pulmonary alveolar proteinosis treated with …

Taiwan Crit. Care Med.2010;11:267-274Pulmonary alveolar proteinosis treated with

whole lung lavage in intensive care unit

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PULMONARY ALVEOLAR PROTEINOSIS TREATED WITH WHOLE

LUNG LAVAGE IN INTENSIVE CARE UNIT

Yao-Chang Wang1, Jau-Yeong Lu1, Wein-Shung Kuo2,Ming-Teng Chung3, Pen-Fang Yeh1

Abstract

Pulmonary alveolar proteinosis (PAP) is an unusual interstitial lung disease.The characteristic of the disease is the revealing of periodic acid Schiff (PAS) positivelipoproteinaceous material-filled alveoli on chest radiographs. The standard treatmentof PAP is to remove the lipoproteinaceous materials from the lung through thewhole lung lavage (WLL) procedure, which is mostly performed in operating roomsunder general anaesthesia. In this article, we report the case of a 53-year-old malepatient who visited to our chest outpatient clinic due to progressive shortness ofbreath for 2 months prior to being hospitalized. Chest radiographs indicated bilateralperihilar infiltrate with haziness. A high resolution computed tomography (HRCT)scan of the chest showed ground glass opacification of alveolar spaces with typicalcrazy paving pattern. A subsequent bronchoscopic lung biopsy confirmed thediagnosis of PAP. The patient underwent the WLL procedure in the intensive careunit and significant improvements have been observed on patient symptoms andchest radiographs after the treatment. A one year of follow up showed that thepatient is in stable condition. Thus, we conclude that the lung lavage procedurecan also be safely performed in the intensive care unit instead of in an operatingroom.

Key words: Pulmonary alveolar proteinosis (PAP), Whole lung lavage (WLL)

Correspondence: Dr. Jau-Yeong LuDivision of Chest Medicine, Department of Internal Medicine, Cheng Hsin General Hospital, No. 45, Cheng Hsin Street,Pai Tou District, Taipei City 112, Taiwan1

Phone: 0975-359-875; E-mail: [email protected] of Anesthesiology, Department of Critical Care2, Department of Pathology3

Introduction

Pulmonary alveolar proteinosis (PAP), alsoknown as pulmonary alveolar phospholipo-proteinosis, was first described by Rosen et alin 1958.1 It is an unusual diffuse lung diseasecharacterized by the accumulation of amorphous,periodic acid-Schiff (PAS) positive lipopro-

teinaceous material in the distal air spaces.1-3

There is little or no lung inflammation, and theunderlying architecture is preserved. The medianage at diagnosis is 39 years. The ratio of maleto female is 2.65:1.2 The clinical presentation ofpatients with PAP is generally marked by variabledegrees of dyspnea associated with concomitanthypoxemia. More than 90% of all cases of PAP

Yao-Chang Wang et al.Taiwan Crit. Care Med.2010;11:267-274

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occur as a primary (or idiopathic) disorder ofunknown etiology, not associated with any fa-miliar predisposition. Occasionally, the conditionis secondary to other conditions or inhalation ofchemicals. The typical routine laboratory is usuallynormal. The serum level of LDH is frequentlyslightly elevated. Asymmetric unilateral or bi-lateral patchy consolidation is found on chestradiography. The appearances on the HRCT scanof the thorax often suggest the diagnosis, andit should be confirmed by examination ofbronchoalveolar lavage fluid or biopsy specimens.

In a retrospective analysis of 343 cases, thefive-year survival rate was about 75%2 of thedeaths in that study, 72% were directly due torespiratory failure from PAP and 20% were dueto PAP with uncontrolled infection. Because ofthe unknown pathogenesis, WLL remains themost effective form of treatment, and it is a safertechnique in experienced hands. However, thesevere hypoxemia in PAP patients and the dif-ficulty of the technique have limited its appli-

cation to medical centers. Now, we would liketo report our experience in treating a 53-year-old man with PAP using the lung lavage techniquein the ICU. He has experienced clinical andfunctional improvement persistently for morethan one year.

