Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Comparison of remission and low disease activity states with DAPSA, MDA and VLDA in a clinical trial setting in psoriatic arthritis patients: 2-year results from the FUTURE 2 study.

OBJECTIVES: Remission (REM) or low disease activity (LDA) states were compared in a clinical trial setting of the FUTURE 2 study (NCT01752634) using Disease Activity Index for Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) composite indices in secukinumab treated PsA patients. METHODS: The proportion of patients reaching DAPSA-REM (cut-off ≤4) or REM+LDA (≤14), and very low disease activity (VLDA; achieving 7/7 criteria) or MDA (≥5/7), were compared in the overall population, by prior use of anti-TNF therapy, and by time since diagnosis using as observed data. The proportion of patients who met individual core component and other variables of interest were also computed to assess residual disease activity in DAPSA-REM/REM+LDA states and VLDA/MDA responses. The relationship between DAPSA/MDA and patient reported outcomes (PROs), including health-related quality of life, physical function, and fatigue were assessed using mixed model for repeated measures. RESULTS: More patients could achieve DAPSA-REM or DAPSA-REM+LDA status than VLDA or MDA responses, respectively, at all the time points in the overall population, irrespective of anti‒TNF status and time since diagnosis. Higher proportion of patients reaching DAPSA-REM or VLDA achieved more thresholds of core components (joints, pain, patient and physician global assessments, and function) than DAPSA-REM+LDA or MDA over Week 104. There were differences with numerically higher proportion of patients achieving patient global assessment ≤10 mm and ≤20 mm, and physician global assessment ≤10 mm with MDA than with DAPSA-REM+LDA, and patient pain VAS ≤15 mm, PASI ≤1, HAQ ≤0.5 with VLDA or MDA than with DAPSA-REM or DAPSA-REM+LDA, respectively, through 104 weeks. Improvements in PROs were significantly better for patients in DAPSA-REM+LDA versus DAPSA-moderate+high disease activity status, and for MDA responders versus non-responders. CONCLUSION: These analysis add to the evidence that both DAPSA and MDA composite index measures can be used for evaluation of the status and treatment response utilizing a treat to target approach in PsA patients in a clinical trial setting and improve patient health related outcomes. FUNDING: The study and analysis was funded by Novartis Pharma AG, Basel, Switzerland.

Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies.

BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. METHOD: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. RESULTS: A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3-6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. CONCLUSION: Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. TRIAL REGISTRATION: FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013).

Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial.

BACKGROUND: The ELIANA trial showed that 61 (81%) of 75 paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia achieved overall remission after treatment with tisagenlecleucel, a chimeric antigen receptor targeted against the CD19 antigen. We aimed to evaluate patient-reported quality of life in these patients before and after tisagenlecleucel infusion. METHODS: ELIANA, a global, single-arm, open-label, phase 2 trial, was done in 25 hospitals across Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Norway, Spain, and the USA. Patients with B-cell acute lymphoblastic leukaemia aged at least 3 years at the time of screening and 21 years or younger at the time of initial diagnosis who were in second or greater bone marrow relapse, chemorefractory, relapsed after allogeneic stem-cell transplantation, or were otherwise ineligible for allogeneic stem-cell transplantation were enrolled. Patients received a single intravenous administration of a target dose of 0·2-5 × 106 transduced viable T cells per kg for patients weighing 50 kg or less or 0·1-2·5 × 108 transduced viable T cells for patients weighing more than 50 kg. The primary outcome, reported previously, was the proportion of patients who achieved remission. A prespecified secondary endpoint, reported here, was patient-reported quality of life measured with the Pediatric Quality of Life Inventory (PedsQL) and European Quality of Life-5 Dimensions questionnaire (EQ-5D). Patients completed the questionnaires at baseline, day 28, and months 3, 6, 9, and 12 after treatment. The data collected were summarised using descriptive statistics and post-hoc mixed models for repeated measures. Change from baseline response profiles were illustrated with cumulative distribution function plots. The proportion of patients achieving the minimal clinically important difference and normative mean value were reported. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT02435849. FINDINGS: Between April 8, 2015, and April 25, 2017, 107 patients were screened, 92 were enrolled, and 75 received tisagenlecleucel. 58 patients aged 8-23 years were included in the analysis of quality of life. At baseline, 50 (86%) patients had completed the PedsQL questionnaire and 48 (83%) had completed the EQ-5D VAS. Improvements in patient-reported quality-of-life scores were observed for all measures at month 3 after tisagenlecleucel infusion (mean change from baseline to month 3 was 13·3 [95% CI 8·9-17·6] for the PedsQL total score and 16·8 [9·4-24·3] for the EQ-5D visual analogue scale). 30 (81%) of 37 patients achieved the minimal clinically important difference at month 3 for the PedsQL total score and 24 (67%) of 36 patients achieved this for the EQ-5D visual analogue scale. INTERPRETATION: These findings, along with the activity and safety results of ELIANA, suggest a favourable benefit-risk profile of tisagenlecleucel in the treatment of paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. FUNDING: Novartis.

