An mTOR feedback loop mediates the 'flare' ('rebound') response to MET tyrosine kinase inhibition.

Targeted therapy significantly impairs tumour growth but suffers from limitations, among which the 'flare' ('rebound') effect. Among cancers driven by tyrosine kinase receptors, those relying on alterations of the MET oncogene benefit from treatment by specific inhibitors. Previously, we reported that discontinuation of MET tyrosine kinase receptor inhibition causes 'rebound' activation of the oncogene, with a post-treatment transient hyperphosphorylation phase that culminates into a dramatic increase in cancer cell proliferation. The molecular mechanisms behind the 'MET burst' after treatment cessation are unknown but critically important for patients. Here we identify a positive feedback loop mediated by the AKT/mTOR pathway leading to (a) enhanced MET translation by activating p70S6K and 4EBP1 and (b) MET hyper-phosphorylation by inactivation of the tyrosine-phosphatase PTP1B. The latter effect is due to m-TOR-driven PTP1B phosphorylation of the inhibitory residues Ser50 and Ser378. These data provide in vitro evidence for the use of mTOR inhibitors to prevent the 'flare effect' in MET targeted therapy, with potential applicative ramifications for patient clinical management.

Real-world patient data on immunity and COVID-19 status of patients with MPS, Gaucher, and Pompe diseases from Turkey.

BACKGROUND: COVID-19 and lysosomal storage disorders (LSDs) share a common immunological pathway as they cause the release of cytokines in a similar pattern. We aimed to evaluate the immunity status and reveal the course of COVID-19 in patients with LSDs. RESULTS: The median age of 110 patients with LSDs was 129 months (range: 21-655), and all but one patient with mucopolysaccharidosis (MPS) type III were regularly receiving enzyme replacement therapy (ERT). In 53.6% (n = 56) of the patients (23 patients with Gaucher disease [10 type III, 13 type I], 26 patients with MPS [8 type VI, 11 type IVA, 1 type III, 3 type II, and 3 type I], and 7 patients with Pompe disease), an abnormality in at least one of the autoimmunity or immunodeficiency parameters was reported. Furthermore, 12 (57%) of 21 Gaucher cases (7 type III, 5 type I), 18 (40.9%) of 44 MPS cases (9 type IVA, 5 type VI, 1 type I, 2 type II, and 1 type III), and six (66%) of nine Pompe cases were reported to involve abnormalities in at least one of the parameters related to immunodeficiency. Immunoglobulin (Ig) M and IgA levels were reported to be lower, and there were abnormalities in the lymphocyte counts and subgroups in the MPS group. ANA was reported to be positive in one patient with Gaucher type III, anti-DNA in two patients with Gaucher type I and one patient with MPS type VI, antithyroglobulin in two patients with Gaucher type I, anti-TPO in one patient with Gaucher type I, TRAB in one patient with Gaucher type I, antiphospholipid IgM in three patients with Gaucher type III and one patient with Gaucher type I, anticardiolipin IgM in one patient with Gaucher type I, one patient with Gaucher type III, and one patient with MPS type II. However, no clinical presentation was consistent with the laboratory results except for one patient with Gaucher type I disease with Hashimoto thyroiditis. Two of the four patients who survived the COVID-19 infection with mild symptoms had a diagnosis of Gaucher type I, and no abnormality was detected in their laboratory tests. The other two patients had a diagnosis of MPS types VI and II. Immune dysfunction was detected in the patient with a diagnosis of MPS type II. Four of our patients were discharged without any sequelae. CONCLUSION: Problems with immunity did not cause any noticeable clinical results. Being well protected by reducing social contact might have played a role. However, we believe that it should be borne in mind that cardiac and pulmonary involvement, as well as immune dysfunction in LSDs, may cause an increased need for intensive care because of secondary bacterial infections.

Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene.

