The effects of sulfur oxides on nasal and lung function in adolescents with extrinsic asthma

Ten adolescent subjects with extrinsic asthma were exposed during intermittent exercise to filtered air, 0.5 ppm of sulfur dioxide (SO2), or 100 micrograms/m3 of sulfuric acid (H2SO4) on 5 separate days. The purpose of the study was to compare changes in nasal power (the work of nose breathing) with pulmonary functional changes depending on the route of inhalation of the sulfur oxide pollutants, oral inhalation through a rubber mouthpiece or oronasal inhalation via a face mask. Nasal power was measured with a modified skin diving mask equipped with two differential pressure transducers. Statistically significant changes in total respiratory resistance, FEV1, and maximum flow calculated at 50% and 75% vital capacity were observed after all exposures to SO2 and H2SO4. The magnitude of change in FEV1 and maximum flow calculated at 50% vital capacity was higher after oral compared to oronasal inhalation of SO2. The nasal work of breathing increased 32% after SO2 exposure by mouthpiece and 30% after SO2 exposure via face mask (p less than 0.05). The nasal power changes after the H2SO4 exposures were not different from the sham exposures. We conclude that oronasal inhalation of 0.5 ppm of SO2 produces a significant increase in the nasal work of breathing and that the route of exposure reduces but does not eliminate the lower airway reactions observed on oral exposure.     

Ipratropium bromide (Atrovent) in childhood asthma: a cumulative dose-response study

Thirteen children with perennial bronchial asthma, with a mean age of 11.2 years, were studied concerning the bronchodilatory effect of ipratropium bromide in cumulative doses. All the children had reduced basal forced expiratory flow (FEV1) and bronchial reversibility of at least 20% after inhalation of salbutamol. The study had a double-blind design with a crossover technique. The inhaled dose of ipratropium bromide solution was increased stepwise from 25 micrograms to 500 micrograms and saline was used as the placebo. FEV1 was recorded 20, 40, and 60 minutes after inhalation of the test solution. At the lower ipratropium bromide dose levels no bronchodilatory effect was seen, but 60 minutes after the inhalation of 500 micrograms ipratropium bromide the increase in the FEV1 was significantly greater than that after placebo. Additional inhalation of salbutamol caused no further rise in FEV1. At the 500-micrograms level a fall in the heart rate was noted. No side effects occurred. We concluded that ipratropium bromide has bronchodilatory properties in childhood asthma when given in sufficiently high doses.     

The effects of albuterol on sulfur dioxide-induced bronchoconstriction in allergic adolescents

Ten allergic subjects with exercise-induced bronchospasm were studied to determine whether albuterol could prevent sulfur dioxide (SO2)-induced bronchoconstriction. Albuterol or placebo (180 micrograms) were administered by metered-dose inhaler 20 minutes before a 10-minute exposure to SO2 or clean air during moderate exercise on a treadmill at an exercise level that by itself did not produce exercise-induced bronchospasm. Pulmonary functions (FEV1 and total respiratory resistance [RT]) were measured before the drug, after the drug, and after exposure to SO2 or clean air. Albuterol treatment produced significant bronchodilation and also prevented SO2-induced bronchoconstriction. Following SO2 inhalation after placebo, FEV1 decreased 15% (p less than 0.02) and RT increased 50% (p less than 0.03). Following SO2 inhalation after albuterol treatment, neither FEV1 or RT changed significantly. We conclude that albuterol, a beta 2-agonist, inhibits SO2-induced bronchoconstriction. This result suggests that the adrenergic nervous system or mast cell degranulation are involved in SO2-induced bronchoconstriction.     

Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children

A study was performed to compare the efficacy and safety of two therapeutic regimens for the treatment of children presenting to the emergency department with acute asthma. A regimen of inhaled salbutamol alone was compared to inhaled salbutamol combined with ipratropium bromide. Twenty-five children ranging in age from 5 to 15 years were enrolled in the study. Children with FEV1 less than or equal to 55% predicted were eligible to participate in the study. Subjects were randomized in a double-blind fashion into one of two treatment groups. Both groups received an initial dose of salbutamol by nebulizer of 150 micrograms/kg (0.03 cc/kg), followed by six consecutive doses of 50 micrograms/kg (0.01 cc/kg) at 20-minute intervals. In one group of subjects, 250 micrograms (1.0 ml) of ipratropium bromide respirator solution was added to the salbutamol administered at the time of the initial inhalation, and at 40 and 80 minutes, whereas the remaining subjects received a placebo with salbutamol at those times. Formal one-way statistical ANOVA with change in percent predicted FEV1 as a response variable confirmed there was a statistically significant difference at all time points caused by drug regimen during the 150-minute observation period. There was no significant difference in side effects reported in the two groups. Significant additional bronchodilation achieved with salbutamol and ipratropium bromide together indicates that there is likely a substantial cholinergic element to the bronchospasm observed in acute exacerbations of asthma in the pediatric age group.     

The evaluation of the distal airway inflammation of well controlled asthmatic patients using sputum induction by inhalation of 10% hypertonic saline for 15 minutes

Background: As the clinical importance of treatment to asthmatic distal airway has been recognized, this study aimed to evaluate the efficacy of the 10% hypertonic saline-induced 15 minutes long-inhaled method to assess the inflammatory situation in the distal airways. Methods: The subjects were 16 healthy volunteers and 29 patients with well controlled asthma. They inhaled 5% or 10% hypertonic saline for 15 minutes and the sputum induction rates and induced times were measured. We also investigated the values of surfactant protein D (SP-D) and eosinophil cationic protein (ECP) both in early- and late-phase induced sputum, together with pulmonary function indexes, and the patients' impressions of the method. Results: The sputum induction rates with 10% hypertonic saline inhalation in both healthy volunteer group and well controlled asthmatic patients group were significantly high compared with those with 5% hypertonic saline inhalation; 75.0% (p=0.004) and 75.9% (p=0.007), respectively. The SP-D levels in late-phase sputum in both healthy volunteer group and well controlled asthmatic patients group significantly elevated compared with those in the early-phase: p=0.045 and p=0.007, respectively. The SP-D levels in late-phase sputum significantly correlated to those of ECP in the well controlled asthmatic patients group (r=0.527, p=0.017). The pulmonary function index FEV1.0% of 18 well controlled asthmatic patients (62.1%) attenuated 2.9+/-2.5% soon after finishing the 10% hypertonic saline inhalation, and recovered after an additional 15 minutes rest. 70 approximately 80% of the subjects in both groups answered that they felt no strain in using the inhaled method. Conclusion: The late-phase sputum obtained by the 10% hypertonic saline-induced 15 minutes long-inhaled method may be useful in evaluating the inflammatory situation in the distal airways.     

The short-term bronchodilator effects of fenoterol and ipratropium in asthma

We studied the bronchodilator effects of inhaled fenoterol, a relatively selective beta-2 adrenergic agent, and ipratropium an anticholinergic drug, singly and in combination in 10 patients with asthma. The period of observation was 6 hr after aerosol administration. The six drug regimens used were fenoterol 100 micrograms, fenoterol 200 micrograms fenoterol 50 micrograms combined with 20 micrograms of ipratropium, fenoterol 100 micrograms combined with 40 micrograms of ipratropium, 40 micrograms of ipratropium, and placebo. Measurements consisted of spirometry with determination of forced expiratory volume in one second (FEV1), maximal expiratory flow at 50% of vital capacity (V50), specific airway conductance, lung volumes, and heart rate. Bronchodilation with regimens containing fenoterol was rapid, with 75% of the maximum response achieved by 5 min, while the peak effect of ipratropium was delayed for 1 to 2 hr. Fenoterol 100 micrograms produced approximately half the degree of improvement in FEV1 and V50 compared with 200 micrograms of fenoterol. The addition of 40 micrograms of ipratropium to 100 micrograms of fenoterol resulted in bronchodilation equivalent to 200 micrograms fenoterol and was associated with a more prolonged effect than fenoterol 100 micrograms. Tremor was observed in two-subjects inhaling fenoterol 200 micrograms but was not observed with any other regimen. It is concluded that the combination of inhaled ipratropium and fenoterol is an effective bronchodilator in asthma, achieving efficacy similar to that of fenoterol alone but with fewer side effects.     

