bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal variation in community-acquired pneumonia
Authors: Lieberman D , Lieberman D , Porath A
Published: April 2003

Seasonal variation in the incidence of disease in general, and of infectious diseases in particular, is vitally important information for epidemiologists and for clinicians who deal with these diseases. In relation to community-acquired pneumonia (CAP), the seasonal distribution of the disease and, in particular, of each of the specific aetiological agents is important. All 346 adult patients who were admitted to a regional hospital in southern Israel for CAP over a period of 1 year were included in a prospective study. As part of the study, a comprehensive diagnostic work-up was performed to identify the specific causative agents for CAP. The study findings were analysed and are presented in terms of the seasonal distribution of the disease. Thirty four percent of CAP cases occurred in the spring and only 18% in the autumn (p = 0.036). Respiratory viruses CAP were predominant in the winter and spring (p = 0.009), whilst Mycoplasma pneumoniae CAP reached its peak incidence of 41% in the spring compared with 15% during the winter months (p = 0.054). No significant seasonal predominance was observed for the other specific aetiological agents of CAP. In 58% of the CAP patients who were hospitalized in the autumn we identified a pneumococcal aetiology, whilst this agent was found in only 32% of the cases in the winter. In contrast with popular public opinion, winter with its low temperatures is not the main reason for the development of community-acquired pneumonia. Most of the specific aetiologies for community-acquired pneumonia, with the exception of respiratory viruses and Mycoplasma pneumoniae, have no seasonal predilection.
Interferon-gamma in 388 immunocompromised and immunocompetent patients for diagnosing pleural tuberculosis
Authors: Villena V , Lopez-Encuentra A , Echave-Sustaeta J , Martin-Escribano P , Ortuno-de-Solo B , Estenoz-Alfaro J
Published: April 2003

The level of interferon-gamma (IFN-gamma) in pleural fluid has been reported to be increased in pleural tuberculosis. Nevertheless, its diagnostic value has not yet been well-established, and immunocompromised patients have not previously been evaluated. The aim of this study was to determine the value of the IFN-gamma level in pleural fluid for diagnosing tuberculous pleurisy in immunocompetent and immunocompromised patients. Three hundred and eighty eight consecutive patients were studied prospectively (73 with tuberculous pleural effusions, including nine with concurrent human immunodeficiency virus (HIV) infection and one after liver transplantation, and 315 with nontuberculous effusions). IFN-gamma was measured by radioimmunoassay. The sensitivity of the test, using a 3.7 U.mL-1 cut-off point, was 0.99 (95% confidence interval (95% CI) 0.93-1.00) and the specificity was 0.98 (95% CI 0.96-1.00). The sensitivity of the test did not differ in HIV-positive and HIV-negative patients. Patients with lymphoma, vasculitis or vascular connective tissue disease did not have abnormal IFN-gamma values. In conclusion, the level of interferon-gamma in pleural fluid is a very good diagnostic marker of tuberculous pleural effusion, even in immunocompromised patients.
Pulmonary hyperinflation a clinical overview
Authors: Gibson GJ
Published: April 2003

Pulmonary hyperinflation is usually defined as an abnormal increase in functional residual capacity, i.e. lung volume at the end of tidal expiration. As such, it is virtually universal in patients with symptomatic diffuse airway obstruction. Hyperinflation inferred from a standard chest radiograph implies an increase in total lung capacity. The relaxation volume of the respiratory system (Vr) increases in patients with chronic airway disease as a result of changes in the elastic properties of the lungs and chest wall. In addition, a variable degree of dynamic hyperinflation may be present. This results from the onset of inspiration before lung volume has fallen to Vr. Dynamic hyperinflation is frequently present at rest in patients with moderate-to-severe airway obstruction, and it increases further on exercise, thereby increasing the mechanical load on the inspiratory muscles and at the same time reducing their mechanical advantage. Important clinical consequences and associations of hyperinflation include: distortions of chest wall motion; impaired inspiratory muscle function; increased oxygen cost of breathing; greater likelihood of hypercapnia; impaired exercise performance; and greater severity of breathlessness. The symptomatic improvement after treatment with a bronchodilator may be due, in part, to lessening of hyperinflation.
The role of the host defence response in the progression and outcome of ARDS: pathophysiological correlations and response to glucocorticoid treatment
Authors: Meduri GU
Published: April 2003

The host defence response (HDR) to insults is similar regardless of the tissue involved and consists of an interactive network of simultaneously activated pathways that act in synergy to increase the host's chance of survival. Among this cascade of integrated pathways, three aspects of the HDR, inflammation, coagulation and tissue repair, are analysed separately to explain the histological and physiological changes occurring at the tissue level in unresolving acute respiratory distress syndrome (ARDS). Cellular responses in HDR are regulated by a complex interaction among cytokines, and cytokines have concentration-dependent biological effects. The degree of initial HDR may determine the progression of ARDS. On Day 1 of mechanical ventilation and over time, nonsurvivors of ARDS have significantly higher plasma and bronchoalveolar lavage inflammatory cytokine levels than survivors. In the absence of inhibitory signals, the continued production of HDR mediators prevents effective restoration of lung anatomy and function by sustaining inflammation with tissue injury, intra- and extravascular coagulation and proliferation of mesenchymal cells (fibroproliferation) with deposition of extracellular matrix resulting in fibrosis. Glucocorticoids inhibit the HDR cascade at virtually all levels; their gradual and generalized suppressive influence protects the host from overshooting. In patients with exaggerated HDR, however, cytokine elevation may cause a concentration-dependent resistance to glucocorticoids by reducing glucocorticoid receptor binding affinity. Recent clinical and experimental studies have shown that effective containment of the HDR in unresolving ARDS may be achieved only if glucocorticoid administration is prolonged. A double-blind randomized study is in progress to evaluate the role of prolonged glucocorticoid treatment in unresolving ARDS.
Nitric oxide in exhaled air
Authors: Lundberg JO , Weitzberg E , Lundberg JM , Alving K
Published: April 2003

