1. Small Volume Nebulizer

   The use of a small volume nebulizer and related compressor is considered medically necessary durable medical equipment (DME) for any of the following indications:

   1. To administer beta-adrenergics (albuterol, isoproterenol, isoetharine, levalbuteral, metaproterenol), anticholinergics (ipratropium), corticosteroids (budesonide), and cromolyn for the management of obstructive pulmonary diseases (chronic bronchitis, emphysema, asthma, etc.);* or
   2. To administer dornase alfa** to members with cystic fibrosis; or
   3. To administer antibiotics (gentamicin, amikacin, or tobramycin,***) to members with cystic fibrosis or bronchiectasis; or
   4. To administer pentamidine to members with HIV, pneumocystosis, or complications of organ transplants; or
   5. To administer mucolytics (other than dornase alpha) (acetylcysteine) for persistent thick or tenacious pulmonary secretions; or
   6. To administer iloprost via a controlled dose inhalation drug delivery system to members with pulmonary hypertension; or
   7. To administer formoterol (Perforomist) or arformoterol (Brovana) for the management of chronic obstructive pulmonary disease when medical necessity criteria in Pharmacy CPB on Long-Acting Beta Agonists are met.

   Small volume nebulizers and related compressors are considered experimental and investigational for all other indications.

   * For criterion (a) to be met, the physician must have considered use of a metered dose inhaler (MDI) with and without a reservoir or spacer device and decided that, for medical reasons, it was not sufficient for the administration of needed inhalation drugs.

   ** More than one nebulizer may be considered medically necessary for members who are prescribed nebulized dornase alpha (Pulmozyme) plus other nebulized medications. The FDA-approved product labeling of dornase alpha instructs that it should not be diluted or mixed with other drugs in the nebulizer. The labeling explains that mixing of dornase alpha with other drugs could lead to adverse physicochemical and/or functional changes in dornase alpha or the admixed compound.

   *** Note on use of Pari-C Plus Vented Jet Nebulizer: Aetna considers the Pari-C Plus breath-enhanced or vented jet nebulizer medically necessary for pulmonary administration of aerosolized tobramycin because there is some evidence from direct comparative studies with standard unvented jet nebulizers to suggest that the Pari-C Plus vented jet nebulizer is necessary to deliver adequate concentrations of tobramycin to the lung (see, e.g., Coates, et al., 1998; Campbell & Saiman, 1999; Weber, et al., 1994; Eisenberg, et al., 1997; Ramsey, et al., 1999). Consensus guidelines from the Cystic Fibrosis Foundation recommend use of the Pari-C Plus Jet Nebulizer for delivery of tobramycin to individuals with cystic fibrosis (Campbell & Saiman, 1999). Aetna does not consider the Pari-LC Jet Plus brand of nebulizer medically necessary for nebulization of budesonide inhalation suspension (Pulmicort Respules). The Pari-LC Jet Plus Nebulizer was used in controlled clinical trials of nebulized budesonide for FDA approval. However, subsequent studies have demonstrated that brands of jet nebulizers other than Pari-LC Jet Plus are also capable of delivering a clinically effective dose of inhaled budesonide (Szefler, 1999). By contrast, ultrasonic nebulizers have been found in clinical studies to be inefficient at delivering inhaled budesonide and are not recommended for this indication (Nikander, 1994; Nikander, 1999). 

2. Large Volume Nebulizer:
   

   A large volume nebulizer, related compressor, and water or saline are considered medically necessary DME to deliver humidity to a person with thick, tenacious secretions, with any of the following indications:

   1. Cystic fibrosis;
   2. Bronchiectasis;
   3. Tracheostomy;
   4. Tracheobronchial stent;

   5. Administration of pentamidine for members with HIV, pneumocystosis, and complications of organ transplants.

   A large volume nebulizer and related compressor is considered experimental and investigational for all other indications.

3. Ultrasonic Nebulizers:
   

   The use of ultrasonic nebulizers is considered medically necessary DME for delivery of tobramycin (Tobi) for members with cystic fibrosis who meet the criteria for a standard nebulizer.

   Because there is no proven medical benefit to nebulizing particles of other drugs to diameters smaller than achievable with a pneumatic model, ultrasonic nebulizers are considered medically necessary only when all of the following criteria are met:

   1. The member meets the criteria for a standard nebulizer; and
   2. The use of a standard nebulizer has failed to control the member's disease and prevent the member from utilizing the hospital or emergency room; and

   3. The primary care physician and specialist indicate that the member has been compliant with other nebulizer and medication therapy.