Case Report

A 53-year-old man who was a punchingmachine worker and heavy cigarette smoker of30 years visited our outpatient clinic due toprogressive shortness of breath for 2 months. Hehas had a history of allergic rhinitis for 10 years.Physically, he was mildly tachypneic but was notcyanotic. Clubbing fingers were also noted. Therewere diffused crackles over both lungs. His chestradiograph revealed bilateral perihilar infiltrateand haziness with normal heart size (Fig. 1). Ahigh resolution computed tomography (HRCT)scan showed ground glass opacification of al-veolar spaces and thickening of the interlobular

Fig. 1. Chest radiograph on presentation showing bilateral perihilar alveolar infiltrates and normalsize of heart.



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and intralobular septa with no architecturaldistortion, giving the typical “crazy paving”appearance of alveolar proteinosis (Fig. 2). Theair space opacification was demarcated fromsurrounding normal lung tissue creating a “geo-graphic” pattern. No mediastinal or hilar lym-phadenopathy was noted. Echocardiogram re-vealed normal heart function.

His PaO2 at the time of hospital admissionwas 87.9 mmHg and PCO2 was 28.7mmHg inbreathing room air. A pulmonary function testrevealed a TLC of 89% and a DLCO of 48%predicted. Other laboratory data revealed slightelevation of LDH: 220 IU/L. PAP was diagnosedvia transbronchoscopic lung biopsy. Micro-scopically, the section showed that the alveolarsepta were only slightly thickened and the al-veolar architecture was preserved. The alveoliwere filled with a pink homogeneous material

that was PAS positive. He was scheduled forWLL.

The procedure was performed in the ICUwith standard monitoring of heart rate, respira-tory rate, blood pressure and oxygen saturation.The patient was sedated with intravenous Propofoland muscle relaxant. A double lumen endotra-cheal tube was inserted by anesthetist. Then, bothlungs were ventilated at 1.0 FiO2 with a mechani-cal ventilator for 15 min to wash out the nitrogen.The right lung was gradually filled with normalsaline warmed to 37°C until a volume equal tothe calculated functional residual capacity (FRC)of the lung. Thereafter, aliquots of 500 ml wererun in and out . The effluent fluid was drainedinto a bottle by gravitational flow. The returninglavage fluid was initially milky (Fig. 3) andgradually became clearer. We also applied bothmanual percussion and portable ultrasonic vibra-

Fig. 2. HRCT shows ground glass opacification of alveolar spaces and thickening of the interlobularand intralobular septa with no architectural distention giving the typical crazy paving appearanceof alveolar proteinosis.


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tors on the patient’s chest wall alternately forcontinuous vibration during lavage. Periodictransbronchoscopic suction with fiberoptic bron-choscope by pulmonologist and periodic arterialblood gas was collected in case of SaO2 dropping.

One week after the first lavage, bron-choalveolar lavage on the left lung was performedin the same manner. Follow up chest radiographrevealed almost complete clearing of alveolarinfiltrate (Fig. 4) and HRCT revealed much re-solved ground glass opacity and thickened in-terlobular and intralobular septa (Fig. 5). Furtherfollow up chest radiographs revealed muchimprovement compared with the one taken justafter lavage. The patient’s clinical status has beenstable for more than one year with regular followup.

Discussion

Before therapeutic bronchoalveolar lavagewas introduced by Ramirez and his colleaguesin 1965,4 initial therapies were empirical. Theseincluded corticosteroids, heparin, antibiotics,trypsin, and acetylcysteine,2 but none was effective.

