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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinical findings and the results of inhalation challenge with toluene diisocyanate (TDI) and methacholine in 113 subjects with a history of exposure to TDI and work-related respiratory symptoms. Only some of the subjects (40.7%) had isocyanate asthma, diagnosed by a positive TDI inhalation challenge. Most reactors had a dual (30.4%) or a late (41.3%) response. The interval between the last occupational exposure and the specific challenge was significantly shorter in reactors, and among this group the number of immediate reactions to TDI decreased progressively with an increasing interval. The reactors had a significantly higher proportion of positive responses to methacholine and a significantly lower mean PD15 FEV-1 (provocative dose of methacholine which provoke a 15% decrease in forced expiratory volume in 1 second) (reactors: 557 micrograms, SEM 92.3; nonreactors: 1346 micrograms, SEM 128, P less than .01). Methacholine challenge could not identify subjects with isocyanate asthma.
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PMID:Toluene diisocyanate-induced asthma: clinical findings and bronchial responsiveness studies in 113 exposed subjects with work-related respiratory symptoms. 165 Aug 20

An increased level of airway responsiveness has been proposed as a risk factor associated with the onset and prognosis of chronic airway obstruction. To determine this, longitudinal studies are necessary, with measurement of both the level of airway responsiveness and of additional risk factors, such as cigarette smoking, made before measurement of pulmonary function decline. The association of airways responsiveness with decline in FEV1 has been prospectively studied in a random sample of the Dutch population. Longitudinal data from 921 males, providing 2,376 paired observations, and 698 females, providing 1,682 paired observations, were used for analysis. Differences between responders and nonresponders (PC10 < or = 16 mg/ml of histamine) were estimated from linear regression analyses stratified by gender and smoking status, with adjustment for age, residential area, the presence of respiratory symptoms, indicators for each interval, and residuals of FEV1 at the beginning of the interval. Responders had a greater mean yearly decline in FEV1, and the differences between responders and nonresponders were similar for all gender and smoking subgroups. In an overall regression model, subjects with airway hyperresponsiveness had a significantly steeper decline in FEV1, independent of the other variables (males: beta = -12.5 ml/yr, SEM = 3.22, p < 0.001; females: beta = -11.50 ml/yr, SEM = 2.98, p < 0.001). The current analyses conclusively demonstrated that increased airway responsiveness is an independent risk factor for an accelerated decline in FEV1 and, hence, for the development of chronic obstructive lung disease. The mechanisms by which increased airway responsiveness leads to an accelerated decline in FEV, are imperfectly understood and require further study.
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PMID:Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1. 773 88

We wished to determine which resting spirometric parameters best reflect improvements in exercise tolerance and exertional dyspnea in response to acute high-dose anticholinergic therapy in advanced COPD. We studied 29 patients with stable COPD (FEV(1) = 40 +/- 2% predicted [%pred]; mean +/- SEM) and moderate to severe chronic dyspnea. In a double-blind placebo-controlled cross-over study, patients performed spirometry and symptom-limited constant-load cycle exercise before and 1 h after receiving 500 micrograms of nebulized ipratropium bromide (IB) or saline placebo. There were no significant changes in spirometry, exercise endurance, or exertional dyspnea after receiving placebo. In response to IB (n = 58): FEV(1), FVC, and inspiratory capacity (IC) increased by 7 +/- 1%pred, 10 +/- 1%pred, and 14 +/- 2%pred, respectively (p < 0.001), with no change in the FEV(1)/FVC ratio. After receiving IB, exercise endurance time (Tlim) increased by 32 +/- 9% (p < 0.001) and slopes of Borg dyspnea ratings over time decreased by 11 +/- 6% (p < 0.05). Percent change (%Delta) in Tlim correlated best with DeltaIC%pred (p = 0.020) and change in inspiratory reserve volume (DeltaTLC%pred) (p = 0.014), but not with DeltaFVC%pred, DeltaPEFR%pred, or DeltaFEV(1)%pred. Change in Borg dyspnea ratings at isotime near end exercise also correlated with DeltaIC%pred (p = 0.04), but not with any other resting parameter. Changes in spirometric measurements are generally poor predictors of clinical improvement in response to bronchodilators in COPD. Of the available parameters, increased IC, which is an index of reduced resting lung hyperinflation, best reflected the improvements in exercise endurance and dyspnea after IB. IC should be used in conjunction with FEV(1) when evaluating therapeutic responses in COPD.
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PMID:Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. 1043 Jul 26

Gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitter. Recently, the presence of GABA and its receptors has been confirmed in peripheral tissues, including the lungs. GABA and the GABA agonist baclofen have been shown in animal studies to inhibit airway responsiveness to various bronchoconstricting agents. The results of these investigations suggest the possibility of a role for baclofen in the therapy of human airway hyperreactivity. To investigate this question, a randomized, double-blind, placebo-controlled, cross-over study was performed to evaluate the effect of a 14-day course of oral baclofen (10 mg three times daily) on pulmonary function and bronchial responsiveness to methacholine in a group of six stable asthmatics. In five of six subjects, hyperresponsiveness was enhanced after therapy with baclofen. Mean (+/- SEM) log PC(20)pre-and post-baclofen were 0.160 +/- 0.247 and -0.223 +/- 0.282, respectively (P=0.023). Baseline pulmonary function (FEV(1)) was unaffected by baclofen. The mechanism(s) underlying this apparent paradoxical enhancement by baclofen of bronchial responsiveness remains speculative, but may be relevant to the recently-proposed concept of dysfunction in asthmatics of prejunctional GABA receptors, whose normal role may be to inhibit cholinergic contraction of bronchial smooth muscle.
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PMID:Effect of the GABA-agonist baclofen on bronchial responsiveness in asthmatics. 1050 5

Exacerbations of asthma are often associated with rhinovirus infections. However, it has not been investigated whether rhinovirus infection can induce variable airway obstruction in asthma. We examined the effect of experimental rhinovirus 16 (RV16) infection on daily home recordings of FEV(1) in 27 subjects (nonsmoking, atopic, mildly asthmatic) who participated in a parallel placebo-controlled study. The subjects used a microspirometer to record FEV(1) three times daily from 4 d before until 10 d after RV16 (n = 19) or placebo (n = 8) inoculation. In addition, symptoms of asthma and symptoms of common cold were scored. Airway hyperresponsiveness to histamine was measured 3 d before and on Days 4 and 11 after RV16/placebo administration. Home recordings of FEV(1) decreased significantly after RV16 infection, reaching a minimum 2 d after inoculation (ANOVA, p </= 0.005), which was significantly different from placebo (p </= 0.004). In the RV16 group the lowest FEV(1) (expressed as a percentage of personal best) during Days 0-3 after infection (mean +/- SEM: 78.7 +/- 2.6% versus baseline: 85.6 +/- 1.2%, p = 0.008) correlated significantly with the cold score (r = -0.47, p = 0.04), asthma score (r = -0.47, p = 0.04), and with the decrease in airway hyperresponsiveness on Day 4 as compared with baseline (r = 0.50, p = 0.03). We conclude that experimental RV16 infection augments variable airway obstruction in subjects with asthma. This favors a causative role for rhinovirus colds in asthma exacerbations, and is in keeping with rhinovirus-induced worsening of airway inflammation.
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PMID:Experimental rhinovirus 16 infection causes variable airway obstruction in subjects with atopic asthma. 1050 32

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.
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PMID:A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. 1055 7

We performed an association study of plasma eotaxin levels, eosinophil counts, total IgE levels, asthma diagnosis, and lung function in an ethnically diverse and geographically dispersed population. We studied 515 asthmatic and 519 normal subjects, none of whom was taking inhaled or oral corticosteroids. Logistic regression analysis demonstrated a direct relationship between asthma diagnosis and eotaxin levels (p < 0.0001). The odds of an asthma diagnosis increased with eotaxin quartile, with the highest quartile having an odds ratio of 5.4 (95% CI 3.2 to 9.2, p < 0.001) compared with the lowest eotaxin quartile. Eotaxin levels were inversely related to lung function (p < 0.001), with the mean percent predicted FEV(1) in the highest eotaxin quartile being 13.5 percentage points (SEM 2.1, p < 0.001) less than that in the lowest quartile. Plasma eotaxin levels were associated with asthma and inversely related to lung function independent of age, race, sex, or smoking status. When combined with eosinophil counts and IgE levels, eotaxin levels contributed to the odds of an asthma diagnosis and of impaired lung function. Our results are the first to associate eotaxin levels with asthma diagnosis and compromised lung function in a large geographically and ethnically diverse population.
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PMID:Eotaxin and impaired lung function in asthma. 1058 12

It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an expression of airway inflammation, but no studies have been reported of ENO and exercise-induced bronchoconstriction (EIB). We assessed the effect of a treadmill exercise challenge on ENO concentration in 24 asthmatic children aged 11.2 +/- 0.4 yr (mean +/- SEM). According to the presence or absence of EIB, the children were divided into an EIB group (n = 10) and a non-EIB group (n = 14). ENO was measured with a single-breath reservoir technique. FEV(1), ENO, and heart rate were measured at baseline and 1, 6, 12, and 18 min after the end of exercise. We also measured ENO in 18 healthy control children aged 10.8 +/- 0.6 yr, of whom nine underwent an exercise challenge identical to that of the asthmatic children. After the exercise test, the mean decrease in FEV(1) was 34% in the EIB group and 5% in the non-EIB group. The EIB group had higher baseline ENO values (12.3 +/- 1.6 ppb) than the healthy children (6.1 +/- 0.2 ppb) (p < 0.01). The time course of ENO was similar in the EIB, non-EIB, and control groups, with no significant changes after exercise (p = NS). In the overall group of asthmatic children there was a significant correlation (r = 0.61, p < 0.01) between baseline (preexercise) ENO and magnitude of the maximal decrease in FEV(1) after exercise. In conclusion, our study shows that ENO levels do not change during acute airway obstruction induced by exercise challenge in asthmatic children. In addition, baseline ENO values correlate with the magnitude of postexercise bronchoconstriction, suggesting that NO may be a predictor of airway hyperresponsiveness to exercise.
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PMID:Exhaled nitric oxide and exercise-induced bronchoconstriction in asthmatic children. 1071 61

