Clinical Physiology (1992) 12,575-585
Distribution of radioactive aerosol in the airways of children and adolescents with bronchial hyper-responsiveness V. Backer* and J. Mortensent 'Laboratory of Respiratory Physiology, Department of Medicine B, and Clinical Physiology and Nuclear Medicine, University Hospital, Rigshospitalet,Copenhagen, Denmark
(Received 31 July 1991; accepted 25 February 1992)
Summary. The purpose of this study was to examine the relationship between the pulmonary distribution of inhaled radioaerosol, bronchial responsiveness, and lung function in children and adolescents. The participating subjects (n = 39) were divided into three groups: (1) 14 asthmatics with bronchial hyper-responsiveness (BHR), (2) five non-asthmatic subjects with BHR, and (3) 20 controls without BHR. Pulmonary distribution of [Tc") albumin radioaerosol, maximal expiratory flow when 25% of forced vital capacity remain to be exhaled (MEF,), and bronchial responsiveness to inhaled histamine were measured. Twenty subjects (52%) had irregular central distribution and 19 subjects (48%) had regular distribution of radioaerosol in their lungs. No difference in distribution of radioaerosol was found between the three groups of children. The median MEF, among non-asthmatic subjects (80% predicted) was lower than that found in controls (92% predicted) but higher than that found in asthmatic subjects (55% predicted). A relationship was found between reduced flow at the peripheral airways, as indicated by MEF, and the degree of central distribution of radioaerosol. Furthermore, subjects with irregular central distribution of radioaerosol had an increased degree of bronchial responsiveness. In conclusion, children and adolescents who have flow rates in the peripheral airways or increased degree of bronchial responsiveness tend to have abnormal distribution of radioaerosols.
Key words: small airway dysfunction, asthmatic, non-asthmatic, healthy control, respiratory flow rates, radioaerosol. Introduction Increasing evidence supports the belief that development of chronic obstructive pulmonary disease in adults may begin in the peripheral airways (Cosio et al., 1977; Agnew et al., 1981;Burrows et al., 1988; Voter et al. , 1988). However, traditional tests of pulmonary function in asymptomatic adults do not reveal the extent of the airway Correspondence: Vibeke Backer, Jagtvej 200,2100 - Copenhagen, Denmark.
575
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V. Backer & J . Mortensen
disease in the early stage (Hedenstierna et al., 1981; Matsuba et al., 1987), whereas pulmonary deposition of radioaerosol may provide a sensitive test for peripheral airway obstruction (Dolovich et al., 1976; Emmet et al., 1984; Agney et al., 1985). As yet, there is no convincing evidence that tests based on radioaerosol are superior to other ‘small airways tests’ in adults (Agnew et al., 1981,1984; Marazzini et al., 1989). In children, reduced airflow rates may be a risk factor for subsequent development of pulmonary disease. However, few studies have dealt with small airway dysfunction in healthy children, as use of radioaerosols in children is very uncommon. On the other hand, bronchial hyper-responsiveness (BHR), regularly studied in population samples, has frequently been found to precede the development of bronchial asthma in children (Peat et al., 1989; Hop et al., 1990). Therefore, bronchial hyperresponsiveness seems to be a risk factor for subsequent development of pulmonary disease and although at present unknown, a relationship may exist between BHR and obstruction of the peripheral airways. The purpose of this study was to examine the distribution of radioaerosol in the airways of asthmatic subjects, non-asthmatic subjects with BHR and control children and adolescents. Furthermore, we wanted to examine the possible relationship between bronchial responsiveness, expiratory flow rate and small airway dysfunction as estimated by radioaerosol deposition, in the airways of children and adolescents.
