bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive mechanical ventilation in acute hypoxaemic respiratory failure
Authors: Wysocki M. , Antonelli M.
Published: October 2002

In acute hypoxaemic respiratory failure (HRF), oxygenation, reduction in the work of breathing and in dyspnoea may be achieved by delivering noninvasive mechanical ventilation (NIMV).

Several uncontrolled and 13 randomized controlled studies (RCS) were reviewed. Uncontrolled studies confirmed the feasibility and the possibility to improve arterial blood oxygenation with NIMV. The 13 RCS compared NIMVversusa conventional approach in a total of 720 patients with HRF. Endotracheal intubation was required in 186 of the 358 patients (median (95% confidence interval (CI)) 51%, (40–63%)) assigned to a conventional approach and in 107 of the 362 patients (29% (20–39%)) assigned to NIMV. Eleven of the 13 RCS found a reduction in the rate of endotracheal intubation with NIMV with an absolute risk reduction of 31% (30–33%).

Ten of the 13 RCS found a reduction in the mortality rate which was 30% (19–40%) in the control group and 19% (13–26%) in the NIMV group. The mean absolute risk reduction was 15% (10–20%).

In conclusion, noninvasive ventilation appears to be a useful method in avoiding endotracheal intubation and probably in reducing the morbidity of patients with hypoxaemic respiratory failure.
The reproducibility and sample size requirements of exercise-induced bronchoconstriction measurements
Authors: Dahlén B. , O'Byrne P.M. , Watson R.M. , Roquet A. , Larsen F. , Inman M.D.
Published: October 2002

Dry air exercise challenges are frequently used to screen medications that have potential utility in the management of exercise−induced bronchoconstriction (EIB). The purpose of this study was to determine the reproducibility of three outcome measurements made using such challenges, and sample size requirements for drug evaluation studies based on these outcomes.

Forty adult subjects with asthma, who tested positively on a screening exercise challenge, were subjected to two further identical challenges, separated by 1 to >35 days. Outcome measurements included the maximum per cent fall in forced expiratory volume in one second (FEV1), after exercise (% fallmax), and the area under the per cent fall in FEV1/time curve for 30 min (AUC30) and 60 min (AUC60) after exercise.

The reproducibility of these outcomes, as assessed by intraclass correlation coefficients was 0.72, 0.53 and 0.35 for % fallmax, AUC30and AUC60measurements, respectively. The sample size requirements to demonstrate an attenuation of EIB equivalent to a 50% reduction in % fallmaxwas 9, 14 and 19 subjects for the % fallmax, AUC30and AUC60responses, respectively (90% power).

It is concluded that the maximum percentage fall in forced expiratory volume in one second has greater reproducibility and results in greater power in clinical trials than area under the curve measurements. Sample size calculation curves are provided which may be used in study design and interpretation of published studies.
Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema
Authors: Montnémery P. , Svensson C. , Ädelroth E. , Löfdahl C-G. , Andersson M. , Greiff L. , Persson C.G.A.
Published: October 2002

Little information is available on associations between rhinitis and chronic bronchitis/emphysema (CBE).

Self-reported upper airway symptoms, asthma, and CBE were examined in 12,079 adults living in southern Sweden.

The response rate was 70% (n=8,469), of whom 33% reported significant nasal symptoms: a blocked nose was reported by 21%; sneezing by 18%; nasal discharge by 17%; and thick yellow nasal discharge by 5.7%. Nasal symptoms and combined nasal and self-reported bronchial disease were generally more common among smokers than nonsmokers. There was little overlap between asthma and CBE, but 46% of those with asthma and 40% of those with CBE had significant nasal symptoms. Best predicting factors (odds ratios >3) for asthma and CBE were nasal symptoms due to exposure to animals and damp/cold air, respectively.

One-third of an adult, southern Swedish population, had significant allergic and/or nonallergic nasal symptoms. Nasal symptoms were frequently found to coexist with both asthma and chronic bronchitis/emphysema, suggesting that pan-airway engagement is common in both diseases. Differing associations between types of nasal symptoms and allergic and irritant triggers of nasal symptoms, with regard to asthma and chronic bronchitis/emphysema, emphasize the different natures of these bronchial diseases.
Effect of whole-body x-irradiation on antigen-induced airway response in sensitized guinea pigs
Authors: Liu Y. , Tamura G. , Iijima H. , Taniguchi H. , Kikuchi T. , Ohkawara Y. , Shirato K.
Published: October 2002

The objectives of this study were to test the hypothesis that x-irradiation inhibits the late asthmatic response (LAR) without influencing the early asthmatic response (EAR) and to examine the mechanism of the inhibitory effect.

Twenty sensitized guinea pigs were irradiated at a dose of 8 Gy. The next day, one-half of the animals were injected intravenously with spleen cells (2×108) collected from unirradiated sensitized guinea pigs, whilst the other half were injected with vehicle only. Ten additional unirradiated sensitized guinea pigs also received vehicle only. Antigen inhalation challenge took place two days later. Pulmonary resistance was measured for 6 h after antigen exposure, and bronchoalveolar lavage and lung fixation were then undertaken. The area under the percentage pulmonary resistance curve 2–6 h after allergen inhalation was used for analysis of the LAR, while the maximal percentage change in pulmonary resistance was used for analysis of the EAR.

