Survey of breast-feeding practices and outcomes in the cystic fibrosis population

The aim of this study was to survey cystic fibrosis (CF) patients to determine the frequency of breast-feeding and its association with onset and severity of CF symptoms. Three thousand, two hundred questionnaires were sent to 30 accredited CF centers for anonymous completion. Eight hundred and sixty-three questionnaires were returned and scanned into a database. All results were adjusted for age at time of filling out the questionnaire. Age at onset of symptoms, percent forced expired volume in 1 sec (FEV1%) predicted, and intravenous (IV) antibiotic use were analyzed based on breast-feeding history. Approximately 49% of respondents received human breast milk at some time, but only 18% were exclusively breast-fed. Breast-feeding exclusively for greater than 6 months was associated with a decrease in disease severity based on recent intravenous antibiotic use compared to no breast-feeding (P = 0.03). There was no statistically significant change in onset of symptoms in the setting of breast-feeding; however, a trend toward delayed onset was seen in those receiving human milk. Fifty-three percent of those who breast-fed exclusively > or = 6 months had FEV1% values > 90%, compared to 47% of those not breast-fed. This is a suggestive but not statistically significant difference. In conclusion, breast-feeding for > or = 6 months is associated with decreased use of intravenous antibiotics in the 2 years prior to administering the questionnaire. This survey indicates that breast-feeding is not harmful to children with CF, and may be beneficial.     

Fertility and pregnancy in patients with cystic fibrosis.

Issues related to fertility and pregnancy, once moot, are now extremely relevant to the care of a growing number of CF patients entering adulthood. With rare exception, men are infertile, due to the almost universal presence of malformations of the reproductive tract causing obstructive azoospermia. Emphasis in the care of these patients should be directed toward confirmation of infertility and counseling to allay anxieties. In contrast, a significant albeit unknown proportion of women are fertile and a steadily increasing number of these women are conceiving. The accumulated clinical experience has demonstrated that pregnancy is well-tolerated by patients with mild disease while associated with increased maternal and fetal complications in those with severe disease. In light of current uncertainties in accurately predicting outcome in all but the most clear-cut cases, the physician must exercise clinical judgment in providing a realistic assessment of the medical risks involved and of the advisability of pregnancy. This assessment should be based on a thorough and objective evaluation of the pulmonary, cardiac, and nutritional status of the patient. Future efforts, assisted by data collected for the national CF patient registry, should be directed toward better defining the long-term impact of pregnancy on the natural history of CF and more precisely defining the pregravid parameters useful in predicting outcome for both mother and child.     

Infertility in men with cystic fibrosis.

The majority of men with cystic fibrosis (CF) have associated congenital bilateral absence of the vas deferens (CBVAD). This congenital defect results in the absence of the anatomic ducts through which spermatozoa pass from the testes to the urethra. No spermatozoa are found in the semen, a condition referred to as obstructive azoospermia. This abnormality of the genital-urinary system is associated with the same genetic mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR ), which leads to the classic presentation of a patient with CF. However, patients may have CBVAD and CFTR mutations without symptoms of CF. Screening for the common mutations may miss a milder rare gene alteration: a DNA variant in the 5T allele. With the advent of assisted reproductive technologies, fertility is now possible for these men. The National Institutes of Health recommend genetic counseling for any couple attempting assisted reproductive techniques when the man has CF or presents with obstructive azoospermia and is positive for a CF mutation.     

Patient-reported outcomes in cystic fibrosis

Over the past 20 years, there has been tremendous progress in the area of patient-reported outcomes (PROs). A PRO instrument is defined as any measure of a patient's health status that is elicited directly from the patient and assesses how the patient "feels or functions with respect to his or her health condition." The advances seen in clinical research regarding PROs has been mirrored in research in cystic fibrosis (CF). A large number of instruments have been used for both therapeutic and nontherapeutic clinical research for many chronic conditions. This review will summarize a history of the development of PROs and how PROs are viewed by the U.S. Food and Drug Administration. We will then review the current state of the art of patient-reported outcomes in CF, specifically addressing the evaluation of different PRO instruments in terms of their reliability and validity. Finally, we will delineate further areas for development of PROs in CF. We believe that the future of CF research will incorporate a more diverse selection of PRO outcome measures; these outcome measures ultimately may be incorporated into clinical care to standardize symptom assessment and provide information regarding the need for specific clinical interventions to improve the quality of care delivered to these patients.     

