Barry Linnane

Bronchiectasis in Infants and Preschool Children Diagnosed with Cystic Fibrosis after Newborn Screening

OBJECTIVESnTo determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection.nnnSTUDY DESIGNnChildren were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96). Scans were analyzed for the presence and extent of abnormalities.nnnRESULTSnThe prevalence of bronchiectasis was 22% and increased with age (P = .001). Factors associated with bronchiectasis included absolute neutrophil count (P = .03), neutrophil elastase concentration (P = .001), and Pseudomonas aeruginosa infection (P = .03).nnnCONCLUSIONSnPulmonary abnormalities are common in infants and young children with CF and relate to neutrophilic inflammation and infection with P. aeruginosa. Current models of care for infants with CF fail to prevent respiratory sequelae. Bronchiectasis is a clinically relevant endpoint that could be used for intervention trials that commence soon after CF is diagnosed after NBS.

Lung Function in Infants with Cystic Fibrosis Diagnosed by Newborn Screening

RATIONALEnProgressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies.nnnOBJECTIVESnTo measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation.nnnMETHODSnInfants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied. Forced vital capacity, FEV(0.5), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume rapid thoracoabdominal compression technique. Forty-eight hours later, infants with CF had bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation.nnnMEASUREMENTS AND MAIN RESULTSnIn the CF group, the deficit in FEV(0.5) z score increased by -0.77 (95% confidence interval, -1.14 to -0.41; P < 0.001) with each year of age. The mean FEV(0.5) z score did not differ between infants with CF and healthy control subjects less than 6 months of age (-0.06 and 0.02, respectively; P = 0.87). However, the mean FEV(0.5) z score was lower by 1.15 in infants with CF who were older than 6 months of age compared with healthy infants (P < 0.001). FVC and FEF(75) followed a similar pattern. Pulmonary infection and inflammation in BAL samples did not explain the lung function results.nnnCONCLUSIONSnLung function, measured by forced expiration, is normal in infants with CF at the time of diagnosis by newborn screening but is diminished in older infants. These findings suggest that in CF the optimal timing of therapeutic interventions aimed at preserving lung function may be within the first 6 months of life.

Role of high-resolution computed tomography in the detection of early cystic fibrosis lung disease

High-resolution computed tomography (HRCT) has been demonstrated to be sensitive at detecting early lung disease in cystic fibrosis (CF), often before it is apparent clinically. There is emerging evidence that structural changes in the lung occur earlier in life than previously appreciated. Despite this, the role of HRCT in young children with CF has yet to be defined, principally because the repeated exposure of children to X-ray doses several multiples that of a standard chest X-ray raises the concern of the long-term risks of ionizing radiation. With the challenges of acquiring HRCT images in young children in mind, we review scanning protocols and settings specific to young children, and review the best available evidence that describes early structural lung disease in young children with CF. The role of CT scoring and quantitative measures of CF lung disease are reviewed. The challenge for the future is to develop techniques that provide clinically useful information at the lowest possible radiation risk.

Induced sputum compared to bronchoalveolar lavage in young, non-expectorating cystic fibrosis children.

BACKGROUNDnInduced sputum (IS) is feasible and safe in young CF children and is a readily accessible, non-invasive technique. However, it has not been compared to bronchoalveolar lavage (BAL), the gold standard for diagnosing lower airway infection.nnnMETHODSnWe compared bacterial yield from IS and BAL in 11 non-expectorating CF children, aged 3 to 7.4 years. IS samples were obtained in 10/11 cases.nnnRESULTSnEight out of ten had the same predominant bacteria cultured from IS and BAL: Pseudomonas aeruginosa and Stenotrophomonas maltophilia[1], Staphylococcus aureus[3], and upper respiratory tract flora [4]. In one, Serratia marcescens and Haemophilus parainfluenzae were cultured from IS alone, whereas in one, non-group B Haemophilus influenzae was cultured from BAL alone.nnnCONCLUSIONSnAs proof of principle, IS samples showed good bacteriologic correlation with BAL. Larger studies are recommended to confirm IS as a clinically valuable tool and measure for early intervention studies in young CF children.

