bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of resistance measured by the interrupter technique and by passive mechanics in sedated infants
Authors: Chavasse R.J. , Bastian-Lee Y. , Seddon P.
Published: July 2002

Airways resistance measured by the interrupter technique (Rint) requires little patient cooperation and has been successfully used in young children, but little studied in infants. The authors aimed to evaluate the measurement ofRintin infants, using a commercially available device (the MicroRint), by comparing it with an established technique to measure respiratory resistance: the single breath occlusion technique (SBT); and a measure of airflow obstruction during forced expiration.

Infants <18 months old with a history of wheeze, sedated with triclofos for pulmonary function testing, had measurements taken and compared toRint(using the MicroRint), respiratory system resistance (Rrs) by SBT, and to maximal flow at functional residual capacity (V′maxFRC).

Paired data from 25 of 37 infants studied was obtained. There was a significant difference betweenRint(mean 2.94±0.68) andRrs(4.02±0.87), but the two measures were strongly correlated (r=0.7).Rintwas negatively correlated withV′maxFRC(r=−0.63). Smaller infants failed to trigger the MicroRint.

Interrupter resistance values in infants are significantly lower than values of respiratory system resistance obtained by passive mechanics. However, there is a strong correlation between the two measurements, as well as between resistance measured using the interrupter technique and maximal flow at functional residual capacity, which indicates that resistance measured using the interrupter technique may be a useful marker of airway obstruction in infants. There remain a number of theoretical and technical problems which require further exploration.
Nasal continuous positive airway pressure in stroke patients with sleep apnoea: a randomized treatment study
Authors: Sandberg O. , Franklin K.A. , Bucht G. , Eriksson S. , Gustafson Y.
Published: July 2002

The authors have investigated whether treatment of sleep apnoea with nasal continuous positive airway pressure (nCPAP) improves depressive symptoms, personal activities of daily living (ADL), cognitive functioning and delirium in patients that have suffered a stroke.

Sixty-three patients consecutively admitted to a stroke rehabilitation unit 2–4 weeks after a stroke, with an apnoea/hypopnoea index ≥15, were randomized to either nCPAP treatment (n=33) or a control group (n=30). Four patients dropped out after randomization. Both groups were assessed at baseline and after 7 and 28 nights using the Montgomery-Åsberg Depression Rating Scale (MADRS), Barthel-ADL index, and the Mini-Mental State Examination (MMSE) scale.

Compared to the control group, depressive symptoms (MADRS total score) improved in patients randomized to nCPAP treatment (p=0.004). No significant treatment effect was found with regard to delirium, MMSE or Barthel-ADL index. Delirium and low cognitive level (MMSE score) explained poor compliance with nCPAP.

Depressive symptoms are reduced through nasal continuous positive airway pressure treatment in patients with severe stroke and sleep apnoea. Compliance with nasal continuous positive airway pressure treatment is a problem in stroke patients, especially when delirium and severe cognitive impairment occur.
Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study
Authors: Antonucci G. , Girardi E. , Raviglione M. , Vanacore P. , Angarano G. , Chirianni A. , Pagano G. , Suter F. , Lauria F.N. , Ippolito G. ,   GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS)
Published: July 2002

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme.

Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis.

Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT.

Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.
The effect of exposure to sulphuric acid on the early asthmatic response to inhaled grass pollen allergen
Authors: Tunnicliffe W.S. , Evans D.E. , Mark D. , Harrison R.M. , Ayres J.G.
Published: July 2002

Particulate sulphates, including sulphuric acid (H2SO4), are important components of the ambient aerosol in some areas and are regarded as air pollutants with potentially important human health effects. Challenge studies suggest little or no effect of H2SO4exposure on lung function in asthmatic adults, although some epidemiological studies demonstrate an effect of acid species on symptoms in subjects with asthma. To date, the effect of H2SO4on allergen responsiveness has not been studied.

The effect of exposure to particulate H2SO4on the early asthmatic response to grass pollen allergen has been investigated in 13 adults with mild asthma. After establishment of the provocative dose of allergen producing a 15% fall in forced expiratory volume in one second (FEV1) (PD15) for each subject, they were exposed to air, 100 µg·m−3or 1,000 g·m−3H2SO4for 1 h, double-blind in random order ≥2 weeks apart, through a head dome delivery system 14 h after each exposure subject underwent a fixed-dose allergen challenge (PD15).

Ten subjects completed the study. The mean early asthmatic responses (maximum percentage change in FEV1during the first 2 h after challenge) following air, 100 µg·m−3H2SO4, and 1,000 µg·m−3H2SO4, were −14.1%, −16.7%, and −18.4%, respectively. The difference between 1,000 µg·m−3H2SO4and air was significant (mean difference: −4.3%, 95% confidence interval (CI: −1.2–−7.4%, p=0.013). The difference between air and 100 µg·m−3H2SO4approached significance (mean difference: −2.6%, 95% CI: 0.0–−5.3%, p=0.051).

