Bronchial provocation testing with dry powder mannitol in children with cystic fibrosis

Minasian, Caro; Wallis, Colin; Metcalfe, Chris; Bush, Andrew

doi:10.1002/ppul.20903

Cited by 18 publications

(9 citation statements)

References 43 publications

(76 reference statements)

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“…The dose of mannitol utilised for the airway challenge has been previously reviewed 22. It may be that utilising a slightly lower cumulative dose of mannitol for the airway challenge will allow more children to be recruited to a therapeutic trial.…”

Section: Discussionmentioning

confidence: 99%

“…All subjects underwent a bronchial provocation challenge with dry powder mannitol prior to study entry 22. Children were pretreated with bronchodilator, following which they received incrementally increasing doses of mannitol up to a maximum cumulative dose of 475 mg. FEV 1 was measured at the start of the challenge and after each increase in dose.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of inhaled mannitol, daily rhDNase and a combination of both in children with cystic fibrosis: a randomised trial

Minasian

Wallis

Metcalfe

et al. 2009

Thorax

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Background: Osmotic agents, such as inhaled dry powder mannitol, may increase mucociliary clearance by rehydrating the airway surface liquid and thus act as disease-modifying treatments in cystic fibrosis (CF). This is the first therapeutic trial of inhaled mannitol in children with CF; it was compared with recombinant human deoxyribonuclease (rhDNase), the current best established mucolytic treatment. Methods: 38 children were recruited to an open crossover study. Subjects underwent an initial bronchial provocation challenge with dry powder mannitol. Those children with a negative challenge were randomly allocated to one of three consecutive 12-week treatment blocks (inhaled mannitol alone, nebulised rhDNase alone and mannitol + rhDNase). The primary outcome was forced expiratory volume in 1 s (FEV 1 ). A number of secondary outcome measures were also studied. Results: Twenty children completed the study. Bronchoconstriction and cough associated with mannitol administration contributed to the high attrition rate. The mean increase in FEV 1 following 12 weeks of treatment was 0.11 litres (6.7%) (p = 0.055) for mannitol alone, 0.12 litres (7.2%) (p = 0.03) for rhDNase alone and 0.03 litres (1.88%) (p = 0.67) for rhDNase and mannitol. None of the secondary clinical outcomes was statistically significantly different between treatments. Conclusions: Inhaled mannitol was at least as effective as rhDNase after 3 months treatment. There was a marked individual variation in tolerance to mannitol and in response to treatment however. Children who do not respond to rhDNase many benefit from a trial of inhaled mannitol. The combination of mannitol and rhDNase was not useful. Trial registration number: NCT00117208Many processes contribute to airway obstruction and progressive lung damage in cystic fibrosis (CF), including the production of abnormally viscid mucus, mucus hypersecretion and defective mucociliary clearance (MCC). Previous therapeutic approaches aimed at improving airway clearance have included suppression or eradication of bacterial infection and attenuation of inflammation. Mucolytic agents have also been used to reduce sputum viscosity. Recombinant human deoxyribonuclease (rhDNase) is a now a well established and widely used adjunctive treatment for CF. DNA derived from neutrophil degradation is present in very high concentrations in the sputum of patients with CF and is a major contributor to the viscosity of airway secretions. rhDNase cleaves this extracellular DNA, improving mucus rheology. Several studies have now clearly demonstrated improvements in lung function and fewer chest exacerbations in patients treated with rhDNase.1-3 It may also reduce neutrophilic airway inflammation. 4 There is widespread variation in the individual responses to rhDNase, 3 5 however, and a significant number of patients derive no clinical benefit.Epithelial airway surface liquid (ASL) volume regulation is critical for normal MCC, and airway dehydration is now thought to be a key initiating event in the pathogenesi...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Comparison of inhaled mannitol, daily rhDNase and a combination of both in children with cystic fibrosis: a randomised trial

Minasian

Wallis

Metcalfe

et al. 2009

Thorax

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“…Another contributor may be chronic infection with Pseudomonas aeruginosa , with at least one study finding this to be a strongly linked to BHR . Furthermore, BHR is of further clinical relevance in CF, as bronchoconstriction can complicate administration of nebulised antibiotics or inhaled mannitol …”

Section: Diagnosis Of Asthma In Cf Patientsmentioning

confidence: 99%

Asthma and cystic fibrosis: A tangled web

Kent

Lane

Beek

et al. 2014

Pediatric Pulmonology

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Successfully diagnosing concomitant asthma in people with cystic fibrosis (CF) is a challenging proposition, and the utility of conventional diagnostic criteria of asthma in CF populations remains uncertain. Nonetheless, the accurate identification of individuals with CF and asthma allows appropriate tailoring of therapy, and should reduce the unnecessary use of asthma medication in broader CF cohorts. In this review, we discuss the diagnostic challenge posed by asthma in CF, both in terms of clinical evaluation, and of interpretation of pulmonary function testing and non-invasive markers of airway inflammation. We also examine how the role of cross-sectional thoracic imaging in CF and asthma can assist in the diagnosis of asthma in these patients. Finally, we critically appraise the evidence base behind the use of asthma medications in CF populations, with a particular focus on the use of inhaled corticosteroids and bronchodilators. As shall be discussed, the gaps in the current literature make further high-quality research in this field imperative.

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“…Mannitol also find its application in making illicit drugs or as adulterants for heroin, methamphetamines. Mannitol is also commonly used in the intensive care unit; also in cerebral oedema and acute renal failure for assessment of renal function [ 1 , 8 ].…”

Section: Properties and Commercial Applicationsmentioning

confidence: 99%

Challenges in Enzymatic Route of Mannitol Production

2013

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Mannitol is an important biochemical often used as medicine and in food sector, yet its biotechnological is not preffered in Industry for large scale production, which may be due to the multistep mechanism involved in hydrogenation and reduction. This paper is a comparative preview covering present chemical and biotechnological approaches existing today for mannitol production at industrial scale. Biotechnological routes are suitable for adaptation at industrial level for mannitol production, and whatever concerns are there had been discussed in detail, namely, raw materials, broad range of enzymes with high activity at elevated temperature suitable for use in reactor, cofactor limitation, reduced by-product formation, end product inhibition, and reduced utilization of mannitol for enhancing the yield with maximum volumetric productivity.

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Bronchial provocation testing with dry powder mannitol in children with cystic fibrosis

Abstract: We report that 24% of children with CF had a positive airway challenge with inhaled mannitol. This compares with a previously reported 12% of subjects in a study including both adults and children. We could not identify factors predictive of a positive mannitol challenge in our children.

Cited by 18 publications

References 43 publications

Comparison of inhaled mannitol, daily rhDNase and a combination of both in children with cystic fibrosis: a randomised trial

Comparison of inhaled mannitol, daily rhDNase and a combination of both in children with cystic fibrosis: a randomised trial

Asthma and cystic fibrosis: A tangled web

Challenges in Enzymatic Route of Mannitol Production

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