Luigi Mappa

Comparison of esophageal pH and multichannel intraluminal impedance testing in pediatric patients with suspected gastroesophageal reflux.

Background: Multichannel intraluminal impedance (MII) is a pH-independent method of assessing gastroesophageal reflux. Aim: To evaluate the diagnostic accuracy of MII-pH as compared with conventional pH monitoring in detecting reflux events (REs) and symptom association in different age groups. Methods: A prospective direct comparison of 2 diagnostic techniques on 291 consecutive patients referred for suspected gastroesophageal reflux disease. Sensitivity and diagnostic accuracy of MII-pH versus pH monitoring and symptom association were measured. Results: MII-pH detected 13631 REs, 6260 (46%) of which were nonacid. The prevalence of weakly acid refluxes in the 24 hours and postprandial period as well as the proximal extension of refluxate were significantly greater in infants as compared with children (P < 0.001, P < 0.001, and P < 0.01, respectively). The diagnostic accuracy of combined MII-pH in revealing all RE and acid RE were significantly higher in infants as compared with children (92% vs 82%, P < 0.01 and 83% vs 76%, P < 0.04, respectively). The addition of MII to conventional pH monitoring significantly increases the diagnostic yield of symptom association analysis in revealing an association between atypical symptoms and refluxes irrespective of age, whereas in studying typical symptoms it was true only for infants. Conclusions: Addition of MII to conventional pH monitoring significantly increases the diagnostic yield in detecting REs, prevalently in infants, and in revealing an association between refluxes and symptoms, prevalently respiratory ones and in infants group.

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 chemiluminescences 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 (MEF25‐‐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.

Phenotypic expression of genotype-phenotype correlation in cystic fibrosis patients carrying the 852del22 mutation.

Currently, more than 1,000 mutations have been identified in the cystic fibrosis transmembrane regulator (CFTR) gene. While some mutations are common worldwide, the majority are restricted in certain ethnic groups. We have found that in Southern Italy, the 852del22 mutation is well represented with a frequency of 3.5%. We have screened, by reverse dot blot, denaturing gradient gel electrophoresis (DGGE), and gene sequencing, the entire coding regions of CFTR gene in 371 consecutive cystic fibrosis (CF) patients from Southern Italy and have identified 17 patients carrying rare genotypes, among which 13 [6 M; median age 21.7 years (range: 4.5–47.7 years)] carry the 852del22 mutation. To assess the phenotypic expression of CF in patients with the 852del22 mutations we have compared these patients with a group of age and gender matched patients homozygous for the ΔF508 mutation [n = 34; 19 M; median age 19.9 years (range: 3.8–34.6 years)]. Overall, we found no difference in terms of complications, patient survival (17.6% vs. 30.7%; P = NS), estimated time needed to develop a severe lung disease (22.1 vs. 24.5 years; P = NS), nutritional status, and rate of infection or colonization by most common pathogens between patients in the two groups. Finally, we have found that a late diagnosis was associated with a poor outcome (severe lung disease) regardless of genotype. Our data show that 852del22 mutation results in a phenotypic expression of disease as severe as that determined by the more typical ΔF508 and, as in the latter case, there is no strict genotype/phenotype correlation.

ATYPICAL CYSTIC FIBROSIS ASSOCIATED WITH COMPLEX ALLELE: DIAGNOSTIC AND MANAGEMENT DILEMMAS

trans with a 5 thymidines (5T) sequence within the intron 8 Splice Variant (IVS8) region. 5T is responsible of an exacerbated skipping of exon 9, decreasing the functional product levels. It has been demonstrated that 5T phenotypic expression is influenced by another adjacent polymorphic region, constituted by 9 to 13 TG repeats. In particular, 5T/TG13 combination was found only in affected subjects. Case Report: We report a case regarding two sisters, aged 23 and 18 years, carriers of the F508del mutation associated with the 5T/TG13 combination. DHPLC investigation did not detect a second mutation. Both sisters present mild pulmonary symptoms started in puberty, bronchiectasis, pancreatic sufficiency and border-line chloride values at the sweat test. However, they differ because the elder patient has more evident bronchiectasis, and she also presents pansinusitis, a positive sputum culture and a slightly reduced FEV1. Conclusions: The natural history of non classic CF is poorly understood. It may be asymptomatic for years but a significant lung involvement may occur, as seen in the elder sister. This finding suggests that a prevention therapy could be necessary also in mild, non classic CF and an early diagnosis may prevent the organ deterioration, as in the younger sister. Early diagnosis may be supported by TG repeats testing in individuals carrying the 5T variant; in fact, our report confirms that the presence of 5T allele, in trans with a severe CFTR mutation, is associated with non classic CF and that TG13 variant acts as a real mild mutation, enhancing the 5T penetrance and determining the onset of a mild symptomatology in all patients.