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During the period 1990-1999 84 PCD patients were identified and characterized. The expression of inherited abnormalities in primary ciliary dyskinesia after ciliogenesis was investigated in 41 patients with dynein deficiency, 6 patients with absence of the central pair of microtubules and 24 PCD patients with normal ultrastructure. In patients with dynein deficiency, the outer dynein arms counts were 1.9 +/- 1.0 in the biopsies and 1.6 +/- 0.7 after ciliogenesis. Secondary abnormalities were found in 15.8 +/- 20.4% of the transverse sections of cilia and only in 1.0 +/- 1.3% after ciliogenesis. Ciliary orientation was 28 +/- 11 degrees and 24 +/- 10 degrees respectively in biopsies and cultures. In patients with absence of the central pair this was found in 15 +/- 16% in biopsies and 21 +/- 19% after ciliogenesis. The values for the outer dynein arm were 8.4 +/- 0.3 and 8.7 +/- 0.2 and for the secondary abnormalities were 11.7 +/- 7.3% and 0.5 +/- 1.3% in the biopsies, respectively after ciliogenesis. In patients with normal ultrastructure the scores for the dynein arms were similar. Secondary abnormalities were found in 12.2 +/- 11.7% in the biopsies and 0.6 +/- 0.9% after ciliogenesis while ciliary orientation was respectively 21 +/- 7 degrees and 25 +/- 8 degrees. In conclusion, inherited abnormalities in primary ciliary dyskinesia are expressed after ciliogenesis, while secondary abnormalities are virtually absent, thereby facilitating the ultrastructural diagnosis.

Cystic fibrosis (CF) is an hereditary disease with pancreatic insufficiency and chronic respiratory tract infections leading to irreversible lung damage as its main features. The typical pathogen for the respiratory disease is Pseudomonas aeruginosa. Although the insight into the pathophysiology and genetics of CF have evolved over the past 10 years, there is not yet a full understanding of the increased susceptibility for respiratory infections, specifically with Pseudomonas aeruginosa. In this overview we elucidate the current knowledge and describe the existing hypothesis on the possible links between the pathophysiological defects and the failure of the local defense mechanism in CF airways.

We appreciate the comments made by De Boeck et al. To prove the relationship between gastroesophageal reflux disease and respiratory disease in intractable patients is challenging. Our study included a population of symptomatic patients with respiratory symptoms whose conditions did not respond to aggressive medical therapy and in whom a bronchoscopy was clinically indicated. We recognize that this limits the generalizability of the data; however, we feel that our population does represent the “typical” intractable patient who undergoes bronchoscopy at …

Few data are available on the bronchodilator response in preschool children. This study was set up to study baseline lung function and bronchodilator responses in healthy and asthmatic children younger than 7 yrs old. In 281 preschool children attending kindergarten (age range 2.7-6.6 yrs old) respiratory system resistance (Rrs) and reactance (Xrs) by impulse oscillation system at 5, 10, 15, 20, 25 and 35 Hz as well as resonance frequency (f0) were measured before and 20 min after 200 microg inhaled salbutamol by a metered-dose inhaler connected to a spacer device. Thirty-four of them were diagnosed as asthmatics based on a validated standardized questionnaire. The mean Rrs (+/-SD) at 5 Hz (Rrs,5) was 1.03 (+/-0.24) kPa x L(-1) x s for healthy children and 1.09 (+/-0.26) kPa x L(-1) x s for stable asthmatics. The mean change in Rrs,5 after salbutamol was -0.13 (+/-0.20) kPa x L(-1) x s for the healthy children and -0.09 (+/-0.25) kPa x L(-1) x s for the asthmatic group. The scatter for the measurements was striking. Neither baseline values of impulse oscillation nor its changes after bronchodilator administration was significantly different between healthy and stable asthmatic children. A change in respiratory system resistance at 5 Hz of 40% is to be considered the cut-off for a " positive" bronchodilator response.

