Pulmonary Alveolar Proteinosis in Children: Diagnosis and Treatment Outcomes.

Background: Pulmonary Alveolar Proteinosis (PAP) is an uncommon pulmonary disease characterized by the accumulation of surfactant composed of proteins and lipids due to disruption of surfactant clearance by alveolar macrophages. The current standard treatment is lung lavage. There are no specific criteria for lavage, but in case of observing these signs it is recommended to perform lavage for the patient: progressive respiratory failure, no labored breathing at rest, and drop in oxygen level during activity (>5%). Materials and Methods: In this study, patients with PAP admitted to Pediatric ward of Masih Daneshvari Hospital were studied. The required data were collected including the patient's demographic data, clinical signs and radiographic data, the number of admissions, the age of diagnosis, detection and treatment methods, number of lavage, current condition of the patient, and in case of death, the cause of death. Results: In this study, 17 patients with PAP who were admitted during the past 15 years were examined; among which 7 patients were boys (41.2%) and 10 were girls (58.8%). The mean age of population was 11.79±7.21 years. Transbronchial Lung Biopsy (TBLB) (47.1%) and open lung biopsy (52.9%) were used for diagnosis of patients. Lung lavage was used to treat patients, 15 of whom were treated by this method. Five of the patients died because of their serious conditions. Conclusion: Therapy method in the present study was lavage for both lungs, and it was performed for all patients except for two patients due to their anatomical complications. This method is still considered as the gold standard for PAP. Considering the findings from previous studies and the present study, it seems that Whole Lung Lavage (WLL) was fruitful for patients who had the indication for using this therapy and it played a significant role in improving the prognosis of patients. Besides, it is recommended to do follow-up regularly in order to have more therapeutic efficacy and increased patient longevity.

Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare congenital condition characterized by a selective predisposition to infections caused by weakly virulent mycobacteria and other types of intra-macrophagic pathogens. The 16 genes associated with MSMD display a considerable level of allelic heterogeneity, accounting for 31 distinct disorders with variable clinical presentations and prognosis. Most of MSMD deficiencies are isolated, referred to as selective susceptibility to mycobacterial diseases. However, other deficiencies are syndromic MSMD, defined by the combination of the mycobacterial infection with another, equally common, infectious, specific phenotypes. Herein, we described a series of 32 Iranian MSMD cases identified with seven distinct types of molecular defects, all of which are involved in the interferon gamma (IFNγ) immunity, including interleukin IL-12 receptor-ß1 (IL-12Rß1) deficiency (fifteen cases), IL-12p40 deficiency (ten cases), and IL-23R deficiency (three cases), as well as IFNγ receptor 1 (IFNγR1) deficiency, IFNγ receptor 2 (IFNγR2) deficiency, interferon-stimulated gene 15 (ISG15) deficiency, and tyrosine kinase 2 (TYK2) deficiency each in one case. Since the first report of two MSMD patients in our center, we identified 30 other affected patients with similar clinical manifestations. As the number of reported Iranian cases with MSMD diagnosis has increased in recent years and according to the national vaccination protocol, all Iranian newborns receive BCG vaccination at birth, early diagnosis, and therapeutic intervention which are required for a better outcome and also prevention of similar birth defects. Therefore, we investigated the clinical and molecular features of these 32 patients. The current report also defined novel classes of pathological mutations, further expanding our knowledge of the MSMD molecular basis and associated clinical manifestations.

Pulmonary complications of predominantly antibody immunodeficiencies in a tertiary lung center.

BACKGROUND AND AIMS: Respiratory infections are expressed very soon in the life in humoral immunodeficiencies and often lead to chronic irreversible complications such as bronchiectasis and chronic airflow limitation. This study was conducted to evaluate the pulmonary complications of predominantly antibody immunodeficiencies to show the benefits of timely diagnosis and appropriate therapy. PATIENTS AND METHODS: The information of 48 patients involved with a type of predominantly antibody immunodeficiencies, including sex, type of primary immunodeficiency, age at the onset of symptoms, age at diagnosis, recurrent infections, respiratory symptoms, and pulmonary radiological and functional abnormalities were recorded and analyzed. RESULTS: In 48 patients evaluated, the mean age at diagnosis was 25.63 years. The mean diagnostic delay was estimated to be 13.62 years. The most recurring clinical manifestations, sinusitis (69.6%), otitis (43.5%), and recurrent pneumonia were the cause of frequent admissions in 68.8% of these patients. Bronchiectasis was frequently found (58.3%) in these patients mostly involving the middle and lower lobes (48.8% and 41.5%, respectively). CONCLUSIONS: Respiratory complications, infectious or non-infectious, determine the prognosis of the disease in patients with predominantly antibody immunodeficiencies. Timely diagnosis and appropriate management may improve life expectancy and the quality of life in these patients.

