Theophylline Medication Research Articles

Oral Candidal Load and Oral Health Status in Chronic Obstructive Pulmonary Disease (COPD) Patients: A Case-Cohort Study.

Objective The objective of this study was to determine the candidal load of the patients with Chronic Obstructive Pulmonary Disease (COPD) and evaluate the oral health status of subjects with COPD. Material and Methods. N = 112 COPD subjects and N = 100 control subjects were included in the study. The selection of COPD cases was confirmed based on the set criteria from the American College of Physicians. The oral health status was assessed as per WHO criteria to determine the score of decayed, missing, and filled teeth (DMFT), significant caries index (SiC), community periodontal index and treatment needs (CPITN), and oral hygiene index-simplified (OHI-S). Gram staining was performed to identify Candida using the whole saliva. Quantitative evaluation of the candidal load was carried out using Sabouraud Dextrose Agar (SDA). Chrome agar was used to differentiate between the commensal carriages. A statistical analysis paired t-test and 95% confidence interval (CI) for proportions was carried out using STATA software. Results Candidal growth was found in 21.42% (n = 24) of COPD cases and 1.1% (n = 11) of control cases (p < 0.05) (95% CI 0.45, 0.59). The DMFT score was 8.26 in COPD subjects and 4.6 in controls, the SiC score was 16.42 in COPD subjects and 10.25 in controls, and the CPITN score for both COPD and control cases was score 2. Conclusion In conclusion, there was a higher candidal load among subjects suffering from COPD. Theophylline medication can be a risk factor for increased candidal load in COPD patients.

Effects of caffeine and theophylline on coronary hyperemia induced by adenosine or dipyridamole

The aims of this review are to examine the biochemical features of theophylline, caffeine, adenosine, and dipyridamole, their effects on coronary hyperemia, and to make recommendations on performing hyperemic lesion assessment after taking caffeine or theophylline. It is commonly thought that caffeine and theophylline interfere with adenosine and dipyridamole induced coronary hyperemia, thus frequently delaying scheduled assessments after inadvertent consumption. However, a limited amount of studies address the interactions of these substances thus leaving no clear consensus on when to delay coronary assessment after their intake. For biochemical information on each substance, online and textbook references were utilized. For studies on the interactions of the substances with coronary hyperemia, broad search terms such as "caffeine AND adenosine" were applied in the major research data bases. A serum caffeine level of 3 to 4 mg/L at the time of an adenosine-hyperemia study does not affect the ability of perfusion stress imaging to detect coronary artery disease. The interactions of theophylline with adenosine-hyperemia are less clear while both caffeine and theophylline show significant interaction with dipyridamole-hyperemia. For dipyridamole-stress myocardial perfusion studies, caffeine products and theophylline medications should be discontinued for 24 hr. For adenosine-stress myocardial perfusion studies, theophylline medications should be discontinued for 12 hr; however, one cup of coffee may be taken up to 1 hr before the test without necessitating a delay or cancellation of the study. These same considerations hold true for patients undergoing cardiac catheterization and intravenous adenosine-induced hyperemia.

Daten zum wirkspiegelgerechten Einsatz von Theophyllinpräparaten

Background: Theophylline has been widely used for decades in the treatment of asthma and chronic obstructive pulmonary disease because of its bronchodilator activity as well as its immunomodulatory, anti inflammatory, and bronchoprotective effects. On the other hand, its use has declined with the advent of potent steroid inhalants. In Austria, the current frequency of prescription is 6 in 1,000 insurants, according to Austrian health insurance data. Slow-release theophylline has become an established medication for asthma, and the development of adequate assays made drug monitoring readily available. Since the efficacy and toxicity of theophylline are closely related to the serum drug concentration, reflected by an adequate serum level of 10 - 20 mg/l, monitoring of its serum concentration is essential. Methods: This was an open-label, 1-year prospective, monocenter study, performed in male as well as female patients consecutively admitted to the Department of Environmental Dermatology, Medical University of Graz, Austria. The only inclusion criterion was taking a theophylline medication at the time of admission. Test parameters were gender, age, body mass index, nicotin abuse, medication, blood levels of the transaminases as well as serum levels of theophylline (measured by EIA). Results: 25 patients could be included (17 female, 8 male). At the time of admission, only 20% of the patients under theophylline medication had an adequate theophylline serum level, in 76% of the patients the drug was underdosed, in 4% the theophylline was found to be overdosed. After 3 days of controlled intake of theophylline preparations in 74% of the patients, an adequate theophylline level could be measured, but 36% of the patients continued to be underdosed. Conclusions: Because of the wide variation in theophylline metabolism between individuals and the narrow therapeutic index of its use, monitoring of theophylline serum levels is essential to reach an effective steady state. Despite this common knowledge, the data of our study suggest that the majority of outpatients may be below an effective level. Limitation of our study is the small number of patients included, and a larger study may be necessary to confirm the results.

