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Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, postlung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP. [ABSTRACT FROM AUTHOR]

Abstract Background Pseudomonas aeruginosa is the major respiratory pathogen causing severe lung infections among CF patients, leading to high morbidity and mortality. Once infection is established, early antibiotic treatment is able to postpone the transition to chronic lung infection. In order to optimize the early detection, we compared the sensitivity of microbiological culture and quantitative PCR (qPCR) for the detection of P. aeruginosa in respiratory samples of not chronically infected CF patients. Results In this national study, we followed CF patients during periods between 1 to 15 months. For a total of 852 samples, 729 (86%) remained P. aeruginosa negative by both culture and qPCR, whereas 89 samples (10%) were positive by both culture and qPCR. Twenty-six samples were negative by culture but positive by qPCR, and 10 samples were positive by culture but remained negative by qPCR. Five of the 26 patients with a culture negative, qPCR positive sample became later P. aeruginosa positive both by culture and qPCR. Conclusion Based on the results of this study, it can be concluded that qPCR may have a predictive value for impending P. aeruginosa infection for only a limited number of patients.

Abstract Background Pseudomonas aeruginosa is the major pathogen involved in the decline of lung function in cystic fibrosis (CF) patients. Early aggressive antibiotic therapy has been shown to be effective in preventing chronic colonization. Therefore, early detection is important and sensitive detection methods are warranted. In this study, we used a dilution series of P. aeruginosa positive sputa, diluted in a pool of P. aeruginosa negative sputa, all from CF patients - to mimick as closely as possible the sputa sent to routine laboratories - to compare the sensitivity of three culture techniques versus that of two conventional PCR formats and four real-time PCR formats, each targeting the P. aeruginosa oprL gene. In addition, we compared five DNA-extraction protocols. Results In our hands, all three culture methods and the bioMérieux easyMAG Nuclisens protocol Generic 2.0.1, preceded by proteinase K pretreatment and followed by any of the 3 real-time PCR formats with probes were most sensitive and able to detect P. aeruginosa up to 50 cfu/ml, i.e. the theoretical minimum of one cell per PCR mixture, when taking into account the volumes used in this study of sample for DNA-extraction, of DNA-elution and of DNA-extract in the PCR mixture. Conclusion In this study, no difference in sensitivity could be found for the detection of P. aeruginosa from sputum between microbiological culture and optimized DNA-extraction and real-time PCR. The results also indicate the importance of the optimization of the DNA-extraction protocol and the PCR format.

Objective: Antibiotics are prescribed too often in acutely ill children in primary care. We examined whether a Point-of-Care (POC) C-reactive Protein (CRP) test influences the family physicians’ (FP) prescribing rate and adherence to the Evidence Based Medicine (EBM) practice guidelines. Design: Cluster randomized controlled trial. Setting: Primary care, Flanders, Belgium. Intervention: Half of the children with non-severe acute infections (random allocation of practices to perform POC CRP or not) and all children at risk for serious infection were tested with POC CRP. Subjects: Acutely ill children consulting their FP. Main outcome measure: Immediate antibiotic prescribing. Results: 2844 infectious episodes recruited by 133 FPs between 15 February 2013 and 28 February 2014 were analyzed. A mixed logistic regression analysis was performed. Compared to episodes in which CRP was not tested, the mere performing of POC CRP reduced prescribing in case EBM practice guidelines advise to prescribe antibiotics (adjusted odds ratio (aOR) 0.54 (95% Confidence Interval (CI) 0.33-0.90). Normal CRP levels reduced antibiotic prescribing, regardless of whether the advice was to prescribe (aOR 0.24 (95%CI 0.11-0.50) or to withhold (aOR 0.31 (95%CI 0.17-0.57)). Elevated CRP levels did not increase antibiotic prescribing. Conclusion: Normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing. Key points: What is previously known or believed on this topic •Antibiotics are prescribed too often for non-severe conditions. Point-of-care (POC) C-reactive Protein (CRP) testing without guidance does not reduce immediate antibiotic prescribing in acutely ill children in primary care. What this research adds •FPs clearly consider CRP once available: normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. •Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing. [ABSTRACT FROM AUTHOR]

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a major complication in cystic fibrosis (CF) patients. Risk factors for ABPA and clinical deterioration in CF patients, negative for Pseudomonas aeruginosa (Pa), were explored. Methods: We performed a retrospective case‐control study in 73 Pa‐negative patients. Each patient was matched with 2 controls for age, gender, pancreas sufficiency, DeltaF508 mutation (homozygous or heterozygous), and Pa colonization. Results: Median FEV1 at the year of diagnosis (index year) was significantly lower in patients with ABPA. The median of cumulative values of FEV1 and FVC before the index year was not significantly different. After the index year, the median of cumulative data for FEV1 and FVC was significantly lower; there were significantly more hospitalization days and more IV antibiotic days compared to controls. Comparing pre‐ and post‐index year data in patients with ABPA, significantly more hospitalization days and more IV antibiotic days were observed after the index year. During the period preceding the index year, significantly more ABPA patients were treated with rhDNase and inhaled corticosteroids. Conclusions: Bronchial damage cannot be considered as a facilitating factor for ABPA. ABPA causes a significant increase in bronchial damage. In patients with ABPA, further bronchial damage can be controlled by an increase in hospitalization days and use of IV antibiotics. rhDNase and inhaled corticosteroids were associated with the development of ABPA. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 16-year-old boy with recurrent episodes of fever, without any respiratory problems but with concomitant abdominal and sometimes thoracic pain and arthralgia. It mentions that genetic evaluation was performed to identify the molecular cause of Primary ciliary dyskinesia (PCD) as well as Familial Mediterranean fever (FMF). It informs that the patient was treated with colchicine.

