Unfinished battle with childhood tuberculosis: is it curable with less drugs and shorter duration?

INTRODUCTION: Tuberculosis is still a global health problem all over the world despite its mortality has been decreased with effective treatment regimens. Poor treatment adherence, acquired drug resistance, treatment failure and relapse are the major problems during the course of the tuberculosis treatment. Intermittent regimens have the advantages of reducing the side effects and the cost of the therapy and increasing the adherence, especially in resource-limited areas; and have been documented to be as effective as daily regimen in the paediatric population. In this study, we compared the results of 6-month and 9-month intermittent-therapy regimens with two drugs, given to the children with pulmonary and extrapulmonary tuberculosis at our hospital. MATERIALS AND METHODS: One hundred and fifteen patients with pulmonary and extrapulmonary tuberculosis other than meningitis, who had been given intermittent anti-tuberculosis therapy between 1986 and 2001, were evaluated retrospectively. Fifty one patients were given isoniazid and rifampin daily for 15 days, followed by the same drugs and doses twice weekly for a total of 9-months. Also, 64 patients were treated with the same regimen for a total of 6-months. RESULTS: Clinical recovery was observed in 75% and 79% of pulmonary tuberculosis patients at the first month of therapy in group 1 (9-month group) and group 2 (6-month group), respectively. Radiological recovery was noted between 0-6 months in 81% of the patients in group 1 and 86% of the patients in group 2. According to the clinical and radiological recovery times, no significant difference was detected between the two groups (p> 0.05). Similar results had been observed in extrapulmonary tuberculosis (p> 0.05). Follow-up periods ranged from 7 months to 15 years. There was no case of early relapse. Late relapse was noted in 4 patients, who had been received 9-month therapy (group 1). CONCLUSION: Six-month intermittent therapy with two drugs is as efficacious as 9-month intermittent-therapy in childhood pulmonary and extrapulmonary tuberculosis, other than meningitis.

Pediatric pleural effusions: etiological evaluation in 492 patients over 29 years.

Pediatric pleural effusions present a changing profile over time, both in terms of etiological subgroups and causative microorganisms in parapneumonic effusions. This retrospective study aimed to review pediatric pleural effusions in a large cohort over a 29-year period, with special emphasis on the etiological subgroups and microbiological causes of parapneumonic effusions. The medical records of 492 pediatric patients were reviewed for a comparison of subgroups of pleural effusions and microbiological causes of parapneumonic effusions between three decades. Parapneumonic effusions (381 patients) made up 77.4% of the group. Tuberculous pleurisy decreased, but malignant effusions doubled in number over time. A causative microorganism was identified in 34.6% overall, with Staphylococcus aureus and Streptococcus pneumoniae being the two most common. Relative frequency of S. aureus decreased, whereas pneumococci and Haemophilus influenzae were more frequent in recent years.

Pleural fluid PCR method for detection of Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in pediatric parapneumonic effusions.

BACKGROUND: Parapneumonic effusions cause significant morbidity and mortality despite current developments in diagnostic and therapeutic approaches. Causative microorganisms may remain unidentified in a significant number of patients by cultures and Gram smears. Polymerase chain reaction (PCR) is a molecular technique for the detection of causative bacteria; however, its efficiency in pleural fluids is less known. OBJECTIVES: The present study was performed to compare the efficiency of PCR in the detection of the three most common organisms (Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae) with conventional methods. METHODS: Twenty-eight consecutive patients with parapneumonic pleural effusions were studied. On admission, pleural fluid samples were obtained for Gram staining, routine culture and PCR analysis for S. aureus, S. pneumoniae and H. influenzae. RESULTS: PCR analysis allowed detection of 11 microorganisms in 10 patients (35.7%), whereas pleural fluid cultures detected the etiological agent in only 2 (7.1%). S. pneumoniae was the most frequent agent. CONCLUSIONS: Pleural fluid cultures may have low diagnostic yields, partly due to prior antibiotic use. Pleural fluid PCR analysis may improve the etiologic diagnosis in parapneumonic pleural effusions, with technical advances leading to higher yields than obtained in this study.

