1. Clinical Practice of Nebulized Therapy in China:
A National Questionnaire Survey
Zheng Zhu, MMed, Jinping Zheng, MD, FCCP, Zhongping Wu, MB,
Yanqing Xie, PhD, Yi Gao, MMed, Liping Zhong, MB, and Mei Jiang, MMed
Abstract
Background: Despite having been used in the clinical practice of respiratory diseases for decades in China, the
overall description of nebulized therapy has not been reported to date. The purpose of this study was to
investigate the basic characteristics and information on the application of nebulized therapy in the clinical
practice of respiratory diseases in China.
Methods: A questionnaire survey with 17 questions relating to nebulized therapy was carried out in three levels
(tertiary, secondary, and primary) of hospitals throughout mainland China. The perspectives of various pro-
fessional degrees of the medical staffs from different levels of hospitals were further studied.
Results: A total of 6,449 effective questionnaires were collected from 1,328 hospitals or clinics located in 27
provinces or autonomous regions of mainland China. Nebulized therapy was applied in 91.1% of the hospitals,
significantly more in tertiary and secondary levels of hospitals than in the primary level of hospitals. Jet and
ultrasonic nebulizers were used in 53.3% and 47.7% of the hospitals, respectively. Only 50.8% of the re-
sponders identified the brands of the devices. 82.5 Percent of the responders had prescribed nebulized therapy.
68.8 Percent and 41.5% of responders agreed that nebulized therapy can be used for the treatment of asthma and
COPD, respectively. 86.5 Percent of responders agreed that nebulized therapy can be used for patients with
acute exacerbation, whereas 27.5% stated that it can be used for stable patients. The most commonly used
medicines were short-acting bronchodilators, followed by corticosteroids, mucolytics, and antibiotics. 17.2
Percent of the responders reported adverse events of nebulized therapy experienced by the patients. Continuous
medical education and training on nebulized therapy were required by 72.1% of responders.
Conclusions: The present national survey, firstly, provided the basic characteristics and information on the
application of nebulizer therapy in the clinical practice of respiratory diseases in China. Certainly, this will help
facilitate nebulized therapy, especially in the community hospitals. Continuous medical education and technical
training are essential to improve the clinical application of nebulized therapy.
Key words: inhalation therapy, nebulizer, clinical application, questionnaire survey, China
Introduction
Inhalation therapy with the advantages of rapid onset,
low administered dose, and less systemic adverse effects
over routine administrations (oral or intravenous routes) has
been used for decades.(1)
Three major types of inhalation
devices are available nowadays, i.e., metered dose inhalers
(pMDIs), dry powder inhalers (DPIs), and nebulizers.(2)
When used with proper technique, the various devices are
equally efficacious.(3)
Inhalation therapy by pMDIs and DPIs
remain the first-line choice for maintenance treatment of
asthma and chronic obstructive pulmonary disease (COPD);
nevertheless, for those with severe illness, the weak, the el-
derly, or those with poor compliance in the usage of pMDI or
DPI, treatment with a nebulizer does present user-friendly
benefits and provides better treatment effects. Nebulizers also
can deliver higher doses and more kinds of drugs at the same
time for the treatment of COPD, asthma, and other respira-
tory diseases. Medicine will be delivered when patients
use general or natural tidal-volume breathing.(4)
Although
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of
Guangzhou Medical University, Guangzhou 510120, China.
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY
Volume 27, Number 5, 2014
ª Mary Ann Liebert, Inc.
Pp. 386–391
DOI: 10.1089/jamp.2013.1053
386

2. nebulized therapy has been used for decades, the overall
description of the application of nebulized therapy in China
has not been reported to date.
The purpose of this national questionnaire survey is to
provide the basic characteristics and information on the ap-
plication of nebulized therapy in the clinical practice of re-
spiratory diseases in China, including but not limited to asthma
and COPD. Certainly, this should help facilitate the application
of nebulizer aerosol inhalation therapy by chest physicians,
respiratory patients, and nebulizer device producers in China,
and will also provide evidence for the development of the
Chinese guidelines for aerosol therapy used in COPD, asthma,
and other respiratory diseases in the near future.
