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Persisting airway obstruction in asymptomatic children with asthma with normal peak expiratory flow rates.

Twice-daily symptom scores and peak expiratory flow readings were compared with spirometric values (FEV1 and forced expiratory flow rate between 25% and 75% of FVC [FEF 25-75]) measured at 2-week intervals in assessing airway obstruction in 20 children with asthma studied during 16 weeks. Of 56 2-week periods during which symptoms were absent, peak flow was decreased in 30 (54%), FEV1 in 20 (36%), and FEF 25-75 in 37 periods (66%). Peak flow readings were normal in 13 of 70 periods (16%) in which FEV1 was decreased, and in 33 of 113 periods (29%), in which FEF 25-75 was decreased. Of 25 periods in which symptoms were absent and peak flow was normal, 19 (76%) were associated with decreased FEF 25-75. The results confirm previous studies that indicate peak flow readings are a useful addition to symptom diaries. More importantly, they demonstrate that airway obstruction may be present in a large proportion of asymptomatic children with asthma who have normal peak flow rates and suggest that frequent assessment of FEF 25-75 is required, as well as daily monitoring of symptoms and peak flow both in trials of drug therapy and for more optimal assessment of the effectiveness of therapy in clinical practice.

Adolescent↗

Variability of pulmonary function tests in stable corticosteroid dependent asthma patients.

We studied 24 corticosteroid dependent asthmatic patients over a period of 10 months to establish a baseline for future therapeutic trials with corticosteroid sparing agents. Clinical symptoms, steroid dose, peak expiratory flow rate (PF), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) were recorded at clinic visits. Correlation was sought between PF and FEV1, steroid dose versus PF and symptom severity, and PF versus time and symptoms. There was considerable weekly variability of PF and FEV1. However, when viewed over almost a year, 54% had no significant change in PF. 29% actually worsened and 17% improved. The data suggest that to assess the effect of a steroid-sparing agent accurately, one must first establish a reliable baseline over several months to eliminate weekly variability. The current trend of obtaining a baseline over a 1 to 2 month interval is inadequate in this study population. We also found that neither patient assessment of severity of symptoms nor corticosteroid dosage correlate with objective spirometric measurements.

Adult↗

[A study on peak expiratory flow monitoring maneuver as compared to forced expiratory flow maneuver].

In this study, we tried to clarify the characteristics of peak expiratory flow (PEF) measurement maneuver as a tool of daily monitoring severity of asthma in accordance with peak expiratory flow rate (PEFR) of forced expiratory maneuver. PEF did not differ when measured either in the standing or sitting position. However, obese individuals may have higher PEF when measured in the standing position and subjects with emphysematous change may have higher PEF when measured in the sitting than in the standing position. PEF did not differ when measured either with or without nose clip. Expiration time and volume in PEF measurement requires only one fifth and a half of that of forced expiratory flow volume measurement, respectively. In 36% of asthmatic patients in whom PEF is measured daily, PEF measurements were thought to be measured after inspiring at about 90% of forced vital capacity. Although PEF is a well tolerated useful clinical parameter in the management of bronchial asthma, it has different characteristics from peak expiratory flow rate (PEFR) of forced expiratory volume measurement.

Adult↗

The bronchodilator effect of Garcinia Kola.

This work investigated the bronchodilator effect of Garcinia Kola (Bitter Kola) in normal Nigerians. Nineteen undergraduate male students (17-25 years) were used for the study which involved the consumption of Garcinia Kola (15 grammes per subject) and the measurement of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at intervals of 30 minutes up to a maximum of 90 minutes. Each subject served as his own control. There was time-dependent increases in the measured parameters. However, only the PEFR showed significant (p < 0.05) increase and this was observed at the 60th minute. This probably shows a mild bronchodilator effect of this Kola.

Adolescent↗

The effect of timolol drops on respiratory function.