How Should Health-Related Quality of Life Be Assessed in Patients With COPD?

The traditional approach of caring for patients with chronic respiratory disease has been to rely on pulmonary function tests to quantify the severity and to assess response to therapy. However, patients with respiratory conditions seek medical attention because of symptoms, particularly dyspnea, and impaired ability to function, which clearly impact on an individual's health-related quality of life (HRQOL). Accordingly, instruments have been developed to provide a standardized method to measure health status and levels of impairment. One of the major reasons for measuring HRQOL is to detect how much HRQOL has changed in response to therapy (an evaluative instrument). A minimum clinically significant change has been established for some HRQOL instruments in order to indicate the relative value of any measured change and to guide the interpretation as to whether the change is "clinically meaningful." Selected studies using disease-specific instruments have demonstrated that beta(2)-agonist, anticholinergic, and theophylline medications can improve HRQOL, as compared with placebo therapy.

Circadian Rhythms in the Pharmacokinetics and Clinical Effects of Beta-agonist, Theophylline, and Anticholinergic Medications in the Treatment of Nocturnal Asthma

Published asthma consensus reports now acknowledge that asthma is a nocturnal disease in as many as 75% of those afflicted by this medical condition. Nonetheless, the treatment of this chronic obstructive pulmonary disease in the clinic continues to be based primarily on homeostatic considerations in that it relies on long-acting bronchodilator and other therapies formulated and scheduled to ensure constant or near-constant levels of medication during the 24h. The need of asthma patients prone to nighttime attacks is not the same during the day and night; the therapeutic requirements of patients who experience nocturnal asthma, especially ones with the more severe forms of the disease, are often not satisfied by conventional medications. The therapeutic response and patient tolerance to bronchodilator medications can be improved markedly when the medications are proportioned during the 24h as a chronotherapy, that is, when more medication is delivered during nighttime sleep than daytime activity, as verified by numerous studies. This article reviews how the body's circadian rhythms influence the pharmacokinetics and effects of commonly prescribed asthma therapies and addresses why and how they must be taken into consideration to increase the effectiveness of asthma treatment.

Social Factors Associated With Behavioral Problems in Children With Asthma

The objective of this study was to describe the proportion of children with a behavior problem and examine which independent variables are associated with the presence of a behavior problem in a group of 392 inner-city children with asthma. Data on child asthma symptoms, medication use, health-care utilization, and school absences were obtained from the parent during a structured telephone interview. Included in the interview was a measure of behavior problems and social support questions. Children classified with a high level of asthma symptoms were more than twice as likely to experience a behavior problem than children classified with a low level of asthma symptoms (P = 0.002). Use of theophylline medication was not correlated with behavior problems (P = 0.45). Significant variables were low level of social support and high or moderate level of asthma symptoms. We have identified a group of children at risk for behavior problems, specifically in families that lack adequate social and financial resources.

Respiratory illness, beta-agonists, and risk of idiopathic dilated cardiomyopathy. The Washington, DC, Dilated Cardiomyopathy Study.

