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[Lung transplantation in chronic obstructive lung diseases].

Lung transplantation (uni- or bilateral) is an accepted treatment option for patients with end-stage chronic obstructive pulmonary disease. Pulmonary function improves significantly and 5-year-actuarial survival is more than 70% at acceptable early mortality rates. Careful evaluation of risks and benefits in necessary because of the known donor-organ shortage and the risks of life-long immunosuppressive treatment. The bronchiolitis obliterans syndrome is still a nonsolved problem in the long-term course after LTx and it can influence late graft function and patient survival.

Adult↗

The mitochondrial activation of silicate and its role in silicosis, black lung disease and lung cancer.

Silicate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxy-butyrate is the substrate. Uncoupling is blocked by rutamycin. Just as in the case when phosphate is combined with hydrazine, ATP, ADP, PPi, and Mg++ protect against hydrazine when silicate is combined with hydrazine. A high level of ADP in the absence of added phosphate, but in the presence of silicate, induces a pseudo state three of the mitochondria. Silicate, like sulfate and arsenate which have been reported previously, is activated by the enzymes which mediate oxidative phosphorylation. These results serve to explain a role for silicate in silicosis, black lung disease, and cancer. In addition, since there is suggestive evidence in the literature that lung tissue solubilizes asbestos fibers, these results not only expand the confluence between oxidative phosphorylation and chemical carcinogenesis but are correlated with the synergistic carcinogenicity of asbestos and smoking observed by epidemiologists.

Adenosine Diphosphate↗

Assessment of functional abnormalities in infants and children with lung disease.

Lung function testing in infants and children has to cover a wide palette of various investigational procedures and the fact that babies can predominantly only be tested asleep and young children may not cooperate accurately must be taken into account. There is still a life-span between 2 and 5 years in which lung function testing is impossible. Different techniques for infants lung function testing (spirometry, squeeze-jacket method, forced oscillation technique, occlusion technique, whole-body infant-plethysmography, multibreath nitrogen washout (MBNW), interruption technique), which helps already in early childhood to evaluate objectively clinical findings in infants after infant respiratory distress syndrome (iRDS) with/or without hyaline membrane disease (HMD), developing or not developing broncho-pulmonary dysplasia (BPD), wheezy bronchitis or cystic fibrosis (CF) are available. Lung function techniques in children include spirometry, whole-body plethysmography, multibreath nitrogen washout (MBNW), interruption technique, bronchial challenge tests, exercise testing.

Child↗

Use of beta-adrenoreceptor blockers in combination with beta-stimulators in patients with obstructive lung disease.

Lung function can be reduced not only by a non-selective beta-blocker but also by a selective beta1-receptor blocker. If both types of drug are without intrinsic sympathomimetic activity, the effect of the non-selective drug is more pronounced than that of a beta1-receptor selective drug under basal conditions. The effect of a beta2-receptor stimulating drug on the bronchi is inhibited by a non-selective drug, but much less by a selective beta1-receptor blocker. A selective beta1-receptor blocker can be used in asthmatics when it is combined with optimal anti-asthmatic therapy, while a non-selective drug is contra-indicated in patients with broncho-obstructive diseases. It is necessary to induce bronchodilatation (e.g. with a beta2-stimulator) in order to test whether or not a beta-blocker can be used in broncho-obstructive disease.

Adrenergic beta-Agonists↗

Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review was to assess the risks and benefits of administration of a diuretic acting on the loop of Henle (loop diuretic) in preterm infants with or developing chronic lung disease (CLD). Primary objectives were to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives were to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least 5 days of age were all randomly allocated to receive a loop diuretic either enterally or intravenously. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included toxicity and pulmonary mechanics (e.g., lung compliance and airway resistance). DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: The only loop diuretic used in the studies which met the selection criteria was furosemide. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants < 3 weeks of age developing CLD, furosemide administration has either inconsistent effects or no detectable effect. In infants > 3 weeks of age with CLD, a single intravenous dose of 1 mg/kg of furosemide improves lung compliance and airway resistance for 1 hour. Chronic administration of furosemide improves both oxygenation and lung compliance. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of furosemide improve lung compliance. Chronic administration of intravenous or enteral furosemide improves oxygenation. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of systemic loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. Randomized trials are needed to assess the effects of furosemide administration on survival, duration of ventilatory support and oxygen administration, length of hospital stay, potential complications and long-term outcome.

Chronic Disease↗

[Coexistence of obstructive lung diseases and lung cancer].

Connection between histological type of lung cancer and existence of clinical and spirometric symptoms of COPD was analysed in 110 lung cancer patients (64 small cell, 23 adenocarcinoma, and 23 squamous). It was shown that adenocarcinoma was significantly more frequent among subjects with values of FEV1%VC over 70 than among subjects with small cell and squamous lung cancer. Also subjects with values of FEV1% VC over 70 had significantly higher oxygen blood pressure, and clinical and radiological symptoms of COPD were less intensive than in subjects with values of this index below 70. There was no correlation between histological type of lung cancer and bronchoscopic symptoms of bronchitis and radiological symptoms of emphysema.