Adding 3D automated breast ultrasound to mammography screening in women with heterogeneously and extremely dense breasts: Report from a hospital-based, high-volume, single-center breast cancer screening program.

PURPOSE: The aim of this study was to evaluate the impact of the 3D automated breast ultrasound (3D ABUS) when added to full field digital screening mammography (FFDSM), on breast cancer detection and recall rates in asymptomatic women with dense breasts examined in a high-volume breast cancer screening mammography center. METHODS AND MATERIAL: 1668 asymptomatic women, age 40-74 years, with heterogeneously dense parenchyma (ACR3) or extremely dense breast (ACR4) were included in the study. FFDSM was performed using standard craniocaudal (CC) and mediolateral oblique (MLO) views followed by anteroposterior (AP); lateral (LAT) and medial (MED) acquisitions of 3D ABUS in both breasts. All mammograms were double read by two dedicated breast radiologists. The 3D ABUS was read by the first radiologist immediately after reading the mammograms. The second reader looked at the 3D ABUS only if there was a need for consensus discussion because of unclear or abnormal mammograms or 3D ABUS. RESULTS: The combined FFDSM and 3D ABUS generated a total of 6.6 cancers per 1000 women screened (95% CI: 3.0, 10.2; p<0.001) compared with 4.2 cancers per 1000 women screened (95% CI) for FFDSM alone. The difference in yield was an additional 2.4 detected cancers per 1000 women screened (95% CI: 0.6, 4.8; p<0.001). The corresponding recall rate per 1000 women screened was 13.8 (95% CI: 9.0, 19.8) for FFDSM alone and 22.8 for combined FFDSM and ABUS (95% CI: 16.2, 30.0), yielding a difference of an additional 9.0 recalls per 1000 women screened (95% CI: 3.0, 15.0; p=0.004). CONCLUSION: The addition of 3D ABUS to FFDSM in women with ACR3 or ACR4 breast density significantly improved invasive breast cancer detection rate with an acceptable recall increase.

Antibiotic treatment of signs and symptoms of pulmonary exacerbations: a comparison by care site.

BACKGROUND: Antibiotic treatment of cystic fibrosis pulmonary exacerbations is inconsistent. Previous research has indicated that intravenous antibiotics are used more frequently at sites with better pulmonary function but it is not clear under what circumstances they are prescribed. METHOD: Pediatric care sites enrolled in the Epidemiologic Study of Cystic Fibrosis were ranked by median FEV1 % predicted of children they followed. Reported presence of new signs and symptoms of a pulmonary exacerbation (PEx) and antibiotic treatment within 21 days were compared between those in the highest vs. those in the other quartiles, and adjusted for sociodemographic and clinical characteristics of patients. RESULT: Highest quartile sites had a total of 2,454 children eligible for this analysis; lower quartile sites had a total of 5,487. The odds of having a PEx at highest vs. lower sites varied with how the PEx was defined, but high quartile sites were uniformly more likely to treat PEx with antibiotics. The adjusted odds ratio for treatment with any antibiotics of a PEx defined by the occurrence of one or two new signs and symptoms was 1.24 (95% CI 1.10, 1.40); for treatment of a PEx defined by the occurrence of three or four new signs and symptoms was 1.50 (95% CI 1.06, 2.11); and for treatment of a PEx defined by a drop of FEV(1) by ≥-15% was 1.33 (1.10, 1.60). The adjusted OR for treatment of these PEx with IV antibiotics was 1.11 (0.94, 1.32), 1.90 (1.32, 2.72), and 1.33 (1.10, 1.60), respectively. CONCLUSION: ESCF care sites in the highest quartile for FEV(1) were more likely to prescribe antibiotics when patients present with either mild or overt evidence of PEx. While this may not be the only reason that their patients have superior median FEV(1), it is likely an important contributor.

Oral, inhaled, and intravenous antibiotic choice for treating pulmonary exacerbations in cystic fibrosis.

RATIONALE: Patients with cystic fibrosis (CF) experience frequent pulmonary exacerbations (PExs). Clinicians manage these episodes of worsening signs and symptoms in a variety of ways. OBJECTIVES: To characterize the antibiotic management and associated change in lung function following PExs. METHODS: We used 2003-2005 data from the Epidemiologic Study of Cystic Fibrosis to examine antibiotic treatment and the immediate and long-term lung function change associated with clinician reported PExs. RESULTS: A total of 45,374 PExs were reported in 13,194 unique patients. Most PExs (73%) were treated with oral antibiotics, while 39% were treated IV and 24% were treated with inhaled antibiotics. The likelihood of non-IV versus IV antibiotic treatment was associated with the patient's age, stage of lung disease, and magnitude of lung function drop prior to the PEx. Following treatment, the average improvement in the FEV1 was 3.4 ± 12.2% predicted with a greater (5.1 ± 12.7% predicted) improvement following IV antibiotic treatment than with non-IV treatment (2.0 ± 11.6% predicted). When the best FEV1 from the year before was compared with 180 days following the PEx there was an average fall of 3.8 ± 10.5% predicted with little difference observed between antibiotic treatment routes. Patients with only one exacerbation during the 3-year study had a similar loss of lung function to patients with no reported exacerbations. CONCLUSION: Clinicians treat the majority of PExs with oral antibiotics, particularly in younger, healthier patients. Pulmonary function improves with antibiotic therapy, however, PExs are associated with lung function deterioration over time.

Risk factors for rate of decline in FEV1 in adults with cystic fibrosis.

BACKGROUND: Previously we assessed risk factors for FEV(1) decline in children and adolescents using the Epidemiologic Study of Cystic Fibrosis (J Pediatr 2007;151:134-139); the current study assessed risk factors in adults. METHODS: Risk factors for FEV(1) decline over 3-5.5 years for ages 18-24 and ≥25 years were assessed using mixed-model regression. RESULTS: Mean rates of FEV(1) decline (% predicted/year) were -1.92 for ages 18-24y (n=2793) and -1.45 for ages ≥25y (n=1368). For the 18-24y group, B. cepacia, pancreatic enzyme use, multidrug-resistant P. aeruginosa, cough, mucoid P. aeruginosa, and female sex predicted greater decline; low baseline FEV(1) and sinusitis predicted less decline. For the ≥25y group, only pancreatic enzyme use predicted greater decline; low baseline FEV(1) and sinusitis predicted less decline. CONCLUSIONS: Risk factors for FEV(1) decline in adults <25 years are similar to those previously identified in children and adolescents; older adults had few statistically significant risk factors.

Multiple antibiotic-resistant Pseudomonas aeruginosa and lung function decline in patients with cystic fibrosis.

BACKGROUND: The goal of this study was to determine the association of multiple antibiotic-resistant Pseudomonas aeruginosa (MARPA) acquisition with lung function decline in patients with cystic fibrosis (CF). METHODS: Using data from Epidemiologic Study of Cystic Fibrosis (ESCF), we identified patients with spirometry data and MARPA, defined as PA (1) resistant to gentamicin and either tobramycin or amikacin, and (2) resistant to ≥1 antipseudomonal beta lactam. MARPA had to be detected in a respiratory culture after ≥2 years of PA-positive but MARPA-negative respiratory cultures. Multivariable piecewise linear regression was performed to model the annual rate of decline in forced expiratory volume in 1 second (FEV(1)) % predicted 2 calendar years before and after the index year of MARPA detection, adjusting for patient characteristics and CF therapies. RESULTS: In total, 4349 patients with chronic PA and adequate PFT data were identified; 1111 subsequently developed MARPA, while 3238 patients were PA positive but MARPA negative. Compared with patients who did not acquire MARPA, MARPA-positive patients had lower FEV(1) and received more oral (p<0.013) and inhaled (p<0.001) antibiotic therapy. Mean FEV(1) decline did not change significantly after MARPA detection (-2.22% predicted/year before detection and -2.43 after, p=0.45). There was no relationship between persistent infection or FEV(1) quartile and FEV(1) decline. CONCLUSIONS: Newly detected MARPA was not associated with a significant change in the rate of FEV(1) decline. These results suggest that MARPA is more likely to be a marker of more severe disease and more intensive therapy, and less likely to be contributing independently to more rapid lung function decline.