An epidemiologic study was carried out to examine the possible role of beta-agonists and other respiratory medications in the development of idiopathic dilated cardiomyopathy. Associations with respiratory medications, bronchial asthma, emphysema, and chronic bronchitis were examined by comparing newly diagnosed cases (n = 129) ascertained from five Washington, DC, area hospitals for the period 1990-1992 with neighborhood controls (n = 258) identified by using a random digit dialing technique. The cases and controls were matched on sex and 5-year age intervals and were compared in the analysis using conditional logistic regression methods. A statistically significant association was observed between idiopathic dilated cardiomyopathy and history of emphysema or chronic bronchitis (adjusted odds ratio (OR) = 4.4, 95% confidence interval (CI) 1.6-12.4). The association with bronchial asthma was of borderline significance (adjusted OR = 1.9, 95% CI 0.9-4.2). Associations were also observed with use of oral beta-agonists (adjusted OR = 3.4, 95% CI 1.1-11.0) and beta-agonist inhalers or nebulization (adjusted OR = 3.2, 95% CI 1.4-7.1), as well as with use of oral corticosteroids, inhaled corticosteroids or cromolyn, and theophylline medications. A total of 20.0% (23 of 115) of the cases had a reported history of beta-agonist inhaler use compared with 6.7% (17 of 254) of the controls. The strength of these associations was diminished when the temporal relation between exposure to beta-agonist inhalers or oral preparations and clinical diagnosis of idiopathic dilated cardiomyopathy was taken into account, however, and the associations with duration of beta-agonist medication use were not statistically significant (p > 0.05). The results of this study suggest, but do not prove, that use of beta-agonists has an etiologic role in idiopathic dilated cardiomyopathy.

Infantile spasms associated with theophylline toxicity

We report on a 6-month-old infant with asthma who developed spasms and hypsarrhythmia on the electroencephalogram (EEG) shortly after starting oral theophylline medication. Theophylline levels at that time were just above the upper normal range. The spasms stopped and the EEG normalized when theophylline was discontinued and nitrazepam therapy started. On follow-up over the next 3 years there was no recurrence of seizures and the child's neurodevelopment has been normal. Nitrazepam was stopped at 10 months and the waking and sleeping EEG were normal at 14 months. We believe that the infantile spasms were caused by theophylline.

Comparison of Patients' Compliance With Prescribed Oral and Inhaled Asthma Medications

Noncompliance with medications is one of the most serious problems facing health care today. However, methods to measure compliance have many limitations. To measure specific drug compliance and dosing frequency of two asthma medications, we used medical records data and pharmacy claims data from 276 patients who had concurrent prescriptions for inhaled anti-inflammatory agents and oral theophylline. Patients were randomly selected from the pharmacy claims data files of a health maintenance organization. The patients' medical records were reviewed, and records that did not contain clear documentation of the medication, dose, and dosing frequency were excluded. Data from the remaining 119 medical records were compared with data from pharmacy claims to calculate compliance rates for each medication. Our calculations showed that patients were significantly more compliant with prescribed theophylline medication than with two inhaled anti-inflammatory medications (P = .0001). No significant differences in compliance were found relative to prescribed dosing frequency (twice daily or less compared with three times daily or more) for either medication (P = .6517). Comparison of medical record data with pharmacy claims data is an effective indirect measure of patients' compliance with prescribed oral theophylline and inhaled anti-inflammatory agents. Additional interventions must be pursued for patients with asthma regarding adherence to regimens for their prescribed inhaled anti-inflammatory agents.

The Mystery Ingredients: Sweeteners, Flavorings, Dyes, and Preservatives in Analgesic/Antipyretic, Antihistamine/Decongestant, Cough and Cold, Antidiarrheal, and Liquid Theophylline Preparations

Pharmaceutical preparations may contain a variety of excipients ("inert ingredients"). These excipients are generally inactive; however, rare adverse effects caused by excipients have been reported. Information about the excipients in a particular preparation is not readily available. The information about sweeteners, flavorings, dyes, and preservatives for the chewable and liquid preparations of over-the-counter and prescription products of antidiarrhea, cough and cold, antihistamine/decongestant, analgesic/antipyretic, and liquid theophylline medications was collected. Information about excipients in 102 chewable and liquid preparations was compiled. An average preparation contained two sweeteners. Saccharin and sucrose were the most common sweeteners found--each was present in 52 preparations--followed by sorbitol, glucose, fructose, and others. For 36 of the 102 preparations, type of flavoring was not specified. In the remaining preparations, cherry was the most common flavoring, followed by vanilla and lemon. Twenty-one different dyes and coloring agents were used. Red dye No. 40 was the most common (42/102), followed by yellow No. 6 (27/102). Of the eight preservatives used, sodium benzoate and methylparabens were present in 42 and 27 of the preparations, respectively. Tables detailing these excipients and adverse effects reported are presented. The tables should be helpful to physicians in selecting preparations containing different excipients when an adverse reaction occurs. The mandatory labeling of excipients in all pharmaceutical preparations is the only way that physicians and patients can be fully informed.

