Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.

Among genetic disorders of vesicular trafficking, there are three causing recurrent acute liver failure (RALF): NBAS, RINT1, and SCYL1-associated disease. These three disorders are characterized by liver crises triggered by febrile infections and account for a relevant proportion of RALF causes. While the frequency and severity of liver crises in NBAS and RINT1-associated disease decrease with age, patients with SCYL1 variants present with a progressive, cholestatic course. In all three diseases, there is a multisystemic, partially overlapping phenotype with variable expression, including liver, skeletal, and nervous systems, all organ systems with high secretory activity. There are no specific biomarkers for these diseases, and whole exome sequencing should be performed in patients with RALF of unknown etiology. NBAS, SCYL1, and RINT1 are involved in antegrade and retrograde vesicular trafficking. Pathomechanisms remain unclarified, but there is evidence of a decrease in concentration and stability of the protein primarily affected by the respective gene defect and its interaction partners, potentially causing impairment of vesicular transport. The impairment of protein secretion by compromised antegrade transport provides a possible explanation for different organ manifestations such as bone alteration due to lack of collagens or diabetes mellitus when insulin secretion is affected. Dysfunction of retrograde transport impairs membrane recycling and autophagy. The impairment of vesicular trafficking results in increased endoplasmic reticulum stress, which, in hepatocytes, can progress to hepatocytolysis. While there is no curative therapy, an early and consequent implementation of an emergency protocol seems crucial for optimal therapeutic management.

The N-terminus region of Drp1, a Rint1 family protein is essential for cell survival and its interaction with Rad50 protein in fission yeast S.pombe.

BACKGROUND: Defects in DNA repair pathway can lead to double-strand breaks leading to genomic instability. Earlier we have shown that S.pombe Drp1, a Rint1/Tip1 family protein is required for the recovery from DNA damage. METHODS: Various truncations of Drp1 protein were constructed and their role in DNA damage response and interaction with Rad50 protein has been studied by co-immunoprecipitation and pull-down assays. RESULTS: The structural and functional analysis of Drp1 protein revealed that the N-terminus region of Drp1 is indispensable for the survival. The C-terminus truncation mutants, drp1C1Δ and drp1C2Δ exhibit temperature sensitive phenotype and are hypersensitive against DNA damaging agents with elevated level of Rad52-YFP foci at non-permissive temperature indicating the impairment for DNA damage repair pathway. The essential N-terminus region of Drp1 interacts with the C-terminus region of Rad50 and might be involved in influencing the MRN/X function. Small-angle X-ray (SAXS) analysis revealed three-domain like shapes in Drp1 protein while the C-terminus region of Rad50 exhibit unusual bulges. Computational docking studies revealed the amino acid residues at the C-terminus region of Rad50 that are involved in the interaction with the residues present at the N-terminal region of Drp1 indicating the importance of the N-terminal region of Drp1 protein. CONCLUSIONS: We have identified the region of Drp1 and Rad50 proteins that are involved in the interaction and their role in the DNA damage response pathway has been analyzed. GENERAL SIGNIFICANCE: The functional and structural aspects of fission yeast Drp1 protein and its interaction with Rad50 have been elucidated.

RINT1 Bi-allelic Variations Cause Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities.

