Showing papers in "European Respiratory Journal in 1998"

Pulmonary rehabilitation in chronic obstructive pulmonary disease.

Abstract: "Pulmonary rehabilitation is a process which systematically uses scientifically based diagnostic management and evaluation options to achieve the optimal daily functioning and health-related quality of life of individual patients, suffering from impairment and disability due to chronic respiratory disease as measured by clinically and/or physiologically relevant outcome parameters." This recent definition by the European Respiratory Society (ERS) task force "Rehabilitation and chronic care" [1] stresses the aims of a pulmonary rehabilitation treatment: "optimal daily functioning" and "quality of life". It also indicates that outcome parameters should be measured, and that they should be clinically and physiologically relevant. The ERS-position paper further requires that all existing treatment options available for the widest possible range of patients with chronic lung disease should be applied in rehabilitation. Components of such a programme are: exercise training; gymnastic exercise; respiratory muscle training; chest physiotherapy and breathing retraining; education; psychological counselling; nutritional therapy; ventilatory support, long-term oxygen therapy, and nursing care. Consequently, pulmonary rehabilitation is a very complex and expensive treatment, and should be performed by a team of several professionals working in close co-operation in one institute. The cost is such, that a careful selection of motivated patients, a scientifically based diagnosis and a meticulous quantification of the outcome is mandatory. The place for rehabilitation in asthma, cystic fibrosis, or in the context of lung volume reduction surgery has been outlined by several authors, but remains outside the scope of this editorial. The above suggests that the efficacy of all treatment modalities is unequivocal. This is not always true. Previously, there was an almost universal agreement that the impairment at the level of lung function can hardly be improved by rehabilitation. However, recent findings by C AS A BURI [2] showed that in patients with severe chronic obstructive pulmonary disease (COPD), the forced expiratory volume in one second (FEV1) can also improve by 9%. This seems to be a small change in FEV1, but considering the hyperbolic relationship between airway resistance and FEV1, this modest improvement in the low ranges of FEV1 means a considerable decrease in airway resistance. It is not clear how and why this change in FEV1 was brought about; it must have contributed to the improvement in exercise performance of 36%, probably by a less dynamic hyperinflation during exercise? The latter will contribute to a lower level of exercise dyspnoea [3]. Impairment of peripheral muscle function occurs in patients with COPD, due to a reduced amount of oxidative enzymes [4, 5]. Apart from the ventilatory limitation due to airway obstruction and limited respiratory muscle function, this peripheral muscle weakness substantially contributes to the exercise limitation in patients with COPD. G OS S E LI N K et al. [6] showed that the maximal oxygen consumption (V 'O2,max) and the 6 min walking distance correlated significantly with the maximal force of the quadriceps muscle. Nutritional depletion can be one of the factors in the malfunctioning of peripheral and respiratory muscles: the energy expenditure of patients with COPD often exceeds the caloric intake. Nutritional supplementation, anabolic steroids, and training can improve the function of these muscle groups, and also improve exercise performance [7, 8]. Dysfunction of peripheral muscles can be substantially reversed by training in patients with COPD. An increase in oxidative enzyme content in peripheral muscles was shown to occur after endurance training at 60% of pretreatment work loads, in patients with severe COPD (FEV1 36% pred), thus improving oxidative exercise capacity. The lactate threshold increased, and exercise hyperpnoea decreas

Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone

Abstract: Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 11 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons

Costs of asthma according to the degree of severity.

Abstract: An increase in asthma-related morbidity and mortality has been reported recently, resulting in a substantial increase in the economic impact of this condition. Little information is available relating to the costs of asthma depending on the degree of severity of the disease. Total, direct and indirect costs generated by asthma patients who sought medical care for asthma control over a one-year period in a northern area of Spain were determined. Data were obtained from the patients themselves and severity of illness was classified into mild, moderate and severe according to the International Consensus Report on Diagnosis and Treatment of Asthma, 1992. The average total annual asthma-derived cost was estimated at US$2,879 per patient, with averages of US$1,336 in mildly asthmatic patients, US$2,407 in moderate asthma and US$6,393 in severe asthma. At all levels of severity, indirect costs were twice as high as direct costs, and at the same degree of severity, direct costs due to medication and hospitalization were higher among females than males. A minority of severe asthmatics incurred some 41% of the total costs. The cost of asthma was surprisingly high and varied substantially depending on the degree of severity of the disease. Further knowledge of the costs of asthma across various levels of severity will contribute to a better characterization of optimal intervention strategies for asthma care.

