Evaluation of safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells in pediatric bronchiolitis obliterans syndrome (BoS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

BACKGROUND: Allo-HSCT is a definite approach for the management of a wide variety of lethal and debilitating malignant and non-malignant disorders. However, its two main complications, acute and chronic graft-versus-host disease (GVHD), exert significant morbidities and mortalities. BoS, as a manifestation of chronic lung GVHD, is a gruesome complication of allo-HSCT, and for those with steroid-refractory disease, no approved second-line therapies exist. Mesenchymal stem cells (MSCs) exert anti-inflammatory and growth-promoting effects, and their administration against a wide range of inflammatory and neurologic disorders, as well as GVHD, has been associated with promising outcomes. However, literature on the safety and effectiveness of MSC therapy for BoS and pediatric cGVHD is scarce. METHODS: We designed a single-arm trial to administer adipose tissue (AT)-derived MSCs to pediatric patients with refractory BoS after allo-HSCT. AT-MSCs from obese, otherwise healthy donors were cultured in an ISO class 1 clean room and injected into the antecubital vein of eligible patients with a dose of 1 × 106/kg. The primary endpoints included a complete or partial response to therapy [in terms of increased forced expiratory volume in one second (FEV1) values and steroid dose reduction] and its safety profile. RESULTS: Four eligible patients with a median age of 6.5 years were enrolled in the study. Steroid-induced osteoporosis and myopathy were present in three cases. A partial response was evident in three cases after a single injection of AT-MSCs. The treatment was safe and tolerable, and no treatment-related adverse events were noted. Two patients developed manageable COVID-19 infections one and 4 months after AT-MSC injection. After a median follow-up duration of 19 months, all cases are still alive and have had no indications for lung transplantation. CONCLUSIONS: AT-MSCs could be safely administered to our pediatric cases with BoS post-allo-HSCT. Considering their advanced stage of disease, their sub-optimal functional capacity due to steroid-induced complications, and COVID-19 infection post-treatment, we believe that AT-MSC therapy can have possible efficacy in the management of pediatric BoS. The conduction of further studies with larger sample sizes and more frequent injections is prudent for further optimization of AT-MSC therapy against BoS. Trial registration Iranian Registry of Clinical Trials (IRCT), IRCT20201202049568N2. Registered 22 February 2021, https://en.irct.ir/trial/53143 .

Neurologic Manifestations of Coronavirus Disease 2019 in Children: An Iranian Hospital-Based Study.

BACKGROUND: COVID-19 infection and its neurological manifestations were seen in children although less common than adults. The aim of this study was to determine the frequency of different types of neurologic findings of hospitalized children with COVID-19. ]. METHODS: This retrospective study was performed on hospitalized pediatric patients aged≤18 years with confirmed SARS-CoV-2 at Children's Medical Center Hospital. Neurological manifestations were defined as the presence of any of the following symptoms: seizure, altered mental status, behavioral/personality change, ataxia, stroke, muscle weakness, smell and taste dysfunctions, and focal neurological disorders. RESULTS: Fifty-four children with COVID-19 were admitted and their mean age was 6.94±4.06 years. Thirty-four of them (63%) were male. The most frequent neurological manifestation was seizure (19 [45%]) followed by muscle weakness (11 [26%]), loss of consciousness (10 [23%]), and focal neurological disorders (10 [23%]). Other neurological manifestations consisted of headache (n=7), movement disorders (n=6), behavioral/personality change (n=5), ataxia (n=3), and stroke (n=3). Twenty-nine percent of our patients had leukocytosis. A neutrophil count above 70% was seen in 31% of participants. Among our patients, 81% had a positive reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2. CONCLUSION: During the current pandemic outbreak, hospitalized children with COVID-19 should be evaluated for neurological signs because it is common among them and should not be under-estimated.

An unusual site of a pericardial cyst in a child: A case report.

Pericardial cysts are rare congenital anomalies, often clinically silent and incidentally found on imaging. However, patients with pericardial cysts may present with chest pain, tachypnea, and, rarely, symptoms secondary to cardiac tamponade. Echocardiography (transthoracic or transesophageal) and chest computed tomography (CT) scan with contrast are diagnostic modalities of choice in patients with pericardial cysts. Conservative management is justified in asymptomatic patients, while a surgical approach is recommended in symptomatic patients. Here, we describe the case of a 12-year-old boy who underwent imaging during the coronavirus disease 2019 (COVID-19) pandemic and was incidentally found to have a pericardial cyst.

