Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis

Smith, Arnold L.; Redding, Gregory J.; Doershuk, Carl F.; Goldmann, Donald A.; Gore, Edmond J.; Hilman, Bettina C.; Marks, Melvin I.; Moss, Richard B.; Ramsey, Bonnie W.; Roblo, Thomas; Schwartz, Robert H.; Thomassen, Mary Jane; Williams‐Warren, Judy; Weber, Allan; Wilmott, Robert W.; Wilson, Helen; Yogev, Ram

doi:10.1016/s0022-3476(88)80165-3

Cited by 132 publications

(94 citation statements)

References 19 publications

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“…Moreover, increase in viscosity of purulent sputum is correlated with difficulty in expectoration in patients with chronic bronchitis (46). Finally, a recent multicenter study of antibiotic therapy of exacerbations in cystic fibrosis reveals that a reduction in sputum DNA content was correlated with clinical improvement (47). Our studies suggest that inhalation of a rhDNase aerosol may reduce the viscosity of purulent secretions and thereby help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways and breathe more easily.…”

Section: Resultsmentioning

confidence: 54%

Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

Shak¹,

Capon²,

Hellmiss³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

653

399

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Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions.

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Section: Resultsmentioning

confidence: 54%

Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

Shak¹,

Capon²,

Hellmiss³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

653

399

View full text Add to dashboard Cite

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“…Studies of young patients with CF who have recent acquisition of P. aeruginosa and of older patients with non-CF bronchiectasis have shown evidence of eradication (4,13,14,24,37). In contrast, although antibiotic therapy may improve clinical status and reduce bacterial burden by up to 2 log 10 in older CF patients (23,25,33), efforts to eradicate P. aeruginosa in the setting of more established CF airway infections have generally failed. Among a group of CF patients with chronic persistent P. aeruginosa infection, 28 days of tobramycin inhalation decreased the geometric mean bacterial density by only 1.9 log 10 CFU/g (23).…”

Section: Discussionmentioning

confidence: 99%

Clinically Feasible Biofilm Susceptibility Assay for Isolates of Pseudomonas aeruginosa from Patients with Cystic Fibrosis

et al. 2004

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Pseudomonas aeruginosa is the predominant cause of chronic airway infection in cystic fibrosis (CF). CF airway isolates are often tested for antibiotic susceptibility but are rarely eradicated by the antibiotics identified as potentially effective. The growth state of P. aeruginosa in CF airways is probably different from that exhibited under conventional susceptibility testing conditions and may represent a bacterial biofilm. Biofilm susceptibility testing methods were adapted to create an assay for implementation in a clinical microbiology laboratory. This assay gave reproducible results when examined in 300 paired determinations with 12 antimicrobial agents, with a serious error rate of 5.7%. The biofilm assay was used retrospectively to test these 12 agents against 94 isolates from 41 CF patients. The biofilm inhibitory concentrations (BICs) were much higher than the corresponding conventionally determined MICs for the ␤-lactam antibiotics (median values: aztreonam, >128 g/ml versus 4 g/ml; ceftazidime, 128 g/ml versus 2 g/ml; piperacillin-tazobactam, 256 g/ml versus 4 g/ml; and ticarcillin-clavulanate, 512 g/ml versus 16 g/ml, respectively) and doxycycline (>64 g/ml versus 16 g/ml); and similar for meropenem (4 g/ml versus < 1 g/ml), ciprofloxacin (0.5 g/ml versus 1 g/ml), and the aminoglycosides amikacin (32 g/ml versus 16 g/ml), gentamicin (16 g/ml versus 8 g/ml), and tobramycin (4 g/ml versus 2 g/ml). The median BIC for azithromycin was 2 g/ml, whereas isolates were uniformly resistant when tested by standard methods. This demonstrates the feasibility of adapting biofilm susceptibility methods to the clinical microbiology laboratory and opens the way to examining whether biofilm testing might be used to select more effective antibiotic combinations for CF airway infections than methods in current use.

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“…The exact reason for this positive effect remains unclear. CF is characterized by an abnormal rheology of the mucus layer [23,24], due to the presence of an increased amount of DNA, originating especially from neutrophils [7,8]. The effect of rhDNAse is based on depolymerization of this DNA [25].…”

Section: Discussionmentioning

confidence: 99%

“…Mucociliary clearance of the viscous mucus is impaired, which causes an ideal basis for colonization and infection with microorganisms. These infections give local inflammation with an influx of predominantly neutrophils [7,8]. Degradation of these neutrophils causes DNA release, which leads to an increase in viscosity of sputum, further increasing the susceptibility for colonization and infection [9].…”

Section: Introductionmentioning

confidence: 99%

No positive effect of rhdnase on the pulmonary colonization in children with cystic fibrosis

Bonestroo

Slieker

Arets

2016

Monaldi Arch Chest Dis

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Background. Long-term clinical trials have shown that daily treatment with recombinant human deoxyribonuclease (rhDNAse) in patients with mild to moderate cystic fibrosis (CF) improves lung function and decreases the number of respiratory exacerbations. The aim of this study was to analyze the effect of rhDNAse on the bacterial colonization of the airways in children with CF. Methods. This was a retrospective cohort study. From the database of the CF Center Utrecht, we selected two groups, an rhDNAse group (daily 2.5 mg rhDNAse) and a control group (no rhDNAse). Primary outcome parameter was the difference in change in bacterial colonization between the treatment and control group during 1.5-year. Secondary outcome parameters were changes in lung function (FEV1) and pulmonary exacerbations. Results. Children treated with rhDNAse showed no significant changes in bacterial colonization during the treatment period, apart from an increase of P. aeruginosa positive cultures, both compared to baseline (53.1% versus 25%, p<0.05) and control group (no change during study period, 37% versus 37%). The change in FEV1 after one year of treatment was +4.0% in the treatment group versus -0.3% in the control group (p=0.22). There were no significant changes in number of pulmonary exacerbations. Conclusions. This study showed no significant beneficial decrease in bacterial airway colonization during 1.5-year of treatment with rhDNAse. The positive effects of rhDNAse on the lung function can therefore not be explained by a change in airway colonization.

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Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis

Cited by 132 publications

References 19 publications

Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

Clinically Feasible Biofilm Susceptibility Assay for Isolates of Pseudomonas aeruginosa from Patients with Cystic Fibrosis

No positive effect of rhdnase on the pulmonary colonization in children with cystic fibrosis

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