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Biomedical subjects

H Ghezzo

Publications and source records attributed to H Ghezzo.

At least 19 recordsLinked to original sources

Changes in IgE-mediated allergy to ubiquitous inhalants after removal from or diminution of exposure to the agent causing occupational asthma.

BACKGROUND: One possibility, among others, for explaining the persistence of asthma symptoms in occupational asthma (OA) after the cessation of exposure to the causal agents may be that subjects become sensitized to ubiquitous inhalants. OBJECTIVE: The aim of this study was to evaluate the development or increase of IgE-mediated sensitization to ubiquitous allergens, both to high- and low-molecular-weight agents, in 100 subjects with OA after cessation of exposure. METHODS: Subjects were evaluated on a first visit, at the time of diagnosis of OA, coinciding with the cessation or diminution of exposure to the causal agent, and on a second visit, 5.8+/-3.3 years afterwards. At each visit, a history of ocular, nasal and asthmatic symptoms related to exposure to common allergens was obtained together with spirometry and assessment of bronchial responsiveness to methacholine. We analysed total IgE and specific IgE to Dermatophagoides farinae, D. pteronyssinus, birch, ragweed and timothy grass pollens, cat and dog danders, and Alternaria, using enzyme allergosorbent test (EAST) from blood samples taken on each visit. RESULTS: Total IgE levels showed a tendency to diminish. No changes were found in the number of positive EAST (presence of detectable levels of specific IgE) or in the levels of specific IgE. Although significantly more symptoms of rhinoconjunctivitis and asthma in contact with house dust (P < 0.05) and pets (P < 0.01) were reported on the second visit than on the first, no significant changes in the frequency of symptomatic sensitized subjects were found. CONCLUSION: Subjects with OA are unlikely to develop IgE-dependent sensitization to common inhalants after removal from exposure to occupational agents.

Adult

Nasal response in subjects undergoing challenges by inhaling occupational agents causing asthma through the nose and mouth.

BACKGROUND: Subjects with occupational asthma (OA) often report nasal symptoms, but nasal reactions to inhalation challenges with occupational agents have not been well characterized. METHODS: Fifteen subjects with OA (eight due to high-molecular-weight agents--flour and guar gum--and seven due to isocyanates) underwent inhalational challenges using closed-circuit devices (dry particles for high-molecular-weight agents and gas generator for isocyanates) on two occasions, 2-4 weeks apart in a random fashion. On one occasion, they inhaled through the nose and, on another, through the mouth. The FEV1 was monitored for up to 8 h afterward, and symptoms were documented with a standardized questionnaire on nasal symptomatology, assessment of nasal resistance by rhinomanometry, and nasal lavage for the examination of cells and mediators. RESULTS: Inhaling through the mouth and through the nose: 1) yielded similar asthmatic responses (25+/-8% and 22+/-10% maximum changes in FEV1) 2) more than doubled the peak nasal symptoms and nasal resistance when the maximum daily response was compared with prechallenge results. This increase occurred on the days of inhalational challenges through the mouth and through the nose. There were some significant responses assessed by nasal lavage in terms of cells and mediators, again with no differences between the days of challenges through the mouth and through the nose. CONCLUSIONS: Inhaling occupational agents of high or low molecular weight, including isocyanates, whether through the mouth or nose: 1) results in a similar asthmatic response 2) causes a significant nasal response in terms of symptoms and an increase in nasal resistance 3) causes some significant changes in inflammatory cells and mediators.

Administration, Inhalation

Time-course of functional and pathological changes after a single high acute inhalation of chlorine in rats.

