary symptoms, helpful to establish an early diagnosis, is associated with significant BAL lymphocytosis.

Adult↗
PubMed1994

Effects of nedocromil sodium in the treatment of non-allergic subjects with chronic obstructive pulmonary disease.

BACKGROUND: Nedocromil sodium, a nonsteroidal anti-inflammatory drug, is effective in the treatment of asthma. Its efficacy in the treatment of chronic obstructive pulmonary disease (COPD) has not been investigated. METHODS: Fifty four non-allergic patients with COPD were randomised to 10 weeks of treatment with placebo or nedocromil sodium (4 x 8 mg/day) in a double blind study. RESULTS: Nedocromil sodium treatment had no effect on airway responsiveness to histamine, methacholine, and adenosine-5'-monophosphate, pulmonary function, and symptom scores. Both patients and clinicians favoured treatment with nedocromil sodium, however, and the number of dropouts (because of exacerbations) was fewer during treatment with the drug. CONCLUSIONS: Longer trials will be necessary to assess if nedocromil sodium can reduce the frequency of exacerbations and the decrease in pulmonary function, eventually leading to a better quality of life in patients with COPD.

Double-Blind Method↗
PubMed1994

Influence of treatment on peak expiratory flow and its relation to airway hyperresponsiveness and symptoms. The Dutch CNSLD Study Group.

BACKGROUND: Despite effective treatments, the morbidity and mortality of obstructive airways disease (asthma and COPD) remains high. Home monitoring of peak expiratory flow (PEF) is increasingly being advocated as an aid to better management of obstructive airways disease. The few available studies describing effects of treatment on the level and variation of PEF have involved relatively small numbers of subjects and did not use control groups. METHODS: Patients aged 18-60 years were selected with PC20 < or = 8 mg/ml and FEV1 < 95% confidence interval of predicted normal. They were randomised to receive, in addition to a beta 2 agonist, either an inhaled corticosteroid (BA+CS), an anticholinergic (BA+AC), or a placebo (BA+PL). One hundred and forty one of these subjects with moderately severe obstructive airways disease completed seven periods of two weeks of morning and afternoon PEF measurements at home during 18 months of blind follow up. RESULTS: Improvements in PEF occurred within the first three months of treatment with BA+CS and was subsequently maintained: the mean (SE) increase in morning PEF was 51 (8) l/min in the BA+CS group compared with no change in the other two groups. Similarly, afternoon PEF increased by 22 (7) l/min. Diurnal variation in PEF (amplitude %mean) decreased from 18.0% to 10.2% in the first three months of treatment with BA+CS. Within-subject relations between changes in diurnal variation in PEF and changes in PC20 were found to be predominantly negative (median rho-0.40) but with a large scatter. Relations between diurnal variation in PEF and changes in symptom scores, FEV1, and bronchodilator response were even weaker. CONCLUSIONS: In patients with moderately severe obstructive airways disease, PEF rates and variation are greatly improved by inhaled corticosteroids. Since the relation of diurnal PEF variation with PC20, symptoms, FEV1, and bronchodilator response were all weak, these markers of disease severity may all provide different information on the actual disease state. PEF measurements should be used in addition to the other markers but not instead of them.

Adolescent↗
PubMed1994

Reliability and validity of the chronic respiratory questionnaire (CRQ).

BACKGROUND: The Chronic Respiratory Questionnaire (CRQ) is frequently applied to assess quality of life in patients with chronic obstructive pulmonary disease (COPD). However, the reliability and validity of this questionnaire have not yet been determined. This study investigates the reliability and validity of the four separate dimensions of the CRQ. METHODS: The CRQ was administered on two consecutive days to 40 patients with COPD (mean FEV1 44% predicted, FEV1/IVC 37% predicted). Internal consistency reliability of each dimension was investigated by Cronbach's alpha reliability coefficient, test retest reliability by the Spearman-Brown reliability coefficient (p), and content validity by Pearson's correlation coefficient between the CRQ and the symptom checklist (SCL-90). RESULTS: Items of the fatigue, emotion, and mastery dimensions showed a high internal consistency reliability (alpha = 0.71-0.88) as well as a high test retest reliability (p above 0.90). These three dimensions correlated with comparable dimensions of the SCL-90. Items of the dyspnoea dimension showed a low internal consistency reliability (alpha = 0.53) and a test retest reliability of p = 0.73. CONCLUSIONS: Items of the dimensions fatigue, emotion, and mastery of the CRQ are reliable and valid and can be used to assess quality of life in patients with severe airways obstruction. Items of the dyspnoea dimension are less reliable and should not be included in the overall score of the CRQ in comparative research. However, by scoring the items of dyspnoea separately they may be useful for the evaluation of the effects of intervention in a specific patient.

