Tracheal mucociliary transport in patients with cystic fibrosis and its stimulation by terbutaline.

Tracheal mucous velocity was measured by observing the motion of teflon discs across the tracheal mucosa through a fiberoptic bronchoscope. The average rate of movement in 14 adult patients with cystic fibrosis was 2.6 mm per min plus or minus 3.3 SD, compared with 20.1 mm per min plus or minus 6.3 in 20 normal subjects of the same age (P less than 0.001). This failure of mucociliary transport may play a role in the pathogenesis of the pulmonary disease in cystic fibrosis. Administration of a beta-adrenergic agent, terbutaline, increased the average mucous velocity in the patients with cystic fibrosis (to 5.5 mm per min plus or minus 3.6 SD, P less than 0.001) but not in control subjects. This observation has potential therapeutic significance.     

Quantitation and identification of antibodies to outer-membrane proteins of Pseudomonas aeruginosa in sera of patients with cystic fibrosis

Chronic, overwhelming pulmonary infection with Pseudomonas aeruginosa is a frequent problem in patients with cystic fibrosis. Titers of antibody to the outer-membrane proteins of P aeruginosa were 10(1)-10(8) (as measured by an enzyme-linked immunosorbent assay) in the sera of 32 patients with cystic fibrosis. Fifteen patients who had been colonized with P aeruginosa for 18 months to nine years had a geometric mean antibody titer of 1.3 X 10(5)--a value approximately 500-fold higher than that for 13 patients with cystic fibrosis who had never been colonized or for 16 healthy adults without cystic fibrosis (P less than 0.001). A significant correlation was observed between the presence of antibody to outer-membrane proteins and the presence of antibody to mucoid exopolysaccharide (P less than 0.002). Nineteen serum specimens from the patients with cystic fibrosis were allowed to react with Western electophoretic blots of separated outer-membrane proteins. All of these sera contained antibodies to porin protein F. In addition, antibodies to outer-membrane proteins E, H2, and I and to a variety of minor protein components were observed in many sera.     

Phospholipid composition and surface-active properties of tracheobronchial secretions from patients with cystic fibrosis and chronic obstructive pulmonary diseases.

Among the various components of tracheobronchial secretions, lipids and particularly phospholipids have been shown to influence rheological properties of airway secretions in patients with cystic fibrosis. We studied the phospholipid composition of tracheobronchial secretions, collected from patients suffering from cystic fibrosis (CF) and other chronic obstructive pulmonary diseases (COPD), and we analyzed the possible relationship between the phospholipid profile and the wettability of tracheobronchial secretions evaluated by the measurement of contact angle. Although total phospholipid content and contact angle of tracheobronchial secretions were significantly increased (P less than 0.01) in CF compared to COPD, no significant relationship existed between these two parameters. The concentrations of the different phospholipid subclasses were not homogeneously modified according to the origin of the secretions. Compared to COPD secretions, the CF secretions were characterized by a significant (P less than 0.001) increase in rigidifying fractions such as sphingomyelin and phosphatidylserine/phosphatidylinositol and a significant (P less than 0.001) decrease in surface-active fractions, such as phosphatidylcholine and phosphatidylglycerol (PG) (P less than 0.001). In the two groups, the surface-active phospholipid fraction, PG, was negatively correlated to the contact angle of tracheobronchial secretions. These results suggest that a decrease in PG content in CF secretions may be one factor responsible for an increase in their adhesivity to the respiratory mucosa, and, consequently, for mucus stasis and severity of bronchial obstruction in cystic fibrosis.     

Changes in spirometry during consecutive admissions for infective pulmonary exacerbations in adolescent and adult cystic fibrosis.

Changes in spirometry during consecutive admissions for treatment of pulmonary infective exacerbations were studied in 45 patients (24 males, 21 females) with cystic fibrosis (CF) who had required five or more such admissions. Over the overall study period there was a mean (SD) decline in FEV1 of -112.1 (188.0) ml yr-1 (P less than 0.001) and in FVC of -47.9 (82.4) ml yr-1 (P less than 0.001). FEV1 and FVC increased during each admission with treatment; however, the magnitude of this change became less over consecutive admissions by a mean value of -33.3 ml (45.0) (P less than 0.001) for FEV1, and -26.0 (72.2) ml (P less than 0.05) for FVC. In the majority of patients that died or underwent transplantation, FEV1 at the time of the last admission did not rise above 800 ml despite full treatment.     