These results suggest that, at least at high mass concentration, sulphuric acid can potentiate the early asthmatic response of mild asthmatic subjects to grass pollen allergen, although the effect is limited.
Major histocompatibility locus genetic markers of beryllium sensitization and disease
Authors: Saltini C. , Richeldi L. , Losi M. , Amicosante M. , Voorter C. , van den Berg-Loonen E. , Dweik R.A. , Wiedemann H.P. , Deubner D.C. , Tinelli C.
Published: July 2002

Hypersensitivity to beryllium (Be) is found in 1–16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only ∼50% of BeLPT-positive workers present with lung granulomas (i.e.berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation.

A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-;α polymorphism TNF-;α-;308 in 23 individuals presenting as “sensitized” (i.e.BeLPT-positive without lung granulomas) and in 22 presenting as “diseased” (i.e.BeLPT-positive with granulomas in the lung biopsy).

The HLA-DPGlu69 marker was associated with “disease” (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4–10.0), whilst the high TNF-;α production-related TNF-;α-;308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.2–19.1) with no difference between “sensitization” and “disease”. Furthermore, the HLA-DRArg74 marker was associated with “sensitization” without disease (OR 3.96, p=0.005, 95% CI 1.5–10.1).

The data indicate that tumour necrosis factor-;α, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.
International approaches to the prescription of long-term oxygen therapy
Authors: Wijkstra P.J. , Guyatt G.H. , Ambrosino N. , Celli B.R. , Güell R. , Muir J.F. , Préfaut C. , Mendes E.S. , Ferreira I. , Austin P. , Weaver B. , Goldstein R.S.
Published: July 2002

While there is broad agreement about who should receive long-term oxygen therapy (LTOT), there is little information available on how clinicians should decide on the oxygen prescription itself, at rest, during sleep and during exercise. The authors describe the results of an international survey that was undertaken to compare how respirologists prescribed oxygen.

A questionnaire was sent to 100 respirologists in each of seven countries. The questionnaire identified whether resting flow rates were derived in a standard manner or by individualized patient testing. Test targets were ascertained for rest, exercise and sleep, as was the percentage of time that each test target had to reach for the test to be accepted.

The majority of respondents individualized the oxygen prescription at rest (81%). Resting arterial oxygen saturation (Sa,O2) was most commonly targeted at 90–91%. The approach to night prescription varied (p<0.001). Respirologists in Canada and the USA increased the restingSa,O2by 1–2 L·min−1during sleep, while those in Spain used the resting (awake) flow for the night prescription (62%). Respirologists in the Netherlands, France, and Italy individualized the night prescription more frequently. Although oxygen during exercise was individualized in most countries (74%), significant differences remained among countries (p<0.001). The majority of respirologists (62%) aimed to achieve anSa,O2of 90–91% during exercise, while 70% of all respirologists tried to achieve the desiredSa,O2for 90% of the test.

There were substantial differences among countries as to how the oxygen prescription was written. This survey highlights the need for multicentre studies that improve the effectiveness of long-term oxygen therapy utilization.
A prospective comparison of nursing home acquired pneumonia with community acquired pneumonia
Authors: Lim W.S. , Macfarlane J.T.
Published: July 2002

Nursing home acquired pneumonia (NHAP) is thought to be clinically distinct from community acquired pneumonia (CAP). This observation, based on studies conducted mainly in North America, may not be relevant in countries with a different healthcare system.

The authors describe an 18-month prospective cohort study of 437 patients admitted to hospital with CAP, 40 (9%) of whom came from nursing homes. Detailed microbiological tests were performed in a subset of patients over 12 months.

Patients with NHAP were less likely to have a productive cough (odds ratio (OR) 0.4, p=0.02) or pleuritic pain (OR 0.1, p=0.03), but they were more likely to be confused (OR 2.6, p<0.001). They had poorer functional status (p<0.001) and more severe disease (p=0.03). Mortality was higher compared to CAP (53%versus13%), but this was mainly explained by prior functional status (OR 0.5, after adjustment for functional status). Pathogens were identified in 68% of 22 NHAP and 80% of 44 matched CAP patients.Streptococcus pneumoniaewas the most common (55% NHAP, 43% CAP). Atypical pathogens, enteric Gram negative bacilli andStaphylococcus aureuswere uncommon.

In conclusion, differences in functional status accounted for the increased mortality in nursing home acquired pneumonia compared to community acquired pneumonia. The pathogens implicated were similar. No grounds for a difference in choice of empirical antibiotics were apparent.
Controlled, prospective trial of psychosocial function before and after continuous positive airway pressure therapy
Authors: McFadyen T.A. , Espie C.A. , McArdle N. , Douglas N.J. , Engleman H.M.
Published: July 2002

The aim of the study was to investigate psychosocial function before and after continuous positive airway pressure (CPAP) therapy, and establish the determinants and consequences of objective CPAP use.