Cytogenetic study in peripheral blood lymphocytes from asthmatic patients receiving continued therapy with theophylline

Possible cytogenetic effects of theophylline have been investigated in asthmatic patients undergoing continuous therapy with this drug. Sister-chromatid exchanges (SCE), chromosome aberrations (CA) and proliferating rate indices (PRI) were evaluated in cultured peripheral blood lymphocytes from patients receiving theophylline alone, theophylline plus inhaled β 2 adrenergic drugs or theophylline in combination with β 2 adrenergic agents and corticoids. Two samples from each individual were obtained in order to perform a prospective study: before the theophylline medication (sample A) and at a time after the beginning of treatment (sample B). After treatment (66.3 ± 37.8 days), an increase in SCE was observed without modifications either in PRI or in CA. Patients receiving β 2 adrenergics or β 2 adrenergics plus glucocorticoids before and during theophylline treatment, did not respond differently than those on theophylline alone.

Intravenous Theophylline after Beta2-Agonist Treatment in Severe Acute Asthma. Effect on Patients Who Are Not Pre-treated with Theophylline

The effect of i.v. theophylline after high-dose beta 2-agonist treatment in severe acute asthma was studied in 30 patients from a multicentre study who reported not having taken theophylline during the last 24 hours. One hour after the start of inhaled or i.v. salbutamol treatment, all patients received 6 mg/kg of i.v. theophylline. The plasma concentration 30 minutes after the start of the theophylline infusion was 78 +/- 13 mumol/l (mean +/- SD). The mean change (delta) in peak expiratory flow (PEF) was 8 +/- 6% of the predicted 30 minutes after the theophylline infusion and 7 +/- 5% 60 minutes after it. The increase in PEF was greater in this patient group than in a group of 101 patients from the same multicentre study who were on theophylline medication and were therefore given a reduced dose (3 mg/kg) (7 +/- 5 vs. 4 +/- 6% of the predicted value, p < 0.01). The proportion of patients with an increase in PEF of > or = 10% of the predicted at discharge was 27% (8/30) in the patient group in this investigation and 14% (14/101) in the group who was on theophylline treatment.

Sleep Disturbances in Asthma: Theophylline Versus Enprofylline

A double-blind cross-over study was performed on 22 asthmatic patients receiving maintenance treatment with theophylline who, in a previous study, had reported sleep problems. In one of two three-week periods the theophylline medication was replaced by an equipotent dose of slow-release enprofylline. Analysis of sleep questionnaires answered after each treatment period, and sleep diaries filled in throughout the study, showed no significant differences in the quality of sleep between the treatments. Peak expiratory flow (PEF) in the morning did not differ between the treatment periods, but mean PEF in the evening was slightly higher (20 l/min) during theophylline treatment. It was concluded that replacement of theophylline by enprofylline did not improve the quality of sleep subjectively in this group of theophylline treated asthmatics. The results suggest that adenosine receptor antagonism may not be a significant cause of sleep disturbances in asthmatic patients who are receiving theophylline as maintenance treatment.