Early Detection of Lung Disease in Children with Cystic Fibrosis Using Lung Function

Measurement of lung function is routine in older children and adults with cystic fibrosis (CF) but not in infants and preschool children. Pulmonary infection, neutrophil-dominated inflammation and clinical exacerbations in young children similar to those seen in older subjects have been identified and highlight the urgent need to evaluate lung function in early life. Mounting evidence suggests lung function techniques sensitive to changes in peripheral lung function may be required to detect the early functional abnormalities in infants and preschool children with CF. In addition, the majority of studies in young children with CF have not reported longitudinal data and therefore the prognostic potential of existing lung function methods to track disease progression is poorly understood. This review aims to describe recent research findings in infants and preschool children and to outline currently available lung function techniques, issues around their standardization and their relative advantages and disadvantages in young children with CF.

Does splenectomy in cystic fibrosis related liver disease improve lung function and nutritional status? - A case series

Aims: To review the effect of total splenectomy on lung function and nutrition in children with cystic fibrosis related liver disease (CFLD) and associated portal hypertension. The stated indications for surgery and the short and long term risks of the procedure were also documented. Method: Over a 25 year period from January 1980 to June 2005, approximately 650 patients with cystic fibrosis (CF) were treated at the Royal Children’s Hospital, Melbourne, Australia. Nine patients with CFLD who underwent a splenectomy during that time were identified and their medical records were reviewed. Results: FEV1% predicted dropped by −16±11% in the two years pre-splenectomy. This contrasts with the increase in FEV1% predicted of 2±16% in the two years post-splenectomy (pu200a=u200a0.05). The cumulative gain in WAZ score (ΔWAZ pre) over the two years prior to splenectomy of 0.045±0.69 was not significantly different from the cumulative gain in WAZ score (ΔWAZ post) for the two years after splenectomy of 0.15±0.36 (pu200a=u200a0.65). The average age at splenectomy was 14.8 years (SDu200a=u200a3 years). The average weight of an excised spleen was 983 g (SDu200a=u200a414 g). There were no deaths associated with splenectomy. The median length of follow up post-splenectomy was 6.0 years (range 0.7–15.8). There were no episodes of bacterial peritonitis or overwhelming sepsis. Conclusions: Splenectomy may have a beneficial effect on lung function although this may not manifest itself until the second year post-splenectomy. Splenectomy in patients with CFLD appears to be a safe procedure.

The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe

BACKGROUNDnNewborn screening (NBS) for cystic fibrosis (CF) is a well-established public health strategy with international standards. The aim of this study was to provide an update on NBS for CF in Europe and assess performance against the standards.nnnMETHODSnQuestionnaires were sent to key workers in each European country.nnnRESULTSnIn 2016, there were 17 national programmes, 4 countries with regional programmes and 25 countries not screening in Europe. All national programmes employed different protocols, with IRT-DNA the most common strategy. Five countries were not using DNA analysis. In addition, the processing and structure of programmes varied considerably. Most programmes were achieving the ECFS standards with respect to timeliness, but were less successful with respect to sensitivity and specificity.nnnCONCLUSIONSnThere has been a steady increase in national CF NBS programmes across Europe with variable strategies and outcomes that reflect the different approaches.

Pooling of Bronchoalveolar Lavage in Children with Cystic Fibrosis Does Not Affect the Microbiological Yield and May Allow Earlier Detection of Pulmonary Inflammation

The 30th Annual North American Cystic Fibrosis Conference, Orange County Convention Center, Orlando, Florida, October 27–29In Canada all paediatric CF patients are required to transition to the adult CF clinic at the age of 18 regardless of their readiness or desire to transition. We have been told that this can cause anxiety and stress for both the patients and their families. Among the myriad changes encountered include an entirely new team, new clinic location and space, new inpatient setting, and shift to self-care model. Our current transition program starts at age 14 with the initiation of private discussion time with the paediatric health care team and a questionnaire that tracks development of CF knowledge and self-management skills. While this process does provide some level of preparedness in terms of knowledge and skill, patients and family still voiced anxiety about the actual physical experience of transition. Our Transition Night was created to provide an opportunity for transitioning youth and their families to meet and interact with the adult team, be introduced to the new clinic space and routines, meet other parents and be able to present their questions and concerns. Parents were invited to be present but due to infection control guidelines the youth were not able to attend in person. Therefore they were connected via live webinar feed. This gave them an opportunity to view the presentations, meet the adult clinic team and anonymously send in their questions. The evening session was recorded and posted on our CF clinic website and available as a teaching tool. Method: A Transition Evening event was held at a local hotel reception room with easy access to the highway for out-of-town participants. Our target population, identified as those who will be transitioning within the next 5 years, were personally invited with a poster about the event sent by email or regular post. The evening was supported by funds from a pharmaceutical company who provided technological support and equipment. The event was filmed, recorded and aired via confidential live interactive webinar for those at home. All disciplines from both the adult and paediatric teams presented PowerPoint slides with information on various aspects of transitioning to the adult clinic, highlighting the changes patients might expect to encounter. Refreshments and a “meet and greet” session occurred after the presentations. A display table with CF-related information items and equipment was on display. Evaluation forms were available for completion after the session. Results: Eight families from a possible 15 families approaching transition attended with 3 patients logged on remotely. All participants, including those logged in, were actively engaged and asked questions of the staff. Overall, evaluations proved to be extremely positive. Of the 10 evaluations completed, all attendees found the presentations met their learning needs at a very high degree. The same was true for the clarity, organization and understandability of the speakers. All participants found the event to be valuable and helpful. Reflections: Host event every year Take pictures at event Welcome table/sign-in Patient/parent from adult clinic discuss their transition experience Speaker from college disability office Email survey to webcast participants Pre/post participant evaluation 670 SOCIAL COMPLEXITY AS A DETERMINANT OF OUTCOMES IN CYSTIC FIBROSIS AFTER TRANSITION TO ADULT CARE Crowley, E.; Bosslet, G.; Khan, B.; Ciccarelli, M.; Brown, C.D. 1. Pulmonary, Critical Care, Occupational and Sleep Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; 2. Internal Medicine and Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA Objective: This study evaluates the roles of medical and social complexity in health outcomes in cystic fibrosis (CF) after transition into adult care. We hypothesized that individuals with high disease complexity, poor social support systems, or gaps in care experience a more rapid decline in lung function and increased health care utilization after transition. Methods: Using a retrospective cohort design, all CF patients who were transitioned into adult care at Indiana University from our pediatric center between January 1st, 2005 to December 31st, 2014, were included. Along with demographics and comorbidities, the variables included age at transition, gap in care (days) between pediatric and adult CF center visits, treatment complexity score (TCS) (Sawicki GS, et al. J Cyst Fibros. 