bluuebunny/crossref_metadata_2025 huggingface dataset:
The haemodynamic response to exercise in chronic obstructive pulmonary disease: assessment by impedance cardiography
Authors: Bogaard HJ , Dekker BM , Arntzen BW , Woltjer HH , van Keimpema AR , Postmus PE , de Vries PM
Published: January 2003

This study aimed to determine the differences in haemodynamic responses to a standard incremental exercise test between outpatients with chronic obstructive pulmonary disease (COPD) and age-matched controls and to discover the relationship between severity of airflow obstruction and exercise haemodynamics in COPD. Twenty-two male patients with COPD (forced expiratory volume in one second (FEV1)/vital capacity (VC))<80% predicted) and 20 age-matched male controls performed an incremental exercise test (10 W x min(-1)) with ventilatory function and changes in stroke volume (deltaSV) and cardiac output (deltaCO) measured by means of electrical impedance cardiography (EIC). Submaximal deltaSV and deltaCO were lower in COPD patients. Peak exercise deltaSV were equal in patients and controls (128+/-33 versus 129+/-29%, p=0.98), whereas peak deltaCO was lower in patients (COPD versus controls: 232+/-71 versus 289+/-54%, p<0.005). In COPD patients, FEV1 (% pred) was significantly correlated to deltaSV at all submaximal exercise intensities, to peak exercise deltaSV and to peak exercise deltaCO. FEV1/VC (% pred) was significantly correlated to deltaSV at 30 and 60 W. In conclusion, in chronic obstructive pulmonary disease an aberrant haemodynamic response to exercise was found, especially in patients with severe airflow obstruction. This aberrant response is related to the degree of airflow obstruction and may limit exercise performance in patients with severe chronic obstructive pulmonary disease.
Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease
Authors: Pesci A , Balbi B , Majori M , Cacciani G , Bertacco S , Alciato P , Donner CF
Published: January 2003

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD). Although the precise sequence of events that leads a smoker to experience airway obstruction is not completely clear, airway inflammation is a relevant factor. To investigate airway inflammation, 12 nonatopic smoking COPD patients with a forced expiratory volume in one second (FEV1) < or = 75% predicted and 10 normal nonsmoking subjects (NS) were studied with bronchoscopy and bronchial lavage (BL). Serum immunoglobulin (Ig)E levels of COPD patients correlated with the smoking history (r=0.7, p=0.008). In BL of COPD patients there was an increase of neutrophils (median, range) (COPD 62.6x10(3), 1.2-323, NS 1.35, 0-19.2, p=0.001), eosinophils (COPD 1.6, 0-6.9, NS 0.15, 0-3.7, p=0.035), the levels of interleukin (IL)-8 (COPD 1079 pg x mL(-1), 121-2,500, NS 20.4, 7.2-59, p=0.001), myeloperoxidase (MPO) (COPD 752 microg x L(-1), 11-5,500, NS 22.1, 8-70, p=0.001) and eosinophil cationic protein (ECP) (COPD 21.5 microg x L(-1), 1.8-161, NS 2, 1.8-4.9, p=0.001). Significant correlations were found in BL of COPD patients between IL-8 and neutrophils (p=0.02), MPO and neutrophils (p=0.02), IL-8 and MPO (p=0.0001) and ECP and eosinophils (p=0.02). In addition, the ratios between the BL levels of MPO and the number of neutrophils and between ECP levels and eosinophils were higher in COPD patients than in NS (p=0.03 and 0.01, respectively). These data suggest that cigarette smoke is associated with increased amounts of airway interleukin-8, a chemotactic factor for neutrophils and eosinophils. Recruited neutrophils and eosinophils are activated and they release increased amounts of inflammatory mediators capable of damaging the bronchial tissue.
Eosinophilic airway inflammation induced by repeated exposure to cigarette smoke
Authors: Matsumoto K , Aizawa H , Inoue H , Koto H , Takata S , Shigyo M , Nakano H , Hara N
Published: January 2003

Acute exposure to cigarette smoke causes airway hyperresponsiveness (AHR) in guinea-pigs, which resolves within a few hours. Repeated exposure may have a different effect on the airways. To address this question, guinea-pigs were repeatedly exposed to cigarette smoke (six cigarettes for 1 h x day(-1)) for 14 consecutive days. Airway responsiveness to inhaled histamine and differential cell counts in bronchoalveolar lavage fluid (BALF) were evaluated 1 day after the last exposure. Significant neutrophilia in BALF was observed after 3 days of smoke exposure. Significant eosinophilia in BALF and AHR were observed after 14 days of smoke exposure, but not after 3 or 7 days of smoke exposure. These changes persisted until 3 days after the last exposure and resolved 7 days afterwards. Histologically, the recruited eosinophils were observed predominantly in the airways, but not in the alveoli. Treatment with E-6123, a specific platelet-activating factor receptor antagonist (1 mg x kg(-1) x day(-1) p.o. during smoke exposure) significantly inhibited the eosinophil influx and AHR. Repeated exposure to cigarette smoke may induce prolonged airway inflammation and airway hyperresponsiveness in guinea-pigs. Platelet-activating factor or platelet-activating factor-like lipids may play a key role in airway hyperresponsiveness, presumably by the induction of eosinophilic airway inflammation.
Cigarette smoke inhalation and lung damage in smoking volunteers
Authors: Clark KD , Wardrobe-Wong N , Elliott JJ , Gill PT , Tait NP , Snashall PD
Published: January 2003

