Clinical and molecular characteristics of primary ciliary dyskinesia: A tertiary care centre experience.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a ciliopathy with diverse clinical and genetic findings caused by abnormal motile cilia structure and function. In this study, we describe the clinical characteristics of confirmed PCD cases in our population and report the radiological, genetic, and laboratory findings. METHODS: This was a retrospective, observational, single-centre study. We enrolled 18 patients who were diagnosed with confirmed PCD between 2015 and 2019. We then analyzed their data, including clinical findings and workup. RESULTS: In our cohort, 56% of patients had molecularly confirmed PCD, and RSPH9 was the most common gene identified. Transmission electron microscopy (TEM) showed an ultrastructural defect in 64% of samples, all of which matched the genetic background of the patient. Situs inversus (SI) was observed in 50% of patients, and congenital heart disease was observed in 33%. The median body mass index (BMI) was 15.87 kg/m2, with a median z score of -1.48. The median FEV1 value was 67.6% (z score - 2.43). Radiologically, bronchiectasis was noted in 81% of patients at a variable degree of severity. Lung bases were involved in 91% of patients. We were unable to correlate the genotype-phenotype findings. CONCLUSION: We describe the clinical and molecular characteristics of patients with confirmed PCD in a tertiary centre in Saudi Arabia and report 9 new pathogenic or likely pathogenic variants in one of the PCD-associated genes.

Medical Faculty's and Students' Perceptions toward Pediatric Electronic OSCE during the COVID-19 Pandemic in Saudi Arabia.

BACKGROUND: The educational process in different medical schools has been negatively affected by the COVID-19 pandemic worldwide. As a part of the Saudi government's attempts to contain the spread of the virus, schools' and universities' educational activities and face-to-face lectures have been modified to virtual classrooms. The purpose of this study was to explore the perceptions of the faculty and the students of an electronic objective structured clinical examination (E-OSCE) activity that took place during the COVID-19 pandemic in the oldest medical school in Saudi Arabia. METHODS: An e-OSCE style examination was designed for the final-year medical students by the pediatrics department, College of Medicine at King Saud University in Riyadh, Saudi Arabia. The examination was administered by Zoom™ video conferencing where both students and faculty participated through their laptop or desktop computers. In order to explore the students' and the faculty's perceptions about this experience, a newly designed 13-item online questionnaire was administered at the end of the e-OSCE. RESULTS: Out of 136 participants (23 faculty and 112 students), 73 respondents (e.g., 54% response rate) filled out the questionnaire. Most of the respondents (69.8%) were very comfortable with this new virtual experience. Most participants (53.4%) preferred the e-OSCE compared to the classic face-to-face clinical OSCE during the pandemic. Regarding the e-OSCE assessment student tool, 46.6% reported that it is similar to the classic face-to-face OSCE; however, 38.4% felt it was worse. CONCLUSIONS: The e-OSCE can be a very effective alternative to the classic face-to-face OSCE due to the current circumstances that still pose a significant risk of infection transmission. Future studies should examine different virtual strategies to ensure effective OSCE delivery from the perspective of both faculty and students.

An SFTPC gene mutation causes childhood interstitial lung disease: first report in the Arab region.

BACKGROUND: Surfactant protein C dysfunction is one of the causes of childhood interstitial lung disease but has not previously been reported in Arabian countries. CASE PRESENTATION: A six-year-old girl had presented at the age of eight months old with bronchiolitis followed by a persistent cough, dyspnea and hypoxaemia. She was found to have gastroesophageal reflux disease, but her symptoms did not resolve despite her therapy being optimised. Further tests, including a chest computed tomographic scan, lung biopsy and genetic testing, confirmed a diagnosis of surfactant protein C dysfunction. CONCLUSION: We report the first case in the Arab region of childhood interstitial lung disease caused by surfactant protein C deficiency.

Anti-IgE therapy for asthma: an audit at atertiary care centre in Saudi Arabia.

