Frailty, post-operative delirium and functional status at discharge in patients with hip fracture.

OBJECTIVE: To explore the effect of frailty, alone and in combination with post-operative delirium (POD), on the risk of poor function at discharge in patients with hip fracture (HF). METHODS: This is a prospective cohort study of patients with HF admitted to an Orthogeriatric Unit (OGU) between October 1, 2011 and March 15, 2019. POD was assessed using the 4AT and the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5-edition criteria. A 22-items Frailty Index (FI) was created using the data collected on admission. The outcome measure was the Cumulated Ambulation Score (CAS) score at discharge. A log-binomial regression model was used to assess the effect of frailty and POD on CAS. RESULTS: A total of 988 patients (median age = 84.9 years, Interquartile range = 80.6-89.2) were included: 360 patients (36.4%) were frail and 411 (42%) developed POD. Poor functional status at discharge (CAS score ≤2) was more common in frail than non-frail patients (68.3% vs. 53.8%, p < 0.001) In a regression adjusted for confounders, frailty alone (Relative Risk, RR = 1.33, 95% Confidence Intervals, CI = 1.14-1.55) and POD alone (RR 1.38, 95% CI = 1.2-1.59) were associated with poor functional status at discharge; when combined, frailty and POD had an interaction, yielding a mild increase in the risk of poor outcome (RR 1.47, 95% CI = 1.28-1.69). CONCLUSIONS: In older patients undergoing HF surgery, frailty, POD and their combination, are associated with poor functional status at discharge.

The Effect of Sodium Bicarbonate, a Beneficial Adjuvant Molecule in Cystic Fibrosis, on Bronchial Epithelial Cells Expressing a Wild-Type or Mutant CFTR Channel.

Clinical and experimental results with inhaled sodium bicarbonate as an adjuvant therapy in cystic fibrosis (CF) are promising due to its mucolytic and bacteriostatic properties, but its direct effect has not been studied on respiratory epithelial cells. Our aim was to establish and characterize co-culture models of human CF bronchial epithelial (CFBE) cell lines expressing a wild-type (WT) or mutant (deltaF508) CF transmembrane conductance regulator (CFTR) channel with human vascular endothelial cells and investigate the effects of bicarbonate. Vascular endothelial cells induced better barrier properties in CFBE cells as reflected by the higher resistance and lower permeability values. Activation of CFTR by cAMP decreased the electrical resistance in WT but not in mutant CFBE cell layers confirming the presence and absence of functional channels, respectively. Sodium bicarbonate (100 mM) was well-tolerated by CFBE cells: it slightly reduced the impedance of WT but not that of the mutant CFBE cells. Sodium bicarbonate significantly decreased the more-alkaline intracellular pH of the mutant CFBE cells, while the barrier properties of the models were only minimally changed. These observations indicate that sodium bicarbonate is beneficial to deltaF508-CFTR expressing CFBE cells. Thus, sodium bicarbonate may have a direct therapeutic effect on the bronchial epithelium.

Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome.

KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies.

The impact of psychomotor subtypes and duration of delirium on 6-month mortality in hip-fractured elderly patients.

OBJECTIVE: Studies exploring the incidence and impact of the psychomotor subtypes of postoperative delirium (POD) on the survival of hip fracture patients are few, and results are inconsistent. We sought to assess the incidence of POD subtypes and their impact, in addition to delirium duration, on 6-month mortality in older patients after hip-fracture surgery. METHODS: This is a prospective study involving 571 individuals admitted to an Orthogeriatric Unit within a 5-year period with a diagnosis of hip fracture. Survival status was assessed 6 months after posthip fracture surgery. Postoperative delirium was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. Postoperative delirium subtypes were classified according to Lipowski's criteria. Cox regressions were used to evaluate the associations between POD subtypes, POD duration, and 6-month mortality, adjusting for covariates. RESULTS: The incidence of psychomotor POD subtypes was hypoactive 57 (10.0%), hyperactive 84 (14.7%), and mixed 79 (13.8%). Six-month mortality rates were 8.3%, 10.7%, 36.8%, and 29.1% in the no-delirium, hyperactive, hypoactive, and mixed-delirium subgroups, respectively. In adjusted models, the hypoactive subgroup (Hazard Ratio, HR = 3.14, 95% Confidence Intervals, CI, 1.63-6.04) and mixed subgroup (HR = 2.89, 95% CI, 1.49-5.62) showed high mortality rates and a significantly increased risk of mortality associated with POD duration as well. CONCLUSIONS: Hyperactive delirium was the most common POD psychomotor subtype, but hypoactive and mixed POD were associated with 6-month mortality risk. Moreover, the risk of death 6 months after surgery increased for both subgroups (hypoactive and mixed) with increasing duration of POD.

