Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands.

Primary ciliary dyskinesia (PCD), cystic fibrosis (CF), and chronic obstructive airway disease are characterized by neutrophilic inflammation in the lungs. In CF and chronic obstructive airway disease, improper functioning of neutrophils has been demonstrated. We hypothesized that the pulmonary damage in PCD might be aggravated by abnormal functioning neutrophils either as a primary consequence of the PCD mutation or secondary to chronic inflammation. We analyzed chemotactic responses and chemoattractant receptor expression profiles of peripheral blood neutrophils from 36 patients with PCD, 21 healthy children and 19 healthy adults. We stimulated peripheral blood monocytes from patients and healthy controls and measured CXCL8 and IL-1ß production with ELISA. PCD neutrophils displayed reduced migration toward CXCR2 ligands (CXCL5 and CXCL8) in the shape change, microchamber and microslide chemotaxis assays, whereas leukotriene B4 and complement component 5a chemotactic responses were not significantly different. The reduced response to CXCL8 was observed in all subgroups of patients with PCD (displaying either normal ultrastructure, dynein abnormalities or central pair deficiencies) and correlated with lung function. CXCR2 was downregulated in about 65% of the PCD patients, suggestive for additional mechanisms causing CXCR2 impairment. After treatment with the TLR ligands lipopolysaccharide and peptidoglycan, PCD monocytes produced more CXCL8 and IL-1ß compared to controls. Moreover, PCD monocytes also responded stronger to IL-1ß stimulation in terms of CXCL8 production. In conclusion, we revealed a potential link between CXCR2 and its ligand CXCL8 and the pathogenesis of PCD.

Primary ciliary dyskinesia: critical evaluation of clinical symptoms and diagnosis in patients with normal and abnormal ultrastructure.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare disorder with variable disease progression. To date, mutations in more than 20 different genes have been found. At present, PCD subtypes are described according to the ultrastructural defect on transmission electron microscopy (TEM) of the motile cilia. PCD with normal ultrastructure (NU) is rarely reported because it requires additional testing. Biallelic mutations in DNAH11 have been described as one cause of PCD with NU.The aim of our study was to describe the clinical characteristics of a large population of patients with PCD, in relation to the ultrastructural defect. Additionally, we aimed to demonstrate the need for biopsy and cell culture to reliably diagnose PCD, especially the NU subtype. METHODS: We retrospectively analyzed data from 206 patients with PCD. We compared the clinical characteristics, lung function, microbiology and imaging results of 68 patients with PCD and NU to those of 90 patients with dynein deficiencies and 41 patients with central pair abnormalities. In addition, we aimed to demonstrate the robustness of the diagnosis of the NU subtype in cell culture by data from genetic analysis. RESULTS: PCD with NU comprised 33% (68/206) of all patients with PCD. Compared to other subtypes, patients with PCD and NU had a similar frequency of upper and lower respiratory tract problems, as well as similar lung function and imaging. With the currently widely applied approach, without cell culture, the diagnosis would have been missed in 16% (11/68) of patients with NU. Genetic analysis was performed in 29/68 patients with PCD and NU, and biallelic mutations were found in 79% (23/29) of tested patients. CONCLUSIONS: We reported on the clinical characteristics of a large population of patients with PCD and NU. We have shown that systematic performance of biopsy and cell culture increases sensitivity to detect PCD, especially the subtype with NU.PCD with NU has similar clinical characteristics as other PCD types and requires biopsy plus ciliogenesis in culture for optimal diagnostic yield.

Sonographic assessment of the retroperitoneal position of the third portion of the duodenum: an indicator of normal intestinal rotation.

BACKGROUND: The diagnosis of intestinal malrotation is based on an upper gastrointestinal contrast series (UGI), which is considered the imaging reference standard. It may however be challenging even for experienced paediatric radiologists. OBJECTIVE: The purpose of this study was to demonstrate the agreement between UGI and US in assessing the position of the third portion of the duodenum (D3) and to show that a retroperitoneal duodenum indicates normal forgut rotation. MATERIALS AND METHODS: In a prospective study, US assessment of the duodenum and the superior mesenteric vessels was performed in consecutive children who were referred for clinically indicated UGI at a single institution. RESULTS: Eighty-five children, 5 months to 14 years old, were studied. In 82/85 (96%), both US and UGI suggested normal forgut rotation. In three children, US demonstrated a normal position of the D3 whereas UGI showed an abnormal position of the duodeno-jejunal junction. CONCLUSION: US is a non-invasive, easily performed technique for excluding malrotation. UGI may be reserved for situations where US does not demonstrate a normal position of the D3.

