MicroRNA Levels in Exhaled Breath Condensate of Patients with Esophageal Atresia.

MicroRNAs (miRNAs) are noncoding RNAs that play an important role in the regulation of inflammation and have not been evaluated in exhaled breath condensates (EBC) of patients with esophageal atresia and tracheoesophageal fistula (EA-TEF). It is aimed to evaluate the levels of miRNA-21 and miRNA-24 in EBC of patients with EA-TEF. Patients who received surgery for EA-TEF (EA) were assessed for age, sex, types of anomaly, surgical treatments, and respiratory problems. A 500-1000 mL of EBC was obtained from each participant with EcoScreen. The levels of miRNA-21 and miRNA-24 in the EBC were analyzed by real-time polymerase chain reaction and compared between the EA group and the control group consisting of healthy children with no history of respiratory problems (n = 17). The levels of miRNAs in relation to respiratory problems and gastroesophageal reflux (GER) were also assessed. A total of 19 patients were enrolled in the EA group with a mean age of 7.8 ± 3.2 years and a male-to-female ratio of 10:9 EA cases had significantly lower levels of miRNA-21 (P < 0.05) compared to that in control group. The miRNA-24 levels did not differ between groups (P > 0.05). EA patients with positive pH testing for GER (n = 6) and fundoplication (n = 6) had higher levels of miRNA-21 than those with normal pH testing and without fundoplication, respectively (n = 13, P < 0.05). The levels of miRNA-21 and miRNA-24 did not differ between patients with and without proton pump inhibitor treatment (P > 0.05). The lower levels of miRNA-21 in the EBC of EA patients suggest a hyperreactive airway problem, which may be associated with GER and its surgical treatment.

Primary Immunodeficiency Disorders in children with Non-Cystic Fibrosis Bronchiectasis.

Summary: Introduction. Primary immunodeficiency diseases (PID) are common in patients with non-cystic fibrosis bronchiectasis (NCFB). Our objective was to determine ratio/types of PID in NCFB. Methods. Seventy NCFB patients followed up in a two-year period were enrolled. Results. Median age was 14 years (min-max: 6-30). Male/female ratio was 39/31; parental consanguinity, 38.6%. Most patients with NCFB (84.28%) had their first pulmonary infection within the first year of their lives. Patients had their first pulmonary infection at a median age of 6 months (min-max: 0.5-84), were diagnosed with bronchiectasis at about 9 years (114 months, min-max: 2-276). PID, primary ciliary dyskinesia (PCD), bronchiolitis obliterans, rheumatic/autoimmune diseases, severe congenital heart disease and tuberculosis were evaluated as the most common causes of NCFB. About 40% of patients (n=16) had bronchial hyperreactivity (BH) and asthma. Twenty-nine patients (41.4%) had a PID, and nearly all (n=28) had primary antibody deficiency, including patients with combined T and B cell deficiency. PID and non-PID groups did not differ according to gender, parental consanguinity, age at first pneumonia, age of onset of chronic pulmonary symptoms, bronchiectasis, presence of gastroesophageal reflux disease (GERD), BH and asthma (p greater-than 0.05). Admission to immunology clinic was about 3 years later in PID compared with non-PID group (p less-than 0.001). Five patients got molecular diagnosis, X-linked agammaglobulinemia (n=2), LRBA deficiency (n=1), RASGRP1 deficiency (n=1), MHC Class II deficiency (n=1). They were given monthly IVIG and HSCT was performed for three patients. Conclusions. PID accounted for about 40% of NCFB. Early diagnosis/appropriate treatment have impact on clinical course of a PID patient. Thus, follow-up in also immunology clinics should be a routine for patients who experience pneumonia in the first year of their lives and those with NCFB.

The success of the different eradication therapy regimens for Pseudomonas aeruginosa in cystic fibrosis.

WHAT IS KNOWN AND OBJECTIVE: Antibiotic therapy aimed at eradicating Pseudomonas aeruginosa (Pa), and improved regimens to treat chronic Pa infection have played a major role in increasing the median survival of patients with cystic fibrosis (CF). However, different clinical centres use varying eradication regimens. The aim of this study was to evaluate the efficacy of multiple eradication treatments against initial Pa infection and to determine the factors affecting the treatment success. METHODS: This study was conducted at the Hacettepe University Department of Pediatric Pulmonology. We examined the demographic, clinical and microbiological data of 146 CF patients with first Pa isolation in sputum culture from all 630 patients with CF studied. We aimed to identify the factors that affected the eradication of Pa infection and assessed the success rates of the different eradication protocols used. RESULTS AND DISCUSSION: The mean age of the patients was 71·5 months (2 months-29 years) when Pa was first isolated; the mean duration from CF diagnosis to first Pa isolation was 40 months. The most common treatment choices consisted of 2 weeks of intravenous ceftazidim-amikacin for severe exacerbation or 3 months of inhaled gentamycin combined with 3 weeks of oral ciprofloxacin for mild exacerbation in asymptomatic patients. With these treatment regimens, eradication was observed in 47 patients (32%), intermittent colonization in 42 patients (28%) and chronic colonization in 57 patients (40%). Forced expiratory volume in 1 s decline was statistically significant in patients with chronic colonization (P = 0·006). Being older than 2 years of age or having symptoms at the first Pa isolation was negatively associated with the treatment success. WHAT IS NEW AND CONCLUSION: Early antibiotic treatment for Pa can eradicate the bacteria, prevent or delay the development of chronic colonization and improve the general health status. The acquisition of Pa at an older age and having symptoms at first isolation negatively affected the success of eradication. The use of intravenous antibiotics may increase the efficacy of therapy. Inhaled tobramycin for Pa eradication was approved for reimbursement in Turkey from August 2014. The relatively low eradication rate may be explained by a lack of reimbursement for inhaled tobramycin and colistin in our country during the study period.