Background: Antibiotics are overprescribed for non-severe acute infections in children in primary care.Aim: To explore two different interventions that may reduce inappropriate antibiotic prescribing for non-severe acute infections.Design and Setting: A cluster randomised, factorial controlled trial in primary care, in Flanders, Belgium.Method: Family physicians (FPs) enrolled children with non-severe acute infections into this study. The participants were allocated to one of four intervention groups according to whether the FPs performed: (1) a point-of-care C-reactive protein test (POC CRP); (2) a brief intervention to elicit parental concern combined with safety net advice (BISNA); (3) both POC CRP and BISNA; or (4) usual care (UC). Guidance on the interpretation of CRP was not provided. The main outcome was the immediate antibiotic prescribing rate. A mixed logistic regression was performed to analyse the data.Results: In this study 2227 non-severe acute infections in children were registered by 131 FPs. In comparison with UC, POC CRP did not influence antibiotic prescribing, (adjusted odds ratio [AOR] 1.01, 95% confidence interval [CI] = 0.57 to 1.79). BISNA increased antibiotic prescribing (AOR 2.04, 95% CI = 1.19 to 3.50). In combination with POC CRP, this increase disappeared.Conclusion: Systematic POC CRP testing without guidance is not an effective strategy to reduce antibiotic prescribing for non-severe acute infections in children in primary care. Eliciting parental concern and providing a safety net without POC CRP testing conversely increased antibiotic prescribing. FPs possibly need more training in handling parental concern without inappropriately prescribing antibiotics. [ABSTRACT FROM AUTHOR]

Objectives: Antibiotic therapy is of vital importance for the control of infectious exacerbations in cystic fibrosis (CF) patients. However, very little is known regarding the fraction of systemically administered antibiotics reaching the lower respiratory tract secretions. We developed and validated a method to measure the concentrations of piperacillin, ceftazidime, meropenem and aztreonam in CF sputum, and present the validation data.Methods: Ultra-performance LC coupled to tandem MS was used. A single sample can be measured in 2.5 min with multiple reaction monitoring in positive electrospray ionization mode. Deuterated internal standards were used and a concentration range of 0.7-160 mg/L was covered. The method was validated according to the EMA guideline on analytical method validation.Results: The boundaries within which a reliable measurement in CF sputum can be performed were determined. A few constraints are linked to the instability of the antibiotics in sputum. Piperacillin showed limited stability at room temperature and during freeze-thaw cycles. Autosampler instability was observed after 15 h for aztreonam at low concentrations.Conclusions: The method allows a reliable measurement of the selected antibiotics, if precautions are taken regarding the limited stability of piperacillin at room temperature. Due to freeze-thaw instability, piperacillin should always be analysed on the day of sampling. Quick review of the analytical data and reanalysis are needed as low concentrations of aztreonam are not stable in the autosampler. [ABSTRACT FROM AUTHOR]

Background: Achromobacter xylosoxidans is increasingly being recognized as an emerging pathogen in cystic fibrosis. Recent severe infections with A. xylosoxidans in some of our cystic fibrosis (CF) patients led to a re-evaluation of the epidemiology of CF-associated A. xylosoxidans infections in two Belgian reference centres (Antwerp and Ghent). Several of these patients also stayed at the Rehabilitation Centre De Haan (RHC). In total, 59 A. xylosoxidans isolates from 31 patients (including 26 CF patients), collected between 2001 and 2014, were studied. We evaluated Matrix Assisted Laser Desorption Ionisation -Time of Flight mass spectrometry (MALDI-TOF) as an alternative for McRAPD typing. Results: Both typing approaches established the presence of a major cluster, comprising isolates, all from 21 CF patients, including from two patients sampled when staying at the RHC a decade ago. This major cluster was the same as the cluster established already a decade ago at the RHC. A minor cluster consisted of 13 isolates from miscellaneous origin. A further seven isolates, including one from a non-CF patient who had stayed recently at the RHC, were singletons. Conclusions: Typing results of both methods were similar, indicating transmission of a single clone of A. xylosoxidans among several CF patients from at least two reference centres. Isolates of the same clone were already observed at the RHC, a decade ago. It is difficult to establish to what extent the RHC is the source of transmission, because the epidemic strain was already present when the first epidemiological study in the RHC was carried out. This study also documents the applicability of MALDI-TOF for typing of strains within the species A. xylosoxidans and the need to use the dynamic cutoff algorithm of the BioNumerics® software for correct clustering of the fingerprints. [ABSTRACT FROM AUTHOR]