Subjects and methods SUBJECTS
A randomly selected population sample consisting of 983 children and adolescents living in Copenhagen was drawn from the civil registration list in 1986. Five-hundred and twenty-seven (54%) unselected children and adolescents were examined (Backer et al., 1989). Seventy-nine individuals (15%) had BHR, i.e. a PC20 of less than 8 mg ml-’ histamine, of whom 28 children had asthma and BHR and 51 children had nonasthmatic BHR. The remaining 448 children and adolescents, the controls, had no previous symptoms of asthma and were without BHR in 1986. Eighteen months later, in 1988, the subjects with BHR (n = 41) and 29 consecutively selected healthy controls were invited to participate in a re-examination and 39 children and adolescents (56%) agreed to participate in this study involving inhalation of radioaerosol. The 39 participants in the present study, all non-smokers, were divided into three groups: (1) asthmatics with BHR, (2) non-asthmatics with BHR, and (3) healthy controls without BHR. Group 1. Asthmatic children and adolescents+ BHR (n = 14). The questionnaireand criteria for asthma used were of Hopp and co-workers (Hopp et al., 1984). All asthmatic children (1) had asthma diagnosed prior to the present examination, (2) were wheezy, (3) had shortness of breath, (4) had pulmonary symptoms caused by exercise or allergen exposure, and (5) were treated with anti-asthmatic drugs. Six of
Radioaerosol dktribution in children
577
the asthmatics (43%) had daily respiratory symptoms and eight (57%) were treated with inhaled corticosteroids. Group 2. Non-asthmatic children and adolescents+ BHR (n =5). Individualswho had never complained of symptomsindicating the presence of asthma, but had BHR in 1986 and 1988. One of the subjects reported dry coughing at the examination in 1986but had no respiratory symptomsduring the last 18months. At the present study another subject reported an occasional dry cough during the day, but never during the night. Group 3. Nora-asthmatic children and adolescents- BHR (Controls) (n = 20). This group included subjects without BHR in both 1986 and 1988, and no earlier or present symptoms indicating asthma. The protocol was evaluated and approved by the local ethical committee and informed consent was obtained from all participating subjects and their parents. The Helsinki I1 declaration was adhered to throughout the study. METHODS
All participants had a baseline lung function measured and a histamine challenge performed. The MEF, and FEVl was measured with a pneumotachograph (Vitalograph@).Predicted values based on the height of the subjects were calculated according to Zapletal(l987) and lung function parameters were listed as a percentage of predicted values ('YO predicted). The bronchial histamine challenge tests were performed according to the protocol by Cockcroft and co-workers (Cockcroft et al., 1977), using a Wright@nebulizer with an output of 0.14*0-015 ml min-' and an inhalation period of 2 min. The inhaled histamine dose was determined as a relationship between nebulizer output, inhalation period and histamine concentration. O'Connor and co-workers defined dose-response slope (DRS) as the maximal percentage reduction in FEVl per pmol (A%FEVI pmol-') of the last inhaled dose of histamine and DRS was used to express the degree of bronchial responsiveness (O'Connor et al., 1987). A PC20 of 8 mg ml-' is found to be equal to a log doseresponse slope of 0-29A%FEVl/pmol-' (Backer et al., 1991). The patients inhaled a P c m ]albumin colloid solution (Venticoll, Solco@)from an ultrasonical nebulizer (Vrisonifl). Our earlier studies with ultrasonically nebulized [99Tc"] albumin suggest a high degree of labelling efficiency because (1) less than 1% dissociation occurs during 24 hours in vifro, (2) in vivo only 7% of the initially deposited radioaerosol was detected in 24 h urine sample, and (3) the initial radioactivity clearance was in accordance with the clearance of Tc-venticoll(0-1-0.5% min-') and not the clearance of free Tc (5% min-') (Mortensen et al., 1991a). Furthermore, in the present study we measured four control subjects and two subjects with asthma, during the first 60 min, a median total lung clearance of Tc-albumin colloid of 7% (range 2%-12%) corresponding to a 0.13% min-' (range 0.04%0.99% min-I). Moreover, the instability of [Tc"] DTPA radioaerosol with the same ultrasonical nebulizer as used herein was negligible (Groth et al., 1989). The particle
578
V . Backer & J . Mortemen
