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Biomedical subjects

J Molema

Publications and source records attributed to J Molema.

At least 19 recordsLinked to original sources
PubMed1999

Effect of inhaled corticosteroids on bronchial responsiveness in patients with "corticosteroid naive" mild asthma: a meta-analysis.

BACKGROUND: Inhaled corticosteroids are the most efficacious anti-inflammatory drugs in asthma. International guidelines also advocate the early introduction of inhaled corticosteroids in corticosteroid naive patients. A study was undertaken to assess the effects of inhaled corticosteroids on bronchial hyperresponsiveness in patients with corticosteroid naive asthma by conventional meta-analysis. METHODS: A Medline search of papers published between January 1966 and June 1998 was performed and 11 papers were selected in which the patients had no history of treatment with inhaled or oral corticosteroids. Bronchial responsiveness to bronchoconstricting agents was considered as the main outcome parameter. Doubling doses (DD) of histamine or methacholine were calculated. RESULTS: The total effect size of inhaled corticosteroids (average daily dose 1000 microg) versus placebo in the 11 studies was +1.16 DD (95% confidence interval (CI) +0.76 to +1.57). When only the eight short term studies (2-8 weeks) were analysed the effect size of the bronchoconstricting agent was +0.91 DD (95% CI +0.65 to +1.16). No relationship was found between the dose of inhaled corticosteroid used and the effect on bronchial responsiveness. CONCLUSION: This meta-analysis in patients with corticosteroid naive asthma indicates that, on average, high doses of inhaled corticosteroids decrease bronchial hyperresponsiveness in 2-8 weeks. It remains unclear whether there is a dose-response relationship between inhaled corticosteroids and effect on bronchial hyperresponsiveness.

Administration, Inhalation↗
PubMed1998

Are anti-oxidant and anti-inflammatory treatments effective in different subgroups of COPD? A hypothesis.

The treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids or anti-oxidants is still under debate and the identification of sub-groups of COPD patients who may benefit from either anti-inflammatory or anti-oxidant treatment is needed. We re-analysed data from an earlier study of inhaled beclomethasone therapy in COPD (n = 28) and asthma (n = 28) patients in order to determine patient characteristics that predict a favourable inhaled steroid treatment effect. A higher bronchodilatory response, a faster decline of FEV1 prior to the treatment period and a lower Tiffeneau index were significantly related to more beneficial treatment effects. Increased smoking tended to be related to less steroid treatment benefits, though it was not statistically significant. In this paper these findings are presented in light of the available literature on anti-inflammatory and anti-oxidant COPD treatment. On this basis the hypothesis is presented that anti-oxidant treatment might be relatively more effective among those COPD patients who respond less well to inhaled steroids (low reversibility and heavy smoking).

Anti-Inflammatory Agents↗
PubMed1998

The role of "fear of corticosteroids" in nonparticipation in early intervention with inhaled corticosteroids in asthma and COPD in general practice.

Treatment of chronic airflow obstruction with inhaled corticosteroids at an early stage has been shown to preserve the lung function. We tested the hypothesis that "fear of corticosteroids" may be an important reason for nonparticipation in the Detection, early Intervention and Monitoring programme on Chronic obstruction pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred and forty nine adult subjects from 10 general practices were invited to participate in the several parts of the "DIMCA" programme. Refusers were questioned about the reason(s) for nonparticipation. Together the screening, monitoring and three drug interventions of the study showed on average 25-35% refusers. The most frequent reasons for nonparticipation were absence of pulmonary symptoms and lack of time. For those invited to take part in one of the three drug interventions, "dislike of medication" was the most important reason for nonparticipation (33, 45 and 67% of the refusers). "Fear of corticosteroids" specifically was the reason for nonparticipation in 8% of the refusers on the basis of "dislike of medication". We concluded that a specific fear of corticosteroids was not a major obstacle for early intervention with inhaled corticosteroids.

Administration, Inhalation↗
PubMed1998

How to avoid underdiagnosed asthma/chronic obstructive pulmonary disease?

