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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency.

ISG15 is an interferon (IFN)-α/ß-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes-granulocyte, in particular-reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity.

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.

Chest CT Manifestations in Children with CVID: A 10-Year Report.

BACKGROUND: This study aimed at evaluating HRCT pulmonary manifestations in children with Common Variable Immunodeficiency (CVID) hospitalized in the Pediatric Ward of Masih Daneshvari Hospital during a 10-year period. MATERIALS AND METHODS: This retrospective study evaluated 25 children hospitalized with the diagnosis of CVID in the Pediatric Ward of Masih Daneshvari Hospital from 2001 to 2011 and their pulmonary HRCT scans were evaluated. RESULTS: The most common pulmonary HRCT findings were lymphadenopathy (66.7%), bronchiectasis (50%), air trapping (33.3%) and peribronchial wall thickening (33.3%). The highest percentage of CT-scan findings was detected in patients aged 13-17 yrs. CONCLUSION: Most of the pulmonary changes due to CVID are preventable or treatable. Also, it is possible to prevent irreversible complications of disease if it is diagnosed early. Therefore, HRCT is strongly recommended as an accurate and effective method for monitoring and fast recognition of pulmonary manifestations of the disease especially bronchiectasis which is a very common finding indicative of poor prognosis.

Methacoline Challenge test as an Evaluator of Response to Statins in Bronchial Hyperresponsiveness.

3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins), are effective serum cholesterol-lowering agents which also have anti-inflammatory properties. The objective of this study was to evaluate the effect of atorvastatin on bronchial hyperresponsiveness. Adult patients (age 14 to 65 years) with bronchial hyperresponsiveness (BHR) diagnosis based on the spirometry with methacholine challenge test were entered into the study. The study was conducted in the National Research Institute of Tuberculosis and Lung Disease. Patients were randomized to receive either atorvastatin 20 mg/day or placebo for 4 weeks. Spirometric parameters were determined at baseline and at completion of the study. Twenty two patients with the age of 32.95±10.30 years completed the trial. Changes in airway responsiveness categories (moderate to severe, mild, borderline, normal) after the intervention were not significant in atorvastatin group as in placebo group (p-value= 0.131 for atorvastatin group and p-value = 0.305 for placebo group). Also, changes in methacholine solution number (different concentrations of methacholine) which caused at least 20% decrease in FEV1 were not significant between groups (p-value = 0.089). Although we could not find a significant difference, the patients' fall in FEV1 in atorvastatin group was observed in higher concentrations of methacholine. Median before treatment versus after treatment in atorvastatin group was 1 versus 4 mg/mL, while those were 2 versus 1 mg/mL in placebo group. This study showed a better but not significant hyperresponsiveness control in the treatment group. The result might be presented more pronounced, if we could increase the sample size.

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.

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.