Irradiation abolished the LAR (364.4±49.4versus62.8±10.4) without inhibiting the EAR (229.3±27.2versus278.7±40.2) and significantly inhibited the accumulation of eosinophils and lymphocytes in the airways. Transfer of spleen cells restored the LAR (334.4±66.8) and the recruitment of cells to the levels seen in unirradiated sensitized guinea pigs. In addition, transfer of only CD4+ T-lymphocytes separated from the spleen cells restored the LAR (439.4±62.1) and the cell infiltration into the airways.

These inhibitory effects of x-irradiation were due to decreases in numbers of CD4+ T-lymphocytes.
Serum procalcitonin in pneumococcal pneumonia in children
Authors: Korppi M. , Remes S.
Published: October 2002

Serum procalcitonin (PCT), a marker of bacterial infection, was measured in children with pneumonia to examine whether PCT can be used to screen pneumococcal (PNC) from viral pneumonia.

The number of patients was 132; mean age 3.0 yrs, and 64% were males. In all cases, pneumonia was radiologically confirmed, being alveolar in 46 and interstitial in 86 cases. The aetiology of infection was studied by a panel of serological tests for PNC, for five other respiratory bacteria and for seven common respiratory viruses. PNC infection was found in 25, mixed viral-PNC infections in 13 and viral infection in 17 cases.

In general, serum PCT was not associated with the type or aetiology of pneumonia. PCT values were >1.0 mg·L−1in 40% of PNC cases, as compared to 12–15% in viral or mixed cases, respectively (p<0.05). PCT values were significantly higher in >2 yrs old children than in younger ones. The cut-off limits of 0.5 ng·mL−1, 1.0 ng·mL−1and 2.0 ng·mL−1were tested for screening between PNC and viral pneumonia. The highest sensitivity of 55% was found at the 0.5 ng·mL−1cut-off level, whereas the highest specificity of 88% was reached at the level of 1.0 ng·mL−1. The likelihood ratios, however, were far from optimal for both the positive and negative results.

Although marginally higher in pneumococcal pneumonia than in viral pneumonia, serum procalcitonin cannot be used to discriminate between these two types of pneumonia.
Nosocomial bacterial pneumonia in human immunodeficiency virus infected subjects: incidence, risk factors and outcome
Authors: Tumbarello M. , Tacconelli E. , de Gaetano Donati K. , Bertagnolio S. , Cataldo M. , Pirronti T. , Ardito F. , Cauda R.
Published: October 2002

The presented study examined the incidence, risk factors and outcome of nosocomial bacterial pneumonia (NBP) in human immunodeficiency virus (HIV)-infected subjects. Forty-two cases of NBP were ascertained by a 5-yr prospective surveillance and were matched to 84 controls. NBP incidence was 10.8 per 10,000 hospital patient-days. In particular, the incidence of NBP was 13.9 per 10,000 patient-days in the period 1994–1996 and 5.6 per 10,000 patient-days in the period 1997–1998 (p=0.01).

By using regression analysis, predictors for developing NBP were an increasing value of Acute Physiology and Chronic Health Evaluation (APACHE) III score (p<0.01) and the presence of acquired immune deficiency syndrome (AIDS)-related central nervous system (CNS) diseases (p=0.01). The additional hospital stay attributable to NBP was 15 days. The attributable mortality rate was estimated to be 29%.

Nosocomial bacterial pneumonia is more common in patients with advanced human immunodeficiency virus infection, high Acute Physiology and Chronic Health Evaluation III score and central nervous system diseases. Although the incidence of nosocomial bacterial pneumonia, as well of other opportunistic infections, decreased considerably in the era of highly active antiretroviral therapy, it still represents an important cause of mortality.
Prognostic significance of blood coagulation tests in lung cancer
Authors: Ferrigno D. , Buccheri G. , Ricca I.
Published: October 2002

Previous studies have shown that activation of coagulation has an impact on the clinical course of lung cancer.

This study was carried out to assess the potential prognostic significance of platelet count (P), prothrombin time (PT), partial thromboplastin time (PTT), anti-thrombin III (AT-III), fibrinogen (F), D-dimer (DD), factor II (F-II), factor VII (F-VII), factor X (F-X), protein C clotting (PCC), plasminogen (PL), and antiplasmin (AP) in 343 consecutive new lung cancer patients. A set of 32 anthropometric, clinical, physical, laboratory, radiological, and pathological variables was recorded prospectively for all patients. Patients were carefully followed-up, and their subsequent clinical course recorded.

The most frequent abnormalities were of DD, F, and AT-III followed by F-VII, F-X, and F-II. Among the 12 clotting variables, the strongest relationships were those of F-II and F-X (Spearman rank (rs)=0.565), PT and F-VII (rs=0.562), F-VII and F-X (rs=0.514), PL and AP (rs=0.515), F and P (rs=0.490), AT-III and PCC (rs=0.476). Univariate analyses of survival showed that prolonged PT (p<0.043), and abnormally elevated DD (p<0.003), F (p<0.031), and P (p<0.047) were all associated with a poor prognosis. The multivariate model, however, did not confirm the prognostic significance of the coagulation factors.