Prevalence and genetic diversity of Staphylococcus aureus small-colony variants in cystic fibrosis patients.

Staphylococcus aureus small-colony variants (SCVs) are being isolated more frequently in cystic fibrosis (CF) patients. We aimed to determine the prevalence of S. aureus SCVs and their phenotypic and genotypic properties in CF patients admitted to a university hospital. Specimens of 248 patients were examined during a period of 11 months. Colonies supposed to be SCVs were evaluated on Columbia blood agar, mannitol salt agar, and brain-heart infusion agar with 5% NaCl (BHIA 5% NaCl). Strains were confirmed by S. aureus nucA PCR. Antibiotic susceptibilities of SCVs and simultaneously isolated S. aureus strains were determined for oxacillin, gentamicin, trimethoprim-sulphamethoxazole, vancomycin, ciprofloxacin, linezolid, and tigecycline. Genetic relatedness between SCVs and normal S. aureus strains was determined with a pulsed-field gel electrophoresis (PFGE) method. S. aureus SCVs were detected in 20 of 248 patients (8.1%). The highest SCV isolation rate was obtained with MSA, followed by BHIA 5% NaCl. Auxotrophism for thymidine was demonstrated in six SCVs. The tigecycline susceptibilities of 48 SCV strains isolated in this study showed higher MIC values than those of 33 simultaneously isolated normal S. aureus strains. Whereas SCVs and normal S. aureus strains showed identical genotypes in 14 of the patients, five patients showed different genotypes. This first study from Turkey evaluating S. aureus SCVs in CF patients has indicated the importance of considering and reporting SCVs in chronic infections such as CF. The presence of SCVs will probably indicate persistent infection, and this might impact on antibiotic treatment decisions, as they are more resistant to antibiotics.

Interferon-gamma assays for the diagnosis of tuberculosis infection before using tumour necrosis factor-alpha blockers.

OBJECTIVES: Patients who receive tumour necrosis factor-alpha (TNF-alpha) blockers are mostly immunosuppressed. A study was performed to investigate whether an interferon-gamma (IFN-gamma) assay could represent an alternative approach to the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) in these patients. DESIGN: We prospectively enrolled 106 individuals into the study in two groups. Group 1 consisted of 38 healthy individuals and Group 2 included 68 patients with chronic inflammatory diseases evaluated for LTBI before the use of TNF-alpha blockers. RESULTS: Of all participants, nine had indeterminate IFN-gamma test results. Agreement between the two tests was poor in both groups (kappa values respectively -0.54 and 0.18). In a total of 97 subjects, 10 (10.3%) were positive by the IFN-gamma test and 49 (50.5%) by TST. CONCLUSION: We found poor agreement between TST and the IFN-gamma test in our study. Our limited preliminary data should be accepted as a basis for designing future studies that will be helpful for physicians to decide whether the IFN-gamma test is more sensitive than the TST test in detecting LTBI before the use of TNF-alpha blockers.

Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis.

BACKGROUND: The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti-inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF). AIM: To evaluate the effects of a macrolide antibiotic [clarithromycin (CAM)] on the process of inflammation [by measuring IL-8, TNF-alpha, IL-10 levels and cell profiles in bronchoalveolar lavage (BAL) fluid], pulmonary function and sputum production in children with steady-state bronchiectasis, secondary to causes other than CF or primary immunodeficiencies. METHODS: Seventeen patients randomized to the treatment group received CAM and supportive therapies for 3 months and 17 patients in the control group were given supportive therapies only. RESULTS: Compared with the control group, the treatment group showed a significant decrease in IL-8 levels, total cell count, neutrophil ratios in BAL fluid and daily sputum production at the end of the third month. There was also a significant increase in the treatment group's BAL fluid macrophage ratios. The differences in pulmonary function test parameters were not significant. CONCLUSION: Use of CAM in children with steady-state bronchiectasis results in laboratory improvement by reducing the inflammatory processes in the lungs. No corresponding clinical improvement could be shown but although this is possible with long-term use, trial validation is necessary.

Congenital hydrocephalus as a rare association with ligneous conjunctivitis and type I plasminogen deficiency.

