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Biomedical subjects

D S Postma

Publications and source records attributed to D S Postma.

At least 19 recordsLinked to original sources
PubMed1995

Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy.

BACKGROUND: Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma. METHODS: We studied 303 children and grandchildren of 84 probands with asthma selected from a homogeneous population in the Netherlands. Ventilatory function, bronchial responsiveness to histamine, and serum total IgE were measured. The association between the last two variables was evaluated. Using analyses involving pairs of siblings, we tested for linkage between bronchial hyperresponsiveness and genetic markers on chromosome 5q31-q33, previously shown to be linked to a genetic locus regulating serum total IgE levels. RESULTS: Serum total IgE levels were strongly correlated (r = 0.65, P < 0.01) in pairs of siblings concordant for bronchial hyperresponsiveness (defined as a > or = 20 percent decrease in the forced expiratory volume in one second produced by histamine [threshold dose, < or = 16 mg per milliliter]), suggesting that these traits are coinherited. However, bronchial hyperresponsiveness was not correlated with serum IgE levels (r = 0.04, P > 0.10). Analyses of pairs of siblings showed linkage of bronchial hyperresponsiveness with several genetic markers on chromosome 5q, including D5S436 (P < 0.001 for a histamine threshold value of < or = 16 mg per milliliter). CONCLUSIONS: This study demonstrates that a trait for an elevated level of serum total IgE is coinherited with a trait for bronchial hyperresponsiveness and that a gene governing bronchial hyperresponsiveness is located near a major locus that regulates serum IgE levels on chromosome 5q. These findings are consistent with the existence of one or more genes on chromosome 5q31-q33 causing susceptibility to asthma.

Adolescent↗
PubMed1995

Persistence and new onset of asthma and chronic bronchitis evaluated longitudinally in a community population sample of adults.

BACKGROUND: Some patients with chronic obstructive pulmonary disease may share the clinical characteristics of those with asthma; their disease is sometimes called "asthmatic bronchitis." Whether there is a difference between asthmatics who do and do not develop chronic bronchitis is not yet clear. We investigated whether asthma and chronic bronchitis may share some "allergic" phenotypes and whether asthmatic individuals who develop chronic bronchitis subsequently have steeper declines in lung function. METHODS: Known risk factors for decline in lung function were analyzed in a representative community population of adults followed up longitudinally since 1972 in Tucson, Ariz, in groups with persistent, newly developed, and past diagnoses of asthma and chronic bronchitis. We evaluated contributions of initial level of forced expiratory volume in 1 second (FEV1), reversibility with isoproterenol hydrochloride nebulized aerosol bronchodilator treatment, percentage of blood eosinophils to determine eosinophilia, and IgE level. RESULTS: The concurrence of chronic bronchitis and asthma is associated with a steeper decline in FEV1 than is asthma as the sole diagnosis. Asthmatics (those with persistent asthma with and without chronic bronchitis) had the greatest prevalence of increased reversibility with isoproterenol therapy and with eosinophilia. The prevalence of eosinophilia was also high in those with newly diagnosed chronic bronchitis without asthma; however, this was not the case in those with persistent chronic bronchitis without asthma. Larger bronchodilator responses were related to steeper declines in FEV1, both in persistent asthma and in chronic bronchitis. CONCLUSIONS: Bronchodilator response and eosinophilia are generally believed to be hallmarks of asthma. We show that these characteristics may be present in chronic bronchitis as well. The presence of a large (> 25%) bronchodilator response is associated with a steeper decline in FEV1.

Adult↗
PubMed1995

Inflammatory cell number and mediators in bronchoalveolar lavage fluid and peripheral blood in subjects with asthma with increased nocturnal airways narrowing.

