- Record: found
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Practical guidelines: lung transplantation in patients with cystic fibrosis.
Author(s):
T O Hirche
1 ,
C Knoop
2 ,
H Hebestreit
3 ,
D Shimmin
4 ,
A Solé
5 ,
J S Elborn
6 ,
H Ellemunter
7 ,
P Aurora
8 ,
M Hogardt
9 ,
T O F Wagner
10
Publication date (Electronic):
2014
Journal:
Pulmonary medicine
Publisher:
Hindawi Limited
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Abstract
There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.
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Most cited references250
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Normothermic ex vivo lung perfusion in clinical lung transplantation.
Marcelo Cypel, Jonathan C Yeung, Mingyao Liu … (2011)
More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital. During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).
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International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation.
Allan R Glanville, Paul Corris, Scott Palmer … (2006)
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Clinical Care Guidelines for Cystic Fibrosis–Related Diabetes
Antoinette Moran, Carol Brunzell, Richard C. Cohen … (2010)
Cystic fibrosis–related diabetes (CFRD) is the most common comorbidity in people with cystic fibrosis (CF), occurring in ∼20% of adolescents and 40–50% of adults (1). While it shares features of type 1 and type 2 diabetes, CFRD is a distinct clinical entity. It is primarily caused by insulin insufficiency, although fluctuating levels of insulin resistance related to acute and chronic illness also play a role. The additional diagnosis of CFRD has a negative impact on pulmonary function and survival in CF, and this risk disproportionately affects women (2 –4). In contrast to patients with other types of diabetes, there are no documented cases of death from atherosclerotic vascular disease in patients with CFRD, despite the fact that some now live into their sixth and seventh decades. These guidelines are the result of a joint effort between the Cystic Fibrosis Foundation (CFF), the American Diabetes Association (ADA), and the Pediatric Endocrine Society (PES). They are intended for use by CF patients, their care partners, and health care professionals and include recommendations for screening, diagnosis, and medical management of CFRD. This report focuses on aspects of care unique to CFRD. A comprehensive summary of recommendations for all people with diabetes can be found in the ADA Standards of Medical Care, published annually in the January supplement to Diabetes Care (5). METHODS In 2009, CFF in collaboration with ADA and PES convened a committee of CF and diabetes experts to update clinical care guidelines for CFRD. Investigators at Johns Hopkins University conducted evidence reviews on relevant clinical questions identified by the guidelines committee. The reviews were provided to the committee to use in developing recommendations. Where possible, the evidence for each recommendation was considered and graded by the committee using the ADA (5) and the U.S. Preventive Services Task Force (USPSTF) (6) grading systems (Table 1). Recommendations from existing published guidelines were used when available and appropriate, and these are indicated as consensus statements. The committee also made consensus recommendations for topics not included in the evidence reviews or for which limited evidence was available in the literature. Recommendations will be updated as warranted by new evidence, and the guidelines will be reviewed 3 years after release date to determine if an update is needed. A summary of the committee's recommendations is presented in Table 2. Table 1 Evidence-grading system for clinical practice recommendations ADA classification system Level of evidence Description A Clear evidence from well-conducted, generalizable, randomized, controlled trials that are adequately powered, including Evidence from a well-conducted multicenter trial Evidence from a meta-analysis that incorporated quality ratings in the analysis Compelling nonexperimental evidence, i.e., “all-or-none” rule developed by the Centre for Evidence-Based Medicine at Oxford Supportive evidence from well-conducted, randomized, controlled trials that are adequately powered, including Evidence from a well-conducted trial at one or more institutions Evidence from a meta-analysis that incorporated quality ratings in the analysis B Supportive evidence from well-conducted cohort studies, including Evidence from a well-conducted prospective cohort study or registry Evidence from a well-conducted meta-analysis of cohort studies Supportive evidence from a well-conducted case-control study C Supportive evidence from poorly controlled or uncontrolled studies, including Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls) Conflicting evidence with the weight of evidence supporting the recommendation E Expert consensus or clinical experience USPSTF recommendation classification system Estimate of effect Quality of evidence Substantial Moderate Small Zero/negative* High A B C D Moderate B B C D Low Insufficient (I) *A study