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Selected Reports - Chest - American College of Chest Physicians

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CHEST <strong>Selected</strong> <strong>Reports</strong><br />

Cavitating Invasive Pulmonary<br />

Aspergillosis Visualized and<br />

Diagnosed by Ultrathin<br />

Bronchoscopy*<br />

Masahide Oki, MD; Hideo Saka, MD, FCCP;<br />

Chieko Sako, MD; Shigeru Tanaka, MD;<br />

Yoshihiro Kawata, MD; Chiyoe Kitagawa, MD; and<br />

Nobuyoshi Minemura, MD<br />

A definitive diagnosis <strong>of</strong> invasive pulmonary aspergillosis<br />

(IPA), which usually occurs in immunocompromised<br />

patients, is <strong>of</strong>ten difficult. We report<br />

two cases <strong>of</strong> cavitating IPA in a peripheral pulmonary<br />

region in patients who were receiving corticosteroids,<br />

in whom the cavity was successfully visualized<br />

and sampled during ultrathin bronchoscopy.<br />

Ultrathin bronchoscopy provides a new option for<br />

definitive diagnosis <strong>of</strong> cavitating IPA.<br />

(CHEST 2006; 129:475–479)<br />

Key words: bronchoscopy; cavity; invasive pulmonary aspergillosis;<br />

transbronchial biopsy; ultrathin bronchoscope<br />

Abbreviations: IPA invasive pulmonary aspergillosis;<br />

TBB transbronchial biopsy<br />

Invasive pulmonary aspergillosis (IPA), which commonly<br />

occurs in immunocompromised patients, is a lifethreatening<br />

infectious disease. Not only are such patients<br />

difficult to treat, the diagnosis is especially difficult.<br />

Although bronchoscopic procedures such as BAL and<br />

transbronchial biopsy (TBB) have been used to establish<br />

the diagnosis <strong>of</strong> IPA, their diagnostic yield is insufficient. 1<br />

The diagnostic yield <strong>of</strong> TBB is particularly low, 2 so its<br />

value for the diagnosis <strong>of</strong> IPA remains controversial. 3<br />

Recently, ultrathin bronchoscopes <strong>of</strong>fering a smaller<br />

outer diameter and higher image quality have been developed.<br />

Such a bronchoscope with an outer diameter <strong>of</strong> 2.8<br />

mm is now commercially available and permits the observation<br />

and manipulation <strong>of</strong> more peripheral bronchi than<br />

was previously possible with a standard bronchoscope. The<br />

*From the Departments <strong>of</strong> Respiratory Medicine (Drs. Oki, Saka,<br />

Sako, Tanaka, Kawata, and Kitagawa) and Internal Medicine (Dr.<br />

Minemura), Nagoya Medical Center, Nagoya, Japan.<br />

Manuscript received July 11, 2005; revision accepted August 20,<br />

2005.<br />

Reproduction <strong>of</strong> this article is prohibited without written permission<br />

from the <strong>American</strong> <strong>College</strong> <strong>of</strong> <strong>Chest</strong> <strong>Physicians</strong> (www.chestjournal.<br />

org/misc/reprints.shtml).<br />

Correspondence to: Masahide Oki, MD, Department <strong>of</strong> Respiratory<br />

Medicine, Nagoya Medical Center, 4-1-1 Sannomaru, Nakaku,<br />

Nagoya 460-0001, Japan; e-mail: Masahideo@aol.com<br />

ultrathin bronchoscope has been reported to be a valuable<br />

diagnostic tool for peripheral pulmonary lesions. 4–6 Although<br />

various diseases can be diagnosed histologically<br />

using the ultrathin bronchoscope, there is, to our knowledge,<br />

no report in the literature about its contribution to<br />

the diagnosis <strong>of</strong> IPA. We herewith report two cases <strong>of</strong> IPA<br />

diagnosed in patients were receiving corticosteroids, in<br />

whom the cavity was visualized and sampled during<br />

ultrathin bronchoscopy.<br />

Case 1<br />

Case <strong>Reports</strong><br />

A 57-year-old man with dermatomyositis was referred for<br />

bronchoscopic evaluation <strong>of</strong> progressive radiographic changes<br />

consisting <strong>of</strong> an enlarging cavity despite antibiotic therapy. For 3<br />

months, he had received prednisolone, 40 to 80 mg/d, and<br />

azathioprine, 100 mg/d, for intractable dermatomyositis. Two<br />

weeks earlier, he complained <strong>of</strong> fever, increased cough, purulent<br />

sputum, and dyspnea. The chest radiograph showed a cavity with<br />

surrounding infiltrates in the upper lobe <strong>of</strong> the right lung.<br />