Erratum to: Psychometric evaluation of the Cystic Fibrosis Questionnaire-Revised in a national, US sample.

PURPOSE: The psychometric properties of a health-related quality of life (HRQOL) instrument, the Cystic Fibrosis Questionnaire-Revised (CFQ-R), were evaluated in a national, US sample of patients with cystic fibrosis (CF). This is the first psychometric evaluation of the revised version of this instrument. METHODS: The Epidemiologic Study of CF is a national, US multicenter longitudinal cohort study containing CFQ-R and health outcomes data. Developmentally appropriate versions of the CFQ-R were available from 7,330 patients aged 6-70 years and a proxy version from 2,728 parents of school-age children. The CFQ-R was completed during a "stable" or "sick" visit before recording health outcomes such as weight, lung function, and pulmonary exacerbations. RESULTS: There were few floor and ceiling effects and strong internal consistency (Cronbach alpha ≥0.70) for most scales. The CFQ-R consistently discriminated between patients seen for sick-versus-well visits, and among stages of disease severity based on lung function. As predicted, women with CF reported worse HRQOL than men on scales not related to body image and weight. Strong parent-child agreement was found on scales measuring observable behaviors (respiratory symptoms). Convergence between CFQ-R scales and health outcomes provided evidence of construct validity. CONCLUSIONS: The CFQ-R demonstrated robust psychometric properties and consistent associations with health outcomes in a large national, US sample. Normative data are available to aid in interpretation.

Psychometric evaluation of the Cystic Fibrosis Questionnaire-Revised in a national sample.

PURPOSE: The psychometric properties of a health-related quality of life (HRQOL) instrument, the Cystic Fibrosis Questionnaire-Revised (CFQ-R), were evaluated in a national sample of patients with cystic fibrosis (CF). METHODS: The Epidemiologic Study of CF is a national, multicenter, longitudinal cohort study containing CFQ-R and health outcomes data. Developmentally appropriate versions of the CFQ-R were available from 7,330 patients aged 6-70 years and a proxy version from 2,728 parents of school-age children. The CFQ-R was completed during a "stable" or "sick" visit before recording health outcomes such as weight, lung function, and pulmonary exacerbations. RESULTS: There were few floor and ceiling effects and strong internal consistency (Cronbach alpha ≥0.70) for most scales. The CFQ-R consistently discriminated between patients seen for sick-versus-well visits, and among stages of disease severity based on lung function. As predicted, women with CF reported worse HRQOL than men on scales not related to body image and weight. Strong parent-child agreement was found on scales measuring observable behaviors (respiratory symptoms). Convergence between CFQ-R scales and health outcomes provided evidence of construct validity. CONCLUSIONS: The CFQ-R demonstrated robust psychometric properties and consistent associations with health outcomes in a large national sample.

Longitudinal assessment of health-related quality of life in an observational cohort of patients with cystic fibrosis.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly used to evaluate the efficacy of new treatments and the progression of chronic diseases. The Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a disease-specific, PRO measure of health-related quality of life (HRQOL). We evaluated associations between changes in health status over time and HRQOL in a national CF database. METHODS: Using the Epidemiologic Study of Cystic Fibrosis (ESCF) data, we identified participants who had completed age-appropriate CFQ-R assessments on two occasions separated by 9-15 months. Next, we developed multivariate regression models to test whether associations existed between (1) changes in respiratory signs/symptoms and changes in the respiratory health domains of the CFQ-R, (2) changes in nutritional health status and changes in the nutritional health domains of the CFQ-R, and (3) changes in treatment complexity and changes in the Treatment Burden scale of the CFQ-R. RESULTS: We analyzed 1,947 pairs of assessments: 337 child (mean age 8.9, range 6-13 years), 581 parent (mean age of child 8.8, range 6-13 years), 398 adolescent (mean age 15.3, range 14-17 years), and 631 adult (mean age 26.9, range 18-73 years). On average, we found little change in both health status indicators and CFQ-R domain scores over 1 year. Significant associations over time, however, were found between increases in respiratory symptoms and worse CFQ-R Respiratory Symptom scores, declining weight and worsening scores on CFQ-R nutritional health domains, and increases in treatment complexity and worsening CFQ-R Treatment Burden scores for parent respondents. CONCLUSION: Health status and HRQOL changes were small over a 1-year period in this CF population. However, changes in respiratory symptoms and weight were associated with significant changes on relevant CFQ-R scores, indicating that this PRO is sensitive to changes in health status over time.

