Suhail Al-Saleh

Asymmetric Dimethylarginine Contributes to Airway Nitric Oxide Deficiency in Patients with Cystic Fibrosis

RATIONALE Airway nitric oxide is reduced in cystic fibrosis airways. Asymmetric dimethylarginine is an endogenous nitric oxide synthase inhibitor that may contribute to nitric oxide deficiency in cystic fibrosis. OBJECTIVES To test the hypothesis that asymmetric dimethylarginine is increased in cystic fibrosis and contributes to nitric oxide deficiency and airway obstruction. METHODS The concentrations of asymmetric dimethylarginine, symmetric dimethylarginine, and l-arginine were measured in sputum of clinically stable patients with cystic fibrosis, in patients with cystic fibrosis before and after treatment for a pulmonary exacerbation, and in healthy control subjects, using liquid chromatography-tandem mass spectrometry. MEASUREMENTS AND MAIN RESULTS Asymmetric dimethylarginine was increased in cystic fibrosis compared with control sputum, and the l-arginine/asymmetric dimethylarginine ratio was decreased. Symmetric dimethylarginine exceeded asymmetric dimethylarginine concentrations in control sputum, but this ratio was reversed in cystic fibrosis. Treatment for pulmonary exacerbation resulted in a decrease in sputum asymmetric dimethylarginine and an improved l-arginine/asymmetric dimethylarginine ratio. The treatment-related decrease in asymmetric dimethylarginine correlated significantly with an increase in sputum nitric oxide metabolites and improvement in pulmonary function. The activity of the asymmetric dimethylarginine-metabolizing enzyme, dimethylarginine dimethylaminohydrolase, was higher in cystic fibrosis sputum before rather than after treatment, suggesting that the accumulation of asymmetric dimethylarginine is caused by increased production, not decreased degradation, of asymmetric dimethylarginine. CONCLUSIONS Asymmetric dimethylarginine is increased in cystic fibrosis airways and may contribute to airway obstruction in patients with cystic fibrosis by reducing nitric oxide formation.

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

Descriptive analysis of central sleep apnea in childhood at a single center.

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.

Sleep-related disordered breathing in children with syndromic craniosynostosis

Data on central sleep apnea (CSA) and its significance in children are limited. Our objectives were to describe the polysomnogram (PSG) characteristics and clinical features of children with significant CSA at a single pediatric sleep center.

Longitudinal Evaluation of Sleep-Disordered Breathing in Children with Prader-Willi Syndrome during 2 Years of Growth Hormone Therapy

BACKGROUND Syndromic craniosynostosis patients are at risk for sleep-related disordered breathing (SRDB) but the role of polysomnography (PSG) in assessing these patients has not been fully explored. Our aim was to evaluate the prevalence or severity of SRDB in children with syndromic craniosynostosis or the impact of treatments on their SRDB. METHODS We conducted a retrospective review of all patients with syndromic craniosynostosis referred between 1996 or 2008 for an initial PSG to rule out SRDB. For those with SRDB, we reviewed the interventions post PSG. RESULTS 35 patients (18 females) were included. Specific diagnoses were Crouzons (n=18), Aperts (n=14), Pfeiffer (n=2) or Saethre-Chotzen (n=1) syndromes. Their mean age was 4.5 years or their mean body mass index (BMI) was 16.9 kg/m(2). Of these patients, 26/35 (74%) had evidence of SRDB. The median obstructive apnoea index was 6.6/h (range 0.5-36.4/h) or median central apnoea index was 1.0/h (range 0.0-66.4/h). A total of 16 children had interventions to treat SRDB, of which 14/16 had a follow up PSG or only 10/14 (x%) had a significant improvement of their SRDB. CONCLUSION This review confirms a high prevalence SRDB in this referred population. Despite various interventions, complete resolution of SRDB could not be achieved.