size (MMAD) from the ultrasonic nebulizer used has earlier been measured to be c2.4 pm (manufacturers data). The radioaerosol was inhaled during 2 min of tidal breathing of approximately 500 ml per breath from functional residual capacity (FRC). The volume of breathing was monitored by a wet bellows spirometer (Expirograph) and each inhalation and exhalation was performed slowly, although the exact airflow was not recorded. One of the authors (VB)was standing beside the subjects during radioaerosol inhalation to ensure tidal breathing with low airflow rates. Immediately following the radioaerosol inhalation the subjects rinsed their mouths three times and swallowed water to remove any particles from the mouth, pharynx, and oesophagus. The distribution of the radioactivity in the lungs was detected by placing the subjects against a posteriorly positioned gamma camera. The data acquisition was obtained as a 1 x 5 min static gamma camera exposure (detected in 64x64 pixels) due to the relatively low count rates (median 161 OOO; range 97 000-195 OOO). This corresponds to a retained dose of less than 10 MBq [ v c m ]in the thorax (Mortensen et al., 1991a). A photoscintigram (colour) was also obtained from the static gamma camera acquisition. A [81Kr"'] ventilation scintigram (median 167 OOO counts, range 131 OOO-190 OOO) was used to measure the ventilation in different regions of the lungs and to define the outline of the lungs (Fig. 1). The distribution of the ventilation correlates with the volume of the lungs at which the breathing has been performed (FRC plus the 500 ml tidal volume). The lung zones used were created after visual inspection of the central airways from [Vc"] albumin scintigrams obtained in previous studies (Mortensen et al., 1991b). Central zone, i.e. 17% of total pixel area, mainly covered the trachea and the main bronchi. Mid zones, i.e. 24% of pixels, covered mainly the lobar, segmental and subsegmentalbronchi. Peripheral zones, i.e. 59% of pixels, covered the subsequent bronchial generations. Each zone also included alveoli. As indicated from the [81Kf'] ventilation scintigrams the proportion of lung volume in the central, mid, and peripheral zones were - median (range) 15% (1217%), 35% (27-42), and 50% (42-61), respectively. ' ' of ' the c w aerosol and the ["KP] in the lung was visually The ]distribution classified, semiquantitatively,from the photoscintigrams as regular (l), almost regular (2), irregular (3), and severely irregular (4). Grades 1and 2 were grouped as regular and grades 3 and 4 as irregular deposition. The visual inspection and classification of the distribution irregularity was performed 'blind' by one of the authors (JM). In addition, the radioaerosol distribution was also characterized quantitatively by calculating the penetration index, i.e. the ratio of peripheral to central zone radioactivity ] ' " for cT [ albumin divided by the same ratio for [81Kf'] (Mortensen et al., 1991b). A high penetration index indicates a predominantly peripheral aerosol distribution in the lung, whereas a low penetration index indicates an aerosol distribution predominantly in the central airways. Furthermore, a penetration ratio of the right and the left lung was calculated, as the ratio of the peripheral zone divided by the middle zone.
Radioaerosol distribution in children
Fig. 1. Lung zones and distribution of radioaerosols (a: [ ' ' P ventilation I scintigrams, b: [-I?'] scintigam) in an asthmatic child with severe irregular distribution of radioaerosol.
579
albumin
V. Backer & J . Mortensen
580 DATA ANALYSIS
Comparison of the possible intra-subject differences in peripheral distribution of radio-aerosolsof the left and right lung, and of the maximal and minimal radioaerosol distribution was analysed using a paired Wilcoxon signed rank test. The association between irregularity of distribution of aerosol in the lung and BHR or respiratory symptoms was analysed by a Chi-square test; Fischer's exact test was used in case of frequenciess5. Differences in penetration index, dose-response slope, FEVl, MEFzs, age and height between the three groups were analysed using the Kruskal-Wallis test. When appropriate, the Mann-Whitney test was used to analyse differences between the various parameters. The Kendall rank correlation test was used for analysis of a possible correlation between the distribution of radioaerosol and lung function (FEV, and MEF,), height and bronchial responsiveness (DRS) and Spearman rank (r,) correlation was used for analysis of a possible correlation between penetration index and visual classification. ReSUltS
The non-asthmatic subjects+BHR (group 2) had significantly decreased FEVl compared with the non-asthmatic-BHR healthy controls ( P < 0-01), whereas the difference in FEVl between the +BHR non-asthmatic and the asthmatic subjects was non-significant (Table 1). In addition, the non-asthmatic+BHR subjects had MEFzs Table 1. Age (years), height (cm), baseline lung function (FF!Vl and MEFv % predicted), dose-response slope (DRS), penetration index and visual classification of radioaerosol in 39 subjects. Median values and (ranges)