Antimicrobial susceptibility and genotyping of microorganisms isolated from sputum culture of children with cystic fibrosis in an Iranian referral children's hospital.

BACKGROUND: Chronic bacterial infections of the airways are present in most patients with cystic fibrosis (CF). Although most pathogens are acquired from the environment, there is great evidence of patient-to-patient transmission. Therefore, evaluating the genetic variation of strains isolated from CF patients is recommended for the purpose of examining hospital infection. AIM: The aim of this study was to determine the antibiotic susceptibility pattern and genotyping of Staphylococcus aureus and Pseudomonas aeruginosa strains isolated from sputum samples of children with CF referred to a single pediatric CF center in Tehran, Iran. METHODS: In this cross-sectional study, the antimicrobial susceptibility profiles of strains isolated from patients with CF during 1 year were determined. Pseudomonas aeruginosa and S. aureus isolates were genotyped using the random amplified polymorphic DNA polymerase chain reaction method and were analyzed using GelCompar II software. RESULTS: Of 534 patients with CF, 384 had negative sputum cultures (72%), and 94 strains of P. aeruginosa (18%) and 53 strains of S. aureus (10%) were isolated. The mean age of the patients was 8.22 ± 5.7 years (range, 2 months to 18 years). The P. aeruginosa strains showed high sensitivity to ceftazidime (96%), piperacillin/tazobactam (96%), and imipenem (94%). All strains of S. aureus were susceptible to vancomycin, and 13% of the strains were methicillin-resistant S. aureus. High resistance to penicillin (92%) and erythromycin (88.5%) were reported. The results of P. aeruginosa genotyping revealed that there were six major clusters in this hospital. Also, based on the analysis of genotyping results, S. aureus strains were obtained from five clusters, most of which were located in cluster B1 (34 isolates, 64%). CONCLUSION: The results of this study show the possibility of strains being transferred from one part of the hospital to another (especially from the respiratory ward to other areas). Hence, high attention should be paid to the basic methods of preventing infection.

The Value of Sputum Polymerase Chain Reaction for Detection of Nontuberculous Mycobacteria in Cystic Fibrosis Patients with Negative Nontuberculous Mycobacteria Sputum Culture.

Background: Cystic Fibrosis (CF) is a life-threatening autosomal recessive disease. The purpose of this study was to evaluate the value of Polymerase Chain Reaction (PCR) in CF patients with Nontuberculous Mycobacteria (NTM) negative sputum culture. Methods: This is a descriptive cross-sectional study. The population included all children with CF, aged between 5 - 18 years old, with an NTM negative sputum culture. The patient's sputum samples were sent for smear and culture of NTM, RFLP PCR, and PCR sequence. Results: In total, 57 CF patients with negative NTM sputum culture were enrolled. Nine patients (15.78%) had positive sputum PCR for NTM. Among these strains, Mycobacterium simiae was the most common one with 5 cases (8.77% of total positive cases). Conclusion: PCR can be used as an alternative diagnostic method for NTM in CF patients with negative NTM sputum culture, always under clinical suspicion of the disease.

The Correlation of Health-Related Quality of Life with Cystic Fibrosis Severity Markers in Chest CT Scan and 6-Minute Walk Test: A Cross-Sectional Study.

OBJECTIVE: To investigate the correlation between severity of lung disease determined by chest computed tomography (CT) and 6-min walk test (6MWT) with health-related quality of life (HRQoL) score in cystic fibrosis (CF) patients. METHODS: This cross-sectional study evaluated 76 CF patients referred to CF Clinic, aged 7-14 y. Subjects were asked to complete Pediatric quality of life (PedsQL4.0) forms, during their outpatient visits to determine their HRQoL score. Patients' lung disease severity was quantified by Bhalla score determined by the child's chest CT and their 6MWT. These three variables were then analyzed to determine whether there is correlation between HRQoL with severity of lung disease. RESULTS: The mean distance of patients 6MWT score was 447.4 ± 81.4 m. There was a positive correlation between distance and HRQoL score in total, social, school and emotional function (p < 0.05). However, in physical function the correlation lacked significance (p = 0.07). Patients with a Bhalla score of less than 15 were older than patients with a Bhalla score of more than 15 (p < 0.001). Physical, emotional, social, school, and total function scores were significantly lower in patients with Bhalla score less than 15, compared to those with Bhalla score greater than 15 (p < 0.05). CONCLUSIONS: The correlation among Bhalla score on CT scan, 6-min walk test, and HRQoL indicates that pulmonary disease has a clear impact on the quality of life of CF patients. HRQoL can be used in the care program of children with CF.

