Search PubMed⌕ Search

Biomedical subjects

A K Bewtra

Publications and source records attributed to A K Bewtra.

54 records · Page 3Linked to original sources
PubMed1989

Effect of terfenadine on pulmonary function, histamine release, and bronchial challenges with nebulized water and cold-air hyperventilation.

To assess the effectiveness of terfenadine on bronchoconstriction in asthmatics, 12 asthmatic patients between the ages of 19 and 43 were challenged with ultrasonically nebulized distilled water (UNDW) and treated with terfenadine, 120 or 240 mg, or placebo in a three-way crossover double-blind study. A similar study of 12 asthmatics (nine from the UNDW trial) was performed using cold-air hyperventilation challenge (CAHC). In vitro analyses were also made of samples from ten mild asthmatics to determine the effect of terfenadine on basophil histamine release. Terfenadine, 240 mg, showed significant (P = .012) benefit over placebo in improving pulmonary function after UNDW challenge. Modest but significant (P less than .05) bronchodilator benefits were also demonstrated by terfenadine, 240 and 120 mg, after CAHC. Finally, the in vitro study showed significant inhibition by terfenadine of anti-IgE-induced histamine release from human basophils.

Adult↗
PubMed1989

Effect of terfenadine on cold air-induced bronchospasm.

Cold air hyperventilation challenge (CAHC) has been shown to induce bronchoconstriction in asthmatics. We investigated whether terfenadine, a non-sedating H1 antihistamine, had a protective effect against CAHC. Twelve mild-moderate asthmatics, sensitive to both methacholine and CAHC, underwent a double-blind 3-way crossover study of terfenadine at doses of 0, 120, and 240 mg. For four hours after administration of the study drug, pulmonary responses were measured, followed by a CAHC. There was a significant improvement in pulmonary function on the 120-mg and 240-mg days. The percent drop in FEV1 to CAHC was determined by comparing the pre-challenge baseline to the challenge responses. There was a significant attenuation in the FEV1 fall immediately after challenge on active drug days, but it was not sustained. Terfenadine appears to have an attenuating effect against CAHC-induced bronchoconstriction.

Air↗
PubMed1988

Effect of terfenadine on the bronchoconstriction induced by ultrasonically nebulized distilled water.

Ultrasonically nebulized distilled water (UNDW) has been shown to induce bronchoconstriction in asthmatics. The proposed mechanism is through changes in osmolarity of the airway fluids and subsequent release of mediators from airway mast cells. We investigated whether terfenadine has a protective effect on UNDW challenges. Twelve mild-to-moderate asthmatics responded to screening a methacholine and UNDW challenge. For four hours after the ingestion of 0, 120, and 240 mg of terfenadine pulmonary responses were performed, followed by a UNDW challenge. Nine of 12 subjects dropped 20% after 120 mg and after 240 mg. There was a suggestion of a protective effect at 120 mg (P = .054), which was significant at 240 mg (P = .012) when the areas under the dose-response curves were compared. Bronchoconstriction induced by UNDW may in part be caused by histamine release and was attenuated by an oral antihistamine.

Adolescent↗
PubMed1988

Bronchial reactivity pattern in nonasthmatic parents of asthmatics.

Genetic mechanisms have been proposed to explain the presence of asthma in families. A methacholine challenge can identify individuals with bronchial reactivity (a hallmark of asthma). It may then be possible to determine whether the presence of non-specific bronchial reactivity, as detected by a methacholine response, has potential as a genetic marker. Thirty-one non-asthmatic parent pairs of asthmatic children were selected from asthma (AF) families enrolled in a Natural History of Asthma study. Parent pairs were chosen if both gave negative responses to a modified National Heart, Lung and Blood Institute questionnaire on asthma. The methacholine response of these parents of asthmatic children had a bimodal distribution. These results show that the methacholine response can mark bronchial reactivity without the presence of clinical asthma and that a familial component of bronchial reactivity exists which may be transmitted from one generation to the next.

Asthma↗
PubMed1988

Incorporation and analysis of ultrasonically nebulized distilled water challenges in an epidemiologic study of asthma and bronchial reactivity.