Pulmonary function tests were obtained in 11 patients with primary ciliary dyskinesia. Their mean age was 15 years (range 6-32). Their pulmonary function was obstructive, with a vital capacity (mean+/-SD) of 75%+/-20% predicted, a forced expiratory volume in 1s (FEV1) of 63%+/-20% predicted and a raised residual volume of 169%+/-50% predicted. After inhalation of 200 microg of salbutamol the mean change in FEV1 was + 13.2%+/-9.6% of the baseline value. In the 10 oldest patients, lung function had been measured at regular intervals during 3 20 years. Interestingly, during childhood and adolescence the evolution was not unfavourable: vital capacity increased by 8%+/-20% and FEV1 remained stable (mean change 0.3%+/-12%). Only 2 patients had an unfavourable evolution.At time of diagnosis, patients with primary ciliary dyskinesia have partially reversible obstructive airway disease. During regular follow up and therapy, there is no evidence of a further decline in lung function. Patients with associated immunodeficiency or important damage at the start of therapy may have a worse prognosis.

In cystic fibrosis patients with Pseudomonas aeruginosa colonization and increasing pulmonary infection, ceftazidime 150 mg/kg/day was compared with 320 mg/kg/day. Changes in clinical findings, laboratory tests, pulmonary function and chest radiographs were evaluated after 14 days of treatment in hospital. Both treatments were associated with a significant improvement, but the higher dose did not offer an additional benefit. An increase in alanine aminotransferase (ALT) occurred after both treatments; with a significantly greater increase after the high-dose therapy (mean increase +/- S.E.M. 8% +/- 2% vs 2% +/- 1 %; P0.01). All but one of the ALT values after treatment were within normal limits.

We describe a child with DiGeorge syndrome due to a del22(q11) and a symbrachydactyly of the left hand. The underlying cardiovascular malformations in DiGeorge syndrome may lead to an increased susceptibility to vascular disruptions, giving further support to the subclavian-artery-disruption-sequence theory.

123 A shotgun metaproteomics approach to study the faecal microbiome of patients with cystic fibrosis reveals a reduction of butyrate-producing bacteria G. Debyser1, B. Mesuere2, L. Clement2, G. Duytschaever1, P. Van Hecke1, P. Dawyndt2, K. De Boeck3, P. Vandamme1, B. Devreese1. 1Ghent University, Department of Biochemistry and Microbiology, Ghent, Belgium; 2Ghent University, Department of Applied Mathematics and Computer Science, Ghent, Belgium; 3University Hospital of Leuven, Department of Pediatrics, Leuven, Belgium

Burkholderia cepacia has become an increasingly recognized pathogen among cystic fibrosis (CF) patients and its potential role in declining pulmonary function or unexpected fatal outcome has caused widespread concern. Direct person-to-person transmission has been documented and a segregation policy of CF patients colonized with B.cepacia from non-colonized CF patients is widely adopted. Since this policy has a dramatic impact on social behaviour of CF patients it is imperative that clinical laboratories accurately isolate and identify B.cepacia in the respiratory secretions. In order to comprehend the epidemiology of B.cepacia in the Belgian CF population a multicentre study was conducted during a period of 1 year (March'93-February'94). B.cepacia was isolated in only 12 of 465 CF patients (2.6%). Routine biochemical tests identified these strains as authentic B.cepacia. However, the combined data from protein and DNA-DNA hybridization analyses revealed that the Belgian CF "B.cepacia" isolates showed patterns different from reference B.cepacia isolates and belong to 3 different, newly identified Burkholderia genomovars, but not to B.cepacia. Comparative analysis of the selective media used for recovery of these "B.cepacia" strains from respiratory secretions indicated that the commercial medium (Mast) containing polymyxin B and ticarcillin as the selective agents was the best and most user-friendly. Molecular typing of these Burkholderia isolates by arbitrarily-primed PCR (AP-PCR) and pulsed-field gel electrophoresis (PFGE) showed that spread of a single strain within a same centre occurred but the mode of transmission remains unknown; inter-centre spread of strains was not observed. Interestingly, neither colonization with a distinct or an epidemic strain (belonging to either of the three newly identified Burkholderia genomovars) nor colonization for a prolonged period of time, led to a rapid deterioration of lung function in these CF patients. It appears essential to determine the prevalence of these "new" Burkholderia genomovars in larger populations of CF patients and to evaluate their virulence and other features as this may have important clinical and practical implications.