In a prospective, parallel-group study, changes in psychosocial scores were compared with conservative management or CPAP therapy for the sleep apnoea/hypopnoea syndrome (SAHS). Patient/partner couples from the top (CPAP treated, n=44) or bottom (conservatively treated, n=25) of a CPAP waiting list rated marital satisfaction (evaluation and nurturing relationship issues, communication and happiness (ENRICH), behavioural questionnaire), health/functional status (Short-Form-36 Health Survey, functional outcomes of sleep questionnaire) and sleepiness (Epworth sleepiness scale). Both groups' ratings at baseline were completed while on conservative therapy.

Baseline variables did not differ between groups. At follow-up, all seven summary psychosocial scores were statistically better in CPAP-treated patients, effect sizes (ES) ranging from moderate (0.5 sd: marital satisfaction) to very large (>1.0 sd: patients health, functional status and sleepiness scores). Scores in conservatively-treated patients deteriorated to a small or moderate degree (ES −0.2– −0.7 sd), while those in the CPAP-treated group improved to a larger degree (0.3–1.3 sd). Baseline polysomnographical and psychosocial scores, including marital satisfaction, did not predict objective CPAP use (r<0.3). CPAP use was modestly correlated (r=0.3–0.6) with improvement in all psychosocial areas.

Continuous positive airway pressure produced statistically and clinically significant psychosocial improvements, some of large magnitude, in psychosocial function. Determinants of usage were not identified, but benefits and usage were positively correlated.
Physiological responses of the airway wall and lung in hyperresponsive pigs
Authors: Turner D.J. , Gray P.R. , Taylor S.A. , Thomas J. , Mitchell H.W.
Published: July 2002

Airway hyperresponsiveness (AHR) might be driven by mechanisms inherent to the airway wall, and/or by factors arising from outside the airways. A porcine model of allergen-induced AHR was utilized to investigate physiological responses in intact airwaysin vitroand their contribution to responsivenessin vivo.

Responsiveness to acetylcholine (ACh) was measured in eight ovalbumin (OA)-sensitized/challenged pigs (tests) and eight saline-challenged controls.In vivoresponsiveness to ACh was determined from pulmonary resistance (RL).In vitroresponsiveness to ACh was determined from airway pressure in isovolumic bronchial segments, after exposureviathe adventitial or the luminal surface.

Test pigs had lung (255±26% increase inRL, p<0.0001) and skin responses to OA, and AHR to ACh (p<0.0001).In vitro, test bronchi were less sensitive than controls to ACh applied to the airway adventitia (negative log of the ACh concentration producing half the maximum response (pD2)=4.18 and 4.58 respectively, p<0.01), but not the lumen. Test bronchi had an increased amount of smooth muscle normalized for airway sizeversuscontrols (p<0.05). Maximum responses to lumenal AChin vitroshowed a weak positive correlation with maximum changes to AChin vivo(r=0.599, p=0.05).

This study concludes that the effect of antigen challenge on bronchial responsiveness varies with the route of exposure to acetylcholine.In vitroresponses to lumenal acetylcholine are increased despite a possible reduction in responsiveness of airway smooth muscle. Responsiveness of the bronchial wall only partially explains responsiveness of the lungsin vivo.
Chemotherapy in small cell lung cancer
Authors: Østerlind K.
Published: July 2002

Chemotherapy is the backbone in the treatment of small cell lung cancer (SCLC) and radiotherapy is an important adjunct in limited stage disease. The role of chest irradiation is now documented in three meta-analysis, based on the same body of data. Trials on timing, scheduling and fractionation could have followed a more stringent development line but altogether, the highest efficacy seems to be obtained with early, concurrent twice-daily chest irradiation. Patients in complete remission should have prophylactic cranial irradiation, which reduces the risk of brain metastases and of death from SCLC.

Four series of chemotherapy seem to be sufficient in limited-stage disease while six is recommended in extensive disease. The combination of etoposide plus cis- or carboplatin is appropriate in both stages and addition of other agents has no clinically important impact on the survival. Use of haematological growth factors such as granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) may enable higher doses or more frequent dosage. Three randomized trials on GM-CSF showed a negative outcome while G-CSF support may result in better survival rates, but a more cost-efficient policy must be found. High-dose chemotherapy plus haematological stem-cell support is still under investigation but disappointing long-term survival rates means there is not much optimism for this strategy.

New strategies in general are requested in the treatment of extensive-stage disease and of elderly patients. Phase II trials suggest that good-risk patients with extensive disease should be treated aggressively, intermediate-risk patients more gently, and palliation must be the primary aim in the treatment of poor-risk patients. In elderly patients impressive survival rates are obtained with 3–4 series of chemotherapy and radiation delivered in 5–10 fractions.