The usefulness of an ultrasonically nebulized distilled water (UNDW) challenge as a screening procedure was tested in an on-going epidemiologic study of asthma and bronchial reactivity. Sixty-six individuals underwent a methacholine challenge, an UNDW challenge, and were administered a standardized respiratory disease questionnaire. To perform the UNDW challenge, subjects inhaled increasing volumes of nebulized distilled water while breathing tidally. Thirty-eight asthmatics, two former asthmatics, 14 normal, and 12 allergic subjects, were included. Sixty-six percent of the asthmatics dropped 20% from their baseline FEV1 during the UNDW challenge. Only one allergic or normal subject had a similar drop. The Pearson's correlation coefficient between methacholine and UNDW challenges was 0.60. If positive, an UNDW seems to be highly specific in supporting a diagnosis of asthma, while methacholine challenges are more useful in verifying the presence of non-specific bronchial reactivity.

Asthma↗
PubMed1987

A simple and sensitive radioreceptor assay for leukotrienes.

A simple and sensitive radioreceptor assay (RRA) for leukotrienes (LTs) was developed using a highly specific [3H]leukotriene D4 (LTD4) binding to guinea pig lung membrane homogenates. The assay can detect down to 0.15 pmol of LTD4. The values for fifty percent inhibition of bound [3H]LTD4 was 1.5 nM for LTD4, 45 nM for LTC4 and 24 nM for LTE4. LTB4 at 3.0 X 10(-5)M had no effect on [3H]LTD4 binding. The RRA for LTs in the absence of serine-borate complex was bi-specific for both LTC4 and LTD4. However, in the presence of 20 mM serine-borate this method was highly specific for LTD4. Recovery rate averaged 87.2% after ethanol extraction and evaporation of known amounts of LTD4. When the radioreceptor assay and radioimmunoassay data for leukotriene levels in the samples were compared to each other, an excellent correlation was observed with a correlation coefficient 'r' of 0.992. The assay was also validated by quantitation of Lts released from human granulocytes stimulated with calcium ionophore, A23187. The method is simpler, less expensive, and more specific for LTD4 than the other methods such as high pressure liquid chromatography and radioimmunoassay and is suitable for routine measurement of either LTD4 specifically or LTC4 plus LTD4 simultaneously in one cell system.

Animals↗
PubMed1987

Distribution of methacholine inhalation challenge responses in a selected adult population.

To determine bronchial reactivity patterns in adults, 211 subjects, 22 to 86 years of age, underwent a methacholine challenge in a Natural History of Asthma study. The diagnosis of asthma or nonasthmatic allergic diseases was based on a standardized respiratory questionnaire. Subjects were nonsmokers and had not had an infection for 1 month. Intradermal skin tests were done to a battery of common antigens. The methacholine challenge response was expressed as the area under the dose-response curve integrated to a 35% fall in the FEV1 or 800 breath units. Thirty-three subjects with asthma, 47 normal subjects from normal families (NF), 59 normal subjects from families with asthma (AF), 31 allergic subjects without asthma, 23 subjects with questionable asthma, and 18 subjects with prior asthma were studied. Overall, 50% of the subjects without asthma had a negative response to methacholine. There was a difference (p less than 0.02) in the distribution of log10 methacholine area under the dose-response curve integrated to a 35% fall in the FEV1 or 800 breath units responses in normal subjects from NFs compared to normal subjects from AFs. The allergic subjects from AF had a greater degree of bronchial reactivity compared to normal individuals from NF. The age of the normal subjects had an influence on the degree of bronchial reactivity. Methacholine challenge studies in adult patients need to be interpreted with age and family history in mind.

Administration, Inhalation↗
PubMed1987

Interpretation of the results of methacholine inhalation challenge tests.

Methacholine inhalation challenge studies are conventionally expressed as the provocative cumulative dose of methacholine that causes a 20% fall in FEV1 (PD20). This method is widely used and most suitable for expressing results for challenges in subjects with asthma. However, it is impossible to present results in this manner in other circumstances. Normal subjects and many subjects with allergic rhinitis do not have significant bronchial reactivity and will not reach a 20% fall during standard challenge protocols. This limitation precludes the use of this large population in the quantitative analysis necessary in epidemiologic, genetic, or drug studies. To compound this difficulty, a subset of patients with allergic rhinitis may demonstrate a 20% drop but have a subsequent plateau drop in FEV1. Expressing the results of their methacholine challenge with only a PD20 loses valuable information available in the test. We demonstrate that expressing results as the area beneath a dose-response curve provides useful parametric data on all studied subjects and distinguishes among subjects who might otherwise be classified as equivalent when results are expressed solely as a PD20.