The benefits of exercise combined with physiotherapy in the treatment of adults with cystic fibrosis.

The impact of exercise, physiotherapy, and combinations of exercise and physiotherapy upon sputum expectoration were compared in 18 adults with cystic fibrosis. Any treatment which included physiotherapy either alone or in combination with exercise produced a significantly higher sputum weight during treatment time than did exercise alone (P < 0.01). This trend was true for both high (greater than 35 g in 24 h) and low (less than 35 g in 24 h) sputum producers (P < 0.05). There were no significant changes in FEV1 and FVC 30 min after any treatment. The treatment option preferred by patients to continue at home was exercise followed by physiotherapy (P < 0.001). Exercise alone was less productive than the other three modalities in clearing sputum (P < 0.001).     

Levels of free granulocyte elastase in bronchial secretions from patients with cystic fibrosis: effect of antimicrobial treatment against Pseudomonas aeruginosa

Large amounts of free granulocyte elastase (GE), an enzyme capable of mediating airway damage, have been found in bronchial secretions of patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. This finding indicates an imbalance between GE and its antiproteases, alpha 1-proteinase inhibitor (alpha 1-PI) and bronchial mucosal inhibitor (BMI), in the airways of these individuals. The effect of intravenous antimicrobial treatment against P. aeruginosa on activity and concentration of GE, BMI, and alpha 1-PI was evaluated in 30 treatment courses of 20 patients with cystic fibrosis. Although sputum volume and level of immunoreactive GE decreased and concentrations of alpha 1-PI and BMI increased significantly (P less than .05), a high level of free GE persisted. No active alpha 1-PI and BMI were detectable after treatment. High levels of GE correlated with a poor pulmonary condition (rs = .98, P less than .001). In vitro, elastolytic activity of bronchial secretions from patients with cystic fibrosis was significantly inhibited by eglin C and an oxidation-resistant variant of alpha 1-PI, both compounds currently produced by recombinant DNA technology.     

Ion transport abnormalities in rectal suction biopsies from children with cystic fibrosis

Abnormalities in transepithelial electrolyte transport in cystic fibrosis rectum were analyzed by short-circuit current measurements on 11 control subjects and 11 subjects with cystic fibrosis in a modified Ussing chamber. As judged by the amiloride-sensitive component of the short-circuit current, electrogenic sodium absorption appeared unmodified in cystic fibrosis. In contrast, the short-circuit current response to specific stimuli of both cyclic adenosine monophosphate (cAMP)- and calcium-mediated chloride secretion was drastically altered in all of the cystic fibrosis biopsy specimens examined. Stimulation of the cAMP pathway by 8-bromo cAMP or forskolin resulted in a sustained increase in short-circuit current in control tissues (+ 2.51 +/- 0.63 microA/cm2) but in a slight change in the opposite direction in cystic fibrosis (-0.56 +/- 0.49 microA/cm2; P less than 0.05). Carbachol, a calcium-linked secretagogue, provoked a transient increase in short-circuit current in all of the control tissues (peak response, + 26.69 +/- 3.63 microA/cm2) but a transient change in the opposite direction in 6 of 11 cystic fibrosis tissues (-12.46 +/- 4.64 microA/cm2; P less than 0.05). In 2 of 11 patients with cystic fibrosis, however, a significant but subnormal and transient increase in short-circuit current was observed (+ 2.62 +/- 0.04 microA/cm2; P less than 0.05), whereas in 3 of 11 patients with cystic fibrosis a transient change in the opposite direction (-9.83 +/- 2.20 microA/cm2; P less than 0.05) was followed by a small and transient increase (+ 2.89 +/- 0.83 microA/cm2; P less than 0.05). Using the calcium-mediated secretory response therefore, patients with cystic fibrosis could be divided into two categories: a major population showing defective anion secretion but active cation secretion and a subclass (including three siblings) showing residual but subnormal anion secretion. The easy accessibility of rectal samples and the inversed direction of the cAMP- or calcium-provoked short-circuit current is of considerable advantage in the diagnosis of cystic fibrosis.     