Primary ciliary dyskinesia: diagnosis and standards of care

Abstract: Primary ciliary dyskinesia (PCD) is characterized by disease of the upper and lower respiratory tract, in association with visceral mirror image arrangement in 50% of cases, due to abnormal structure and/or function of cilia. The purpose of this paper is to review the clinical features, diagnosis and management of PCD. Presentations include neonatal respiratory distress, recurrent lower respiratory tract infection, chronic rhinosinusitis and male infertility. PCD enters the differential diagnosis of bronchiectasis, atypical asthma, and unusually severe upper airway disease. Diagnosis is by a cascade of investigations, starting with the saccharin test in patients older than 10 yrs; ciliary beat frequency and pattern on light microscopy; and electron microscopy to assess ciliary morphology and orientation. It is important not to confuse primary and secondary ciliary abnormalities. Nasal nitric oxide is low in PCD, and this measurement shows promise as a screening test for PCD. Diagnosis is important, in order to prevent the development of bronchiectasis and to avoid any unnecessary otorhinolaryngological procedures. Regular follow-up is essential, and management should be multidisciplinary, with input from centres with a special interest in PCD, having access to paediatric and adult chest physicians, otolaryngologists and audiological physicians, physiotherapists, counselling services and fertility clinics. The prognosis is good, but morbidity can be considerable if PCD is incorrectly managed.

Randomized controlled trial of pulmonary rehabilitation in severe chronic obstructive pulmonary disease patients, stratified with the MRC dyspnoea scale

Abstract: This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation. In this randomized, controlled study, 126 patients with chronic obstructive pulmonary disease (COPD) were stratified for dyspnoea using the Medical Research Council (MRC) dyspnoea score into MRC3/4 (Moderate) (n=66) and MRC 5 (Severe) dyspnoeic (n=60) groups. The patients were randomly assigned to an eight week programme of either exercise plus education (Exercise group) or education (Control group). Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting. Severely dyspnoeic patients were all treated at home. Those in the Exercise group received an individualized training programme. There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group, who received exercise training; baseline (mean+/-SEM) 191+/-22 m, post-rehabilitation 279+/-22 m (p<0.001). There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise. Neither group of control patients improved. Health status, assessed by the Total Chronic Respiratory Disease Questionnaire score, increased in the moderately dyspnoeic patients receiving exercise from 80+/-18 to 95+/-17 (p<0.0001) after rehabilitation. Much smaller changes were seen in the other three groups. Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea.

Pulmonary vascular disorders in portal hypertension

Abstract: The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance is elevated. Since hepatopulmonary syndrome and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the common factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in the hepatopulmonary syndrome and haemodynamic failure in portopulmonary hypertension. The severity of hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome is common after liver transplantation, which has an uncertain effect in portopulmonary hypertension. The pathophysiology of both syndromes may involve vasoactive mediators and angiogenic factors.

Reactive oxygen species in acute lung injury

Abstract: The acute respiratory distress syndrome (ARDS) in adults is associated with a wide variety of precipitating factors, often not directly involving the lung, and has an associated mortality of 50-80%. ARDS is almost invariably associated with sepsis, either as an initiating factor or as a secondary complication, which increases the expression of a number of cytokines impacting upon several cellular systems. Specifically, activation of neutrophils sequestered in the pulmonary circulation by this process, causes the release of free radicals and reactive oxygen species (ROS), increasingly regarded as key substances modulating the endothelial dysfunction and disruption responsible for the principal clinical manifestations of the syndrome. Here we discuss briefly the pathophysiology of ARDS and its impact upon pulmonary vascular control; the biological origins of free radicals and other ROS involved, the mechanisms of their damaging effects, their contribution to the modification of pulmonary vascular control mechanisms in lung injury and possible therapeutic perspectives.

Transcription factors and asthma.

Abstract: Asthma is characterized by the expression of multiple genes for inflammatory proteins, such as cytokines, enzymes, receptors and adhesion molecules. This is orchestrated by transcription factors, which are proteins that bind to the promoter regions of these genes and may be activated by inflammatory stimuli, such as cytokines. Several transcription factors are involved in asthmatic inflammation, including nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), nuclear factor of activated T-cells (NF-AT), cyclic AMP response element binding protein (CREB) and signal transduction-activated transcription factors (STAT). These transcription factors lead to coordinated expression of multiple inflammatory genes. There is increasing evidence that synergistic interaction of these transcription factors (e.g. NF-kappaB and AP-1) results in the optimal expression of particular genes, resulting in the specific inflammatory pattern seen in asthmatic airways. Transcription factors are a target for antiasthma therapy. Corticosteroids activate glucocorticoid receptors, which themselves are transcription factors, and interact with other transcription factors to inhibit their actions. The interaction between transcription factors may be important in amplifying and inhibiting the inflammatory process. Many transcription factors interact with a large co-activator molecule CREB-binding protein (CBP) that coordinates the activation of several transcription factors and controls transcription through the regulation of deoxyribonucleic acid coiling around histone residues in the chromatin structure. Understanding transcription factors in asthma has given new insights into the complex chronic inflammatory process, the mechanism of action of corticosteroids, and may lead to new approaches to therapy in the future.

Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease

Abstract: Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD). Although the precise sequence of events that leads a smoker to experience airway obstruction is not completely clear, airway inflammation is a relevant factor. To investigate airway inflammation, 12 nonatopic smoking COPD patients with a forced expiratory volume in one second (FEV1) < or = 75% predicted and 10 normal nonsmoking subjects (NS) were studied with bronchoscopy and bronchial lavage (BL). Serum immunoglobulin (Ig)E levels of COPD patients correlated with the smoking history (r=0.7, p=0.008). In BL of COPD patients there was an increase of neutrophils (median, range) (COPD 62.6x10(3), 1.2-323, NS 1.35, 0-19.2, p=0.001), eosinophils (COPD 1.6, 0-6.9, NS 0.15, 0-3.7, p=0.035), the levels of interleukin (IL)-8 (COPD 1079 pg x mL(-1), 121-2,500, NS 20.4, 7.2-59, p=0.001), myeloperoxidase (MPO) (COPD 752 microg x L(-1), 11-5,500, NS 22.1, 8-70, p=0.001) and eosinophil cationic protein (ECP) (COPD 21.5 microg x L(-1), 1.8-161, NS 2, 1.8-4.9, p=0.001). Significant correlations were found in BL of COPD patients between IL-8 and neutrophils (p=0.02), MPO and neutrophils (p=0.02), IL-8 and MPO (p=0.0001) and ECP and eosinophils (p=0.02). In addition, the ratios between the BL levels of MPO and the number of neutrophils and between ECP levels and eosinophils were higher in COPD patients than in NS (p=0.03 and 0.01, respectively). These data suggest that cigarette smoke is associated with increased amounts of airway interleukin-8, a chemotactic factor for neutrophils and eosinophils. Recruited neutrophils and eosinophils are activated and they release increased amounts of inflammatory mediators capable of damaging the bronchial tissue.

Thoracoscopy--state of the art

Abstract: "Medical" thoracoscopy as compared with "surgical" thoracoscopy (which is more precisely known as video-assisted thoracic surgery (VATS)) has the advantage that it can be performed under local anaesthesia or conscious sedation, in an endoscopy suite, using nondisposible rigid instruments. Thus, it is considerably less invasive and less expensive. The main diagnostic and therapeutic indications for medical thoracoscopy are pleural effusions and pneumothorax. Due to its high diagnostic accuracy, approaching almost 100% in malignant and tuberculous pleural effusions, it should be used when pleural fluid analysis and needle biopsy are nondiagnostic. In addition, medical thoracoscopy provides staging for lung cancer and diffuse malignant mesothelioma. Talc poudrage, as the best conservative method for pleurodesis in 1998, can also be performed with medical thoracoscopy. It can also be effectively used in the early management of empyema. In spontaneous pneumothorax it allows staging, thereby facilitating treatment decisions, and in addition coagulation of eventual blebs and talc poudrage for efficient pleurodesis. Medical thoracoscopy is a safe procedure which is even easier to learn than flexible bronchoscopy. Due to its high diagnostic and therapeutic efficiency, it should be applied increasingly in the management of the above-mentioned pleuropulmonary diseases.

Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP

Abstract: Based on past difficulties in clinically differentiating patients with idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans-organizing pneumonia (BOOP), and nonspecific interstitial pneumonia/fibrosis (NSIP), which all manifest clinically as interstitial lung disease, experience with pathologically confirmed examples of the three diseases was reviewed to compare clinical profiles and prognosis and to define NSIP more clearly. Thirty-one patients (15 males and 16 females) were pathologically identified as NSIP and subclassified into either the cellular (n=16) or fibrotic group (n=15). All 31 patients were clinically considered to be idiopathic NSIP cases. Patients with idiopathic BOOP (n=16) and IPF (n=64) were compared with the NSIP patients. Subacute presentation of interstitial lung disease characterized both idiopathic NSIP and idiopathic BOOP. NSIP patients showed volume loss on a chest radiograph (29.0%) and honeycombing on a computed tomography scan (25.8%); these features were not found in BOOP patients. Bronchoalveolar lavage lymphocytosis was characteristic of both BOOP and NSIP. Two subgroups of NSIP can be recognized histologically: patients in the fibrotic group had a less favourable outcome than those in the cellular group. BOOP and NSIP had a more favourable outcome than IPF. In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopathic interstitial pneumonia, both pathologically and clinically.

Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients.

