Variability of monthly nitrogen multiple-breath washout during one year in children with cystic fibrosis

Background

Knowledge of between-session variability of nitrogen multiple-breath washout (N₂MBW) indices is crucial when designing longitudinal interventional studies and in disease monitoring using N₂MBW as end-point. Such information is currently sparse.

Variability of lung clearance index in clinically stable cystic fibrosis lung disease in school age children

Background

Data on long term variability of Lung Clearance Index (LCI) in Cystic Fibrosis (CF) is urgently needed to guide test result interpretation. Our aim was to evaluate LCI variability in clinically stable CF lung disease in school age children.

Agreement between multiple-breath nitrogen washout systems in children and adults

Background

Comparability of multiple breath washout (MBW) systems has been little explored. We assessed agreement in lung clearance index (LCI) from two similar, commercial nitrogen MBW setups in patients with Cystic Fibrosis (CF) and controls.

Effect of posture on lung ventilation distribution and associations with structure in children with cystic fibrosis

Background

We assessed the effect of posture on ventilation distribution and the impact on associations with structural lung disease.

The application of 3D-printed transparent facemask for facial scar management and its biomechanical rationale

Introduction

Deep facial burns leave conspicuous scar to the patients and affect their quality of life. Transparent facemask has been adopted for the prevention and treatment of facial hypertrophic scars for decades. Recently, with the advancement of 3D printing, the transparent facemask could facilitate the fitting of the facial contour. However, the effectiveness of the device and its biomechanical characteristics on pressure management of hypertrophic scar would need more objective evaluation.

Colon cancer in lung transplant recipients with CF: Increased risk and results of screening

Objective

To determine the incidence of colon cancer in lung transplant recipients with cystic fibrosis (CF) and review screening colonoscopic findings in other recipients with CF.

Methods

A retrospective chart review was performed for all patients with CF transplanted at the University of Wisconsin Hospital and Clinics (January 1994 through December 2010).

Results

Four of 70 transplant recipients with CF developed fatal colon carcinoma following transplantation, and the cancer was advanced in all 4 recipients (age 31, 44, 44, 64) at the time of diagnosis. In contrast, only one of 287 recipients transplanted for non-CF indications developed colon cancer. Of all recipients with CF who did not develop colon cancer, 20 recipients underwent screening colonoscopy at 1 to 12 years following transplantation. Seven (35%) of the screened transplant recipients (ages 36, 38, 40, 41, 43, 49, 51) had colonic polyps in locations ranging from cecum to sigmoid colon and up to 3 cm in diameter.

Conclusions

In contrast to non-CF recipients, patients with CF displayed a significant incidence of colon cancer (4 of 70 recipients; 5.7%) with onset ranging from 246 days to 9.3 years post-transplant, which may be due to a combination of their underlying genetic disorder plus intense, sustained immunosuppression following lung transplantation. Colonoscopic screening may identify patients with pre-malignant colonic lesions and prevent progression to colonic malignancy.     

Long-term outcome of lung transplantation for cystic fibrosis — Danish results

Objective: Over the last decades improvements in medical therapies have delayed the progression of lung disease in cystic fibrosis (CF). However, lung disease is still the most common cause of premature death, and lung transplantation today is the only treatment for end-stage lung disease in patients with CF. We present a retrospective review of the outcome of CF patients transplanted in Denmark since start of the national lung transplantation programme in 1992. Methods: In a 10-year period, 47 patients with CF were listed for lung transplantation; 29 patients underwent transplantation and 18 patients died while waiting for donor organs. Eleven patients received en block double lung transplantation with direct bronchial artery revascularization and 18 patients received bilateral sequential lung transplantation. Median age at transplantation was 29 years (range 11–50). Results: The perioperative mortality (≤30 days) was 3.5% (1/29 patients). Actuarial survival of transplanted patients at 1, 3, 5 and 8 years was 89, 80, 80 and 70%, respectively. Actuarial survival of non-transplanted patients on the waiting list at 1 and 2 years was 28 and 11% (P<0.0001). Causes of death of transplanted patients were: respiratory failure on day 7 (n=1), bronchiolitis obliterans syndrome (n=2), infection (Cytomegalovirus, Aspergillus fumigatus) (n=2), bronchial anastomosis dehiscence (n=1). Pulmonary function (FEV₁% predicted) improved from median 20% (range 13–31) pre-transplant to 71% (range 19–118) after 5 years (P<0.0001). Renal function (⁵¹Cr-EDTA clearance) decreased from median 97 ml/min (range 45–190) pre-transplant to 32 ml/min (range 8–84) 6 months after transplantation (P<0.001). Three patients (11%) received dialysis post-transplant of whom two underwent kidney transplantation. Immunosuppressive induction therapy with rabbit-antithymocyte-globulin compared to daclizumab resulted in fewer treatments for acute rejection within the first 3 months post-transplant (P=0.05 at 5–8 weeks). Burkholderia multivorans was present in three patients pre-transplant with satisfying long-term outcome in one patient. Conclusions: Lung transplantation is a well-established life-extending treatment for patients with CF and end-stage lung disease. The operative mortality is low and CF patients have a significant early survival benefit after lung transplantation. Satisfying long-term results can be achieved in this young and severely ill group of patients.     

