Correlation between acoustic rhinometry and subjective nasal patency during nasal challenge test in subjects with suspected occupational rhinitis; a prospective controlled study.

OBJECTIVES: To assess the correlation between acoustic rhinometry and visual analogue scale endpoints in the context of nasal challenge with occupational agents. DESIGN: Prospective controlled study. SETTING: University teaching hospital. PARTICIPANTS: Sixty-seven subjects with a history of work-related rhinitis and asthma symptoms. MAIN OUTCOMES MEASURES: Subjects underwent nasal challenge with control and specific agent on consecutive days. Nasal congestive response to challenge was monitored by acoustic rhinometry and visual analogue scale. RESULTS: Results showed no correlation between visual analogue scale and acoustic rhinometry measurements at baseline on the control (r=-0.13, P=0.3) and active (r=0.14, P=0.2) challenge days. No correlation was found between acoustic rhinometry and visual analogue scale when analysing all measurements obtained at all times after challenge with the control and active agent (control: r=0.09, P=0.04; active: r=0.001, P=0.9). The correlation between acoustic rhinometry and visual analogue scale was good and significant (r=-0.62, P=<0.01) when the analysis was restricted to cases showing a decrease in nasal volume>40% from baseline values. CONCLUSIONS: We showed that the correlation between acoustic rhinometry and subjective nasal patency was poor on steady conditions. However, a significant correlation was observed in those cases showing a greater nasal congestive response after challenge measured by acoustic rhinometry.

Occupational rhinitis in workers investigated for occupational asthma.

BACKGROUND: The links between asthma and rhinitis are now referred to as united airways disease (UAD). Current evidence shows that the UAD model seems to be applicable to occupational rhinitis (OR) and occupational asthma (OA). A study was undertaken to objectively assess, in the context of specific inhalation challenge (SIC) testing, the concomitance of bronchial and nasal reaction in the investigation of OR and OA. METHODS: 43 subjects with a history of work-related asthma symptoms underwent SIC for confirmation of OA and investigation of OR. Changes in bronchial calibre were measured by spirometry and nasal patency and airway inflammation were assessed by acoustic rhinometry and nasal lavage. RESULTS: A positive nasal challenge was observed in 25 SIC tests and a positive bronchial challenge was observed in 17 SIC tests. A concomitant positive nasal and bronchial challenge was observed in 13 instances. This association was significant (risk ratio = 1.7; 95% CI 1.0 to 2.4; p = 0.04) and more frequent in subjects challenged with high molecular weight agents (n = 11/22) than with low molecular weight agents (n = 2/21). In subjects with a positive nasal challenge, nasal lavage showed a significant increase in eosinophils 30 min after exposure which correlated with changes in nasal patency. CONCLUSION: The results of this study provide objective evidence to support the concept of UAD using OR and OA as a model to demonstrate a significant concomitant physiological reaction of the nose and lungs after challenge. This study shows that OR can be assessed by objective means; it often coexists with OA but can be present without OA.

Thermal Dynamics Effects using Pulse-Shaping Laser Sintering of Printed Silver Inks.

In recent years, additive manufacturing has been evolving towards flexible substrates for the fabrication of printable electronic devices and circuits. Generally polymer-based, these emerging substrates suffer from their heat sensitivity and low glass-transition temperatures. As such they require new highly-localized sintering processes to treat the electronic inks without damaging the polymer-based substrate. Laser-based sintering techniques have shown great promises to achieve high-quality sintering locally, while controlling the heat penetration to preserve the polymer substrates integrity. In this report, we explore new optimization pathways for dynamic laser-based sintering of conductive silver inks. Multiple passes of a pulsed laser are first performed while varying pulse train frequencies and pulse energies as an attempt to optimize the properties of the silver inks. Then, time-domain pulse shaping is performed to alter the properties of the conductive inks. Together, these pathways allow for the careful control of the time-domain laser energy distribution in order to achieve the best electronic performances while preserving the substrate's integrity. Sheet resistance values as low as 0.024Ω/□ are achieved, which is comparable to conventional 1-hour oven annealing, with the processing time dramatically reduced to the milisecond range. These results are supported by finite element modeling of the laser-induced thermal dynamics.

Graphene dispersions in alkanes: toward fast drying conducting inks.

