Potassium handling in health and disease: lessons from inherited tubulopathies

The tight regulation of plasma potassium levels, a mostly intracellular cation, is essential given the severe consequences of hyper- and hypokalemia. Basic renal physiology studies in the past have identified the complex pathway of potassium reabsorption in the proximal tubule followed by the fine-tuning of its secretion or reabsorption at the distal tubule, including the thick ascending limb of Henle's loop, the distal convoluted tubule and the cortical collecting duct. Genetic studies in recent years have clarified the role of specific tubular channels and transporters in the pathogenesis of unique hyperand hypokalemic tubulopathies, some of them non-hypertensive (pseudohypoaldosteronism, Bartter and Gitelman syndromes) and others hypertensive by definition (including Liddle and Gordon syndromes). This article reviews the genetic and clinical spectrum of hypokalemic and hyperkalemic tubulopathies. Abbreviations: K: potassium, Na: sodium; Cl: chloride; BS: Bartter syndrome; PHA: pseudohypoaldosteronism; NKCC2: bumetanide-sensitive Na-K-2Cl- co-transporter; ROMK: inwardly rectifying K channel; ClC-Kb: basolateral Cl channel; TAL: thick ascending limb of Henle's loop; TSC: thiazide-sensitive NaCl co-transporter; CCD: cortical collecting duct; ENaC: epithelial Na channel.     

The carriage of the type 1 diabetes‐associated R262W variant of human LNK correlates with increased proliferation of peripheral blood monocytes in diabetic patients

Lavrikova EY, Nikitin AG, Kuraeva TL, Peterkova VA, Tsitlidze NM, Chistiakov DA, Nosikov VV. The carriage of the type 1 diabetes‐associated R262W variant of human LNK correlates with increased proliferation of peripheral blood monocytes in diabetic patients. Objective: Lymphocyte adaptor protein (LNK) plays a pivotal role as a suppressor of T‐cell receptor‐mediated immune signaling and negative regulator of lymphopoiesis and early hematopoiesis. Recently, association between the R262W (c.784T>C) variant of the SH2B3 gene (rs3184504) encoding human LNK and type 1 diabetes (T1D) was found in several populations. In this study, we aimed to check whether this marker is associated with T1D in a Russian population. Methods: Using a Taqman allele discrimination assay, we genotyped 1062 unrelated Russian individuals with diabetes at childhood and adolescence onset and 1020 healthy controls. T‐cell proliferation assay based on the measurement of incorporation of bromo‐2′‐deoxyuridine incorporation into newly synthesized DNA was used to evaluate whether carriage of SH2B3 784T>C correlates with T‐cell proliferation in patients' peripheral mononuclear blood cells (PMBCs) stimulated with anti‐CD28 and anti‐CD3 antibodies. Results: The allele 784C of SH2B3 was related to a higher risk of T1D (odds ratio of 1.52, p = 1.2 × 10^?12). A correlation between the carriage of the predisposing C/C variant of LNK and increased proliferation of T lymphocytes was shown in PMBCs of both diabetic [C/C vs. C/T vs.T/T = optical density at 450 nm (OD₄₅₀) 6.3 ± 0.8 vs. 4.4 ± 0.7 vs. 2.7 ± 0.5, p = 0.0007] and non‐diabetic (C/C vs. C/T vs.T/T = OD₄₅₀2.9 ± 0.6 vs. 2.2 ± 0.4 vs. 1.7 ± 0.4, p = 0.022) patients. Conclusions: The SH2B3 784T>C variant could contribute to the pathogenesis of T1D through impaired immune response that promotes activation and expansion of self‐reactive lymphocytes in susceptible individuals.     

The safety of a nitric oxide inhalation system with high frequency oscillatory ventilation

Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV) has been indicated in infants with severe respiratory failure. The purpose of the present study was to evaluate the safety of an NO inhalation system with HFOV in terms of nitrogen dioxide (NO₂) production. The NO inhalation system consisted of a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen (O₂) concentration was changed from 21 to 100%. The NO and NO₂ concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO₂ concentration was increased when either the O₂ or the NO concentration was increased. The interposition of the endotracheal tubes increased NO₂ concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway pressure produced a significant increase in NO₂ production at 4 p.p.m. NO. The increase in NO₂ production was prevented by placing a one-way valve at the joint of the NO gas line to the inspired limb. It was concluded that the NO inhalation system with HFOV can be safely used when a one-way valve is placed at the joint of the NO gas line to the inspired limb and when inhaled NO is at a relatively low concentration.     