Cigarette smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD) but only 10-15% of smokers develop the condition. Risk does not relate closely to cumulative cigarette consumption, perhaps because smokers vary in the degree and depth of smoke inhalation. This study examined the role of smoke inhalation in the development of COPD. Eighty current smokers and 20 lifetime nonsmoking volunteers (aged 35-65 yrs) were recruited. Lung function variables were measured and high-resolution computed tomography (HRCT) scans performed. Smoke inhalation was assessed by CO boost (the increment of expired carbon monoxide 5 min after smoking a cigarette) and serum cotinine. Mean CO boost was 6.3 parts per million (ppm) in smokers with low CO transfer coefficients (KCO) and 2.9 ppm in those with normal KCO (p=0.006); 7.2 ppm in smokers with both HRCT-defined emphysema and a low KCO and 2.6 ppm in those with neither abnormality (p=0.002); 4.5 ppm in smokers with HRCT-defined emphysema alone and 2.8 ppm in those without (p=0.08). Mean serum cotinine was 328 ng x mL(-1) in smokers with chronic productive cough and 243 ng x mL(-1) in those without (p=0.005). Lifetime nonsmokers had normal HRCT scans, lung function and serum cotinine. Emphysema is associated with high alveolar smoke exposure as measured by CO boost. Productive coughing is associated with high nicotine uptake, probably from airway smoke particle deposition.
Regulation of breathing in hyperthyroidism: relationship to hormonal and metabolic changes
Authors: Pino-Garcia JM , Garcia-Rio F , Diez JJ , Gomez-Mendieta MA , Racionero MA , Diaz-Lobato S , Villamor J
Published: January 2003

We sought to examine the breathing pattern, inspiratory drive and chemosensitivity of hyperthyroid patients and to explore the interactions between their thyroid hormones, basal metabolism and chemosensitivity. We studied 15 hyperthyroid patients and 15 sex- and age-matched controls. Thyroid hormone levels, arterial blood gas tensions, lung volumes, diffusing capacity for CO, maximal respiratory pressures and oxygen uptake measurements were performed. Breathing pattern and mouth occlusion pressure (P0.1), as well as ventilatory and P0.1 responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia, were also evaluated. Compared with the control subjects, the hyperthyroid patients showed significantly lower resting arterial CO2 tension, tidal volume and significantly higher mean inspiratory flow and P0.1. Ventilatory and P0.1 responses to CO2 and hypoxia were also greater in the hyperthyroid patients than in the control group. All these changes returned to normal after treatment. In the patients, significant relationships between tri-iodothyronine and P0.1, P0.1 response to hypoxia, and P0.1 response to hypercapnia were found. In contrast, in hyperthyroidism there was no relationship between oxygen uptake and P0.1 response to hypoxia. We conclude that hyperthyroid patients exhibit a significant relationship between their thyroid hormone levels and their increased inspiratory drive and chemosensitivity.
Effects of high-altitude periodic breathing on sleep and arterial oxyhaemoglobin saturation
Authors: Salvaggio A , Insalaco G , Marrone O , Romano S , Braghiroli A , Lanfranchi P , Patruno V , Donner CF , Bonsignore G
Published: January 2003

This study aimed to investigate the effect of periodic breathing (PB) at high altitude on sleep structure and arterial oxygen saturation (Sa,O2). Five healthy subjects underwent polysomnographic studies at sea level, and during the first and the fourth week of sojourn at 5,050 m. Their breathing pattern, sleep architecture and Sa,O2 were analysed. PB was detected in the high-altitude studies during nonrapid eye movement (NREM) sleep and tended to increase from the first to the fourth week. Stages 3-4 were absent in four subjects at the first week, but only in one at the fourth week, irrespective of the amount of PB. The arousal index was 11.6+/-3.8 at sea level, 30.1+/-15.5 at the first week at altitude and 33.0+/-18.2 at the fourth week. At altitude, arousal index in NREM sleep was higher during PB than during regular breathing. In NREM sleep, the mean highest Sa,O2 levels in NREM epochs with PB were higher than in those with regular breathing by 2.8+/-1.7% at the first week and 2.9+/-1.5% at the fourth week (p<0.025). From the first to the fourth week, mean Sa,O2 increased significantly during wakefulness (5.6%), NREM (5.2% with regular breathing and 5.3% with PB) and rapid eye movement sleep (7.6%). The data demonstrate a slight role of periodic breathing in altering sleep architecture at high altitude and also show that periodic breathing induces only a minor improvement in arterial oxygen saturation during nonrapid eye movement sleep.
Treatment of Cheyne-Stokes respiration with nasal oxygen and carbon dioxide
Authors: Andreas S , Weidel K , Hagenah G , Heindl S
Published: January 2003