Graphene inks are becoming widely popular. However the vast majority of these inks are formulated in polar solvents with high-boiling points. Their slow evaporation is a bottleneck factor in roll-to-roll printing processes. Here, we developed a highly-conductive fast-drying graphene ink in isooctane, a non-polar and low-boiling solvent. For this purpose, a diblock copolymer containing pendant cholesterol groups was used during the exfoliation of natural graphite in isooctane. The polymer develops non-covalent supramolecular interactions with the graphene conjugated system, resulting in the formation of stable graphene dispersions (up to c = 4 mg mL-1). These dispersions were used for direct writing on a variety of substrates, and were shown to dry instantly after application. The influence of polymer concentration on graphene characteristics, on colloidal stability and on electrochemical characteristics has been studied. The lowest sheet resistance (80 Ω â–¡-1) was obtained when 23% of the graphene surface was covered by the polymer. In this case, the flakes were constituted of 2-5 graphene layers. More extensive exfoliation, down to single-layer graphene, was achieved at greater surface coverage, but led to inks with higher sheet resistance. Thus, by combining a tailored polymeric dispersant, a smooth exfoliation process and a low-boiling non-polar ink solvent, we were able to prepare highly-conductive fast-drying graphene inks which should have a high potentital for the development of roll-to-roll printed electronics.

A novel parasite-derived suicide gene for cancer gene therapy with specificity for lung cancer cells.

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) expressed by the parasite Trypanosoma brucei (Tb) can convert allopurinol, a purine analogue, to corresponding nucleotides with greater efficiency than its human homologue. We have developed a retroviral system that expresses the parasitic enzyme and tested its capacity to activate the prodrug allopurinol to a cytotoxic metabolite. Cytotoxicity assays demonstrated that five non-small cell lung carcinoma cell lines transduced with the construct were sensitized to the prodrug by 2.1- to 7.6-fold compared with control values. This selectivity was not observed in seven other cell lines also expressing the construct, such as breast carcinoma. Assays indicated that enhanced cytotoxicity to allopurinol correlated with induction of apoptosis in lung cancer cells. The selectivity of this suicide gene was not explained either by the TbHGPRT expression or by the allopurinol accumulation. Our study shows that this novel system may represent a therapeutic tool for gene prodrug targeting of lung cancer, considering the fact that allopurinol is well tolerated in humans.

Duration of effect of loratadine and terfenadine administered once a day for one week on cutaneous and inhaled reactivity to histamine.

STUDY OBJECTIVE: The duration of action of several new non-sedative antihistamine preparations as assessed by skin and bronchial reactivity to histamine has still not been well established. The aim of the study was to evaluate the duration of effect of loratadine (10 mg) and terfenadine (120 mg) administered once a day for one week on cutaneous and inhaled reactivity to histamine by comparison with a placebo. SUBJECTS: Twenty-four adult asthmatic subjects were included in a parallel group study that compared the duration of effect of two antihistamines and a placebo on cutaneous and inhaled reactivity to histamine. STUDY DESIGN: Baseline cutaneous and inhaled reactivity (concentration causing a fall of 20 percent in FEV1 [PC20]) to histamine was obtained on three consecutive days. Loratadine (10 mg), terfenadine (120 mg) and a placebo loratadine were administered daily for 1 week to 3 groups of subjects. The PC20 was measured at the end of the medication period, 3 days later, and weekly until PC20 returned to baseline value (upper limit of 2 SD from the mean baseline value). RESULTS: The mean blocking duration on cutaneous reactivity for loratadine was 6.9 days and for terfenadine, 7.2 days. The mean duration of the blocking effect on PC20 histamine was 8.5 days for loratadine and 7.2 days for terfenadine. These figures were significantly longer than for the placebo. CONCLUSION: These data suggest that terfenadine and loratadine have a comparable blocking effect on reactivity to cutaneous and inhaled histamine. A daily dose taken for one week will result in a mean blocking effect of one week.

Comparison of four-times-a-day and twice-a-day dosing regimens in subjects requiring 1200 micrograms or less of budesonide to control mild to moderate asthma.

