CONFERENCE NEWS UPDATE:
13TH ANNUAL NORTH AMERICAN
CYSTIC FIBROSIS CONFERENCE

Sleep disturbances and iron deficiency are common among cystic fibrosis (CF) patients, according to new findings presented at the 13th Annual North American Cystic Fibrosis Conference in Seattle, Wash. Other highlights of the meeting included studies showing a relationship between menstruation and lung function changes in women with CF and the efficacy of nebulized fentanyl in the treatment of dyspnea.

HIGH-RESOLUTION CT DETECTS LUNG ABNORMALITIES IN INFANTS

High-resolution computed tomography (HRCT) may be useful in detecting early pathological changes in the lungs of infants or children with CF, according to findings by R. G. Castile, MD, who is from the Children's Hospital in Columbus, Ohio, and colleagues.

The study population consisted of 32 infants or children with CF who were between age 10 and 285 weeks (mean age, 121 weeks). Four HRCT images were taken near full inflation (25 cm H2O) and at end-expiration (0 cm H2O) during controlled pauses in ventilation. Fourteen infants who were undergoing HRCT for other clinical indications served as controls.

Abnormalities were found in 90.6% of the CF subjects but in only 28.5% of the control subjects. The total HRCT severity scores (which measured the extent of the abnormalities) were 13.8 for the CF subjects and 0.6 for the control subjects. The most frequently identified abnormalities were airway wall thickening and gas trapping (Figure 1). The abnormalities in the CF subjects were equally distributed in the right upper, right lower, left upper, and left lower lung fields.

Figure 1 Airway Abnormalities in Infants and Children with CF

MANY CF PATIENTS ARE IRON DEFICIENT

Iron deficiency is common among adult CF patients. Furthermore, this deficiency does not appear to be related to other markers of malabsorption, according to S. Hansen, MD, and colleagues from McMaster University in Hamilton, Ontario.

The study population consisted of 36 patients age 18 to 50 years (mean age, 28 years) who underwent routine yearly blood work. Two of the patients had borderline anemia, and 19 were iron deficient (transferrin saturation below 16%). Although mean corpuscular volume (MCV) was normal (87.5 fL), mean transferrin saturation was reduced (16.4%). In addition, mean serum ferritin concentrations were low (31.0 µg/L) in this group; in fact, 13 of the patients had concentrations of less than 18 µg/L.

Iron deficiency was not correlated with hemoglobin level; MCV; serum levels of vitamins A, E, B12, or 25-hydroxyvitamin D; folate concentrations in red blood cells or serum; or a reduced dietary intake.

The researchers also found that serum ferritin assays were "inadequate" for the routine diagnosis of iron deficiency in CF patients because serum ferritin measurements had a sensitivity of 42% and a specificity of 75% for the detection of iron deficiency in this study. The researchers concluded that further studies are needed to determine the effects of iron supplementation in CF patients.

LUNG FUNCTION CHANGES LINKED TO THE MENSTRUAL CYCLE

Lung function changes occur during the menstrual cycles of women with CF, a new study suggests. These changes are probably related to hormonal changes, reported M. Johannesson, MD, who is from the Children's Hospital in Uppsala, Sweden, and colleagues.

Previous studies have shown that estrogen and progesterone affect CF gene expression, smooth muscle tone in the airways, immune response, and cytology in the tracheobronchial epithelium. To study the influence of the hormonal variations on airway symptoms, these researchers asked 12 women with CF (mean age, 30 years) to keep daily records of lung function, sputum quality, and the need for intravenous antibiotics during three menstrual cycles.

The mean forced expiratory volume in one second (FEV1) was significantly higher during the luteal phase (66%) than during menstruation (61%). Similarly, the mean forced vital capacity was significantly higher during the luteal phase (75%) than during menstruation (70%; P < .001). In contrast, no significant change in sputum quality or the use of intravenous antibiotics was found during the cycles.

NEBULIZED FENTANYL HELPS COMBAT DYSPNEA

Nebulized fentanyl appears to be a safe and effective treatment for dyspnea in many CF patients, reported J. M. Alderman, MD, and colleagues from the Children's Hospital and Ohio State University in Columbus.

In an attempt to alleviate symptoms of respiratory failure in CF patients with advanced disease, many physicians prescribe systemic benzodiazepines and narcotics. However, these agents may actually worsen respiratory function, the researchers noted. Over the past four years, they have used nebulized fentanyl to treat the symptoms of dyspnea and anxiety associated with end-stage CF.

To determine the effectiveness of this treatment, the researchers conducted a retrospective chart review, along with prospective patient interviews, of 16 patients with advanced CF who were treated with nebulized fentanyl between July 1995 and May 1999. Most patients experienced symptom reduction, and none reported discomfort related to use of the drug. Nebulized fentanyl administration was associated with a reduced need for benzodiazepines and narcotics.

The authors concluded that there were two major advantages associated with the use of nebulized fentanyl:

• It prevents (or at least reduces) the need for systemic narcotics and/or benzodiazepines and, thus, lowers the risk of the adverse reactions related to such drugs; and
• It does not require intravenous administration, so it is likely to be less expensive and may make outpatient therapy feasible.

WHAT FORM OF EXERCISE IS BEST FOR CHILDREN WITH CF?

When it comes to selecting an exercise program for a child with CF, consider your goals: Resistance training provides better improvements in FEV1 and weight gain, whereas aerobic training provides better improvements in quality of life and aerobic capacity.

H. C. Selvadurai, MD, and colleagues from the Royal Alexandra Hospital for Children in Sydney, Australia, examined 66 children (age 8 to 16 years) with CF of varying degrees of severity who were admitted to a hospital for intercurrent chest infection. The mean duration of hospital stay was 18.7 days.

