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Genitourin Med 1995;71:280-285
Open lung biopsy for investigation of acuterespiratory episodes
in patients with HIVinfection and AIDS
Robert F Miller, Wilfred B Pugsley, Meryl H Griffiths
AbstractBackground-Open lung biopsy (OLB) israrely necessary for
investigation of HIVpositive patients with acute
respiratoryepisodes because of the high yield fromfibreoptic
bronchoscopy with bron-choalveolar lavage (BAL).Methods-A
retrospective review of OLBin HIV positive patients admitted to
aspecialist inpatient unit with acute respi-ratory symptoms was
carried out in orderto define clinical indications,
diagnosticyield, impact on management, complica-tions and
outcome.Results-OLB was performed in 23patients; 21 had undergone
one or morebronchoscopies with BAL (5 also hadnegative results from
transbronchialbiopsy). Indications for OLB were:Group A, 15
patients thought clinically tohave pneumocystis pneumonia but
notresponding to treatment; Group B, 4patients with focal chest
radiographicabnormalities; Group C, 4 patients withdiffuse
radiographic abnormalities andmiscellaneous conditions.
PreoperativePaO, (on air) ranged from 4*4 to 14*5(mean = 9.5) kPa.
The results of OLBwere in Group A 5 patients had non spe-cific
interstitial pneumonitis (NIP), 1 alsohad Kaposi's sarcoma, 4 had
pneumocys-tis pneumonia (1 also had bronchiolitisobliterans
organising pneumonia[BOOP]), 3 had Kaposi's sarcoma and 1had BOOP
and emphysema, 1 had pul-monary infarction and no infection and
1had normal lung tissue. In Group B diag-noses were NIP, B cell
lymphoma, occultalveolar haemorrhage and Pseudomonasaeruginosa
pneumonia with BOOP; InGroup C 2 patients had NIP and 2
hadpneumocystis pneumonia (1 also hadcytomegalovirus pneumonitis).
Allpatients survived surgery and nonerequired mechanical
ventilation. OLBresults significantly affected manage-ment; in
Group A inappropriate treat-ment was discontinued in 11
patientsfound not to have pneumocystis pneumo-nia, and alternative
therapy was begun inthe 4 with pneumocystis and in Groups Band C 6
patients began specific therapy;unnecessary therapy was avoided in
oneand antimicrobial treatment was modi-fied in
one.Conclusions-Open lung biopsy in HIVpositive patients with focal
and diffuseradiographic abnormalities has a high
diagnostic yield and low morbidity. Thisinvestigation should be
considered inthose with acute respiratory episodes andnegative
results from bronchoscopicinvestigations or who have
contra-indica-tions to this procedure.
(Genitourin Med 1995;71:280-285)
Keywords: HIV; AIDS; lung biopsy
IntroductionBefore the onset of the AIDS pandemic openlung
biopsy was well established as a diagnos-tic tool for investigation
of immunosup-pressed patients with diffuse or focalpulmonary
infiltrates. 1-3 Early in the AIDSpandemic open lung biopsy was
also fre-quently performed in order to evaluate respi-ratory
symptoms.4 Subsequently the perceivedpoor prognosis of patients
undergoing biopsy,together with the realisation that diagnosiscould
frequently be made by fibreoptic bron-choscopy with bronchoalveolar
lavage with orwithout transbronchial biopsy5-8 meant thatopen lung
biopsy was rarely carried out.
Despite the high yield from bronchoalveo-lar lavage and
transbronchial biopsy occasion-ally HIV positive patients with
symptoms andsigns of lower respiratory tract disease havenegative
results from these investigations andopen lung biopsy is necessary
to provide adiagnosis and enable specific treatment to begiven. In
this study we describe the clinicalindications, diagnostic yield
and impact onmanagement, complications and outcome ofopen lung
biopsy in HIV positive patients whohad acute respiratory episodes,
many ofwhom had negative bronchoscopic investiga-tions.