Abstract: Primary pulmonary hypertension (PPH) is characterized by intimal fibrosis and cell proliferation (including fibroblasts, smooth muscle and endothelial cells) in the distal pulmonary arterial tree. Considerable interest has been generated by recent reports of PPH in human immunodeficiency virus (HIV)-1-infected individuals. Although the lack of evidence for a pulmonary artery infection has suggested that in such cases HIV may act through mediator release rather than by direct endothelial infection, the mechanisms underlying HIV-associated PPH remain poorly defined. Platelet-derived growth factor (PDGF) has the ability to induce smooth muscle cell and fibroblast proliferation and migration. Given these considerations, we have attempted to document a possible role for PDGF in PPH occurring in HIV seropositive and seronegative patients. Using semiquantitative polymerase chain reaction (PCR), PDGF A-chain messenger ribonucleic acid (mRNA) expression was analysed in surgical lung biopsies from 13 HIV seronegative patients and one HIV seropositive patient, all displaying severe PPH. In parallel, lung samples from two patients with HIV-1-associated PPH were studied by immunohistochemistry and in situ hybridization. Results were compared to those obtained in three HIV-1-infected individuals with no pulmonary complication (as demonstrated by clinical, radiological, bacteriological, and necropsy findings) and five control lung biopsies. As compared to controls, PDGF A-chain mRNA expression is elevated in lung biopsies from patients displaying PPH (p=0.029). In HIV-1-associated PPH, interstitial perivascular cells expressing PDGF A-chain mRNA and protein could be detected by in situ hybridization and immunohistochemistry, respectively. Platelet-derived growth factor expression is elevated in lung biopsies of patients displaying primary pulmonary hypertension. Growth factors such as platelet-derived growth factor may play a part in the initiation and/or progression of primary pulmonary hypertension.

References values for forced spirometry. Group of the European Community Respiratory Health Survey

Abstract: The European Coal and Steel Community (ECSC) prediction equations exemplify a significant effort carried out approximately 15 yrs ago to provide uniform standards for lung function testing, but this set of equations has not been properly validated as yet. The present study evaluates the ECSC reference values and four other sets of prediction equations, using spirometric data collected in 12,900 nonasthmatic subjects (43% lifetime nonsmokers and 36% active smokers) aged 20-44 yrs from the European Community Respiratory Health Survey (ECRHS). Standardized spirometric measurements were obtained using a common protocol in 34 centres in 14 countries. For each prediction equation, the prediction deviations (i.e. observed minus predicted value) for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined for the whole study population and for each centre. For the age range included, the errors about the ECSC equations showed the most prominent underestimation of both predicted FVC (+355 and +360 mL on average in males and females, respectively) and predicted FEV1 (+211 and +200 mL, respectively) among the five studies examined. As expected, FVC and FEV1 in active smokers from the ECRHS were significantly lower than in lifetime nonsmokers (each p<0.01). We conclude that the present European recommendations on lung function reference values should be reconsidered, but further data for nonsymptomatic subjects above the age of 44 yrs are needed.

Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension

Abstract: In a subset of patients with primary pulmonary hypertension (PPH), high doses of oral calcium-channel blockers (CCB) produce a sustained clinical and haemodynamic improvement. However, significant side-effects have been reported during acute testing with CCB. Therefore, to identify accurately patients who may benefit from long-term CCB therapy, there is a need for a safe, potent and short-acting vasodilator. The aim of this study was to compare the acute response to inhaled nitric oxide (NO) and oral high doses of CCB in 33 consecutive patients with PPH. A significant acute vasodilator response was defined by a fall in both mean pulmonary artery pressure and total pulmonary resistance by >20%. Ten patients responded acutely to NO, nine of whom responded acutely to CCB, without any complications. The 23 other patients failed to respond to NO and CCB. In these nonresponders, nine serious adverse events were observed with CCB (38%). There was no clinical or baseline haemodynamic feature predicting acute vasodilator response. Long-term oral treatment with CCB was restricted to the nine acute responders and a sustained clinical and haemodynamic improvement was observed in only six patients. In primary pulmonary hypertension, the acute response rate to high doses of calcium-channel blockers is low (27%). Serious adverse reactions to high doses of calcium-channel blockers during acute testing are frequently observed in nonresponders. It is concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who respond acutely to calcium-channel blockers and may benefit from long-term treatment with these agents.

Pulmonary fibrosis: cytokines in the balance

Abstract: Pulmonary fibrosis can complicate diverse pulmonary and systemic pathologies. In many cases the underlying cause remains unidentified. Mortality from the disease is increasing steadily in the UK and USA. The clinical features are well-described, but patients frequently present at an advanced stage, and current treatments have not improved the poor prognosis. There is a compelling need to identify the fibrotic process earlier and to develop new therapeutic agents. Increased collagen deposition is central to the pathology and interest over the last decade has focused on the role of cytokines in this process. These polypeptide mediators are believed to be released from both circulating inflammatory and resident lung cells in response to endothelial and epithelial injury. Key cytokines currently implicated in the fibrotic process are transforming growth factor-beta, tumour necrosis factor-alpha and endothelin-1. This article outlines the evidence implicating these mediators in the pathogenesis of pulmonary fibrosis and also considers the possible role of cytokines with antifibrotic effects, such as interferon-gamma. The "balance" of positively and negatively regulating cytokines is discussed, and the potential for interaction with other factors including viruses, hormones and altered antioxidant status is also considered. Finally, potential novel therapeutic approaches are discussed, together with suggestions for future studies and clinical trials. As the outcomes of different avenues of research over the last ten years are brought together, it is clear that there is now a hitherto unrivalled opportunity to begin to tackle the treatment of this devastating disease.