Adolescent↗
PubMed1986

Methacholine inhalation challenge studies in a selected pediatric population.

To determine bronchial reactivity patterns, 400 subjects, 5 to 21 yr of age, underwent a methacholine challenge in a Natural History of Asthma study. The diagnosis of asthma or allergy was based on a respiratory questionnaire. Subjects were nonsmokers and had had no respiratory infections for 1 month. Intradermal skin tests were done. The methacholine challenge response was expressed as the area beneath the dose-response curve (Area 35). Fifty-five asthmatics, 113 normal subjects from normal families, 103 normal subjects from asthma families, 60 normal twins, and 69 allergic subjects without asthma were studied. Overall, 52% of nonasthmatics and 47% of nonallergic subjects had an Area 35 less than 4,000 (800 breath units). There was a difference (p less than 0.05) in the distribution of methacholine Area 35 responses in normal subjects from that in normal families compared with normal subjects from asthma families. The age of the nonasthmatic subjects had an influence on the degree of bronchial reactivity. Methacholine challenge studies in pediatric patients must be interpreted with age, personal atopic status, and family asthma history in mind.

Adolescent↗
PubMed1986

A group comparative study of the safety and efficacy of nedocromil sodium (Tilade) in reversible airways disease: a preliminary report.

Nedocromil sodium in a dose of 4 mg b.i.d. or q.i.d. by inhalation was used to treat asthmatic patients in a double-blind, placebo-controlled, randomized, parallel study. 80 patients (39 active drug and 41 placebo) received q.i.d. dosage and 87 patients (45 active drug and 42 placebo) received b.i.d. dosage. The patients selected were not on oral or inhaled steroids but required oral sustained-release theophylline with or without an inhaled beta-agonist aerosol. There was a significant reduction in daytime asthma symptoms (p = 0.04) and asthma severity (p less than 0.01) 6 weeks after the onset of therapy in the nedocromil sodium q.i.d. treated group as compared with placebo. In the nedocromil sodium b.i.d. treated group, the following variables showed statistically significant improvements compared with placebo: daytime and night-time asthma (p = 0.002 in both instances), wheezing assessed by auscultation (p = 0.03) and overall asthma severity (p less than 0.01). All these variables showed improvements within 2 weeks of the onset of therapy and became statistically significant at 6 weeks. Side-effects were minor and occurred only in a small number of patients. It can be concluded from this study that nedocromil sodium is a safe and effective drug in the management of asthma.

Adrenal Cortex Hormones↗
PubMed1986

Correlation of methacholine-induced non-specific bronchial reactivity and cold air hyperventilation challenge.

The degree of bronchoconstriction seen with cold air hyperventilation challenge was determined in 48 adult subjects with known degrees of methacholine-induced bronchial reactivity. The degree of bronchial reactivity as determined by the cold air hyperventilation challenge significantly correlated with the non-specific bronchial reactivity determined by a methacholine inhalation challenge. Cold air hyperventilation challenge can accurately confirm the presence of reactive airway disease.

Adult↗
PubMed1984

Specificity and sensitivity of methacholine inhalation challenge in normal and asthmatic children.

The provocative dose of inhaled methacholine required to cause a 20% drop in the forced expiratory volume in 1 sec was evaluated in two selected pediatric populations. On the basis of a standardized respiratory questionnaire, 165 individuals 5 to 21 yr of age were identified. Included were 110 normal nonatopic individuals and 55 current asthmatic subjects. Methacholine inhalation challenges were performed by use of a standard inhalation procedure. Fifty-four (98.1%) of the asthmatic subjects responded to methacholine with a 20% drop in the forced expiratory volume in 1 sec. Seventy (63.1%) of the normal individuals did not respond to methacholine. The specificity and sensitivity of the methacholine challenge was best obtained at a provocative dose of 100 breath units of methacholine.