A case of occupational allergic bronchopulmonary aspergillosis unique to Japan

A 15-year-old female was diagnosed in 1980 as having allergic bronchopulmonary aspergillosis (ABPA) due to Aspergillus fumigatus based on Rosenberg and Patterson's criteria for the disease. The patient is the eldest daughter of a family of domestic brewers of soy sauce and bean paste in a small village, an occupation unique to Japan. The brewing process involved the use of Aspergillus oryzae as a fermenting agent. The patient had experienced episodic wheezing and pulmonary infiltrates during the same seasons in the previous three years, corresponding to the time of the highest A oryzae spore concentrations in the living area, suggesting high exposure to the Aspergillus spores in the aetiology of her exacerbations. She had a prominent family history of atopy and was demonstrated to be sensitive to a variety of aeroallergens in addition to A fumigatus. She was treated effectively by bronchial toiletting via broncho-fibrescope and theophylline medication until April 1981, when she moved to another city. During her life there, chest X-rays repeatedly showed abnormal shadows, and she was treated with inhalations of amphotericin B and bronchial toiletting several times at a hospital. She returned to her home town after seven years in April 1988 and visited the hospital to check her condition. Although she had been away from heavy exposure to A oryzae spores for seven years, precipitins to the culture medium of A oryzae were demonstrated to be far more prominent than those to A fumigatus antigen. Although her family had been exposed to A oryzae spores continuously, the patient was the only family member with ABPA due to A fumigatus and possibly due to A oryzae.(ABSTRACT TRUNCATED AT 250 WORDS)

Theophylline and School Performance-Reply

In Reply —The major finding of our study was that children with moderate to severe asthma had average to slightly above average scores for academic performance. Only a small percentage of children scored less than 1 SD below the mean for either reading or math. Having scores at the lower end of these relatively normal values correlate with certain features of the asthma, as reiterated by DuHamel and Furukawa in their letter. A number of other variables defining asthma and its treatment, including being taken at the time of the evaluation were considered, but did not correlate with performance (p 474). Use of theophylline medication was recorded (Table 1, p 472) and included in this analysis. Theophylline medication may not have correlated with because such a high percentage (94%) of the children were using the medication. It is also possible that theophylline had an effect on performance, but

Theophylline Minimally Inhibits Bronchoconstriction Induced by Dry Cold Air Inhalation in Asthmatic Subjects

The aim of this study was to evaluate the effect of a sustained-release theophylline preparation on bronchial responsiveness to cold dry air inhalation in asthmatic subjects. Sixteen adult subjects with asthma in a clinical steady state underwent 3 isocapnic cold air challenges on 3 consecutive days at a time when they had not received oral theophylline medication over the past 3 days. The dose of cold air causing a 20% (PD20) fall in FEV1 was obtained from each subject's dose-response curve. Subjects were then administered active or placebo sustained-release theophylline preparations according to a double-blind, randomized, two-treatment crossover design. Medication was given for a minimum of 3 consecutive days. PD20 was reassessed on 4 different days, 3 to 4 h after receiving active or placebo medication (two visits for each medication). We found a significant bronchodilator effect of theophylline as compared to the placebo (mean +/- SD differences in changes of FEV1 of 8.8 +/- 1.9%). We also documented a significant blocking effect of the active medication as opposed to the placebo on PD20 (p = 0.01). This difference (mean = 0.18 on the loge scale) was statistically beyond the intraindividual between-day variability observed on the 3 control days (p less than 0.001) but was physiologically minimal. This blocking effect was also partially related to changes in airway caliber. We conclude that theophylline showed a blocking effect on bronchial responsiveness to dry cold air, which was physiologically minimal and was partially related to changes in airway caliber.

Asthma and pregnancy: a prospective study of 198 pregnancies.

A study was designed to investigate whether asthma, when carefully managed, is associated with an increased risk of complications in connection with pregnancy. One hundred and eighty one asthmatic women were monitored during 198 pregnancies. Antiasthmatic treatment consisted of inhaled beta 2 adrenergic drugs, beclomethasone, sodium cromoglycate, oral theophylline, and systemic corticosteroids as needed. Postpartum information on asthmatic symptoms and infant feeding was collected by means of a questionnaire. A control group of 198 non-asthmatic pregnant women was matched for age and parity. Atopic women had less severe asthma than non-atopic women. During pregnancy 40% of the patients were managed with the same antiasthmatic medication as before pregnancy; 18% needed less and 42% more medication. Pre-eclampsia occurred more often in asthmatic than control subjects, especially in patients with severe asthma. Hypoglycaemia occurred more often in infants of mothers with severe asthma than in infants of mothers with less severe disease. Theophylline medication at term did not influence labour or delivery. Asthma caused no emergencies during labour. Among the asthmatic subjects 28% of babies were delivered by caesarean section compared with 17% in the control group. There was no difference between asthmatic and control subjects with regard to length of gestation, birth weight, incidence of perinatal deaths, low Apgar scores, neonatal respiratory difficulties, hyperbilirubinaemia, or malformations. It is concluded that severe asthma or systemic corticosteroid treatment (or both) during pregnancy seems to increase the incidence of mild pre-eclampsia in the mother and hypoglycaemia in the infant. The findings suggest that careful supervision of asthma during pregnancy and labour by obstetricians and chest physicians working in close collaboration should prevent most of the serious obstetric and neonatal complications of asthma in pregnancy reported by previous authors.