Sputum cultures grew Pseudomonas aeruginosa and Candida<br />

glabrata. The patient had been treated with IV cefozopran and<br />

fluconazole for 2 weeks without any clinical improvement.<br />

A CT scan <strong>of</strong> the chest the day before bronchoscopy revealed<br />

a thick wall cavity in the anterior segment <strong>of</strong> the right upper lobe<br />

that had not been present 2 months previously (Fig 1). Bronchoscopic<br />

examination using a standard bronchoscope with an<br />

external diameter <strong>of</strong> 6.1 mm (BF-6C240; Olympus; Tokyo, Japan)<br />

[Fig 2] was first performed. The bronchoscope reached the<br />

segmental bronchus <strong>of</strong> the right upper lobe and revealed no<br />

abnormalities. Then, for peripheral investigation, a 2.8 mm in<br />

diameter ultrathin bronchoscope with a 1.2-mm working channel<br />

(BF-XP40; Olympus) [Fig 2] was employed. The ultrathin bronchoscope<br />

was inserted into the right B3 and advanced through<br />

the fifth-generation bronchus under direct observation, and then<br />

entered a cavity, as confirmed by fluoroscopy (Fig 3). A whitish<br />

intracavitary lesion was seen (Fig 4, left, A). Biopsies using a<br />

miniforceps (FB-56D-1; Olympus) and washing were performed<br />

with bronchoscopic visualization, and then amphotericin B, 5 mg,<br />

was instilled into the cavity through the ultrathin bronchoscope<br />

for treatment <strong>of</strong> a presumptive fungal infection. Biopsy specimens<br />

showed septate-branching hyphae suggestive <strong>of</strong> aspergillosis<br />

and cultures <strong>of</strong> the cavital washing grew Aspergillus flavus.<br />

Unfortunately, 9 days later the patient suddenly died <strong>of</strong> cerebral<br />

hemorrhage.<br />

Case 2<br />

A 69-year-old man with systemic lupus erythematosus was<br />

admitted to the hospital with cough, bloody sputum, fatigue,<br />

decreased appetite, and enlarging left lower lobe pulmonary<br />

cavity. For 6 months before hospital admission, he had received<br />

prednisolone, 20 to 30 mg/d, for systemic lupus erythematodes.<br />

Two months earlier, he complained <strong>of</strong> bloody sputum, and a<br />

chest CT showed cavitary infiltrates in the superior segment <strong>of</strong><br />

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Figure 1. <strong>Chest</strong> CT on the day before bronchoscopy showed a thick wall cavity in the anterior segment<br />

<strong>of</strong> the right upper lobe (right) that had not been present 2 months previously (left).<br />

the left lower lobe (Fig 5, left). Sputum cultures showed A flavus.<br />

Clinical deterioration with an enlarging cavity had occurred<br />

despite antibiotic treatments including itraconazole (Fig 5, right).<br />

Bronchoscopic examination was performed using a 2.8-mm<br />

ultrathin bronchoscope (BF-XP260F; Olympus), which could be<br />

inserted into the seventh-generation bronchus under direct vision<br />

and then advanced into the cavity. A yellowish white intracavitary<br />

lesion was noted (Fig 4, right, B). Biopsies and washing were<br />

Figure 2. A comparison <strong>of</strong> bronchoscopes. Left: a standard bronchoscope with an external diameter<br />

<strong>of</strong> 6.1 mm and a working channel <strong>of</strong> 2.0 mm (BF-6C240; Olympus); right: an ultrathin bronchoscope<br />

with an external diameter <strong>of</strong> 2.8 mm and a working channel <strong>of</strong> 1.2 mm (BF-XP40; Olympus).<br />

