bluuebunny/crossref_metadata_2025 huggingface dataset:
Markers of airway inflammation and airway hyperresponsiveness in patients with well-controlled asthma
Authors: Leuppi J.D. , Salome C.M. , Jenkins C.R. , Koskela H. , Brannan J.D. , Anderson S.D. , Andersson M. , Chan H.K. , Woolcock A.J.
Published: July 2002

In steroid-naïve asthmatics, airway hyperresponsiveness correlates with noninvasive markers of airway inflammation. Whether this is also true in steroid-treated asthmatics, is unknown.

In 31 stable asthmatics (mean age 45.4 yrs, range 22–69; 17 females) taking a median dose of 1,000 µg inhaled corticosteroids (ICS) per day (range 100–3,600 µg·day−1), airway responsiveness to the “direct” agent histamine and to the “indirect” agent mannitol, lung function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory cells in induced sputum as a percentage of total cell count were measured.

Of the 31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose-response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol were not related to basic lung function, eNO, per cent sputum eosinophils and ICS dose. In addition, NO was not related to basic lung function and per cent sputum eosinophils.

In clinically well-controlled asthmatics taking inhaled corticosteroids, there is no relationship between markers of airway inflammation (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness to either direct (histamine) or indirect (mannitol) challenge. Airway hyperresponsiveness in clinically well-controlled asthmatics appears to be independent of eosinophilic airway inflammation.
Bronchodilator responsiveness and atopy in 5–10-yr-old coughers
Authors: McKenzie S.A. , Mylonopoulou M. , Bridge P.D.
Published: July 2002

Cough-variant asthma is considered by some to be an asthma phenotype. Bronchodilator responsiveness (BDR) is an undisputed feature of asthma. Of school-aged wheezers, 90% are atopic. Are school-aged coughers who demonstrate BDR also atopic? If so, then it would be reasonable to reserve the diagnosis cough-variant asthma for this particular group.

Airway resistance was measured by the interrupter technique (Rint) before and after salbutamol in controls (n=73), coughers (n=63) and previous wheezers (n=63) aged 5–10 yrs. Immunoglobulin (Ig)-E was measured in coughers and wheezers. BDR was expressed as the ratio baseline:post-salbutamolRint.

Groups were of similar age (mean 6.7, range 5–9.9 yrs). Geometric mean baselineRintwas similar in controls and coughers (0.66 and 0.68 kPa·L−1·s), but the baselineRintfor wheezers (0.73 kPa·L−1·s) was greater than that for controls (p=0.05) but not significantly different from coughers (p=0.17). Geometric mean BDR in coughers was 1.22, controls 1.13 and wheezers 1.30 (p=0.01 for coughers and controls; p=0.08 for coughers and wheezers; p<0.001 for controls and wheezers). IgE was lower in coughers than wheezers (geometric means 36 and 364 International Units (IU)·L−1, p<0.001) and was unrelated to BDR in both groups.

In summary, atopy, and not bronchodilator responsiveness, distinguishes groups of coughers from groups of wheezers. A diagnosis of cough-variant asthma cannot be reserved for even those school-aged coughers, who demonstrate bronchodilator responsiveness.
Forced oscillation measurements do not affect upper airway muscle tone or sleep in clinical studies
Authors: Badia J.R. , Farré R. , Rigau J. , Uribe M.E. , Navajas D. , Montserrat J.M.
Published: July 2002

Upper airway obstruction in the sleep apnoea/hypopnoea syndrome (SAHS) can be easily assessed by measuring respiratory impedance with the forced oscillation technique (FOT). This methodology has been proposed as a useful clinical tool both for the diagnosis of sleep breathing disorders and for continuous positive airway pressure (CPAP) titration. However, previous studies suggest that the application of high-frequency pressure oscillation to the upper airway may induce changes in the electroencephalogram (EEG) or upper airway muscle function. The effect of FOT measurements on upper airway muscle tone and EEG in clinical sleep studies was examined. Seven patients with moderate SAHS were included (age: 54±11 yrs; apnoea/hypopnoea index: 43±21 events·h−1; body mass index: 30±2 kg·m−2). Genioglossus surface electromyogram activity (EMGgg) and EEG signal were analysed with and without FOT application (frequency: 5 Hz and 30 Hz; peak-to-peak pressure oscillation: 1 cmH2O) during stable sleep. Measurements were carried out in two different situations. Step 1: applying FOT during episodes of obstructive events or flow limitation; and step 2: during prolonged periods of normal breathing at optimal CPAP. The root mean square of EMGgg activity and fast Fourier analysis (alpha and delta bands) of the EEG signal were performed.