Adenocarcinoma↗

Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants.

BACKGROUND: Many preterm babies who survive, having had respiratory distress syndrome (RDS) or not, go on to develop chronic lung disease (CLD). This is probably due to persistence of inflammation in the lung. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established CLD. However it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES: To determine if late (> 3 weeks) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the treatment of chronic lung disease (CLD) in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment initiated at > 3 weeks of age in preterm infants with CLD were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality before discharge, failure to extubate, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), gastrointestinal bleeding, bowel perforation, echodensities on ultrasound scan of brain, need for home oxygen, glycosuria, need for late rescue with dexamethasone, cerebral palsy in survivors and blindness in survivors were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Delayed steroid treatment had no effect on mortality. The only beneficial effects were reductions in failure to extubate by 7 or 28 days, need for late rescue treatment with dexamethasone, chronic lung disease at 36 weeks, and discharge to home on oxygen therapy. There was no increase in risk of infection, necrotising enterocolitis, or gastrointestinal bleeding. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no effect on blindness. There were increases in long-term neurologic sequelae including abnormal neurologic examination and cerebral palsy, the latter of borderline statistical significance. REVIEWER'S CONCLUSIONS: The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. There is a worrying increase in adverse neurological outcomes in infants treated with postnatal steroids (see also Review of Early Postnatal corticosteroids). Corticosteroids should be reserved for infants who cannot be weaned from mechanical ventilation. The dose of dexamethasone and the duration of any course of treatment should be minimised.

Anti-Inflammatory Agents↗

Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants.

BACKGROUND: Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat CLD because of their potent anti-inflammatory effects. OBJECTIVES: To determine if postnatal corticosteroid treatment is of benefit in the prevention of chronic lung disease (CLD) in the preterm infant. This review examines the outcome of trials where preterm infants at risk of CLD were given postnatal steroids within 96 hours after birth. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Controlled Trials Register, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment within 96 hours of birth (early) in high risk preterm infants were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, failure to extubate, pulmonary air leak, survival without chronic lung disease, CLD defined at 28 days postnatal age and 36 weeks post menstrual age, patent ductus arteriosus (PDA), severe intraventricular hemorrhage (IVH), infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), gastrointestinal bleeding and longterm outcome were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Fifteen randomised controlled trials of early postnatal corticosteroid treatment of preterm babies at risk of developing CLD were identified. A meta-analysis of these trials demonstrates benefits as regards earlier extubation, decreased risks of CLD at both 28 days and 36 weeks, death or CLD at 28 days, and PDA. There was an almost significant reduction in the risk of pulmonary air leak and in death or CLD at 36 weeks in the babies treated with early corticosteroids. There were no differences in the rates of neonatal mortality, infection, severe ROP, severe IVH, NEC and pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects and the risks of hyperglycaemia and hypertension were also increased. Several adverse neurological effects were found at follow-up examinations of survivors treated with early steroids: abnormal neurological examination, cerebral palsy and developmental delay. REVIEWER'S CONCLUSIONS: The benefits of early postnatal corticosteroid treatment (< 96 hours) may not outweigh the known or potential adverse effects of this treatment. Gastrointestinal effects early in the neonatal period and neurological effects seen at follow-up mean that current use of early postnatal steroids needs to be reconsidered. There is a compelling need for the long term follow-up and reporting of late outcomes, especially neurologic and developmental outcomes, among surviving infants who participated in all randomized trials of early postnatal corticosteroid treatment. The role of inhaled steroids remains to be elucidated.

Anti-Inflammatory Agents↗

Exercise testing determines survival in patients with diffuse parenchymal lung disease evaluated for lung transplantation.

STUDY OBJECTIVES: Diffuse parenchymal lung disease is associated with a high risk of mortality despite early referral and listing for lung transplantation. We hypothesized that cardiopulmonary exercise test results and the distance walked in 6min (6MWTD) would be associated with survival in patients with diffuse parenchymal lung disease referred for lung transplantation. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: We included 51 consecutive patients with diffuse parenchymal lung disease who underwent exercise testing after referral to the Lung Transplant Program at the New York Presbyterian Hospital between January 2000 and December 2002. Thirty-three patients were listed, and 7 underwent transplantation during the study period. There were 17 deaths with 1 death post-transplantation. RESULTS: A 6MWTD < 350 m was associated with an increased risk of death (HR = 4.6, 95% CI 1.5-14.2, P = 0.009). Oxygen saturation with unloaded exercise (HR = 0.91, 95% CI 0.84-0.98, P = 0.015) and oxygen consumption at peak exercise adjusted for weight (HR = 0.88, 95% CI 0.79-0.99, P = 0.039) were also associated with the risk of death. A patient with oxygen saturation <95% during unloaded exercise had a 75% chance of dying on the list for transplantation. A patient with 6MWTD < 350 m had a 67% chance of dying on the list. CONCLUSIONS: Cardiopulmonary exercise test parameters and the 6MWTD were associated with the risk of death. Measures during exercise may be useful for determination of prognosis and for prioritizing patients with diffuse parenchymal lung disease for lung transplantation.

Adult↗