ALPHA-THALASSAEMIA IN SINGAPORE *

The α-thalassaemias seen in Singapore include Bart's hydrops foetalis and Hb H thalassaemia, the former being confined exclusively to the Chinese, and the latter to both Chinese and Malays. Bart's hydrops foetalis is a homozygous condition of an autosomally recessively inherited gene known as the α-thalassaemia 1 gene. Hb H thalassaemia could be due to a double heterozygote state, viz αth₁/αth₂. Evidence that such a 2 gene hypothesis is tenable is given, and it is estimated that at least 50,000 Chinese in Singapore possess the α-thalassaemia gene. The possibility of more than 2 genes being responsible for α-chain production is also discussed.     

Ventilatory response to 100% and 15% O2 during wakefulness and sleep in preterm infants

To examine the ventilatory response to 100% and 15% O₂during wakefulness and sleep, we studied eleven preterm infants birthweight 1770 ± 102 g; gestational age 32 ±1 weeks; postnatal age 31 ±5 days) on two occasions each. Wakefulness (W) was present around feeding time and was defined by open eyes for more than 2 min plus presence of purposeful movements. Rapid eye movement (REM) and non-rapid eye movement (N-REM) sleep were defined using electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), and body movements. During 100% O₂ breathing, immediate (30 s) decreases of 28, 39 and 37% followed by late (5 min) increases in ventilation (_E) of 42, 49 and 27% were observed during W, REM and N-REM sleep (P > 0.05 between states). PaCO₂decreased significantly towards the end of 5 min of breathing 100% 0₂in W, REM and N-REM sleep (P>0.05). Average duration of apnea following sudden administration of 100% O₂was 8.5, 11.1 and 8.8 s during W, REM and N-REM sleep (P > 0.05 between states). During inhalation of 15% O₂, there was a late decrease in ventilation of 19 and 23% during wakefulness and REM sleep, and a sustained increase in V_E of 17% during N-REM sleep (P < 0.05). PaCO₂ at the end of hypoxia (5 min) was significantly decreased in N-REM sleep only (P < 0.05). We suggest that (i) peripheral chemoreceptor activity is qualitatively intact during W and sleep, as reflected by (a) the immediate changes in V_E during inhalation of high and low O₂, and (b) apnea following administration of 100% O₂: (ii) The late decrease in ventilation with hypoxia is absent in N-REM sleep.     

A simplified surfactant dosing procedure in respiratory distress syndrome: the "side-hole" randomized study

Abstract The aim of this study was to compare the incidence of acute adverse events and long-term outcome of two different surfactant dosing procedures in respiratory distress syndrome (RDS). The effects of two surfactant dosing procedures on the incidence of transient hypoxia and bradycardia, gas exchange, ventilatory requirements and 28 d outcome were compared. The patients, comprising 102 infants (birthweight 600–2000 g) with RDS on mechanical ventilation with F_iO₂ 0.4, were randomized at 2–24 h to receive 200 mg kg^-1 of Curosurf® in 56 it was given by bolus delivery, and in 55 by a simplified technique (dose given in 1 min via a catheter introduced through a side-hole in the tracheal tube adaptor. The baby's position was not changed and ventilation was not interrupted). Two additional surfactant doses (100 mg kg^-1) were also given, by the same method, if ventilation with F_iO₂ 0.3 was needed 12 and 24 h after the initial dose. The number of episodes of hypoxia and/or bradycardia was similar in both groups. A slight and transient increase in Paco₂ was observed in the side-hole group. The efficacy of the surfactant, based on oxygenation improvement, ventilator requirements, number of doses required and incidence of air leaks, was similar. No differences were observed in the incidence of intraventricular haemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia or survival. In conclusion, a simplified surfactant dosing procedure not requiring fractional doses, ventilator disconnection, changes in the baby's position or manual bagging was found to be as effective as bolus delivery. The number of dosing-related transient episodes of hypoxia and bradycardia was not decreased by the slow, 1 min, side-hole instillation procedure.     

