bluuebunny/crossref_metadata_2025_split huggingface dataset:
Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia
Authors: Notarangelo Lucia D. , Mazza Cinzia , Giliani Silvia , D'Aria Chiara , Gandellini Francesca , Ravelli Chiara , Locatelli Maria Grazia , Nelson David L. , Ochs Hans D. , Notarangelo Luigi D. 
Published: October 2002

AbstractMutations of the WASP gene have been previously shown to be responsible for classical Wiskott-Aldrich syndrome, isolated X-linked thrombocytopenia, and severe, congenital X-linked neutropenia. We report herewith 2 families in which affected males had a history of intermittent thrombocytopenia with consistently reduced platelet volume, in the absence of other major clinical features, and carried missense mutations of the WASP gene that allowed substantial protein expression. This observation broadens the spectrum of clinical phenotypes associated with WASP gene defects, and it indicates the need for molecular analysis in males with reduced platelet volume, regardless of the platelet number.
Time domain and flow indices of bronchial hyperresponsiveness: association with asthma symptoms, atopy and smoking
Authors: Miller M.R. , Sigsgaard T. , Omland O. , Pedersen O.F. 
Published: October 2002

Conventional measures of bronchial hyperresponsiveness (BHR) are only weakly associated with respiratory symptoms in epidemiological studies. Partial and maximal forced expiratory manoeuvres were recorded during histamine challenge testing in 1,959 young male farmers. Analysis was performed to test whether novel measures of BHR, using alternative flow and time domain indices, are more closely associated with asthma symptoms, smoking status and atopy than forced expiratory volume in one second (FEV1) and conventional measures of BHR.The first moments to 75% and 90% of the forced vital capacity (FVC) were calculated from full (F) and partial (P) forced expiratory manoeuvres (i.e.α175%F, α175%P), together with the instantaneous flows when 40% and 30% of the FVC remained to be expired (MEF40and MEF30). BHR was measured by the provocative dose causing a 20% change (PD20) in the FEV1and α175%, and also by the method of log dose slopes (LDS).Asthma was diagnosed from symptoms associated with asthma in 158 (8.1%) of the subjects. PD20FEV1could only be recorded in 190 subjects (9.7%), of whom only 48 had asthma, whereas LDSFEV1was recorded in 1,725 (88%) subjects. From the prechallenge data, α175%, expressed as standardised residuals, showed the largest difference between smokers with and without asthma symptoms, and no indices showed significant differences between nonsmokers with and without asthma symptoms. From BHR data in both smokers and nonsmokers, LDSFEV1showed one of the largest differences between those with and without asthma symptoms. With smoking status and atopy accounted for, the greatest partial correlation with asthma diagnosis was found for LDSMEF40P, and then for LDSFEV1, but LDSMEF40P was measurable in only just over one-half of the subjects.The authors conclude that time-domain indices are promising measures for longitudinal epidemiological studies concerning the relationship between bronchial hyperresonsiveness and environmental exposures. However, indices from the partial flow-volume loop suffer from censored data.
Snoring detection during auto-nasal continuous positive airway pressure
Authors: Lofaso F. , Leroux K. , Quera-Salva M.A. , Mroue G. , D'Ortho M.P. , Isabey D. , Louis B. 
Published: October 2002

A bench study using an artificial lung model was performed to evaluate the snoring detection sensitivity of six (commercially available) auto-nasal continuous positive airway pressure (NCPAP) devices.Snoring was simulated by a loudspeaker connected to the lung model and abruptly activated during 1 s of each inspiratory period to induce pressure oscillation. The oscillation frequencies chosen were 30, 60, 90, and 120 Hz. For each frequency, the amplitude of the pressure oscillation produced by the loudspeaker was adjusted to find the threshold at which the auto-nCPAP devices detected snoring.Differences in pressure-amplitude thresholds of up to three-fold were found across auto-nCPAP devices. A randomized clinical study to compare the effects of the least sensitive (Virtuoso LX; Respironics, Nantes, France) and one of the most sensitive, (Goodknight 418A; Malinckrodt, Nancy, France) devices, in two groups of six patients with obstructive sleep apnoea syndrome was then conducted. Goodknight 418A was more sensitive than Virtuoso LX for detecting snoring (mean±sd 92±11%versus50±39% respectively, p=0.03).To conclude, striking differences exist between auto-nasal continuous positive airway pressure devices in sensitivity for detecting snoring.
Perinatal predictors of respiratory symptoms and lung function at a young adult age
Authors: Boezen H.M. , Vonk J.M. , van Aalderen W.M.C. , Brand P.L.P. , Gerritsen J. , Schouten J.P. , Boersma E.R. 
Published: October 2002