Adolescent↗
PubMed1984

Genetic analysis of allergic disease in twins.

One hundred seven pairs of twins, sixty-one MZT and forty-six DZT, were investigated for allergic disease by a questionnaire, reaginic antibody levels, bronchial reactivity to inhaled methacholine, and skin test responses. Intrapair correlation coefficients (ri) of measured clinical markers of atopy were determined and a heritability analysis was performed. The intrapair correlation coefficient for serum IgE was 0.82 for MZT and 0.52 for DZT. The methacholine area demonstrated greater correlation in MZT with an ri of 0.67 compared to 0.34 for DZT. The total ISTS had an intrapair correlation coefficient of 0.82 in MZT and 0.46 in DZT. Our analysis demonstrates that methacholine sensitivity, total serum IgE levels, and total skin test scores to be heritable traits and suggests a genetic contribution to their expression.

Adolescent↗
PubMed1984

Protection by ipratropium bromide and metaproterenol against methacholine and histamine bronchoconstriction.

To establish relative protection against methacholine and histamine, 40 micrograms of ipratropium bromide, an anticholinergic compound, 1.3 mg of metaproterenol or placebo aerosols were administered by metered-dose inhaler prior to inhalation challenge with methacholine or histamine in nine asthmatic subjects. Double-blind, randomized challenges were performed. Subjects required a mean methacholine dose of 1.72 +/- 0.73 and 2.46 +/- 0.72 (Ln inhalation units), and mean histamine dose of 2.16 +/- 0.65 and 2.68 +/- 0.49, to cause a drop of 20% and 35% respectively in the FEV1 following the placebo. In the methacholine challenges, both ipratropium bromide and metaproterenol had significant protection as compared to placebo (P less than 0.001). There was no statistical difference in the degree of protection against methacholine between ipratropium bromide and metaproterenol. In histamine challenges, metaproterenol had significant protection as compared to the placebo, while ipratropium bromide did not protect against histamine.

Adolescent↗
PubMed1980

Protective effect opf lodoxamide tromethamine on allergen inhalation challenge.

Lodoxamide tromethamine (U-42,585E) is a new drug intended for prophylaxis of mast cell-mediated allergic disease. It is a water-soluble, cromolyn-like agent with demonstrated activity in rat peritoneal mast cell assay, rat percutaneous anaphylaxis (rat PCA) and sensitized rhesus monkey airway system. Ten allergen-sensitive asthmatics were pretreated with lodoxamide (0.01, 0.1, or 1.0 mg) or placebo, then challenged with serial dilutions of allergen extract. Analysis of allergen dose-response curve parameters shows that pretreatment with lodoxamide offers significant protection against experimental allergen-induced bronchoconstriction. At 0.01 mg, lodoxamide was effective in over half the subjects tested. Administration of lodoxamide by inhalation at doses of 0.1 and 1.0 mg uniformly allowed subjects to tolerate significantly larger doses of inhaled allergen. Side effects observed at these doses were minimal.

Adolescent↗
PubMedDate not supplied

The usefulness of questionnaire-derived information to predict the degree of nonspecific bronchial hyperresponsiveness.

Nonspecific bronchial hyperresponsiveness (BHR) is a hallmark of clinical asthma, but can be present in nonasthmatics as well. The diagnosis of asthma is based on clinical grounds, and no laboratory procedure can definitely establish its presence. This poses a problem in studies of asthma. If epidemiological studies are to provide valid information, the tools used must have a relative degree of predictive or diagnostic ability. This report determined whether the American Thoracic Society-Division of Lung Disease (ATS-DLD) respiratory questionnaire has the ability to predict different degrees of non-specific BHR. In the years 1983-1990, when the ATS-DLD questionnaire was used in our Natural History of Asthma study, 192 subjects completed the ATS-DLD questionnaire and underwent a standardized methacholine challenge. A recursive partitioning analysis of the ATS-DLD questionnaire was able to predict which questions would likely be answered if the subject had nonspecific bronchial reactivity to inhaled methacholine of 100 and 200 breath units. Positive responses for questions concerning treatment for asthma, wheezing, or shortness of breath, and emergency treatment for asthma predicted the presence of increased bronchial reactivity.

Adolescent↗