Reactive airways dysfunction syndrome (RADS) is an asthma-like condition that follows exposure to very high concentrations of an irritant material. We assessed the time-course of pathophysiological alterations in a model of RADS. Sprague-Dawley rats were exposed to 1,500 parts per million (ppm) of chlorine for 5 min. Lung resistance (RL), responsiveness to inhaled methacholine (MCh), the airway epithelium and bronchoalveolar lavage (BAL) were assessed over a 3 month period after exposure. RL increased significantly up to 3 days after exposure, reaching a maximal change of 110+/-16% from baseline. There was a significant decrease in the concentration of MCh required to increase RL by 0.20 cmH2O x mL(-1) x s from days 1-7 after exposure. In some rats, MCh hyperresponsiveness and RL changes persisted after exposure for as long as 1 and 3 months, respectively. Histological evaluation with morphometric evaluation revealed epithelial flattening, necrosis, increase in smooth muscle mass and evidence of epithelial regeneration. BAL showed an increased number of neutrophils. The timing of maximal abnormality in the appearance of the epithelium (days 1-3) corresponded to that of the maximal functional changes. Acute high chlorine exposure results in functional and pathological abnormalities that resolve in the majority of animals after a variable period; however, these changes can persist in some animals. Functional abnormalities in the initial stages may be related to airway epithelial damage.

Administration, Inhalation

Determinants of the bronchial response to high molecular weight occupational agents in a dry aerosol form.

In occupational challenge tests with isocyanate vapours, bronchial responsiveness is determined by the total dose rather than the concentration or duration of exposure. Whether the same applies for high molecular weight (HMW) agents in powder form is unknown. The aim of this study was to determine whether the total dose of HMW agents in powder form is responsible for the immediate reaction documented in specific challenge tests. Included in the study were nine subjects (seven males and two females) with a diagnosis of occupational asthma proved by specific challenge tests carried out on a preliminary visit. Two challenge tests (using a closed-circuit exposure chamber) were performed at an interval of 2 weeks; the concentrations administered in a random order on these two visits were half and double the one that had caused a 20% fall in forced expiratory volume in one second (FEV1) on a preliminary visit. The duration of exposure was adjusted until a significant fall in FEV1 (target of 20%) occurred. The two concentrations obtained were significantly different, by 2.07+/-0.36-fold (SD). The observed durations of exposure leading to a 20% fall in FEV1 on the two visits also differed significantly by 0.46+/-0.32-fold. Consequently, the cumulative efficient doses were not significantly different between the two visits: 12+/-5.4 and 9+/-5 mg x mL(-1) x min(-1), respectively. The corresponding cumulative dose ratio was 0.96+/-0.61. The expected duration of exposure (10.8+/-24 min) was not significantly different from the observed duration (5.4+/-9 min). The mean and 95% confidence interval for the difference in concentration between the two visits was 1.83-fold (1.48-2.21). In conclusion, the total dose rather than the concentration or duration of exposure per se determines bronchial responsiveness to high molecular weight agents in powder form.

Adult

Follow-up of occupational asthma after removal from or diminution of exposure to the responsible agent: relevance of the length of the interval from cessation of exposure.

STUDY OBJECTIVE: We set the hypothesis that follow-up surveys of occupational asthma (OA) could now show better improvement in the asthmatic condition because of a more prolonged interval since removal from exposure than in previously reported studies. PATIENTS/METHODS: Ninety-nine subjects with OA were assessed and were separated into two groups according to the duration of cessation of exposure: (1) group removed for > or = 5 years: 48 subjects studied 8.9+/-2.2 years after cessation of exposure; (2) group removed for <5 years: 51 subjects with OA, comparable in terms of history and functional results at time of diagnosis, with a time lapse from last exposure of 3.1+/-1.2 years. On the follow-up visit, questionnaires including information on the current and previous use of inhaled steroids, spirometry, and methacholine tests were administered and results were compared with those obtained at the time of diagnosis. RESULTS: At the follow-up visit, no significant changes in spirometry were observed in the two groups. However, a significant improvement in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from a mean value of 1.5 to 3.7 mg/mL was documented (p<0.001). The proportion of subjects having normal PC20 at the follow-up visit was significantly higher in the group removed from exposure for >5 years than in the group removed for < or = 5 years (16/33 vs 8/42; p=0.01). Stepwise logistic regression showed that follow-up PC20 could be predicted from baseline PC20 (p<0.001, odds ratio [OR]=4.1, 95% confidence interval [CI]=1.8 to 9.1), duration of exposure (p=0.04, OR=0.9, 95% CI=0.8 to 1.0), the interval since removal from exposure (p=0.002, OR=1.7, 95% CI=1.2 to 2.5), and the type of agent; subjects with OA due to high-molecular-weight agent showed a less favorable outcome (p=0.04, OR=0.2, 95% CI=0.03 to 1.0). Current and past treatments with inhaled steroids were not significant predictors. CONCLUSION: Results obtained in the group of this study removed for >5 years show better prognostic figures than those reported in most previous studies. Comparison with the group removed for a shorter interval and the stepwise logistic regression analysis suggest that the longer duration of the interval from cessation of exposure appears to be a factor determining this difference.