Cheyne-Stokes respiration (CSR) is common in patients with congestive heart failure (CHF) and is associated with significant nocturnal O2 desaturation, arousals and sympathetic activation. Nocturnal O2 reduces CSR by only about 50%. More complete suppression of CSR may be achieved by adding CO2 to O2. This study therefore aimed to evaluate the effects of nocturnal O2 plus CO2 on CSR, sleep and sympathetic activation. Nine patients with CHF (age 59+/-5 yrs; left ventricular ejection fraction 17.8+/-1.2% (mean+/-SEM) were studied in a cross-over, single-blind, placebo-controlled trial. After an accommodation night the patients were randomly assigned to one night each of O2 plus CO2 as well as air applied by nasal prongs. Nocturnal O2 plus CO2 reduced the duration of CSR as percentage of total sleep time (48.0+/-10 versus 7.4+/-2.0%; p=0.008) and increased arterial oxygen saturation (Sa,O2) as well as mean transcutaneous carbon dioxide tension (Ptc,CO2) (5.2+/-0.3 kPa (39+/-2 mmHg) versus 5.7+/-0.3 kPa (43+/-2 mmHg) p=0.011). Sleep did not improve and arousals were not reduced. Plasma noradrenaline was higher on the treatment night (486+/-116 versus 669+/-163 ng x L(-1); p=0.035). In conclusion, nocturnal O2 plus CO2 improves Cheyne-Stokes respiration in patients with congestive heart failure but has adverse effects on the sequel of Cheyne-Stokes respiration, namely sympathetic activation.
Effect of oxygen on breathing irregularities during haemodialysis in patients with chronic uraemia
Authors: Yap JC , Wang YT , Poh SC
Published: January 2003

Hypoxaemia and breathing irregularities have been shown to occur during haemodialysis in patients with chronic renal failure. This study examined the role of hypoxia in the genesis of the irregular breathing during haemodialysis. The ventilatory patterns using respiratory inductance plethysmography and arterial blood gases were studied in seven males with chronic renal failure on long-term haemodialysis. The study was carried out before and during dialysis on one day without (D1) and another day with intranasal oxygen at 4 L x min(-1) (D2). On D1, mean (SD) arterial oxygen tension (Pa,O2) fell 1.9 (0.9) kPa (p<0.001) and mean minute ventilation (V'E) fell 1.9 (1.1) L x min(-1) (p<0.01) during dialysis. The arterial carbon dioxide tension (Pa,CO2) did not show a significant decrease (4.7 (0.2) kPa before and 4.6 (0.2) kPa during dialysis). Cumulative number of apnoeas was 64 and the coefficients of variation (COV) of respiratory frequency (fR) and tidal volume (VT) were 29.6 (11.9) and 38.2 (11.9)%, respectively. On D2, mean Pa,O2 remained stable (20.4 (4.1) kPa before, 21.3 (4.1) kPa during dialysis). There was no significant change in mean V'E (6.4 (0.9) L x min(-1) before, 5.5 (0.5) L x min(-1) during dialysis). Pa,CO2 decrease was not significant but the fall was greater (4.8 (0.1) kPa before, 45 (0.5) kPa during dialysis). Cumulative number of apnoeas was 94 and the COVs offR and VT were 35.8 (5.1) and 40.5 (11.3)%, respectively. Oxygen administration did not significantly affect the haemodialysis-induced changes in ventilation and breathing pattern, despite a significant protective effect from the fall in arterial oxygen tension. It was concluded that the fall in arterial oxygen tension is not the main determinant of breathing irregularities during haemodialysis.
Cough and sleep in inner-city children
Authors: Fuller P , Picciotto A , Davies M , McKenzie SA
Published: January 2003

This study aimed to determine whether cough at night keeps children awake, to describe the relationship between children's cough and sleep and to report parents' perceptions of their children's cough and sleep. Thirty-nine children with reported persistent cough at night (>3 weeks) were recruited and studied for 6 nights by video-recording. Coughs were counted and sleep state was coded for awake, restless sleep and quiet sleep. The relationships between cough and sleep state between subjects and within subjects were examined by correlation and regression. After night 2 the parents were asked whether their child had coughed or had disturbed sleep and after night 6 they were asked whether there had been any change. There was a weak relationship between log percentage of the night awake and log number of coughs (r=0.13, SE 0.036), and log (percentage of the night awake plus restless sleep) and log number of coughs (r=0.016, SE 0.0071). If the relationship between cough and sleep state is causal, halving the number of coughs will reduce the percentage of the night awake by 9% (95% confidence interval (CI) 4-15%) and percentage awake and restless by 1% (95% CI 0-2%). All but one parent correctly identified coughing and 82% detected change. Most could not comment on their child's sleep. Improvement in cough would result in little reduction in either the percentage of the night awake or awake and restless in the average child in the population studied. Parents could detect whether their children were coughing but not whether their sleep was disturbed.
Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe
Authors: Bjorksten B , Dumitrascu D , Foucard T , Khetsuriani N , Khaitov R , Leja M , Lis G , Pekkanen J , Priftanji A , Riikjarv MA
Published: January 2003

