REFRACTORINESS OF AIR-FLOW OBSTRUCTION ASSOCIATED WITH ISOLATED LYMPHOCYTIC BRONCHIOLITIS BRONCHITIS IN PULMONARY ALLOGRAFTS

The clinical significance of an isolated ''lymphocytic bronchiolitis/b ronchitis'' (grade B) as detected in transbronchoscopic biopsy specime ns (TBB) is unclear. We therefore have reviewed the spirometric respon ses associated with isolated grade B diagnoses and contrasted them wit h episodes of ''acute cellular rejection'' (grade A); the latter are m anifested by ''perivascular lymphocytic infiltration.'' Because lympho cytic bronchiolitis/ bronchitis is considered a nonspecific histologic pattern that may be observed with either allograft rejection or respi ratory infections, episodes were analyzed with respect to the presence (grade B [+] CMV) or absence (grade B [-] CMV) of cytomegalovirus inf ection. The maximum forced expiratory volume in 1 second (FEV1) during the preceding 3 months was used as a baseline for computing percent c hange in FEV, coincident with transbronchoscopic biopsies (Delta%FEV1 PRE) and maximum values obtained during the 3 months subsequent to spe cific therapies (Delta%FEV1 POST). All episodes of acute cellular reje ction (grades Al to 4) and symptomatic lymphocytic bronchiolitis/bronc hitis (grade B) were treated with ''pulsed-dose'' methylprednisolone, whereas intravenous ganciclovir was administered to patients at risk f or recrudescence of cytomegalovirus. Between March 1, 1989, and Septem ber 1, 1995, 366 TBB procedures were performed for clinical indication s in 57 lung transplant recipients. Histologic diagnoses with acceptab le serial spirometric values included grade A(1) (n = 9), grade A(2) ( n = 27), grade A(3) (n = 2), grade B(-)CMV (n = 25) and grade B(+)CMV (n = 9). The Delta%FEV1 PRE coincident with TBB were not statistically different for the different histologic groups. For grade A(1), Delta% FEV1 PRE was -14.6% +/- 5.2% (X +/- SEM); A(2), -7.6% +/- 1.8%; B(-)CM V, -14.8% +/- 3.9%; and B(+)CMV, -14.8% +/- 2.3%. After treatment, the Delta%FEV, POST, relative to baseline values, were for grade A(1), -8 .8% +/- 7.1%, A(2), +0.26% +/- 2.6%; B(-)CMV, -12.0% +/- 3.8%; and B()CMV, -6.2% +/- 2.8%. The Delta%FEV1 POST values after pulsed methylpr ednisolone were significantly greater for histologic grade A(2) than g rade B(-)CMV (unpaired Student's t test, P < 0.01; 95% confidence inte rval for the difference of means: 3.34% to 21.2%). Grade A(2) rejectio n was associated with spirometric improvement to within 10% of baselin e values in 52% of episodes; whereas with grade B(-)CMV, this salutary response was observed in only 32% of episodes. Bronchiolitis oblitera ns syndrome stage Ib developed in 13 of 20 (65%) recipients, approxima tely 7.9 +/- 3.4 months after detection of histologic grade B and 21.2 +/- 9.5 months after transplantation. We conclude that the relative ' 'refractoriness'' of histologic grade B most likely reflects a continu um of bronchiolitis obliterans after lung transplantation and, hence, may warrant different immunosuppressive strategies. Furthermore, spiro metric decrement associated with acute cellular rejection (grade A) ma y be ameliorated, but often not completely reversed, after pulsed meth ylprednisolone. We speculate that surveillance TBB may prove rewarding by enabling an earlier detection of these histologic diagnoses before the development of physiologic impairment.