Академический Документы
Профессиональный Документы
Культура Документы
ORIGINAL ARTICLE
I NTRODUCTION
Use of inhaled corticosteroids is a major treatment
strategy for bronchial asthma. The guidelines for the
treatment of bronchial asthma worldwide recommend the
use of inhaled corticosteroids (1) because they are highly
effective as a controller and have few adverse effects.
Inhaled steroids can have a positive impact on asthmatic
patients quality of life. An important adverse effect of
inhaled corticosteroids is the appearance of local side
effects, such as pharyngeal discomfort, hoarseness, and oral
candidiasis. These adverse effects can sometimes be
difficult to avoid, even with gargling or the use of spacer.
We previously evaluated the relationship between inhaled
corticosteroids and oral candidiasis and found that Candida
was detected on the pharyngeal walls of only some
asthmatic patients using fluticasone (about 25%) and that
its presence depended on the amount of fluticasone inhaled
(2). Most cases became negative after gargling with
amphotericin B, and the others required oral administration
of fluconasole. In these two groups, however, there was no
difference in the character of the Candida species detected.
Oral candidiasis usually occurs in patients with immunosuppressive conditions. Several reports have stated that
local immunity components, such as salivary IgA, histatin
(3, 4), defensin (5), and lactoferin (6), were related to the
occurrence of oral candidiasis. In patients with acquired
immunodeficiency syndrome (AIDS), the suppression of
cytotoxic immunity was reportedly related to oral candidiasis (7). Inhaled corticosteroids have no systemic immu-
Patients
The study consisted of 37 patients with bronchial asthma
(18 men and 19 women; mean SD age: 51.6 13.4 years)
who were receiving ambulatory treatment with inhaled
corticosteroid for more than 1 year at the Second
Department of Internal Medicine in Nagasaki University
Hospital, and 18 healthy volunteers (7 men and 11 women;
mean SD age: 32 2.5 years). Of the 37 asthmatic patients, 26 were treated with fluticasone propionate diskhaler, 5 were treated with fluticasone propionate discus
(Flutide Diskhaler; GlaxoWellcome; London, UK), and the
remaining 6 were treated with beclomethasone dipropionate
(Aldesin; Schering Plough; Kenilworth, USA). The background characteristics of patients were summarized in
Table 1. Beclomethasone was inhaled by using a pressurized metered-dose inhaler with a spacer (Inspire Ease;
Schering Plough), whereas fluticasone was inhaled by using
a dry powder inhaler. All asthmatic patients treated with
inhaled corticosteroids gargled with water immediately
after inhalation therapy. The study protocol was approved
by the Human Ethics Review Committee of Nagasaki
University School of Medicine, and written informed consent was obtained from each patient.
Collection of Saliva
After gargling with water, saliva was collected and then
centrifuged at 4000g for 15 minutes. The supernatant was
collected and stored at 80C until evaluation. At the same
time, a quantitative fungal culture was performed by
601
Order reprints of this article at www.copyright.rightslink.com
AND METHODS
602
C. FUKUSHIMA ET AL.
T ABLE 1.Characteristics of the patients.
Men:Women
Age (mean SD)
Severity
Mild persistent
Moderate persistent
Severe persistent
Type
Atopic
Non-atopic
Oral corticosteroid
Inhaled corticosteroid
Fluticasone diskhaler
Fluticasone diskus
Beclomethasone
Candida-positive
Candida-negative
11:6
55.1 12.6
7:13
53.9 14.4
4
10
3
5
12
3
6
11
3
7
13
3
12
3
2
14
2
4
Statistical Analysis
All data were expressed as means SD. Differences
between groups were examined for statistical significance
by using the unpaired Students t-test and the MannWhitney U-test as appropriate. A p-value less than 0.05
denoted the presence of a statistically significant difference.
Measurement of Protein
The protein content in each saliva sample was quantified
by the BCA protein assay kit (Pierce) by using bovine
serum albumin as the standard.
Data Eionxpress
The concentration of each antibody was normalized to
the total protein concentration of each sample, respectively,
and expressed as micrograms per microgram of protein
(total IgA) or OD450 per microgram of protein (Candidaspecific IgA).
FIGURE 2.(a) Salivary Candida-specific IgA/protein of controls, Candidanegative asthmatic patients using inhaled corticosteroid and Candida-positive
patients (mean SD). (b) Correlation between the amount of Candida and
salivary Candida-specific IgA/protein.