The results show subclinical activation of blood coagulation in lung cancer patients with early disease. In addition, clotting activation is confirmed as a predictor of survival, although not independently of other prognostic factors.
Diaphragmatic angiogenic growth factor mRNA responses to increased ventilation caused by hypoxia and hypercapnia
Authors: Siafakas N.M. , Jordan M. , Wagner H. , Breen E.C. , Benoit H. , Wagner P.D.
Published: October 2002

This study investigates the effect of increased ventilation on the expression of messenger ribonucleic acid (mRNA) levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor-β1(TGF-β1) in the diaphragm of intact, awake, spontaneously breathing rats, compared with responses in paralysed, mechanically-ventilated animals at similar blood gas and ventilatory levels.

Four groups of intact, rats were studied in a body box, each group breathing one of four gases: room air, 12% oxygen (O2), 5% carbon dioxide (CO2), or 12% O2+5% CO2for 1 h. Another 4 groups of paralysed, mechanically-ventilated animals were matched for arterial blood gas and ventilatory level.

The results showed that VEGF mRNA abundance was increased three-fold and that of bFGF 1.5-fold when 12% O2+5% CO2were breathed, but TGF-β1did not change. A significant linear relationship of VEGF and bFGF mRNA to minute ventilation was observed in awake animals (r0.98, p<0.02 and r=0.87, p<0.03, respectively). The paralysed, mechanically-ventilated animals showed no mRNA increases for any probe. Systemic hypoxia had no additional effect on VEGF or bFGF levels in the diaphragm.

It was concluded that messenger ribonucleic acid for vascular endothelial growth factor and basic fibroblast growth factor in the diaphragm rises significantly as a result of active ventilation and not due to blood gas/pH changes or to passive muscle shorteningper se.
Whistle mouth pressure as test of expiratory muscle strength
Authors: Chetta A. , Harris M.L. , Lyall R.A. , Rafferty G.F. , Polkey M.I. , Olivieri D. , Moxham J.
Published: October 2002

Expiratory muscle strength is a determinant of cough function. Mouth pressures during a maximal static expiratory effort (PE,max) are dependent on patient motivation and technique and low values are therefore difficult to interpret. This study hypothesized that a short, sharp and maximal expiration through a narrow aperture, a “whistle”, might provide a complementary test of expiratory muscle strength.

To obtain a maximal whistle, subjects (27 healthy volunteers and 10 patients with amyotrophic lateral sclerosis) were asked to perform a short, sharp blow as hard as possible, from total lung capacity, through a reversed paediatric inhaler whistle, connected to a flange-type mouthpiece.

In both healthy subjects and patients, whistle mouth pressure (Pmo,W) was closely related to the pressure measured in the oesophagus and stomach during the same manoeuvre. In healthy subjects,Pmo,WandPE,maxcorrelated with wide limits of agreement, althoughPmo,Wvalues were significantly higher thanPE,max(131±31 cmH2Oversus101±27 cmH2O, p<0.0001). In patients, it was also found thatPmo,WandPE,maxvalues were strongly related (r=0.937, p<0.0001). In healthy subjects, the intraclass correlation coefficient and the variation coefficient forPmo,Wrepeated measurements were respectively 0.88 and 7.0%. HoweverPmo,WandPE,maxwere always smaller than the gastric pressure generated by a maximal cough.

It is concluded that mouth whistle pressure, a noninvasive, reproducible and simple test, provides a reliable measure of expiratory muscle strength in healthy subjects that is acceptable to patients and can be used in a complementary fashion to maximal static expiratory effort.
Familial aggregation and heritability of adult lung function: results from the Busselton Health Study
Authors: Palmer L.J. , Knuiman M.W. , Divitini M.L. , Burton P.R. , James A.L. , Bartholomew H.C. , Ryan G. , Musk A.W.
Published: October 2002

Decreased spirometric indices are characteristic of asthma and other respiratory diseases. The aim of this study was to investigate the genetic and environmental components of variance of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured in adulthood in an Australian population-based sample of 468 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits with asthma and atopic rhinitis were also investigated.

Serial cross-sectional studies were conducted in the town of Busselton in Western Australia between 1966 and 1981 and follow-up of previous attendees was undertaken in 1995. Data from each subject included in this study were from a single survey in adulthood (25–60 yrs of age) when the subject was as close to age 45 yrs as possible.

Multivariate analysis suggested that FEV1and FVC levels were associated with age, sex, height, tobacco smoke exposure, asthma and atopic rhinitis. After adjustment for relevant covariates, FEV1levels had a narrow-sense heritability (h2N) of 38.9% (SE 9.1 %). FVC levels had anh2Nof 40.6% (SE 8.9%). Extended modelling demonstrated little overlap in the genetic determinants of asthma or atopic rhinitis and either FEV1or FVC levels.