MethodsBetween October 1987 and March 1994 754HIV-1 antibody
positive patients were admit-ted to a specialist inpatient unit for
investiga-tion of acute respiratory episodes and wereunder the care
of a respiratory physician.During this period 23 HIV antibody
positivepatients underwent open lung biopsy. In eachcase we
recorded the clinical indications forbiopsy, the type and number of
any investiga-tions performed and treatment given beforebiopsy,
arterial blood gases (on air), the diag-nosis obtained and impact
on management,and complications arising from open lungbiopsy.
Department ofMedicineR F MillerDepartment
ofHistopathology,University CollegeLondon MedicalSchoolM H
GriffithsDepartment ofCardiothoracicSurgery, MiddlesexHospital,
LondonW1N 8AA, UKW B PugsleyAddress correspondence to:Dr R F
Miller, Departrnentof Medicine, UCLMS, FirstFloor Cross
Piece,Middlesex Hospital, LondonW1N 8AA, UK.Accepted for
publication9 June 1995
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Open lung biopsy for investigation of acute respiratory episodes
in patients with HIV infection andAIDS
In those who underwent fiberoptic bron-choscopy before open lung
biopsy the tech-nique was performed as previouslydescribed,79 and
bronchoalveolar lavage fluidroutinely stained and cultured for
bacteria,fungi, mycobacteria and viruses. Trans-bronchial biopsy
specimens were taken with-out fluoroscopic control; four or
morespecimens being obtained on each occasion.Biopsies were stained
and cultured as forbronchoalveolar lavage fluid.79Twenty two
patients were male (21 were
homosexual Caucasians and one was a hetero-sexual African) and
the one female was a het-erosexual Caucasian. Their ages ranged
from24 to 56 (mean 42.5) years. All had normalrenal function,
platelet count and clottingscreen. Open lung biopsy was
performedusing the technique described by Venn et al.'0In summary
surgery was performed via ananterolateral mini-thoracotomy, on the
right ifthere was bilateral symmetrical disease radi-ographically,
otherwise on the side of maxi-mum radiographic abnormality.
Arepresentative portion of abnormal lung wastaken. A chest drain
was routinely left in placefollowing closure, placed on 2kPa
suction andremoved at 24 to 48 hours. Each sample oflung tissue was
split and part was processedfor histology, the remainder was
cultured toidentify bacteria, fungi, mycobacteria andviruses.
ResultsThe clinical indications for open lung biopsywere; Group
A, 15 patients who were thoughtclinically to have Pneumocystis
carinii pneumo-nia. All had presented with typical symptoms
Investgations, treatment and diagnosis in patients undergoing
open lung biopsy
Negative investigations Treatment prior to PaO2Group/No prior to
open lung biopsy open lung biopsy (kPa) Final diagnosis
Group A1 BAL (x 2) IV co-trimoxazole 8-7 Normal lung2 BAL + TBB
(x 2) IV pentamidine 11-2 Kaposi's sarcoma3 BAL (x 2) Neb
pentamidine 10-1 BOOP + emphysema4 IS, BAL, BAL + TBB IV
co-trimoxazole 9.5 Granulomatous PCP5 IS (x 2), BAL (x 3) Neb
pentamidine 13-9 Granulomatous PCP6 IS, BAL Neb pentamidine 8-0 PCP
+ BOOP7 IS, BAL (x 3) IV co-trimoxazole 9.9 NIP8 IS, BAL (x 2) Neb
pentamidine 9.1 Granulomatous PCP9 BAL IV co-trimoxazole 8-7
Kaposi's sarcoma10 BAL + TBB IV co-trimoxazole 4-4 NIP11 BAL IV
co-trimoxazole 11-4 NIP12 BAL (x 2) IV co-trimoxazole 6-0 NIP +
Kaposi's sarcoma13 BAL (x 2) IV pentamidine 9 9 Pulmonary
infarction14 BAL IV co-trimoxazole 9.9 Kaposi's sarcoma15 BAL IV
co-trimoxazole 6-7 NIP
Group B16 BAL - 10-7 Non-Hodgkin's
lymphoma17 BAL - 10-3 Occult alveolar
haemorrhage18 BAL, BAL + TBB - 14-5 NIP19 BAL (x 2) IV
cefuroxime 11.6 Pseudomonas aeruginosa
pneumonia + BOOP
Group C20 BAL + TBB - ND NIP21 BAL - 91 NIP22 NIL IV
co-trimoxazole 6-3 PCP + CMV
pneumonitis23 NIL IV pentamidine 8-9 Granulomatous PCP
BAL = Bronchoalveolar lavage, TBB = Transbronchial biopsy, IS =
Induced sputum, ND =not done, BOOP = Bronchiolitis obliterans
organizing pneumonia, NIP = Non specific intersti-tial pneumonitis,
PCP = Pneumocystis carinii pneumonia, CMV = cytomegalovirus, Neb
=Nebulised, IV = Intravenous.