Methods
Organized by the steering committee of the Respiratory
Therapy and Pulmonary Function Testing Division, Chinese
Thoracic Society, the cross-sectional questionnaire survey was
carried out in three levels of hospitals (tertiary: provincial
hospitals or teaching hospitals; secondary: district hospitals or
clinics; and primary: community hospitals or clinics). A
questionnaire consisting of 17 questions relating to the basic
information of the hospitals or clinics, devices, commonly used
medicines, indications, adverse events, and attitudes toward the
use of nebulized therapy, etc., was developed (Table 1). The
perspectives of medical staff with various professional degrees
and from different levels of hospitals were further studied.
Descriptive statistical analysis was applied to the study data.
Results
Overall description
A total of 6,449 effective questionnaires were collected
from 1,328 hospitals or clinics located in 27 provinces or
autonomous regions of mainland China. The survey was
carried out between March and June 2012. The hospitals
were located in the following areas of mainland China:
19.4% in the north, 11.5% in the northeast, 20.3% in the
east, 27.7% in the south and middle, 11.3% in the southwest,
and 9.8% in the northwest of China. They were evenly
distributed regarding the geography, population distribution,
and availability of medical facility (Fig. 1). Among all of the
collected questionnaires, 4,812 (74.6%) were from tertiary
hospitals, 1,088 (16.9%) were from secondary hospitals, and
549 (8.5%) were from primary hospitals. It was reported that
nebulized therapy had been used in 91.1% of the hospitals.
The application of nebulized therapy in primary hospitals
(47.3%) was significantly less than that in tertiary (95.8%)
and secondary (92.1%) levels of hospitals ( p < 0.001).
Nebulized therapy has been used for more than 20 years in
10.8% of hospitals, and for less than 5 years in 9.8% of
hospitals. The basic characteristics and information of the
investigated hospitals or clinics is presented (Table 2).
Devices
Jet and ultrasonic nebulizers were used in 53.3% and 47.7%
of hospitals, respectively. No vibrating mesh nebulizer use was
reported. Only 50.8% (3,274/6,449) of responders identified
the brand of the nebulizers. The most commonly used brands
of the devices were as follows: PARI (made in Germany),
23.0% (1,484/6,449); OMRON (made in China), 2.2%: GINA
(made in China), 1.7%: YUYUE (made in China), 1.0%; as
well as some other brands. Photos of the four popular nebu-
lizers are shown in Figure 2.
Medicines
The most frequently used medicines were bronchodilators,
followed by corticosteroids, mucolytics, and antibiotics. In-
haled salbutamol, ipratropium, and terbutaline were used in
63.5%, 43.4%, and 18.1% of hospitals or clinics, respectively.
Budesonide suspensions (available in doses of 0.25mg/2mL,
0.5 mg/2 mL, and 1 mg/2mL in China) were the most com-
monly prescribed inhaled corticosteroids (used in 56.7% of
hospitals), but dexamethasone, a systemic corticosteroid, was
also prescribed for nebulized therapy in 6.3% of hospitals.
Ambroxol hydrochloride, gentamicin, and tobramycin were
used in 10.8%, 3.7%, and 0.4% of hospitals, respectively.
Nebulized therapy with combination medication was reported
by 63.9% of responders. The commonly prescribed combi-
nation formulations were reported as follows: short-acting b2-
agonist (SABA) combined with corticosteroids (GCS) was
Table 1. Questionnaire Administered
to The Study Sample
1. Please name the hospital or clinic you work in.
2. The level of the hospital or clinic:
2.1. Tertiary
2.2. Secondary
2.3. Primary
3. Is it a specialized or general hospital or clinic?
4. What is your professional level: professor or chief
physician, attending, resident, or intern?
5. Medical specialty:
5.1. Respiratory medicine
5.2. Emergency department
5.3. Pediatrics
5.4. Surgical departments
5.5. General internal medicine
5.6. ICU
5.7. Others, please indicate
6. Has nebulized therapy been used in your hospital? (If
not, answer the 16th
question directly.)