Background: Despite huge public campaigns, there is still overconsumption of antibiotics in children with self-limiting diseases. Possible explanations may be the physicians’ and parents’ uncertainty about the gravity of the disease and inadequate communication between physicians and parents leading to lack of reassurance for the parents. In this paper we describe the design and methods of a trial aiming to rationalize antibiotic prescribing by decreasing this uncertainty and parental anxiety. Methods/Design: Acutely ill children without suspected serious disease consulting their family physician will be consecutively included in a four-armed cluster randomized factorial controlled trial. The intervention will consist a Point-of-Care C-reactive protein test and/or a brief intervention with safety net advice. The control group will receive usual care. We intend to include 2560 patients in 88 family practices. Patients will be followed up until cure. The primary outcome measure is the immediate antibiotic prescribing rate. Secondary outcomes are: comparison between groups of speed of clinical recovery, parental concern, parental perception of the quality of the communication, parental satisfaction, use of medication, use of diagnostic tests and medical services during the illness episode, and cost-effectiveness of the interventions. Besides this, we will observationally analyse data of the children included in the large ERNIE2-trial, but excluded in the cluster randomized trial, namely children suspected of serious disease presenting in primary care and children who initially present at the out-patient paediatric clinic or emergency department. We will search for predictors of antibiotic prescribing, speed of clinical recovery, parental concern, parental perception of communication, parental satisfaction, use of medication, diagnostic tests and medical services. Discussion: This is a unique multifaceted intervention, in that it targets both physicians and parents by aiming specifically at their uncertainty and concerns during the consultation. Both interventions are easy to implement without special training. When proven effective, they could offer a feasible way to decrease inappropriate antibiotic prescribing for children in family practice and thus avoid emergence of bacterial resistance, side effects and unnecessary healthcare costs. Moreover, the observational part of the study will increase our insight in the course, management and parent’s concern of acute illness in children. [ABSTRACT FROM AUTHOR]

Background: Cystic Fibrosis (CF) patients are vulnerable to airway colonization with Pseudomonas aeruginosa. In case eradication fails after antibiotic treatment, patients become chronically colonized with P. aeruginosa, with recurrent pulmonary exacerbation, for which patients typically are hospitalized for 2 weeks and receive intravenous antibiotic treatment. Normally, improvement of the patients' health is established. Aim: Determination of the correspondence between patient improvement and changes of the P. aeruginosa and total bacterial load in the sputum. Methods: Eighteen CF patients with exacerbation were included for a total of 27 hospitalization episodes. At day 1, 8 and 15, inflammation and lung function parameters were determined, together with the P. aeruginosa load in the sputum using culture, quantitative PCR (qPCR) and propidium monoazide qPCR. Results: Patients improved during hospitalization (decrease in levels of C-reactive protein, white blood cell counts and erythrocyte sedimentation rate, increase of FEV1), reaching normal values already after one week. Also the P. aeruginosa load and the total bacterial load decreased during the first week of antibiotic treatment (p<0.05), except for patients with a low lung function (FEV1≤39.4%), for whom no significant decrease of P. aeruginosa was established. Comparison of culture-based and propidium monoazide qPCR-based quantification of P. aeruginosa showed that at the end of the treatment on average 62% of the P. aeruginosa cells are not cultivable, indicating that many cells are alive but dormant, or dead but still structurally intact. Conclusion: Improvement of the clinical status is accompanied with a decrease of the P. aeruginosa load, whereby both occur mainly during the first week of antibiotic treatment. However, for patients with a low lung function, no decrease of the P. aeruginosa load is observed. Comparison of detection techniques shows that a large amount of noncultivable or dead bacteria are present in the samples. [ABSTRACT FROM AUTHOR]

The article presents the case of a 20-year-old white female who was diagnosed with common variable immunodeficiency (CVID) while she was 13 years old. After examination, she was diagnosed of restrictive lung disease and hypogammaglobulinemia with poor antibody responses. She was found to be suffering from CVID linked with granulomatous disease (GD-CVID).

Background: Pseudomonas aeruginosa is the major respiratory pathogen causing severe lung infections among CF patients, leading to high morbidity and mortality. Once infection is established, early antibiotic treatment is able to postpone the transition to chronic lung infection. In order to optimize the early detection, we compared the sensitivity of microbiological culture and quantitative PCR (qPCR) for the detection of P. aeruginosa in respiratory samples of not chronically infected CF patients. Results: In this national study, we followed CF patients during periods between 1 to 15 months. For a total of 852 samples, 729 (86%) remained P. aeruginosa negative by both culture and qPCR, whereas 89 samples (10%) were positive by both culture and qPCR. Twenty-six samples were negative by culture but positive by qPCR, and 10 samples were positive by culture but remained negative by qPCR. Five of the 26 patients with a culture negative, qPCR positive sample became later P. aeruginosa positive both by culture and qPCR. Conclusion: Based on the results of this study, it can be concluded that qPCR may have a predictive value for impending P. aeruginosa infection for only a limited number of patients. [ABSTRACT FROM AUTHOR]