bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of formoterol Turbuhaler® at cumulative dose of 90 µg in patients with acute bronchial obstruction
Authors: Malolepszy J. , Böszörményi Nagy G. , Selroos O. , Larsson P. , Brander R. 
Published: July 2002

This study compared the safety of formoterol (Oxis® Turbuhaler®; 90 µg delivered dose; 120 µg metered dose) with terbutaline (Bricanyl® Turbuhaler®; 10 mg), in patients with acute bronchoconstriction.Forty-eight patients (31 females) with a mean age of 45 yrs, were randomized into two parallel groups (double-blind design). Mean baseline forced expiratory volume in one second (FEV1) was 0.98 L (33% of predicted normal). Study drugs were administered on six occasions during 3 h (formoterol 4.5 µg or terbutaline 0.5 mg·inhalation−1, 20 inhalations). Patients received intravenous prednisolone after 1.5 h and oxygen during the first 3 h. Pulse rate, serum potassium, 12-lead electrocardiogram (ECG), Holter ECG, arterial blood gases and FEV1were assessed during 12 h after the first dose.Four patients (one formoterol, three terbutaline) discontinued. The 12-h mean values of serum potassium decreased from 4.02 to 3.89 mmol·L−1for formoterol and from 4.22 to 3.76 mmol·L−1for terbutaline. Mean 12-h pulse rate was significantly (p<0.01) higher in the terbutaline group (101.7 beats per minute (bpm)) than in the formoterol group (93.5 bpm). No individual patient value was considered clinically important or alarming. FEV1improved in both groups but with no statistically significant difference between treatments.Oxis® Turbuhaler® (90 µg) was at least as safe and well tolerated as terbutaline (110 mg) in patients with acute bronchoconstriction.
Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases
Authors: Wennergren G. , Kristjánsson S. 
Published: July 2002

Evidence from a large number of prospective case-control studies shows that respiratory syncytial virus (RSV) bronchiolitis in infancy is often associated with recurrent wheezing and asthma during subsequent years. However, wheezing tends to diminish and most studies show no significant increase in wheezing compared to controls by school age or adolescence. An unresolved question is whether severe RSV infection during infancy causes the respiratory sequelae or inherent abnormalities predispose an infant to develop severe respiratory infection and sequelae,i.e.RSV is associated with the development of pulmonary sequelae.Studies on long-term outcome of RSV bronchiolitis are reviewed from an evidence-based perspective.The majority of prospective placebo-controlled studies do not show any long-term beneficial effects of corticosteroid treatment,i.e.the risk of subsequent wheezing is not diminished by the treatment. The evidence for an increased risk of allergic sensitization after RSV bronchiolitis is not nearly as strong as the evidence for an increased risk of subsequent wheezing. In fact, most studies do not show any significant increase in atopy after RSV bronchiolitis. This suggests that the increased risk of wheezing after RSV is not linked to an increased risk of atopy. There are some indications that infants who develop severe RSV and subsequent wheezing may have aberrations that predate the RSV infection.To decide whether respiratory syncytial virus bronchiolitis causes, or is associated with the respiratory sequelae (or with subsequent allergy), it will be necessary to conduct prospective, randomized studies, where the cytokine profile prior to bronchiolitis onset is known. Such studies should preferably include some form of intervention against respiratory syncytial virus. A more complete understanding of the risk factors for severe respiratory syncytial virus infection and the role of respiratory syncytial virus infection in the initiation of asthma is needed as a basis for large-scale and cost-effective programmes to prevent respiratory syncytial virus-related morbidity.
Ultrasonicversusjet nebulization of iloprost in severe pulmonary hypertension
Authors: Gessler T. , Schmehl T. , Hoeper M.M. , Rose F. , Ghofrani H.A. , Olschewski H. , Grimminger F. , Seeger W. 
Published: July 2002