A longitudinal cohort of 2,957 babies, born in 1975–1978, was used to investigate whether perinatal factors predict respiratory morbidity at a young adult age.In 1997, the presence of asthmatic (wheeze, nocturnal dyspnoea) and bronchitic (cough, phlegm, dyspnoea grade 3) symptoms and the level of lung function was determined in this cohort. The independent association between smoking during pregnancy, being first-born, birth weight and respiratory symptoms and lung function at young adult age was investigated using multiple regression models, taking other potential risk factors into account.Of 1,568 responders, 608 (39%, aged 18–22 yrs) had at least one respiratory symptom. The young adults who had a mother that smoked during pregnancy had a significantly lower level of lung function than their nonintra-uterine exposed peers (regression coefficient (B) (standard error): peak expiratory flow (PEF) −0.257 (0.131) L·s−1; forced expiratory flow when 25% of the forced vital capacity has been exhaled (FEF25) −0.290 (0.129) L·s−1), although they were not at increased risk of having respiratory symptoms. Young adults who were first-born had better levels of lung function (B (se): forced expiratory volume in one second (FEV1) 0.090 (0.042) L) and were less likely to have asthmatic symptoms (odds ratio (95% confidence interval): 0.58 (0.35–0.95)) than those not first-born. Low birth weight (FEV1−0.013 (0.004) L for a reduction of 100 g) was also predictive of reduced achieved levels of lung function at young adult age, independent of other potential risk factors,e.g.current smoking habits or familial predisposition.This study adds to the knowledge of the role of perinatal factors, such as smoking during pregnancy, as important predictors of respiratory morbidity.
Effects of insulin-like growth factor on nitrogen balance during hypoxic exposure
Authors: Iioka Y. , Tatsumi K. , Sugito K. , Moriya T. , Kuriyama T. 
Published: October 2002

Acute exacerbations of chronic obstructive pulmonary disease (COPD) accompanied with hypoxaemia may induce net protein catabolism and hypoxaemia could be an important trigger of a systemic catabolic response. The aim of this study was to examine the anabolic effects of recombinant human insulin-like growth factor‐I (IGF‐I) in rats exposed to hypoxia. Although acute hypoxia is usually accompanied with a decrease in dietary intake, the usual nitrogen intake was maintained in this study.Sprague-Dawley rats were maintained by continuous infusion of solution for total parenteral nutrition for 6 days. The animals were then randomly assigned to a normoxic (N) or a hypoxic (H) group. During the last 3 days of the experiment N and H rats were randomised to receive either IGF‐I or vehicle.Exposure to hypoxia caused a decrease in body-weight gain accompanied by a negative nitrogen balance, which was mainly due to increased urinary nitrogen excretion. No effect of recombinant human IGF‐I treatment on body weight was observed during exposure to hypoxia, although nitrogen balance normalised.The co-infusion of recombinant human insulin-like growth factor‐1 and total parenteral nutrition has a significant net anabolic effect, as demonstrated by nitrogen retention and reduction in urine protein excretion observed in rats. Insulin-like growth factor‐1 may help to ameliorate the protein catabolism observed under hypoxic conditions.
Inpatient resource utilisation in younger (2–5 yrs) and older (6–14 yrs) asthmatic children in Finland
Authors: Valovirta E. , Sazonov Kocevar V. , Kaila M. , Kajosaari M. , Koivikko A. , Korhonen K. , Linna O. , Mäkelä M. , Remes K. , Ben-Joseph R.H. 
Published: October 2002