Mechanical obstruction of a Roux-Y limb

Two cases of mechanical obstruction of the defunctionalized limb of a Roux-en-Y loop of a bilioenteric conduit are reported. Both patients developed recurrent jaundice and acholic stools after apparently successful surgery for biliary atresia, and were initially diagnosed as having ascending cholangitis. However, the symptoms failed to respond to conservative treatment. At surgery, a mechanical obstruction of the Roux-Y limb due to adhesions was found. The jaundice disappeared and the stool color became normal after lysis of the adhesions.     

Association Between Outdoor Air Pollution Levels and Inpatient Outcomes in Pediatric Pneumonia Hospitalizations, 2007 to 2008

ObjectivePneumonia is a leading cause of pediatric admissions. Although air pollutants are associated with poor outcomes, few national studies have examined associations between pollutant levels and inpatient pediatric pneumonia outcomes. We examined the relationship between ozone (O₃) and fine particulate matter with a diameter ≤2.5 µm (PM_2.5) and outcomes related to disease severity.MethodsIn this cross-sectional study, we obtained discharge data from the 2007 to 2008 Nationwide Inpatient Sample and pollution data from the Air Quality System. Patients ≤18years with a principal diagnosis of pneumonia were included. Discharge data were linked to O₃ and PM_2.5 levels (predictors) from the patient's ZIP Code (not publicly available) from day of admission. Outcomes were mortality, intubation, length of stay (LOS), and total costs. We calculated weighted national estimates and performed multivariable analyses adjusting for sociodemographic and hospital factors.ResultsThere were a total of 57,972 (278,871 weighted) subjects. Median PM_2.5 level was 9.5 (interquartile range [IQR] 6.8–13.4) µg/m³. Median O₃ level was 35.6 (IQR 28.2–45.2) parts per billion. Mortality was 0.1%; 0.75% of patients were intubated. Median LOS was 2 (IQR 2–4) days. Median costs were $3089 (IQR $2023–$5177). Greater levels of PM_2.5 and O₃ were associated with mortality, longer LOS, and greater costs. Greater O₃ levels were associated with increased odds of intubation.ConclusionsGreater levels of O₃ and PM_2.5 were associated with more severe presentations of pneumonia. Future work should examine these relationships in more recent years and over a longer time period.     

Effects of prolactin on Na+K(+)-ATPase activity in the nephron during maturation in the rat.

The effect of prolactin (PRL) on renal Na+K(+)-ATPase was investigated in 7-d-old neonatal rats. Animals were treated by bromocriptine (Br; a blocker of endogenous PRL secretion), and the enzyme activity was compared with that of untreated controls. Na+K(+)-ATPase was determined in renal sections in the medullary thick ascending limb of Henle's loop and in the distal tubule by cytochemistry. In the distal tubule, Na+K(+)-ATPase activity was significantly lower in Br-treated animals than in controls (330 +/- 169 versus 558 +/- 146 pmol inorganic phosphate/mm/h, respectively); values did not differ in the medullary thick ascending limb of Henle's loop between Br-treated and control animals (132 +/- 74 versus 165 +/- 113 pmol inorganic phosphate/mm/h, respectively). In vitro effects of PRL were investigated by determining the enzyme activity after incubation of renal sections from Br-treated and untreated animals with different concentrations of PRL. Results suggest that PRL may affect renal Na+K(+)-ATPase activity in the distal tubule in the neonatal period but do not support a major role of PRL in the enzyme maturation.     

Hypocalcemic heart failure masquerading as dilated cardiomyopathy

Hypocalcemia is a rare, but reversible, cause of congestive heart failure. We report a 4-month-old boy diagnosed as dilated cardiomyopathy who had prolonged Q_OT_C with low blood levels of calcium, normal phosphate, elevated alkaline phosphatase and findings suggestive of rickets. In view of non response to calcium and vitamin D₃, a possible diagnosis of VDDR I (Vitamin Ddependent rickets) was made and he was treated with calcium and calcitriol. The serum calcium levels normalised within 10 days, along with resolution of the signs and symptoms of heart failure, near normal left ventricular function and normalisation of Q_OT_C. Pediatricians should be aware of the association of hypocalcemia with cardiac dysfunction and should keep it as a possible reversible cause of heart failure in children.     