In July 1964, Ramirez proceeded with a trial ofWLL, under local anesthesia, using up to 3 Lof saline with added heparin or acetylcysteine.4

The procedure provided significant improvementsin symptoms and pulmonary function. Over thenext four decades, this original procedure hasbeen repeatedly improved through the routine useof general anesthesia,4,5 increased lavage volumes,6 the use of saline alone,7,8 the addition ofconcomitant chest percussion,7,9 and the success-ful completion of bilateral sequential WLL in thesame treatment session.10

Therapeutic bronchoalveolar lavage can beperformed by several techniques: segmentalirrigation through a catheter,11 WLL through acatheter,6 catheter lobal lavage,12 or lobar lavageby fiberoptic bronchoscopy (FOB).13

Kariman et al reported that 24% of PAPpatients had either spontaneous remission orwere free of symptoms despite the presence ofroentgenographic abnormalities.14 In general, thesepatients were less symptomatic and the pulmo-nary functioned and their gas exchange measure-ments revealed only a mild to moderate arterialhypoxemia.

Fig. 3. The milky lavage fluid collected from lung lavage.



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Fig. 4. Radiograph taken after bilateral lung lavage showing almost complete clearing of alveolarinfiltrate.

Fig. 5. HRCT scan after bilateral lungs lavage shows decrease in both the patchy lung opacities andthickened interlobular and intralobular septa.


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WLL is now considered the most effectiveform of treatment for PAP. The main indicationfor WLL is limitation in daily activities due todyspnea. Specific indications for lung lavageinclude a definitive histologic diagnosis and thatpatients with a PaO2 of less than 70 mm Hg ora P(A-a)O2 of more than 40 mmHg.14

Some centers use manual chest percussionduring lavage to improve the removal of intra-alveolar proteinaceous substances. Hammon etal reported that optical density of recovered lavagefluid for manual percussion was significantlysuperior to mechanical percussion or no percus-sion and increased the therapeutic results ofbroncho- pulmonary lavage for PAP.9

The major adverse effect from WLL ishypoxemia which can be improved by ventilationwith a high inspired oxygen concentration.5,15,16

Arterial oxygenation improves during the fillingphase due to the increase in alveolar pressure,regional pulmonary capillaries are collapsed andblood flow ceases. Pulmonary blood flow isshifted to the contralateral non-liquid-filledventilated lung causing an increase of PaO2.Emptying of the lung causes a decrease in airwaypressure and perfusion of the proteniaceous materialfilled alveoli creates a shunt in the lung under-going treatment and hence a fall in PaO2.16

Hamodynamic changes occur with single lungventilation15,17 but invasive monitoring is unnec-essary in most cases.18

The process of WLL is slow (2-4 h) andrequires an experienced team and postoperativefacilities. The key components to ensuring safetyis an anesthetist who is very skillful in theplacement of the double lumen endotracheal tubeand is capable of frequently checking and ad-justing the tube during the lavage procedure.Avoid leakage of the lavage fluid into thecontralateral ventilated lung. Slow instillation oflarge volumes of fluid to prevent barotrauma.14,19

Many articles14,19,20 have reported no majorcomplications after therapeutic lavage.

Multiple segmental or lobar lavage byfibreoptic bronchoscopy (FOB) is a possiblealternative to WLL13,21 Cheng and colleagues

reported that lobar therapeutic lavage performedthrough FOB is useful for patients with PAP forwhom lavage of an entire lung with generalanesthesia may be hazardous, and for patientswith less advanced disease from whose lungproteinaceous substances can be removed witha small volume of lavage fluid. The yield bythis method is small with limited volume oflavage fluid and multiple lavages are required.

After WLL, patients feel dramatically betterwith improvement in exertional dyspnea. Litera-ture revealed the clinical course is variable afterWLL. 30-40% of patients require only one la-vage,19,22 while others require repeated lung lavagesat intervals of 6 to 24 months.

WLL is now considered the treatment ofchoice for patients with PAP. An experiencedlavage team including nursing, anesthesiology,respiratory therapy, and pulmonary medicine isessential in performing this procedure. We per-formed WLL safely and efficiently to our PAPpatient in the intensive care unit without theexpense and difficulty of scheduling an operatingroom.

References

01. Rosen SH, Castleman B, Liebow AA. Pulmonaryalveolar proteinosis. N Engl J Med 1958;258:1123-1142.

02. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis:Progress in the first 44 years. Am J Respir Crit CareMed 2002;166:215-235.

