To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes asso... more To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. Randomised, double blind, placebo controlled trial. Community based study in Southampton. 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. After a run in period of 2-6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 micrograms or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. During the treatment period there was a significant ...
The role of airway inflammation in the pathogenesis of asthma in childhood is uncertain. In the p... more The role of airway inflammation in the pathogenesis of asthma in childhood is uncertain. In the present study, 27 atopic and nonatopic children aged 7-9 yrs who had > or = 5 episodes of wheeze and symptoms of exercise-induced asthma (EIA) in the previous 12 months, performed a methacholine challenge and exercise test on separate days at monthly intervals. The subjects had not received oral or inhaled corticosteroids for 12 months prior to the study. The dose-response relationship to inhaled methacholine was expressed as the cumulative dose provoking a 20% decrease in forced expiratory volume in one second (PD20). Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were measured prior to the exercise test and at 0, 3, 5, 10, 15 and 20 min following maximal exercise. Following the first methacholine challenge and exercise test, the children were randomized in a double-blind manner to receive inhaled beclomethasone dipropionate (BDP) 200 micrograms b.i.d. or...
American Journal of Respiratory and Critical Care Medicine, 1995
Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild... more Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.
The development of inadvertent positive end-expiratory pressure (PEEPi) in ventilated infants is ... more The development of inadvertent positive end-expiratory pressure (PEEPi) in ventilated infants is of clinical relevance and difficult to measure non-invasively. A method for estimating end-expiratory alveolar pressure by applying a multiple regression analysis to airway opening pressure, flow and volume recordings during mechanical ventilation was evaluated. In eight open-chested, paralysed and mechanically ventilated mongrel dogs, alveolar pressure was measured directly with "alveolar capsules". Alteration of ventilation patterns and addition of a resistive element were used in three dogs to induce different levels of PEEPi. End-expiratory alveolar pressure measured directly and determined from multilinear regression of airway opening pressure correlated well (mean error 0.06 +/- 0.53 (+/- SD) hPa, limits of agreement -1.16 to +1.04 hPa). The other five dogs received inhalation challenges, two with histamine, two with hypertonic saline and one with methacholine resulting i...
Respiratory symptoms such as cough and wheeze are associated with significant morbidity, includin... more Respiratory symptoms such as cough and wheeze are associated with significant morbidity, including school absenteeism. A respiratory questionnaire was sent to the parents of all 5727 children aged 7-9 years of age registered with 95 general practitioners in the Southampton area to determine (a) the prevalence of asthma, cough and wheeze, (b) the effects of respiratory symptoms on school absenteeism, and (c) the use of anti-asthma medication. A total of 4830 parents replied (response rate 86%). The 12 month prevalence of wheeze in the absence of cough was 5.5%, cough in the absence of wheeze was 10.0%, and 7.6% reported cough and wheeze; 15.2% of children had been diagnosed. Of the 4830 who replied, 12.7% were receiving bronchodilators, 0.6% xanthine derivatives, 1.7% sodium cromoglycate, and 4.1% inhaled corticosteroids. In all, 348 (7.2%) children had missed more than five days of schooling in the preceding year for respiratory symptoms, while 43 children (0.9%) had missed more tha...
Journal of applied physiology (Bethesda, Md. : 1985), 1993
The relationship between respiratory mechanics, changes in pulmonary blood flow (PBF), pulmonary ... more The relationship between respiratory mechanics, changes in pulmonary blood flow (PBF), pulmonary arterial pressure, and left atrial pressure is unclear. Conventional methods for the measurement of respiratory mechanics model the respiratory system as a single compartment, which may not adequately represent the respiratory system in a diseased state. The interrupter technique models the respiratory system as two compartments, with the "flow resistance" of the conducting airways and chest wall (Raw) considered separately from Pdif, a measure of the viscoelastic properties of the lung and chest wall, together with any pendelluft present. The respiratory mechanics of 15 infants in the first year of life were studied during cardiac catheterization with the use of conventional methods and the interrupter technique. The infants had a PBF-to-systemic blood flow ratio ranging from 0.6 to 4.0:1. The specific dynamic compliance of the respiratory system was not related to the PBF; ho...