The correlation between 6-min walk test and respiratory parameters in children with cystic fibrosis.

BACKGROUND: The 6-min walk test (6MWT) is a sub-maximal exercise test and has been widely used for evaluating of exercise capacity of patients with cystic fibrosis (CF) in recent years. Few studies have examined the relationship between 6MWT and parameters used to assess the severity of the disease in children with CF. In this study, we have examined this relationship to find out if 6MWT can be a marker of the severity of cystic fibrosis. METHODS: A cross-sectional study was done to analyze the correlations among spirometry parameters, body mass index (BMI), chest tomography (CT), and 6MWT. CF patients, aged 7-14 years, were involved. RESULTS: Seventy-six patients, 32F/44M, mean age 10.49 ± 3.18 years, were studied. The mean distance in 6MWT was 447 ± 84.1. The following correlations versus distance were found: FEV1 (r = 0.255, p = 0.026), FVC(r = 0.285, p = 0.013), FEF25-75% (r = 0.546, p < 0.001), BMI (r = 0.163, p = 0.160), and CT (r = 0.075, p = 0.520).The following correlations versus O2 saturation (SpO2) decline were found: FEV1 (r = -0.393, p < 0.001), FVC (r = -0.431, p < 0.001), FEF25-75% (r = -0.296, p = 0.010), BMI (r = 0.042, p = 0.721), and CT (r = -0.196, p = 0.090). There was a significant correlation between 6MWT (distance and SpO2 decline) and pulmonary function test. There was no significant correlation between BMI, chest CT, and 6MWT. CONCLUSIONS: 6MWT can be applied beside spirometry and chest CT for CF patients follow up.

Evaluation of respiratory complications in patients with X-linked and autosomal recessive agammaglobulinemia.

BACKGROUND: Congenital agammaglobulinemia is the first primary immunodeficiency disorder characterized by a defect in B lymphocyte development and subsequently decreased immunoglobulin levels. These patients are prone to suffer from recurrent infections mostly involving the respiratory tract. In this study, we aimed to describe in detail respiratory tract complications as the most prominent clinical feature among agammaglobulinemic patients. METHODS: A total number of 115 patients were included. Demographic, clinical, and genetic data were collected from the patients' medical records. Among the available patients, pulmonary function tests (PFTs) and/or high-resolution computed tomography (HRCT) were performed. RESULTS: Respiratory tract complications (85.2%) especially pneumonia (62.6%) were the most prominent clinical features in our cohort. Among patients with abnormal PFT results (N = 19), a mixed respiratory pattern was observed in 36.8%. HRCT was carried out in 29 patients; Bhalla scoring-based evaluation of these patients indicated excellent (44.8%), followed by good (34.5%) and mild (20.7%) results. Bronchiectasis was found in 13 patients undergoing HRCT (44.8%). We found significant inverse correlations between the Bhalla score and incidence rate of pneumonia, as well as the presence of bronchiectasis. Patients with abnormal PFT results had statistically significant higher bronchiectasis frequency and lower Bhalla scores compared to those with normal results. Forty-one patients were deceased, and here, respiratory failure was the most common cause of death (45.5%). CONCLUSION: High prevalence of respiratory tract infections among agammaglobulinemic patients and subsequent progression to permanent lung damage highlights the importance of implementing respiratory evaluation as part of routine follow-up program of agammaglobulinemic patients. Physicians should be aware of this and regularly monitor the respiratory function of these patients to allow for timely diagnosis and treatment initiation aiming to improve patients' prognosis and quality of life.

