bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.