Combined heart-lung-liver, double lung-liver, and isolated liver transplantation for cystic fibrosis in children

Abstract Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF) who were accepted either for combined transplantation or isolated liver transplantation died while waiting for a graft; 11 underwent transplantation and 5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group 1) underwent one of the following procedures: heart-lung-liver ( n = 4), sequential double lung-liver ( n = 2), or bilateral lobar lung from a split left lung and reduced liver ( n = 1). During the same period, the four other children (group 2) underwent isolated liver transplantation (three full-size livers, one partial liver). There was one perioperative death in each group. Pulmonary infection was the most common cause of morbidity in group 1. Other complications in group 1 included tracheobronchial stenosis ( n = 2), biliary stricture ( n = 2), and severe ascites ( n = 2). All were successfully treated. Oblit-erative bronchiolitis developed in three patients. This was treated with FK 506. In group 2, pulmonary function tests improved or remained stable after liver transplantation. Surgical complications in group 2 included severe ascites ( n = 1), biliary stricture ( n = 1), and abscess of the liver ( n = 1). Actuarial survival was 85.7 %% 2 % in group 1 at 1 year; it remained unchanged at 3 years and was 64.2 % at 5 years.     

Prevalence,geographic risk factor,and development of a standardized protocol for fungal isolation in cystic fibrosis: Results from the international prospective study “MFIP”

Background

Fungi are increasingly recognized for their potential role in contributing to pulmonary damage in Cystic Fibrosis (CF). We therefore designed a prospective international study aimed at (i) determining the prevalence of fungi isolated from sputum samples collected from a large CF population, (ii) comparing the performance of different media used for fungal culture, and (iii) proposing a standardized protocol suitable for CF routine microbiology.

Combined heart-lung-liver,double lung-liver,and isolated liver transplantation for cystic fibrosis in children

Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF) who were accepted either for combined transplantation or isolated liver transplantation died while waiting for a graft; 11 underwent transplantation and 5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group 1) underwent one of the following procedures: heartlung-liver (n = 4), sequential double lung-liver (n = 2), or bilateral lobar lung from a split left lung and reduced liver (n = 1). During the same period, the four other children (group 2) underwent isolated liver transplantation (three full-size livers, one partial liver). There was one perioperative death in each group. Pulmonary infection was the most common cause of morbidity in group 1. Other complications in group 1 included tracheobronchial stenosis (n = 2), biliary stricture (n = 2), and severe ascites (n = 2). All were successfully treated. Obliterative bronchiolitis developed in three patients. This was treated with FK 506. In group 2, pulmonary function tests improved or remained stable after liver transplantation. Surgical complications in group 2 included severe ascites (n =1), biliary stricture (n = 1), and abscess of the liver (n = 1). Actuarial survival was 85.7 % ± 2 % in group 1 at 1 year; it remained unchanged at 3 years and was 64.2 % at 5 years.     

Respiratory rate in infants with cystic fibrosis throughout the first year of life and association with lung clearance index measured shortly after birth

Background

Lung impairment in cystic fibrosis (CF) starts in infancy. However, tools to monitor early lung disease are limited. Respiratory rate (RR) as a key vital sign is easy to assess during sleep and is elevated during acute respiratory disease. Thus, elevated RR could indicate early lung impairment and potentially serve as a diagnostic tool in disease monitoring.