Age (years) Height (cm) FEVl (% predicted) MEF,(% predicted)
DRS-histamine Penetration index Visual classification
Asthmatic Group 1 n = 14)
Non-asthmatic Group 2
Control Group 3
Kruskal-Wallis
n=5
n=U)
(PI
14 (8-18) 160 (135-175)
12(10-13-) 144 (135-158) 75(67-90) 80 (50-100) 0*4** (0*346)
84
(63-126) 55. (25-95)
0.9 (0.3-2-3) 0.75 (0.41-144) 3.0 (14)
0.60
(0.55-0.76) 3.0 (1-4)
15 (10-18) 169 (136-195) 102+** (82-127) g p *
(36-168) 0.1'(0. 042) 0.73 (044-1*00) 2.0 (1-4)
*P=0*09(1 w. 2), **P
Distribution of radioactive aerosol in the airways of children and adolescents with bronchial hyper-responsiveness V. Backer* and J. Mortensent 'Laboratory of Respiratory Physiology, Department of Medicine B, and Clinical Physiology and Nuclear Medicine, University Hospital, Rigshospitalet,Copenhagen, Denmark
(Received 31 July 1991; accepted 25 February 1992)
Summary. The purpose of this study was to examine the relationship between the pulmonary distribution of inhaled radioaerosol, bronchial responsiveness, and lung function in children and adolescents. The participating subjects (n = 39) were divided into three groups: (1) 14 asthmatics with bronchial hyper-responsiveness (BHR), (2) five non-asthmatic subjects with BHR, and (3) 20 controls without BHR. Pulmonary distribution of [Tc") albumin radioaerosol, maximal expiratory flow when 25% of forced vital capacity remain to be exhaled (MEF,), and bronchial responsiveness to inhaled histamine were measured. Twenty subjects (52%) had irregular central distribution and 19 subjects (48%) had regular distribution of radioaerosol in their lungs. No difference in distribution of radioaerosol was found between the three groups of children. The median MEF, among non-asthmatic subjects (80% predicted) was lower than that found in controls (92% predicted) but higher than that found in asthmatic subjects (55% predicted). A relationship was found between reduced flow at the peripheral airways, as indicated by MEF, and the degree of central distribution of radioaerosol. Furthermore, subjects with irregular central distribution of radioaerosol had an increased degree of bronchial responsiveness. In conclusion, children and adolescents who have flow rates in the peripheral airways or increased degree of bronchial responsiveness tend to have abnormal distribution of radioaerosols.
Key words: small airway dysfunction, asthmatic, non-asthmatic, healthy control, respiratory flow rates, radioaerosol. Introduction Increasing evidence supports the belief that development of chronic obstructive pulmonary disease in adults may begin in the peripheral airways (Cosio et al., 1977; Agnew et al., 1981;Burrows et al., 1988; Voter et al. , 1988). However, traditional tests of pulmonary function in asymptomatic adults do not reveal the extent of the airway Correspondence: Vibeke Backer, Jagtvej 200,2100 - Copenhagen, Denmark.
575
576
V. Backer & J . Mortensen
disease in the early stage (Hedenstierna et al., 1981; Matsuba et al., 1987), whereas pulmonary deposition of radioaerosol may provide a sensitive test for peripheral airway obstruction (Dolovich et al., 1976; Emmet et al., 1984; Agney et al., 1985). As yet, there is no convincing evidence that tests based on radioaerosol are superior to other ‘small airways tests’ in adults (Agnew et al., 1981,1984; Marazzini et al., 1989). In children, reduced airflow rates may be a risk factor for subsequent development of pulmonary disease. However, few studies have dealt with small airway dysfunction in healthy children, as use of radioaerosols in children is very uncommon. On the other hand, bronchial hyper-responsiveness (BHR), regularly studied in population samples, has frequently been found to precede the development of bronchial asthma in children (Peat et al., 1989; Hop et al., 1990). Therefore, bronchial hyperresponsiveness seems to be a risk factor for subsequent development of pulmonary disease and although at present unknown, a relationship may exist between BHR and obstruction of the peripheral airways. The purpose of this study was to examine the distribution of radioaerosol in the airways of asthmatic subjects, non-asthmatic subjects with BHR and control children and adolescents. Furthermore, we wanted to examine the possible relationship between bronchial responsiveness, expiratory flow rate and small airway dysfunction as estimated by radioaerosol deposition, in the airways of children and adolescents.
