What is a Nebulizer?
A nebulizer is a machine that turns water-based solutions into drops that are inhaled and small enough to reach the lungs (1 to 5 μm). It is usually used with drugs that help expand the lung passages, bronchi (bronchodilators). The direct delivery of the medication to the lungs reduces the dose and side effects [1, 2].
Nebulizers are mostly used in patients that cannot use a specific breathing technique (exhale, slowly and deeply inhale, hold breath, exhale) or coordinate their movements (hand-eye-breath coordination), such as in young children and the elderly. Nebulizers are easily used as long as the person is breathing normally .
The use of home nebulizers is also recommended for patients with frequent airflow obstruction or low volume of breathing, or for those that need medications or doses not available for regular inhalers (dry-powder or metered-dose inhalers) .
Currently, portable nebulizers are available on the market .
The droplets are generated using different methods: air-blast atomization, high-frequency vibrations, and colliding liquid jets (more information is in the Components section). These often determine the kind of drugs used with the device and its cost .
In a test with 12 patients with asthma, smaller drops (1.5 μm) entered the lungs deeper, but due to their small size, a greater amount was exhaled before it was absorbed. For larger drops (up to 6 μm), a slower inhalation was better .
The nebulizer should be carefully washed according to the manufacturer’s instructions to avoid the growth of microbes and to extend its life .
In jet nebulizers, compressed gas generates the drops (as an aerosol) containing the medication. A reservoir tube that helps maintain a continuous flow is commonly used. A collection bag that collects the drops not inhaled is another option [2, 8].
Other forms of jet nebulizers are the breath-actuated and breath-enhanced. While both help reduces the loss of medicine, their different designs also help minimize treatment times or deliver the desired dose more precisely [8, 9].
The main disadvantage of jet nebulizers is that they are noisy. They also take more time for each treatment and tend to cool the solvent, which can be uncomfortable for the patient .
In this case, a crystal vibrates at high frequencies (more than 20 kHz) to create the drops. They usually are smaller, silent, and have shorter dosing times. However, they should not be used with suspensions or with medications that are damaged by heating (proteins) [7, 10].
In mesh nebulizers, a vibrating mesh creates the drops and determines their size. They have faster treatment times and reduce drug waste. However, highly concentrated or very thick solutions can damage the mesh [2, 10, 11].
The interface is one of the most important parts of the equipment, as it’s the part that delivers the medicine. The choice of an interface depends on the age and ability of the patient to cooperate (children or the elderly) .
In hospitals, a mouthpiece is preferred for patients and children older than 3 years. For younger children, a face mask that covers both nose and mouth is used. It is very important that the face mask fits tightly and comfortably to avoid leaks [2, 3].
3) Nebulizer Cup or Medication Reservoir
The indicated amount of medicine is placed in this container. It should be rinsed and dried after each use, and periodically disinfected according to the manufacturer’s instructions .
Certain nebulizer models have plastic tubing that connects the aerosol generator to the nebulizer cup and the interface. It should be carefully assembled before every use, and should not be washed .
Some nebulizers have special models for children that include accessories to keep the child entertained during the course of the treatment.
Nebulizer Mechanism of Action
Drops with a size 2 to 5 μm reach the higher parts of the airway while smaller drops (1 to 2 μm) can reach deeper .
They reach the airways in different ways, such as by:
- Impaction, when big drops with a high-speed crash with the walls of the airway, usually in the upper parts. This also happens during exhalation 
- Sedimentation, which usually happens in the middle of the airway, where particles at a lower speed settle on the surface due to gravity. This is increased by holding your breath 
- Diffusion, the random movement of very small particles that eventually causes them to crash with the walls of the airway 
The nebulized drug must pass several barriers to be able to reach its target. In the upper airway, a layer of mucus covers the surface and removes foreign particles by “pushing” them out into the throat to be swallowed .
In the lower airway, white blood cells (macrophages) “eat” foreign particles 1 to 2 μm in size. The nebulized drug must be small enough to reach the lower airway, and have a chemical composition that interferes with sticking to the mucus or that helps cross it [15, 14].
The use of a mask is recommended for conditions such as allergic rhinitis. When looking to deliver a greater amount of aerosol into airways, a mouthpiece should be used to avoid being filtered by the nose .
The size of the inhaled particles should ideally be between 1 to 3 μm, breathing slow and steady .
Asthma is a disease where the entire airway is swollen. Inhaled drugs help treat this inflammation by allowing high doses of drugs to reach their target site directly .