Inhalation of iloprost, a stable prostacyclin analogue, is a promising perspective in the treatment of pulmonary hypertension. In initial clinical studies, a conventional jet nebulizer system was successfully used to decrease pulmonary vascular resistance and pressure, requiring however, up to twelve inhalations of 12–15 min per day. The aim of this study was to investigate if the application of an equal dose of iloprost at a drastically reduced duration of inhalation with the use of a more efficient ultrasonic nebulizer, leads to comparable haemodynamic effects, without escalation of side effects.The physical features of the jet nebulizer system (Ilo-NebTM) and the ultrasonic nebulizer (Multisonic CompactTM) were characterized by laser diffractometry and a Tc99m-tracer technique. Mass median aerodynamic diameters were 3.2 µm for the jet and 3.9 µm for the ultrasonic nebulizer. Total output (mean±sd) was 60±7 µL·min−1(jet) and 163±15 µL·min−1(ultrasonic), and efficiency of the devices was 39±3% (jet) and 86±5% (ultrasonic). Based on these data, a total inhalative dose of 2.8 µg iloprost was delivered by jet nebulization within 12 min and by ultrasonic nebulization within 4 min, in 18 patients with severe primary and secondary pulmonary hypertension (New York Heart Association class III and IV), in a randomized crossover design. Haemodynamics were assessed by right heart catheterization.Inhalation with the ultrasonic device and jet nebulizer, reduced mean±sem pulmonary artery pressure from 54.3±2.1 to 47.1±2.0 and from 53.5±2.2 to 47.0±2.2 mmHg, respectively, and mean±sem pulmonary vascular resistance from 1073±109 to 804±87 and from 1069±125 to 810±83 dyn·s·cm−5, respectively. Both modes of aerosolization were well tolerated.In conclusion, due to the markedly higher efficiency and output of the ultrasonic device, wastage of drug is largely avoided and the duration of inhalation can be shortened to one-third, with comparable haemodynamic effects and without enforcing side effects.
Reappraisal of the aetiology and prognostic factors of severe acute respiratory failure in HIV patients
Authors: Alves C. , Nicolás J.M. , Miró J.M. , Torres A. , Agustì C. , Gonzalez J. , Rañó A. , Benito N. , Moreno A. , Garcìa F. , Millá J. , Gatell J.M. 
Published: July 2002

The introduction of highly active antiretroviral therapy with protease inhibitors in 1996 has changed the morbidity and mortality of acquired immune deficiency syndrome patients. Therefore, the aetiologies and prognostic factors of human immunodeficiency virus (HIV)-infected patients with life-threatening respiratory failure requiring intensive care unit (ICU) admission need to be reassessed.From 1993 to 1998, we prospectively evaluated 57 HIV patients (mean±sem age 36.5±1.3 yrs) admitted to the ICU showing pulmonary infiltrates and acute respiratory failure.A total of 21 and 30 patients were diagnosed as havingPneumocystis cariniiand bacterial pneumonia, respectively, of whom 13 and eight died during their ICU stay (p=0.01). Both groups of patients had similar age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and severity in respiratory failure. The number of cases with bacterial pneumonia admitted to ICU decreased after 1996 (p=0.05). Logistic regression analysis showed that (APACHE) II score >17, serum albumin level <25 g·L−1, and diagnosis ofP. cariniipneumonia were the only factors at entry associated with ICU mortality (p=0.02).Patients with bacterial pneumonia are less frequently admitted to the intensive care unit after the introduction of highly active antiretroviral therapy with protease inhibitors in 1996. Compared to the previous series, it was observed that the fewPneumocystis cariniipneumonia patients that need intensive care still have a bad prognosis.
In defence of the carbon monoxide transfer coefficientKCO(TL/VA)
Authors: Hughes J.M.B. , Pride N.B. 
Published: July 2002

The carbon monoxide transfer factor (TL,CO) is the product of the two primary measurements during breath-holding, the CO transfer coefficient (KCO) and the alveolar volume (VA).KCOis essentially the rate constant for alveolar CO uptake (Krogh'skCO), and in healthy subjects, increases whenVAis reduced by submaximal inflation, or when pulmonary blood flow increases. Recently, new reference values were proposed for clinical use which included the observedVAat full inflation; this was claimed to “eliminate the need forKCO”.In this commentary, some mechanismse.g.respiratory muscle weakness, lung resection, diffuse alveolar damage and airflow obstruction, which decrease or increase total lung capacity (TLC) are reviewed.Even when alveolar structure and function are normal, the change inKCOat a givenVAvaries according to the underlying pathophysiological mechanism. The advantages and disadvantages of normalizingKCOandTL,COto predisease predicted TLC or to the patient's actualVA(using lack of expansion or loss of alveolar units models) are considered.Examination of carbon monoxide transfer coefficient and alveolar volume separately provides information on disease pathophysiology which cannot be obtained from their product, the carbon monoxide transfer factor.
Clinical diagnosis of current asthma: predictive value of respiratory symptoms in the SAPALDIA study
Authors: Sistek D. , Tschopp J-M. , Schindler C. , Brutsche M. , Ackermann-Liebrich U. , Perruchoud A-P. , Leuenberger P. ,   SAPALDIA team
Published: July 2002