of non-productive cough, increasing exer-tional dyspnoea and
fever." Chest radi-ographs were abnormal showing diffuseinfiltrates
ranging in severity from subtle peri-hilar changes to more marked
bilateral inter-stitial shadowing; patients were variablyhypoxic.
CD4 lymphocyte cell counts in thesepatients ranged from 10 to 260
(median60)/mm.3 Despite specific anti-pneumocystistherapy, patients
were deteriorating withworsening dyspnoea, falling arterial
oxygentensions (PaO2), and many had increasingchest radiographic
abnormalities (table);Group B, four patients who had fever andfocal
radiographic abnormalities. A diagnosisof non Hodgkin's lymphoma
had been made,following lymph node and bone marrowbiopsy, six
months previously in patient 17.Patient 19 failed to respond to IV
cefuroximefor an Hemophilus influenzae infection diag-nosed at
bronchoalveolar lavage; Group C,four patients with specific
clinical problems.Patient 20 had extensive cutaneous
Kaposi'ssarcoma. He presented with dyspnoea and achest radiograph
showed diffuse bilateralinterstitial infiltrates. He was thought
clini-cally to have pulmonary Kaposi's sarcoma, forwhich
chemotherapy was planned. Patient 21had no AIDS defining illness, a
CD4 count of440 (normal 350-2200)/mm3 and a lympho-cytic
bronchoalveolar lavage sample, havingpresented with 12 weeks
progressive dyspnoeaand diffuse bilateral radiographic
infiltrates.He was thought clinically not to have pneu-mocystis
pneumonia, but sarcoidosis or a lym-phoproliferative disorder were
suggested bythe bronchoalveolar lavage findings. Patient22, a
Caucasian female had presented witha severe pneumonia and was
treated forpresumed pneumocystis pneumonia with IVco-trimoxazole
and methylprednisolone.Mechanical ventilation was required
initially.Following an initial recovery, with improve-ment in PaO2
and extubation, there was sub-sequent deterioration with worsening
hypoxiaand radiographic abnormalities. The finalpatient (23)
presented with a pneumothorax,thus bronchoscopy was
contra-indicated. Thechest radiograph showed in addition,
bilateralapical bullae and diffuse interstitial shadow-ing.
Intercostal tube drainage of the pneu-mothorax was unsuccessful
because ofpersistent air leak through the bullae.
Surgicalbullectomy and pleuradesis were carried outtogether with
open lung biopsy.