A number of new agents are active but more trials are required before each has found a place, if any, in the treatment of small cell lung cancer. To conclude, the randomized trial is still an important instrument in clinical oncology, and trials in small cell lung cancer must be large, which is why the cooperation of organizations and multicentres is urgent.
The new World Health Organization classification of lung tumours
Authors: Brambilla E. , Travis W.D. , Colby T.V. , Corrin B. , Shimosato Y.
Published: July 2002

Tumour classification systems provide the foundation for tumour diagnosis and patient therapy and a critical basis for epidemiological and clinical studies. This updated classification was developed with the aim to adhere to the principles of reproducibility, clinical significance, and simplicity in order to minimize the number of unclassifiable lesions.

Major changes in the revised classification as compared to the previous one (WHO 1981 1) include the addition of two pre-invasive lesions to squamous dysplasia and carcinomain situ; atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Another change is the subclassification of adenocarcinoma: the definition of bronchioalveolar carcinoma has been restricted to noninvasive tumours. There has been substantial evolution of concepts in neuroendocrine lung tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now recognized as a histologically high grade non small cell carcinoma showing histopathological features of neuroendocrine differentiation as well as immunohistochemical neuroendocrine markers. The large cell carcinoma class has been enriched with several variants, including the LCNEC and the basaloid carcinoma, both with a dismal prognosis. Finally, a new class was defined called carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which brings together a number of proliferations characterized by a spectrum of epithelial to mesenchymal differentiation.

Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but our intention was to render the classification simple and practical to every surgical laboratory, so that most lung tumours could be classified by light microscopic criteria.
Nebulized heparin inBurkholderia cepaciacolonized adult cystic fibrosis patients
Authors: Ledson M. , Gallagher M. , Hart C.A. , Walshaw M.
Published: July 2002

Viscous negatively charged cystic fibrosis (CF) sputum allows colonization by pathogens, inducing a chronic inflammatory response. Heparin thins sputum by decreasing the mucin molecule amino group negative charge, altering its intermolecular hydrogen bonding, and ionically shielding its polyionic moieties. It also has an anti-inflammatory effect within the lung. It may, therefore, be useful in the treatment of CF patients.

In order to test this, six fully informedBurkholderia cepaciacolonized stable adult CF patients, received 25,000 IU nebulized heparin sulphate daily for 7 days. Subjective sputum parameters, spirometry, platelets, coagulation parameters, and serum and sputum interleukin (IL)‐6 and ‐8 were measured before and after treatment.

All patients tolerated the heparin with no evidence of bleeding, thrombocytopenia or change in coagulation parameters. There was no change in spirometry, but a reduction in interleukins (sputum IL‐6, p=0.01; sputum IL‐8, p=0.002; serum IL‐6, p=0.02; serum IL‐8, p=0.02). Sputum was easier to expectorate (p<0.04), with a trend towards thinner sputum (p=0.07) but no change in sputum volume.

Heparin therapy was well tolerated and had an anti-inflammatory effect, with subjective sputum mucolysis. Further studies are necessary to define the role of heparin in the treatment of cystic fibrosis patients.
Yellow nail syndrome: does protein leakage play a role?
Authors: D'Alessandro A. , Muzi G. , Monaco A. , Filiberto S. , Barboni A. , Abbritti G.
Published: July 2002

Yellow nail syndrome is characterized by primary lymphoedema, recurrent pleural effusion and yellow discoloration of the nails. Although mechanical lymphatic obstruction is assumed to be the underlying pathology, it cannot explain the common finding of high albumin concentration in the pleural space. This paper describes a case of yellow nail syndrome presenting with the classical triad of lymphoedema, recurrent pleural effusion and yellow discoloration of the nails, associated with persistent hypoalbuminaemia and increased enteric loss of albumin. Based on the findings in this case and those in the literature, it is speculated that increased microvascular permeability may contribute to the pathogenesis of this syndrome.
Sleep apnoea and Turner's syndrome
Authors: Orliaguet O. , Pépin J.L. , Bettega G. , Ferretti G. , Mignotte H.N. , Lévy P.
Published: July 2002

A 32-yr-old female with Turner's syndrome and anatomical craniofacial abnormalities, presented with obstructive sleep apnoea syndrome. This was initially treated by nasal continuous positive airway pressure and secondarily cured by maxillomandibullar advancement osteotomy. Anatomical upper airway abnormalities and hormonal factors, which predispose Turner patients to develop obstructive sleep apnoea syndrome, are discussed. A systematic assessment and treatment of sleep-disordered breathing is probably of interest in these patients.
Hypertonic saline alters ion transport across the human airway epithelium
Authors: Middleton P.G. , Pollard K.A. , Wheatley J.R.
Published: July 2002

Aerosolized hypertonic saline is currently being investigated as a new agent for the treatment of impaired mucociliary clearance which occurs in many respiratory diseases. Mannitol aerosols, in particular dry powder inhalers, have been proposed as an alternative treatment to saline, offering the same osmotic load with other benefits. However, the effects of these hypertonic aerosols on airway epithelial ion transport processes have not been tested in human subjectsin vivo. This report examines the effect of these solutions on airway ion transport using the nasal potential difference (PD) technique.

