Longitudinal Assessment of Curaçao Criteria in Children with Hereditary Hemorrhagic Telangiectasia.

OBJECTIVE: To assess the utility of the Curaçao criteria by age over time in children with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This was a single-center, retrospective analysis of patients attending the HHT clinic at the Hospital for Sick Children (Toronto, Canada) between 2000 and 2019. The evaluation of the Curaçao criteria was completed during initial and follow-up visits. Screening for pulmonary and brain arteriovenous malformations was completed at 5 yearly intervals. RESULTS: A total of 116 patients with genetic confirmation of HHT were included in the analysis. At initial screening at a median (IQR) age of 8.4 (2.8, 12.9) years, 41% met criteria for a definite clinical diagnosis (≥3 criteria). In children <6 years at presentation, only 23% fulfilled at least 3 criteria initially. In longitudinal follow-up, 63% reached a definite clinical diagnosis, with a median (IQR) follow-up duration of 5.2 (3.2, 7.9) years (P = .005). Specifically, more patients met the epistaxis and telangiectasia criteria at last visit compared with initial (79% vs 60%; P = .006; 47% vs 30%; P = .02) but not for the arteriovenous malformation criterion (59% vs 57%; P = .65). CONCLUSIONS: In the pediatric population, most patients do not meet definite clinical criteria of HHT at initial presentation. Although the number of diagnostic criteria met increased over time, mainly due to new onset of epistaxis and telangiectasia, accuracy remained low during follow-up visits. Relying solely on clinical criteria may lead to underdiagnosis of HHT in children.

Lower Airway Nitrogen Oxide Levels in Children with Primary Ciliary Dyskinesia Is Linked to Neutrophilic Inflammation.

Treatment of primary ciliary dyskinesia pulmonary exacerbations resulted in an increase in sputum nitric oxide (NO) metabolites and decrease in neutrophilic inflammation. The association between the 2 suggests that neutrophilic inflammation contributes to airway NO deficiency in primary ciliary dyskinesia and that reducing inflammation may lead to improved airway NO homeostasis. TRIAL REGISTRY: ClinicalTrials.gov: NCT01155115.

Growth of Pulmonary Arteriovenous Malformations in Pediatric Patients with Hereditary Hemorrhagic Telangiectasia.

The evolution of pulmonary arteriovenous malformations (PAVMs) over time in children with hereditary hemorrhagic telangiectasia (HHT) is not well-defined. Herein we demonstrate that, although new PAVMs did not evolve in children with HHT, existing PAVMs exhibit quantitative growth over time highlighting the need for ongoing follow-up throughout childhood.

Echocardiography Grading for Pulmonary Arteriovenous Malformation Screening in Children with Hereditary Hemorrhagic Telangiectasia.

Transthoracic contrast echocardiography (TTCE) has high sensitivity but low specificity in screening for pulmonary arteriovenous malformations (pAVMs) in children with hereditary hemorrhagic telangiectasia (HHT). Here we describe characteristics of TTCE that might be used to reduce the need for confirmatory computed tomography scans in children with HHT.

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis.

OBJECTIVE: To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). STUDY DESIGN: Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. RESULTS: Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P < .006) but no differences in anxiety or vulnerability (P > .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. CONCLUSION: Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families.

Índice de aclaramiento pulmonar en pediatría / Lung clearance index

The rate of lung clearance is a measure of the ventilation inhomogeneity determined during multiple breath washout (MBW). Higher values of lung clearance index (LCI) indicate greater ventilation inhomogeneity. The test is performed during tidal breathing, needs little cooperation and coordination, and can be done in all age groups. Different tracer gases can be used; the most common are gas nitrogen as resident gas and sulfohexafluoride (SF6) as an exogenous gas.LCI has been used in various pediatric diseases, such as asthma, bronchopulmonary dysplasia and especially in patients with cystic fibrosis (CF), where high LCI values had been a more sensitive tool that spirometry to detect the early disease and bronchiectasis. It has also been used to monitor the progression of early lung disease, since the value of LCI in preschoolers predicted FEV1 in children of school age. Finally, in patients older than 6 years LCI has proven to be a useful tool to assess response to interventions in patients with normal lung function test. In conclusion the use of LCI is very promising in CF patients with early stages of the disease, and in the clinical monitoring of patients with CF. Its role in other respiratory diseases such as asthma, is still to be determined.

El índice de aclaramiento de pulmón (LCI) es una medida de la falta de homogeneidad de ventilación determinado durante el lavado pulmonar de múltiples respiraciones (MBW). Los valores más altos de LCI indican mayor inhomogeneidad de ventilación. La prueba se realiza durante respiración corriente y necesita poca cooperación y coordinación, por lo que se puede realizar en todos los grupos de edad. Pueden utilizarse diferentes gases trazadores; los más comunes son el nitrógeno como gas residente y sulfohexafluoride (SF6) como gas exógeno.LCI ha sido utilizado en diferentes enfermedades en pediatría, tales como asma, displasia broncopulmonar y especialmente fibrosis quística (FQ). En esta última los valores elevados de LCI son una herramienta más sensible quela espirometría para la detección de la enfermedad pulmonar precoz y bronquiectasias. También ha sido utilizado para monitorizar la progresión de la enfermedad pulmonar, ya que el valor de LCI en los niños en edad preescolar predice el VEF1 en edad escolar. Finalmente en pacientes mayores de 6 años LCI ha demostrado ser una herramienta útil para evaluarla respuesta a intervenciones en pacientes con función pulmonar normal. En conclusión el uso de LCI es muy prometedor en pacientes con FQ en etapa precoz de la enfermedad, su rolen el monitoreo clínico de los pacientes con FQ. En otras enfermedades de las vías respiratorias, como el asma, esto aún está por definirse.