Bronchial asthma is a very common disease which often remains underdiagnosed. The aim of this study was to determine the predictive value of the most common respiratory symptoms and to explore the best symptom combinations to predict diagnosis of asthma.A questionnaire comprising common respiratory symptoms was submitted to 9,651 subjects aged 18–60 yrs, randomly selected from the Swiss population, of whom 225 subjects (2.3%) had current asthma as confirmed by their general practitioner. Based on these data the authors calculated the predictive values of single symptoms and symptom combinations to diagnose asthma.Wheezing was the most sensitive single symptom (sensitivity 75%). Simple symptoms such as wheezing with dyspnoea, chronic phlegm or chronic cough had specificity greater than 95%. Wheezing with dyspnoea (WD) or nocturnal dyspnoea (ND) had the best positive predictive value (PPV) as isolated symptoms (24% and 21%, respectively). When combining symptoms, wheezing associated with daily dyspnoea at rest or nocturnal dyspnoea showed the best PPV (42% and 39%, respectively), almost double single symptoms such as WD or ND. Wheezing associated with at least two of the three nocturnal symptoms (nocturnal dyspnoea, nocturnal cough or nocturnal chest tightness) had a sensitivity of 80% to diagnose asthma.In conclusion, respiratory symptoms obtained by medical history are reliable predictors of asthma. The findings suggest that particular combinations of symptoms are clinically useful in the differential diagnosis of asthma.
Improved delivery of fenoterol plus ipratropium bromide using Respimat® compared with a conventional metered dose inhaler
Authors: Goldberg J. , Freund E. , Beckers B. , Hinzmann R. 
Published: July 2002

Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) deliveredviaRespimat®, a soft mist inhaler, and to establish the Respimat® dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 µg) which is deliveredviaa conventional metered dose inhaler (MDI).In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 µg deliveredviaRespimat®; F/I 50/20 or 100/40 µg deliveredviaMDI.Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1than placebo. A log-linear dose-response was obtained for the average increase in FEV1up to 6 h (AUC0–6 h) and peak FEV1across the dose range administered by Respimat®. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat® compared with the MDI. However 12.5/5 and 25/10 µg F/I administeredviaRespimat® were closest (slightly superior) to the F/I dose of 100/40 µg deliveredviaMDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat® compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events.In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromideviaRespimat®, is as effective and as safe as higher doses givenviaa metered dose inhaler.
Mycoplasma pneumoniaeandChlamydia pneumoniaeinfections in children with pneumonia
Authors: Esposito S. , Blasi F. , Bellini F. , Allegra L. , Principi N. 
Published: July 2002

The most common clinical signs, host responses and radiographic patterns were studied in 203 Italian children hospitalized for community-acquired pneumonia in order to clarify the role of clinical and radiological characteristics in the diagnosis ofMycoplasma pneumoniaeand/orChlamydia pneumoniaeinfections.Antibody measurements in paired sera and polymerase chain reaction on nasopharyngeal aspirates were used to establish the diagnoses of acuteM. pneumoniaeandC. pneumoniaeinfection, and the aetiologic data were correlated with the clinical, laboratory and radiographic data obtained on admission.No significant association was observed between evidence ofM. pneumoniaeand/orC. pneumoniaeinfection and periods of episode during the year, mean age of the study subjects, individual symptoms, physical findings or laboratory test results. Furthermore, no significant correlation was observed in relation to the radiological findings andM. pneumoniaeand/orC. pneumoniaeinfection.This study shows that neither clinical findings nor laboratory parameters distinguishedMycoplasma pneumoniaeand/orChlamydia pneumoniaeinfection in children with pneumonia. Radiological findings also have a limited capacity to differentiate aetiologic agents. The priorities for future research include the development of rapid, easily accessible and cost-effective diagnostic tests useful for each episode of pneumonia in children.
Parents' quality of life and respiratory symptoms in young children with mild wheeze
Authors: Osman L.M. , Baxter-Jones A.D.G. , Helms P.J. 
Published: July 2002

The Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), measures the impact of child asthma symptoms on family activity (CGAct) and parental anxiety (CGEmot). It has not been validated for families of children <7 yrs, with wheezing illness. This study assessed the sensitivity of the PACQLQ to symptom change in 62 preschool children with wheezing illness. The median age of children was 3 yrs (range 0.8–6 yrs). At entry and 3-month follow-up, parents recorded child respiratory symptoms in a 1-month diary and completed the PACQLQ. On average, children in the study had 7 symptomatic days per month.On entry, mothers ≤30 yrs had worse scores than those >30 (p<0.02), and mothers in less affluent socioeconomic groups had worse scores than those in higher groups (p=0.05). Change in symptom scores and symptom free days between entry and follow-up was associated with change in PACQLQ scores (r=0.54–0.57, p<0.001). Thirty-three parents had absolute change in PACQLQ of <0.5 over three months (which has been previously defined as not being clinically significant). Compared to parents with higher PACQLQ change, parents with PACQLQ scores <0.5, did not differ in frequency of child symptoms or in social-demographic factors, but had better quality of life scores on entry to the study (p<0.01).It is concluded that the Paediatric Asthma Caregiver's Quality of Life Questionnaire is sensitive to group measures of child symptom change over 3 months, among preschool children, and this supports its use as an outcome measure in clinical trials. The absolute impact of child symptoms on parent quality of life varies among parents.
Audit of acute admissions of COPD: standards of care and management in the hospital setting
Authors: Roberts C.M. , Ryland I. , Lowe D. , Kelly Y. , Bucknall C.E. , Pearson M.G. 
Published: July 2002

Despite publication of several management guidelines for COPD, relatively little is known about standards of care in clinical practice.Data were collected on the management of 1400 cases of acute admission with Chronic Obstructive Pulmonary Disease in 38 UK hospitals to compare clinical practice against the recommended British Thoracic Society standards. Variation in the process of care between the different centres was analysed and a comparison of the management by respiratory specialists and nonrespiratory specialists made.There were large variations between centres for many of the variables studied. A forced expiratory volume in one second measurement was found in only 53% of cases. Of the investigations recommended in the acute management arterial blood gases were performed in 79% (interhospital range 40–100%) of admissions and oxygen was formally prescribed in only 64% (range 9–94%). Of those cases with acidosis and hypercapnia 35% had no further blood gas analysis and only 13% received ventilatory support. Long-term management was also deficient with 246 cases known to be severely hypoxic on admission yet two-thirds had no confirmation that oxygen levels had returned to levels above the requirements for long-term oxygen therapy. Only 30% of current smokers had cessation advice documented.To conclude, the median standards of care observed fell below those recommended by the guidelines. The lowest levels of performance were for patients not under the respiratory specialists, but specialists also have room for improvement. The substantial variation in the process of care between hospitals is strong evidence that it is possible for other centres with poorer performance to improve their levels of care.
Proportional positive airway pressure: a new concept to treat obstructive sleep apnoea
Authors: Juhász J. , Becker H. , Cassel W. , Rostig S. , Peter J‐H. 
Published: July 2002