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA. METHODS: Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Clinical and demographic features of patients, serum immunoglobulin levels, percentage of B cells and BTK gene mutations were reviewed retrospectively. RESULTS: We identified 12 different mutations in 22 patients from 12 unrelated families. The most frequent type of mutation was premature stop codon (33.3%). Ten mutations had been reported previously including three missense mutations (c.1774T>C, c.1684C>T, c.83G>T), three premature stop codons (c.1558C>T, c.1573C>T, c.753G>A), two splice-site (c.683-1G>A, c.1567-12_1567-9delTTTG) and two small nucleotide deletions (c.902-904_delAAG, c.179_181delAGA). Two novel mutations of the BTK gene were also presented and included one splice-site mutation (c.391+1G>C) and one premature stop codon mutation (c.1243_1243delG). Six out of 12 mutations of the BTK gene were located in the SH1 domain, two in the PH domain, two in the SH3 domain and two in the SH2 domain. Three patients had a history of severe infection before diagnosis. We did not identify any correlation between severity of clinical symptoms and the genotype. CONCLUSIONS: Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA.

Prevalence of and risk factors for atopic dermatitis: A birth cohort study of infants in southeast Turkey.

BACKGROUND: Atopic dermatitis (AD) is most common in the first year of life. The aim of this study was to determine the prevalence of and risk factors for AD in a birth cohort of infants from southeast Turkey. METHODS: Adana Paediatric Allergy Research (ADAPAR) birth cohort study was derived from 1377 infants who were born in Cukurova University, Medical Hospital, Adana, Turkey between February 2010 and February 2011. At birth, a physical examination was performed, cord blood samples were taken, and the mother completed a baseline questionnaire that provided data on gestational conditions, family history of allergic diseases and environmental exposures. Follow-up visits scheduled at 3, 6, and 12 months included an infant physical examination and an extended questionnaire. Skin prick test was performed and food-specific IgE levels were measured at 6 and 12 months. Atopic dermatitis was diagnosed based on confirmatory examination by a physician. RESULTS: Of the 1377 infants enrolled, 59 (4.3%) were diagnosed with AD as of 12 months. Maternal allergic disease (ORs 6.28, 95% CI 1.03-38.30; p=0.046), maternal infection during gestation (ORs 3.73, 95% CI 1.25-11.09; p=0.018), and presence of food allergy (ORs 13.7, 95% CI 3.07-61.0; p=0.001) were identified as risk factors for AD. Breastfeeding and cord blood IgE levels were not identified as risk factors. CONCLUSIONS: In this cohort we found prevalence of AD as 4.3% during the first year of life. Positive family history of atopic diseases, prenatal infections and presence of food allergy are the risk factors for early presentation of AD.

Direct cooperation between androgen receptor and E2F1 reveals a common regulation mechanism for androgen-responsive genes in prostate cells.

We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulatory region. The gene is also regulated by the E2F1 transcription factor. Using knockdown and chromatin immunoprecipitation technique approaches, we could demonstrate that AR and E2F1 functionally collaborate and physically interact between each other. From the analysis of chromatin conformation, we conclude that this cooperation results from a chromatin looping over the ATAD2 promoter region between the ARBS and E2F1 binding site in an androgen-dependent manner. Furthermore, we could show that several genes overexpressed in prostate cancer and potentially involved in several aspects of tumor development have an ARBS and an E2F1 binding site in their regulatory regions and exhibit the same mechanism of regulation by both transcription factors as ATAD2.

Cell cycle regulated expression of NCoR might control cyclic expression of androgen responsive genes in an immortalized prostate cell line.

In this work we have studied the mechanisms of regulation of expression of androgen receptor (AR) target genes. We have used an immortalized non-tumorigenic prostate cell line RWPE-1-AR(tag) constitutively expressing an exogenous AR as a model. We observed that all studied AR target genes exhibited a specific expression during the G1 phase of the cell cycle despite the constitutive expression of AR. Importantly, we found that the expression of NCoR, an AR co-repressor, was downregulated during the G1 phase and expressed as mRNA and protein specifically during the S phase. The role of NCoR in repressing androgen-induced expression of AR target genes in S phase was further demonstrated by altering expression of NCoR during the cell cycle through knockdown or induced overexpression. Using two alternative techniques we show that AR binds directly to target DNA in the chromatin only during the G1 phase. These data support the hypothesis that NCoR might control a cell cycle dependent regulation of expression AR target genes in prostate cells.