Genetic polymorphisms as biomarkers of sensitivity to inhaled sulfur dioxide in subjects with asthma.

BACKGROUND: Individuals with asthma are sensitive to inhaled sulfur dioxide (SO2); decrements in pulmonary function occur after exposure to low concentrations even for a short duration of time. There is a great amount of interindividual variation in response to SO2. OBJECTIVE: It was our objective to determine whether one of the following polymorphism locations linked with asthma is associated with the bronchial hyperresponsiveness to SO2 observed in some asthmatic patients: the beta2-adrenergic receptor, interleukin-4 (IL-4) receptor alpha subunit, Clara cell secretory protein (CC16), TNF-alpha gene promoter, and first intron of the lymphotoxin alpha (LT-alpha) gene. METHODS: Subjects were volunteers with physician-diagnosed asthma requiring regular asthma medication. Spirometry was performed before and after a 10-minute exposure to 0.5 ppm SO2. Subjects were classified as SO2 responders if forced expiratory volume in 1 second (FEV1) decreased > or = 12%. DNA obtained from buccal cell samples was analyzed for genetic polymorphisms. RESULTS: Of the 62 subjects (21 male and 41 female), 13 had a 12% or greater decrement in FEV1 after SO2 exposure (range + 19% to -49%). Response to SO2 was associated with the wild-type allele of the TNF-alpha promoter polymorphism (12 of 12 SO2 responders versus 28 of 46 nonresponders; P < .05) but with no other polymorphisms. Medication category and atopic status showed no association with SO2 sensitivity. CONCLUSIONS: The wild-type allele of the TNF-alpha promoter polymorphism may be associated with mechanisms of asthmatic sensitivity to inhaled SO2.     

Validity of air-helium DVmax measurements in trials of bronchodilators

The authors studied the intraindividual variability of DVmax50 He-air in a large homogeneous group of 57 young healthy subjects. They found a 95% confidence interval for a true change between two repeated measurements of DVmax50 of +/- 28%. They compared the discriminant power of FEV1, Vmax50 and DVmax50 in 27 asthmatic young males and 12 normal controls, challenged on different days with fenoterol and ipratropium bromide aerosols given in random order under standardized conditions. FEV1 was not able to discriminate between the effect of the drugs in the normals or asthmatics. Vmax50 increased significantly more after fenoterol than after ipratropium in the asthmatics. DVmax50 was sometimes increased after fenoterol in the asthmatics but not by ipratropium in this group. These results suggest that sympathomimetics are more active on peripheral airways than the antimuscarinics.     

Within- and between- subject variability of indices from the closing volume and flow volume traces

The within-subject variability of consecutive measurements of indices derived from the closing volume (CV) trace and from the maximal expiratory flow volume (MEFV) curve was studied in 24 subjects. The variability of the closing volume and of the maximal expiratory flow rates at 50 percent (Vmax. 50) and 75 percent (Vmax. 75) of the expired vital capacity was about three to eight times greater than that of the FEV1, FVC or FEV1 percent. The lung volume measured from total lung capacity to the onset of airway closure (OAC) was about five times more reproducible than the CV. The coefficients of variation for the CV (as a percentage of the vital capacity), the Vmax. 75, and the OAC, both in litres and as a percentage of the vital capacity, were significantly correlated with age. No difference in the mean coefficients of variation for the CV, OAC, Vmax. 50 or Vmax. 75 were found with respect to sex, smoking habit or previous experience with the test routines. The between-subject variability of the FEV1, FVC, FEV1 percent, transfer factor, diffusion coefficient, Vmax. 50, Vmax. 75, CV and OAC was evaluated from a study of 75 asymptomatic lifetime non-smokers. The variability of the Vmax. 50, Vmax. 75 and CV was about two to eight times greater than that of the other tests used, irrespective of sex. The OAC (percent VC) was three to four times less variable than the CV. The variability of the Vmax. 50 and Vmax. 75 was reduced by, on average, 7 percent when these flow rates were expressed per litre of FVC.     