Pediatric acute liver failure (ALF) is life threatening with genetic, immunologic, and environmental etiologies. Approximately half of all cases remain unexplained. Recurrent ALF (RALF) in infants describes repeated episodes of severe liver injury with recovery of hepatic function between crises. We describe bi-allelic RINT1 alterations as the cause of a multisystem disorder including RALF and skeletal abnormalities. Three unrelated individuals with RALF onset ≤3 years of age have splice alterations at the same position (c.1333+1G>A or G>T) in trans with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del) in RINT1. ALF episodes are concomitant with fever/infection and not all individuals have complete normalization of liver function testing between episodes. Liver biopsies revealed nonspecific liver damage including fibrosis, steatosis, or mild increases in Kupffer cells. Skeletal imaging revealed abnormalities affecting the vertebrae and pelvis. Dermal fibroblasts showed splice-variant mediated skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay. Fibroblasts also revealed decreased RINT1 protein, abnormal Golgi morphology, and impaired autophagic flux compared to control. RINT1 interacts with NBAS, recently implicated in RALF, and UVRAG, to facilitate Golgi-to-ER retrograde vesicle transport. During nutrient depletion or infection, Golgi-to-ER transport is suppressed and autophagy is promoted through UVRAG regulation by mTOR. Aberrant autophagy has been associated with the development of similar skeletal abnormalities and also with liver disease, suggesting that disruption of these RINT1 functions may explain the liver and skeletal findings. Clarifying the pathomechanism underlying this gene-disease relationship may inform therapeutic opportunities.

Interrupter technique in infancy: Higher airway resistance and lower short-term variability in preterm versus term infants.

BACKGROUND: In preschool children, measurement of airway resistance using interrupter technique (Rint) is feasible to assess the degree of bronchial obstruction. Although some studies measured Rint in infancy, values of Rint and its variability in preterm infants are unknown. In this study, Rint and its variability was measured at infancy and compared between healthy term and preterm infants. METHODS: High quality Rint measurements in term (n = 50) and preterm (n = 48) infants were obtained at postmenstrual age of 42-50 weeks in two study centers in Switzerland. Intra-measurement variability of Rint in one measurement and inter-measurement variability between two subsequent measurements was assessed by coefficient of variation (CV). RESULTS: Mean Rint in term infants was 4.2 ± (SD; 1.9) kPa · s · L-1 and in preterm infants was 5.6 ± (2.8) kPa · s · L-1 . Mean CV in term infants was 29.6 ± (14.9)% and in preterm infants was 20.2 ± (8.4)%. Rint was significantly lower (95%CI -2.31 to -0.38; P = 0.007) and CV significantly higher (95%CI 4.53-14.3; P < 0.001) in term compared to preterm infants. There were no differences in mean Rint and mean CV between the first and the second measurement obtained in a subgroup of term (n = 24, 48%) and preterm (n = 22, 45%) infants. CONCLUSIONS: Our results suggest that differences in airway mechanics between term and preterm infants can be assessed with the interrupter technique during early infancy. Before clinical application of Rint measurements in this age group, reasons underlying the variability of measurements should be further investigated.

Body fat mass distribution and interrupter resistance, fractional exhaled nitric oxide, and asthma at school-age.

BACKGROUND: Obesity and asthma often coexist. We hypothesized that detailed body fat distribution measures might be more strongly associated than body mass index (BMI) with childhood asthma. OBJECTIVE: We examined the associations of total body and abdominal fat measures with respiratory resistance (Rint), fractional exhaled nitric oxide (Feno), and risks of wheezing and asthma in school-aged children. METHODS: In a population-based prospective cohort study among 6178 children aged 6 years, we measured BMI, fat mass index, android/gynoid ratio, and preperitoneal and subcutaneous fat mass by physical examinations, dual-energy x-ray absorptiometry, and ultrasound, respectively. We performed Rint and Feno measurements, and assessed physician-diagnosed wheezing and asthma by questionnaires. RESULTS: A higher BMI was associated with a higher Rint (Z score [95% CI], 0.06 [0.01-0.12]) and increased risk of wheezing (odds ratio [95% CI], 1.07 [1.00-1.14], per Z score BMI increase), but not with Feno or asthma. A high fat mass index was associated with a higher Rint (Z score [95% CI], 0.40 [0.13-0.68]). A high android/gynoid fat mass ratio was associated with a lower Feno (Sym% [95% CI], -9.8 [-16.3 to -3.4]), whereas a high preperitoneal fat mass was associated with a higher Feno (Sym% [95% CI], 6.5 [0.1-12.9]). Subcutaneous fat mass was not associated with any respiratory outcome. CONCLUSIONS: Studying detailed body fat distribution measures might provide better insight into the obesity-asthma paradigm.

