Airway colonisation by Candida and Aspergillus species in Iranian cystic fibrosis patients.

Cystic fibrosis (CF) is associated with increased rates of morbidity and mortality due to fungal and bacterial colonisation of the airways or respiratory infections. The prevalence of fungi in Iranian CF population has been underestimated. Therefore, the current study was conducted to define the frequency of fungi in respiratory specimens obtained from Iranian CF patients based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed on the obtained isolates according to the guidelines from the Clinical and Laboratory Standards Institute. A cohort of 42 CF patients, including 29 males and 13 females, were categorised according to the referenced diagnostic criteria. Candida albicans (n = 24, 80%), C. dubliniensis (n = 2, 6.6%), C. parapsilosis (n = 2, 6.6%), C. tropicalis (n = 1, 3.3%), C. glabrata (n = 1, 3.3%) and Meyerozyma caribbica (n = 1, 3.3%) were isolated from 73.8% of the CF patients. Aspergillus terreus (n = 3, 42.8%) was identified as the most common Aspergillus species, followed by A. fumigatus (n = 2, 28.5%), A. oryzae (n = 1, 14.2%) and A. flavus (n = 1, 14.2%). Bacterial and fungal co-colonisation was detected in 7 (16.6%) and 22 (52.3%) samples that were positive for Aspergillus and Candida species, respectively. However, Scedosporium species and Exophiala dermatitidis never were detected. In terms of geometric mean (GM) minimum inhibitory concentrations (MICs), posaconazole (0.018 µg/mL) and caspofungin (0.083 µg/mL) exhibited the highest antifungal activities against all Candida species. In addition, posaconazole exhibited the lowest MIC range (0.008-0.063 µg/mL) against all Aspergillus species, followed by caspofungin (0.016-0.125 µg/mL) and voriconazole (0.125-0.25 µg/mL). To conclude, it is essential to adopt a consistent method for the implementation of primary diagnosis and determination of treatment regimen for the CF patients. However, further studies are still needed to better define the epidemiology of fungal organisms in CF patients from the Middle East and the clinical significance of their isolation.

Bronchoalveolar galactomannan in invasive pulmonary aspergillosis: a prospective study in pediatric patients.

BACKGROUND: Elevations in the number of immunocompromised patients in the past decade has lead to progressive increase in the incidence of Invasive Pulmonary Aspergillosis (IPA) among children; however, early diagnosis remains a challenge. Detection of galactomannan (GM) in the bronchoalveolar lavage (BAL) fluid appears to possess higher sensitivity and specificity than serum in immunocompromised adult patients but, it rarely has been investigated in pediatric patients. METHODS: We performed a prospective case-control study to evaluate the efficacy of BAL GM in immunocompromised pediatric patients. Cases were subjects fulfilling the host factor criteria as defined by the EORTC/MSG and met established definitions for proven or probable IPA. Control group was patients with possible IPA in whom diagnoses other than IPA were confirmed and patients without risk factors of IPA who underwent bronchoscopy for other diagnostic purpose. Galactomannan testing was performed on BAL fluid samples using platelia Aspergillus seroassay. RESULTS: Sixteen cases of IPA (4 proven, 12 probable) and 54 controls (6 possible IPA and 48 no IPA) were documented according to EORTC/MSG definitions. The sensitivity and positive predictive values of BAL GM using an OD index of ≥0.5 were 87.5% and 93.33% respectively. We found seven cases of IPA with negative serum GM while their BAL GM was positive. CONCLUSION: We found high diagnostic value of BAL GM in immunocompromised pediatric patients with IPA. The lower OD index is necessary in children to avoid missing the cases of IPA in children.

Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations.

Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.

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.

Corneal opacification, an atypical presentation of cystic fibrosis: a case report and review of the literature.

BACKGROUND: Respiratory and gastrointestinal manifestations are the main causes of mortality and morbidity in cystic fibrosis. Although these symptoms are well recognized, ophthalmic involvement of cystic fibrosis secondary to vitamin A deficiency is uncommon and has been reported very rarely in the medical literature. CASE PRESENTATION: Here, we report a 2.5-year-old Iranian boy who presented with bilateral corneal xerosis and corneal opacity secondary to vitamin A deficiency related to cystic fibrosis malabsorption. CONCLUSION: Malabsorption of fat-soluble vitamins is a common presentation in cystic fibrosis, but corneal opacity secondary to vitamin A deficiency as the initial presentation of cystic fibrosis is a very rare manifestation of fat malabsorption. This highlights the importance of complete systemic examination besides ophthalmic examination in approaching a child with ophthalmic complaint.

