Very low birth weight survivors have reduced peak bone mass and reduced insulin sensitivity.

CONTEXT: Increasing numbers of very low birth weight (VLBW) infants are surviving into adulthood because of improvements in neonatal intensive care. Adverse events in early life can have long-term effects through reprogramming of metabolic systems. OBJECTIVE: To determine whether young adult VLBW survivors have abnormalities of skeletal development or endocrine function. DESIGN: Cross-sectional, observational, case-control study. PARTICIPANTS: Thirty-seven VLBW subjects and 27 healthy controls at peak bone mass (mean age 23). MEASUREMENTS: Differences between cases and controls in body size, body composition, bone mass and bone geometry [assessed by dual-energy X-ray absorptiometry (DXA), hip structure analysis and peripheral quantitative computed tomography (pQCT)], bone turnover [urine N-terminal telopeptide of type I collagen (NTX), serum C-terminal telopeptide of type I collagen (CTX)], aminoterminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase), hormones (sex steroids, IGF-1, PTH and 25-OH vitamin D) and insulin sensitivity (HOMA-IR and oral glucose tolerance testing). RESULTS: VLBW subjects had lower bone density at the lumbar spine (5.7%) and femoral neck (8.6%), which persisted after correction for bone size by the estimation of volumetric density (bone mineral apparent density). Urine NTX was higher in VLBW subjects than in controls, but there were no significant differences in other bone turnover markers. VLBW survivors had lower insulin sensitivity (mean INS-30 controls = 57.0, VLBW subjects = 94.3, P < 0.01), but there were no differences in whole body fat mass or truncal fat mass between VLBW subjects and controls. CONCLUSIONS: Young adult VLBW survivors have reduced bone density for their bone size and reduced insulin sensitivity, which may have significant implications for their risk of fracture and diabetes in later life.

Methacholine challenge in pre-school children--which outcome measure?

The aim of our study was to evaluate the utility of interrupter resistance (R(int)), transcutaneous oximetry and auscultation as outcome measures for a recently suggested tripling-dose methacholine (Mch) challenge in pre-school children. We studied 57 children aged 3-6 years. R(int) was measured at baseline and after each Mch dose. Oxygen saturation (SaO(2)) and transcutaneous oxygen pressure (tcpO(2)) were monitored during the challenge. Mch concentrations of 0.22, 0.66, 2.0, 6.0 and 18.0 mg/ml were nebulised during tidal breathing. The challenge was terminated if there was wheeze, SaO(2) below 91% or persistent cough; this final Mch dose was considered as PCW. Nine healthy children, 17 with cough and 25 with wheeze performed the study up to the point of PCW or all five Mch inhalations. If a change of 20% of predicted R(int) or termination by wheeze, desaturation or cough is taken as a completed test, then 39 out of 51 children (78%) had adequate R(int) measurements on each occasions from start to completion. The success rate for tcpO(2) measurements was similar: 38 out of 51 (76%) had complete tcpO(2) data until a 15% fall of tcpO(2) or clinical endpoint was reached. Using the above-mentioned cut-off levels significant change in R(int) or tcpO(2) preceded PCW in most of the cases. Both R(int) and tcpO(2) measurements may allow detection of bronchial hyper-responsiveness at lower Mch doses and also provide a less subjective measure, but will not be feasible in all children.

Feasibility of shortened methacholine challenge in preschool children.

The aim of our study was to assess the feasibility and safety of a recently suggested tripling-dose methacholine (Mch) challenge in preschool children. Fifty-seven children aged 3-6 years were studied. Mch challenge was carried out using a tidal breathing method, with concentrations of 0.22, 0.66, 2.0, 6.0, and 18.0 mg/ml, at 5-min intervals, given by a Pari Turbo Boy compressor and Pari LC Plus nebulizer, for 1 min only. Oxygen saturation (SaO(2)) was monitored during the challenge. The challenge was terminated if there was wheeze, SaO(2) below 91%, or persistent cough. This final Mch dose was considered the provocative concentration inducing audible wheeze (PCW). Nine healthy children, 17 with cough and 25 with wheeze, completed the study. Mean output from nebulizers (SD) in these 51 children was 0.30 (0.05) ml/min. Geometric means for PCW in these groups were 2.88, 2.58, and 1.28 mg/ml Mch, respectively. The wheezing children were significantly more hyperresponsive than the coughing children (P < 0.05). A tripling-dose Mch protocol is safe and practicable in children over 3 years of age. A further reduction in nebulized dose may be needed for a more discriminatory test.