The results of this study were consistent with the existence of important genetic determinants of adult lung function that are independent of asthma or other atopic disease, cigarette smoking, height, age or sex.
Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and gene polymorphisms
Authors: Barceló A. , Elorza M.A. , Barbé F. , Santos C. , Mayoralas L.R. , Agustí A.G.N.
Published: October 2002

The prevalence of several cardiovascular diseases is increased with obstructive sleep apnoea syndrome (OSAS), due to, as yet, unclear reasons. Angiotensin converting enzyme (ACE) abnormalities have been implicated in the pathogenesis of various cardiovascular diseases. In this study, plasma ACE activity and the distribution of an insertion (I)/deletion (D) polymorphism of the ACE gene were determined in OSAS patients and in healthy controls.

A total of 63 patients with OSAS (mean±sem 54.5±2.5 apnoea/hypopnoeas·h-1) and 32 healthy subjects were studied. To avoid potential confounding factors, patients treated with ACE inhibitors or continuous positive airway pressure were excluded, as well as controls in whom a blood sample was not obtained early in the morning. ACE activity was determined spectrophotometrically in 46 OSAS patients and 25 controls. The I/D ACE polymorphism was determined by polymerase chain reaction in 44 patients and 32 controls.

ACE activity was higher in OSAS patients (53.9±2.5 IU·L-1) than in healthy controls (42.4±3.1 IU·L-1, p<0.01). This was independent of the presence of arterial hypertension. The frequency distribution of the DD, II and ID genotypes in OSAS patients (30%, 16%, 54%, respectively) was not significantly different from that seen in healthy subjects (31%, 28%, 41%, respectively, p=0.356).

These results indicate that ACE plasma activity is increased in untreated OSAS patients. This increased activity may contribute to the pathogenesis of the cardiovascular disease in these patients.
Health effects of diesel exhaust emissions
Authors: Sydbom A. , Blomberg A. , Parnia S. , Stenfors N. , Sandström T. , Dahlén S-E.
Published: October 2002

Epidemiological studies have demonstrated an association between different levels of air pollution and various health outcomes including mortality, exacerbation of asthma, chronic bronchitis, respiratory tract infections, ischaemic heart disease and stroke. Of the motor vehicle generated air pollutants, diesel exhaust particles account for a highly significant percentage of the particles emitted in many towns and cities. This review is therefore focused on the health effects of diesel exhaust, and especially the particular matter components.

Acute effects of diesel exhaust exposure include irritation of the nose and eyes, lung function changes, respiratory changes, headache, fatigue and nausea. Chronic exposures are associated with cough, sputum production and lung function decrements. In addition to symptoms, exposure studies in healthy humans have documented a number of profound inflammatory changes in the airways, notably, before changes in pulmonary function can be detected. It is likely that such effects may be even more detrimental in asthmatics and other subjects with compromised pulmonary function.

There are also observations supporting the hypothesis that diesel exhaust is one important factor contributing to the allergy pandemic. For example, in many experimental systems, diesel exhaust particles can be shown to act as adjuvants to allergen and hence increase the sensitization response.

Much of the research on adverse effects of diesel exhaust, bothin vivoandin vitro, has however been conducted in animals. Questions remain concerning the relevance of exposure levels and whether findings in such models can be extrapolated into humans. It is therefore imperative to further assess acute and chronic effects of diesel exhaust in mechanistic studies with careful consideration of exposure levels. Whenever possible and ethically justified, studies should be carried out in humans.
The infant lung function model: a mechanical analogue to test infant lung function equipment
Authors: Frey U. , Reinmann B. , Stocks J.
Published: October 2002

To facilitate international multicentre studies and quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society (ERS-ATS) working group for infant lung function testing aims to develop specifications for standardized infant lung function equipment and software. However, a standardized test device is also needed to test whether existing infant lung function equipment is able to meet these requirements.

The authors have built a “mechanical model baby” consisting of a linear pump which can reproduce prerecorded tidal flow waveforms with a precision of 0.5% (full stroke), enabling the simulation of tidal and forced flow patterns. This linear pump can be connected to a series of copper lung volumes (range 50–300 mL) with known time constants, so that lung volumes can be reproduced with a precision of ±1% at frequencies 10–120 bpm. Five airflow resistors were built using sinter material.

When assessed using flows 0–300 mL·s−1all resistors showed a quasilinear pressure/flow relationship, with slopes 1.0–5.6 kPa·L−1·s. These resistances could be reproduced with a precision of ±2.5%. The infant lung model can also be used to assess frequency responses of infant lung function equipment, since the pump is capable of delivering low amplitude volumes up to 20 Hz in a pseudorandom noise manner.

In summary, based on error estimations, this infant lung model is able to test whether or not infant lung function equipment meets the requirements suggested by the European Respiratory Society-American Thoracic Society standardization group, that is: flow measurements within ±2.5%, volume and resistance measurements within ±5%, frequency response: magnitude attenuation <±10% and phase shift <±3 degrees at 10 Hz.
Assessment of an infant whole-body plethysmograph using an infant lung function model
Authors: Reinmann B. , Stocks J. , Frey U.
Published: October 2002

In order to facilitate international multicentre studies and improve the quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society Task Force for infant lung function testing has recently developed specifications for standardized infant lung function equipment and software. A mechanical infant lung model analogue has been developed to assess whether infant lung function equipment is able to meet these requirements. However, the practical testing of infant lung function equipment using such models is highly complex because of the need to use very small pressure and flow changes, and the numerous potentially confounding factors associated with both the design of the device and the testing procedure.

