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Detection of CF-associated liver disease
Follow-up of newborns with elevated screening thyroxine concentrations The detailed information and evaluation of 101 infants whose neonatal screening test results showed elevated T4 concentrations will be useful for pediatricians and especially for pediatric endocrinologists who frequently are queried. Investigations of these 101 infants detected no infant who required treatment. The editorial by Fisher helps put in perspective the place of these tests as knowledge gained from screening large populations matures. —Sarah S. Long, MD Page 296
Dead space and mechanical ventilation A major goal of new strategies of mechanical ventilation is to keep the lungs well inflated at end expiration to maintain a normal to high-normal functional residual capacity (FRC) and to ventilate with as low a tidal volume as possible to achieve an acceptable Pco2. Tidal volume measurements for infants are made using flow sensors inserted between the endotracheal tube and the ventilator. Although the dead space volume of the sensors is small (about 1 mL), it adds to the normally increased ratio of dead space to alveolar ventilation characteristic of the preterm lung. Ventilation strategies that increase FRC will further increase dead space. Thus, ventilation to achieve a relative high FRC and low tidal volumes using volume sensors have the additive adverse effect of increasing dead space, making mechanical ventilation less efficient and requiring higher tidal volumes to overcome the added dead space. Claure et al demonstrate that the dead space of the sensor can be overcome by permitting a gas leak between the sensor and the endotracheal tube. This is a clever and safe way to wash out the sensor with fresh gas from the ventilator circuit. —Alan H. Jobe, MD, PhD Page 315
Steroids, cytokines, and Kawasaki disease There is mounting evidence that corticosteroid treatment may be beneficial for patients with Kawasaki disease. This is helpful because it adds to our armamentarium for treating this disease. Because for years it was thought that corticosteroids might actually have a deleterious effect, few studies were performed using these agents. In this issue of The Journal, Okada et al report on an investigation of the mechanisms by which corticosteroids might improve outcome in patients with Kawasaki disease. They found that corticosteroids in addition to intravenous immune globulin (IVIG) reduced cytokine concentrations within 24 hours, whereas IVIG alone did not. The duration of symptoms was also shorter in the group that received both IVIG and steroids. These results suggest that corticosteroids may improve symptoms by reducing cytokine levels in children with Kawasaki disease. —Stephen R. Daniels, MD, PhD Page 363 The Journal of Pediatrics
Detection of CF-associated liver disease As the life expectancy for patients with cystic fibrosis (CF) is extended through improved pulmonary, nutritional, and general medical care, hepatobiliary complications (especially focal biliary cirrhosis) are being recognized more frequently. Liver disease now accounts for the majority of the nonpulmonary causes of death in patients with CF. The problem is the fact that the appearance of clinically overt liver disease in patients with CF is unpredictable. Clinical identification has been difficult and inaccurate because of the general lack of symptoms due to the developing fibrotic liver lesion until obvious portal hypertension is present. Because the abnormalities are insidious and the patient is often asymptomatic, it is difficult to screen for or monitor liver disease in patients with CF. There is no specific genetic marker or biochemical harbinger of nascent liver disease. Clinical findings may not be appreciated until late in the progression of portal fibrosis when changes in liver size and consistency may be palpated or splenomegaly or hypersplenism detected. Assessment of parenchymal or biliary epithelial damage using standard enzymatic determinations (AST, GGT) is common practice; however, liver function abnormalities are intermittent and the histological lesions may be heterogeneous, leading to biopsy sampling error. Specific function tests gauging synthetic activity, metabolic activity, or clearance are also popular, but not validated. Analysis of hepatic structure using ultrasound (US) has gained popularity as an imaging modality to screen for liver disease in CF patients. The ultrasonographic abnormality most closely related to elevated liver enzymes were those that suggested portal hypertension. However, findings at ultrasonography may be subjective and operator-dependent. Lenaerts et al followed a large cohort of children with CF—all had normal US findings at entry. The authors then assessed the longitudinal evolution of US findings over a 10-year period; 18% developed US signs of liver disease and half of this subgroup developed portal hypertension. US findings were the first indication of liver disease. This study supports the concept of routine (annual) US monitoring for liver disease in children with CF, especially those at greatest risk. —William F. Balistreri, MD Page 343
