Influence of particle size on regional lung deposition - What evidence is there?

https://mukoviscidoz.org/doc/konsensus/k_en/2009JCF_article.pdf

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis : A European consensus

Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating a...

Current therapies and technological advances in aqueous aerosol drug delivery.

Drug delivery by inhalation is the principal strategy to treat obstructive lung diseases, which affect about 15% of the population in the United States. Aerosol delivery devices have evolved over more than 60 years from the basic pressurized metered-dose inhaler and nebulizer to numerous types of inhalers and devices, including valved holder chambers, dry powder inhalers, soft mist inhalers, as well as smart inhalers and nebulizers. Although these devices improve a patient's ability to self-administer medication, many problems with optimal delivery still exist. Appropriate selection and repeated patient education can help lessen the problems with these devices. Aerosol science is evolving, with methods of measurement that include radio-scintigraphy and magnetic resonance imaging, to provide a better understanding of aerosol delivery and effects. Understanding the science and clinical application of aerosol drug delivery can substantially aid clinicians in optimizing these therapies for their patients.

http://rc.rcjournal.com/content/respcare/63/6/708.full.pdf

Aerosol Delivery Devices for Obstructive Lung Diseases.

Reason for withdrawal from publication
This review has been withdrawn because it has been split into the following reviews: 'Long-acting inhaled bronchodilators for cystic fibrosis' and 'Short-acting inhaled bronchodilators for cystic fibrosis'.

Inhaled bronchodilators for cystic fibrosis

This study was conducted to compare pulmonary deposition following inhalation with an ultrasonic and a jet nebulizer in CF patients under conditions relevant to practice. The marker substance used to estimate the relative lung bioavailability was sodium cromoglycate (SCG), which is poorly absorbed from the gastrointestinal tract, but is completely absorbed from the lungs. Ten CF patients (aged 9-21 years) used an ultrasonic nebulizer (Multisonic compact 2.4 MHz) and a jet nebulizer (Parimaster, LC Plus Turbo) in a crossover design to inhale a solution containing 20 mg of SCG and a beta(2)-agonist. Urine was collected in five fractions until 12 h p. a., and the excreted SCG was determined by means of HPLC. Prior to each inhalation, the patients' pulmonary function was measured employing a Pneumoscope. Using the ultrasonic nebulizer, the amount of SCG excreted in urine was significantly greater than that after inhalation with the jet nebulizer (1.43 +/- 0.47 mg vs. 1.04 +/- 0.47 mg; p = 0.002), despite the larger residual volume in the ultrasonic nebulizer. The absorption half-life for SCG following ultrasonic nebulization was significantly shorter when compared with jet nebulization (84 +/- 14 min vs. 101 +/- 19 min; p = 0.005), being suggestive of a more peripheral deposition. Furthermore, an inverse relationship was found between absorption half-life and FEV(1) (% pred.) (r = -0.655, p = 0.04) or MMEF(75/25) (% pred.) (r = -0.844, p = 0.031), but only with the ultrasonic nebulizer. In conclusion, the ultrasonic nebulizer tested when used for inhalation in CF patients was found to be at least equivalent to the jet nebulizer.

Lung deposition in cystic fibrosis patients using an ultrasonic or a jet nebulizer.

The present work aimed to investigate whether lung deposition can be improved by using a device that optimizes the breathing pattern through electronic control. The relative lung deposition was estimated by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. Thirteen cystic fibrosis (CF) patients (aged 8-20 years) received 20 mg of SCG as nebulizer solution by means of (a) conventional inhalation (Parimaster + Pari LC Star nebulizer, manual interrupter) and (b) electronically breath-controlled inhalation (AKITA + Pari LC Star nebulizer). Inhalations were trained and supervised by a physiotherapist. Patients were asked to provide answers to a questionnaire about the convenience of electronically breath-controlled inhalation. Urine was collected in five fractions until 12 h p.a., and the excreted SCG was determined by means of high-performance liquid chromatography (HPLC). Following breath-controlled inhalation, the amount of SCG excreted in urine was significantly greater than after conventional inhalation (2.22 +/- 0.61 mg vs. 1.63 +/- 0.59 mg, p < 0.001). The absorption half-life for SCG following breath-controlled inhalation was significantly shorter when compared with conventional inhalation (78 +/- 23 min vs. 107 +/- 29 min; p < 0.01), suggestive of a more peripheral deposition for the former. Ninety-two percent of the patients judged that the electronically breath-controlled inhalation was good or very good. In conclusion, inhalation with an electronically optimized breathing pattern yields a greater and more peripheral lung deposition of SCG compared with the manually triggered conventional nebulizer technique in CF patients with several years of aerosol inhalation experience.

Lung deposition after electronically breath-controlled inhalation and manually triggered conventional inhalation in cystic fibrosis patients.

Using nebulization, only a small proportion of the dose reaches the lungs, while the remainder is swallowed, exhaled into the atmosphere, or remains in the nebulizer. It was the purpose of this study to investigate whether wearing a noseclip during inhalation can improve lung deposition. Relative lung deposition was compared by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. The SCG absorption half-life allows one to differentiate indirectly between a more or less peripheral deposition. Ten CF patients (9–18 years old) inhaled, under routine conditions, a solution containing 20 mg of SCG in a randomized crossover design through a mouthpiece, without and with a noseclip being worn. Following inhalation without and with a noseclip, no statistically significant difference was seen in the amount of SCG excreted in urine (0.9 ± 0.4 mg vs. 1.0 ± 0.5 mg; p = 0.402) and absorption half-life (93 ± 25 min vs. 113 ± 36 min; p = 0.083). In conclusion, wearin...

Does wearing a noseclip during inhalation improve lung deposition

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Lung deposition in cystic fibrosis patients using an ultrasonic or a jet nebulizer.

Lung deposition after electronically breath-controlled inhalation and manually triggered conventional inhalation in cystic fibrosis patients.

Does wearing a noseclip during inhalation improve lung deposition