Much interest is now being focused on measurements of nitric oxide (NO) in exhaled air. In healthy subjects exhaled NO seems to originate mainly in the nasal airways, whereas the contribution from the lower respiratory tract is low. In certain inflammatory airway disorders, the excretion of NO into the airways is altered resulting in changes in the levels of NO in exhaled air. New techniques have been developed to measure NO release at different levels of the airways: asthmatics show increased orally-exhaled NO levels, whereas patients with cystic fibrosis or Kartagener's syndrome exhibit a marked reduction in nasal release of NO. It has been suggested that measurements of exhaled NO may be clinically useful in noninvasive diagnosis and monitoring of inflammatory airway diseases. To further evaluate the potential clinical usefulness of measurement of exhaled NO, it is vital to explore how airway NO production is normally regulated and what factors influence airway NO excretion.
Evaluation of the THRESHOLD trainer for inspiratory muscle endurance training: comparison with the weighted plunger method
Authors: Johnson PH , Cowley AJ , Kinnear WJ
Published: April 2003

Inspiratory muscle training (IMT) has been shown to enhance exercise performance. The weighted plunger (WP) system of inspiratory threshold loading is the most commonly used method of IMT, but is expensive and cumbersome. We have evaluated a commercially available portable spring-loaded IMT device, the THRESHOLD trainer. The WP and THRESHOLD trainer devices were evaluated with their opening pressures set, in random order, at 10, 20, 30 and 40 cmH2O. Using an airpump, pressure at the valve inlet was recorded at the point at which the valve opened, and at airflow rates of 20, 40, 60, 80 and 100 L.min-1.Ten THRESHOLD trainers were then compared using the same opening pressures and airflow rates. Finally, 10 patients with stable chronic heart failure (CHF) inspired, in random order, through the WP and THRESHOLD trainer for 4 min each. The pressure-time product (PTP) was calculated for each 4 min period, to compare the work performed on inspiring through each device. The mean measured opening pressures for the WP set at 10, 20, 30 and 40 cmH2O, were 9.0, 19.3, 27.9 and 39.2 cmH2O, respectively, and there was little change over the range of flow tested. Corresponding values for the THRESHOLD trainer were 7.5, 16.9, 26.2 and 39.1 cmH2O, with the pressure being closer to the set pressure as flow increased to that seen in clinical practice. The 10 different trainers tested performed very similarly to one another. Work performed (as measured by PTP) on inspiring through the WP and THRESHOLD trainer was not significantly different. Although less accurate than the weighted plunger, the THRESHOLD trainer is an inexpensive device of consistent quality. In a clinical setting it would be a satisfactory option for inspiratory muscle training in most patients, but less so in patients with very low inspiratory flow rates.
Adult respiratory distress syndrome and pancytopenia associated with miliary tuberculosis in a HIV-infected patient
Authors: Mofredj A , Guerin JM , Leibinger F , Masmoudi R
Published: April 2003

Adult respiratory distress syndrome (ARDS) is a rare but severe complication of miliary tuberculosis, which may appear even after introduction of antituberculosis therapy. Mortality has been reported to be as high as 100% if there is associated pancytopenia. We report a case of a patient infected with the human immunodeficiency virus who presented with miliary tuberculosis associated with pancytopenia and adult respiratory distress syndrome.
Connective tissue disease due to intentional inhalation of scouring powder
Authors: Vincent M , Pouchelle C , Martinon S , Gerard F , Arthaud Y
Published: April 2003

There have been reports in the literature of acute and chronic silicosis and connective tissue disease induced by occupational exposure to silica in factories producing scouring powder. Reports of connective tissue diseases induced by intentional inhalation of such a powder are rare and perhaps underestimated. We report the case of a young woman who developed Sharp's syndrome 5 yrs after diagnosis of acute silicosis due to scouring powder inhalation. The frequency of diseases from scouring powder as well as physiopathological and therapeutical issues of the association of pneumoconiosis and connective tissue disease are discussed.
Pneumonitis during interferon and/or herbal drug therapy in patients with chronic active hepatitis
Authors: Ishizaki T , Sasaki F , Ameshima S , Shiozaki K , Takahashi H , Abe Y , Ito S , Kuriyama M , Nakai T , Kitagawa M
Published: April 2003

