Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients.

Patients with interstitial lung disease due to surfactant protein C (SFTPC) mutations are rare and not well characterised. We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations. 17 patients (seven male) were followed over a median of 3 years (range 0.3-19). All patients were heterozygous carriers of autosomal dominant SFTPC mutations. Three mutations (p.L101P, p.E191 K and p.E191*) have not been described before in the context of surfactant protein C deficiency. Patients with alterations in the BRICHOS domain of the protein (amino acids 94-197) presented earlier. At follow-up, one patient was healthy (2 years), six patients were "sick-better" (2.8 years, range 0.8-19), seven patients were "sick-same" (6.5 years, 1.3-15.8) and three patients were "sick-worse" (0.3 years, 0.3-16.9). Radiological findings changed from ground-glass to increasing signs of fibrosis and cyst formation with increasing age. Empiric treatments had variable effects, also in patients with the same genotype. Prospective studies with randomised interventions are urgently needed and can best be performed in the framework of international registers.

Predictive values of antibodies against Pseudomonas aeruginosa in patients with cystic fibrosis one year after early eradication treatment.

BACKGROUND: Patient dependent parameters to predict the long-term success of early eradication treatment of Pseudomonas aeruginosa have not yet been defined. For this purpose we assessed serum antibodies against P. aeruginosa in CF patients after early eradication treatment. METHODS: Retrospective analyses of all consecutive patients with first P. aeruginosa detection 2005 to 2008. Absence of P. aeruginosa in the third year was defined as successful long-term eradication. Main outcome was to determine the predictive value of P. aeruginosa antibody results one year after initiation of early eradication treatment using antibodies against alkaline protease, elastase, and exotoxin A with regard to long-term success of eradication treatment. RESULTS: Antibodies against P. aeruginosa correlated well with success of eradication; positive and negative predictive values after one year were 75% and 82% respectively. The incidence of new detection of P. aeruginosa was 8.5%. Long-term eradication was successful in 32 of 53 patients (60%). CONCLUSIONS: Determination of serum antibodies against P. aeruginosa one year after first detection of P. aeruginosa and early eradication treatment can predict success of long-term eradication.

The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients - clinical analysis of Trichosporon positive patients in a Munich cohort.

BACKGROUND: The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated. METHODS: The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated. RESULTS: In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition. CONCLUSIONS: This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients.