Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada.

Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.

Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific Advisory Group, Investigators, and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

OBJECTIVES: Using the large database from the Epidemiologic Study of Cystic Fibrosis (ESCF), the objectives of this study were to (1) estimate the reported prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF); (2) compare reported prevalence rates across geographic regions; (3) compare reported prevalence rates between patient subgroups based on demographic and disease characteristics; and (4) describe the ABPA group with regard to their sex, age, and disease severity. STUDY DESIGN: All patients > or = 5 years of age enrolled in ESCF between December 1993 and May 1996 were eligible. Criteria for the diagnosis of ABPA were defined by the ESCF guidelines. Prevalence rates for ABPA were calculated, and potential risk factors for the diagnosis of ABPA were analyzed, including sex, age, pulmonary function, diagnosis of asthma, presence of wheeze, and positive respiratory culture for Pseudomonas. RESULTS: There were 14,210 eligible patients enrolled in ESCF during this period, and ABPA was diagnosed in 281 patients (2%). Regional prevalence varied from 0.9% in the Southwest to 4.0% in the West. Increased prevalence rates occurred in female patients, the adolescent age group, and subjects with lower lung function, wheeze, asthma, and positive Pseudomonas cultures. Although most ABPA patients had evidence of airway obstruction, 10% had an FEV1 of > 100% of predicted. The rates of wheeze (17%) and asthma (30%) were lower than expected in the ABPA group. CONCLUSIONS: This observational study found a reported prevalence rate of ABPA of 2% of CF patients in a large database. This rate was lower than the 5 to 15% rate reported in smaller studies, suggesting that ABPA is underdiagnosed in the CF population. There was wide regional variation in reported prevalence rates, which is unexplained at this time. The characteristics of the patients with ABPA and the epidemiologic risk factors for diagnosis of ABPA were described. Simplified diagnostic criteria were adapted for ESCF with the intent of increasing awareness of ABPA among the participants in this study.

Impact of microbiology practice on cumulative prevalence of respiratory tract bacteria in patients with cystic fibrosis.

Investigators participating in the Epidemiologic Study of Cystic Fibrosis project began to collect microbiological, pulmonary, and nutritional data on cystic fibrosis (CF) patients at 180 North American sites in 1994. Part of this study was a survey undertaken in August 1995 to determine microbiology laboratory practices with regard to pulmonary specimens from CF patients. The survey included a section on test ordering, completed by a site clinician, and a section on test performance and reporting, completed by each site's clinical microbiology laboratory staff. Seventy-nine percent of the surveys were returned. There was intersite consistency of microbiology laboratory practices in most cases. The majority of sites follow most of the CF Foundation consensus conference recommendations. There were differences in the frequency at which specimens for culture were obtained, in the use of selective media for Staphylococcus aureus and Haemophilus influenzae, and in the use of a prolonged incubation for Burkholderia cepacia. These variations in practice contribute to prevalence differences among sites and may result in differences in clinical care.

International practice patterns by age and severity of lung disease in cystic fibrosis: data from the Epidemiologic Registry of Cystic Fibrosis (ERCF).

The Epidemiologic Registry of Cystic Fibrosis provides clinical profiles for more than 6,800 patients and descriptions of practice patterns across eight European countries. Preliminary cross-sectional analysis has been performed by age and pulmonary function as an assessment of disease severity. In general, pulmonary treatments including inhaled bronchodilators and rhDNase increased as lung disease became more severe. Use of a number of treatments, including mucolytic agents and inhaled corticosteroids, varied markedly from country to country. Several widely used therapies are not yet supported by controlled clinical trials, particularly in patients under 6 years of age. Nutritional intervention was more common in patients with advanced lung disease regardless of age. Patients with nasal polyps had less severe lung disease at each age than patients without polyps. It is clear that studies of early interventions are needed to determine the optimal types of treatments and the ages at which to begin treatment.

Patterns of linear growth in rural Guatemalan adolescents and children.

Length and weight data from a longitudinal study of rural Guatemalan subjects birth to 7 y of age and height and weight data from a cross-sectional study of the same subjects when they were 11-24.9 y old are compared to reference data for the USA general population and for Mexican-Americans. At birth, the median length of Guatemalan children is at approximately the 16th percentile of the USA reference or approximately 2 cm shorter. By 6 mo of age, Guatemalan children are shorter, on average, than the 5th percentile of the reference curves and, in absolute terms, are approximately 5 cm below the median; by 3 y, the difference increases to approximately 10 cm. As adults, Guatemalans have about the same absolute level of deficit (approximately 13 cm) as they did at age 3 y. If the general USA population is used for comparison, Guatemalans can be said to grow as expected during adolescence, neither recuperating the growth retardation of early childhood nor falling further behind in size. If the Mexican-American sample is selected instead, it would appear that some catch-up in growth occurs in Guatemalan adolescents. Regardless of the choice of reference population, growth is markedly retarded only in early childhood; adolescence is not a period when growth is significantly constrained.