Aerosolized 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 is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are 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 Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006). In addition, we hand searched several abstract books of national and international American and European Societies. The search of MEDLINE and of CENTRAL was last updated in March 2006. SELECTION CRITERIA: For the purpose of this analysis, we included trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included need for ventilator support, chronic lung disease, mortality and other important clinical outcomes. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. 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: We identified eight studies that met selection criteria. 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. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. AUTHORS' CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence.More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g., washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Reduced vital capacity in insulin-dependent diabetes.

Spirometry was performed on 88 children with insulin-dependent diabetes mellitus (IDDM) and 216 healthy controls living in Sheffield. Children with IDDM had significantly lower percentage predicted forced vital capacity (FVC) than did control children or reference norms. There was no evidence that the reduced FVC was confined to a subgroup of children, and there was no correlation with duration of IDDM or glycemic control. A longitudinal study of 27 children with IDDM did not show progressive deterioration in percentage predicted FVC with age. These findings suggest that a tendency toward reduced lung volumes exists in IDDM and may not be a direct result of the metabolic disturbances in the disease.

Regional variation of airway hyperresponsiveness in children with asthma.

Families with asthmatic children were recruited to take part in a multi-centre collaborative study into the genetics of asthma. Detailed phenotypic information was collected on all family members including: lung function, anthropomorphic measurements, response to methacholine challenge, skin prick testing, serum IgE measurements and a detailed nurse-administered questionnaire. Families were eligible for entry into the study if they had two children with a doctor-diagnosis of asthma. Bennett/Twin nebulisers were supplied to each centre from a single source and these were calibrated to determine gravimetric nebuliser output prior to use. Asthmatic probands from each centre had similar degrees of asthma severity and atopy. There was no significant difference in the sex ratios or ages of the probands or numbers of parents with a history of smoking in the families recruited at each centre. However, there was a significant difference in the number of children with airway hyperresponsiveness, with 90% of the North Staffordshire group but only 60% of the Sheffield group having a PC20 of <8 mg/ml for methacholine. This difference highlights the difficulty of using families from different centres in genetic and epidemiological studies.

Necrosis of the pancreas in the haemolytic uraemic syndrome.

A case of haemolytic uraemic syndrome in a three year old boy is described. The clinical course was complicated by hyperglycaemia, and biochemical assay of plasma showed an almost total lack of pancreatic insulin. Extensive necrosis of the exocrine and endocrine pancreas was found at necropsy. The possible pathological physiology of this complication and its prognostic importance are discussed.

Antioxidant status in asthma.

Reduced levels of glutathione peroxidase (GSH-Px) have been observed in adults with asthma. This study examines the antioxidant status in children with asthma compared with a control group in a cross-sectional analysis. Red blood cell GSH-Px, superoxide dismutase (SOD), and plasma concentrations of retinol, vitamin C, alpha tocopherol, and cholesterol were measured in 37 subjects (26 males) with stable controlled asthma. Thirty-five subjects (20 males) without eczema, hayfever, or recurrent respiratory symptoms were used as a control group. Children with asthma had significantly reduced red blood cell GSH-Px activity compared with controls [median (inter-quartile range) for asthma group, 10.25 (9.25-11.91); for control group, 11.75 (10.34-12.26) IU/g Hb; P = 0.006]. There were no significant differences in activity of SOD or vitamin C, retinol, or alpha tocopherol/cholesterol ratio. The reduction in GSH-Px activity may have therapeutic and etiological implications for asthma. The effects of disease activity and treatment on antioxidant status needs for further study.

Arterial oxygen saturation profiles in healthy preterm infants.

AIM: To construct a reference range of SpO2 values in healthy preterm infants using a simple data logging device. METHODS: Thirty three healthy preterm infants were monitored for a continuous period of 4 hours at rest using an Ohmeda Biox 3700 E Pulse Oximeter and an electronic data logger (Rustrack Ranger). Stored data were downloaded and saved as individual files on a personal computer. RESULTS: The study group median and 5th and 95th percentiles were used to construct a cumulative frequency curve of time against SpO2 value, representing the normal reference range of SpO2 profiles in healthy preterm infants. CONCLUSION: Comparison of an infant's SpO2 profile against this curve may be more helpful in guiding supplemental oxygen treatment in that individual than a figure for a mean SPO2 and its standard deviation.