Adult

Exercise limitation in obstructive lung disease.

OBJECTIVE: To study the relationship of resting pulmonary function to maximal exercise power output (Wmax) in obstructive lung disease (OLD). SETTING: University Hospital Pulmonary Function Laboratory. SUBJECTS: Twenty-five patients with OLD (6 with asthma and 19 with COPD). METHODS: Measurement of pulmonary lung function, resting arterial blood gases, and maximal symptom-limited exercise on a cycle ergometer. RESULTS AND CONCLUSIONS: In OLD, the only significant contributor to Wmax was the inspiratory capacity (r2 = 0.66; p < 0.001).

Blood Gas Analysis

Airway smooth muscle orientation in intraparenchymal airways.

Airway smooth muscle (ASM) shortening is the central event leading to bronchoconstriction. The degree to which airway narrowing occurs as a consequence of shortening is a function of both the mechanical properties of the airway wall as well as the orientation of the muscle fibers. Although the latter is theoretically important, it has not been systematically measured to date. The purpose of this study was to determine the angle of orientation of ASM (theta) in normal lungs by using a morphometric approach. We analyzed the airway tree of the left lower lobes of four cats and one human. All material was fixed with 10% buffered Formalin at a pressure of 25 cmH2O for 48 h. The fixed material was dissected along the airway tree to permit isolation of generations 4-18 in the cats and generations 5-22 in the human specimen. Each airway generation was individually embedded in paraffin. Five-micrometer-thick serial sections were cut parallel to the airway long axis and stained with hematoxylin-phloxine-saffron. Each block yielded three to five sections containing ASM. To determine theta, we measured the orientation of ASM nuclei relative to the transverse axis of the airway by using a digitizing tablet and a light microscope (x250) equipped with a drawing tube attachment. Inspection of the sections revealed extensive ASM crisscrossing without a homogeneous orientation. The theta was clustered between -20 degrees and 20 degrees in all airway generations and did not vary much between generations in any of the cats or in the human specimen. When theta was expressed without regard to sign, the mean values were 13.2 degrees in the cats and 13.1 degrees in the human. This magnitude of obliquity is not likely to result in physiologically important changes in airway length during bronchoconstriction.

Animals

Influence of inhaled steroids on recovery from occupational asthma after cessation of exposure: an 18-month double-blind crossover study.