Comprehensive assessment of respiratory complications in patients with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by recurrent upper and lower respiratory tract infections and some noninfectious clinical complications. OBJECTIVE: To provide a detailed evaluation of respiratory presentations and complications in a cohort of Iranian patients with CVID. METHODS: A retrospective cohort study was conducted on 245 CVID patients who were recorded in the Iranian primary immunodeficiency disorders registry network. Respiratory manifestations were evaluated by reviewing clinical hospital records, immunologic findings, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. RESULTS: Most of the patients (n = 208, 85.2%) had experienced at least 1 episode of acute respiratory manifestation, and pneumonia was observed in 31.6 % (n = 77) of cases as a first disease manifestation. During the follow-up, pneumonia, sinusitis, and otitis media were documented in 166 (68.6%), 125 (51.2%), and 103 (42.6%) cases, respectively. Abnormal PFT measurements were documented in 53.8% of patients. Among these patients, 21.5% showed restrictive changes, whereas 18.4% of patients showed an obstructive pattern. Bronchiectasis was the most frequent radiological finding, confirmed in 27.2% of patients. Patients with bronchiectasis were older at the time of immunodeficiency diagnosis (P < .001) and had longer diagnosis delay (P < .001) when compared with patients without bronchiectasis. CONCLUSION: This study highlights the importance of monitoring the respiratory tract system even in asymptomatic patients. Pulmonary function tests and CT scans are the most commonly used techniques aiming to identify these patients early, aiming to reduce the rate of long-term respiratory complications.

Cost-effectiveness of home mechanical ventilation in children living in a developing country.

BACKGROUND: Home mechanical ventilation is a promising option for children requiring long-term mechanical-assisted ventilation, while data on cost-effectiveness of this approach is limited. AIMS: To investigate the cost-effectiveness of home mechanical ventilation in children requiring long-term mechanical-assisted ventilation. METHODS: A retrospective cohort was conducted on 67 children (32 girls, 47.7%) requiring mechanical-assisted ventilation. Underlying diseases of children were congenital airway malformations in 24, cystic fibrosis in 4, severe laryngomalacia in 16, poly neuropathy syndrome in 6, mitochondrial myopathy in 5, hypoxic ischemic encephalopathy in 6, and cerebral palsy in 2. Children were admitted in pediatric intensive care units (ICU) for 2 weeks. After discharge, they were on home mechanical ventilation and were followed for 1 year. Data on daily costs of admission at ICU, rehospitalizations, weaning, educational performance and muscle strength were gathered. RESULTS: Mean age of children at time of initiation of mechanical-assisted ventilation was 5.8 years (ranged from 2 months to 15 years). Mean number of re-hospitalizations was 3.4_4.9 times with mean duration of 9.44_2.53 days. Of children on mechanical ventilation, 1 attended school, 2 were weaned, and 21 experienced improvement in muscle strength. No fatal or serious complications were observed while children were on home mechanical ventilation. Mean costs of daily ICU admission was 912_1028 $, while the mean daily cost of home mechanical ventilation was 60.86_4.95 $ (p < 0.001). CONCLUSIONS: Home mechanical ventilation is more cost-effective compared to ICU admission for only mechanical-assisted ventilation. < p > < /p >.

Respiratory Complications in Patients with Hyper IgM Syndrome.

PURPOSE: Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome. METHODS: A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. RESULTS: Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%). CONCLUSIONS: Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.

Primary ciliary dyskinesia in six patients with bronchiectasis.

INTRODUCTION: Primary ciliary dyskinesia [PCD] is generally considered as a rare autosomal recessive disorder. Previous studies reported various prevalence of PCD among patients with bronchiectasis. MATERIAL AND METHODS: Six PCD patients who were diagnosed during the investigation of 40 patients with bronchiectasis were enrolled in this study. Ultra structural studies for both epithelium and cilia were performed, and the deformities in detailed electron microscopic images confirmed the diagnosis of PCD. RESULTS: Four patients experienced the first symptoms shortly after the birth, 1 by the age of 1 and 1 by the age of 4 years. Except of 1 case that was diagnosed 2 months after the onset of disease, diagnosis delay was longer than 5 years in all patients. Consanguineous marriage was observed in the parents of all patients. Upper respiratory tract infections were documented for all patients. CONCLUSIONS: PCD should be considered as a probable underlying disorder in patients with bronchiectasis. Past medical history of otitis media and history of similar clinical findings in family members should raise suspicion toward PCD.