Pneumocystis carinii pneumonia in HIV-infected patients: effect of steroid therapy on surfactant level.

Previous studies have suggested alterations in pulmonary surfactant lipid in the setting of Pneumocystis carinii pneumonia in HIV-infected patients. Because pulmonary surfactant lipid is composed of a variety of lipid products and because other phospholipids might be present in bronchoalveolar lavage (BAL) lipid determinations, a single molecular species of phospholipid which comprises a substantial portion of the surfactant lipid fraction, dipalmitoyl phosphatidylcholine (DPPC), was measured by capillary column gas chromatography in BAL samples taken at the time of the diagnosis of P. carinii pneumonia, and 10 days after treatment for P. carinii pneumonia. DPPC was measured at day 0 and day 10 in seven patients who had been randomized to receive methylprednisolone adjuvant therapy for P. carinii pneumonia and in six patients who had been randomized to not receive methylprednisolone therapy. The level of DPPC in BAL from all patients at day 0 was 0.49 +/- 0.06 microgram ml-1 BAL. This level is significantly lower that the level of DPPC determined in BAL from five normal volunteers 2.48 +/- 0.40 micrograms ml-1. At day 0, the BAL level of DPPC in patients treated with methylprednisolone was not different from the BAL level of DPPC in patients not treated with methylprednisolone. By day 10 of therapy for P. carinii pneumonia, BAL levels of DPPC in all patients had increased to 1.05 +/- 0.19 micrograms ml-1 BAL. At day 10 DPPC levels in the methylprednisolone treated group were not different from the group not treated with methylprednisolone. We conclude that in HIV-infected patients, lung surfactant lipid is reduced in the setting of P. carinii pneumonia. The lipid levels return toward normal levels with treatment. Adjuvant therapy with corticosteroids does not alter the rate of recovery of surfactant lipid levels at least after 10 days of therapy.

Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins (PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A2 (PLA2) and have been implicated in the host response to micro-organisms. Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant corticosteroids vs. placebo, in addition to standard antimicrobial therapy. Re-bronchoscopy was offered at day 10. BAL fluid was available for 26 patients who had follow-up bronchoscopy performed. At diagnosis, IL-8 levels were elevated in patients with PCP, compared to healthy controls, and correlated with relative BAL neutrophilia and P(A-a)O2. LTB4 was also elevated in PCP, but failed to correlate with either BAL neutrophilia or P(A-a)O2. PLA2 activity in patients correlated with IL-8 levels and BAL neutrophilia, but not with P(A-a)O2. A trend towards a decrease in IL-8 levels in BAL fluid was detected in the corticosteroid-treated patients from days 0-10, whereas no change was detected in the placebo group. No change in levels of LTB4, LTC4, PGE2, PGF2a and PLA2 were detected cover time in either treatment group. This study establishes a correlation between IL-8, BAL neutrophilia and P(A-a)O2, and suggests a role of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear.

Leukotriene B4 and interleukin-8 in human immunodeficiency virus-related pulmonary disease.

STUDY OBJECTIVE: To investigate the pathogenesis of lung injury in Pneumocystic carinii pneumonia and nonspecific interstitial pneumonitis (NIP), common pulmonary complications of human immunodeficiency virus (HIV) infection. The efficacy of corticosteroid therapy in P carinii pneumonia and the observation that bronchoalveolar lavage (BAL) neutrophilia predicts a poor prognosis support the premise that the lung injury of P carinii pneumonia is due to the host's inflammatory response to the infection. DESIGN: In vitro measurements on previously collected BAL fluid samples. SETTING: The Clinical Center of the National Institutes of Health, a research hospital and tertiary care referral center. PATIENTS: Five normal volunteers, 5 asymptomatic HIV-positive patients, 10 HIV-positive patients with NIP (5 asymptomatic and 5 with respiratory symptoms), and 19 HIV-positive patients with P carinii pneumonia. MEASUREMENTS AND RESULTS: BAL leukotriene B4 (LTB4), interleukin 8 (IL-8), and phospholipase A2 (PLA2) were measured. IL-8 and PLA2 were elevated in patients with P carinii pneumonia, and IL-8 correlated with BAL fluid absolute neutrophil count. LTB4, IL-8, and PLA2 levels were elevated in patients with NIP; LTB4 and PLA2 levels correlated with absolute neutrophil count, and IL-8 correlated with alveolar-arterial oxygen pressure difference. IL-8 was elevated in the asymptomatic HIV-positive patients, and there was a trend toward elevation of PLA2 in this group. CONCLUSION: IL-8 appears to play a role in the pathogenesis of lung injury in P carinii pneumonia and may be the principal neutrophil chemotaxin in this disease; PLA2 may also be involved in the pathogenesis of P carinii pneumonia. Both LTB4 and IL-8 may be involved in the recruitment of neutrophils and subsequent lung injury of NIP. These data suggest that there are varying mechanisms by which inflammatory cells are recruited to the lung in different HIV-related lung diseases.

Approach to the immunocompromised host with pulmonary symptoms.

Respiratory disease is common in patients who are immunocompromised, which may be because of opportunistic infection, non-infectious processes related to the underlying disease, or therapy instituted for treatment. Approaching pulmonary symptoms in an immunocompromised host is a complex challenge because the symptoms represent a diverse spectrum of disease. In addition to the routine clinical evaluation, this article reviews four diagnostic procedures to characterize pulmonary disease. Current concepts regarding the prevention of infection are also addressed.