Necrotizing pneumonia complicated by early and late pneumatoceles

OBJECTIVE To review longitudinal polysomnography data to assess sleep-related disordered breathing (SRDB) before and up to 2 years after initiation of growth hormone (GH) therapy in children with Prader-Willi syndrome (PWS). STUDY DESIGN This was a retrospective review of systematic polysomnography evaluations performed in children with PWS before and at 6 weeks, 6 months, 1 year, and 2 years after initiation of GH therapy. RESULTS A total of 15 children with PWS were reviewed. At baseline, the median age was 3.7 years (range, 0.8-15.4 years), and the median body mass index percentile was 82.4 (range, 0-100). GH was discontinued in 2 of these 15 children owing to the occurrence of severe obstructive sleep apnea after 6 weeks of GH therapy. The remaining 13 children who were followed for up to 2 years on GH therapy demonstrated no statistically significant trends over time for any adverse sleep-related outcomes, specifically obstructive or central sleep apnea. CONCLUSION In young children with PWS with known SRDB at baseline, the first few weeks after initiation of GH therapy may represent a vulnerable time for the development of significant SRDB. However, most children with PWS did not show significant changes in SRDB after 2 years of GH therapy. We conclude that long-term GH therapy appears to be safe after an initial period of increased risk in the context of SRDB in children with PWS.

Utility of Contrast Echocardiography for Pulmonary Arteriovenous Malformation Screening in Pediatric Hereditary Hemorrhagic Telangiectasia

Community-acquired pneumonia generally has a benign course when treated, but can be complicated by pleural effusion, empyema, lung abscesses, necrotizing pneumonia or pneumatoceles. Pneumatoceles can cause cardiorespiratory compromise requiring urgent intervention. A child with a severe necrotizing pneumonia, as well as a large early pneumatocele complicating mechanical ventilation, is presented. While pneumonectomy resulted in transient improvement, the course was further complicated by multiple late occurring pneumatoceles that ultimately led to the patients death.

Symptomatic Liver Involvement in Neonatal 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.

The Association between Sleep-Disordered Breathing and Magnetic Resonance Imaging Findings in a Pediatric Cohort with Chiari 1 Malformation

High-flow hepatic vascular anomalies with arteriovenous shunting commonly manifest during the neonatal period with signs and symptoms of congestive heart failure, but to our knowledge, they have never been described in patients with hereditary hemorrhagic telangiectasia (HHT). We report here our experience with 3 patients with hepatic arteriovenous malformations (AVMs) who presented with symptoms of high-output congestive heart failure during the neonatal period and were subsequently diagnosed with HHT. Imaging showed large hypervascular lesions and multiple hepatic arteriovenous shunts that differentiated these lesions from liver hemangiomas. Transcatheter embolization was performed in all cases. One infant died of sepsis shortly after embolization; follow-up at the age of 2.5 years of the surviving infants revealed involution of the vascular lesions and no evidence of symptom recurrence. We conclude that severe symptoms related to hepatic AVMs in HHT can occur in the neonatal period and that HHT should therefore be included in the differential diagnosis of symptomatic neonatal hepatic vascular malformations. Imaging plays a key role in differentiating hepatic AVMs from hemangiomas, because the latter require additional pharmacologic treatments. Early transcatheter embolization seems to be effective, but long-term outcomes still need to be assessed.

The utility of a portable sleep monitor to diagnose sleep-disordered breathing in a pediatric population

BACKGROUND The prevalence of sleep-disordered breathing (SDB) reported in the literature for Chiari malformation type 1 (CM1) is uniformly high (24% to 70%). In Canada, there is limited access to pediatric polysomnography (PSG). Therefore, the identification of clinical features would be invaluable for triaging these children. OBJECTIVE To identify demographic features, clinical symptoms/signs and radiological findings associated with SDB in a large pediatric cohort with CM1. METHODS A retrospective review was conducted on children with CM1 who underwent baseline PSG. Data were collected on patient demographics (age, sex, weight, height, body mass index), clinical symptoms (chart review and clinical questionnaires), diagnostic imaging of the brain and cervicothoracic spine, and medical history at the time of referral. RESULTS A total of 68 children were included in the review. The mean (± SD) age of the children at the time of PSG was 7.33 ± 4.01 years; 56% (n=38) were male. There was a 49% prevalence of SDB in this cohort based on the overall apnea-hypopnea index. Obstructive sleep apnea was the predominant type of SDB. Tonsillar herniation was significantly correlated with obstructive apnea-hypopnea index (r=0.24; P=0.036). CONCLUSIONS A direct relationship between the degree of cerebellar tonsillar herniation and obstructive sleep apnea was demonstrated. However, further prospective studies that include neurophysiological assessment are needed to further translate the central nervous system imaging findings to predict the presence of SDB.