Trends in the use of routine therapies in cystic fibrosis: 1995-2005.

Many therapies are used to treat manifestations of cystic fibrosis (CF). Trends in routine therapy use in Epidemiologic Study of Cystic Fibrosis patients were studied from 1995 to 2005. Patients (15,087) were assessed in 1995; 12,778 in 2005. Observed differences in therapy use of ≥2% were statistically significant at P < 0.001. Comparing the 1995 and 2005 populations, mean age was 13.9 versus 15.5 years; weight-for-age percentile was 30.3 versus 36.9; and mean forced expiratory volume in 1 sec (FEV(1)) was 73.7% (n = 7065) versus 78.7% (n = 7867) predicted. Use of several therapies increased, including airway clearance (69.9-89.6%), inhaled bronchodilators (72.0-84.0%), dornase alfa (44.8-67.2%), inhaled corticosteroids (16.0-49.3%), inhaled antibiotics (6.5-43.1%), oral nutritional supplements (18.3-24.5%), and insulin/oral hypoglycemic agents (4.9-10.2%). Use of mast cell stabilizers (from 22.0% to 5.3%) and oral bronchodilators (from 10.4% to 1.5%) decreased. Less dramatic changes occurred for pancreatic enzymes (92.6-91.0%), oral nonquinolone antibiotics (44.7-39.8%), oral corticosteroids (7.8-5.2%), mucolytics (4.4-2.5%), NSAIDs/high-dose ibuprofen (3.6-3.3%), enteral nutrition (5.2% vs. 8.2%), and oxygen (4.7-4.5%). Therapies not tracked in 1995 were evident in 2005, including oral macrolide antibiotics (33.8%), leukotriene inhibitors/antagonists (10.8%), and inhaled hypertonic saline (2.6%). Routine therapies were generally used more often by older patients and those with lower FEV(1). Notable increases in use of therapies, particularly of inhaled therapies, suggest that overall patient treatment burden must have risen correspondingly.

Impact of socioeconomic status, race, and ethnicity on quality of life in patients with cystic fibrosis in the United States.

BACKGROUND: Patient-reported outcomes are increasingly used in clinical trials to assess the natural history of chronic diseases and the efficacy of new treatments. Understanding the effects of socioeconomic and minority status on health-related quality of life (HRQOL) will facilitate interpretation of the results of clinical trials and suggest targets for interventions to improve patient care and outcomes. The objective of this study was to examine the effects of socioeconomic and minority status on HRQOL in patients with cystic fibrosis (CF) from childhood through adulthood in a large, comprehensive database containing medical and HRQOL data for patients with CF. METHODS: A cross-sectional study was performed using data obtained from the Epidemiologic Study of Cystic Fibrosis on 4,751 patients and 1,826 parents who were non-Hispanic white, African-American, or Hispanic and who completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a disease-specific HRQOL measure, during a stable clinic visit. RESULTS: Multivariate models assessed the main effects of socioeconomic and minority status on clinical and HRQOL outcomes. Regression models that controlled for disease severity identified the contributions of these two variables to HRQOL. Low socioeconomic status was associated with significantly lower CFQ-R scores for children, parents, and adults on the majority of domains. After controlling for disease severity and socioeconomic status, African-American and Hispanic patients reported worse emotional and social functioning. CONCLUSIONS: Low socioeconomic and minority status may affect important clinical and patient-reported outcomes for patients with CF across their life span.

The impact of incident methicillin resistant Staphylococcus aureus detection on pulmonary function in cystic fibrosis.

