Adjunctive corticosteroid therapy decreases lung permeability in patients with Al OS-related Pneumocystis carinii pneumonia

SILVIA G UILLEMI MD, ALLAN BELZBERG MD FRCPC FACP, LINDSAY M LAWSON MD FRCPC, MARTIN T SCHECHTER MD OBC PhD FRCPC, JULIO S G MONTANER MD FRCPC FCCP AIDS Research Program, Department of Medicine, Nuclear Medicine-Department of Laboratories, Respiratory Division, and British Columbia Centre for Excellence in HIV/A IDS, St Paul's Hospital; Departments of Health Care and Epidemiology and Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia

Despill' the unc4uivocal clinical hL•nct'il of adjunct ive curticostcroiJ use in thi s context.the ultimate mechani sm responsible for this cl'kcl is not known ( 1-()).It has been widely specu lated.however, lhal corticosteroids decrease lhc alveolar inlfammalion associated with active PCP.and this would in turn rl'duce lung pnmcabilily leading to improwd gas exchange, L'Xercisc tolerance and ullirnatcly survival (.5 .7).Although attral'live , thi s remain s an untested hypot hesis.
All 16 patients included in the sllldy had a baseline Tc-DTPA lung clearance scan performed wilhin 48 h or starting antimicrohia ls. as previously desnihed I 1 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).In hrieL an aerosol containing 92-'i MBq or l)t)mTc-DTPA in isotonic saline was generated by a radio aerosol kit (Mcdipart.Inc RNC.Illinois).ivlcdian mass diameter orthc aerosol p,1rticles was 1.8±1.65 µ111.While wearin g a nose clip.study subjects inhaled the aerosol 1<11' ,l period or :?. mi ns at normal tidal volume in an upright position through a mouth piece.Lung radioactivity was monitored by an Anger A camera during the inhalation period and for the next 7 mins.Counts were acquired with 30 s rrames with the areas or interest located over the right and left lung a., identified using sumdard sol't ware ( I Ci).Counts were plolled against time and the least squares best fit slope or the data was calculated rrom the time at which peak radioactivity was observed ( 16).Follow-up Tc-DTPA lung scan was pcrrormed using the same equi pmen t and protocol during the second week of therapy.All scans were analyzed and interpreted at once by a single experienced observer who was blinded to the p;:itient's treatment.Lung elearance half time (T{).expressed in minutes.was compared hetween groups using the Wilcoxon rank sum test.

RESULTS
A total or I (1 patients were .,tudied:six received adjunctive rnrticosteroid therapy and IO did 1101.All pati ents were amhulatory and had mild lo rnrnkrale AIDS-related PCP.All patients rc.,pondcd l'avourahly to treatment.Nearly all patients had an improvement in lung permeability between lung .scans.as dcmonstrnlcd by a prolongation in Tc-DTPA lung clearance (Fi gure I).

DISCUSSION
These results show that Tc-DTPA lung clearance is innea,ed around the time of PC P diagnosis and improves slowly over the rirst two weeks of antimicrohial treatment in patients with AIDS-related PCP.More important.our data demons trate that adjuncti ve corticosteroid., significantly decrease Tc--DTP/\ lung clearance.This lends support to the hypothesis that the hcndicial effect or corticosteroids may he related to their ability to accelerate the resolution or the underlying permeability defect associated with AIDS-related PCP.
Our data support previous reports demonstratin g an accelerated clearance or Tc-DTP A in patients with AIDS-related PCP (11)(12)(13)(14).We extend this observation hy demonstrating that Tc-DTPA lung cle,1rance rem,1ins increased during the second week or therapy.hut this was.ignificantly improved by the use or adjunctive corticosteroid therapy.
Tc-DTPA has hcen shown lo he a sensitive method lo Can Respir J Vol 2 No 1 Spring 1995 Corticosteroids in AIDS-related PCP assess lung permeability in a variety or settings, including acute exposure to cigarette smoke.respiratory distress syndrome or any process a.,.,oeiatcd with alveolar inflammation such as intrinsic allergic alveolitis (8)(9)(10).In all instances the increased Tc-DTPA clearance has been attributed to an incre,1se in lung permeability.Similarly.improvement of the underlying process has been associated \vith a consistent decrea e in Tc-DTPA lung clearance also attrihuted to an improvement in lung permeability.
A majm limitation or our study is that patients were not randomly allocated to receive or not receive corticosteroid therapy.Gi ven current recommendations for the use of corticosteroids and the prevalent hiases among treating physicians. it is reasonable lo expect that adjunctive corticosteroids were preferenti ally prcscrihed ror patients with re latively more seve re disease.Thi., i., supported hy the !'act that Tc-DTPA lung clearance tended to he raster at hascline :mmng those patients who were treated with adjunctive corticosteroids, indicating that rnrtieosteroid treated patients tended to have a greater permeability defect at baseline and therefore more severe PCP than thme treated without corticosteroids.A second limitation related to the nonrandom ized nature or the study was the lack or sta11danli1.ation of ,rntimicrob ial use.However.we are not aware of ,my data supporting the notion that different antiminohial regimens have a differential ert'eet on lung permcahility as measured by Tc-DTPA lung clearance.
We conclude that the beneficial elkct or adjunctive corticosteroi ds is at least partially attrihutablc to their ability lo reverse the perm eab ility dct'cct characteri.,tic of A IDSrelated PCP.