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Corresponding author at: Connecticut Children's Medical Center, Division Pediatric Pulmonary Medicine, 282 Washington St., Hartford, CT 06106, United States.
Pediatric Pulmonary Medicine, Connecticut Children's Medical Center, Hartford, CT, United StatesPediatrics, University of Connecticut School of Medicine, Farmington, CT, United States
Pediatric Pulmonary Medicine, Connecticut Children's Medical Center, Hartford, CT, United StatesPediatrics, University of Connecticut School of Medicine, Farmington, CT, United States
Quinnipiac University, Frank H. Netter School of Medicine, North Haven, CT, United StatesInfectious Disease and Immunology, Connecticut Children's Medical Center, Hartford, CT, United States
Currently, cystic fibrosis patients require daily nebulized treatments to achieve optimal lung health. Growth of pathogenic bacteria in patient nebulizers is well known, and disinfection guidelines have been established. In this short communication, we sought to discover what effect, if any, repeated nebulization/disinfection cycles had on nebulizer output. We nebulized saline repeatedly after exposure to boiling water, steam, and alcohol disinfection methods. While alcohol disinfection did not affect nebulizer output, boiling water and steam significantly decreased nebulizer output from baseline, 74.1 ± 5.9% (p = 0.022) and steam 63.6 ± 6.5% (p = 0.0048) after 60 cycles respectively. This decrease in nebulizer output could significantly increase the duration of nebulizer treatment time and negatively impact the burden of care on patients with cystic fibrosis.
], as CF pathogens (e.g. Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia,) have been recovered from patient nebulizers, creating the potential for bacterial aerosolization into the lower airways [
Home-use nebulizers: a potential primary source of Burkholderia cepacia and other colistin-resistant, gram negative bacteria in patients with cystic fibrosis.
]. Given the popularity of heat based and chemical disinfection methods, our goal was to determine whether any of these methods altered nebulizer function.
2. Methodology
2.1 Nebulizer selection and disinfection
The Pari LC Plus® jet nebulizer was selected (FDA approved for use with multiple CF medications) to undergo repeated rounds of nebulization and disinfection. Nebulizers were maintained in original sets and paired with compressors for consistency. Nebulization was performed with 5 ml Addipak® 0.9% sterile saline using compressed air (Pulmo-Aide Compressor, Model 3655). Three disinfection methods were compared: boiling, steam, and alcohol [
]: 1) boiling: disassembled nebulizers were placed in boiling distilled water (temperature maintained 100 °C) for 5 min. 2) steam: 100 ml distilled water was added to the Avent® 3-in-1 Electric Steam Sterilizer (Philips) and the disassembled nebulizer steamed until the water evaporated and the machine turned off (approximately 8.5 min). After either heat method, nebulizers were cooled and air dried prior to use. 3) alcohol: Disassembled nebulizers were submerged in 70% isopropyl alcohol for 5 min, rinsed with distilled water and air dried. Isopropyl alcohol concentration was regularly monitored (measured every 10–20 rounds of disinfection) and percentage alcohol maintained between 64 and 70% [
]. A distilled water rinse was performed after each nebulization and control nebulizers were rinsed only without disinfection. Five nebulizers per group were used. The control and heat (boiling and steam) disinfection studies were repeated with a second group of five different nebulizers to confirm observed differences.
2.2 Measurement of nebulizer output
Nebulizer output (ml/min) was measured at baseline (averaging two measurements after two nebulizations to prime the machine [
]) and after every 10–20 rounds of nebulization/disinfection. At each measurement point, the nebulizer was weighed three times (1) while empty and dry, (2) with 5 ml of saline, and (3) after 7 min of nebulization (preliminary experiments showed sputtering began between after 8–10 min of nebulization [
], and so nebulizers were compared to baseline as well as controls. Compressor output was measured by an acrylic oxygen flow meter (Dakota Instruments, Orangeburg, NY) at the beginning and end of each day of experimentation to ensure no changes to output with repetitive use [
The volume of a daily CF nebulizer regimen for a "typical" patient was calculated to demonstrate the impact of nebulizer output on daily CF care. Frequently, this includes at least the following: albuterol (twice at 3 ml each), dornase alpha (2.5 ml), hypertonic saline (twice at 4 ml each) and inhaled tobramycin (twice at 5 ml each), resulting in a minimum of 26.5 ml nebulized daily; this total volume was applied to the nebulizer outputs in each disinfection group to calculate the expected time spent in daily treatments.
