Sinus surgery postpones chronic Gram-negative lung infection: cohort study of 106 patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined by Leeds criteria. RESULTS: One hundred and six CF patients underwent ESS; 27 had improved lung infection status after three years. The prevalence of patients free of lung colonization with GNB significantly increased from 16/106 patients (15%) preoperatively to 35/106 patients (33%) after three years. The total cohort had decreasing lung function during follow-up; however, in 27 patients with improved lung infection status lung function was stable. Revision surgery was performed in 31 patients (28%). CONCLUSION: ESS with adjuvant therapy significantly improves the lung infection status for at least three years in our cohort of patients with CF and may postpone chronic lung infection with GNB and thus stabilize lung function.

Nitric oxide production by polymorphonuclear leucocytes in infected cystic fibrosis sputum consumes oxygen.

Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by persisting mucoid biofilms in hypoxic endobronchial mucus. These biofilms are surrounded by numerous polymorphonuclear leucocytes (PMNs), which consume a major part of present molecular oxygen (O(2)) due to production of superoxide (O(2)(-)). In this study, we show that the PMNs also consume O(2) for production of nitric oxide (NO) by the nitric oxide synthases (NOS) in the infected endobronchial mucus. Fresh expectorated sputum samples (n = 28) from chronically infected CF patients (n = 22) were analysed by quantifying and visualizing the NO production. NO production was detected by optode measurements combined with fluorescence microscopy, flow cytometry and spectrophotometry. Inhibition of nitric oxide synthases (NOS) with N(G) -monomethyl-L-arginine (L-NMMA) resulted in reduced O(2) consumption (P < 0·0008, n = 8) and a lower fraction of cells with fluorescence from the NO-indicator 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM) (P < 0·002, n = 8). PMNs stained with DAF-FM and the superoxide indicator hydroethidine (HE) and host cells with inducible NOS (iNOS) were identified in the sputum. In addition, the production of the stable end-products of NO in CF sputum was correlated with the concentration of PMNs; NO(3)(-) (P < 0·04, r = 0·66, n = 10) and NO(2)(-) (P< 0·006, r = 0·78, n = 11). The present study suggests that besides consumption of O(2) for production of reactive oxygen species, the PMNs in CF sputum also consume O(2) for production of NO.

Clinical effects of sinus surgery and adjuvant therapy in cystic fibrosis patients - can chronic lung infections be postponed?

BACKGROUND: The paranasal sinuses can be a bacterial reservoir for pulmonary infections in patients with cystic fibrosis (CF) METHODOLOGY: In this prospective, non-randomised, uncontrolled, intervention cohort study, the clinical effect of sinus surgery followed by two weeks` intravenous antibiotics, 6 months` antibiotic nasal irrigations was assessed in 106 CF patients. RESULTS: One year after sinus surgery, the prevalence of intermittently colonised patients had decreased by 38%, while the prevalence of non-colonised patients had increased by 150%. The frequency of pulmonary samples with CF pathogens was reduced after surgery. Specific IgG against P. aeruginosa decreased after six months. Additionally, the self reported symptoms of chronic rhinosinusitis and quality of life improved. CONCLUSION: Combined sinus surgery and postoperative systemic and topical antibiotic treatment significantly reduced the frequency of pulmonary samples positive for CF pathogens in the first year after sinus surgery.

Extensive endoscopic image-guided sinus surgery decreases BPI-ANCA in patients with cystic fibrosis.

Antineutrophil cytoplasm autoantibodies (ANCA) directed against bactericidal/permeability-increasing protein (BPI) are common in patients with cystic fibrosis (CF), and serum levels are correlated with lung colonization by Pseudomonas aeruginosa and the severity of lung damage. The production of BPI-ANCA may be due to the costimulation of BPI when mounting an immune response against P. aeruginosa. The effect of surgery aiming to eradicate bacteria and infected tissue on BPI-ANCA levels is sparsely described. A cohort of patients with CF were included: 53 patients having extensive image-guided sinus surgery (EIGSS) with topical postoperative antibiotic treatment, 131 non-operated controls and 36 who had double lung transplantation (LTX). In all 219 patients, serum samples before and after surgery or at similar intervals were analysed for IgG and IgA BPI-ANCA. The EIGSS group showed a highly significant decrease in both IgA and IgG BPI-ANCA levels compared with their own preoperative values and control group values (P < 0.001-0.02). The LTX patients also showed a highly significant decrease in both IgA and IgG BPI-ANCA levels (P < 0.001). EIGSS and LTX decrease IgA and IgG BPI-ANCA levels in patients with CF, indicating that extensive removal of infected tissue influences the pathogenic process of autoantibody production. The results shown herein are in favour of applying EIGSS in selected patients with CF and for using BPI-ANCA as a surrogate marker for guiding further therapeutic interventions.

Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study.

AIMS/HYPOTHESIS: Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis-related glucose intolerance. METHODS: We enrolled 898 cystic fibrosis patients from Sweden, Norway and Denmark. Vitamin D intake was assessed using a seven-day food record. Serum 25-hydroxyvitamin D (s25OHD) and HbA(1c) were measured, and an OGTT was carried out. Multiple linear and logistic regressions were used for HbA(1c) and cystic fibrosis-related diabetes/OGTT result as outcome variables, respectively. Each model was controlled for country, and for known cystic fibrosis-related diabetes risk factors: age, sex, genotype, liver dysfunction, long-term corticosteroid treatment, and lung and pancreatic function. RESULTS: Degree of vitamin D insufficiency (OR 1.36; p = 0.032) and s25OHD < 30 nmol/l (OR 1.79; p = 0.042) were significant risk factors for cystic fibrosis-related diabetes. Accordingly, HbA(1c) value was positively associated with s25OHD < 30 nmol/l and < 50 nmol/l, as well as with degree of vitamin D insufficiency (adjusted R (2) = 20.5% and p < 0.05 in all). In subgroup analyses, s25OHD < 30 nmol/l determined the HbA(1c) value in paediatric patients (adjusted R (2) = 20.2%; p = 0.017), but not in adults. CONCLUSIONS/INTERPRETATION: Vitamin D status is associated with HbA(1c) and diabetes in cystic fibrosis, particularly in children. The study justifies prospective studies on the proposed role of vitamin D deficiency in the pathophysiology of diabetes mellitus.

Long-term, low-dose azithromycin treatment reduces the incidence but increases macrolide resistance in Staphylococcus aureus in Danish CF patients.

BACKGROUND: Since 2001, long-term, low-dose azithromycin treatment has been used for CF patients chronically infected with Pseudomonas aeruginosa in the Copenhagen CF centre. Our study investigates changes in incidence of colonization with Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and changes in macrolide sensitivity in these microorganisms during azithromycin treatment. METHODS: CF patients treated continuously with azithromycin for at least 3 months were included. Results of microbiological examination, including phage typing results of S. aureus, obtained during treatment were compared to results obtained 2 years before treatment. RESULTS: 70 patients (median age 29.1 years) treated for a median of 4 years (range 0.7-5.1) were included. Before treatment, 44 patients had at least one culture positive for S. aureus compared to 25 patients during treatment (p<0.01). Mean percentage of sputum samples with growth of S. aureus decreased from 12.1% (range 0-82.6%) before treatment to 6.1% (range 0-93.2) during treatment (p<0.0006). Prevalence's of H. influenzae and S. pneumoniae also decreased significantly. Fifteen of 214 isolates (7%) of S. aureus were macrolide resistant before treatment, increasing to 95 of 181 isolates (52.5%) during treatment (p<0.001). Macrolide resistant strains were found in 3 of 44 S. aureus colonized patients before treatment and in 11 of 25 patients at some time during treatment (p<0.03), all belonging to different phage types. First resistant S. aureus isolate was isolated after a median treatment duration of 1.5 years (range 0.3-2.9). No MRSA were isolated. Only 1 macrolide resistant isolate of M. catarrhalis was found during treatment. No macrolide resistance was found in H. influenzae or S. pneumoniae. CONCLUSION: Long-term, low-dose treatment with azithromycin in CF patients leads to reduced prevalence of S. aureus, S. pneumoniae, and H. influenzae, but increased macrolide resistance in S. aureus. Reduction in the prevalence of S. aureus will make increasing macrolide resistance clinically insignificant in these patients.

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test.

BACKGROUND: Early signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk. METHODS: A retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984-2015. RESULTS: Three-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p < 0.001). Test sensitivity was 100% (95% CI 40-100) and specificity 77% (95% CI 72-81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay. CONCLUSIONS: Antibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high- and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.

Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience.

BACKGROUND: Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment. METHODS: All isolates of P. aeruginosa from CF-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non-mucoid or mucoid phenotype. RESULTS: 146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1-14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up to 80% of patients for up to 15 years. 613 colistin/ciprofloxacin treatments were given. There was no difference in pseudomonas-free interval comparing 3 weeks (5 months) and 3 months (10.4 months) of colistin and ciprofloxacin, but a significant difference compared to no treatment (1.9 months). Patients developing chronic infection had significantly shorter pseudomonas-free interval after treatment of first ever isolate compared to patients remaining intermittently colonized (p<0.003). Treatment failure (P. aeruginosa-positive culture immediately after ended treatment of first ever isolate) was a strong risk factor for development of chronic infection after 3-4 years, OR 5.8. 1093 pseudomonas-isolates were evaluated (86.6% non-mucoid). No colistin-resistance was found. Ciprofloxacin-resistance was found in 4% of isolates. CONCLUSION: Treatment of intermittent P. aeruginosa colonization in CF-patients using colistin and ciprofloxacin can protect up to 80% of patients from development of chronic infection for up to 15 years. A positive culture immediately after treatment of first ever isolate is a strong risk factor for development of chronic infection. We found no colistin-resistance and minimal ciprofloxacin-resistance.

Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis.

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF.

Individual pharmacokinetic variation leads to underdosing of ciprofloxacin in some cystic fibrosis patients.

BACKGROUND: Ciprofloxacin (CIP) is frequently used when treating cystic fibrose (CF) patients with intermittent Pseudomonas aeruginosa (P. aeruginosa) lung colonization. However, approximately 20% of the patients progress to chronic infection despite early intervention. The aim of this study, was to investigate the pharmacokinetics of CIP, to evaluate if CYP3A4-related metabolism is involved and to find the optimal dose needed to eradicate intermittently colonizing bacteria in the lungs of CF patients. Methods An open-label, prospective pharmacokinetic study was performed. Twenty-two adult CF-patients were each given 500 mg CIP orally. One blood sample was taken at t = 0, and the following 12 hr, nine blood samples were collected. The optimal dose and interval was then calculated by Monte Carlo simulation. CYP3A4-activity was mesured using the Erythromycin Breath Test (ERMBT). Results A 14-fold variation in AUC for the 500 mg CIP (median 473.5 µg/ml × min), and a 30-fold variation in Cmax for CIP (median 2 µg/ml) was found. For CYP3A4-activity the variation was 8-fold. No correlation was found between the CYP3A4-activity and CIP-concentrations. The probability of eradicating intermittent P. aeruginosa colonization in the lungs of CF patients was found to be 57% (3 doses/day), when 500 mg CIP was given. It was calculated to be 89% (2 doses/day) and 94% (3 doses/day), respectivly if 750 mg CIP had been given. Conclusion A large pharmacokinetic difference of CIP in CF patiens was found, not explained by CYP3A4 variation. CIP should be given at 750 mg two or three times daily to adult CF patients with intermittently colonization. Pediatr Pulmonol. 2017;52:319-323. © 2016 Wiley Periodicals, Inc.

Erratum to: Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

[This corrects the article DOI: 10.1186/s40064-016-2862-5.].

Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF. METHODS: We administered three standardized questionnaires to 67 patients with CF aged 18-30 years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised. RESULTS: There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (p < 0.01) with medium to large deficits across on all HRQoL domains (Cohen's d 0.60-1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (r = -0.412, p < 0.001). CONCLUSIONS: Despite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed.

Eradication of early Pseudomonas aeruginosa infection.

Chronic pulmonary infection with Pseudomonas aeruginosa is responsible for most of the morbidity and mortality in cystic fibrosis (CF). Once established as a biofilm, chronic P. aeruginosa infection caused by the mucoid phenotype cannot be eradicated. However, a period of intermittent colonization with P. aeruginosa precedes the establishment of the chronic infection. This window of opportunity can be utilized to eradicate P. aeruginosa from the respiratory tract of CF patients by means of oral ciprofloxacin in combination with nebulized colistin for 3 weeks or, even better, for 3 months or by means of inhaled tobramycin as monotherapy for 4 weeks or longer. This early, aggressive eradication therapy has now been used for 15 years without giving rise to resistance to the antibiotics and without serious side effects. The therapeutic results have been very successful and have completely changed the epidemiology in the Danish Cystic Fibrosis Center and a few other centers which have used this strategy for several years. The chronic P. aeruginosa lung infection is not seen in CF infants and children anymore due to the aggressive therapy, and no other bacteria have replaced P. aeruginosa in these young patients. The aggressive therapy has been shown to very cost-effective, and a European Consensus report recommends this approach.

The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type.

Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF -P) chronic P. aeruginosa lung infection. The specific production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by peripheral blood mononuclear cells was determined. Cells from CF +P patients had lower IFN-gamma (p<0.05) and higher IL-4 (p<0.005) production as compared to cells from CF -P patients. Furthermore, a positive correlation between IFN-gamma production and lung function was found (FVC: Rho = 0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1-dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might improve the prognosis in these patients.

Acute promyelocytic leukemia with t(15;17) and t(2;17;15).

Cytogenetic examination in a case of acute promyelocytic leukemia (FAB-M3) demonstrated a stem line with t(15;17) and a side line with t(2;17;15). This observation indicates either clonal evolution from the standard translocation or a de novo complicated translocation. Previous cases with three-way translocations in acute promyelocytic leukemia have been reviewed. Three-way translocations seem to occur with similar frequency in M2 and M3 types of acute myeloid leukemia and in chronic myelocytic leukemia.

Pharmacokinetics of erythrocyte methotrexate in children with acute lymphoblastic leukemia during maintenance treatment.

The concentration of methotrexate (MTX) in erythrocytes (E-MTX) was measured in 47 children with acute lymphoblastic leukemia during maintenance treatment with MTX 1.7-21.6 mg/m2/week and 6-mercaptopurine 25-75 mg/m2/day. At the time of measurement the plasma MTX concentration was less than 2 nmol/l. The steady state E-MTX varied between 51 and 202 nmol/l erythrocytes. Alterations in the E-MTX took place over 8-12 weeks after a change in dosage. A significant correlation was found between the E-MTX and the weekly dose of MTX administered. Noncompliance was revealed in two patients. A very low E-MTX was found in one patients, probably caused by inhibition of erythropoiesis. No correlation was found between E-MTX and the total amount of MTX administered or the length of treatment. A terminal half-life of 2-5 weeks after discontinuation of the drug showed that the erythrocytes functioned as a slow-changing compartment for MTX. Unexpectedly low E-MTX could mean noncompliance, impaired erythropoiesis, altered metabolism, or poor drug absorption.

Immunoglobulin allotypes and IgG subclass antibody response to Aspergillus fumigatus in cystic fibrosis patients.

BACKGROUND: A majority of patients with cystic fibrosis (CF) become colonised with Aspergillus fumigatus (Af.), but only a minority develops allergic bronchopulmonary aspergillosis (ABPA). ABPA is associated with increased levels of specific immunoglobulin G (IgG) anti-Af. antibodies with a characteristic IgG subclass distribution. We examined whether this characteristic immune response was under the influence of GM and KM allotypes, which are genetic markers (antigenic determinants) on gamma- and kappa-light chains, respectively. METHODS: Sera from 233 CF patients were typed for seven GM determinants and two KM determinants. The types were correlated to IgG subclass anti-Af. antibody levels and to the presence or absence of Af. colonisation as well as ABPA. RESULTS: The IgG2 antibody level was significantly higher in heterozygous GM (1,2,17 23 5,21 and 1,3,17 23 5,21) compared to homozygous GM allotypes (p = 0.02). Patients with the same allotypes tended to have higher IgG1 (p = 0.051). In patients with ABPA, being heterozygous for G1M and G3M was linked to higher IgG4 and lower IgG3 as compared to the other genotypes. The KM markers did not influence the antibody levels. The allotype GM(3 23 5), associated with atopic bronchial asthma, tended to make a relatively larger group in ABPA patients compared to non-ABPA and patients not colonised with Af. (p = 0.09). CONCLUSIONS: An influence of the GM allotypes on the immune response to Af. and on the development of ABPA in patients with CF is suggested.

IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection.

Chronic bronchopulmonary infection with alginate-producing, mucoid Pseudomonas aeruginosa is characteristically associated with cystic fibrosis (CF). A significant correlation between the antibody response to alginate and poor lung function has been reported. Enzyme-linked immunosorbent assays were developed for the quantitation of human IgG1, IgG2, IgG3, and IgG4 antibodies to P. aeruginosa alginate. We investigated the pattern of IgG subclass antibodies against P. aeruginosa alginate in serum of patients with CF, others with chronic P. aeruginosa infection, and healthy controls. Healthy controls and patients with CF, before they acquired P. aeruginosa infection, had no or very low titers of antibodies against P. aeruginosa alginate. The latter with chronic infection had significantly higher antibody levels than all others groups, including patients with chronic P. aeruginosa infection but no CF. CF with chronic P. aeruginosa infection led to an inverse correlation between lung function parameters and levels of IgG3 and IgG4. Fifty-seven patients with CF have been followed for an average of 12 years with multiple antibody assays covering the preinfection, early, and late stage of chronic infection. All of them developed IgG1 and IgG3 antibodies to alginate at the start of infection. IgG2 antibodies developed later and showed only a slow increase during the chronic infection. Patients who died had significantly higher IgG2 anti-alginate antibody levels than other investigated groups. Elevated levels of IgG2 and IgG3 antibodies to P. aeruginosa alginate are a sign of poor prognosis in CF.

Correlation between specific IgG subclass antibodies to Pseudomonas aeruginosa and opsonic activity in serum from patients with cystic fibrosis.

Heat-stable opsonins from sera of patients with cystic fibrosis (CF) non-CF patients with chronic Pseudomonas aeruginosa infection, healthy children, and adults were investigated for their ability to promote phagocytosis of 35S-labeled P. aeruginosa by human polymorphonuclear neutrophils. Healthy children had significantly lower levels of opsonic activity than adults. Sera from patients with CF without chronic P. aeruginosa lung infection showed significantly higher levels of opsonic activity compared to healthy children. Sera from patients with CF in the early stage of chronic infection had similar opsonic activity as non-CF patients with chronic infection. Sera from patients with CF in the late stage of chronic infection had higher opsonic activity than other infected patients, but not different from adult controls. An inverse correlation was found between levels of specific antibodies to P. aeruginosa and opsonic activity in the group of patients in a late stage of infection. An inverse correlation was also found between levels of IgG1 and IgG3 to P. aeruginosa St-Ag and opsonic activity during the late stage of infection. Infection with P. aeruginosa in CF did not induce significantly increased opsonic activity. It seems that antibodies to P. aeruginosa may have inhibitory opsonic activity.