POSTNATAL DEVELOPMENT OF RENAL FUNCTION IN PRE-TERM AND FULL-TERM INFANTS

ABSTRACT. Aperia, A., Broberger, B., Klinder, G., Herin, P. and Zetterström, R. (Department of Paediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm and Huddinge Hospital, Huddinge, Sweden). Postnatal deveopment of renal function in preterm and full-term infants. Acta Paediatr Scand, 70:183, 1981. –This study has been designed to examine the effect of gestational age (GA) on the postnatal development of renal function and has been performed in pre-term (PT) infants (GA=30–34 weeks) and in full-term (FT) infants (GA=39–41 weeks). Postnatal age has ranged from 1–35 days. From 8 hour urine samples collected after spontaneous voiding and a capillary blood sample, determinations have been made of the clearance of creatinine (C_Cr), the fractional excretion of β₂-microglobulin (FE_β2) and the fractional excretion of sodium (FE_Na). In some infants receiving fluid parenterally, simultaneous determinations were made of the clearance of creatinine and inulin. As judged from this study, C_Cr is a reliable indicator of the glomerular filtration rate (GFR). GFR was almost the same in newborn PT and FT, but from 0.3–1 week of age GFR increased significantly more rapidly in FT than in PT. From 1–5 weeks of age GFR increased at approximately the same rate in PT and FT infants. The absolute value for GFR in 3–5 weeks old infants was lower in PT than in FT. FE_β2 was higher in PT than in FT infants during the entire first month of life and FE_Na was higher in PT than in FT infants during the first week of life, suggesting a glomerular tubular imbalance at least at the level of the proximal tubule in PT infants. It is concluded that different stages of maturation will alter the preconditions for the renal adaptation to extrauterine life during at least the first month of life. Therefore special attention must be paid to the limited renal function in PT during their entire first month of life.     

THE EXCRETION OF C6–C10-DICARBOXYLIC ACIDS IN THE URINE OF NEWBORN INFANTS DURING STARVATION

ABSTRACT. Gregersen, N. and Ingerslev, J. (Research Laboratory for Metabolic Disorders, University Department of Clinical Chemistry and University Department of Obstetrics and Gynaecology, Aarhus kommunehospital, Aarhus, Denmark). The excretion of C₆–C₁₀-dicarboxylic acids in the urine of newborn infants during starvation. Acta Paediatr Scand, 68: 677, 1979.—The excretion of C₆–C₁₀-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, was measured during the three first days of life in 3 fasting newborns, 2 newborns fed with isocaloric glucose and 2 newborns given mothers'-milk. On the second and third day of life the starved children excreted 27–84 mmol adipic acid/mol creatinine, 6–22 mmol suberic acid/mol creatinine and 4–7 mmol sebacic acid/mol creatinine. The excretion of C₆–C₁₀-dicarboxylic acids in the neonates given glucose or mothers'-milk was, for the first three days of life, 0–9 mmol adipic acid/mol creatinine, 0–10 mmol suberic acid/mol creatinine and 0–4 mmol sebacic acid/mol creatinine. The latter amounts are equivalent to the excretion of dicarboxylic acids in older children. It is argued that the detected dicarboxylic acids are formed by ω-oxidation of long-chain monocarboxylic acids followed by β-oxidation, and that the excreted amounts reflect ω-oxidation activity. It is speculated that the substantial ω-oxidation activity in the starving newborn serve to provide succinyl-CoA-substrate for the citric acid cycle and for gluconeogenesis.     

Intestinal ischemia secondary to volvulus of gastroschisis within a silo: detection,confirmation and reversal of near infra-red spectroscopy detected O2 saturation

A neonate with gastroschisis had silo placement and near-infrared spectroscopy (NIRS) monitoring of intestinal haemoglobin oxygen saturation (RSO₂). An ischemic loop of bowel demonstrated decreased RSO₂, with reversal of clinical ischemia and RSO₂ postoperatively. This demonstrates possible advantage of monitoring intestinal RSO₂ in neonates at risk of ischemia, and response to intervention.     