Severe type I plasminogen deficiency is the underlying cause of ligneous conjunctivitis (LC). Furthermore, pseudomembranes may also be found on other mucous membranes (gastrointestinal tract, bronchial system, genital tract). In very rare cases, congenital hydrocephalus has been associated with the more severe forms of the disease and may even precede LC. The pathophysiological mechanism is unclear at present. It is advisable to look for plasminogen deficiency in patients with congenital hydrocephalus, because obstruction of ventriculoperitoneal shunts is possible when such a condition is overlooked. Here, we report a case of LC with hydrocephalus. This report reemphasizes the association of LC with hydrocephalus which is not well known.

Xanthoma disseminatum: a child with respiratory system involvement and bronchiectasis.

Xanthoma disseminatum (XD) is a rare normolipemic mucocutaneous xanthomatosis due to the proliferation of non-x histiocytes. Occasional involvement of the upper respiratory system has been reported, but lower respiratory tract involvement is very rare. Here, we present a child with severe involvement of the upper and lower respiratory tract by XD and bronchiectasis in the lower lobes of both lungs. The patient was an 8-year-old boy who was admitted to our hospital because of red-brown papules which developed on the skin and progressive dyspnea. He was diagnosed as having XD by skin biopsy. Physical examination revealed disseminated, numerous yellow-reddish brown papular xanthomas on the forehead and eyelids, around the neck and axillary area, and in the oral cavity and pharynx. He had respiratory distress and clubbing of the fingers. Chest x-rays showed hyperaeration and segmental atelectasis. High-resolution CT of the thorax revealed diffuse thickening of the whole tracheal and bronchial wall, and bronchiectasis in the lower lobes. Flexible fiberoptic bronchoscopy revealed numerous xanthomatous lesions in the nasal cavity, nasopharynx, oropharynx, subglottic area, trachea, bifurcation, both main bronchi, and smaller bronchi. To the best of our knowledge, this is the first report of a child with typical lesions of XD with severe involvement of the lower respiratory tract and bronchiectasis.

Tracheoesophageal fistula due to disc-battery ingestion.

Ingestion of a disc battery can lead to hazardous complications including tracheoesophageal fistula (TEF), especially when the battery is impacted in the esophagus. Urgent esophagoscopic removal of the battery is essential in all cases. Persisting respiratory symptoms and/or feeding difficulty after removal should alert the surgeon to evaluate for TEF. Esophagography and/or esophagoscopy should be performed. Once the TEF is identified, conservative management is the initial treatment of choice. Delayed primary repair can be tried if spontaneous closure does not occur. The authors present a case of TEF secondary to disc-battery ingestion with review of the current literature and discuss the management of this rare but potentially life-threatening complication.

Antioxidant effect of beta-carotene in cystic fibrosis and bronchiectasis: clinical and laboratory parameters of a pilot study.

UNLABELLED: The carotenoids are potent antioxidants with the ability to quench singlet oxygen and other toxic oxygen species. The aim of this pilot study was to investigate the protective effect of beta-carotene on oxidant system in patients with cystic fibrosis (CF) and in patients with bronchiectasis (BE) caused by a reason other than CF. Eighteen children with CF and 15 children with BE followed in the Pediatric Chest Disease Unit of Hacettepe University, and 15 healthy children participated in the study. Compared with the controls, significantly lower plasma levels of beta-carotene were found in the CF group and significantly lower plasma levels of vitamin E in the CF and BE groups. The standardization of carotenoid levels for total cholesterol did not significantly attenuate these differences. In addition, there were significantly higher levels of malondialdehyde (a marker of lipid peroxidation) and tumour necrosis factor-alpha (TNF-alpha) in children with CF and in children with BE than in normal subjects. After 6 mo of beta-carotene supplementation, the plasma levels of beta-carotene and vitamin E increased and the plasma levels of TNF-alpha and malondialdehyde decreased in both groups. CONCLUSION: Potent antioxidants, beta-carotene and vitamin E are deficient in patients with CF and in patients with BE, and they are more susceptible to oxidative damage. These patients may benefit from beta-carotene supplementation.

Diploid-triploid and tetraploid mosaicism in a child with cryptogenic cirrhosis and membranous glomerulonephritis: a causal relationship or coincidental association?

We present a seven-year-old boy with cryptogenic cirrhosis, membranous glomerulonephritis, mild mental retardation and mildly dysmorphic changes. Chromosomal analysis showed diploid, triploid and tetraploid mosaicism which was detected both by cytogenetic study and flow cytometric analysis of nuclear DNA content. Complete tetraploidy and triploidy, usually lethal, are rare chromosomal disorders. This is the first reported case of diploid-triploid-tetraploid mosaicism with cryptogenic cirrhosis and membranous glomerulonephritis.

Peripheral arterial thrombosis in systemic lupus erythematosis and nephrotic syndrome: possible association with protein S deficiency.

Arterial thrombosis in systemic lupus erythematosus (SLE) and nephrotic syndrome have been infrequently reported. A 16-year-old boy with SLE and longstanding nephrotic syndrome presented with peripheral arterial thrombosis when his lupus was at an inactive stage. He did not have antiphospholipid antibodies but had low serum antithrombin III and protein S levels. We suggest that the thrombotic event is not related to antiphospholipid antibodies but to nephrotic syndrome and possibly to acquired protein S deficiency.