Association of specific viral infections with childhood asthma exacerbations.

INTRODUCTION: Asthma exacerbations may occur due to a variety of triggers including respiratory viruses. The aim of this study was to determine the role of particular viral infections in asthma exacerbations in children. MATERIALS AND METHODS: The study was performed at Dr. Daneshvari Hospital Pediatric Emergency Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2014 and 2015. A nasopharyngeal aspirate or swab was obtained from each patient during admission. All samples were maintained at 4 °C until submission to the virology laboratory and were tested for respiratory viruses by nucleic acid testing. RESULTS: A total of 60 patients with asthma exacerbations were recruited for this study. Of the 60 samples collected from the patients with acute asthma exacerbations, rhinovirus was detected in 12 patients (20%), respiratory syncytial virus in 5 (8%), adenovirus in 5 (8%), and influenza virus in 1 (1.6%). Respiratory pathogens were not detected in 37 (61%) samples. All the samples investigated showed single viral infection. CONCLUSIONS: To conclude, the most common viruses detected were rhinovirus followed by respiratory syncytial virus (RSV) and adenovirus. RSV was more commonly associated with more severe attacks. Both the study design (e.g., time of sampling, age of the patients, etc.) and also the method used for viral detection influence the frequency of detection of the respiratory viruses.

Long term outcome of cystic fibrosis patients with multisystem evaluation.

INTRODUCTION: Cystic fibrosis is a chronic disease with multiple organ involvement and chiefly results in chronic respiratory infections, pancreatic insufficiency and associated complications. The age at diagnosis, clinical presentation, rate of disease progression and prognosis is variable among patients. This study is designed to evaluate the behavior of disease to provide epidemiologic data for early recognition and proper management. MATERIAL AND METHODS: The study was designed as an active surveillance of 192 patients diagnosed with cystic fibrosis in a tertiary lung disease centre between 2008 and 2015. The diagnosis of cystic fibrosis was established in all patients accordingly to conventional criteria, including two positive sweat chloride tests and clinical signs and symptoms. Demographic, clinical and laboratory data were obtained from these patients in each hospitalization and also every follow-up visit and carefully evaluated for complications of this chronic disease. RESULTS: The majority of patients showed positive culture for Pseudomonas aeroginosa. Bronchiectasis was the most prevalent finding in chest CT scan. 44.3% of patients had been treated for allergic bronchopulmonary aspergillosis and all had sinus disease. Increased pulmonary artery pressure was observed in 40% of patients with cystic fibrosis. 33 patients died which consisted 17.1% of all the patients.The mean age of mortaliy was 18.15 year. CONCLUSIONS: The clinical outcome of cystic fibrosis is variable in different countries which may reflect environmental influences and the role of early diagnosis on long term outcomes. However, the role of early diagnosis in long-term outcomes of the disease can not be ignored.

Amyloidosis as a Renal Complication of Chronic Granulomatous Disease.

Chronic granulomatous disease is a rare primary immunodeficiency disorder, which leads to increased susceptibility to recurrent infections and severe inflammatory manifestations.  There have been reports regarding different aspects of genitourinary involvement in chronic granulomatous disease, some of which are hydronephrosis, granulomatous cystitis, and glomerulonephritis, but among these complications, amyloidosis is rather rare. We report a patient with chronic granulomatous disease that developed amyloidosis later in the course of the disease.

Evaluation of the relationship between smear positivity and high-resolution CT findings in children with pulmonary tuberculosis.