BACKGROUND: Although anti-IgE therapy has been shown to offer numerous benefits, we suspect it is underutilized locally. To date, there are no studies on any aspect of its use in the Arab region. There is also no information on whether physicians follow current guidelines nor on patient response to this form of therapy. OBJECTIVE: Assess the use of omalizumab for patients with difficult asthma at a tertiary care center. DESIGN: Retrospective, descriptive. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Information was collected from medical records and interviews of all patients who received a minimum of 6 months of omalizumab, including data on practices of the prescribing physician (pulmonary versus allergy), indications, dose, subjective response, number of emergency room visits and hospitalizations, changes in asthma medications, adverse effects, and the setting for delivery of therapy. MAIN OUTCOME MEASURES: Extent to which current guidelines for prescribing omalizumab were followed. Patient subjective and objective responses to treatment as reflected by changes in the use of medications and lung function before and after therapy. SAMPLE SIZE: 50 patients. RESULTS: Of the 50 consecutive patients, 35 were female and the mean (SD) age was 46.3 (9.2) years. Only 28 patients (56 %) met all the criteria for the prescription of omalizumab as per current guidelines; 18 (64%) by pulmonary and 10 (36%) by allergy physicians (P less than .05). Pulmonary physicians performed more tests for conditions complicating or simulating asthma (P less than .05). The mean (SD) duration of treatment by omalizumab of 35 (22) months was longer in patients managed by allergists (42 [24] months) than pulmonary physicians (30 [21] months) (P greater than .05). Both physician groups prescribed a lower initial dose than recommended (P less than .05 recommended vs. prescribed). Patients reported a significant improvement in symptoms, reduction in the use of broncho-dilators and oral steroids and in the use of healthcare services (from 16.28 [7.9] to 2.08 [1.78], P less than .0001) mean values from sum of hospitalizations/year, ER visits/year, exacerbations/year, but not in other medications or pulmonary function tests (P greater than .05). CONCLUSION: Despite several benefits, notably a reduction in utilization of health services and asthma medication, anti-IgE therapy is probably underutilized locally. Pulmonary physicians are more likely to follow the guidelines than allergy physicians. This study suggests that there is room for improvement in the prescription practices, particularly in dosing and the setting for delivery. Further multicenter prospective studies are required to identify gaps in the current practices and improve asthma management. LIMITATIONS: Too few patients met inclusion criteria, lack of control group, and use of a subjective assessment for patient symptoms as opposed to validated questionnaires. CONFLICT OF INTEREST: None.

Pediatric sickle cell disease and obstructive sleep apnea: A cross-sectional study in a tertiary pediatric center in Saudi Arabia.

OBJECTIVE: The aim of the study was to evaluate snoring and obstructive sleep apnea (OSA) in Saudi children with sickle cell disease (SCD). MATERIALS AND METHODS: This cross-sectional study was conducted among children with SCD attending a hematology clinic were recruited. Demographics, clinical data, and sleep questionnaires were collected and overnight polysomnographies performed. RESULTS: Seventy children (31 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.5, 11) years and their body mass index z-score was -1.2 (-2.0, -0.4). Seventy-four percent of SCD patients snored and 32 (46%) had evidence of OSA (obstructive apnea-hypopnea index [OAHI] ≥2 events per hour of sleep), 13 of whom had moderate OSA (OAHI ≥5 and <10 events per hour of sleep) and 10 had severe OSA (OAHI ≥10 events per hour of sleep). CONCLUSION: Snoring and the proportion of OSA were high in children with SCD. This underlines the importance of screening for OSA in all children with SCD.

Admission predictability of children with acute asthma.

OBJECTIVES: We aimed to evaluate the seasonal variations of acute asthma presentation in children and the utility of the pediatric asthma score (PAS) and its components in early admission prediction. METHODS: As part of a randomized controlled trial addressing the clinical efficacy of budesonide nebulization in the treatment of acute asthma in children, the PAS was measured at baseline, 1st, 2nd, 3rd, and 4th h from the start of medications. Decision of admission was taken at or beyond the 2nd h. RESULTS: Out of a total 906 emergency department (ED) visits with moderate-to-severe acute asthma, 157 children were admitted. June to September had the lowest number of visits. The admission-to-discharge ratio varied throughout the year. During the ED stay, between baseline and 3rd h, admission predictability of the total score improved progressively with a small difference between the 2nd and 3rd h. The total score remained the strongest predictor of admission at every time point compared to its individual components. The drop of PAS from baseline to the 2nd h was not a good predictor of admission. Oxygen saturation (OS) and respiratory rate (RR) had relatively higher predictability than other components. CONCLUSIONS: Decision of admission could be made to many children with moderate-to-severe acute asthma at the 2nd h of ED stay based on their total PAS. OS and RR should be part of any scoring system to evaluate acute asthma in children.