There is evidence that the prevalence of allergies and asthma differs between populations in western and eastern Europe. This study investigated the prevalence of wheezing, rhinitis and eczema among schoolchildren in urban and rural areas of Scandinavia and the formerly socialist countries of Eastern Europe. A total of 79,000 children from two age groups (13-14 yrs and 6-7 yrs) in 18 study centres responded to a questionnaire within the International Study of Asthma and Allergy in Children (ISAAC). The 12 month period prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema was calculated. The prevalence of wheezing among the 13-14 yr old children was 11.2-19.7% in Finland and Sweden, 7.6-8.5% in Estonia, Latvia and Poland and 2.6-5.9% in Albania, Romania, Russia, Georgia and Uzbekistan (except Samarkand). The prevalence of itching eyes and flexural dermatitis varied in a similar manner between the three regions. The regional differences were less pronounced among the 6-7 yr old children in the seven participating centres. The highest prevalence of rhinitis was recorded in April-July in Scandinavia and during the winter months in the other countries. The prevalence of atopy-related disorders was higher in Scandinavia than in Estonia, Latvia and Poland, which in turn had a higher prevalence than five other countries of eastern Europe with a culture less similar to western Europe. This supports the hypothesis that "Western life style" is associated with a high prevalence of childhood allergy.
Bronchodilator response in 3-6.5 years old healthy and stable asthmatic children
Authors: Hellinckx J , De Boeck K , Bande-Knops J , van der Poel M , Demedts M
Published: January 2003

Few data are available on the bronchodilator response in preschool children. This study was set up to study baseline lung function and bronchodilator responses in healthy and asthmatic children younger than 7 yrs old. In 281 preschool children attending kindergarten (age range 2.7-6.6 yrs old) respiratory system resistance (Rrs) and reactance (Xrs) by impulse oscillation system at 5, 10, 15, 20, 25 and 35 Hz as well as resonance frequency (f0) were measured before and 20 min after 200 microg inhaled salbutamol by a metered-dose inhaler connected to a spacer device. Thirty-four of them were diagnosed as asthmatics based on a validated standardized questionnaire. The mean Rrs (+/-SD) at 5 Hz (Rrs,5) was 1.03 (+/-0.24) kPa x L(-1) x s for healthy children and 1.09 (+/-0.26) kPa x L(-1) x s for stable asthmatics. The mean change in Rrs,5 after salbutamol was -0.13 (+/-0.20) kPa x L(-1) x s for the healthy children and -0.09 (+/-0.25) kPa x L(-1) x s for the asthmatic group. The scatter for the measurements was striking. Neither baseline values of impulse oscillation nor its changes after bronchodilator administration was significantly different between healthy and stable asthmatic children. A change in respiratory system resistance at 5 Hz of 40% is to be considered the cut-off for a " positive" bronchodilator response.
Diffuse panbronchiolitis in rheumatoid arthritis
Authors: Homma S , Kawabata M , Kishi K , Tsuboi E , Narui K , Nakatani T , Uekusa T , Saiki S , Nakata K
Published: January 2003

The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.
Chest radiographic staging in allergic bronchopulmonary aspergillosis: relationship with immunological findings
Authors: Kiely JL , Spense L , Henry M , Hurley MF , Kelleher N , Bredin CP
Published: January 2003

The question of whether a chest radiographic severity staging system could be correlated with standard blood/serum diagnostic indices in allergic bronchopulmonary aspergillosis (ABPA) was addressed in 41 patients. Asthma and positive Aspergillus fumigatus (AF) serology were considered essential diagnostic inclusion criteria. Eosinophil count, serum immunoglobulin (Ig)E and immediate skin hypersensitivity were also tested to grade patients as "definite" or "likely" ABPA. Definite cases had all five of these factors present, whereas likely cases had three or more. Chest radiographs were examined by experienced radiologists blinded to the clinical data. The six-stage radiographic score (0-5) was based on the severity and duration of changes seen: stage 0: normal; stage 1: transient hyperinflation; stage 2: transient minor changes; stage 3: transient major changes; stage 4: permanent minor changes; and stage 5: permanent major changes. Significant positive correlations (p<0.05) were observed between peak AF titres (expressed as an index), peak eosinophil count and radiographic severity stage. When considered as subgroups, these correlations approached, but did not reach, significance for the group with "likely" ABPA (n=28), but in the group with definite ABPA (n=13), there was a high correlation between radiographic score and peak AF index (r=0.59), as well as peak eosinophil count (r=0.62). This study suggests that the peak Aspergillus fumigatus index and eosinophil counts correlate best with the severity of radiographic stages in allergic bronchopulmonary aspergillosis. This chest radiographic staging system may be useful in the clinical assessment and management of patients with allergic bronchopulmonary aspergillosis, particularly in those patients with more severe radiographic stages.
Assessment of accuracy and applicability of a new electronic peak flow meter and asthma monitor
Authors: Richter K , Kanniess F , Mark B , Jorres RA , Magnussen H
Published: January 2003

The aim of this study was to assess the accuracy and applicability of a portable electronic peak flow meter combined with an asthma monitor (AM1, Jaeger, Germany) which measures peak expiratory flow (PEF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The technical accuracy in PEF, FEV1 and FVC measurement was tested according to American Thoracic Society (ATS) criteria for monitoring devices using a flow generator. In addition, the effect of connecting a heated screen pneumotachograph (PT) to the AM1 was determined and the accuracy in FEV1 determinations was evaluated by simultaneous measurements in 49 normal volunteers. The devices tested fulfilled all ATS criteria for monitoring devices with respect to the accuracy of PEF, FEV1, and FVC measurements. The conditions of intra- and interdevice variability were satisfied in all cases. Compared with the PT, the AM1 showed about 4% lower values in FEV1, as measured in the 49 subjects. In conclusion, the electronic peak flow meter and asthma monitor AM1 yielded valid measurements of peak expiratory flow and forced expiratory volume in one second, which matched the accuracy criteria of the American Thoracic Society standards for monitoring devices.
Drug output from nebulizers is dependent on the method of measurement
Authors: Barry PW , O'Callaghan C
Published: January 2003