Aged↗
PubMed1994

Relation of lung function, maximal inspiratory pressure, dyspnoea, and quality of life with exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Several studies have shown that both objective and subjective measurements are related to exercise capacity in patients with chronic obstructive pulmonary disease (COPD). In this study the relative contribution of lung function, maximal inspiratory pressure, dyspnoea, and quality of life to the performance in a walking distance test and a bicycle ergometer test was investigated. METHODS: Static lung volumes, forced expiratory volume in one second (FEV1), inspiratory slow vital capacity (IVC), transfer factor for carbon monoxide (TLCO) divided by the alveolar volume (TLCO/VA), static compliance (Cst), and maximal inspiratory peak pressure (PImaxPOES) were measured in 40 patients with COPD with severe airways obstruction (mean FEV1 44% predicted, mean FEV1/IVC 37% predicted). Quality of life was assessed by the Chronic Respiratory Questionnaire (CRQ) and dyspnoea by the Borg category scale. Exercise capacity was measured by both a six minute walking distance (test) and a maximal work load of the bicycle ergometer test (Wmax). RESULTS: Spirometric values and maximal inspiratory pressure were modestly correlated with both the six minute walking test and Wmax, r values ranging from 0.50 to 0.58. The TLCO was strongly correlated with the six minute walking test (r = 0.62) and with Wmax (r = 0.78). Quality of life showed no correlation with exercise capacity, while there was a correlation between dyspnoea and the six minute walking test (r = -0.41). Backward linear regression analysis selected TLCO and PImaxPOES as the most significant determinants for exercise performance. They explained 54% and 69% of the variance in the six minute walking test and Wmax, respectively. CONCLUSIONS: The results show that exercise capacity in patients with COPD with severe airways obstruction is more strongly related to inspiratory muscle strength and lung function than to dyspnoea and quality of life. The significant correlation between dyspnoea and the six minute walking test suggests that subjective variables are more strongly related to walking tests than to bicycle ergometer tests.

Aged↗
PubMed1994

Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group.

BACKGROUND: Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain. METHODS: Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment. RESULTS: In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids. CONCLUSIONS: No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.

Administration, Inhalation↗
PubMed1994

Partial inhibition of the early and late asthmatic response by a single dose of salmeterol.

The long-acting beta 2-agonist salmeterol has been suggested to have other pharmacologic activities, that is, antiinflammatory capacities, in addition to its bronchodilator properties. We investigated the protective effect of 50 micrograms salmeterol in a placebo-controlled study on house dust mite-induced early- and late-phase reactions in 19 atopic asthmatic subjects. FEV1 and methacholine airway reactivity (AR) were measured. Eosinophils and their activation markers in peripheral blood were counted as indirect parameters of inflammation. Corrections were made for confounding of bronchodilator effects by salmeterol and the spontaneous diurnal variation, using saline inhalation as a control. Salmeterol completely inhibited the fall in FEV1 up to 10 h after the house dust mite challenge. Nevertheless, after correction, a biphasic response was present in the salmeterol group. Salmeterol protected against the allergen-associated increase in AR 3 h after the challenge, but no protection was observed after 24 h. Salmeterol did not inhibit the allergen-induced changes in total number of eosinophils and their activation markers in peripheral blood. These data suggest that a single dose of salmeterol modifies allergen-induced airway responses, above all by sustained bronchodilation.

Adrenergic beta-Agonists↗
PubMed1994

Nedocromil sodium versus albuterol in the management of allergic asthma.

In a double-blind, double-placebo, randomized crossover study, we compared the effects of 6 wk of treatment with the anti-inflammatory drug nedocromil sodium (16 mg/day) with 6 wk of treatment with the bronchodilator drug albuterol (800 micrograms/day) in 29 adults with allergic asthma. After 3 and 6 wk of treatment with nedocromil sodium, patients were significantly less hyperresponsive to propranolol (p = 0.002 and p = 0.02) and almost significantly less hyperresponsive to histamine (p = 0.071 and p = 0.065). FEV1 and FVC percent predicted tended to be higher, morning PEF values increased significantly (p = 0.038 and p = 0.03), and diurnal and day-to-day PEF variation decreased (p = 0.03 and p = 0.093, p = 0.005 and p = 0.096, respectively) with nedocromil sodium treatment compared with albuterol treatment. Almost all symptoms (daytime and nighttime asthma, wheezing, shortness of breath) and the additional bronchodilator use were significantly reduced with nedocromil sodium treatment compared with albuterol treatment. Treatment with the anti-inflammatory drug nedocromil sodium was shown to be superior to treatment with the bronchodilator drug albuterol. The patient's clinical situation may deteriorate when beta 2-agonists are used continuously. Nedocromil sodium has good clinical effect, and it may serve as a first-line choice for antiinflammatory therapy in asthma.

Administration, Inhalation↗
PubMed1994

Inflammation in nocturnal asthma?

At present there is some indirect evidence for increased nocturnal inflammation in patients suffering from nocturnal asthma: 1. Circulating eosinophil numbers and activation, as reflected by increased levels of ECP and EDN and low-density eosinophils, are increased at night. 2. Circulating histamine levels are increased at night. 3. Hyperresponsiveness to AMP at night is increased compared with hyperresponsiveness to methacholine. However, most results of various studies point to nocturnal asthma's being an expression of more severe asthma: 1. Both AMP and propranolol responsiveness, indirect measures of airway hyperresponsiveness, are lower both at 4:00 A.M. and 4:00 P.M. in asthmatics with nocturnal asthma than those without nocturnal asthma. 2. Patients with nocturnal asthma have higher circulating numbers of eosinophils at both 4:00 A.M. and 4:00 P.M. than those without nocturnal asthma, and eosinophil survival is not different at these times. 3. Patients with nocturnal asthma have higher PGD2 levels in BAL both at 4:00 A.M. and 4:00 P.M. than those without nocturnal asthma, but show no significant difference between levels at these two times. 4. Two studies have shown no difference in BAL eosinophil numbers and activation parameters at night in nocturnal asthma. 5. Histamine levels in BAL fluid are comparable day and night in patients with and without nocturnal asthma. 6. Inflammatory mediators in BAL are higher in asthmatic patients than in normal subjects, but are not different between patients with and without nocturnal asthma. Thus, patients with nocturnal asthmatic symptoms show an overall increased burden of mediators released from mast cells and other inflammatory cells. In conclusion, we feel that the term "nocturnal asthma" is misleading, in that it does not describe a unique entity in certain patients with asthma. We prefer, in view of the previous arguments, to consider nocturnal asthma a mere expression of more severe asthma. Thus we suggest the term "nocturnal asthma" be changed to "asthma with nocturnal symptoms."

Asthma↗
PubMed1994

Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home.

We have developed a rehabilitation programme at home and have investigated its effects on quality of life (QOL), lung function, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). We studied 43 patients with severe airflow obstruction: forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 l (mean +/- SD), FEV1/inspiratory vital capacity (IVC) 37 +/- 7.9%. After stratification, 28 patients were randomly allocated in a home rehabilitation programme for 12 weeks. Fifteen patients in a control group received no rehabilitation. The rehabilitation group received physiotherapy by the local physiotherapist, and supervision by a nurse and a general practitioner. Quality of life was assessed by the four dimensions of the Chronic Respiratory Questionnaire (CRQ). We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea, emotion, and mastery. Lung function showed no changes in the rehabilitation group. The exercise tolerance improved significantly in the rehabilitation group compared to the control group. The improvement in quality of life was not correlated with the improvement in exercise tolerance. Rehabilitation of COPD patients at home may improve quality of life; this improvement is not correlated with an improvement in lung function and exercise tolerance.

Breathing Exercises↗
PubMed1994

Distribution of peak expiratory flow variability by age, gender and smoking habits in a random population sample aged 20-70 yrs.

Peak expiratory flow (PEF) variability can be considered as an index of bronchial lability. Population studies on PEF variability are few. The purpose of the current paper is to describe the distribution of PEF variability in a random population sample of adults with a wide age range (20-70 yrs), and to assess relationships to age, gender and smoking habits. PEF data were collected in 511 participants of the Dutch part of the European Community Respiratory Health Survey. A training effect was found, absolute PEF values on the first measurement day being significantly lower. Females had greater PEF variability (adjusted for age, height and pack-years) and lower absolute PEFs than males. The mean within-day variation (amplitude % mean) was 3.66% (SD 2.03%), whereas the mean day-to-day variation was relatively small: 0.08% (SD 1.53%). Absolute PEFs were lower and amplitude % mean were significantly higher in older age groups. Smoking was significantly associated with lower mean PEFs and greater amplitude % mean. We observed lower mean values of the amplitude % mean than other investigators, possibly related to lower frequency of PEF recording (twice daily). We conclude that PEF and PEF variability have a normal or log-normal distribution. When studying PEF variability, age, gender and smoking habits should be taken into account.