Occupational asthma (OA) is a useful model for the study of asthma in humans. The possibility that inhaled corticosteroids, in addition to withdrawal from the workplace, could improve clinical and functional recovery from OA can be hypothesized. We assessed clinical, functional, and behavioral characteristics of 32 subjects (22 male, 10 female), in all but one of whom OA was confirmed by specific inhalation challenges induced by either high- (n=13) or low-molecular-weight (n=19) agents within 3 mo after cessation of exposure. In this randomized, crossover, double-blind study, subjects (paired for baseline PC20 and duration of symptoms after exposure) received either placebo or 1,000 micrograms of inhaled beclomethasone daily for 1 yr, followed by the alternate medication for 6 mo. Various clinical, functional, and behavioral parameters were examined at each 3-mo visit. Significant improvement in clinical (nocturnal symptoms, cough), functional (morning and evening peak expiratory flow rates), and behavioral (quality of life) parameters were detected in the active-treatment period, although the magnitude of the improvement was relatively small. Side effects (oropharyngeal, reduced cortisol) were similar in the placebo and treatment groups. Distinguishing subjects who started with the active preparation from those who were given placebo first showed that most clinical and behavioral parameters improved in the former instance, whereas there was no significant difference in the latter. We conclude that inhaled corticosteroids induce a small but significant overall improvement of the asthmatic condition in subjects with occupational asthma caused by high- and low-molecular-weight agents after withdrawal from exposure. The beneficial effect is, however, more pronounced if inhaled steroids are given early after diagnosis.

Administration, Inhalation

Outcome of specific bronchial responsiveness to occupational agents after removal from exposure.

A decrease in specific bronchial responsiveness (SBR) could occur after removal from exposure to an agent causing occupational asthma as a result of loss of immunologic and/or nonspecific bronchial reactivity (NSBR). We studied 15 subjects with occupational asthma (eight to a high- and seven to a low-molecular-weight agent, isocyanate in all instances), proved by specific inhalation challenges (SIC) done 2 yr or more before. Subjects were reexposed in the same way as in the initial SIC: for subjects who did not react, the exposure was increased until either an asthmatic reaction occurred or a maximum of 2 h was reached. NSBR was assessed before and after SIC. Subjects had a decrease in their SBR if the total dose of agent necessary to induce asthmatic reaction was greater by twofold compared with the initial SIC. There was a significant improvement in NSBR in seven of 15 subjects. Nine of 15 subjects (60%) had a decrease in their SBR. Only one had a complete loss of SBR. Changes in NSBR, molecular weight of the offending agent, decrease of antibody level against offending agents, or duration of exposure at work did not explain the decrease in SBR. We conclude that after removal from exposure to the offending agent a majority of subjects (60%) show a decrease but a persistence of SBR to high- and low-molecular-weight agents.

Asthma

Skin bruising in asthmatic subjects treated with high doses of inhaled steroids: frequency and association with adrenal function.

High doses of inhaled corticosteroids (ICS) (budesonide and beclo-methasone > or = 800 micrograms.day-1) are commonly used in the treatment of asthma. Some investigators have presented evidence for cutaneous effects (bruising), which suggests systemic absorption. This study aimed to assess the prevalence of skin bruising, relate the occurrence of skin bruising to adrenocortical function, and determine the risk factors for skin bruising. One hundred adult asthmatic subjects taking high doses (800-2,000 micrograms.day-1) of ICS for 3 months or more were recruited in an asthma clinic, and 100 control subjects paired for sex and age were recruited from an ophthalmology out-patient clinic. A detailed questionnaire on asthma, general habits and cutaneous lesions was administered. A cutaneous examination was performed. Urine cortisol levels were assessed on two consecutive days. Blood cortisol level and the response to Cortrosyn injection (60 min test) were evaluated. One hundred adult asthmatics (66 females and 34 males), 73 on beclomethasone and 27 on budesonide, were included. The prevalence of skin bruising was 71% based on the questionnaire (32% in controls) and 48% (39 out of 81 subjects) based on direct examination of the skin. We found a satisfactory association between the response to questionnaire and examination of the skin. Adrenocortical function testing showed that a minority of subjects (14 with at least one abnormal test) had lower urinary or blood cortisol levels. These low cortisol levels occurred in subjects who reported skin bruising. By multiple logistic regression, being a female (odds ratio (OR) = 20; 95% confidence interval (95% CI) = 13-33) and taking ICS for asthma (OR = 12; 95% CI = 8-18) were significantly (t = 5.4) related to the likelihood of developing skin bruising. In addition, among the asthmatic subjects, being older (OR = 1.6; 95% CI = 1.1-2.4/10 yrs interval) (t = 2.3) and being a female (OR = 22; 95% CI = 7-75) (t = 5.0) influenced the occurrence of skin bruising as documented by questionnaire. In asthmatic subjects, taking high doses of ICS is associated with: 1) increased occurrence of skin bruising by comparison with controls, particularly in older subjects; and 2) a generally normal adrenocortical function, although this function is significantly lower in subjects reporting skin bruising.

