Cystic Lung Changes, Bronchiectasis, and a Heterozygous-Primary Ciliary Dyskinesia-Associated Variant in the DNAH5 Gene: A Diagnostic Challenge.

BACKGROUND Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease that can present at different ages with different phenotypes. Missed and delayed diagnoses are fairly common. Many variants in the DNAH5 gene have been described that confirm the diagnosis of PCD. Advances in medicine, especially in molecular genetics, have led to increasingly early discoveries of such cases, especially in those with nonclassical presentations. CASE REPORT This report describes a patient with bronchiectasis, lung cysts, finger clubbing, and failure to thrive who was misdiagnosed for several years as having asthma. Many differentials were suspected and worked up, including a suspicion of PCD. Genetic tests with whole-exome sequencing (WES) and whole-genome sequencing (WGS) detected a heterozygous, likely pathogenic, variant in the DNAH5 gene associated with PCD. CONCLUSIONS Despite a thorough workup done for this case, including a genetic workup, a PCD diagnosis was not established. We plan to reanalyze the WGS in the future, and with advent of technology and better coverage of genes, a genetic answer for this challenging case may resolve this diagnostic quandary in the future.

Residual Cough and Asthma-like Symptoms Post-COVID-19 in Children.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and is characterized by different presentations ranging from asymptomatic to severe pneumonia. COVID-19 affects all age groups, including pediatric patients. We observed numerous children complaining of a cough post-COVID-19, even if it was trivial. The most reported persistent symptoms after recovery from COVID-19 were insomnia, coughing, fatigue, dyspnea, loss of taste and/or smell, and headache. To date, residual cough post-COVID-19 has been reported in pediatrics and adolescents. METHOD: we conducted a retrospective study, with a self-administered questionnaire by the patient or caregiver, 12 months post-COVID-19-infection. RESULT: A total of 94.8% of patients were Saudi citizens and were mainly from the southern region of Saudi Arabia (50.0%). Mothers (64.4%) submitted most of the results. The ages were as follows: 6-14 years (51.0%), 3-5 years (32.3%), and younger than 2 years of age (only 16.7%). Females accounted for 41.7% of those studied. Nearly half of the patients (48.5%) had had a previous COVID-19 infection in 2022, with only 2.1% infected in 2019. Only 27/194 (13.9%) patients required hospital admission, and 7 of them (4.2%) required intensive care treatment. A total of 179 (92.2%) patients still reported persistent symptoms 4 weeks post-COVID-19-infection. A cough was reported in 69.8% of patients, followed by cough and wheezing in 12.3%. The cough was described as dry in 78.0% and nocturnal in 54.1%, while 42.5% did not notice any diurnal variation. For those reporting residual cough, 39.3% found that it affected school attendance and daily activities, 31.1% reported associated chest pain, 51.9% associated it with wheezing, and 27.1% associated it with shortness of breath. For 54.4%, the residual cough lasted less than one month, while 31.4% reported a 1-2 month duration. Only 1.0% had a duration of cough of more than 3 months. For cough relief, 28.2% used bronchodilators, 19.9% used cough syrup, 16.6% used a combination of bronchodilators and steroid inhalers, and 1.7% used antibiotics. Surprisingly, 33% attempted herbal remedies for cough relief. Sesame oil was used the most (40.0%), followed by a mixture of olive oil and sesame oil (25.0%), and 21.7% used male frankincense. The majority (78.4%) sought medical advice for their post-infection cough, either from general pediatricians (39.5%) or via specialist pediatric pulmonology consultations (30.9%). A total of 11.0% with a residual cough reported having pets at home, while 27.2% reported secondhand smoke exposure in the household. Before infection with COVID-19, only 32.6% were diagnosed with asthma, while 68.2% reported a diagnosis of atopic skin. CONCLUSIONS: There was a high prevalence of residual cough post-COVID-19, extended for a minimum of two months, and the characteristics of the cough were very similar to those of asthmatic patients. There was still a high prevalence of using cough syrup and herbal remedies, especially olive oil, sesame oil, and male frankincense. A residual cough adversely affected school attendance in daily activities, and there was a high prevalence of other siblings in the family being affected. The study showed that a minority of patients were seen by the pulmonologist; luckily, long COVID was rare in our study, and so further studies are highly needed to confirm the association with asthma. More educational programs are highly needed regarding herbal remedies and cough syrup.

Primary Ciliary Dyskinesia and Type 1 Diabetes: True Association or Circumstantial?