In patients with cystic fibrosis (CF) and chronic colonisation with Pseudomonas aeruginosa, specific anti-pseudomonal IgG and IgA, as well as serum immunoreactive protein C, WBC and differential count, ESR, pulmonary function and chest radiograph score were determined before and after a 2 week intravenous course of anti-pseudomonal antibiotics in 32 cases of acute exacerbation of pulmonary infection. Specific anti-pseudomonal IgA but not specific anti-pseudomonal IgG decreased significantly after treatment. Log of anti-pseudomonal IgA but not log anti-pseudomonal IgG correlated well with disease severity as assessed by the Brasfield chest radiograph score (r 0.57), forced expiratory volume in 1 s (r 0.6) as well as C-reactive protein (r 0.62).Specific anti-pseudomonal IgA may be a better parameter than specific IgG in the follow up of lung infection in patients with CF, probably because it more closely reflects ongoing endobronchial infection, the major pathology in CF lungs.

Worldwide almost no epidemiologic data are available on the prevalence or incidence of interstitial lung diseases (ILD) in the general population. Therefore, a registration programme of ILD-prevalence was organised by the VRGT (Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding), among about 100 Flemish pneumologists since 1990. Most categories of the classification by Crystal et al. (1) were included and the diagnostic criteria (histology, laboratory tests, clinic, radiology) were registered. The present paper presents the results of 1992-1994: twenty pneumologists had forwarded the summary files of 237 patients to the central office in 1992 (n = 68), 1993 (n = 90) and 1994 (n = 79). The diagnoses that were most frequently made were: sarcoidosis in 27%, idiopathic pulmonary fibrosis in 20%, hypersensitivity pneumonitis in 14% (of which 68% by birds) and collagen-vascular disease in 10% (of which 54% in rheumatoid arthritis). Less frequent causes were eosinophilic pneumonia (4%), inhalation of inorganic material (4%, anthracosilicosis being excluded), histiocytosis X (3%), drugs (3%), angiitis and granulomatosis (2%), pulmonary hemosiderosis (1%), lymphocytic infiltrative lung disease (1%) and lymphangioleiomyomatosis (1%). The order of relative frequencies of the different categories of diseases was the same in the 3 registration years. In 9% of the patients the diagnosis was confined to "undefined fibrosis". The diagnosis was confirmed by histology in 63% of the cases. The overall male-female ratio was nearly one, with, however, a male preponderance in hypersensitivity pneumonitis (22/12), UIP(8/3) and "undefined fibrosis" (14/7).(ABSTRACT TRUNCATED AT 250 WORDS)

WS7.1 LCI measured with nitrogen multiple breath washout is higher than mass spectrometer SF6 washout in children with cystic fibrosis A. Lindblad1, B. Houltz2, M. Rosberg3, L. Bergh2, P. Gustafsson4. 1Sahlgrenska University Hospital, Pediatrics, Gothenburg, Sweden; 2Sahlgrenska University Hospital, Clinical Physiology, East Hospital, Gothenburg, Sweden; 3Queen Silvia Childrens Hospital, Paediatric Clinical Physiology, Gothenburg, Sweden; 4Central Hospital, Pediatrics, Skovde, Sweden

WS7.1 LCI measured with nitrogen multiple breath washout is higher than mass spectrometer SF6 washout in children with cystic fibrosis A. Lindblad1, B. Houltz2, M. Rosberg3, L. Bergh2, P. Gustafsson4. 1Sahlgrenska University Hospital, Pediatrics, Gothenburg, Sweden; 2Sahlgrenska University Hospital, Clinical Physiology, East Hospital, Gothenburg, Sweden; 3Queen Silvia Childrens Hospital, Paediatric Clinical Physiology, Gothenburg, Sweden; 4Central Hospital, Pediatrics, Skovde, Sweden

Background Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder characterized by short-limbed skeletal dysplasia. Some patients also develop defects in cellmediated immunity and antibody production. Granulomatous inflammation has been described in patients with various forms of primary immunodeficiencies but, to date, has not been reported in patients with Cartilage-hair hypoplasia.

The pulmonary consequences during childhood of corrected congenital esophageal atresia and its treatment have not been extensively studied. In the literature, there are only a few reports with small numbers of patients [1–3]. We, therefore, made a study of a larger group of patients treated at our institution.

