Epidemiologic Study Of Cystic Fibrosis Research Articles

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

BackgroundThe 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). MethodsUsing 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 ≥2years 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 1second (FEV1) % predicted 2 calendar years before and after the index year of MARPA detection, adjusting for patient characteristics and CF therapies. ResultsIn 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 FEV1 and received more oral (p<0.013) and inhaled (p<0.001) antibiotic therapy. Mean FEV1 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 FEV1 quartile and FEV1 decline. ConclusionsNewly detected MARPA was not associated with a significant change in the rate of FEV1 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.

Risk factors for onset of persistent respiratory symptoms in children with cystic fibrosis

To characterize the onset of persistent signs and symptoms of cystic fibrosis (CF) lung disease and identify characteristics that predict onset. Patients in the Epidemiologic Study of CF who were <4 years of age at enrollment and had ≥2 years of follow-up were included. We defined persistence as a sign or symptom that was present during two consecutive encounters separated by 60-365 days, and persistent clubbing as ≥50% of encounters with clubbing within 365 days. Predictors were assessed in a Cox proportional hazards model for age at first occurrence of each symptom. Each sign or symptom met the criterion of persistence in a substantial proportion of patients during a follow-up period of 7 ± 3 years (mean ± SD; range 2-12). Risk factors that predicted earlier onset of signs and symptoms included pancreatic enzyme use, Pseudomonas aeruginosa infection, and prior diagnosis of asthma. Other risk factors had variable effects on signs and symptoms. Signs and symptoms of lung disease begin early in CF. Risk factors previously reported for lower forced expiratory volume in 1 sec are also associated with earlier onset of persistent signs and symptoms of CF lung disease, but their impact varies.

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

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. 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. 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. 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.

PND67 A Mixed-Effects Piecewise Linear Model of the Rate of Lung Function Decline Before and After the Clinical Use of Dornase Alfa in an Observational Study of Cystic Fibrosis

To evaluate lung function decline before and after the initiation of dornase alfa (DA) through a multivariable mixed-effects piecewise linear model using data from the Epidemiologic Study of Cystic Fibrosis (ESCF). Patients aged 8-38 years enrolled in ESCF for 2 or more years prior to initial treatment with DA were selected if they remained on treatment for at least 2 years. A comparator group included cystic fibrosis patients not yet reported to have received DA. FEV1 percent predicted (pp) was analyzed before and after an index measurement within 30 days of either DA initiation (DA group) or an encounter within 1 year following the 8th or subsequent even-numbered birthday (comparator group). For each patient, we fit a regression line to FEV1 pp separately for the pre-index and post-index periods (both 2 years in duration) using a mixed-effects piecewise linear model adjusted for age, gender, pulmonary exacerbations, respiratory therapies, and nutritional supplements. Patients were categorized by age group or by age-adjusted deciles of the index FEV1 pp. The DA group (n=2,230) had a lower FEV1 pp at index and a more rapid decline during the pre-index period. There was an acute improvement in FEV1 pp (change in intercept) associated with the initiation of DA therapy. Furthermore, the mean rate of FEV1 pp decline was more attenuated for the DA group than for the comparator group (n=5,970) across age groups and deciles. The use of DA for a 2-year period is associated with both an acute improvement in FEV1 pp (previously shown in clinical trials) and a reduction in the rate of FEV1 pp decline (shown for the first time). These results demonstrate the value of using mixed-effects piecewise linear models in observational studies to evaluate the effect of instituting a therapy on both the slope and intercept of a continuous outcome.

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

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). 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. 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. The CFQ-R demonstrated robust psychometric properties and consistent associations with health outcomes in a large national sample.

Lung function decline from adolescence to young adulthood in cystic fibrosis

Despite improving survival in cystic fibrosis (CF) patients, there is a mortality peak in early adulthood. Defining risk factors that predict significant worsening of lung disease in young adulthood may identify opportunities to improve outcomes in adults. We identified 4,680 patients in the Epidemiologic Study of Cystic Fibrosis 1994-2005 with data in both adolescence (age 14.0-17.4 years) and young adulthood (age 18.5-22.0 years) and analyzed 2,267 who had ≥5 encounters and ≥5 measurements of forced expiratory volume in 1 second (FEV(1) ) spanning ≥1 year during both adolescence and young adulthood, and ≥1 encounter with weight and height and ≥1 FEV(1) measurement age 17.5-18.5 years. We compared the annualized rates of decline in FEV(1) during adolescence and young adulthood stratified by best FEV(1) around age 18. Logistic regression was used to identify risk factors associated with substantial decline (>20 points) in FEV(1) % predicted in young adulthood. Annual rate of decline was greater in young adulthood than in adolescence. Risk factors for substantial decline included slower rate of FEV(1) decline, greater FEV(1) variability, faster body mass index (BMI) decline, male sex, chronic inhaled antibiotics, Haemophilus influenzae detection, and absence of multidrug-resistant Pseudomonas aeruginosa in adolescence, and lower than expected FEV(1) and BMI around age 18. Decline in lung function accelerates in young adults with CF, especially in those with early stage lung disease. Adolescents at risk for substantial decline in lung function in young adulthood have higher FEV(1) and worse nutritional status, among other identifiable risk factors.