PURPOSE: Recently, attention has been focused on the adverse drug reactions of topical timolol, especially with regard to respiratory function in the elderly. This study was designed to assess whether timolol causes an alteration in lung function in patients without pre-existing respiratory disease and who have not suffered the impact of long-term beta 2 blockade. METHODS: A placebo-controlled randomised, double-masked, cross-over study was carried out on 20 ocular hypertensive patients with intraocular pressures over 21 mmHg, normal optic discs and full visual fields by Humphrey perimetry. Subjects received single-dose units of timolol maleate 0.5% drops or normal saline drops. Both were instilled in one eye or systemically (sublingually). The peak expiratory flow rate (PFR), forced expiratory volume (FEV), vital capacity (VC) and FEV/VC (%) ratio were all measured both before and after each type of drop and route of administration. RESULTS: Two hours after instillation of timolol there was no change in PFR (p = 0.67) or VC (p = 0.40), but there was a fall in FEV (p = 0.038) and the FEV/VC (%) ratio (p = 0.041). The fall was greatest after topical administration. CONCLUSIONS: Our results show that in our group of patients there was a tendency towards mild bronchial obstruction after topical timolol, although this was not clinically significant.

Administration, Oral↗

Prospective randomized trial of heliox-driven continuous nebulizers in the treatment of asthma in the emergency department.

The purpose of this study was to evaluate the efficacy of heliox-driven continuous nebulizers in the management of moderate to severe asthma exacerbations in the Emergency Department (ED). The trial was a prospective, randomized, double-blind, controlled trial in a university Emergency Department (volume 65,000 patients/year) of patients 18-55 years of age with acute asthma exacerbations. Patients were placed on continuous nebulizers driven by 70:30 heliox or air with 30% O(2). Respiratory rate, peak expiratory flow rate (PEFR), forced expiratory volume at 1 s (FEV1), and Borg dyspnea scale were measured at 0 and 2 h. Disposition and patient satisfaction were also assessed. A total of 36 patients completed the study (18 heliox, 18 air). There was no difference between groups in baseline variables. There was significant interval improvement within both groups at 2 h in PEFR, FEV1, Borg, and respiratory rate. There was no significant difference between heliox 70:30 and air/oxygen in PEFR [mean between-group improvement difference 17 liters/min, 95% confidence interval (CI) -20-51], FEV1 (0.03 liters/sec, 95% CI -0.22-0.30), or respiratory rate (mean between-group improvement difference 0.5, 95% CI -2.7-3.8). There was a significant improvement in the patients' perceived dyspnea as measured by the Borg dyspnea scale at 2 h in the heliox group (1.6, 95% CI 0.3-3.0). In this trial of patients with moderate-severe asthma exacerbation, heliox-driven continuous nebulizers failed to demonstrate an improvement in respiratory rate, oxygen saturation, PEFR, or FEV1 at 2 h. However, there was a significant improvement in the patients' perceived dyspnea on heliox over air/oxygen measured by the Borg dyspnea scale.

Adolescent↗

Ozone inhalation effects in females varying widely in lung size: comparison with males.

It has been suggested that lung size accounts for observed gender differences in responsiveness to the same total inhaled dose of O3. To test the hypothesis that lung size is a determinant of magnitude of response within a gender, two groups of 14 healthy young adult females differing significantly in forced vital capacity [FVC; i.e., small-lung group mean = 3.74 liters (range 3.2-4.0) and large-lung group mean = 5.11 liters (range 4.5-6.2] were exposed for 1 h to filtered air (FA) and to 0.18 and 0.30 ppm O3. On each occasion, subjects exercised continuously on a cycle ergometer at a work rate that elicited a mean minute ventilation of approximately 47 l/min. For the small-lung group [mean total lung capacity (TLC) = 4.52 liters] exercise O2 uptake was 67% of maximal O2 uptake (VO2max), and that for the large-lung group (TLC 6.37 liters) was 61% of VO2max. Statistical analysis revealed significant decrements for both groups in FVC, forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow rate in the middle half of FVC on exposure to 0.18 and 0.30 ppm O3. Exercise respiratory frequency increased, and tidal volume decreased significantly in both groups in response to 0.18 and 0.30 ppm O3 exposure. On exposure to 0.30 ppm O3, the number of individual subjective symptoms reported and their severity were significantly greater for both groups than those reported for the FA and 0.18 ppm O3 exposures. Both groups evidenced similar percent changes in pulmonary function and exercise ventilation response, and in subjective symptom response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The value of atropine in the documentation of reversible airways obstruction.