BACKGROUND: Increased nocturnal airways narrowing (NAN) in asthma is thought to occur as the result of intensification of inflammatory processes in the airways. In this study we investigated the presence of inflammatory cells and mediators in bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) and assessed their relationship with the occurrence of increased NAN. METHODS: BAL fluid and PB samples were assessed at 16:00 and 04:00 hours, separated by 7 days or more, in eight nonatopic healthy subjects (group 1) and 17 atopic subjects with asthma who were using inhaled bronchodilators only. The latter subjects were prospectively assigned to groups with and without NAN, as defined by a mean circadian peak expiratory flow variation of less than 15% (group 2) and 15% or more (group 3), respectively. RESULTS: Significantly higher eosinophil numbers and inflammatory activation products (eosinophil cationic protein, eosinophil-derived neurotoxin, histamine) were found in BAL fluid and PB from subjects with asthma in comparison with control subjects. However, increased NAN was not generally associated with a circadian fluctuation in cell number and inflammatory mediators in BAL fluid and PB. No differences in inflammatory cell numbers existed that distinguished between groups 2 and 3. However, in group 3 significantly higher BAL prostaglandin D2 levels (70 vs 24 pg/ml; range, 28 to 102 vs 11 to 90 pg/ml; p = 0.04) and serum eosinophil cationic protein levels (17.6 vs 16.1 ng/ml; range, 6.3 to 17.5 vs 6.3 to 60.3 ng/ml; p = 0.03) at 16:00 hours were detected compared with group 2. CONCLUSIONS: Our findings suggest that increased NAN is more likely to occur in subjects with asthma with ongoing increased cellular activation during the day.

Adolescent↗
PubMed1995

Relation between respiratory symptoms, pulmonary function and peak flow variability in adults.

BACKGROUND: A study was carried out to determine whether subjects with respiratory symptoms are more likely to have impaired lung function or increased airway lability, and to quantify these relationships in a population of adults. METHODS: Data were collected from 511 participants (aged 20-70 years) from the Dutch part of the European Community Respiratory Health Survey (ECRHS). The symptoms analysed were: wheeze, dyspnoea > or = grade 3, nocturnal dyspnoea, cough and phlegm, and history of allergy. Lung function was measured by peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). PEF variability was used as an index for bronchial lability. RESULTS: Both FEV1 and PEF were decreased with increasing numbers of symptoms. Subjects with one symptom had an increased risk of having an FEV1 value of < 70% (OR = 4.2) and this risk increased with an increasing number of symptoms. Subjects with three or more symptoms had an increased risk of having a PEF value of < 70%, a diurnal variation in PEF of > 10% (both OR = 4.4), and an increased risk of high between day variation (OR = 6.6). CONCLUSIONS: Subject-reported symptoms are related to impaired lung function and to increased variability of peak flow.

Adult↗
PubMed1995

Long term benefits of rehabilitation at home on quality of life and exercise tolerance in patients with chronic obstructive pulmonary disease.

BACKGROUND--Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease (COPD). However, appropriately controlled studies have not previously been performed, nor have the benefits of different types of continuation programme for rehabilitation been investigated. Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD. METHODS--Thirty six patients with severe airways obstruction (mean SD) forced expiratory volume in one second (FEV1) 1.3(0.4) 1, FEV1/inspiratory vital capacity (IVC) 37.2(7.9)%) were studied. Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner. During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session. Thereafter, 11 patients (group A) received a session of physiotherapy once weekly while 12 patients (group B) received a session of physiotherapy once a month. The control group C (13 patients) received no rehabilitation at all. Quality of life was assessed by the Chronic Respiratory Questionnaire, exercise tolerance by the six minute walking distance, and lung function by FEV1 and IVC. Outcome measures were assessed at baseline and at three, six, 12, and 18 months. RESULTS--Long term improvements in quality of life were found in patients in groups A and B, but not in those in group C compared with baseline, but these only reached significance in group B at all time points. Patients in group B had a higher quality of life than those in group C only at three and 12 months. There was a decrease in both six minute walking distance (at 12 and 18 months) and IVC (at three, 12, and 18 months) in patients in group C compared with the baseline measurement. Between groups analysis showed no differences for six minute walking distance, FEV1, and IVC. CONCLUSIONS--This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months. The change in quality of life was not associated with a change in exercise tolerance.

Exercise Tolerance↗
PubMed1995

Lymphocyte and macrophage activation in bronchoalveolar lavage fluid in nocturnal asthma.

