Human inherited CCR2 deficiency underlies progressive polycystic lung disease.

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Association between sputum culture results and pulmonary changes in children with cystic fibrosis.

Background and Objectives: Despite the significant improvement in the prognosis of cystic fibrosis (CF), it is still regarded as the most common life-shortening genetic disease in Caucasian populations. This disease is the most important cause of chronic lung disease and exocrine pancreatic insufficiency in infancy and childhood. The aim of our study was to assess the potential association between bacterial colonization detected by sputum cultures and pulmonary structural and functional changes in Iranian children with CF. Materials and Methods: In this cross-sectional study, 76 CF children ≥6 years old registered in the CF Foundation of Children's Medical Center Hospital, Tehran, Iran, who underwent high resolution CT scan (HRCT), pulmonary function test, and sputum cultures within a month of each other during the study period were included. For each patient, demographic characteristics (age and sex), results of sputum cultures, forced expiratory volume in 1st second (FEV1), and chest HRCT findings based on the Bhalla scoring system were recorded in a check list. Results: Sixty seven percent of the patients had positive sputum cultures, with the most commonly isolated microorganism being Pseudomonas aeruginosa (mucoid strain). Based on categorization of Bhalla scores, none of the patients had severe pulmonary involvement. FEV1 was mainly >70%. There was a statistically significant correlation between colonization with mucoid P. aeruginosa and lower Bhalla scores in children aged 14-16 years (P=0.001). Colonization with mucoid P. aeruginosa was also significantly associated with patient's age (P=0.020) and FEV-1 (P=0.001). Conclusion: Severity of lung involvement in CF children is clearly dependent to mucoid P. aeruginosa colonization in airways and this notorious bacterium is the most prevalent one in Iranian CF children. Prompt identification and eradication by proper nebulized and systemic antibiotics can have valueless effects on patients' quality of life and prevent lifelong destructive complications such as bronchiectasis. Timely lung CT scan wisely advised by expert CF treatment team can meticulously detect injuries and it seems to act more efficacious than -still helpful-clinical scores and pulmonary function tests.

Comparison of culture and PCR-DGGE methods to evaluate the airways of cystic fibrosis patients and determination of their antibiotic resistance profile.

Background and Objectives: Respiratory infections are the most serious condition in cystic fibrosis (CF) patients; therefore, a thorough comprehension of the diversity and dominant microbial species in CF airways has a crucial role in treatment. Our objective was to determine the antibiotic resistance profile of CF airways microbiota and compare culture methods and PCR-DGGE to evaluate bacterial diversity. Materials and Methods: Pharyngeal swabs from 121 CF patients were collected. The samples were then cultured, identified and antibiotic resistance testing was performed. Thirty samples were subjected to further molecular surveys. DNA contents of these samples were extracted and amplified using nested-PCR technique and their bacterial diversity was assessed by DGGE. The DGGE patterns were visualized and certain bands were excised and purified. Next, the DNA was amplified by another round of PCR and sent out for sequencing. Results: Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most prevalent species isolated using culture methods. S. aureus was the most common bacteria among 6 years and younger patients; while, P. aeruginosa had more prevalence among older ones. The PCR-DGGE results showed more diversity than culture methods, particularly in younger patients who exhibited more bacterial diversity than the older groups. Sequencing results unveiled the presence of certain bacterial species including Haemophilus parainfluenzae and Stenotrophomonas maltophilia which were completely missed in culture. Conclusion: Even though culture-dependent methods are cost-effective, PCR-DGGE appeared to be more efficient to determine bacterial diversity. PCR-DGGE detects less abundant species, though their viability could not be determined using this method.

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 bronchocele attenuation in pulmonary computed tomography in assessment of allergic bronchopulmonary aspergillosis in the background of cystic fibrosis: A cross-sectional study.

Background: There is no specific test in the definitive diagnostic approach to Allergic bronchopulmonary aspergillosis (ABPA) especially in the background of cystic fibrosis, but comprehensive and simultaneous clinical, radiological and serological examination will be the basis of ABPA diagnosis. The increasing in attenuation of bronchoceles in imaging has recently been proposed as a valuable diagnostic criterion. Purpose: The present study aimed to assess bronchocele attenuation in pulmonary CT scan of patients with complicated cystic fibrosis for diagnosis of ABPA. Methods: This cross-sectional study was performed on 74 consecutive patients aged 3-18 years suffering cystic fibrosis presented with exacerbation of pulmonary symptoms and were suspected of having ABPA. All were examined by 16 Slice CT Scan and the density of bronchoceles above 5 mm in diameter were measured in Hounsfield unit. The total serum IgE titer, skin prick test for aspergillus and anti-aspergillus IgG and IgE level were obtained for all subjects and both cutoff values of IgE level (>500 IU/mL and >1000 IU/mL) were considered as the criteria for ABPA diagnosis. Results: Considering IgE level of greater than 500 IU/mL and 1000 IU/mL as the diagnostic criteria, 24.3% and 10.8% had evidence of ABPA, respectively. Considering the two pointed diagnostic IgE ranges and based on the analysis of the area under the ROC curve, bronchocele attenuation could effectively predict the presence of ABPA with the best cutoff values of 37.25 (with a sensitivity of 70.6% and a specificity of 66.7%) and 40.00 (with a sensitivity of 85.7% and a specificity of 65.1%), respectively. Conclusion: The presence of bronchocele and an increase in its attenuation on CT scan will be diagnostic for the occurrence of ABPA.