Comparison of nebulized ipratropium bromide with salbutamol vs salbutamol alone in acute asthma exacerbation in children.

BACKGROUND: Despite multiple doses of beta2-agonists in the treatment of acute asthma exacerbation, significant residual airways obstruction often remains. OBJECTIVE: To determine whether the addition of inhaled ipratropium bromide to salbutamol provides improvement in lung function and clinical asthma symptoms in young children with acute asthma exacerbation. METHODS: This study was a prospective, double-blind randomized control trial of children aged 3 to 15 years who presented with an acute asthma exacerbation at the emergency department or outpatient clinic of Thammasat University Hospital, Pathumthani, Thailand, between September 2001 and February 2003. Subjects were randomized to receive 3 doses of nebulized salbutamol mixed with isotonic sodium chloride solution (control) or ipratropium bromide (treatment) every 20 minutes. Additional doses of salbutamol were given every 30 minutes as needed. Asthma outcome measures were evaluated 40, 70, 100, and 120 minutes after baseline. Primary outcomes were the differences in percent change in asthma clinical score and percent change in peak expiratory flow rate (PEFR) from baseline. Secondary outcomes included change in percent predicted PEFR. RESULTS: Of 74 children randomized and enrolled in the trial, 71 had complete data for analysis. Thirty-three children were in the control group and 38 were in the treatment group. Both the percent change in PEFR and the change in percent predicted PEFR at any time were higher in the treatment group, but these findings were not statistically significantly different. The number of subjects with at least a 100% percent predicted PEFR at any time point was greater in the treatment group. CONCLUSION: Although this study did not demonstrate a significant advantage in clinical score and PEFR, the trend toward additional effect of ipratropium bromide was consistent with previous studies.     

Bronchial hyperreactivity and spirometric impairment in patients with perennial allergic rhinitis

BACKGROUND: Allergic disorders are characterized by a systemic involvement of the immune response. There is a clear link between allergic rhinitis and asthma. Bronchial hyperreactivity (BHR) may be present in rhinitics. Smaller airways may also be impaired in mild asthma. This study aimed at evaluating a group of subjects suffering from perennial allergic rhinitis alone to investigate the presence of BHR and spirometric impairment. METHODS: One hundred rhinitics sensitized only to perennial allergens were evaluated. Spirometry and methacholine bronchial challenge were performed. RESULTS: Five rhinitics showed reduced values of forced expiratory volume/1 s (FEV(1)) without symptoms of asthma. Forty-eight rhinitics had reduced forced expiratory flow at 25 and 75% of pulmonary volume (FEF(25-75)) values. Seventy-two patients showed a positive methacholine challenge. In this group, reduced values of FVC (p < 0.05), FEV(1) (p < 0.05), and FEF(25-75) (p < 0.01) were demonstrated in comparison with BHR-negative rhinitics. There was a relationship between the degree of BHR and FEV(1) values (p < 0.05) and FEF(25-75) values (p < 0.01). CONCLUSIONS: This study evidences that an impairment of spirometric parameters may be observed in patients with perennial allergic rhinitis alone. A high percentage of these patients have BHR. Thus, new management strategies should be employed in rhinitics.     