Clinical use of dornase alfa is associated with a slower rate of FEV1 decline in cystic fibrosis

Randomized controlled trials of dornase alpha have shown forced expiratory volume in 1 sec (FEV(1) ) to improve in patients with cystic fibrosis (CF) but have not assessed change in the rate of lung function decline. We assessed the relationship of dornase alpha use and FEV(1) decline using the Epidemiologic Study of Cystic Fibrosis (ESCF). Patients aged 8-38 years who had been enrolled in ESCF for 2 years when initially treated with dornase alpha were selected if they remained on treatment during the following 2 years. A comparator group included patients aged 8-38 who were not yet reported to have received dornase alpha. For each patient we estimated the annual rate of decline in FEV(1) % predicted before and after the index using a mixed-effects model adjusted for age, gender, pulmonary exacerbations, respiratory therapies, and nutritional supplements. The dornase alpha group (n = 2,230) had a lower FEV(1) % predicted at index and a more rapid decline during the pre-index period. The mean rate of FEV(1) decline improved for the dornase alpha group; the improvement was similar in adults and children 8-17 years old but was not statistically significant in adults. The comparator group (n = 5,970) showed no change among adults and an increased rate of decline among children 8-17 years old. The use of dornase alpha for a 2-year period is associated with a reduction in the rate of FEV(1) decline. These results also demonstrate the value of using an observational study to assess the association of instituting new therapies in the clinical setting with changes in the rate of FEV(1) decline in patients with CF.

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

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. 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. 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. 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.

Pulmonary outcome prediction (POP) tools for cystic fibrosis patients

Loss of lung function in patients with cystic fibrosis (CF) is associated with increased mortality and varies between individuals and over time. Predicting this decline could improve patient management. To develop simple pulmonary outcome prediction (POP) tools to estimate lung function at age 6 in patients aged 2-5 years (POP(2-5)) and lung function change over a 4-year period in patients aged 6-17 years (POP(6-17)). Analyses were conducted using patients from the Epidemiologic Study of CF (ESCF). To be included in any analysis, patients had to have 1 year of clinical history recorded in ESCF prior to a clinically stable routine Index Clinic Visit (ICV). In addition to this criterion, for the POP(2-5) tool patients had to be between 2 and 5 years old at ICV and have a second clinically stable visit with spirometric measures at age 6. For the POP(6-17) tool, patients had to be between the ages of 6 and 17 years old at an ICV that included spirometric measures and had to have a second clinically stable visit with spirometric measures from 3 to 5 years after ICV. All patients enrolled in ESCF who met these inclusion criteria were studied. POP(2-5) and POP(6-17) populations were further divided into development groups (with ICV before January 1, 1998) and validation groups (with ICV after that date). Development groups were used to model forced expiratory volume in 1 sec (FEV(1)) percent predicted at age 6 years (for POP(2-5)) and annualized FEV(1) % predicted change from ICV to the second visit (for POP(6-17)) by multivariable linear regression using age, sex, weight-for-age percentile, cough, sputum production, clubbing, crackles, wheeze, sinusitis, number of exacerbations requiring intravenous antibiotics in the past year, elevated liver enzymes, pancreatic enzyme use, and respiratory tract culture status, plus height-for-age percentile (POP(2-5)) and index FEV(1) (POP(6-17)). Integer-based POP(2-5) and POP(6-17) tools created from selected variables were evaluated by Pearson correlation and then prospectively validated with separate data collected later from ESCF patients with ICV after January 1, 1998. POP(2-5) and POP(6-17) development groups included 2,709 and 6,113 patients and validation groups included 3,458 and 7,086 patients, respectively. Variables retained were weight-for-age percentile, clubbing, crackles, wheeze, number of exacerbations, and Pseudomonas aeruginosa culture status (both tools), daily cough (POP(2-5)), and age, sex, and index FEV(1) % predicted (POP(6-17)). Correlation coefficients for POP(2-5) and POP(6-17) tools prospectively applied to validation groups were +0.32 and +0.37, respectively. These simple integer-based POP algorithms employ variables available at clinic visits and can be used to predict the probability of different future pulmonary outcomes for individual patients and patient populations.

