Pulmonary alveolar proteinosis(45 mg/day) and therapeutic BAL. BAL was performed weekly with 100 to
150 mL of saline instilled
through a fiberoptic bronchoscope into a segmental
bronchus under local anesthesia. The recovered lavage fluid was initiallymilky, and the lavage wasrepeated until the fluid became clear. After 3 seriesof therapeutic lavages, hisradiographic infiltrates
have cleared significantly(Fig. 1b). He is now living
and well 2 years following
our treatment with no evidence of recurrence of thedisease.

Fig. 2a. Photomicrograph of lung biopsy. Alveolar spaces are filled withdense, periodic acid Schiff (PAS)-positive and proteinaceous material.
Alveolar septa are thin throughout the section. PAS stain, × 400.

consists of lipid bilayer membranes separated
by amorphous proteinaceous material containDiscussion
ing phospholipids and proteins similar to surfactant or one of its components. The lung surPAP is characterized by the deposition of pro- factant system is a mixture of phospholipids
teinaceous material in air spaces, originally de- and protein synthesized and secreted in the alscribed in 1958 (Roen et al., 1958). Associated veolar spaces primarily by type II pneumocytes.
conditions include immunocompromised states, Its main function is the reduction of surface tenwhich suggests that malfunction of alveolar sion to insure stability of alveolar units. Surmacrophages allow for the accumulation of ab- factant is also thought to be involved in mucus
normal intra-alveolar material. This material transport and to interact with the pulmonary
defense system (Luisetti etal., 1987). SP-A is a majorhydrophilic (28 to 36 kDa)
glycoprotein of pulmonary
surfactant and is specificfor pulmonary surfactant,synthesized by type II cells
and secreted into the alveolar space. An immunohistochemical study using apolyclonal antibody to surfactant-specific apoprotein
has demonstrated that SPA is a useful immunohistochemical marker for thediagnosis of PAP (Honda etFig. 2b. Immunostaining for surfactant protein A (SP-A) of lung biopsy al., 1993). In our case, theconcentration of SP-A inspecimens shows positivity, × 100.
177

H. Suyama et al.

BAL fluid was significantly higher, confirming
the diagnosis of PAP.
The established treatment of choice for PAP
is therapeutic whole lung lavage (WLL), performed under general anesthesia, although thismethod may be associated with severe hypoxia.
After such WLL, migration of alveolar macrophages increases to supernormal levels, andsubsequent clinical relapse is associated with adecreased level of migration. These results support the conclusion of a previous study that theabnormal alveolar macrophage function in PAP
is an acquired defect (Robert et al., 1989).
Problems with WLL include hypoxia, flooding of the contralateral lung, ipsilateral hydrothorax, airway trauma, hypothermia and electrolyte disequilibrium, and thus WLL requires atrained and experienced staff of physicians andnurses (Rodi et al., 1995). So this techniquemust be reserved for clinically progressive
forms of the disease and for experienced hands(Diaz et al., 1984). In our patient, after treatment with oral ambroxol hydrochloride andtherapeutic BAL the radiographic infiltrates
have cleared.
The main pharmacodynamic effects ofambroxol hydrochloride are surfactant stimulation, mucokinetic activity and some secretagogue activity (Karl, 1987). The lung surfactant system is a mixture of phospholipids andprotein synthesized and secreted in the alveolar
spaces primarily by type II pneumocytes. So
type II pneumocyte stimulation with ambroxolhydrochloride can lead to chemico-physical andfunctional changes in alveolar macrophages,
probably through an increase in surfactant
secretion and uptake (Luisetti et al., 1987).
Thus, we propose that oral ambroxol hydrochloride and therapeutic BAL should be thefirst choice in treating PAP.

Acknowledgments: The authors wish to thank Dr.
Masanori Shiratori, Third Department of Internal
Medicine, Sapporo Medical College, Sapporo, Japanfor measurement of SP-A.

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(Received April 20, Accepted June 4, 1999)

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