We report four cases of acute pneumonitis due either to interferon, or a herbal drug, "Sho-saiko-to", or both in combination, in patients with chronic active hepatitis, focusing on its pathogenesis and response to prednisolone therapy. These cases shared common clinical features: fever, dry cough, dyspnoea, hypoxaemia, diffuse infiltrates both on chest radiography and chest computed tomography, restrictive pulmonary functional impairment, and alveolitis on examination of transbronchial lung biopsy, all of which suggest acute interstitial pneumonia. Furthermore, lymphocytosis was observed in association with the dominant CD8+ T-cell subset in bronchoalveolar lavage fluid. A lymphocyte stimulation test using peripheral blood was positive to interferon in one case and to Sho-saiko-to in another. All patients responded to oral prednisolone therapy. Peripheral soluble interleukin-2 receptor levels decreased in parallel with improvement in the clinical course. All patients were free of symptoms with a follow-up of 1-3 yrs. We conclude that interferon- and/or Sho-saiko-to-induced acute pneumonitis may be due to allergic-immunological mechanisms rather than toxicity, and that peripheral levels of soluble interleukin-2 receptor appear to be good markers of disease activity.
Radiation pneumonitis complicating mediastinal radiotherapy postpneumonectomy
Authors: Shulimzon T , Apter S , Weitzen R , Yellin A , Brenner HJ , Wollner A
Published: April 2003

Radiation pneumonitis is a well-characterized clinicopathological syndrome. The severity of radiation-induced lung injury correlates, among other factors, with the extent of lung volume incorporated within the field of radiation. The present article describes the cases of two patients with radiation pneumonitis following pneumonectomy and mediastinal radiotherapy. Postpneumonectomy pulmonary-mediastinal shift of the remaining lung towards the operated side, with inclusion of lung parenchyma within the "mediastinal" radiation portals, resulted in a substantial (albeit clinically unsuspected) radiation pneumonitis. Chest computed tomography in the postpneumonectomy patient may be helpful to evaluate the degree of pulmonary-mediastinal shift and optimization of the radiotherapy field.
Gas exchange at extreme altitude: results from the British 40th Anniversary Everest Expedition
Authors: Peacock AJ , Jones PL
Published: April 2003

Since Messner and Habeler climbed to the summit of Mount Everest (8,848 m) without oxygen in 1978, there has been controversy between scientists trying to explain this feat. Field studies have suggested better respiratory performance than that found during a simulated climb in a hypobaric chamber, but the lack of data at extreme altitude has hampered the debate. We measured arterial oxygen saturation (Sa,O2) and alveolar partial pressure of oxygen (PA,O2) in nine subjects as they climbed from 3,500 to 8,000 m. Four of the climbers reached 8,000 m and one reached the summit. We also tested the effects of breathing supplementary oxygen on Sa,O2 at 6,550 and 8,000 m. At all altitudes tested, we found that both PA,O2 and Sa,O2 were higher than expected from low pressure chamber studies. We also found that standard rates of supplementary oxygen (2 L x min(-1)) were insufficient to restore Sa,O2 above 90% at 8,000 m. The respiratory performance of climbers at extreme altitude is better than expected from sea-level chamber studies, which may, in part, explain why humans can reach the summit (8,848 m) without added oxygen. The better performance is likely to be due to more appropriate acclimatization.
Detection of adenovirus E1A DNA in pulmonary fibrosis using nested polymerase chain reaction
Authors: Kuwano K , Nomoto Y , Kunitake R , Hagimoto N , Matsuba T , Nakanishi Y , Hara N
Published: April 2003

The history of patients with idiopathic pulmonary fibrosis (IPF) shows that the disease may be preceded by a viral-like illness. Although viruses have not been demonstrated, it is possible that viruses were not detected in culture because they do not replicate during latency. We investigated the presence of adenovirus in IPF and interstitial pneumonia associated with collagen vascular disease (CVD-IP), using the nested polymerase chain reaction (PCR) and in situ hybridization (ISH) for the E1A region of the adenovirus genome. Studies were performed on lung tissues obtained by transbronchial lung biopsy from 19 patients with IPF, 10 patients with CVD-IP and, for comparison, from 20 patients with sarcoidosis. The E1A DNA was present in 3 out of 19 (16%) cases of IPF, in 5 of 10 (50%) cases of CVD-IP, and in 2 of 20 (10%) cases of sarcoidosis. The incidence of E1A DNA in CVD-IP was significantly higher than that in sarcoidosis (p<0.05). In patients with IPF and CVD-IP, E1A DNA was more prevalent in patients treated with corticosteroids (6 out of 9 cases; 67%) than in those without it (2 out of 20 cases; 10%) (p<0.01). ISH studies showed that 1 out of 8 cases of IPF and CVD-IP, in which E1A DNA was detected by PCR, was positive for E1A DNA. We conclude that adenovirus E1A is unlikely to be aetiologically involved in the pathogenesis of idiopathic pulmonary fibrosis or interstitial pneumonia associated with collagen vascular disease. However, a latent adenovirus infection may be reactivated or may newly infect the host following corticosteroid administration.
Early diagnosis of lentivirus-induced infiltrative lung disease in sheep by high resolution computed tomography
Authors: Cadore JL , Loubeyre P , Vuillermoz S , Court-Fortune I , Revel D , Mornex JF
Published: April 2003