Environmental tobacco smoke exposure and respiratory morbidity in children.

Environmental tobacco smoke (ETS) contains carcinogenic and toxic agents. Smoking might have a more serious effect on children than adults. We aimed to examine the effects of passive smoking on pulmonary function and respiratory health in children and to assess the concordance between parental self-reported smoking habits and urinary cotinine levels in their children. This cross-sectional study was conducted in the winter with the participation of 131 children (9-12 yr old). The procedure for each subject consisted of administration of a questionnaire to the parents, and collection of a urine sample and measurement of lung function in each child. Cotinine level excreted into urine was analyzed with respect to parental self-reported smoking behavior. Working mothers and mothers with higher level of education tended to smoke more at home (p values, respectively, .002 and .005). There was a statistical difference between the urinary cotinine levels of children when divided into two groups according to their fathers' smoking behavior at home (p = .0001). No statistically significant difference was determined in the mean episodes of respiratory infections treated during the last 12 mo among the groups formed according to daily number of cigarettes smoked by the parents at home (1: not exposed; 2: < 5 cigarettes; 3: 5-10 cigarettes; 4: > 10 cigarettes), or among the groups formed according to urinary cotinine levels (1: < 10 ng/ml; 2: > or =10 ng/ml). No significant difference was demonstrated in any of the respiratory function parameters investigated between the groups considered. The reliability of the declarations of the parents in the estimation of ETS exposure of children was low. Children are unable to remove themselves from ETS exposure. It is better to reduce the percentage of parents who smoke rather than to isolate smokers or increase ventilation.

Medical treatment of pulmonary hydatid disease: for which child?

There have been many encouraging studies on medical treatment of pulmonary hydatid disease due to Echinococcus granulosus infection. Our aims were to demonstrate the safety and efficacy of medical treatment in pulmonary hydatid disease and to describe a pediatric population who would benefit from medical treatment, especially in respect to the diameter of the hydatid cyst. All patients were treated with mebendazole or albendazole. Treatment outcome was defined as cure, improvement or failure. Among 82 patients, 34.1% were cured, 34.1% improved and 31.8% failed. When 102 cysts were individually evaluated, 36.31% were cured, 32.4% improved and 31.3% failed. The cure and the failure rates were statistically insignificant in cysts treated with mebendazole and albendazole; however statistically significantly more cysts were improved with albendazole. The results were statistically insignificant between continuous and cyclic albendazole treatment. The mean size of successfully treated cysts was 5.3+/-3.4 cm, but "failed" for cyst with a mean size of 7.3+/-4.3 cm. There was a positive, weak and statistically significant correlation between the cyst size and treatment results. The major complication was infection. We suggest that selected pediatric patients with uncomplicated pulmonary hydatid cysts sized less than 5 cm should have a trial of medical treatment with a very close follow up.

Cardiac hydatid cyst and pulmonary hydatidosis in a child.

Hydatidosis in the lungs is unusual, and a cardiac localization occurs rarely. We report a child with cardiac hydatid cyst that developed during albendazole treatment for preceding multiple pulmonary hydatid lesions. The cardiac lesion was treated by surgical excision, and the pulmonary cysts improved with a combination of praziquantel and albendazole therapy.

Congenital lobar emphysema: evaluation and long-term follow-up of thirty cases at a single center.