Results of investigations performed withnegative results and
treatment received beforeopen lung biopsy, arterial blood gases
imme-diately before biopsy and the diagnosis pro-vided by
histological and microbiologicalanalysis of lung tissue are shown
in the table. Itmay be noted that no patient was mechani-cally
ventilated at the time of biopsy and onlypatients 10, 12, 15 and 22
had receivedsteroids.Open lung biopsy provided diagnostic his-
tological material in all patients. The results ofopen lung
biopsy had a significant impact onmanagement. In Group A in the 1 1
patientswithout Pneumocystis carinii pneumonia
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unnecessary and potentially toxic treatmentwas stopped and in
addition the four patientswith pulmonary Kaposi's sarcoma
(includingthe one who also had non specific
interstitialpneumonitis) began chemotherapy with vin-cristine and
bleomycin, the patient with bron-chiolitis obliterans organising
pneumonia(BOOP) and paraseptal emphysema beganprednisolone, as did
the five patients with nonspecific interstitial pneumonitis. Three
of thefour patients with P carinii pneumonia hadbeen treated with
nebulised pentamidine.This therapy was stopped and IV
co-trimoxa-zole started in two patients (the third, whowas allergic
to co-trimoxazole, was given IVpentamidine). In the fourth patient,
who wasalready receiving IV co-trimoxazole, therapywas continued
unchanged. In Group Bpatient 16 with non Hodgkin's lymphomabegan
chemotherapy, patient 17 with occultalveolar haemorrhage avoided
antibiotics,
patient 18 with non specific interstitial pneu-monitis began
prednisolone and the patientwith Pseudomonas aeruginosa and BOOP
dis-continued cefuroxime and began ceftazidime.In Group C patient
20 avoided chemotherapyand instead received corticosteroids.
Thistherapy was also given to patient 21. Inpatient 22 IV
ganciclovir was added as treat-ment for cytomegalovirus pneumonitis
andco-trimoxazole continued for the confirmeddiagnosis of
pneumocystis pneumonia.Patient 23 was given IV pentamidine
(beingallergic to co-trimoxazole).
All patients survived open lung biopsy anddespite some patients
being profoundlyhypoxaemic none required post-operativemechanical
ventilation. Lower respiratorytract infection requiring
physiotherapy andantibiotics occurred post operatively in
twopatients, one ofwhom also had a persistent airleak and so the
chest drain was left in place,
4*
la
..:::...
c,1..:
b
lc ld
(a) Chest radiograph ofPatient 4: Diagnosis = Granulomatous
Pneumocystis carinii pneumonia. The arrow indicates thesite of
biopsy. (b) Chest radiograph ofPatient 14: Diagnosis = Pulmonary
Kaposi's sarcoma. The arrow indicates the siteof biopsy. (c) Chest
radiograph ofPatient 15: Diagnosis = Non specific Interstitial
Pneumonitis. The arrow indicates thesite of biopsy. (d) Chest
radiograph ofPatient 21: Diagnosis = Non specific Interstitial
Pneumonitis. The arrow indicatesthe site of biopsy.
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Open lung biopsy for investigation of acute respiratory episodes
in patients with HIV infection andAIDS
on suction, for 72 hours. Two other patientshad superficial
wound infections not requiringwound toilet but responding to
antibiotics.None of the patients with postoperative infec-tions had
received steroids. Subcutaneousemphysema or hydrothorax did not
occur inany patient. All but two patients were eventu-ally
discharged from hospital; patients 12 and13 died 42 and 69 days
respectively afterbiopsy, from the effects of progressive
HIVdisease. Examples of chest radiographicabnormalities and the
site of open lung biopsyare shown in the figure.
DiscussionWe have previously undertaken a prospectivestudy
comparing the value of transbronchialbiopsy and bronchoalveolar
lavage in the diag-nosis of pulmonary disease in HIV
infectedindividuals with respiratory episodes.7 Wefound that
bronchoalveolar alveolar lavagewas superior to transbronchial
biopsy fordiagnosis of P carinii pneumonia (90 vs
56%)cytomegalovirus infection (100 vs 33%) andother pathogens. The
diagnosis of pulmonaryKaposi's sarcoma was not made by
eitherbronchoalveolar lavage or transbronchialbiopsy. In no case
was the diagnosis missed bylavage but made by transbronchial
biopsy. Wefound a complication rate of 22% in thoseinvestigated
with transbronchial biopsy,including pneumothorax and profuse
haemor-rhage (fatal in one patient); complicationswere especially
likely in those with P cariniipneumonia. In contrast there were no
signifi-cant complications in patients investigatedwith lavage
alone.7 On the basis of this studyand data from others,5 8 we
perceived nocost/benefit advantage in continuing to carryout
transbronchial biopsies in our patientsand so stopped doing them at
the end of1989.