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive inherited heterogeneous respiratory disorder. The diagnosis of PCD is challenging and necessitates a multi-test diagnostic approach because there are no gold standard diagnostic tests available to confirm PCD. However, rapid advancement in understanding the molecular genetic basis of PCD has greatly improved PCD diagnosis. Studies have reported that PCD may increase the risk of rheumatoid arthritis, congenital heart disease, severe esophageal diseases, and others. Therefore, the present study aimed to assess the risk of type 1 diabetes mellitus (T1DM) in a genetically confirmed PCD patient. In this case study, an 11-year-old girl with autosinopulmonary infections and her younger brother were diagnosed with PCD. The patient's DNA was extracted for next-generation exome sequencing. Our analysis of the exome sequencing data revealed the PCD-causing genetic variant p.Glu286del in the RSPH9 gene on chromosome 6p21.1. In addition, the biochemical findings at the time of patient's admission showed elevated glutamic acid decarboxylase antibodies, HbA1c, and ketone levels, with impaired glucose tolerance, which indicated the presence of T1DM. In conclusion, the clinical features, biochemical reports, and genetic testing confirmed PCD in this patient and the possible association between PCD and T1DM.

Prevalence of sleep problems and habits among children in Saudi Arabia: A cross-sectional study.

OBJECTIVES: To investigate children's sleep problems, habits, and lifestyle changes. METHODS: A cross-sectional study was carried out in Riyadh, Saudi Arabia, over a period of 2 months, from August through September 2022, with parents of children aged 2-14 years after reviewing the literature and formulating a validated Google questionnaire containing 30 questions related to sleep habits, problems, and disorders. RESULTS: In total, 585 questionnaires were included in the analysis. The sample comprised 345 (59%) males and 240 (41%) females. The mean age of patients was 7 (range: 2-14) years. Bed-time resistance was the most prevalent sleep problem (70.3%), followed by sleep-onset delay (58.1%), difficulty waking up in the morning on weekdays (41.3%), weekends (38%), and interrupted sleep (31%). An alarmingly high prevalence of hyperactivity (41.8%) and aggressive behaviour (42.2%) was noted. Co-sleeping with parents was reported in 41% of children. Night terror was reported in 20.6% and 26.5% in nightmares. Statistically significant associations were noted between screen time, snoring, and witnessed apnoea with sleep problems. CONCLUSION: Sleep problems are common among children in Saudi Arabia. The study sheds some light on sleep habits and practices in this age group in Saudi Arabia, such as the high prevalence of bed-time resistance and sleep-onset delay, hyperactivity, and sleep-affecting culprits such as screen time, snoring, and witnessed apnoea.

A Niemann-Pick Disease Type C2 with Severe Pulmonary Involvement and Limited Therapeutic Options: A Case Report.

Niemann-Pick disease type C (NPC) is an autosomal recessive lipid storage disorder. There are two types, NPC1, which is the predominant form (95%), and the rare NPC2, which represents less than 5% of the reported cases. Niemann-Pick disease type C2 usually presents with respiratory symptoms, cholestasis, neurological impairment, and hepatosplenomegaly. Case report: Here, we report a 3-year-old boy who presented to our hospital with exacerbation of chronic lung disease requiring invasive ventilatory support. He was previously diagnosed with interstitial lung disease. His parents used to instill olive oil in his nose (a few drops in each nostril daily for several months) to treat frequent nasal bleeding. A detailed history revealed prolonged neonatal jaundice for four months, with hepatosplenomegaly. In his second year, generalized hypotonia and delayed psychomotor development were observed. Upon presentation to our institute, chest CT showed evidence of intraparenchymal fat; therefore, lipoid pneumonia and lipid storage disease were suspected. The bronchoalveolar lavage results suggested pulmonary alveolar proteinosis (PAP). Whole-exome sequencing (WES) revealed a class one homozygous pathogenic variant in the NPC2 gene. Our patient faced a range of difficulties, including prolonged mechanical ventilation and diagnostic and therapeutic challenges. Conclusion: Niemann-Pick disease type C2 is a progressive and lethal condition that requires a high index of suspicion to pinpoint the diagnosis. Gene study remains the method of choice to confirm the diagnosis. There are limited choices of therapeutic interventions; therefore, genetic counseling and the prevention of recurrence should be the ultimate goal for affected families.

Adverse Drug Reactions (ADRs) of Montelukast in Children.

Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies have reported several adverse events, such as neuropsychiatric disorders and sleep disturbances, among children. OBJECTIVE: To obtain more insight into the safety profile of montelukast for children with asthma, allergic rhinitis and sleep-related breathing disorders. METHOD AND RESULTS: We retrospectively studied all adverse drug reactions to montelukast among 385 children 6 months or older in six tertiary centers over a two-year period. A total of 89.6% were asthmatic, 50% had allergic rhinitis and 13.6% had sleep-related breathing disorders; Singulair was the most common type of montelukast used (67.9%). This study reported a high prevalence of adverse drug reactions among 123 patients (31.9%), predominantly in those aged 4-9 years (52.8%), followed by adolescents (24.4%) and toddlers (22.8%). Two (ADRs) were reported in 9.8% of the children, while three or more were reported in 5.5%. Sleep disturbance was the most common (ADRs), affecting 15.1% of participants (overlap was common; 5.5% of children experienced sleep difficulties, 4.4% experienced sleep interruption and decreased sleep, and 1.82% experienced nightmares), followed by agitation (10.4%), pain (9.4%) and hyperactivity (6.8%). No serious (ADRs) were reported. Eleven percent of families faced difficulties in purchasing montelukast, and only 57% of families had insurance. Misconceptions were common (9.8% reported it to be a steroid, while 30.6% believed it to be a bronchodilator). Although 81% of the families believed it was an effective and preventive medication, 5.3% stopped the drug due to concern about side effects, especially agitation (3%) and nightmares (0.6%). CONCLUSION: These data demonstrate that montelukast is effective, but the associated adverse neuropsychiatric drug reactions are more prevalent than those reported in the literature. In particular, sleep disturbance, agitation, pain and hyperactivity were observed. Pediatricians should be aware of such (ADRs). Misconceptions about montelukast are still common, and parental counseling and urgent epidemiological studies are needed to quantify the risk for management plans.

An Under-Recognized Disease: A Rare Case of Idiopathic CD4 Lymphopenia Mislabeled as Primary Ciliary Dyskinesia.

Idiopathic CD4 Lymphopenia is a heterogeneous condition, recognized in the late 20th century, with a wide spectrum of presentations, requiring a high index of suspicion to avoid misdiagnosing the condition. This case highlights the diversity in its clinical presentations in the context of an autosomal dominant pattern of inheritance. We are reporting a case of a nine-year-old child, initially labelled by her primary treating hospital as primary ciliary dyskinesia after presenting with chronic cough, purulent nasal discharge, and recurrent chest infections. She was referred to our facility, a tertiary center, as her condition marginally improved. After the patient has undergone a comprehensive diagnostic workup, including a gene study, she was found to be carrying a mutation known to cause idiopathic CD4 lymphopenia. Extended work up of her family showed that two of her siblings have inherited an autosomal dominant mutation from their mother who had a milder form of the disease. This condition is an extremely rare condition in children, which can be easily mislabeled. Thus, healthcare providers should avoid labeling certain long-standing diseases unless the diagnosis has been established. We encourage leveraging the use of the latest revolutionary genetic testing techniques to confirm the diagnosis of such puzzling cases.

Lung Abscess Case Series and Review of the Literature.

(1) Background: Lung abscess is a lung infection that leads to the destruction of the lung parenchyma, resulting in a cavity formation and central necrosis filled with purulent fluids. It is an uncommon pediatric problem, and there is a paucity of literature reviews on this subject, especially for the pediatric age group. Lung abscess is commonly divided into those considered primary in previously well children or secondary in those with predisposing co-morbidities. The predominant pathogens isolated from primary lung abscesses are the aerobic organisms, including streptococcal species, Staphylococcus aureus, and Klebsiella pneumoniae, while anaerobic bacteria such as Bacteroides species are predominant in secondary groups. Children usually present with fever, cough, shortness of breath, chest pain, and sputum. While physical examination may reveal diffuse crackles on auscultation, the diagnosis is usually confirmed by chest X-ray. (2) Methods: We report four different cases with lung abscesses from both primary and secondary group with similar presentations and radiological findings, but the approach was different in each according to the underlining cause. (3) Conclusions: Conservative therapies with a prolonged course of antibiotics remain the cornerstone of therapy for both primary and secondary lung abscesses. The underlying cause should be considered when there is a suboptimal response. However, invasive intervention is becoming more popular with better yield, shorter duration of antibiotics and admission, and excellent prognosis.

Invasive Pulmonary Aspergillosis in Children: A Case Report and Literature Review.

