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| Voriconazole used for Treatment of Tracheobronchial Aspergillosis: A
Report of Two Cases |
| Chang Ran Zhang, Ming Li*, Jian Cong Lin*, Wen Ming XU*, Yuan Yuan Niu and Hui Shao Ye |
| Huang Pu Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, China |
| *Corresponding authors: |
Jian Cong Lin
Huang Pu Hospital of the First Affiliated
Hospital
Sun Yat-sen University
Guangzhou 510700, China
Tel: 86-020-
82379627
E-mail: zhcr2303@sina.com.cn |
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Ming Li
Huang Pu Hospital of the First Affiliated Hospital
Sun Yat-sen University
Guangzhou 510700, China
Tel: 86-020-82379627 |
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Wen Ming XU
Huang Pu Hospital of the First Affiliated Hospital
Sun Yat-sen
University
Guangzhou 510700, China
Tel: 86-020-82379627 |
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| Received May 15, 2012; Accepted June 25, 2012; Published July 02, 2012 |
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| Citation: Zhang CR, Li M, Lin JC, Wen Ming XU, Niu YY, et al. (2012) Voriconazole
used for Treatment of Tracheobronchial Aspergillosis: A Report of Two Cases. J
Clin Trials 2:117. doi:10.4172/2167-0870.1000117 |
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| Copyright: © 2012 Zhang CR, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited. |
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| Abstract |
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| Tracheobronchial aspergillosis mainly involves the trachea, primary bronchus and segmental bronchus. The main
symptoms including dyspnea, asthma and cough. Bronchoscopic findings supply the main evidence for diagnosis.
Voriconazole has been widely used as azole antifungal agent in recent years, which is also a first-line drug in the
treatment of invasive pulmonary aspergillosis (IPA), but rare report exists in the treatment of tracheobronchial
aspergillosis. Two patients have been remitted with Voriconazole in this study, and it was found that Voriconazole could
improve therapeutic effect and shorten therapeutic time with less adverse effects. |
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| Keywords |
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| Tracheobronchial aspergillosis; Aspergillus fumigatus;
Voriconazole; Therapy |
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| Introduction |
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| Tracheobronchial aspergillosis mainly involves the trachea, primary
bronchus and segmental bronchus. the main symptoms including
dyspnea, asthma and cough [1]. Based on clinical, bronchoscopic,
and pathological presentations, Kramer and coworkers proposed a
classification of tracheobronchial aspergillosis, they distinguished
saprophytic, allergic, and invasive tracheobronchial aspergillosis
(ITBA) [2]. Alternative treatments include liposomal or lipid complex
form of amphotericin B, caspofungin, micafungin, posaconazole, and
itraconazole [3]. The latest Infectious Diseases Society of America
guidelines which recommend voriconazole for primary treatment of
invasive Aspergillus tracheobronchitis [4], but only few reports on
voriconazole for primary treatment of tracheobronchial aspergillosis
[5-8], and evidence is limited. In this study, two cases on the adoption
of voriconazole for the treatment of tracheobronchial aspergillosis
were observed and reported as follows: |
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| Case 1 |
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| A male patient of 54 years old was admitted for “cough, sputum
and wheezing for one week” on July 22, 2007. The smoking status
of case 1 was 30 packs/year, and the patient had chronic obstructive
pulmonary disease (COPD) for 12 years, One week before admission,
the symptoms as a result of cold occurred to the patient, such as
irritable cough, slight white sticky sputum and obvious wheezing,
while no bloody sputum, chest pain nor fever existed. The patient had
a medical history of Type-2 diabetes but no bronchial asthma, and an
occupational history of exposure to coal dust. The examination after
admission showed body temperature of 37°C, respiratory rate of 30
times/min, heart rate of 105 beats/min and blood pressure of 115/75
mmHg. The physical examination indicated that wheezes were heard
in bilateral lungs, while other pulmonary sounds were negative. Blood
routine examination showed WBC of 21.5 × 109/L and eosinophils
(E) percentage of 12%. There was pulmonary function test, the FEV1/
FVC was 65%, and FEV1 was 400 ml larger or >12% after inhaled
bronchodilator, the bronchodilator reversibility testing was positive.
Biochemical test indicated glucose of 8.91 µmol/L and erythrocyte
sedimentation rate (ESR) of 39 mm/h. Besides, no significant
changes were found in chest X-ray film on the day of admission.
Two days later (on July 24), the patient had Type-I respiratory
failure and fever with body temperature of 39°C. The symptoms
were improved gradually after anti-infective therapies (Levofloxacin,
Cefoperazone), expectorant therapy (Mucosolvan), anti-spastic
and anti-asthmatic therapies (intravenous Doxofylline, intravenous
injection of Methylprednisolone of 40-80 mg/day, Combivent,
inhaled corticosteroids and. bronchodilator). However, wheezing was
aggravated after withdrawal of corticosteroid methylprednisolone. In
sputum culture, aspergillus grew in a small amount. On July 27, bedside
bronchoscopy showed that white masses adhered to the bronchial
wall inside the left and right main bronchus (Figure 1), and bronchial
wall were easy to bleed after touching. The bronchial secretions were
taken for culture with subsequent pathological examination. A large
number of aspergillus hyphae under the microscope were shown in the
pathological results (Figure 2). Voriconazole was injected intravenously
at 0.2 mg/kg twice daily. A week later (on Aug. 15), re-examination was
taken under fibrobronchoscope, and it was found that white masses
almost disappeared (Figure 3). Voriconazole was administered orally
at 0.2 kg/mg twice daily for two months in the course of treatment. No
recurrence was observed after three years of follow-up visits. |
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Figure 1: White Masses Adhered to the Bronchial Wall Under the Fibrobronchoscope. |
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Figure 2: Hyphae of Aspergillus Fumigatus Were Observed in the Tissues (Arrow) (10X20). |
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Figure 3: White Masses Disappeared After One Week with the Treatment of Voriconazole. |
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| Case 2 |
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| A male retired worker of 70 years old was admitted for “cough
with thick white sputum and dyspnea for one week” on Feb. 21, 2008.