7. How long has it been used?
8. Please clarify the nebulizer devices used in your hospital:
8.1. Jet
8.2. Ultrasonic
8.3. Others
9. Please identify the brand and manufacture of the
devices used in your hospital.
10. Do you agree that nebulized therapy is one of the
essential drug delivery methods for respiratory diseases?
11. Please state the indications for nebulized therapy.
12. In which situation is the nebulized therapy used: acute
exacerbation, stable, or both conditions of the diseases?
13. What are the drugs you often prescribe for nebulized
therapy?
14. What are the combination forms you often use for
nebulized therapy?
15. What are the adverse events reported by your patients
during the nebulized therapy?
16. Please explain the reasons if nebulized therapy has not
been used in your hospital.
17. Do you require continuous medical education and
training of nebulized therapy?
A NATIONAL SURVEY OF NEBULIZED THERAPY 387

3. reported by 39.6% (2,552/6,449); SABA combined with
short-acting muscarinic antagonists (SAMA) by 13.5% (868/
6,449); antibiotics combined with GCS by 5.1% (331/6,449);
SAMA combined with GCS by 10.2% (659/6,449); SABA
combined with expectorant by 3.4% (220/6,449); GCS
combined with expectorant by 5.0% (323/6,449); and anti-
biotics combined with expectorant by 1.7% (107/6,449).
Triple therapy of SABA and SAMA combined with GCS was
reported by 15.6% (1,008/6,449) of responders.
The frequently prescribed medicines and their combina-
tion formulations in different levels of hospitals are dis-
played in Table 3.
Indications
83.3 Percent of responders agreed that nebulized therapy
should be considered as one of the major routes of drug
delivery for respiratory diseases, and it had been prescribed
by 82.5% of responders. The agreement of the indication of
nebulized therapy for asthma was 68.8% of responders,
which was much higher than that of COPD (41.5% of re-
sponders). Other indications suggested by responders were:
lung infection (29.6%), laryngopharyngitis (16.7%), upper
airway infection (5.2%), eosinophilic bronchitis (9.0%),
and bronchiectasis (3.4%). 86.5 Percent of responders
agreed that nebulized therapy could be used for the treat-
ment of patients with acute exacerbation, whereas only
27.5% of responders stated that it can be used for stable
patients.
Adverse events
17.2 Percent of responders reported adverse events ex-
perienced by their patients. Complaints of adverse events
were: tremor, 17.2% (1,110/6,449); palpitation, 16.2%
(1,044/6,449); arrhythmia, 10.8% (695/6,449); shortness of
FIG. 1. The area distribu-
tion of recruited hospitals in
mainland China.
Table 2. Basic Information Of Responders From Departments And Their Professional Levels
Tertiary (n = 4,812) Secondary (n = 1,088) Primary (n = 549)
Departments
Respiratory department 42.8% (2,060) 42.8% (466) 4.7% (26)
Pediatric department 34.5% (1,658) 33.3% (362) 6.4% (35)
Emergency department 3.0% (142) 2.2% (24) 0.4% (2)
Internal medicine (excluding Respiratory) 5.2% (250) 13.1% (142) 65.8% (361)
Surgery 2.2% (108) 0.6% (7) 1.6% (9)
Intensive care unit 2.0% (95) 0.8% (9) 0 (0)
Other departments 10.3% (499) 7.1% (78) 20.8% (114)
Doctor levels
Chief physician 33.7% (1,622) 26.6% (289) 5.8% (32)
Attending physician 37.7% (1,813) 44.2% (481) 47.2% (259)
Resident physician 28.5% (1,373) 27.1% (295) 39.0% (214)
Intern 0.1% (4) 2.1% (23) 8.0% (44)
388 ZHU ET AL.

4. breath, 8.4% (542/6,449); nausea or vomiting, 5.4% (349/
6,449); irritating cough, 4.9% (316/6,449); uncomfortable
taste, 4.4% (284/6,449); allergic reaction to the drugs, 4.0%
(262/6,449); and cross infection, 2.4% (152/6,449).