Asthma is the most common chronic disorder among Finnish children, however, the economic burden of paediatric asthma in Finland has not yet been comprehensively evaluated. The objective of this study was to compare inpatient resource utilisation between younger (2–5 yrs) and older children (6–14 yrs) with asthma in Finland.A national database of inpatient resource utilisation was applied to determine use of hospital services among children with asthma in 1999. Regional estimates of charges were combined with hospitalisation episodes to determine total inpatient cost.The results indicate that younger asthmatic children consume 3‐times more inpatient resources per capita. Incidence of first admissions because of asthma was 3‐times higher in younger children. Hospitalisation and rehospitalisation rates were also 3‐ and 4‐times higher, respectively.The total annual inpatient cost of asthma in children aged 2–5 and 6–14 yrs was E 1.98 million with each group accounting for E 1.12 million and E 0.86 million, respectively. Regional and age-related differences in hospitalisation rates and costs were likely related to variable clinical practice on the primary level, difficulties with diagnosis and compliance among younger children.
Lung cancer risk in a population-based cohort of patients hospitalized for asthma in Sweden
Authors: Boffetta P. , Ye W. , Boman G. , Nyrén O. 
Published: October 2002

It has been suggested that asthma increases the risk of lung cancer in males but not in females. However, previous studies may suffer from report bias and are based on a small numbers of cases.The objective of the present study was to assess the incidence of lung cancer in males and females using a nationwide Swedish cohort of asthma patients.Patients (n=92,986) aged ≥20 yrs with a hospital-discharge diagnosis of asthma and who were alive and free from malignancy 1 yr after first hospitalization were followed-up, for incidence of lung cancer during the period 1965–1994 (average duration of follow-up, 8.5 yrs). Their incidence of lung cancer was compared with that of the national population.The authors observed 713 lung cancers (standardized incidence ratio (SIR) 1.58, 95% confidence interval (CI) 1.47–1.70). The SIR was 1.51 in males (95% CI 1.38–1.65, 492 cases) and 1.78 in females (95% CI 1.55–2.03, 221 cases). The SIR decreased with duration of follow-up and increased with calendar period and age at first hospitalization. The risk of lung cancer was higher for squamous cell and small cell carcinoma than for adenocarcinoma, and it was higher in patients with other diseases as the main diagnosis and in patients hospitalized in departments other than internal and respiratory medicine.It was confirmed that asthma patients are at increased risk of lung cancer, but there is no heterogeneity in risk between the sexes. Several indirect arguments point towards a noncausal explanation of these findings; in particular, confounding by tobacco smoking is a plausible explanation.
Enhanced IL‐4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy
Authors: Pala P. , Bjarnason R. , Sigurbergsson F. , Metcalfe C. , Sigurs N. , Openshaw P.J.M. 
Published: October 2002

Infants who recover from respiratory syncytial virus (RSV)-induced bronchiolitis are at high risk of developing asthma and recurrent wheezing. It is not known whether severe RSV infection itself causes persistent effects or is a marker of a “wheezy” predisposition. To determine the long-term immunological correlates of infantile bronchiolitis, interleukin (IL)‐4 and interferon (IFN)‐γ responses to a panel of antigens were studied in a well-characterised cohort of 7–8‐yr-old children with a history of severe RSV bronchiolitis in infancy.Peripheral blood lymphocytes from 37 children who were hospitalised with RSV bronchiolitis in infancy and from 69 age-, sex- and location-matched controls were stimulatedin vitrowith RSV, house-dust mite, birch and cat antigens. Cellular proliferation, and enzyme-linked immunoSPOT IFN‐γ and IL‐4 production were measured.IL‐4 producing T‐cells responding to RSV and cat antigens were significantly more frequent in exbronchiolitics. Other responses (including the IFN‐γ response to RSV) were equally strong in exbronchiolitics and controls.Respiratory syncytial virus infection primes memory T‐cells that make interferon‐γ, but virus and aeroallergen-specific and interleukin‐4 producing T‐cells are also frequently primed in bronchiolitics. Respiratory syncytial virus bronchiolitis in infancy may increase the risk of allergic sensitisation by providing a local interleukin‐4‐rich environment, in which airborne allergens are first encountered.
Exhaled nitric oxide and bronchial responsiveness in healthy subjects exposed to organic dust
Authors: Sundblad B-;M. , Larsson B-;M. , Palmberg L. , Larsson K. 
Published: October 2002