Proportional positive airway pressure (PPAP) was designed to optimize airway pressure for the therapy of obstructive sleep apnoea (OSA). In a randomized crossover prospective study, the clinical feasibility of PPAP and its immediate effects on the breathing disorder and sleep in comparison with continuous positive airway pressure (CPAP) was evaluated. Twelve patients requiring CPAP therapy underwent CPAP and PPAP titration in a random order.Obstructive and mixed respiratory events could be completely abolished with both forms of treatment. This efficacy could be achieved at a significantly lower mean mask pressure during PPAP titration (8.45±2.42 cmH2O) compared to CPAP (9.96±2.7 cmH2O) (p=0.002). The mean minimal arterial oxygen saturation (Sa,O2) (82.8±6.5%) on the diagnostic night increased significantly (p<0.001) to an averageSa,O2of 93.35±1.71% and 93.19±2.9% during CPAP and PPAP titration. Total sleep time, slow wave sleep and rapid eye movement (REM) sleep increased significantly by the same amount during both CPAP and PPAP titration (p<0.001), while sleep stage nonrapid eye movement (NREM) 1 and 2 decreased. Six patients preferred the PPAP titration night, four patients did not have a preference, and two patients preferred CPAP.The present data show that proportional positive airway pressure is as effective as continuous positive airway pressure in eliminating obstructive events and has the same immediate effect on sleep. The lower average mask pressure during proportional positive airway pressure implies potential advantages compared to continuous positive airway pressure. Proportional positive airway pressure presents a new effective therapeutic approach to obstructive sleep apnoea.
Genetic deficiency of α1‐PI in mice influences lung responses to bleomycin
Authors: Cavarra E. , Martorana P.A. , Bartalesi B. , Fineschi S. , Gambelli F. , Lucattelli M. , Ortiz L. , Lungarella G. 
Published: July 2002

It has recently been suggested that proteinase inhibitors modulate the fibrotic response in the lung. This study investigated the development of bleomycin-induced pulmonary changes in pallid mice, deficient in serum α1‐proteinase inhibitor, and with a lower elastase inhibitory capacity, and in congenic C57Bl/6J mice.Male pallid and C57Bl/6J mice received a single intratracheal instillation of either saline or bleomycin. The investigation was carried out by means of biochemical, morphological and morphometrical methods.In both strains, 21 and 72 h after bleomycin, the lungs showed foci of inflammatory cell infiltration associated with emphysema. Fibrosis developed with time after bleomycin. At 14 days fibrosis affected 23.46±9.48% (mean± sd) and 40.62±13.34% (p<0.01) of the lungs of C57Bl/6J and pallid mice, respectively. Emphysema affected 3.68±3.11% and 12.57±4.13% (p<0.01) of lung in C57Bl/6J and pallid mice, respectively. In C57Bl/6J mice bleomycin increased lung hydroxyproline content by 34% and desmosine content by 44% (p<0.01 for both). In pallid mice these increases were only 21% (p<0.01) and 6%, which may reflect parenchymal loss.Thus, the lung destructive response (emphysema) and the subsequent proliferative reaction (fibrosis) to bleomycin are potentiated in α1‐proteinase inhibitor deficiency.
New anti-asthma therapies: suppression of the effect of interleukin (IL)‐4 and IL‐5
Authors: Kips J.C. , Tournoy K.G. , Pauwels R.A. 
Published: July 2002

Asthma is currently defined as a chronic inflammatory disorder of the airways. The central role of allergen-specific Th2 cells in the regulation of this mucosal airway inflammation has been highlighted. Hence, there is large interest in the therapeutic potential of an anti-Th2 cell approach. One of the strategies which has been developed, is to inhibit the effect of interleukin (IL)‐4 or IL‐5, two main Th2 cell derived cytokines.Interleukin‐4 is pivotal in the pathogenesis of allergic disorders through its wide range of effects. An important observation, especially during secondary antigen exposure, is the possible redundancy with IL‐13. Both cytokines share common elements in their receptor and intracellular signalling pathway. As a result, compounds can be developed that selectively inhibit the effect of either IL‐4 or IL‐13, or alternatively, by interfering with the common pathway, inhibit the effect of both cytokines.Eosinophils are generally seen as a particularly harmful element in the allergic inflammation. The importance of IL‐5 on eosinophil biology has clearly been established. Conversely, in man, the biological effects of IL‐5 are largely limited to eosinophil function. Therefore, IL‐5 antagonists offer the unique opportunity of selectively neutralizing the effect of eosinophils.Several strategies have now been developed that successfully inhibit the biological effect of interleukin‐4 or interleukin‐5. Some of these compounds have proven to be biologically active in man. The challenge now is to establish their therapeutic role in asthma.