2.3 Statistical analysis
Data were expressed as mean ± standard error values and analyzed with StatView 4.5 (Abacus Concepts, Inc., Berkeley, CA). Baseline nebulizer output between groups was compared using analysis of variance (ANOVA). Within group changes in nebulizer output over time compared to baseline were assessed by 1-factor repeated-measures analysis of variance (RM-ANOVA) and by paired t-tests incorporating Bonferonni corrections to account for multiple comparisons. Time-related differences in nebulizer output were measured for the different disinfection groups and a control, non-disinfected group by 2-factor RM-ANOVA. For RM-ANOVA analysis, p values < 0.05 were considered significant.
3. Results
Baseline nebulizer output did not differ across different groups (p = 0.30), but disinfection method significantly affected nebulizer function (Fig. 1). Within group analysis comparing nebulizers to their baseline showed no change through 60 cycles in the control, non-disinfected group (p = 0.40 by paired t-tests). In contrast, a significant decrease in output from baseline was shown for both boiling, 74.1 ± 5.9% (p = 0.022), and steam 63.6 ± 6.5% (p = 0.0048) at 60 cycles. Alcohol disinfection showed no decrease in output 104.7 ± 5.2% (p = 0.50) from baseline. When extended to 120 cycles, there was still no change in output with alcohol (96.1 ± 8.3%; p = 0.24). Because the decrease in nebulizer output for heat based methods was observed by 20 cycles (Fig. 1), the experiment was repeated with a new set of five nebulizers, measuring output every three cycles (data not shown). A decrease in output compared with baseline was observed over time for steam disinfection (0.240 ± 0.036 to 0.196 ± 0.020 ml/min, p < 0.0001) with a statistically significant decrease seen as early as 6–10 cycles (p = 0.0024). There was a decrease in output after boiling compared with baseline over 20 cycles that was not statistically significant (p = 0.30).
Fig. 1Data represent mean ± S.E. values for control (circles), boiling (squares), steam (diamonds), and alcohol (triangles) sterilization. N = 5 in each group. Overlapping error intervals are not shown.
Average time per daily treatment was calculated for each disinfection method (Fig. 2). After 60 cycles of nebulization, corresponding to approximately two months of daily disinfection, heat based methods of disinfection resulted in clinically significant increase in treatment time, 36.8 ± 8.8 min/day for boiling (p = 0.014) and 57.4 ± 12.6 min/day for steam (p = 0.010), above baseline treatment times of 101.5 and 90.4 min respectively. There was no change with alcohol (−4.9 ± 5.2 min; p = 0.39) (Fig. 2).
Fig. 2Data represent mean ± S.E. values for control (circles), boiling (squares), steam (diamonds), and alcohol (triangles) sterilization. N = 5 in each group. Overlapping error intervals are not shown.
As nebulizer composition and disinfection techniques evolve, it is important to periodically confirm that optimal methods for destroying pathogens do not alter nebulizer function. While heat based methods are effective at killing bacteria ([
]), these data suggest repeated heat exposure may reduce nebulizer output over time, increasing the burden of home care. Bakuridze et al. demonstrated no effect of steam disinfection on the output of the eflow® nebulizer after 60 cycles, which may be due to aerosol output being generated by metal vibrating mesh, rather than plastic like most jet nebulizers including the Pari LC Plus® [
]. Ozone based disinfection, also effective at killing bacteria without altering nebulizer function, requires further investigation of this technique in the home setting [
Strengths of this study are 1) repeated cycles of disinfection and nebulization to mimic home use 2) the number of nebulizers tested per method is larger than previous studies 3) the pairing of nebulizers and compressors to minimize confounding variables. However, this study was also performed under ideal experimental conditions using a relatively inert solution (saline). Future work will examine whether our observation holds true during daily medication-based nebulizer use and disinfection in the home. It is interesting that our study showed significant decrease in nebulizer output after as few as 20 cycles. With routine use, this is well before replacement is recommended by the manufacturer (after 6 months).
In summary, we demonstrated that heat-based disinfection practices impair nebulizer output. This decrease in nebulizer efficiency could add approximately 30–50 min to the daily burden of CF care, further reducing adherence to important inhaled therapies [
]. Accordingly, non-heat-based disinfection methods may be preferable.
This study was funded through internal funds provided by the Frank H Netter MD School of Medicine at Quinnipiac University.
The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
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Home nebulizer use among patients with cystic fibrosis.
Home-use nebulizers: a potential primary source of Burkholderia cepacia and other colistin-resistant, gram negative bacteria in patients with cystic fibrosis.
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