Year-to-year changes in lung function in individuals with cystic fibrosis

Background We examined the year-to-year change in FEV 1 for individuals and the overall cystic fibrosis population to better understand how individual trends may differ from population trends. Methods We calculated individual yearly changes using the largest annual FEV 1 percent predicted (FEV 1%) measurement in 20,644 patients (6–45 years old) included in the Epidemiologic Study of Cystic Fibrosis. We calculated yearly population changes using age-specific medians. Results FEV 1% predicted decreased 1–3 points per year for individuals, with maximal decreases in 14–15 year olds. Population changes agreed with individual changes up to age 15; however after age 30, yearly population change approximated zero while individual FEV 1% predicted decreases were 1–2 points per year. Conclusions Adolescents have the greatest FEV 1% predicted decreases; however, loss of FEV 1 is a persistent risk in 6–45 year old CF patients. Recognizing individual year-to-year changes may improve patient-specific care and may suggest new methods for measuring program quality.

Impact of Socioeconomic Status, Race, and Ethnicity on Quality of Life in Patients With Cystic Fibrosis in the United States

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. 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. 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. Low socioeconomic and minority status may affect important clinical and patient-reported outcomes for patients with CF across their life span.

Association of Socioeconomic Status with the Use of Chronic Therapies and Healthcare Utilization in Children with Cystic Fibrosis

To determine whether previously reported socioeconomic status (SES)-related disparities in cystic fibrosis (CF) health outcomes vary by the indicator used (median household income by zip code [MIZ], maternal educational attainment [MEA], and state insurance coverage [MA]), and whether these disparities can be explained by differences in medical treatment. A cross-sectional analysis of data on patients age <18 years from the Epidemiologic Study of Cystic Fibrosis (ESCF). Disease severity showed a similar inverse correlation with all 3 SES measures. The number of stable clinic visits was unrelated to SES. Patients with MA had more sick outpatient visits and more courses of intravenous (IV) antibiotics for pulmonary exacerbations, and were more likely to be prescribed all chronic therapies. Low-MIZ patients had slightly fewer sick visits and more courses of IV antibiotics, and were more likely to receive oral nutrition supplements but less likely to receive macrolide prescriptions. Low-MEA patients were less likely to receive IV antibiotics at home, more likely to receive oral nutrition supplements, but less likely to receive macrolide prescriptions. CF health outcomes are correlated with the SES spectrum, but these disparities are not explained by differential use of health services or prescription of chronic therapy. Future investigations should focus on the possible impact of environmental exposures and differences in disease self-management.

Patient registries for cystic fibrosis: New answers to old questions but are they definitive?

There has been a long standing controversy concerning the efficacy of inhaled steroids for cystic fibrosis lung disease because earlier studies yielded conflicting results. In this issue of The Journal, the data from the Epidemiologic Study of Cystic Fibrosis were studied by Ren et al using multivariate analysis. Their results show that initiation of inhaled corticosteroids was associated with a significant reduction in the rate of fall of FEV1. However, the therapy was also associated with decreased linear growth and increased use of hypoglycemic agents. McPhail et al from Cincinnati Children's Hospital Medical Center performed a single center analysis of outcomes in two 7-year birth cohorts. The later cohort (1993-2000) had significantly improved lung function, a slower rate of decline in lung function, and improved nutrition. Better lung function was associated with good nutrition, absence of chronic Pseudomonas aeruginosa pulmonary infection, and starting dornase alfa aerosols before age 9 years. These studies are discussed in a related editorial by Schechter of Emory University, who emphasizes the use of disease registries for evaluating clinical effectiveness and the safety of new therapies. While acknowledging their value, he also points out the limitations of observational studies which, in general, should lead to caution with the interpretation of results.

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

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. 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. 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. 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.

Shifting patterns of inhaled antibiotic use in cystic fibrosis

Antibiotic inhalation has become widely accepted as a standard treatment for cystic fibrosis (CF) airway infection. We assessed the prevalence and context of inhaled antibiotic use in the North American CF population. Our working hypothesis was that a shift from acute to chronic use of inhaled antibiotics has coincided with increased prevalence of use among CF patients. Descriptive statistics were collected for 30,833 patients enrolled in the Epidemiologic Study of CF (ESCF) during 1996 through 2005. A multivariate analysis was performed on data from a subgroup of 18,021 patients enrolled in ESCF during 2003 through 2005. The prevalence of inhaled antibiotic use in the North American CF population increased during 1996 through 2005 due to increased chronic use, while acute use to treat pulmonary exacerbations decreased. In 2005, 50% of CF patients used inhaled tobramycin and 9% used inhaled colistin chronically; most of the latter used both agents concurrently. Airway obstruction severity and airway infection status were predictors of inhaled antibiotic use. Increased chronic use and decreased acute use of inhaled antibiotics presumably reflect a shift toward more proactive management of airway infections in the North American CF population. The effects of these usage patterns on long-term clinical outcomes and emergence of antibiotic-resistant Pseudomonas aeruginosa strains warrant further study.