2013;12:461-7), diagnosis of depression and anxiety, and an objective scoring measure of their social complexity (Bob’s Level of Social Support, BLSS). Relationships between FEV1 % predicted and TCS and BLSS were assessed using bivariate linear regression. The relationships between gap in care and FEV1 % predicted as well as gap in care with TCS and BLSS were assessed using analysis of variance (ANOVA). TCS and BLSS tertiles were compared with hospitalization and outpatient visit rates using ANOVA. Lastly bivariate linear regression was used for correlations between TCS, BLSS, and hospitalization rates and preand post-transition outpatient visit rates. Results: The average age of the patients (N = 110) at the time of transition was 22.8 ± 6.4 years. The average FEV1 at transition was 66.2 ± 23.7% predicted. Half of the patients were male and 97% were white. Sixty-three percent had a high school diploma and 29% had Medicaid insurance. There were no correlations between TCS (R = -0.07, p = 0.29) or BLSS (R = -0.01, p = 0.91) and decline of FEV1. Between groups of gap in care, there was significant difference in decline of FEV1 (p = 0.01). Higher TCS and BLSS correlated with increased hospitalization rate (R = 0.72, p < 0.001) prior to transition. A higher TCS predicted more outpatient visits. However, higher BLSS was associated with a lower number of outpatient visits with a significant drop after transition (See Table). Conclusions: Greater treatment complexity and social complexity are related to increased health care utilization. Patients with higher treatment complexity have more frequent outpatient follow-up visits as well as hospitalizations, while patients with more psychosocial issues tend to have increased hospitalizations and fewer outpatient visits. Screening young adults for social complexity and providing further support may reduce avoidable health care use. Table: Correlation between Social Complexity, Treatment Complexity, and Health Care Utilization *P < 0.05, **P < 0.001 194-485_NACFC16_Abstracts-6.indd 450 8/26/16 2:59 PM Poster Session Abstracts 451 671 NEUROPSYCHOLOGICAL, SLEEP, AND BRAIN ASSESSMENT IN ADULT CF HOMOZYGOUS F508DEL Woo, M.S.; Roy, B.; Afshar, K.; Rao, A.; Fukushima, L.; Eshaghian, P.; Woo, M.; Kumar, R. 1. Pediatrics, Mattel Children’s Hosp-UCLA, San Marino, CA, USA; 2. UCLA Sch of Nursing, Los Angeles, CA, USA; 3. Pulmonary Med, UCSD, San Diego, CA, USA; 4. Pulmonary and Critical Care Med, Keck School of Medicine USC, Los Angeles, CA, USA; 5. Pulmonary and Critical Care Medicine, David Geffen School of Medicine UCLA, Los Angeles, CA, USA; 6. Anesthesiology, Radiological Sciences, and Bioengineering, David Geffen School of Medicine UCLA, Los Angeles, CA, USA Introduction: CFTR is expressed in several brain areas. Patients (pts) show a variety of symptoms, including mood, cognitive, respiratory, and autonomic issues. These abnormal symptoms suggest possible brain injury that can be examined with noninvasive MRI procedures. Methods: 5 CF pts homozygous F508del (3 M; age 29.7±3.7 y; BMI 22.0±0.7 kg/m) and 5 controls (4 M; age 28.5±5.1 y; BMI 21.3±5.4 kg/m). Vital signs and demographics were collected. All were in baseline good health. All completed mood, cognitive, and sleep surveys: Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), Epworth Sleepiness Scale (ESS), Montreal Neurocognitive Assessment (MoCA), Trail Making Tests (TMT) and Pittsburgh Sleep Quality Index (PSQI). Diffusion tensor imaging (DTI) procedures (2 DTI series/subject) were performed using a 3.0-Tesla MRI scanner. Using diffusion and nondiffusion images, mean diffusivity (MD) values, which indicate average motion of water molecules within tissue and show microstructural changes, with decreased values in acute and increased in chronic pathological condition, were calculated at each voxel from each DTI series. Both MD maps, derived from each DTI series, were realigned and averaged, normalized to a common space, smoothed, and compared between groups using ANCOVA (covariates, age and gender; SPM12, p<0.005; extended threshold, 10 voxels). Results: No significant differences in age, gender, or BMI between CF and controls. Initial SpO2 was 97% (range 97-98%) on room air, but dropped to 91% (range 90-92%) when CF subjects were supine in MRI scanner. Of 5 CF subjects, one on BDI-II, 3 on BAI, 5 on PSQI, and 2 on the MoCA had abnormal scores. Various brain areas showed significantly reduced MD values in CF, indicating predominant acute tissue changes, over controls. Sites with reduced MD values included bilateral prefrontal and frontal, parietal, and occipital cortices, bilateral corona radiate, anterior, mid, posterior cingulate cortices; insula, cerebellar vermis, middle cerebellar peduncles, cerebellar cortices and deep nuclei, and ventral medulla. Only a few areas, including basal-forebrain and right occipital cortex, showed increased MD values in CF, suggesting chronic tissue damage, over controls. Conclusions: Adult CF pts homozygous for F508del had poor sleep, unsuspected low oxygen saturation during rest, but few CF subjects showed mood and cognitive issues. CF subjects show predominant acute tissue changes in areas that control mood, cognition, respiratory, and autonomic functions. However, current mood and cognitive screening tests appear to be less sensitive, and show only limited issues. Speculation: Altered brain structure may be due to CFTR protein dysfunction, malnutrition, or hypoxemia. Further study is needed to determine if thes