The visna-maedi lentivirus can induce an interstitial pneumonitis in sheep, and provides a convenient example to study natural or experimental lentiviral pathology. We wanted to determine whether high resolution computed tomography (HRCT) is able to detect early morphological changes following lentiviral infection in the lungs. Spontaneously infected adult sheep (n=3) and experimentally infected lambs (n=5) were compared to uninfected controls (n=4). The HRCT scans generally showed abnormal features in infected animals, including: increased parenchymal density; alveolar oedema; thickened interlobular septa; and increased density in peribronchiolar areas. HRCT was more sensitive than chest radiography for the early diagnosis of interstitial pneumonitis, although one sheep with advanced disease and radiographic and histopathological abnormalities had a paradoxically normal scan. One control animal showed minor abnormalities on scanning, which were probably due to the procedure used for anaesthesia. The HRCT observations were confirmed by postmortem histological examination of the lungs. In conclusion, high resolution computed tomography provides a noninvasive means of following the development of lung pathology in a natural ovine model of lentiviral disease.
Higher asthma occurrence in an urban than a suburban area: role of house dust mite skin allergy
Authors: Wieringa MH , Weyler JJ , Van Bastelaer FJ , Nelen VJ , Van Sprundel MP , Vermeire PA
Published: April 2003

Understanding of geographical differences in asthma prevalence may be helpful in explaining recent increases in the occurrence of asthma. We wondered whether differences in allergic sensitization or other factors could explain differences in reported occurrence of asthma between an urban centre and a neighbouring suburban area. From the European Community Respiratory Health Survey (ECRHS) questionnaire, responses on asthma symptoms and risk factors and results of 11 skin allergy tests were available from 656 young adults living in urban or south suburban Antwerp, Belgium. Answers to five asthma questions were selected as dependent variables, and eight personal or environmental risk factors, as well as house dust mite (HDM) allergy, as independent variables. The effect of each independent variable on the association of asthma variables with area was assessed. Prior asthma diagnosis, present asthma symptoms, the selected risk factors and HDM allergy were all more frequently recorded in urban Antwerp. Difference in HDM allergy accounted for most of the difference in prior (mostly childhood) asthma diagnosis, since correction for it decreased the odds ratio from 2.10 to 1.65. On the contrary, the regional differences in recent asthma symptoms were not explained by HDM allergy differences nor by any other factor under study. This urban-suburban comparison indicated that house dust mite allergy is a major determinant of prior (childhood) asthma, whereas factors contributing to higher urban prevalence of present asthma symptoms could not be identified. Furthermore, our results indicate that it may be inappropriate to combine data from neighbouring areas, when their similarity has not been verified.
Allergen-induced release of GM-CSF and IL-8 in vitro by nasal polyp tissue from atopic subjects prolongs eosinophil survival
Authors: Park HS , Jung KS , Shute J , Roberts K , Holgate ST , Djukanovic R
Published: April 2003

Eosinophilia is a feature of nasal polyposis. The aim of this study was to determine the role of cytokines and allergen in maintaining the eosinophilic infiltrate in this condition. Polyp fragments from house dust mite (HDM)-sensitive atopic individuals and nonatopic individuals were cultured in the presence of HDM, or phytohaemagglutinin (PHA) or culture medium alone. Culture supernatants were assayed for interleukins (IL) 3, 5, and 8 and granulocyte macrophage colony stimulating factor (GM-CSF), and eosinophil survival enhancing activity (ESEA) in vitro. Significant ESEA was produced spontaneously. When polyp tissue from atopics, but not from nonatopics, was stimulated with allergen for 2 days there was a further increase in ESEA associated with a median 12 and fourfold increase in IL-8 and GM-CSF, respectively. This increased ESEA was markedly reduced with anti-GM-CSF and, to a lesser extent, anti-IL-8 blocking antibodies. When stimulated with PHA, polyp tissue from atopic subjects also produced increased ESEA, implicating possible T-cell involvement. This was associated with a small (twofold), but significant, increase in IL-8 and a less consistent increase in GM-CSF. However, anti-IL-8 or anti-GM-CSF blocking antibodies failed to reduce the ESEA in these supernatants, suggesting involvement of other mechanisms. This study suggests that in sensitized individuals, allergen may contribute to polyp eosinophilia by stimulating the production of granulocyte/macrophage colony stimulating factor and interleukin 8.
Effect of short- and long-acting inhaled beta2-agonists on exhaled nitric oxide in asthmatic patients
Authors: Yates DH , Kharitonov SA , Barnes PJ
Published: April 2003

Increased concentrations of exhaled nitric oxide (NO) occur in patients with asthma, and exhaled NO may be useful for assessing the effect of drug therapy on airway inflammation. Beta2-agonists have been proposed to have both proinflammatory and anti-inflammatory effects. We therefore assessed exhaled NO after beta2-agonists in asthmatic patients. Two randomized, double-blind, placebo-controlled studies were conducted. Firstly, exhaled NO was measured in 18 asthmatics (9 taking inhaled glucocorticosteroids (GCS)) before and after nebulized salbutamol (5 mg), or identical placebo (0.9% saline). Exhaled NO and forced expiratory volume in one second (FEV1) were measured at 15 min intervals for 1 h (Study 1). Secondly, the effect of 1 week of treatment with the long-acting beta2-agonist, salmeterol (50 microg b.i.d.), added to either budesonide (800 microg b.i.d.) or placebo, was studied in eight mild asthmatic subjects (Study 2). Exhaled NO was measured by a chemiluminescence analyser, adapted for on-line recording. In Study 1, exhaled NO showed no significant change at any time-point in patients not taking inhaled GCS. In asthmatics on inhaled GCS, exhaled NO increased compared to placebo at 15 and 30 min, but this did not reach statistical significance. In Study 2, treatment with salmeterol increased FEV1, but exhaled NO levels were not significantly changed, either after budesonide treatment (143+/-35 to 179+/-67 ppb), or after placebo (201+/-68 to 211+/-65 ppb). Our results confirm that single high dose salbutamol does not increase exhaled nitric oxide in asthmatics not taking inhaled glucocorticosteroids. Salbutamol may increase exhaled nitric oxide in asthmatics taking inhaled glucocorticosteroids. However, regular use of salmeterol resulted in no change in exhaled nitric oxide, either used alone or in combination with inhaled glucocorticosteroids.
Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil survival and GM-CSF secretion
Authors: Roca-Ferrer J , Mullol J , Lopez E , Xaubet A , Pujols L , Fernandez JC , Picado C
Published: April 2003

