Z. Arıkan-Ayyıldız

Survival of an infant with homozygous surfactant protein C (SFTPC) mutation

Lung diseases caused by surfactant protein C (SFTPC) mutations are inherited as autosomal traits with variable penetrance and severity or as sporadic disease caused by a de novo mutation on one allele. Here, we report the case of a child surviving with a homozygous surfactant protein C mutation after aggressive clinical management unlike his six siblings who died in infancy. This presentation raises the suspicion of an autosomal recessive inheritence that is discussed in this report. Pediatr Pulmonol. 2014; 49:E112–E115.

Beneficial effects of arginase inhibition and inhaled L-arginine administration on airway histology in a murine model of chronic asthma.

BACKGROUND Increased arginase activity in the airways induces reduced bioavailability of L-arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled L-arginine and arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue. METHODS Forty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled L-arginine, nor-NOHA, l-arginine-nor-NOHA combination, budesonide and placebo. Interleukin(IL)-4 and IL-5 levels are determined in lung homogenates with ELISA. RESULTS L-Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA. CONCLUSION We demonstrated that inhaled l-arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment.

Plasminogen activator inhibitor-1 and angiotensin converting enzyme gene polymorphisms in Turkish asthmatic children.

BACKGROUND Polymorphisms of plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes have been implicated in susceptibility to asthma. In this study, we aimed to investigate whether there was any association between childhood asthma and polymorphisms of the PAI-1 and ACE genes. METHODS Two hundred and three Turkish children aged 5-15 years, including 102 asthmatic patients and 101 healthy control subjects were included in this study. The asthma group was divided into two groups as follows: Group I: Asthmatic children with positive family history for atopy (n=53), Group II: Asthmatic children without any family history for atopy (n=49). One hundred and twenty-eight atopic family members were also included in the study. The insertion/deletion (I/D) polymorphism of the ACE and PAI-1 4G/5G gene polymorphisms was carried out by polymerase chain reaction. RESULTS The prevalence of the PAI-1 4G allele was significantly greater in asthmatic children compared to control group (p<0.05, OR: 1.64 (1.11-2.43)) but there was no significant relation between ACE I/D genotypes and childhood asthma. No significant difference was detected between Groups I and II in terms of these ACE and PAI-1 genotypes and allele frequencies. No significant relationship was found between both gene polymorphisms and total serum IgE and skin prick test results. CONCLUSION It has been established that PAI-1 4G allele may be a genetic risk factor for childhood asthma but ACE gene I/D polymorphisms do not play a role in the development of asthma in the sample of Turkish children.

Anaphylaxis in an infant caused by menthol-containing cologne.

Severe allergic reactions to cologne or perfumes are rarely reported. Perfumes or colognes may aggravate respiratory symptoms in patients with asthma and they are also targeted as one of the most common causes of cosmetic allergic contact dermatitis.1,2 However, there is only one case of anaphylaxis to perfume reported in the literature.2 We report the case of an infant who developed anaphylaxis after application of cologne to his face by his mother. An otherwise healthy 2-month-old infant was admitted to the emergency department due to facial oedema, shortness of breath and cyanosis after application of menthol-containing cologne to his face. On physical examination, oedema of face, eyelids and lips and urticarial lesions on cheeks were noted. Cyanosis and respiratory distress were apparent. He was treated with intramuscular epinephrine, methylprednisolone, diphenhydramine and nebulised salbutamol. He was hospitalized for observation and discharged after his urticarial lesions and angioedema regressed. He had no history of wheezing, allergies or reactions to soap, perfumes or fragrances. There was no family history of atopy. The parents refused any diagnostic evaluation with the cologne or mint/menthol products. Avoidance of menthol-containing products was recommended to the parents. Anaphylaxis is a severe life-threatening systemic allergic reaction that occurs suddenly after contact with an allergycausing substance. To our knowledge, this is the first case of anaphylaxis caused by cologne in an infant. There has been only one case of anaphylaxis to perfume spray reported in a health-care worker.2 One might think that reactions by cologne or perfume may be due to chemoreceptors. But as respiratory symptoms are concerned in the previous and in our case, we think that the mechanisms of these reactions are IgE-mediated although this has not been proven. In our case, cologne might also enter systemic circulation quickly because of the thin skin of the infant besides its odour and mucosa related effects. There are allergic reactions to menthol (cyclic alcohol derivative of mint) reported in the literature. Immediate hypersensitivity reactions to menthol ranges from urticaria and rhinitis to asthma.3--5 Anaphylaxis induced by menthol containing toothpaste has also been reported recently in a metamizol allergic woman.6 This is a rare case of an infant with anaphylaxis to menthol containing cologne. It emphasizes the possibility of an allergen in a form of cologne and investigation of the contents could lead to the diagnosis in relevant cases.

Sinomenine ameliorates the airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in a murine model of chronic asthma

BACKGROUND Sinomenine (SIN), an alkaloid isolated from the root of Sinomenium acutum which has a variety of pharmacological effects, including anti-inflammation, immunosuppression and anti-angiogenesis. The present study aimed to evaluate the effects of SIN on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. METHODS Twenty-two BALB/c mice were divided into four groups; I (control), II (placebo), III, IV. Mice in groups III and IV received the SIN (100mg/kg), and dexamethasone (1mg/kg) respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide in bronchoalveolar lavage fluid (BALF) and ovalbumin-specific immunoglobulin (Ig) E in serum were quantified by standard ELISA protocols. RESULTS The dose of 100mg/kg SIN treatment provided beneficial effects on all of the histopathological findings of airway remodelling compared to placebo (p<0.05). All cytokine levels in BALF and serum and immunohistochemical scores were significantly lower in 100mg/kg SIN treated group compared to the placebo (p<0.05). CONCLUSIONS These findings suggested that the dose of 100mg/kg SIN improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.

Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma

BACKGROUND AND AIMS In previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. METHODS Twenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone received the UDCA (50mg/kg), UDCA (150mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified. RESULTS The dose of 150mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo. CONCLUSIONS These findings suggested that the dose of 150mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.

Allergic reactions to Hymenoptera stings in Turkish school children

BACKGROUND Reported prevalence of the insect stings and rates of allergic reactions vary among studies. The aim of the present study was to carry out the first epidemiological study on the prevalence of Hymenoptera allergy among school children in Izmir, Turkey. METHODS We planned to reach 6100 children, assuming the frequency of allergic reactions to Hymenoptera stings as 20%. Thirty-seven and eight schools were chosen from rural and urban areas, respectively. Parents were asked to complete a questionnaire which included questions about history of insect stings and the presence of atopic disease. All cases with severe systemic reactions and a representative sample from the remaining population were surveyed by telephone afterwards. RESULTS A total of 8565 questionnaires were distributed and the response rate was 70.8%. Of the 5602 children, 61.6% were stung at least once in their lifetime. Of these, 24.3% had a LLR, 8.1% had a MSR, 0.8% had a SSR. Overall reliability of the questionnaire was calculated as 40.7% for SSR and 91.6% for other reactions after telephone survey. On logistic regression analysis, male sex and rural residence were associated with a higher risk of being stung (OR: 1.39; CI 1.25-1.56; OR: 4.37; CI 3.36-5.69, respectively). Male subjects and asthmatic children were more likely to experience a SSR (OR: 2.44; CI 1.06-5.65; OR: 3.3; CI 1.52-7.19, respectively). CONCLUSION Hymenoptera stings are common in our population and large local reactions are the most common type of reactions. Prevalence of severe reactions is low in our population compared to previous studies.