Single-centre prospective evaluation of the first 5†years of cystic fibrosis newborn screening in Germany.

Background: In 2016, nationwide cystic fibrosis newborn screening (CFNS) was newly implemented in Germany, using an immunoreactive trypsin/pancreatitis-associated protein/DNA screening algorithm that differs from most other nationwide screening programmes. Methods: We analysed real-life feasibility of the confirmation process with respect to our pre-specified procedural objectives. These included overall accuracy through false-negative and false-positive results, effectiveness of the Bavarian tracking system, and accuracy of Macroduct and Nanoduct sweat conductivity compared with quantitative chloride determination. All consecutive CFNS-positive newborns assigned to our CF centre and born between 1 September 2016 and 31 August 2021 (n=162) were included. Results: The German CFNS was feasible at our CF centre as all procedural objectives were met. The positive predictive value (PPV) of positive CFNS was low (0.23) and two initially negatively screened children were later diagnosed with CF. The tracking system was highly efficient with a 100% tracking rate. The Macroduct and Nanoduct systems had comparable success rates (93.2% versus 95.9%). Importantly, conductivity via Macroduct was more accurate than via Nanoduct (zero and four false-positive newborns, respectively). Conclusions: CF confirmation diagnostics of neonates in a certified regional CF centre was well managed in daily routine. The PPV of the German CFNS needs to be improved, e.g. by extending the DNA analysis within the screening algorithm and by increasing the number of variants tested. The Bavarian tracking system can serve as a successful model for other tracking systems. We preferred the Macroduct system because of its more accurate sweat conductivity readings.

Eradication of methicillin resistant Staphylococcus aureus detected for the first time in cystic fibrosis: A single center observational study.

OBJECTIVE: To retrospectively identify CF patients with methicillin resistant Staphylococcus aureus (MRSA) and to assess the long-term success of an eradication scheme introduced in 2002 for all newly colonized patients. PATIENTS: All microbiological results from all 505 CF patients followed between 2002 and 2012 were analyzed focusing on the detection of MRSA. METHODS: Retrospective patient record analysis of MRSA positive CF patients regarding eradication and clinical outcome. RESULTS: We identified 57 patients with MRSA, mean age 15.3 years (range: 0.6-36.9, incidence 0.9%/year). Of these, nine patients were lost to follow-up; seven chronically colonized patients were excluded from the intervention. Eradication was suggested to all patients, 37/41 gave their consent to the following two-step approach: (i) dual iv antibiotic treatment over 3 weeks, accompanied by hygienic directives and topical therapy for 5 days followed by a 6-week period with dual oral antibiotic therapy and inhalation with vancomycin. (ii) Each new MRSA detection was treated with 6 weeks inhalation of vancomycin and topical therapy for 5 days. Long-term eradication was rated by the microbiological status in the third year after first detection. MRSA was eradicated in 31 of 37 patients (84%) whose clinical course was stable (mean FEV1 one year before MRSA 80.4%, 3 years after MRSA 81.0%). CONCLUSIONS: MRSA colonization mandates complex and expensive hygienic measures which are not well accepted by patients. Therefore, MRSA eradication is desirable. Intensive therapy regimens may be successful in patients with CF and might help to maintain a stable clinical course. Pediatr Pulmonol. 2016;51:1010-1019. © 2016 Wiley Periodicals, Inc.

Categorizing diffuse parenchymal lung disease in children.

BACKGROUND: Aim of this study was to verify a systematic and practical categorization system that allows dynamic classification of pediatric DPLD irrespective of completeness of patient data. METHODS: The study was based on 2322 children submitted to the kids-lung-register between 1997 and 2012. Of these children 791 were assigned to 12 DPLD categories, more than 2/3 belonged to categories manifesting primarily in infancy. The work-flow of the pediatric DPLD categorization system included (i) the generation of a final working diagnosis, decision on the presence or absence of (ii) DPLD and (iii) a systemic or lung only condition, and (iv) the allocation to a category and subcategory. The validity and inter-observer dependency of this workflow was re-tested using a systematic sample of 100 cases. RESULTS: Two blinded raters allocated more than 80% of the re-categorized cases identically. Non-identical allocation was due to lack of appreciation of all available details, insufficient knowledge of the classification rules by the raters, incomplete patient data, and shortcomings of the classification system itself. CONCLUSIONS: This study provides a suitable workflow and hand-on rules for the categorization of pediatric DPLD. Potential pitfalls were identified and a foundation was laid for the development of consensus-based, international categorization guidelines.

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.

Long-term pulmonary outcome after meconium ileus in cystic fibrosis.

OBJECTIVE: To identify cystic fibrosis (CF) patients with a history of meconium ileus (MI) and to compare long-term outcome of these patients with CF patients without MI. PATIENTS: 370 CF patients who were treated at the Munich CF centre in 2006, mean age 17.1 years (range: 0-48), were classified with regard to a history of MI. METHODS: Retrospective chart analysis regarding history of MI, age, and lung function and first detection of Pseudomonas aeruginosa as the primary outcome variables. RESULTS: We identified 60 patients with MI (16.2% of all patients with a mean age of 16.2 +/- 9 years (0-41) who did not differ in age from patients without MI (17.3 +/- 10; 0-48), whereas the mean age of CF diagnosis was different (0.4 vs. 21.8 months, P < 0.001). Cross sectional analysis of best Forced expiratory volume (FEV% predicted) in 2006 was not different between patients with MI (89 +/- 23%, 17-134) and those without (88 +/- 27%, 21-148, P = 0.73). Longitudinal analysis using FEV1 values of more than 9,000 lung function tests also showed no difference in FEV1 although first detection of P. aeruginosa in patients with MI was significantly earlier. CONCLUSION: MI was associated with hospitalization, surgery, and early infection with P. aeruginosa. However, the long-term outcome of CF patients with or without MI was the same. This finding might be explained by the considerably earlier CF diagnosis in CF patients with MI including the benefit of an early initiation of appropriate CF therapy.

European best practice guidelines for cystic fibrosis neonatal screening.

There is wide agreement on the benefits of NBS for CF in terms of lowered disease severity, decreased burden of care, and reduced costs. Risks are mainly associated with disclosure of carrier status and diagnostic uncertainty. When starting a NBS programme for CF it is important to take precautions in order to minimise avoidable risks and maximise benefits. In Europe more than 25 screening programmes have been developed, with quite marked variation in protocol design. However, given the wide geographic, ethnic, and economic variations, complete harmonisation of protocols is not appropriate. There is little evidence to support the use of IRT alone as a second tier, without involving DNA mutation analysis. However, if IRT/DNA testing does not lead to the desired specificity/sensitivity ratio in a population, a screening programme based on IRT/IRT may be used. Sweat chloride concentration remains the gold standard for discriminating between NBS false and true positives, but age-related changes in sweat chloride should be taken into account. CF phenotypes associated with less severe disease often have intermediate or normal sweat chloride concentrations. Programmes should include arrangements for counselling and management of infants where the diagnosis is not clear-cut. All newborns identified by NBS should be managed according to internationally accepted guidelines. CF centre care and the availability of necessary medication are essential prerequisites before the introduction of NBS programmes. Clear explanation to families of the process of screening and of implications of normal and abnormal results is central to the success of CF NBS programmes. Effective communication is especially important when parents are told that their child is affected or is a carrier. When establishing a NBS programme for CF, attention should be given to ensuring timely and appropriate processing of results, to minimise potential stress for families.