Congenital myasthenic syndromes and transient myasthenia gravis.

Hypotonia in the neonatal period and early infancy is a common clinical finding. It can be caused by various heterogeneous disorders of different origin which might lead to diagnostic difficulties. Disorders of the neuromuscular junction, such as congenital myasthenic syndromes and neonatal transient myasthenia gravis are among the aetiologies. We report on a case of congenital myasthenia caused by mutation in the long cytoplasmic loop of the epsilon subunit of the acetylcholine receptor and a neonate of a myasthenic mother diagnosed with transient myasthenia gravis.

Neonatal Screening for Cystic Fibrosis in Hungary-First-Year Experiences.

The aim of this study is to evaluate the strategy of the cystic fibrosis newborn screening (CFNBS) programme in Hungary based on the results of the first year of screening. A combined immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) CFNBS protocol (IRT/IRT×PAP/IRT) was applied with an IRT-dependent safety net (SN). Out of 88,400 newborns, 256 were tested screen-positive. Fourteen cystic fibrosis (CF) and two cystic fibrosis-positive inconclusive diagnosis (CFSPID) cases were confirmed from the screen-positive cases, and two false-negative cases were diagnosed later. Based on the obtained results, a sensitivity of 88% and a positive predictive value (PPV) of 5.9% were calculated. Following the recognition of false-negative cases, the calculation method of the age-dependent cut-off was changed. In purely biochemical CFNBS protocols, a small protocol change, even after a short period, can have a significant positive impact on the performance. CFNBS should be monitored continuously in order to fine-tune the screening strategy and define the best local practices.

Corticosteroids in the prevention and treatment of infants with bronchopulmonary dysplasia: Part I. systemic corticosteroids.

Bronchopulmonary dysplasia (BPD) is the most significant respiratory complication of prematurity, and its consequences last from birth into adulthood. Unfortunately, the dramatic improvements in the management of premature infants have not led to a decreased incidence of BPD, or to breakthroughs in treatments offered for this long-lasting chronic respiratory disorder. Over recent decades the pathological picture of BPD has changed from inflammation, interstitial fibrosis and emphysema attributed to volu-, barotrauma and oxygen toxicity to larger, simplified alveoli and dysmorphic vessels related to arrested alveolarization and vasculogenesis with inflammation maintaining a central role. Corticosteroids (CSs) play a key role in the development of respiratory epithelial cells and lung maturation. These potent anti-inflammatory agents have long been used for the prevention and treatment of BPD; however, the risk/benefit ratio of their use remains unresolved. CSs administered antenatally have contributed to reduce mortality and respiratory distress syndrome, no such effect on BPD reduction has been observed. Postnatal systemic CSs reduced the rate and severity of BPD, yet their long-term neurodevelopmental and respiratory consequences markedly limit routine administration. This is the first in a two-part State-of-the-Art series that reviews the latest relevant clinical trials investigating the short-term and long-term effects of CSs in the prevention and treatment of BPD.

Corticosteroids in the prevention and treatment of infants with bronchopulmonary dysplasia: Part II. Inhaled corticosteroids alone or in combination with surfactants.

