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Biomedical subjects

A Cartier

Publications and source records attributed to A Cartier.

At least 109 records · Page 6Linked to original sources
PubMed1992

Sustained improvement in asthma with long-term use of formoterol fumarate.

Inhaled formoterol fumarate, a long acting beta 2 agonist, produces bronchodilatation that is sustained for approximately 12 hours. To determine whether such bronchodilator effects are maintained and asthma control sustained during chronic administration, we monitored airflow indices and clinical control in 112 asthmatic patients who self administered formoterol twice daily for periods ranging from 9 to 12 months. Subjects were recruited immediately following completion of a 3-month double-blind comparison of formoterol, 12 micrograms, bid versus salbutamol, 200 micrograms, qid. Assessments were conducted at baseline, 3, 6, and 9 months, where baseline represents the final visit of the 3-month comparative study. Patients were asked to complete diary cards and twice daily PEFR for a 2-week period before each assessment. Throughout the follow-up study, there was no indication of worsening of asthma control or deteriorating lung function. For the patients who continued to receive formoterol, the previous improvement in asthma control and lung function was maintained at the level reached in the 3-month study. There was an improvement in flow rates and asthma symptoms in the group switched from salbutamol to formoterol by the first clinic visit. This improvement in asthma control and lung function was maintained over the subsequent 6 months. Formoterol was well tolerated during the study period. We conclude that prolonged use of formoterol fumarate twice daily results in sustained improvement in symptoms and flow rates in asthma with no evidence of tachyphylaxis.

Adolescent↗
PubMed1992

Occupational asthma: validity of monitoring of peak expiratory flow rates and non-allergic bronchial responsiveness as compared to specific inhalation challenge.

The sensitivity and specificity of monitoring peak expiratory flow rates (PEFR) and bronchial responsiveness to the provocative concentration of histamine or methacholine (PC20) has been determined as compared to specific inhalation challenges in the diagnosis of occupational asthma. A prospective study of 61 subjects referred for occupational asthma to various agents was performed. PEFR was assessed every 2 h during a period away from work for at least 2 weeks. The period at work was 2 weeks, or less if there was increased symptomatology or marked changes in PEFR. At least one PC20 assessment was obtained at work and away from work. Graphs of PEFR and PC20 values were interpreted in blind fashion by three experienced readers. There was complete agreement among the three in 54 out of 61 instances (78%). Twenty five out of 61 subjects (41%) had positive specific inhalation challenges. The best index for comparing results of PEFR with specific inhalation challenges was the visual analysis of PEFR with sensitivity and specificity of 81% and 74%. All of the numerical indices were significantly less satisfactory. We conclude that visual analysis of PEFR is an interesting tool for investigating occupational asthma, although sensitivity and specificity values do not seem satisfactory enough to warrant using it alone.

Adult↗
PubMed1991

Reassessment of the temporal patterns of bronchial obstruction after exposure to occupational sensitizing agents.

Typical asthmatic reactions after exposure to common or occupational allergens have been classified as isolated immediate, early late, late, and dual (Pepys and Hutchcroft, 1975). Atypical reactions can also occur, but their temporal behavior and frequency are unknown. We analyzed 69 bronchospastic reactions after exposure to three types of occupational sensitizers in the laboratory: isocyanates, western red cedar, and IgE sensitizing agents. Graphs of the reactions were presented to three observers in a blind, randomized way. Reactions were defined as follows: (1) typical patterns, that is, isolated immediate, early late, late, and dual, as put forward by Pepys and Hutchcroft, and (2) atypical patterns including progressive (onset, during, or minutes after exposure, progressing to a maximum reaction 5 to 6 hours later) and square waved (similar to a dual reaction but with only partial recovery [less than 10%] between the immediate and late falls in FEV1). Some curves were also analyzed by polynomial regression. The three observers agreed in 59/69 cases (86%), and a consensus was reached after discussion for the remaining subjects. Fifteen of 63 (22%) reactions were atypical. IgE-mediated reactions and reactions to red cedar were, respectively, mainly of the immediate and late types. The distribution of reactions to isocyanates, however, was significantly different (chi-square, 6.1; p = 0.01), the "progressive" pattern occurring in 7/23 instances (30%). There was a satisfactory concordance between visual assessment and polynomial fit analysis in distinguishing dual from square-waved reactions. We conclude that isocyanates frequently cause atypical progressive bronchospastic reactions that are rarely observed after exposure to IgE agents and western red cedar.