Reasons for nebulized therapy not being used
Several reasons were given by the responders. The lack of
medicines and devices were reported by 76.2% (577/757)
and 75.7% (573/757) of responders, respectively. In addi-
tion, the lack of knowledge about how to use nebulizers
correctly was reported by 72.1% (546/757) of responders.
7.9 Percent of responders (60/757) reported that the cost of
the devices and drugs for nebulized therapy was expensive.
The necessity for technical training and continuous medical
education of nebulized therapy was addressed by most of the
responders; even 75.4% of them were from tertiary hospi-
tals.
Discussion
The present study was the first national survey on the
clinical application of nebulized therapy in China. It was
administered by a wide-ranging (27 provinces of mainland
China) and large number of responders (6,449) from dif-
ferent levels (tertiary, secondary, and primary) of hospitals
(1,328). About one third of the responders that came from
tertiary hospitals were chief physicians, whereas most of the
responders from the secondary and primary levels of hos-
pitals were attending and resident physicians. The answers
to the questionnaire might be influenced by the knowledge
and experience of the responders, which should be taken
into account when interpreting the results of the study.
Certainly, the basic and essential information on the appli-
cation of nebulized therapy provided by this survey will be
helpful by providing real-life evidence of nebulized therapy
that may be useful in adjusting the treatment policies of
health authorities, medical staffs, as well as medicine and
nebulizer device producers.
In this survey, we found that nebulized therapy was used
much less in the primary or community hospitals. In China,
around 80% of the patients were treated in the primary or
community hospitals that are equipped with basic medical
facilities. It is important to transfer the knowledge of neb-
ulized therapy to community hospitals, as most patients will
be treated there. This might be one of the most important
findings in the present survey.
National and international guidelines(2,3,5–7)
recommend
inhalation therapy as one of the preferred routes of drug
delivery for the treatment of respiratory diseases, such as
asthma and COPD. However, prior to inhalation therapy
being prescribed, the doctors should take into account the
medicines (e.g., available formulation, combined use), de-
vices (jet, ultrasonic, or vibrating mesh nebulizer), compli-
ance of the patient (child, elderly, or the weak), disease
situation (stable or exacerbated), as well as adverse
events.(5–8)
FIG. 2. Photos of four popular neb-
ulizers. (A) PARI (from Germany),
(B) OMRON (from China), and (C)
GINA (from China) are jet nebulizers.
(D) YUYUE (from China) is an ul-
trasonic nebulizer.
A NATIONAL SURVEY OF NEBULIZED THERAPY 389

5. Not all medicines are appropriate for nebulized therapy.
For instance, dexamethasone, a nontopical corticosteroid
with less effective and long half-life that can be harmful to
the hypothalamic–pituitary–adrenal axis, was prescribed as
a nebulized medicine by 6.5% of responders in the present
survey. Theoretically, topical steroids such as budesonide
are preferred as the ideal inhaled corticosteroid, as revealed
by Brogden and McTavish.(9)
In terms of antibiotics, only
a few antimicrobial agents were recommended for nebu-
lized therapy by the Society of Infectious Diseases Phar-
macists for treatment or prevention of bronchopulmonary
infection.(10)
Among these antimicrobial agents, only to-
bramycin has been well evaluated and used for cystic
fibrosis, hospital-acquired pneumonia, and non-cystic fi-
brosis bronchiectasis. However, in the present survey, we
found that gentamicin was used nearly 10 times more than
tobramycin, although the efficacy and safety of gentamicin
have not been evaluated.
In addition, an appropriate aerosol delivery device is also
critical for successful therapy. The features (advantages and
disadvantages) of various types of nebulizer devices should
be recognized.(11,12)
In the survey, we found that jet nebu-
lizers were used in 53.3% of hospitals, whereas ultrasonic
nebulizers were used in 47.7% of hospitals, which was
consistent with the literature we searched. Nevertheless, by
considering the potential heating activity that could damage
some medicines, including proteins or corticosteroids, it was
recommended that jet nebulizers were superior to ultrasonic
nebulizers.