with significant findings against something is given a grade of D. Table 2 Summary of recommendations for the clinical care of CFRD Screening recommendations The use of A1C as a screening test for CFRD is not recommended. (ADA-B; USPSTF-D) Screening for CFRD should be performed using a 2-h 75-g OGTT. (ADA-E; Consensus) Annual screening for CFRD should begin by age 10 years in all CF patient s who do not have CFRD. (ADA B; USPSTF-B) CF patients with acute pulmonary exacerbation requiring intravenous antibiotics and/or systemic glucocorticoids should be screened for CFRD by monitoring fasting and 2-h postprandial plasma glucose levels for the first 48 h. If elevated blood glucose levels are found by SMBG, the results must be confirmed by a certified laboratory. (ADA-E; Consensus) Screening for CFRD by measuring mid- and immediate postfeeding plasma glucose levels is recommended for CF patients on continuous enteral feedings, at the time of gastrostomy feeding initiation and then monthly by SMBG. Elevated glucose levels detected by SMBG must be confirmed by a certified laboratory. (ADA-E; Consensus) Women with CF who are planning a pregnancy or confirmed pregnant should be screened for preexisting CFRD with a 2-h 75-g fasting OGTT if they have not had a normal CFRD screen in the last 6 months. (ADA-E; Consensus) Screening for gestational diabetes mellitus is recommended at both 12–16 weeks' and 24–28 weeks' gestation in pregnant women with CF not known to have CFRD, using a 2-h 75-g OGTT with blood glucose measures at 0, 1, and 2 h. (ADA-E; Consensus) Screening for CFRD using a 2-h 75-g fasting OGTT is recommended 6–12 weeks after the end of the pregnancy in women with gestational diabetes mellitus (diabetes first diagnosed during pregnancy). (ADA-E; Consensus) CF patients not known to have diabetes who are undergoing any transplantation procedure should be screened preoperatively by OGTT if they have not had CFRD screening in the last 6 months. Plasma glucose levels should be monitored closely in the perioperative critical care period and until hospital discharge. Screening guidelines for patients who do not meet diagnostic criteria for CFRD at the time of hospital discharge are the same as for other CF patients. (ADA-E; Consensus) Diagnosis recommendations During a period of stable baseline health the diagnosis of CFRD can be made in CF patients according to standard ADA criteria. Testing should be done on 2 separate days to rule out laboratory error unless there are unequivocal symptoms of hyperglycemia (polyuria and polydipsia); a positive FPG or A1C can be used as a confirmatory test, but if it is normal the OGTT should be performed or repeated. If the diagnosis of diabetes is not confirmed, the patient resumes routine annual testing. (ADA-E; Consensus) 2-h OGTT plasma glucose ≥200 mg/dl (11.1 mmol/l) FPG ≥126 mg/dl (7.0 mmol/l) A1C ≥ 6.5% (A1C 90th percentile for age and sex for pediatric patients should have repeat measurement on a separate day to confirm a diagnosis of hypertension. (ADA-E; Consensus) Annual monitoring for microvascular complications of diabetes is recommended using ADA guidelines, beginning 5 years after the diagnosis of CFRD or, if the exact time of diagnosis is not known, at the time that FH is first diagnosed. (ADA-E; Consensus) Patients with CFRD diagnosed with hypertension or microvascular complications should receive treatment as recommended by ADA for all people with diabetes, except that there is no restriction of sodium and, in general, no protein restriction. (ADA-E; Consensus) An annual lipid profile is recommended for patients with CFRD and pancreatic exocrine sufficiency or if any of the following risk factors are present: obesity, family history of coronary artery disease, or immunosuppressive therapy following transplantation. (ADA-E; Consensus) SCREENING CFRD is often clinically silent. In other populations, the primary consequences of unrecognized diabetes are macrovascular and microvascular disease. In CF, the nutritional and pulmonary consequences of diabetes are of greater concern. CFRD is associated with weight loss, protein catabolism, lung function decline, and increased mortality (2,3,7 –17), and thus regular screening is warranted. Screening tests for CFRD Although hemoglobin A1C (A1C) may become the standard screening test for type 2 diabetes (5), the committee concluded that it is not sufficiently sensitive for diagnosis of CFRD and thus should not be used as a screening test. Eight studies were identified that assessed A1C as a screening test in this population (7,18 –24). The authors of one prospective cohort study of 62 participants with CF and 107 healthy control subjects reported that A1C levels were higher in the CF group than among the control subjects, leading them to suggest that the use of A1C was appropriate (18). However, six studies (including two prospective cohort studies [7,21], two cross-sectional studies [19,20], one case-control study [23], and one case series [22[) with a total of 477 participants demonstrated low degrees of correlation between A1C and glucose tolerance status (7,19 –23). Additionally, a cross-sectional study of 191 participants