Nebulizers are recommended for patients, such as children, that cannot adequately use conventional inhalers (pressurized metered-dose inhalers). Nebulizers are also recommended during acute asthma attacks to deliver medications that help expand the airways (such as albuterol) .
In patients with occasional asthma attacks, short-acting beta-2 agonists are used whenever needed. They expand the airway by relaxing the muscles that surround it and quickly relieve the symptoms. Salbutamol and terbutaline are most used .
Long-acting beta-2 agonists (such as formoterol and salmeterol) are also used when asthma cannot be controlled by corticosteroids alone .
Another class of drugs that relaxes the airway muscles, such as muscarinic antagonists like ipratropium or tiotropium, are used in adults combined with beta-2 agonists to help improve breathing in severe acute asthma [20, 21].
Patients using short-acting beta-2 agonists can also take sodium cromoglicate and nedocromil sodium, but their efficacy is low .
Nebulized magnesium sulfate in addition to beta-2 agonists can be used in children only in cases of acute severe asthma attacks .
Nebulized furosemide can be added to beta-2 agonists for acute asthma, but there is no clear evidence of benefits .
2) Cystic Fibrosis
Cystic fibrosis is a genetically-inherited disorder that causes the buildup of very thick and viscous mucus in the airways and diminishes the ability of the airway to “clean” itself. This leads to constantly obstructed airways, chronic bacterial infections, and widening of the airways .
Nebulized dornase alfa is used to help break down mucus .
Nebulization with N-acetylcysteine, which helps break down mucus, did not achieve a positive enough effect to recommend its use in cystic fibrosis patients (according to a meta-analysis) .
Opioids are reserved only for very severe cases. Nebulized morphine helped ease breathing in 3 patients (10,13, and 48 years old) with end-stage cystic fibrosis. Nebulized fentanyl also helped improve breathing in a 17-year-old patient with terminal cystic fibrosis [28, 29, 30, 31].
3) Lung Infections
The use of antibiotics through nebulization has the advantage of delivering large doses directly to the infected lungs. However, the risk of developing multi-drug resistant infections limits nebulized antibiotic therapy only for specific cases [32, 33].
Antibiotics in Cystic Fibrosis Patients
In patients with cystic fibrosis, chronic P. aeruginosa infections are a significant problem. Use of the nebulized antibiotic tobramycin twice a day can be used, or alternatively, azithromycin or aztreonam [34, 26].
Nebulized pentamidine, a strong anti-infective drug, is used to prevent protozoa (Pneumocystis jiroveci) infections in people with compromised immunity (including transplant patients allergic to trimethoprim/sulfamethoxazole) [36, 35].
Pneumonia can also be caused by a virus, such as the respiratory syncytial virus. Nebulized ribavirin, an anti-viral, is approved for use in patients with a compromised immune system .
A retrospective study in 280 patients after stem cell transplant confirmed treatment with nebulized ribavirin increased survival from this viral infection .
In another study in 14 transplanted adults (randomized controlled trial), nebulized ribavirin helped prevent pneumonia and decreased the amount of virus (viral load). However, a different study in 21 transplant patients found no benefit to the nebulized ribavirin over oral form [39, 40].
The use of nebulized liposomal amphotericin B in patients who received a lung transplant to avoid infection (Aspergillus spp.) proved effective in a study of 412 patients (retrospective observational) .
Antibiotics for Mechanically Ventilated Patients
Nebulized antibiotics (like colistin or aminoglycosides), antivirals, or antifungals are advised only if conventional (IV) therapy is not an option for mechanically ventilated patients; although, in practice, it is used in hospitals around the world [33, 42].
4) Help Relieve Symptoms of Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease (COPD) is a condition that makes breathing difficult for the patient. Most patients have inflammation of the bronchial tubes, damage to the air sacs, and excessive production of mucus .
Nebulized fentanyl citrate or low doses of nebulized morphine helped improve breathing during exercise in 12 patients with COPD and in 11 patients (9 with advanced COPD) in 2 double-blind randomized controlled trials. However, nebulized morphine resulted in no improvement in breathing in different double-blind randomized controlled trials with COPD patients [46, 47, 48, 49, 50].
5) May Help Relieve Difficulty Breathing
Difficulties in breathing can be caused by different diseases, like cancer or diseases of the heart and kidneys .