476 <strong>Selected</strong> <strong>Reports</strong><br />

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Figure 3. Tip <strong>of</strong> the ultrathin bronchoscope shown entering a<br />

cavity.<br />

performed under ultrathin bronchoscopic visualization. Histologic<br />

examination <strong>of</strong> biopsy specimens showed septate-branching<br />

hyphae, and cultures <strong>of</strong> the cavital washing grew Aspergillus<br />

fumigatus. IV amphotericin B was administered at a total dose <strong>of</strong><br />

2,000 mg, and the patient showed clinical improvement with<br />

resolution <strong>of</strong> the extracavitary and intracavitary infiltrates but<br />

persistence <strong>of</strong> a thin wall cavity.<br />

Discussion<br />

IPA occurs mainly in severely immunocompromised<br />

patients, particularly those with prolonged severe granu-<br />

locytopenia. 7 Although the incidence is relatively uncommon,<br />

mildly immunocompromised patients, such as those<br />

receiving corticosteroids similar to our cases, can also<br />

acquire IPA. 8,9 Palmer et al 9 reported six patients with<br />

lung disease receiving corticosteroids who acquired IPA,<br />

and they indicated that IPA should be included in the<br />

differential diagnosis when pneumonia and cavitary infiltrates<br />

occur in such patients.<br />

Although the diagnosis <strong>of</strong> IPA is <strong>of</strong>ten admittedly<br />

difficult, 10 when compatible clinical and radiographic findings<br />

are supported by the presence <strong>of</strong> positive culture<br />

results for Aspergillus species from respiratory secretions,<br />

it is highly likely that the patient has IPA. BAL during<br />

bronchoscopy has proved helpful in diagnosing IPA. In<br />

one review article, 11 it was reported that the diagnostic<br />

sensitivity <strong>of</strong> BAL was 43% in histologically proven IPA.<br />

However, the reported diagnostic sensitivity <strong>of</strong> BAL for<br />

IPA appears to vary with the investigator. Saito et al 12<br />

reported that BAL was diagnostic for pulmonary aspergillosis<br />

in none <strong>of</strong> nine patients with leukemia. Most specific<br />

diagnoses for pulmonary aspergillosis were established<br />

solely from autopsy, so BAL was reportedly useless in most<br />

cases. Moreover, the specificity <strong>of</strong> BAL for IPA is good,<br />

but it may be difficult to exactly distinguish infection from<br />

colonization.<br />

The definitive diagnosis <strong>of</strong> IPA requires histopathologic<br />

demonstration <strong>of</strong> septate acute branching hyphae with<br />

positive culture results for Aspergillus. 13 TBB is a safe and<br />

established bronchoscopic method in the histopathologic<br />

diagnosis <strong>of</strong> pulmonary infections in immunocompromised<br />

patients. As for diagnosing IPA, however, the<br />

diagnostic sensitivity <strong>of</strong> TBB has been reported to be quite<br />

low. 2 Some authors 14,15 advocate the use <strong>of</strong> invasive surgical<br />

procedures for the diagnosis and treatment <strong>of</strong> IPA. In<br />

our case 2, the clinical and radiologic progress was relatively<br />

less acute, and the immunosuppression was mild, so<br />

it might be categorized as subacute IPA. However, a<br />

Figure 4. Ultrathin bronchoscopic views <strong>of</strong> the lung cavity. A whitish intracavitary lesion caused by A<br />

flavus was seen in case 1 (left, A), and a yellowish white lesion caused by A fumigatus was seen in case<br />

2(right, B).<br />

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Figure 5. A cavity in the superior segment <strong>of</strong> the left lower lobe shows enlargement (right) compared<br />

to 2 months previously (left).<br />

precise distinction has not been made between IPA and<br />

other chronic forms <strong>of</strong> Aspergillus, such as subacute IPA<br />

or chronic necrotizing pulmonary aspergillosis. Moreover,<br />

the diagnostic yield <strong>of</strong> TBB for chronic cavitary pulmonary<br />

