Nebulizer

In medicine, a nebulizer[1] (spelled nebuliser in British English)[2] is a device used to administer medication in the form of a mist inhaled into the lungs.

Nebulizers are commonly used for treatment of cystic fibrosis, asthma, COPD and other respiratory diseases.

Nebulizers use oxygen, compressed air or ultrasonic power to break up medical solutions/suspensions into small aerosol droplets that can be direclty inhaled from the mouthpiece of the device. The definition of an aerosol is a "mixture of gas and liquid particles," and the best example of a natural occurring aerosol is "mist" (being formed when small vaporized water particles mixed with hot ambient air are cooled down and condense into a fine cloud of visible airborne water droplets). When using a nebulizer for inhalation therapy with medicine to be administered directly to the lungs, it is important to note that inhaled aerosol droplets can only penetrate into the narrow branches of the lower airways if they have a small diameter of 1–5 micrometers. Otherwise they are only absorbed by the mouth cavity, where the effect is low.[3]

Contents

History

The first "powered" or pressurized inhaler was invented in France by Sales-Girons in 1858. This device used pressure to atomize the liquid medication. The pump handle is operated like a bicycle pump. When the pump is pulled up it draws liquid from the reservoir, and upon the force of the users hand the liquid is pressured through an atomizer, to be sprayed out for inhalation near the users mouth.[4]

In 1864 the first steam driven nebulizer was invented in Germany. This inhaler, known as: “Siegle’s steam spray inhaler”, used the Venturi principle to atomize liquid medication, and this was the very beginning of nebulizer therapy. The importance of droplet size was not yet understood, so the efficacy of this first device was unfortunately mediocre for many of the medical compounds. The Siegle steam spray inhaler consisted of a spirit burner, which boils water in the reservoir into steam, that flow across the top and into a tube suspended in the pharmaceutical solution. The passage of steam draws the medicine into the vapor, and the patient inhales this out-sprayed vapor through a mouthpiece made of glass.[5]

The first electrical nebulizer was invented in the 1930s and called a Pneumostat. With this device a medical liquid (typically being Adrenalin Chloride, used as a bronchial muscle relaxant to reverse restriction) was made aerosol by the power from an electrical compressor.[6] As an alternative to the expensive electrical nebulizer, many people in the 1930s however continued to use the much more simple and cheap hand driven nebulizer, known as the Park-Davis Glaseptic.[7]

In 1956 a competing technology against the nebulizers was launched by Riker Laboratories (3M), in the form of pressurized metered-dose inhaler, with Medihaler-iso (isoprenaline) and Medihaler-epi (adrenaline) as the two first products.[8] In these devices the drug is cold-fill and delivered in exact doses through some special metering valves, driven by a gas propellant technology (i.e. Freon or a less environmental-damaging HFA).[9]

In 1964 new type of electronic nebulizers were introduced in the form of "Ultrasonic wave nebulizers".[10] Today the nebulizing technology is not only used for medical purpose. Ultrasonic wave nebulizers are for instance also used in humidifier apparatus, with the purpose to spray out water aerosols to moisten dry air in buildings.[11]

Some of the first models of electronic cigarettes featured an ultrasonic wave nebulizer (having a piezoelectric element vibrating at high-frequency ultrasound waves, to cause vibration and atomization of nicotine liquid) in combination with a vapouriser (build as a spray nozzle with an electric heating element).[12] The most common type of electronic cigarettes currently sold, however chose to omit the ultrasonic wave nebulizer, as it was not found to be efficient enough for this kind of device. Instead the electronic cigarettes now use an electric vaporizer, either in direct contact with the absorbent material in the "impregnated atomizer," or in combination with the nebulization technology related to a "spraying jet atomizer" (in the form of liquid droplets being out-sprayed by a high speed air stream, that passes through some small venturi injection channels, drilled in a material absorbed with nicotine liquid).[13]