In this study we found that open lungbiopsy produced a specific
diagnosis in 22patients, (a yield of 95%), with acute respira-tory
episodes and diffuse or focal radiographicabnormalities, most of
whom had negativebronchoscopic investigations. These resultsare in
keeping with other studies in patientsimmunosuppressed by HIV
infection4 or byother causes,'-3 with reported yield in thosewith
diffuse radiographic infiltrates ofbetween 83 and 95%, and up to
71% in thosewith focal infiltrates.' 4
In a study from New York by Fitzgerald etal, 42 HIV positive
patients underwent openlung biopsy, 29 had previously
undergonefibreoptic bronchoscopy and bronchoalveolarlavage (18 had
also undergone transbronchialbiopsy) with negative results, four
werethought clinically to be too ill for bron-choscopy or had
abnormal coagulationresults, and nine patients were
deterioratingdespite specific treatment for bronchoscopi-cally
diagnosed disease. Overall the diagnosticyield was 95%, in those
with negative bron-choscopic investigations the commonest
diag-noses were Pneumocystis carinii pneumonia innine patients,
Kaposi's sarcoma in seven,
interstitial fibrosis without infection in fiveand Mycobacterium
tuberculosis in two patients;a specific diagnosis was obtained in
all fourwho had not undergone bronchoscopy,including Kaposi's
sarcoma in one case, butin those deteriorating despite a
confirmeddiagnosis, new diagnostic information requir-ing a change
of treatment was obtained inonly two patients.4
In our study the finding of Kaposi's sar-coma at open lung
biopsy in four patients withdiffuse radiographic infiltrates
thought clini-cally to have P carinii pneumonia was not sur-prising
as pulmonary Kaposi's sarcoma hasbeen described mimicking this
condition.'2"3Parenchymal lung involvement by Kaposi'ssarcoma may
also occur even if tracheobron-chial disease is not evident at
bronchoscopy.'2The diagnosis of lung parenchymal Kaposi'ssarcoma
may be missed by transbronchialbiopsy. This may be due to the
patchy natureof parenchymal infiltration, together with thefact
that lesions rarely show cytological fea-tures of malignancy and
biopsy specimencrush artefact, haemorrhage and granulationtissue
appearances may all mimic Kaposi'ssarcoma.'2 14 In one study, where
trans-bronchial biopsy was routinely performed fordiagnosis, the
yield from this technique forpulmonary Kaposi's sarcoma was only
23%.'4The diagnosis of Kaposi's sarcoma wasmissed by transbronchial
biopsy in the patientin our study, and in seven of the eight
patientswith this diagnosis in Fitzgerald's study.4These data
suggest that the need for openlung biopsy would not have been
obviated inour patients with pulmonary Kaposi's sar-coma even if we
had routinely performedtransbronchial biopsy at bronchoscopy.Occult
alveolar haemorrhage, found in one ofour patients at open lung
biopsy was oncethought to be specific for the diagnosis of
pul-monary Kaposi's sarcoma,"3 but is now knownto be a non specific
finding in HIV positivepatients with respiratory symptoms,'5 and
isalso seen in P carinii pneumonia, bacterial andmycobacterial
infection.
Four of our patients received nebulisedpentamidine. This therapy
was formerly veryfashionable for the treatment of mild to mod-erate
severity P carinii pneumonia.'6 It is nowknown that patients
receiving this form oftherapy take longer to respond to
treatment,compared with patients treated with IV co-trimoxazole;
arterial blood gases and chestradiographs may worsen during the
first10-14 days of treatment, before eventualrecovery.'6 There is
also a higher rate of earlyrelapse following successful treatment
and astreatment is not systemically delivered it maynot suppress
extra pulmonary pneumocysto-sis. For these reasons nebulised
pentamidineis rarely, if ever, used now for treatment. Ifwehad used
IV co-trimoxazole or pentamidineinstead of nebulised pentamidine in
thesepatients then we might have anticipatedrecovery, without need
for open lung biopsy,in the three who had P carinii pneumonia.The
histological variant form granulomatousP pneumonia, diagnosed in
four patients in
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our study is well described in HIV positivepatients. The
diagnosis cannot be made byconventional histochemical staining of
bron-choalveolar lavage fluid as the organisms donot lie within
alveoli, instead they are "walledoff' by palisades of histiocytes.