RINT-1 interacts with MSP58 within nucleoli and plays a role in ribosomal gene transcription.

The nucleolus is the cellular site of ribosomal (r)DNA transcription and ribosome biogenesis. The 58-kDa microspherule protein (MSP58) is a nucleolar protein involved in rDNA transcription and cell proliferation. However, regulation of MSP58-mediated rDNA transcription remains unknown. Using a yeast two-hybrid system with MSP58 as bait, we isolated complementary (c)DNA encoding Rad50-interacting protein 1 (RINT-1), as a MSP58-binding protein. RINT-1 was implicated in the cell cycle checkpoint, membrane trafficking, Golgi apparatus and centrosome dynamic integrity, and telomere length control. Both in vitro and in vivo interaction assays showed that MSP58 directly interacts with RINT-1. Interestingly, microscopic studies revealed the co-localization of MSP58, RINT-1, and the upstream binding factor (UBF), a rRNA transcription factor, in the nucleolus. We showed that ectopic expression of MSP58 or RINT-1 resulted in decreased rRNA expression and rDNA promoter activity, whereas knockdown of MSP58 or RINT-1 by siRNA exerted the opposite effect. Coexpression of MSP58 and RINT-1 robustly decreased rRNA synthesis compared to overexpression of either protein alone, whereas depletion of RINT-1 from MSP58-transfected cells enhanced rRNA synthesis. We also found that MSP58, RINT-1, and the UBF were associated with the rDNA promoter using a chromatin immunoprecipitation assay. Because aberrant ribosome biogenesis contributes to neoplastic transformation, our results revealed a novel protein complex involved in the regulation of rRNA gene expression, suggesting a role for MSP58 and RINT-1 in cancer development.

Reevaluation of RINT1 as a breast cancer predisposition gene.

Rad50 interactor 1 (RINT1) has recently been reported as an intermediate-penetrance (odds ratio 3.24) breast cancer susceptibility gene, as well as a risk factor for Lynch syndrome. The coding regions and exon-intron boundaries of RINT1 were sequenced in 2024 familial breast cancer cases previously tested negative for BRCA1, BRCA2, and PALB2 mutations and 1886 population-matched cancer-free controls using HaloPlex Targeted Enrichment Assays. Only one RINT1 protein-truncating variant was detected in a control. No excess was observed in the total number of rare variants (truncating and missense) (28, 1.38 %, vs. 27, 1.43 %. P > 0.999) or in the number of variants predicted to be pathogenic by various in silico tools (Condel, Polyphen2, SIFT, and CADD) in the cases compared to the controls. In addition, there was no difference in the incidence of classic Lynch syndrome cancers in RINT1 rare variant-carrying families compared to RINT1 wild-type families. This study had 90 % power to detect an odds ratio of at least 2.06, and the results do not provide any support for RINT1 being a moderate-penetrance breast cancer susceptibility gene, although larger studies will be required to exclude more modest effects. This study emphasizes the need for caution before designating a cancer predisposition role for any gene based on very rare truncating variants and in silico-predicted missense variants.

RINT1 functions as a multitasking protein at the crossroads between genomic stability, ER homeostasis, and autophagy.

RINT1 was first identified as an RAD50-interacting protein and its function was therefore linked to the maintenance of genomic stability. It was also shown that RINT1 was a key player in ER-Golgi trafficking as a member of an ER tethering complex interacting with STX18. However, due to early embryonic lethality of rint1-null mice, the in vivo functions of RINT1 remained for the most part elusive. We recently described the consequences of Rint1 inactivation in various neuronal cells of the central nervous system. We observed that lack of RINT1 in vivo triggers genomic instability and ER stress leading to depletion of the neural progenitor pool and neurodegeneration. Surprisingly, we also observed inhibition of autophagy in RINT1-deficient neurons, indicating an involvement of RINT1 in the regulation of neuronal autophagy. Here, we summarize our main RINT1 findings and discuss its putative roles in autophagy.