The incidence of methicillin resistant Staphylococcus aureus (MRSA) infection is increasing in cystic fibrosis (CF), but the impact of MRSA detection on clinical outcomes is unclear. Our objective was to determine whether incident detection of MRSA is associated with a change in pulmonary function over time in CF patients. We analyzed data from the Epidemiologic Study of Cystic Fibrosis (ESCF), a prospective observational study of CF patients in North America. Multivariable piecewise linear regression was used to model the impact of incident detection of MRSA on pulmonary function over time, measured by percent predicted forced expiratory volume in one second (FEV(1)% predicted), adjusting for potential confounders. There were 5,090 patients >or=6 years old who were MRSA negative for at least 2 calendar years. Five hundred ninety-three (12%) of these patients acquired MRSA during the years 2001-2003, with detection rates of MRSA during those years rising from 4.4% to 6.9%. MRSA positive patients had a lower FEV(1)% predicted and received more antibiotic and other therapies than patients who remained MRSA negative. After adjusting for antibiotic therapy and other potential confounders, MRSA positive patients also had a higher rate of decline in FEV(1)% predicted both before and after the incident culture, although the rate of FEV(1)% predicted decline did not change significantly after MRSA detection. In conclusion, although MRSA in CF was a marker for more aggressive therapy and may reflect increased disease severity, incident MRSA detection was not associated with a changing rate of FEV(1)% predicted decline.

Relationship between inhaled corticosteroid therapy and rate of lung function decline in children with cystic fibrosis.

OBJECTIVE: To assess the relationship between inhaled corticosteroids (ICS) use and lung function decline in children with cystic fibrosis (CF) using the Epidemiologic Study of Cystic Fibrosis, an observational study of patients with CF in North America. STUDY DESIGN: We analyzed data from 2978 patients 6 to 17 years old enrolled in ESCF between 1994 to 2004. We estimated the rate of decline in forced expiratory volume in 1 second (FEV(1)) before and after starting ICS therapy with a piecewise linear continuous single change point model, adjusting for potentially confounding covariates. RESULTS: Before initiation of ICS, mean FEV(1) decline was -1.52% predicted/year (95% CI: -1.96 to -1.08% predicted/year). After initiation of ICS therapy, mean FEV(1) decline was -0.44% predicted/year (95% CI: -0.85 to -0.03% predicted/year), which was a significant change (P = .002). ICS use was associated with decreased height for age Z scores and increased insulin/oral hypoglycemic use. CONCLUSIONS: In this retrospective analysis of prospectively collected data, ICS therapy in patients with CF was associated with a significant reduction in the rate of FEV(1) decline, decreased linear growth, and increased insulin/oral hypoglycemic use.

Trends in the clinical characteristics of the U.S. cystic fibrosis patient population from 1995 to 2005.

RATIONALE: Respiratory signs and symptoms (cough, sputum production, or crackles) are considered bellwethers of underlying cystic fibrosis (CF) lung disease. If respiratory signs and symptoms predict future lung function loss, then improvements in population lung function over the past decade should have been paralleled by a decrease in the prevalence of these variables in the same population. Additionally, changes in these variables over the past decade may provide insight into the improving health of the CF population. METHODS: Cross-sectional data from the Epidemiologic Study of Cystic Fibrosis for each year between 1995 and 2005 were analyzed to characterize changes in pulmonary function and respiratory signs and symptoms over time. Patients were separated into five age groups: <6, 6-12, 13-17, 18-24, and >or=25 years. RESULTS: Serial cross-sectional analyses of an average of 13,381 patients per year indicated that mean pulmonary function for the CF population improved and the percent of patients reporting cough or sputum production or having crackles or wheeze at their clinic visit decreased over the study period. Observed changes in pulmonary function were not consistently mirrored by changes in symptoms, which differed as a function of the variable studied and the age group. CONCLUSIONS: Reductions in respiratory signs and symptoms have paralleled improvements in pulmonary function. Both the absolute and relative magnitude of changes in prevalence for cough, sputum production, crackles, and wheeze differed among age groups and among variables. These results suggest the possibility that differences in respiratory signs and symptoms may arise from different underlying pathologies and may be influenced differently by therapeutic interventions.

Risk factors associated with persistent airflow limitation in severe or difficult-to-treat asthma: insights from the TENOR study.

BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study is among the largest to assess persistent airflow limitation and the first to evaluate a wide range of potential risk factors in high-risk patients with severe or difficult-to-treat asthma. A better understanding is needed regarding factors associated with persistent airway obstruction; this study was performed to determine demographic and clinical characteristics associated with persistent airflow limitation. METHODS: Data from adult patients (>or= 18 years old) with severe or difficult-to-treat asthma were evaluated. Patients with COPD, obesity with a restrictive respiratory pattern, or a >or= 30 pack-year history of smoking were excluded. Patients with persistent airflow limitation (postbronchodilator FEV1/FVC ratio