Topical anti-inflammatory drugs decrease eosinophil infiltration. This action may be due to an effect on the release of epithelial cell products responsible for promoting eosinophil survival. We investigated the effect of fluticasone propionate, budesonide, beclomethasone dipropionate and nedocromil sodium on the release of granulocyte/macrophage colony-stimulating factor (GM-CSF) and on eosinophil survival induced by secretions from cultured nasal epithelial cells. Human epithelial cell-conditioned media (HECM) were generated by cultured epithelial cells obtained from healthy subjects undergoing corrective nasal surgery. Normodense eosinophils isolated from peripheral blood were incubated with HECM generated with and without the drugs. All of the drugs tested inhibited eosinophil survival, and response was dose-dependent. Fluticasone propionate had the highest inhibitory potency (25% inhibitory concentration (IC25) 1x10(-9) M), followed by budesonide (IC25 3.3x10(-8) M), beclomethasone dipropionate (IC25 1.5x10(-6) M), and nedocromil sodium IC25 5x10(-6) M). Likewise, fluticasone was the strongest steroid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M), followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25 13x10(-8) M), and nedocromil sodium (IC25 >10(-5) M). A significant correlation was found between both inhibitory effects (r=0.955; p<0.05). Topical anti-inflammatory drugs may decrease eosinophil survival by abrogating the promoting effect of epithelial cells. These drugs may exert part of their therapeutic effect by modulating GM-CSF release. The following rank of potency was observed: fluticasone propionate > budesonide > beclomethasone dipropionate > nedocromil sodium. The study of the interaction between epithelial cells and eosinophils may be a useful method for investigating and comparing the potency of topical drugs.
Distribution of inhaled fluticasone propionate between human lung tissue and serum in vivo
Authors: Esmailpour N , Hogger P , Rabe KF , Heitmann U , Nakashima M , Rohdewald P
Published: April 2003

High retention of inhaled glucocorticoids in the airways means prolonged anti-inflammatory action and low delivery into the serum. The objective of this study was to investigate the retention in and distribution of inhaled fluticasone propionate (FP) between central and peripheral human lung tissue and serum in vivo. In 17 patients undergoing lung resection surgery, a single 1.0 mg dose of FP was inhaled at varying time-points (range 2.8-21.7 h) preoperatively. Peripheral and central lung tissue was obtained, and blood was drawn simultaneously. FP concentrations in central lung tissue were approximately three to four times higher than peripheral lung tissue concentrations, which in turn, exceeded those found in serum by 10 times. FP was detectable up to 21 and 16 h, respectively, after inhalation, with drug levels falling almost in parallel in peripheral lung tissue and in serum. The results of this study demonstrate that fluticasone propionate is retained in lung tissue for a long time. Serum concentrations after a single inhaled dose are low. Retention of high concentrations of fluticasone propionate in the airways may promote high topical anti-inflammatory activity.
Nedocromil sodium in obstructive airways disease: effect on symptoms and plasma protein leakage in sputum
Authors: Schoonbrood DF , Out TA , Hart AA , Habets FJ , Roos CM , Jansen HM
Published: April 2003

In patients with asthma or chronic obstructive pulmonary disease, there is chronic airway inflammation with increased leakage of plasma proteins into the airway lumen, which can be reduced by inhaled glucocorticosteroids. Nedocromil sodium is an anti-inflammatory drug, and we questioned whether it also affects the leakage of plasma proteins. In a double-blind placebo-controlled study we investigated the effect of 12 weeks of treatment with nedocromil on forced expiratory volume in one second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20), peak flow, symptom scores, and plasma protein leakage in sputum, in 31 patients with obstructive airways disease and sputum production (mean (range) FEV1 61% of predicted (42-87%); geometric mean (range) PC20 0.39 (0.04-2.9) mg x mL(-1)). As a measure for plasma protein leakage we calculated the relative coefficients of excretion (RCE) of proteins from serum to the soluble phase of sputum. There was a small increase in morning and evening peak flow (p<0.05) and a decrease in night-time bronchodilator use (p<0.02) in favour of nedocromil. The RCE of alpha2-macroglobulin to albumin significantly decreased after treatment with nedocromil (p=0.03). The results show limited clinical efficacy of nedocromil in our study group. They further suggest that the anti-inflammatory properties of nedocromil extend to inhibition of plasma protein leakage into the airways.
Prevalence and intensity of rhinoconjunctivitis in subjects with occupational asthma
Authors: Malo JL , Lemiere C , Desjardins A , Cartier A
Published: April 2003