Inflammatory myofibroblastic tumor of the trachea.

This report described a 2-year-old boy who was presented with severe respiratory distress and stridor. Bronchoscopy and CT revealed a mass in the left anterolateral tracheal wall and histopathology showed a tracheal inflammatory myofibroblastic tumor. Initial removal by rigid bronchoscopy resulted in prompt recurrence of the tumor. Therefore, he underwent tracheal surgical resection. A bronchoscopy at 12 months after surgery did not show any recurrence sign.

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.

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.

Scimitar syndrome.

Scimitar syndrome or congenital pulmonary venolobar syndrome is a rare anomaly most commonly consisting of partial pulmonary venous drainage into the hepatic portion of the inferior vena cava, right lung hypoplasia, dextroposition of the heart, and anomalous systemic arterial supply from aorta or one of its branches to the right lung. We report a four-year-old girl with recurrent pneumonia and failure to thrive, who was diagnosed as having scimitar syndrome.

Reappraisal of Frequency of Common Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Iranian Cystic Fibrosis Patients.

BACKGROUND: Cystic Fibrosis (CF) is a life-threatening recessive genetic disorder resulting from mutations in the gene encoding the fibrosis transmembrane conductance regulator protein (CFTR). The CF clinical phenotype shows wide variation ranging from severe disease in early childhood in those homozygous for the p.Phe508del mutation to absence of the vas deferens in otherwise healthy men homozygous for the p.Arg117His mutation. MATERIALS AND METHODS: DNA was extracted from whole blood from 62 patients with CF. The CFTR mutation was determined by Allele-Specific PCR assay. The spearman and linear regression analysis were used to obtain the correlation between phenotype and genotype relationship. RESULTS: Out of total 62 patients, 35 (56.4%) were male. The mean age of the patients was 15.56 ± 6.65 years. Mutations in CFTR were detected in 64.5% of the patients. The commonest mutations were p.Phe508del (33.9%), p.Arg117His; [5T] (5.64%), p.Arg117His; [7T] (4.03%) and p.Trp1282X (5.64%). Mutations p.Ile507del (4%), p.Gly542X (4%), p.Asn1303Lys (2.42%), c.489+1G>T (1.6%), p.Gly551Asp (1.6%) and c.1585-1G>A (1.6%) were also detected. Most mutations were detected in west and south of Iran, while p.Phe508del mutation was dominant mutation (75%) in east and southeast of Iran. The study showed either an association between this mutation with severity of disease and sex or an association between p.Arg117His mutations and age at diagnosis. CONCLUSION: The geographic distribution of gene mutation in Iranian cystic fibrosis patients was very heterogenic. In spite of the study that showed a correlation between p.Phe508del and severity of disease, to find any correlation between genotype and phenotype a broad and multi-centered study is recommended.

Transmission of Mycoba cterium tuberculosis to households of tuberculosis patients: a comprehensive contact tracing study.

BACKGROUND: Tuberculosis (TB) continues to be a major health problem in developing countries. Contact investigation is the most appropriate strategy to interrupt transmission and subsequent development of TB. METHODS: This cross-sectional study was conducted to assess the impact of contact screening on case-finding by using tuberculin skin test chest radiography. Contacts of smear-positive patients with pulmonary TB (index cases) were diagnosed and registered in our center during 2002 - 2004. Contacts, defined as household members living with index cases for >30 days, were screened by sputum examination, tuberculin skin test, and chest radiography. RESULTS: Sixty-eight patients with smear-positive pulmonary TB were considered as index cases. A total of 224 close contacts with index cases (an average of 3 contacts for each index case) were detected. Age among contacts ranged from 6 months to 74 years. Eighty-three percent of contacts were Iranians and 17% were Afghans. Abnormal radiographs were seen in 49.6% of contacts. Sixteen point five percent of contacts had a positive tuberculin skin test of >10 mm; 7.6% had a positive sputum smear. The mean +/- SD age of Iranian contacts (29.1 +/- 16.6 years) was significantly (P < 0.001) higher than that of Afghans (18.6 +/- 14.1 years). Cavitary formation, nodular pattern, and infiltration were found to have a strong association with a positive sputum smear for acid fast bacilli (100%, 100%, and 87%, respectively). CONCLUSION: The rate of TB in contacts was higher than other similar studies. Earlier detection and treatment of adults with TB could interrupt transmission and be a step towards eliminating childhood TB. Contact control and source-case investigations should be emphasized for TB control. Novel strategies are needed to maximize the number of contacts who are not only identified and evaluated, but also completely treated.

