Natalie E. West

Appropriate Goal Level for 25-Hydroxyvitamin D in Cystic Fibrosis

BACKGROUNDnVitamin D deficiency is common in patients with cystic fibrosis (CF), and guidelines recommend 25-hydroxyvitamin D (25OHD) levels ≥ 30 ng/mL. This threshold was selected because serum parathyroid hormone (PTH) rises in healthy individuals when the 25OHD level falls below 30 ng/mL. PTH levels > 50 pg/mL are associated with an increased risk of bone loss. However, the relationship between 25OHD and PTH has not been studied in CF. We sought to determine the appropriate goal 25OHD level in patients with CF by identifying the level below which the risk of PTH > 50 pg/mL begins to increase.nnnMETHODSnLevels of 25OHD and PTH in 216 individuals with CF were collected prospectively. Individuals with 25OHD < 30 ng/mL were treated with vitamin D2, and levels were reevaluated.nnnRESULTSnMean 25OHD level was 25.7 ± 12.4 ng/mL, and mean PTH level was 46.7 ± 25.9 pg/mL. In 63% of individuals, 25OHD level was < 30 ng/mL, and in 38.0% it was ≤ 20 ng/mL. Low 25OHD levels were significantly associated with elevated PTH levels, with a mean PTH of 53.1 ± 29.8 pg/mL for 25OHD level 0 to 19 ng/mL; 51.1 ± 30.7 pg/mL for 25OHD level 20 to 29 ng/mL; 38.4 ± 16.4 pg/mL for 25OHD level 30 to 39 ng/mL; and 37.2 ± 16.4 pg/mL for 25OHD level ≥ 40 ng/mL (P = .006). We assessed the sensitivity of different 25OHD thresholds to identify individuals meeting the goal of a PTH level < 50 pg/mL to reduce the risk of bone loss. To obtain 90% sensitivity, a 25OHD level ≥ 35 ng/mL was required. Strikingly, 23% of individuals with 25OHD levels 30 to 34 ng/mL still had a PTH level > 50 pg/mL. This decreased to 14% for 25OHD level ≥ 35 ng/mL.nnnCONCLUSIONSnInadequate serum 25OHD levels are common in adults with CF and are associated with elevated PTH levels. Aiming to maintain 25-OHD levels ≥ 35 ng/mL in individuals with CF decreases the risk of having a PTH level associated with secondary hyperparathyroidism and bone loss.

Standardized Treatment of Pulmonary exacerbations (STOP) study: Physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary exacerbations

BACKGROUNDnPulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx.nnnMETHODSnThe Standardized Treatment of Pulmonary Exacerbations (STOP) observational study enrolled 220 participants ≥12years old admitted to the hospital for PEx at 11 U.S. CF centers. Spirometry and daily symptom scores were collected during the study. Physicians were surveyed on treatment goals and their management practices were observed. Treatment outcomes were compared to stated goals.nnnRESULTSnThe mean (SD) duration of IV antibiotic treatment was 15.9 (6.0) days. Those individuals with more severe lung disease (<50% FEV1) were treated nearly two days longer than those with >50% FEV1. Physician-reported FEV1 improvement goals were 10% (95% CI: 5%, 14%) lower for patients with 6-month baseline FEV1 ≤50% predicted compared with those with 6-month baseline FEV1 >50% predicted. There were clinically and statistically significant improvements in symptoms from the start of IV antibiotic treatment to the end of IV antibiotic treatment and 28days after the start of treatment. The mean absolute increase in FEV1 from admission was 9% predicted at end of IV antibiotic treatment, and 7% predicted at day 28. Only 39% fully recovered lost lung function, and only 65% recovered at least 90% of lost lung function. Treatment was deemed successful by 84% of clinicians, although 6-month baseline FEV1 was only recovered in 39% of PEx.nnnCONCLUSIONSnIn this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physicians treatment goals, yet treatment was deemed successful.