Hyperglycemia in Children Hospitalized with Acute Asthma.

Hyperglycemia is frequently observed in adults with acute asthma. We aimed to assess the frequency of hyperglycemia and its relation to outcomes in children admitted with acute asthma. In this retrospective study, we reviewed medical records of non-diabetic 166 children (66 girls) with the mean age of 5.4 ± 2.6 years (range of 2-12 years), who were hospitalized with acute asthma between January 2012 through December 2014. Data pertaining to demographics, vital signs, oxygen saturation, serum blood glucose level, electrolytes, blood gases, and admission were collected. Children with other chronic conditions were excluded. The findings were that hyperglycemia (blood glucose ≥ 11.1 mmol/l) was observed in 38.6% of children. The median baseline blood glucose (IQR) was 9.8 mmol/l (7.2-13.3 mmol/l). Blood glucose level was associated with the length of hospitalization, with a median extension of 1.8 days, but was inversely associated with the serum potassium and bicarbonate levels. There were no associations between baseline blood glucose and age, gender, baseline respiratory rate, oxygen saturation, or intensive care admission. Hyperglycemia resolved spontaneously in all affected children. We conclude that hyperglycemia is common in children hospitalized with acute asthma. Hyperglycemia could be considered as a marker of a longer hospital stay.

The Saudi Thoracic Society guidelines for diagnosis and management of noncystic fibrosis bronchiectasis.

This is the first guideline developed by the Saudi Thoracic Society for the diagnosis and management of noncystic fibrosis bronchiectasis. Local experts including pulmonologists, infectious disease specialists, thoracic surgeons, respiratory therapists, and others from adult and pediatric departments provided the best practice evidence recommendations based on the available international and local literature. The main objective of this guideline is to utilize the current published evidence to develop recommendations about management of bronchiectasis suitable to our local health-care system and available resources. We aim to provide clinicians with tools to standardize the diagnosis and management of bronchiectasis. This guideline targets primary care physicians, family medicine practitioners, practicing internists and respiratory physicians, and all other health-care providers involved in the care of the patients with bronchiectasis.

Co-Circulation of 72bp Duplication Group A and 60bp Duplication Group B Respiratory Syncytial Virus (RSV) Strains in Riyadh, Saudi Arabia during 2014.

Respiratory syncytial virus (RSV) is an important viral pathogen of acute respiratory tract infection (ARI). Limited data are available on molecular epidemiology of RSV from Saudi Arabia. A total of 130 nasopharyngeal aspirates were collected from children less than 5 years of age with ARI symptoms attending the Emergency Department at King Khalid University Hospital and King Fahad Medical City, Riyadh, Saudi Arabia between October and December, 2014. RSV was identified in the 26% of the hospitalized children by reverse transcriptase PCR. Group A RSV (77%) predominated during the study as compared to group B RSV (23%). The phylogenetic analysis of 28 study strains clustered group A RSV in NA1 and ON1 genotypes and group B viruses in BA (BA9) genotype. Interestingly, 26% of the positive samples clustered in genotypes with duplication in the G protein gene (ON1 for group A and BA for group B). Both the genotypes showed enhanced O-linked glycosylation in the duplicated region, with 10 and 2 additional sites in ON1 and BA respectively. Selection pressure analysis revealed purifying selection in both the ON1 and BA genotypes. One codon each in the ON1 (position 274) and BA genotypes (position 219) were positively selected and had high entropy values indicating variations at these amino acid positions. This is the first report describing the presence of ON1 genotype and the first report on co-circulation of two different genotypes of RSV with duplication in the G protein gene from Saudi Arabia. The clinical implications of the simultaneous occurrence of genotypes with duplication in G protein gene in a given population especially in the concurrent infections should be investigated in future. Further, the ongoing surveillance of RSV in this region will reveal the evolutionary trajectory of these two genotypes with duplication in G protein gene from largest country in the Middle East.

Adenosine triphosphate-binding cassette member A3 gene mutation in children from one family from Saudi Arabia.