This paper is the second in a two-part State-of-the-Art series that reviews the latest relevant clinical trials investigating the short-term and long-term effects of corticosteroids in the prevention and treatment of bronchopulmonary dysplasia (BPD). Inhaled postnatal corticosteroids demonstrate low systemic bioavailability and rapid systemic clearance with high pulmonary deposition and were expected to reduce the incidence of BPD with reduced adverse effects, however, increased rate of mortality in the neonatal period and at the 18-24 months follow-up was observed. In a milestone study, intratracheal instillation of corticosteroids combined with surfactant decreased the incidence of BPD without increasing the mortality or the long-term neurodevelopmental adverse outcomes. However, subsequent trials using different types of surfactants, different surfactant to budesonide ratio, different time of the drug administration for infants with different severity of respiratory distress syndrome could not reproduce all the beneficial effects. Future perspectives for the identification of premature infants at high risk of BPD and the prevention or treatment of established BPD are discussed.

Detection and follow-up of torque teno midi virus ("small anelloviruses") in nasopharyngeal aspirates and three other human body fluids in children.

Torque teno midi virus/small anellovirus (TTMDV/SAV) is a member of the family Anelloviridae. It has a single-stranded, circular, negative-sense DNA genome. Its pathogenic role in human disease remains to be confirmed. In this study, viral shedding, molecular epidemiology and genetic diversity of TTMDV/SAV were studied in human body fluids. Nasopharyngeal aspirates collected from children with acute respiratory disease were tested by PCR/nested PCR for TTMDV/SAV in two seasons (2005/2006, 2006/2007). Two years later, additional urine, stool, and serum samples and nasopharyngeal aspirates were collected from eight symptomless children for follow-up investigation. Forty-three (46.7%) of the 92 nasopharyngeal aspirates collected contained TTMDV/SAV. High genetic diversity was observed; however, identical sequences were also detected in two patients. The mean age of the infected children was 3 years (1 months-8 years), and 58% of them were female. Co-infection with RSV was detected in 23% of the samples. In a follow-up study, nasopharyngeal aspirates and serum of six (75%), stool samples of four (50%) and urine samples of two (25%) of the eight children were anellovirus-positive. None of the anellovirus sequences were identical in the two collection periods, but identical sequences were detected in different body fluids collected at the same time from the same child. TTMDV/SAVs shedding was detected in four human body fluids. As a consequence, it is possible that generalized infection and fecal/uro-oral transmission of TTMDV/SAV occur. TTMDV/SAVs are frequently present in nasopharyngeal aspirates, although the variants may only be transient agents. Further research is needed to investigate the pathogenesis and pathogenic role of TTMDV/SAV.

The predictive value of the Kobayashi and Kawanet score systems regarding immunoglobulin resistance and cardiac complications in patients with Kawasaki disease: A pilot study / A Kobayashi- és a Kawanet-pontrendszer prediktív értéke Kawasaki-kóros betegeink immunglobulin-rezisztenciája és kardiológiai szövodményei szempontjából: Pilotvizsgálat