Subjects and methods SUBJECTS
A randomly selected population sample consisting of 983 children and adolescents living in Copenhagen was drawn from the civil registration list in 1986. Five-hundred and twenty-seven (54%) unselected children and adolescents were examined (Backer et al., 1989). Seventy-nine individuals (15%) had BHR, i.e. a PC20 of less than 8 mg ml-’ histamine, of whom 28 children had asthma and BHR and 51 children had nonasthmatic BHR. The remaining 448 children and adolescents, the controls, had no previous symptoms of asthma and were without BHR in 1986. Eighteen months later, in 1988, the subjects with BHR (n = 41) and 29 consecutively selected healthy controls were invited to participate in a re-examination and 39 children and adolescents (56%) agreed to participate in this study involving inhalation of radioaerosol. The 39 participants in the present study, all non-smokers, were divided into three groups: (1) asthmatics with BHR, (2) non-asthmatics with BHR, and (3) healthy controls without BHR. Group 1. Asthmatic children and adolescents+ BHR (n = 14). The questionnaireand criteria for asthma used were of Hopp and co-workers (Hopp et al., 1984). All asthmatic children (1) had asthma diagnosed prior to the present examination, (2) were wheezy, (3) had shortness of breath, (4) had pulmonary symptoms caused by exercise or allergen exposure, and (5) were treated with anti-asthmatic drugs. Six of
Radioaerosol dktribution in children
577
the asthmatics (43%) had daily respiratory symptoms and eight (57%) were treated with inhaled corticosteroids. Group 2. Non-asthmatic children and adolescents+ BHR (n =5). Individualswho had never complained of symptomsindicating the presence of asthma, but had BHR in 1986 and 1988. One of the subjects reported dry coughing at the examination in 1986but had no respiratory symptomsduring the last 18months. At the present study another subject reported an occasional dry cough during the day, but never during the night. Group 3. Nora-asthmatic children and adolescents- BHR (Controls) (n = 20). This group included subjects without BHR in both 1986 and 1988, and no earlier or present symptoms indicating asthma. The protocol was evaluated and approved by the local ethical committee and informed consent was obtained from all participating subjects and their parents. The Helsinki I1 declaration was adhered to throughout the study. METHODS
All participants had a baseline lung function measured and a histamine challenge performed. The MEF, and FEVl was measured with a pneumotachograph (Vitalograph@).Predicted values based on the height of the subjects were calculated according to Zapletal(l987) and lung function parameters were listed as a percentage of predicted values ('YO predicted). The bronchial histamine challenge tests were performed according to the protocol by Cockcroft and co-workers (Cockcroft et al., 1977), using a Wright@nebulizer with an output of 0.14*0-015 ml min-' and an inhalation period of 2 min. The inhaled histamine dose was determined as a relationship between nebulizer output, inhalation period and histamine concentration. O'Connor and co-workers defined dose-response slope (DRS) as the maximal percentage reduction in FEVl per pmol (A%FEVI pmol-') of the last inhaled dose of histamine and DRS was used to express the degree of bronchial responsiveness (O'Connor et al., 1987). A PC20 of 8 mg ml-' is found to be equal to a log doseresponse slope of 0-29A%FEVl/pmol-' (Backer et al., 1991). The patients inhaled a P c m ]albumin colloid solution (Venticoll, Solco@)from an ultrasonical nebulizer (Vrisonifl). Our earlier studies with ultrasonically nebulized [99Tc"] albumin suggest a high degree of labelling efficiency because (1) less than 1% dissociation occurs during 24 hours in vifro, (2) in vivo only 7% of the initially deposited radioaerosol was detected in 24 h urine sample, and (3) the initial radioactivity clearance was in accordance with the clearance of Tc-venticoll(0-1-0.5% min-') and not the clearance of free Tc (5% min-') (Mortensen et al., 1991a). Furthermore, in the present study we measured four control subjects and two subjects with asthma, during the first 60 min, a median total lung clearance of Tc-albumin colloid of 7% (range 2%-12%) corresponding to a 0.13% min-' (range 0.04%0.99% min-I). Moreover, the instability of [Tc"] DTPA radioaerosol with the same ultrasonical nebulizer as used herein was negligible (Groth et al., 1989). The particle
578
V . Backer & J . Mortemen