   Ultrasonic nebulizers are considered experimental and investigational for all other indications.

4. Battery Powered Compressors:

   A battery-powered compressor is rarely medically necessary. Accompanying documentation must be submitted justifying its medical necessity.

5. Accessories:

   1. Disposable large volume nebulizers are considered convenience items. A non-disposable unfilled nebulizer filled with water or saline by the member/caregiver is an acceptable alternative.

   2. Note: Kits and concentrates for use in cleaning respiratory equipment are not covered. This is consistent with Medicare's policy.

6. Replacement:

   For members with DME benefits, replacement of nebulizers is considered medically necessary on an individual basis if both of the following criteria are met:

   1. The warranty has expired; and

   2. The primary care physician and/or specialist confirm that the member has been compliant with the nebulizer and anticipate the need for continued use to prevent a hospital admission or emergency room visits.

   The following table lists the usual maximum frequency of replacement for accessories that is considered medically necessary.

   1. Face tent: one/month
   2. Tracheostomy mask or collar: one/month
   3. Nebulizer, durable glass or autoclavable plastic, bottle type, not used with oxygen: one/3 years
   4. Immersion external heater for nebulizer: one/3 years
   5. Administration set, small volume non-filtered pneumatic nebulizer, disposable: two/month
   6. Small volume non-filtered pneumatic nebulizer, disposable: two/month
   7. Administration set, small volume non-filtered pneumatic nebulizer, non-disposable: one/6 months
   8. Administration set, small volume filtered pneumatic nebulizer: one/month
   9. Corrugated tubing, disposable, used with large volume nebulizer: 100 feet/2 months
   10. Corrugated tubing, non-disposable, used with large volume nebulizer: 10 feet/year
   11. Water collection device, used with large volume nebulizer: two/month
   12. Filter, disposable, used with aerosol compressor: two/month
   13. Filter, non-disposable, used with aerosol compressor or ultrasonic generator: one/3 months
   14. Aerosol mask, used with DME nebulizer: one/month

   15. Dome and mouthpiece, used with small volume ultrasonic nebulizer: two/year.

7. Nebulized Opioids

   The use of nebulized morphine or other opioids for the relief of dyspnea in persons with chronic obstructive pulmonary diseases is considered experimental and investigational.

8. Nebulized Corticosteroids for the Treatment of Nasal Polyps

   The use of nebulized corticosteroids for the treatment of nasal polyps, including in the pre- and post- polypectomy periods, is considered experimental and investigational because of insufficient evidence of the clinical value of nebulized corticosteroids over established forms of nasal corticosteroid administration (e.g., nasal spray, metered-dose nasal inhaler).

See also CPB 593 - Aerosolized Anti-infective for Sinusitis.

In this policy, the actual equipment (i.e., electrical devices) are referred to as either a compressor (when nebulization of liquid is achieved by means of air flow) or as a generator (when nebulization of liquid is achieved by means of ultrasonic vibrations). The term nebulizer is generally used for the actual chamber in which the nebulization of liquid occurs and is an accessory to the equipment. The nebulizer is attached to an aerosol compressor or an ultrasonic generator in order to achieve a functioning delivery system for aerosol therapy.

The plan of care must contain the specific condition of the patient justifying the medical necessity of each item. The order for any drug must clearly specify the type of solution to be dispensed to the patient and the administration instructions for that solution. The type of solution is described by a combination of (1) the name of the drug and the concentration of the drug in the dispensed solution and the volume of solution in each container, or (2) the name of the drug and the number of milligrams/grams of drug in the dispensed solution and the volume of solution in that container.

A narrative diagnosis and/or an ICD-9 diagnosis code describing the condition must be present on each order. An ICD-9 code describing the condition that necessitates nebulizer therapy must be included on each claim for equipment, accessories, and/or drugs. The patient's medical record must contain information that supports the medical necessity for all equipment, accessories, drugs and other supplies that are ordered.

Chronic infection with Pseudomonas aeruginosa is associated with progressive deterioration in lung function in cystic fibrosis (CF) patients. Nebulized antibiotics/anti-infectives (e.g., colistin and tobramycin) have been used in the management of these patients.

In a prospective double-blind placebo-controlled study, Jensen et al (1987) assessed the effects of colistin inhalation in 40 patients with CF and chronic broncho-pulmonary P. aeruginosa infection. Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline. Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group (18 versus 11). Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score, maintenance of pulmonary function and inflammatory parameters. The authors recommended colistin inhalation therapy for CF patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy.