Congenital lobar emphysema (CLE) is characterized by overdistension and air-trapping in the affected lobe, and is one of the causes of infantile respiratory distress. In this report, we review our 27 years of experience with 30 CLE patients. Patients' medical records were evaluated with regard to age, clinical presentation, diagnostic methods, associated diseases, treatment, histopathologic findings, and final clinical and laboratory findings at the end of a long-term period. The mean age of 30 patients (18 male) at diagnosis was 4.9 +/- 6.7 months (range, 2 days-2.5 years). Tachypnea, dyspnea, cough, cyanosis, wheezing, hoarseness, and decreased breath sounds on the affected side were the main symptoms and clinical findings. On chest X-rays, emphysema was seen in all patients; shift/herniation to the opposite lung, atelectasis, and pneumothorax were observed in 16, 5, and 2 cases, respectively. Computerized tomography of the thorax was performed in 16 cases and revealed emphysema at affected lobe/lobes in all, a shift/herniation to the opposite side in 12 cases, and atelectasis of neighbor lobe/lobes in 7 cases. All 8 patients who had perfusion scintigraphy showed reduced perfusion in the affected lobe. Narrowed and flaccid bronchi were detected in one patient by using flexible bronchoscopy. Blood gas analysis was performed in 11 patients, and hypoxia and hypercarbia were revealed in 9 and 7 of these patients, respectively. The most common affected lobe was the left upper lobe (57%), followed by the right upper lobe (30%) and right middle lobe (27%). Two lobes were involved in 4 patients. Associated abnormalities were observed in 5 patients. Twenty-one patients underwent lobectomy; 9 were followed conservatively. Ages at diagnosis were significantly younger in surgically treated patients. Emphysema was detected in all pathological specimens, with an additional bronchial cartilage deficiency in 2 patients. In the surgically treated group, 2 patients died and 2 patients were lost to follow-up. In the conservatively treated group, one patient was lost to follow-up. Mean follow-up duration of all patients was 63.2 +/- 56.2 months (range, 1-209 months). At follow-up visits, all patients were doing well. In surgically treated patients, chest X-rays were normal (9 cases), or showed hyperlucency on the operated side (6 cases) or chronic changes in the operation area (2 cases). Hyperexpansion in the affected lobe was found to be reduced in all cases in the conservatively treated group.

Hodgkin's disease and ataxia telangiectasia with pulmonary cavities.

Ataxia telangiectasia (AT) homozygotes have an increased risk for development of Hodgkin's disease (HD). Parenchymal lung involvement is not uncommon in HD; however, cavitary pulmonary lesions are quite unusual. We report on 3 cases of AT with HD who had mediastinal disease and parenchymal pulmonary involvement with cavitation. Of 6 AT patients in our HD series, 3 developed pulmonary cavities. The patients displayed pulmonary infiltration, cavitation in the lung parenchyma, and mediastinal enlarged lymph nodes on both plain chest X-rays and thoracic computed tomographies. No infectious etiologies were established for the pulmonary findings. Histopathological examination of open lung and mediastinal biopsies revealed HD, and all patients received multiagent chemotherapies. The outcome was fatal in all 3 patients. Respiratory infections are the principle cause for morbidity and mortality in AT patients. Reports on cavitating pulmonary lesions in HD are quite rare. Furthermore, data regarding the patterns of pulmonary involvement in AT patients with or without HD are lacking. The increased incidence of malignancies in AT patients may relate to immunodeficiency and to the chromosomal alterations identified.

Hepatobiliary manifestations of cystic fibrosis in children: correlation of CT and US findings.

MATERIAL AND METHODS: Abdominal US and CT scans of 50 pediatric cystic fibrosis (CF) patients were evaluated to search for specific data that can be attributed to the involvement of the hepatobiliary system. The liver findings of the two patients who were HBs antigen carriers were excluded from the study. RESULTS: 30 out of 48 patients had at least one abnormal finding of liver on CT and/or US. Although increased echogenicity of the liver was detected in 24 of 48 patients (50%), only six of these (12%) were regarded as steatosis according to CT criteria of low attenuation values. CT and US scans both showed unique multilobular fatty pattern, described as "pseudomasses" in three patients. Increased periportal echogenicity was seen in 18 (37%) patients on US, while CT could not demonstrate any sign of increased periportal thickness. Findings of cirrhosis were present in five patients with either modalities. Lymph nodes of less than 10-15 mm in diameter were detected at the hepatico-duodenal ligament in 18 (37%) patients. Anomalies of the gallbladder (absence or microgallbladder or stone) were detected in 12 cases (24%). CONCLUSION: Although US is the most widely used modality in CF patients, CT and US correlation will help to better delineate the abnormalities between steatosis and periportal fibrosis and increase the sensitivity of the imaging methods to achieve the most accurate diagnosis.