Dornase alfa and progression of lung disease in cystic fibrosis

Obstruction, infection, and inflammation lead to progressive and irreversible lung destruction in cystic fibrosis (CF). Neutrophil-derived DNA contributes to thick, viscous secretions. Dornase alfa hydrolyzes DNA, reducing the viscosity of CF sputum. Clinical trials have shown that dornase alfa improves forced expiratory volume in one second (FEV1). Immediate improvement is important, but long term survival requires slowing the rate of lung function decline. Demonstrating changes in rate of decline requires long term studies with many patients, which are impractical for clinical trials. Observational studies such as the Epidemiologic Study of Cystic Fibrosis (ESCF) can address rate of decline in lung function, and is being used to evaluate the long-term effectiveness of dornase alfa. CF patients age 8–38 years when initially treated with dornase alfa (index event) were compared to patients not treated (for 2 years before and 2 years after index). In a preliminary analysis, FEV1 at index for the dornase alfa group (n = 2,706) was 80.5% predicted, and for the comparator group (n = 3,991) 86.7% predicted. The estimated rate of FEV1 decline before index for the dornase alfa group was −2.81 and for the comparator group −0.85% predicted/year. After index, the rate of decline for the dornase alfa group was −1.53% predicted/year (46% reduction, P < 0.001), with no change in the comparator group. These preliminary results suggest that initiating dornase alfa is associated with both an acute improvement in FEV1 and a slowing of the rate of FEV1 decline. Analysis is ongoing to further evaluate this association. Pediatr Pulmonol. 2008; 43:S24–S28. © 2008 Wiley-Liss, Inc.

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

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. 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. 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. 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.

Presence of methicillin resistant Staphylococcus aureus in respiratory cultures from cystic fibrosis patients is associated with lower lung function

The prevalence of methicillin resistant Staphylococcus aureus (MRSA) infections is increasing in both the general population and cystic fibrosis (CF) patients. We hypothesized that MRSA infection of the conductive airways as seen in CF would be associated with more severe disease than that seen with methicillin sensitive S. aureus (MSSA). To test this hypothesis, we used data from the Epidemiologic Study of Cystic Fibrosis (ESCF), a large observational study of CF patients in North America, to compare CF patients with MRSA in their respiratory tract cultures to those with MSSA. During a 1-year time period from January 1, 2001 to December 31, 2001, data from 20,451 patients were collected by the ESCF, and 1,834 (7.5%) patients had respiratory tract cultures that were positive for S. aureus only. Compared to patients with MSSA only, patients with MRSA only had significantly more airflow obstruction, as measured by forced expiratory volume in 1 sec (FEV1). The mean FEV1 for patients 6-17 years old with MRSA was 80.7% predicted compared to 89.4% in the MSSA group (P<0.001). The likelihood of hospitalization and treatment with oral, inhaled, and intravenous antibiotics were all significantly increased in patients with MRSA compared to those with MSSA. Similar results were seen in patients >or=18 years old. The results of our study highlight the growing clinical impact of MRSA infections in CF patients.

Impact of Pregnancy on Women With Cystic Fibrosis

Improvements in the health and survival of patients with cystic fibrosis (CF) have led to increasingly normal lifestyles, including successful pregnancies in women with CF. Concern exists among care providers about the impact of pregnancy on the health of women with CF. We examined data from a large longitudinal observational study, the Epidemiologic Study of Cystic Fibrosis (ESCF), to characterize health outcomes and CF-related therapies in women who became pregnant. This analysis was conducted using ESCF data from 1995 to 2003. A total of 216 women, aged 15 to 38 years, who met the criteria for a qualifying pregnancy, were compared with a matched group of never-pregnant women during three time periods (ie, baseline, during pregnancy, and follow-up). None. The baseline pulmonary function (FEV(1)) values were 74.5% and 66.4% predicted, respectively, in the pregnant and nonpregnant women. Declines in FEV(1) values of 6.8% and 4.7%, respectively, were observed from baseline to follow-up in the pregnant and nonpregnant women (p = 0.61). During pregnancy, outpatient visits were 33% more frequent compared to baseline and 62% more frequent than in the nonpregnant group (7.19 vs 4.45, respectively, visits annually). Annual rates of respiratory exacerbation and hospitalization were similar at baseline but increased during pregnancy. The prevalence of treatment for diabetes more than doubled, from 9.3% at baseline to 20.6% during pregnancy, and was 14.4% at follow-up. In contrast, 18.7% of the never-pregnant women were being treated for diabetes at baseline, rising to 25.2% at follow-up. These findings suggest that, over the same time period, women with CF who become pregnant experienced similar respiratory and health trends as nonpregnant women. However, pregnant women use a greater number of therapies and receive more intense monitoring of their health. These findings have implications for clinicians providing prepregnancy counseling for women with CF.