Adult↗
PubMed1991

Is the clinical history a satisfactory means of diagnosing occupational asthma?

In some countries a diagnosis of occupational asthma for medicolegal purposes is made when a questionnaire is suggestive and the individual is exposed to a product known to be a sensitizer. The value of an open questionnaire administered by physicians with experience in occupational asthma is unknown, however. We prospectively assessed all subjects (162) referred to our clinic because their physicians thought their asthma might be work related. The medical questionnaire included questions about the nature of the symptoms (dyspnea, wheezing, cough, and chest tightness) and the timing (worse at work or after a shift at work or improved during weekends or holidays). An initial clinical assessment was set by the physician on a scale that ranged from highly probable to probable, uncertain, unlikely, or absent. Subjects then underwent objective assessment with specific inhalation challenges (n = 72), serial monitoring of peak expiratory flow rates for periods at work and away from work (n = 29), or both (n = 61), to confirm or rule out the diagnosis of occupational asthma. A total of 75 subjects (46%) were shown to have occupational asthma. Symptoms alone (type and timing) did not provide a satisfactory differentiation between those subjects with and those without occupational asthma. For example, 66 of 75 (88%) subjects with occupational asthma said that their symptoms improved during holidays, but 66 of 87 (76%) subjects without occupational asthma experienced a similar improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma.

We compared the efficacy of inhaled formoterol, a long-acting beta 2-agonist, with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial. Patients were allocated in randomized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications. Patients were allowed to use "rescue" 100-micrograms albuterol puffs on an as-needed basis. Mean baseline FEV, in the morning before bronchodilator was 2.14 +/- 0.76 L and 1.98 +/- 0.71 L for the formoterol and albuterol groups, respectively, these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1. Measured at each clinic visit, morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group, the greatest difference being in Week 8 (2.40 +/- 0.77 versus 1.92 +/- 0.66 L, p less than 0.001). Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8, the trend not reaching statistical significance at other times. Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial (17 versus 42 L/min at Week 12, p less than 0.0001). The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4, 8, and 12 as were the number of sleep disruptions during Weeks 2, 4, 6, 8, and 12. Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Comparison of peak expiratory flow rate and FEV1 in assessing bronchomotor tone after challenges with occupational sensitizers.

Bronchial responses to occupational sensitizers measured by peak expiratory flow rate (PEFR) and forced expiratory volume in 1 s (FEV1) during late reactions (between 90 minutes and 8 hours after exposure) were compared in two groups of 88 subjects who had undergone specific inhalation challenges in the laboratory. The first group had what was considered a positive reaction (a fall of at least 15 percent in FEV1) whereas the second group's reaction was interpreted as negative (fall in FEV1 less than 15 percent). Although the correlation in terms of percentage of change from baseline values was statistically significant, the correspondence was poor. PEFR proved far less sensitive than FEV1 in detecting a reaction. Whereas the mean maximum change in FEV1 overall was 27 percent, the mean maximum change in PEFR at the same time interval was only 16 percent. Moreover, individual correlations between the percentage of change in FEV1 and PEFR were satisfactory (r2 greater than 0.80) in only 32/88 subjects (36 percent). No subject who was considered to have a negative challenge according to FEV1 had a change in PEFR greater than 20 percent. We therefore conclude that changes in PEFR are far less sensitive than changes in FEV1 in detecting responses during late reactions to occupational sensitizers.

Adult↗
PubMed1990

Late asthmatic reactions to occupational sensitizing agents: frequency of changes in nonspecific bronchial responsiveness and of response to inhaled beta 2-adrenergic agent.