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.

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.

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 searched MEDLINE (1966-October 2001), EMBASE (1974-November 2001) and the Cochrane Controlled Trials Register (CCTR) (Cochrane Library, Issue 4, 2001). 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.

Aerosolized 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 is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are 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 five days of age were all randomly allocated to receive an aerosolized loop diuretic. 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 pulmonary mechanics and potential complications of therapy. 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: We identified eight studies which met selection criteria. 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. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g. , washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Aerosolized 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 is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are 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. The search of MEDLINE was updated in January, 2001. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. 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 pulmonary mechanics and potential complications of therapy. 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: We identified eight studies which met selection criteria. 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. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g., washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard 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 (1999, issue 2). 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 CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. 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: Of six studies fulfilling entry criteria, most 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 with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Chronic administration of diuretics (thiazide with spironolactone) reduces mortality in intubated patients. Large studies are needed to assess (1) whether chronic diuretic administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients without long-term toxicity and (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard method of the Cochrane Neonatal Review Group. We searched MEDLINE (1966-November 2001), EMBASE (1974-November 2001) and the Cochrane Controlled Trials Register (CCTR) (Cochrane Library Issue 4, 2001). 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 CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. 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: Of six studies fulfilling entry criteria, most 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 with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants who did not have access to corticosteroids, bronchodilators or aminophylline. However, there is little or no evidence to support any benefit of diuretic administration on need for ventilatory support, length of hospital stay, or long-term outcome in patients receiving current therapy. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Studies are needed to assess (1) whether thiazide administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients exposed to corticosteroids and bronchodilators (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard 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 (1999, issue 2). 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 CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. 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: Of six studies fulfilling entry criteria, most 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 with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants who did not have access to corticosteroids, bronchodilators or aminophylline. However, there is little or no evidence to support any benefit of diuretic administration on need for ventilatory support, length of hospital stay, or long-term outcome in patients receiving current therapy. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Studies are needed to assess (1) whether thiazide administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients exposed to corticosteroids and bronchodilators (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Reproducibility of electrical impedance tomographic spectroscopy (EITS) parametric images of neonatal lungs.

The reproducibility of electrical impedance tomographic spectroscopy (EITS) images of neonatal lungs have been investigated in 11 clinically stable babies. We have used the Sheffield Mark IIIa EITS system. An average inspiration frame was generated from the data frames associated with maximum inspiration. Frequency images were reconstructed from these frames. The frequency images were analysed to locate the pixel with the maximum change in the right lung field. The change was defined as the 614 kHz measurement relative to 9.6 kHz. A 3 x 3 pixel region of interest was centred at this point. The changes in impedance with frequency for this region of interest show good overall reproducibility between electrode applications for eight frequencies (95% limits of agreement +/- 28%). This reproducibility is improved (95% limits of agreement +/- 13%) by omitting the highest frequency (1.2 MHz) which is most subject to system noise. The parameters for the Cole model derived from data with the highest frequency omitted are less reproducible between electrode applications (95% limits of agreement, R/S +/- 0.83, fc +/- 81.6, RC +/- 0.52, SC +/- 0.39). We suspect that the parametric model used may have an effect on this. The signals recorded at the highest frequency (1.2 MHz) are a major source of variability. The reproducibility results are improved by omitting this frequency from the analysis.

Multifrequency and parametric EIT images of neonatal lungs.

The aims of the study were to investigate the problems involved in making multifrequency EIT measurements on neonates and to compare the images obtained with the results from a group of normal adults. The Sheffield electrical impedance tomographic spectroscopy (EITS) system acquires multifrequency data using a set of eight drive and eight receive electrodes. EITS measurements were made on an inhomogeneous group of 10 neonates admitted to the special care baby unit for observation and feeding. R/S, characteristic frequency, RC and SC parameters were generated using the Cole equation. Comparisons of the parameters were made with data collected from normal adults in another study. We have shown that it is possible to obtain EITS parametric images of neonatal lungs and that there are some differences in Cole parameters between the adult and neonatal groups.