The aim of this study was to determine whether the infant lung model is capable of assessing the overall function of an whole-body infant- plethysmograph, using the only infant plethysmograph that was commercially available at the time as an example.

The mechanical characteristics of the model such as vibrations or noise did not disturb the delicate plethysmographic measurements and thereby allowed a reliable assessment of the system. A series of tests revealed that the plethysmograph was able to measure airway resistance 1–3.5 kPa·L−1·s with an accuracy of ±2.5% and lung volumes 75–300 mL with an accuracy of ±2.5% underin vitroconditions.

To conclude, the infant lung model is a useful means of assessing the overallin vitroperformance of infant whole-body plethysmographs, but thermal, mechanical and frequency response characteristics of such a device must be taken into account when interpreting the results of such assessments.
Allergy markers in respiratory epidemiology
Authors: Baldacci S. , Omenaas E. , Oryszczyn M.P.
Published: October 2002

Assessing allergy by measurement of serum immunoglobulin (Ig) E antibodies is fast and safe to perform. Serum antibodies can preferably be assessed in patients with dermatitis and in those who regularly use antihistamines and other pharmacological agents that reduce skin sensitivity.

Skin tests represent the easiest tool to obtain quick and reliable information for the diagnosis of respiratory allergic diseases. It is the technique more widely used, specific and reasonably sensitive for most applications as a marker of atopy.

Measurement of serum IgE antibodies and skin-prick testing may give complimentary information and can be applied in clinical and epidemiological settings.

Peripheral blood eosinophilia is less used, but is important in clinical practice to demonstrate the allergic aetiology of disease, to monitor its clinical course and to address the choice of therapy. In epidemiology, hypereosinophilia seems to reflect an inflammatory reaction in the airways, which may be linked to obstructive airflow limitation.
The role of positron emission tomography with
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F-fluoro-2-deoxy-D-glucose in respiratory oncology
Authors: Vansteenkiste J.F. , Stroobants S.G.
Published: October 2002

In the past 5 yrs, positron emission tomography (PET) with
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F-fluoro-2-deoxy-d-glucose (FDG) has become an important imaging modality in lung cancer patients. At this time, the indication of FDG-PET as a complimentary tool to computed tomography in the diagnosis and staging of non-small cell lung cancer has gradually gained more widespread acceptance and also reimbursement in many European countries.

This review focuses on the data of FDG-PET in the diagnosis of lung nodules and masses, and in locoregional and extrathoracic staging of non-small cell lung cancer. Emphasis is put on the potential clinical implementation of the currently available FDG-PET data. The use of FDG-PET in these indications now needs further validation in large-scale multicentre randomized studies, focusing mainly on treatment outcome parameters, survival and cost-efficacy.

Interesting findings with
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F-fluoro-2-deoxy-d-glucose-positron emission tomography have also been reported for the evaluation of response to radio- or chemotherapy, in radiotherapy planning, recurrence detection and assessment of prognosis. Finally, a whole new field of application of positron emission tomography in molecular biology, using new radiopharmaceuticals, is under extensive investigation.
Successful treatment of severe respiratory papillomatosis with intravenous cidofovir and interferon α-2b
Authors: Armbruster C. , Kreuzer A. , Vorbach H. , Huber M. , Armbruster C.
Published: October 2002

In contrast to uncomplicated juvenile laryngeal papillomas which may regress spontaneously, papillomatosis involving pulmonary parenchyma is associated with a poor outcome.

This report represents the case of a 34 yr-old female in whom respiratory papillomatosis resulted in voice problems and recurrent pneumonias due to bronchial obstruction. A computed tomographic scan of the chest showed worsening bilateral round cavitating consolidations. Bronchoscopy revealed polypoid lesions of the right vocal cord and the midtrachea which were confirmed as squamous papillomatosis by histology.

Interferon (IFN)α-2b treatment was inefficient as was cidofovir monotherapy on a maintenance basis. Six months of IFN-α-2b and cidofovir in combination led to a complete macroscopic disappearance of the laryngeal lesions and to an impressive regression of the tracheal papillomas and of the intrapulmonary consolidations.

These data provide support that severe respiratory papillomatosis can be safely treated by interferon α-2b and cidofovir in combination. Probably the same mechanisms as in ribavirin plus interferon α-2b, in the treatment of patients with chronic hepatitis C, are responsible for the therapeutic success in this case.
Reduced late asthmatic response by repeated low-dose allergen exposure
Authors: Palmqvist M. , Cui Z-H. , Sjöstrand M. , Lindén A. , Lötvall J.
Published: October 2002

Allergic asthmatic individuals are often exposed to low-doses of allergen in their everyday life. Extended exposure to allergen has lead to down-regulation of the allergic process in cell systems and in animal models. The aim of this study was to evaluate whether any such inhibitory mechanism of allergic responses can be seen in manin vivo.

Patients with mild asthma were repeatedly and double-blindly exposed to 25% of the individual dose of allergen that caused an early (EAR) and late asthmatic reaction (LAR). One day after the low-dose allergen or placebo exposure periods, the same individual was given a high-dose allergen challenge. Sputum and blood were collected for the evaluation of eosinophils.