Late asthmatic reactions have been demonstrated, generally, to increase bronchial responsiveness and are believed to respond poorly to inhaled bronchodilator. To assess the frequency of changes in bronchial responsiveness, we reviewed the records of 101 subjects with late asthmatic reactions and of 63 subjects with isolated immediate reactions after specific inhalation challenges to various occupational agents. These subjects had undergone nonspecific inhalation challenges to histamine or methacholine on a control day and after the late reaction when FEV1 had returned to +/- 10% baseline. We also reviewed 99 cases of subjects with late reactions who were administered an inhaled beta 2-agent (albuterol, 200 micrograms) during the late reaction. Fifty-seven/101 (56%) subjects with late reactions and 24/63 (38%) subjects with isolated immediate reactions demonstrated a twofold or greater change in provocative concentration of histamine or methacholine causing a 20% change in FEV1 (PC20) from baseline (p = 0.02; odds for the presence of significant changes in PC20 in subjects with late reactions, 56%; odds for the absence of significant changes in PC20 in subjects with immediate reactions, 62%). Changes in FEV1 greater than 20% after administering albuterol at the time of the late reactions occurred in 78% of the subjects tested; in 66%, FEV1 returned to greater than 90% baseline. This retrospective study demonstrates that changes in bronchial responsiveness after late reactions are not constant and do not appear to distinguish satisfactorily late from immediate reactions. Furthermore, late reactions respond well to beta 2-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1990

A 3-month evaluation of the efficacy of nedocromil sodium in asthma: a randomized, double-blind, placebo-controlled trial of nedocromil sodium conducted by a Canadian multicenter study group.

Nedocromil sodium is a pyranoquinoline dicarboxylic acid derivative, formulated in a metered-dose inhaler. Because nedocromil sodium has in vitro and in vivo anti-inflammatory properties, it was evaluated in a group of steroid-dependent patients with asthma to observe how well it might be tolerated and for evidence of any beneficial effects. In a double-blind, group-comparative study, 127 patients received nedocromil sodium and 61 received placebo, administered as two puffs of 2 mg, four times per day, for 12 weeks. Ten patients developed adverse reactions, seven receiving active drug and three patients receiving placebo. Two patients of each group withdrew because of worsening asthma. Despite selecting patients whose asthma was stable, when they were receiving established therapeutic regimens that included steroids and bronchodilators, it was found that diary-card symptom scores, morning and evening peak expiratory flow rate values, and inhaled beta-agonist usage all demonstrated slight but significant benefit with addition of nedocromil sodium. It is concluded that the inhaled, anti-inflammatory agent, nedocromil sodium, may be added to asthma-treatment regimens with the reasonable expectation of further modest symptomatic benefit.

Adult↗
PubMed1990

Duration of the effect of astemizole on histamine-inhalation tests.

The aim of the study was to investigate if astemizole, a new, long-acting antihistamine preparation, has an effect on histamine-inhalation tests and to assess the duration of action of this medication. The study included a group of 15 adult subjects with asthma in a clinically stable state. The subjects all demonstrated mild to severe bronchial hyperresponsiveness (geometric mean provocative concentration causing a 20% fall in FEV1 (PC20) histamine, 0.57; range, 0.20 to 4.7 mg/ml). The first part of the study was a double-blind, 7-day trial of astemizole (10 mg/day) or placebo, assigned in random order for the first eight subjects. The seven subjects entering the trial subsequently were administered active medication only. PC20 histamine was assessed on the 3 consecutive days before starting the trial, on the last day of medication, 3 days later, and once a week thereafter until PC20 returned to baseline. PC20 methacholine was also assessed before the trial and regularly thereafter to ensure functional stability. No significant changes in PC20 histamine were documented in the placebo-treated group, but the four subjects receiving active medication demonstrated marked changes in PC20 histamine (from a tenfold to a greater than 100-fold difference) (p = 0.001). There were no significant differences in changes in PC20 methacholine between the two treatment groups (p = 0.27). The duration of recovery of bronchial response to histamine in all 15 subjects ranged from 12 to 102 days (mean, 42 days) and was in some subjects, longer than the duration of the blocking effect of histamine reactivity found with skin testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Occupational asthma caused by guar gum.