Omalizumab for exacerbations of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

Anti-IgE therapy was proposed to two teenagers with cystic fibrosis (CF) with allergic bronchopulmonary aspergillosis (ABPA) exacerbation, reluctant to a further course of oral steroids. Both patients experienced ABPA exacerbations within the past 3 years, requiring oral steroid bursts. Clinical, laboratory and radiographic features were consistent with ABPA exacerbations (representing at the time of evaluation the fourth and third episodes for patient 1 and 2, respectively). Total serum IgE was very high, >1000 kU/litre in both cases. Treatment consisting of subcutaneous injections of 375 mg anti-IgE (omalizumab) twice monthly was successful in rapidly improving respiratory symptoms and lung function. Based on clinical and functional improvement, interval between injections was progressively increased and treatment could be withdrawn after 11 injections, without recurrence at 20 weeks of follow-up after withdrawal.

Towards zero prevalence of chronic Pseudomonas aeruginosa infection in children with cystic fibrosis.

BACKGROUND: Data from the Belgian Cystic Fibrosis Registry consistently show that in one of the seven reference centres, the prevalence of Pseudomonas aeruginosa is half that observed at the national level. OBJECTIVES: To report the characteristics of non-transplanted patients in this clinic at the end of 2003, with special focus on paediatric patients. To describe and discuss our policy of inhaled antibiotic therapy. FINDINGS: The prevalence of P. aeruginosa among 116 patients is 20.7%. The chronic colonization rate is 19.8% but only 2.8% in patients aged under 18 (n=72). Serologic data strongly support these results. Most paediatric patients (95%) are prescribed inhaled antibiotics, at least on an intermittent basis but the mean number of days of intravenous antibiotic treatment is four times lower than in other CF children in Belgium. 70% of children have an FEV1> or =90% predicted. DISCUSSION: We have reported a distinctly low rate of chronic colonization by P. aeruginosa in a cohort of CF children and suspect that a strategy of early, often <> use of inhaled antibiotics, progressively implemented for over 15 years has substantially contributed to these results. Given the major impact of chronic P. aeruginosa colonization on prognosis in CF, it is suggested that a large prospective study of this approach is warranted.

Does in utero exposure to heavy maternal smoking induce nicotine withdrawal symptoms in neonates?

Maternal drug use during pregnancy is associated with fetal passive addiction and neonatal withdrawal syndrome. Cigarette smoking-highly prevalent during pregnancy-is associated with addiction and withdrawal syndrome in adults. We conducted a prospective, two-group parallel study on 17 consecutive newborns of heavy-smoking mothers and 16 newborns of nonsmoking, unexposed mothers (controls). Neurologic examinations were repeated at days 1, 2, and 5. Finnegan withdrawal score was assessed every 3 h during their first 4 d. Newborns of smoking mothers had significant levels of cotinine in the cord blood (85.8 +/- 3.4 ng/mL), whereas none of the controls had detectable levels. Similar findings were observed with urinary cotinine concentrations in the newborns (483.1 +/- 2.5 microg/g creatinine versus 43.6 +/- 1.5 microg/g creatinine; p = 0.0001). Neurologic scores were significantly lower in newborns of smokers than in control infants at days 1 (22.3 +/- 2.3 versus 26.5 +/- 1.1; p = 0.0001), 2 (22.4 +/- 3.3 versus 26.3 +/- 1.6; p = 0.0002), and 5 (24.3 +/- 2.1 versus 26.5 +/- 1.5; p = 0.002). Neurologic scores improved significantly from day 1 to 5 in newborns of smokers (p = 0.05), reaching values closer to control infants. Withdrawal scores were higher in newborns of smokers than in control infants at days 1 (4.5 +/- 1.1 versus 3.2 +/- 1.4; p = 0.05), 2 (4.7 +/- 1.7 versus 3.1 +/- 1.1; p = 0.002), and 4 (4.7 +/- 2.1 versus 2.9 +/- 1.4; p = 0.007). Significant correlations were observed between markers of nicotine exposure and neurologic-and withdrawal scores. We conclude that withdrawal symptoms occur in newborns exposed to heavy maternal smoking during pregnancy.

Postcricoid hemangioma: an overlooked cause of dysphagia in infants?-a case report.

Feeding and swallowing disorders in children remain a major challenge owing to a wide differential diagnosis. Hemangioma of the upper aerodigestive tract represents one of the numerous non-neoplastic causes of dysphagia. We report two cases of postcricoid hemangioma causing inhalation and recurrent respiratory infections, treated successfully with systemic corticotherapy alone. To our knowledge, these are the second and third cases described in the literature. After a short review of the literature, the diagnostic procedures are discussed and a management strategy is proposed for this clinical entity, by far underestimated.