Pai and Nahata (2001) noted that aerosolized tobramycin doses ranging from 80 mg twice or three times daily to 600 mg three times daily have been used in various clinical trials. At an 80-mg dose, preservation of pulmonary function with little or no improvement over the baseline was reported. Tobramycin, nebulized at 600 mg three times daily, significantly improved clinical and pulmonary functions and reduced the density of P. aeruginosa in the sputum. No ototoxicity or nephrotoxicity was reported at either dose. An increased risk of emergence of resistant strains of P. aeruginosa was noted at all doses, after prolonged use.

Tobramycin solution for inhalation (TOBI) received U.S. Food and Drug Administration approval for the maintenance therapy of patients 6 years or older with CF who have between 25% and 75% of predicted forced expiratory volume in 1 second (FEV(1)), are colonized with P. aeruginosa, and are able to comply with the prescribed medical regimen. TOBI was not approved for the therapy of acute pulmonary exacerbations in patients with CF, nor was it approved for use in patients without CF (Prober et al, 2000).

In a randomised clinical trial, Hodson et al (2002) evaluated the safety and effectiveness of tobramycin nebulizer solution (TNS) and nebulized colistin in CF patients chronically infected with P. aeruginosa. A total of 115 patients, aged 6 yrs or older, were randomized to receive either TNS or colistin, twice daily for 4 weeks. The primary end point was an evaluation of the relative change in lung function from baseline, as measured by forced expiratory volume in one second % predicted. Secondary end points included changes in sputum P. aeruginosa density, tobramycin/colistin minimum inhibitory concentrations and safety assessments. TNS produced a mean 6.7 % improvement in lung function (p = 0.006), whilst there was no significant improvement in the colistin-treated patients (mean change 0.37 %). Both nebulized antibiotic regimens produced a significant decrease in the sputum P. aeruginosa density, and there was no development of highly resistant strains over the course of the study. The safety profile for both nebulized antibiotics was good. Tobramycin nebulizer solution significantly improved lung function of patients with CF chronically infected with P. aeruginosa, but colistin did not, in this study of 1-month's duration. Both treatments reduced the bacterial load.

In a review on the role of nebulized antibiotics for the treatment of respiratory infections, Klepser (2004) stated that data regarding this topic are scarce. At this time, data support the use of aerosolized tobramycin solution for inhalation in CF patients infected or colonized by P. aeruginosa. Apart from this situation, widespread aerosolized administration of other agents in CF and non-CF patient populations should not be advocated.

Foral, et al. (2004) performed a structured review of the evidence for the use of nebulized morphine for the relief of dyspnea in persons with chronic obstructive pulmonary disease. The investigators concluded that there is inadequate evidence from placebo-controlled studies to support the use of nebulized morphine for the relief of dyspnea in patients with COPD. The investigators reported that published studies vary considerably in the dose, opioid used, administration schedule, and methodology. One study found improved exercise capacity in 11 patients not reproducible in a larger sample, and another study found benefit in 54 terminal patients. All other studies found no benefit. The investigators noted, furthermore, that recently published Global Initiative for Lung Disease guidelines have specifically stated that opioids are contraindicated in COPD management due to the potential respiratory depression and worsening hypercapnia. Foral, et al. concluded that nebulized opiods should be discouraged in COPD, as current data do not support their use.

There is insufficient evidence of the clinical value of nebulized corticosteroids for the treatment of nasal polyps, including in the pre- and post- polypectomy periods, over established forms of nasal corticosteroid administration (e.g., nasal spray, metered-dose nasal inhaler). Bikhazi (2004) states, 'no clinical studies have yet documented nebulized nasal steroid benefit'.

In a Cochrane review that compared holding chambers (spacers) versus nebulizers for beta-agonist treatment of acute asthma (Cates et al, 2006a), it was found that MDIs with spacer produced outcomes that were at least equivalent to nebulizer delivery.  Spacers may have some advantages compared to nebulizers for children with acute asthma.

In a Cochrane review that compared holding chambers versus nebulizers for inhaled steroids in chronic asthma (Cates et al, 2006b), it was concluded that budesonide in high dose delivered by the particular nebulizer used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 ug via a large volume spacer.  However, it is unclear if this was an effect of nominal dose delivered or delivery system.  Cost, compliance and patient preference are important determinants of clinical effectiveness that still require further assessment.  Future studies are needed to ascertain the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebulizer/compressor compared to holding chamber.  Moreover, further studies evaluating these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulized corticosteroids.