The application of FOT did not increase EMGgg activity in any of the situations studied. In addition, no evidence of the effects on EEG was found: alpha/delta relationship: awake:0.70, baseline sleep:0.13, FOT(5 Hz):0.18, FOT(30 Hz):0.11.

The presented results suggest that the use of forced oscillation technique over the ranges of frequency and amplitude proposed for clinical sleep studies does not induce changes in upper airway muscle activity and neurological variables in patients with sleep apnoea/hypopnoea syndrome.
l-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophagesin vitro
Authors: Muijsers R.B.R. , ten Hacken N.H.T. , Van Ark I. , Folkerts G. , Nijkamp F.P. , Postma D.S.
Published: July 2002

Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO)in vitrodespite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesisin vitrois due to limited availability of the NOS substrate l-;arginine, and putative NOS inhibiting factors present in foetal serum preparations, both alveolar macrophages (AM) and monocyte derived macrophages (MDM) were incubated in various circumstances.

Nitrite production measured using stimulated AM was typically <5 pmol·min−1·10−6cells. A range of stimuli were tested, but without result. Furthermore, incubation of MDMs with normal human serum or purified bovine serum albumin instead of foetal calf serum failed to enhance NO production. Moreover, neither the use of arginase inhibitors nor the addition of surplus l-;arginine resulted in an increased NO synthesis. Interestingly, addition of the NOS intermediateNω-;hydroxy-;l-;arginine (100 µM) to AM led to nitrite release, which was unaffected by the NOS inhibitor amino guanidine showing that this effect is NOS independent.

It is concluded that the limited nitric oxide production of human macrophagesin vitrocan neither be explained by limited availability of l-;arginine, nor by nitric oxide synthase inhibiting substances in foetal serum. Furthermore, it is shown that nitrite release fromNω-;hydroxy-;l-;arginine by alveolar macrophages is nitric oxide synthase independent.
Forced expiratory manoeuvres in children: do they meet ATS and ERS criteria for spirometry?
Authors: Arets H.G.M. , Brackel H.J.L. , van der Ent C.K.
Published: July 2002

The aim of this study was to evaluate the applicability of American Thoracic Society and European Respiratory Society criteria for spirometry in children.

Maximal expiratory flow/volume (MEFV) measurements from 446 school-age children, experienced in performing MEFV manoeuvres, were studied and acceptability (start-of-test (backward extrapolated volume as a percentage of forced vital capacity (FVC) (Vbe%FVC) or as an absolute value (Vbe), end-of-test (forced expiratory time (FET)) and reproducibility criteria (absolute and percentage difference between best and second-best FVC and forced expiratory volume in one second (FEV1) (ΔFVC, ΔFVC %, ΔFEV1and ΔFEV1%)) were applied to these manoeuvres.

TheVbe%FVC criterion was met by 91.5%, theVbe<0.15 L criterion by 94.8% and theVbe<0.10 L by 60.1% of children.Vbe<0.15 L appeared to be a more useful parameter thanVbe%FVC. The FET criterion was met by only 15.3% of children. ΔFVC <0.2 L and ΔFEV1<0.2 L were met by 97.1% and 98.4%, and ΔFVC <0.1 L and ΔFEV1<0.1 L by 79.8% and 84.3% of the children, respectively. These criteria appeared to be less useful compared to percentage criteria (ΔFVC % and ΔFEV1%). Even experienced children did not meet all international criteria for spirometry. However, most of their MEFV curves are useful for interpretation.

Based on the performance of these children, a re-evaluation of criteria for maximal expiratory flow/volume measurements in children is proposed.
A case-control study of lifestyle risk factors associated with tuberculosis in Liverpool, North-West England
Authors: Tocque K. , Bellis M.A. , Beeching N.J. , Syed Q. , Remmington T. , Davies P.D.O.
Published: July 2002

The aim of this study was to identify the subtle influences of exposure and individual lifestyles on the risk of developing tuberculosis.

A retrospective case-control study (with matching by sex, age, postcode and ethnicity) of all tuberculosis cases notified over a 7-yr period in Liverpool, UK, was carried out.

