Michelle E. Wood

Ivacaftor in severe cystic fibrosis lung disease and a G551D mutation

Ivacaftor is gene‐specific oral therapy for patients with cystic fibrosis who have a cystic fibrosis transmembrane conductance regulator mutation, G551D. To date, limited information is available about the benefit in patients with severe CF related lung disease, as such patients were excluded from the phase III trials. We report the early results on clinical outcomes, sweat electrolytes and C‐reactive protein in three adults with a G551D mutation and advanced lung disease. A mean increase of 6% in FEV1 was observed at 2 weeks and a mean reduction in sweat chloride of −48.9 mmol/L. While improvements in spirometry, weight gain and reduction in sweat electrolytes are similar with those reported in the phase III trials, a formal comparison was not performed.

Tropical Australia is a potential reservoir of non-tuberculous mycobacteria in cystic fibrosis

Improved survival rates and increased treatment intensity of people with cystic fibrosis have been accompanied by a rising incidence of multi-antibiotic resistant and difficult-to-treat respiratory pathogens, including non-tuberculous mycobacteria (NTM) [1]. NTM epidemiology in cystic fibrosis varies globally, with a prevalence of >20% in some geographical locations [2]. In particular, there are concerns that active NTM disease from rapidly growing mycobacteria (Mycobacterium abscessus complex) may be increasing and causing accelerated pulmonary decline [3, 4]. NTM are found naturally in ecological niches such as soil and water, and susceptible individuals may also acquire infection from potable water in their homes [5, 6]. Recent reports demonstrate person-to-person transmission [7, 8], which might occur via fomites and cough aerosols [8] and further emphasise the potential clinical importance of these organisms. Living in tropical Australia is associated with NTM acquisition, whilst long-term azithromycin is protective in CF http://ow.ly/FrJi309W8DK

Face Masks and Cough Etiquette Reduce the Cough Aerosol Concentration of Pseudomonas aeruginosa in People with Cystic Fibrosis

Rationale: People with cystic fibrosis (CF) generate Pseudomonas aeruginosa in droplet nuclei during coughing. The use of surgical masks has been recommended in healthcare settings to minimize pathogen transmission between patients with CF. Objectives: To determine if face masks and cough etiquette reduce viable P. aeruginosa aerosolized during coughing. Methods: Twenty‐five adults with CF and chronic P. aeruginosa infection were recruited. Participants performed six talking and coughing maneuvers, with or without face masks (surgical and N95) and hand covering the mouth when coughing (cough etiquette) in an aerosol‐sampling device. An Andersen Cascade Impactor was used to sample the aerosol at 2 meters from each participant. Quantitative sputum and aerosol bacterial cultures were performed, and participants rated the mask comfort levels during the cough maneuvers. Measurements and Main Results: During uncovered coughing (reference maneuver), 19 of 25 (76%) participants produced aerosols containing P. aeruginosa, with a positive correlation found between sputum P. aeruginosa concentration (measured as cfu/ml) and aerosol P. aeruginosa colony‐forming units. There was a reduction in aerosol P. aeruginosa load during coughing with a surgical mask, coughing with an N95 mask, and cough etiquette compared with uncovered coughing (P < 0.001). A similar reduction in total colony‐forming units was observed for both masks during coughing; yet, participants rated the surgical masks as more comfortable (P = 0.013). Cough etiquette provided approximately half the reduction of viable aerosols of the mask interventions during voluntary coughing. Talking was a low viable aerosol‐producing activity. Conclusions: Face masks reduce cough‐generated P. aeruginosa aerosols, with the surgical mask providing enhanced comfort. Cough etiquette was less effective at reducing viable aerosols.

Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study

Background Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis (CF). The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We investigated the association between pulmonary artery enlargement (PA:A>1), a marker of pulmonary vascular disease, and exacerbations. Methods We analyzed clinical, computed tomography (CT), and prospective exacerbation data in a derivation cohort of 74 adult CF patients, measuring the PA:A at the level of the PA bifurcation. We then replicated our findings in a validation cohort of 190 adult CF patients. Patients were separated into groups based on the presence or absence of a PA:A>1 and were followed for 1-year in the derivation cohort and 2-years in the validation cohort. The primary endpoint was developing ≥1 acute pulmonary exacerbation during follow-up. Linear and logistic regression models were used to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine time to first exacerbation in the validation cohort. Findings We found that PA:A>1 was present in n=37/74 (50%) of the derivation and n=89/190 (47%) of the validation cohort. In the derivation cohort, n=50/74 (68%) had ≥1 exacerbation at 1 year and n=133/190 (70%) in the validation cohort had ≥1 exacerbation after 2 years. PA:A>1 was associated with younger age in both cohorts and with elevated sweat chloride (100.5±10.9 versus 90.4±19.9mmol/L, difference between groups 10.1mmol/L [95%CI 2.5–17.7], P=0.017) in the derivation group. PA:A>1 was associated with exacerbations in the derivation (OR 3.49, 95%CI 1.18–10.3, P=0.023) and validation (OR 2.41, 95%CI 1.06–5.52, P=0.037) cohorts when adjusted for confounders. Time to first exacerbation was shorter in PA:A>1 versus PA:A<1 [HR 1.66 (95%CI 1.18–2.34), P=0.004] in unadjusted analysis, but not when adjusted for sex, BMI, prior exacerbation, positive Pseudomonas status, and FEV1/FVC [HR 1.14 (95%CI 0.80–1.62), P=0.82]). Interpretation PA enlargement is prevalent in adult CF patients and is associated with acute pulmonary exacerbation risk in two well-characterized cohorts. PA:A may be a predictive marker in CF.