Types of nebulizers

The most commonly used nebulizers are Jet nebulizers, which are also called "atomizers".[14] Jet nebulizers are connected by tubing to a compressor, that causes compressed air or oxygen to flow at high velocity through a liquid medicine to turn it into an aerosol, which is then inhaled by the patient. Currently there seems to be a tendency among physicians to prefer prescription of a pressurized Metered Dose Inhaler (pMDI) for their patients, instead of a Jet nebulizer that generates a lot more noise (often 60dB during use) and is less portable due to a heavier weight. However Jet nebulizers are commonly used for patients in hospitals who have difficulty using inhalers, such as in serious cases of respiratory disease, or severe asthma attacks.[15] The main advantage of the Jet nebulizer is related to its low operational cost. If the patient needs to inhale medicine on a daily basis the use of a pMDI can be rather expensive. Today several manufacturers have also managed to lower the weight of the Jet nebulizer down to 635 grams (22.4 oz), and thereby started to label it as a portable device. Compared to all the competing inhalers and nebulizers, the noise and heavy weight is however still the biggest draw back of the Jet nebulizer.

Ultrasonic wave nebulizers were invented in 1964 as a new more portable nebulizer. The technology inside an ultrasonic wave nebulizer is to have an electronic oscillator generate a high frequency ultrasonic wave, which causes the mechanical vibration of a piezoelectric element. This vibrating element is in contact with a liquid reservoir and its high frequency vibration is sufficient to produce a vapor mist.[11] As they create aerosols from ultrasonic vibration instead of using a heavy air compressor, they only have a weight around 170 grams (6.0 oz). Another advantage is that the ultrasonic vibration is almost silent. Examples of these more modern type of nebulizers are: Omron NE-U17 and Beurer Nebulizer IH30.[16]

A new significant innovation was made in the nebulizer market around 2005, with creation of the ultrasonic Vibrating Mesh Technology (VMT). With this technology a mesh/membrane with 1000-7000 laser drilled holes vibrates at the top of the liquid reservoir, and thereby pressures out a mist of very fine droplets through the holes. This technology is more efficient than having a vibrating piezoelectric element at the bottom of the liquid reservoir, and thereby shorter treatment times are also achieved. The old problems found with the ultrasonic wave nebulizer, having too much liquid waste and undesired heating of the medical liquid, have also been solved by the new Vibrating Mesh nebulizers. A partial list of available VMT nebulizers includes: Pari eFlow,[17] Respironics i-Neb,[18] Omron MicroAir,[19] Beurer Nebulizer IH50,[20] and Aerogen Aeroneb.[21] As the price of the ultrasonic VMT nebulizers carry a higher price compared to the previous models, most of the manufacturers continue also to sell the more "old fashioned" Jet nebulizer. The most recent innovation in nebulizer technology is the human-powered nebulizer being developed by Dr. Lars E. Olson of Marquette University.

The medical company Boehringer Ingelheim also invented a new device named Respimat Soft Mist Inhaler in 1997. This new technology provides a metered dose to the user, as the liquid bottom of the inhaler is rotated clockwise 180 degrees by hand, adding a build up tension into a spring around the flexible liquid container. When the user activates the bottom of the inhaler, the energy from the spring is released and imposes pressure on the flexible liquid container, causing liquid to spray out of 2 nozzles, thus forming a soft mist to be inhaled. The device features no gas propellant and no need for battery/power to operate. The average droplet size in the mist was measured to a somewhat disappointing 5.8 micrometers, which could indicate some potential efficiency problems for the inhaled medicine to reach the lungs. Subsequent trials have proven this was not the case. Due to the very low velocity of the mist, the Soft Mist Inhaler in fact has a higher efficiency compared to a conventional pMDI.[22] In 2000, arguments were launched towards the European Respiratory Society (ERS) to clarify/expand their definition of a nebulizer, as the new Soft Mist Inhaler in technical terms both could be classified as a "hand driven nebulizer" and a "hand driven pMDI".[23]

Use and attachments

Nebulizers accept their medicine in the form of a liquid solution, which is often loaded into the device upon use. Corticosteroids and Bronchodilators such as salbutamol (albuterol USAN) are often used, and sometimes in combination with ipratropium. The reason these pharmaceuticals are inhaled instead of ingested is in order to target their effect to the respiratory tract, which speeds onset of action of the medicine and reduces side effects, compared to other alternative intake routes.[15]

Usually, the aerosolized medicine is inhaled through a tube-like mouthpiece, similar to that of an inhaler. The mouthpiece, however, is sometimes replaced with a face mask, similar to that used for inhaled anesthesia, for ease of use with young children or the elderly, although mouthpieces are preferable if patients are able to use them since face-masks result in reduced lung delivery because of aerosol losses in the nose.[14]

After use with corticosteroid, it is theoretically possible for patients to develop a yeast infection in the mouth (thrush) or hoarseness of voice (dysphonia), although these conditions are clinically very rare. To avoid these adverse effects, some clinicians suggest that the person who used the nebulizer should rinse his or her mouth. This is not true for bronchodilators; however, patients may still wish to rinse their mouths due to the unpleasant taste of some bronchodilating drugs.