aspergillosis has also been reported to be quite low. 16<br />

A commercially available ultrathin bronchoscope with<br />

an external diameter <strong>of</strong> 2.8 mm has been used as a<br />

diagnostic 4–6 and therapeutic tool 17 in the peripheral<br />

airways. It can reach the peripheral area <strong>of</strong> the lung and<br />

occasionally even the visceral pleura. 18 Nevertheless, the<br />

closer the ultrathin bronchoscope is brought to the peripheral<br />

bronchi, the poorer the visibility is. S<strong>of</strong>t peripheral<br />

bronchi, which easily collapse under bronchoscopic<br />

suction, and bronchial secretions obstruct the visibility.<br />

However, a cavitary lesion in the peripheral area <strong>of</strong> the<br />

lung may be a good indication for ultrathin bronchoscopy.<br />

Once the tip <strong>of</strong> the ultrathin bronchoscope enters the<br />

cavity through a small bronchus, the range <strong>of</strong> vision<br />

becomes broad. Biopsy <strong>of</strong> a lesion with bronchoscopic<br />

visualization should result in higher diagnostic yield.<br />

Moreover, a biopsy with direct visualization using miniforceps<br />

may decrease the risks <strong>of</strong> bleeding.<br />

Visualization <strong>of</strong> intracavitary lesions during bronchoscopy<br />

in patients with pulmonary aspergillosis, mostly<br />

aspergilloma, which is characterized by mycelial growth in<br />

a preexisting lung cavity and usually has a good prognosis<br />

without any treatments, has been rarely reported. 19–21<br />

However, there may be only a limited number <strong>of</strong> cases in<br />

which the diameter <strong>of</strong> the bronchus leading to the cavity is<br />

relatively large. In our case 1, a conventional bronchoscope<br />

could reach no farther than the segmental bronchus.<br />

Our results indicate an ultrathin bronchoscope can enter a<br />

cavity more frequently than a conventional bronchoscope.<br />

In some cases, it appears that ultrathin bronchoscopy can<br />

be useful in the diagnosis <strong>of</strong> cavitating IPA. Further<br />

studies are needed to elucidate in more detail its utility for<br />

the diagnosis <strong>of</strong> IPA.<br />

References<br />

1 Reichenberger F, Habicht J, Matt P, et al. Diagnostic yield <strong>of</strong><br />

bronchoscopy in histologically proven invasive pulmonary<br />

aspergillosis. Bone Marrow Transplant 1999; 24:1195–1199<br />

2 Albelda SM, Talbot GH, Gerson SL, et al. Role <strong>of</strong> fiberoptic<br />

bronchoscopy in the diagnosis <strong>of</strong> invasive pulmonary aspergillosis<br />

in patients with acute leukemia. Am J Med 1984;<br />

76:1027–1034<br />

3 Stevens DA, Kan VL, Judson MA, et al. Practice guidelines<br />

for diseases caused by Aspergillus: Infectious Diseases Society<br />

<strong>of</strong> America. Clin Infect Dis 2000; 30:696–709<br />

4 Saka H, Oki M, Kumazawa A, et al. Diagnosis <strong>of</strong> pulmonary<br />

peripheral lesions using ultrathin bronchoscope. J Jpn Soc<br />

Bronchol 2000; 22:617–619<br />

5 Shinagawa N, Yamazaki K, Onodera Y, et al. CT-guided<br />

transbronchial biopsy using an ultrathin bronchoscope with<br />

virtual bronchoscopic navigation. <strong>Chest</strong> 2004; 125:1138–1143<br />

6 Yamamoto S, Ueno K, Imamura F, et al. Usefulness <strong>of</strong><br />

ultrathin bronchoscopy in diagnosis <strong>of</strong> lung cancer. Lung<br />

Cancer 2004; 56:43–48<br />

7 Gerson SL, Talbot GH, Hurwitz S, et al. Prolonged granulocytopenia:<br />

the major risk factor for invasive pulmonary aspergillosis<br />

in patients with acute leukemia. Ann Intern Med<br />

1984; 100:345–351<br />

8 Karam GH, Griffin FM. Invasive pulmonary aspergillosis in<br />

478 <strong>Selected</strong> <strong>Reports</strong><br />

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nonimmunocompromised, nonneutropenic hosts. Rev Infect<br />