Administration, Inhalation

Fever and leucocytosis accompanying asthmatic reactions due to occupational agents: frequency and associated factors.

Fever is sometimes associated with asthmatic reactions following specific inhalation challenges with occupational agents. Our aims were to estimate the prevalence of fever in subjects with occupational asthma confirmed by specific inhalation challenge and to examine the characteristics and clinical correlates of subjects who develop fever on specific inhalation challenge. We performed a retrospective analysis of 317 subjects who had positive specific inhalation challenge to occupational agents and a comparison of subjects who developed fever after specific inhalation challenge with a random sample of those who did not. Fifteen subjects (5%) developed fever associated with positive specific inhalation challenge. They were compared with a random sample of 60 subjects who did not develop fever. The fever group: 1) showed a larger increase in absolute number of blood neutrophils, and a larger decrease both of blood lymphocytes and forced vital capacity after specific inhalation challenge; 2) included fewer atopics; 3) had been exposed more frequently to low rather than high molecular compounds; and 4) always experienced a late reaction and had more atypical reactions. We conclude that after positive specific inhalation challenge; fever occurs infrequently, and is associated with an increase in blood neutrophils and a decrease in blood lymphocytes and forced vital capacity. Such reactions seem more likely to occur in nonatopic subjects exposed to low molecular weight agents.

Adult

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)

Administration, Topical

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.

Adult

Morphometry of small airways in smokers and its relationship to emphysema type and hyperresponsiveness.

Based on our previous finding, of increased small airways disease in centrilobular emphysema (CLE) when compared with panlobular emphysema (PLE), we hypothesized that smokers who develop CLE would have increased airway responsiveness associated with airway inflammation and exaggerated airway narrowing, but not smokers with PLE. We compared preoperative methacholine challenge with the morphologic and cellular inflammatory characteristics of the airways in the lungs of six nonsmokers, 10 smokers with CLE, and five smokers with PLE. The airways of the CLE group were narrower than those of the nonsmokers (KS < 0.05) and the PLE group (KS < 0.05), but perimeters were not different. A greater percentage of airways in the CLE group showed infolding of the epithelium and lumen deformity than in the PLE group and nonsmokers (p < 0.05). Airway inner wall thickening (WI) was increased in the CLE group when compared with the PLE group and nonsmokers (p < 0.05), and WI correlated significantly with PC20 in the CLE group (r = -0.64, p < 0.01) but not in the PLE group and nonsmokers. The number of T lymphocytes in the airway walls correlated with PC20 in the CLE group (r = -0.50, p < 0.05) but not in the PLE group. In conclusion, despite similar age, smoking history, and range of airflow limitation, there was a clear difference in the methacholine responsiveness between the emphysema groups, suggesting that responsiveness is not just a reaction to smoking but either a reaction developing in some smokers or an abnormality initially present in some smokers which, in combination with exposure to cigarettes, determines the development of a type of lung disease: CLE.

Aged

Alveolar inflammation and its relation to emphysema in smokers.