Nebulizer use by those with Asthma

Guidelines

Various asthma guidelines, such as the Global Initiative for Asthma Guidelines [GINA], the British Guidelines on the management of Asthma, The Canadian Pediatric Asthma Consensus Guidelines, and United States Guidelines for Diagnosis and Treatment of Asthma each recommend metered dose inhalers in place of nebulizer-delivered therapies.[24] The European Respiratory Society acknowledge that although nebulizers are used in hospitals and at home they suggest much of this use may not be evidence-based.[25]

Effectiveness

Recent evidence show that nebulizers are no more effective than metered-dose inhalers (MDIs) with spacers and that MDIs may offer advantages in children with acute asthma.[24][26][27]

European Respiratory Society highlighted a risk relating to dosage reproducibility caused by selling nebulizer devices separately from nebulized solution. They found this practice could vary dosages 10-fold or more by changing from an inefficient nebulizer system to a highly efficient one. [25][26] Two advantages attributed to nebulizers, compared to MDIs with spacers(inhalers), were their ability to deliver larger dosages at a faster rate, especially in acute asthma; however, recent data suggests actual lung deposition rates are the same. In addition, another trial found that a MDI (with spacer) — had a lower required dose for clinical result — compared to a nebulizer (see Clark, et al. other references).[24]

See also

Instead of using nebulizers to deliver a medical liquid to the lungs in the form of aerosol droplets, its also possible to use inhalers or vaporizers for the same purpose.