The effects of meteorological factors and Alternaria spore concentrations on children sensitised to Alternaria

Background: Alternaria is the most important fungal species belonging to the class Deuteromycetes which causes allergic respiratory diseases. The fungus pattern often shows a pronounced seasonal periodicity and with fluctuations related to meteorological conditions. In this study, we aimed to investigate the effect of outdoor Alternaria spore concentrations on monthly lung function tests, symptoms, and medication scores in children sensitised only to Alternaria. Additionally, we planned to determine the Alternaria spores of the outdoor environment in Adana, with special respect to their relationships with meteorological conditions and their seasonal changes. Methods: Twenty-five patients with a clinical diagnosis of asthma and/or rhinitis sensitised only to Alternaria were enrolled in the prospective study. Meteorological data and outdoor samples of airborne fungi were obtained between November 2006 and October 2007. Results: The outdoor Alternaria spore concentrations were significantly correlated with the monthly average temperature (r=0.626, p=0.03) and monthly average barometric pressure (r= -0.613, p=0.03). Similarly, the outdoor Alternaria spore concentrations were significantly correlated with mean monthly asthma medication score (r=0.599, p=0.04), value monthly PEF (r= -0.737, p=0.006), value monthly FEF25–75% (r= -0.914, p=0.0001) and, variation in PEF (r=0.901, p=0.0001). Conclusions: The atmospheric concentration of Alternaria spores are markedly affected by meteorological factors such as air temperatures and barometric pressures. In hypersensitive patients, Alternaria spores can induce decreases in respiratory functions and development of allergic symptoms between May and September, being especially more influential in August

The effects of meteorological factors and Alternaria spore concentrations on children sensitised to Alternaria.

BACKGROUND: Alternaria is the most important fungal species belonging to the class Deuteromycetes which causes allergic respiratory diseases. The fungus pattern often shows a pronounced seasonal periodicity and with fluctuations related to meteorological conditions. In this study, we aimed to investigate the effect of outdoor Alternaria spore concentrations on monthly lung function tests, symptoms, and medication scores in children sensitised only to Alternaria. Additionally, we planned to determine the Alternaria spores of the outdoor environment in Adana, with special respect to their relationships with meteorological conditions and their seasonal changes. METHODS: Twenty-five patients with a clinical diagnosis of asthma and/or rhinitis sensitised only to Alternaria were enrolled in the prospective study. Meteorological data and outdoor samples of airborne fungi were obtained between November 2006 and October 2007. RESULTS: The outdoor Alternaria spore concentrations were significantly correlated with the monthly average temperature (r=0.626, p=0.03) and monthly average barometric pressure (r=-0.613, p=0.03). Similarly, the outdoor Alternaria spore concentrations were significantly correlated with mean monthly asthma medication score (r=0.599, p=0.04), value monthly PEF (r=-0.737, p=0.006), value monthly FEF25-75% (r=-0.914, p=0.0001) and, variation in PEF (r=0.901, p=0.0001). CONCLUSIONS: The atmospheric concentration of Alternaria spores are markedly affected by meteorological factors such as air temperatures and barometric pressures. In hypersensitive patients, Alternaria spores can induce decreases in respiratory functions and development of allergic symptoms between May and September, being especially more influential in August.

Potential association between allergic diseases and pertussis infection in schoolchildren: results of two cross-sectional studies seven years apart.