Cytokine patterns in cystic fibrosis patients with different microbial infections in oropharyngeal samples.

BACKGROUND: Cytokines play a crucial role in the immune system's regulation by mediating protective responses to infections. anti-inflammatory and pro-inflammatory cytokines are in equilibrium. Therefore, any alteration in cytokine production or cytokine receptor expression might result in pathological illnesses and health issues. Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane regulator (CFTR) gene. Lung infection in these patients is related to chronic bacterial airway infection and inflammation, which is triggered by some inflammatory cytokines. Our goal was to compare the cytokine patterns in CF patient's serum and PBMCs caused by microbial pathogens that colonized their airways to controls. METHODS: ELISA and Real-time PCR were used to determine the levels of IL-10, IFN-γ, IL-4, TGF-ß, IL-8, and IL-17 in serum and PBMC cells. Blood parameters in both patients and healthy people were studied. RESULTS: An increase in IL-10, IFN-γ, IL-4 (p-v = 0.03, 0.024 and 0.003) levels and a decrease in IL-17 (p-v = 0.004) was found in Pseudomonas aeruginosa positive patients. There were no different in TGF-ß and IL-8 (p-value = 0.778 and 0.903) in this patients. IL-10, IFN-γ, and IL-4 (p-value = 0.023, 0.001 and 0.002) levels were high in Staphylococcus aureus positive patients and TGF-ß, IL-17, and IL-8 (p-value = 0.085, 0.167 and 0.362) were not significantly different in the patient and control groups. IFN-γ and IL-4 levels were higher in patients without infection who had normal microbiota (p-v = 0.002 and 0.024). In patients with P. aeruginosa, WBC and platelets increased, and MCH and MCV decreased. Patients with normal microbiota had less MCV. CONCLUSION: According to our research, patients with P. aeruginosa, S. aureus, and normal microbiota are exposed to cytokine alterations and changes in blood factors. The link between the CF patient's airway microbiota and the kind of generated cytokines might lead to the modulation of inflammatory cytokines alone or in combination with antibiotics, reducing disease-causing effects while avoiding drug resistance.

Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19.

BACKGROUND: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. OBJECTIVE: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. METHODS: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. RESULTS: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. CONCLUSIONS: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.

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.

Cough in adolescent with cystic fibrosis, from nightmare to COVID-19 stigma: A qualitative thematic analysis.

PURPOSE: Cough is part of the daily life of patients with Cystic fibrosis (CF) and its most common symptom. This study explored the experiences of adolescents with CF in Iran during the COVID-19 pandemic in relation to their cough. DESIGN AND METHODS: In this qualitative study, we conducted 32 semi-structured interviews with 21 adolescents with CF. We analyzed the data thematically. RESULTS: We identified three main themes among adolescents with CF in relation to coughing: 1. Cough is a permanent companion; 2. Coughing raises fear of double stigma; 3. Patients' individualized coping strategies to deal with coughing. Participants complained that cough interrupted daily tasks and sleep, drew unwanted attention in public places, and elicited questions about whether they were COVID-19 patients or substance users-both highly stigmatized identities. CONCLUSION: Although coughing is a protective mechanism for CF patients, frequent coughing often causes major challenges, particularly during the COVID pandemic, when people were acutely sensitive and aware about coughing. During the COVID-19 pandemic, in addition to taking care of themselves and managing the disease, CF patients therefore had to also overcome issues related to social stigma and isolation. PRACTICE IMPLICATIONS: Healthcare workers play an important role in increasing public awareness about CF and its symptoms, including cough. During the pandemic, healthcare workers can help reduce the stigma of coughing through public education. Healthcare workers can actively communicate with patients to identify severe and ineffective cases of cough due to exacerbation of the disease and refer them to a specialist.

Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome.

BACKGROUND: Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. OBJECTIVES: To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. METHODS: Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. RESULTS: We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. CONCLUSIONS: Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.

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.

Genetic modification of cystic fibrosis with ΔF508 mutation of CFTR gene using the CRISPR system in peripheral blood mononuclear cells.

OBJECTIVES: Cystic fibrosis (CF) is an inherited autosomal recessive disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The present study aimed to investigate the genetic modification of CF with ΔF508 mutation of the CFTR gene using CRISPR in peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: Two single guide RNAs were designed to target sequences in the CFTR gene. The transfection efficiency of PBMC cells was examined through evaluation of green fluorescent protein (GFP) expression using fluorescent microscopy. Moreover, a sgRNA-Cas9 plasmid was tested to target the CFTR gene. The ΔF508 gene modification was evaluated and confirmed by PCR and Sanger sequencing methods. RESULTS: Our results indicate the feasibility of site-specific gene targeting with the CRISPR/Cas9 system. 33% of the samples were corrected using CRISPR in mutant locus and confirmed by sequence blast at NCBI databases and primers outside the arm locus. CRISPR/Cas9 approach represents an efficient tool to repair the ΔF508 mutation of the CFTR gene in PBMC Cells. CONCLUSION: Therefore, the CRISPR system can be highly efficient and specific and provides a powerful approach for genetic engineering of cells and model animals. Generally, the proposed method opens new insights into the treatment of human diseases.