Összefoglaló. Bevezetés: A Kawasaki-szindróma immunvasculitis, amely kezeletlenül kardiológiai szövodményekhez vezethet. A korai intravénás immunglobulin-terápia mérsékli a szövodményeket, de az esetek 10-20%-a rezisztens a kezelésre. Ennek elorejelzésére világszerte számos rizikóbecslo pontrendszert használnak. Célkituzés: A Kobayashi- és a Kawanet-pontrendszer prediktív értékének vizsgálata betegeink intravénás immunglobulin-rezisztenciája és kardiológiai szövodményei vonatkozásában. Tudomásunk szerint ez az elso magyarországi vizsgálat, amely Kawasaki-szindróma esetében pontrendszerek prediktív értékét méri fel. Módszer: Retrospektív pilotvizsgálatunkban kigyujtöttük a 2005. január és 2020. április között Kawasaki-szindróma miatt ápolt betegeink adatait. Mindegyiküknél Kobayashi-, illetve Kawanet-pontot számoltunk, valamint megvizsgáltuk azok specificitását, szenzitivitását az intravénás immunglobulin-rezisztencia, illetve a kardiológiai szövodmények elorejelzése szempontjából. A Kobayashi-pontrendszerben 4, a Kawanet-pontrendszerben pedig 2 pont vagy annál magasabb érték jelez rizikót. Eredmények: Kawasaki-szindrómát 28 gyereknél véleményeztünk, 13 esetben észleltünk mérsékelt, 4 esetben súlyos szövodményt. 4 betegünk bizonyult intravénás immunglobulinra rezisztensnek. A rezisztencia szempontjából a Kobayashi-pontrendszer alacsony szenzitivitást (25%), illetve magas specificitást (91,6%), míg a Kawanet-pontrendszer mérsékelt szenzitivitást (50%) és specificitást (50%) mutatott. A szövodmények szempontjából hasonló eredményeket kaptunk, Kobayashi-pontrendszer: szenzitivitás: 17%; specificitás: 100%, illetve Kawanet-pontrendszer: szenzitivitás: 47%; specificitás: 45%. Következtetés: A legtöbb, nem ázsiai országban készült tanulmányhoz hasonlóan az intravénás immunglobulin-rezisztencia elorejelzésében a Kobayashi-pontrendszer vizsgálatunkban sem bizonyult hatékonynak. Ezzel szemben, magasabb szenzitivitása miatt, a Kawanet-pontrendszer intravénás immunglobulin-rezisztenciát elore jelzo hatékonyságát érdemes lenne nagyobb esetszámban vizsgálni a hazai populációban is. A kardiológiai szövodmények elorejelzésére egyik pontrendszer sem bizonyult alkalmasnak. Orv Hetil. 2021; 162(47): 1885-1890. INTRODUCTION: Kawasaki disease is an immunovasculitis, which, without treatment, leads to cardiac complications. Early intravenous immunoglobulin therapy moderates complications, however, 10-20% of patients are resistant to the therapy. Numerous risk score systems are used worldwide to predict this. OBJECTIVE: To assess the predictive value of the Kobayashi and Kawanet score systems regarding intravenous immunoglobulin resistance and cardiac complications in our department's patient cohort. To our best knowledge, this is the first study in Hungary, which examines the predictive value of score systems in the case of Kawasaki disease. METHOD: In our study, we identified the patients treated for Kawasaki disease between January 2005 and April 2020. In each case, we calculated both the Kobayashi and the Kawanet score, and we examined their specificity and sensitivity regarding the prediction of intravenous immunoglobulin resistance and cardiac complications. In the Kobayashi score system, values above 4, in the Kawanet score system, values above 2 signal risk. RESULTS: We identified 28 patients with Kawasaki disease. We observed moderate complications in 13, severe complications in 4 cases. 4 of our patients were resistant to intravenous immunoglobulin therapy. Regarding intravenous immunoglobulin resistance in our patient cohort, we detected low sensitivity (25%) and high specificity (91.6%) in the case of Kobayashi score, and moderate sensitivity (50%) and specificity (50%) in the case of Kawanet score. Regarding complications, we found similar results in the case of Kobayashi (sensitivity: 17%; specificity: 100%) and the Kawanet (sensitivity: 47%; specificity: 45%) score system. CONCLUSION: Similarly to the majority of non-Asian studies, we found the Kobayashi score system ineffective in predicting intravenous immunoglobulin resistance. However, due to its higher sensitivity, the predictive value of the Kawanet score system regarding intravenous immunoglobulin resistance is worth examining in a larger patient population in Hungary. Regarding the prediction of cardiac complications, both score systems were found to be ineffective. Orv Hetil. 2021; 162(47): 1885-1890.

[Detection and molecular epidemiology of respiratory syncytial virus type A and B strains in childhood respiratory infections in Hungary]. / A légúti óriássejtes vírus A és B típusának molekuláris kimutatása és epidemiológiája gyermekkori légúti fertozésekben.