Breastfeeding and asthma outcomes at the age of 6 years: The Generation R Study.

BACKGROUND: Breastfeeding is associated with a lower risk of asthma symptoms in early childhood, but its effect at older ages remains unclear. We examined the associations of duration and exclusiveness of breastfeeding with asthma outcomes in children aged 6 years, and whether these associations were explained by atopic or infectious mechanisms. METHODS: We performed a population-based prospective cohort study among 5675 children. Information about breastfeeding was collected by questionnaires. At age 6 years, we measured interrupter resistance (Rint) and fractional exhaled nitric oxide (FeNO). Information about wheezing patterns (early (≤3 years only), late (>3 years only), persistent (≤3 and >3 years)), and current asthma at 6 years was derived from repeated questionnaires. RESULTS: Compared to children who were ever breastfed, those who were never breastfed had lower FeNO levels (sympercent (95% CI): -16.0 (-24.5, -7.5)) and increased risks of late and persistent wheezing (OR(95% CI): 1.69 (1.06, 2.69) and 1.44 (1.00, 2.07), respectively). Shorter duration of breastfeeding was associated with early wheezing and current asthma (1.40 (1.14, 1.73) and 2.19 (1.29, 3.71), respectively). Less exclusive breastfeeding was associated with early wheezing (1.28 (1.08, 1.53)). Breastfeeding duration and exclusiveness were not associated with FeNO or Rint. The associations were not explained by inhalant allergies, partly by lower respiratory tract infections in early life, and to a lesser extent by lower respiratory tract infections in later life. CONCLUSIONS: Breastfeeding patterns may influence wheezing and asthma in childhood, which seems to be partly explained by infectious mechanisms.

Associations of maternal and fetal 25-hydroxyvitamin D levels with childhood lung function and asthma: the Generation R Study.

BACKGROUND: Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma. OBJECTIVE: We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children. METHODS: We performed a population-based prospective cohort study among 3130 mothers and their children. Maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6. RESULTS: Maternal levels of 25-hydroxyvitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25-hydroxyvitamin D levels at birth had a higher Rint (Z-score (95% confidence interval [95% CI]): -0.42 (-0.84, -0.01), P-value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxyvitamin D level was taken into account [Z-score (95% CI): -0.55 (-1.08, 0.01)]. CONCLUSION AND CLINICAL RELEVANCE: Low levels of 25-hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long-term consequences.

Maternal fatty acid levels during pregnancy, childhood lung function and atopic diseases. The Generation R Study.

BACKGROUND: Maternal fatty acid status during pregnancy might influence foetal immunological development and subsequently the risk of childhood atopic diseases. OBJECTIVE: To examine the associations of maternal fatty acid levels during pregnancy with airway resistance and inflammation, asthma and eczema, in school-age children. METHODS: This study among 4976 subjects was embedded in a population-based prospective cohort study. We measured maternal plasma glycerophospholipid fatty acid levels by gas chromatography during the second trimester of pregnancy (mean gestational age: 20.7 (± 1.1) weeks). At the age of 6 years, airway resistance and inflammation were measured by interrupter technique (Rint) and fractional exhaled nitric oxide (FeNO), and current physician-diagnosed asthma and eczema were assessed by ISAAC-based questionnaires. Multiple linear and logistic regression models were adjusted for socio-demographic, lifestyle and anthropometric factors. RESULTS: We did not observe consistent associations of maternal total polyunsaturated fatty acid (PUFA), total n-6 PUFA, total n-3 PUFA levels and n-6/n-3 PUFA ratio during pregnancy with child's Rint and FeNO. Higher maternal total PUFA and total n-6 PUFA levels were associated with a decreased risk of childhood asthma (odds ratios (95% confidence interval): 0.76 (0.60, 0.97) and 0.71 (0.52, 0.96) per standard deviation score (SDS) increase of total PUFA and total n-6 PUFA levels, respectively) and with an increased risk of childhood eczema (1.16 (1.05, 1.28) and 1.21 (1.07, 1.37)). The observed associations were partly explained by Linoleic acid (LA, C18:2n-6) levels. Maternal total n-3 PUFA levels and n-6/n-3 PUFA ratio were not associated with current asthma and eczema. The observed associations were not explained by child's PUFA intake. CONCLUSIONS AND CLINICAL RELEVANCE: Higher maternal total PUFA and total n-6 PUFA levels during pregnancy seem to influence the risk of atopic diseases in childhood. The underlying mechanisms need to be further explored.