The prevalence of asthma and chronic obstructive pulmonary disease (COPD) is rising in most countries, including The Netherlands. It has been suggested that a majority of these cases of (self-reported) symptoms related to asthma/COPD are not diagnosed in general practice. We compared a population screening for underdiagnosed asthma/COPD with a high-risk approach by a questionnaire form with specified questions about asthma/COPD-related symptoms. A case-controlled study including a record review was performed of cases and controls. The results of a population screening were used to classify patients as (a) asthma/COPD, (b) at risk for asthma/COPD, or (c) no asthma/COPD. Eleven hundred fifty-five patients were screened. One hundred fifty-five patients reported previous asthma/COPD-related care (cases). The difference between number of cases and controls in asthma/COPD diagnosis was chosen as main outcome measure. The population screening revealed 85 subjects with a diagnosis of asthma/COPD and 154 subjects with an increased risk. Nineteen diagnoses could be made in cases, and eight diagnoses in controls. The chart review showed that only seven cases and two controls were known to the general practitioner. From this study it can be concluded that in order to reduce the number of un- and underdiagnosed patients, all listed patients in general practice should be screened. However, if screening of all patients is not feasible, active case finding by asking a few questions about shortness of breath or wheezing to all patients in the group of listed individuals is recommended.

Adult↗
PubMed1997

Testing bronchial hyper-responsiveness: provocation or peak expiratory flow variability?

BACKGROUND: Assessing bronchial hyper-responsiveness (BHR) is a main diagnostic criterion of asthma. Provocation testing is not readily available in general practice, but peak expiratory flow (PEF) is. Several guidelines promote the use of PEF variability as a diagnostic tool for BHR. This study tested the agreement between histamine challenge testing and PEF variability, and the consequences for diagnosing asthma. AIM: To investigate the possibility of assessing BHR by PEF variability, using a histamine provocation test as a reference. METHOD: Subjects with signs of symptoms indicating asthma (persistent or recurrent respiratory symptoms or signs of reversible bronchial obstruction) (n = 323) were studied. They had been identified in a population screening for asthma. A histamine provocation test and PEF variability were assessed over a three-week period. Asthma was defined as signs or symptoms together with a reversible airflow obstruction or BHR to the histamine challenge test. BHR was defined as a PC20 histamine of < or = 8 mg/ml or a PEF variability of > or = 15%. Overall correlation between PC20 and PEF variability was calculated using Spearman's rho. Furthermore, a decision tree was constructed to clarify the role of BHR in diagnosing asthma. RESULTS: Thirty-two patients had a reversibility in forced expiratory volume in 1 second (FEV1) of > or = 9% predicted, 131 patients showed a PC20 of < or = 8 and 11 patients had a PEF variability of > or = 15%. Overall correlation was poor at only -0.27 (P < 0.0001). One hundred and fourteen of the 131 patients diagnosed as having asthma when the histamine challenge test was used were not diagnosed by PEF variability. CONCLUSION: PEF variability cannot replace bronchial provocation testing in assessing BHR. This indicates that PEF variability and bronchial provocation do not measure the same aspects of BHR. If BHR testing is required in diagnosing asthma, a bronchial provocation test has to be used in general practice as well.

Adult↗
PubMed1996

Treatment of mild asthma with inhaled corticosteroids: is discontinuation of therapy possible?