BACKGROUND: In this study, we aimed to investigate the relationship between pertussis infections and allergic diseases in two cross-sectional questionnaire-based surveys carried out in 1997 and 2004. We also measured serum level of antibody to B. pertussis. MATERIAL AND METHODS: Two cross-sectional, questionnaire-based surveys were carried out in 1997 (n = 3164) and 2004 (n = 3728). 361 cases and 465 controls were recruited from both surveys. The skin tests were performed using standardised extracts. The level of pertussis specific IgG was measured in 136 allergic and 168 non-allergic children. RESULTS: We found that allergic diseases prevalence was significantly higher in the children suffering from pertussis infections (22.3 % fi rst and 8.8 % second survey) compared to children who did not suffer from pertussis infections (6.6 % fi rst and 4.5 % second survey) (p = 0.001 and p = 0.035, respectively). Asthma prevalence was also significantly higher in children suffering from pertussis infection (37.6 % fi rst and 26.2 % second survey) compared to children who did not suffer from pertussis (7.4 % fi rst and 5.0 % second survey) (p = 0.001 and p = 0.001, respectively). However, the mean serum levels of anti-pertussis IgG were similar in allergic and non-allergic groups (p > 0.05). CONCLUSION: Although pertussis antibody levels in atopic and non-atopic children were similar to each other, pertussis infection still seemed to have a significant effect on the development of atopic diseases.

A multicenter survey of childhood asthma in Turkey. II: Utilization of asthma drugs, control levels and their determinants.

Many surveys worldwide have consistently demonstrated a low level of asthma control and under-utilization of preventive asthma drugs. However, these studies have been frequently criticized for using population-based samples, which include many patients with no or irregular follow-ups. Our aim, in this study, was to define the extent of asthma drug utilization, control levels, and their determinants among children with asthma attending to pediatric asthma centers in Turkey. Asthmatic children (age range: 6-18 yr) with at least 1-yr follow-up seen at 12 asthma outpatient clinics during a 1-month period with scheduled or unscheduled visits were included and were surveyed with a questionnaire-guided interview. Files from the previous year were evaluated retrospectively to document control levels and their determinants. From 618 children allocated, most were mild asthmatics (85.6%). Almost 30% and 15% of children reported current use of emergency service and hospitalization, respectively; and 51.4% and 53.1% of children with persistent and intermittent disease, respectively, were on daily preventive therapy, including inhaled corticosteroids. Disease severity [odds ratio: 12.6 (95% confidence intervals: 5.3-29.8)], hospitalization within the last year [3.4 (1.4-8.2)], no use of inhaled steroids [2.9 (1.1- 7.3)], and female gender [2.3 (1.1-5.4)] were major predictors of poor asthma control as defined by their physicians. In this national pediatric asthma study, we found a low level of disease control and discrepancies between preventive drug usage and disease severity, which shows that the expectations of guidelines have not been met even in facilitated centers, thus indicating the need to revise the severity-based approach of asthma guidelines. Efforts to implement the control-based approach of new guidelines (Global Initiative for Asthma 2006) would be worthwhile.

Indices of lower airway inflammation in children monosensitized to house dust mite after nasal allergen challenge.

BACKGROUND: There are few available data assessing the united airway disease and its systemic aspects in children. With this study, we aimed to investigate the inflammation markers of upper and lower airways before and after nasal allergen challenge in mite sensitive children with different clinical expression of the allergic disease. METHODS: Four study groups were formed: rhinitis only, without bronchial hyper-responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22), atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10). Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic protein (ECP) and cys-LTs, and serum ECP levels were measured before and 24 h after nasal allergen challenge. RESULTS: The groups were comparable in terms of age and gender. Cumulative symptom scores recorded during and 1 h after nasal challenge were not significantly different between patients with R, R + A and AA groups. At T(24), the children belonging to R, R + A and AA showed significant increases in nasal eosinophils (P < 0.01, P < 0.001, and P = 0.01, respectively), sputum eosinophils (P = 0.01, P < 0.001, and P < 0.05, respectively) and blood eosinophils (P < 0.01, P < 0.001, and P < 0.05, respectively). Similarly, increases in sputum ECP (P < 0.01, P < 0.001, and P = 0.07, respectively) and sputum cys-LT levels (P = 0.07, P < 0.001, and P < 0.05, respectively) were detected in children belonging to these three groups at T(24). Sputum eosinophils significantly correlated with blood eosinophils (r = 0.54, P < 0.001) and sputum ECP (r = 0.58, P < 0.001) at T(24). CONCLUSIONS: This study showed that nasal allergen challenge increased markers of eosinophilic inflammation in both upper and lower airways of children monosensitized to mites, even before the onset of clinical symptoms.