Seven healthy nonsmoking adult volunteers were studied. On different days, a dose-response curve was constructed for the saline added to Krebs N-[2-hydroxyethyl] piperazine-N′-[2-ethanesulphonic acid] (HEPES) diluent. The reversibility of this saline effect was measured, and the response to additional saline (500 mM) and mannitol (1 M) compared.

Hypertonic saline decreased nasal PD in a dose-related manner, with mean (sem) decreases in PD (less negative) of 6.6 (1.5), 7.6 (1.6), 10.0 (2.0), 13.1 (2.9) and 14.8 (3.2) mV (n=4) for addition of 150 mM, 250 mM, 500 mM, 1,200 mM and 2,000 mM NaCl to the Krebs HEPES diluent, respectively. The effect of hypertonic saline was fully reversible with washout for 3 min (presaline 15.9 (0.5) mV, postwashout 15.8 (1.1) mV, (n=4)). The hypertonic saline response was rapid in onset, sustained for at least 4 min, and decreased PD from 13.7 (1.7) mV to 5.1 (1.3) mV (n=7, p<0.001). In contrast, addition of mannitol to the perfusate did not significantly alter nasal PD, with a nonsignificant trend towards an increase (more negative) in the PD, (premannitol 13.9 (1.6) mV, postmannitol 15.3 (2.0) mV, n=7).

As the osmotic stimulus of the 1 M mannitol is similar to that of the 500 mM sodium chloride, the divergent nasal potential difference responses suggest that the response to the saline was specific to the sodium chloride itself and not the simultaneous change in osmolarity. This demonstrates that the human airway epitheliumin vivocan respond to topical hypertonic saline independent of the altered osmolarity.
Defining prognostic factors in the elderly with community acquired pneumonia: a case controlled study of patients aged ≥75 yrs
Authors: Lim W-S. , Macfarlane J.T.
Published: July 2002

Severity assessment in the elderly with community acquired pneumonia (CAP) may be different compared with younger patients. In particular, ageper semay not be of prognostic significance in older patients. A case-control study in 158 patients aged ≥75 yrs with CAP was conducted to determine the factors associated with in-hospital mortality.

Cases were drawn from all patients aged ≥75 yrs with CAP who died in 1997 in five hospitals in the mid-Trent region of the UK (Nottingham City Hospital, University Hospital Nottingham, Derby Royal Infirmary, Derby City General Hospital and Kings Hill Hospital). Controls were randomly selected from survivors also aged ≥75 yrs. Factors associated with mortality were identified following a review of the medical casenotes and the contribution of these factors to mortality was determined using multivariate analysis.

Absence of fever, tachycardia and chest radiograph features of bilateral involvement or an effusion were independently associated with mortality on multivariate analysis. The British Thoracic Society (BTS) severity rule was 50% sensitive and 64% specific in predicting death while the modified BTS rule displayed 67% sensitivity and 58% specificity.

Age was not significantly associated with mortality in this group of patients aged ≥75 yrs. Similarly, the clinical features employed in the British Thoracic Society rule, namely respiratory rate, diastolic blood pressure and blood urea, were not of prognostic significance and the rule itself performed poorly. The modified British Thoracic Society rule performed better.
Beta agonists, inhaled steroids, and the risk of intensive care unit admission for asthma
Authors: Eisner M.D. , Lieu T.A. , Chi F. , Capra A.M. , Mendoza G.R. , Selby J.V. , Blanc P.D.
Published: July 2002

Although inhaled corticosteroid (ICS) use is associated with a decreased risk of hospitalization for asthma, the impact of ICS on the risk of life-threatening asthma exacerbation is less clear. The effect of ICS and inhaled beta agonist (IBA) dispensing on the risk of intensive care unit admission for asthma, a surrogate for life-threatening exacerbation, is evaluated.

Using computerized International classification of diseases (ICD)-9 discharge diagnoses, a cohort of all 2,344 adult Northern California members of a health maintenance organization hospitalized for asthma over a 2-yr period were identified. Computerized pharmacy data was used to ascertain asthma medications dispensed during the 3-, 6-, and 12-month intervals preceding index hospitalization for asthma.

During the 3-months preceding hospitalization, a minority of subjects had no IBA units dispensed (34%), with 14% receiving low level (1 unit), 20% medium level (2–3 units), and 32% high level (≥4 units) therapy. A substantial proportion received no ICS units (55%), whereas 13% had low, 16% medium, and 15% high level therapy. In multiple logistic regression analysis, high level IBA use was associated with a greater risk of intensive care unit (ICU) admission for asthma after controlling for asthma severity. There was no relationship, however, between low or medium level IBA use and ICU admission. Conversely, medium level and high level ICS use were associated with a reduced risk of ICU admission. Analysing 6- and 12-month medication dispensing data, similar risk patterns were observed.