Hypercalciuria and nephrocalcinosis in cystic fibrosis patients.

The objective of this study was to determine the frequency of nephrocalcinosis and hypercalciuria in cystic fibrosis (CF) patients, and to search possible causes of this phenomenon. Forty-three CF children (24 boys, 19 girls; mean age 64.9 months, range 5 months-18 years) were included in this study. Plasma sodium, potassium, chloride, BUN, creatinine, calcium, phosphorus, magnesium, alkaline phosphatase; spot urine sodium, potassium, chloride, creatinine, calcium, magnesium; and serum 25-hydroxyvitamin-D levels were measured in all patients. Urine samples were examined for microscopic hematuria. Fractional sodium, potassium, chloride excretion and estimated glomerular filtration rate (GFR) were calculated. All patients underwent renal ultrasonography. Hypercalciuria, nephrocalcinosis and microscopic hematuria were detected in 15 patients (34.2%), 10 patients (23.2%) and two patients (5%), respectively. There was no significant but borderline correlation between 25-hydroxyvitamin-D levels and hypercalciuria (r: 0.308, p:0.05). There were no correlations between Shwachman clinical scoring system results and hypercalciuria (r: 0.221, p: 0.148) and age and hypercalciuria (r: -0.229, p: 0.135). Patients with chronic Pseudomonas colonization showed no hypercalciuria or nephrocalcinosis. There was no difference for plasma biochemical results, renal function tests, hypercalciuria and nephrocalcinosis between CF patients who had or had not experienced pseudo Bartter's syndrome (PBS) before. There was no relation between detected CF mutations of the patients and hypercalciuria and nephrocalcinosis. These results suggested that it is a primary abnormality of calcium metabolism in the kidney.

Using computer based data acquisition and analysis system for nasal potential difference measurement in cystic fibrosis.

Nasal potential difference (PD) measurement has been used as a diagnostic test for cystic fibrosis (CF). It has been shown that large differences in reproducibility of nasal PD measurement can exist between different study sites. These differences reduce the validity of studies. In our study we tried to measure nasal PD values for a group of Turkish CF patients by using a computer based data acquisition system, which could eliminate the bias due to using different voltmeters. The CF group (n=40, mean age 9.3 years) value was -39.21+/-1.74 mV, and the control group (n=36, mean age 17.08 years) value was -18.24+/-1.48 mV (mean+/-SEM). Using the electronic data acquisition and analysis systems gave reliable results with high specificity (92%), sensitivity (79%), positive predictive value (95%) and negative predictive value (72%). Computer based data acquisition and analysis system provides suitable monitoring and continuous recording during measurements and facilitates repeat readings at the same distances along the nasal floor. Using electronic data acquisition may help to minimize the subjectivity in voltmeter measurements and hand analysis.

[Isolation frequency of Burkholderia cepacia from cystic fibrosis patients]. / Kistik fibrozisli hastalarda Burkholderia cepacia izolasyon sikligi.

Microorganisms such as Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae frequently cause colonization and infection in airways of patients with cystic fibrosis. Burkholderia cepacia has also been isolated in patients with cystic fibrosis since 1980. In this study, we aimed to determine the colonization rate of B. cepacia in 286 sputum samples obtained from 129 cystic fibrosis patients. Selective media for B. cepacia were used besides the routine microbiological media in order to increase the isolation rate. The colonies were identified by biochemical tests and the antibiotic susceptibilities of the strains were determined by disc diffusion method. Pathogenic bacteria (S. aureus, P. aeruginosa, Enterobacteriaceae, Streptococcus pneumoniae, H. influenzae) were isolated in 52 of 129 patients (40%) and 66 of 286 sputum samples (23%). In addition 2 B. cepacia strains were isolated from two different patients (1.55%). B. cepacia is now being considered as a pathogen isolated from sputum samples of patients with cystic fibrosis with an increasing frequency and causing severe clinical features. According to these results it can be concluded that, the use of selective media for B. cepacia isolation, should be taken into consideration especially by the clinical microbiology laboratories collaborating with the cystic fibrosis centers.