Standardized Treatment of Pulmonary Exacerbations (STOP) study: Observations at the initiation of intravenous antibiotics for cystic fibrosis pulmonary exacerbations

BACKGROUNDnThe Standardized Treatment of Pulmonary Exacerbations (STOP) program has the intent of defining best practices in the treatment of pulmonary exacerbations (PEx) in patients with cystic fibrosis (CF). The objective of this analysis was to describe the clinical presentations of patients admitted for intravenous (IV) antibiotics and enrolled in a prospective observational PEx study as well as to understand physician treatment goals at the start of the intervention.nnnMETHODSnWe enrolled adolescents and adults admitted to the hospital for a PEx treated with IV antibiotics. We recorded patient and PEx characteristics at the time of enrollment. We surveyed treating physicians on treatment goals as well as their willingness to enroll patients in various study designs. Additional demographic and clinical data were obtained from the CF Foundation Patient Registry.nnnRESULTSnOf 220 patients enrolled, 56% were female, 19% were adolescents, and 71% were infected with P. aeruginosa. The mean (SD) FEV1 at enrollment was 51.1 (21.6)% predicted. Most patients (85%) experienced symptoms for ≥7days before admission, 43% had received IV antibiotics within the previous 6months, and 48% received oral and/or inhaled antibiotics prior to IV antibiotic initiation. Forty percent had ≥10% FEV1 decrease from their best value recorded in the previous 6months, but for 20% of patients, their enrollment FEV1 was their best FEV1 recorded within the previous 6months. Physicians reported that their primary treatment objectives were lung function recovery (53%) and improvement of symptoms (47%) of PEx. Most physicians stated they would enroll patients in studies involving 10-day (72%) or 14-day (87%), but not 7-day (29%), treatment regimens.nnnCONCLUSIONSnBased on the results of this study, prospective studies are feasible and physician willingness for interventional studies of PEx exists. Results of this observational study will help design future PEx trials.

Transitions in Health Care: What Can We Learn from Our Experience with Cystic Fibrosis

Numerous individuals with chronic disease age into adulthood each year, necessitating transition from a pediatric to an adult medical care team. Transition should start early in adolescence and occur gradually over years, preparing the individual for the transfer to the adult team. Cystic fibrosis (CF) has a growing population of adults, as survival over the past several decades has increased. The CF Foundation has implemented guidelines for the transition process. The transition process for individuals with CF provides an example that could be adapted into other chronic disease populations, to provide a successful and meaningful transition into adult care.

189 Standardized treatment of pulmonary exacerbation (STOP) study: Symptomatic treatment response

Objectives Pulmonary exacerbations (PEx) are common in patients with CF, but there are few studies evaluating symptomatic resolution with intravenous (IV) antibiotics. Careful delineation of symptomatic response could provide an important tool to future studies. Methods STOP is an observational study projected to enroll over 200 participants over 12 years old who are admitted to the hospital for treatment of a PEx. The CF Respiratory Symptom Diary-Chronic Respiratory Infection Symptom Scale (CFRSD-CRISS) was given to participants daily during the 28-day study. The CFRSD-CRISS is a validated unidimensional scale based on 8 items, with a total score ranging 0–100 (higher score indicates greater symptom severity). Prior analyses have suggested the responder criteria is 11.0 points. Results 204 patients (56% female) have entered the study. 112 subjects had completed diaries at admission, at end of treatment, and at day 28. The mean CFRSD-CRISS of these 112 patients was 48.7 (SD = 10.9) at the beginning of treatment, 21.7 (SD = 16) at the end of treatment, and 27.0 (15.5) at day 28. The mean and median time to lowest CFRSD-CRISS was 11.6 (SD = 6.1) days and 11.5 (95% CI: 10.0,13.0) days respectively. Ninety-six (85.7%) had a ≥11 point reduction at the end of treatment compared to 86 (76.8%) subjects by day 28 of the study. Conclusion While the study is still ongoing, clear treatment responses have been noted in the CFRSD-CRISS. A high percentage of these patients had experienced a clinically meaningful improvement in the CFRSD-CRISS by the end of treatment and to a lesser degree by day 28. Final analysis data will be presented. We thank the CFFT TDN. Funding: CFF.

ATS core curriculum 2015 Part I: Adult pulmonary medicine series editor: Carey Thomson

Gaëtane C. Michaud, Colleen L. Channick, Chad R. Marion, Robert M. Tighe, James A. Town, Andrew M. Luks, Jeremy B. Richards, Sucharita Kher, Prerna Mota, Gina Hong, Natalie E. West, Craig Rackley, Luke Neilans, Josanna Rodriguez-Lopez, Hilary DuBrock, Cassie C. Kennedy, Diana J. Kelm, and Carey C. Thomson Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut; Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, Washington; Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts; Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota; and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston, Massachusetts

Unmet needs in cystic fibrosis: the next steps in improving outcomes

ABSTRACT Introduction: Cystic fibrosis (CF) outcomes and survival have improved over the last century primarily due to advancements in antibiotics, nutritional, and pulmonary therapies. Reviewed here are the significant unmet needs that exist for individuals with CF. Areas covered: With the recent development of medications that address the underlying defect in the CF protein, there is hope that there will be continued improvement in CF outcomes. However, there remains a need to prevent or stop progression of CF-related complications, as the CF protein is important to several body systems. As end stage lung disease is the primary cause of mortality in CF, a need exists for advancements in pulmonary therapies to reduce time burden, identification of best practices for the treatment of pulmonary exacerbations, further development of anti-infective and anti-inflammatory therapies, and appropriately timed referral for lung transplantation at end-stage lung disease. Extra-pulmonary complications are increasingly recognized and better understanding of such problems as CF related liver disease is needed. Expert commentary: While CFTR modulators are available for the majority of CF patients, there remains a need for effective therapies to address infection, inflammation, irreversible lung disease, and extrapulmonary complications of CF.

F508del genotype in endoscopic sinus surgery: do differences in outcomes exist between genotypic subgroups?

The impact of endoscopic sinus surgery (ESS) on pulmonary function in cystic fibrosis (CF) patients with chronic rhinosinusitis remains unclear, as studies have demonstrated conflicting results. To date, no study has looked specifically at the impact of CF genotype on lung function after ESS. In this study, we reviewed changes in pulmonary function test (PFT) results after ESS in F508del homozygotes and heterozygotes.

WS07.1 Standardized treatment of pulmonary exacerbations (STOP) study: Treatment goals for pulmonary exacerbations

Objectives Pulmonary exacerbations (PEx) are common in individuals with CF, but there are no standard treatment recommendations. STOP collects information to define the primary endpoint for studies of treatment of PEx, and to access the feasibility for future trials to use the CF Foundation Patient Registry (CFFPR) for data capture. Methods STOP is an observational pilot study using the CFFPR and projected to enroll over 200 patients (age >12 years) at 10 sites admitted to the hospital for PEx treatment. A survey of admitting physicians was performed to ascertain treatment goals and physician willingness to enroll the patient in hypothetical interventional trials. Results After 12 months, 204 patients (56% female) have entered the study, with a mean age of 27.2±9.2 years and 53% homozygous F508del. The primary objective of treatment was recovery of lung function (53%) and improvement of symptoms (45%). The mean lung function recovery goal (target FEV1 – admission FEV1) was 13.7% predicted (range: 0–65.7%). For CF centers with a treatment protocol, the average planned treatment duration was 13.9±1.6 days. A majority of physicians were willing to enroll their patients in a trial of differing durations [10 days (71%) and 14 days (87%)], specified antibiotics (86%), and other treatments (83%), but less so for treatment of 7 days (30%). Conclusion The primary goals for treatment of PEx are recovery of lung function, targeting almost 14% recovery, and symptom improvement. Most sites express willingness to enroll patients into interventional trials of treatments. Early experience suggests the CFFPR can be used successfully for clinical trials. Supported by CFFT.