Dis 1986; 8:357–363<br />

9 Palmer LB, Greenberg HE, Schiff MJ. Corticosteroid treatment<br />

as a risk factor for invasive aspergillosis in patients with<br />

lung disease. Thorax 1991; 46:15–20<br />

10 Denning DW, Marinus A, Cohen J, et al. An EORTC<br />

multicentre prospective survey <strong>of</strong> invasive aspergillosis in<br />

haematological patients: diagnosis and therapeutic outcome.<br />

EORTC Invasive Fungal Infections Cooperative Group. J Infect<br />

1998; 37:173–180<br />

11 Reichenberger F, Habicht JM, Gratwohl A, et al. Diagnosis<br />

and treatment <strong>of</strong> invasive pulmonary aspergillosis in neutropenic<br />

patients. Eur Respir J 2002; 19:743–755<br />

12 Saito H, Anaissie EJ, Morice RC, et al. Bronchoalveolar<br />

lavage in the diagnosis <strong>of</strong> pulmonary infiltrates in patients<br />

with acute leukemia. <strong>Chest</strong> 1988; 94:745–749<br />

13 Tablan OC, Anderson LJ, Besser R, et al. Guidelines for<br />

preventing health-care-associated pneumonia, 2003: recommendations<br />

<strong>of</strong> CDC and the Healthcare Infection Control<br />

Practices Advisory Committee. MMWR Morb Mortal Wkly<br />

Rep Recomm Rep 2004; 53:1–36<br />

14 Baron O, Guillaume B, Moreau P, et al. Aggressive surgical<br />

management in localized pulmonary mycotic and nonmycotic<br />

infections for neutropenic patients with acute leukemia:<br />

report <strong>of</strong> eighteen cases. J Thorac Cardiovasc Surg 1998;<br />

115:63–69<br />

15 Reichenberger F, Habicht J, Kaim A, et al. Lung resection for<br />

invasive pulmonary aspergillosis in neutropenic patients with<br />

hematologic diseases. Am J Respir Crit Care Med 1998;<br />

158:885–890<br />

16 Denning DW, Riniotis K, Dobrashian R, et al. Chronic<br />

cavitary and fibrosing pulmonary and pleural aspergillosis:<br />

case series, proposed nomenclature change, and review. Clin<br />

Infect Dis 2003; 37:265S–280S<br />

17 Oki M, Saka H, Kumazawa A, et al. Extraction <strong>of</strong> peripheral<br />

endobronchial foreign body using an ultrathin flexible bronchoscope.<br />

J Bronchol 2004; 11:37–39<br />

18 Oki M, Saka H, Kitagawa C, et al. Visceral pleural perforation<br />

in two cases <strong>of</strong> ultrathin bronchoscopy. <strong>Chest</strong> 2005; 127:<br />

2271–2273<br />

19 Hargis JL, Bone RC, Stewart J, et al. Intracavitary amphotericin<br />

B in the treatment <strong>of</strong> symptomatic pulmonary aspergillomas.<br />