Some vegetable gums have been reported to cause asthma. We describe three subjects who were exposed at work to guar gum, which is derived from the outer part of Cyanopsis tetragonolobus, a vegetable that grows in India. The first subject worked for a pharmaceutical company; the second and third subjects worked at a carpet-manufacturing plant. All three subjects developed symptoms of rhinitis and asthma after the onset of exposure to guar gum. All subjects were atopic and demonstrated mild bronchial hyperresponsiveness to inhaled histamine at the time they were observed. Skin prick tests demonstrated an immediate skin reaction to guar gum. All three subjects had high levels of serum IgE antibodies to guar gum. Specific inhalation challenges in which the three subjects were exposed for short intervals (less than or equal to 4 minutes) to powder of guar gum elicited isolated immediate bronchospastic reactions in two subjects and a dual reaction in the other subject.

Adult↗
PubMed1990

Urinary leukotriene E4 levels during early and late asthmatic responses.

The sulphidopeptide leukotrienes C4 and D4 (LTC4, LTD4) are potent bronchoconstrictor mediators, released from human lung fragments after challenge with specific allergens in vitro. The purpose of this study was to measure urinary LTE4 (metabolite of LTC4 and LTD4) in subjects undergoing inhalation challenges with allergens or occupational sensitizing agents in the laboratory. Eighteen subjects with previously documented isolated early asthmatic responses (EARs), isolated late asthmatic responses (LARs), or dual (both early and late) asthmatic responses were studied. Urinary LTE4 levels increased in subjects who developed either isolated EARs (mean fall in FEV1, 27.98%) or early responses preceding LARs (mean fall in FEV1, 15.01%). The baseline levels of LTE4 were 150.26 (SEM, 49.5) pg/mg of creatinine in the isolated responders and 66.60 (SEM, 13.5) pg/mg of creatinine in the dual responders. These levels increased to 1816 (SEM, 606.1) pg/mg of creatinine (p = 0.041) and 174.80 (SEM, 40.1) pg/mg of creatinine (p = 0.025), respectively, after the EAR. The degree of maximal bronchoconstriction during the EAR correlated with the levels of LTE4 (r = 0.68; p = 0.001). No significant increase in urinary LTE4 levels occurred during the LAR. These results suggest that the LTE4 precursors, LTC4 and LTD4, are important bronchoconstrictor mediators causing EARs after allergen inhalation.

Administration, Inhalation↗
PubMed1990

The use of an immunoassay index for antibodies against isocyanate human protein conjugates and application to human isocyanate disease.

Serum IgG and IgE to isocyanate haptenized human serum albumin (HSA) were estimated by ELISA in 55 isocyanate workers who underwent isocyanate inhalation challenge studies in Montreal, Canada. The challenges were negative in 29 workers and positive in 26 workers. Isocyanate antibodies were estimated by ELISA index. The mean IgG indices were found to be significantly higher in the challenge-positive workers, and there was a similar trend for the IgE indices. Antibody specificities for toluene diisocyanate-HSA, diphenylmethane diisocyanate-HSA, and hexamethylene diisocyanate-HSA were determined by inhibition studies with a variety of isocyanate haptenized carriers. The other isocyanate substituted carriers were either noninhibitory or caused only partial inhibition as contrasted with the complete inhibition achieved by HSA conjugated to the isocyanate to which the worker was exposed. We interpret these specificity studies as indicating that the inhalation of isocyanates results in production of antibody that recognizes new antigenic determinants that develop from the coupling of isocyanates to homologous proteins.

Antibodies↗
PubMed1990

Prevalence of occupational asthma and immunologic sensitization to guar gum among employees at a carpet-manufacturing plant.

Guar gum is a high-molecular-weight agent that can cause occupational rhinitis and asthma. We surveyed the employees at a carpet-manufacturing plant in which guar gum is used to adhere the dye to the fiber; 162/177 of the employees (92%) participated in the first part of the survey that included a questionnaire and skin prick tests with common allergens and guar gum (1 mg/ml). IgE and IgG antibodies to guar gum were also measured in those subjects (133/162 or 82%) who agreed to blood tests. Thirty-seven subjects (23%) had a history suggestive of occupational asthma and 59 (36%), of occupational rhinitis. Eight subjects (5%) demonstrated immediate skin reactivity to guar gum. Eleven subjects (8.3%) had serum IgE antibodies to guar gum. All subjects, except one subject who had a history suggestive of occupational asthma (n = 37) or positive skin tests (n = 4), participated in the second part of the study. A methacholine-inhalation test was performed during a workshift or in the 3 to 4 hours after the workshift. Five subjects had a concentration of methacholine causing a 20% fall in FEV1 of less than 16 mg/ml (significant bronchial hyperresponsiveness) and positive skin reactions to guar gum. Four of these subjects underwent specific inhalation challenges. The remaining subject had a history of severe bronchospastic reaction on exposure to guar gum, and his FEV1 of 1.6 L made specific challenges impossible. Two subjects had typical isolated immediate reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1990

