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Study Objectives: Aerosol interferon-gamma (IFN-gamma) is a potential immunomodulator in the treatment of pulmonary tuberculosis (TB). Previous investigations demonstrated conversion of sputum smears in five patients with multidrug-resistant TB after 12 treatments over 1 month, and induction of signaling molecules in 10 of 11 drug-sensitive TB patients using BAL. The objective of the current study was to evaluate particle size and deposition pattern in patients with TB receiving aerosol IFN-gamma treatment.Design: Particle size was determined with a cascade impactor, and deposition of IFN-gamma mixed with (99m)Tc-labeled human serum albumin was assessed using a gamma camera. Local levels of IFN-gamma were measured in BAL using enzyme-linked immunosorbent assays. Study patients/intervention: Fourteen patients with pulmonary TB received IFN-gamma aerosol (500 micro g) for 12 treatments in addition to antimycobacterial therapy with BAL before and after IFN-gamma aerosol treatment. Eight patients with minimal-to-moderate parenchymal involvement underwent deposition studies. Deposited (99m)Tc-labeled IFN-gamma aerosol was partitioned between upper airways and lungs using attenuation correction measurements. (133)Xe equilibrium scanning, (133)Xe washout, and (99m)Tc- macroaggregate injection defined regional lung volume, ventilation, and perfusion.Results: Upper airway deposition was significant often exceeding lung deposition (53.9 +/- 7.09 micro g vs 35.8 +/- 2.73 micro g, respectively [mean +/- SE]). IFN-gamma levels measured in BAL fluid were significantly increased with aerosol treatment (0.83 +/- 0.43 micro g before vs 24.76 +/- 8.71 micro g after, p Conclusions: Aerosol therapy with IFN-gamma in patients with pulmonary TB is widely distributed and results in significant enhancement of IFN-gamma levels in the lower respiratory tract. In patients without lung destruction, IFN-gamma aerosol may be an adjuvant to enhance the local immune response. [ABSTRACT FROM AUTHOR]

Study objectives: Aerosol interferon-γ (IFN-γ) is a potential immunomodulator in the treatment of pulmonary tuberculosis (TB). Previous investigations demonstrated conversion of sputum smears in five patients with multidrug-resistant TB after 12 treatments over 1 month, and induction of signaling molecules in 10 of 11 drug-sensitive TB patients using BAL. The objective of the current study was to evaluate particle size and deposition pattern in patients with TB receiving aerosol IFN-γ treatment. Design: Particle size was determined with a cascade impactor, and deposition of IFN-γ mixed with 99mTc-labeled human serum albumin was assessed using a gamma camera. Local levels of IFN-γ were measured in BAL using enzyme-linked immunosorbent assays. Study patients/intervention: Fourteen patients with pulmonary TB received IFN-γ aerosol (500 µg) for 12 treatments in addition to antimycobacterial therapy with BAL before and after IFN-γ aerosol treatment. Eight patients with minimal-to-moderate parenchymal involvement underwent deposition studies. Deposited 99mTc-labeled IFN-γ aerosol was partitioned between upper airways and lungs using attenuation correction measurements. 133Xe equilibrium scanning, 133Xe washout, and 99mTc- macroaggregate injection defined regional lung volume, ventilation, and perfusion. Results: Upper airway deposition was significant often exceeding lung deposition (53.9 ± 7.09 µg vs 35.8 _ 2.73 µg, respectively [mean ± SE]). IFN-γ levels measured in BAL fluid were significantly increased with aerosol treatment (0.83 ± 0.43 µg before vs 24.76 ± 8.71 µg after, p < 0.017), and IFN-γ levels correlated with regional deposition of IFN-γ aerosol (r = 0.823). Four-quadrant analysis of regional lung deposition best correlated with regional perfusion (r = 0.422, p = 0.013) with penetration of aerosol into areas of obvious radiographic infiltration on chest radiograph. Conclusions: Aerosol therapy with IFN-γ in patients with pulmonary TB is widely distributed and results in significant enhancement of IFN-γ levels in the lower respiratory tract. In patients without lung destruction, IFN-γ aerosol may be an adjuvant to enhance the local immune response. [ABSTRACT FROM AUTHOR]