Multiple logistic regression showed that, before diagnosis, cases were 7.4 times more likely to have had visitors from abroad; 4.0 times more likely to have been born abroad; and 3.8 times more likely to have lived with someone with tuberculosis. Subtle socioeconomic factors were also evident with cases 4.0 times less likely to have additional bathrooms. Lifestyle factors emerged with cases 2.3 times more likely to have smoked for at least 30 yrs, 3.8 times less likely to eat dairy products every week and 2.6 times less likely to have had high blood pressure. At interview, these factors were still evident, but cases, unlike controls, had reduced their smoking and alcohol consumption and were less likely to go out of the home or exercise than before their illness.

Within individuals, lifestyle consequences of tuberculosis lead to a “healthier” lifestyle on the one hand (less smoking and alcohol consumption), but a reduced quality of life (social activity) on the other.
Evaluation of the interrupter technique in healthy, unsedated infants
Authors: Hall G.L. , Wildhaber J.H. , Cernelc M. , Frey U.
Published: July 2002

The interrupter technique may be used to monitor respiratory resistance and does not require active patient cooperation, but has yet to be applied in unsedated, spontaneously breathing infants. The aim of this study was to determine if the interrupter technique is feasible in spontaneously breathing infants and to investigate the influence of facemask types and analysis techniques on the interrupter resistance (Rint).

Rintwas measured in 14 healthy, unsedated, sleeping infants (aged 38.4 (31–56) days (mean (range)). Paired measurements were made using large volume, compliant (Mcomp) and small volume, rigid (Mrigid) facemasks. Flow and pressure were measured at the airway opening prior to- and following a brief airway occlusion (500 ms).Rintwas calculated using four previously reported analysis techniques.

Rintcould be measured in all infants. Mcomp, independent of the analysis method significantly underestimatedRint(p<0.001). The variability and magnitude ofRintwere significantly influenced by the choice of analysis method.

The conclusion is that the interrupter technique is feasible in spontaneously breathing, unsedated infants. Equipment design and analysis method significantly influences interrupter resistance. Studies standardizing equipment and identifying the most appropriate analysis technique in this age group are needed.
Diagnostic strategies for suspected pulmonary embolism
Authors: Donkers-van Rossum A.B.
Published: July 2002

Pulmonary embolism often remains a difficult diagnosis for the clinician, particularly in patients with comorbidity factors. This is in contrast with the availability of effective treatment, which should be prescribed as soon as possible.

To date, there is still no ideal diagnostic test that is accurate, safe, readily available and cost-effective.

Recent technical advances in computed tomography, magnetic resonance imaging and laboratory findings have raised new possibilities in the diagnosis of pulmonary embolism.

This review covers the performance of different diagnostic tests, and focuses on the advantages and limitations of single diagnostic tests and the clinical usefulness of these tests in diagnostic strategies.
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.
Imaging guided thoracic interventions
Authors: Ghaye B. , Dondelinger R.F.
Published: July 2002

Interventional Radiology is a technique based medical specialty, using all available imaging modalities (fluoroscopy, ultrasound, computed tomography, magnetic resonance, angiography) for guidance of interventional techniques for diagnostic or therapeutic purposes.

Actual, percutaneous transthoracic needle biopsy includes core needle biopsy besides fine needle aspiration. Any pleural, pulmonary or mediastinal fluid or gas collection is amenable to percutaneous pulmonary catheter drainage.

Treatment of haemoptysis of the bronchial artery or pulmonary artery origin, transcatheter embolization of pulmonary arteriovenous malformations and pseudoaneurysms, angioplasty and stenting of the superior vena caval system and percutaneous foreign body retrieval are well established routine procedures, precluding unnecessary surgery. These techniques are safe and effective in experienced hands.

Computed tomography is helpful in pre- and postoperative imaging of patients being considered for endobronchial stenting. Many procedures can be performed on an outpatient basis, thus increasing the cost-effectiveness of radiologically guided interventions in the thorax.
M. tuberculosis: immunology and vaccination
Authors: Rook G.A.W. , Seah G. , Ustianowski A.
Published: July 2002

Tuberculosis is increasing. Current treatment regimens require at least 6 months, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and “directly observed therapy short course” (DOTS) is having less impact than expected. This worrying situation is aggravated by coinfection with human immunodeficiency virus (HIV), and by the increase in drug-resistant strains.

We need new insights that lead to more rapid therapies and immunotherapies, and more reliable vaccines.