Moonlighting functions of the NRZ (mammalian Dsl1) complex.

The yeast Dsl1 complex, which comprises Dsl1, Tip20, and Sec39/Dsl3, has been shown to participate, as a vesicle-tethering complex, in retrograde trafficking from the Golgi apparatus to the endoplasmic reticulum. Its metazoan counterpart NRZ complex, which comprises NAG, RINT1, and ZW10, is also involved in Golgi-to-ER retrograde transport, but each component of the complex has diverse cellular functions including endosome-to-Golgi transport, cytokinesis, cell cycle checkpoint, autophagy, and mRNA decay. In this review, we summarize the current knowledge of the metazoan NRZ complex and discuss the "moonlighting" functions and intercorrelation of their subunits.

Fission yeast Drp1 is an essential protein required for recovery from DNA damage and chromosome segregation.

DNA double strand breaks (DSBs) are the most critical types of DNA damage that can leads to chromosomal aberrations, genomic instability and cancer. Several genetic disorders such as Xeroderma pigmentosum are linked with defects in DNA repair. Human Rint1, a TIP1 domain containing protein is involved in membrane trafficking but its role in DNA damage response is elusive. In this study we characterized the role of Drp1 (damage responsive protein 1), a Rint1 family protein during DNA damage response in fission yeast. We identified that Drp1 is an essential protein and indispensable for survival and growth. Using in vitro random mutagenesis approach we isolated a temperature sensitive mutant allele of drp1 gene (drp1-654) that exhibits sensitivity to DNA damaging agents, in particular to alkylation damage and UV associated DNA damage. The drp1-654 mutant cells are also sensitive to double strand break inducing agent bleomycin. Genetic interaction studies identified that Rad50 and Drp1 act in the same pathway during DNA damage response and the physical interaction of Drp1 with Rad50 was unaffected in drp1-654 mutant at permissive as well as non permissive temperature. Furthermore Drp1 was found to be required for the recovery from MMS induced DNA damage. We also demonstrated that the Drp1 protein localized to nucleus and was required to maintain the chromosome stability.

Evaluación de la medición de las resistencias pulmonares por técnica de interrupción / Assessing the measurement of airway resistance by the interrupter technique