Inhalation of organic dust from swine houses causes an intense inflammatory reaction in the respiratory tract, and increased bronchial responsiveness to methacholine in healthy subjects. The aims of the present study were to investigate whether exhaled nitric oxide (NO) is a marker of the inflammation caused by exposure to organic dust (swine dust), whether there is a relationship between an increase in exhaled NO and bronchial responsiveness, and also whether wearing a half-mask influences the airway reaction (assessed by exhaled NO) and the increased bronchial responsiveness.Thirty-three healthy nonatopic, nonsmoking subjects were exposed during 3 h of light work in a swine confinement building. Eleven of the subjects were wearing a half-mask and 22 were unprotected. Lung function, bronchial responsiveness and exhaled NO were measured before and after exposure.The provocative concentration causing a 20% fall in forced expiratory volume in one second fell by 2.7 (2.1–4.1) (median (25th–75th percentiles)) doubling concentration steps in subjects without a half-mask and by 1.5 (0.9–2.9) doubling concentration steps in subject wearing a mask. Exhaled NO increased from 7.5 (5.7–13.7) parts per billion (ppb) before to 13.4 (10.5–17.5) ppb after exposure in the unprotected group and was unaltered (8.3 (6.1–14.1) to 8.6 (6.6–14.6) ppb) in the group wearing a half-mask. There was no correlation between NO increase and provocative dose causing a 20% fall in the forced expiratory volume in one second decrease.In conclusion, bronchial responsiveness and exhaled nitric oxide increased after exposure to a swine confinement facility. Half-mask abolished the increase in exhaled nitric oxide levels, but influenced the increase in bronchial responsiveness to a minor extent. These results indicate that these two outcome measures reflect different aspects of airway inflammation induced by exposure to a farming environment.
Bronchial reactions to the inhalation of high-dose tobramycin in cystic fibrosis
Authors: Nikolaizik W.H. , Trociewicz K. , Ratjen F. 
Published: October 2002

It has been established that inhaled tobramycin has a positive effect on respiratory function inPseudomonas-aeruginosapositive patients with cystic fibrosis (CF). In a previous study the authors reported that low-dose tobramycin preparations containing the preservative phenol caused significant bronchial obstruction. Recently, high-dose tobramycin preparations with and without preservatives/phenol have become available.To assess the airway response to these preparations flow/volume curves in 12 patients with CF (four males, eight females, mean age±sd=19.0±7.4 yrs) were measured. The tobramycin preparations: Nebicina® 2.0 mL (150 mg, containing the preservative phenol), Distobram® 3.0 mL (150 mg, containing preservatives), Tobi® 5.0 mL (300 mg), Tobi® 2.5 mL (150 mg), and Tobi® 5.0 mL, were used after bronchodilator application.Immediately and/or 5 min after the tobramycin inhalations there was a significant fall in lung function with the different preparations. There was no significant difference between preparations with and without preservatives/phenol. The bronchial obstruction was comparable to that observed after the inhalation of low-dose tobramycin and after saline. After 10 min of inhalation, the lung function returned to baseline values. Most patients preferred the Tobi® 2.5 mL and disliked the Nebicina® preparation due to the unpleasant taste. Preceding treatment with bronchodilators prevented the decline in lung function.Assessment of bronchial response at the first nebulisation of high-dose tobramycin and, in case of significant obstruction, β‐agonists in combination with the antibiotic inhalation are recommended.
Some factors affecting cerebral tissue saturation during obstructive sleep apnoea
Authors: Valipour A. , McGown A.D. , Makker H. , O'Sullivan C. , Spiro S.G. 
Published: October 2002

Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA) may provide additional information to conventional peripheral oxygen saturation.Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7±27.9) were monitored using full polysomnography and monitoring of near-infrared cerebral tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen saturation (Sa,O2) dip, minimumSa,O2, TOI dip and minimum TOI. Cerebral TOI is a measure of cerebral tissue saturation of haemoglobin with oxygen, calculated using near-infrared spatially resolved spectroscopy, which has been shown to have a high specificity for intracranial changes.Decreases in cerebral oxygenation were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1–73.0% and mean apnoea/hypopnoea related TOI dips ranged from 1.43–6.85%. MeanSa,O2dips varied from 3.8–21.7%. In regression analysis, factors significantly predicting the magnitude of the TOI dip wereSa,O2dip, minimumSa,O2, apnoea duration and rapid eye movement sleep stage. The effect of apnoea duration and sleep stage remained significant afterSa,O2was included in the regression equation.Near-infrared spectroscopy provides a noninvasive technique for monitoring cerebral tissue saturation during obstructive sleep apnoea.
Upregulation of nerve growth factor expression by human airway smooth muscle cells in inflammatory conditions
Authors: Freund V. , Pons F. , Joly V. , Mathieu E. , Martinet N. , Frossard N. 
Published: October 2002

Recent studies have suggested that nerve growth factor (NGF) may play a role in inflammation and bronchial hyperresponsiveness in asthma. Neither the types of cells that produce NGF in the human airways nor the effect of inflammation on NGF expression are clear. The two-fold aim of the present study was to determine whether airway smooth muscle produces NGFin vitro, and, if so, whether the pro-inflammatory cytokine interleukin-1β (IL-1β) affects this expression.Human airway smooth muscle cells in culture were incubated in the presence or absence of IL-1β. NGF production was measured by enzyme-linked immunosorbent assay. NGF messenger ribonucleic acid (mRNA) was measured using a specific real-time fluorescent polymerase chain reaction technique, and expressed in relation to glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mRNA levels.Human airway smooth muscle cellsin vitroexpressed NGF constitutively (21.4±7.8 pg·mL−1; 14.6±5.4 pg NGF complementary deoxyribonucleic acid (cDNA)·pg GAPDH cDNA−1(mean±sem)). Stimulation with IL–1β (0.1–30 U·mL−1) for 24 h induced a dose-dependent increase in NGF production (22.1 pg·mL−1at 10 U·mL−1; p<0.05). The IL-1β (10 U·mL−1)-induced increase in NGF expression was time-dependent. It was highest for NGF protein at 10 h (1.6-fold increase over control; p<0.001) and for NGF mRNA at 2.5 h (2.4-fold increase over control; p<0.05).In conclusion, the present study clearly shows that the human airway smooth muscle cell is a source of nerve growth factor, the expression of which is upregulated in inflammatory conditions, mimickedin vitroby the addition of interleukin-1β.
Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: anin vitrostudy
Authors: Peinado V.I. , Santos S. , Ramírez J. , Roca J. , Rodriguez-Roisin R. , Barberà J.A. 
Published: October 2002

Patients with chronic obstructive pulmonary disease (COPD) show impaired hypoxic pulmonary vasoconstriction that might contribute to abnormal gas exchange and could be related to endothelial dysfunction in pulmonary arteries. The aim of the study was to investigate the response of PA to hypoxic stimulusin vitroin COPD, and the role of endothelium-derived nitric oxide (NO) in this response.The pulmonary arteries of 25 patients who underwent lung resection were studied. Patients were divided into controls, COPD+normoxaemia (COPDN) and COPD+hypoxaemia (COPDH). Hypoxic vasoconstriction (HV) was evaluated before and after stimulation or inhibition of the endothelial release of NO, and in the presence of exogenous NO.Compared with the other groups, HV was reduced in COPDH. The magnitude of HV correlated with the oxygen tension in arterial blood. The hypoxic stimulus induced greater contraction after stimulating endothelial release of NO, whereas its inhibition practically abolished HV. Exogenous NO completely inhibited HV. Maximal relaxation induced by endothelium-dependent vasodilators correlated with the magnitude of HV.In conclusion, pulmonary arteries of patients with chronic obstructive pulmonary disease and hypoxaemia have an impaired response to hypoxic stimulus, and the endothelial release of nitric oxide modulates hypoxic vasoconstriction. The depressed response of pulmonary arteries to hypoxia may contribute to abnormal gas exchange in chronic obstructive pulmonary disease.