Recent insights have come from: understanding of the relationship betweenMycobacterium tuberculosisand macrophages; the multiple T cell types that recognise mycobacterial peptides, lipids and glycolipids; the critical role of interferon‐γ (IFNγ) and interleukin‐12 (IL‐12) in human mycobacterial infection revealed by genetically defective children; quantitation of the presence and importance of Th2 lymphocyte activation in human tuberculosis; the role of local conversion of inactive cortisone to active cortisol in the lesions; the recognition that some effective prophylactic vaccines also work as immumotherapeutics whereas others do not. In the longer term the recent sequencing of theM. tuberculosisgenome will lead to further advances.

In the short term, effective immunotherapy remains the most accessible breakthrough in the management of tuberculosis. The types of practical advance that will result from sequencing the genome are discussed speculatively, but cannot yet be predicted with certainty.
X‐linked agammaglobulinaemia and squamous lung cancer
Authors: Echave-Sustaeta J.M. , Villena V. , Verdugo M. , López-Encuentra A. , de Agustín P. , Alberti N.
Published: July 2002

A 32 yr-old nonsmoking male, diagnosed as having X‐linked agammaglobulinemia, presented with fever, cough with purulent sputum, a very intense back pain and a mass of 10 centimetres in lower left lobe. Diagnostic evaluation revealed a squamous cell carcinoma with very aggressive metastases at L3. Malignancies are the second leading cause of death in children and adults with congenital immunodeficiency disorders, mostly non-Hodgkin lymphomas and gastric and colon adenocarcinomas, but this is the first report of lung cancer in a patient with X‐linked agammaglobulinemia. Lung cancer incidence has been reported to be higher in patients with other diseases of the lung, however, there is no clear evidence of the role of bronchiectasis in developing lung cancer. It is possible that a longer survival for patients with X‐LA recently diagnosed, and an association of chronic bronchial infection, could favour the development of pulmonary neoplasm.
Magnetic resonance analysis of abnormal diaphragmatic motion in patients with emphysema
Authors: Iwasawa T. , Kagei S. , Gotoh T. , Yoshiike Y. , Matsushita K. , Kurihara H. , Saito K. , Matsubara S.
Published: July 2002

The purpose of this study was to quantitatively evaluate paradoxical diaphragmatic motion using magnetic resonance (MR) imaging.

A total of 27 subjects were examined, including 12 normal young adults, six control individuals, and nine patients with emphysema. With subjects in the supine position, 30 sequential sagittal MR images of the entire right lung were obtained during tidal and deep slow breathing.

Diaphragmatic movement between sequential images was estimated as the displacement area and the total diaphragmatic movement in a respiratory cycle was calculated. The paradoxical motion of the diaphragm, representing the inverted movement to increase or decrease lung area, since paradoxical movement ratio (Mpr=(total paradoxical diaphragmatic movement/total diaphragmatic movement)×100), was evaluated.

In patients with emphysema, paradoxical diaphragmatic motion was observed on MR images during deep breathing. The mean Mprin emphysematous patients during deep breathing was 10±4%, which was significantly higher than 0.5±0.2% in young adults (p<0.05), and 1.2±0.6% in aged-matched controls (p<0.05).

The present results indicate that magnetic resonance images could be used to detect paradoxical diaphragmatic motion in patients with emphysema.
Associations between markers of respiratory morbidity in European children
Authors: Timonen K.L. , Schwartz J. , Nielsen J. , Brunekreef B.
Published: July 2002

School-aged children often experience acute respiratory symptoms. In a multicentre European study, the association between chronic respiratory symptoms (reported in a questionnaire), skin-prick test results, and lung function, and the occurrence of acute respiratory morbidity, was examined among children aged 6–12 yrs with chronic respiratory symptoms.

Children with chronic respiratory symptoms, living in 10 European countries, were selected from a parent-completed questionnaire (n=4,307). Atopy was measured with skin-prick tests, and lung function with spirometry. A total of 1,854 (86% of those in the initial cohort) children kept a successful daily diary regarding their respiratory symptoms for 2–3 months.

In multivariate logistic regression analyses, children with asthmatic symptoms, particularly those with doctor-diagnosed asthma, had a greater risk of occurrence of lower respiratory symptoms (odds ratio (OR): 6.12; 95% confidence interval (CI): 4.99–8.35) than children with a dry nocturnal cough as their only symptom. Atopy, particularly a positive reaction to indoor allergens, was significantly associated with occurrence of lower respiratory symptoms. For atopy the OR was 1.62 (95% CI: 1.34–1.96). A reduced level of maximal mid-expiratory flow was associated with an increased risk of lower respiratory symptoms, cough and phlegm. The associations were similar in Scandinavia, Central Eastern, Western and Southern Europe.