Thirteen randomly selected outpatient asthmatics were treated with nebulized atropine sulfate, isoproterenol and the combination of these drugs in a randomized double-blind trial. Sequential pulmonary function parameters, cardiovascular changes and side effects were monitored over a 60-minute period following drug administration. Both atropine and isoproterenol produced significant and equivalent improvement in mean forced expiratory flow rates; the combination of drugs produced significantly greater improvement at each time interval without producing significant cardiovascular changes or side effects. Four patients failed to show clinically significant increases in expiratory flow rates following isoproterenol alone; two of these four improved following atropine alone, while two improved only when given the combination of drugs. The addition of an anti-cholinergic agent may provide a more precise assessment of reversibility of obstructive airways disease in the individual patient.

Adult↗

Comparison of real and simulated acupuncture and isoproterenol in methacholine-induced asthma.

In a double-blind (patient and evaluator), crossover study effects of real acupuncture, simulated acupuncture, nebulized isoproterenol, nebulized saline and no treatment in reversing methacholine-induced bronchospasm were compared in 12 asthmatics (ages 16 to 64). Saline and simulated acupuncture did not result in any significant improvement in specific airway conductance (SGaw), thoracic gas volume (Vtg) or forced expiratory flow rates compared with no treatment following methacholine-induced bronchospasm. Isoproterenol and real acupuncture were both followed by increases in SGaw and flow rates and decreases in Vtg which were significantly different from the changes observed following no treatment, saline or simulated acupuncture, although isoproterenol produced greater improvement than real acupuncture, although isoproterenol produced greater improvement than real acupuncture. These findings suggest that stimulation of specific acupuncture loci reduces methacholine-induced bronchospasm and hyperinflation to an extent greater than can be attributed to placebo phenomena.

Acupuncture Therapy↗

Anatomical dead space and airway resistance after glycopyrrolate or atropine premedication.

The effects of atropine and glycopyrrolate on anatomical dead space, one and three second forced expiratory volume, maximal expiratory flow rate, and total forced expiratory volume were determined in ten healthy volunteers. Using Fowler's single breath nitrogen analyzing technique, atropine was found to increase dead space by 19.2 per cent at one hour, declining to 11.02 per cent at four hours. Glycopyrrolate increased dead space by 21.57 per cent at one hour, 29.28 per cent at two hours, and 26.65 per cent at four hours. When compared to the effects of saline control injection, the dead space increases are significant. The difference between glycopyrrolate and atropine is significant only at four hours. Increases in maximal expiratory flow rate induced by atropine and glycopyrrolate were significant at one-half hour, while atropine alone induced a significant increase in one second forced expiratory volume. Three second forced expiratory volume and total forced expiratory volume were not significantly altered.

Adult↗

Pulmonary response to nasal-challenge testing of atopic subjects with stable asthma.

Nasal deposition of allergen or histamine could cause bronchoconstriction in subjects with asthma by a reflex mechanism. To investigate this possibility, six atopic subjects with stable asthma and five normal control subjects were studied by nasal-challenge testing with saline, Bermuda grass-pollen allergen, and histamine on paper disks. Challenges were done on 3 separate days by use of a double-blind, randomized trial design. Fivefold serial dilutions were used to determine threshold doses for provocation of at least a twofold increase in the postsaline nasal airway resistance. No patient developed cough or wheezing or required treatment at the end of the nasal-challenge tests, even when persistent sneezing was provoked or in the subject who had a dual nasal response to nasal challenge. In spite of changes in nasal airway resistance that generally conformed to expectations, there were no significant effects of nasal challenge on lung function, including forced expiratory flow rates, vital capacity, residual volume, and partial expiratory flow-volume curves.

Adult↗

Long-term safety and efficacy of a chlorofluorocarbon-free beclomethasone dipropionate extrafine aerosol.