Airway obstruction and airway wall instability in cystic fibrosis: the isolated and combined effect of theophylline and sympathomimetics.

Multiple aspects of lung function were measured in 17 cystic fibrosis (CF) patients on four occasions: without therapy (0); with oral theophylline medication (Th); after inhalation of salbutamol (beta 2); and with combined medication (Th + beta 2). In addition to routine measurements, partial and maximum expiratory flow-volume (MEFV) curves were superimposed, and the flow transient equivalent of the MEFV curve was determined. Its volume dimension (volume of airway contribution, VACMEFV) partially reflects airway distensibility. Changes in airway compressibility--the other consequence of airway wall instability--were assessed by observing changes in end-expiratory flow rate. Airway resistance, expired volumes, and early expired flow rates, as well as VACMEFV improved significantly after beta 2 medication. Mean end-expiratory flow also increased after beta 2; in two patients, however, it decreased significantly, indicating that enhanced airway compression dominated over the release of bronchospasm. The alone had only minor effects on lung function. Early expired volume and flow rates as well as VACMEFV showed no significant difference between beta 2 alone and Th + beta 2; airway resistance even decreased significantly with this drug combination. End-expiratory flow rate, however, was significantly lower after Th + beta 2 than after beta 2 alone. Although theophylline does not alter lung function in most patients with CF, sympathomimetics relieve bronchospasm in many, but they enhance airway compressibility and thereby decrease peripheral expiratory airflow in some.(ABSTRACT TRUNCATED AT 250 WORDS)

The interaction of erythromycin with theophylline.

We have studied the interaction of erythromycin with theophylline. We gave ten healthy volunteers theophylline as an intravenous loading dose (5 mg X kg-1) over 1 h, followed by a maintenance infusion (0.5 mg X kg-1 X h-1) for 5 h. A second infusion of theophylline was given after 9 days of treatment with 1 g erythromycin base daily, and the concentrations of theophylline were determined during the infusion periods. The concentrations of erythromycin were measured for 8 h, after one week of treatment, and also after the last erythromycin dose, simultaneously with the second theophylline infusion. Concentrations within the therapeutic range were obtained with both drugs. A significant increase in both AUC and mean plasma concentrations of theophylline was seen during erythromycin treatment. The plasma clearance of theophylline was reduced in 9 of the 10 subjects. Renal clearance increased correspondingly, but the change was not statistically significant. Serum concentrations of erythromycin fell significantly, by more than 30%, with concurrent theophylline medication. We conclude that an interaction between theophylline and erythromycin, affecting both drugs, can be shown with concentrations of the drugs within the therapeutic range.

Oesophageal function and symptoms in moderate and severe asthma.

Fifty-five children and adolescents, 8 to 19 years of age, with moderate or severe asthma, and 28 healthy volunteers, 11 to 16 years of age, were interviewed about oesophageal and bronchial symptoms and investigated with oesophageal manometry combined with pH-reflux tests, an acid perfusion test and an acid clearing test. Oesophageal dysfunction (OD) was significantly more common in asthmatic (60%) than in healthy (14%) subjects (p less than 0.01). Ten of 18 subjects (56%) with frequent nocturnal or morning asthma had a positive acid perfusion test as compared to 16% of patients with less severe asthma (p less than 0.01). Non-allergic asthma was not significantly more related to OD than was allergic asthma. Presence of OD was not related to present beta 2-stimulant or theophylline medication. Symptoms of OD had a sensitivity of 52% and a specificity of 100% regarding OD in the asthmatic subjects. In conclusion, asthma was frequently associated with OD. There is indirect evidence that OD, especially acid hypersensitivity of the oesophagus, can aggravate asthma.