The aim of this study was to compare the efficacy, compliance and side-effects of budesonide administered twice daily (b.d.) and four times a day (q.d.) with a Turbuhaler device in asthmatic subjects requiring < or = 1200 micrograms daily. The randomized, parallel group study design included a 2-week baseline period followed by a 6-12-month treatment period. Subjects were assessed at regular intervals in hospital through FEV1, PC20 methacholine, adrenal function and throat swabs. They were asked to record their symptoms and PEF values morning and evening at home. An asthmatic flare-up, which was the main outcome resulting in a patient's termination of the study, was defined beforehand as (a) 25% or greater diurnal variability in PEF for 2 consecutive days, and/or (b) nocturnal awakenings due to asthma symptoms 2 days or more in the same week and/or (c) an increase (doubling or more) in the need for inhaled bronchodilator 2 days in the same week. Fifty-eight adult asthmatic subjects (20 males and 38 females) entered the study, one-half being randomly assigned to the b.d. regimen and one half to the q.d. regimen. Fourteen subjects were on 400 micrograms, 15 subjects on 800 micrograms and 29 subjects on 1200 micrograms of budesonide daily. Seventeen flare-ups were recorded in the b.d. regimen group as opposed to 11 in the q.d. regimen (P = 0.05), significant differences being found in the 800 and 1200 micrograms groups (a total of 13 flare-ups in the b.d. group and eight flare-ups in the q.d. group for the two doses, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiological study of parasite infection in a cow-calf beef herd in Quebec.

The patterns of gastrointestinal and pulmonary nematode infections in a previously untreated Aberdeen Angus cow-calf herd were observed between May 1988 and December 1990. The cow-calf herd and replacement heifers were on separate pastures. The relatively high mean faecal egg counts of cows and heifers at the time of turnout were mainly owing to the maturation of hypobiotic worms. The strongyle egg counts of calves began to rise soon after turnout onto pasture and reached peak levels at the end of the grazing season. The number of infective larvae on pasture was highest during September/October. Ostertagia, Cooperia and Nematodirus were the most prevalent genera found at necropsy and on pasture. Larvae of these nematodes were able to overwinter on pasture and Ostertagia larvae, additionally, were able to overwinter in the host as arrested early fourth stage larvae. The high egg output of cows at the time of turnout may serve as a source of infection for their calves and be responsible for the late-season rise in pasture larval counts.

Efficacy of moxidectin against naturally acquired nematode infections in cattle.

The efficacy of moxidectin, a new endectocide against natural nematode infections, was evaluated. Twenty-five calves were divided into two groups of eight calves each and a third group of nine calves. Moxidectin was administered s.c. to two groups (I, 0.2 mg kg-1 body weight (BW); II, 0.3 mg kg-1 BW) and the third group (III) received the vehicle (placebo) s.c. Two pre-treatment and one post-treatment faecal nematode egg count determinations were made from all calves, and they were necropsied 2 weeks after treatment for the identification and enumeration of nematode parasites. Group III calves, which received the drug-free vehicle, harboured eight species of nematodes (Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora, Cooperia punctata, Nematodirus helvetianus, Trichuris discolor, Oesophagostomum radiatum and Dictyocaulus viviparus). The mean total worm burden for this group was 8935. There was a significant reduction in the numbers of many species of nematodes (Ostertagia, Trichostrongylus, Cooperia and Nematodirus) in both treated groups. Cooperia oncophora was reduced by 94% in Group I and by 96% in Group II, while all other nematode species were reduced by 99%. Immature stages of Ostertagia and Nematodirus were significantly reduced in the two treated groups. Two weeks after treatment, the mean faecal egg counts of both treated groups were reduced by more than 98%. There was no significant difference in mean total worm burdens or egg counts between the two treated groups.

Nematode reinfection following treatment of cattle with doramectin and ivermectin.

A study was conducted to investigate reinfection with nematodes in calves following treatment with doramectin or ivermectin administered subcutaneously at a dose rate of 200 micrograms kg-1 of body weight under conditions of natural challenge. Thirty calves were allocated to three groups of 10 calves each based on body weight, sex, breed and pre-treatment faecal egg counts (FEC) after grazing together on a common pasture for three months. Treatments were doramectin, ivermectin and no treatment. Calves were returned to the same pasture for 56 days, placed on dry lot from days 56 to 63 and then necropsied over days 64-66. Faecal egg counts were done at days -1 and 0, then bi-weekly from day 14 to 56 and day 63. Mean FEC in control calves continued to rise throughout the grazing period. Trichostrongyle FEC were significantly (P < 0.05) greater in the control group compared to either treated group at each sample time following treatment. At necropsy, a total geometric mean of 19,847 nematodes per calf was recovered from untreated controls, of which eight genera were identified. The predominant nematode genera were Ostertagia (8749), Nematodirus (3702) and Cooperia (1927). In the ivermectin-treated calves, geometric mean worm burden was similar to that of the untreated controls: A total of 20,349 nematodes per calf was present including the genera Nematodirus (8633), Ostertagia (4700) and Cooperia (1740). In contrast, the geometric mean worm burden in doramectin-treated calves was 12,173, including Ostertagia (4310), Cooperia (1141) and Nematodirus (1667). Doramectin was more effective than ivermectin in protecting calves from reinfection over a 56-day post-treatment grazing period under conditions of natural challenge as measured by accumulated mean worm burdens.