September 2003
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Dead space and mechanical ventilation A major goal of new strategies of mechanical ventilation is to keep the lungs well inflated at end expiration to maintain a normal to high-normal functional residual capacity (FRC) and to ventilate with as low a tidal volume as possible to achieve an acceptable Pco2. Tidal volume measurements for infants are made using flow sensors inserted between the endotracheal tube and the ventilator. Although the dead space volume of the sensors is small (about 1 mL), it adds to the normally increased ratio of dead space to alveolar ventilation characteristic of the preterm lung. Ventilation strategies that increase FRC will further increase dead space. Thus, ventilation to achieve a relative high FRC and low tidal volumes using volume sensors have the additive adverse effect of increasing dead space, making mechanical ventilation less efficient and requiring higher tidal volumes to overcome the added dead space. Claure et al demonstrate that the dead space of the sensor can be overcome by permitting a gas leak between the sensor and the endotracheal tube. This is a clever and safe way to wash out the sensor with fresh gas from the ventilator circuit. —Alan H. Jobe, MD, PhD Page 315
Steroids, cytokines, and Kawasaki disease There is mounting evidence that corticosteroid treatment may be beneficial for patients with Kawasaki disease. This is helpful because it adds to our armamentarium for treating this disease. Because for years it was thought that corticosteroids might actually have a deleterious effect, few studies were performed using these agents. In this issue of The Journal, Okada et al report on an investigation of the mechanisms by which corticosteroids might improve outcome in patients with Kawasaki disease. They found that corticosteroids in addition to intravenous immune globulin (IVIG) reduced cytokine concentrations within 24 hours, whereas IVIG alone did not. The duration of symptoms was also shorter in the group that received both IVIG and steroids. These results suggest that corticosteroids may improve symptoms by reducing cytokine levels in children with Kawasaki disease. —Stephen R. Daniels, MD, PhD Page 363 The Journal of Pediatrics
Detection of CF-associated liver disease As the life expectancy for patients with cystic fibrosis (CF) is extended through improved pulmonary, nutritional, and general medical care, hepatobiliary complications (especially focal biliary cirrhosis) are being recognized more frequently. Liver disease now accounts for the majority of the nonpulmonary causes of death in patients with CF. The problem is the fact that the appearance of clinically overt liver disease in patients with CF is unpredictable. Clinical identification has been difficult and inaccurate because of the general lack of symptoms due to the developing fibrotic liver lesion until obvious portal hypertension is present. Because the abnormalities are insidious and the patient is often asymptomatic, it is difficult to screen for or monitor liver disease in patients with CF. There is no specific genetic marker or biochemical harbinger of nascent liver disease. Clinical findings may not be appreciated until late in the progression of portal fibrosis when changes in liver size and consistency may be palpated or splenomegaly or hypersplenism detected. Assessment of parenchymal or biliary epithelial damage using standard enzymatic determinations (AST, GGT) is common practice; however, liver function abnormalities are intermittent and the histological lesions may be heterogeneous, leading to biopsy sampling error. Specific function tests gauging synthetic activity, metabolic activity, or clearance are also popular, but not validated. Analysis of hepatic structure using ultrasound (US) has gained popularity as an imaging modality to screen for liver disease in CF patients. The ultrasonographic abnormality most closely related to elevated liver enzymes were those that suggested portal hypertension. However, findings at ultrasonography may be subjective and operator-dependent. Lenaerts et al followed a large cohort of children with CF—all had normal US findings at entry. The authors then assessed the longitudinal evolution of US findings over a 10-year period; 18% developed US signs of liver disease and half of this subgroup developed portal hypertension. US findings were the first indication of liver disease. This study supports the concept of routine (annual) US monitoring for liver disease in children with CF, especially those at greatest risk. —William F. Balistreri, MD Page 343
September 2003
3A