03. Trapnell BC, Whitsett JA, Nakata K. Pulmonaryalveolar proteinosis. N Engl J Med 2003;349:2527-2539. Review

04. Ramirez J, Kieffer RF Jr, Ball WC Jr. Bronchop-ulmonary lavage in man. Ann Intern Med 1965;63:819-828.

05. Wasserman K, Blank N, Fletcher G. Lung lavage(alveolar washing) in alveolar proteinosis. Am J Med1968;44:611-617.

06. Ramirez J.Pulmonary alveolar proteinosis. Treatmentby massive bronchopulmonary lavage. Arch InternMed 1967;119:147-156.

07. Kao D, Wasserman K, Costley D, Benfield JR. Advancesin the treatment of pulmonary alveolar proteinosis.Am Rev Respir Dis 1975;111:361-363.

08. Sunderland WA, Klein RL. Heparin absorption during



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heparin-saline lung lavage in a patient with pulmo-nary alveolar proteinosis. Chest 1973;63:1033-1034.

09. Hammon WE, McCaffree DR, Cucchiara AJ. Acomparison of manual to mechanical chest percussionfor clearance of alveolar material in patients withpulmonary alveolar proteinosis (phospholipidosis).Chest 1993;103:1409-1412.

10. Shah PL, Hansell D, Lawson PR, Reid KB, MorganC. Pulmonary alveolar proteinosis: clinical aspectsand current concepts on pathogenesis. Thorax 2000;55:67-77.

11. Mclaughlin JS, Ramirez J .Pulmonary alveolar pro-teinosis. Treatment by pulmonary segmental flooding.Am Rev Respir Dis 1964;89:745-752.

12. Harris JO, Castle JR, Swenson EW, Block AJ. Lobarlavage. Therapeutic benefit in pulmonary alveolarfilling disorders. Chest 1974;65:655-659.

13. Brach BB, Harrell JH, Moser KM. Alveolar proteinosis.Lobar lavage by fiberoptic bronchoscopic technique.Chest 1976;69:224-227.

14. Kariman K, Kylstra JA, Spock A Pulmonary alveolarproteinosis. Prospective clinical experience in 23patients for 15 years. Lung 1984;162:223-231.

15. Rogers RM, Szidon JP, Shelburne J, Neigh JL, ShumanJF, Tantum KR. Hemodynamic response of thepulmonary circulation to bronchopulmonary lavagein man. N Engl J Med 1972;286:1230-1243.

16. Smith JD, Millen JE, Safar P, Robin ED. Intrathoracic

pressure, pulmonary vascular pressures and gas exchangeduring pulmonary lavage. Anesthesiology 1970;33:401-405.

17. Aguinaga MA, Santos P, Renes E, Alvaro PF, LorenteJA, Maudes A, Diaz RR, Landin L, Liste D. He-modynamic changes during whole bronchoalveolarlavage in two cases of pulmonary alveolar proteinosis.Intensive Care Med 1991;17:421-423.

18. Hemstad JR, Spiess BD, Marchioro TL, Raghu G.Pulmonary artery and noninvasive hemodynamicsduring lung lavage in primary alveolar proteinosis.Chest 1994;105:1605-1608.

19. Prakash UB, Barham SS, Carpenter HA, Dines DE,Marsh HM. Pulmonary alveolar phospholipoproteinosis:experience with 34 cases and a review. Mayo ClinProc 1987;62:499-518.

20. Du Bois RM, McAllister WA, Branthwaite MA. Alveolarproteinosis: diagnosis and treatment over a 10-yearperiod. Thorax 1983;38:360-363

21. Cheng SL, Chang HT, Lau HP, Lee LN, Yang PC.Pulmonary alveolar proteinosis: treatment by bron-chofiberscopic lobar lavage. Chest 2002;122:1123-1124.

22. Rogers RM, Levin DC, Gray BA, Moseley LW Jr.Physiologic effects of bronchopulmonary lavage inalveolar proteinosis. Am Rev Respir Dis 1978;118:255-264.


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