A decline in the pulmonary diffusing capacity does not indicate opportunistic lung disease in asymptomatic persons infected with the human immunodeficiency virus

We enrolled 1,353 subjects in a multicenter study to evaluate the spectrum of pulmonary complications associated with human immunodeficiency virus (HIV) infection and the feasibility of detecting pulmonary infections in asymptomatic members of this group. There were 1,171 who were HIV- seropositive; the remaining 182 were HIV-seronegative, but they belonged to high-risk transmission groups (homosexual/bisexual, or injection drug users). Single-breath carbon monoxide diffusing capacity (DL(CO)) was measured serially (at 3- to 12-month intervals) in a prospective fashion to determine whether a decline of ≥ 20% predicted the presence of Pneumocystis carinii pneumonia or other pulmonary infections in the absence of new pulmonary symptoms and no new abnormalities on chest roentgenograms. In 64 subjects (6% of the group who had two or more measurements) DL(CO) declined ≥ 20% from a prior value within 2 yr of entry, unassociated with fever, increased cough or dyspnea, or new chest roentgenogram abnormalities. Induced sputum was analyzed for the presence of P. carinii and mycobacteria in 44; fiberoptic bronchoscopy was performed with bronchoalveolar lavage in 14, six of whom also had transbronchial lung biopsy. All 64 subjects with the asymptomatic decline in DL(CO) were followed for an additional 3 to 12 months with additional clinical evaluations, chest roentgenograms, and DL(CO) determinations, or until death (one subject). In no case was the decline in DL(CO) due to P. carinii pneumonia or other pulmonary infection. Two subjects were found to have nonspecific interstitial pneumonitis by transbronchial lung biopsy; none had this disorder confirmed by open lung biopsy or autopsy, and no patient developed a clinical/roentgenographic picture that was suggestive of nonspecific interstitial pneumonitis. Eight subjects were thought to have a reduced DL(CO) because they were unable to perform the test properly. Of the 63 subjects for whom follow-up DL(CO) measurements were available, improvement was noted in 45 (71%); DL(CO) remained stable in seven (11%), and DL(CO) declined further in 11 (17%). Nonspecific interstitial pneumonitis or lymphocytic alveolitis may have caused the asymptomatic decline of DL(CO) in HIV-infected subjects. An alternative explanation is the amount of intraindividual variability of the test. We conclude that a decline in the DL(CO) without concomitant respiratory symptoms or new chest roentgenographic abnormalities does not warrant further evaluation. Moreover, serial measurements of DL(CO) should not be performed to screen HIV-infected persons for lung diseases.