Exposure to repeated low doses of allergen induced increased bronchial methacholine responsiveness 6 h after the final allergen exposure (p=0.018), and an increase in the number of eosinophils in sputum. By contrast, the late asthmatic response after challenge with a high dose of allergen was significantly attenuated by ∼30% at 24 h after the final low-dose allergen exposure (p=0.03).

In summary, repeated low doses of allergen given directly to the airways, attenuate the high-dose allergen-induced late response, despite enhanced bronchial hyperresponsiveness to methacholine and elevated sputum eosinophils prior to allergen challenge.
The feasibility of airways hyperresponsiveness as an inclusion criterion for studies on childhood asthma
Authors: Kamps A.W.A. , Visser M.J. , de Vries T.W. , van Aalderen W.M.C. , Postma D.S. , Brand P.L.P.
Published: October 2002

The feasibility of moderately severe airway hyperresponsiveness (AH) was examined as an inclusion criterion for clinical trials in asthmatic children.

During the baseline period of a long-term clinical trial in asthmatic children, maintenance therapy with fluticasone (200 µg·day−1) was stopped for a maximum of 8 weeks and methacholine challenges were performed at 2-week intervals or earlier if the patients' condition deteriorated. Patients were eligible to continue the study if the provocative dose of methacholine causing a 20% fall in forced expired volume in one second (FEV1) (PD20) was <80 µg.

Fifty-one per cent of the children did not develop a PD20<80 µg after withdrawal of fluticasone. Patients with or without a PD20<80 µg did not differ in duration of asthma, duration of treatment, or peak flow variation. Patients with a PD20<80 µg had higher levels of total and specific immunoglobulin-E, and lower levels of FEV1and mean maximal expiratory flow than patients with a PD20≥80 µg. Forty-four per cent of the patients with a PD20≥80 µg did not have any symptoms during the wash-out period and 39% of these patients remained free from symptoms during one year follow-up.

The results of this study suggest that recruiting asthmatic children for clinical trials may be difficult if airways hyperresponsiveness is used as the sole inclusion criterion.
Respiratory illness and healthcare utilization in children: the primary and secondary care interface
Authors: Cropper J.A. , Frank T.L. , Frank P.I. , Laybourn M.L. , Hannaford P.C.
Published: October 2002

The aim of the present study was to quantify the healthcare utilization of a child population according to level of respiratory illness.

A stratified random sample of 713 children was selected from respondents to a postal respiratory questionnaire, carried out in two general practice populations in 1993. Children were stratified into four groups according to the number of positive responses to five key questions. These groups were used as indicators of likelihood of asthma diagnosis. A search was made of these childrens' practice records covering a 2-yr period, to include both primary and secondary healthcare.

There was a significant increase across positive response groups in the proportion of children having primary and secondary care based consultations, particularly for respiratory conditions (p=0.001). There was also a significant increase in prescribing. Of those children considered to be “likely asthmatics” from their questionnaire responses, 8.1% (n=31) did not receive any primary or secondary care for a respiratory problem over the 2-yr period.

As the likelihood of respiratory illness increased in this population, more demand was made upon resources for the treatment of respiratory illness. Quantification of this demand enables evidence based resource allocation decisions to be made. This method of quantification could be applied in other populations.
Exhaled nitric oxide in chronic obstructive pulmonary disease: relationship to pulmonary function
Authors: Ansarin K. , Chatkin J.M. , Ferreira I.M. , Gutierrez C.A. , Zamel N. , Chapman K.R.
Published: October 2002

The following study was undertaken in order to determine how exhaled nitric oxide (eNO) levels in former smokers with chronic obstructive pulmonary disease (COPD) compared to eNO levels in patients with asthma and in healthy nonsmoking volunteers. The study also aimed to determine any relationship between eNO levels in COPD and: 1) conventional measures of lung function; and 2) inhaled corticosteroid (ICS) use.

In former smokers with COPD, nonsmokers with asthma and volunteers, eNO levels, spirometry, lung volumes, carbon monoxide diffusion capacity of the lung (DL,CO) and resting oxygen saturation (Sa,O2) were measured.

Median eNO was significantly higher among patients with COPD than among healthy volunteers (p=0.003) but lower than among patients with asthma (p<0.01). There was no significant difference in eNO levels between COPD patients using ICS and those not using ICS. By contrast, eNO was lower among asthma patients who used ICS (median 32 parts per billion (ppb); 25–75% range 16–54) than among asthma patients who did not (51 ppb; 32–87) (p=0.034). Among patients with COPD, eNO was inversely correlated with forced expiratory volume in one second,DL,COandSa,O2, and was positively correlated with the residual lung volume/total lung capacity ratio. Among patients with asthma, no significant correlations were found.

Exhaled nitric oxide is increased in patients with chronic obstructive pulmonary disease, an increase that is influenced by structural abnormalities of tobacco-induced lung damage.
Metabolic characteristics of the deltoid muscle in patients with chronic obstructive pulmonary disease
Authors: Gea J.G. , Pasto M. , Carmona M.A. , Orozco-Levi M. , Palomeque J. , Broquetas J.
Published: October 2002

The purpose of this study was to analyse key enzyme activities of the deltoid muscle (DM) in chronic obstructive pulmonary disease (COPD) patients.

