Yonago Acta medica 1999;42:175–178

Pulmonary Alveolar Proteinosis Treated with Oral Ambroxol Hydrochloride and Bronchoalveolar Lavage
Hisashi Suyama, Naoto Burioka, Takanori Sako, Yuji Kawasaki, Yutaka Hitsuda,
Keiji Shigeshiro* and Yukio Matsumoto
Third Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago 6830826 and *Clinic of Internal Medicine, Hakuai Hospital, Yonago 683-0853, Japan
A 59-year-old man visited our hospital in June 1997 because of cough and dyspnea atrest. He was diagnosed as pulmonary alveolar proteinosis (PAP) by bronchoalveolar
lavage (BAL) and transbronchial lung biopsy. The alveoli were distended with pinkhomogeneous material that showed staining with the periodic acid Schiff method. The
concentration of surfactant protein A in BAL fluid was significantly increased. We
treated the patient with oral ambroxol hydrochloride and therapeutic BAL. We believethat this combination of therapies is the first choice for the treatment of PAP.
Key words: ambroxol hydrochloride; bronchoalveolar lavage; flexible bronchofiberscope; pulmonary alveolar proteinosis; surfactant protein A

Pulmonary alveolar proteinosis (PAP) is characterized by the presence of copious eosinophilic, periodic acid Schiff (PAS)-positive material in the alveoli and by an excess of surfactant components (both lipids and proteins) inlung lavage. It may be present during the neonatal period or later in life. PAP is the consequence of a genetic defect involving the lungs,
such as a mutation of the surfactant protein B(SP-B) gene, or it can represent an aspect of adifferent genetic disease, such as lysinuric protein intolerance. PAP may also be associatedwith infections, malignancies, exposure todusts, or the use of certain drugs. In most cases,
however, it occurs as an isolated entity with noapparent cause, and is known as idiopathic alveolar proteinosis (Antonella et al., 1996). The
cause is likely related to either overstimulationof type II pneumocytes or an impairment of themechanism for removal of alveolar phospholipids (Cesar et al., 1995). In the alveoli of patients with PAP, the alveolar clearance of proteinaceous materials is impaired. Many investigators have reported biochemical studies ofbronchoalveolar lavage (BAL) fluid in the patients with PAP, including analyses of proteinsand phospholipids (Sahu et al., 1976; Akino etal, 1978; Onodera et al., 1983; Honda et al.,1989). Amounts of protein and phospholipid
were found to be significantly increased relative
to those in contrast to normal subjects. Surfactant protein A (SP-A) is the predominant phospholipid-associated glycoprotein in pulmonary
surfactant and is specific to the lung. The contents of SP-A in BAL fluid can be measured todiagnose PAP (Honda et al., 1993). We report acase of PAP diagnosed by an increase of SP-A
in BAL fluid, and treated by oral ambroxolhydrochloride and BAL.

Patient report
A 59-year-old Japanese man who lives in Tottori
Prefecture, Japan was admitted to our hospitalin June 1997 because of cough and dyspnea atrest. His past medical history included 2 admissions for pneumonia in 1994 and 1995. He
had smoked 20 cigarettes per day for over 30years and had been employed as a garbage manof a building for over 18 years.

Abbreviations: BAL, bronchoalveolar lavage; PAS, periodic acid Schiff; PAP, pulmonary alveolar proteinosis; SP-A, surfactant protein A; SP-B, surfactant protein B; WLL, whole lung lavage

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ment and a transbronchiallung biopsy was performedon the right B4 and B8 segments. The specimens werestained with hematoxylin
and eosin. Light microscopy of the transbronchial lungbiopsy showed distended
alveoli with a pink homogeneous material that was
PAS-positive, and slightthickening of the alveolar
walls with minimal infiltration of lymphocytes (Fig.
2a). Immunostaining for SPA of lung biopsy specimens
Fig. 1a. Computed tomogram of the chest on admission.
resulted in positive staining(Fig. 2b). No atypical lymAlthough physical examination on admis- phocytes were detected in the infiltrating cells.
sion showed respiratory distress, he complained The BAL fluid contained phospholipid and was
only of mild dyspnea. He had a non-productive sent to Sapporo Medical College, Sapporo,cough. Auscultation of the lung showed coarse Japan to measure SP-A. The concentration ofinspiratory crackles in both lung fields. There SP-A in the BAL fluid was significantly inwas mild clubbing of the nail beds. The labora- creased at 482.2 µg/mL (normal range, 1.3 totory findings showed high levels of lactic acid 5.2 µg/mL). Also the ratio of SP-A to phosdehydrogenase (421 IU/L), C-reactive protein pholipid was 3.58 µg/nmol (normal range, 0.05
(1.27 mg/dL) and carcinoembryonic antigen to 0.11 µg/nmol) (Honda et al., 1993). There(7.3 ng/mL). Sputum cultures for bacteria, fun- fore, we made a diagnosis of PAP, and treatedgi and tuberculosis were negative. His chest the patient with oral ambroxol hydrochloride
radiograph showed diffuse
bilateral interstitial reticular and alveolar densities of both lung fields.
Computed tomography ofthe chest showed diffuse,non-segmental densities ofvarious degrees, with a peripheral clear zone, primarily in the mid-lung field,
and honeycombing shadowsin the lower lung field (Fig.
1a). Analysis of arterial
blood gases showed hypoxia (arterial oxygen pressure, 54.1 mm Hg). On the
3rd day after admission, thepatient developed respira- Fig. 1b. Computed tomogram of the chest obtained after oral admintory failure. BAL was per- istration of ambroxol hydrochroloride and therapeutic bronchoalveolar
formed on the right B4 seg- lavage (BAL).
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