Effect of hypertonic saline, amiloride, and cough on mucociliary clearance in patients with cystic fibrosis.

Regnis, J. A.; Bailey, Dale L.; King, Malcolm; Bautovich, George J.; Bye, Peter T. P.

doi:10.1164/ajrccm.153.5.8630593

Cited by 202 publications

(148 citation statements)

References 23 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Exacerbations were defined by the need for intravenous antibiotics or using a symptom score involving increased sputum production, lethargy, dyspnea, and fever. In previous smaller studies of CF subjects, a single nebulized dose of 6 -7% HS increased mucociliary clearance at 60 and 90 min, as measured by radionucleotide imaging (3,5). Increased mucociliary clearance was dose-dependent up to 12% HS in 10 adults treated with a single dose and tested at 90 min (4).…”

Section: Discussionmentioning

confidence: 80%

See 1 more Smart Citation

Hypertonic Saline Therapy in Cystic Fibrosis

Levin

Sullivan

Nielson

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Recent data indicate the clinical benefit of nebulized hypertonic saline in cystic fibrosis lung disease, with a proposed mechanism involving sustained increase in airway surface liquid volume. To account for the paradoxical observation that amiloride suppresses the beneficial effect of hypertonic saline, it has been previously concluded (Donaldson, S. H., Bennett, W. D., Zeman, K. L., Knowles, M. R., Tarran, R., and Boucher, R. C. Cystic fibrosis (CF)3 is a relatively common hereditary disease in Caucasians caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. Morbidity and mortality in CF result primarily from chronic airway infection, which results in progressive deterioration of lung function.Two recent clinical studies have demonstrated short and long term benefits of nebulized hypertonic saline in improving lung function in CF (1, 2). Prior clinical studies also support the efficacy of various inhaled hyperosmolar agents in CF (3-6). The recent study by Donaldson et al. (1) concludes that hypertonic saline produces sustained elevation in airway surface liquid (ASL) volume, which improves mucociliary clearance in the airways. However, a paradoxical effect was found when amiloride was administered together with hypertonic saline. Rather than improving lung function because of its inhibitory effect on ENaC and consequent prevention of ASL absorption, amiloride negated the beneficial effect of hypertonic saline. To account for these findings, Donaldson et al.(1) postulated the involvement of airway AQPs in establishing ASL volume (Fig. 1) and reported strong amiloride inhibition of osmotic water permeability in airway epithelial cells. In their model, ENaC hyperactivity dehydrates the ASL in CF airways (Fig. 1, left panel), and hypertonic saline restores ASL volume (middle panel). If amiloride acts only on ENaC, then amiloride is predicted to increase ASL volume (Fig. 1, right, top panel). To account for the clinical data, they hypothesize that amiloride inhibits airway AQPs, which prevents water from entering the airways (Fig. 1, right, bottom panel).The proposed involvement of AQPs in ASL regulation is surprising, as is the inhibition of AQP water permeability by amiloride. Osmotically induced water transport across airways has been shown to be high and likely AQP-dependent in microperfused small airways (7) and later in cultured human tracheal epithelial cells (8) and in spheroids composed of airway epithelial cell monolayers (9). Despite this, the reduction of airway epithelial water permeability by deletion of the various lung/ airway aquaporins (AQPs 1, 3, 4 and 5) in transgenic mice did not affect ASL volume or ionic composition (10). Inhibition of AQP water permeability by amiloride is surprising, because amiloride has no aquaretic effect at concentrations that inhibit ENaC in the renal distal tubule.Here, we tested the hypothesis of Donaldson et al.(1) by characterizing water permeability and amiloride effects in human bronchial epithelial cell cultures, stably ...

show abstract

Section: Discussionmentioning

confidence: 80%

“…Prior clinical studies also support the efficacy of various inhaled hyperosmolar agents in CF (3)(4)(5)(6). The recent study by Donaldson et al (1) concludes that hypertonic saline produces sustained elevation in airway surface liquid (ASL) volume, which improves mucociliary clearance in the airways.…”

Section: Cystic Fibrosis (Cf)mentioning

confidence: 98%

Hypertonic Saline Therapy in Cystic Fibrosis

Levin

Sullivan

Nielson

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…HS has a favorable effect on mucus rheology in vitro through hydration of the airway surface [40]. Another postulated effect of HS is that by increasing salt concentrations on the luminal side of the respiratory epithelium the viscous mucus will hydrate, improving mucociliary clearance [41,[56][57][58][59][60][61]. The landmark trial by Elkins et al (evidence level 1B) demonstrated that 48-weeks treatment with 7% HS nebulized twice daily improved the absolute difference in pulmonary function between groups, but not the decline in pulmonary function over time.…”

Section: Hypertonic Salinementioning

confidence: 99%

“…Nebulized HS can induce acute airway narrowing or bronchospasm and cough (Supplementary Tables 2), [11,[55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] but in most cases these symptoms decrease after a few weeks so that the majority of patients find HS tolerable [55,62,63,68]. Rodwell et al were the first to describe acute airway responsiveness to inhaled 10% saline in a group of CF subjects with asthma-like symptoms [11].…”

Section: Hypertonic Salinementioning

confidence: 99%

“…Although excessive coughing can be an unpleasant adverse effect, the tussive effect of HS is an important mechanism to improve mucociliary clearance [57,58,68,69]. A meta-analysis of studies examining regular HS inhalations in patients with CF indicated that intolerance due to cough occurs in 3% and due to any symptom in 8% of patients [68].…”

Section: Hypertonic Salinementioning

confidence: 99%

See 1 more Smart Citation

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

Eyns¹

2014

J Pulm Respir Med

View full text Add to dashboard Cite

It is presumed that bronchial hyperreactivity (BHR) can occur with any inhaled agent and may be a reason for discontinuation of inhalation therapy in cystic fibrosis (CF) patients. On the other hand, inhalation of antibiotics is being increasingly used to eradicate or treat infections.This review focuses on identifying the mechanisms of BHR for a better understanding of its impact on inhalation treatment. BHR in CF is suggested to be secondary to underlying airway disease (associated to poor pulmonary function, chronic inflammation and aerosol distribution) or to be a separate condition occurring more in CF. Furthermore, certain characteristics of the aerosol solution itself, such as the active molecule, chemical additives and particle size, can cause BHR.Recombinant human DNase (rhDNase), hypertonic saline (HS) and the antibiotics tobramycin, colistin and aztreonam lysine for inhalation (AZLI) are frequently used inhalation drugs in the treatment of CF. Prevalence of BHR related to both short and long-term inhalation of these drugs as reported in the literature was investigated. Acute BHR is documented in up to two thirds of CF patients. Despite the widespread use of rhDNase, HS, tobramycin, colistin and AZLI, only one long-term trial looked for, but did not demonstrate, BHR at the end of the trial period.

show abstract