Safety issues of nebulized therapy should always be of
concern. In the present survey, palpitation, tremor, nausea or
vomiting, and allergic reaction to the drugs encountered by
patients with nebulized therapy were reported. These ad-
verse events can be caused by either the medicine (i.e., b2-
agonist) or the nebulized breathing maneuver. Recognizing
the potential adverse events will help to avoid or reduce
such unhappy experiences. Cross infection reported by 2.4%
of responders is another important adverse effect that should
be emphasized and avoided. A filter to capture aerosol ex-
halation during nebulized therapy was not being used in
most parts of China due to economic conditions or un-
awareness, which may be one of the potential causes of
cross infection. The cleaning of the devices is also very
important to avoid cross infections.
Continuous medical education and training are essential
for better management of nebulizer therapy. Even in tertiary
hospitals, 75.4% of responders requested more training of
nebulized therapy, which would be helpful for their future
clinical practice. Consensus statements of aerosol inhalation
therapy for chronic pulmonary diseases in adults(13)
and
pediatrics(14)
are recommended in China.
It is essential to emphasize that inhalation therapy by
pMDIs and DPIs should always be recommended as the
first-line inhalation therapy, if these devices are used prop-
erly. Plaza et al. also addressed the importance of effective
educational strategies for the improvement of prescribers’
knowledge of inhalers and inhalation techniques, especially
for the use of MDIs and DPIs.(15)
This study was the first national questionnaire survey on
the application of nebulized therapy in China. A few
weaknesses are worth mentioning. Firstly, the study sites
were not randomly selected. Hospitals that had not con-
ducted nebulized therapy might not provide a response to
the survey and, hence, led to an underestimation of the
unavailability of nebulized therapy, especially in commu-
nity hospitals. Secondly, the departments in which the re-
sponders served were not evenly distributed; thus, more
responders from respiratory departments could lead to an
overestimation of the use of nebulized therapy. Thirdly,
most responders were chief and attending doctors; less
trained doctors might not master the nebulized technique
well. In spite of these limitations, the data in the present
study still provided a strong evidence of how nebulized
therapy is being used in China.
Table 3. Most Commonly Prescribed Medicines In Different Levels Of Hospitals
Tertiary (n = 4,812) Secondary (n = 1,088) Primary (n = 549)
SABA
Salbutamol 68.3% (3,288) 64.5% (702) 19.9% (109)
Terbutaline 20.8% (999) 12.7% (138) 5.6% (31)
SAMA
Ipratropium 48.1% (2,313) 40.3% (439) 8.9% (49)
GCS
Budesonide 61.6% (2,966) 54.8% (596) 17.1% (94)
Dexamethasone 6.0% (291) 7.8% (85) 5.1% (28)
Mucolytics
Ambroxol 11.9% (575) 9.5% (103) 2.9% (16)
Antibiotics
Gentamicin 3.7% (177) 3.4% (37) 4.9% (27)
Tobramycin 0.4% (20) 0.2% (2) 0.5% (3)
Combination therapy
SABA + GCS 43.5% (2,093) 36.9% (401) 10.6% (58)
SABA + SAMA 14.1% (677) 16.4% (178) 2.4% (13)
SABA + SAMA + GCS 18.1% (869) 11.7% (127) 2.2% (12)
SAMA + GCS 11.1% (535) 0.9% (108) 2.9% (16)
GCS, corticosteroids; SABA, short-acting b2-agonist; SAMA, short-acting muscarinic antagonists.
390 ZHU ET AL.

6. Conclusions
The present national survey is the first to report the
clinical application of nebulized therapy in China. It is
necessary to be aware of the medicines, devices, indications,
adverse events, as well as preparations of nebulized therapy.
All levels of doctors were in need of continuous medical
education and technical training of nebulized therapy, in
particular, those serving in community hospitals.
Acknowledgments
This study was supported by the Development Plan of
Changjiang Scholars and Innovative Research Team
(ITR0961) and The National Key Technology R&D Pro-
gram of the 12th National Five-Year Development Plan
(2012BAI05B00). All authors would like to acknowledge all
responders and sites for their great contribution regarding
data collection.
Zheng Zhu and Jinping Zheng drafted the manuscript.