UNLABELLED: Human respiratory syncytial virus (hRSV) is one of the major causes of respiratory infection of infants and children worldwide. The molecular epidemiology of hRSV is unknown in Hungary. AIMS: Our aims were the molecular detection and genetic analysis of hRSV from childhood respiratory infections in Hungary. MATERIALS AND METHODS: Nasopharyngeal aspirates were collected from children under the age of 10 years with acute respiratory infections provided by the Pediatric Department of the Hospital for Chest Diseases in Mosdós. Samples were taken from 15 October to 15 May in seasons of 2005/2006 and 2006/2007. The clinical and epidemiological data were collected prospectively. The amplification of the surface fusion glycoprotein (F) and the attachment glycoprotein (G) genes of viral RNA was made by RT-PCR method. PCR-products were sequenced and analyzed by phylogenetic analysis. RESULTS: Nasopharyngeal aspirates of 104 children were examined out of which 23 (22.1%) samples - 16 males (69.6%) and 7 females (30.4%) - (first season: 1/49, 2%; second season: 22/55, 40%) contained hRSV. The hRSV infections were taking place from December to March. The average age was 2.1 years (1 month to 8 years). The leading symptoms were dropping nose, fever, cough and wheezing. Thirty-nine point one percent of the hRSV infected children had underlying disease. Based upon the F region 22 (96%), viruses genetically belonged to type A and 1 (4%) was classified as type B hRSV. Based upon the G region, out of the 11 type A viruses 8 (72.7%) belonged to group GA5 and 3 (27.3%) to group GA2. Viral nucleotide sequence was identical in several cases. CONCLUSIONS: To our knowledge, this is the first report on molecular detection and genetic analysis of the two types (A and B) of hRSV of children under the age of 10 with respiratory infections in Hungary. In winter and spring hRSV is an important cause of childhood respiratory infections, particularly in infants, often requiring hospitalization.

Pontocerebellar hypoplasia type 1.

Pontocerebellar hypoplasias are heterogeneous disorders that share a reduction in the size of brainstem and cerebellum. We describe a patient with features of the rare combination of pontocerebellar hypoplasia and spinal motor neuron disease. Parental consanguinity, low Apgar scores, facial weakness, dysphagia, tongue fasciculations, stridor, generalized hypotonia, severe muscle weakness, areflexia, and congenital joint contractures were evident. Cranial magnetic resonance imaging revealed a small cerebellum and brainstem, and a muscle biopsy revealed neurogenic changes. These abnormalities suggested pontocerebellar hypoplasia type 1.

X-linked myotubular myopathy: report of a case with novel mutation.

Myotubular myopathy is a well-defined entity within the centronuclear myopathy subgroup of congenital myopathies. The authors present a patient with the most severe X-linked recessive type (XLMTM). A baby boy presented at birth with severe hypotonia, weak spontaneous movements, arthrogryposis, and respiratory insufficiency. Muscle biopsy showed features of myotubular myopathy. The diagnosis was confirmed and further specified by genetic analysis, revealing a novel frameshift mutation (1314-1315insT) of the myotubularin-coding MTM1 gene. This case underlines the importance of interdisciplinary analysis of congenital muscle diseases, including histomorphological and genetic investigations.

[Myotubular myopathy. Case report and review of the literature]. / Myotubularis myopathia. Esetismertetés és irodalmi áttekintés.

The first Hungarian report of a case of myotubular myopathy is presented here, which is a recessive congenital disorder linked to X chromosome. The patient presented at birth with severe hypotonia, weak spontaneous movements, arthrogryposis and respiratory insufficiency. The biopsy showed the appearance of myotubular myopathy. The diagnosis was further confirmed by genetic analysis revealing a novel frameshift mutation (1314-1315insT) of the myotubularin-coding MTM1 gene.

[First detection of human metapneumovirus in a child with respiratory syndrome in Hungary]. / Humán metapneumovírus elso hazai kimutatása gyermekkori légúti fertozésbol.