Inhaled corticosteroid dispensing was associated with reduced risk of intensive care unit admission among adults hospitalized for asthma, whereas the opposite applied for high dose beta agonist usage. This suggests that ICS prescription to adults with moderate-to-severe asthma could reduce the risk of life-threatening exacerbation.
Inhaled corticosteroids reduce growth. Or do they?
Authors: Brand P.L.P.
Published: July 2002

The class label warning in the United States for inhaled corticosteroids (ICS's) states that these drugs may reduce growth velocity in children. In this paper, the evidence for this warning is reviewed from a clinical point of view.

Children with asthma tend to grow slower than their healthy peers during the prepubertal years because they go into puberty at a later age. However, asthmatic children do achieve a (near) normal adult height. In randomized controlled clinical trials, the use of inhaled beclomethasone, budesonide and fluticasone is associated with a reduced growth during the first months of therapy, in the order of magnitude of approximately 0.5–1.5 cm·yr−1. It is, however, unlikely that such an effect continues or persists because accumulating evidence shows that asthmatic children, even when they have been treated with ICS for years, attain normal adult height. Individual rare cases have been reported, however, where ICS use was associated with clinically relevant growth suppression.

Inhaled corticosteroids are the most effective therapy available for maintenance treatment of childhood asthma. Fear of reduced growth velocity is based on exceptional cases and not on group data. It should, therefore, not be a reason to withhold or withdraw such highly effective treatment in children with asthma.
Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and Allergies in Childhood (ISAAC) data
Authors: Ellwood P. , Asher M.I. , Björkstén B. , Burr M. , Pearce N. , Robertson C.F
Published: July 2002

Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data.

Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6–7 and 13–14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995).

The 13–14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13–14 yr olds and the ISAAC data for 6–7 yr olds showed similar patterns for these foods.

A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.
Effects of mechanical ventilation of isolated mouse lungs on surfactant and inflammatory cytokines
Authors: Veldhuizen R.A.W. , Slutsky A.S. , Joseph M. , McCaig L.
Published: July 2002

Mechanical ventilation of the lung is an essential but potentially harmful therapeutic intervention for patients with acute respiratory distress syndrome. The objective of the current study was to establish and characterize an isolated mouse lung model to study the harmful effects of mechanical ventilation.

Lungs were isolated from BalbC mice and randomized to either a nonventilated group, a conventionally ventilated group (tidal volume 7 mL·kg−1, 4 cm positive end-expiratory pressure (PEEP)) or an injuriously ventilated group (20 mL·kg−1, 0 cm PEEP). Lungs were subsequently analysed for lung compliance, morphology, surfactant composition and inflammatory cytokines.

Injurious ventilation resulted in significant lung dysfunction, which was associated with a significant increase in pulmonary surfactant, and surfactant small aggregates compared to the other two groups. Injurious ventilation also led to a significantly increased concentration of interleukin-6 and tumour necrosis factor-α in the lavage.

It was concluded that the injurious effects of mechanical ventilation can effectively be studied in isolated mouse lung, which offers the potential of studying genetically altered animals. It was also concluded that in this model, the lung injury is, in part, mediated by the surfactant system and the release of inflammatory mediators.
The bias flow nitrogen washout technique for measuring the functional residual capacity in infants
Authors: Morris M.G. , Gustafsson P. , Tepper R. , Gappa M. , Stocks J.
Published: July 2002

The functional residual capacity (FRC) is the most commonly measured static lung volume in infants. It is important for interpreting volume-dependent pulmonary mechanics,e.g.airway resistance, and defining normal lung growth. The bias flow nitrogen washout technique is widely used for measuring FRC because the dead space and circuit resistance are low, making it suitable for small or sick infants. Moreover, data acquisition and calculation are easily programmed for a personal computer.

The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for functional residual capacity measurements. While measuring the functional residual capacity is regarded as physiologically and clinically important, the accuracy of the measurement is undoubtedly equally important. Hence, the paper also emphasizes factors influencing the accuracy of functional residual capacity measurements independent of equipment requirements. These recommendations represent the “State of the Art” in 2000.
Tracheobronchial stenosis in Keutel syndrome
Authors: Meier M. , Weng L.P. , Alexandrakis E. , Rüschoff J. , Goeckenjan G.
Published: July 2002

In 1971 Keutelet al. described a new syndrome in two siblings presenting with peripheral pulmonary stenoses, brachytelephalangism, neural hearing loss and abnormal cartilage calcification. Recent investigations provided evidence that mutations in the gene encoding the human matrix GLA protein cause Keutel syndrome. With these new insights in the disease the symptomatology of Keutel syndrome was reassessed. The follow-up of the two siblings was studied by clinical andpost mortemexamination.