BACKGROUND: The aim of this study is to find a relationship between the radiological manifestations of childhood tuberculosis on a high-resolution computed tomography (HRCT) and the results of sputum smear. This study aims to propose an alternative indicator of infectivity in terms of prevention of disease transmission through selective isolation policy in children whose clinical condition is highly suggestive of tuberculosis. MATERIAL/METHODS: This retrospective comparative study was performed on 95 children under 15 years of age diagnosed with tuberculosis based on both WHO criteria and positive sputum culture for mycobacterium Tuberculosis. The children were admitted for TB screening in the pediatric department of national research institute of tuberculosis and lung disease (NRITLD) between 2008-2012. Direct smear collected from sputum or gastric lavage, as well as HRCT were performed in all children prior to administration of medical therapy. Children were divided into 2 groups based on positive and negative smear results. HRCT abnormalities, as well as their anatomical distribution were compared between these 2 groups using multivariate analytic model. RESULTS: The most prevalent abnormalities in the positive smear group were consolidation, tree-in-bud pattern, upper lobe nodular infiltration and cavitation. The negative smear group featured lymphadenopathy, consolidation, collapse and nodular infiltration in the upper lobe. Cavity, tree- in-bud pattern and upper lobe nodular infiltration were highly associated with smear positivity in children. Conversely, lymphadenopathy and collapse had significant association with a negative smear. CONCLUSIONS: This study revealed that cavity, tree-in-bud and upper lobe nodular infiltration has significant association with smear positivity in childhood tuberculosis. On the other hand, lymphadenopathy and collapse were closely associated with smear negativity in this age group. It was also demonstrated that children with a positive smear most likely presented with radiological features of post primary tuberculosis, while the negative smear group most often manifested with primary tuberculosis.

Knowledge and Practice of Asthmatic Children's Parents About Daily Air Quality.

BACKGROUND: Knowledge and practice about air pollution are essential subjects in special groups such as cardio-pulmonary patients. For children with air pollution-related diseases, knowledge and attitude of parents play a determining role in this respect. Since providing a coherent curriculum needs evidence-based information, this survey was conducted to assess the knowledge and practice of asthmatic children's parents about daily air quality since asthmatic children are among the most vulnerable at-risk groups when it comes to air pollution. MATERIALS AND METHODS: All parents of asthmatic children referred to the Pediatric Clinic of Masih Daneshvari Hospital during one year period (250 people) completed knowledge and practice questionnaire on air pollution. Knowledge questions consisted of familiarity with pollution standard index (PSI), ways to find out about it, respiratory effects of air pollution and etc. Practice questions consisted of reducing outdoor presence and activity of children and actions taken to reduce air pollution in polluted days. RESULTS: In general, 3.2% of parents were familiar with PSI, 12.5% were aware of ways to find out about daily air quality, 65.2% were aware of air pollution respiratory effects, 65.6% were aware of air pollution effects on asthmatic children and 4.4% were aware of ineffectiveness of surgical masks in prevention of air pollution health effects. The obtained practice score ranged from 4 to 16, and the participants' mean score was equal to 11.79. CONCLUSION: This study revealed that parents of asthmatic children were aware of air pollution hazards for their children and wanted to prevent them but they did not know how. Therefore, asthmatic children in Tehran are still exposed to risks of air pollution.

Primary immunodeficiency in children: report of seven years study.

BACKGROUND: Primary immunodeficiency diseases (PIDs) are a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, T and B lymphocytes. These disorders are rare, with an estimated prevalence of 1:10,000 live births. OBJECTIVES: This study aimed at describing the clinical features, disease complications, treatment modalities and overall outcome of patients with Primary Immunodeficiency Diseases (PID) in Masih Daneshvari hospital during a 7-year period (2001-2008). MATERIALS AND METHODS: This was a retrospective study based on the review of patients' medical records. Clinical, laboratory, and epidemiological data including personal and family history were obtained by reviewing records of patients admitted to the Pediatric Pulmonary Ward of NRITLD, a referral center for tuberculosis and lung diseases. The diagnosis was made based on WHO criteria for primary immunodeficiency disorders. RESULTS: Data collected from 59 patients were evaluated and analyzed. There were 35 (59.3%) males and 24 (40.69%) females. The age of patients ranged from 6 months to 14.5 years and the mean age was 7.4 years. Positive family history was detected in 20 (33.9%) cases and parents of 36 patients (61.2%) were consanguineous. Twenty patients (33.9%) had a family history of PID. Phagocytic disorder (57.2%) was the most common form of PID, followed by antibody deficiency (33.7%) and T-cell or combined deficiency (8.2%). No case of complement deficiency was detected. In this group of under study patients, 2 cases expired as the result of respiratory failure due to drug resistant pneumonia (chronic granulomatous disease cases). CONCLUSION: Based on studied results, Phagocytic disorders (57.2%) were the most common disorders among our PID patients. This may be due to the large number of CGD patients referred with the pathologic finding of granuloma misdiagnosed with tuberculosis. Considering the high prevalence of PID in this study, cases with unusual, chronic, severe or recurrent infections should be evaluated for immunodeficiency disorders.