Respiratory tract colonization with Pseudomonas aeruginosa in cystic fibrosis: correlations between anti-Pseudomonas aeruginosa antibody levels and pulmonary function

Chronic Pseudomonas aeruginosa respiratory tract colonization in patients with cystic fibrosis is associated with development of antibodies to the organism. In contrast to the protection usually afforded by humoral immunity to a bacterial pathogen, the immune response to P. aeruginosa may help perpetuate infection and contribute to pulmonary damage in cystic fibrosis. To determine if specific anti-P. aeruginosa antibody levels correlated with pulmonary dysfunction, we measured antibodies to seven P. aeruginosa serotypes, and correlated the geometric mean titer with pulmonary function tests. Patients were divided into groups without P. aeruginosa colonization (n = 20), with recent colonization (n = 20), and with chronic colonization (n = 60). Noncolonized patients had normal pulmonary function or mild obstructive lung disease, and low anti-P. aeruginosa titers. Pulmonary function tests in recently colonized patients were not different from those of noncolonized patients, but antibody titers were higher. Following colonization FEV1 declined and titers increased rapidly. Patients with chronic colonization had worse pulmonary function and higher titers, but while the former were stable the latter gradually increased. An inverse correlation was found between anti-P. aeruginosa titer and FVC, FEV1, and FEF25-75 (P less than 0.001) in these patients; age was not a factor. The strong correlation between severity of lung disease and anti-P. aeruginosa titer demonstrates that an exaggerated immune response to P. aeruginosa is associated with pulmonary damage in patients with cystic fibrosis.     

Immunochemical characterization of the mucoid exopolysaccharide of Pseudomonas aeruginosa

Alginic acid-like mucoid exopolysaccharide was isolated from three strains of Pseudomonas aeruginosa obtained from the sputa of patients with cystic fibrosis. Purified mucoid antigens were greater than 99% uronic acid. With a hemagglutination assay, antibody responses to the mucoid exopolysaccharide were documented after immunization of rabbits with either whole mucoid organisms or purified mucoid exopolysaccharide. The mucoid antigen from one strain (no. 2192) was composed predominantly of a single serologic epitope shared among 40 alginate exopolysaccharides from different clinical isolates. The mucoid exopolysaccharide from the other two strains (nos. 1 and 258) had a serotype-specific determinant in addition to the common epitope. Analyses of antibody in sera from normal adults, children, and patients with cystic fibrosis culture-positive and culture-negative for mucoid P. aeruginosa showed a highly significant (P less than 0.001) association between increased hemagglutination titers and positive cultures for mucoid P. aeruginosa.     

Association of systemic immune complexes, complement activation, and antibodies to Pseudomonas aeruginosa lipopolysaccharide and exotoxin A with mortality in cystic fibrosis

The relevance of circulating immune complexes, plasma complement activation, and serum antibodies against discrete antigens of Pseudomonas aeruginosa, to the clinical course in patients with cystic fibrosis (CF) is unknown. We related these factors to outcome in 49 patients with CF colonized by P. aeruginosa, comparing 14 who died of lung disease with 35 survivors of similar age and duration of colonization, as well as 9 uncolonized patients with CF, 24 patients with other bronchorrheic lung disease, and 10 healthy control subjects. The patients with CF colonized by P. aeruginosa who died had a higher incidence of immune complexes than did survivors (71 versus 40%, p less than 0.05). Moreover, C4 activation was highly associated with immune complexes and mortality (p less than 0.001 for each). Those who died also had much higher levels of IgG antibodies to P. aeruginosa lipopolysaccharide (LPS) and exotoxin A than did survivors colonized by P. aeruginosa (p less than 0.005 and p = 0.01, respectively), whereas both groups had similar levels of P. aeruginosa sonicate, elastase, alkaline protease, and endotoxin core antibodies. We conclude that increasing levels of serum IgG antibodies to P. aeruginosa LPS and exotoxin A and the presence of systemic immune complexes and complement activation are associated with poor prognosis in CF, and may provide useful noninvasive markers for studying the possible immunopathogenesis of CF lung disease.     

Serum bioactive parathyroid hormone in hemodialysis patients

In 41 hemodialysis patients with bone disease (histological diagnosis with histomorphometric confirmation of PTH activity) results from a serum immunoreactive PTH (iPTH) assay correlated with results from a new serum bioactive PTH (bio-PTH) assay (r = 0.84; P less than 0.001). The serum bio-PTH values correlated well with osteoclast numbers (r = 0.70; P less than 0.001), resorption surfaces (r = 0.55; P less than 0.001), and presence of marrow fibrosis (P less than 0.02). The serum iPTH values also correlated with osteoclast numbers (r = 0.61; P less than 0.001), resorption surfaces (r = 0.47; P less than 0.003), and presence of marrow fibrosis (P less than 0.02). Serum bio-PTH and iPTH values were higher in patients with severe hyperparathyroidism than in other patients. The assays were equally useful in identifying dialysis patients with severe hyperparathyroidism. Patients with osteomalacia or low turnover bone disease had low serum bio-PTH and/or iPTH values. Low bio-PTH values (less than or equal to 3.6 pmol/L) had a sensitivity and a specificity of 93% for osteomalacia or low turnover bone disease. Low bio-PTH values also were useful in identifying those patients with positive aluminum staining in bone. The serum bio-PTH assay was useful in identifying patients with osteomalacia, low turnover bone disease, or aluminum accumulation.     

Tobramycin in patients with cystic fibrosis. Adjustment in dosing interval for effective treatment

The efficacy of the dosing regimen of tobramycin was investigated in 28 patients with cystic fibrosis who had an acute exacerbation of chronic pulmonary infection with Pseudomonas aeruginosa. The initial dose of tobramycin was 3.3 mg/kg of body weight three times daily (ie, 10 mg/kg/day). A highly significant relationship was found between the serum concentration of tobramycin before the dose and the change in the forced expiratory volume in one second (FEV1), both measured on the tenth day of treatment (rs = 0.75; p less than 0.001). In nine of the 16 patients who had a six-hour serum concentration of 1 mg/L or less on the tenth day of treatment, the eight-hour dosing interval of tobramycin was shortened to achieve a serum concentration of tobramycin of about 1 mg/L before the dose. In the other seven patients, the dosage of tobramycin was not changed. On the 20th day, seven of the nine patients in whom the dosing interval was shortened exhibited an increase in FEV1 of 20 percent or more. Such an increase was observed only in one of the seven patients in whom the dosing interval was not reduced (p less than 0.05). We conclude that individualizing the dosage of tobramycin in patients with cystic fibrosis results in a better clinical outcome.     

Spirometry and chest roentgenographic appearance in adults with cystic fibrosis.

The pathophysiologic manifestations of cystic fibrosis are continually evolving as more patients survive into their adult years. Although the correlation between chest roentgenographic appearance and pulmonary function testing is well described in children with cystic fibrosis, to our knowledge, there are no data that evaluate this relationship in adults. We analyzed 66 paired studies of chest roentgenographic appearance (Brasfield score) and spirometry in 27 adults with cystic fibrosis between the ages of 18 and 40 years. There was a very good correlation between spirometry and the Brasfield score in adults with cystic fibrosis. The strongest correlation was between the percent predicted FEV1 and the Brasfield score (r = 0.68, p less than 0.001). These correlations were found to remain significant in the patients in whom longitudinal data were available. The FEV1 declined 104 +/- 26 ml/yr in 11 patients who were followed up for a mean duration of 5.8 +/- 0.5 years. The decline in FEV1 per year in adults with cystic fibrosis was significantly greater than in nonsmoking or smoking adults of similar age.     

Pancreatic morphology and function in adult patients with cystic fibrosis.

To determine the relation between pancreatic morphology and pancreatic exocrine and endocrine function, we have studied 8 adult cystic fibrosis patients and 14 normal control subjects by ultrasonography and pancreatic function testing. In the patients with cystic fibrosis the maximum anteroposterior diameter of the pancreatic head was significantly increased over that in control subjects (p less than 0.01), whereas the maximum diameter of the body was significantly decreased (p = 0.05). Increased echogenicity of the pancreatic body was observed in most patients. In the cystic fibrosis patients postprandial insulin secretion was reduced in the 1st h (p less than 0.005 versus control), whereas pancreatic polypeptide secretion was virtually abolished for at least 3 h (p less than 0.01 versus control). All cystic fibrosis patients had evidence of exocrine pancreatic dysfunction as reflected by a diminished urinary para-aminobenzoic acid excretion. Intraduodenal enzyme and bicarbonate output in response to secretin-cholecystokinin was reduced in all of three patients studied. It is concluded that loss of endocrine and exocrine pancreatic function in adult cystic fibrosis patients is accompanied by a small and echo-dense pancreatic body relative to a large pancreatic head.     

Relation of complex ventricular arrhythmias to presenting features and prognosis in dilated cardiomyopathy

To evaluate whether complex ventricular arrhythmias relate to presenting features and prognosis of dilated cardiomyopathy, 104 patients were studied from 1977 to 1987. At diagnosis, the 19 patients with complex ventricular arrhythmias (18%), as compared to the 85 patients without (82%), had a higher incidence of palpitation (P less than 0.01), severe dyspnea (P less than 0.001) and atrial fibrillation (P less than 0.01). They showed also higher mean right atrial pressures (10 +/- 5 vs 6 +/- 4 mm Hg, P less than 0.001) and higher right ventricular end-diastolic pressures (11 +/- 4 vs. 7 +/- 4 mm Hg, P less than 0.001) than patients without complex ventricular arrhythmias. Histologic samples were collected from the 32 patients (31%) studied since 1984 and semiquantitatively graded. The 11 patients with complex ventricular arrhythmias showed a higher frequency of severe interstitial fibrosis than the 21 patients without (64% vs. 24%, P less than 0.05), but they were otherwise similar as to the frequency of marked myocellular hypertrophy, changes of myocardial regression, endocardial fibrosis, attenuation of myocytes, hyperplasia of smooth muscle cells and infiltration by inflammatory cells. During a follow-up of 3.8 +/- 3.5 years, 35 patients (34%) died. Mortality was 58% (11 out of 19) in patients with complex ventricular arrhythmias and 28% (24 out of 85) in patients without (P less than 0.025). These results show that complex ventricular arrhythmias in dilated cardiomyopathy are associated with impairment of function of the right heart and severe interstitial fibrosis of the left ventricle, rather than with left ventricular dysfunction. Presence of complex ventricular arrhythmias also seems to identify those at high risk for death.     

Skin reactivity to atypical mycobacteria in cystic fibrosis

Atypical mycobacterial disease has been described in a small number of patients with cystic fibrosis. Apart from one uncontrolled study, there is little information regarding atypical mycobacterial skin reactivity in this group of patients. We evaluated delayed cutaneous hypersensitivity to purified extracts of Mycobacterium avium, Mycobacterium intracellular, Mycobacterium kansasii and Mycobacterium bovis in 23 healthy controls and 43 adult and adolescent patients with cystic fibrosis. Fifteen of the cystic fibrosis group were receiving regular corticosteroids. Additionally, direct smear examination and Lowenstein Jensen culture were performed on sputum from the cystic fibrosis group. The prevalence of positive skin reactions was similar in the group with cystic fibrosis (30%) and in the control group (57%). Subgroup analysis showed that those cystic fibrosis patients receiving corticosteroids had a markedly lower prevalence of positive reactions (7%) compared to controls (P less than 0.01). When this subgroup was excluded from analysis, the prevalence of positive skin reactions among patients with cystic fibrosis was 43%. In the prospective sputum bacteriology study, one of the 43 cases grew Mycobacterium avium-intracellulare and had clinical and radiological evidence of this disease. Of note, this patient showed positive skin tests to all four mycobacterial species tested. Our data show no difference in the prevalence rate of positive skin reactions to atypical mycobacterial antigens between a control population and an adult cystic fibrosis population. In addition, the predictive value of skin testing is low in cystic fibrosis due to the high prevalence of cross-reactivity between different mycobacterial species and the high prevalence of anergy among those patients with advanced disease receiving treatment with corticosteroids.     

Relationships among digital clubbing, disease severity, and serum prostaglandins F2alpha and E concentrations in cystic fibrosis patients

Nine patients with cystic fibrosis but without digital clubbing (Group A) were matched, prospectively, by sex and approximate age to 9 cystic fibrosis patients with digital clubbing (Group B) and to 9 normal persons (control subjects). Patients in Group B had significantly (P less than 0.05) lower clinical scores and forced vital capacity than did those in Group A, indicating more severe pulmonary disease in the former; however, other spirometer tests of pulmonary function revealed no differences between Groups A and B. The degree of digital clubbing had significant (P less than 0.05) linear relationships to forced vital capacity (r = -0.73) and clinical scores (r = 0.853) for Groups A and B. Plasma concentrations of prostaglandins F2alpha and E were significantly increased (P less than 0.05) in both Group A (X +/- SE, 0.48 +/- 0.03 and 0.87 +/- 0.10 ng per ml, respectively) and Group B (X +/- SE, 0.68 +/- 0.04 and 1.81 +/- 0.16 ng per ml, respectively) compared to the control group (X +/- SE, 0.14 +/- 0.01 and 0.39 +/- 0.02 ng per ml, respectively). Group B had significantly larger concentrations than did Group A; however, plasma concentrations of prostaglandin 15-keto-13, 14-dihydro metabolite were not different in Groups A and B, and were significantly smaller than in the control group. These studies suggest that the degree of digital clubbing in cystic fibrosis is related to the severity of the pulmonary involvement and that the prostaglandin system may play an important role in this disease.     

Histological improvement of chronic hepatitis B, and non-A, non-B with interferon treatment: application of a numerical scoring system for evaluating sequential morphologic changes

In order to assess the sequential changes of liver pathology after interferon therapy, 70 liver biopsy specimens, collected from 23 HBeAg-positive patients with chronic hepatitis B and 12 patients with chronic non-A, non-B hepatitis, were studied using a numerical scoring system proposed by Knodell et al. The biopsy specimens were obtained immediately prior to the administration of interferon and within one week following the termination of interferon therapy. Three patients with chronic hepatitis B were negative for DNA-polymerase (DNA-P) prior to the interferon administration. Ten patients (50%) lost DNA-P activity. HBeAg became negative in 8 patients (34.8%), of whom 2 seroconverted to anti-HBe. Serum alanine aminotransferase levels normalized in 9 patients with chronic hepatitis B, and non-A, non-B hepatitis. The total Histological Activity Index (HAI) scores in both patients with chronic hepatitis B, and non-A, non-B decreased significantly (P less than 0.001 and P less than 0.005, respectively) after interferon treatment. There was also a significant improvement (0.02 less than P less than 0.001) in each histological category except for fibrosis. When the changes of the HAI scores in patients with chronic hepatitis B were correlated to the outcome in the DNA-P and HBeAg/anti-HBe system after treatment, the histological improvement did not significantly correlate to the outcome of these serological parameters.     

Urinary excretion of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in normal children and those with cystic fibrosis.

The urinary excretion of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) was examined in 98 normal children and 46 children with cystic fibrosis between the ages of 9 months and 18 yr. Diurnal variations in cyclic AMP and cyclic GMP excretion were observed in subjects from either group, and peak levels of cyclic nucleotide excretion were generally observed during the period of 0700 to 2100 h. Excretion rates (mumol/day) of cyclic AMP and cyclic GMP increased significantly with age. When cyclic AMP and cyclic GMP excretion rates were normalized for urinary creatine, or body weight, the values declined significantly with age in both groups of patients. Cyclic GMP excretion normalized for body surface area also decreased with age, while the value for cyclic AMP (2.86 plus or minus 0.08 mumol/day/m2, mean plus or minus SE) was constant with age in both normals and cystic fibrosis children. With some comparisons of age groups there were significant differences in cyclic nucleotide excretion between normal subjects and children with cystic fibrosis. The differences noted were dependent upon the methods used to normalize excretion rates (urinary creatine, body weight, surface area, and the ratio of cyclic AMP to cyclic GMP excreated). In general patients with cystic fibrosis excreted greater amounts of cyclic GMP than did normals. The most striking comparison was the ratio of cyclic AMP to cyclic GMP excreted which was 9.09 plus or minus 0.50 in all normal children and 4.41 plus or minus 0.32 in children with cystic fibrosis (P smaller than 0.001).     

Passive smoking in cystic fibrosis

The families of 32 children with cystic fibrosis (CF) were interviewed about both their tobacco consumption and their childrens physical activities. Hospital records informed about treatment frequency, lung function and clinical score. Cystic fibrosis families smoked far more than the Swedish average and the passive smokers among our patients seemed to fare less well in all parameters. The children of smoking mothers required significantly longer periods of intravenous antibiotic treatment (P greater than 0.05). Frequent physical exercise seemed to compensate for the potential harmful effects of passive smoking and children with high physical activity living in families who smoked needed significantly less frequent antibiotic treatment than the inactive children (P greater than 0.02). Although this series is small, the results indicate that a smoke-free environment may be important for CF patients. General information is insufficient and extensive psychological support to the families is probably necessary.