with CF demonstrated a low positive predictive value of the A1C test (24). Use of A1C as a screening test for CFRD is not recommended. (ADA-B; USPSTF-D) Fructosamine, urine glucose, and random glucose levels have low sensitivity in the CF population (20,23,25). Continuous glucose monitoring is not recommended as a screening tool because intermittent hyperglycemia detected in this fashion is not diagnostic for diabetes and there are no outcome data to determine its clinical significance. Fasting plasma glucose (FPG) identifies patients with CFRD with but not those without fasting hyperglycemia (FH), and thus this test will miss the diagnosis of diabetes in approximately half of CF patients (1). Self-monitoring of blood glucose (SMBG) with home meters is also not sufficiently accurate to screen for CFRD given that the International Organization for Standardization only requires that 95% of readings be within 20% of the actual glucose level (26). Because of the poor performance of A1C and other tests, the oral glucose tolerance test (OGTT) is the screening test of choice for CFRD. Although it is an imperfect test due to the inherent variability of the test and the variability observed in individual CF patients over time, longitudinal studies demonstrate that a diabetes diagnosis by OGTT correlates with clinically important CF outcomes including the rate of lung function decline over the next 4 years (12), the risk of microvascular complications (27), and the risk of early death (1,2). In a multicenter, multinational study, the OGTT identified patients who benefited from insulin therapy (28). The OGTT should be performed in the morning during a period of stable baseline health (at least 6 weeks since an acute exacerbation) using the World Health Organization protocol (5). Patients fast for at least 8 h (water is permitted) and should consume a minimum of 150 g (600 kcal) of carbohydrate per day for the preceding 3 days (generally not an issue because CF patients have high-calorie diets). The patient drinks a standard beverage containing 1.75 g/kg glucose (maximum 75 g) dissolved in water and sits or lies quietly for 2 h. Glucose levels are measured at baseline and 2 h. Unless the patient is experiencing classical symptoms of polyuria and polydipsia in the presence of a glucose level >200 mg/dl (11.1 mmol/l) or has two more diagnostic criteria for diabetes (such as both fasting and 2-h glucose elevation or a diabetes pattern on OGTT in the presence of an A1C level >6.5%), the test should be confirmed by repeat testing. Screening for CFRD should be performed using the 2-h 75-g OGTT. (ADA-E; Consensus) The age of screening for CFRD Three studies with a total of 811 participants were identified that provided information about the appropriate age at which to start screening for CFRD (1,21,24). These studies—a retrospective cohort study (1), a prospective cohort study (21), and a cross-sectional study (24)—reported a significantly higher prevalence and incidence of CFRD beyond the first decade of life. Screening included both pancreatic sufficient and insufficient patients. The committee concluded that these findings suggest that annual screening for CFRD should start by age 10 years in all CF patients. Because clinical deterioration in nutritional and pulmonary status begins 6–24 months prior to a diagnosis of CFRD (29,30), early detection by annual screening is warranted. Annual screening for CFRD should begin by age 10 years in all CF patients who do not have CFRD. (ADA-B; USPSTF-B) Screening of CF patients during acute illness CF patients experience frequent pulmonary exacerbations, some of which require treatment either in the hospital or at home with intravenous antibiotics. Treatment at times includes systemic glucocorticoids. In clinical experience, hyperglycemia that develops during acute illness occasionally resolves after a day or two of medical therapy, but usually lasts for at least 2–6 weeks. CF patients are frequently ill, and hyperglycemia returns with each subsequent bout of illness, often several times a year. Insulin deficiency and insulin resistance generally progress over time. Long-term microvascular (27) and pulmonary (1,2) outcomes correlate with duration of CFRD first diagnosed during acute illness, even with intervening periods of normal or impaired glucose tolerance (IGT). During acute illness and/or a pulse of systemic glucocorticoid therapy, glucose levels should be monitored for at least the first 48 h, preferably fasting and 2 h postprandially. If glucose levels do not meet diagnostic criteria for CFRD, testing can be discontinued after 48 h. For patients receiving therapy at home, SMBG can be performed. However, SMBG levels are not sufficiently accurate to make a diagnosis of CFRD, and hyperglycemia should be confirmed by laboratory plasma glucose measurement. CF patients with acute pulmonary exacerbation requiring intravenous antibiotics and/or systemic glucocorticoids should be screened for CFRD by monitoring fasting and 2-h postprandial plasma glucose levels for the first 48 h. If elevated blood glucose levels are found by SMBG, the results must be confirmed by a certified