As a new feature of Keutel syndrome tracheobronchial stenosis and concentric calcification of pulmonary, coronary, hepatic, renal, meningeal and cerebral arteries were described.

Complementary to the results in molecular genetics the symptomatology of Keutel syndrome could be revised by clinical andpost mortemexamination.
Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis
Authors: App E.M. , Baran D. , Dab I. , Malfroot A. , Coffiner M. , Vanderbist F. , King M.
Published: July 2002

The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug, Nacystelyn (NAL), for the treatment of cystic fibrosis (CF) lung disease.

In study 1, involving 10 CF patients, the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo, in order to establish an optimal dose for further testing. On five consecutive scheduled treatment days, patients inhaled either from two (4 mg) to eight puffs (16 mg) of a single dose of NAL from the range, administered in an open-label fashion, or 12 puffs of active NAL (24 mg)versus12 puffs of placebo, administered in a randomized double-blind fashion. Pulmonary function data were unaffected and clinically-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug. Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity, accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations.

In study 2, involving 12 CF patients, the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days, 7 days apart, patients inhaled a single dose of 12 puffs of active NAL (24 mg) or 12 puffs of placebo drug in a randomized, double-blind sequence, with sputum samples taken at intervals before and after inhalation. Mucus rigidity decreased following NAL inhalation, with the maximum effect observed at 4 h; the 1-, 2- and 4-h NAL rheology results were significantly different from placebo. No adverse effects were observed.

The drug was well tolerated in both studies. Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms.
Interpreting thresholds for a clinically significant change in health status in asthma and COPD
Authors: Jones P.W.
Published: July 2002

Health status (or Health-Related Quality of Life) measurement is an established method for assessing the overall efficacy of treatments for asthma and chronic obstructive pulmonary disease (COPD). Such measurements can indicate the potential clinical significance of a treatment's effect.

This paper is concerned with methods of estimating the threshold of clinical significance for three widely used health status questionnaires for asthma and COPD: the Asthma Quality of Life Questionnaire, Chronic Respiratory Questionnaire and St George's Respiratory Questionnaire. It discusses the methodology used to obtain such estimates and shows that the estimates appear to be fairly reliable;i.e.for a given questionnaire, similar estimates may be obtained in different studies.

These empirically derived thresholds are all mean estimates with confidence intervals around them. The presence of these confidence intervals affects the way in which the thresholds may be used to draw inferences concerning the clinical relevance of clinical trial results. A new system of judging the magnitude of clinically significant results is proposed.

Finally, an attempt is made to translate these thresholds into scenarios that illustrate what a clinically significant change with treatment may mean to an individual patient.
Induced sputum: time from expectoration to processing
Authors: Efthimiadis A. , Jayaram L. , Weston S. , Carruthers S. , Hargreave F.E.
Published: July 2002

One of the limitations in the use of induced sputum to measure indices of airway inflammation is the perceived need to process the sample within 2 h. Therefore, the authors investigated whether the processing of induced sputum could be delayed.

Induced sputum samples obtained from asthmatic subjects (n=30) were examined. Each sample was stored at 4°C. A portion was selected and processed within 2 h and the remaining expectorate (sputum plus saliva) was refrigerated. Later an equal amount was selected and processed at either 9 (n=15) or 18 (n=15) h. The sputum was examined for cell counts and viability, fluid-phase eosinophil cationic protein (ECP), interleukin‐8 (IL‐8) and fibrinogen. Repeatability of measurements was assessed by the interclass correlation coefficient (ICC).

Measurements obtained at 9 h did not differ from those made at 2 h and the repeatability was excellent (ICC 0.88–0.99). However, by 18 h the median cell viability was reduced from 65.0% to 43.0% and the ICC was generally lower: 0.10 for total cell count, 0.24 for viability, 0.60 for neutrophils, 0.90 for eosinophils, 0.56 for macrophages, 0.76 for ECP, 0.82 for IL‐8 and 0.84 for fibrinogen.

The results indicate that when induced sputum from subjects with asthma is kept at 4°C, examination of cell counts can be delayed for ⩽9 h and for the fluid-phase indices measured for ⩽18 h. Further investigation of this issue is required for spontaneous sputum, other airway diseases and other inflammatory markers.
Obstructive sleep apnoea and urine catecholamines in hypertensive males: a population-based study
Authors: Elmasry A. , Lindberg E. , Hedner J. , Janson C. , Boman G.
Published: July 2002

Studies addressing the relationship between obstructive sleep apnoea (OSA) and sympathoadrenal activity have been criticized for poor control of factors known to confound sympathetic function, including hypertension. The aim of this study was to investigate the relationship between OSA and urinary catecholamines in a population-based sample of hypertensive males.

In 1994, 2,668 males aged 40–79 yrs answered a questionnaire regarding sleep disorders and somatic diseases. Of those who reported hypertension, an age-stratified sample of 116 was selected for monitoring of breathing during sleep and overnight urine analysis.