Comparing effects of low glycemic index/high-fat, high-calorie diet and high-fat, high-calorie diet on cytokine levels of patients with cystic fibrosis: A randomized controlled clinical trial.

The importance of the host inflammatory response, as a central pathological feature of cystic fibrosis, is well recognized. Additionally, hyperglycemia can induce an immune response and consecutively may exacerbate symptoms of this disease. Hence, adherence to a low glycemic index diet, through normalizing blood glucose levels, may reduce inflammation in patients with this disease. This study aimed to compare effects of a low glycemic index/high-fat, high-calorie diet and routine high-fat, high-calorie diet on inflammatory biomarkers in patients with cystic fibrosis. In this randomized clinical trial, 44 children and adolescents with cystic fibrosis were randomly assigned to receive for three months either a high-fat, high-calorie diet (n = 22) or a low glycemic index/high-fat, high-calorie diet (n = 22) with similar calorie and macronutrients composition to the control diet. Patients in first arm were allowed to use all sources of carbohydrates with different glycemic indices, whereas those in another arm consumed carbohydrates from low glycemic index sources. Serum levels of the pro-inflammatory cytokines IL-6, IL-17A, and IFNγ, and the anti-inflammatory cytokine IL-10 were measured at baseline and after the end of the trial. There were significant differences between groups for IL-6 (P = 0.02) and IL-17 (P = 0.01), in favor of the low glycemic diet, but no between-group differences were detected in IL-10 and IFN-γ. Although serum levels of IL-17 were reduced in both the groups as compared with the baseline values, this reduction was only significant in the group assigned to the low glycemic diet (P= 0.007), In addition, IL-6 serum levels decreased and those of IL-10 increased significantly as compared with the baseline values in the low glycemic diet (P= 0.01). It seems that adherence to a low glycemic index/high-fat, high-calorie diet for three months can improve some inflammatory biomarkers in children and adolescents with cystic fibrosis compared with the high-fat, high-calorie diet.

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.

Effects of low glycemic index/high-fat, high-calorie diet on glycemic control and lipid profiles of children and adolescence with cystic fibrosis: A randomized double-blind controlled clinical trial.

PURPOSE: Low glycemic index diets seem to be potentially effective to improve glycemic control and reduce lipid profiles. Hence, this study aimed to evaluate the effect of a low glycemic index/high fat, high-calorie diet on glycemic status and lipid profiles of patients with cystic fibrosis. METHODS: In this randomized clinical trial, 44 children and adolescents with cystic fibrosis were randomized to receive for three months either a high fat, high-calorie diet (n = 22) or a low glycemic index/high fat, high-calorie diet (n = 22) with similar calorie and macronutrients composition. Patients in high fat, high-calorie diet arm were allowed to use all sources of carbohydrates with different glycaemic indices; whereas those in another arm consumed carbohydrates from low glycemic index sources. Serum levels of lipid profiles (triglyceride, total cholesterol, HDL cholesterol, LDL cholesterol), insulin, fasting blood glucose, and glycated hemoglobin were measured at baseline and after the intervention. RESULTS: Between-group differences were significant only for fasting blood glucose (P < 0.001). However, fasting blood glucose (P = 0.003) and glycated hemoglobin (P = 0.002) significantly decreased after the intervention in the low glycemic index group, while in another group a significant increase in fasting blood glucose (P = 0.038) and triglyceride (P = 0.004) was found. No significant within-group differences were observed in other variables in both groups. CONCLUSIONS: It seems that adherence to a low glycemic index/high fat, high-calorie diet can improve glycemic indices in children and adolescents with cystic fibrosis compared to the high fat, high-calorie diet. TRIAL REGISTRATION: IRCT2017102325267N5.

Farber disease: report of three cases with joint involvement mimicking juvenile idiopathic arthritis.

Farber disease is a rare recessive autosomal disorder presented with three main features of joint involvement, subcutaneous nodules and hoarseness. Hereby we describe three new cases of Farber disease. All three cases were first misdiagnosed as juvenile idiopathic arthritis (JIA) due to the presentation of joint swelling. Addition of hoarseness and subcutaneous nodules to the initial joint swelling questioned the diagnosis of JIA and further evaluations led to the diagnosis of Farber disease. The first case was a 4-year old girl in whom a novel genetic mutation in ASAH1 gene was found. The second patient was a 4-year old girl presented with joint swelling at 7 month of age. The third patient was a 9-month boy complicated with severe respiratory distress. All patients were treated with symptomatic and supportive care. Two cases died due to respiratory ailure and infection, but one patient follow up for 2 years after diagnosis. Farber disease should be considered as differential diagnosis in children with early onset of poly articular involvement with subcutaneous nodules and/or hoarseness.

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.