laboratory. (ADA-E; Consensus) Screening of CF patients during continuous drip enteral feedings Supplemental continuous drip feedings are commonly prescribed for malnourished CF patients. Although there are few data available specific to this situation, mid-feeding hyperglycemia may compromise efforts to gain weight. The Committee felt that glucose levels in the middle and immediately after the gastrostomy tube feeding should be measured in the hospital and at these same time points once a month at home using SMBG. SMBG levels are not sufficiently accurate to make a diagnosis of CFRD, and hyperglycemia detected by SMBG should be confirmed by laboratory plasma glucose measurement. Screening for CFRD by measuring mid- and immediate postfeeding plasma glucose levels is recommended for CF patients on continuous enteral feedings, at the time of gastrostomy tube feeding initiation and then monthly at home. Elevated glucose levels detected by SMBG must be confirmed by a certified laboratory. (ADA-E; Consensus) Screening CF patients who are pregnant or planning a pregnancy Pregnancy is a state of marked insulin resistance, and many women with CF cannot produce the extra insulin required to meet this demand (31 –33). In addition to the usual concerns about the effect of hyperglycemia on the fetus, diabetes can exacerbate the difficulties many women with CF have in achieving a positive protein balance and sufficient weight gain during pregnancy (32). Women with CF not known to have CFRD who are contemplating pregnancy should be evaluated prior to conception to rule out preexisting CFRD or be tested immediately upon confirmation of the pregnancy if they have not had an OGTT in the previous 6 months. Because women with CF are at high risk for development of hyperglycemia during pregnancy (gestational diabetes mellitus), the 2-h 75-g OGTT should be performed at the end of both the first and second trimesters. Women with CF who are planning a pregnancy or confirmed pregnant should be screened for preexisting CFRD with a 2-h 75-g fasting OGTT if they have not had a normal CFRD screen in the last 6 months. (ADA-E; Consensus) Screening for gestational diabetes mellitus is recommended at both 12–16 weeks' and 24–28 weeks' gestation in pregnant women with CF not known to have CFRD, using a 2-h 75-g OGTT with blood glucose measures at 0, 1, and 2 h. (ADA-E; Consensus) Screening for CFRD using a 2-h 75-g fasting OGTT is recommended 6–12 weeks after the end of the pregnancy in women with gestational diabetes mellitus (diabetes first diagnosed during pregnancy). (ADA-E; Consensus) Screening CF patients undergoing transplantation There is an almost universal requirement for insulin in the immediate critical care postoperative period in CF patients undergoing transplantation procedures, and many have long-term insulin requirements after transplantation (34 –36). A diagnosis of CFRD prior to transplantation may increase complications of surgery and has a negative impact on survival, at least in the early postoperative period when infection, bleeding, and multiorgan failure are the most common causes of death (34,37). Aggressive management may have a positive impact on outcomes (35). CF patients not known to have diabetes who are undergoing any transplantation procedure should be screened preoperatively by OGTT if they have not had CFRD screening in the last 6 months. Plasma glucose levels should be monitored closely in the perioperative critical care period and until hospital discharge. Screening guidelines for patients who do not meet diagnostic criteria for CFRD at the time of hospital discharge are the same as for other CF patients. (ADA-E; Consensus) DIAGNOSIS (Fig. 1) Figure 1 Criteria for the diagnosis of CFRD under different conditions. The spectrum of glucose tolerance abnormalities in CF Diabetes is part of a continuum of glucose tolerance abnormalities defined by ADA (supplementary Table 1, available at http://care.diabetesjournals.org/cgi/content/full/dc10-1768/DC1). Few CF patients have truly “normal” glucose tolerance. Many patients with normal fasting and 2-h glucose levels have elevation in the middle of the OGTT (indeterminate glycemia [INDET]) or when assessed randomly or by continuous glucose monitoring. Impaired fasting glucose (IFG) (100–125 mg/dl [5.6–6.9 mmol/l[) may also be present (20,38). The clinical significance of IFG or INDET in CF is not known. In the general population, they are considered pre-diabetic conditions, associated with a high risk of future development of diabetes (39). In prepubertal children with CF both IGT and INDET are associated with early-onset CFRD (40). Criteria for the diagnosis of CFRD in stable outpatients ADA has established diagnostic criteria for diabetes that include specific fasting glucose levels, 2-h OGTT glucose levels (5), and A1C levels. They are based on the population risk of microvascular disease, and patients with CF are also at risk for these complications (27,41 –43). The committee questioned whether the diagnostic thresholds should be lower for the CF population as CFRD is known to have a negative impact on CF pulmonary status (2,10,11), given that pulmonary disease is