Increased nocturnal airway narrowing is thought to occur as a consequence of an intensification of inflammatory processes at night. Lymphocyte and alveolar macrophage (AM) activation are thought to be associated with the clinical expression of asthma, and may be important in the occurrence of nocturnal asthma as well. The expression of CD25 and HLA-DR receptors on lymphocytes from bronchoalveolar lavage (BAL) and peripheral blood (PB) CD4+, as well as of CD14, IgG Fc, and CD11/CD18 leukocyte adhesion receptors on AM in BAL fluid and monocytes in PB, were determined at 16.00 and 04.00 h by flow cytometry. Their relationship with the occurrence of nocturnal asthma was investigated in eight nonatopic controls (Group 1) and 17 atopic asthmatic subjects, prospectively assigned to groups with a mean circadian peak expiratory flow (PEF) variation < 15% (Group 2) and > or = 15% (Group 3). The occurrence of an increased circadian variation in PEF in asthmatic subjects was on the whole not associated with a day-night fluctuation in lymphocyte numbers and subsets in PB or BAL fluid, nor with day-night changes in receptor expression on AM from BAL or monocytes from PB. The only exception was the presence of a greater day-night change in the proportion of HLA-DR-expressing CD4+ lymphocytes in the BAL fluid along with an increasing circadian PEF rhythm in asthmatic subjects (r = 0.68, p = 0.03). A further finding was that a lower number of BAL CD4+ lymphocytes at daytime was significantly related to a higher circadian PEF variation in asthmatic subjects (r = -0.66, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Importance of total serum IgE for improvement in airways hyperresponsiveness with inhaled corticosteroids in asthma and chronic obstructive pulmonary disease. The Dutch CNSLD Study Group.

Airways hyperresponsiveness is a hallmark of asthma, and many patients with COPD also demonstrate hyperresponsiveness. Inhaled corticosteroids improve hyperresponsiveness, but the extent of improvement may vary considerably between patients. This study was designed to determine which patient characteristics predict these differences in response. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if PC20 < or = 8 mg/ml and FEV1 < 95% confidence interval of predicted normal. They were followed for 2.5 yr, during which one-third received inhaled corticosteroids. The independent influences of baseline FEV1/IVC, bronchodilator response, PC20, smoking habits, allergy, age, and sex on the improvement in airways hyperresponsiveness with inhaled corticosteroids were analyzed. Total serum IgE was taken as a parameter of allergy, next to specific IgE for house dust mite, skin tests, and blood eosinophils. Total serum IgE was found to be the most important and single independent predictor of change in PC20 with inhaled corticosteroids: patients with a higher IgE had a greater increase in PC20 when administered inhaled corticosteroids than those with lower IgE levels. Alternatively, patients with a higher IgE who did not receive corticosteroids had a decrease in PC20 compared with patients with a lower IgE. This effect was most prominent in asthma but was inconsistent in asthmatic bronchitis and COPD. The level of IgE cannot be used to predict the response to inhaled corticosteroids in individuals accurately. Total serum IgE is the single most important predictor of change in PC20 with and without inhaled corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Chronic respiratory symptoms and airway responsiveness to methacholine are associated with eosinophilia in older men: the Normative Aging Study.

Identification of subsets of patients with chronic obstructive lung disease (COLD) in order to determine disease outcomes and, possibly, the effects of treatment is an area of clinical interest. At present, it remains unclear which patients with COLD are most likely to benefit from anti-inflammatory therapy. We investigated this question in a community-dwelling sample of men. In this study, the relationship of chronic respiratory symptoms, airway responsiveness to methacholine, and skin test reactivity to peripheral-blood eosinophil and neutrophil counts was examined among 894 male participants in the Normative Aging Study (mean age 60 yrs; range 41-90 yrs). The symptoms considered were asthma, persistent wheeze, dyspnoea, chronic cough and phlegm. Responsiveness to methacholine was defined as a provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of < or = 8.6 mumol, a positive skin test as a wheal diameter of > or = 5 mm after subtraction of the diameter of any wheal reaction to a glycerin control, and eosinophilia as an eosinophil count of > or = 275 cells.mm-3 in peripheral blood. Chronic symptoms (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.4-2.7), airway responsiveness (OR 1.7; CI 1.1-2.7), and the combination of symptoms and airway responsiveness (OR 3.4; CI 2.0-5.6) were positively and significantly related to peripheral-blood eosinophil counts. These relationships remained significant after adjustment for the effects of age and smoking, and after exclusion of asthmatic subjects. Symptoms and airway responsiveness combined were not significantly related to neutrophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Peak inspiratory mouth pressure in healthy subjects and in patients with COPD.