Subjects with occupational asthma may also report symptoms of rhinoconjunctivitis. The aims of this study were: 1) to assess the prevalence of rhinoconjunctivitis in association with occupational asthma, and the severity of rhinoconjunctivitis according to the type of agent (high (HMW) and low (LMW) molecular weight agents) causing occupational asthma; and 2) to evaluate the timing of occurrence of symptoms of rhinoconjunctivitis in relation to those of occupational asthma. A questionnaire on symptoms of rhinoconjunctivitis and its timing in relation to the development of chest symptoms was prospectively addressed to 143 subjects consecutively referred to an occupational asthma clinic. Objective testing through specific inhalation challenges confirmed the diagnosis of occupational asthma in 40 subjects. Symptoms of rhinitis were reported at some time by 37 of the 40 subjects (92%), and of conjunctivitis by 29 of the 40 subjects (72%). The prevalence of symptoms was not different for HMW and LMW agents, although rhinitis was more intense for HMW (19 out of 24 subjects with three or more of the following symptoms: runny nose, itchy nose, nasal blockage, and sneezing) than for LMW (5 out of 14 subjects) (p<0.01). There were significantly fewer subjects with occupational asthma due to LMW agents, with rhinitis appearing before asthma (p=0.03). Figures for conjunctivitis showed a similar trend, but did not reach statistical significance. In conclusion, symptoms of rhinoconjunctivitis are often associated with occupational asthma. Rhinitis is less pronounced in the case of low molecular weight agents, but more often appears before occupational asthma in the case of high molecular weight agents.
Effects of repeated swine building exposures on normal naive subjects
Authors: Cormier Y , Duchaine C , Israel-Assayag E , Bedard G , Laviolette M , Dosman J
Published: April 2003

Exposure to swine confinement buildings has a negative impact on respiratory health. A short exposure to this environment results in an acute airway inflammatory response. The present study was performed to confirm and further define the acute effects of working in a swine building, and to determine whether these effects are reproducible. Seven previously nonexposed normal subjects underwent evaluations that included hourly measurement of forced expiratory volume in one second (FEV1), methacholine challenge (the provocative concentration producing a 20% fall in FEV1 (PC20)), bronchoalveolar lavage (BAL), nasal lavage (NL), and blood analyses, before (control) and after each of two 5 h exposures to a swine building environment. The exposures were conducted 8 days apart. The levels of total dust, endotoxins, and ammonia (NH3) in the confinement building were measured on each day of exposure. Both exposures resulted in a significant reduction in FEV1 (mean+/-SEM change in FEV1: control = 7+/-2%; exposure 1 = 15+/-3%; exposure 2 = 23+/-3%), decrease in PC20 (median value (25th-75th percentile): 223 (23-256), 20 (15-198) and 20 (11-71), respectively; p=0.05) and increase in BAL cells (129+/-20, 451+/-43 and 511+/-103x10(3) cells x mL(-1), respectively) and NL cells (6+/-4, 126+/-58 and 103+/-26x10(3) cells x mL(-1), respectively), mostly neutrophils. Levels of interleukin-8 (IL-8), but not interleukin-1 (IL-1) or tumour necrosis factors (TNF-alpha), increased both in BAL and nasal fluids with exposure. In normal naive subjects, repeated exposure to the environment of a swine building induced a marked and reproducible reduction in forced expiratory volume in one second, increase in airway responsiveness, and increased neutrophilic inflammatory response. These results could not be accounted for by any of the environmental factors measured.
Community-acquired pneumonia: the annual cost to the National Health Service in the UK
Authors: Guest JF , Morris A
Published: April 2003

The aim of this study was to estimate the direct annual healthcare costs to the UK National Health Service (NHS) of managing community-acquired pneumonia. Using a prevalence-based burden of illness approach, health service resource use and corresponding costs attributable to the management of community-acquired pneumonia during 1992/1993 in the UK were obtained from published sources and commercial databases, and supplemented by a telephone survey of general practitioners, finance directors, community nurses, receptionists and nurses in out-patient respiratory clinics, ambulance services, and consultant respiratory physicians. The study was appraised by a Peer Review Panel, representing a cross-section of experts from different locations. This study was a predefined subgroup analysis of a previous, larger study that estimated the annual cost to the NHS of treating all community-acquired lower respiratory tract infections. The analysis shows that there are 261,000 episodes of community-acquired pneumonia annually in the UK, costing 440.7 million pounds at 1992/1993 prices (32% of the annual cost for all community-acquired lower respiratory tract infections). Approximately 83,153 annual cases of community-acquired pneumonia are treated in hospital (32% of all episodes) and account for 96% of the annual cost. The average cost for managing pneumonia in the community is 100 pounds per episode, compared to 1,700-5,100 pounds when the patient is hospitalized, depending on the length of hospitalization. Hospitalization accounts for 87% of the total annual cost. In conclusion, community-acquired pneumonia in the UK incurs a direct healthcare cost of 440.7 million pounds annually at 1992/1993 prices. Developing and implementing strategies to prevent and minimize hospitalization will significantly reduce this annual cost and should be assessed in future studies.
Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment
Authors: De Flora S , Grassi C , Carati L
Published: April 2003