References

  1. ^ Medical Dictionary. "Nebulizer". http://medical-dictionary.thefreedictionary.com/nebulizer. Retrieved 2010-11-01. 
  2. ^ British Spelling of Nebulizer Medical Dictionary. [url=http://science.thomsonreuters.com/support/patents/dwpiref/reftools/usukdict/ "Definition"]. url=http://science.thomsonreuters.com/support/patents/dwpiref/reftools/usukdict/. Retrieved 2010-11-01. 
  3. ^ Lungenliga Schweiz, "Guidelines for the aerosol therapy of lung diseases".
  4. ^ Inhalatorium. "Pressurized inhaler invented by Sales-Girons". http://www.inhalatorium.com/page148.html. Retrieved 2010-04-05. 
  5. ^ Inhalatorium. "Siegle's steam spray inhaler". http://www.inhalatorium.com/page113.html. Retrieved 2010-04-05. 
  6. ^ Inhalatorium. "First electrical nebulizer (Pneumostat)". http://www.inhalatorium.com/page131.html. Retrieved 2010-04-05. 
  7. ^ Inhalatorium. "The hand driven nebulizer "Park-Davis Glaseptic". http://www.inhalatorium.com/page90.html. Retrieved 2010-04-05. 
  8. ^ Riker Laboratories (1956-03-21). "Self-propelling pharmaceutical compositions (for a pMDI)". GB patent. http://v3.espacenet.com/publicationDetails/biblio?CC=GB&NR=830426A&KC=A&FT=D&date=19600316&DB=EPODOC&locale=en_EP. Retrieved 1960-03-16. 
  9. ^ Sanders M (April 2007). "Inhalation therapy: an historical review" (PDF). Prim Care Respir J 16 (2): 71–81. doi:10.3132/pcrj.2007.00017. PMID 17356785. http://www.thepcrj.org/journ/vol16/16_2_71_81.pdf. 
  10. ^ Devilbiss (1964-02-10). "Method and apparatus for producing aerosols (ultrasonic nebulizer)". GB patent. http://v3.espacenet.com/publicationDetails/biblio?CC=GB&NR=1069048A&KC=A&FT=D&date=19670517&DB=EPODOC&locale=en_V3. Retrieved 1967-05-17. 
  11. ^ a b BOGA Gmbh. "Operating principle of ultrasonic humidifier". http://www.airwin-luftbefeuchter.de/html/en/operating_principle.html. Retrieved 2010-04-05. 
  12. ^ Hon Lik (2004-04-14). "An aerosol electronic cigarette". CN patent. http://v3.espacenet.com/publicationDetails/biblio?CC=EP&NR=1736065A1&KC=A1&FT=D&date=20061227&DB=EPODOC&locale=en_V3. Retrieved 2006-12-27. 
  13. ^ Hon Lik (2006-05-16). "Emulation aerosol sucker". CN patent. http://v3.espacenet.com/publicationDetails/biblio?CC=EP&NR=2022350A1&KC=A1&FT=D&date=20090211&DB=EPODOC&locale=en_V3. Retrieved 2009-02-11. 
  14. ^ a b Finlay, W.H. (2001). The Mechanics of Inhaled Pharmaceutical Aerosols: An Introduction. Academic Press. 
  15. ^ a b Hickey, A.J. (2004). Pharmaceutical Inhalation Aerosol Technology (2nd ed.). New York: Marcel Dekker. 
  16. ^ Knoch, M.; Finlay, W.H. (2002). "Ch. 71 Nebuliser Technologies". In Rathbone, Hadgraft, Roberts. Modified-Release Drug Delivery Technology. Marcel Dekker. pp. 849–856. 
  17. ^ PARI Pharma (2008). "Leading aerosol therapies worldwide, delivery with eFlow". http://www.paripharma.com/technologies1.htm. Retrieved 2010-04-09. 
  18. ^ Philips Respironics (2010). "Active Aerosol Dilevery, The I-neb and Vibrating Mesh Technology". http://ineb.respironics.com/AADHow.asp. Retrieved 2010-04-09. 
  19. ^ Omron (2010). "Talking about nebulization method: Ultrasonic nebulizer and Vibrating Mesh nebulizer". http://www.healthcare.omron.co.jp/english/neu_method.html. Retrieved 2010-04-09. 
  20. ^ Beurer (2010). "Product details of IH50 nebulizer, with a vibrating membrane". http://www.beurer.com/web/en/product/nebulization/detail.php?pk=31&id=5707&bek=165&bct=%26nbsp%3B%26gt%3B%26nbsp%3Bproduct+details%26nbsp%3B%26gt%3B%26nbsp%3BIH50. Retrieved 2010-04-09. 
  21. ^ Aerogen (2009). "Micropump nebulizers, Aeroneb, Vibrating Mesh Technology". http://aerogen.com/technology.html. Retrieved 2010-04-09. 
  22. ^ Boehringer Ingelheim (2003). "How it works: Respimat Soft Mist Inhaler". http://www.respimat.com/com/Main/functions/howitworks/index.jsp. Retrieved 2005-08-16. 
  23. ^ Denyer J, et al. (2000). "New liquid drug aerosol devices for inhalation therapy". Eur Respir Rev 10: 187–191. 
  24. ^ a b c Clark NM, Houle C, Partridge MR, Leo HL, Paton JY (2010). "The puzzle of continued use of nebulized therapy by those with asthma". Chron Respir Dis 7 (1): 3–7. doi:10.1177/1479972309357496. PMID 20103617. http://crd.sagepub.com/cgi/pmidlookup?view=long&pmid=20103617. 
  25. ^ a b Boe J, Dennis JH, O'Driscoll BR, et al. (July 2001). "European Respiratory Society Guidelines on the use of nebulizers". Eur. Respir. J. 18 (1): 228–42. PMID 11510796. http://erj.ersjournals.com/cgi/pmidlookup?view=long&pmid=11510796. 
  26. ^ a b Cates CJ, Crilly JA, Rowe BH (2006). "Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma". Cochrane Database Syst Rev (2): CD000052. doi:10.1002/14651858.CD000052.pub2. PMID 16625527. http://dx.doi.org/10.1002/14651858.CD000052.pub2. 
  27. ^ Epling J, Chang MH (January 2003). "Are metered-dose inhalers with holding chambers better than nebulizers for treating acute asthma?". Am Fam Physician 67 (1): 62–4. PMID 12537167. http://www.aafp.org/link_out?pmid=12537167.