BACKGROUND Invasive pulmonary aspergillosis (IPA) is the major cause of mortality and morbidity in immunocompromised patients with prolonged neutropenia and is associated with poor prognosis. Multiple factors are associated with an increased risk of invasive aspergillosis, including persistent neutropenia, impaired lymphocyte engraftment following bone marrow transplantation, cytomegalovirus disease, respiratory virus infection, cytotoxic chemotherapy, and Aspergillus colonization. Unfortunately, attempts at fungal isolation are often unsuccessful. CASE REPORT We describe a 15-year-old girl with a known case of acute myeloid leukemia (AML) with unusual cause of chest infection accompanied with a persistent radiological finding that worsened with time despite multiple levels of intervention. The optimal treatment was unclear, given that all cultures were negatives and the condition did not improve. Very interesting radiological findings will be elaborated in this case. Despite the typical radiological findings, we struggled to confirm the underlying cause of lung infection, which was demonstrated to be Aspergillus fumigatus by thoracoscopy and lavage. Eventually, when the patient started to improve, catastrophic bleeding occurred, confirming the angio-invasive nature of this organism. CONCLUSIONS IPA is still associated with very high morbidity and mortality. A high index of suspicion is needed for such cases. We recommend lavage on the third or fourth day of febrile neutropenia illness in patients who did not show clear improvement with the standard neutropenia protocol, and we suggest considering combined antifungal therapies at an earlier time point. IPA is angio-invasive and can lead to catastrophic bleeding. Earlier surgical intervention might be considered, especially in refractory localized Aspergillus.

When is asthma not guilty?

Asthma is a common childhood condition. Its prevalence in Saudi Arabia is high, increasing, and could exceed 20% at the current trajectory. Asthma is a syndrome with different clinical presentations and phenotypes. Many conditions are often misdiagnosed as asthma because they share the same symptoms, particularly coughing and shortness of breath; physical findings, such as wheezing; radiological findings, such as hyperinflation on chest X-ray; or even responses to asthma therapies, as in some patients with bronchiolitis. When treating the younger age group (>5 years old), there should be a high degree of suspicion of alternative causes when evaluating patients presenting with clinical features suggestive of asthma or patients who do not respond well to asthma therapies. This study will highlight common conditions that may mimic asthma and, as a result of incorrect treatment, unnecessarily expose patients to steroids and other therapies for extended periods. Furthermore, we seek to alert healthcare providers to common symptoms and signs that suggest a cause other than asthma and suggest when to refer the patient to subspecialists.

Application of aerosol therapy in respiratory diseases in children: A Saudi expert consensus.

The Saudi Pediatric Pulmonology Association (SPPA) is a subsidiary of the Saudi Thoracic Society (STS), which consists of a group of Saudi experts with well-respected academic and clinical backgrounds in the fields of asthma and other respiratory diseases. The SPPA Expert Panel realized the need to draw up a clear, simple to understand, and easy to use guidance regarding the application of different aerosol therapies in respiratory diseases in children, due to the high prevalence and high economic burden of these diseases in Saudi Arabia. This statement was developed based on the available literature, new evidence, and experts' practice to come up with such consensuses about the usage of different aerosol therapies for the management of respiratory diseases in children (asthma and nonasthma) in different patient settings, including outpatient, emergency room, intensive care unit, and inpatient settings. For this purpose, SPPA has initiated and formed a national committee which consists of experts from concerned specialties (pediatric pulmonology, pediatric emergency, clinical pharmacology, pediatric respiratory therapy, as well as pediatric and neonatal intensive care). These committee members are from different healthcare sectors in Saudi Arabia (Ministry of Health, Ministry of Defence, Ministry of Education, and private healthcare sector). In addition to that, this committee is representing different regions in Saudi Arabia (Eastern, Central, and Western region). The subject was divided into several topics which were then assigned to at least two experts. The authors searched the literature according to their own strategies without central literature review. To achieve consensus, draft reports and recommendations were reviewed and voted on by the whole panel.

Diagnosis and management of childhood sleep-disordered breathing. Clinical approach.

Sleep-disordered breathing (SDB) includes disorders of breathing that affect airway patency, which impair children's sleep and lead to negative consequences. Obstructive sleep apnea, hypoventilation and upper airway resistance syndrome are common causes of morbidity and mortality in childhood. These clinical practice guidelines, intended for use by pediatricians and primary care clinicians, provide a clear recommendation for the diagnosis and management of sleep-disordered breathing, focusing on the most serious disorder, obstructive sleep apnea syndrome (OSAS). These clinical guidelines formulate clear recommendations to identify patients with suspected OSAS. Further, the manuscript will highlight the potential consequences of SBD in children, and how to overcome such difficulties, what could be the therapeutic options, a 12 recommendations and what are the future direction for pediatric sleep medicine.