Persistent efficacy of doramectin pour-on against artificially induced infections of nematodes in cattle.

Two studies were conducted to determine the persistent efficacy of doramectin pour-on against an artificial, trickle challenge of mixed nematodes in calves. In each study, 42, 4-8 months old calves were randomly assigned into four groups of 10 animals each (T1-T4), plus two larval-viability monitor animals. All animals were treated with fenbendazole (10 mg kg(-1)) 14 days prior to the start of the study to clear any existing infection. Doramectin pour-on at 500 microg kg(-1) was used on each animal in Groups T2, T3, and T4 with intervals of 1 week (Day 0, 7, and 14, respectively). Calves in Group T1 were treated with saline solution on Day 0 and at the same volumetric rate (1 ml 10 kg(-1)) as the doramectin treated animals. All treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Subsequently, trickle inoculations with infective larvae were administered to all calves for 22 consecutive days (Days 14-35). Doramectin pour-on provided > or = 91.9% efficacy against challenge with Dictyocaulus viviparus, Haemonchus spp., and Ostertagia ostertagi for up to 35 days post-treatment and against challenge with Cooperia oncophora, Cooperia punctata, and Oesophagostomum radiatum for up to 28 days post-treatment.

[Duration of bronchial protective effect of salmeterol in asthma induced by hyperventilation with dry cold air]. / Durée de l'effet bronchoprotecteur du salmétérol dans l'asthme induit par l'hyperventilation d'air froid sec.

The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200 micrograms) and placebo was compared in a double-blind study carried out in 12 adult asthmatic subjects who underwent hyperventilation tests with cold dry air on 4 study days. On the first day, the hyperventilation test was carried out at various time intervals with spontaneous functional recovery between each test. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV1 (PD20). On the three other days, the active or placebo medications were administered. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated at various time intervals after administering the drug. The mean duration of the blocking effect was 0.25 hour for placebo, 3.5 hours for albuterol, and of 15.9 hours for salmeterol. Eight of the 12 subjects still showed some blocking effect eight hours after salmeterol by comparison with only one subject after albuterol. The authors conclude that salmeterol has a significantly longer effect than albuterol on bronchoconstriction induced by hyperventilation.

Using restrictive messages to limit high-fat foods or nonrestrictive messages to increase fruit and vegetable intake: what works better for postmenopausal women?

BACKGROUND/OBJECTIVES: To compare the effects of two dietary approaches on changes in dietary intakes and body weight: (1) an approach emphasizing nonrestrictive messages directed toward the inclusion of fruits and vegetables (HIFV) and (2) another approach using restrictive messages to limit high-fat foods (LOFAT). SUBJECTS/METHODS: A total of 68 overweight-obese postmenopausal women were randomly assigned to one of the two dietary approaches. The 6-month dietary intervention included three group sessions and ten individual sessions with a dietitian. Dietary food intake and anthropometric variables were measured at baseline, at 3 months and at 6 months. RESULTS: Energy density decreased in both groups after the intervention compared with baseline (HIFV, -0.3+/-0.2 kcal/g; LOFAT, -0.3+/-0.3 kcal/g; P<0.0001). Although body weight decreased significantly in both groups after the intervention compared with baseline (HIFV, -1.6+/-2.9 kg; LOFAT, -3.5+/-2.9 kg; P<0.0001), women in the LOFAT group lost significantly more body weight than women in the HIFV group (P=0.01). In the HIFV group, the decrease in energy density was found to be an independent predictor of body weight loss. CONCLUSIONS: The LOFAT approach induces more weight loss than does the HIFV approach in our sample of overweight-obese postmenopausal women.

Should we monitor peak expiratory flow rates or record symptoms with a simple diary in the management of asthma?