The correlation of brody high resolution computed tomography scoring system with clinical status and pulmonary function test in patients with cystic fibrosis.

BACKGROUND: To reduce the mortality and morbidity rates of cystic fibrosis (CF) patients, and to have an effective clinical management, it is important to monitor the progression of the disease. The aim of this study was to evaluate the progression of lung disease in CF patients by means of assessing the correlation of the CT scoring system with clinical status and pulmonary function test at the Pediatric Pulmonary Ward of Masih Daneshvari Hospital in 2008. METHODS: Pulmonary high resolution computed tomography (HRCT) was performed in 23 CF patients using the Brody's scoring system. Morphologic signs as well as the extent and severity of each sign were scored, and the total score was calculated. The correlation of HRCT scores (total score as well as the score for each parameter) with Shwachman Kuczycki scoring system and pulmonary function test were examined. RESULTS: The study included 9 female and 14 male patients with an age range of 5-23 years (mean: 13.42 years). Bronchiectasis (100%) and peribronchial wall thickening (100%) were the most frequent CT abnormalities. Mucus plugging, air trapping and parenchymal involvements were respectively seen in 95.7%, 91.3% and 47.8% of patients. The overall CT score for all patients was 57.6±24.2 (means±SD). The results of pulmonary function test showed a restrictive pattern; however, in 5.3% of the patients PFT was normal. The overall Shwachman-Kulczycki score was 53.48±13.8. There was a significantly (P=0.015) negative correlation between the total CT score and Shwachman-Kulczycki score; however, there was no significant correlation between total CT score and the results of PFT (P=0.481)CONCLUSION: The Brody's scoring system for high resolution computed tomography seems to be a sensitive and efficient method to evaluate the progression of CF, and can be more reliable when we combine the CT scores with clinical parameters.

Determination of mortality from cystic fibrosis.

BACKGROUND: Assessing the prognosis of cystic fibrosis (CF) and evaluating the effect of indicators of mortality is very important in predicting the life expectancy of the CF patients. OBJECTIVE: Determining the effect of seven variables including sex, Forced Expiratory Volume in one second (FEV1), Body Mass Index (BMI), bacteriology, hemoglobin (Hb), pulmonary arterial pressure (PAP) and the number of previous admissions on the survival of 27 patients admitted in Pediatric Pulmonary Ward of Masih Daneshvari Hospital in 2007-2009. METHODS: 27 CF patients were enrolled in a retrospective cross-sectional study. Patients data were collected during 2 years of study. Data of patients who died and those who remained alive were compared by independent samples t-tests and Chi-square. RESULTS: Twenty seven CF patients (11 female, 10 male) with age range of 5-19 years and mean age of 13.11 +/- 4.69 were studied. There was no difference in age, sex, FEV1, BMI, Hb between the deceased and alive group (p > 0.05). Mean PAP for expired patients and alive patients was 40 +/- 15.1 and 68 +/- 11.5 respectively. The number of admissions during last 6 months was dominant in those patients who died. 50% of the alive patients were colonized with Pseudomonas. This is compared to deceased patients which 100% were colonized with Pseudomonas. There was a strong correlation between death and number of previous admissions, PAP and Pseudomonas infection (p < 0.05). CONCLUSION: Pseudomonas infection, number of previous admissions and the severity of pulmonary hypertension has shown to be the major predictors of mortality in our study.

Phylogenetic analysis of human bocavirus isolated from children with acute respiratory illnesses and gastroenteritis in Iran.