Relation of bone mineral density with clinical and laboratory parameters in pre-pubertal children with cystic fibrosis.

To study bone mineral density (BMD) of pre-pubertal cystic fibrosis (CF) children, and its relation with clinical and laboratory parameters, we enrolled 16 CF (8 girls) (4-8 years), and 16 control children (8 girls) (4-8 years). After anthropometric measurements, BMD, serum calcium, phosphorus, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), parathyroid hormone, osteocalcin, tumor necrosis factor (TNF)-alpha, soluble TNF-alpha receptor 2 (sTNFR2), and soluble IL-2 receptor (sIL-2R) levels, and urinary calcium and hydroxyproline excretions were assessed. Disease severity of CF patients was determined with Shwachman-Kulczycki clinical and Brasfield radiological scoring systems.The mean Shwachman-Kulczycki and Brasfield scores of CF patients were indicating well-controlled disease. The anthropometric measurements, mean BMD values, and serum calcium, phosphorus and parathyroid hormone levels were within normal range and similar in both groups. Serum osteocalcin levels were lower, and ALP and 25-OHD levels were higher in CF. Although 24-hr urinary calcium excretions was higher in CF patients, hydroxyproline excretions were similar in both groups. There was no difference between two groups for the serum levels of sIL-2R, TNF-alpha and sTNFR2. Children with low vertebral z-scores had higher serum sIL-2R levels in both groups, but the same relation could not be shown for TNF-alpha and sTNFR2.We may speculate that younger, healthier and well-nourished patients with CF may have normal BMD, but the bone disease develop as patients get older because of the other contributing factors. Future well-designed longitudinal studies with large cohorts might show a relation with BMD and cytokines in CF.

Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs. We identified six homozygous exonic mutations in the seven unrelated patients with PAM we studied. Three of the mutations were frameshifts, one was a chain termination, one was an amino acid substitution, and one was a deletion spanning the minimal promoter and the first exon. Absence of functional protein product of the gene is compatible with calcium phosphate deposition in alveolar airspaces. We show that impaired activity of the phosphate transporter is presumably responsible for the microliths and that PAM is a recessive monogenic disease with full penetrance. Testicular microlithiasis (TM) is a disease that is more common than PAM. It is often associated with cancer and infertility. Since the gene we identified is also expressed in testis, we searched for mutations in subjects with TM. In 2 of the 15 subjects with TM we studied, we identified two rare variants, one synonymous and the other noncoding, that are possibly associated with the condition.

Bronchiectasis: the consequence of late diagnosis in chronic respiratory symptoms.

Bronchiectasis is still common among some developing countries like Turkey. The aim of this study was to document the number of children with non-cystic fibrosis (CF) bronchiectasis, to evaluate the risk factors and to emphasize early diagnosis and treatment. All children, except those diagnosed with CF, with bronchiectasis established by chest radiogram, bronchography and/or computed tomography or biopsy material, were retrospectively reviewed. They were tested for serum total eosinophil count, nasal smear, serum levels of immunoglobulins A, G, M, E, and serum alpha-1 antitrypsin level. Pulmonary function tests, rigid bronchoscopy, nasal biopsy, lung scintigraphy, and echocardiogram were also performed. There were 204 patients whose most common presenting symptoms were cough, sputum expectoration, and dyspnea. Bronchiectasis was present mostly in the left lower lobe. The cause could not be determined in 49 per cent of patients. Among the identified causes, infection was present in most patients, followed by asthma, primary ciliary dyskinesia, congenital immune deficiency, and foreign body aspiration. It is possible to prevent bronchiectasis in children with vaccinations and improved nutrition in developing countries. Early diagnosis and treatment will increase the quality of life and survival of patients with bronchiectasis, which has irreversible and progressive complications if untreated.