As for medical history, the patient had chronic obstructive pulmonary
disease (COPD) for 10 years, and underwent meningioma surgery on
Nov. 27, 2007, but without receiving chemotherapy. The patient had no
bronchial asthma in the past. The examination after admission showed
the patient presented chronic illness characterized by barrel chest,
bilaterally decreased vocal fremitus, hyperresonnant sound heard by
palpitation, fine moist rales and wheezes heard in bilateral lungs. Blood routine examination showed WBC of 9.8 × 109&L and eosinophils (E) percentage of 15%. There was pulmonary function test, the FEV1/FVC was 76%, and FEV1 was 300 ml larger or >12% after inhaled bronchodilator, bronchodilator reversibility testing was positive. The chronic bronchitis was shown in chest X-ray film. No space occupying lesions were found in the lungs by chest CT scan. On Feb. 25, bedside bronchoscopy showed that white masses adhered to the bronchial
wall inside the left and right main bronchus (Figure 4). The bronchial
secretions were taken for culture with subsequent pathological
examination. The pathological results showed aspergillus growth and
a large number of aspergillus hyphae under the microscope (Figure 5).
Voriconazole was injected intravenously at 0.2 mg/kg twice daily. A
week later, white masses disappeared, which had adhered to bronchial
wall previously (Figure 6), and wheezing was alleviated gradually.
Voriconazole was administered orally at 0.2 mg/kg twice daily for
one and a half months in the course of treatment. No recurrence was
observed after two years of follow-up visits. |
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Figure 4: White Masses Adhered to the Bronchial Wall Under the Fibrobronchoscope. |
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Figure 5: Aspergillus fumigatus hyphae were observed in the tissues (arrow) (10X20). |
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Figure 6: One week after treatment Voriconazole, the bronchial lumen was smooth, and the pathological results showed some aspergillus hyphae still remained in the tissues. |
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| Discussions |
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| The two patients were induced by hypersensitivity reaction to Aspergillus fumigatus, with wheezing as its main clinical symptom,
possibly manifested by elevated eosinophils, but no positive
radiological findings (central bronchiectasis or pulmonary infiltrates).
Because this form of pulmonary aspergillosis is not usually associated
with pulmonary infiltrates in its initial stages, radiographic images
may not identify the infection, which is otherwise easily seen during
bronchoscopic examination. Bronchaoscopic evaluation is necessary
for early diagnosis. As we did not detect serum IgE and aspergillus skin test, the two cases did not meet the diagnostic criteria of Allergic
bronchopulmonary aspergillosis (ABPA). In this study, identification
and diagnosis was mainly by means of collecting tracheal and bronchial
tissues under the bronchoscope. It was found that aspergillus hyphae
in tissues were useful for tracheobronchial aspergillosis, so we think it
is more fit to diagnoses Aspergillus hypersensitive bronchial asthma,
which was caused by tracheobronchial aspergillosis [9]. Due to high
potential risk in fibrobronchoscopy for asthma patients, currently,
the patients with bronchial asthma are required bronchoscopy to rule
out the possibility of developing Aspergillus hypersensitive bronchial
asthma. The diagnosis of Aspergillus hypersensitive bronchial asthma
was greatly limited. Patients with impaired immune function, bronchial
asthma but no medical history of bronchial asthma may have secondary
Aspergillus hypersensitive bronchial asthma. In this study, one case
with diabetes history but no history of bronchial asthma might also
have secondary the diagnosis. In addition, one case had brown sputum,
which was rarely observed for other diseases. it is also mentioned that
some patients may have brown sputum, which is of great significance
to determination and diagnosis [4]. |
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| In the past decades, several new antifungal agents have been used
clinically, of which therapeutic effects on deep fungal infection have
been significantly improved [10-13]. Stevens et al. [14] conducted
a randomized double-blind trial of treatment with either 200 mg
of itraconazole twice daily or placebo for 16 weeks in patients with
ABPA. There were responses in 13 of 28 patients in itraconazole
group (46 percent), and adverse events occurred in 25 of 28 patients in
itraconazole group (89 percent). The adverse events are shown as hair
loss, dry mouth, hand tremors, loose bowel movements, constipation,
forgetfulness and increased fatigue. Voriconazole widely dispersed in
mammalian tissues with a half-life of 6 hours is mainly metabolized via
the liver. In this study, it was found that voriconazole had fast effect and
short course of treatment, while few adverse effects in the treatment
of tracheobronchial aspergillosis. The two cases showed no obvious
adverse effects such as liver and kidney dysfunction, visual abnormality
and gastrointestinal reactions [13]. Due to the small size of observation
cases, it is necessary to have further studies. |
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| References |
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