The objective of this study was to determine whether current regulatory methods for assessing the output of nebulizers are appropriate for the delivery of nebulized steroid suspensions to patients. We studied a conventional jet nebulizer (the Intersurgical Cirrus), an open-vent nebulizer (the Medicaid Sidestream) and a breath-enhanced nebulizer (the Pari LC Plus), using a constant sampling flow or a sinusoidal pump to represent the breathing pattern of children from 6 months to adulthood. Recovery of budesonide released from the nebulizers onto filters was reduced when using breathing simulation compared with constant flow, and this reduction was greatest for the conventional nebulizer (Cirrus, 103 microg with constant flow to 4.4 microg with a 50 mL tidal volume; Pari, 176 microg to 25 microg). The open-vent nebulizer deposited very little budesonide on the filter at lower tidal volumes (4.5 microg with a 50 mL tidal volume), possibly because the enhanced flow of aerosol laden air was greater than the inspiratory flow from the breathing simulator. The output of the LC plus was reduced at high flow, from 176 microg at 20 L x min(-1) to 93 microg at 60 L x min(-1). Overall, the measured output varied by up to 700%, depending on the method used. These results suggest that breathing patterns dramatically alter the measured output of different nebulizers and that breathing simulation should be included as part of their assessment.
A new method for measuring aerosol nebulizer output using radioactive tracers
Authors: Gatnash AA , Chandler ST , Connolly CK
Published: January 2003

Reproducibility and comparability of bronchial challenge tests depends critically on accurate assessment of nebulizer output. Evaporation during nebulization means that simple weighing is inaccurate, overestimating the delivered dose of active ingredient. We wanted to quantify this effect in the context of intermittent nebulization, using a dosimeter as used in bronchial provocation tests. Output of three types of nebulizer, from the MEFAR dosimeter, was measured by radioactive tracer, using a standard solution of technetium-99m-pertechnetate (1.5 kBq x mL(-1)) in 4 mL of normal saline. The aerosol was impacted by suction onto a microfilter, and the radioactivity measured. Nebulizers were weighed before and after nebulization. Ratio of nebulized volume calculated from the radioactivity on the filter, to the total volume loss by weight, was expressed as nebulized ratio. The effect on output of two concentrations of methacholine, two tracers of different weights, and change in temperature, were assessed. Nebulized ratio varied between 44.1-71.6%. Results were more consistent within the same type of nebulizer than between different makes. Neither changes in molar concentration nor molecular weight affected nebulizer output or nebulized ratio. Mean nebulized ratio was 58.5%, showing that calibration by weighing, overestimates the delivered dose by a factor of approximately two. Measuring radioactivity eluted from a microfilter, onto which nebulized output had been impacted proved to be a satisfactory method of calibration.
In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children
Authors: Berg E , Madsen J , Bisgaard H
Published: January 2003

The performance of pressurized metered dose inhalers (pMDIs) and spacers in correct dose recommendations is important, but limited information on dose delivery and fine-particle dose from different combinations of spacers and pMDIs is available. In this study, three combinations of spacers and pMDIs were investigated: NebuChamber and AeroChamber with budesonide pMDI and Babyhaler with fluticasone propionate pMDI. Doses were withdrawn onto a filter either with a breathing simulator (dose to ventilator) or with constant flow (maximal dose). The fine-particle dose was assessed with a cascade impactor (Andersen Sampler). The effect of repeated use and cleaning of the spacers on the passive fallout of aerosol within the spacers was determined by evacuating the dose on a filter 2, 5, 10 and 30 s after actuating the spray. The drugs were quantified by liquid chromatography. The NebuChamber delivered the highest doses, both maximal dose and dose to ventilator. The recovered doses (means+/-SD) were 55+/-6% and 51+/-2%, respectively, of the delivered dose from the pMDI. The corresponding results for the Babyhaler were 41+/-7% and 24+/-4% and for the Aerochamber 27+/-3% and 17+/-3%. The passive fallout of aerosol, determined as half-life (t1/2) was around approximately 30 s for the NebuChamber, 9-15 s for the Babyhaler and approximately 10 s for the AeroChamber. The present study confirms that there are significant differences in dose output from different combinations of pressurized metered dose inhalers and spacers, with the NebuChamber giving the highest dose, both as delivered dose and in droplets <4.7 microm. Interactions with the spacer material, dead space in the inspiratory line and entrainment of air during inhalation due to inefficient valve control could account for these differences.
Development and validation of a screening test for 12 common mutations of the cystic fibrosis CFTR gene
Authors: Robertson NH , Weston SL , Kelly SJ , Duxbury NJ , Pearce SR , Elsmore P , Webb MB , Newton CR , Little S
Published: January 2003