Cystic fibrosis pathogens survive for extended periods within cough-generated droplet nuclei

The airborne route is a potential pathway in the person-to-person transmission of bacterial strains among cystic fibrosis (CF) populations. In this cross-sectional study, we investigate the physical properties and survival of common non-Pseudomonas aeruginosa CF pathogens generated during coughing. We conclude that Gram-negative bacteria and Staphylococcus aureus are aerosolised during coughing, can travel up to 4 m and remain viable within droplet nuclei for up to 45 min. These results suggest that airborne person-to-person transmission is plausible for the CF pathogens we measured.

A Novel Method and Its Application to Measuring Pathogen Decay in Bioaerosols from Patients with Respiratory Disease

This work aimed to develop an in vivo approach for measuring the duration of human bioaerosol infectivity. To achieve this, techniques designed to target short-term and long-term bioaerosol aging, were combined in a tandem system and optimized for the collection of human respiratory bioaerosols, without contamination. To demonstrate the technique, cough aerosols were sampled from two persons with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Measurements and cultures from aerosol ages of 10, 20, 40, 900 and 2700 seconds were used to determine the optimum droplet nucleus size for pathogen transport and the airborne bacterial biological decay. The droplet nuclei containing the greatest number of colony forming bacteria per unit volume of airborne sputum were between 1.5 and 2.6 μm. Larger nuclei of 3.9 μm, were more likely to produce a colony when impacted onto growth media, because the greater volume of sputum comprising the larger droplet nuclei, compensated for lower concentrations of bacteria within the sputum of larger nuclei. Although more likely to produce a colony, the larger droplet nuclei were small in number, and the greatest numbers of colonies were instead produced by nuclei from 1.5 to 5.7 μm. Very few colonies were produced by smaller droplet nuclei, despite their very large numbers. The concentration of viable bacteria within the dried sputum comprising the droplet nuclei exhibited an orderly dual decay over time with two distinct half-lives. Nuclei exhibiting a rapid biological decay process with a 10 second half-life were quickly exhausted, leaving only a subset characterized by a half-life of greater than 10 minutes. This finding implied that a subset of bacteria present in the aerosol was resistant to rapid biological decay and remained viable in room air long enough to represent an airborne infection risk.

Seasonal variation and living alone are related to non-completion in a pulmonary rehabilitation program

Despite the prevalence of acute cough in children (<2 weeks duration), the burden to parents and families is largely unknown. The objectives of this study were to determine the parental burden of children’s acute cough, and to evaluate psychological and other infl uences on the reported burden of acute cough in children. Methods Parents of children with a current acute cough (<2 weeks) at enrolment completed 4 questionnaires (state trait anxiety inventory (STAI); short form health survey (SF-8); depression, anxiety and stress 21-item scale (DASS21); and our preliminary 48-item parent acute cough specifi c quality of life (PAC-QOL48) questionnaire). In PAC-QOL48, lower scores refl ect worse QOL. Results Median age of the 104 children enrolled was 2.63 (IQR 1.42, 4.79) years, 54 were boys. Median length of cough at enrolment was 3 (IQR 2, 5) days. Median total PAC-QOL48 score of parents enrolled at presentation to the emergency department (n = 70) was signifi cantly worse than of parents enrolled through the community (n = 24) (p < 0.01). More than half (n = 55) had sought medical assistance more than once for the current acute coughing illness. PAC-QOL48 score was signifi cantly negatively correlated to verbal category descriptive and visual analogue scale cough scores (Spearman r = −0.26, p = 0.05 and r = −0.46, p = 0.01 respectively) and DASS21 total score (r = −0.36, p = 0.01), but not to child’s age. Conclusions Consistent with data on chronic cough, stress was the predominant factor of parental burden. This study highlights the ongoing need for clinicians to be cognizant of parental worries and concerns when their children are coughing, and for further research into safe and effective therapies for acute cough in children.

Work environment risks for health care workers with cystic fibrosis: Guide for health care workers with CF

In Australia and New Zealand, >50% of people with cystic fibrosis (CF) are adults and many of these people are pursuing vocational training and undertaking paid employment. More than 6% of adults with CF are working in health care. There is limited guidance in literature to support health care workers with CF (HCWcf) in training and in employment to support safe practice and to provide protection for themselves and their patients from the acquisition of health care associated infection. A multidisciplinary team of CF and Infectious Disease Clinicians, Infection Prevention and Control Practitioners, HCWcf, academic experts in medical ethics and representatives from universities, appraised the available evidence on the risk posed to and by HCWcf. Specific recommendations were made for HCWcf, CF health care teams, hospitals and universities to support the safe practice and appropriate support for HCWcf.

Face Masks Reduce the Release of Pseudomonas aeruginosa Cough Aerosols when Worn for Clinically-Relevant Time Periods

We recruited 25 people with CF and chronic P. aeruginosa infection (6) from the Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, Australia. Ten healthy volunteers were recruited from hospital and research staff to assess mask comfort and mask weight change. All participants performed up to five randomly ordered tests in a validated cough system (7): uncovered cough, coughing with surgical mask worn for 10 minutes, coughing with surgical mask worn for 20 minutes, coughing with surgical mask worn for 40 minutes, and coughing with N95 mask worn for 20 minutes (3, 7). The N95 test was an optional test based on the poor comfort ratings observed in our earlier mask study (3).

Face masks and cough etiquette reduce cough-generated bioaerosols containing pseudomonas aeruginosa in patients with cystic fibrosis

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