Guidelines for management of adult community-acquired lower respiratory tract infections

Abstract: The management of a community-acquired lower respiratory tract infection (LRTI) should follow a systematic step-by-step process (fig. 1), beginning with a detailed history and clinical examination. Attempts to identify the type of LRTI (pneumonia, acute bronchitis, superinfection of chronic bronchitis, or viral infection) are probably unhelpful outside hospital, since several studies have demonstrated that the sensitivity and specificity of clinical signs and symptoms are low for establishing such a classification. Therefore, the main goal of initial clinical evaluation is to determine whether the patient can be managed at home or whether there is evidence that suggests potential or immediate severity, or that the illness will follow a complicated course (table 1, fig. 2). All these features will guide the decision on hospital referral and admission (fig. 2).

Chronic Chlamydia pneumoniae infection and asthma exacerbations in children

Abstract: This study was undertaken to investigate the reported association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and the expression of asthma-related symptoms. One hundred and eight children with asthma symptoms, aged 9-11 yrs, completed a 13 month longitudinal study. The children maintained a daily diary of respiratory symptoms and peak flow rates. When respiratory symptoms were reported an investigator was called and a nasal aspirate obtained. In total 292 episodes were reported. After the study 65 children provided samples when asymptomatic. The presence of infection was investigated by the polymerase chain reaction for C. pneumoniae and M. pneumoniae and C. pneumoniae secretory immunoglobulin A (IgA) was detected by amplified enzyme immunoassay. C. pneumoniae detections were similar between the symptomatic and asymptomatic episodes (23 versus 28%, respectively). Children who reported multiple episodes also tended to remain PCR positive for C. pneumoniae suggesting chronic infection (p< 0.02). C. pneumoniae-specific secretory-IgA antibodies were more than seven times greater in subjects who reported four or more exacerbations in the study compared to those who reported just one (p<0.02). M. pneumoniae was found in two of 292 reports and in two of 65 asymptomatic samples. In conclusion, chronic Chlamydia pneumoniae infection is common in schoolage children and immune responses to C. pneumoniae are positively associated with frequency of asthma exacerbations. We suggest that the immune response to chronic C. pneumoniae infection may interact with allergic inflammation to increase asthma symptoms. In contrast Mycoplasma pneumoniae was not found to be important in this study.

Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression

Abstract: This investigation studied the general conditions and prognostic factors of pulmonary epithelioid haemangioendothelioma (PEH), which is a rare disease. Twenty-one patients were collected throughout Asia by a questionnaire. Age at the detection or onset of symptoms of PEH was 14-64 yrs (mean 44 yrs). Males were more likely to be detected by symptoms (4/8, 50%) than were females (1/13, 8%). Fifteen showed bilateral multiple nodular opacities. Partial spontaneous regression occurred in three asymptomatic patients (one male and two females, all with bilateral multiple nodular opacities) 5, 13 and 15 yrs after detection. Two of the three patients with pleural effusion died within 1 yr, while the 16 patients with no effusion were alive more than 1 yr later (p<0.05). Histologically, two patients with fibrinofibrous pleuritis and extrapleural proliferation of tumour cells died within 2 yrs, while only one of 14 patients lacking such manifestations died within the same period (p<0.05). All three patients without spindle tumour cells survived for 12 yrs after the diagnosis, while all four patients with such cells died during the same period (p<0.05). In conclusion, 21 patients with pulmonary epithelioid haemangioendothelioma were reported, of whom three demonstrated partial spontaneous regression, and adverse prognostic features were identified.

Noninvasive pressure support ventilation in COPD patients with postextubation hypercapnic respiratory insufficiency

Abstract: Patients with chronic obstructive pulmonary disease (COPD) who have been intubated and mechanically ventilated may prove difficult to wean. Noninvasive ventilation may be used in an attempt to avoid new endotracheal intubation. The efficacy of administration of noninvasive pressure support ventilation was evaluated in 30 COPD patients with postextubation hypercapnic respiratory insufficiency, compared with 30 historically matched control patients who were treated conventionally. Patients were included in the study if, within 72 h postextubation, they presented with respiratory distress, defined as the combination of a respiratory frequency >25 breaths x min(-1), an increase in the arterial carbon dioxide tension (Pa,CO2) of at least 20% compared with the value measured after extubation, and a pH <7.35. Noninvasive pressure support ventilation was effective in correcting gas exchange abnormalities. The use of noninvasive ventilation significantly reduced the need for endotracheal intubation: 20 of the 30 patients (67%) in the control group required endotracheal intubation, compared with only six of the 30 patients (20%) in the noninvasive-ventilation group (p<0.001). In-hospital mortality was not significantly different between the two groups, but the mean duration of ventilatory assistance for the treatment of the postextubation distress, and the length of intensive care unit stay related to this event, were both significantly shortened by noninvasive ventilation (p<0.01). In conclusion, noninvasive ventilation may be used in the management of patients with chronic obstructive pulmonary disease and postextubation hypercapnic respiratory insufficiency.