Features of Adolescents Tuberculosis at a Referral TB's Hospital in Tehran, Iran.

OBJECTIVE: To identify the pattern of the clinical, radiological, diagnostic procedures and loss to follow-up of the diagnosed cases of active tuberculosis (TB) adolescents. METHODS: This study was a retrospective analysis of the medical records of 143 adolescents aged 10 to 18 years with tuberculosis who were admitted TB wards of National Research Institute of Tuberculosis and Lung Disease (NRITLD) in Tehran, Iran, between March 2006 and March 2011. RESULTS: Of the 143 patients identified, 62.9% were females. Median age of the patients was 16 years. The contact source was identified in 47.5%. The most common presenting symptom was cough (86%). Isolated pulmonary TB (PTB) was detected in 113 patients (79%), 21 patients (14.7%) had extrapulmonary TB(EPTB), and 9 patients (6.3%) had PTB and EPTB. The most common site of EPTB was pleural (14%). The most common radiographic finding was infiltration (61%). Positive acid fast smears were seen in 67.6%. Positive cultures for Mycobacterium tuberculosis (M. TB) were seen in 44.7%. Positive Polymerase chain reaction (PCR) results were seen in 60%. The adolescents aged 15 to 18 years were more likely to lose weight (p=0.001), smear positive (p=0.001), culture positive (p<0.001) and have positive PCR results (p=0.009). The type of TB (p=0.017) was a significant factor influencing loss to follow-up. CONCLUSIONS: The study has revealed that the clinical and radiological findings of TB in adolescents are combination as identified in children and adults. The TB control programs should pay more attention to prevention and treatment of TB in adolescents.

Cotinine level is associated with asthma severity in passive smoker children.

Asthma environmental triggers play important roles in severity of disease. Passive smoking could exacerbate asthma symptoms and enhance the decrease in lung function. Cotinine levels could be a reflection of passive exposure to the cigarette both in adults and pediatrics. The aim of this study was to determine degree of association of asthma severity and cotinine level as a marker of passive smoking. In a cross-sectional study, 100 pediatric patients (under 10 years old) with asthma were enrolled, 50 of whom, had been exposed to passive smoking and 50 others included as controls. A complete clinical history, lab exam, and spirometry were performed. A sample of urine, serum and saliva was collected from all attendant patients and controls in the study after confirmation of diagnosis and determination of severity of asthma. The results revealed that age, sex, age of onset of asthma, family history and allergic history were not significantly different between two groups of patients. According to GINA classification, percentage of patients with severe asthma was significantly higher in passive smoker group (p=0.001). Cotinine was significantly higher in passive smoker group compared to control group in serum (p=001), saliva (p=0.001), and urine (p=0.0014). In passive smoker group, cotinine levels were significantly higher in serum (p=0.001), urine (p=0.007), and saliva (p=0.01) of patients with severe asthma than moderate and mild asthma. Serum cotinine (OR: 1.81, 95% CI: 1.35-2.32, p=0.024), urine cotinine (OR: 3.56,95% CI = 1.29-5.53, p=0.01) and saliva cotinine (OR: 1.66, 95% CI: 1.23-1.98, p=0.031) were also significantly associated with higher risk of severe asthma. Cotinine levels were higher in passive smokers compared to non-passive smokers. Besides, cotinine was a predictive risk factor for severe asthma.

Allergic and nonallergic asthma in children: are they distinct phenotypes?

The aim of current study is to describe clinical similarities and differences between atopic and non-atopic asthma in children. In a cross-sectional study, 95 asthmatic children (75 allergics and 20 nonallergics) were included in the study. Demographic, clinical, and familial history were compared between two groups. There was no significant differences between variables like sex, age of onset (p=0.75), severity (p=0.70), and family history among the two groups (p=0.42). Patients with allergic asthma were significantly older than those with non- allergic asthma (11.28 ± 3.19 and 9.75 ± 2.35 years, respectively, p=0.02). The controversy lingers over the presence of a completely distinct phenotype of non-atopic asthma in children. Our study suggested that phenotypes of allergic and non-allergic asthma in children were not entirely distinct.

Characterization of CSF2RA mutation related juvenile pulmonary alveolar proteinosis.