The precision of anthropometric assessment of body fat distribution in children.

Precision estimates are given for indices of body mass, fatness and body fat distribution in a sample of n = 19 subjects selected at random from a larger study of cardiovascular disease risk in school-aged children. The value of this study is that little is known about the measurement precision of ratio indices and multivariate constructs of body fat distribution in children or any other age group. Intra- and inter-observer precisions were highest for weight, height, body mass index and six body circumferences (0.95-0.99), and were lower and more variable for five skinfold thicknesses (0.80-0.99). The measurement precision of ratio indices derived from the circumferences (waist/hip and waist/thigh) and the skinfolds (subscapular/thigh and triceps/subscapular) were lower and more variable than precisions of the single variables. Circumference ratio precisions varied from 0.81 to 0.96 and skinfold ratios varied from 0.28 to 0.94. Precisions of a multivariate construct of central fat distribution from five skinfold measures were better (0.77-0.95), suggesting its greater efficacy. Inter-examiner precisions tended to be significantly lower than intra-examiner precisions for skinfold thicknesses and all composite indices. The lower precisions of ratio indices, compared to the measurement accuracy of the variables which make them up, needs to be considered in epidemiological studies of body fat distribution.

Body circumferences as alternatives to skinfold measures of body fat distribution in children.

The ratios of circumferences (waist/hip, waist/thigh) have been proposed in lieu of skinfold measurements for studies of obesity and body fat distribution in adults. The skinfold method has been used successfully in children to study the growth and development of patterns of body fat distribution, but circumferences have not. We studied the relationship between these two methodologies as indicators of body fat and its anatomical distribution among 365 normal children aged 6-11 years, using canonical correlation analysis. With this method, weighted vectors of four body circumferences on the one hand and five skinfolds on the other are formed in such a way that the correlation between the two sets of variables is maximized. Weights (regression coefficients) are assigned each variable and their strength and sign help us to select the best combination of circumferences which describe a component of centralised obesity. A first canonical correlation was substantial in both boys and girls (0.84) and was independent of age. It appeared to relate to fatness level. A second canonical correlation was low (0.34 in boys, 0.35 in girls) (p less than 0.01). It too was age independent and in both sexes it reflected differences between fat on the trunk and on the lower extremity, and was thus a component of centralised fat distribution. The simple waist/thigh ratio correlated better with this canonical variable (0.67-0.88) than the more commonly used waist/hip ratio (0.45-0.79). The 'best' index of centralised fat in children is therefore, the waist/thigh circumference ratio, the same one that has been suggested for adults.

Bone marrow in HIV infection. A comparison of fluorescent staining and cultures in the detection of mycobacteria.

Fifty-one bone marrow aspirates and biopsies from 47 human immunodeficiency virus-(HIV) infected patients (42 with acquired immune deficiency syndrome [AIDS], 5 with AIDS-related complex [ARC]) were processed by standard methods for smears and paraffin sections. Aspirates were cultured for Mycobacteria. The sections, imprints, and smears were examined by fluorescent microscopy with the use of Truant's modification of the auramine-rhodamine stain. Mycobacterial cultures had positive results from 35%. Sensitivity of fluorescent staining was 72% and specificity was found to be 94%. If the fluorescent stain had positive results, the positive predictive value for recovering Mycobacteria on culture was 87%. Fluorescent microscopy with the use of Truant's auramine-rhodamine staining of routinely processed bone marrow aspirates and biopsies is a fairly sensitive, very specific, and rapid technique for determining the presence of Mycobacteria in bone marrow specimens from patients with HIV infection.

Infections caused by central venous catheters in patients with acquired immunodeficiency syndrome.

We assessed infectious complications of long-term percutaneous central venous catheterization in patients with acquired immunodeficiency syndrome (AIDS). We evaluated 98 consecutive patients, accounting for 6,298 catheter days. Catheter-associated bacteremia occurred in 3% of patients, a rate of 0.128%/patient-catheter day. Only bacterial pathogens--Pseudomonas, Serratia, and Staphylococcus species--were isolated. Five patients had infection at the catheter exit site. The length of time catheters were indwelling was not significantly different in patients with and those without infections. Percutaneous, multiple-use central venous catheters are safe and well accepted by patients with AIDS.