Approach to childhood asthma in the era of COVID-19: The official statement endorsed by the Saudi Pediatric Pulmonology Association (SPPA).

Coronaviruses are a large family of viruses that infect humans, which may result in mild symptoms similar to those of the common cold. COVID-19 is most recent subtype similar or even worse than the two previous pandemic strains which were the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). The first cases of COVID-19 emerged in December 2019. Since then, the virus causing the disease has infected more than four million people around the globe and led to hundreds of thousands deaths. We think addressing the management of asthma in the era of this pandemic is important for several reasons: high prevalence of asthma in Saudi Arabia, further, majorities were uncontrolled disease. The statement will provide special instructions and answers to common questions of physicians dealing with asthmatic children during this pandemic.

Bronchiolitis in children: The Saudi initiative of bronchiolitis diagnosis, management, and prevention (SIBRO).

Bronchiolitis is the leading cause of admissions in children less than two years of age. It has been recognized as highly debated for many decades. Despite the abundance of literature and the well-recognized importance of palivizumab in the high risk groups, and despite the existence of numerous, high-quality, recent guidelines on bronchiolitis, the number of admissions continues to increase. Only supportive therapy and few therapeutic interventions are evidence based and proved to be effective. Since Respiratory Syncytial Virus (RSV) is the major cause of bronchiolitis, we will focus on this virus mostly in high risk groups like the premature babies and children with chronic lung disease and cardiac abnormalities. Further, the prevention of RSV with palivizumab in the high risk groups is effective and well known since 1998; we will discuss the updated criteria for allocating infants to this treatment, as this medication is expensive and should be utilized in the best condition. Usually, diagnosis of bronchiolitis is not challenging, however there has been historically no universally accepted and validated scoring system to assess the severity of the condition. Severe RSV, especially in high risk children, is unique because it can cause serious respiratory sequelae. Currently there is no effective curative treatment for bronchiolitis. The utility of different therapeutic interventions is worth a discussion.

Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation in Saudi Arabia.

Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare disease, but could be fatal if not diagnosed early. It mimics many other diseases and it may take few years after the onset of rapid obesity to have the other clinical features. Therefore, any patient with rapid-onset obesity after the age of 2 years should have high index of suspicion and long term follow up. We report a case of ROHHAD in Saudi Arabia and we highlight the clinical features and the importance of early diagnosis and management.

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.

Flexible bronchoscopy in children: Utility and complications.

BACKGROUND AND OBJECTIVES: The flexible bronchoscope has become widely used by pediatric pulmonologists as a diagnostic and therapeutic tool. Nevertheless, there are several gaps in our knowledge to help refine its use and reduce its complications. In this study, we aimed to evaluate the utility and complications of pediatric bronchoscopy. DESIGN AND SETTING: We conducted a retrospective review of bronchoscopy cases between March 2006 and April 2015 at a tertiary care medical center (King Fahad Medical City). One-hundred forty nine patients were studied. PATIENTS AND METHODS: We evaluated how bronchoscopy contributed to the patients' diagnosis, assessed the accuracy of bronchoalveolar lavage white blood cell count (BAL WBC) to differentiate between infectious and non-infectious conditions, assessed the ability of clinical factors to predict high risk of desaturation during bronchoscopy, and finally summarized the reported procedural complications. RESULTS: We found pediatric bronchoscopy was a crucial diagnostic (confirming, ruling out, and discovering unexpected diagnosis) and therapeutic tool. The accuracy of BAL WBC counts is poor (AUC (95% CI) = 0.609 (0.497-0.712)); however, using two cutoff values (≤10 WBCs (sensitivity = 84.44% and specificity = 29.27%) to rule out, and ≥400 WBCs (sensitivity = 33.33% and specificity 81.49%) to rule in infection) helped in early differentiation between infectious and non-infectious conditions. From the factors that we test, none we found predictive of desaturation. The most common procedural complication was desaturation (pooled incidence (95% CI) = 13 (8-19)%) followed by cough, mild airway bleeding, and spasm. CONCLUSIONS: Flexible bronchoscopy is an important and relatively safe diagnostic and therapeutic tool in pediatric medicine, and utilization of this service should be encouraged after a careful consideration of which patient needs this procedure and a rigorous estimate of its pros and cons.

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.