the chief morbidity in CFRD. Even less severe glucose tolerance abnormalities such as IGT are associated with lung function decline (12,17). However, sufficient outcome-based data are not available at present to determine whether more stringent diagnostic glucose thresholds more appropriately reflect risk for the CF population. During a period of stable baseline health, the diagnosis of CFRD can be made in CF patients according to standard ADA criteria. Testing should be done on two separate days to rule out laboratory error unless there are unequivocal symptoms of hyperglycemia (polyuria and polydipsia); a positive FPG or A1C can be used as a confirmatory test, but if it is normal the OGTT should be performed or repeated. If the diagnosis of diabetes is not confirmed, the patient resumes routine annual testing. (ADA-E; Consensus) 2-h OGTT plasma glucose ≥200 mg/dl (11.1 mmol/l) FPG ≥126 mg/dl (7.0 mmol/l) A1C ≥6.5% (A1C 10-year duration CFRD, those with retinopathy and/or microalbuminuria had average A1C levels of 8.0% compared with 5.8% in CFRD patients with no eye or kidney changes, and 83% of those with microvascular complications had A1C levels ≥7.0% (27), consistent with data in the general diabetes population. For a given patient, the rise and fall in A1C may be a useful indicator of trends in glycemic control. Thus, regular monitoring of A1C is advised. A1C measurement is recommended quarterly for patients with CFRD. (ADA-E; Consensus) For most patients with CFRD, the A1C treatment goal is ≤7% to reduce the risk of microvascular complications, bearing in mind that higher or lower goals may be indicated for some patients and that individualization is important. (ADA-B; USPSTF-B) Diet and exercise in CFRD CF patients have nutrition requirements which are well established (62 –64). Because adequate caloric intake to maintain BMI is critical to their health and survival, the additional diagnosis of CFRD does not alter usual CF dietary recommendations (Table 3). The goal is to achieve and maintain good nutritional status and normalize blood glucose levels. Table 3 Dietary recommendations for CFRD Nutrient Type 1 and type 2 diabetes CFRD Calories As needed for growth, maintenance, or reduction diets 1.2–1.5 times DRI for age; individualized based on weight gain and growth Carbohydrate Individualized. Monitor carbohydrates to achieve glycemic control; choose from fruits, vegetables, whole grains and fiber-containing foods, legumes, and low-fat milk. Sugar alcohols and nonnutritive sweeteners are safe within U.S. Food and Drug Administration–established consumption guidelines. Individualized. Carbohydrates should be monitored to achieve glycemic control. Artificial sweeteners should be used sparingly due to lower calorie content. Fat Limit saturated fat to 90th percentile for age and sex for pediatric patients should have repeat measurement on a separate day to confirm a diagnosis of hypertension. (ADA-E; Consensus) Annual monitoring for microvascular complications of diabetes is recommended using ADA guidelines, beginning 5 years after the diagnosis of CFRD or, if the exact time of diagnosis is not known, at the time that fasting hyperglycemia is first diagnosed. (ADA-E; Consensus) Patients with CFRD diagnosed with hypertension or microvascular complications should receive treatment as recommended by ADA for all people with diabetes, except that there is no restriction of sodium and, in general, no protein restriction. (ADA-E; Consensus) An annual lipid profile is recommended for patients with CFRD and pancreatic exocrine sufficiency or if any of the following risk factors are present: obesity, family history of coronary artery disease, or immunosuppressive therapy following transplantation. (ADA-E; Consensus) FUTURE RESEARCH CONSIDERATIONS The CFRD Guidelines Committee identified the following as the most pressing research questions in CFRD: 1) Do nondiabetic CF patients with abnormal glucose tolerance benefit from diabetes therapy and, if so, what method of treatment has the greatest impact on nutritional and pulmonary status? 2) What are the obstacles to OGTT screening of the CF population and how can they best be overcome? 3) What are the mechanisms by which CFRD impacts pulmonary function and survival in CF? 4) Should target goals for glucose and/or A1C in CFRD differ from ADA target goals? 5) How can we assess and improve patient acceptance of the diagnosis of CFRD to improve diabetes self-management and psychosocial well-being?
Author and article information
Journal
Journal ID (iso-abbrev): Pulm Med
Title:
Pulmonary medicine
Publisher:
Hindawi Limited
ISSN:
2090-1836
ISSN
(Print):
2090-1844
Publication date
(Electronic):
2014
Volume: 2014
Affiliations
[7
]
Cystic Fibrosis Center, Department of Pediatrics, Medical University Innsbruck, Innsbruck,
Austria.
[8
]
Paediatric Respiratory Medicine and Lung Transplantation, Great Ormond Street Hospital,
London, UK.
[9
]
Institute for Medical Microbiology and Infection Control, Goethe University Hospital
Frankfurt, Germany.
Article
DOI: 10.1155/2014/621342
PMC ID: 3988894
PubMed ID: 24800072
SO-VID: e7855456-221e-4f65-98e1-32aeeb11457f
History
Data availability: