Pulmonary function in hospitalized infants and toddlers with cystic fibrosis.

UNLABELLED: In older children with cystic fibrosis (CF), well-documented improvements in lung function occur during hospitalization for treatment of pulmonary exacerbations. OBJECTIVES: (1) To test the hypothesis that improvement in lung function occurs in infants and toddlers hospitalized because of CF pulmonary exacerbations. (2) To compare changes in lung function measured during forced expiratory flow and tidal breathing. STUDY DESIGN: Seventeen infants and toddlers with CF were evaluated at the beginning and end of hospitalization by the rapid thoracic compression technique to yield maximal flow at forced residual capacity. Tidal mechanics were measured by the esophageal balloon technique to yield lung conductance and compliance. RESULTS: Lung function improved during the course of hospitalization. The greatest change was observed in measurements of maximal flow at functional residual capacity (.VmaxFRC), increasing from 38.5% +/- 6% predicted (mean +/- SEM) to 59.8% +/- 6% at the end (p < 0.005). Lung conductance (GL) increased from 60% +/- 6% to 78% +/- 8% (p < 0.02); lung compliance (CL) increased from 66% +/- 5% to 75% +/- 5% (p < 0.03). The degree of improvement of .VmaxFRC, GL, and CL was related to baseline measurements; those with poorer pulmonary function at baseline had the greatest degree of improvement during hospitalization. CONCLUSION: Assessments of airflow obstruction from measurements of .VmaxFRC and GL do not necessarily demonstrate similar findings in a given infant with CF, perhaps because these two techniques measure different physiologic properties. Changes in .VmaxFRC may best reflect the predominant pathophysiology of lung disease in infants and toddlers with CF.

Safety of repeated intermittent courses of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

OBJECTIVES: To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis. DESIGN: A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed. RESULTS: Detectable anti-rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes in their symptoms from the time they entered the trial. Antibodies detected were all of the IgG isotype. Increases in both forced expired volume in 1 second and forced vital capacity were noted from the beginning to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase was not associated with allergic reactions and had no relationship on improvement in pulmonary function. CONCLUSIONS: Development of anti-rhDNase antibodies occurred in a small number of patients and was not associated with side effects. Intermittent administration of rhDNase for 24 weeks to patients with cystic fibrosis was well tolerated and was not associated with anaphylaxis in any patient. Pulmonary function improved significantly during the 14-day cycles while rhDNase was administered and returned to baseline when rhDNase was discontinued.

A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group.

The purpose of this study was to evaluate the efficacy and safety of alternate-day prednisone therapy in treating patients with mild-to-moderate cystic fibrosis during a 4-year period. In 15 North American cystic fibrosis centers, we screened 320 patients and enrolled 285 patients from April 1986 to December 1987. Patients were randomly assigned to take prednisone, 1 mg/kg per dose or 2 mg/kg per dose, or a matching placebo given on alternate days. Lung function, clinical status, hospitalizations, growth, and steroid side effects were monitored. During the first 24 months the percentage of the predicted forced vital capacity was greater in the 1 mg/kg group (p < 0.0001) and the 2 mg/kg group (p < 0.01) when each was compared with placebo. Patients in the 1 mg/kg group had a higher percentage of predicted forced vital capacity than placebo patients during the entire 48 months (p < 0.0025), but only in the group of patients who were colonized with Pseudomonas aeruginosa at baseline. For 48 months, the 1 mg/kg group had a higher percentage of predicted forced expiratory volume in 1 second than patients given placebo (p < 0.02). The prednisone-treated groups had a reduction in serum IgG concentrations (1 mg/kg vs placebo, p < 0.007; 2 mg/kg vs placebo, p < 0.003). From 6 months onward, height z scores fell in the 2 mg/kg group compared with those given placebo (p < 0.001). For the 1 mg/kg group, height z scores were lower from 24 months. An excess of abnormalities in glucose metabolism was seen in the 2 mg/kg group compared with the placebo group (p < 0.005). Our findings suggest a role for alternate-day prednisone therapy at a dose of 1 mg/kg in patients with mild to moderate cystic fibrosis. The benefit of improved lung function appears to outweigh the potential for adverse effects when the treatment period is less than 24 months.

Reduction of eicosanoid production by essential fatty acid depletion does not attenuate the inflammatory response induced by Pseudomonas aeruginosa pneumonia in rat lung.

Sipid mediators of inflammation have been implicated in the pathogenesis of Pseudomonas aeruginosa (PA) related pulmonary damage in patients with cystic fibrosis. We studied the role of these mediators in a rat model of PA endobronchitis using essential fatty acid deficient (EFAD) animals. Whole blood from EFAD animals produced significantly less leukotriene B4 (LTB4) and hydroxyheptadecatrienoic acid when stimulated ex vivo than did whole blood from control animals (p less than 0.005). Similarly, lung lavage fluid from EFAD animals infected with PA contained less LTB4 and thromboxane B2 (TXB2) than that from control animals. Despite these differences, cellular infiltration of airways in response to PA infection was virtually identical in animals from the regular diet and the EFAD groups. Both EFAD and control animals had a significant increase in white blood cells (WBC) in lung lavage fluid at 1, 3 and 6 days following infection with PA when compared to animals receiving sterile beads. Localized areas of consolidation and nodularity were grossly evident in the lungs of all PA infected animals irrespective of their ability to generate the lipid inflammatory mediators. Microscopic examination of lung sections demonstrated similar changes in all infected animals. We conclude that LTB4 and TXB2 production occurs early in the course of PA pulmonary infection in rats. This early rise in lipid mediators is temporally associated with an influx of WBC into the airways. However, attenuation of eicosanoid production by use of an EFAD diet does not lead to a reduction in the inflammatory response to PA infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Thymolipoma: computed tomographic appearances.

The computed tomographic (CT) appearances of a thymolipoma are described in a 5 1/2-year-old girl. The location and CT appearances of the tumor appear to be specific for the diagnosis of thymolipoma.

Mechanics and energetics of breathing in newly diagnosed infants with cystic fibrosis: effect of combined bronchodilator and chest physical therapy.

Response to bronchodilator (BD) and chest physical therapy (CPT) was evaluated in newly diagnosed infants with cystic fibrosis (n = 13; age, 6.9 +/- 1.5 SE months) who were asymptomatic for lung disease at the time of the study. Lung function was assessed from the mechanics and energetics of breathing prior to and following combined BD and CPT. After therapy, respiratory rate, tidal volume, minute ventilation, and pulmonary compliance were not statistically different from values under baseline conditions. In contrast, there was a significant decrease in pulmonary resistance (-34%; P less than 0.05) and the resistive work of breathing (-26%; P less than 0.05) following the combined treatment. The effect of combined BD and CPT in decreasing the resistive respiratory load may be related to relief of subclinical bronchospasm, reduction in mucosal edema, and mobilization of mucous secretions.

Pseudomonas cepacia in the hospital setting: lack of transmission between cystic fibrosis patients.

Possible mechanisms of transmission of Pseudomonas cepacia in hospitalized patients with cystic fibrosis were examined. Twelve patients were colonized with P. cepacia prior to admission (group 1), and 15 patients were not (group 2). Daily contact occurred between both groups. Sputum cultures were obtained from all patients at admission and discharge, and 3 and 6 months after discharge in group 2 patients. Environmental cultures included cough plates, settle plates, spirometry tubing, stethoscopes, sinks, wall outlets, and hands of patients, physicians, nurses, and respiratory therapists. Specimens were plated on a P. cepacia-selective medium. All group 1 patients remained colonized with P. cepacia at discharge. None of the group 2 patients acquired P. cepacia during hospitalization or follow-up. P. cepacia was recovered from three of 151 environmental cultures; two of these were presumably patient related. P. cepacia contamination of pulmonary function equipment, wall outlets, hands, and stethoscopes was not documented. We conclude that transient aerosol environmental contamination is uncommon and restricted to the immediate patient environment.

Pseudomonas cepacia colonization in patients with cystic fibrosis: risk factors and clinical outcome.

During the period of 1979 to 1983, 38 patients with cystic fibrosis (CF) at the CF center of St. Christopher's Hospital for Children in Pennsylvania developed respiratory tract colonization with Pseudomonas cepacia. Seventeen (45%) of the patients with colonization died. Yearly incidence rates of P. cepacia colonization fluctuated between 1.3% and 6.1%, suggesting an endemic phenomenon. Case-control studies showed that severe underlying CF, use of aminoglycosides, and having a sibling with CF and P. cepacia colonization were significant risk factors for P. cepacia colonization. Once colonized with P. cepacia, patients with CF were likely to be hospitalized longer (P = 0.008) and to die sooner (P = 0.0001) than control patients with CF. Environmental and microbiologic studies did not identify a common source or mode of transmission of P. cepacia among patients. The results of this investigation suggest that P. cepacia colonization of patients with CF was endemic in the hospital, occurred more frequently in those with severe disease, and was associated with adverse clinical outcome.