The diagnostic yield of rescreening for arteriovenous malformations in children with hereditary hemorrhagic telangiectasia.

The diagnostic yield of rescreening children with hereditary hemorrhagic telangiectasia at regular intervals for arteriovenous malformations is unclear. Here, we show that when children with initially negative screening were reassessed after 5 years, no new arteriovenous malformations were detected suggesting that longer intervals between screenings may be adequate.

Prevalence of pulmonary arteriovenous malformations in children versus adults with hereditary hemorrhagic telangiectasia.

It is unclear whether pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia develop later in life or are preformed in childhood. We show that the prevalence of PAVMs in children is similar to that in their parents, providing evidence against de novo PAVM formation in hereditary hemorrhagic telangiectasia.

Utility of contrast echocardiography for pulmonary arteriovenous malformation screening in pediatric hereditary hemorrhagic telangiectasia.

OBJECTIVE: To evaluate the utility of transthoracic contrast echocardiography (TTCE) as a screening tool for pulmonary arteriovenous malformations (PAVMs) in children with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This was a single-center study of children who underwent baseline screening for PAVMs using both TTCE and chest computed tomography (CT) for evaluation of HHT. The CT and TTCE results were prospectively reviewed independently by 2 radiologists and 2 cardiologists blinded to the study results. RESULTS: Both intraobserver and interobserver agreement for interpreting TTCE results were excellent (κ = 0.97 and 0.92, respectively) and higher than the interobserver agreement for CT interpretation (κ = 0.75). The sensitivity and specificity of TTCE to predict PAVMs were 1 and 0.82, respectively, and the positive predictive and negative predictive values were 0.39 and 1, respectively. CONCLUSION: TTCE is a sensitive test for PAVMs in children with suspected HHT and can be a useful initial screening tool in pediatric HHT.

Diagnostic value of nasal nitric oxide measured with non-velum closure techniques for children with primary ciliary dyskinesia.

OBJECTIVES: Nasal nitric oxide (nNO) is a reliable non-invasive screening test for primary ciliary dyskinesia (PCD), but the recommended technique, exhalation against resistance (ER), requires cooperation limiting its use in young children. Our objectives were to determine whether easier non-velum closure techniques have the ability to discriminate PCD and longitudinal reproducibility. STUDY DESIGN: We conducted a case-control study evaluating 5 breathing techniques (ER, breath hold, tidal breathing mouth open, tidal breathing mouth closed, and humming) for measuring nNO in patients with PCD compared with control subjects (cystic fibrosis [CF], non-PCD non-CF bronchiectasis, and healthy). A subgroup repeated measurements 1 month later. Sensitivity, specificity, and intraclass correlation coefficient of each nNO technique were determined. RESULTS: We tested 85 children (20 PCD, 32 CF, 14 broncheoctasis, and 19 healthy), aged 5 to 18 years (mean age, 11.5 years); 52% of children were male. All breathing techniques discriminated patients with PCD from control subjects with high specificity (>90%), 100% sensitivity, and intraclass correlation coefficient >0.8. nNO output cutoff values for diagnosing PCD varied with techniques (ER, 59 nL/min; breath hold, 61 nL/min; tidal breathing mouth open, 37 nL/min; tidal breathing mouth closed, 30 nL/min; humming, 41 nL/min). CONCLUSION: Non-velum closure techniques are reproducible and valid to discriminate PCD; however, they generally yield lower values than ER.

Sputum induction in routine clinical care of children with cystic fibrosis.

OBJECTIVE: To determine the microbiological yield of induced sputum (IS) samples compared with conventional airway samples, spontaneously expectorated sputum and throat swabs, in children with cystic fibrosis (CF) attending an outpatient clinic. STUDY DESIGN: Ninety-five children with CF (75 able to spontaneously expectorate sputum) were included in this prospective cross-sectional comparative study. After obtaining expectorated sputum or throat swabs samples, IS was obtained by performing the sputum induction procedure using an eFlow device (PARI, Starnberg, Germany). CF bacterial culture results were compared between the two procedures. RESULTS: Differences in culture results between samples were observed in 25 of 94 (27%) patients. IS had a significantly higher yield for CF pathogens, with 80% of the differences being due to detection of additional organisms in IS samples. Overall, SI was well tolerated, but 12 of 95 cases had a >20% postinduction decline in forced expiratory volume in 1 second. The whole SI procedure took 30 to 85 minutes of clinic time, and its estimated additional cost was $150 (US)/patient. CONCLUSIONS: Induced sputum has a higher microbiological yield compared with the conventional samples in children with CF, even in patients capable of expectorating sputum spontaneously. Although sputum induction is safe and tolerable, it is time-consuming and expensive in routine clinical settings.

Airway nitric oxide in Duchenne muscular dystrophy.

The expression of muscle membrane-associated neuronal nitric oxide synthase (NOS1) is significantly impaired in Duchenne muscular dystrophy. Mean (+/- SEM) exhaled NO in 13 male patients with Duchenne muscular dystrophy was significantly lower than in 11 healthy age-matched male control subjects (7.5 +/- 1.4 vs 16.6 +/- 3.2 parts per billion, P <.02) or 17 adult male control subjects (18.5 +/- 1.8 parts per billion, P <.001). These findings provide indirect evidence that NOS1 contributes significantly to fractional exhaled nitric oxide in healthy children.