BACKGROUND: This study investigated if long-term therapy with inhaled corticosteroids could be discontinued in mild asthma when patients are in a clinically stable phase of the disease. Data were derived from a 2-year randomized, controlled, bronchodilator intervention study in family practice. METHODS: The experimental (stop-steroid) group consisted of 19 asthmatic patients who had used inhaled corticosteroids daily during at least the year preceding this study and who stopped using these drugs because of participation in the bronchodilator intervention study. The control (no-steroid) group consisted of 70 patients with asthma who had not used corticosteroids in the year preceding the study. At the start of the study (8 weeks after stopping steroids), the two groups were completely comparable in all other relevant characteristics. During the 2-year study, patients were treated only with a bronchodilator (salbutamol or ipratropium bromide). Outcome measures were: exacerbations, symptoms, annual decline in forced expiratory volume in 1 second (FEV1), annual change in nonspecific bronchial responsiveness (PC20-histamine), and the need for additional corticosteroid therapy because of symptoms of increased airway obstruction. RESULTS: In the stop-steroid group, 12 of 19 patients (63%) dropped out during the study period because of a deterioration of their clinical condition and need for additional (inhaled) corticosteroid treatment. In the no-steroid group, only eight patients dropped out for this reason (11%). In the stop-steroid group, who did not use steroids for at least 1 year, the annual FEV1 decline was much larger than in the comparison subjects (165 vs 40 ml/yr). CONCLUSIONS: Stopping maintenance treatment with inhaled corticosteroids may not be advisable in all patients with mild asthma. Instead of stopping or interrupting treatment, family physicians are advised to determine the minimal effective daily dose of inhaled corticosteroids for each individual patient that provides adequate control of the disease.

Administration, Inhalation↗
PubMed1995

Periodic treatment regimens with inhaled steroids in asthma or chronic obstructive pulmonary disease. Is it possible?

OBJECTIVE: To determine whether inhaled corticosteroids can be discontinued in the stable phase of asthma or chronic obstructive pulmonary disease (COPD) or if this therapy should be continued. DESIGN: Nonrandomized open uncontrolled 5-year trial. SETTING: Prospective study in general practice. PATIENTS: Forty-eight patients with steroid-dependent asthma or COPD who had shown a decline in forced expiratory volume in 1 second (FEV1) of at least 80 mL per year and at least one exacerbation per year during the first 2 years of bronchodilator treatment. Subjects were treated additionally with inhaled steroids for another 2 years and were finally given the option to stop using steroids. Sixteen patients were willing to stop using beclomethasone and were studied for another year. No recruitment bias took place in this consecutive sample in the fifth year of follow-up. Two of 16 patients developed carcinomas and dropped out. INTERVENTIONS: Two years of bronchodilator treatment alone (400 micrograms of salbutamol or 40 micrograms of ipratropium bromide four times daily), followed by 2 years of additional inhaled corticosteroid treatment (400 micrograms of beclomethasone two times daily), and finally 1 year of bronchodilator treatment alone. MAIN OUTCOME MEASURES: Decline in lung function (FEV1), change in bronchial hyperresponsiveness, indicated by a provocative concentration of histamine causing a 20% fall in FEV1 (PC20), morning peak expiratory flow rate (PEFR), diurnal PEFR, week-to-week variation of PEFR, bronchial symptoms, and exacerbations. RESULTS: The course of FEV1 during the year in which beclomethasone was discontinued was not significantly different when compared with the 2-year period of beclomethasone treatment. Neither did the course of PC20, morning PEFR, diurnal PEFR, symptom score, and exacerbation rate change. Only the week-to-week variation of the PEFR increased after discontinuing steroids. CONCLUSIONS: Discontinuing inhaled steroids is possible in some patients with asthma or COPD after 2 years of regular treatment. This might indicate that for certain groups of patients with mild asthma or COPD, periodic treatment schedules with inhaled steroids is the treatment policy for the future.

Administration, Inhalation↗
PubMed1995

Asthma and chronic bronchitis. Can family physicians predict rates of progression?