Sex steroids and body composition in men with cystic fibrosis

OBJECTIVE: Delayed sexual maturation and low body weight is common in cystic fibrosis (CF). Concomitant data on sex hormones and concomitant body composition are lacking in men with CF. DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Serum levels of testosterone, 17beta-oestradiol (E(2)), 25-hydroxyvitamin D (25(OH)D), sex hormone-binding globulin (SHBG) and LH were measured by RIA and total and regional lean body mass (LBM), fat body mass (FBM), bone mineral content and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry, in men with CF (n=40; age 24.7+/-5.4 years) and age-matched healthy controls (n=28; age 25.7+/-3.7). Only men without acute disease exacerbation or systemic glucocorticoid treatment were included. RESULTS: Mean levels of hormonal serum parameters differed significantly between healthy controls (testosterone=20.2+/-5.5 nmol/l; E(2)=95.0+/-20.2 pmol/l; 25(OH)D=62.8+/-28.3 nmol/l) and patients (testosterone=15.9+/-4.1 nmol/l; E(2)=60.7+/-19.4 pmol/l; 25(OH)D=39.5+/-17.8 nmol/l; P<0.001) while no difference was found for SHBG or LH. Eleven (for E(2), 19 of 40, for 25(OH)D, 20 of 40) out of 40 patients had serum testosterone levels 2 s.d. below the mean of normal. Men with CF showed a relative shift from FBM to LBM and a different body fat distribution compared with healthy controls (P<0.01). Testosterone was not correlated with weight, total or regional LBM or FBM, but significantly with BMD (r=0.32; P<0.05) independently from body height and 25(OH)D levels. E(2) was correlated with regional and total FBM (r=0.48; P<0.05). In a multiple regression analysis of the joint effect of testosterone and body components on E(2), a testosterone-independent effect was found for FBM. CONCLUSIONS: CF patients with stable disease have moderately reduced serum testosterone levels. This might already imply detrimental effects on bone. The change in LBM of patients appears to have no direct association with sex hormone levels while low FBM might cause reduced net conversion of serum testosterone to E(2) with possible effects on FBM distribution.     

Lung transplantation for cystic fibrosis: an update and practical considerations for referring candidates

In this article, the authors provide an update to Maurer and Chaparro's 1995 review in this journal of lung transplantation for cystic fibrosis. Bilateral (sequential) cadaver donor transplantation is the usual procedure of choice. The four-year survival rate for adult, all-disease, double-bilateral lung transplantation has improved to 53%. Because of lower [corrected] survival rate among adults, living-donor lobar transplantation should be performed only when cadaver lungs are unlikely to become available. The International Society for Heart and Lung Transplantation and the Cystic Fibrosis Foundation have promulgated uniform guidelines for transplantation candidate selection. Issues of diabetes mellitus, mechanical ventilation, osteoporosis, malnutrition, fungi and drug-resistant bacteria, pleural fibrosis, and sinusitis in relation to transplantation candidacy are discussed. Some practical points regarding transplantation center referral are presented, and a list of cystic fibrosis transplantation centers in the United States is supplied.     

Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience

Liver disease develops in one‐third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.     

Fertility and pregnancy: common concerns of the aging cystic fibrosis population

Due to dramatically improved survival, cystic fibrosis (CF) is now considered a chronic disease of adults. Many men and women who have CF are interested in starting families and have questions regarding fertility and pregnancy, making discussion of these issues important in routine CF care. This article addresses key issues of fertility in men and women who have CF and discusses pregnancy, including maternal and fetal outcomes, highlighting advances over the last decade.     

Diagnosis and treatment of cystic fibrosis. An update

Cystic fibrosis is the most common fatal inherited disease of Caucasians. At present, cystic fibrosis accounts for most cases of chronic progressive pulmonary disease and for many other clinical features in the first three decades of life. Thus, it is a challenge to both pediatricians and internists, particularly chest physicians. The diagnosis is based on the triad of chronic obstructive pulmonary disease, pancreatic insufficiency, and increased levels of electrolytes in the sweat. The cardinal test for confirmation of the diagnosis is the "sweat test," which is an excellent discriminant for cystic fibrosis, even in adults. Ancillary features of cystic fibrosis may be of diagnostic assistance (eg, nasal polyposis, Pseudomonas aeruginosa in sputum, azoospermia, and others). Treatment of the pulmonary disease must be emphasized. Choice of antibiotics should be based on the results of sputum culture, but P aeruginosa is the most common pathogen. Removal of secretions by regular postural drainage and percussion is an integral part of the program. Pneumothorax, massive hemoptysis, cor pulmonale, and other complications may be encountered. Sinusitis is almost universal, and nasal polyposis is frequently present. Pancreatic insufficiency occurs in over 80 percent of the patients with cystic fibrosis and may result in intestinal malabsorption. Massive salt loss through the sweat in hot weather, a distinctive type of biliary cirrhosis without jaundice, gallbladder abnormalities, cholelithiasis, and diabetes mellitus also may be found. Of special importance are intestinal obstructive complications (meconium ileus in newborn infants with cystic fibrosis and intestinal obstruction due to fecal accumulation or intussusception in adults). Azoospermia is present in 95 percent of men and there is reduced fertility in women; however, pregnancy does occur in cystic fibrosis. This chronic and ultimately fatal disease produces a predictable set of psychosocial complications.     