size (MMAD) from the ultrasonic nebulizer used has earlier been measured to be c2.4 pm (manufacturers data). The radioaerosol was inhaled during 2 min of tidal breathing of approximately 500 ml per breath from functional residual capacity (FRC). The volume of breathing was monitored by a wet bellows spirometer (Expirograph) and each inhalation and exhalation was performed slowly, although the exact airflow was not recorded. One of the authors (VB)was standing beside the subjects during radioaerosol inhalation to ensure tidal breathing with low airflow rates. Immediately following the radioaerosol inhalation the subjects rinsed their mouths three times and swallowed water to remove any particles from the mouth, pharynx, and oesophagus. The distribution of the radioactivity in the lungs was detected by placing the subjects against a posteriorly positioned gamma camera. The data acquisition was obtained as a 1 x 5 min static gamma camera exposure (detected in 64x64 pixels) due to the relatively low count rates (median 161 OOO; range 97 000-195 OOO). This corresponds to a retained dose of less than 10 MBq [ v c m ]in the thorax (Mortensen et al., 1991a). A photoscintigram (colour) was also obtained from the static gamma camera acquisition. A [81Kr"'] ventilation scintigram (median 167 OOO counts, range 131 OOO-190 OOO) was used to measure the ventilation in different regions of the lungs and to define the outline of the lungs (Fig. 1). The distribution of the ventilation correlates with the volume of the lungs at which the breathing has been performed (FRC plus the 500 ml tidal volume). The lung zones used were created after visual inspection of the central airways from [Vc"] albumin scintigrams obtained in previous studies (Mortensen et al., 1991b). Central zone, i.e. 17% of total pixel area, mainly covered the trachea and the main bronchi. Mid zones, i.e. 24% of pixels, covered mainly the lobar, segmental and subsegmentalbronchi. Peripheral zones, i.e. 59% of pixels, covered the subsequent bronchial generations. Each zone also included alveoli. As indicated from the [81Kf'] ventilation scintigrams the proportion of lung volume in the central, mid, and peripheral zones were - median (range) 15% (1217%), 35% (27-42), and 50% (42-61), respectively. ' ' of ' the c w aerosol and the ["KP] in the lung was visually The ]distribution classified, semiquantitatively,from the photoscintigrams as regular (l), almost regular (2), irregular (3), and severely irregular (4). Grades 1and 2 were grouped as regular and grades 3 and 4 as irregular deposition. The visual inspection and classification of the distribution irregularity was performed 'blind' by one of the authors (JM). In addition, the radioaerosol distribution was also characterized quantitatively by calculating the penetration index, i.e. the ratio of peripheral to central zone radioactivity ] ' " for cT [ albumin divided by the same ratio for [81Kf'] (Mortensen et al., 1991b). A high penetration index indicates a predominantly peripheral aerosol distribution in the lung, whereas a low penetration index indicates an aerosol distribution predominantly in the central airways. Furthermore, a penetration ratio of the right and the left lung was calculated, as the ratio of the peripheral zone divided by the middle zone.
Radioaerosol distribution in children
Fig. 1. Lung zones and distribution of radioaerosols (a: [ ' ' P ventilation I scintigrams, b: [-I?'] scintigam) in an asthmatic child with severe irregular distribution of radioaerosol.
579
albumin
V. Backer & J . Mortensen
580 DATA ANALYSIS
Comparison of the possible intra-subject differences in peripheral distribution of radio-aerosolsof the left and right lung, and of the maximal and minimal radioaerosol distribution was analysed using a paired Wilcoxon signed rank test. The association between irregularity of distribution of aerosol in the lung and BHR or respiratory symptoms was analysed by a Chi-square test; Fischer's exact test was used in case of frequenciess5. Differences in penetration index, dose-response slope, FEVl, MEFzs, age and height between the three groups were analysed using the Kruskal-Wallis test. When appropriate, the Mann-Whitney test was used to analyse differences between the various parameters. The Kendall rank correlation test was used for analysis of a possible correlation between the distribution of radioaerosol and lung function (FEV, and MEF,), height and bronchial responsiveness (DRS) and Spearman rank (r,) correlation was used for analysis of a possible correlation between penetration index and visual classification. ReSUltS
The non-asthmatic subjects+BHR (group 2) had significantly decreased FEVl compared with the non-asthmatic-BHR healthy controls ( P < 0-01), whereas the difference in FEVl between the +BHR non-asthmatic and the asthmatic subjects was non-significant (Table 1). In addition, the non-asthmatic+BHR subjects had MEFzs Table 1. Age (years), height (cm), baseline lung function (FF!Vl and MEFv % predicted), dose-response slope (DRS), penetration index and visual classification of radioaerosol in 39 subjects. Median values and (ranges)
Age (years) Height (cm) FEVl (% predicted) MEF,(% predicted)
DRS-histamine Penetration index Visual classification
Asthmatic Group 1 n = 14)
Non-asthmatic Group 2
Control Group 3
Kruskal-Wallis
n=5
n=U)
(PI
14 (8-18) 160 (135-175)
12(10-13-) 144 (135-158) 75(67-90) 80 (50-100) 0*4** (0*346)
84
(63-126) 55. (25-95)
0.9 (0.3-2-3) 0.75 (0.41-144) 3.0 (14)
0.60
(0.55-0.76) 3.0 (1-4)
15 (10-18) 169 (136-195) 102+** (82-127) g p *
(36-168) 0.1'(0. 042) 0.73 (044-1*00) 2.0 (1-4)
*P=0*09(1 w. 2), **P