OBJECTIVE: To investigate whether the progression rate of asthma or chronic bronchitis can be predicted from a cross-sectional assessment of features that can be measured by family physicians. DESIGN: Secondary analysis of data from a 2-year randomized, controlled bronchodilator intervention study in family practice. SETTING: Twenty-nine general practices in the eastern part of The Netherlands. PATIENTS: One hundred sixty patients (101 with chronic bronchitis, 59 with asthma) from the 29 general practices. INTERVENTIONS: Predictors were related to the annual decline in lung function (the forced expiratory volume in one second) by means of multiple analysis of variance, controlling for age, sex, smoking habits, initial FEV1 level, bronchial hyperresponsiveness, reversibility of obstruction, and medication during the study. MAIN OUTCOME MEASURES: Predictors of the annual decline in lung function (FEV1), which is believed to be the most important measure for progression. RESULTS: Only three variables predicted the decline in lung function: having a barrel-shaped chest, experiencing wheezing, and an unusual diurnal peak-flow rate index. Wheezing was the best predictor of the annual decline in lung function. In chronic bronchitis, the decline in FEV1 of wheezing patients was 133 mL/y compared with 62 mL/y for non-wheezing patients (P < 0.05). In asthma with more severe symptoms, wheezing patients had a tendency to decline 156 mL/y compared with 57 mL/y among non-wheezing patients (P = 0.08). CONCLUSIONS: It is nearly impossible to predict the progression rate of asthma or chronic bronchitis from symptoms, physical signs of the chest, and the PEFR. Therefore, patients with a rapid progression rate can probably be detected only by monitoring progression of the disease through repeated lung function testing.

Asthma↗
PubMed1994

Does bronchial hyperresponsiveness precede or follow airway obstruction in asthma or COPD?

OBJECTIVE: The following hypothesis was tested: The degree of bronchial hyperresponsiveness (BHR) is a risk factor for the progression of airway obstruction in asthma, while in chronic obstructive pulmonary disease (COPD) it reflects the existing airway obstruction. METHODS: The relationships between the (annual change in) PC20 histamine and the (annual change in) FEV1 were investigated in a 2-year prospective controlled study. The FEV1 and the PC20 histamine were assessed at 6-month intervals. 183 patients (74 asthma, 109 COPD) participated. The investigated relationships were assessed by means of multiple analysis of variance (ANOVA). Patients used bronchodilator therapy alone. No steroids were permitted during the study. RESULTS: The results demonstrated that the PC20 at the start of the study was related to the subsequent annual decline of FEV1 in asthma (r = 0.32, p < 0.05) but not in COPD (r = -0.10, p = 0.89). Asthmatic patients with a PC20 value < or = 2 mg/ml had an average decline of 118 ml/yr, those with a PC20 value > 2 mg/ml of 27 ml/yr. The change in PC20 histamine during the 2-year study period was related to the annual change in FEV1 in COPD (r = 0.45, p < 0.05), but not in asthma (r = 0.06, p = 0.90). The disturbing influence of possible confounders was investigated and if necessary controlled for. CONCLUSIONS: It was concluded that BHR, assessed with PC20 histamine, is probably involved in the progression of airway obstruction in asthma. In COPD, however, the degree of BHR probably only reflects the degree of existing airway obstruction. This conclusion may contribute to the ongoing debate whether it is useful to combine the diagnosis of asthma, COPD and emphysema under the umbrella-term CARA (or CNSLD = chronic non-specific lung disease). The so-called "Dutch hypothesis" which laid the foundation for this term, suggested that bronchial hyperresponsiveness plays a central role in the pathogenesis of CNSLD. The present study supports evidence that at least BHR does not seem to play the same role in the pathogenesis of asthma and COPD.

Adult↗
PubMed1993

Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. A 4-year prospective study.