To conclude, asthmatic symptoms reported in a questionnaire, atopic status and a reduced level of maximal mid-expiratory flow were associated with the occurrence of acute respiratory symptoms, especially those of lower respiratory symptoms.
Aerosolized iloprost induces a mild but sustained inhibition of platelet aggregation
Authors: Beghetti M. , Reber G. , de Moerloose P. , Vadas L. , Chiappe A. , Spahr-Schopfer I. , Rimensberger P.C.
Published: July 2002

Pathological studies have revealed that one of the main features encountered in the pulmonary vasculature of patients with pulmonary hypertension is the presence of thrombotic lesions. Open pilot studies have indicated that aerosolized iloprost may have beneficial effects in patients with pulmonary hypertension. The effects of aerosolized iloprost on platelet function and plasma cyclic adenosine monophosphate (cAMP) were studied.

Platelet aggregation and plasma cAMP were measured at baseline, 30 min, 4 and 6 h after inhalation of 15 µg iloprost in 10 healthy volunteers. Maximal platelet aggregation in response to adenosine diphosphate (ADP) (2 and 6 µmol·L−1), collagen (2.5 and 5 µg·mL−1), epinephrine (1.25 and 5 µmol·L−1) and arachidonic acid (0.5 mg·mL−1) was measured.

Platelet aggregation was significantly inhibited at 30 min in response to ADP (2 and 6 µmol·L−1, epinephrine (1.25 and 5 µmol·L−1) and collagen (2.5 µg·mL−1). It was still inhibited at 4 h in response to the same agents, but normalized at 6 h. cAMP increased at 30 min, from 27.3±1.2 to 31.8±1.2 nmol·L−1, remained increased at 4 h (29.2±1.3 nmol·L−1) and normalized at 6 h (27.4±1.1 nmol·L−1).

Aerosolized iloprost induced a mild but sustained inhibition of platelet aggregation. Platelet aggregation inhibition may be one of the mechanisms which explains the beneficial effect of repeated inhalation of iloprost in pulmonary hypertension.
Clinical significance of histological classification of idiopathic interstitial pneumonia
Authors: Flaherty K.R. , Toews G.B. , Travis W.D. , Colby T.V. , Kazerooni E.A. , Gross B.H. , Jain A. , Strawderman R.L. , Paine R. , Flint A. , Lynch J.P. , Martinez F.J.
Published: July 2002

Patients with idiopathic interstitial pneumonias (IIPs) can be subdivided into groups based on the histological appearance of lung tissue obtained by surgical biopsy. The quantitative impact of histological diagnosis, baseline factors and response to therapy on survival has not been evaluated.

Surgical lung biopsy specimens from 168 patients with suspected IIP were reviewed according to the latest diagnostic criteria. The impact of baseline clinical, physiological, radiographic and histological features on survival was evaluated using Cox regression analysis. The predictive value of honeycombing on high-resolution computed tomography (HRCT) as a surrogate marker for usual interstitial pneumonia (UIP) was examined. The response to therapy and survival of 39 patients treated prospectively with high-dose prednisone was evaluated.

The presence of UIP was the most important factor influencing mortality. The risk ratio of mortality when UIP was present was 28.46 (95% confidence interval (CI) 5.5–148.0; p=0.0001) after controlling for patient age, duration of symptoms, radiographic appearance, pulmonary physiology, smoking history and sex. Honeycombing on HRCT indicated the presence of UIP with a sensitivity of 90% and specificity of 86%. Patients with nonspecific interstitial pneumonia were more likely to respond or remain stable (9 of 10) compared to patients with UIP (14 of 29) after treatment with prednisone. Patients remaining stable had the best prognosis. The risk ratio of mortality for stable patients compared to nonresponders was 0.32 (95% CI 0.11–0.93; p=0.04) in all patients and 0.33 (95% CI 0.12–0.96; p=0.04) in patients with UIP.

The histological diagnosis of usual interstitial pneumonia is the most important factor determining survival in patients with suspected idiopathic interstitial pneumonia. The presence of honeycombing on high-resolution computed tomography is a good surrogate for usual interstitial pneumonia and could be utilized in patients unable to undergo surgical lung biopsy. Patients with nonspecific interstitial pneumonia are more likely to respond or remain stable following a course of prednisone. Patients remaining stable following prednisone therapy have the best prognosis.