N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has been in clinical use for more than 30 yrs as a mucolytic drug. It has also been proposed for and/or used in the therapy and/or prevention of several respiratory diseases and of diseases involving an oxidative stress, in general. The objective of the present study was to evaluate the effect of long-term treatment with NAC on influenza and influenza-like episodes. A total of 262 subjects of both sexes (78% > or = 65 yrs, and 62% suffering from nonrespiratory chronic degenerative diseases) were enrolled in a randomized, double-blind trial involving 20 Italian Centres. They were randomized to receive either placebo or NAC tablets (600 mg) twice daily for 6 months. Patients suffering from chronic respiratory diseases were not eligible, to avoid possible confounding by an effect of NAC on respiratory symptoms. NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group. Frequency of seroconversion towards A/H1N1 Singapore 6/86 influenza virus was similar in the two groups, but only 25% of virus-infected subjects under NAC treatment developed a symptomatic form, versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment. Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H1N1 virus influenza infection but significantly reduced the incidence of clinically apparent disease.
Pulmonary infection with Nocardia species: a report of 10 cases and review
Authors: Menendez R , Cordero PJ , Santos M , Gobernado M , Marco V
Published: April 2003

Pulmonary nocardiosis (PN) is an infrequent and severe infection due to Nocardia spp., microorganisms that may behave both as opportunists and as primary pathogens. The aim of this study and review was to evaluate the clinical features, evolution and prognostic factors of PN. The study group comprised 10 consecutive patients with pulmonary nocardiosis acquired in a community setting, diagnosed and followed in a tertiary teaching hospital. Chronic obstructive pulmonary disease (COPD), neoplastic disease and human immunodeficiency virus (HIV) infection were the most frequent predisposing factors. Four patients were receiving corticosteroid treatment. Clinical course was chronic and diagnosis was delayed 3 weeks or more in seven of the patients. Lobar or multilobar condensation was the most frequent radiographic pattern. Antimicrobial susceptibility testing showed: 100% sensitivity for amikacin; 83% for imipenem; 71% for cefotaxime; and 71% for trimethoprim-sulphamethoxazole. The disease remained localized in the lung in five cases, with a trend toward chronicity in one with bronchiectasis. In the other five, the disease disseminated, affecting subcutaneous tissue, the central nervous system and the kidney. Three patients died, one with disseminated disease and two who were receiving corticosteroid therapy. The following conclusions were reached: 1) pulmonary nocardiosis is difficult to diagnose, diagnosis is frequently delayed and a high level of suspicion is, thus, required in patients with underlying diseases or chronic corticosteroid therapy; 2) there is frequent dissemination and high mortality; and 3) antimicrobial combinations with proven synergy, such as imipenem and amikacin, are recommended for initial therapy.
Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging
Authors: Gdeedo A , Van Schil P , Corthouts B , Van Mieghem F , Van Meerbeeck J , Van Marck E
Published: April 2003

Precise mediastinal lymph node (LN) staging is imperative in otherwise operable non-small cell lung cancer (NSCLC), as it determines subsequent treatment and possible inclusion in a neoadjuvant trial. The roles of mediastinoscopy and computed tomography (CT) remain controversial. To determine the accuracy of current CT scanners, a prospective study was performed. From April 1993 until September 1995, 100 consecutive patients with NSCLC without distant metastases underwent staging by CT and cervical mediastinoscopy. Naruke's map was used for classification, and LNs larger than 1 cm were considered CT positive. There were 91 males and 9 females, with a mean age of 64 (range 45-82) yrs. Fifty nine tumours were central and 41 peripheral, 64 right-sided and 36 left-sided. Thoracotomy with mediastinal LN sampling was performed in 74 patients, nonoperated patients having multilevel stage IIIA or stage IIIB disease. Twenty five (25%) mediastinoscopies were positive and three were false-negative (3%). There were 29 false-positive CT scans and 12 false-negative. Overall sensitivity and specificity of CT were 63 and 57%, respectively, and of mediastinoscopy 89 and 100%, respectively. Positive and negative predictive values of CT were 41 and 77%, respectively, and of mediastinoscopy 100 and 96%, respectively. Accuracy of CT was 59% and of mediastinoscopy 97%. Accuracy of CT was lowest for left-sided and centrally located tumours, and for LN station 7. Even with current computed tomography scanners, sensitivity and specificity remain low. Although overall cost may increase, routine cervical mediastinoscopy is necessary for precise staging of non-small cell lung cancer, and subcarinal lymph nodes should be routinely sampled.
Survey on the treatment of non-small cell lung cancer (NSCLC) in England and Wales
Authors: Crook A , Duffy A , Girling DJ , Souhami RL , Parmar MK
Published: April 2003

As an adjunct to a meta-analysis of chemotherapy for non-small cell lung cancer (NSCLC), a survey was conducted in England and Wales of clinicians' views on the role of chemotherapy in NSCLC and the benefits it would have to offer to lead them to change their practice. Radiotherapists, medical oncologists, surgeons and physicians specializing in thoracic medicine, and physicians of palliative medicine were asked their views on the treatment of three case histories of 65 yr old men: Case 1, resected tumour involving a hilar lymph node (tumour (T)2, node (N)1, metastasis (M)0); Case 2, tumour that had spread to mediastinal lymph nodes bilaterally (T2, N3, M0); and Case 3, metastatic cancer (M1) accompanied by minor haemoptysis. Six hundred and ninety eight (85%) of the 821 clinicians responded. For Case 1, 74% would not recommend any adjuvant treatment, 24% would recommend radiotherapy, and <1% chemotherapy, and there was little expectation that adjuvant treatment would improve survival. For Case 2, 68% would recommend radiotherapy, 11% chemotherapy, and 1% surgery, 7% recommending a combination. Adjuvant treatment, regardless of modality, was expected to improve survival. For Case 3, only 11% would recommend chemotherapy, but 26% if the patient was aged < or = 50 yrs. There was little expectation of survival beyond 1 yr, or of improving survival with chemotherapy. For all three cases, most of those not recommending chemotherapy would require it to achieve substantially improved survival for them to use it routinely. Surgery alone is currently considered sufficient for resectable non-small cell lung cancer. Chemotherapy is rarely recommended for disease of any stage.
Exercise testing in the preoperative evaluation of patients with bronchogenic carcinoma
Authors: Richter Larsen K , Svendsen UG , Milman N , Brenoe J , Petersen BN
Published: April 2003