BACKGROUND: Juvenile pulmonary alveolar proteinosis (PAP) due to CSF2RA mutations is a rare disorder with only a few cases described worldwide. METHODS: We identified nine children with severe diffuse interstitial lung disease due to CSF2RA mutations. Clinical course, diagnostic findings and treatment were evaluated and correlated to the genotype. Functional impairment of the intracellular JAK/pStat5 signaling pathway was assessed using flow-cytometry of peripheral mononuclear cells (PBMC) and granulocytes. RESULTS: We identified six individuals with homozygous missense/nonsense/frameshift mutations and three individuals homozygous for a deletion of the complete CSF2RA gene locus. Overall, four novel mutations (c.1125 + 1G > A, duplication exon 8, deletion exons 2-13, Xp22.3/Yp11.3) were found. Reduced STAT5 phosphorylation in PBMC and granulocytes was seen in all cases examined (n = 6). Pulmonary symptoms varied from respiratory distress to clinically silent. Early disease onset was associated with a more severe clinical phenotype (p = 0.0092). No association was seen between severity of phenotype at presentation and future clinical course or extent of genetic damage. The clinical course was favorable in all subjects undergoing whole lung lavage (WLL) treatment. CONCLUSIONS: Our cohort broadens the spectrum of knowledge about the clinical variability and genotype-phenotype correlations of juvenile PAP, and illustrates the favorable outcome of WLL treatment in severely affected patients.

Visceral leishmaniasis in two brothers; diagnostic dilemma due to hemophagocytic syndrome.

Visceral Leishmaniasis (VL), a systemic infection of the reticuloendotherlial system, is caused by a parasitic infection. The co-occurrence of VL and hemophagocytic syndrome (HPS) has been previously reported in several studies. In this report we present two cases of HPS and VL among members of the same family.

Pediatric pulmonary alveolar microlithiasis: a case report.

Pulmonary alveolar microlithiasis is a rare infiltrative pulmonary disease characterized by deposition of microliths in the alveoli. In this case report, we present a case of a 5 year-old girl with complaints of common cold and loss of appetite. Chest radiograph showed innumerable small, dense nodules, diffusely involving both lungs. High-resolution CT scan illustrated widespread micro-nodular infiltration, diffuse ground-glass attenuation areas predominantly in upper anterior regions and septal thickening. Trans-bronchial biopsy confirmed the diagnosis.

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.

Correlation of anxiety-depression and sleep quality in mothers of children with cystic fibrosis and asthma.

BACKGROUND: Cystic fibrosis and asthma are considered among the chronic respiratory diseases. Taking care of the sick child by the mother-which is usually the main care taker- can be associated with high loads of stress and result in behavioral problems like anxiety, depression and change in sleep quality. This study aimed at evaluating the correlation between depression-anxiety and sleep quality in mothers of children suffering from cystic fibrosis and asthma hospitalized in Masih Daneshvari Hospital. MATERIALS AND METHODS: This was an analytical descriptive cross-sectional study conducted on 148 subjects (mothers of children with cystic fibrosis and asthma hospitalized in Masih Daneshvari Hospital) during 2008-2010. Data were collected using a questionnaire for demographic characteristics, sleep quality and Hospital Anxiety and Depression Scale (HADS). Pittsburgh sleep quality index questionnaire (PQSI) was developed by Dr. Buysse and colleagues at the University of Pittsburgh's Western Psychiatric Institute and Clinic in the late 1980s. The PSQI was created after observing that most patients with psychiatric disorders had sleep disorders as well. Also, required data regarding the pulmonary function of patients was extracted from their medical records. RESULTS: In this study, high levels of anxiety and depression and poor sleep quality requiring clinical intervention were seen in 37.2%, 29.1% and 39% of mothers, respectively. A significant association was detected between sleep quality and depression-anxiety (P-value < 0.005). Also, depression-anxiety was significantly correlated with number of children and smoking (P-value < 0.005). A total of 20% of mothers suffering from depression and 14.3% of mothers with anxiety disorder had a history of cigarette smoking (P-value < 0.005). No significant association was found between substance abuse and occupation with depression-anxiety. Susceptibility was only correlated with anxiety (P-value < 0.005). CONCLUSION: Our study showed a significant association between sleep quality and depression-anxiety in mothers of children suffering from cystic fibrosis and asthma. Greater attention should be paid to prevent development and aggravation of these conditions in susceptible mothers who are the main care taker of their sick child with chronic diseases.

Mediastinal lymphangioma in a child.

We report a case of a male child with a cystic mass in his left side of the neck with extension to the mediastinum. This article highlights the clinical and para-clinical findings and management of these cases. In conclusion, it is necessary to evaluate the mediastinum for extension of the cyst in cases with cystic hygromas of the neck. Surgical resection of the tumor through a cervical incision can be considered.