Adult↗
PubMed1994

Effects of positive expiratory pressure breathing during exercise in patients with COPD.

The effect of breathing with a positive expiratory pressure of 5 cm H2O was investigated in eight patients with COPD (mean [SD]FEV1 = 54 [13] percent predicted). Specific work of breathing (Wsp) and myoelectrical activity of the following respiratory muscles were measured at rest: scalene muscle, parasternal muscle, and abdominal muscles. Minute ventilation (VE), end-tidal CO2 (FETCO2), physiologic dead space ventilation (VD/VT), oxygen uptake (VO2), and carbon dioxide output (VCO2) were measured at rest and during an incremental bicycle exercise test. Dyspnea sensation during exercise was quantified using the CR10 Borg-scale. All measurements were performed with and without positive expiratory pressure (PEP). During PEP breathing at rest mean (SEM) Wsp increased from 0.54 (0.13) J/L to 1.08 (0.10) J/L. The SEM VE decreased from 12.4 (1.0) L/min to 10.5 (1.1) L/min, and SEM VD/VT decreased from 0.39 (0.03) to 0.34 (0.03). There was a tendency for an increased phasic respiratory muscle activity during PEP breathing of all three muscles as compared with undisturbed breathing, but the changes were not statistically significant. During the exercise test with PEP, VE, VD/VT, VO2, and VCO2 were significantly lower, and FETCO2 was significantly higher as compared with the values obtained during the exercise test with undisturbed breathing. Dyspnea sensation during the exercise test with PEP, however, was higher than during the test with undisturbed breathing. The PEP breathing at rest may be useful in patients with COPD as it increases the efficiency of ventilation by reducing dead space ventilation. This beneficial effect also occurs during exercise, but here it is accompanied by increased dyspnea sensation.

Dyspnea↗
PubMed1993

Bronchoalveolar lavage cell analysis and lung function impairment in patients with systemic lupus erythematosus (SLE).

We examined the relationship between peripheral blood and bronchoalveolar lavage (BAL) lymphocyte phenotypes and lung function in 19 patients with SLE, and evaluated their association with disease activity. Lung function assessment showed a mildly restrictive pattern with frequent impairment of transfer factor for carbon monoxide (T1,co) and diffusing capacity of the alveolocapillary membrane (Dm), of late-expiratory airflow rates and with a high prevalence of increased airway resistance. T1,co, Kco and Dm correlated inversely with the numbers of CD8+ cells and CD56+/CD16+/CD3- (NK) cells in BAL. Oxygen radical production, both by stimulated and unstimulated BAL cells and blood polymorphonuclear leucocytes (PMN) was significantly increased in SLE. In comparison with healthy controls, patients with SLE had a lower percentage of CD19+ B cells in the BAL versus an increased percentage of these cells in peripheral blood. HLA-DR expression on CD4+ and CD8+ lung lymphocytes was markedly increased in SLE. Current SLE disease activity was not associated with changes in BAL or peripheral blood lymphocyte phenotypes. Our data suggest that an ongoing cell-mediated immune response is present in the lungs in SLE, particularly involving activated CD8+ T cells and CD56+/CD16+/CD3- NK cells. It is associated with up-regulated local production of oxygen radicals and with impaired pulmonary diffusing capacity. This inflammatory process seems to be independent of general SLE disease activity.

Adult↗
PubMed1993

Variability of bronchodilator response and effects of inhaled corticosteroid treatment in obstructive airways disease. Dutch CNSLD Study Group.