The results obtained using deoxyribonucleic acid (DNA) amplification-based tests must be accurate and reproducible. One such test that simultaneously detects any of 12 of the most common mutations of the cystic fibrosis transmembrane conductance regulator gene is presented in this report. An investigation was conducted into how changes of primer, DNA template and Taq DNA polymerase concentrations and of polymerase chain reaction annealing temperatures affect the test. A total of 383 DNA samples obtained from different laboratories was then examined. The preliminary studies defined the conditions under which accurate results are obtained even if the test is performed under suboptimal conditions. Subsequently, 377 (98.4%) of the DNA samples analysed were in full agreement with DNA typing results derived by other methods. The remaining 1.6% of samples were not mistyped, rather they were not scored owing to failure to detect control DNA sequences. These were also archival DNA preparations rather than freshly prepared samples from venous blood. Careful primer design and optimization of reaction conditions are important in the development of multiplex deoxyribonucleic acid amplification-based diagnostic tests. Providing the recommended protocols are followed, the test described here is simple to carry out, gives accurate results and works well if performed within defined operational windows for each reaction variable.
Hydrogen peroxide in exhaled air of healthy children: reference values
Authors: Jobsis Q , Raatgeep HC , Schellekens SL , Hop WC , Hermans PW , de Jongste JC
Published: January 2003

An increased content of hydrogen peroxide (H2O2), a marker of inflammation, has been described in the condensate of exhaled air from adults and children with inflammatory lung disorders, including asthma. However, the normal range of [H2O2] in the exhaled air condensate from healthy children has not been established. Therefore, the aim of this study was to determine the reference range of exhaled [H2O2] in healthy school-aged children. Ninety-three healthy nonsmoking children (48 female and 45 male, mean age 10 yrs, range 8-13 yrs), with a negative history for allergy, eczema or respiratory disease and with a normal lung function, participated. Exhaled air condensate was examined fluorimetrically for the presence of H2O2. In addition, the reproducibility of [H2O2] within subjects and between days and the stability of [H2O2] during storage at -20 degrees C were assessed. The median [H2O2] in the exhaled air condensate of all children was 0.13 microM, with a 2.5-97.5% reference range of <0.01-0.48 microM. No significant difference existed between males and females. There was no correlation between exhaled [H2O2] and age or lung function. Repeated [H2O2] measurements on 2 consecutive days showed satisfactory within-subject reproducibility and [H2O2] in stored samples remained stable for at least 1 month at -20 degrees C. In conclusion, this study provides reference data for exhaled hydrogen peroxide in a large group of healthy children. The observed levels were lower than those reported previously for healthy adults and were independent of age, sex and lung function.
Quality-of-life assessment in children and adolescents with asthma
Authors: Rutishauser C , Sawyer SM , Bowes G
Published: January 2003

Health-related quality of life has become an essential part of health outcome measurement in chronic disorders. However, it is only recently that health professionals have focused on quality-of-life assessment in children and adolescents. Several generic, as well as the asthma-specific quality-of-life instruments specifically designed for use in children and adolescents are reviewed in this article with particular regard to the conceptual and methodological features of the measures and their applicability in clinical studies. The recently published Child Health Questionnaire is a useful generic instrument to comprehensively assess quality of life, in particular when comparing young people with different chronic disorders. The Pediatric Asthma Quality-of-life Questionnaire has shown responsiveness to change over time, but it lacks age-specificity with regard to psychosocial issues and comprehensiveness of quality-of-life assessment. In contrast, the Childhood Asthma Questionnaire provides three different versions for different target ages. However, its generic part is not reflective of the respondent's health status. The other asthma-specific instruments have major conceptual deficiencies when used as a single measure for quality-of-life assessment. In the absence of a single ideal instrument, the use of batteries of quality-of-life instruments is therefore recommended and further research is required to identify the impact that age and developmental status have on quality-of-life assessment.
Central sleep apnoea in congestive heart failure despite vagal denervation after bilateral lung transplantation
Authors: Solin P , Snell GI , Williams TJ , Naughton MT
Published: January 2003

Nonhypercapnic central sleep apnoea is a disorder of respiratory control characterized by hyperventilation previously attributed to the stimulation of either pulmonary vagal afferent nerve fibres or respiratory chemoreceptors. This report describes central sleep apnoea in a patient with congestive heart failure following bilateral lung transplant in whom pulmonary vagal afferent nerve activity was absent.
Resolution of obstructive sleep apnoea with growth in the Robin sequence
Authors: Kiely JL , Deegan PC , McNicholas WT
Published: January 2003

A 12 year old female with the Robin sequence presented with a one year history of snoring, witnessed apnoeas and daytime sleepiness. Surgery in early childhood had consisted of cleft palate repair, tonsillectomy and adenoidectomy and, later, revision palatoplasty. Overnight polysomnography (PSG) demonstrated severe obstructive sleep apnoea syndrome with an apnoea/hypopnoea index (AHI) of 49 events x h(-1), and repetitive oxygen desaturations below 50%. Nasal continuous positive airway pressure (nCPAP) effectively controlled her sleep abnormalities. After 3 yrs of nCPAP therapy, she requested discontinuation and was fully reassessed. PSG without nCPAP revealed an AHI <5 events x h(-1) with no desaturations below 90% and normal sleep quality. A repeat lateral cephalometrogram showed increased mandibular length and posterior airway space and reduced soft palate length. The patient remains asymptomatic 9 months following nCPAP discontinuation. This case indicates that nasal continuous positive airway pressure is an effective nonsurgical therapy in children with obstructive sleep apnoea syndrome and the Robin sequence. It is likely that mandibular growth, increase in mandibular length and enlargement of the posterior airway space was responsible for the resolution of obstructive sleep apnoea syndrome in this case.
Eosinophilic lung disease associated with Candida albicans allergy
Authors: Pacheco A , Cuevas M , Carbelo B , Maiz L , Pavon MJ , Perez I , Quirce S
Published: January 2003