Furosemide is a drug that helps lower the amount of fluid accumulated in the body by increasing the amount of urine the body produces. Studies in healthy patients (double-blind randomized controlled trial) show nebulized furosemide helps relieve induced difficulties in breathing [52, 53, 54].
However, in different double-blind randomized controlled trials, furosemide did not improve breathing difficulty after exercise with or without chest restraints (an inelastic strap secured around the chest) [55, 56].
6) May Help Treat Acute Lung Injury
Often, bleeding disorders with increased coagulation occur after acute lung injury. Nebulization of anticoagulants, drugs that stop excessive blood clotting, can deliver the required high concentrations to the lungs .
Nebulized heparin reduced blood clotting in 2 studies on 66 mechanically ventilated patients (open-label and double-blind randomized controlled trial) with no serious negative effects. The treatment reduced the amount of time mechanical ventilation was needed [61, 62].
7) May Help Breathing in Advanced Cancer Patients
Nebulized morphine was as effective as injected (subcutaneous) morphine in relieving breathing difficulties, in a study of 11 patients with advanced cancer (double-blind randomized controlled trial), and in 15 cancer patients (pilot study); nebulized morphine had no severe adverse effects [63, 64].
However, a study (double-blind randomized controlled trial) of 17 patients found no benefits to nebulized morphine compared to a salt water solution, while 2 systematic reviews found no evidence of benefits either [65, 66, 67].
Nebulized hydromorphone helped improve breathing after 10 minutes of receiving the drug in a trial of 20 advanced cancer patients (pilot study) .
Nebulized furosemide helped ease breathing in case reports of 3 and a study of 15 terminal cancer patients, while there was no improvement in other studies with 7 and 15 patients with advanced cancer (pilot studies) [69, 70, 71, 72].
8) Insulin through a Nebulizer
Less invasive alternatives for insulin administration are being studied. Nebulized insulin helps patients control their glucose levels, although not clearly as effective as injected insulin (1 meta-analysis and 2 open-label studies) [74, 75, 76].
Nevertheless, an inhaled insulin treatment was approved by the FDA but was discontinued after poor sales. Other pharmaceutical companies also halted their research on this subject. Rapid-Onset nebulized insulin is now being studied, which was effective in 13 patients with type 2 diabetes [73, 77, 78].
9) May Help with Scarred Lungs
The use of nebulized morphine helped improve the exercise capacity of 2 patients with idiopathic pulmonary fibrosis in one study (double-blind randomized controlled trial of 11 patients, the other 9 had COPD), and had no effect in one patient in another study (double-blind randomized controlled trial, 1 idiopathic pulmonary fibrosis patient and 9 with COPD) [47, 79].
Side Effects and Drug Interactions with Nebulizers
- Most of the side effects or drug interactions due to nebulizer use correspond to the drug being taken. However, difficulties in breathing due to contraction of the airway may occur as effects of the temperature or nature (tonicity) of the nebulized solution .
- Eye irritation may occur with the use of a face mask if not worn correctly .
- The risk of bacterial infection increases (S. aureus and P. aeruginosa) if the device is not cleaned correctly .
- The use of facemasks should be avoided when corticosteroids are used since they can cause side effects on the skin of the face and eyes .
- In adults and children with swollen airways and increased secretion of mucus, more drops are deposited in the upper airway .
- To avoid the contamination of the nebulizer with bacteria, the nebulizer cup, and the interface should be rinsed and dried after every use, and disinfected once or twice a week according to the manufacturer’s instructions .
Limitations and Caveats
- In some cases, a given medicine should be administered with a specific nebulizer, which should be stated on the drug label .
- Recommendations for drug treatments are made by panels of experts after reviewing the available literature. Physicians might adjust individual treatments according to specific patients’ needs .
Nebulizer Use in Infants
A study attempting to treat 30 infants (under 2 years) in their sleep found most of them woke up and refused the treatment. A special mask that incorporated the babies’ own pacifier was successfully used in 10 babies (under 12 months) to administer the medicine without waking them up [85, 86].
Those who use nebulizers at home generally look for one that is that is silent, easy to assemble and use, and one that has adequate pressure so treatment takes a reasonable amount of time.
Patients that use nebulizers daily recommend buying also a portable nebulizer to have at school/work. Some require AA batteries while other models have rechargeable batteries. Some of the rechargeable models have a car adapter, which people who travel a lot see as a great advantage.
Frequent users also recommend to always have a spare facemask/mouthpiece and keep close control of the service life of the filters/mesh. Thorough cleaning and drying are also advised to be very important.