BACKGROUND: In the day to day care of obstructive airways diseases (asthma and chronic obstructive pulmonary disease) important decisions such as disease classification and choice of therapy are based on assessment of the bronchodilator response. However, surprisingly little is known of the long term course of the bronchodilator response in patients with obstructive airways disease. METHODS: Data from a multicentre trial were used in which 274 patients aged 18-60 years with airways obstruction were selected with PC20 < 8 mg/ml and FEV1 < 95% CI of predicted. FEV1 was measured before and 20 minutes after 1000 micrograms terbutaline and 40 minutes after an additional 80 micrograms ipratropium bromide. Data were analysed from 185 patients who were followed up for 21 months (five measurements). Four different expressions of bronchodilator response (BDR) were examined for change under long term therapy, long term variability, and prognostic value in predicting response to inhaled corticosteroids. RESULTS: There was a significant reduction in BDR of 117 ml after three months of treatment with a beta 2 agonist plus a corticosteroid (BA + CS), but not after bronchodilators only. Significant reductions with BA + CS were also found in BDR as a percentage of initial FEV1, and in BDR as a percentage of predicted FEV1. Bronchodilator tests were quite variable (SD 186 ml or 11% of initial value) and less than half of the patients could consistently be classified as "irreversible" with recommended cutoff levels. The bronchodilator response at the start of the study proved to be a poor predictor of improvement in FEV1 under BA + CS treatment (correct prediction 60%). CONCLUSIONS: Bronchodilator responses decrease substantially with inhaled corticosteroid therapy, and within subject variability is considerable both in asthma and chronic obstructive pulmonary disease. Dichotomous decisions on whether patients are "irreversible" according to any single bronchodilator measurement should therefore be made with great caution. The bronchodilator response cannot be used accurately as a predictor of response to inhaled corticosteroids in obstructive airways disease.

Administration, Inhalation↗
PubMed1993

Circadian variation in airway responsiveness to methacholine, propranolol, and AMP in atopic asthmatic subjects.

Increased airway hyperresponsiveness is thought to be one of the phenomena underlying nocturnal airway obstruction in asthma. To investigate the mechanisms that influence and modulate this phenomenon, we compared circadian variations in airway responsiveness with AMP and propranolol with the circadian variation in airway responsiveness to methacholine. Inhalation provocation tests were performed at 16.00 and 04.00 h in 16 nonsmoking atopic asthmatic subjects (18 to 42 yr of age), prospectively assigned to Group 1 (mean circadian peak expiratory flow rate [PEFR] variation > or = 15%) and Group 2 (< 15%). The circadian change in airway responsiveness to AMP, in contrast to methacholine, was significantly related to the circadian PEFR-variation of the 16 subjects (r = 0.81, p < 0.001). In Group 1 (n = 7) geometric mean PC20 AMP decreased more than PC20 methacholine during the night (2.3 and 0.9 doubling concentrations respectively, p < 0.05), whereas no difference in baseline FEV1 was found at the same time points during the different study days. Geometric mean PC20 propranolol did not change during the night. Daytime PC20 propranolol and PC20 AMP, in contrast to PC20 methacholine, were significantly lower in Group 1 as compared with Group 2. Together, the results show a higher susceptibility to stimulation of "indirect" airway responsiveness in the subjects with increased circadian PEFR amplitude. This suggests that mast cell activation rather than primary changes in smooth muscle cell contraction may play a role in the development of nocturnal airway obstruction.

Adenosine Monophosphate↗
PubMed1993

Airway responsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease is determined by smoking.

In contrast to methacholine, a stimulus that induces airway constriction mainly by "direct" stimulation of airway smooth muscle cells, AMP airway responsiveness reflects "indirectly" induced airway narrowing via inflammatory or neural reflex mechanisms. In order to determine inflammatory contribution to airway narrowing in COPD, we performed AMP and methacholine inhalation provocation tests in nonatopic subjects with COPD and compared the results with those obtained from atopic nonsmoking asthmatics and from healthy smoking volunteers. AMP caused airway narrowing in all but two subjects with COPD and in only three of the 12 healthy smoking subjects. Patients with COPD were significantly more responsive to AMP and methacholine than were healthy smoking volunteers. Geometric mean PC20 AMP was significantly lower in the smokers with COPD (7.2 mg/ml) than in the nonsmokers with COPD (58.5 mg/ml), whereas PC20 methacholine values and baseline FEV1 were comparable. In the nonatopic nonsmoking subjects with COPD, PC20 AMP was significantly higher than in the atopic nonsmoking asthmatics (3.8 mg/ml), whereas they responded similar to methacholine provocation. These results indicate that most subjects with COPD respond to AMP provocation and that smoking determines the degree of airway responsiveness to AMP in COPD. We suggest that increased susceptibility to mediator release by mast cells or neural reflex mechanisms are involved in AMP-induced airway constriction in asthma and in COPD.

Adenosine Monophosphate↗