Jinping Zheng, Yanqing Xie, and Yi Gao steered study
design and data collection. Zheng Zhu and Mei Jiang per-
formed statistical analysis. Zhongping Wu and Liping
Zhong collected survey forms.
Author Disclosure Statement
The authors declare that there are no conflicts of interest.
They also disclose no financial support for this survey.
References
1. Newhouse MT, and Dolovich MB: Control of asthma by
aerosols. N Engl J Med. 1986;315:870–874.
2. Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R,
Rau JL, Smaldone GC, and Guyatt G: Device selection and
outcomes of aerosol therapy: evidence-based guidelines:
American College of Chest Physicians/American College of
Asthma, Allergy, and Immunology. Chest. 2005;127:335–371.
3. Dhand R, Dolovich M, Chipps B, Myers TR, Restrepo R,
Farrar JR: The role of nebulizing therapy in the manage-
ment of COPD: evidence and recommendations. COPD.
2012;9:58–72.
4. Geller DE: Comparing clinical features of the nebulizer,
metered-dose inhaler, and dry powder inhaler. Respir Care.
2005;50:1313–1321.
5. Everard ML: Guidelines for devices and choices. J Aerosol
Med. 2001;14 (Suppl 1):S59–S64.
6. Burchett DK, Darko W, Zahra J, Noviasky J, Probst L, and
Smith A: Mixing and compatibility guide for commonly
used aerosolized medications. Am J Health Syst Pharm.
2010;67:227–230.
7. Hess DR: Aerosol delivery devices in the treatment of
asthma. Respir Care. 2008;53:699–723.
8. Devadason SG, and Le Souef PN: Age-associated factors
influencing the efficacy of various forms of aerosol therapy.
J Aerosol Med. 2002;15:343–345.
9. Brogden RN, and McTavish D: Budesonide: an updated
review of its pharmacological properties and therapeutic
efficacy in asthma and rhinitis. Drugs. 1992;44:375–407.
10. Le J, Ashley ED, Neuhauser MM, Brown J, Gentry C,
Klepser ME, Marr AM, Schiller D, Schwiesow JN, Tice S,
VandenBussche HL, and Wood GC; Society of Infectious
Diseases Pharmacists Aerosolized Antimicrobials Task
Force: Consensus summary of aerosolized antimicrobial
agents: application of guideline criteria. Insights from the
Society of Infectious Diseases Pharmacists. Pharma-
cotherapy. 2010;30:562–584.
11. Dolovich MB, and Dhand R. Aerosol drug delivery: devel-
opments in design and clinical use. Lancet. 2011;377:1032–
1045.
12. Rau JL, Ari A, and Restrepo RD: Performance comparison
of nebulizer designs: constant-output, breath-enhanced, and
dosimetric. Respir Care. 2004;49:174–179.
13. China Expert Committee of Nebulizer Inhalation Therapy
in Chronic Respiratory Disorders: China expert consensus
on nebulization inhalation therapy in chronic respiratory
disorders. Chin J Respir Crit Care Med. 2012;11:105–
110.
14. Hong J, Chen Q, Chen Z, Deng L, Li C, Liu E, Nong G,
Shang Y, Zhao D, and Zhao S: China expert consensus on
nebulization inhalation therapy in common pediatric re-
spiratory disorders. Chin J Pract Pediatr. 2012;27:265–269.
15. Plaza V, Sanchis J, Roura P, Molina J, Calle M, Quirce S,
Viejo JL, Caballero F, and Murio C: Physicians’ knowledge
of inhaler devices and inhalation techniques remains poor
in Spain. J Aerosol Med Pulm Drug Deliv. 2012;25:16–22.
Received on April 11, 2013
in final form, October 31, 2013
Reviewed by:
David Geller
Myrna Dolovich
Address correspondence to:
Dr. Jinping Zheng
State Key Laboratory of Respiratory Disease
National Clinical Research Center
for Respiratory Disease
First Affiliated Hospital of Guangzhou Medical University
151 Yanjiang Road
Guangzhou 510120
China
E-mail: jpzhenggy@163.com
A NATIONAL SURVEY OF NEBULIZED THERAPY 391