BACKGROUND: Beclomethasone dipropionate (BDP) extrafine aerosol, a newly developed pressurized metered dose inhaler (pMDI) with a hydrofluoroalkane-134a (HFA) propellant (HFA-BDP; Qvar, 3M Pharmaceuticals, St. Paul, MN), has been shown to be effective in controlling asthma symptoms at approximately half the daily dose of chlorofluorocarbon (CFC)-BDP. OBJECTIVE: This study evaluated the long-term efficacy and safety of switching patients with asthma maintained on a stable dose of CFC-BDP pMDI to therapy with HFA-BDP pMDI at approximately half their previous daily dose of CFC-BDP. METHODS: This was an open-label, randomized, parallel-group multicenter trial. Patients with at least a 6-month history of asthma whose symptoms were controlled on CFC-BDP, 400 to 1600 microg daily, during a 2-week run-in period were randomized in a 1:3 ratio to CFC-BDP at the same daily dose or HFA-BDP at approximately half the daily dose of CFC-BDP for 12 months. RESULTS: A total of 473 patients were randomized: 354 to HFA-BDP, 119 to CFC-BDP. There were no statistically significant differences between groups in mean change from baseline in morning (AM) peak expiratory flow rate or forced expiratory volume in one second throughout the study. There were no consistent differences between treatment groups in individual asthma symptoms or daily beta2-agonist use during the study. There was an increase in the percentage of symptom-free days between baseline and month 12 in the HFA-BDP group (11.5%) and the CFC-BDP group (4.6%). No statistically significant differences in serum osteocalcin levels or adverse events were seen during the study or in AM plasma cortisol levels at month 12. CONCLUSIONS: Asthma control was maintained in patients switched from a stable dose of CFC-BDP (400 to 1600 microg daily) to HFA-BDP at approximately half the CFC-BDP dose (200 to 800 microg daily), and was maintained over the next 12 months. HFA-BDP demonstrated a similar safety profile to CFC-BDP; there were no differences between the agents with regard to systemic effects.

Administration, Inhalation↗

Evaluation of metoprolol in suppressing complex ventricular arrhythmias.

This study documents the extent of suppression of premature ventricular beats which can be achieved with metoprolol, a semiselective beta-adrenergic blocking agent, at doses of 100 to 200 mg daily, utilizing a single-blind placebo-controlled 10-day protocol with continuous ambulatory electrocardiographic recording of 20 patients with cardiac disease and complex ventricular arrhythmias. Metoprolol (200 mg/day) resulted in suppression of 60% of total premature ventricular beats, with couplets (pairs) and ventricular tachycardia decreased 84% and 94%, respectively (all p less than 0.01). Exercise-induced premature ventricular beats, especially ventricular tachycardia, were effectively suppressed. The peak plasma metoprolol level to achieve these results was 72 +/- 34 ng/ml (mean +/- 1 standard deviation). At this plasma concentration, the mean 24-hour heart rate during normal activity was reduced from 78 +/- 8 beats/min (placebo) to 62 +/- 4 (metoprolol 200 mg/day) (p less than 0.001). Beta blockade also was demonstrated by a 20% reduction in heart rate during maximal Bruce exercise testing with metoprolol 200 mg/day. Although resting left ventricular function was not affected by metoprolol, pulmonary function tests show a statistically significant decrease in forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow rates (25-75) reversible with a beta-2 agonist.

Aged↗

Effect of closed mitral valvotomy on spirometric pulmonary function tests in mitral stenosis.

The effect of closed mitral valvotomy on the spirometric pulmonary functions was studied in 25 patients with mitral stenosis. The tests were performed before and after operation, the latter at varying intervals (4 to 6 weeks and 8 to 12 months). The preoperative values were considerably low. After 4 to 6 weeks following surgery, further significant reduction in Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) was observed. This was ascribed to the residual healing process and thoracotomy pain. However, Forced expiratory flow rate during mid segment of FVC (FEF25-75%), which reflects obstruction in small airways, did not show any variation. There was improvement in all the above parameters, 8-12 months after surgery. This suggests definite reversibility in the pulmonary functions following valvotomy.

Adult↗

Dietary chloride as a possible determinant of the severity of exercise-induced asthma.