The prevalent theory in the pathogenesis of emphysema proposes that increased numbers of activated neutrophils and/or alveolar macrophages produce large amounts of proteases, an activity that cannot be regulated by alpha 1-antiproteases, resulting in lung destruction. However, the cells in the lung parenchyma of smokers have not been properly identified. We characterized and quantitated the inflammatory cell load in the lungs of smokers and correlated these findings with the degree of lung destruction. Twenty-one patients, six nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes were fixed and stained for light microscopy and neutrophil identification and immunohistochemically stained for identification of lymphocytes and macrophages. By point counting, we determined the extent of emphysema by the volume density of the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01), whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = -0.78) correlated negatively with the Vvalv. The number of T-lymphocytes correlated negatively with the number of neutrophils (r = -0.58) and positively with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung. However, the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly implicated in the pathogenesis of emphysema in smokers.

Adult

The reversibility of airway obstruction to an inhaled beta 2-adrenergic agent is less satisfactory after methacholine testing in asthmatic subjects.

AIMS: The aim of this work was to compare the response to an inhaled beta 2-adrenergic agent in two situations: (1) spontaneous airway obstruction in asthmatic subjects who had withheld treatment with the medication for more than 12 hs; and (2) after methacholine-induced airway obstruction once airway caliber had recovered to the premethacholine test value. SUBJECTS AND METHODS: Sixteen asthmatic subjects who showed a 20% or more improvement in FEV1 after inhaled beta 2-adrenergic agent (B2) (salbutamol, 200 micrograms) entered a double-blind crossover randomized trial in which the following tests were carried out: (1) FEV1 response after inhaling a placebo or active B2; (2) FEV1 response after inhaling a placebo or active B2 after a methacholine test that had induced a 20% or more reduction in FEV1, once FEV1 had recovered to the premethacholine value after inhaling salbutamol in an open fashion. RESULTS: As expected, the mean percent improvement in FEV1 in the spontaneous airway obstruction situation was 21.7 +/- 8.5% after inhaling the active B2 and 2.2 +/- 1.8% after placebo B2 (p < 0.001). Following recovery after methacholine challenge, the FEV1 was slightly superior (mean difference of 146 mL) to the premethacholine value before inhaling the active or placebo B2. In this situation, the percent improvement in FEV1 after inhaling the active B2 was only 7.5 +/- 4.4% and not significantly different from after inhaling placebo B2 (4.9 +/- 5.4%). Consequently, the end FEV1 value after inhaling active B2 was significantly higher in a situation of spontaneous airway obstruction than after methacholine-induced airway obstruction (mean difference = 110 mL; p = 0.02). CONCLUSION: After a methacholine test, the reversibility of an inhaled beta 2 agent is not significantly different from a placebo and is less satisfactory than in a situation of spontaneous airway obstruction. The mechanism for this needs to be explored but it is not secondary to persisting airway obstruction.

Adult

Comparison of circadian variations using FEV1 and peak expiratory flow rates among normal and asthmatic subjects.

BACKGROUND: Most studies that describe circadian variations in asthma have used maximum rate of peak expiratory flow (PEF) rather than forced expiratory volume in one second (FEV1) to assess airway calibre. This study was designed to assess circadian variations in PEF and FEV1 measured simultaneously and to compare variations in these measurements in normal and asthmatic subjects in a stable clinical state. METHODS: Twenty nine subjects (nine asthmatic subjects on bronchodilators, 10 on inhaled steroids, and 10 normal controls) were asked to record their PEF and FEV1 with a new portable instrument every two hours during the day and once on waking at night for two weeks. Circadian variations were examined in different ways using arithmetical indices and cosinor analysis. RESULTS: 78% of PEF values and 75% of FEV1 values were considered to be reproducible and were included in the analysis. Variations obtained using PEF did not differ from those obtained using FEV1. Significant cosinor variations were found in at least 50% of recording days for most of the subjects and showed the same features as for arithmetical indices. Daily variations in PEF and FEV1 were significantly correlated with airway calibre and PC20 methacholine (r approximately 0.5 to approximately 0.6). CONCLUSIONS: PEF is as satisfactory as FEV1 for describing circadian variations among normal subjects and stable asthmatic subjects.

Adolescent