OBJECTIVE: To determine if deterioration in patients with asthma or chronic obstructive pulmonary disease (COPD) during bronchodilator therapy could be slowed by additional treatment with an inhaled corticosteroid. DESIGN: A 4-year prospective study. SETTING: Twenty-nine general practices in the catchment area of the University of Nijmegen, Nijmegen, the Netherlands. PATIENTS: The study included 56 patients (28 with asthma and 28 with COPD) who showed an annual decrease in the forced expiratory volume in 1 second (FEV1) of at least 80 mL in combination with at least two exacerbations per year during bronchodilator therapy alone. Forty-eight patients completed the study. INTERVENTION: During the first 2 years of treatment, patients received only bronchodilator therapy (salbutamol, 400 micrograms, or ipratropium bromide, 40 micrograms). During years 3 and 4, they received additional treatment with beclomethasone dipropionate, 400 micrograms two times daily. RESULTS: Prebronchodilator FEV1 increased 458 mL/y (95% CI, 233 to 683 mL/y) during the first 6 months of beclomethasone treatment; FEV1 then decreased 102 mL/y (CI, 57 to 147 mL/y) during months 7 to 24. The annual decline in FEV1 during beclomethasone treatment was less than the decline of 160 mL/y seen before beclomethasone therapy (difference, 58 mL/y; 95% CI, 2 to 87 mL/y). Only in patients with asthma did beclomethasone treatment improve bronchial hyperresponsiveness (assessed by determining the concentration of histamine that provoked a 20% decrease in FEV1 [PC20]) by 3.0 doubling doses per year (95% CI, 0.8 to 5.2 doses per year). Beclomethasone treatment was associated with improvement in peak expiratory flow rate, alleviation of symptoms, and a decrease in the number of exacerbations in both patient groups. CONCLUSIONS: Adding beclomethasone, 800 micrograms daily, slowed the unfavorable course of asthma or COPD seen with bronchodilator therapy alone. This effect was most evident in asthmatic patients.

Administration, Inhalation↗
PubMed1992

Treatment with inhaled steroids in asthma and chronic bronchitis: long-term compliance and inhaler technique.

We investigated compliance and inhaler technique in 50 patients with airway obstruction (26 asthma, 24 chronic bronchitis) being treated with inhaled steroid (beclomethasone dipropionate, BDP) via a dry powder inhaler (Rotahaler omega). Patients had already participated for one year in a 2-year trial of BDP in general practice. They were treated daily with two dry powder inhalations of 400 micrograms BDP in combination with a bronchodilator. Compliance with BDP was measured by counting capsules (single-blind) at the end of a 4-month period and through a questionnaire. Counting capsules revealed non-compliance in 46% of the patients. Compliance was not related to age, sex, diagnosis or side-effects of BDP. In chronic bronchitis, but not in asthma, compliance was related to the outcome parameters of steroid treatment (pulmonary symptoms, change in lung function and non-specific bronchial responsiveness). The inhaler technique was judged insufficient in 27% of the patients. This study stresses the importance of regular instruction in inhaler technique and proper information about prophylactic steroid treatment by the general practitioner during the treatment of asthma and chronic bronchitis.

Administration, Inhalation↗
PubMed1992

Early detection of patients with fast progressive asthma or chronic bronchitis in general practice.

The morbidity and mortality due to asthma and chronic bronchitis are still rising in several countries. The aim of this study was to investigate whether early detection of patients with fast progressive asthma or chronic bronchitis in general practice was possible from a cross-sectional assessment of symptoms, smoking behaviour, quality of life, physical signs of the chest, allergy, and lung function. Data of 162 patients who had participated in a long-term randomized controlled intervention study in general practice were analysed. Fifty-six out of the 162 patients showed fast progressive disease (FPD, a rapid annual decline in FEV1 in combination with a high exacerbation rate). Measurements at the start of the study were used in a logistic regression analysis in order to detect the patients at risk (with FPD). A lower maximal expiratory flow at 50% of expired volume (MEF50) was related to an increased risk of FPD in both asthma and chronic bronchitis (relative risks of 16.8 and 8.0 respectively, p less than 0.05). Most lung function indices, but also quality of life and pack years, were significant predictors of FPD in chronic bronchitis (p less than 0.05). However, it was not possible to detect FPD reliably with these predictors separately or even with the combination of several relevant clinical variables; 18% of the patients with chronic bronchitis and 22% of the patients with asthma were still misclassified. It was concluded from this study that more than one measurement over time (monitoring) is necessary to detect the patients at risk. Monitoring should include assessments of objective ventilatory function indices (PEFR, FEV1 or MEF50).