A significant number of cases of chronic eosinophilic pneumonia remain idiopathic in spite of a comprehensive search of associated causes. This study reports a patient with a classical clinical presentation of chronic eosinophilic pneumonia and peripheral blood eosinophilia in whom selective sensitization to Candida albicans was demonstrated. This yeast was present in the bronchoalveolar lavage culture and specific serum immunoglobulin (Ig)E and IgG against C. albicans were found in the patient's serum. Levels of these specific immunoglobulins diminished with corticosteroid treatment and increased coinciding with a new outbreak of symptoms after lowering the dosage of corticosteroids. To the author's knowledge, this is the first case described of chronic eosinophilic pneumonia associated with sensitization to C. albicans. Evaluation of allergy to C. albicans should be performed in chronic eosinophilic pneumonia before labelling cases as idiopathic.
Standardized tuberculosis treatment outcome monitoring in Europe. Recommendations of a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) for uniform reporting by cohort analysis of treatment outcome in tuberculosis patients
Authors: Veen J , Raviglione M , Rieder HL , Migliori GB , Graf P , Grzemska M , Zalesky R
Published: January 2003

Consensus-based recommendations have been developed by a Working Group of the World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis (TB) treatment outcome data in countries in Europe. The main purpose of treatment monitoring is to find out how many of the potential infectious TB patients notified were declared cured at the end of treatment. Following the uniform case definitions as defined in 1996, emphasis is placed on cohort analysis of definite cases of pulmonary TB. The Working Group recommends using a minimal set of six mutually exclusive categories of treatment outcome: cure, treatment completed, failure, death, treatment interrupted, and transfer out. More detailed subsets may be chosen. Treatment outcome is expressed as a percentage of the total number of cases notified. Analysis should be separate for new and retreatment cases. Treatment outcome data have to be collected at the local level and passed on to regional and national authorities on an ongoing basis. Evaluation of treatment results becomes, preferably, an inbuilt component of national monitoring of programme performance. Because of the long duration of treatment, it is recommended that analysis is carried out in the first quarter of the calendar year that follows a full year after the last patient was enrolled. Feedback is essential. Treatment outcome results should become an inseparable part of the annual report on tuberculosis.
Incidence of schizophrenia in south-east London between 1965 and 1997
Authors: Boydell J. , Van Os J. , Lambri M. , Castle D. , Allardyce J. , McCreadie R. G. , Murray R. M.
Published: January 2003

Background

There has been much debate about changes in the incidence of schizophrenia.

Aims

To identify any changes in incidence of schizophrenia in Camber well, south-east London, between 1965 and 1997.

Method

Research Diagnostic Criteria and DSM–III–R diagnoses were generated for all first contacts by the OPCRIT computer program, and incidence rates of schizophrenia in seven time periods were measured. Indirect standardisation and Poisson models were used to measure the effect of time period and to examine interactions with age and gender.

Results

There was a continuous and statistically significant increase in the incidence of schizophrenia, which was greatest in people under 35 years of age and was not gender-specific.

Conclusions

The incidence of schizophrenia has doubled in south-east London over the past three decades.
Trends in the use of Part II of the Mental Health Act 1983 in seven English local authority areas
Authors: Lelliott Paul , Audini Bernard
Published: January 2003

Background

Data collected by the Department of Health show a continuing increase in the rate of formal detention in hospital under Part II of the Mental Health Act 1983.

Aims

To establish whether the increase in formal detentions is uniform across subgroups of the population.

Method

Data related to use of Part II of the Act between 1991 and 1997 collected by seven English local authorities were examined. Rates of compulsory admission were standardised to age, gender and ethnicity-specific populations.

Results

Over the 8-year period the overall rate of detention under Part II increased by 32%. It increased in all three major ethnic groupings; the rate of increase was greater for men than for women (38% v. 26%) and, in particular, for younger men compared with younger women (43% v. 28%).

Conclusions

A combination of factors probably accounts for these findings, including service factors (particularly reduction in bed numbers), a culture of risk aversion, and changes in the effect of substance misuse on the presentation of mental illness.
Urinary Free Cortisol Increases in Adolescent Caucasian Females during Perimenarche
Authors: Legro Richard S. , Lin Hung Mo , Demers Laurence M. , Lloyd Tom
Published: January 2003

