Association of beta-defensin-1 gene polymorphisms with Pseudomonas aeruginosa airway colonization in cystic fibrosis.

Lung disease and Pseudomonas aeruginosa (P. aeruginosa) airway colonization represent a major cause of morbidity and mortality in cystic fibrosis (CF). Human beta-defensin (hBD)-1 is believed to play an important role in mucosal innate immunity in the lung. This study aimed to investigate whether three single-nucleotide polymorphisms (SNPs) in the 5'-untranslated region of DEFB1, G-52A, C-44G and G-20A were associated with P. aeruginosa airway colonization in CF. A total of 224 CF patients and 196 control subjects were studied. DEFB1 SNPs were characterized by restriction fragment length polymorphisms. Patients' sputum samples were collected and analyzed by standard methods. Single SNP analysis suggested that CF patients carrying the -52AA and the -20GG genotypes had a higher rate of P. aeruginosa airway colonization than patients homozygous and heterozygous for the -52G and -20A alleles (P=0.01 and P=0.007, respectively). A significant association between the ACG haplotype and chronic P. aeruginosa infection was also identified (odds ratio (95% confidence interval): 3.00 (1.42-6.36), P=0.004). These results indicate that variant alleles in DEFB1 might contribute to the colonization of P. aeruginosa in CF.

Exaled nitric oxide and air trapping correlation in asthmatic children.

Exhaled nitric oxide (eNO) levels have been shown to correlate with atopy and with airway hyperresponsiveness but not with standard spirometry. The aim of our study was to evaluate the correlation between eNo levels and functional residual capacity (FRC), residual volume (RV), RV to total lung capacity (TLC) ratio, and pulmonary resistances in asthmatic children ages 6-13 years. Forty-nine patients (35 males) were enrolled in the study. Nineteen of them were not receiving inhaled corticosteroids. The eNO levels were measured by chemiluminescence's analyzer and lung function study were performed by body box plethysmography. As expected, there was no correlation between eNO levels and forced vital capacity (FVC); forced expiratory volume in the first second (FEV1); mid respiratory flow between 25 and 75% of the vital capacity (MEF(25 -75)), FEV1/FVC, and pulmonary resistances. Instead a correlation was found between eNO level and RV both considering all the study population together (r = 0.51, P = 0.001) and separately the asthmatic children not receiving ICS (r = 0.6, P = 0.003). In the patients receiving ICS the correlation was still present (r = 0.43, P = 0.01). The correlation between eNo levels and RV may reflect the effect of airway inflammation on NO production and diffusion as well as peripheral airway trapping and consequent RV.

Impairment of nasal mucociliary clearance after radiotherapy for childhood head cancer.

BACKGROUND: Radiotherapy of the head region in children is known to cause long-term sequelae, such as facial, dental, and ocular abnormalities. We investigated whether a decreased nasal mucociliary function occurs after radiotherapy of the head in children. METHODS: A saccharin/charcoal test was performed in 20 children treated with radiotherapy of the head and in 20 controls, age-matched and gender-matched. RESULTS: We found a decreased nasal mucociliary clearance (lower percentage of responses (p = 0083) and longer mucociliary transport times (p =.0001) in the patients compared with the controls. The radiotherapy dosage influenced the response to the test (p =.0046). CONCLUSIONS: Irradiation of the head in children may cause impairment of mucociliary function, even permanently, which may predispose children to upper respiratory infections. We would suggest careful monitoring of such patients to detect as early as possible the clinical effects of the functional changes and to prevent the evolution to chronic diseases.

Effect of Cromoglycate on Gas Changes, During Bronchial Challenge by UNCDW in Children with Asthma.

Eighteen asthmatic children were challenged with ultrasonically nebulized cold distilled water (UNCDW). Blood gas composition was monitored transcutaneously (tcpO(2) and tcpCO(2)) during and after the challenge. Assuming as basal the response to this UNCDW test, nine children (Group A) were then chosen at random to inhale cromoglycate by aerosol delivery for 8 days. Nine children (Group B), acting as a control, inhaled saline for 8 days. At the end of this therapy, each child repeated the UNCDW test. Statistical analysis with t-test for paired data was used to compare the results of each child to both tests. Mean basal tcpO(2) and tcpCO(2) were all within the expected normal range. In all children, both mean tcpO(2) and tcpCO(2) were reduced during and after UNCDW inhalation. Mean tcpCO(2) values during the challenge were significantly (p < 0.001) lower than the corresponding steady state 2 rain after the UNCDW challenge, with a mean drop of -7% (2.1 S.D.). Mean tcpO(2) values remained significantly decreased (p < 0.001) from the fifth mitt of the UNCDW challenge to the end of the observation period, with a mean drop of -20% (15.5 S.D.). After treatment with cromoglycate (Group A), the mean tcpCO(2) values during UNCDW did not change significantly from those ofsteady state conditions: -0.8% (0.5 S.D.); whereas mean tcpO(2) values decreased by -4% (4.9 S.D.). The control children treated with saline (Group B) showed mean tcpCO(2) and tcpO(2) values which were significantly different (p < 0.001) from those of the steady state conditions: mean drop of tcpCO(2), -6% (4.2 S.D.); mean drop of tcpO(2), -20% (4.7 S.D.). In conclusion, it emerges that: UNCDW induces nonspecific broncho-constriction in asthmatic children with a typical drop of tcpCO(2) and tcpO(2); the treatment with cromoglycate normalizes the time course of tcpCO(2) (hyper-reactivity) and reduces dramatically the drop of tcpO(2) time course (hyper-responsivity) during and after the UNCDW test.

Cold air challenge in children with asthma.

A study was designed to determine the sensitivity and specificity of a cold air bronchial provocation test. A total of 18 children with asthma (mean age 12 years) and 18 normal children (mean age 14 years) were studied. The cold air challenge consisted of a 4 min period of isocapnic hyperventilation of subfreezing air (mean temperature -15 degrees C). In-Induced response in forced expiratory volume in 1 sec (FEV1) expressed as a percentage of predicted normal values was obtained at 4, 6, and 8 min post-challenge. The average response to the cold air was a 27% decrease of FEV1 in asthmatics, which was significantly different from that of the normal children, who showed no statistically significant drop. In both the asthmatic and normal groups, the maximal drop in FEV1 had occurred by the time measurements 4 min post-challenge had been made. At that time, the smallest overlap was observed between normal and asthmatic children. This suggests that the fourth minute post-challenge can be chosen as a cut-off time to distinguish normal from asthmatic children. Considering a decrease of FEV1 greater than 10% as a positive test, the sensitivity of the cold air challenge was 95% and the specificity was 89%.