The activities of one oxidative enzyme (citrate synthase (CS)), two glycolytic enzymes (lacatate dehydrogenase (LD); and phosphofructokinase (PFK)) and one enzyme related to the use of energy stores (creatine kinase (CK)) were determined in the DM of 10 patients with COPD and nine controls. Exercise capacity (cycloergometry) and the handgrip strength were also evaluated.

Although exercise capacity was markedly reduced in COPD (57±20% predicted), their handgrip strength was relatively preserved (77±19% pred). The activity of LD was higher in the COPD patients (263.9±68.2versus184.4±46.5 mmol·min−1·g−1, p<0.01), with a similar trend for CS (67.3±33.3versus46.0±17.4 mmol·min−1·g−1, p=0.07). Interestingly, the activity of the latter enzyme was significantly higher than controls if only severe COPD patients were considered (81.8±31.2 mmol·min−1·g−1, p<0.01). PFK and CK activities were similar for controls and COPD.

Chronic obstructive patients show a preserved or even increased (severe disease) oxidative capacity in their deltoid muscle. This coexists with a greater capacity in the anaerobic part of the glycolysis. These findings are different to those previously observed in muscles of the lower limbs.
Quality of life of idiopathic pulmonary fibrosis patients
Authors: Vries J. De , Kessels B.L.J. , Drent M.
Published: October 2002

Little attention has been paid to quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to address this issue and study the relationship between QOL, depressive symptoms, and breathlessness in these patients.

Forty-one IPF patients and 41 healthy persons matched for age and sex completed the World Health Organization Quality of Life assessment instrument-100. The IPF patients also completed the Beck Depression Inventory, the Bath Breathlessness Scale, a social support questionnaire and a question concerning perceived seriousness of illness.

Compared to the control group, QOL in IPF patients was mainly impaired in the domains “physical health” and “level of independence”. A number of relationships were found between pulmonary function tests and QOL. The QOL facet “negative feelings” was highly associated with scores on depression. Subjective breathlessness was related to depressive symptoms and QOL. Moreover, sex and effective/emotional breathlessness predicted overall QOL.

In conclusion, the impairment of the quality of life areas “physical health” and “level of independence” are important issues in idiopathic pulmonary fibrosis. Subjective breathlessness, especially the effective/emotional scale, seems related to quality of life and depressive symptoms. Rehabilitation programmes are needed that are aimed at physiological aspects and psychosocial aspects of idiopathic pulmonary fibrosis in order to enhance the quality of life of these patients.
Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia
Authors: Tateno H. , Nakamura H. , Minematsu N. , Amakawa K. , Terashima T. , Fujishima S. , Luster A.D. , Lilly C.M. , Yamaguchi K.
Published: October 2002

Chronic eosinophilic pneumonia (CEP) is characterized by chronic or recurrent pulmonary infiltrates with eosinophils, but the precise mechanism of eosinophil accumulation has not been fully elucidated. Eotaxin is one of the CC chemokines that selectively recruits eosinophils and contributes to the pathogenesis of allergic airway diseases including asthma, but its roles in pathogenesis of CEP have not been fully elucidated.

The authors measured concentrations of eotaxin and other CC chemokines, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted, macrophage inflammatory protein-1α, and the eosinophil activating Th2 cytokine interleukin (IL)-5 in bronchoalveolar lavage (BAL) fluid from CEP patients (n=11), and compared these concentrations with those from control subjects (n=6).

The eotaxin (904±203versus29±7 pg·mL−1, p=0.0001), MCP-1 (194±57versus15±2 pg·mL−1, p<0.05), and IL-5 (7.8±2.0versus2.7±0.6 pg·mL−1, p<0.05) levels were significantly higher for cases with CEP in comparison to those serving as controls. Proportions of eosinophil and lymphocyte counts were greater in BAL fluid from CEP patients. Eotaxin and IL-5 levels correlated with the proportion of eosinophils in BAL fluid from CEP patients. MCP-1 correlated with the relative lymphocyte numbers.

In short, eotaxin, interleukin-5, and monocyte chemoattractant protein-1 levels were higher in the BAL fluid of CEP patients and these levels may contribute to eosinophil and lymphocyte recruitment and activation in the airways as found with this disorder.
Epidemiology of chronic obstructive pulmonary disease
Authors: Antó J.M. , Vermeire P. , Vestbo J. , Sunyer J.
Published: October 2002

Chronic obstructive pulmonary disease (COPD) is a leading cause of world-wide mortality and disability. On average ∼5–15% of adults in industrialized countries have COPD defined by spirometry. In 1990, COPD was considered to be at the twelfth position world-wide as a cause of combined mortality and disability but is expected to become the fifth cause by the year 2020.

COPD has a chronic long-lasting course characterized by irreversible decline of forced expiratory volume in one second (FEV1), increasing presence of dyspnoea and other respiratory symptoms, and progressive deterioration of health status. After diagnosis the 10-yr survival rate is ∼50% with more than one-third of patients dying due to respiratory insufficiency.