Clostridium difficile carriage in adult cystic fibrosis (CF); implications for patients with CF and the potential for transmission of nosocomial infection

Clostridium difficile is an anaerobic Gram-positive, spore-forming, toxin-producing bacillus transmitted among humans through the faecal–oral route. Despite increasing carriage rates and the presence of C. difficile toxin in stool, patients with CF rarely appear to develop typical manifestations of C. difficile infection (CDI). In this study, we examined the carriage, toxin production, ribotype distribution and antibiotic susceptibility of C. difficile in a cohort of 60 adult patients with CF who were pre-lung transplant. C. difficile was detected in 50% (30/60) of patients with CF by culturing for the bacteria. C. difficile toxin was detected in 63% (19/30) of C. difficile-positive stool samples. All toxin-positive stool samples contained toxigenic C. difficile strains harbouring toxin genes, tcdA and tcdB. Despite the presence of C. difficile and its toxin in patient stool, no acute gastrointestinal symptoms were reported. Ribotyping of C. difficile strains revealed 16 distinct ribotypes (RT), 11 of which are known to be disease-causing including the hyper-virulent RT078. Additionally, strains RT002, RT014, and RT015, which are common in non-CF nosocomial infection were described. All strains were susceptible to vancomycin, metronidazole, fusidic acid and rifampicin. No correlation was observed between carriage of C. difficile or any characteristics of isolated strains and any recorded clinical parameters or treatment received. We demonstrate a high prevalence of hypervirulent, toxigenic strains of C. difficile in asymptomatic patients with CF. This highlights the potential role of asymptomatic patients with CF in nosocomial transmission of C. difficile.     

Outcome of total splenectomy with portosystemic shunt for massive splenomegaly and variceal bleeding in cystic fibrosis

Multilobular biliary cirrhosis and portal hypertension are frequent complications of cystic fibrosis liver disease, leading to esophageal varices and splenomegaly. Therapy is focused on variceal bleeding control; however, reduction of spleen volume is also important to restore gastric volume and resolve invalidating abdominal discomfort. We report long-term follow up (median duration, 5.5 years; range, 14 months-21.5 years) of 6 patients with cystic fibrosis (4 men, 2 women; median age, 14 years; range, 8-18 years) who underwent splenectomy with a splenorenal shunt operation. Three patients received elective surgery for massive splenomegaly with important abdominal discomfort, recurrent variceal bleeding, and hypersplenism. Three were urgently treated to control variceal bleeding after several sessions of sclerotherapy. All but 2 received antipneumococcal vaccination before surgery. Four patients had a weight gain of 10% within 3 months of surgery, and 3 developed spontaneous puberty. Lung function remained stable, and there was an overall reduction of respiratory tract infections. The youngest patient, however, died of overwhelming septicemia during treatment with steroids. Although total splenectomy has important risks, in well-selected cases, it can have benefits. Immuno- and chemoprophylaxis, combined with patient awareness of supplementary risk of infections is indispensable to minimize septic complications.     

Acute lung injury monitored with radiolabelled transferrin and lung volume measurements

Anesthetized pigs (n = 12) were given oleic acid (OA) to induce acute lung injury. Three additional pigs were used as uninjured controls. Six of the animals were pretreated with terbutaline before OA infusion. 113mIn-labeled transferrin and 99mTc-labeled erythrocytes were used for tracing of extravascular plasma leakage. A computerized gamma camera supplied image analysis of the radioactivities over the heart and lungs. A lung transferrin index (LTI), which describes the net accumulation of plasma equivalents in the lung, was calculated. OA caused an immediate increase in LTI and concurrent, correlated decreases in functional residual capacity, lung thorax compliance and arterial PO2. LTI was also correlated to the content of plasma equivalents in lung tissue samples and also to the wet weight/dry weight-ratios of the same tissue samples. Finally, LTI was correlated to the calculated plasma loss from the circulation. Changes in all these parameters were correlated to the dose of OA. We conclude that this noninvasive double radioisotope technique can detect plasma protein leakage in lung injury of different degrees. We found no significant anti-edema effect of terbutaline.     

Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease

Objective

To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting.

双肺移植治疗儿童囊性纤维化的多学科综合诊疗

目的  通过多学科综合诊疗（MDT）模式提高双肺移植治疗儿童囊性纤维化的外科疗效。方法  对1例国内罕见的终末期囊性纤维化10岁患儿进行肺移植术前MDT讨论,制定对应治疗方案。结果  患儿确诊囊性纤维化5年,肺移植指征明确,经过MDT讨论决定行Clam-shell切口下双肺移植术,术中维持生命体征稳定,术后给予呼吸机辅助通气、抗感染、免疫抑制、抑酸和预防应激性溃疡等治疗,并根据患儿特点给予个体化治疗方案,术后恢复良好。结论  通过肺移植术前MDT讨论,肺移植治疗儿童囊性纤维化的手术效果满意,减少了术后并发症的发生风险,值得临床推广。