Gaudenz Hafen

False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms

Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package.

Microbiota Present in Cystic Fibrosis Lungs as Revealed by Whole Genome Sequencing

Determination of the precise composition and variation of microbiota in cystic fibrosis lungs is crucial since chronic inflammation due to microorganisms leads to lung damage and ultimately, death. However, this constitutes a major technical challenge. Culturing of microorganisms does not provide a complete representation of a microbiota, even when using culturomics (high-throughput culture). So far, only PCR-based metagenomics have been investigated. However, these methods are biased towards certain microbial groups, and suffer from uncertain quantification of the different microbial domains. We have explored whole genome sequencing (WGS) using the Illumina high-throughput technology applied directly to DNA extracted from sputa obtained from two cystic fibrosis patients. To detect all microorganism groups, we used four procedures for DNA extraction, each with a different lysis protocol. We avoided biases due to whole DNA amplification thanks to the high efficiency of current Illumina technology. Phylogenomic classification of the reads by three different methods produced similar results. Our results suggest that WGS provides, in a single analysis, a better qualitative and quantitative assessment of microbiota compositions than cultures and PCRs. WGS identified a high quantity of Haemophilus spp. (patient 1) or Staphylococcus spp. plus Streptococcus spp. (patient 2) together with low amounts of anaerobic (Veillonella, Prevotella, Fusobacterium) and aerobic bacteria (Gemella, Moraxella, Granulicatella). WGS suggested that fungal members represented very low proportions of the microbiota, which were detected by cultures and PCRs because of their selectivity. The future increase of reads’ sizes and decrease in cost should ensure the usefulness of WGS for the characterisation of microbiota.

Mycoplasma hominis necrotizing pleuropneumonia in a previously healthy adolescent

BackgroundMycoplasma hominis is a fastidious micro-organism causing systemic infections in the neonate and genital infections in the adult. It can also be the cause of serious extra-genital infections, mainly in immunosuppressed or predisposed subjects.Case PresentationWe describe a case of severe pneumonia and pericarditis due to Mycoplasma hominis in a previously healthy adolescent who did not respond to initial therapy.ConclusionsMycoplasma hominis could be an underestimated cause of severe pneumonia in immunocompetent patients and should be particularly suspected in those not responding to standard therapy.

Time invested in the global respiratory care of cystic fibrosis paediatrics patients.

Respiratory therapy is a keystone of the treatment for cystic fibrosis (CF) lung disease, but it is time consuming.

Lack of concordance in parapneumonic effusion management in children in central Europe

Treatment of parapneumonic effusion in children remains controversial in the literature and in clinical practice. The aim of this study was to determine whether mutual consensus exists in the diagnosis and treatment of parapneumonic effusion in Central European countries. A questionnaire was sent to all directors of pediatric respiratory units in four adjacent Central European countries (Austria, France, Germany, Switzerland). The response rate was 61.8%. Responses reflected acceptable agreement regarding initial diagnostic procedures, as most centers performed chest X‐ray and biological exams, followed by ultrasound, thoracocentesis, or computed tomography. However, antibiotic regimens were very heterogeneous, and the survey revealed complete lack of agreement on the indications and effusion volume threshold for invasive procedures, such as fibrinolytic instillation and thoracoscopy. In conclusion, apart from initial diagnostic procedures, this study showed a lack of mutual consensus among the four countries regarding the management of pediatric parapneumonic effusion. Multicenter prospective trials are clearly needed to acquire more evidence on the management of childhood parapneumonic effusion, enabling the development of evidence‐based algorithms that could help to avoid unnecessary examinations with potential long‐term side effects, such as radiation exposure at a young age. Pediatr Pulmonol. 2016;51:411–417.

Lower exhaled nitric oxide in infants with Cystic Fibrosis compared to healthy controls

Exhaled nitric oxide (FENO) is a well-known, non-invasive airway biomarker. In patients with Cystic Fibrosis (CF) FENO is decreased. To understand if reduced FENO is primary related to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction or an epiphenomenon of chronic inflammation, we measured FENO in 34 infants with CF prior to clinical symptoms and in 68 healthy controls. FENO was lower in CF compared to controls (p=0.0006) and the effect was more pronounced in CF infants without residual CFTR function (p<0.0001). This suggests that FENO is reduced in CF early in life, possibly associated with underlying CFTR dysfunction.

Death after cessation of treatment by cystic fibrosis patients: An international survey of clinicians

Background: Little is known about cystic fibrosis patients, who are not considered to be terminally ill, and who die after voluntary cessation of treatment. Aim: This study was undertaken to provide an international snapshot of this issue. Design: An online survey was distributed across three continents. Setting: Distribution to the medical directors of the cystic fibrosis centres affiliated with the US Cystic Fibrosis Foundation, Cystic Fibrosis Australia (inclusion of New Zealand) and to every clinician member of the European Cystic Fibrosis Society. Results: More than 200 cystic fibrosis patients not considered to be terminally ill and, who voluntarily ceased treatment, were reported by the clinicians surveyed. Detailed data were reported in 102 patients (4 children, 25 adolescents and 73 adults). Only one child, six adolescents and one adult were judged by clinicians not to be competent to make the decision to stop treatment. Time-consuming and low immediate-impact therapies, such as respiratory physiotherapy, were most frequently discontinued. Resignation was the main reported reason for discontinuing treatment, followed by reactive depression and lack of familial support. A total of 69% of the patients received palliative care and 72% died in the 6u2009months following cessation of treatment. Conclusion: Death of cystic fibrosis patients, not considered to be terminally ill, is reported in Europe, the United States and Australia due to voluntary cessation of treatment.

Idiopathic desquamative interstitial pneumonia in a child: a case report.

BackgroundDesquamative interstitial pneumonia is a rare form of interstitial lung disease in children. Respiratory symptoms appear progressively, are often subtle, and diagnosis is often delayed by a mean of 6 months after onset. High resolution chest computed tomography is the most sensitive imaging technique for demonstrating and identifying interstitial pneumonia. The typical histologic pattern of desquamative interstitial pneumonia, with prominent clustered alveolar macrophages, diffuse reactive alveolar epithelial hyperplasia and globular proteinaceous material, is diagnostic. Desquamative interstitial pneumonia in children can be idiopathic, though it is mostly related to an inborn error of surfactant metabolism.Case presentationWe present the complex clinical course and pathologic findings of a 30-months-old Mauritian and Senegalese girl with idiopathic desquamative interstitial pneumonia and multiple extrapulmonary manifestations. To our knowledge, this is the first case report of desquamative interstitial pneumonia to occur as part of a syndrome with multiple organ involvement.ConclusionWe believe that desquamative interstitial pneumonia is not always associated with mutations of the surfactant proteins, and can still be idiopathic, especially when occurring as part of a syndrome with multiple organ involvement, as described in other interstitial lung diseases.

The Swiss Primary Ciliary Dyskinesia registry: objectives, methods and first results

Primary Ciliary Dyskinesia (PCD) is a rare hereditary, multi-organ disease caused by defects in ciliary structure and function. It results in a wide range of clinical manifestations, most commonly in the upper and lower airways. Central data collection in national and international registries is essential to studying the epidemiology of rare diseases and filling in gaps in knowledge of diseases such as PCD. For this reason, the Swiss Primary Ciliary Dyskinesia Registry (CH-PCD) was founded in 2013 as a collaborative project between epidemiologists and adult and paediatric pulmonologists. The registry records patients of any age, suffering from PCD, who are treated and resident in Switzerland. It collects information from patients identified through physicians, diagnostic facilities, and patient organisations. The registry dataset contains data on diagnostic evaluations, lung function, microbiology and imaging, symptoms, treatments, and hospitalizations. By May 2018, CH-PCD has contacted 566 physicians of different specialties and identified 134 patients with PCD. At present this number represents an overall 1 in 63,000 prevalence of people diagnosed with PCD in Switzerland. Prevalence differs by age and region; it is highest in children and adults younger than 30 years, and in Espace Mittelland. The median age of patients in the registry is 25 years (range 5-73), and 49 patients have a definite PCD diagnosis based on recent international guidelines. Data from CH-PCD are contributed to international collaborative studies and the registry facilitates patient identification for nested studies. CH-PCD has proven to be a valuable research tool that already has highlighted weaknesses in PCD clinical practice in Switzerland. Development of centralised diagnostic and management centres and adherence to international guidelines are needed to improve diagnosis and management—particularly for adult PCD patients.

341 Implementation and evaluation of a therapeutic educational multidisciplinary program within the paediatric clinic for cystic fibrosis

Introduction: Cystic Fibrosis (CF) is a life shortening genetic disease. Life expectancy has increased as a result of more complex, demanding daily treatments. Including prolonged airway clearance sessions, inhalations, oral antibiotics, pancreatic enzymes and high caloric diet. There is a strong correlation between knowledge about the disease, reduction of anxiety and improved adherence to treatment. Goal: To assess an experiential learning program about CF treatment provided within a supportive framework to children with CF aged 6 to 12 years and their families. Method: Four 3-hour interactive workshops were provided for the children, related to infection, airway clearance, nutrition and emotional aspects of CF respectively. The sessions were run by the social worker and nurse in Arabic and Hebrew. In parallel, the psychologist led a parental support group accompanied by members of the multidisciplinary team according to the topic. At the end of the program a satisfaction survey was completed by all the participants. Results: Participants included: 9 children with CF (4 girls, 5 boys), average 8.5 years, 9 siblings/friends and 12 parents (7 mothers, 5 fathers). The average satisfaction score out of 4 was 3.8 for the children and 3.2 for the parents. The meetings enabled attainment of knowledge (less for parents), sharing and legitimization of feelings associated with the CF illness. Conclusion: Providing knowledge about CF within a supportive and interactive framework to children with CF and their families had high satisfaction levels for both parents and children. Parents have a greater need for emotional and social support than information about the illness.