Several environmental exposures such as air pollution increase the risk of death in COPD patients. The aetiology of COPD is overwhelmingly dominated by smoking although many other factors could play a role. Particular genetic variants are likely to increase the susceptibility to environmental factors although little is known about which are the relevant genes. There is clear evidence about the role of the α-1-antitrypsin but the fraction of COPD attributable to the relevant variants is only 1%. Phenotypic traits that are considered to play a role in the development of COPD include sex, with females being at a higher risk, bronchial responsiveness and atopy. There is strong causal evidence regarding the relationship between smoking and COPD with decline in FEV1levelling off after smoking cessation. Passive smoking has been found to be associated with a small though statistically significant decline in FEV1. Other risk factors that are likely to be relevant in the development of COPD are occupation, low socioeconomic status, diet and possibly some environmental exposures in early life.

Although there is accumulating evidence that oxygen therapy, pharmacological treatment and rehabilitation may improve the course of chronic obstructive pulmonary disease, preventing smoking continues to be the most relevant measure, not only to prevent chronic obstructive pulmonary disease, but also to arrest its development.
Bacteria, antibiotics and COPD
Authors: Wilson R.
Published: October 2002

Bacterial infection is one of several important causes of exacerbations of chronic obstructive pulmonary disease (COPD) that may coexist. COPD is a heterogeneous condition and the incidence of bacterial infection is not uniform; mucus hypersecretion may be an important risk factor.

The bacteriology of infections varies depending on the severity of the underlying airway disease. There is now a much better understanding of the pathogenesis of bacterial infections of the respiratory mucosa. Lower airway bacterial colonization may be a stimulus for chronic inflammation and may influence the interval between exacerbations.

Antibiotic resistance has increased in all the major pathogens. Antibiotics are an important part of the treatment of acute exacerbations of COPD and the decision about whether to give an antibiotic can be made on clinical grounds. It is more difficult to decide, on the available evidence, whether patient characteristics and the risk of antibiotic resistance should influence choice of empiric antibiotic treatment.

Most new antibiotics are modifications of existing structures, suggesting that every effort should be made to conserve the sensitivity of current antibiotics by using them appropriately.
Urban air pollution and chronic obstructive pulmonary disease: a review
Authors: Sunyer J.
Published: October 2002

There is consistency in the findings that relate the acute increases in urban air pollution (mainly the particulate matter) and the short-term health effects (i.e.mortality and hospital admissions) on patients suffering from chronic obstructive pulmonary disease (COPD). Beyond the acute effects, a relevant public health and scientific question is to what extent chronic exposure to air pollution is related with lung function impairment and development of COPD.

The few cross-sectional studies showed an increase of self-reported diagnosis of chronic bronchitis and emphysema, breathlessness and mucus hypersecretion and lower levels of lung function in the more polluted areas. The two cohort studies in children have found a retardation of pulmonary function growth, and the only cohort in adults a faster decline of lung function.

Given the intrinsic limitations of cross-sectional studies to separate the timing between exposure and effects, and the weaknesses of the cohorts (i.e.few areas, short follow-up, only one retest, lack of individual weighting of air pollution measure) there is a need for new prospective studies. These should be performed in a large number of geographical areas and with a long follow-up to asses the impact of long-term air pollution on lung function growth and decline, and on incidence, duration, severity and survival of chronic obstructive pulmonary disease.
Human leukocyte antigen genes may outweigh racial background when generating a specific immune response in sarcoidosis
Authors: Grunewald J. , Eklund A.
Published: October 2002

Presented is a sarcoidosis patient of African origin, who was adopted at an early age and grew up in Sweden.

This patient displayed an immune response identical to that previously reported in human leukocyte antigen (HLA)-DR17 positive Caucasian sarcoidosis patients in Scandinavia, with T-cell receptor AV2S3+ T-cells accumulating in the lungs. HLA typing also established that she was DR17 positive, which is a rare HLA type for individuals of African origin.

To the authors' knowledge, this specific immune response has not previously been reported in patients of African origin. Moreover, the clinical manifestations of sarcoidosis were similar to those known to be strongly linked to HLA-DR17 in Scandinavians,i.e.with Löfgren's syndrome.

The case presented here suggests certain human leukocyte antigen genes to be strongly linked to specific immune responses that are identical irrespective of the racial background. If such an immune response were important for the subsequent clinical manifestations, this case would argue for the importance of human leukocyte antigen genes in the genetic predisposition to sarcoidosis.
Interleukin-12 as successful adjuvant in tuberculosis treatment
Authors: Greinert U. , Ernst M. , Schlaak M. , Entzian P.
Published: October 2002

Interleukin-12 (IL-12) proved to be an effective and successful adjuvant to a standard antituberculotic medication in a patient suffering from progressive clinical tuberculosis (TB).

IL-12 is a potent enhancer of interferon-γ production which is necessary for killing intracellular bacteria like mycobacteria. This patient's TB was progressive, although sensitivity to first-line antituberculotics was proven and medication was given as directly observed therapy over more than 8 months. The 3-month adjuvant therapy with IL-12 significantly and convincingly improved results.

It is believed that this case, the first in the literature to describe adjuvant interleukin-12 therapy in tuberculosis, strongly encourages the study of adjuvant interleukin-12 therapy on a more systematic basis.