The children performed 30 minutes of aerobic training, resistance training, or no specific training (controls) five times a week for one month after discharge. Upon study admission, at hospital discharge, and one month later, the children underwent a treadmill exercise test, spirometry, and lower limb strength assessment. In addition, they were evaluated using a validated Quality of Well-Being (QWB) Scale upon admission and one month after discharge.

Compared with the other two groups, the children who performed aerobic exercise achieved significantly greater improvements in the QWB scores and in oxygen consumption (Vo2). For example, the mean scores on the QWB Scale increased by 14.28% in the aerobic group but rose by only 2.54% in the resistance group and decreased by 0.38% in the control group. Mean Vo2 increased by 21.64% in the aerobic group and by 2.14% in the resistance group but decreased by 3.58% in the control group.

In contrast, the resistance group showed significantly greater improvements in FEV1, weight gain, and strength compared with the other groups. Mean FEV1 increased by 10.09% in the children who underwent resistance training but by only 6.54% and 2.51% in the aerobic and control groups, respectively. Mean weight increased by 7.34% in the resistance group, by 2.09% in the aerobic group, and by 2.81% in the control group.

SLEEP DISORDERS ARE COMMON IN CF

The prevalence of sleep disturbances and daytime sleepiness is high among CF patients, a recent pilot study has determined. Furthermore, pulmonary function test results do not appear to influence the likelihood of sleep problems. These findings suggest that sleep disturbances in CF patients are multifactorial and can only partially be explained by gastrointestinal and pulmonary disease, reported R. S. Amin, MD, and colleagues from the Children's Hospital Medical Center in Cincinnati.

These authors studied 46 CF patients (mean age, 18.2 years) with varying degrees of disease severity. All patients completed a sleep questionnaire that examined six variables: demographic factors, respiration during sleep, perception of sleep disturbance, duration of sleep/frequency of awakening, daytime sleepiness, and daytime performance. The patients' family members completed a similar questionnaire.

According to the survey responses, 33% of patients reported that CF affected the quality of their sleep, 61% reported morning sleepiness, and 48% reported daytime sleepiness. A significantly greater proportion of patients who reported excessive daytime sleepiness also reported difficulty falling asleep (72% vs 29%), frequent nighttime coughing (69% vs 31%), and frequent use of the bathroom at night (81% vs 19%) than did those who did not report excessive daytime sleepiness.

Logistic regression analysis showed that frequent bathroom use at night was a significant predictor of excessive daytime sleepiness. There was also a trend toward a positive correlation between excessive daytime sleepiness and nighttime awakening from sleep because of difficulty breathing. However, none of the sleep variables correlated with FEV1.

The researchers noted agreement between the self-reported responses and the responses from family members on the following variables: difficulty falling asleep, sweating during sleep, nighttime use of the bathroom, degree of daytime sleepiness, and feeling tired during the day.

HOW BEST TO IMPROVE SPUTUM EXPECTORATION?

In a study comparing two treatments for aiding sputum expectoration in CF patients, the Test of Incremental Respiratory Endurance (TIRE) was found to be more effective than standard chest physiotherapy. K. Chatham, MD, and colleagues from the University of Wales College of Medicine in Cardiff reported the findings.

At the onset of treatment for exacerbations of respiratory symptoms, 10 men and 10 women with CF were randomized to one of the two treatments on four alternate days. The TIRE was performed at 80% of sustained maximal inspiratory pressure until failure; sputum was collected during and for 30 minutes after the session. Physiotherapy consisted of a supervised 30-minute treatment session, which included postural drainage, percussion, and the forced expectoration technique, followed by 30 minutes of posttreatment expectoration. Sputum clearance was significantly greater after the TIRE than after physiotherapy.

A positive correlation between lean body mass, FEV1, and inspiratory muscle function was found. In the 11 patients with low lean body mass, there was an inverse correlation between FEV1 and the total amount of protein and elastase expectorated during both of the treatments. Thus, neither treatment was limited by disease severity (as indicated by FEV1 and low lean body mass).

"Repeated inspiratory maneuvers can therefore be used in patients with CF because the level of effort is set to the individual's capacity and maintained using biofeedback," the researchers concluded.

NONINVASIVE VENTILATION SHOWS PROMISE FOR ATELECTASIS

Noninvasive positive pressure ventilation (NIPPV) was safe and effective in the treatment of atelectasis in CF patients, reported D. Costantini, MD, of the Cystic Fibrosis Center in Milan, Italy, and colleagues.

The study population consisted of 18 CF patients (mean age, 18.2 years) with lobar or segmental atelectasis who were admitted to a hospital for intravenous antibiotic therapy and ventilatory treatment. The patients' degree of respiratory drainage ranged from minimal deficiency to severe obstruction; their mean FEV1 was 69.3%. Atelectasis occurred during acute exacerbations in half of the group and was detected only occasionally in the other half.

Sixteen of the patients underwent physiotherapy with a positive expiratory pressure mask (n = 13) or autogenic drainage (n = 3). Bilevel ventilation was applied with a nasal or facial mask; mean inspiratory and expiratory pressures were 12.3 and 6.8 cm H2O, respectively.

The patients underwent NIPPV for five minutes followed by the forced expiratory technique and then coughing; this sequence was repeated five times. The session was repeated four times a day for a mean duration of 13.1 days.

After treatment, 10 (56%) of the 18 patients had partial or complete resolution of atelectasis. Among the 13 patients in whom FEV1 was measured, 10 (77%) showed an increase in FEV1 (mean increase, 76.6%). A small increase in oxygen saturation was also detected, but the change was not significant. None of the patients reported major side effects, but two patients experienced epigastric pain during ventilation.

--Kristin Della Volpe

Return to table of contents