Dietary sodium chloride (NaCl) has been shown to alter the severity of exercise-induced asthma, but it is not known if the sodium and chloride ions have independent effects in this regard. The hypothesis tested in the present study was that both a low sodium, low chloride diet and a high sodium, low chloride diet would improve post-exercise pulmonary function in subjects with exercise-induced asthma (EIA) compared to a normal NaCl diet (NSD); but that neither of these diets would have an effect on post-exercise pulmonary function in control (non-EIA) subjects. Eight subjects who suffered from EIA and eight subjects who did not (control) took part in a double-blind crossover study. Pre- and post-exercise pulmonary function was assessed after 2 weeks on a NSD, a low NaCl diet (LSD, low sodium, low chloride) or a sodium bicarbonate diet (NaHCO3 diet, high sodium, low chloride). A 1 week washout period occurred between diets. Altering dietary sodium or chloride had no effect on pre-exercise (baseline) pulmonary function in either group or on post-exercise pulmonary function in control subjects. However, both the LSD and the NaHCO3 diet lessened the deterioration in post-exercise pulmonary function in EIA subjects. Comparing results from pre- to post-exercise, forced expiratory volume in 1 s (FEV1) at 15 min post-exercise differed significantly (P < 0.05) between diets [mean (SEM) 7 (4)% on the LSD, 14 (4)% on the NaHCO3 diet, and 19 (2)% on the NSD]. Similar patterns were observed for forced vital capacity (FVC), forced expiratory flow rate at 25%-75% FVC and peak expiratory flow rate. The NaHCO3 diet lessened the deterioration of post-exercise pulmonary function, but not to the extent of LSD. These data suggest that both sodium and chloride contribute to the worsening of EIA symptoms seen after consuming a normal or high NaCl diet.

Acidosis↗

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.

Airway Resistance↗

Pharmacodynamic evaluation of azelastine in subjects with asthma.

A broad antiallergic compound called azelastine was studied pharmacodynamically in 34 subjects to correlate bronchodilator effect with blood levels of azelastine and desmethyl azelastine, its major metabolic product in man. Despite azelastine and desmethyl azelastine blood levels that were proportionate to the dosage range, the bronchodilator effect as measured by FEV1 and forced expiratory flow rate between 25% and 75% of FVC was proportionately greater with 4 mg of azelastine during the 8-hour study period than the anticipated bronchodilator response with the 8 and 16 mg doses. Azelastine, already proven effective in allergic rhinitis, has a bronchodilator effect at doses that do not produce intolerable side effects.

Adolescent↗

Prolonged endurance challenge at moderate altitude: effect on serum eosinophil cationic protein, eosinophil dynamics, and lung function.

BACKGROUND: Eosinophils contain granule proteins such as eosinophil cationic protein (ECP) that have proinflammatory effects on airways. ECP may be released on activation of eosinophils into the plasma and is widely used as a marker of bronchial hyperreactivity and allergic inflammation. Environmental factors as well as intense physical exertion may influence eosinophil-related bronchial hyperreactivity. STUDY OBJECTIVES: To investigate the effect of endurance exercise at moderate altitude on levels of circulating eosinophils, serum ECP, serum osmolality (sOS), and dynamic pulmonary function parameters in healthy mountaineers. SETTING: Alpine field study performed in the Alps of Upper Styria in Austria. Type of exercise: Ascent of a mountain at maximal speed. PARTICIPANTS: Thirty healthy male volunteers from a troop of military mountaineers. RESULTS: Mean ECP concentration increased by 66% at the summit checkpoint (H2) and remained at 63% above baseline (base checkpoint [H0]) after descent (H4), while the blood eosinophil count decreased concomitantly from 250/microL at H0 (preexercise) to 118/microL (53%) at H2 and to 22/microL (81%) at H4. The total serum ECP concentration adjusted to sOS correlated negatively with blood eosinophil count (r = - 0.37; p < 0.0001) and PaO(2) (r = - 0.34; p < 0.001), but positively with the peak expiratory flow (PEF) [r = 0.45; p < 0.0001]. Although sOS correlated with serum ECP at H2 (r = 0.47; p = 0.02) and at 12 h after the start of the experiment (H12) [r = 0.57; p = 0.003], the relationship between total ECP and sOS (r = 0.19; p = 0.034) was less pronounced. FEV(1) in percentage of FVC (%FEV(1)/FVC) [the Tiffenau test], forced expiratory flow rate at 25% of vital capacity, and PEF were significantly higher at H2 than at H0 and H4. %FEV(1)/FVC decreased to 88% (p < 0.01) and 83% (p < 0.001) predicted at H12 and 24 h after start of the experiment, respectively. CONCLUSION: Results provide strong evidence for nonspecific activation of blood eosinophils during prolonged intense aerobic exercise at moderate altitude, modifying both eosinophil dynamics and regulation of ECP release in healthy subjects.

Adult↗