BACKGROUND: Various means of monitoring asthma severity have been proposed to reduce morbidity and mortality rates. We compared two means of assessing asthma flare-ups: monitoring peak expiratory flow rate (PEFR) and keeping a symptom diary. METHODS: This was a crossover randomized study. After a 2-week baseline period during which spirometry and PC20 methacholine were assessed, subjects were asked to record either PEFRs or to keep a symptom diary morning and evening for 6 months; a second baseline assessment separated the two periods. Subjects were asked to contact the study coordinator if the following occurred: (1) in the period of PEFR monitoring, daily fluctuations in PEFR were > 20% or the absolute value fell to < 80% of baseline or both occurred; (2) in the period of symptom diary monitoring there were nocturnal symptoms or a persistence of morning dyspnea after inhaled bronchodilator or a reduction in the duration of effect of the bronchodilator or it was impossible to go to work or school or all occurred. In that case they were asked to come to the hospital to confirm the flare-up through investigation for significant changes in FEV1 or PC20 or both. Forty subjects completed a 6-month symptom diary or PEFR recording period respectively, and 20 completed both. RESULTS: A total of 31 exacerbations were reported in 28 different subjects; three subjects had two flare-ups. Thirteen of 19 (69%) flare-ups were confirmed during the symptom diary period and 9 of 12 (75%) during PEFR monitoring. Nocturnal awakenings and morning falls in PEFR > or = 20% were the most frequent occurrences. CONCLUSIONS: We conclude that a simple symptom diary may be as useful as serial PEFR monitoring in documenting asthmatic flare-ups.

Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle.

Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two-way cross-over design. Blood samples were taken serially over a 72-h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post-treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5-0.75 h up to 32 h post-administration, with a Cmax for the zwitterion suspension of 1.21 +/- 0.13 micrograms/ml and AUC of 18.55 +/- 1.45 micrograms.h/ml, respectively, which were significantly higher (P less than 0.01) than the Cmax (0.67 +/- 0.12 micrograms/ml) and AUC (8.57 +/- 0.91 micrograms.h/ml) for the trisamine solution. ABZSO2 was detected in plasma between 0.75 and 48 h post-administration. The zwitterion suspension resulted in a Cmax (2.91 +/- 0.10 micrograms/ml) and AUC (51.67 +/- 1.95 micrograms.h/ml) for ABZSO2, which were significantly higher (P less than 0.01) than those obtained for the trisamine solution (Cmax = 1.67 +/- 0.11 micrograms/ml and AUC = 22.77 +/- 1.09 micrograms.h/ml). The ratio of AUC for ABZSO2/ABZSO was 2.92 +/- 0.26 (zwitterion) and 2.80 +/- 0.20 (trisamine). The MRT for ABZSO2 was significantly longer (P less than 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Do subjects investigated for occupational asthma through serial peak expiratory flow measurements falsify their results?

BACKGROUND AND AIM: Serial assessment of peak expiratory flow (PEF) rates has been advocated as a sensitive and specific means of investigating occupational asthma. The possibility that, for several reasons, subjects do not accurately report their values has been raised. The availability of portable instruments that assess PEF and store timings and values now make it possible to estimate compliance and accuracy of results. METHODS: Twenty-one subjects consecutively investigated for occupational asthma were asked to assess their PEF every 2 hours during the day, both at work and away from work, with a VMX instrument (Clement Clarke International, Columbus, Ohio) and record the times and values on a sheet of paper. The subjects were not aware that the data were also being stored on a computer chip. The diagnosis was occupational asthma in eight subjects, personal asthma in four subjects, and neither condition in nine subjects. RESULTS: The mean duration of recording was 36 days (range, 14 to 79 days). At least 6048 values should have been recorded, but only 4839 (80%) were either recorded or stored. Reported values corresponded precisely to stored values in 2533 of 4839 recordings (52%). The timing of the recording was also examined in relation to the time at which the recording was solicited; values recorded within 1 hour of the solicited time were judged as acceptable. Of the total of 3342 recordings stored, 2375 (71%) satisfied this criterion. Compliance was significantly less satisfactory in those referred by the Workers' Compensation Board (n = 11). CONCLUSION: In this survey of 21 subjects investigated for possible occupational asthma, compliance with PEF recording, as assessed by comparing recorded and stored results and the time at which the recording was solicited, was poor.