Adult↗
PubMed1992

Effect of inhaled beclomethasone and nedocromil sodium on bronchial hyperresponsiveness to histamine and distilled water.

In a randomized, cross-over study we compared the effects of inhaled nedocromil sodium, 4 mg q.i.d., with inhaled beclomethasone dipropionate, 200 micrograms q.i.d. in 23 atopic asthmatic patients. After a 3 week single-blind placebo period, regarded as the baseline, and after 4 and 8 weeks of active treatment, drug effects were assessed with regard to bronchial hyperresponsiveness to histamine and distilled water, lung function and beta 2-agonist use. After 4 and 8 weeks of treatment, nedocromil sodium reduced the histamine responsiveness (p < 0.005 and p < 0.0005), but not the distilled water responsiveness, and did not improve lung function and peakflow measurements compared to baseline. After 4 and 8 weeks of treatment, beclomethasone caused a significant increase in lung function (p < 0.005) and decrease in bronchial hyperresponsiveness to histamine (p < 0.0005) and distilled water (p < 0.0005) as compared to baseline. beta 2-agonist use was significantly diminished after an 8 week treatment with beclomethasone, whereas nedocromil sodium had no effect. Treatment with beclomethasone was superior to treatment with nedocromil sodium with regard to bronchial hyperresponsiveness to histamine and distilled water (p < 0.0005 and p < 0.005), lung function (p = 0.003), peakflow measurements (p < 0.05) and beta 2-agonist use (p < 0.005).

Administration, Inhalation↗
PubMed1992

Inhaled beclomethasone improves the course of asthma and COPD.

The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six-monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of -158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

A comparison of six different ways of expressing the bronchodilating response in asthma and COPD; reproducibility and dependence of prebronchodilator FEV1.

Various indices are used to express the bronchodilating response. It is unclear, however, which index is most informative. The aim of this study was to compare six expressions of the bronchodilating response and to examine: 1) the independence of the prebronchodilator forced expiratory volume in one second (FEV1); and 2) the reproducibility of the bronchodilating response. Bronchodilating responses (increases in FEV1 60 min after salbutamol 400 micrograms and ipratropium bromide 80 micrograms) on six test occasions, during two years, of 183 patients (72 asthma, 111 chronic obstructive pulmonary disease (COPD)) from a large bronchodilator intervention study were used. The dependence of the prebronchodilator FEV1 was investigated both between patients (cross-sectional analysis) and within patients (longitudinal analysis) by means of linear regression analysis. The reproducibility of the bronchodilating response was calculated by means of the coefficients of variation (CVs) of the six bronchodilating responses during two years. The CVs of the six expression indices were compared by analysis of variance (ANOVA). No index was independent of the prebronchodilator FEV1. However, some indices were significantly more dependent on the prebronchodilator lung function and, therefore, less reproducible than others. The "% initial" index (change as a percentage of the prebronchodilator value) was the most dependent on the prebronchodilator lung function and had the worst reproducibility (CV ranged from 50-61%). The "% possible" (change as a percentage of the predicted minus prebronchodilator value) and "% achievable" (change as a percentage of the maximal postbronchodilator minus prebronchodilator value) indices were the least dependent on the prebronchodilator value and had the highest reproducibility (CV ranging from 34-53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Chronic extrinsic allergic alveolitis in a family with idiopathic pulmonary fibrosis: the importance of histological diagnosis.

We report a patient who presented with progressive exertional dyspnoea, chronic cough and radiographic signs of interstitial lung disease. Since several of his family members were known to have familial idiopathic pulmonary fibrosis he was also suspected to suffer from this disease. After thorough investigation, including histological examination of lung biopsies obtained by thoracoscopy, a diagnosis of chronic extrinsic allergic alveolitis was made. Current knowledge of familial idiopathic pulmonary fibrosis is discussed. This case report underlines the importance of a histological diagnosis in interstitial lung disease.

Alveolitis, Extrinsic Allergic↗