Subjects with OSA, defined as apnoea-hypopnoea index ≥10·h−1, had higher concentrations of urinary normetanephrine (182±57versus141±45 µmol·mol−1creatinine, p<0.001) and metanephrine (70±28versus61±28 µmol·mol−1creatinine, p<0.05) in comparison to subjects without OSA. In a multiple regression analysis, there was an association between variables of sleep-disordered breathing and normetanephrine and metanephrine concentrations, independent of major confounding factors.

The authors concluded that, in a population-based sample of hypertensive males, obstructive sleep apnoea is associated with increased urinary concentrations of extraneuronal metabolites of catecholamines independent of major confounding factors, suggesting increased sympathoadrenal activity. Elevated sympathoadrenal activity may explain the increased cardiovascular morbidity associated with obstructive sleep apnoea.
Anti-Chlamydophila immunoglobulin prevalence in sarcoidosis and usual interstitial pneumoniae
Authors: Gaede K.I. , Wilke G. , Brade L. , Brade H. , Schlaak M. , Müller-Quernheim J.
Published: July 2002

Sarcoidosis and usual interstitial pneumoniae (UIP) are diseases of unknown aetiology affecting the lower respiratory tract. Although there are a number of studies investigating the causal role of these disorders, no micro-organism could be identified as the causal agent. The high incidence ofChlamydophila pneumoniaeinfections associated with lung injury encouraged the present investigations to screen patients with sarcoidosis and with UIP for their Chlamydophila-specific immune response.

Thirty-nine patients with sarcoidosis, 26 patients with UIP and 34 controls were tested for the prevalence of Chlamydophila-specific antibodies in bronchoalveolar lavage fluids (BALF) and sera. Samples were tested for the presence of antibodies in a genus-specific test for Chlamydophila-lipopolysaccharide (LPS) and in a species-specific test forC. pneumoniae.

This study revealed a significantly higher prevalence of Chlamydophila LPS-specific immunoglobulin (Ig)-G in the BALF of sarcoidosis patients (36.8%) compared to controls (8.8%) and patients with UIP (12.0%). Similar findings were observed in sera. The prevalence ofC. pneumoniae-specific antibodies in BALF was significantly higher in sarcoidosis patients for IgG and IgA (IgG: 74.4%; IgA: 46.2%) and in UIP for IgG (IgG: 50.0%; IgA: 11.5%) compared to controls (IgG: 14.7%; IgA: 14.7%).

The elevated prevalence of Chlamydophila-specific antibodies in sarcoidosis patients might implicate Chlamydophila as a causal agent. However, considering the high prevalence of Chlamydophila antibodies in the healthy population, the data presented might reflect Chlamydophila co-infections in pre-injured lungs seen in these patients.
Potential masking effect on dyspnoea perception by short- and long-acting β2-agonists in asthma
Authors: van Schayck C.P. , Bijl-Hofland I.D. , Cloosterman S.G.M. , Folgering H.T.M. , van der Elshout F.J.J. , Van Weel C.
Published: July 2002

Asthma patients evaluate the effect of medication treatment through the degree of their asthma symptoms, which might be affected by their ability to perceive these symptoms. It has been suggested that β2-agonists may mask the effects of an increase in airway inflammation. This study compared the perception of histamine-induced bronchoconstriction during monotherapy with short- or long-acting β2-agonists.

Asthmatic patients (68 male and 60 female, mean age 35±11 yrs, forced expiratory volume in one second (FEV1) 86±15% of the reference value, provocative concentration causing a 20% fall in FEV1(PC20) geometric mean 0.97 mg·mL−1(95% confidence interval (CI): 0.73–1.30)) were selected and randomly allocated to use either a short-acting (salbutamol, n=41) or long-acting β2-agonist (formoterol, n=46) or placebo (n=41) for 12 weeks. Perception of dyspnoea provoked by histamine-induced bronchoconstriction was measured at the start and every 4 weeks thereafter. Subjects quantified their sensation of breathlessness during the challenge tests on a modified Borg scale at the start of the study and every 4 weeks thereafter. The sensitivity to changes in FEV1was analysed by the linear regression slope (α) Borgversus% fall in FEV1. The absolute perceptual magnitude (PS20) was determined by the perception score at the 20% fall in FEV1.

Although the geometric mean PC20decreased significantly within the group using short-acting β2-agonists (in the group with initial PC20≥2 mg·mL−1there was a drop from 5.26–1.94 mg·mL−1; p=0.013), repeated measurement analysis showed no difference in the course of time of perception (both slope α and PS20) between the three medication groups.

This study showed that chronic use of short- or long-acting β2-agonists in asthmatics for a period of 12 weeks, did not significantly change the perception of histamine-induced bronchoconstriction compared with placebo. Further investigation is required to establish whether this suggests that these drugs do not mask a deterioration of asthma.