Effect of salbutamol on dynamic hyperinflation in chronic obstructive pulmonary disease patients

Abstract: Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1 <10% pred). In conclusion, patients with chronic obstructive pulmonary disease and expiratory flow limitation, even if nonresponders in terms of forced expiratory volume in one second, may benefit from bronchodilators because they can breathe, still in a flow-limited manner, at a lower lung volume.

Sarcoidosis: immunopathogenetic concepts and their clinical application

Abstract: Our understanding of the immunopathogenesis of sarcoidosis has been advanced by studies of bronchoalveolar lavage cells. Activated macrophages and T-cells have been identified in different compartments of the sarcoid lung and the characteristics of the activation suggest that the cells become activated in the course of a normal immune response. The immune cells communicate via a cytokine network and the measuring of cytokine levels yields subgroups of sarcoidosis patients with different courses of the disease indicating different states of activation of the disease-mediating immune cells. The causative agent of sarcoidosis has not yet been identified; however, some of the described mechanisms can be clinically applied either to detect patients at risk of deterioration or to develop new therapeutic strategies. Using these approaches methotrexate, pentoxifylline and thalidomide have been identified as drugs which effectively suppress sarcoid inflammation and the serum level of soluble interleukin-2 receptors has been delineated to be a serum marker of sarcoid inflammation. Furthermore, analysing the pulmonary cytokine network in sarcoidosis will yield new staging parameters possibly supplying prognostic information and guiding therapeutic intervention.

Subjective scoring of cough in children: parent-completed vs child-completed diary cards vs an objective method

Abstract: Cough is often used as an outcome measure, although the reporting of cough is unreliable. Using a 24 h ambulatory cough meter to measure cough frequency, the aim of this study was to compare: 1) the correlation of child-completed diary cards to the objective measurement, with that of parent-completed diary cards; and 2) the visual analogue scale (VAS) to the verbal category descriptive (VCD) score. The cough meter consisted of a previously validated Holter monitor and a cough processor. Eighty four children (39 with recurrent cough and 45 controls, aged 6-17 yrs) used a cough meter at least once. Thirty three subjects used the cough meter twice. Parents and children completed separate diary cards using the VAS and VCD scores. The strength of the relationship between the subjective scores and the objective recordings was analysed by spearman's rank correlation coefficient. For daytime cough, child-completed diary cards and the VCD correlated better to the objective measurement than parent-completed diary cards and the VAS, respectively. In subjects that used the cough meter twice, the difference between the cough frequency correlated to the difference in the subjective scores. The confidence intervals for the correlation coefficients were wide. The agreement between the objective and subjective presence of daytime cough was good but that for night-time cough was poor. We conclude that the severity of cough defined on diary cards may not represent cough frequency. Objective readings are first choice but currently not yet practical. The verbal category descriptive diary card completed by children and assisted by parents has the highest correlation to cough frequency measured objectively.

Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe

Abstract: There is evidence that the prevalence of allergies and asthma differs between populations in western and eastern Europe. This study investigated the prevalence of wheezing, rhinitis and eczema among schoolchildren in urban and rural areas of Scandinavia and the formerly socialist countries of Eastern Europe. A total of 79,000 children from two age groups (13-14 yrs and 6-7 yrs) in 18 study centres responded to a questionnaire within the International Study of Asthma and Allergy in Children (ISAAC). The 12 month period prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema was calculated. The prevalence of wheezing among the 13-14 yr old children was 11.2-19.7% in Finland and Sweden, 7.6-8.5% in Estonia, Latvia and Poland and 2.6-5.9% in Albania, Romania, Russia, Georgia and Uzbekistan (except Samarkand). The prevalence of itching eyes and flexural dermatitis varied in a similar manner between the three regions. The regional differences were less pronounced among the 6-7 yr old children in the seven participating centres. The highest prevalence of rhinitis was recorded in April-July in Scandinavia and during the winter months in the other countries. The prevalence of atopy-related disorders was higher in Scandinavia than in Estonia, Latvia and Poland, which in turn had a higher prevalence than five other countries of eastern Europe with a culture less similar to western Europe. This supports the hypothesis that "Western life style" is associated with a high prevalence of childhood allergy.

Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children

Abstract: We assessed the clinical and biochemical effects in asthmatic children of fish oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty acids. Thirty nine asthmatic children aged 8-12 yrs participated in a double-blind, randomized, controlled trial for 6 months during which they received fish oil capsules plus canola oil and margarine (omega-3 group) or safflower oil capsules plus sunflower oil and margarine (omega-6 group). Plasma fatty acids, stimulated tumour necrosis factor alpha (TNFalpha) production, circulating eosinophil numbers and lung function were measured at baseline and after 3 and 6 months of dietary modification. Day and night symptoms, peak flow rates and medication use were recorded for 1 week prior to laboratory visits. Plasma phospholipid omega-3 fatty acids were significantly greater in the omega-3 group at 3 and 6 months compared to the omega-6 group (p<0.001). In the omega-3 group TNFalpha production fell significantly compared with baseline (p=0.026), but the magnitude of change between groups did not reach significance (p=0.075). There were no significant changes in clinical outcome measures. Dietary enrichment of omega-3 fatty acids over 6 months increased plasma levels of these fatty acids, reduced stimulated tumour necrosis factor alpha production, but had no effect on the clinical severity of asthma in these children.

Heart block in patients with obstructive sleep apnoea: pathogenetic factors and effects of treatment

Abstract: Heart block during sleep has been described in up to 10% of patients with obstructive sleep apnoea. The aim of this study was to determine the relationship between sleep stage, oxygen desaturation and apnoea-associated bradyarrhythmias as well as the effect of nasal continuous positive airway pressure (nCPAP)/nasal bi-level positive airway pressure (nBiPAP) therapy on these arrhythmias in patients without electrophysiological abnormalities. Sixteen patients (14 males and two females, mean age 49.6+/-10.4 yrs) with sleep apnoea and nocturnal heart block underwent polysomnography after exclusion of electrophysiological abnormalities of the sinus node function and atrioventricular (AV) conduction system by invasive electrophysiological evaluation. During sleep, 651 episodes of heart block were recorded, 572 (87.9%) occurred during rapid eye movement (REM) sleep and 79 (12.1%) during nonrapid eye movement (NREM) sleep stages 1 and 2. During REM sleep, the frequency of heart block was significantly higher than during NREM sleep: 0.69+/-0.99 versus 0.02+/-0.04 episodes of heart block x min(-1) of the respective sleep stage (p<0.001). During apnoeas or hypopnoeas, 609 bradyarrhythmias (93.5%) occurred with a desaturation of at least 4%. With nCPAP/ nBiPAP therapy, apnoea/hypopnoea index (AHI) decreased from 75.5+/-39.6 x h(-1) to 3.0+/-6.6 x h(-1) (p<0.01) and the number of arrhythmias from 651 to 72 (p<0.01). We conclude that: 1) 87.9% of apnoea-associated bradyarrhythmias occur during rapid eye movement sleep; 2) the vast majority of heart block episodes occur during a desaturation of at least 4% without a previously described threshold value of 72%; and 3) nasal continuous positive airway pressure or nasal bi-level positive airway pressure is the therapy of choice in patients with apnoea-associated bradyarrhythmias.

Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy.

Abstract: Under the clinical impression that patients with chronic obstructive pulmonary disease (COPD) may demonstrate signs compatible with hypogonadism, we investigated whether oral glucocorticoid therapy is associated with testosterone deficiency. Thirty six men with COPD of whom 16 were receiving oral glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were investigated in a cross-sectional cohort study. Patients with or without oral glucocorticoid therapy were not different in terms of age, smoking history and additional therapy. Vital capacity, forced expiratory volume in one second, airway resistance, intrathoracic gas volume and blood gases at rest were not different between the groups. However, patients receiving glucocorticoids had a shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02) compared to patients without oral steroid therapy. Serum levels of testosterone (mean+/-SEM 13.7+/-0.9) were below normal (<12 nM) in 15 of 36 patients. Serum testosterone did not correlate with any other evaluated parameter. Serum levels of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of the 36 patients, including all patients receiving glucocorticoid treatment. In the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index (r=0.241; p=0.037). All other parameters examined revealed no significant correlations in multiple regression analysis. Glucocorticoid treatment appears to aggravate hypogonadism and a therapeutic study using testosterone in patients with chronic obstructive pulmonary disease receiving glucocorticoid medication appears warranted.

