Pulmonary interstitial glycogenosis - A systematic analysis of new cases.

BACKGROUND: Pulmonary interstitial glycogenosis (PIG) is a rare paediatric interstitial lung disease of unknown cause. The diagnosis can only be made by lung biopsy. Less than 100 cases have been reported. Clinical features, treatment and outcomes have rarely been assessed systematically in decent cohorts of patients. METHODS: In this retrospective multicentre study, the clinical presentation, radiologic findings, pattern of lung biopsy, extrapulmonary comorbidities, treatment and outcome of eleven children with PIG were collected systematically. RESULTS: 10/11 children presented with respiratory distress immediatly after birth and 8/11 needed invasive ventilation. In 8/11 children extrapulmonary comorbidities were present, congenital heart defects being the most common. 7/11 children received systemic glucocorticoids and of these four showed a clear favorable response. During a median follow-up of 3.0 years (range 0.42-12.0) one child died, while 10 patients improved. Chest CT-scans showed ground-glass opacities (7/10), consolidations (6/10), linear opacities (5/10) and mosaic attenuation (4/10) without uniform pattern. Besides interstitial thickening related to undifferentiated glycogen positive mesenchymal cells all tissue samples showed growth abnormalities with reduced alveolarization. CONCLUSIONS: PIG is associated with alveolar growth abnormalities and has to be considered in all newborns with unexplained respiratory distress. Apparent treatment benefit of glucocorticosteroids needs to be evaluated systematically.

Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany.

Objectives: Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Methods: Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Results: Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Münster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. Conclusions: This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.

Development of a quantitative immunofluorescence assay for detection of Stenotrophomonas maltophilia antibodies in patients with cystic fibrosis.

BACKGROUND: To describe a simple quantitative immunofluorescence assay (IFA) for the detection of specific Stenotrophomonas maltophilia antibodies in serum of CF patients. METHODS: A total of 100 sera (64 CF patients and 36 healthy subjects) were collected over a period of 2 years at the University Hospital Essen, Germany. Sputum culture status classified CF patients into groups. Serologic response was determined after Pseudomonas aeruginosa absorption by indirect IFA to Sm whole cell. RESULTS: CF patients with "chronic S. maltophilia" showed significantly higher S. maltophilia antibody levels compared with healthy individuals (P<0.0001) and CF patients with "intermittent" (P=0.0315) or "never S. maltophilia/P. aeruginosa" (P=0.0002). A discriminant cut-off value of >1:120 titre was established to differentiate "CF chronic S. maltophilia" from the other groups. For "CF chronic S. maltophilia", the IFA showed sensitivity and specificity values of 70.7% and 84.7%, respectively. CONCLUSION: Our data demonstrated that quantitative IFA is a simple serological assay for the detection of specific S. maltophilia antibodies, which could be useful as a diagnostic tool for monitoring immune response of CF patients to S. maltophilia.

Respiratory failure in Pompe disease: treatment with noninvasive ventilation.

In this study, noninvasive ventilation (NIV) was prospectively applied to eight patients (35.8 +/- 11.4 years) with late-onset Pompe disease and respiratory failure apparent from severe restrictive lung disease, nocturnal hypoxemia (83 +/- 8%), and daytime hypercapnia (66.7 +/- 17.9 mm Hg). The impact of NIV on respiratory function was followed for 34 +/- 17 months. Despite further decrease of vital capacity and inspiratory muscle strength, NIV normalized oxygen saturation during sleep (96 +/- 1%), daytime carbon dioxide tensions (44.1 +/- 3.6 mm Hg), and symptoms.