Prostaglandin D2 (PGD2) is a potent bronchoconstrictor, and is thought to have a role in the path... more Prostaglandin D2 (PGD2) is a potent bronchoconstrictor, and is thought to have a role in the pathogenesis of asthma. PGD2 causes vasodilation acting via the prostaglandin (DP) receptor on vascular smooth muscle, and myocontraction acting via the thromboxane (TP) receptor on bronchial smooth muscle. To determine the relative contribution of these mechanisms we have studied the degree to which a potent TP receptor antagonist inhibits PGD2-induced broncho- constriction. Twelve atopic asthmatic subjects underwent baseline PGD2 bronchial challenges to determine the cumulative concentration of PGD2 required to reduce forced expi- ratory volume in one second (FEV1) by 20%. At four subsequent randomized vis- its, subjects received this concentration of PGD2 90 min after dosing with placebo or 20, 50 or 100 mg of BAY u 3405, a potent competitive TP receptor antagonist. Serum was taken for drug assay at 90 min. After each dose of PGD2, FEV1 was measured for 30 min, and the area under the perc...
Significant concern remains over the long-term side effects of inhaled steroids. This cross-secti... more Significant concern remains over the long-term side effects of inhaled steroids. This cross-sectional study evaluates the effect of high-dose inhaled fluticasone propionate (FP) on biochemical markers of bone metabolism and bone density in children with asthma. Children with chronic asthma using FP >/= 1,000 mcg daily for at least 6 months, and healthy controls, were entered in the study. No children had taken oral prednisolone within the previous month. Fasting morning serum was analyzed for bone formation markers, and spot urine for bone resorption markers. Dual-energy X-ray absorptiometry (DEXA) results were reviewed in a subgroup of patients. Forty-nine children with asthma and 32 controls were recruited. The mean FP dose was 771.2 +/- 253.35 mcg/m2/day. Unpaired t-test analysis revealed no significant difference in biochemical markers studied. In subjects with asthma; 13 of 37 (35.1%) had lumbar spine density more than one standard deviation below the mean (P = 0.001). This fell to 6/37 (16.2%) with bone age correction (NS). In conclusion, no significant reduction in bone metabolism or bone age-corrected bone mineral density was observed in children with asthma on prolonged high doses of inhaled FP.
International Archives of Allergy and Immunology, 2006
We evaluated the impact of impermeable bed covers on asthma in asthmatics with clinically relevan... more We evaluated the impact of impermeable bed covers on asthma in asthmatics with clinically relevant house dust mite (HDM) sensitization. The study included 32 HDM-sensitized asthmatics in whom HDM allergy was considered as a significant factor in their asthma. They were randomized into either an intervention group whose bedding was encased with impermeable covers, or a control group who received cotton covers. Before and 3 and 6 months after encasement, dust samples were collected from the bedding and assayed for Der p 1. Clinical outcomes included quality of life, lung function, bronchial reactivity to methacholine, symptoms, medications and peak flow rates. Baseline Der p 1 levels in both the active and the placebo groups were comparable and high (19.2 vs 18.9 microg/g of dust). There was a significant reduction in Der p 1 levels in the active group after 6 months, but not in the placebo group (7.3 vs 21.9 microg/g of dust). Quality of life improved significantly in both the intervention and control groups, but there was no significant difference in the improvements between the groups. There was no significant change in lung function, symptoms, and requirements for medications. Encasement of bedding significantly reduced the Der p 1 levels. However, this was not sufficient to produce worthwhile clinical improvement in those in whom dust mite avoidance might well have been recommended as part of their clinical management.
Bronchiectasis is generally classified into cystic fibrosis and non-cystic fibrosis bronchiectasi... more Bronchiectasis is generally classified into cystic fibrosis and non-cystic fibrosis bronchiectasis. This review article describes non-cystic fibrosis bronchiectasis in adults. Bronchiectasis can be considered a heterogeneous condition characterized by irreversible airway dilatation with chronic bronchial infection/inflammation. It remains a common condition and is a major cause of respiratory morbidity. Many factors are associated with bronchiectasis, but most commonly patients will have idiopathic disease. Important clinical findings include chronic productive cough, rhinosinusitis, fatigue and bi-basal crackles. Patients have usually had symptoms for many years. Diagnosis is confirmed by high-resolution computed tomography scanning using standardized criteria. Spirometry shows moderate airflow obstruction and there is a high prevalence of bronchial hyperreactivity. The most common pathogens are non-typeable Haemophilus influenzae and Pseudomonas aeruginosa. There may be considerable overlap with other chronic airway diseases. Treatment regimens are still not well defined. Patients tend to have ongoing symptoms and decline in respiratory function despite treatment.