Mutation in ABCA3, which is adenosine triphosphate-binding cassette member A3, a member of protein transporter family for phospholipids into the lamellar bodies during synthesis of surfactant, can cause lung disease related to surfactant dysfunction with autosomal recessive pattern. We reported three cases from same family with ABCA3 mutation, their gene, clinical course, and outcomes mentioning that one patient had successful lung transplantation, one started the process of the lung transplantation while the third one died during infancy. We concluded that the patients with ABCA3 gene mutations are increasing in numbers may be due to the availability of the genetic testing and high index of suspicion among physicians. Lung transplantation is the definitive treatment, but availability is limited in our region.

Lung disease associated with filamin A gene mutation: a case report.

BACKGROUND: Mutations in the gene encoding filamin A (FLNA) lead to diseases with high phenotypic diversity including periventricular nodular heterotopia, skeletal dysplasia, otopalatodigital spectrum disorders, cardiovascular abnormalities, and coagulopathy. FLNA mutations were recently found to be associated with lung disease. In this study, we report a novel FLNA gene associated with significant lung disease and unique angiogenesis. CASE PRESENTATION: Here, we describe a 1-year-old Saudi female child with respiratory distress at birth. The child then had recurrent lower respiratory tract infections, bilateral lung emphysema with basal atelectasis, bronchospasm, pulmonary artery hypertension, and oxygen and mechanical ventilation dependency. Molecular testing showed a new pathogenic variant of one copy of c.3153dupC in exon 21 in the FLNA gene. CONCLUSIONS: Our data support previous reports in the literature that associate FLNA gene mutation and lung disease.

Clinical presentation of air leak in an infant with undiagnosed cystic fibrosis: a case report.

INTRODUCTION: Air leak is a well-recognized complication of advanced cystic fibrosis in older children and adults but is extremely rare in infants. To the best of our knowledge, this is the youngest reported pediatric case of an air leak from a major airway. CASE PRESENTATION: A 4-month-old Yamani baby girl with a family history of cystic fibrosis initially presented with a history of a persistent paroxysmal cough for 3 weeks and vomiting for 1 week. Laboratory evaluation indicated pseudo-Bartter's syndrome. Imaging showed a tracheal tear with pneumomediastinum and subcutaneous emphysema that was treated conservatively. CONCLUSIONS: This case highlights the possibility of air leak in the population of young patients with cystic fibrosis and it shows a successful conservative management of tracheal tear. Physicians should consider cystic fibrosis in infants presenting with air leak.

The management of acute severe asthma in a pediatric intensive care unit.

OBJECTIVE: The hospitalization and mortality rates incurred from acute childhood asthma continue to rise in the past decade. The purpose of this study is to examine the outcome, morbidity and the management of children admitted with acute asthma to our pediatric intensive care unit (PICU) and compare it with those described in the literature. METHODS: Medical records of all children admitted with acute severe asthma to PICU at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia over an 8-year period (1994-2001) were reviewed. RESULTS: Fifty-six patients were analyzed. The male to female ratio was 1.3:1 and the mean age was 3.6 +/- 2.8 years. The mean duration of symptoms prior to admission was 2 +/- 1.5 days with 39.3% <24 hours. A positive family history of allergy was present in two third of patients. The average stay in PICU was 2 +/- 0.9 days. Seventy-three percent of patients received prophylaxis bronchodilator therapy before hospital admission including inhaled steroid in 62%. All the patients received nebulized salbutamol and intravenous corticosteroid. Two third of our patients received nebulized ipratropium bromide and 62% intravenous aminophylline. From arterial blood gases analysis, 46.4% had hypercapnia (PaCO2 >45 mmHg). None of our patients required mechanical ventilation. Only 2 patients developed pneumomediastinum with pneumothorax that has resolved spontaneously without intervention. There were no deaths among our 56 patients admitted to PICU. CONCLUSION: We conclude that the mortality and morbidity in children with severe asthma, who require PICU admissions are minimal, provided optimal early use of bronchodilators and intravenous steroids. Using this approach, it could also be possible to avoid mechanical ventilation and shorten the duration of hospital admission.

The diagnostic approach to suspected asthma in a Primary Care Center in Riyadh.

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