The aim of this study was to evaluate which parameters of preoperative spirometry and cardiopulmonary exercise test are the best predictors of postoperative morbidity and mortality in patients with bronchogenic carcinoma. Ninety seven patients were prospectively and consecutively examined. All patients had preoperative maximal exercise test and dynamic spirometry. Postoperative complications and causes of death were registered. Logistic regression was used and models explaining the relationship between preoperative variables and postoperative complications and deaths were constructed. We found significant differences in preoperative maximal workload and carbon dioxide output between groups, with and without cardiopulmonary-related complications, but not in spirometry variables. Logistic regression showed maximal workload to be the only predictor of cardiopulmonary complications. Maximal oxygen uptake was predictive of cardiopulmonary deaths. Maximal oxygen uptake and forced expiratory volume were predictive of postoperative complications. A maximal oxygen uptake <50% predicted was associated with high risk of death from cardiopulmonary causes. Kaplan-Meier survival curves showed that maximal oxygen uptake was correlated to long-term survival, while spirometric variables were not. Exercise testing can be used in the preoperative evaluation of patients with nonmetastatic bronchogenic carcinoma. A combination of the results of variables from spirometry and exercise testing is proposed to be used as a preoperative criterion for operability.
Urokinase-type plasminogen activator in carcinomatous pleural fluid
Authors: Ishikawa H , Satoh H , Hasegawa S , Yazawa T , Naito T , Yamashita YT , Ohtsuka M , Ogata T , Kamma H
Published: April 2003

Urokinase-type plasminogen activator (u-PA) is known to be secreted by malignant cells during proliferation and migration, and is associated with tumour cell invasion and metastasis. This study was undertaken to evaluate whether u-PA is significantly increased in carcinomatous pleural fluids compared to those due to other aetiologies, and to identify the cells in the pleural space that are involved in its accumulation. Using an enzyme-linked immunosorbent assay, we quantified u-PA in the pleural fluid specimens of 40 patients with carcinomatous pleuritis, 18 with tuberculosis, 18 with parapneumonic pleuritis and 11 with congestive heart failure (CHF). The level of u-PA was elevated in carcinomatous pleural fluid compared with the level in transudative pleural fluid from patients with CHF (p<0.0001). The levels of u-PA were not statistically different between patients with cancer and tuberculosis, or between patients with cancer and pneumonia. The levels of u-PA in patients who did not respond to chemical pleurodesis were significantly higher than those who had complete response (p=0.0001). In immunocytochemical and immunoblotting studies, cancer cells in pleural fluids as well as mesothelial cells contained u-PA. u-PA was detected in the culture supernatants of viable pleural cells in the majority of patients with carcinomatous pleuritis. Our results suggest that local release of urokinase-type plasminogen activator by viable cells, including cancer cells and mesothelial cells, may affect the levels of urokinase-type plasminogen activator in pleural fluids.
Home assessment of activities of daily living in patients with severe chronic obstructive pulmonary disease on long-term oxygen therapy
Authors: Okubadejo AA , O'Shea L , Jones PW , Wedzicha JA
Published: April 2003

In patients with severe chronic obstructive pulmonary disease (COPD) using long-term oxygen therapy (LTOT), few studies have investigated activities of daily living (ADL). We examined the relationships between ADL, quality of life, mood state and airways obstruction in patients using long-term oxygen therapy (LTOT) and in patients not requiring LTOT. We studied 23 patients (14 males, 9 females; median age 71, range 60-84 yrs) with COPD who received LTOT using oxygen concentrators (LTOT group). We also studied a control group of 19 patients (14 males, 5 females; median age 72, range 62-75 yrs) with COPD but without severe hypoxaemia (non-LTOT group). We found no significant difference between groups in health status using the St George's Respiratory Questionnaire (SGRQ). Median Nottingham Extended Activities of Daily Living (EADL) total scores were: LTOT group 10, non-LTOT 17; (p=0.01). Significant correlations (p<0.001) with Nottingham EADL score were found for Hospital Anxiety and Depression (HAD) score (rho=0.59), SGRQ Total score (rho=0.65) and percentage predicted forced expiratory volume in one second (FEV1) (rho=0.66). In conclusion, in patients with severe chronic obstructive pulmonary disease and broadly similar health status, those using long-term oxygen therapy were less independent in activities of daily living than those not requiring long-term oxygen therapy. Reduced independence in activities of daily living is, however, associated with the extent of airflow limitation, depression and poor health status, and does not, therefore, appear to be simply a result of restriction in movements imposed by the stationary device.