The validity of peak inspiratory mouth pressure (P.PI-max) as a measure of inspiratory muscle strength was investigated by comparing it with sniff Pes in patients with COPD with respect to (1) learning effect, (2) reproducibility, and (3) measures of agreement. To assess the discriminating capacity of P.PImax, we compared the values in patients with COPD with those of healthy elderly subjects. Thirty-four patients (mean age, 62.5 years) with severe airways obstruction (FEV1, 44% predicted; FEV1/IVC, 37% predicted) and 149 healthy subjects (age > or = 55 years) were included. P.PImax was assessed during a maximal static inspiratory maneuver, while sniff Pes was assessed during a maximal sniff maneuver. Both maneuvers were performed from residual volume ten times on the same day. P.PImax showed no learning effect, while the sniff maneuver used seven attempts to obtain a maximal value. The intraindividual coefficients of variation of P.PImax and sniff Pes were 11.2% and 6.0%, respectively. Measures of agreement showed no significant discrepancies between the mean P.PImax and mean sniff Pes (0.29 kPa, p = 0.49). There was a significant correlation (r = 0.57, p < 0.001) between both measurements. P.PImax was significantly (p < 0.001) lower in both male (8.2 kPa) and female (6.2 kPa) patients with COPD compared with healthy men (11.0 kPa) and healthy women (8.8 kPa). We conclude that P.PImax is a valid and noninvasive assessment of inspiratory muscle strength.

Age Factors↗
PubMed1995

Adverse effects of eosinophilia and smoking on the natural history of newly diagnosed chronic bronchitis.

BACKGROUND: Little is known about risk factors for the progression of disease in individuals with newly developed chronic bronchitis (CB). In addition to the effects of smoking, there was specific clinical and epidemiologic interest in the importance of traits such as eosinophilia and wheezing, more commonly associated with asthma, in the progression of this disease. METHODS: We evaluated adult individuals with and without diagnosed CB longitudinally in a representative community population in Tucson, Ariz. These subjects were followed up for 13 years since 1972. Because we were interested in CB specifically, those with diagnoses of emphysema and asthma were removed from the data set. Initial level of FEV1 (%FEV1) and slopes in FEV1 were corrected for covariates and other important variables. RESULTS: As expected, persistent and newly diagnosed CB was significantly more common in current and ex-smokers. Furthermore, initial lung function was lower, and decline in FEV1 was steeper in smokers with persistent and newly diagnosed CB. Newly diagnosed cases had steeper declines in FEV1 (-6.84 mL/yr below grand mean of -11.18 mL/yr) than normal subjects (+0.95 mL/yr). The incidence rate of newly diagnosed CB was significantly higher in those with eosinophilia (13.7%) than without eosinophilia (6.7%). Finally, new cases with eosinophilia had similar initial %FEV1 (95.4 +/- 1%) but much larger declines in function than new cases without eosinophilia: -24.5 versus -16.6 mL/yr. Adverse effects of wheeze were largely explained by smoking and eosinophilia. CONCLUSION: Eosinophilia is an important aspect of CB in addition to smoking, and it should be considered in its evaluation. The presence of eosinophilia in newly diagnosed CB, with or without wheeze, may warn the clinician of the possibility of a rapid decline in FEV1.

Adult↗
PubMed1995

Evidence for two unlinked loci regulating total serum IgE levels.

Studies investigating the genetic control of total serum IgE levels are of major importance in understanding basic pathophysiologic mechanisms in atopy and asthma, since IgE levels predict onset and correlate with the clinical expression of these disorders. Previous analysis of data from 92 families, ascertained through a parent with asthma, showed evidence for recessive inheritance of high IgE levels with linkage to chromosome 5q. Since there was significant residual familial correlation in the one-locus segregation analysis, two-locus segregation and linkage analyses were performed. Segregation analyses provided evidence for a second major locus unlinked to the locus on 5q. Utilization of this two-locus model corroborates the previous evidence for linkage between this trait and markers on 5q31-q33. The LODs for the most informative marker D5S436 increased from 3.00 at 10% recombination to 4.67 at 9% recombination, when the two-locus model was used. Additional linkage studies are needed to map this second locus. These results demonstrate the importance of performing multilocus segregation and linkage analyses for quantitative traits that are related to the phenotype of a complex disorder. This approach has given further insight into the genetics of allergy and asthma by providing evidence for a two-locus model.

Asthma↗
PubMed1994

Evidence for a locus regulating total serum IgE levels mapping to chromosome 5.

Genetics studies of total serum IgE levels were performed since high IgE levels correlate with clinical expression of allergy and asthma. Families ascertained through a parent with asthma were genotyped for markers on 5q where there are multiple candidate genes that may influence the control of IgE and inflammation. Evidence for linkage of the IgE phenotype to 5q was obtained by both sib-pair and lod score analysis with evidence for recessive inheritance of high IgE levels from segregation analysis. These findings represent a major step in mapping genes important in the regulation of allergic responses and the pathogenesis of asthma.

Adult↗
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↗