Factors influencing outcomes in cystic fibrosis: a center-based analysis

CONTEXT: Guidelines for managing cystic fibrosis (CF) patients have been widely circulated, but little is known about the variations in practice between sites and their association with outcomes. OBJECTIVE: To determine whether differences in lung health existed between groups of patients attending different CF care sites and to determine whether these differences are associated with differences in monitoring and intervention. DESIGN: The analysis was conducted using data from the Epidemiologic Study of Cystic Fibrosis from 1995 through 1996. SETTING: This was an observational database collecting prospective information from a large number of CF patients undergoing routine care in North America. PARTICIPANTS: Participating sites that had at least 50 CF patients who had each made at least one visit to a center during the 2-year study period were ranked on the basis of median values for FEV(1) within each of three age groups (6 to 12 years, 13 to 17 years, and >or= 18 years). INTERVENTIONS: There were no prespecified interventions in this observational study. MAIN OUTCOME MEASURES: The frequency of patient monitoring and the use of therapeutic interventions were compared between sites in the upper and lower quartiles after stratification within the site for disease severity. RESULTS: Within-site rankings tended to be consistent across the three age groups. Patients who were treated at higher ranking sites had more frequent monitoring of their clinical status, measurements of lung function, and cultures for respiratory pathogens. These patients also received more interventions, particularly IV antibiotics for pulmonary exacerbations. CONCLUSION: We found substantial differences in lung health across different CF care sites. We found that frequent monitoring and increased use of appropriate medications in the management of CF are associated with improved outcomes.     

Hemobilia: Historical overview,clinical update,and current practices

Hemobilia refers to macroscopic blood in the lumen of the biliary tree. It represents an uncommon, but important, cause of gastrointestinal bleeding and can have potentially lethal sequelae if not promptly recognized and treated. The earliest known reports of hemobilia date to the 17th century, but due to the relative rarity and challenges in diagnosis of hemobilia, it has historically not been well‐studied. Until recently, most cases of hemobilia were due to trauma, but the majority now occur as a sequela of invasive procedures involving the hepatopancreatobiliary system. A triad (Quincke's) of right upper quadrant pain, jaundice and overt gastrointestinal bleeding has been classically described in hemobilia, but it is present in only a minority of patients. Therefore, prompt diagnosis depends critically on a high index of suspicion based on a patient's clinical presentation and a history of recently undergoing hepatopancreatobiliary intervention or having other predisposing factors. Treatment of hemobilia depends on the suspected source and clinical severity and thus ranges from supportive medical care to urgent advanced endoscopic, interventional radiologic, or surgical intervention. In the present review, we provide a historical perspective, clinical update and overview of current trends and practices pertaining to hemobilia.     

The demographics of adverse outcomes in cystic fibrosis

Understanding variability in cystic fibrosis (CF) health outcomes requires an understanding of factors that go far beyond Cystic Fibrosis Transmembrane Receptor (CFTR) function caused by different gene mutations. Social and environmental factors that influence health have a significant influence on the trajectory of health in CF and in other chronic diseases. In this article, we review demographic factors associated with poorer health outcomes in CF, known and postulated biological mechanisms of these outcomes, and interventions that healthcare teams can implement that may reduce outcome disparities.     

Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on diagnosis and treatment

Although cystic fibrosis (CF) is an irreversible genetic disease, advances in treatment have increased the life expectancy of CF patients. Upper airway involvement, which is mainly due to pathological changes in the paranasal sinuses, is prevalent in CF patients, although many are only mildly symptomatic (with few symptoms). The objective of this literature review was to discuss the pathophysiology and current therapeutic management of chronic rhinosinusitis (CRS) in CF patients. The review was based on current evidence, which was classified in accordance with the Oxford Centre for Evidence-Based Medicine criteria. When symptomatic, CRS with nasal polyps can affect quality of life and can lead to pulmonary exacerbations, given that the paranasal sinuses can be colonized with pathogenic bacteria, especially Pseudomonas aeruginosa. Infection with P. aeruginosa plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Although clinical treatment of the upper airways is recommended as initial management, this recommendation is often extrapolated from studies of CRS in the general population. When sinonasal disease is refractory to noninvasive therapy, surgery is indicated. Further studies are needed in order to gain a better understanding of upper airway involvement and improve the management of CRS in CF patients, with the objective of preserving lung function and avoiding unnecessary invasive procedures.