Introducción. Las pruebas de función pulmonar permiten objetivar el grado de obstrucción bronquial en sujetos colaboradores. La medición de las resistencias pulmonares por métodos pasivos es muy útil en sujetos no colaboradores. El objetivo de este estudio fue evaluar la aplicabilidad de la medición de resistencias por interrupción (Rint) en la edad pediátrica, valorando su reproducibilidad, fabilidad y exactitud en relación con otras técnicas de medición de resistencias. Material y métodos. Estudio transversal en niños de entre 2 y 18 años, sanos y con patología obstructiva. Se midió la Rint con un aparato portátil y se comparó con las resistencias medidas por oscilometría y pletismografía. Se valoró la reproducibilidad de las mediciones y la infuencia de diferentes variables (uso de mascarilla o boquilla, sujeción de mejillas o uso de pinza nasal). Resultados. De 460 niños (47,6% menores de 7 años) se obtuvieron medidas válidas en el 82,6%. La reproducibilidad fue muy buena (CCI= 0,9412; p < 0,00001), sin encontrar diferencias entre las medidas obtenidas separadas en el tiempo (0,75 ± 0,3 contra 0,74 ± 0,28; p= 0,435). Ninguno de los factores antes mencionados afectó la reproducibilidad de las medidas. Los valores de resistencia obtenidos por pletismografía y oscilometría fueron superiores a los obtenidos por Rint, con una correlación positiva entre ambos. La correlación con la pletismografía disminuía cuanto mayor era el grado de obstrucción. Conclusiones. La medición de Rint es factible y reproducible, y se correlaciona bien con las resistencias medidas por oscilometría o pletismografía, por lo que sería de utilidad en los pacientes poco colaboradores. En los pacientes obstruidos, podría infraestimar la resistencia, difcultando su uso para el seguimiento de una patología obstructiva moderada-grave o en las pruebas de provocación bronquial.

Introduction. Pulmonary function tests allow an objective assessment of the degree of bronchial obstruction in collaborative subjects. The measurement of airway resistance using passive methods is very helpful in non-collaborative subjects. The objective of this study was to assess the applicability of measuring airway resistance by the interrupter technique (Rint) in pediatric subjects, determining its reproducibility, reliability and accuracy versus other techniques to measure airway resistance. Material and Methods. Cross-sectional study in healthy children and in children with an obstructive airway disease, all aged 2-18 years old. The Rint was measured using a portable device and results were compared to airway resistance measured by oscillometry and plethysmography. The reproducibility of measurements and the infuence of the different outcome measures (use of mask or mouthpiece, cheek support, or nose clip) were assessed. Results. Valid measurements were obtained in 82.6% of 460 children (47.6% younger than 7 years old). Reproducibility was very good (ICC= 0.9412; p <0.00001), and no differences were found among the measurements obtained at separate time intervals (0.75 ± 0.3 versus 0.74 ± 0.28; p= 0.435). None of the factors indicated before had an effect on the reproducibility of measurements. Resistance values obtained by plethysmography and oscillometry were higher than those obtained using the Rint, with a positive correlation between them. The higher the degree of airway obstruction, the worse the correlation with plethysmography. Conclusions. The Rint measurement is a plausible and reproducible technique, and has an adequate correlation with the resistance measurements obtained using oscillometry or plethysmography, thus making it useful for non-collaborative patients. In patients with airway obstruction, this technique could underestimate resistance, so it would be a hurdle to use it to follow-up subjects with a moderate to severe obstructive disease or in bronchial challenge tests.

Evaluación de la medición de las resistencias pulmonares por técnica de interrupción / Assessing the measurement of airway resistance by the interrupter technique

Introducción. Las pruebas de función pulmonar permiten objetivar el grado de obstrucción bronquial en sujetos colaboradores. La medición de las resistencias pulmonares por métodos pasivos es muy útil en sujetos no colaboradores. El objetivo de este estudio fue evaluar la aplicabilidad de la medición de resistencias por interrupción (Rint) en la edad pediátrica, valorando su reproducibilidad, fabilidad y exactitud en relación con otras técnicas de medición de resistencias. Material y métodos. Estudio transversal en niños de entre 2 y 18 años, sanos y con patología obstructiva. Se midió la Rint con un aparato portátil y se comparó con las resistencias medidas por oscilometría y pletismografía. Se valoró la reproducibilidad de las mediciones y la infuencia de diferentes variables (uso de mascarilla o boquilla, sujeción de mejillas o uso de pinza nasal). Resultados. De 460 niños (47,6% menores de 7 años) se obtuvieron medidas válidas en el 82,6%. La reproducibilidad fue muy buena (CCI= 0,9412; p < 0,00001), sin encontrar diferencias entre las medidas obtenidas separadas en el tiempo (0,75 ± 0,3 contra 0,74 ± 0,28; p= 0,435). Ninguno de los factores antes mencionados afectó la reproducibilidad de las medidas. Los valores de resistencia obtenidos por pletismografía y oscilometría fueron superiores a los obtenidos por Rint, con una correlación positiva entre ambos. La correlación con la pletismografía disminuía cuanto mayor era el grado de obstrucción. Conclusiones. La medición de Rint es factible y reproducible, y se correlaciona bien con las resistencias medidas por oscilometría o pletismografía, por lo que sería de utilidad en los pacientes poco colaboradores. En los pacientes obstruidos, podría infraestimar la resistencia, difcultando su uso para el seguimiento de una patología obstructiva moderada-grave o en las pruebas de provocación bronquial.(AU)