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

The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200 micrograms), and a placebo were compared in a double-blind study in 12 adult subjects with asthma who underwent hyperventilation tests with cold dry air (-20 degrees C) on 4 study days. On the first day, the hyperventilation test was performed at various time intervals (baseline, 1, 4, 6, 8, 12, and 24 hours) with spontaneous functional recovery between each test to determine the within-day within-subject variability of the response. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV1. On the 3 remaining days, separated by an interval of at least 5 days, the active or placebo medication was administered after spontaneous recovery from the first hyperventilation test. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated 4 hours after administration of the drug. The test was repeated 6, 8, 12, and 24 hours later to detect any significant blocking effect. The improvement in FEV1 15 minutes and 1 hour after the drug was administered was 19.8% and 20.4%, as compared to baseline for albuterol, and 16.3% and 16.8% for salmeterol (not significant). The mean duration of the blocking effect was 0.25 hour for the placebo, 3.5 hours for albuterol, and 15.9 hours for salmeterol (F = 24.5; p less than 0.001; Newman-Keul's test was significant for every contrast). Eight of the 12 subjects still demonstrated some blocking effect 8 hours after taking salmeterol; this was true for only one subject receiving albuterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Compliance with and accuracy of daily self-assessment of peak expiratory flows (PEF) in asthmatic subjects over a three month period.

Serial peak expiratory flow (PEF) assessment has been proposed in the clinical evaluation of asthma. In subjects attending the asthma clinic of a tertiary care hospital, we wanted to assess: 1) compliance in performing PEF; and 2) accuracy of a PEF-diary. Twenty adult asthmatic subjects, all using inhaled steroids, were asked to assess their PEF in the morning and evening with a VMX instrument (Clement Clarke Int., Colombus, OH, USA). This instrument, which incorporates a standard mini-Wright peak flow meter, stores PEF data on a computer chip. Subjects were not informed that the values were being stored. The mean duration of PEF monitoring was 89 days (range 44-131 days). For the total of 20 subjects, it was estimated that 3,482 values should have been written down and stored on the VMX computer chip. Whilst 1,897 values (54%) were written down, only 1,533 (44%) were stored, 425 values being invented. Morning and evening values were stored on 34% of days; and values were stored at least once a day on 55% of days. The values written down corresponded precisely to stored values 90% of the time, and were within +/- 20 L 94% of the time. We conclude that: 1) compliance with daily peak expiratory flow assessments is generally poor in chronic stable asthmatic subjects assessed on two visits separated by a 3 month period; and 2) a substantial percentage of values (22%) is invented. The unsatisfactory compliance with peak expiratory flow monitoring in this group of asthmatics on inhaled steroids underlines the need for similar studies on peak expiratory flow monitoring as part of an action treatment plan, and in more severe and brittle asthmatics.

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)

Duration of action of inhaled terbutaline at two different doses and of albuterol in protecting against bronchoconstriction induced by hyperventilation of dry cold air in asthmatic subjects.

Although several studies have examined the duration of the bronchodilator effect of several inhaled beta-2-adrenergic agents, the duration of the blocking effect on bronchial hyperresponsiveness, another key feature of asthma, has seldom been studied. We investigated this problem in eight adult asthmatic subjects who underwent hyperventilation tests with dry cold air on 4 different days. On the first day, five hyperventilation tests with assessment of the level of ventilation causing a 20% fall in FEV1 (PD20) were obtained to evaluate the within-day variability of the test. On the three other visits, after a baseline hyperventilation test, albuterol 200 micrograms, terbutaline 500 micrograms, and terbutaline 1,500 micrograms were administered in a double-blind, randomized way. Hyperventilation tests were carried out 1, 2, 4, and 6 h later. The blocking effect on the treatment days, as assessed by the differences in PD20 for each test compared with baseline PD20 for that day, was corrected for the within-day variability of the control day. There was a significant bronchodilator effect 1 h after administering the drug; it was equivalent for albuterol 200 micrograms (25.6 +/- 14.7%) and terbutaline 1,500 micrograms (21.7 +/- 13.5%) and significantly less for terbutaline 500 micrograms (14.1 +/- 10.0%). Complete or partial blockade on bronchial responsiveness was obtained in the majority (six to seven of eight) of the subjects 1 h after inhaling the bronchodilator, with progressive reduction in the effect later on. Four subjects still showed a blocking effect 6 h after terbutaline 1,500 micrograms was administered, one subject after terbutaline 500 micrograms, and no subjects after albuterol (chi square = 6.6, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)