603
( r2 = 0.19, p < 0.05) (Figure 1), but not the Candidaspecific IgA/protein ( r2 = 0.012, p > 0.1) (Figure 2).
Correlation Between Amount of Inhaled Corticosteroid
and Salivary Total IgA/Protein or Candida-Specific
IgA/Protein
There was no significant correlation between the amount
of inhaled corticosteroid used and salivary total IgA/protein
or Candida-specific IgA/protein (Figure 3).
R ESULT
Candida was cultured from 17 of the 37 (46%) patients. It
was not detected in healthy controls.
Comparison Between Healthy Controls,
Candida-Negative Asthmatic Patients Using Inhaled
Corticosteroids and Candida-Positive Asthmatic
Patients Using Inhaled Corticosteroids
There was no significant difference in salivary total IgA/
protein between healthy controls and Candida-negative
asthmatic patients using inhaled corticosteroid ( p > 0.1,
healthy control 1.21 0.22, Candida-negative asthmaitc
patient 1.39 0.28). However, the salivary total IgA/
protein of Candida-positive asthmatic patients using inhaled corticosteroid was significantly lower than that of
Candida-negative asthmatic patients or healthy controls
( p < 0.05, Candida-positive asthmatic patients 0.64 0.18)
(Figure 1). On the other hand, the amount of salivary
Candida-specific IgA/protein of saliva was not different
between healthy controls, Candida-negative asthmatic patients, and Candida-positive asthmatic patients ( p > 0.1,
healthy controls 1.02 0.19, Candida-negative asthmatic
patients 1.00 0.25, and Candida-positive asthmatic patients 0.93 0.20) (Figure 2).
Correlation Between Amount of Candida and Salivary
Total IgA/Protein or Candida-Specific IgA/Protein
There was a significant negative correlation between the
amount of Candida and the salivary total IgA/protein
D ISCUSSION
Salivary IgA, histatin, lactoferin, and cytotoxic immunity
are thought to be important host factors for the oral
candidiasis. In the present study, we evaluated the role of
salivary IgA. Our results showed that salivary total IgA/
protein was not different between healthy controls and
Candida-negative asthmatic patients. The salivary total
IgA/protein in Candida-positive asthmatic patients was
significantly lower than that in the other two groups.
Moreover, there was a significant negative correlation
between the salivary total IgA/protein and the amount of
Candida. Candida was not detected in healthy controls.
These results suggest that inhaled steroids have the
potential to reduce salivary total IgA and that asthmatic
patients with lower salivary total IgA tend to suffer oral
candidiasis. However, only some asthmatic patients using
inhaled steroid encounter problems with oral candidiasis.
Our previous report showed a weak correlation between the
amount of fluticasone inhaled and the amount of Candida.
In the present study, there was no correlation between the
amount of inhaled steroid and salivary total IgA or
Candida-specific IgA. This implies that it is not just the
effect of steroid per se, but rather that host immunity also
has a large role in development of oral candidiasis. Our data
could not clarify if inhaled corticosteroid decrease salivary
IgA or the patients with just accidentally lower salivary IgA
is susceptible to candidiasis. Our previous report showed
that significantly more candida was detected from the
pharyngeal wall of asthmatic patients with inhaled
corticosteroid than that of asthmatic patients without
inhaled corticosteroid (2). Thus, the inhaled corticosteroid
may have some effects. The measurement of salivary IgA
before and after using inhaled corticosteroid would be
useful. But it is difficult to stop inhaled corticosteroid. The
prospective study should be needed. Among various reports
about salivary IgA in immunodeficient patients, some have
shown that salivary IgA levels in patients with AIDS (9) or
chronic mucocutaneous candidiasis (10, 11) were significantly lower than those of healthy controls. On the contrary,
other studies have reported no difference between salivary
IgA levels in immunodeficient patients and healthy controls
(12), or the salivary IgA levels in AIDS patients with oral
candidiasis were indeed higher than those in AIDS patients
without oral candidiasis (7). Clearly, further studies are
required. It is of interest that in the absence of a systemic
effect, inhaled corticosteroids can change local immunity.
We did not investigate serum IgA in this study, because
inhaled steroids are thought to have only rare systemic
effects. There have been various conflicting reports about
604
C. FUKUSHIMA ET AL.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
1.
20.
21.