Treatment and follow-up of pulmonary alveolar microlithiasis with disodium editronate: radiological demonstration.

A 9-year-old girl with pulmonary alveolar microlithiasis is presented. She was asymptomatic except for failure to thrive. Plain chest radiographs on admission showed sand-like opacities with calcific densities throughout both lung fields, predominantly in the lower zones. A black pleural line was also seen between the ribs and lung parenchyma. High-resolution CT (HRCT) revealed diffuse ground-glass opacities throughout both lungs, micronodular densities, interlobular septal thickening, linear calcifications along the pleura and a few scattered subpleural cysts. Disodium editronate, which is known to inhibit the microcrystal growth of hydroxyapatite, was started at 10 mg/kg per day orally. After 1 year of therapy, considerable regression of the calcific densities was detected on chest radiographs and HRCT scans.

BALF nitrite as an indicator of inflammation in children with cystic fibrosis.

BACKGROUND: A unique substance reflecting the degree of inflammation localized to the lower respiratory tract in patients with cystic fibrosis (CF) has been the concern of several investigators and nitric oxide has gained interest for this purpose in the last decades. OBJECTIVES: The aim of this study was to evaluate the cytokine and nitrite levels by showing the relationship between them in serum and bronchoalveolar lavage fluid (BALF) of patients with CF and patients in which flexible fiberoptic bronchoscopy (FFB) was applied because of indications other than infection. METHODS: 20 children with CF with mean age 8.2 years and 10 children as control group with mean age 4.2 years were included in the study. Cultures for aerobes, anaerobes, fungi and mycobacteria, cell differentials, cytokine and nitrite measurements were made from BALF specimens. White blood cell (WBC) count, erythrocyte sedimentation rate (ESR), quantitative C-reactive protein (QCRP), cytokine and nitrite levels were measured from serum samples. RESULTS: BALF neutrophil, TNF-alpha, IL-8 and nitrite levels were significantly higher in patients with CF than control patients. There was no correlation between serum and BALF cytokine and nitrite levels. However, there was a significantly positive correlation between BALF IL-8 and nitrite levels in patients with CF (r = 0.5) and also in control patients (r = 0.6). CONCLUSIONS: The results suggest that BALF nitrite levels reflect the degree of inflammation localized to lower respiratory tract and may be a useful indicator of airway inflammation for patients with CF.

Postinfectious bronchiolitis obliterans in children: clinical and radiological profile and prognostic factors.

BACKGROUND: Postinfectious bronchiolitis obliterans (BO) designates a clinical syndrome of chronic airflow obstruction associated with inflammatory changes in the small airways. OBJECTIVES: The aim of this study was to determine the etiology, clinical and radiological features and define prognostic factors of postinfectious BO in children. METHODS: We undertook a review of the medical records of 20 children with postinfectious BO, who were followed up between January 1994 and August 2001. RESULTS: Postinfectious BO was diagnosed in 11 boys and 9 girls with a median age of 21.5 months (6-69 months) who were followed up for a median of 23 months. Cough and wheezing persisted since the initial lung infection in all patients. Postinfectious BO was diagnosed in an average of 6 months (1-42 months) after the acute illness. Adenoviruses were the most common etiologic agents identified serologically. The diagnoses of postinfectious BO was made by thoracic high-resolution computed tomography and clinical features. Corticosteroid therapy was used in 17 patients and supportive treatment was applied in all patients. Age at initial lung infection, gender, time of starting corticosteroid treatment, presence of bronchiectasis or atelectasis and etiologic agents identified on presentation did not predict severity in our study. CONCLUSIONS: Despite the prominent role of inflammation in the pathogenesis of postinfectious BO, the use of anti-inflammatory agents remains controversial. We could not identify any prognostic factors related to disease severity. In order to minimize associated complications, patients with postinfectious BO should be closely followed up and receive meticulous lung care.