Specific allergen immunotherapy: effect on immunologic markers and clinical parameters in asthmatic children.

BACKGROUND: Specific allergen immunotherapy (SIT) is the main treatment modality for achieving long-term symptom relief in perennial allergic diseases. OBJECTIVE: The aim of this study was to evaluate the effect of 1 year of house dust mite immunotherapy on the concentrations of 3 immunologic markers: eosinophil cationic protein (ECP), nitric oxide (NO), and monocyte chemoattractant protein 1 (MCP-1). We also compared the effect on asthma symptoms and medication scores, allergen-specific bronchial challenge test, and the skin prick test. METHODS: A total of 31 mite-allergic, asthmatic children (age range, 6-16 years) were enrolled; 19 were treated with SIT and 12 controls who had refused SIT received only drug treatment. Efficacy was evaluated using serum NO, ECP, and MCP-1 levels, and asthma symptom and medication scores, allergen-specific bronchial challenge test, and skin-prick test. The results of the tests were compared at baseline and after 1 year of treatment. RESULTS: Serum NO and ECP levels decreased significantly in the SIT group (P = .01 and P = .018) compared to baseline, whereas control group values remained similar. The serum MCP-1 level decreased significantly in both the SIT and control groups (P = .009 and P = .041, respectively). The SIT group experienced significant improvement in asthma symptoms (P = .001) and medication scores (P = .001) and skin reactivity to Dermatophagoides pteronyssinus (P = .020), whereas the control group did not. The results of bronchial challenge to D pteronyssinus showed a similar pattern at baseline and after 1 year of treatment in both groups. The tolerated allergen concentration increased in both groups (P < .05). Lung function tests, total immunoglobulin (Ig) E and specific IgE to D pteronyssinus and Dermatophagoides farinae did not change after a year of treatment in either group. CONCLUSION: SIT with D pteronyssinus improves immunological and clinical parameters in mite-allergic asthmatic children after 1 year of treatment. The skin prick test may be used as a marker of efficacy of therapy.

Is there any relationship between asthma and asthma attack in children and atypical bacterial infections; Chlamydia pneumoniae, Mycoplasma pneumoniae and Helicobacter pylori.

UNLABELLED: Asthma is a chronic inflammatory airway disease characterized by variable airway obstruction and bronchial hyperresponsiveness. There are many factors affecting the development and severity of childhood asthma such as genetic predisposition, atopy, environmental factors, obesity, diet, socioeconomic status, and infectious triggers. In the present study we aimed to investigate the frequency of Mycdoplasma pneumoniae, Chlamydia pneumoniae, and Helicobacter pylori infections in asthmatic children. We investigated also whether there is a relationship between these agents and asthma attacks. MATERIAL AND METHODS: Seventy-nine asthmatic children (46 males, aged 5-15 years) were included in study. The study group was divided into two groups: group 1 consisted of 37 children with asthma attacks and group 2 consisted of 42 children with stable asthma. As a control group we studied 36 healthy children. Pulmonary function tests, skin prick tests for common allergens were performed; serum total IgE, phadiatop, specific IgM and IgG antibody levels (ELISA) for M. pneumoniae, C. pneumoniae and H. pylori were measured in all patients. RESULTS: Mycoplasma IgM and Chlamidia IgM were positive in 8.1% (3 patients) and 18.9% (7 patients) of group 1 patients, respectively. There was a statistically significant difference for Mycoplasma IgM (p = 0.031) and Chlamidia IgM (p = 0.03) between group1 and other two groups. We have not found significant difference for M. pneumoniae IgG, C. pneumoniae IgG and H. pylori IgM and IgG among groups. CONCLUSION: M. Pneumoniae and C. Pneumoniae may play a role in development of asthma exacerbations in childhood. We could not find a relationship between H. Pylori and asthma.

Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite.