INTRODUCTION: Human metapneumovirus was identified in 2001 as a respiratory-tract pathogen that has been classified as a new genera in family Paramyxoviridae. AIMS: Molecular detection of human metapneumovirus in Hungary. MATERIALS AND METHODS: Human metapneumovirus was identified in nasopharyngeal aspirate amplification of the viral fusion and nucleocapsid genes by reverse transcription-polymerase chain reaction followed by sequencing and phylogenetic analysis. RESULTS: A 4 years-old girl with chronic respiratory syndrome chronically treated with anti-asthma drugs was admitted to hospital in November 2005 with acute respiratory syndrome and atelectasis. Nasopharyngeal aspirate was negative for common bacteria by culture and for influenza and coronavirus by reverse transcription-polymerase chain reaction. By contrast, specimen was positive by reverse transcription-polymerase chain reaction and was confirmed by sequencing both genes (nucleocapsid and fusion) of human metapneumovirus. Human metapneumovirus (HUN 05-L20) clustered into the subgroup B1 has the closest nucleotide similarity (98%) to JPS03-194 (AY530094) detected in Japan. CONCLUSIONS: Human metapneumovirus contributes as an etiological agent of acute lower and upper respiratory tract infection especially in winter season in children with bronchiolitis, pneumonia or episodes of asthma exacerbation in Hungary, too.

Correction: Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs.

[This corrects the article DOI: 10.1371/journal.pone.0160146.].

Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs.

BACKGROUND: The similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins. METHODS: 172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables. RESULTS: A notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs. CONCLUSIONS: This significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs.

Nemaline myopathy type 2 (NEM2): two novel mutations in the nebulin (NEB) gene.

Nemaline myopathy is a type of the heterogeneous group of congenital myopathies. Generalized hypotonia, weakness, and delayed motor development are the main clinical features of the typical congenital form. Histopathology shows characteristic nemaline rods in the muscle biopsy. Mutations in at least 7 genes, including nebulin gene (NEB), proved to be responsible for this muscle disease. We present a boy with nemaline myopathy type 2 (NEM2) caused by compound heterozygosity for 2 novel mutations, a deletion and a duplication in the NEB gene. The deletion was inherited from the father and the duplication from the mother. Testing all family members supports genetic counseling.

Assessment of respiratory mechanics with forced oscillations in healthy newborns.

BACKGROUND: Lung function data in healthy newborn infants are scarce largely due to lack of suitable techniques, although data for developmental and prenatal exposure studies are much needed. We have modified the forced oscillation technique (FOT) for the measurement of respiratory mechanical impedance (Zrs) in unsedated sleeping infants in the first 3 days of life. METHODS: Zrs was measured during 30-s epochs of quiet sleep in term neonates born via spontaneous vaginal delivery with a non-invasive FOT between 8 and 48 Hz. Total respiratory resistance (R), compliance (C) and inertance (I) were obtained by fitting Zrs spectra. Cluster analysis was used to determine a set of minimal Zrs spectra representing optimal respiratory mechanics for each infant. RESULTS: Successful measurements were obtained in each of the first 3 days in 30/38 (78.9%) neonates. Group mean (± SD) values of R, C, I, and resonant frequency pooled for the 3 days were 45.9 ± 16.6 hPa s L(-1), 0.97 ± 0.21 ml hPa(-1), 0.082 ± 0.031 hPa s(2) L(-1) and 19.2 ± 3.2 Hz, respectively. Within-session variability represented by coefficient of variation was 5.34 ± 3.18% for R and 13.80 ± 8.57% for C. Greater between-session variability was observed for the individual infants; however, the only statistically significant change over time was a 13% increase in R from day 1 to day 2. Parameter interdependence was significant (r(2) = 0.63) between R and I reflecting the large contribution of the upper airways to the total Zrs. CONCLUSIONS: Noninvasive measurement of Zrs can be made in neonates during natural sleep with a high success rate, even in the first hours of life.