Tolerance to reduction of oral steroid dosage in severely asthmatic patients receiving nedocromil sodium.

We examined the efficacy of nedocromil sodium as an oral steroid sparing agent in a group of 37 severe, oral steroid-dependent asthmatics. All were receiving daily or alternate-day prednisone. These patients had taken part in an earlier, 12-week double-blind trial of nedocromil sodium 16 mg daily by inhalation or matching placebo. They continued with test treatment (26 patients on nedocromil sodium and 11 on placebo) on a double-blind basis for a further 12 weeks. During this time, patients visited the clinic every 2 weeks, when asthma severity and symptoms were assessed. On the basis of these assessments, the dose of oral steroid was either decreased, or maintained at the same level, or the patient was withdrawn if the asthma had deteriorated to a clinically unacceptable level. The nedocromil sodium group was able to achieve a greater percentage reduction in oral steroid dose (P less than 0.05). The rate of withdrawal due to worsening asthma was 31% from active and 55% from placebo treatment. Trends in other variables (time before withdrawal and numbers of patients able to withstand complete removal of oral steroids) favoured nedocromil sodium but the differences between the groups were not statistically significant.

Adult↗
PubMed1990

Occupational asthma in a pharmaceutical worker exposed to hydralazine.

A pharmaceutical worker developed asthma when exposed to hydralazine, an antihypertensive drug. The diagnosis of occupational asthma was supported by specific inhalation challenges, which produced a late asthmatic reaction and an increase in bronchial responsiveness. No evidence of an IgE or an IgG dependent mechanism could be found.

Adult↗
PubMed1990

Occupational asthma due to tea dust.

Three patients are described who had developed asthma after working as tea packers. In two cases the diagnosis was confirmed by serial monitoring of peak expiratory flow rates, bronchial responsiveness to histamine, and specific inhalation challenges in the laboratory. The third patient experienced isolated changes in bronchial responsiveness to histamine after periods of exposure at work and after specific inhalation challenges in the laboratory without showing spirometric changes. Two of the three subjects were non-atopic; none had an immediate reaction to skin prick testing with a tea solution.

Adult↗
PubMed1990

Formoterol, a new inhaled beta-2 adrenergic agonist, has a longer blocking effect than albuterol on hyperventilation-induced bronchoconstriction.

The duration of effect of inhaled formoterol (24 micrograms) was compared with that of a placebo and that of inhaled albuterol (200 micrograms) in 12 adult asthmatic subjects who underwent hyperventilation tests with cold dry air (-20 degrees C) on 4 study days. On the control day, they were subjected to four hyperventilation tests to ensure functional stability. On the 3 remaining days, after a first hyperventilation test, they inhaled placebo, albuterol, or formoterol in randomized, double-blind fashion. The hyperventilation test was repeated 1, 4, and 8 h and, if the blocking effect was still present, 12 and 24 h after the drug had been administered. The dose of hyperventilation of cold air causing a 20% fall in FEV1 (PD20) was interpolated on the dose-response curve. The magnitude of the blocking effect at each time interval on each study day was assessed by comparing the changes in PD20 from baseline with the within-day variability of PD20 (standardized change in PD20). The acute bronchodilator effect was not significantly different as assessed 15 min (21 +/- 14% for albuterol and 18 +/- 18% for formoterol) and 1 h (20 +/- 13% for albuterol and 18 +/- 17% for formoterol) after administering the medication. The duration of the blocking effect, defined as the return to 2 SD from the standardized change in PD20, was significantly more prolonged for formoterol (8.0 +/- 3.4 h) than for albuterol (3.0 +/- 1.7 h) (t = 4.2, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