To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes asso... more To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. Randomised, double blind, placebo controlled trial. Community based study in Southampton. 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. After a run in period of 2-6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 micrograms or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. During the treatment period there was a significant ...
The role of airway inflammation in the pathogenesis of asthma in childhood is uncertain. In the p... more The role of airway inflammation in the pathogenesis of asthma in childhood is uncertain. In the present study, 27 atopic and nonatopic children aged 7-9 yrs who had > or = 5 episodes of wheeze and symptoms of exercise-induced asthma (EIA) in the previous 12 months, performed a methacholine challenge and exercise test on separate days at monthly intervals. The subjects had not received oral or inhaled corticosteroids for 12 months prior to the study. The dose-response relationship to inhaled methacholine was expressed as the cumulative dose provoking a 20% decrease in forced expiratory volume in one second (PD20). Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were measured prior to the exercise test and at 0, 3, 5, 10, 15 and 20 min following maximal exercise. Following the first methacholine challenge and exercise test, the children were randomized in a double-blind manner to receive inhaled beclomethasone dipropionate (BDP) 200 micrograms b.i.d. or...
American Journal of Respiratory and Critical Care Medicine, 1995
Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild... more Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.
The development of inadvertent positive end-expiratory pressure (PEEPi) in ventilated infants is ... more The development of inadvertent positive end-expiratory pressure (PEEPi) in ventilated infants is of clinical relevance and difficult to measure non-invasively. A method for estimating end-expiratory alveolar pressure by applying a multiple regression analysis to airway opening pressure, flow and volume recordings during mechanical ventilation was evaluated. In eight open-chested, paralysed and mechanically ventilated mongrel dogs, alveolar pressure was measured directly with "alveolar capsules". Alteration of ventilation patterns and addition of a resistive element were used in three dogs to induce different levels of PEEPi. End-expiratory alveolar pressure measured directly and determined from multilinear regression of airway opening pressure correlated well (mean error 0.06 +/- 0.53 (+/- SD) hPa, limits of agreement -1.16 to +1.04 hPa). The other five dogs received inhalation challenges, two with histamine, two with hypertonic saline and one with methacholine resulting i...
Respiratory symptoms such as cough and wheeze are associated with significant morbidity, includin... more Respiratory symptoms such as cough and wheeze are associated with significant morbidity, including school absenteeism. A respiratory questionnaire was sent to the parents of all 5727 children aged 7-9 years of age registered with 95 general practitioners in the Southampton area to determine (a) the prevalence of asthma, cough and wheeze, (b) the effects of respiratory symptoms on school absenteeism, and (c) the use of anti-asthma medication. A total of 4830 parents replied (response rate 86%). The 12 month prevalence of wheeze in the absence of cough was 5.5%, cough in the absence of wheeze was 10.0%, and 7.6% reported cough and wheeze; 15.2% of children had been diagnosed. Of the 4830 who replied, 12.7% were receiving bronchodilators, 0.6% xanthine derivatives, 1.7% sodium cromoglycate, and 4.1% inhaled corticosteroids. In all, 348 (7.2%) children had missed more than five days of schooling in the preceding year for respiratory symptoms, while 43 children (0.9%) had missed more tha...
Journal of applied physiology (Bethesda, Md. : 1985), 1993
The relationship between respiratory mechanics, changes in pulmonary blood flow (PBF), pulmonary ... more The relationship between respiratory mechanics, changes in pulmonary blood flow (PBF), pulmonary arterial pressure, and left atrial pressure is unclear. Conventional methods for the measurement of respiratory mechanics model the respiratory system as a single compartment, which may not adequately represent the respiratory system in a diseased state. The interrupter technique models the respiratory system as two compartments, with the "flow resistance" of the conducting airways and chest wall (Raw) considered separately from Pdif, a measure of the viscoelastic properties of the lung and chest wall, together with any pendelluft present. The respiratory mechanics of 15 infants in the first year of life were studied during cardiac catheterization with the use of conventional methods and the interrupter technique. The infants had a PBF-to-systemic blood flow ratio ranging from 0.6 to 4.0:1. The specific dynamic compliance of the respiratory system was not related to the PBF; ho...