Neutrophil Receptors

We studied two interesting patients with neutrophil dysfunction: one is a patient with hyper-IgE syndrome with the serum inhibitor which belongs to IgE class and the other is characterized by defective phagocytosis confined to S. aureus. These patients suggested to us the presence of IgE receptors and receptors for S. aureus on neutrophils. The presence of IgE receptors on neutrophils was proved by the fact that neutrophils preincubated with 10 μg of pure IgE generated O^-₂ on stimulation with F(ab')₂, fragments of pure anti-K chain antibody or anti-K chain antibody. The presence of IgE receptors was also suggested by the suppressive effect of IgE soluble immune complexes on neutrophil chemotaxis. Neutrophils of the patient with defective phagocytosis confined to S. aureus could not generate O^-₂ with unopsonized S. aureus, while control neutrophils generated a significant amount of O^-₂ on addition of unopsonized S. aureus. Colchicine treated control neutrophils also could not generate O^-₂ by unopsonized S. aureus. These data suggested the presence of receptors for S. aureus on neutrophils.     

Pharmacokinetics of tacrolimus granules in pediatric de novo liver,kidney, and heart transplantation: The OPTION study

Tacrolimus granules were developed for patients who are unable to swallow capsules. Therapeutic drug monitoring (TDM) is required to optimize efficacy and safety, which is based on C_trough for tacrolimus capsules. Pharmacokinetic (PK) data for tacrolimus granules are required to establish the basis for TDM in those who are unable to swallow capsules. In this phase IV study (NCT01371331) of children undergoing liver, kidney, or heart transplantation, patients received tacrolimus granules 0.15 mg/kg twice daily; first dose was administered within 24 hours of reperfusion. PK analysis samples were collected after reperfusion, after first dose of tacrolimus (Day 1), and at steady state (Day 7; >4 days stable dose). Of the 52 transplant recipients enrolled, 38 had two evaluable PK profiles. Mean AUC_tau after first dose of tacrolimus was 211, 97, and 224 hour*ng/mL in liver, kidney, and heart transplant recipients, respectively; corresponding mean AUC_tau at steady state was 195, 208, and 165 hour*ng/mL. C_trough and AUC_tau were positively correlated after first dose of tacrolimus and at steady state (Pearson's coefficients: r = 0.81 and r = 0.87, respectively). This study demonstrated that C_trough is a reliable marker for TDM in pediatric transplant recipients treated with tacrolimus granules, consistent with TDM for other tacrolimus formulations.     

Praktischer Einsatz eines Mikrooxymeters zur Bestimmung der capillären Sauerstoffsättigung in der pädiatrischen Kardiologie und Intensivpflege

After establishing the methodical and technical prerequisites, the microoxymeter OSM 1 (Radiometer, Copenhagen) was used to determine the capillary O₂-saturation in routine clinical practice.

1. Studies on 10 normal neonates in the first 4 days of life showed an initial hypoxia of an average O₂-saturation of 86.3% which then rose to 93.1% on the 4th day of life. This observation has to be taken into consideration when judging the O₂-saturation values of neonates.
2. Studies in the effectiveness of the three different ways of O₂-administration showed that the lowest rise of capillary O₂-saturation occured when O₂ was administered by means of a plastic funnel placed in front of the mouth and nose of the infant; in the O₂ tent (above all by administering large quantities of O₂) and by the use of tightly closing plexiglass hoods the effect on the capillary O₂-saturation was found to be favourable.
3. Even children with cyanotic congenital heart diseases demonstrated a rise of the capillary O₂-saturation after the breathing of O₂. A residual hypoxia remains, irrespective of the normal O₂-saturation of 96%. The use of an “oxygen test” for the differentiation of cardiac and pulmonary cyanosis cannot be sanctioned.
4. The practical use of the apparatus and its importance in paediatric cardiology and intensive care is described and discussed with a few examples.

     

Membrane Peroxidation and Vitamin E

An examination for the membrane oxidation as a cause of oxygen poisoning was carried out by using erythrocyte membrane. 1) The addition of erythrocytes obtained from healthy human adults to retinol, dissolved in ethanol, resulted in hemolysis. The hemolysis induced by retinol was inhibited by added α-tocopheryl acetate to the suspensions. 2) The hemolysis was induced by oxygen bubbling to the erythrocyte suspensions. This hemolysis was also inhibited by α-tocopheryl acetate, while it was accelerated by a previous treatment of the erythrocytes with retinol in a dose of which hemolysis did not occur. The oxygen-induced hemolysis accelerated with retinol, was also inhibited by α-tocopheryl acetate. 3) The treatment of the erythrocyte suspensions with H₂O₂ was carried out in the manner as previously devised by Rose and György, in which the erythrocytes used in this experiment resulted in no hemolysis. When previously treated the erythrocytes with retinol, in a dose of which hemolysis does not occur, hemolysis was induced by adding H₂O₂ in the same manner, while it was inhibited by α-tocopheryl acetate. When first treated with H₂O₂ and subsequently with retinol, no remarkable hemolysis was observed in the erythrocyte suspensions.     