A randomized, double-blind, placebo-controlled trial of the effect of zafirlukast on upper and lower respiratory responses to cat challenge

BACKGROUND: Zafirlukast, a leukotriene antagonist, has been shown to have protective effects against a variety of asthma triggers. OBJECTIVE: Our purpose was to evaluate zafirlukast's effects on upper and lower airway responses to cat allergen exposure with use of a well-characterized cat exposure model. METHODS: In a double-blind, placebo-controlled, cross-over trial 18 subjects with cat-induced asthma were randomly assigned to receive 1 week each of zafirlukast or placebo followed by a 1-hour cat challenge. Upper and lower respiratory symptoms were rated and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject was too uncomfortable or had a >50% decrease in FEV(1). RESULTS: Overall changes in FEV(1) were significantly different with zafirlukast treatment (P = .02). Significant differences in FEV(1) change were detected at 15 and 30 minutes (P = .027 and .05, respectively) but not at 45 and 60 minutes. Changes in acoustic rhinometry were also significantly different at 15 and 30 minutes (P =.05 and .0005, respectively) but not at 45 and 60 minutes. Challenge length was significantly longer with zafirlukast versus placebo after adjustment for differences in allergen exposure (P = .022). Respiratory symptom scores were significantly different (lower respiratory, P < .001; upper respiratory, P = .038) through the first 30 minutes of the challenge after adjustment for allergen exposure. CONCLUSIONS: Zafirlukast was significantly more effective than placebo in preserving pulmonary function and nasal anatomy and extending challenge length when cat-sensitive asthmatic subjects were exposed to high levels of cat allergen.     

Rimiterol and the prevention of exercise-induced asthma

The potential for rimiterol to protect athletes from exercise-induced asthma (EIA) has not been fully established. Ten athletes with asthma (15 to 30 years of age) undertook 8 minutes of submaximal exercise (80% of anaerobic threshold) on the treadmill ergometer, once after inhaling rimiterol and once after inhaling a placebo. Treatment with all bronchodilator drugs was stopped for the 12 hours preceding each exercise test. Two puffs (400 micrograms) of rimiterol or placebo were administered in a double-blind crossover manner 2 minutes before each exercise test. Lung function measurements were made before exercise and immediately, 5, 10, 15, 20, 25, and 30 minutes after completion of exercise. The results of a two-way analysis of variance revealed significant (p less than 0.01) difference in the FEV1 scores obtained after rimiterol inhalation and placebo inhalation, 5, 10, 15, 20, 25, and 30 minutes after cessation of exercise. After inhalation of rimiterol, there were no significant changes in FEV1. After inhaling the placebo, significant reductions (p less than 0.01) in FEV1 occurred after cessation of exercise (5, 10, 15, and 20 minutes). All subjects exhibited EIA after placebo, and none after rimiterol. The mean maximum drop after exercise in FEV1 after inhalation of rimiterol (2.807 +/- 5.55) and placebo (24.54 +/- 8.4) was significantly different (t = 6.849). It was concluded that inhalation of rimiterol 2 minutes before exercise afforded significant protection from EIA in all subjects tested.     

The effectiveness of high-dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children.

BACKGROUND: International guidelines recommend the use of systemic steroids for the treatment of acute asthma attack if it has not been resolved within 24 to 36 hours of home management with regular beta2 mimetic inhalation. Such therapy for infrequent exacerbations is unlikely to have serious systemic effects. Unfortunately, many patients receiving frequent courses are potentially at risk for corticosteroid-induced side effects such as adrenal suppression, depression of linear growth, and osteoporosis. OBJECTIVE: To decrease the use of frequent oral corticosteroid courses in children, this study was designed to evaluate the efficacy of high-dose inhaled steroids in comparison with oral steroids, in the therapy of acute asthma exacerbations in children. METHODS: Sixty children who have experienced an acute exacerbation of asthma unresponsive to home management with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize, were randomized to be treated with either high-dose inhaled budesonide (1,600 microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000 microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow 25% to 75% (FEF25%-75%) were evaluated. RESULTS: The mean number of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid-receiving group (group II). There was a statistically significant difference between the two groups, in favor of group I (P = .038). No statistically significant difference was detected between the two groups with respect to the increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P = .790, .959, .819, respectively). CONCLUSIONS: Short-term high-dose budesonide therapy can be considered an alternative for children who are experiencing an acute asthma attack that is unresponsive to home management with regular use of an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.     

Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma

In a randomized, double-blind, parallel-group trial, 47 children with acute asthma received a combination of ipratropium bromide solution (250 μg) and fenoterol hydrobromide solution (625 μg), fenoterol solution (625 μg) alone, or ipratropium solution (250 μg) alone, administered by face mask and nebulizer, with the dose repeated 60 minutes later. The groups did not differ significantly with regard to age, pulmonary function at baseline, or any other variable. They were monitored at 30, 60, 90, and 120 minutes by use of a clinical score, oxygen saturation, and pulmonary function tests. At the end of the study, albuterol was administered to assess residual bronchoconstriction. Clinical scores improved significantly after treatment in all groups at all times compared with baseline. The greatest improvement in FEV, was seen in the patients treated with ipratropium/fenoterol, whether considered as absolute change, change in percent predicted, or percent change from baseline. ipratropium/fenoterol was significantly better than fenoterol alone only when considered as percent change from baseline. Improvement inflow at mid and low lung volumes was significantly greater for the ipratropium/fenoterol combination than for ipratropium alone; no significant differences were noted between ipratropium/fenoterol and fenoterol for flow at mid and low lung volumes. Treatment with albuterol did not significantly improve pulmonary function in the groups receiving ipratropium/fenoterol or fenoterol alone, but it did increase flow at all lung volumes in the group receiving ipratropium alone. No patient complained spontaneously of any adverse reactions, and no clinically significant changes in heart rate or systolic or diastolic blood pressures occurred. Ipratropium/fenoterol solution will be a useful addition to the therapeutic armamentarium for the treatment of acute asthma episodes in children. (J ALLERGY OLIN iMMUNOL 1988;82:1012-8.)     

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.     

Exposure to a sensitizing occupational agent can cause a long-lasting increase in bronchial responsiveness to histamine in the absence of significant changes in airway caliber

A 58-year-old subject with a history of occupational asthma to red-cedar sawdust underwent specific inhalation challenges with this product. Significant increases in airway responsiveness to histamine (tenfold fall in PC20 FEV1) were documented 7 hours after exposure for 5 minutes to red cedar while baseline spirometry remained unchanged. A dual asthmatic reaction was induced during the following days by exposing the subject to red-cedar sawdust for 30 minutes and plicatic acid for 7 minutes. After recovery of PC20, the subject was reexposed to plicatic acid for 15 and 30 seconds on 2 consecutive days. No significant changes in FEV1, forced vital capacity, and residual volume were demonstrated in the following 8 hours, although minimal changes in forced expiratory flow rate between 25% and 75% of FVC were observed. PC20 dropped significantly and required 2 weeks to recover. This example illustrates that bronchial hyperresponsiveness to histamine can precede the changes in airway caliber after an antigen challenge. It also demonstrates that such changes can persist for up to 2 weeks after the challenge, even when no significant changes in FEV1 are induced.     

Comparison of FEV1 and specific airway conductance in assessing airway response to occupational agents