In a cystic fibrosis (CF) patient a right lower quadrant (RLQ) mass may be a difficult diagnostic problem. Most frequently it is due to a distal intestinal obstruction syndrome [8, 12] also called meconium ileus equivalent [11], but the possibility of intussusception and appendiceal abscess should also be considered. We describe three CF patients with an appendiceal abscess seen in a 4-year period. All three patients had a palpable RLQ mass. Chronicity and obliteration of the appendiceal lumen with abnormally viscid mucus may lead to concealed perforation and be responsible for the atypical presentation.

The efficacy of cefetamet pivoxil (20 mg/kg and 10 mg/kg b.i.d.) was investigated in an open, prospective, randomized, comparative multicenter trial involving 148 children suffering from group A beta-hemolytic streptococcal (GABHS) pharyngo-tonsillitis. Phenoxymethylpenicillin given for 10 days was used as the reference drug and resulted in 15% treatment failures. After treatment with cefetamet pivoxil 20 mg/kg b.i.d., 2 failures (5.8%) were observed in 34 patients treated for 7 days and 2 (6%) in 33 patients after 10 days treatment. In 8 children treated with cefetamet pivoxil 10 mg/kg b.i.d. for 10 days, 7 were cured and 1 relapsed in the late follow-up. Recruitment for this dosage group is being continued. No serious adverse events occurred. Cefetamet pivoxil, given b.i.d., can be considered an alternative to phenoxymethylpenicillin in the treatment of GABHS pharyngo-tonsillitis.

A survey is given of the pathophysiology of the main alterations in the small intestine of cystic fibrosis patients. Special attention is paid to the understanding of meconium ileus in the fetus and the newborn, the repercussion of duodenal acidity on the duodenal mucosa and the intraduodenal digestion, and primary and secondary biochemical alterations in the secretory-digestive-absorptive function of the small-intestinal mucosa. The meconium equivalent syndrome and its connection with the atypical course of intussusception and appendiceal perforation with silent pelvic abscess are also discussed.

The IV formulation of fludarabine phosphate is an effective treatment in patients with B-cell chronic lymphocytic leukemia (B-CLL), yielding overall response rates of 60% to 80%. An oral formulation of fludarabine phosphate has been developed. In a previously published multicenter, open-label, phase II clinical trial, 81 previously untreated B-CLL patients received 10-mg tablets of fludarabine phosphate (Fludara® oral) 40 mg/m2/day for 5 days, repeated every 4 weeks. The primary endpoint of the trial was response rate, and secondary endpoints included safety and quality of life assessments. Of 81 patients (mean age, 61.2 years; range, 30–75 years) with previously untreated B-CLL, 81.5% were classified as Binet stage B or C. The overall response rate (complete response [CR] + partial response [PR]) using National Cancer Institute (NCI) criteria was 80.2% (12.3% CR and 67.9% PR) and the median time to progression was 841 days (range, 28–1,146 days) (Rossi JF, et al. J Clin Oncol2004;22:1260–1267). The most frequently reported grade 3/4 adverse event was myelosuppression: WHO grade 3/4 hematologic toxicities included granulocytopenia (32.1%), anemia (9.9%), and thrombocytopenia (4.9%). This analysis reports on the long-term follow-up of this cohort during the period from November 2001 to November 2004. Of the 74 patients eligible for the survival analysis, 61 were also assessed for duration of response using NCI criteria: 9 CR (14.8%) and 52 PR (82.2%). During the 3-year follow-up period, 22 (29.7%) patients did not progress. For those who progressed, median time to progression was 29.7 months, and median duration of response was 22.9 months. In 41 (80.4%) of these patients, an increase in circulating lymphocytes was reported as evidence of disease progression. In 23 patients (45.1%), an increase in the sum of the products of at least 2 lymph nodes and/or appearance of new palpable nodes was reported as evidence of disease progression. During the indicated follow-up period, 37 patients (50%) received subsequent treatment. Twelve patients (16.2%) died during the follow-up period: 7 patients (58.3%) due to disease progression, 3 patients (25.0%) due to adverse events, and 2 patients (16.7%) due to other causes. Results from this study suggest that oral fludarabine phosphate is clinically effective and well tolerated by patients with previously untreated B-CLL. Moreover, these data demonstrate that oral fludarabine phosphate achieves response rates and duration of response comparable to those achieved with first-line fludarabine phosphate IV therapy.

Assessment of Patient-Ventilation Interaction: in Neonatal Intensive Care by Means of a “On Line” Flow Pressure Plot. 65