Am J Med 1980; 68:389–394<br />

20 Smith RL, Morelli MJ, Aranda CP. Pulmonary aspergilloma<br />

diagnosed by fiberoptic bronchoscopy. <strong>Chest</strong> 1987; 92:948–<br />

949<br />

21 Rohatgi PK, Chasse RT. Endoscopic visualization <strong>of</strong> aspergilloma.<br />

Respiration 1991; 58:112–114<br />

Closure <strong>of</strong> a Bronchopleural<br />

Fistula Using Bronchoscopic<br />

Placement <strong>of</strong> an Endobronchial<br />

Valve Designed for the<br />

Treatment <strong>of</strong> Emphysema*<br />

J. Scott Ferguson, MD, FCCP; Kimberly Sprenger, BSN; and<br />

Timothy Van Natta, MD<br />

Pneumothoraces are sometimes complicated by a<br />

persistent air leak or bronchopleural fistula requiring<br />

prolonged chest tube drainage. Non-surgical<br />

treatment <strong>of</strong> persistent bronchopleural fistulas is<br />

<strong>of</strong>ten performed in patients who are poor surgical<br />

candidates, but the ideal method <strong>of</strong> closure is not<br />

known. Here we report closure <strong>of</strong> a persistent distal<br />

bronchopleural fistula using a one-way endobronchial<br />

valve designed for the treatment <strong>of</strong> emphysema.<br />

(CHEST 2006; 129:479–481)<br />

Key words: bronchial fistula; bronchoscopy; pneumothorax<br />

Abbreviations: BPF bronchopleural fistula; RML right<br />

middle lobe<br />

Pneumothoraces are sometimes complicated by a persistent<br />

air leak or bronchopleural fistula (BPF) requiring<br />

prolonged chest tube drainage. It is generally recommended<br />

that surgical treatment be undertaken when possible. However,<br />

many patients are very poor surgical candidates. In this<br />

article, we report the successful closure <strong>of</strong> a prolonged air<br />

leak with a one-way endobronchial valve originally designed<br />

for the palliative treatment <strong>of</strong> emphysema.<br />

Case Report<br />

A 63-year-old man with widely metastatic breast cancer was<br />

admitted for sudden onset <strong>of</strong> severe dyspnea 8 days after<br />

thoracoscopic placement <strong>of</strong> an indwelling cuffed pleural catheter.<br />

A large hydropneumothorax was discovered, and the indwelling<br />

catheter was connected to suction, relieving the dyspnea. A chest<br />

tube was then placed and connected to a water-seal device. A<br />

large air leak was noted with each exhalation and continued for<br />

the next 9 days. A new chest tube was placed, but the air leak<br />

continued.<br />

The etiology <strong>of</strong> the pneumothorax was not certain but was<br />

assumed to be a delayed complication <strong>of</strong> the thoracoscopy, as<br />

opposed to necrosis and breakdown <strong>of</strong> a metastatic focus <strong>of</strong> tumor.<br />

A thin-section, multidetector CT scan <strong>of</strong> the chest revealed multiple<br />

metastases, hydropneumothorax, and airspace disease <strong>of</strong> the lower<br />

lobes. No radiographic evidence <strong>of</strong> BPF was present.<br />

Surgical correction with plication <strong>of</strong> the <strong>of</strong>fending lobe was<br />

considered but judged to be risky given that the patient’s pulmonary<br />

reserve was limited due to the metastatic disease. Endoscopic<br />

therapies with glue, gel foam, and coiling were considered but were<br />

judged to have a low likelihood <strong>of</strong> success based on the endoscopist’s<br />

previous experience with these methods in other patients. Therefore,<br />

these techniques <strong>of</strong> BPF closure were not attempted in this<br />

patient.<br />

One-way endobronchial valves for the treatment <strong>of</strong> emphysema<br />

became available in the United States last year as part <strong>of</strong> a national<br />

clinical trial. 1 We thought placement <strong>of</strong> an endobronchial valve that<br />

would allow escape <strong>of</strong> air from the <strong>of</strong>fending segment or lobe, but<br />

*From Carver <strong>College</strong> <strong>of</strong> Medicine, Departments <strong>of</strong> Internal<br />

Medicine (Dr. Ferguson and Ms. Sprenger) and Thoracic and<br />

Cardiovascular Surgery (Dr. Van Natta), University <strong>of</strong> Iowa, Iowa<br />

City, IA.<br />

Dr. Ferguson, Ms. Sprenger, and Dr. Van Natta were supported in<br />

part by the Endobronchial Valve for Emphysema Palliation Trial<br />

(VENT) Trial.<br />

Manuscript received August 31, 2005; revision accepted October 1,<br />

2005.<br />

Reproduction <strong>of</strong> this article is prohibited without written permission<br />

from the <strong>American</strong> <strong>College</strong> <strong>of</strong> <strong>Chest</strong> <strong>Physicians</strong> (www.chestjournal.<br />

org/misc/reprints.shtml).<br />

Correspondence to: J. Scott Ferguson, MD, Department <strong>of</strong> Internal<br />

Medicine, C-33 GH 200, Hawkins Dr, Iowa City, IA 52242;<br />

e-mail: john-s-ferguson@uiowa.edu<br />

www.chestjournal.org CHEST / 129 /2/FEBRUARY, 2006 479<br />

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