BACKGROUND: There is theoretical evidence that specific airway conductance (SGaw) could be more reliable than forced expiratory volume in 1 s (FEV1) for assessing changes in airway calibre. We investigated the changes in FEV1 and SGaw when assessing bronchial responses to occupational agents. METHODS: SGaw and FEV1 were measured during inhalation challenges with various occupational agents in 174 consecutive subjects investigated for possible occupational asthma. RESULTS: A decline in SGaw of 50% or greater was documented in 77 of 90 subjects (86%) who showed a >/=20% fall in FEV1 and in 11 of 84 subjects (13%) who failed to demonstrate such a fall in FEV1. Among subjects who developed a >/=20% fall in FEV1, those who failed to develop a >/=50% decline in SGaw had a lower baseline SGaw than those who did. Among the group without a >/=20% fall in FEV1, a >/=50% decrease in SGaw was associated with either an 'intermediate' fall in FEV1 (between 15 and 17% from baseline value) (n = 4), a significant postchallenge increase in nonspecific bronchial hyper-responsiveness to histamine (n = 2), or both features (n = 3). CONCLUSIONS: A decline in SGaw of 50% or greater may provide useful complementary evidence of a bronchial response during challenges that produce equivocal results in FEV1.     

A comparison of the effects of nedocromil sodium and beclomethasone dipropionate on pulmonary function, symptoms, and bronchial responsiveness in patients with asthma

The efficacy of nedocromil sodium (NED) (4 mg twice daily) and beclomethasone dipropionate (BDP) (200 micrograms twice daily) in controlling the symptoms of asthma, the pulmonary function, and bronchial responsiveness to histamine was assessed in a double-blind, double-dummy, crossover study of 39 adult patients with chronic asthma. The patients, most of whom were assessed to be affected to a moderate degree, were insufficiently controlled in their current regimen of inhaled and/or oral bronchodilators. A 2-week baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups demonstrated improvements from baseline in clinical assessment of lung function performed after the first 6 weeks of treatment. No significant differences were observed when the effects of the treatments were compared on FEV1, FVC, and peak expiratory flow. Bronchial reactivity to histamine, measured as the amount of histamine causing a 20% fall in FEV1 (PC20), decreased significantly (p less than 0.05) after 6 weeks of treatment with BDP compared to the effect of NED treatment. Asthma severity, symptom score, and inhaled bronchodilator use demonstrated significantly better results with BDP. After crossover of treatment, the group transferring from NED to BDP continued to improve, whereas the group crossing from BDP to NED tended to demonstrate a major deterioration during the first 3 weeks, after which a stabilization or an increase in FEV1, FVC, and ln PC20 appeared to occur. It is concluded that NED for inhalation is a potent new drug for treatment of both atopic and nonatopic subjects with asthma. With the number of patients and dosages used, the effect on the pulmonary function was not significantly different from that of BDP after the initial 6 weeks of treatment, but BDP had a better effect on asthma severity, overall opinions, symptom score, bronchodilator use, ln PC20, and morning peak expiratory flow.     

Evaluation of the end-expiratory lung volume as an indirect index of bronchial constriction in asthma

The purpose of this study was to evaluate the merits of the end expiratory lung volume as an indirect ventilatory index of bronchial obstruction and to show an application of continuous monitoring of lung volume in asthmatic patients. The accuracy of the external measurements (IS) of functional residual capacity (FRC) was controlled by comparing them with the helium measurements (DS) obtained during nine methacholine tests (IS = 0.06 + 1.065 DS in litres: R2 = 0.99). Seven asthmatics (18-48 yr) were monitored by measuring rib cage and abdominal perimeter variations. This was done in basal condition, after methacholine-induced bronchoconstriction and after bronchodilation by either salbutamol or oxytropium bromide inhalation. All the subjects were investigated on two separate days and were their own control. Bronchoconstriction produced a significant increase (p less than 0.01) of tidal volume (VT: + 67%), external minute ventilation (VE: + 58%), mean inspiratory flow (VT/TI: + 78%) and FRC (+ 26.5%) while frequency (f) and fractional inspiratory time (TI/TT) fluctuated non significantly. In the group of seven tested subjects, there was a significant correlation (p less than 0.01) between forced expiratory volume in one second (FEV1) and VE, FEV1 and VT/TI, FEV1 and FRC. However, the individual regression line showed a significant relationship only between FEV1 and FRC (R2 = 0.80 +/- 0.04). We therefore conclude that the variation of the end expiratory level can be chosen as an indirect index of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)