BACKGROUND: Previous studies have suggested that single-allergen-specific immunotherapy (SIT) may prevent sensitization to other airborne allergens in monosensitized children. We aimed to assess the prevention of new sensitizations in monosensitized children treated with single-allergen SIT injections in comparison with monosensitized patients given appropriate pharmacologic treatment for their disease. METHODS: A total of 147 children with rhinitis and/or asthma monosensitized to house dust mite were studied; 45 patients underwent SIT with adsorbed extracts and 40 patients underwent SIT with aqueous extracts for 5 years. The control group was comprised of 62 patients given only pharmacologic treatment for at least 5 years. Skin prick tests, medication scores for rhinitis and asthma, and atopy scores according to skin prick tests were evaluated at the beginning and after 5 years of treatment. RESULTS: All groups were comparable in terms of age, sex, and disease characteristics. At the end of 5 years, 64 out of 85 (75.3%) in the SIT group showed no new sensitization, compared to 29 out of 62 children (46.7%) in the control group (P = .002). There were no differences between the SIT subgroups with regard to onset of new sensitization (P = .605). The patients developing new sensitizations had higher atopy scores (P = .002) and medication scores for both rhinitis (P = .008) and asthma (P = .013) in comparison to patients not developing new sensitizations after 5 years of SIT. CONCLUSION: According to our data, SIT has the potential to prevent the onset of new sensitizations in children with rhinitis and/or asthma monosensitized to house dust mite.

Life-threatening facial edema due to pine caterpillar mimicking an allergic event.

BACKGROUND: Approximately 150 species of Lepidoptera have been described as causing damage to human skin. One of these species is the pine processionary caterpillar, which is responsible for dermatitis, contact urticaria, ocular lesions and rarely respiratory signs and anaphylactic reactions through IgE-mediated or non-IgE-mediated mechanisms. We report a pediatric case of severe orofacial edema mimicking an allergic reaction after ingestion of a pine processionary caterpillar; urgent airway intubation was required. CASE REPORT: A 15-month-old boy was sleeping under a pine tree when his mother noted a pine caterpillar on his tongue. Because of rapidly developing facial swelling and respiratory distress, the infant was first taken to a local hospital where he received intravenous dexamethasone and pheniramine hydrogen maleate. On arrival at our emergency department, diffuse swelling and edema involving the tongue, perioral, nasal and perimandibular regions, and neck was noted, requiring urgent orotracheal intubation. There were no findings of anaphylaxis. The results of skin prick tests and specific IgE to common aero- and food allergens were negative. A skin prick test with extract of pine caterpillar was also negative. Prednisolone and pheniramine hydrogen maleate were administered for 7 days. The child gradually improved and was successfully extubated 4 days later. CONCLUSION: Although oral contact with a pine processionary caterpillar in the form of ingestion is rare, it may cause significant local reaction and airway compromise mimicking an allergic event. In this situation, early intubation to maintain airway patency is a life-saving measure.

The effects of long term use of inhaled corticosteroids on linear growth, adrenal function and bone mineral density in children.

In this study we aimed to investigate the long term effects of inhaled steroids on linear growth, adrenal function and bone mineral density. Thirty children with moderate asthma were randomly divided into two groups. Fifteen children (8 boys, 7 girls mean age; 10.6 +/- 2.1) were treated with budesonide (group 1), and 15 (9 boys, 6 girls, mean age; 9.6 +/- 2.4). with fluticasone propionate (group 2). Control group included 30 children. Anthropometric assessment, symptom and medication scores, pulmonary functions, bone mineral density, serum and urine cortisol levels and ACTH stimulation test were evaluated at the beginning of the study and after one year period. Symptom and medication scores, pulmonary functions improved significantly in both groups (p < 0.05). The mean annual growth was similar in group 1 and 2 and control group. Bone mineral density was comparable with control group at the beginning of the study and after one year. Mean serum cortisol level diminished at the end of the therapy but no significant differences were found between the initial and end values in respect to urine cortisol levels and cortisol/creatinine ratio. Of three groups ACTH stimulation test revealed that there were no significant difference between study and control groups. In conclusion, although we did not observed any side effects of inhaled corticosteroids we suggest that children treated with inhaled corticosteroids for a long time should be followed closely with respect to side effects.