Human bocavirus (hBoV) was first discovered in respiratory samples from children in 2005, and has been classified in the Parvoviridae family. hBoV has also been detected in children with acute gastroenteritis. This study was performed to analyze the frequency and phylogeny of hBoV in the respiratory and stool samples of children with acute respiratory tract illnesses and gastroenteritis during the time period beginning 2006 and ending 2008, at the Virology Research Centre, Masih Daneshvari Hospital, NRITLD, Tehran, Iran. Respiratory and stool samples were screened for hBoV by nested polymerase chain reaction with primers from the NS-1 gene. Nine out of 133 respiratory samples (6.8%) and 6 out of 47 stool samples (12.8%) were positive for hBoV. Ten positive samples (7 respiratory and 3 stool samples) were subjected to phylogenetic analysis by sequencing a fragment of the VP1/VP2 gene junction. The results showed a high similarity among isolates (>or=99%). It was found that hBoV isolates can be divided into 3 genetic groups.

Extra pulmonary tuberculosis in children: two years study.

Tuberculosis (TB) is an important health problem in developing countries, with varying clinical presentations depending on the organs/systems involved. To study the spectrum of clinical and paraclinical aspects of extra pulmonary TB in children suffering from pulmonary TB. This study has been carried out on 65 children with tuberculosis, admitted in TB wards of National Research Institute of Tuberculosis and Lung Disease (N.R.I.T.L.D) during 2004-2006. All patients were investigated according to specific diagnostic criteria including; history of contact with TB patient, clinical manifestations, radiological findings, tuberculin test and bacteriologic or pathologic results and after confirmation, treatment was administered. Out of 65 cases, 14 had different types of extra pulmonary tuberculosis, and data concerning following factors were studied: age, gender, race, site of involvement, bacteriology, pathology, ADA (ascitic fluid), PCR (tissue specimens), history of close contact, HIV tests (ELISA), tuberculin test, radiological findings, and immunological studies (in disseminated TB). Of 14 cases, 8 were girls and 6 were boys with mean age of 8.75 ± 4.2. Nine patients were Iranian and 5 were Afghan. History of close contact was detected in 4 cases. Type of involvement was: 5 cervical adenitis, 3 osteoarticular disease, 2 peritonitis and 2 disseminated form of tuberculosis, one pericarditis, one renal tuberculosis. Radiological findings showed 4 pulmonary disease and 3 osteoarticular involvement. Tuberculin skin tests greater than 15 mm observed in 5 cases, 9 patients had 0-5 mm induration. 4 cases had concomitant pulmonary and extra pulmonary involvement. Positive AFB in gastric lavage was recognized in 4 cases, in which 3 showed positive cultures for MTB. Pathological examinations in 10 cases revealed granuloma with caseation compatible with tuberculosis, five in lymphadenopathy, three in osteoarticular, two in abdominal tuberculosis. According to this study, 20% of patients had extra pulmonary involvement, which is comparable to other reports (20-25%) and TB lymphadenitis is the most common from of presentation.

Radiologic manifestation of pulmonary tuberculosis in children admitted in pediatric ward-Massih Daneshvari Hospital: a 5-year retrospective study.

Despite the extensive preventive and therapeutic measures present against tuberculosis (TB), this disease still remains as one of the important causes of mortality and morbidity in the world. Considering the high incidence of TB in children, rareness of its' clinical features and complexity of bacteriologic diagnosis in this age group paraclinical studies, especially radiologic evaluations, is useful for reaching a final diagnosis. This 5 year study was conducted in National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Massih Daneshvari Hospital, Tehran, Iran. This retrospective study was conducted on 70 children (43 (61%) female and 27 (38.5%) male) aged between 5 months to 15 years old during a five year period (from 2001-2006) in pediatric ward. It was performed on children who were confirmed to have TB by various clinical, bacteriologic and radiologic features and tuberculin skin test. We studied the radiologic features of pulmonary TB in these children. Right lung involvement was observed in 65%, left lung 23% and bilateral involvement was detected in 12%. Also middle and superior lobes were the most common lobes affected. The commonest radiographic feature was hilar (mediastinal) lymphadenopathy; 70% detected on chest x-ray (CXR) and 85% on CT scan. Lymph nodes on right side were affected more; 25% were calcified. Also nodular infiltration of lung parenchyma was observed in 35% of CXRS and 61% of CT scans. This was followed by patchy consolidation detected in 25% and 35% of CXRs and CT scans respectively. We also observed that children <3 yr. of age had the highest lymph node involvement but the least parenchymal lesions as compared to older children. It is concluded that primary TB is the most common form of pulmonary TB in children. This could be in the form of hilar lymphadenopathy with or without lung parenchymal involvement. Also radiologic features could provide valuable information in regard to diagnosis, treatment and follow-up of pulmonary TB in children.