The granulo-matous response is patchy and transbronchialbiopsy may
also be negative.'7 Molecular bio-logical techniques used to
identify P carinii byDNA amplification using the polymerasechain
reaction with P carinii-specific oligonu-cleotide primers is still
largely a researchtool.'8 Prospective comparisons have shownDNA
amplification to be superior to conven-tional silver staining for
detection of P cariniiin bronchoalveolar lavage fluid and
inducedsputum.'920 More recently the technique hasbeen successfully
applied to patients with his-tologically variant granulomatous P
cariniipneumonia. Here, although silver staining ofbronchoalveolar
alveolar lavage fluid was neg-ative and the diagnosis was made by
openlung biopsy, retrospective analysis of lavagefluid by DNA
amplification confirmed thediagnosis.2' With future refinements
andappropriate calibration this technique mayhave a clinical role
in diagnosis of P cariniipneumonia, in particular patients with
histo-logically atypical disease, and further reducethe need for
open biopsy to confirm the diag-nosis.Non specific interstitial
pneumonitis, which
may clinically and radiographically simulate Pcarinii
pneumonia,22 has been identified in upto 38% of HIV positive
patients undergoingbronchoscopy for evaluation of
respiratorysymptoms.23 It is perhaps surprising that asthe
diagnosis can be made by transbronchialbiopsy, results from this
investigation werenegative in the three patients in our study
whounderwent this procedure.An alternative strategy in those
patients
with focal radiographic abnormalities mighthave been to use
percutaneous lung biopsyunder fluoroscopic or CT guidance.
However,this procedure carries the risk ofpneumothoraxand
uncontrolled bleeding and there arereports of cardiorespiratory
arrest associatedwith the technique.24 In contrast open lungbiopsy
affords the opportunity to view thelung directly and identify an
abnormal areabefore obtaining tissue and larger samplesmay be
obtained for analysis. Haemostasiscan readily be achieved and the
surgicalpleural leak carefully closed: an intercostaldrain placed
on suction prevents pneumo-thorax.The technique of open lung biopsy
in our
patients was safe. The complication rate wassurprisingly low
with minor wound infectionsin only two patients and chest
infections intwo others. These data are in contrast to otherreports
where wound infection and poor heal-ing have been commoner.' 10 25
In these studiesa higher proportion of patients had
receivedglucocorticoids, a factor that might haveencouraged
infection or delayed healing. Ofnote none of our patients who had
receivedsteroids developed infections.
Cardiothoracic surgeons in other centres
may be asked by physician colleagues to per-form open lung
biopsy on HIV positivepatients. They may question the usefulness
ofthe procedure in terms of the risks and likelybenefits to the
patient. Our data, showing ahigh yield and low morbidity, support
the useof this technique in selected patients. Basedon these data
our unit policy is now to pro-ceed to open lung biopsy in patients
with focaland diffuse radiographic abnormalities only ifthere are
negative results from one or morefibreoptic bronchoscopy (with
bronchoalveo-lar lavage) or if a patient has contraindicationsto
bronchoscopy. In addition, in those withdiffuse radiographic
abnormalities, we wouldonly consider open lung biopsy if there
wasclinical and/or radiographic deteriorationdespite specific
anti-pneumocystis therapy.
In conclusion, open lung biopsy in HIVpositive patients with
symptoms and signs oflower respiratory tract disease and focal or
dif-fuse radiographic abnormalities, with eithernegative results
from bronchoscopic investiga-tions or who have contra indications
to theprocedure, has a high diagnostic yield andresults have a
significant impact on manage-ment, enabling specific therapy to be
givenand unnecessary potentially toxic treatment tobe avoided. The
procedure is safe and has lowmorbidity.We thank Jane Healing and
Ursuline Loubser for typing themanuscript.
1 Jaffe JP, Maki DG. Lung biopsy in immunocompromisedpatients;
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