Ethane is produced from lipid peroxidation and can be measured in the exhaled air. Cystic fibrosis (CF) is characterized by recurrent respiratory infections, release of reactive oxygen species by inflammatory cells, and increased oxidative stress. We measured exhaled ethane in 23 CF subjects (mean age +/- SEM, 21 +/- 4 yr; 10 male, FEV(1) 62 +/- 4%) and compared it with two other noninvasive markers of oxidative stress and inflammation, carbon monoxide (CO) and nitric oxide (NO). Exhaled ethane was collected during a flow and pressure-controlled exhalation into a reservoir discarding dead space air contaminated with ambient air. A sample (2 ml) of the expired air was analyzed by chromatography. Ethane levels were elevated in patients not on steroids (n = 13, 1.99 +/- 0.20 ppb) compared with steroid-treated patients (n = 10, 0.67 +/- 0.09 ppb, p < 0.01) and with 14 nonsmoking control (8 men, age 33 +/- 2.8 yr) subjects (0.82 +/- 0.40 ppb, p < 0.05). In patients not on steroid treatment ethane was correlated to airway obstruction as assessed by the ratio of residual volume to total lung capacity (RV/ TLC) (r = 0. 66, p < 0.05) and exhaled CO (r = 0.65, p < 0.05). CO concentrations were also higher in patients not on steroid treatment (3.4 +/- 0.2 ppm) than in steroid-treated patients (2.6 +/- 0.1 ppm, p < 0.05), whereas NO concentrations were not influenced by steroid treatment (3.0 +/- 0.4 ppm and 2.9 +/- 0.2 ppm, p > 0.05) and were lower than in a control group (7.0 +/- 0.4 ppb, p < 0.05). Exhaled ethane is elevated in CF, reduced in steroid-treated patients and correlates with CO and RV/TLC; therefore, it may be a useful noninvasive marker of oxidative stress.
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PMID:Exhaled ethane is elevated in cystic fibrosis and correlates with carbon monoxide levels and airway obstruction. 1076 19

Excessive airway narrowing is a cardinal feature of asthma, and results in closure of airways. Therefore, asthmatic patients in whom airway closure occurs relatively early during expiration might be prone to severe asthma attacks. To test this hypothesis, we compared closing volume (CV) and closing capacity (CC) in a group of asthmatic patients with recurrent exacerbations (more than two exacerbations in the previous year; difficult-to-control asthma), consisting of 11 males and two females, aged 20 to 51 yr, with those in a group of equally severely asthmatic controls without recurrent exacerbations (stable asthma) consisting of 13 males and two females aged 18 to 52 yr. Both groups used equivalent doses of inhaled corticosteroids and were matched for sex, age, atopy, postbronchodilator FEV(1), and provocative concentration of methacholine causing a 20% decrease in FEV(1). They were studied during a clinically stable period of their disease. The patients inhaled 400 microg salbutamol via a spacer device, after which TLC and RV were measured by multibreath helium equilibration, together with the slope of Phase 3 (dN(2)), CV, and CC, by single-breath nitrogen washout. CV and CC were expressed as ratios of VC and TLC, respectively, and all data are presented as % predicted (mean +/- SEM). There was no difference in TLC in patients with difficult-to-control asthma and those with stable asthma (106.7 +/- 4.0% predicted versus 101.7 +/- 4.3% predicted, p = 0.40), RV (113.1 +/- 7.8% predicted versus 100.9 +/- 7.1% predicted, p = 0.26), or dN(2) (142.7 +/- 16.3% predicted versus 116.0 +/- 20.2% predicted, p = 0.23). In contrast, CV and CC were increased in the patients with difficult-to-control asthma as compared with the group with stable asthma (CV: 159.5 +/- 26.8% predicted versus 98.8 +/- 12.5% predicted, p = 0.024; CC: 114.0 +/- 6.4% predicted versus 99.9 +/- 3. 6% predicted, p = 0.030). These findings show that asthmatic individuals with recurrent exacerbations have increased CV and CC as compared with equally severely asthmatic but stable controls, even after bronchodilation during well-controlled episodes. The findings imply that airway closure at relatively high lung volumes under clinically stable conditions might be a risk factor for severe exacerbations in asthmatic patients.
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PMID:Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes. 1085 64


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