The effects of long term use of inhaled corticosteroids on linear growth, adrenal function and bone mineral density in children

In this study we aimed to investigate the long term effects of inhaled steroids on linear growth, adranal function and bone mineral density. Thirty children with moderate asthma were randomly divided into two groups.Fifteen children (8 boys, 7 girls mean age; 10.6 ± 2.1) were treated with budesonide (group 1), and 15 (9 boys, 6 girls, mean age; 9.6 ± 2.4). with fluticasone propionate (group 2). Control group included 30 children. Anthropometric assesment, symptom and medication scores, pulmonary functions, bone mineral density, serum and urine cortisol levels and ACTH stimulation test were evaluated at the beginning of the study and after one year period. Symptom and medication scores, pulmonary functions improved significantly in both groups (p < 0.05). The mean annual growth was similar in group 1 and 2 and control group. Bone mineral density was comperable with control group at the beginning of the study and after one year. Mean serum cortisol level diminished at the end of the therapy but no significant differences were found between the initial and end values in respect to urine cortisol levels and cortisole/creatinin ratio. Of three groups ACTH stimulation test revealed that there were no significant difference between stdy and control groups. In conclusion, although we did not observed any side effects of inhaled corticosteroids we suggest that children treated with inhaled corticosteroids for a long time should be followed closely with respect to side effects

El presente estudio tuvo como objetivo investigar los efectos a largo plazo de los esteroides inhalados sobre el crecimiento lineal, la función adrenal y la densidad mineral ósea. Treinta niños con asma moderada se distribuyeron aleatoriamente en dos grupos: 15 de ellos (8 niños y 7 niñas, con una media de edad de 10,6 ± 2,1 años) se trataron con budesonida (grupo 1), y los otros 15 (9 niños y 6 niñas, con una media de edad de 9,6 ± 2,4 años) con propionato de fluticasona (grupo 2). El grupo de control constaba de 30 niños. Se realizó una exploración antropométrica, una puntuación de los síntomas y la medicación, análisis de la función pulmonar, de la densidad mineral ósea y del nivel de cortisol en sangre y orina, así como pruebas de estimulación de ACTH, tanto al principio del estudio como tras un período de un año. La puntuación de los síntomas y la medicación y la función pulmonar mejoraron significativamente en ambos grupos (p < 0,05). El crecimiento medio anual fue similar en los grupos 1, 2 y el de control. La densidad mineral ósea fue comparable con la del grupo de control en el inicio del estudio y al cabo de un año. El nivel medio de cortisol en sangre descendió al final de tratamiento, pero no se observaron diferencias significativas entre los valores iniciales y finales con respecto al nivel de cortisol en la orina y la proporción entre cortisol y creatinina. La prueba de estimulación de ACTH no reveló diferencias significativas entre los grupos de estudio y el de control. En conclusión, aunque no observamos ningún efecto secundario de los corticosteroides inhalados, sugerimos el control meticuloso de los posibles efectos secundarios en los niños tratados con estos fármacos de forma prolongada

Bronchiectasis: still a problem.

The prevalence of bronchiectasis (BR) has decreased significantly in industrialized countries, but is still commonplace in developing countries. We evaluated the causes and clinical features of BR in 23 children (13 boys (57%) and 10 girls (43%), with a mean age of 8.45 +/- 4.02 years). Infection was the major cause of BR in our region. In 8 patients, BR developed after tuberculosis or pneumonia, was associated with immune deficiency syndromes in 4 children, and with asthma in 4. Cystic fibrosis was diagnosed in 4 cases and ciliary dyskinesia in 3. In 10 patients, only one lobe was involved. Bronchiectatic lesions were most commonly found in the left lower lobe and were observed in 7 patients. Multilobar involvement was found in 13 patients. The initial treatment was primarily medical, but in 2 patients whose medical therapy failed, pulmonary resection was carried out. Three patients died from severe pulmonary infection and respiratory failure.