Urinary free cortisol (UFC) excretion has been thought to be constant during female reproductive maturation when normalized for body surface area. We sought to determine whether there are longitudinal changes in urinary free cortisol excretion during perimenarche in adolescent females. We performed a longitudinal study of 24-h UFC excretion obtained at 6-month intervals over a 4-yr period in a cohort of 112 adolescent non-Hispanic white perimenarchal females from south central Pennsylvania. The overall mean values (mean ± sd) for UFC/24 h for all measurements between ages 12 and 17 yr was 67.4 ± 43.8 μg/24 h (to convert to nanomoles per day, multiply by 2.759). In our model, we found a significant positive association between UFC excretion with both gynecological age (P = 0.002) and chronological age (P = 0.0001). For every incremental increase in Tanner stage, the UFC/BSA increased by 3.0 μg/24 h per square meter. Correcting the UFC values by both creatinine and BSA creates a fairly constant number (6.3 ± 3.1 μg/mg per square meter per 24 h) over the age range 12–17 yr represented in this study. An increase in cortisol excretion may be part of normal reproductive maturation.
Epitope Heterogeneity of Thyroid-Stimulating Antibodies Predicts Long-Term Outcome in Graves’ Patients Treated with Antithyroid Drugs
Authors: Kim Tae Yong , Park Young Joo , Park Do Joon , Chung Hyun-Kyung , Kim Won Bae , Kohn Leonard D. , Cho Bo Youn
Published: January 2003

Differences in the epitopes of thyroid-stimulating antibodies (TSAbs) from patients with untreated Graves’ disease were compared with long-term response to antithyroid drugs. Epitopes were measured using Chinese hamster ovary cells transfected with wild-type human TSH receptor (TSHR) and two receptor chimeras, wherein TSHR residues 9–165 or 90–165 had been substituted with comparable residues of the LH/chorionic gonadotropin receptor. Of 159 patients studied, 52 (32.7%) exhibited positive TSAb activity with one or both chimera lines (heterogeneous group), and 107 (67.3%) had no activity with either (homogeneous group). Independent of all other parameters, patients with heterogeneous epitopes responded more favorably to oral antithyroid drugs than patients with homogeneous epitopes (65.4% vs. 41.9%, P = 0.011: estimated odds ratio by logistic regression, 2.17). Although most clinical parameters were not different at presentation, significant differences in the size of goiters, total T3 concentrations, and titers of TSH-binding inhibitory Igs were evident in the successfully treated group (n = 80) by comparison to the group of patients whose treatment failed (n = 79). Alone, these three parameters did not predict outcome; however, when either of these parameters were considered together with epitope heterogeneity, predictability of a positive therapeutic response was increased to nearly 80%. Thus, the presence of TSAbs with a heterogeneous epitope in a patient with Graves’ disease is not only associated with a favorable response to antithyroid drug treatment, it may help predict the response to treatment when the patient is initially seen.
Cardiovascular Safety of Acute Recombinant Human Thyrotropin Administration to Patients Monitored for Differentiated Thyroid Cancer
Authors: Biondi Bernadette , Palmieri Emiliano A. , Pagano Loredana , Klain Michele , Scherillo Giovanna , Salvatore Marco , Fenzi Gianfranco , Lombardi Gaetano , Fazio Serafino
Published: January 2003

Eleven patients who had undergone total thyroidectomy for differentiated thyroid cancer and who were on chronic TSH-suppressive therapy with levothyroxine (l-T4), underwent 24-h Holter electrocardiogram and Doppler-echocardiography before and after acute recombinant human TSH (rhTSH) administration for disease staging. The treatment, which was generally well tolerated, did not affect circulating thyroid hormones levels, nor did it have measurable effects on heart rate, rhythm, left ventricular morphology, or systo-diastolic function. Notably, arterial blood pressure tended to be slightly reduced after rhTSH administration, although in no instance did the patients become frankly symptomatic. Our data demonstrate that rhTSH does not alter cardiovascular function acutely. Consequently, it can safely be used in the routine staging of patients affected by differentiated thyroid cancer.
Polymorphisms of the Insulin Receptor Subtrate-2 in Patients with Type 2 Diabetes
Authors: D’Alfonso Rossella , Marini Maria Adelaide , Frittitta Lucia , Sorge Roberto , Frontoni Simona , Porzio Ottavia , Mariani Luisa Marina , Lauro Davide , Gambardella Sergio , Trischitta Vincenzo , Federici Massimo , Lauro Renato , Sesti Giorgio
Published: January 2003

We investigated the significance of Gly1057Asp and Leu647Val insulin receptor substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose-tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region (i.e. representative of central Italy), and 123 glucose-tolerant subjects from the Sicily region (i.e. representative of south Italy). The allelic frequency of Gly1057Asp variant did not differ between diabetics (32.9%) and nondiabetic subjects, whatever their ethnicity was (35.8% and 33.7% from Lazio and Sicily, respectively). As compared with Gly/Gly subjects within each group, Asp/Asp individuals showed no differences in quantitative traits, including fasting insulin and C-peptide, and several indices of insulin sensitivity and secretion. Only one of the diabetic patients was heterozygous for the Leu647Val variant, and none of the control subjects carried this variant. This patient had three children who were also heterozygous for this variant. They were glucose tolerant, and their insulin sensitivity and insulin secretion indices were within the range of age-matched controls. We also analyzed IRS-2 function in fibroblasts from carriers of Gly1057Asp or Leu647Val variant. No defects in IRS-2 expression, insulin-stimulated phosphorylation, or binding to the p85 subunit of phosphatidylinositol 3-kinase were observed. These results strongly argue against a major role of IRS-2 polymorphisms in the pathogenesis of type 2 diabetes.