Inhaled Interventions in Cystic Fibrosis: Mucoactive and Antibiotic Therapies

Hurt, Katharine; Bilton, Diana

doi:10.1159/000369533

Cited by 19 publications

(19 citation statements)

References 37 publications

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“…For example, high concentrations of mucoactive agents instilled with liquid plugs could help dissolve the mucus layer formed in the airways by many lung diseases, reducing complications and providing long-term benefits (45). For single cancer lesions, microvolume plugs containing high concentrations of chemotherapeutics can be delivered directly to the site of the tumor as a (neo)adjuvant therapy, especially for poorly vascularized tumors that are less accessible to systemically administered drugs.…”

Section: Discussionmentioning

confidence: 99%

Targeted delivery of liquid microvolumes into the lung

Kim

O’Neill

Dorrello

et al. 2015

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

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The ability to deliver drugs to specific sites in the lung could radically improve therapeutic outcomes of a variety of lung diseases, including cystic fibrosis, severe bronchopneumonia, chronic obstructive pulmonary disease, and lung cancer. Using conventional methods for pulmonary drug administration, precise, localized delivery of exact doses of drugs to target regions remains challenging. Here we describe a more controlled delivery of soluble reagents (e.g., drugs, enzymes, and radionuclides) in microvolume liquid plugs to targeted branches of the pulmonary airway tree: upper airways, small airways (bronchioles), or the most distal alveoli. In this approach, a soluble liquid plug of very small volume (<1 mL) is instilled into the upper airways, and with programmed air ventilation of the lungs, the plug is pushed into a specific desired (more distal) airway to achieve deposition of liquid film onto the lung epithelium. The plug volume and ventilation conditions were determined by mathematical modeling of plug transport in a tubular geometry, and targeted liquid film deposition was demonstrated in rat lungs by three different in vivo imaging modalities. The experimental and modeling data suggest that instillation of microvolumes of liquid into a ventilated pulmonary airway could be an effective strategy to deliver exact doses of drugs to targeted pathologic regions of the lung, especially those inaccessible by bronchoscopy, to increase in situ efficacy of the drug and minimize systemic side effects.pulmonary drug delivery | lung disease | liquid instillation | lung airway | alveoli E ffective treatment strategies for lung diseases such as cystic fibrosis, tuberculosis, bronchopneumonia, and lung cancer would involve a small, highly concentrated dose of drug delivered directly to the pathologic site (1, 2). Unfortunately, delivery of a precise drug dose to specific sites in the lung is challenging using conventional systemic drug administration methods, resulting in inefficient treatments for many lung diseases (3, 4). For example, orally administered drugs often require high doses to achieve therapeutic effects due to first-pass metabolism, which in turn leads to systemic side effects (5). Although drugs administered i.v. can avoid first-pass metabolism, they can still incur a range of side effects (6).On the other hand, inhalation of aerosolized drugs has the advantage of noninvasively bringing a drug locally into the lung, and so it has been a first-line treatment option for many lung diseases in the outpatient setting (7,8). In particular, dry powder inhalers can allow for local delivery of drugs in specific lung regions (9). Because properties of powders such as particle size, density, and cohesiveness strongly affect particle transport behavior, dry powders should be prepared with appropriate properties conducive to delivery into specific locations in the structurally complex pulmonary airway tree (10).Alternatively, microvolumes of a liquid plug containing the drug could be instilled into the lung using ...

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Section: Discussionmentioning

confidence: 99%

Targeted delivery of liquid microvolumes into the lung

Kim

O’Neill

Dorrello

et al. 2015

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

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“…CF is a multisystem disease that affects primarily the respiratory and the digestive systems, and most patients require chest physiotherapy, nutritional supplements, pancreatic enzymes, mucolytics, long-term oral and nebulized antibiotics [8] , frequent courses of intravenous antibiotics and immunosuppressive drugs after transplantation, most of which will have to be continued during pregnancy. Because of its significant impact on obstetrical and neonatal outcomes, health management of CF patients should be maximized and should include preconceptionally an accurate medication review for the reassessment of each medication safety and effectiveness in the light of the upcoming pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Safety of Drugs during Pregnancy and Breastfeeding in Cystic Fibrosis Patients

Panchaud

Paolo²,

Koutsokera³

et al. 2016

Respiration

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Health management of cystic fibrosis (CF) patients should be maximized during pregnancy and breastfeeding because of its significant impact on the maternal and newborn outcomes. Thus, numerous drugs will have to be continued during pregnancy and lactation. Most of the drugs representing CF treatment lines cross the placenta or are excreted into human milk. Research addressing the risks and benefits of drugs used in CF patients during pregnancy and lactation is often incomplete or challenged by limited methodology, which often leads to conflicting or inconclusive results. Yet, potential treatment benefits for CF pregnant patients most often outbalance potential risks for the unborn child.

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“… 11 Therapies to prevent plugging consist of repeated cleaning, bronchoscopies, antibiotics, mucolytics, and hyperosmolar agents. 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

Transtracheal single-point stent fixation in posttracheotomy tracheomalacia under cone-beam computer tomography guidance by transmural suturing with the Berci needle – a perspective on a new tool to avoid stent migration of Dumon stents

Hohenforst-Schmidt¹,

Linsmeier

Freitag

et al. 2015

TCRM

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Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson’s disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50–60€ inclusive of taxes. In our own hospital (tertiary level), it is nearly 30€ per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6€. Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000€ more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.

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Inhaled Interventions in Cystic Fibrosis: Mucoactive and Antibiotic Therapies

Cited by 19 publications

References 37 publications

Targeted delivery of liquid microvolumes into the lung

Targeted delivery of liquid microvolumes into the lung

Safety of Drugs during Pregnancy and Breastfeeding in Cystic Fibrosis Patients

Transtracheal single-point stent fixation in posttracheotomy tracheomalacia under cone-beam computer tomography guidance by transmural suturing with the Berci needle – a perspective on a new tool to avoid stent migration of Dumon stents

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Inhaled Interventions in Cystic Fibrosis: Mucoactive and Antibiotic Therapies

Cited by 19 publications

References 37 publications

Targeted delivery of liquid microvolumes into the lung

Targeted delivery of liquid microvolumes into the lung

Safety of Drugs during Pregnancy and Breastfeeding in Cystic Fibrosis Patients

Transtracheal single-point stent fixation in posttracheotomy tracheomalacia under cone-beam computer tomography guidance by transmural suturing with the Berci needle &ndash; a perspective on a new tool to avoid stent migration of Dumon stents

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Transtracheal single-point stent fixation in posttracheotomy tracheomalacia under cone-beam computer tomography guidance by transmural suturing with the Berci needle – a perspective on a new tool to avoid stent migration of Dumon stents