Prostaglandin D2 (PGD2) is a potent bronchoconstrictor, and is thought to have a role in the path... more Prostaglandin D2 (PGD2) is a potent bronchoconstrictor, and is thought to have a role in the pathogenesis of asthma. PGD2 causes vasodilation acting via the prostaglandin (DP) receptor on vascular smooth muscle, and myocontraction acting via the thromboxane (TP) receptor on bronchial smooth muscle. To determine the relative contribution of these mechanisms we have studied the degree to which a potent TP receptor antagonist inhibits PGD2-induced broncho- constriction. Twelve atopic asthmatic subjects underwent baseline PGD2 bronchial challenges to determine the cumulative concentration of PGD2 required to reduce forced expi- ratory volume in one second (FEV1) by 20%. At four subsequent randomized vis- its, subjects received this concentration of PGD2 90 min after dosing with placebo or 20, 50 or 100 mg of BAY u 3405, a potent competitive TP receptor antagonist. Serum was taken for drug assay at 90 min. After each dose of PGD2, FEV1 was measured for 30 min, and the area under the perc...
Significant concern remains over the long-term side effects of inhaled steroids. This cross-secti... more Significant concern remains over the long-term side effects of inhaled steroids. This cross-sectional study evaluates the effect of high-dose inhaled fluticasone propionate (FP) on biochemical markers of bone metabolism and bone density in children with asthma. Children with chronic asthma using FP >/= 1,000 mcg daily for at least 6 months, and healthy controls, were entered in the study. No children had taken oral prednisolone within the previous month. Fasting morning serum was analyzed for bone formation markers, and spot urine for bone resorption markers. Dual-energy X-ray absorptiometry (DEXA) results were reviewed in a subgroup of patients. Forty-nine children with asthma and 32 controls were recruited. The mean FP dose was 771.2 +/- 253.35 mcg/m2/day. Unpaired t-test analysis revealed no significant difference in biochemical markers studied. In subjects with asthma; 13 of 37 (35.1%) had lumbar spine density more than one standard deviation below the mean (P = 0.001). This fell to 6/37 (16.2%) with bone age correction (NS). In conclusion, no significant reduction in bone metabolism or bone age-corrected bone mineral density was observed in children with asthma on prolonged high doses of inhaled FP.
International Archives of Allergy and Immunology, 2006
We evaluated the impact of impermeable bed covers on asthma in asthmatics with clinically relevan... more We evaluated the impact of impermeable bed covers on asthma in asthmatics with clinically relevant house dust mite (HDM) sensitization. The study included 32 HDM-sensitized asthmatics in whom HDM allergy was considered as a significant factor in their asthma. They were randomized into either an intervention group whose bedding was encased with impermeable covers, or a control group who received cotton covers. Before and 3 and 6 months after encasement, dust samples were collected from the bedding and assayed for Der p 1. Clinical outcomes included quality of life, lung function, bronchial reactivity to methacholine, symptoms, medications and peak flow rates. Baseline Der p 1 levels in both the active and the placebo groups were comparable and high (19.2 vs 18.9 microg/g of dust). There was a significant reduction in Der p 1 levels in the active group after 6 months, but not in the placebo group (7.3 vs 21.9 microg/g of dust). Quality of life improved significantly in both the intervention and control groups, but there was no significant difference in the improvements between the groups. There was no significant change in lung function, symptoms, and requirements for medications. Encasement of bedding significantly reduced the Der p 1 levels. However, this was not sufficient to produce worthwhile clinical improvement in those in whom dust mite avoidance might well have been recommended as part of their clinical management.
Bronchiectasis is generally classified into cystic fibrosis and non-cystic fibrosis bronchiectasi... more Bronchiectasis is generally classified into cystic fibrosis and non-cystic fibrosis bronchiectasis. This review article describes non-cystic fibrosis bronchiectasis in adults. Bronchiectasis can be considered a heterogeneous condition characterized by irreversible airway dilatation with chronic bronchial infection/inflammation. It remains a common condition and is a major cause of respiratory morbidity. Many factors are associated with bronchiectasis, but most commonly patients will have idiopathic disease. Important clinical findings include chronic productive cough, rhinosinusitis, fatigue and bi-basal crackles. Patients have usually had symptoms for many years. Diagnosis is confirmed by high-resolution computed tomography scanning using standardized criteria. Spirometry shows moderate airflow obstruction and there is a high prevalence of bronchial hyperreactivity. The most common pathogens are non-typeable Haemophilus influenzae and Pseudomonas aeruginosa. There may be considerable overlap with other chronic airway diseases. Treatment regimens are still not well defined. Patients tend to have ongoing symptoms and decline in respiratory function despite treatment.
Uploads