Functional evaluation of the lung resection candidate

Abstract: Advances in operative technique and perioperative care have considerably reduced surgical morbidity and mortality after pulmonary resections. Various single and combined parameters of functional operability have been proposed to assess the surgical risk. Pulmonary function tests adequately assess the pulmonary risk, and baseline or stress electrocardiography, echocardiography and nuclear cardiac studies assess the cardiac risk. Patients with normal or only slightly impaired pulmonary function (forced expiratory volume in one second (FEV1) and transfer factor of the lung for carbon monoxide (TL,CO) > or = 80% of predicted) and no cardiovascular risk factors can undergo pulmonary resections up to a pneumonectomy without further investigation. For others, exercise testing, pulmonary split-function studies, or a combination of these two methods are recommended. Exercise testing, most frequently performed as a symptom-limited test with the measurement of maximal oxygen uptake (V'O2,max), assesses both the pulmonary and cardiovascular reserves. A V'O2,max of 20 mL.kg(-1).min(-1) or >75% of predicted normal, safe for major resections. Split-function studies are radionuclide-based estimations of the predicted postoperative (ppo) values of various parameters. The currently used ppo-parameters are FEV1-ppo, TL,CO-ppo and, most recently, V'O2,max-ppo. Suggested cut-off values for safe resection are: for FEV1-ppo and TL,CO-ppo > or = 40% pred; and for V'O2,max > or = 35% pred, combined with an absolute value of > or = 10 mL.kg(-1).min(-1). The lowest acceptable ppo-values will still have to be established by additional prospective studies. In the long-term, resections involving not more than one lobe usually lead to an early functional deficit followed by later recovery. The permanent functional loss in pulmonary function is small (< or = 10%) and exercise capacity is only slightly reduced or not at all. Pneumonectomy, on the other hand, leads to an early permanent loss of about 33% in pulmonary function and 20% in exercise capacity. Thus, pulmonary function tests alone overestimate the functional loss after lung resection.

Standardized tuberculosis treatment outcome monitoring in Europe. Recommendations of a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) for uniform reporting by cohort analysis of treatment outcome in tuberculosis patients

Abstract: Consensus-based recommendations have been developed by a Working Group of the World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis (TB) treatment outcome data in countries in Europe. The main purpose of treatment monitoring is to find out how many of the potential infectious TB patients notified were declared cured at the end of treatment. Following the uniform case definitions as defined in 1996, emphasis is placed on cohort analysis of definite cases of pulmonary TB. The Working Group recommends using a minimal set of six mutually exclusive categories of treatment outcome: cure, treatment completed, failure, death, treatment interrupted, and transfer out. More detailed subsets may be chosen. Treatment outcome is expressed as a percentage of the total number of cases notified. Analysis should be separate for new and retreatment cases. Treatment outcome data have to be collected at the local level and passed on to regional and national authorities on an ongoing basis. Evaluation of treatment results becomes, preferably, an inbuilt component of national monitoring of programme performance. Because of the long duration of treatment, it is recommended that analysis is carried out in the first quarter of the calendar year that follows a full year after the last patient was enrolled. Feedback is essential. Treatment outcome results should become an inseparable part of the annual report on tuberculosis.

Malignant pleural mesothelioma

Abstract: The incidence of malignant pleural mesothelioma (MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now, no single treatment has been proven to be effective and death usually occurs within about 12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has incited little interest. However, certain forms may have a better prognosis when diagnosed early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological analysis of samples obtained by thoracoscopy. This procedure allows the best staging of the pleural cavity with an attempt to detect visceral pleural involvement, which is one of the most important prognostic factors. Although radiotherapy seems necessary and is efficient in preventing the malignant seeding after diagnostic procedures in patients, there has been no randomized phase III study showing the superiority of any treatment compared with another. However, for the early-stage disease (stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodal treatment combining surgery, radiotherapy and chemotherapy should be proposed for a randomized controlled study. Palliative treatment is indicated for stage IV. In any case, each patient should be enrolled in a clinical trial.

Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages

Abstract: Nitric oxide (NO) plays an important role in resistance to Mycobacterium tuberculosis infection. Our aim was to determine whether inducible NO synthase (iNOS) expression and generation of reactive nitrogen intermediates (RNI) by alveolar macrophages (AM) are increased in patients infected with M. tuberculosis. NO levels in the exhaled air of 19 active pulmonary tuberculosis (TB) and 14 control subjects were measured using a chemiluminescence NO analyser. The expression of iNOS on AM was studied by labelling AM with anti-mac iNOS polyclonal antibody analysed with a flow cytometer. The spontaneous generation of RNI by cultured AM was also measured. Data are presented as mean+/-SEM. The level of NO in exhaled air was higher in patients with active TB (16.2+/-1.2 parts per billion (ppb)) compared to control subjects (6.5+/-0.9 ppb), p<0.0001. Exhaled NO decreased with anti-TB treatment. Compared to control subjects (29.0+/-4.5 fluorescence intensity (FI)), iNOS expression on AM was upregulated in TB patients (86.3+/-12.5 FI) p<0.001 and the capacity for spontaneous generation of nitrite was enhanced. Nitrite production was inhibited by N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of iNOS. The expression of iNOS on AM was related to the concentration of exhaled NO (r=0.66, p<0.001) and the nitrite generation capacity of AM (r(s)=0.77, p<0.001). We conclude that the increase in exhaled nitric oxide observed in patients with active pulmonary tuberculosis is due to an upregulation of inhaled NO synthase expression in alveolar macrophages which have an enhanced capacity for nitric oxide production.