Introduction. Pulmonary function tests allow an objective assessment of the degree of bronchial obstruction in collaborative subjects. The measurement of airway resistance using passive methods is very helpful in non-collaborative subjects. The objective of this study was to assess the applicability of measuring airway resistance by the interrupter technique (Rint) in pediatric subjects, determining its reproducibility, reliability and accuracy versus other techniques to measure airway resistance. Material and Methods. Cross-sectional study in healthy children and in children with an obstructive airway disease, all aged 2-18 years old. The Rint was measured using a portable device and results were compared to airway resistance measured by oscillometry and plethysmography. The reproducibility of measurements and the infuence of the different outcome measures (use of mask or mouthpiece, cheek support, or nose clip) were assessed. Results. Valid measurements were obtained in 82.6% of 460 children (47.6% younger than 7 years old). Reproducibility was very good (ICC= 0.9412; p <0.00001), and no differences were found among the measurements obtained at separate time intervals (0.75 ± 0.3 versus 0.74 ± 0.28; p= 0.435). None of the factors indicated before had an effect on the reproducibility of measurements. Resistance values obtained by plethysmography and oscillometry were higher than those obtained using the Rint, with a positive correlation between them. The higher the degree of airway obstruction, the worse the correlation with plethysmography. Conclusions. The Rint measurement is a plausible and reproducible technique, and has an adequate correlation with the resistance measurements obtained using oscillometry or plethysmography, thus making it useful for non-collaborative patients. In patients with airway obstruction, this technique could underestimate resistance, so it would be a hurdle to use it to follow-up subjects with a moderate to severe obstructive disease or in bronchial challenge tests.(AU)

Comparison of Changes Among Airway Resistance, Peak Expiratory Flow Rate, Forced Expiratory Volume in One Second / 소아알레르기및호흡기학회지

PURPOSE: We usually measure the changes of peak expiratory flow rate (PEFR) or forced expiratory volume in one second (FEV1) to check the bronchial response after inhalation of bronchodilator. Airway resistance determined by interrupter technique (Rint) is simple and easily applicable even to the infant. A comparison among PEFR, FEV1 and Rint was done to find out the feasibility of using Rint instead of PEFR or FEV1 in checking the bronchial response after inhalation of bronchodilator. METHODS: We checked PEFR, FEV1, Rint, and oxygen saturation with twenty eight asthmatic children, over 7 years old, visited emergency or out patient department with acute asthmatic attack. The same parameters were checked in 5, 10, 20 minutes after inhalation of bronchodilator. Comparison and relationship of measures as well as changes of measures after inhalation of bronchodilator among them were analyzed to confirm if Rint can replace PEFR or FEV1 in checking bronchial response after inhalation of bronchodilator. RESULTS: PEFR, FEV1 and O2 saturation increased as time goes on but airway resistance decreased. The relationship among the changes of parameters of PEFR, FEV1 and Rint checked in 5, 10 and 20 minutes after inhalation of bronchodilator showed close correlation with was statistically significant. But, the measures checked in 20 minutes after inhalation statistically insignificant. CONCLUSION: Rint can be used instead of PEFR and FEV1 in checking the bronchial response after inhalation of bronchodilator.