Vasodilator Testing with Nitric Oxide and/or Oxygen in Pediatric Pulmonary Hypertension

The objective of this study was to determine whether a combination of inhaled nitric oxide (iNO) and O₂ is more effective than 100% O₂ or iNO alone for acute vasodilator testing in children. An open, prospective, randomized, controlled trial was conducted at 16 centers. Subjects were children 4 weeks to 18 years of age with pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) undergoing right heart catheterization for acute vasodilator testing. All patients were tested with each of three agents (80 ppm iNO, 100% O₂, combination of 80 ppm iNO/100% O₂) in three 10-min treatment periods, and hemodynamic measurements obtained. Primary outcome measures were percentages of acute responders with O₂ alone vs. iNO/O₂ and iNO alone vs. iNO/O₂. More patients on the combination were acute responders compared with O₂ or iNO alone (26% vs. 14%, P = 0.019, and 27% vs. 24%, P = 0.602, respectively). Changes in PVR index and mean pulmonary arterial pressure vs. baseline were greater with iNO/O₂ vs. either O₂ or iNO alone (P < 0.001). Survival at 1-year follow-up included (1) 90.9% of acute responders to the combination, compared with 77.8% of nonresponders to the combination, and (2) 85.7% of acute responders to O₂ alone, compared with 80.6% of nonresponders to O₂. Key conclusions are as follows. In children with PH and increased PVR, more acute responders were identified with the iNO/O₂ combination vs. O₂ alone. While there was no significant difference in acute responder rate with iNO alone vs. iNO/O₂, the combination improved pulmonary hemodynamics acutely better than iNO alone. One-year survival data show similar rates between the iNO/O₂ and the O₂ alone groups; however, the combination may be more effective than O₂ alone in discriminating survivors versus nonsurvivors at long-term follow-up.     

Reproducibility of Muscle Strength Testing for Children with Spina Bifida

Aims: Examine the inter-rater reliability of the Daniels and Worthingham (D&;W) manual muscle test (MMT) protocol for children with spina bifida between experienced and novice physiotherapists. Methods: Thirteen children with spina bifida (two males) aged 6 to 18 years were recruited from a spina bifida service in a state-wide tertiary children's hospital. Each child had the muscle strength of 19, and lower limb muscles were measured bilaterally by one experienced and one novice physiotherapist using the D&;W MMT protocol. Examiner and limb order were counterbalanced. Standard training and recording sheets were used. Agreement between raters was examined with quadratic weighted kappa (κ_w2), percentage exact agreement (%EA), and the Bland–Altmann Limits of Agreement (LoA). Minimal detectable change (MDC) was calculated. Results: Inter-rater agreement between the experienced and novice raters was excellent (κ_w2 = 0.95; 95% confidence interval: 0.94–0.96); %EA was good (72.3%); and clinically appropriate LoA levels were ?1.30–1.40. The MDC was 1.11 points on a six-point MMT scale. Conclusions: The D&;W MMT protocol, when used after standard training and with standard recording sheets, was reproducible for children with spina bifida, aged 6–18 years.     

Effect of surgery on ventilatory requirements in severe pulmonary interstitial emphysema

Pulmonary interstitial emphysema (PIE) is an acquired condition that can develop in premature infants with severe hyaline membrane disease (HMD) who require assisted ventilation. In this study, the effect of surgery on the ventilatory requirements of nine infants with severe and progressive PIE was established to determined the degree to which surgical intervention was beneficial. The median ventilation index for O₂([P_aO₂/(F₂O₂ × MAP)]) and median ventilation index for CO₂ ([PIP-PEEP] × RR × PCO₂) markedly improved following surgery. There was no difference in overall outcome between those infants who had a lobectomy and those who had pleurotomy with diathermy deflation of subpleural cysts (POD). Given that PIE is reversible, POD seems to be preferable to lobectomy because it preserves lung tissue. Correspondence to: S. W. Beasley